greenmedinfo--2020-08-30--Anticancer effects of oridonin on colon cancer are mediated via BMP7/p38 MAPK/p53 signaling.

Colon cancer is a prevalent malignancy affecting the gastrointestinal tract .
Oridonin ( ORI ) is a promising chemotherapeutic drug used in the treatment of colon cancer .
In this study , we examined the anticancer activity of ORI against colon cancer and elucidated the underlying molecular mechanisms .
Cell counting kit-8 , flow cytometric and western blot analyses were conducted to analyze the growth inhibitory effects of ORI on SW620 cells ; we employed BMP7 and p53 recombinant adenovirus to detect the influence of ORI on the p38 MAPK signal pathway ; PT-qPCR , cell immunofluorescence staining and western @ @ @ @ @ @ @ expression of BMP7 , p38 and p-p38 , p53 and p-p53 .
A xenograft tumor model and histological evaluation were introduced to detect the effects of ORI and BMP7 in SW620 cells in vivo .
ORI inhibited the proliferation of SW620 cells and induced apoptosis .
ORI also increased the total and phosphorylated levels of p53 .
The overexpression of p53 was found to enhance the anti-proliferative effects of ORI on the SW620 cells , while the inhibition of p53 partially reversed these effects .
ORI increased the expression of bone morphogenetic protein @ @ @ @ @ @ @ cells .
The overexpression of BMP7 also enhanced the antiproliferative effects of ORI on the SW620 cells and reduced the growth rate of tumors in mice .
BMP7-induced immunosuppression markedly decreased the anti-proliferative effects of ORI .
ORI was not found to exert any substantial effect on the phosphorylation levels of Smad1/5/8 , although it increased the level of p-p38 significantly .
The inhibition of p38 significantly attenuated the ORI-induced increase in the levels of p-p53 .
The overexpression of BMP7 enhanced the promoting effects of ORI on the p-p53 and p-p38 levels @ @ @ @ @ @ @ of ORI on p-p38 and p-p53 .
On the whole , the findings of this study suggest that ORI may be a promising agent for use in the treatment of colon cancer , and the anticancereffects of ORI may be partially mediated through the BMP7/p38 MAPK/p53 signaling pathway .

Colon cancer is a prevalent malignancy affecting the gastrointestinal tract. Oridonin (ORI) is a promising chemotherapeutic drug used in the treatment of colon cancer. In this study, we examined the anticancer activity of ORI against colon cancer and elucidated the underlying molecular mechanisms. Cell counting kit-8, flow cytometric and western blot analyses were conducted to analyze the growth inhibitory effects of ORI on SW620 cells; we employed BMP7 and p53 recombinant adenovirus to detect the influence of ORI on the p38 MAPK signal pathway; PT-qPCR, cell immunofluorescence staining and western blot analysis were used to detect the expression of BMP7, p38 and p-p38, p53 and p-p53. A xenograft tumor model and histological evaluation were introduced to detect the effects of ORI and BMP7 in SW620 cells in vivo. ORI inhibited the proliferation of SW620 cells and induced apoptosis. ORI also increased the total and phosphorylated levels of p53. The overexpression of p53 was found to enhance the anti-proliferative effects of ORI on the SW620 cells, while the inhibition of p53 partially reversed these effects. ORI increased the expression of bone morphogenetic protein 7 (BMP7) in the SW620 cells. The overexpression of BMP7 also enhanced the antiproliferative effects of ORI on the SW620 cells and reduced the growth rate of tumors in mice. BMP7-induced immunosuppression markedly decreased the anti-proliferative effects of ORI. ORI was not found to exert any substantial effect on the phosphorylation levels of Smad1/5/8, although it increased the level of p-p38 significantly. The inhibition of p38 significantly attenuated the ORI-induced increase in the levels of p-p53. The overexpression of BMP7 enhanced the promoting effects of ORI on the p-p53 and p-p38 levels, while BMP7-induced immunosuppression reduced the effects of ORI on p-p38 and p-p53. On the whole, the findings of this study suggest that ORI may be a promising agent for use in the treatment of colon cancer, and the anticancereffects of ORI may be partially mediated through the BMP7/p38 MAPK/p53 signaling pathway.


greenmedinfo--2020-08-30--Oridonin-induced mitochondria-dependent apoptosis in esophageal cancer cells.

Oridonin , an active diterpenoid isolated from Rabdosia rubescens , has been reported for its antitumor activity on several cancers .
However , its effect on human esophageal cancer remains unclear .
In this study , we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo .
Oridonin not only suppressed the proliferation , but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30 , KYSE-150 , and EC9706 cells with dose-dependent manner .
Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating @ @ @ @ @ @ @ B1 and CDK2 , while upregulating p53 and p21 .
Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2 , as well as the increased expression of cleaved caspase-3 , -8 , and -9 .
In addition , oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway .
In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model .
Taken together , these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer .

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported for its antitumor activity on several cancers. However, its effect on human esophageal cancer remains unclear. In this study, we demonstrated that oridonin could inhibit the growth of human esophageal cancer cells both in vitro and in vivo. Oridonin not only suppressed the proliferation, but also induced cell cycle arrest and mitochondrial-mediated apoptosis in KYSE-30, KYSE-150, and EC9706 cells with dose-dependent manner. Further mechanism studies revealed that oridonin led cell cycle arrest in esophageal cancer cells via downregulating cell cycle-related proteins, such as cyclin B1 and CDK2, while upregulating p53 and p21. Oridonin also increased proapoptotic protein Bax and reduced antiapoptotic protein Bcl-2, as well as the increased expression of cleaved caspase-3, -8, and -9. In addition, oridonin treatment could significantly inhibit the PI3K/Akt/mTOR and Ras/Raf signaling pathway. In vivo results further demonstrated that oridonin treatment markedly inhibited tumor growth in the esophageal cancer xenograft mice model. Taken together, these results suggest that oridonin may be a potential anticancer agent for the treatment of esophageal cancer.


greenmedinfo--2020-08-30--Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transi

Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma.

Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival .
Recently , epithelial-mesenchymal transition ( EMT ) is reported as a key event in cancer invasion and metastasis .
Oridonin , a bioactive diterpenoid , has been proved to possess anti-cancer effects .
However , the effect of oridonin on EMT and metastasis of osteosarcoma is unclear .
In this study , we investigated the underlying mechanism of oridonin on EMT and metastasis of osteosarcoma .
We found that oridonin inhibited migration and invasion of MG-63 and 143B cells .
Moreover , oridonin @ @ @ @ @ @ @ decreased that of N-cadherin and Vimentin .
Oridonin upregulated the transcription of E-cadherin and downregulated N-cadherin and Vimentin .
Oridonin inhibited the protein and mRNA levels of Snail and Slug .
Furthermore , oridonin inhibited TGF-β-induced phosphorylation of Smad 2/3 , prevented Smad dimer translocation into the nucleus .
Finally , we established metastatic models of osteosarcoma 143B cells , and found that oridonin inhibited lung metastasis in vivo .
Oridonin increased the protein expression of E-cadherin and reduced N-cadherinand Vimentin .
Oridonin inhibited the protein expression of Snail and Slug as well @ @ @ @ @ @ @ , our study demonstrated that oridonin inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma .

Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival. Recently, epithelial-mesenchymal transition (EMT) is reported as a key event in cancer invasion and metastasis. Oridonin, a bioactive diterpenoid, has been proved to possess anti-cancer effects. However, the effect of oridonin on EMT and metastasis of osteosarcoma is unclear. In this study, we investigated the underlying mechanism of oridonin on EMT and metastasis of osteosarcoma. We found that oridonin inhibited migration and invasion of MG-63 and 143B cells. Moreover, oridonin increased the protein expression of E-cadherin and decreased that of N-cadherin and Vimentin. Oridonin upregulated the transcription of E-cadherin and downregulated N-cadherin and Vimentin. Oridonin inhibited the protein and mRNA levels of Snail and Slug. Furthermore, oridonin inhibited TGF-β-induced phosphorylation of Smad 2/3, prevented Smad dimer translocation into the nucleus. Finally, we established metastatic models of osteosarcoma 143B cells, and found that oridonin inhibited lung metastasis in vivo. Oridonin increased the protein expression of E-cadherin and reduced N-cadherinand Vimentin. Oridonin inhibited the protein expression of Snail and Slug as well as Smad 2/3 activation. In conclusion, our study demonstrated that oridonin inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma.


greenmedinfo--2020-08-30--ROS/JNK/c-Jun axis is involved in oridonin-induced caspase-dependent apoptosis in human colorectal c

ROS/JNK/c-Jun axis is involved in oridonin-induced caspase-dependent apoptosis in human colorectal cancer cells.

Colorectal cancer ( CRC ) is one of the most common malignant neoplasms with high mortality worldwide .
Oridonin , a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens , has been proved to have anticancer effect on various types of cancer cells .
However , the detailed mechanisms of oridonin in CRC cells remain unclear and if oridonin can overcome 5-FU resistance have not been investigated yet .
In this study , we investigated the anticancer effect of oridonin in both 5-FU sensitive and resistant CRC cells and illuminated the underlying mechanisms .
We showed that oridonin induced @ @ @ @ @ @ @ 5-FU sensitive and resistant CRC cells .
Oridonin induced reactive oxygen species ( ROS ) accumulation in both 5-FU sensitive and resistant CRC cells , which resulted in cell apoptosis as oridonin-induced apoptosis was almost abolished when cells were co-treated with the ROS scavenger N-acetyl-L-cysteine ( NAC ) .
Moreover , we found that oridonin induced CRC cell apoptosis via the c-Jun N-terminal kinase ( JNK ) /c-Jun pathway as oridonin activated JNK/c-Jun pathway and the JNK inhibitor SP600125 restored oridonin-induced apoptosis in CRC cells .
Interestingly , when CRC cells were co-treated @ @ @ @ @ @ @ pathway induced by oridonin was nearly reversed , indicating that oridonin induced JNK/c-Jun pathway activation through the accumulation of ROS .
Taken together , these data reveal that oridonin induces apoptosis through the ROS/JNK/c-Jun axis in both 5-FU sensitive and resistant CRC cells , suggesting that oridonin could be a potential agent for CRC treatment .

Colorectal cancer (CRC) is one of the most common malignant neoplasms with high mortality worldwide. Oridonin, a diterpenoid isolated from the Chinese medicinal herb Rabdosia rubescens, has been proved to have anticancer effect on various types of cancer cells. However, the detailed mechanisms of oridonin in CRC cells remain unclear and if oridonin can overcome 5-FU resistance have not been investigated yet. In this study, we investigated the anticancer effect of oridonin in both 5-FU sensitive and resistant CRC cells and illuminated the underlying mechanisms. We showed that oridonin induced proliferation inhibition and caspase-dependent apoptosis in both 5-FU sensitive and resistant CRC cells. Oridonin induced reactive oxygen species (ROS) accumulation in both 5-FU sensitive and resistant CRC cells, which resulted in cell apoptosis as oridonin-induced apoptosis was almost abolished when cells were co-treated with the ROS scavenger N-acetyl-L-cysteine (NAC). Moreover, we found that oridonin induced CRC cell apoptosis via the c-Jun N-terminal kinase (JNK)/c-Jun pathway as oridonin activated JNK/c-Jun pathway and the JNK inhibitor SP600125 restored oridonin-induced apoptosis in CRC cells. Interestingly, when CRC cells were co-treated with NAC, the activation of JNK/c-Jun pathway induced by oridonin was nearly reversed, indicating that oridonin induced JNK/c-Jun pathway activation through the accumulation of ROS. Taken together, these data reveal that oridonin induces apoptosis through the ROS/JNK/c-Jun axis in both 5-FU sensitive and resistant CRC cells, suggesting that oridonin could be a potential agent for CRC treatment.


greenmedinfo--2020-08-30--Effects of oridonin on proliferation apoptosis of human multiple myeloma cells H929 in vitro.

OBJECTIVE : To investigate the effects of oridonin ( ORI ) on the proliferation and apoptosis of human multiple myeloma cell line H929 and its possible mechanism .
METHODS : H929 cells were exposed to ORI 0、4、8、12、16、20、24、28、32 μmol/L for 12 , 24 and 36 hours respectively .
The prolifcration inhibitory effect of ORI on H929 cells was determined by MTT assay and then the working concentrations of ORI were determined .
The morphological changes and apoptosis of H929 cells were observed byTUNEL ( TdT-mediated dUTP Nick-End Labeling ) and fluorescence microscopy .
The apoptosis rate of H929 cells was detected @ @ @ @ @ @ @ .
The protein expressions of pro-caspase-3 , BCL-2，p-PI3K , p-Akt , BAX , Cleaved PARP and p-JNK , p-ERK and p-p38 in H929 cells weredetected by Western blot .
RESULTS : Compared with the control group , the proliferation of H929 cells treated with the ORI of 8-16μmol/L was significantly inhibited and the apoptosis of H929 cells was obviously increased in dose- and time-dependent manners .
As for morphological changes , the characteristics of apoptotic cells were presented in H929 cells treated with ORI for 24 hours .
The protein levels of pro-caspase-3 @ @ @ @ @ @ @ increasing of ORI concentration（r=0.9861 , r=0.9725 , r=0.9413 , r=0.9373） , while the BAX , Cleaved PARP and p-JNK , p-ERK and p-p38 were up-regulated（r=0.9178 , r=0.8877 , r=0.882 , r=0.9645 , r=0.8623） .
CONCLUSION : The ORI possesses anti-myeloma effects , can inhibit the proliferation and induce the apoptosis of H929 cell line in vitro .
Its potential mechanism may be related with up-regulating the MAPK and down-regulating the PI3K/Akt signal pathways .

OBJECTIVE: To investigate the effects of oridonin (ORI) on the proliferation and apoptosis of human multiple myeloma cell line H929 and its possible mechanism.
METHODS: H929 cells were exposed to ORI 0、4、8、12、16、20、24、28、32 μmol/L for 12, 24 and 36 hours respectively. The prolifcration inhibitory effect of ORI on H929 cells was determined by MTT assay and then the working concentrations of ORI were determined. The morphological changes and apoptosis of H929 cells were observed byTUNEL (TdT-mediated dUTP Nick-End Labeling) and fluorescence microscopy. The apoptosis rate of H929 cells was detected by flow cytometry with Annexin V-FITC/PI staining. The protein expressions of pro-caspase-3, BCL-2，p-PI3K, p-Akt, BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 in H929 cells weredetected by Western blot.
RESULTS: Compared with the control group, the proliferation of H929 cells treated with the ORI of 8-16μmol/L was significantly inhibited and the apoptosis of H929 cells was obviously increased in dose- and time-dependent manners. As for morphological changes, the characteristics of apoptotic cells were presented in H929 cells treated with ORI for 24 hours. The protein levels of pro-caspase-3, BCL-2，p-PI3K, p-Akt were down-regulated with increasing of ORI concentration（r=0.9861, r=0.9725, r=0.9413, r=0.9373）, while the BAX, Cleaved PARP and p-JNK, p-ERK and p-p38 were up-regulated（r=0.9178, r=0.8877, r=0.882, r=0.9645, r=0.8623）.
CONCLUSION: The ORI possesses anti-myeloma effects, can inhibit the proliferation and induce the apoptosis of H929 cell line in vitro. Its potential mechanism may be related with up-regulating the MAPK and down-regulating the PI3K/Akt signal pathways.


greenmedinfo--2020-08-30--Oridonin as a potential therapeutic candidate for human Guillain-Barré syndrome and neuropathies.

The diterpenoid compound , Oridonin , extracted from the Chinese herb , , possesses multiple biological activities and properties .
Oridonin exhibited efficient anti-inflammatory activity by inducing a switch in macrophage polarization to the anti-inflammatory phenotype through inhibition of the Notch pathway in ourstudy ; therefore , its potential therapeutic effects were further investigated in the animal model of human Guillain-Barré syndrome ( GBS ) and other polyneuropathies - experimental autoimmune neuritis ( EAN ) .
Either preventive or therapeutic treatments with Oridonin greatly attenuated disease peak severity , suppressed paraparesis , shortened disease duration , and even delayed EAN @ @ @ @ @ @ @ demyelination , inflammatory cellular accumulations , and inflammatory cytokines in peripheral nerves were significantly attenuated .
Meanwhile , accumulation of immune cells in the spinal roots and microglial activation in the lumbar spinal cord were also reduced .
Interestingly , Oridonin treatment significantly increased the proportion of anti-inflammatory macrophages and made them locally dominant among all infiltrated macrophages in the peripheral nerves .
The down-regulation of local Notch pathway proteins , together with ourresults indicated their possible involvement .
Taken together , our results demonstrated that Oridonin effectively suppressed EAN by attenuating local @ @ @ @ @ @ @ immune regulating macrophages in the peripheral nerves , possibly through blockage of the Notch pathway , which suggests Oridonin as a potential therapeutic candidate for human GBS and neuropathies .

The diterpenoid compound, Oridonin, extracted from the Chinese herb,, possesses multiple biological activities and properties. Oridonin exhibited efficient anti-inflammatory activity by inducing a switch in macrophage polarization to the anti-inflammatory phenotype through inhibition of the Notch pathway in ourstudy; therefore, its potential therapeutic effects were further investigated in the animal model of human Guillain-Barré syndrome (GBS) and other polyneuropathies - experimental autoimmune neuritis (EAN). Either preventive or therapeutic treatments with Oridonin greatly attenuated disease peak severity, suppressed paraparesis, shortened disease duration, and even delayed EAN onset. Progression of neuropathic pain,demyelination, inflammatory cellular accumulations, and inflammatory cytokines in peripheral nerves were significantly attenuated. Meanwhile, accumulation of immune cells in the spinal roots and microglial activation in the lumbar spinal cord were also reduced. Interestingly, Oridonin treatment significantly increased the proportion of anti-inflammatory macrophages and made them locally dominant among all infiltrated macrophages in the peripheral nerves. The down-regulation of local Notch pathway proteins, together with ourresults indicated their possible involvement. Taken together, our results demonstrated that Oridonin effectively suppressed EAN by attenuating local inflammatory reaction and increasing the proportion of immune regulating macrophages in the peripheral nerves, possibly through blockage of the Notch pathway, which suggests Oridonin as a potential therapeutic candidate for human GBS and neuropathies.


greenmedinfo--2020-08-30--Oridonin inhibits LPS-induced inflammation in human gingival fibroblasts by activating PPARγ.

Oridonin , the major terpene isolated from Rabdosia rubescens , has been used as dietary supplement .
Recently , it @ @ @ @ @ anti-inflammatory effect .
This study we employed an in vitro model of LPS-stimulated human gingival @ @ @ @ @ effects and mechanism of oridonin .
Oridonin ( 10-30 μg/mL ) was administrated 1 h @ @ @ @ @ results showed that oridonin significantly inhibited inflammatory mediators PGE , NO , IL-6 , and @ @ @ @ @ revealed that oridonin reduced the expression of phosphorylation levels of NF-κB p65 and IκBα .
@ @ @ @ @ PPARγ was up-regulated by the treatment of oridonin .
Further studies showed that PPARγ inhibitor @ @ @ @ @ of oridonin on PGE , NO , IL-6 , and IL-8 production .
In conclusion @ @ @ @ @ activation through activating PPARγ .

Oridonin, the major terpene isolated from Rabdosia rubescens, has been used as dietary supplement. Recently, it has been known to exhibit anti-inflammatory effect. This study we employed an in vitro model of LPS-stimulated human gingival fibroblasts to investigate the anti-inflammatory effects and mechanism of oridonin. Oridonin (10-30 μg/mL) was administrated 1 h before LPS treatment. The results showed that oridonin significantly inhibited inflammatory mediators PGE, NO, IL-6, and IL-8 production. Immunoblotting experiments revealed that oridonin reduced the expression of phosphorylation levels of NF-κB p65 and IκBα. Furthermore, the expression of PPARγ was up-regulated by the treatment of oridonin. Further studies showed that PPARγ inhibitor GW9662 could reverse the inhibition of oridonin on PGE, NO, IL-6, and IL-8 production. In conclusion, oridonin inhibited LPS-induced microglia activation through activating PPARγ.


greenmedinfo--2020-08-30--Oridonin protects against cardiac hypertrophy by promoting P21-related autophagy.

Autophagy is an endogenous protective process ; the loss of autophagy could destabilize proteostasis and elevate intracellular oxidative stress , which is critically involved in the development of cardiac hypertrophy and heart failure .
Oridonin , a natural tetracycline diterpenoid from the Chinese herb Rabdosia , has autophagy activation properties .
In this study , we tested whether oridonin protects against cardiac hypertrophy in mice and cardiomyocytes .
We implemented aortic banding to induce a cardiac hypertrophy mouse model , and oridonin was given by gavage for 4 weeks .
Neonatal rat cardiomyocytes were stimulated with angiotensin II to simulate @ @ @ @ @ @ @ in vitro studies suggested that oridonin treatment mitigated pressure overload-induced cardiac hypertrophy and fibrosis , and also preserved heart function .
Mice that received oridonin exhibited increased antioxidase activities and suppressed oxidative injury compared with the aortic banding group .
Moreover , oridonin enhanced myocardial autophagy in pressure-overloaded hearts and angiotensin II-stimulated cardiomyocytes .
Mechanistically , we discovered that oridonin administration regulated myocardial P21 , and cytoplasmic P21 activated autophagy via regulating Akt and AMPK phosphorylation .
These findings were further corroborated in a P21 knockout mouse model .
Collectively , pressure overload-induced @ @ @ @ @ @ @ resulting in ROS injury while aggravating cardiac hypertrophy .
Thus , our data show that oridonin promoted P21-related autophagic lysosomal degradation , hence attenuating oxidative injury and cardiac hypertrophy .

Autophagy is an endogenous protective process; the loss of autophagy could destabilize proteostasis and elevate intracellular oxidative stress, which is critically involved in the development of cardiac hypertrophy and heart failure. Oridonin, a natural tetracycline diterpenoid from the Chinese herb Rabdosia, has autophagy activation properties. In this study, we tested whether oridonin protects against cardiac hypertrophy in mice and cardiomyocytes. We implemented aortic banding to induce a cardiac hypertrophy mouse model, and oridonin was given by gavage for 4 weeks. Neonatal rat cardiomyocytes were stimulated with angiotensin II to simulate neurohumoural stress. Both in vivo and in vitro studies suggested that oridonin treatment mitigated pressure overload-induced cardiac hypertrophy and fibrosis, and also preserved heart function. Mice that received oridonin exhibited increased antioxidase activities and suppressed oxidative injury compared with the aortic banding group. Moreover, oridonin enhanced myocardial autophagy in pressure-overloaded hearts and angiotensin II-stimulated cardiomyocytes. Mechanistically, we discovered that oridonin administration regulated myocardial P21, and cytoplasmic P21 activated autophagy via regulating Akt and AMPK phosphorylation. These findings were further corroborated in a P21 knockout mouse model. Collectively, pressure overload-induced autophagy dysfunction causes intracellular protein accumulation, resulting in ROS injury while aggravating cardiac hypertrophy. Thus, our data show that oridonin promoted P21-related autophagic lysosomal degradation, hence attenuating oxidative injury and cardiac hypertrophy.


greenmedinfo--2020-08-30--Oridonin protects against lipopolysaccharide-induced acute lung injury.

BACKGROUND : Oxidative stress and the resulting inflammation are essential pathological processes in acute lung injury ( ALI ) .
Nuclear factor erythroid 2-related factor 2 ( Nrf2 ) , a vital transcriptional factor , possesses antioxidative potential and has become a primary target to treat many diseases .
Oridonin ( Ori ) , isolated from the plant Rabdosia Rrubescens , is a natural substance that possesses antioxidative and anti-inflammatory effects .
Our aim was to study whether the anti-inflammatory and antioxidant effects of Ori on LPS-induced ALI were mediated by Nrf2 .
METHODS : MTT assays , Western blotting @ @ @ @ @ @ @ hematoxylin-eosin ( H & E ) staining were employed to explore the mechanisms by which Ori exerts a protective effect on LPS-induced lung injury in RAW264.7 cells and in a mouse model .
RESULTS : Our results indicated that Ori increased the expression of Nrf2 and its downstream genes ( HO-1 , GCLM ) , which was mediated by the activation of Akt and MAPK .
Additionally , Ori inhibited LPS-induced activation of the pro-inflammatory pathways NLRP3 inflammasome and NF-κB pathways .
These two pathways were also proven to be Nrf2-independent by the @ @ @ @ @ @ @ keeping with these findings , Ori alleviated LPS-induced histopathological changes , the enhanced production of myeloperoxidase and malondialdehyde , and the depleted expression of GSH and superoxide dismutase in the lung tissue of mice .
Furthermore , the expression of LPS-induced NLRP3 inflammasome and NF-κB pathways was more evident in Nrf2-deficient mice but could still be reversed by Ori .
CONCLUSIONS : Our results demonstrated that Ori exerted protective effects on LPS-induced ALI via Nrf2-independent anti-inflammatory and Nrf2-dependent antioxidative activities .

BACKGROUND: Oxidative stress and the resulting inflammation are essential pathological processes in acute lung injury (ALI). Nuclear factor erythroid 2-related factor 2 (Nrf2), a vital transcriptional factor, possesses antioxidative potential and has become a primary target to treat many diseases. Oridonin (Ori), isolated from the plant Rabdosia Rrubescens, is a natural substance that possesses antioxidative and anti-inflammatory effects. Our aim was to study whether the anti-inflammatory and antioxidant effects of Ori on LPS-induced ALI were mediated by Nrf2.
METHODS: MTT assays, Western blotting analysis, a mouse model, and hematoxylin-eosin (H&E) staining were employed to explore the mechanisms by which Ori exerts a protective effect on LPS-induced lung injury in RAW264.7 cells and in a mouse model.
RESULTS: Our results indicated that Ori increased the expression of Nrf2 and its downstream genes (HO-1, GCLM), which was mediated by the activation of Akt and MAPK. Additionally, Ori inhibited LPS-induced activation of the pro-inflammatory pathways NLRP3 inflammasome and NF-κB pathways. These two pathways were also proven to be Nrf2-independent by the use of a Nrf2 inhibitor. In keeping with these findings, Ori alleviated LPS-induced histopathological changes, the enhanced production of myeloperoxidase and malondialdehyde, and the depleted expression of GSH and superoxide dismutase in the lung tissue of mice. Furthermore, the expression of LPS-induced NLRP3 inflammasome and NF-κB pathways was more evident in Nrf2-deficient mice but could still be reversed by Ori.
CONCLUSIONS: Our results demonstrated that Ori exerted protective effects on LPS-induced ALI via Nrf2-independent anti-inflammatory and Nrf2-dependent antioxidative activities.


greenmedinfo--2020-08-30--Oridonin derivatives as potential anticancer drug candidates triggering apoptosis.

The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon , oridonin , has been intensively studied .
However , its mechanism studies and clinical applications were hampered by its moderate biological activities .
In order to enlarge the applied range of oridonin and explore its mechanism of action , a series of derivatives were designed and synthesized based on the structure of oridonin .
Some of the derivatives were significantly more potent than oridonin against four cancer cell lines .
Especially , the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly @ @ @ @ @ @ @ low as 1.36 μM and 0.78 μM respectively , while the ICvalues of oridonin are 8.12 μM and 7.41 μM .
We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase .
Moreover , it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential , increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins .
Furthermore , compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect .
Altogether , these results @ @ @ @ @ @ @ lead for liver cancer therapeutics .

The biological function of the natural ent-kaurene diterpenoid isolated from genus Isodon, oridonin, has been intensively studied. However, its mechanism studies and clinical applications were hampered by its moderate biological activities. In order to enlarge the applied range of oridonin and explore its mechanism of action, a series of derivatives were designed and synthesized based on the structure of oridonin. Some of the derivatives were significantly more potent than oridonin against four cancer cell lines. Especially, the most potent compound 20 markedly inhibited the proliferation of well differentiated HepG2 and poorly differentiated PLC/PRF/5 cells, with ICvalues as low as 1.36 μM and 0.78 μM respectively, while the ICvalues of oridonin are 8.12 μM and 7.41 μM. We found that compound 20 inhibited liver cancer cell proliferation via arresting cell cycle at G1 phase. Moreover, it induced liver cancer cell apoptosis by decreasing the mitochondrial membrane potential, increasing intracellular reactive oxygen species level and inducing the expression of apoptosis-related proteins. Furthermore, compound 20 significantly inhibited growth of PLC/PRF/5 xenograft tumors in nude mice and had no observable toxic effect. Altogether, these results indicated that compound 20 is a promising lead for liver cancer therapeutics.


greenmedinfo--2020-08-31--Oridonin combined with capecitabine can synergistically inhibit the proliferation of MDA-MB-231 huma

To investigate the effects of oridonin combined with capecitabine on the proliferaction of MDA-MB-231 human breast cancer cells.Effect of different concentrations ( 10 , 20 and 40μmol/L ) of oridonin , capecitabine and their combination on the proliferation of MDA-MB-231 cells after incubation for 24 or 48 h was studied .
Then , the effect of 5 μmol/L of oridonin , capecitabine and their combination on cell colony formation was detected .
Finally , influence of 20 μmol/L of oridonin , capecitabine and their combination on morphological alteration of nucleus , cell cycle and apoptosis was explored.The inhibition rate on @ @ @ @ @ @ @ or capecitabine for 48 h was 49.5 % and 58.6 % , respectively , while the inhibition rate against proliferation of MDA-MB-231 cells reached 94.6 % with combination of 20 μmol/L oridonin and capecitabine .
Cells incubated with combination of oridonin and capecitabine formed fewer and smaller colonies ( < 0.01 ) .
Meanwhile , cells in the combination group arrested at S and G2/M phases at the same time , and combination of two drugs caused more apoptotic cells ( < 0.01 ) .Oridonin combined with capecitabine can synergistically inhibit the proliferation @ @ @ @ @ @ @

To investigate the effects of oridonin combined with capecitabine on the proliferaction of MDA-MB-231 human breast cancer cells.Effect of different concentrations(10, 20 and 40μmol/L)of oridonin, capecitabine and their combination on the proliferation of MDA-MB-231 cells after incubation for 24 or 48 h was studied. Then, the effect of 5 μmol/L of oridonin, capecitabine and their combination on cell colony formation was detected. Finally, influence of 20 μmol/L of oridonin, capecitabine and their combination on morphological alteration of nucleus, cell cycle and apoptosis was explored.The inhibition rate on MDA-MB-231 cells after incubation with 20μmol/L oridonin or capecitabine for 48 h was 49.5% and 58.6%, respectively, while the inhibition rate against proliferation of MDA-MB-231 cells reached 94.6% with combination of 20 μmol/L oridonin and capecitabine. Cells incubated with combination of oridonin and capecitabine formed fewer and smaller colonies (<0.01). Meanwhile, cells in the combination group arrested at S and G2/M phases at the same time, and combination of two drugs caused more apoptotic cells (<0.01).Oridonin combined with capecitabine can synergistically inhibit the proliferation of MDA-MB-231 human breast cancer cells.


greenmedinfo--2020-08-31--Oridonin protects against the inflammatory response in diabetic nephropathy.

Inflammation plays a pivotal role in the development and progression of diabetic nephropathy ( DN ) .
Oridonin ( Ori ) , a component isolated from Rabdosia rubescens , possesses remarkable anti-inflammatory , immunoregulatory and antitumor properties .
However , the renoprotective effects of Ori and the underlying molecular mechanisms have not been explored in DN .
In this study , we aimed to investigate the protective effects and potential mechanisms responsible for the anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in vitro .
Our results showed that Ori significantly attenuated diabetes-induced renal injury and markedly @ @ @ @ @ @ @ creatinine concentrations and blood urea nitrogen concentrations in rats .
Ori also significantly alleviated infiltration of inflammatory cells ( cluster of differentiation ( CD ) 68 ) in kidney tissues and reduced the levels of pro-inflammatory cytokines , including tumor necrosis factor-α ( TNF-α ) , interleukin-6 ( IL-6 ) , IL-1β and monocyte chemotactic protein 1 ( MCP-1 ) , both in vivo and in vitro .
TLR4 is a principal mediator of innate immune and inflammatory responses and participates in the development of DN .
Our molecular studies indicated that Ori @ @ @ @ @ @ @ .
Additional studies were conducted to investigate the effect of Ori on the p38-mitogen-activated protein kinase ( p38-MAPK ) and nuclear factor ( NF ) -κB pathways .
The results showed that Ori inhibited IκBα , p65 , and p38 phosphorylation , as well as NF-κB DNA-binding activity .
In conclusion , these results demonstrated that Ori exerts protective effects in diabetes-induced renal injury in vivo and in vitro .
These effects may be ascribed to its anti-inflammatory and modulatory effects on the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways .

Inflammation plays a pivotal role in the development and progression of diabetic nephropathy (DN). Oridonin (Ori), a component isolated from Rabdosia rubescens, possesses remarkable anti-inflammatory, immunoregulatory and antitumor properties. However, the renoprotective effects of Ori and the underlying molecular mechanisms have not been explored in DN. In this study, we aimed to investigate the protective effects and potential mechanisms responsible for the anti-inflammatory effects of Ori in diabetes-induced renal injury in vivo and in vitro. Our results showed that Ori significantly attenuated diabetes-induced renal injury and markedly decreased urinary protein excretion levels, serum creatinine concentrations and blood urea nitrogen concentrations in rats. Ori also significantly alleviated infiltration of inflammatory cells (cluster of differentiation (CD)68) in kidney tissues and reduced the levels of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and monocyte chemotactic protein 1 (MCP-1), both in vivo and in vitro. TLR4 is a principal mediator of innate immune and inflammatory responses and participates in the development of DN. Our molecular studies indicated that Ori administration significantly down-regulated TLR4 overexpression in DN. Additional studies were conducted to investigate the effect of Ori on the p38-mitogen-activated protein kinase (p38-MAPK) and nuclear factor (NF)-κB pathways. The results showed that Ori inhibited IκBα, p65, and p38 phosphorylation, as well as NF-κB DNA-binding activity. In conclusion, these results demonstrated that Ori exerts protective effects in diabetes-induced renal injury in vivo and in vitro. These effects may be ascribed to its anti-inflammatory and modulatory effects on the TLR4/p38-MAPK and TLR4/NF-κB signaling pathways.


greenmedinfo--2020-08-31--Oridonin induces apoptosis in human nasopharyngeal carcinoma cells involving ROS generation.

Oridonin , an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens , has been reported to be a potent cytotoxic agent against a wide array of cancer cells .
However , its effect on human nasopharyngeal carcinoma ( NPC ) cells has not been well investigated .
The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms .
Cell viability was examined by 3- ( 4,5-dimethylthiazol-2-yl ) -2,5-diphenyl-tetrazolium bromide assay and colony formation assay .
Apoptosis , mitochondrial membrane potential ( MMP ) , reactive oxygen species ( ROS ) @ @ @ @ @ @ @ analysed by flow cytometry with propidium iodide staining , JC-1 staining , DCFH-DA staining , and Western blot analysis , respectively .
The results showed that oridonin concentration-dependently inhibited the cell viability , decreased the colony formation , and enhanced the apoptotic rate in NPC cells .
Further , oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells , which was confirmed by the loss of MMP , downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2 , upregulation of pro-apoptotic Bcl-2 family member Bax , and activation of caspase-3 and @ @ @ @ @ @ @ generation played an essential role in oridonin-induced apoptosis in NPC cells , as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine .
These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells .
This study supports oridonin to be an interesting candidate drug for the treatment of human NPC .

Oridonin, an ent-kaurene diterpenoid isolated from the traditional Chinese herb Rabdosia rubescens, has been reported to be a potent cytotoxic agent against a wide array of cancer cells. However, its effect on human nasopharyngeal carcinoma (NPC) cells has not been well investigated. The present study aimed to explore the anti-tumour effect of oridonin in NPC cells and its underlying mechanisms. Cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay and colony formation assay. Apoptosis, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and expression of apoptosis-related proteins were analysed by flow cytometry with propidium iodide staining, JC-1 staining, DCFH-DA staining, and Western blot analysis, respectively. The results showed that oridonin concentration-dependently inhibited the cell viability, decreased the colony formation, and enhanced the apoptotic rate in NPC cells. Further, oridonin-induced apoptosis was mediated by the mitochondrial pathway in NPC cells, which was confirmed by the loss of MMP, downregulation of anti-apoptotic Bcl-2 family protein Mcl-1 and Bcl-2, upregulation of pro-apoptotic Bcl-2 family member Bax, and activation of caspase-3 and PARP. Notably, the augmented ROS generation played an essential role in oridonin-induced apoptosis in NPC cells, as the apoptosis-inducing effect was attenuated by ROS scavenger N-acetyl-L-cysteine. These results indicate that oridonin triggers apoptosis through the ROSmediated mitochondrial pathway in NPC cells. This study supports oridonin to be an interesting candidate drug for the treatment of human NPC.


greenmedinfo--2020-08-31--Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mit

Oridonin synergistically enhances JQ1-triggered apoptosis in hepatocellular cancer cells through mitochondrial pathway.

Bromodomain and Extra-Terminal Domain ( BET ) inhibitors , such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer .
However , many solid cancers are resistance to BET inhibitors .
To explore methods for improving the therapeutic potential of BET inhibitors , we investigated the combinational activity of JQ1 with Oridonin , a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma ( HCC ) cells .
Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and @ @ @ @ @ @ @ cells and in HCC cancer stem-like cells .
Moreover , Oridonin dose-dependently inhibited the expression of several anti-apoptotic proteins , such as Bcl-2 , Mcl-1 , and x-linked inhibitor of apoptosis ( xIAP ) in HCC cells .
Cell fractionation and western blotting analysis showed that the enhancement of apoptosis by Oridonin was associated with cytochrome c release , activation of caspase-9 , -3 and cleavage of PARP , indicating the activation of mitochondrial apoptosis pathway .
Altogether , our findings demonstrate that Oridonin may be used to effectively enhance the sensitivity of @ @ @ @ @ @ @ of the expression of multiple anti-apoptotic proteins .

Bromodomain and Extra-Terminal Domain (BET) inhibitors, such as JQ1 have emerged as novel drug candidates and are being enthusiastically pursued in clinical trials for the treatment of cancer. However, many solid cancers are resistance to BET inhibitors. To explore methods for improving the therapeutic potential of BET inhibitors, we investigated the combinational activity of JQ1 with Oridonin, a bioactive molecules derived from Traditional Chinese Medicine in hepatocellular carcinoma (HCC) cells. Our results showed that Oridonin synergistically enhanced the abilities of JQ1 to inhibit cell viability in HCC cells and, significantly augmented JQ1-triggered apoptosis in HCC cells and in HCC cancer stem-like cells. Moreover, Oridonin dose-dependently inhibited the expression of several anti-apoptotic proteins, such as Bcl-2, Mcl-1, and x-linked inhibitor of apoptosis (xIAP) in HCC cells. Cell fractionation and western blotting analysis showed that the enhancement of apoptosis by Oridonin was associated with cytochrome c release, activation of caspase-9, -3 and cleavage of PARP, indicating the activation of mitochondrial apoptosis pathway. Altogether, our findings demonstrate that Oridonin may be used to effectively enhance the sensitivity of BET inhibitors in HCC therapy via downregulation of the expression of multiple anti-apoptotic proteins.


greenmedinfo--2020-08-31--Oridonin exerts anticancer effect on osteosarcoma by activating PPAR-γ and inhibiting Nrf2 pathway.

Osteosarcoma is the most common high-grade human primary malignant bone sarcoma with lower survival in the past decades .
Oridonin , a bioactive diterpenoid isolated from Rabdosia rubescens , has been proved to possess potent anti-cancer effects .
However , its potential mechanism still remains not fully clear nowadays .
In this study , we investigated the anticancer effect of oridonin on human osteosarcoma and illuminated the underlying mechanisms .
In vitro , oridonin inhibited the cell viability of various osteosarcoma cells .
We demonstrated that oridonin induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio , loss of mitochondrial membrane potential @ @ @ @ @ @ @ species ( ROS ) generation and activating caspase-3 and caspase-9 cleavage in MG-63 and HOS cells .
Moreover , we found that oridonin triggered ROS by inhibiting NF-E2-related factor 2 ( Nrf2 ) pathway and induced mitochondrial apoptosis via inhibiting nuclear factor-κB ( NF-κB ) activation by activating Peroxisome Proliferator-Activated Receptor γ ( PPAR-γ ) in MG-63 and HOS cells .
We further confirmed the results by PPAR-γ inhibitor GW9662 , PPAR-γ siRNA as well as overexpression of PPAR-γ and Nrf2 in vitro .
Furthermore , our in vivo study showed that oridonin @ @ @ @ @ @ @ inducing apoptosis through activating PPAR-γ and inhibiting Nrf2 activation in xenograft model inoculated HOS tumor .
Taken together , oridonin exerted a dramatic pro-apoptotic effect by activating PPAR-γ and inhibiting Nrf2 pathway in vitro and in vivo.Therefore , oridonin may be a promising and effective agent for human osteosarcoma in the future clinical applications .

Osteosarcoma is the most common high-grade human primary malignant bone sarcoma with lower survival in the past decades. Oridonin, a bioactive diterpenoid isolated from Rabdosia rubescens, has been proved to possess potent anti-cancer effects. However, its potential mechanism still remains not fully clear nowadays. In this study, we investigated the anticancer effect of oridonin on human osteosarcoma and illuminated the underlying mechanisms. In vitro, oridonin inhibited the cell viability of various osteosarcoma cells. We demonstrated that oridonin induced mitochondrial-mediated apoptosis by increasing Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP), triggering reactive oxygen species (ROS) generation and activating caspase-3 and caspase-9 cleavage in MG-63 and HOS cells. Moreover, we found that oridonin triggered ROS by inhibiting NF-E2-related factor 2 (Nrf2) pathway and induced mitochondrial apoptosis via inhibiting nuclear factor-κB (NF-κB) activation by activating Peroxisome Proliferator-Activated Receptor γ (PPAR-γ) in MG-63 and HOS cells. We further confirmed the results by PPAR-γ inhibitor GW9662, PPAR-γ siRNA as well as overexpression of PPAR-γ and Nrf2 in vitro. Furthermore, our in vivo study showed that oridonin inhibited tumor growth with high safety via inducing apoptosis through activating PPAR-γ and inhibiting Nrf2 activation in xenograft model inoculated HOS tumor. Taken together, oridonin exerted a dramatic pro-apoptotic effect by activating PPAR-γ and inhibiting Nrf2 pathway in vitro and in vivo.Therefore, oridonin may be a promising and effective agent for human osteosarcoma in the future clinical applications.


greenmedinfo--2020-08-31--These findings suggest that oridonin is a promising anti-metastasis agent for melanoma.

Epithelial-mesenchymal transition ( EMT ) has been reported to play pivotal roles in tumor invasion and metastasis .
Inhibition of EMT may exert beneficial effects in regulating metastasis .
Oridonin ( ORI ) , an active diterpenoid compound isolated from , was found to be a potent anti-metastatic agent .
However , the possible involvement of ORI in the EMT in malignant melanoma is unclear .
The present study found that ORI inhibited cell migration , invasion , and adhesion in A375 and B16-F10 melanoma cells .
The transforming growth factor-β1 ( TGF-β1 ) -induced EMT was also inhibited in @ @ @ @ @ @ @ upregulation of E-cadherin , and downregulation of vimentin and Snail .
Similar results were observed in A375 and B16-F10 melanoma cells treated with ORI .
Furthermore , pre-treatment with ORI blocked the TGF-β1-induced phosphoinositide 3-kinase ( PI3K ) /AKT serine/threonine kinase ( Akt ) /glycogen synthase kinase ( GSK ) -3β signaling pathway activation .
These effects mimicked PI3 kinase inhibitor LY294002 treatment .
ORI interfered with the PI3K/Akt/GSK-3β pathway , and reversed TGF-β1-induced EMT , which suppressedthe invasion and metastasis of melanoma cells .
Taken together , the present study demonstrated that @ @ @ @ @ @ @ , and adhesion and TGF-β1-induced EMT through the PI3K/Akt/GSK-3β signaling pathway .
These findings suggest that ORI is a promising anti-metastasis agent for melanoma .

Epithelial-mesenchymal transition (EMT) has been reported to play pivotal roles in tumor invasion and metastasis. Inhibition of EMT may exert beneficial effects in regulating metastasis. Oridonin (ORI), an active diterpenoid compound isolated from, was found to be a potent anti-metastatic agent. However, the possible involvement of ORI in the EMT in malignant melanoma is unclear. The present study found that ORI inhibited cell migration, invasion, and adhesion in A375 and B16-F10 melanoma cells. The transforming growth factor-β1 (TGF-β1)-induced EMT was also inhibited in ORI-treated cells, as reflected in the upregulation of E-cadherin, and downregulation of vimentin and Snail. Similar results were observed in A375 and B16-F10 melanoma cells treated with ORI. Furthermore, pre-treatment with ORI blocked the TGF-β1-induced phosphoinositide 3-kinase (PI3K)/AKT serine/threonine kinase (Akt)/glycogen synthase kinase (GSK)-3β signaling pathway activation. These effects mimicked PI3 kinase inhibitor LY294002 treatment. ORI interfered with the PI3K/Akt/GSK-3β pathway, and reversed TGF-β1-induced EMT, which suppressedthe invasion and metastasis of melanoma cells. Taken together, the present study demonstrated that ORI inhibits melanoma cells migration, invasion, and adhesion and TGF-β1-induced EMT through the PI3K/Akt/GSK-3β signaling pathway. These findings suggest that ORI is a promising anti-metastasis agent for melanoma.


greenmedinfo--2020-08-31--Oridonin inhibits oral cancer growth and PI3K/Akt signaling pathway.

Oridonin , a bioactive diterpenoid purified from Rabdosia rubescens , has been shown to possess anticancer capacity in several cancer types .
However , its effects on oral squamous cell carcinoma ( OSCC ) cells remain unclear .
This study aimed to investigate the anticancer ability of oridonin in OSCC cells , including proliferation , apoptosis and underlying mechanisms using the OSCC cell lines , UM1 and SCC25 .
The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner .
@ @ @ @ @ @ @ the ratio of Bax/Bcl-2 , and activated the cleavage of caspase-3 , caspase-9 and PARP-1 .
Oridonin also induced G2/M phase arrest in OSCC cells via down-regulating the G2/M transition-related proteins such as cyclin B1 or up-regulating cyclin D1 , cyclin D3 , P21 , p-CDK1 and cyclin A2 .
In addition , oridonin treatment significantly inhibited the phosphorylation of PI3K and Akt and inhibited tumor growth of OSCC xenograft in nude mice .
Taken together , these results suggested that oridonin possesses anti-oral cancer capacity via inhibiting the PI3K/Akt signaling and induce @ @ @ @ @ @ @ oridonin may be a potential anticancer drug for the treatment of oral cancer .

Oridonin, a bioactive diterpenoid purified from Rabdosia rubescens, has been shown to possess anticancer capacity in several cancer types. However, its effects on oral squamous cell carcinoma (OSCC) cells remain unclear. This study aimed to investigate the anticancer ability of oridonin in OSCC cells, including proliferation, apoptosis and underlying mechanisms using the OSCC cell lines, UM1 and SCC25. The results showed that oridonin not only inhibited proliferation and clonal formation but also induced G2/M cell cycle arrest and apoptosis in UM1 and SCC25 cells in a dose-dependent manner. Western blot revealed that oridonin treatment increased the ratio of Bax/Bcl-2, and activated the cleavage of caspase-3, caspase-9 and PARP-1. Oridonin also induced G2/M phase arrest in OSCC cells via down-regulating the G2/M transition-related proteins such as cyclin B1 or up-regulating cyclin D1, cyclin D3, P21, p-CDK1 and cyclin A2. In addition, oridonin treatment significantly inhibited the phosphorylation of PI3K and Akt and inhibited tumor growth of OSCC xenograft in nude mice. Taken together, these results suggested that oridonin possesses anti-oral cancer capacity via inhibiting the PI3K/Akt signaling and induce apoptosis and G2/M-phase arrest. Therefore, oridonin may be a potential anticancer drug for the treatment of oral cancer.


greenmedinfo--2020-08-31--Oridonin increases anticancer effects of lentinan in HepG2 human hepatoblastoma cells.

The aim of the present study was to investigate whether oridonin is able to increase the effects of lentinan ( LNT ) in HepG2 human hepatoblastoma cells by MTT , flow cytometry , reverse transcription-quantitative polymerase chain reaction and western blot analysis .
Theresults demonstrated that 20µg/ml of oridonin was a nontoxic concentration for L02 normal liver cells and HepG2 liver cancer cells .
Furthermore , treatment with 0-200 µg/ml LNT was only able to decrease the viability of HepG2 liver cancer cells .
The growth inhibitory rate of the LNT-L ( 100 µg/ml ) treatment group was 20.7 % @ @ @ @ @ @ @ 200 µg/ml ) treatment group was 54.8 % .
Notably , the growth inhibitory rate of the oridonin + LNT-H group was 84.3 % .
The highest percentage of apoptotic cells was observed in the oridonin + LNT-H group ( 20 µg/ml oridonin and 200 µg/ml LNT ) .
The percentage of apoptotic cellsin the oridonin + LNT-H group was significantly different from the percentage of apoptotic cells in the LNT-H ( 26.1 % ) and the LNT-L ( 16.8 % ) groups .
Treatment with LNT produced an increase in caspase-3 , @ @ @ @ @ @ @ , p21 , nuclear factor κB inhibitor-α mRNA and protein expression and a decrease in B-cell lymphoma 2 and nuclear factor-κB expression in HepG2 cells compared with untreated control cells .
Treatment with a combination of oridonin and LNT-H induced a further increase in expression with the biggest differences in expression observed between the oridonin + LNT-H group and control .
It was observed that treatment with oridonin was able to increase the anticancer effects of LNT in HepG2 cells .
Therefore , oridonin may be used to sensitize cells to LNT .

The aim of the present study was to investigate whether oridonin is able to increase the effects of lentinan (LNT) in HepG2 human hepatoblastoma cells by MTT, flow cytometry, reverse transcription-quantitative polymerase chain reaction and western blot analysis. Theresults demonstrated that 20µg/ml of oridonin was a nontoxic concentration for L02 normal liver cells and HepG2 liver cancer cells. Furthermore, treatment with 0-200 µg/ml LNT was only able to decrease the viability of HepG2 liver cancer cells. The growth inhibitory rate of the LNT-L (100 µg/ml) treatment group was 20.7% and the rate of the LNT-H (200 µg/ml) treatment group was 54.8%. Notably, the growth inhibitory rate of the oridonin + LNT-H group was 84.3%. The highest percentage of apoptotic cells was observed in the oridonin + LNT-H group (20 µg/ml oridonin and 200 µg/ml LNT). The percentage of apoptotic cellsin the oridonin + LNT-H group was significantly different from the percentage of apoptotic cells in the LNT-H (26.1%) and the LNT-L (16.8%) groups. Treatment with LNT produced an increase in caspase-3, caspase-9, Bcl-2-like protein 4, p53, p21, nuclear factor κB inhibitor-α mRNA and protein expression and a decrease in B-cell lymphoma 2 and nuclear factor-κB expression in HepG2 cells compared with untreated control cells. Treatment with a combination of oridonin and LNT-H induced a further increase in expression with the biggest differences in expression observed between the oridonin + LNT-H group and control. It was observed that treatment with oridonin was able to increase the anticancer effects of LNT in HepG2 cells. Therefore, oridonin may be used to sensitize cells to LNT.


greenmedinfo--2020-08-31--Mitochondrial ROS contribute to oridonin-induced HepG2 apoptosis through PARP activation.

Oridonin , the main active constituent of , is known to exert antitumor activity via the induction of apoptosis in numerous types of human cancer cells .
However , the underlying regulatory mechanisms of mitochondrial ROS in oridonin-induced HepG2 apoptosis remain largely unknown , due to limitations of subcellular imaging resolution .
Previously , it has been suggested that mitochondria serve a potential role in sensing and signaling cellular redox changes in vital biological processes such as cell death and the abiotic stress response , based on studies involving the mitochondrial-targeted redox-sensitive green fluorescent protein ( GFP ) .
To @ @ @ @ @ @ @ mtGrx1-roGFP2 ) biosensor was implemented to monitor real-time mitochondrial redox changes of HepG2 cells in response to either HO/DTT or oridonin/SS31 treatment .
It was determined that oridonin caused a perturbation in mitochondrial redox status , which in turn contributed to oridonin-induced apoptosis .
Furthermore , a novel mechanism underlying the regulation of mitochondrial redox changes in oridonin-induced HepG2 apoptosis , presumably dependent on PARP cleavage , was proposed .
In conclusion , the present study provides evidence in support of mitochondrial redox changes as a potential mediator in the apoptotic activities of @ @ @ @ @ @ @ insight into the molecular mechanisms by which mitochondrial redox signaling regulates oridonin-induced apoptosis in cancer therapy , and the development of mitochondria-specific oridonin as a promising novel anticancer therapeutic strategy .

Oridonin, the main active constituent of, is known to exert antitumor activity via the induction of apoptosis in numerous types of human cancer cells. However, the underlying regulatory mechanisms of mitochondrial ROS in oridonin-induced HepG2 apoptosis remain largely unknown, due to limitations of subcellular imaging resolution. Previously, it has been suggested that mitochondria serve a potential role in sensing and signaling cellular redox changes in vital biological processes such as cell death and the abiotic stress response, based on studies involving the mitochondrial-targeted redox-sensitive green fluorescent protein (GFP). To address this, a mitochondrial-targeted Grx1-roGFP2 (mtGrx1-roGFP2) biosensor was implemented to monitor real-time mitochondrial redox changes of HepG2 cells in response to either HO/DTT or oridonin/SS31 treatment. It was determined that oridonin caused a perturbation in mitochondrial redox status, which in turn contributed to oridonin-induced apoptosis. Furthermore, a novel mechanism underlying the regulation of mitochondrial redox changes in oridonin-induced HepG2 apoptosis, presumably dependent on PARP cleavage, was proposed. In conclusion, the present study provides evidence in support of mitochondrial redox changes as a potential mediator in the apoptotic activities of oridonin in HepG2 cells, which provides insight into the molecular mechanisms by which mitochondrial redox signaling regulates oridonin-induced apoptosis in cancer therapy, and the development of mitochondria-specific oridonin as a promising novel anticancer therapeutic strategy.


greenmedinfo--2020-08-31--Oridonin inhibits vascular inflammation by blocking NF-κB and MAPK activation.

Oridonin , an active diterpenoid compound isolated from the plant Rabdosia Rrubescens , has various pharmacological activities , including antioxidant , anti-tumor capacities and anti-inflammation .
In the present study , we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism .
Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay .
The protein expression was measured by Western blot .
NF-κB p65 translocation was measured by immunofluorescence .
Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo .
The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin .
Oridonin @ @ @ @ @ @ @ adhesion molecules ( intercellular adhesion molecule-1 ( ICAM-1 ) ; vascular cell adhesion molecule-1 ( VCAM-1 ) and E-selectin ) and the pro-inflammatory cytokine ( IL-6 , IL-8 and monocyte chemoattractant protein-1 ( MCP-1 ) ) .
Oridonin suppressed the penetration of the leukocyte in theacute lung injury mice model .
Furthermore , Oridonin also suppressed the TNF-α-activated MAPK and Nuclear factor kappa B ( NF-κB ) activation .
Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells , at least in part , through the suppression of MAPK and @ @ @ @ @ @ @ potential therapeutic use for inflammatory vascular diseases .

Oridonin, an active diterpenoid compound isolated from the plant Rabdosia Rrubescens, has various pharmacological activities, including antioxidant, anti-tumor capacities and anti-inflammation. In the present study, we explore the role of oridonin in regulating endothelial inflammation and its underlying mechanism. Endothelial cell-monocyte interaction was detected by Leukocyte-endothelium Adhesion Assay. The protein expression was measured by Western blot. NF-κB p65 translocation was measured by immunofluorescence. Acute lung inflammation model was used to evaluate leukocyte infiltration in vivo. The endothelial-leukocyte adhesion and the leukocyte transmigration were profoundly reduced by oridonin. Oridonin dramatically inhibited the expression of TNF-α-induced endothelial adhesion molecules (intercellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1) and E-selectin) and the pro-inflammatory cytokine (IL-6, IL-8 and monocyte chemoattractant protein-1(MCP-1)). Oridonin suppressed the penetration of the leukocyte in theacute lung injury mice model. Furthermore, Oridonin also suppressed the TNF-α-activated MAPK and Nuclear factor kappa B (NF-κB) activation. Our results suggest that oridonin has the anti-inflammatory properties in endothelial cells, at least in part, through the suppression of MAPK and NF-κB activation, which may have a potential therapeutic use for inflammatory vascular diseases.


greenmedinfo--2020-09-01--Oridonin effectively reverses the drug resistance of cisplatin in human acute myeloid leukemia cells

Oridonin effectively reverses the drug resistance of cisplatin in human acute myeloid leukemia cells.

Cisplatin is the first generation platinum-based chemotherapy agent .
However , the extensive application of cisplatin inevitably causes drug resistance , which is a major obstacle to cancer chemotherapy .
Oridonin is a diterpenoid isolated fromwith potent anticancer activity .
The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia ( AML ) cells .
The effect of oridonin on human AML cell proliferation was evaluated by MTT assay , cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells .
Furthermore @ @ @ @ @ @ @ cytometry .
The inhibitive effect of oridoninwas determined using xenografted nude mice .
In addition , the expressions of MMP2 and MMP9 were detected by Western blot .
There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cellsand .
In addition , the combination of cisplatin and oridonin synergistically induced cell apoptosis .
Furthermore , the combination treatment not only inhibited AML cell migration and invasion , but more significantly , decreased the expressions of MMP2 and MMP9 proteins .
Our results suggest that the synergistic effect between @ @ @ @ @ @ @ by the inhibition of MMP expression and the resulting increased apoptosis .

Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated fromwith potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML) cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridoninwas determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cellsand. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.


greenmedinfo--2020-09-01--Oridonin induces G 2/M cell cycle arrest and apoptosis via the PI3K/Akt signaling pathway in hormone

Oridonin induces G 2/M cell cycle arrest and apoptosis via the PI3K/Akt signaling pathway in hormone-independent prostate cancer cells.

Oridonin is an active constituent isolated from the traditional Chinese herb , which exerts antitumor effects in experimental and clinical settings .
However , its antitumor effects and underlying mechanisms on prostate cancer cells have not yet been clearly identified .
In the present study , the androgen-independent prostate cancer PC3 and DU145 cell lines were used as models to investigate the effects and possible mechanisms of oridonin on cellular proliferation and apoptosis .
Results demonstrated that oridonin inhibited cellular proliferation , and was able to significantly induce G/M cell cycle arrest and apoptosis .
Detailed signaling pathway analysis by @ @ @ @ @ @ @ of p53 and p21 were upregulated , whereas the expression of cyclin-dependent kinase 1 was downregulated following oridonin treatment , which led to cell cycle arrest in the G/M phase .
Oridonin also upregulated the proteolytic cleaved forms of caspase-3 , caspase-9 and poly ( ADP-ribose ) polymerase .
Furthermore , the protein expression levels of B-cell lymphoma 2 were decreased and those of Bcl-2-associated X protein were increased following oridonin treatment .
In addition , oridonin treatment significantly inhibited the expression of phosphoiniositide-3 kinase ( PI3K ) p85 subunit and the phosphorylation @ @ @ @ @ @ @ double minute 2 was also downregulated , which may contribute to the elevated expression of p53 following oridonin treatment .
In conclusion , the results of the present study suggested that oridonin is able to inactivate the PI3K/Akt pathway and activate p53 pathways in prostate cancer cells , resulting in the suppression of proliferation and the induction of caspase-mediated apoptosis .

Oridonin is an active constituent isolated from the traditional Chinese herb, which exerts antitumor effects in experimental and clinical settings. However, its antitumor effects and underlying mechanisms on prostate cancer cells have not yet been clearly identified. In the present study, the androgen-independent prostate cancer PC3 and DU145 cell lines were used as models to investigate the effects and possible mechanisms of oridonin on cellular proliferation and apoptosis. Results demonstrated that oridonin inhibited cellular proliferation, and was able to significantly induce G/M cell cycle arrest and apoptosis. Detailed signaling pathway analysis by western blotting demonstrated that the expression levels of p53 and p21 were upregulated, whereas the expression of cyclin-dependent kinase 1 was downregulated following oridonin treatment, which led to cell cycle arrest in the G/M phase. Oridonin also upregulated the proteolytic cleaved forms of caspase-3, caspase-9 and poly (ADP-ribose) polymerase. Furthermore, the protein expression levels of B-cell lymphoma 2 were decreased and those of Bcl-2-associated X protein were increased following oridonin treatment. In addition, oridonin treatment significantly inhibited the expression of phosphoiniositide-3 kinase (PI3K) p85 subunit and the phosphorylation of Akt. The downstream gene murine double minute 2 was also downregulated, which may contribute to the elevated expression of p53 following oridonin treatment. In conclusion, the results of the present study suggested that oridonin is able to inactivate the PI3K/Akt pathway and activate p53 pathways in prostate cancer cells, resulting in the suppression of proliferation and the induction of caspase-mediated apoptosis.


greenmedinfo--2020-09-01--Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling.

BACKGROUND : Oridonin is a diterpenoid isolated fromwith potent anticancer activity .
The aim of our study is to investigate @ @ @ @ @ inhibit growth and metastasis of human breast cancer cells .
METHODS : The effect of @ @ @ @ @ by MTT assay , cell migration and invasion were evaluated by transwell migration and invasion @ @ @ @ @ cells .
The inhibitive effect of oridoninwas determined by using xenografted nude mice .
In @ @ @ @ @ Notch receptors ( Notch 1-4 ) was detected by western blot .
RESULTS : Oridonin @ @ @ @ @ .
In addition , oridonin significantly induced human breast cancer cells apoptosis .
Furthermore , @ @ @ @ @ inhibited cancer cell migration and invasion , but more significantly , decreased the expression of @ @ @ @ @ : Our results suggest that the inhibitive effect of oridonin is likely to be driven @ @ @ @ @ signaling pathway and the resulting increased apoptosis .

BACKGROUND: Oridonin is a diterpenoid isolated fromwith potent anticancer activity. The aim of our study is to investigate the role of oridonin to inhibit growth and metastasis of human breast cancer cells.
METHODS: The effect of oridonin on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in human breast cancer cells. The inhibitive effect of oridoninwas determined by using xenografted nude mice. In addition, the expression of Notch receptors (Notch 1-4) was detected by western blot.
RESULTS: Oridonin inhibited human breast cancer cellsand. In addition, oridonin significantly induced human breast cancer cells apoptosis. Furthermore, the oridonin treatment not only inhibited cancer cell migration and invasion, but more significantly, decreased the expression of Notch 1-4 protein.
CONCLUSION: Our results suggest that the inhibitive effect of oridonin is likely to be driven by the inhibition of Notch signaling pathway and the resulting increased apoptosis.


greenmedinfo--2020-09-01--Oridonin synergizes with Nutlin-3 in osteosarcoma cells by modulating the levels of multiple Bcl-2 f

Oridonin synergizes with Nutlin-3 in osteosarcoma cells by modulating the levels of multiple Bcl-2 family proteins.

The small-molecule inhibitors of p53-murine double minute 2 interaction , such as Nutlin-3 , are effective against cancers bearing wild-type p53 .
However , murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells .
To address this issue , we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells .
We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1 , but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines .
Importantly , in the presence of Oridonin , @ @ @ @ @ @ @ the wild-type p53 osteosarcoma cell lines .
Western blotting analysis showed that Oridonin treatment rapidly and distinctly increased the levels of all three forms of Bim and also markedly reduced the levels of Bcl-2 and Bcl-xl in osteosarcoma cells .
Western blotting analysis further showed that Oridonin considerably enhanced Nutlin-3-triggered activation of caspases-9 and -3 and poly ( ADP-ribose ) polymerase cleavage .
Flow cytometry assay showed that Oridonin significantly enhanced Nutlin-3-mediated apoptosis in wild-type p53 osteosarcoma cells .
Overall , our results suggest that the combined treatment of Nutlin-3 plus Oridonin may @ @ @ @ @ @ @ .

The small-molecule inhibitors of p53-murine double minute 2 interaction, such as Nutlin-3, are effective against cancers bearing wild-type p53. However, murine double minute 2 inhibitors often are unable to completely eliminate solid tumor cells. To address this issue, we investigated the anticancer effects of Nutlin-3 in combination with Oridonin in osteosarcoma cells. We found that Oridonin at sub-toxic concentrations synergistically enhanced Nutlin-3-mediated cell viability inhibition in wild-type p53 U2OS and SJSA-1, but not in p53-mutant MNNG/HOS and in null-p53 Saos-2 osteosarcoma cell lines. Importantly, in the presence of Oridonin, Nutlin-3 could completely abolish cell viability in the wild-type p53 osteosarcoma cell lines. Western blotting analysis showed that Oridonin treatment rapidly and distinctly increased the levels of all three forms of Bim and also markedly reduced the levels of Bcl-2 and Bcl-xl in osteosarcoma cells. Western blotting analysis further showed that Oridonin considerably enhanced Nutlin-3-triggered activation of caspases-9 and -3 and poly(ADP-ribose) polymerase cleavage. Flow cytometry assay showed that Oridonin significantly enhanced Nutlin-3-mediated apoptosis in wild-type p53 osteosarcoma cells. Overall, our results suggest that the combined treatment of Nutlin-3 plus Oridonin may offer a novel therapeutic strategy for osteosarcoma.


greenmedinfo--2020-09-01--Oridonin protects the lung against hyperoxia-induced injury in a mouse model.

Hyperoxic acute lung injury ( HALI ) is caused by prolonged exposure to high oxygen partial pressure .
This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model .
Mice were randomly divided into three groups : the control group , HALI group and oridonin ( ORI ) group .
HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute ( ATA ) for six hours in the HALI and ORI groups .
In the ORI group , mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after @ @ @ @ @ @ @ hours after the hyperoxia exposure , followed by bronchoalveolar lavage fluid ( BALF ) .
Lungs were then collected .
Each lung was processed for HE staining and detection of wet-to-dry weight ratio .
The lactate dehydrogenase ( LDH ) activity and protein content of BALF were determined , and the contents of malonaldehyde ( MDA ) , glutathione ( GSH ) , tumor necrosis factor alpha ( TNF- ? )
and interleukin-10 ( IL-10 ) in the lung were measured .
Our results showed prolonged exposure to hyperoxia significantly damaged the lung @ @ @ @ @ @ @ and TNF- ?
, and reduced GSH and IL-10 in the lung .
However , post-exposure treatment with oridonin was able to improve lung pathology , attenuate lung edema , reduce MDA and TNF- ?
, and increase GSH and IL-10 in the lung .
These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice .

Hyperoxic acute lung injury (HALI) is caused by prolonged exposure to high oxygen partial pressure. This study was undertaken to investigate the protective effects of oridonin on HALI in a mouse model. Mice were randomly divided into three groups: the control group, HALI group and oridonin (ORI) group. HALI was induced by exposing mice to pure oxygen at 2.5 atmospheres absolute (ATA) for six hours in the HALI and ORI groups. In the ORI group, mice were intraperitoneally injected with ORI at 10 mg/kg twice daily after hyperoxic exposure. Animals were sacrificed 24 hours after the hyperoxia exposure, followed by bronchoalveolar lavage fluid (BALF). Lungs were then collected. Each lung was processed for HE staining and detection of wet-to-dry weight ratio. The lactate dehydrogenase (LDH) activity and protein content of BALF were determined, and the contents of malonaldehyde (MDA), glutathione (GSH), tumor necrosis factor alpha (TNF-?) and interleukin-10 (IL-10) in the lung were measured. Our results showed prolonged exposure to hyperoxia significantly damaged the lung, caused lung edema, increased MDA and TNF-?, and reduced GSH and IL-10 in the lung. However, post-exposure treatment with oridonin was able to improve lung pathology, attenuate lung edema, reduce MDA and TNF-?, and increase GSH and IL-10 in the lung. These findings suggest that oridonin can protect the lung against hyperoxia-induced injury in mice.


greenmedinfo--2020-09-01--Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer

Oridonin induces apoptosis and reverses drug resistance in cisplatin resistant human gastric cancer cells.

Gastric cancer is the third most frequent cause of cancer-associated mortality and almost all patients who respond initially to cisplatin ( DDP ) later develop drug resistance , indicating multi-drug resistance ( MDR ) is an essential aspect of the failure of treatment .
The natural diterpenoid component Oridonin ( Ori ) has exhibited efficient inhibition in several types of human cancer .
However , the effect and potential mechanism of Ori-reversed MDR in human gastric cancer has not been fully elucidated .
In the present study , it was found that Ori significantly suppressed DDP-resistant human SGC7901/DDP cell proliferation @ @ @ @ @ @ @ increased caspase-dependent apoptosis , decreased expression of P-glycoprotein ( P-gp ) , encoded by the MDR gene , multi-drug resistance-associated protein ( MRP1 ) , and cyclin D1 .
SGC7901/DDP cells were cultured with different groups of drugs ( Ori , DDP alone , or the combination of Ori and DDP ) .
The drug sensitivity , cell apoptosis and effects on MDR were detected by MTT assay and western blot analysis .
The results revealed that Ori is able to reverse the DDP resistance and has a clear synergistic effect with DDP @ @ @ @ @ @ @ of P-gp , MRP1 , cyclin D1 and cancerous inhibitor of protein phosphatase 2A .
Thus , Ori may be a novel effective candidate to treat DDP-resistant human gastric cancer cells .

Gastric cancer is the third most frequent cause of cancer-associated mortality and almost all patients who respond initially to cisplatin (DDP) later develop drug resistance, indicating multi-drug resistance (MDR) is an essential aspect of the failure of treatment. The natural diterpenoid component Oridonin (Ori) has exhibited efficient inhibition in several types of human cancer. However, the effect and potential mechanism of Ori-reversed MDR in human gastric cancer has not been fully elucidated. In the present study, it was found that Ori significantly suppressed DDP-resistant human SGC7901/DDP cell proliferation, growth and colony formation, causing increased caspase-dependent apoptosis, decreased expression of P-glycoprotein (P-gp), encoded by the MDR gene, multi-drug resistance-associated protein (MRP1), and cyclin D1. SGC7901/DDP cells were cultured with different groups of drugs (Ori, DDP alone, or the combination of Ori and DDP). The drug sensitivity, cell apoptosis and effects on MDR were detected by MTT assay and western blot analysis. The results revealed that Ori is able to reverse the DDP resistance and has a clear synergistic effect with DDP in SGC7901/DDP cells by decreasing the levels of P-gp, MRP1, cyclin D1 and cancerous inhibitor of protein phosphatase 2A. Thus, Ori may be a novel effective candidate to treat DDP-resistant human gastric cancer cells.


greenmedinfo--2020-09-01--Effect of oridonin on apoptosis and intracellular reactive oxygen species level in triple-negative b

Effect of oridonin on apoptosis and intracellular reactive oxygen species level in triple-negative breast cancer MDA-MB-231 cells.

Oridonin , which is an ent-kaurene diterpenoid isolated from traditional Chinese medicine Rabdosia rubescens , displays various bioactivities , including @ @ @ @ @ .
This study aimed to investigate the effect of oridonin on apoptosis of triple-negative breast @ @ @ @ @ underlying mechanisms .
The inhibitory effect of oridonin on proliferation of MDA-MB-231 cells was measured @ @ @ @ @ was analyzed by flow cytometry with PI staining and Annexin V-FITC/PI staining ; Intracellular reactive @ @ @ @ @ level was determined by ROS detection kit , and expressions of PARP , Bcl-2 , @ @ @ @ @ blot .
The results showed that oridonin exhibited a significant effect in inducing apoptosis of @ @ @ @ @ ROS level , down-regulating expression of Bcl-2 protein , and promoting cleavage of caspase-3 and @ @ @ @ @ results indicated that the apoptosis-inducing effect of oridonin on MDA-MB-231 cells might be correlated with @ @ @ @ @ , down-regulation of Bcl-2 protein and activation of caspase-3 .

Oridonin, which is an ent-kaurene diterpenoid isolated from traditional Chinese medicine Rabdosia rubescens, displays various bioactivities, including anti-inflammation, anti-bacteria and anti-tumor. This study aimed to investigate the effect of oridonin on apoptosis of triple-negative breast cancer MDA-MB-231 cells and its underlying mechanisms. The inhibitory effect of oridonin on proliferation of MDA-MB-231 cells was measured by MTT assay; Apoptosis was analyzed by flow cytometry with PI staining and Annexin V-FITC/PI staining; Intracellular reactive oxygen species (ROS) level was determined by ROS detection kit, and expressions of PARP, Bcl-2, caspase-3 were analyzed by Western blot. The results showed that oridonin exhibited a significant effect in inducing apoptosis of MDA-MB-231 cells, enhancing intracellular ROS level, down-regulating expression of Bcl-2 protein, and promoting cleavage of caspase-3 and its substrate PARP. These results indicated that the apoptosis-inducing effect of oridonin on MDA-MB-231 cells might be correlated with increase of intracellular ROS level, down-regulation of Bcl-2 protein and activation of caspase-3.


greenmedinfo--2020-09-01--Synergistic suppression of t(8;21)-positive leukemia cell growth by combining oridonin and MAPK1/ERK

Synergistic suppression of t(8;21)-positive leukemia cell growth by combining oridonin and MAPK1/ERK2 inhibitors.

One of the most common chromosomal translocations in acute myeloid leukemia is t ( 8 ; 21 ) ( q22 @ @ @ @ @ results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO .
Therefore @ @ @ @ @ to be a pertinent and promising target for treating t ( 8 ; 21 ) @ @ @ @ @ have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell @ @ @ @ @ protein ERK2 can mediate activation of most of these pathways .
Here we used a @ @ @ @ @ tetracycline diterpenoid ) , which has been shown to exhibit anti-RUNX1-ETO activity , and ERK2 @ @ @ @ @ that treatment of leukemic t ( 8 ; 21 ) -positive Kasumi-1 cells with oridonin @ @ @ @ @ .
Treatment of these cells with ERK2 inhibitors makes them more sensitive to RUNX1-ETO inhibition @ @ @ @ @ postulate that simultaneous inhibition of RUNX1-ETO and ERK2 cause synergistic effect on survival of leukemic @ @

One of the most common chromosomal translocations in acute myeloid leukemia is t(8;21)(q22;q22), which results in the appearance of abnormal transcripts encoding for the fusion protein RUNX1-ETO. Therefore, this oncoprotein is considered to be a pertinent and promising target for treating t(8;21) leukemia. Previously, we have shown that downregulation of RUNX1-ETO leads to activation of intracellular signaling pathways enhancing cell survival and determined that the protein ERK2 can mediate activation of most of these pathways. Here we used a combination of oridonin (natural tetracycline diterpenoid), which has been shown to exhibit anti-RUNX1-ETO activity, and ERK2 kinase inhibitors. We found that treatment of leukemic t(8;21)-positive Kasumi-1 cells with oridonin cause decrease of phosphorylated ERK1/2. Treatment of these cells with ERK2 inhibitors makes them more sensitive to RUNX1-ETO inhibition with oridonin. Therefore we postulate that simultaneous inhibition of RUNX1-ETO and ERK2 cause synergistic effect on survival of leukemic cells.


greenmedinfo--2020-09-02--Myrtle significantly diminishes burn-induced damage in skin.

Thermal skin burns cause local injury as well as triggers acute systemic inflammation response where the imbalance between oxidative and antioxidative system occurs .
As an alternative treatment , various medicinal herbs are used to treat burn injuries in many countries .
In this study , the possible protective role of oral or topical Myrtle ( Myrtus communis L. ) treatment against burn-induced damage was investigated .
The dorsum of the Wistar Albino rats was shaved and exposed to 90 °C water bath in burn group or 25 °C water bath in control group for 10 s under ether anesthesia @ @ @ @ @ @ @ for 2 days either orally or topically .
In skin samples ; malondialdehyde and glutathione levels , catalase , superoxide dismutase , nitric oxide and tissue factor activities were determined .
Skin tissues were also examined by light microscopy .
Severe thermal skin burn injury caused a significant decrease in glutathione level , superoxide dismutase , catalase and tissue factor activities as well as nitric oxide level , which was accompanied with significant increases in skin malondialdehyde level .
Myrtle treatment reversed all these biochemical indices except topical Myrtle treated group 's nitric @ @ @ @ @ @ @ alterations , which were induced by thermal trauma .
Both oral and topical Myrtle extract treatment was found to have protective role in the burn induced oxidative injury , which may be attributed to the potential antioxidant effect of Myrtle .
As a conclusion , Myrtle significantly diminishes burn-induced damage in skin .

Thermal skin burns cause local injury as well as triggers acute systemic inflammation response where the imbalance between oxidative and antioxidative system occurs. As an alternative treatment, various medicinal herbs are used to treat burn injuries in many countries. In this study, the possible protective role of oral or topical Myrtle (Myrtus communis L.) treatment against burn-induced damage was investigated. The dorsum of the Wistar Albino rats was shaved and exposed to 90 °C water bath in burn group or 25 °C water bath in control group for 10 s under ether anesthesia. Myrtle extract was applied 100 mg/kg/day for 2 days either orally or topically. In skin samples; malondialdehyde and glutathione levels, catalase, superoxide dismutase, nitric oxide and tissue factor activities were determined. Skin tissues were also examined by light microscopy. Severe thermal skin burn injury caused a significant decrease in glutathione level, superoxide dismutase, catalase and tissue factor activities as well as nitric oxide level, which was accompanied with significant increases in skin malondialdehyde level. Myrtle treatment reversed all these biochemical indices except topical Myrtle treated group's nitric oxide level, as well as histopathological alterations, which were induced by thermal trauma. Both oral and topical Myrtle extract treatment was found to have protective role in the burn induced oxidative injury, which may be attributed to the potential antioxidant effect of Myrtle. As a conclusion, Myrtle significantly diminishes burn-induced damage in skin.


greenmedinfo--2020-09-02--An aqueous extract of myrtle possesses a definite wound healing potential in diabetic condition.

BACKGROUND : The medicinal plant Myrtus communis L. ( Myrtle ) has been medicinal properties including antiinflammatory and wound healing in Persian Medicine .
OBJECTIVE : The objective of this study was to explore the wound healing potential of the local application of a gel containing aqueous extract of the plant berry in streptozotocin ( STZ ) -induced diabetic rats .
METHODS : Seven days after diabetes establishment , full-thickness excision skin wounds were made in normal and diabetic rats and treated groups received topical application of a gel containing 6 % aqueous extract of myrtle berries for 3 weeks @ @ @ @ @ @ @ the level of epidermal and dermal maturation in the wound tissue were determined .
RESULTS : The results showed that after 3 and 7 days of wound injury , the gel significantly improved wound healing by accelerating epidermal and dermal maturation in diabetic rats with no significant effect in control group .
However , the wounds of all groups almost completely healed after 3 weeks .
CONCLUSION : These results demonstrate that aqueous extract of myrtle possesses a definite wound healing potential in diabetic condition .
Our present findings may suggest the use @ @ @ @ @ @ @ 6 % to treat and manage intractable diabetic wounds .

BACKGROUND: The medicinal plant Myrtus communis L. (Myrtle) has been medicinal properties including antiinflammatory and wound healing in Persian Medicine.
OBJECTIVE: The objective of this study was to explore the wound healing potential of the local application of a gel containing aqueous extract of the plant berry in streptozotocin (STZ)-induced diabetic rats.
METHODS: Seven days after diabetes establishment, full-thickness excision skin wounds were made in normal and diabetic rats and treated groups received topical application of a gel containing 6% aqueous extract of myrtle berries for 3 weeks. The rate of wound healing and the level of epidermal and dermal maturation in the wound tissue were determined.
RESULTS: The results showed that after 3 and 7 days of wound injury, the gel significantly improved wound healing by accelerating epidermal and dermal maturation in diabetic rats with no significant effect in control group. However, the wounds of all groups almost completely healed after 3 weeks.
CONCLUSION: These results demonstrate that aqueous extract of myrtle possesses a definite wound healing potential in diabetic condition. Our present findings may suggest the use of topical myrtle berries aqueous extract gel 6% to treat and manage intractable diabetic wounds.


greenmedinfo--2020-09-02--M. communis fruits can be an effective alternate in reducing heavy menstrual bleeding.

Objectives Menorrhagia can be defined as heavy uterine bleeding which comes at regular intervals or uterine bleeding extending more than seven days during menses which has become a considerable problem for females , causing discomfort , anxiety , and poor quality of life .
In this study we aimed to compare the effect of Myrtus communis fruits with tranexamic acid in the treatment of menorrhagia .
Methods In this prospective patient blinded standard controlled study , 40 patients of menorrhagia were randomly assigned to receive either test drug ( powdered M. communis fruits ) or active control drug ( tranexamic @ @ @ @ @ @ @ menstrual cycle consecutively for two cycles .
The primary outcome measure was reduction in heavy flow during menses determined by pictorial blood loss assessment chart ( PBAC ) , while improvements in quality of life ( QOL ) by using short form-36 questionnaire and increase in hemoglobin percentage were kept as secondary outcome measures .
Results Both the groups were similar at baseline .
Test and control drugs significantly reduced the PBAC score during treatment cycles with p-value < 0.001 and these changes were not significantly different between the groups .
During second @ @ @ @ @ @ @ PBAC score ( p = 0.024 ) between the groups .
After treatment significant improvement in hemoglobin percentage was noted and marked improvement in overall quality of life was observed in both the groups .
Conclusion These data suggest that M. communis fruits can be an effective alternate in reducing heavy menstrual bleeding .
There is need to confirm these results by designing a trial on large number of patients .
Trial Registration No CTRI/2017/09/009937 .

Objectives Menorrhagia can be defined as heavy uterine bleeding which comes at regular intervals or uterine bleeding extending more than seven days during menses which has become a considerable problem for females, causing discomfort, anxiety, and poor quality of life. In this study we aimed to compare the effect of Myrtus communis fruits with tranexamic acid in the treatment of menorrhagia. Methods In this prospective patient blinded standard controlled study, 40 patients of menorrhagia were randomly assigned to receive either test drug (powdered M. communis fruits) or active control drug (tranexamic acid) for first five days of menstrual cycle consecutively for two cycles. The primary outcome measure was reduction in heavy flow during menses determined by pictorial blood loss assessment chart (PBAC), while improvements in quality of life (QOL) by using short form-36 questionnaire and increase in hemoglobin percentage were kept as secondary outcome measures. Results Both the groups were similar at baseline. Test and control drugs significantly reduced the PBAC score during treatment cycles with p-value <0.001 and these changes were not significantly different between the groups. During second treatment cycle significant difference was found in PBAC score (p = 0.024) between the groups. After treatment significant improvement in hemoglobin percentage was noted and marked improvement in overall quality of life was observed in both the groups. Conclusion These data suggest that M. communis fruits can be an effective alternate in reducing heavy menstrual bleeding. There is need to confirm these results by designing a trial on large number of patients. Trial Registration No CTRI/2017/09/009937.


greenmedinfo--2020-09-02--Hesperidin and SARS-CoV-2: New light on the healthy function of citrus fruits.

Among the many approaches to Coronavirus disease 2019 ( COVID-19 ) prevention , the possible role of nutrition has so far been rather underestimated .
Foods are very rich in substances , with a potential beneficial effect on health , and some of these could have an antiviral action or be important in modulating the immune system and in defending cells from the oxidative stress associated with infection .
This short review draws the attention on some components of citrus fruits , and especially of the orange ( ) , well known for its vitamin and flavonoid content .
Among @ @ @ @ @ @ @ the attention of researchers , because it binds to the key proteins of the Severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) .
Several computational methods , independently applied by different researchers , showed that hesperidin has a low binding energy , both with the coronavirus '' spike '' protein , and with the main protease that transforms the early proteins of the virus ( pp1a and ppa1b ) into the complex responsible for viral replication .
The binding energy of hesperidin to these important components is lower than that of lopinavir @ @ @ @ @ @ @ that it could perform an effective antiviral action .
Furthermore , both hesperidin and ascorbic acid counteract the cell damaging effects of the oxygen free radicals triggered by virus infection and inflammation .
There is discussion about the preventive efficacy of vitamin C , at the dose achievable by the diet , but recent reviews suggest that this substance can be useful in the case of strong immune system burden caused by viral disease .
Computational methods and laboratory studies support the need to undertake apposite preclinical , epidemiological , and experimental studies @ @ @ @ @ @ @ components for the prevention of infectious diseases , including COVID-19 .

Among the many approaches to Coronavirus disease 2019 (COVID-19) prevention, the possible role of nutrition has so far been rather underestimated. Foods are very rich in substances, with a potential beneficial effect on health, and some of these could have an antiviral action or be important in modulating the immune system and in defending cells from the oxidative stress associated with infection. This short review draws the attention on some components of citrus fruits, and especially of the orange (), well known for its vitamin and flavonoid content. Among the flavonoids, hesperidin has recently attracted the attention of researchers, because it binds to the key proteins of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several computational methods, independently applied by different researchers, showed that hesperidin has a low binding energy, both with the coronavirus"spike"protein, and with the main protease that transforms the early proteins of the virus (pp1a and ppa1b) into the complex responsible for viral replication. The binding energy of hesperidin to these important components is lower than that of lopinavir, ritonavir, and indinavir, suggesting that it could perform an effective antiviral action. Furthermore, both hesperidin and ascorbic acid counteract the cell damaging effects of the oxygen free radicals triggered by virus infection and inflammation. There is discussion about the preventive efficacy of vitamin C, at the dose achievable by the diet, but recent reviews suggest that this substance can be useful in the case of strong immune system burden caused by viral disease. Computational methods and laboratory studies support the need to undertake apposite preclinical, epidemiological, and experimental studies on the potential benefits of citrus fruit components for the prevention of infectious diseases, including COVID-19.