greenmedinfo--2020-08-28--Astragaloside IV alleviates puromycin aminonucleoside-induced podocyte cytoskeleton injury through t

Astragaloside IV alleviates puromycin aminonucleoside-induced podocyte cytoskeleton injury through the Wnt/PCP pathway.

Podocyte injury is a common cause of massive proteinuria .
Astragaloside IV ( AS-IV ) has been reported to protect podocytes in diabetic models .
However , the effects and potential mechanism of AS-IV on puromycin aminonucleoside ( PAN ) -induced podocyte injury remains unclear .
The aim of the present study was to investigate the protective effect of AS-IV on PAN-induced podocyte injury bothand.
, we induced a podocytic-injury model in rats via a single tail vein injection of PAN .
The rats in the treatment group received AS-IV intragastrically ( i.g . )
at a dose of 40 @ @ @ @ @ @ @ end of the experiment , 24 h urine , serum and kidney samples were collected for examination.
, we injured podocytes with 30μg/ml PAN and treated them with AS-IV at concentrations of 5 , 25 and 50 μg/ml .
Next , we analyzed podocyte protein expression and the Wnt/planar-cell polarity ( PCP ) pathway using western blot and immunofluorescence ( IF ) .
Our results showed that AS-IV decreased proteinuria in PAN-injured rats , and restored specific protein expression in podocytes .
In PAN-induced injuries to human podocytes , AS-IV restored the expression @ @ @ @ @ @ @ and repaired the morphology of the actin-based cytoskeleton .
Notably , AS-IV could activate the Wnt/PCP pathway by promoting expression of Wnt5a , protein tyrosine kinase 7 ( PTK7 ) , Rho-associated coiled-coil-containing protein kinase 1 ( ROCK1 ) , Ras-related C3 botulinum toxin substrate 1 ( Rac1 ) and phospho-SAPK/JNK ( Thr183/Tyr185 ) ( p-JNK ) and .
In conclusion , we demonstrated that AS-IV alleviated PAN-induced injury to the podocyte cytoskeleton , partially by activating the Wnt/PCP pathway .

Podocyte injury is a common cause of massive proteinuria. Astragaloside IV (AS-IV) has been reported to protect podocytes in diabetic models. However, the effects and potential mechanism of AS-IV on puromycin aminonucleoside (PAN)-induced podocyte injury remains unclear. The aim of the present study was to investigate the protective effect of AS-IV on PAN-induced podocyte injury bothand., we induced a podocytic-injury model in rats via a single tail vein injection of PAN. The rats in the treatment group received AS-IV intragastrically (i.g.) at a dose of 40 mg/kg/day for 10 days. At the end of the experiment, 24 h urine, serum and kidney samples were collected for examination., we injured podocytes with 30μg/ml PAN and treated them with AS-IV at concentrations of 5, 25 and 50 μg/ml. Next, we analyzed podocyte protein expression and the Wnt/planar-cell polarity (PCP) pathway using western blot and immunofluorescence (IF). Our results showed that AS-IV decreased proteinuria in PAN-injured rats, and restored specific protein expression in podocytes. In PAN-induced injuries to human podocytes, AS-IV restored the expression and distribution of F-actin and synaptopodin, and repaired the morphology of the actin-based cytoskeleton. Notably, AS-IV could activate the Wnt/PCP pathway by promoting expression of Wnt5a, protein tyrosine kinase 7 (PTK7), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), Ras-related C3 botulinum toxin substrate 1 (Rac1) and phospho-SAPK/JNK (Thr183/Tyr185) (p-JNK)and. In conclusion, we demonstrated that AS-IV alleviated PAN-induced injury to the podocyte cytoskeleton, partially by activating the Wnt/PCP pathway.


greenmedinfo--2020-08-28--Astragaloside IV sensitizes non-small cell lung cancer cells to cisplatin.

Background : Cisplatin is an effective chemotherapeutic drug for treating various cancers including non-small cell lung cancer ( NSCLC ) , but resistance to cisplatin remains the main limitation to its use in clinic .
Astragaloside IV ( AS-IV ) , which is derived from , has been proven to participate in various anti-cancer activities including anti-cancer , anti-oxidative , and anti-inflammatory functions .
Method : In this study , we explored the role of AS-IV in cisplatin chemoresistance to NSCLC cells by establishing cisplatin-resistant the NSCLC cell lines , A549and H1299 .
Results : Cisplatin inhibited viability and promoted @ @ @ @ @ @ @ manner .
In addition , cisplatin upregulated the levels of autophagy-related proteins ( Beclin1 , LC3 II/I ) and endoplasmic reticulum ( ER ) stress-related proteins ( glucose regulated protein 78 : GRP78 , protein kinase R ( PKR ) -like endoplasmic reticulum kinase : PERK ) , indicating that cisplatin caused autophagy and ER stress in NSCLC cells .
However , treatment combined with AS-IV dose-dependently suppressed cell viability and increased the cell apoptosis rate in A549and H1299cells , suggesting that AS-IV elevated the anti-tumor role of cisplatin in NSCLC cells .
@ @ @ @ @ @ @ and Beclin1 .
Inhibition of ER stress or autophagy both counteracted the inhibitory effect of AS-IV on chemoresistance to cisplatin in NSCLC cells .
Conclusions : AS-IV sensitized NSCLC cells to cisplatin through suppressing ER stress and autophagy .
This study provides a novel strategy of cisplatin combined with AS-IV for the treatment of cisplatin-resistant NSCLC patients .

Background: Cisplatin is an effective chemotherapeutic drug for treating various cancers including non-small cell lung cancer (NSCLC), but resistance to cisplatin remains the main limitation to its use in clinic. Astragaloside IV (AS-IV), which is derived from, has been proven to participate in various anti-cancer activities including anti-cancer, anti-oxidative, and anti-inflammatory functions.
Method: In this study, we explored the role of AS-IV in cisplatin chemoresistance to NSCLC cells by establishing cisplatin-resistant the NSCLC cell lines, A549and H1299.
Results: Cisplatin inhibited viability and promoted apoptosis of A549and H1299cells in a dose-dependent manner. In addition, cisplatin upregulated the levels of autophagy-related proteins (Beclin1, LC3 II/I) and endoplasmic reticulum (ER) stress-related proteins (glucose regulated protein 78: GRP78, protein kinase R (PKR)-like endoplasmic reticulum kinase: PERK), indicating that cisplatin caused autophagy and ER stress in NSCLC cells. However, treatment combined with AS-IV dose-dependently suppressed cell viability and increased the cell apoptosis rate in A549and H1299cells, suggesting that AS-IV elevated the anti-tumor role of cisplatin in NSCLC cells. AS-IV treatment suppressed the expression of GRP78 and Beclin1. Inhibition of ER stress or autophagy both counteracted the inhibitory effect of AS-IV on chemoresistance to cisplatin in NSCLC cells.
Conclusions: AS-IV sensitized NSCLC cells to cisplatin through suppressing ER stress and autophagy. This study provides a novel strategy of cisplatin combined with AS-IV for the treatment of cisplatin-resistant NSCLC patients.


greenmedinfo--2020-08-29--Oridonin relieves hypoxia-evoked apoptosis and autophagy via modulating microRNA-214 in H9c2 cells.

Oridonin ( Orid ) has been diffusely applied to remedy dissimilar cancers .
Howbeit , the influence of Orid in ischemic heart disease ( IHD ) remains imprecise .
The current study uncovered the functions of Orid in hypoxia-caused apoptosis and autophagy in H9c2 cells .
H9c2 cells received hypoxia and Orid manipulation , cell viability , apoptosis , apoptosis-interrelated factors and autophagy-correlative factors were appraised .
After the extraordinary vectors transfections , the impacts of miR-214 inhibition on hypoxia-triggered apoptosis and autophagy were investigated .
Further , dual luciferase reporter assay was enforced for ascertaining the pertinence between miR-214 @ @ @ @ @ @ @ determined using western blot .
We found that , Orid significantly alleviated hypoxia-induced apoptosis and autophagy through regulation their associated proteins in H9c2 cells .
Up-regulation of miR-214 was found in hypoxia and Orid co-managed cells , meanwhile , repression of miR-214 obviously annulled the modulatory functions of Orid in hypoxia-evoked apoptosis and autophagy .
Additionally , PTEN was forecasted to be a firsthand target of miR-214 .
Besides , we observed that Orid evoked PI3K/AKT/mTOR activation through elevation of miR-214 in hypoxia-managed H9c2 cells .
In conclusion , the amusing results corroborated @ @ @ @ @ @ @ via adjusting PI3K/AKT/mTOR pathway through enhancement of miR-214 in H9c2 cells .

Oridonin (Orid) has been diffusely applied to remedy dissimilar cancers. Howbeit, the influence of Orid in ischemic heart disease (IHD) remains imprecise. The current study uncovered the functions of Orid in hypoxia-caused apoptosis and autophagy in H9c2 cells. H9c2 cells received hypoxia and Orid manipulation, cell viability, apoptosis, apoptosis-interrelated factors and autophagy-correlative factors were appraised. After the extraordinary vectors transfections, the impacts of miR-214 inhibition on hypoxia-triggered apoptosis and autophagy were investigated. Further, dual luciferase reporter assay was enforced for ascertaining the pertinence between miR-214 and PTEN. PI3K/AKT/mTOR pathway was finally determined using western blot. We found that, Orid significantly alleviated hypoxia-induced apoptosis and autophagy through regulation their associated proteins in H9c2 cells. Up-regulation of miR-214 was found in hypoxia and Orid co-managed cells, meanwhile, repression of miR-214 obviously annulled the modulatory functions of Orid in hypoxia-evoked apoptosis and autophagy. Additionally, PTEN was forecasted to be a firsthand target of miR-214. Besides, we observed that Orid evoked PI3K/AKT/mTOR activation through elevation of miR-214 in hypoxia-managed H9c2 cells. In conclusion, the amusing results corroborated that Orid relieved hypoxia-caused apoptosis and autophagy via adjusting PI3K/AKT/mTOR pathway through enhancement of miR-214 in H9c2 cells.


greenmedinfo--2020-08-29--Downregulation of lncRNA AFAP1-AS1 by oridonin inhibits the epithelial-to-mesenchymal transition and

Downregulation of lncRNA AFAP1-AS1 by oridonin inhibits the epithelial-to-mesenchymal transition and proliferation of pancreatic cancer cells.

Recent studies have demonstrated that the expression of the long non-coding RNA ( lncRNA ) AFAP1-AS1 in pancreatic cancer is negatively correlated with survival and prognosis .
However , the effects of oridonin and lncRNA AFAP1-AS1 on the epithelial-to-mesenchymal transition ( EMT ) and migration of pancreatic cancer cells have not been fully elucidated .
Surgery is the only potentially curative method for pancreatic cancer , but postoperative recurrence and metastasis are common .
The aim of the present study was to assess the effect of oridonin and lncRNA AFAP1-AS1 silencing on pancreatic cancer cells .
The pancreatic cancer cell @ @ @ @ @ @ @ with siAFAP1-AS1 and its negative control ( siNC ) .
After that , oridonin was used to treat the siAFAP1-AS1-transfected cells .
The expression of lncRNA AFAP1-AS1 was downregulated in the pancreatic cancer cell lines BxPC-3 and PANC-1 .
The apoptosis and cell cycle progression of pancreatic cancer cells were evaluated by flow cytometry and Hoechst 33258 staining .
Metastasis and invasion of BxPC-3 and PANC-1 cells were detected by transwell migration assay , real-time cell analysis , and western blot analysis .
Cells were transfected with the lentiviral siAFAP1-AS1 and siNC , @ @ @ @ @ @ @ mice .
Immunohistochemical examination was used to verify the effects of oridonin and siAFAP1-AS1 on pancreatic cancer .
The results demonstrated that the combination of oridonin and siAFAP1-AS1 inhibited pancreatic cancer cell proliferation , induced apoptosis , arrested cell cycle progression , prevented the migration , regulated EMT-related protein expression in BxPC-3 and PANC-1 cells , and inhibited pancreatic cancer cell tumorigenicity and EMT in nude mice .

Recent studies have demonstrated that the expression of the long non-coding RNA (lncRNA) AFAP1-AS1 in pancreatic cancer is negatively correlated with survival and prognosis. However, the effects of oridonin and lncRNA AFAP1-AS1 on the epithelial-to-mesenchymal transition (EMT) and migration of pancreatic cancer cells have not been fully elucidated. Surgery is the only potentially curative method for pancreatic cancer, but postoperative recurrence and metastasis are common. The aim of the present study was to assess the effect of oridonin and lncRNA AFAP1-AS1 silencing on pancreatic cancer cells. The pancreatic cancer cell lines BxPC-3 and PANC-1 cells were transfected with siAFAP1-AS1 and its negative control (siNC). After that, oridonin was used to treat the siAFAP1-AS1-transfected cells. The expression of lncRNA AFAP1-AS1 was downregulated in the pancreatic cancer cell lines BxPC-3 and PANC-1. The apoptosis and cell cycle progression of pancreatic cancer cells were evaluated by flow cytometry and Hoechst 33258 staining. Metastasis and invasion of BxPC-3 and PANC-1 cells were detected by transwell migration assay, real-time cell analysis, and western blot analysis. Cells were transfected with the lentiviral siAFAP1-AS1 and siNC, and tumorigenesis was evaluated in BALB/C nude mice. Immunohistochemical examination was used to verify the effects of oridonin and siAFAP1-AS1 on pancreatic cancer. The results demonstrated that the combination of oridonin and siAFAP1-AS1 inhibited pancreatic cancer cell proliferation, induced apoptosis, arrested cell cycle progression, prevented the migration, regulated EMT-related protein expression in BxPC-3 and PANC-1 cells, and inhibited pancreatic cancer cell tumorigenicity and EMT in nude mice.


greenmedinfo--2020-08-29--Oridonin enhances TRAIL-induced apoptosis through GALNT14-mediated DR5 glycosylation.

Oridonin is a diterpenoid isolated from the Rabdosia rubescens and has multiple biological effects , such as anti-inflammation and anti-tumor @ @ @ @ @ , we revealed that the sensitizing effect of oridonin on tumor necrosis factor-related apoptosis-inducing ligand @ @ @ @ @ in several cancer cells , but not in normal cells .
Oridonin enhanced death-signaling inducing @ @ @ @ @ and DR5 glycosylation without affecting expression of downstream intracellular apoptosis-related proteins .
Oridonin upregulated peptidyl @ @ @ @ @ and time-dependent manner .
Knockdown of GALNT14 by siRNA and Endo H treatment reduced oridonin-induced @ @ @ @ @ treatment with inhibitor of glycosylation ( benzyl-α-GalNAc ) blocked oridonin plus TRAIL-induced apoptosis .
Collectively @ @ @ @ @ oridonin-induced DR5 glycosylation contributes to TRAIL-induced apoptotic cell death in cancer cells .

Oridonin is a diterpenoid isolated from the Rabdosia rubescens and has multiple biological effects, such as anti-inflammation and anti-tumor activities. In present study, we revealed that the sensitizing effect of oridonin on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in several cancer cells, but not in normal cells. Oridonin enhanced death-signaling inducing complexes (DISC) formation and DR5 glycosylation without affecting expression of downstream intracellular apoptosis-related proteins. Oridonin upregulated peptidyl O-glycosyltransferase GALNT14 in a dose- and time-dependent manner. Knockdown of GALNT14 by siRNA and Endo H treatment reduced oridonin-induced DR5 glycosylation. Furthermore, treatment with inhibitor of glycosylation (benzyl-α-GalNAc) blocked oridonin plus TRAIL-induced apoptosis. Collectively, our results suggest that oridonin-induced DR5 glycosylation contributes to TRAIL-induced apoptotic cell death in cancer cells.


greenmedinfo--2020-08-29--Oridonin induces Mdm2-p60 to promote p53-mediated apoptosis and cell cycle arrest in neuroblastoma.

Oridonin could induce NB ( neuroblastoma ) cells growth inhibition by inducing apoptosis and cell cycle arrest , and the @ @ @ @ @ deserve to be further explored .
Here , oridonin was confirmed to cause the reactivation @ @ @ @ @ antigen p53 ) to promote the expression of a series of apoptosis- and cell cycle @ @ @ @ @ effects .
During the process , oridonin relied on the caspase activation to cleave p53-induced @ @ @ @ @ Mdm2 ) to generate Mdm2-p60 .
The generation of Mdm2-p60 stabilized p53 , and resulted @ @ @ @ @ continuous activation .
In our research , it was also found that the reactivation of @ @ @ @ @ closely related with the generation of ROS ( reactive oxygen species ) .
Taken together @ @ @ @ @ oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells , @ @ @ @ @ for future research of exploring the effects and molecular mechanisms of oridonin .

Oridonin could induce NB (neuroblastoma) cells growth inhibition by inducing apoptosis and cell cycle arrest, and the molecular mechanisms behind the effects deserve to be further explored. Here, oridonin was confirmed to cause the reactivation of p53 (cellular tumor antigen p53) to promote the expression of a series of apoptosis- and cell cycle arrest-related proteins for the biological effects. During the process, oridonin relied on the caspase activation to cleave p53-induced Mdm2 (E3 ubiquitin-protein ligase Mdm2) to generate Mdm2-p60. The generation of Mdm2-p60 stabilized p53, and resulted in p53 accumulation for p53 continuous activation. In our research, it was also found that the reactivation of p53 induced by oridonin was closely related with the generation of ROS (reactive oxygen species). Taken together, these findings explain that oridonin exerts its anticancer activity partially by targeting the Mdm2-p53 axis in NB cells, which lay an experimental base for future research of exploring the effects and molecular mechanisms of oridonin.


greenmedinfo--2020-08-29--Oridonin inhibits metastasis of human ovarian cancer cells by suppressing the mTOR pathway.

Introduction : Oridonin , which is isolated from the Chinese herb Rabdosia rubescens , has been reported to exhibit an anti-tumorous effect on different cancers .
In this study , we investigated the molecular mechanism by which oridonin suppresses human ovarian cancer .
Material and methods : The inhibition of oridonin on cell proliferation was assessed by CCK8 assay .
Cell cycle and apoptosis were analyzed by flow cytometry , staining with propidium iodide ( PI ) or annexin-V/PI respectively .
The metastasis rate was evaluated using a transwell migration assay .
The expression of metastasis-associated genes and mTOR pathway @ @ @ @ @ @ @ .
Results : We demonstrated that oridonin suppressed the proliferation and blocked the cell cycle in G1/S phage and induced apoptosis in SKOV3 and A2780 cells ( < 0.01 ) .
We further found that the mTOR signaling pathway was suppressed by the treatment with oridonin , and the activation of the mTOR pathway attenuated the anti-tumorous effect of oridonin in human ovarian cancer cells , suggesting that the mTOR pathway was involved in the anti-tumorous process of oridonin .
Additionally , the activation of the mTOR pathway by an exogenous activator reduced @ @ @ @ @ @ @ 0.01 ) , thus providing evidence that FOXP3 is a factor that is necessary for the anti-tumorous effect of oridonin , and is negatively regulated by the mTOR pathway .
Conclusions : These results suggested that oridonin suppressed the mTOR signaling pathway , up-regulated the FOXP3 level , and inhibited metastasis of human ovarian cancer cells .

Introduction: Oridonin, which is isolated from the Chinese herb Rabdosia rubescens, has been reported to exhibit an anti-tumorous effect on different cancers. In this study, we investigated the molecular mechanism by which oridonin suppresses human ovarian cancer.
Material and methods: The inhibition of oridonin on cell proliferation was assessed by CCK8 assay. Cell cycle and apoptosis were analyzed by flow cytometry, staining with propidium iodide (PI) or annexin-V/PI respectively. The metastasis rate was evaluated using a transwell migration assay. The expression of metastasis-associated genes and mTOR pathway related genes were detected by western blot.
Results: We demonstrated that oridonin suppressed the proliferation and blocked the cell cycle in G1/S phage and induced apoptosis in SKOV3 and A2780 cells (<0.01). We further found that the mTOR signaling pathway was suppressed by the treatment with oridonin, and the activation of the mTOR pathway attenuated the anti-tumorous effect of oridonin in human ovarian cancer cells, suggesting that the mTOR pathway was involved in the anti-tumorous process of oridonin. Additionally, the activation of the mTOR pathway by an exogenous activator reduced the expression level of FOXP3 (<0.01), thus providing evidence that FOXP3 is a factor that is necessary for the anti-tumorous effect of oridonin, and is negatively regulated by the mTOR pathway.
Conclusions: These results suggested that oridonin suppressed the mTOR signaling pathway, up-regulated the FOXP3 level, and inhibited metastasis of human ovarian cancer cells.


greenmedinfo--2020-08-29--Beneficial effects of oridonin on myocardial ischemia/reperfusion injury.

Oridonin is a diterpenoid isolated from Rabdosia rubescens ( Hemsl . )
Hara , a well-known herbal tea in China @ @ @ @ @ To provide a better understanding of the potential cardioprotective effect of Oridonin , we investigated @ @ @ @ @ tissue and serum of rat subjected to myocardial ischemia/reperfusion ( MI/R ) injury with or @ @ @ @ @ UPLC-MS/MS metabolomics approach .
Rats were randomly divided into groups as follows : Control , @ @ @ @ @ with Oridonin ( 10 mg/kg ) +MI/R .
After 24 h of reperfusion , heart @ @ @ @ @ for biochemical and metabolomic analysis .
Pretreatment with Oridonin significantly decreased infarct size and reversed @ @ @ @ @ in serum .
Moreover , Oridonin regulated several metabolic pathways , including glycolysis , branched @ @ @ @ @ , arginine , glutamine and bile acid metabolism .
Our results suggest that Oridonin indeed @ @ @ @ @ by regulating energy and amino acid metabolism .

Oridonin is a diterpenoid isolated from Rabdosia rubescens (Hemsl.) Hara, a well-known herbal tea in China with many health benefits. To provide a better understanding of the potential cardioprotective effect of Oridonin, we investigated the metabolic alterations in heart tissue and serum of rat subjected to myocardial ischemia/reperfusion (MI/R) injury with or without pretreatment of Oridonin by UPLC-MS/MS metabolomics approach. Rats were randomly divided into groups as follows: Control, Sham, MI/R and pretreated with Oridonin (10 mg/kg)+MI/R. After 24 h of reperfusion, heart tissue and serum were collected for biochemical and metabolomic analysis. Pretreatment with Oridonin significantly decreased infarct size and reversed the abnormal elevated myocardial zymogram in serum. Moreover, Oridonin regulated several metabolic pathways, including glycolysis, branched chain amino acid, kynurenine, arginine, glutamine and bile acid metabolism. Our results suggest that Oridonin indeed displays outstanding cardioprotective effect mainly by regulating energy and amino acid metabolism.


greenmedinfo--2020-08-29--Protective effect of procyanidin B2 on acute liver injury induced by aflatoxin B 1 in rats.

Objective : This study aimed to explore the protective effect of procyanidin B2 ( PCB2 ) on acute liver injury induced by aflatoxin B ( AFB ) in rats .
Methods : Forty Sprague Dawley rats were randomly divided into control , AFB , AFB+ PCB2 , and PCB2 groups .
The latter two groups were administrated PCB2 intragastrically ( 30 mg/kg body weight ) for 7 d , whereas the control and AFBgroups were given the same dose of double distilled water intragastrically .
On the sixth day of treatment , the AFBand AFB+ PCB2 groups were intraperitoneally injected @ @ @ @ @ @ @ The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide ( DMSO ) .
On the eighth day , all rats were euthanized : serum and liver tissue were isolated for further examination .
Hepatic histological features were assessed by hematoxylin and eosin-stained sections .
Weight , organ coefficient ( liver , spleen , and kidney ) , liver function ( serum alanine aminotransferase , aspartate aminotransferase , alkaline phosphatase , total bilirubin , and direct bilirubin ) , oxidative index ( catalase , glutathione , superoxide dismutase , @ @ @ @ @ @ @ factor [ hepatic interleukin-6 ( IL-6 ) mRNA expression and serum IL-6 ] , and bcl-2/bax ratio were measured .
Results : AFBsignificantly caused hepatic histopathological damage , abnormal liver function , oxidative stress , inflammation , and bcl-2/bax ratio reduction compared with DMSO-treated controls .
Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB .
Conclusion : Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B(AFB) in rats.
Methods: Forty Sprague Dawley rats were randomly divided into control, AFB, AFB+ PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFBgroups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFBand AFB+ PCB2 groups were intraperitoneally injected with AFB(2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured.
Results: AFBsignificantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB.
Conclusion: Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB.


greenmedinfo--2020-08-29--Procyanidin B2 improves oocyte maturation and subsequent development in Type 1 diabetic mice by prom

Procyanidin B2 improves oocyte maturation and subsequent development in Type 1 diabetic mice by promoting mitochondrial function.

Type 1 diabetes ( T1D ) results in decreased oocyte quality and compromised early embryonic development .
Procyanidin B2 ( @ @ @ @ @ compound extracted from grape seeds and has strong antioxidant activity in vivo .
This study @ @ @ @ @ on oocyte maturation in diabetic mice .
Diabetic mice were induced by streptozotocin ( STZ @ @ @ @ @ supplemented in the in vitro maturation medium , and the ratio of germinal vesicle breakdown @ @ @ @ @ body extrusion ( PBE ) , reactive oxygen species ( ROS ) levels , mitochondrial @ @ @ @ @ as well as crotonylation at H4K5 were determined in oocytes .
PB2 can promote the @ @ @ @ @ % vs. 75.02 % , P

Type 1 diabetes (T1D) results in decreased oocyte quality and compromised early embryonic development. Procyanidin B2 (PB2) is a natural compound extracted from grape seeds and has strong antioxidant activity in vivo. This study evaluated the effect of PB2 on oocyte maturation in diabetic mice. Diabetic mice were induced by streptozotocin (STZ) injection. PB2 was supplemented in the in vitro maturation medium, and the ratio of germinal vesicle breakdown (GVBD) and polar body extrusion (PBE), reactive oxygen species (ROS) levels, mitochondrial function, developmental ability, as well as crotonylation at H4K5 were determined in oocytes. PB2 can promote the extrusion of PBE (88.34% vs. 75.02%, P < 0.05); reduce the generation of ROS (1.12 vs. 1.96, P < 0.05); and improve the level of mitochondrial membrane potential (0.87 vs. 0.79 Δφm, P < 0.05), ATP level (1.31 vs. 0.71 pmol, P < 0.05), and mitochondria temperature (618.25 vs. 697.39 pixels, P < 0.05). The addition of PB2 also improved the level of oocyte crotonylation at H4K5 (crH4K5) (47.26 vs. 59.68 pixels, P < 0.05) and increased the blastocyst rate (61.51% vs. 36.07%, P < 0.05) after parthenogenetic activation. Our results are the first to reveal a role for PB2 in promoting the viability of oocytes by regulating the mitochondrial function. Moreover, we uncover that PB2 can improve the level of crH4K5, which provides a new strategy to combat the decline in oocyte quality of diabetic.


greenmedinfo--2020-08-29--Protection of procyanidin B2 on mitochondrial dynamics in sepsis associated acute kidney injury.

In septic acute kidney injury ( SAKI ) , the positive feedback between damaged mitochondria and accumulation of reactive oxygen species results in cell and tissue damage through multiple mechanisms .
Removing the damaged mitochondria or neutralizing the reactive oxygen species has been considered beneficial to alleviating cell damage .
The antioxidant Procyanidin B2 has been reported to inhibits reactive oxygen species and thereby reduces cell injury .
However , it is unclear whether this effect is associated with clearance of damaged mitochondria .
Here , we evaluated the efficacy of procyanidin B2 on SAKI , and focused on its @ @ @ @ @ @ @ mitochondria via mitophagy .
The results showed that the renal function , renal tubular cell vacuolization and oxidative stress were decreased in SAKI mice treated with procyanidin B2 , moreover , skewed mitochondrial fusion/fission , mitochondrial mediated apoptosis and impaired mitophagy were improved in SAKI mice treated with procyanidin B2 .
In mechanism , the improvement of procyanidin B2 on mitochondrial dynamics were associated with increased nuclear translocation of the transcription factor , Nrf2 .
In summary , our findings highlighted that the protective efficacy of procyanidin B2 in reducing cellular damage in @ @ @ @ @ @ @ and quality control at least in part by promoting Nrf2 translocation into the nucleus .

In septic acute kidney injury (SAKI), the positive feedback between damaged mitochondria and accumulation of reactive oxygen species results in cell and tissue damage through multiple mechanisms. Removing the damaged mitochondria or neutralizing the reactive oxygen species has been considered beneficial to alleviating cell damage. The antioxidant Procyanidin B2 has been reported to inhibits reactive oxygen species and thereby reduces cell injury. However, it is unclear whether this effect is associated with clearance of damaged mitochondria. Here, we evaluated the efficacy of procyanidin B2 on SAKI, and focused on its effects on mitochondrial dynamics and removing damaged mitochondria via mitophagy. The results showed that the renal function, renal tubular cell vacuolization and oxidative stress were decreased in SAKI mice treated with procyanidin B2, moreover, skewed mitochondrial fusion/fission, mitochondrial mediated apoptosis and impaired mitophagy were improved in SAKI mice treated with procyanidin B2. In mechanism, the improvement of procyanidin B2 on mitochondrial dynamics were associated with increased nuclear translocation of the transcription factor, Nrf2. In summary, our findings highlighted that the protective efficacy of procyanidin B2 in reducing cellular damage in SAKI, and mechanisms improving mitochondrial dynamics and quality control at least in part by promoting Nrf2 translocation into the nucleus.


greenmedinfo--2020-08-29--Colorado School District Superintendent Hires Lobbyists for Vaccine Tracking Bill

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greenmedinfo--2020-08-29--Oridonin elevates sensitivity of ovarian carcinoma cells to cisplatin.

BACKGROUND : Cisplatin resistance has been found to contribute to the failure of ovarian carcinoma treatment .
Oridonin is a natural en-kaurane tetracyclic diterpenoid compound discovered in Rabdosia rubescene ( Henmsl . )
Hara .
Herein , we tested whether oridonin could exert chemo-sensitization activity on cisplatin-resistant ovarian carcinoma cells .
METHODS : Firstly , A2780CP cells and SKOV3/DDP cells were exposed to cisplatin and/or oridonin treatment .
Cell counting kit-8 ( CCK-8 ) kit and Dead Cell Apoptosis Kit with Annexin V-FITC and PI were carried out to test cell viability and apoptosis , respectively .
Then , pBeclin-1 @ @ @ @ @ @ @ ( 3-MA ) acted as autophagy inhibitor , while rapamycin acted as autophagy activator .
Finally , the influence of cisplatin and/or oridonin treatment on human normal ovarian epithelial IOSE 364 cell viability and apoptosis were also detected .
RESULTS : Oridonin incubation notably elevated the cisplatin-caused reduction of A2780CP and SKOV3/DDP cell viabilities and enhancement of cell apoptosis .
Cisplatin-caused A2780CP and SKOV3/DDP cell autophagy was dramatically inhibited by oridonin .
Overexpression of Beclin-1 mitigated the influence of oridonin on cisplatin-caused A2780CP and SKOV3/DDP cell autophagy .
Inhibition of cell autophagy by @ @ @ @ @ @ @ and SKOV3/DDP cell apoptosis , while activation of cell autophagy by rapamycin had opposite effects .
Oridonin and cisplatin co-treatment had no significant effects on IOSE 364 cell viability and apoptosis .
CONCLUSION : The chemo-sensitization activity of oridonin on cisplatin-resistant ovarian carcinoma cells was verified in this study .
Oridonin elevated sensitivity of ovarian carcinoma cells to cisplatin via suppressing cisplatin-mediated autophagy .

BACKGROUND: Cisplatin resistance has been found to contribute to the failure of ovarian carcinoma treatment. Oridonin is a natural en-kaurane tetracyclic diterpenoid compound discovered in Rabdosia rubescene (Henmsl.) Hara. Herein, we tested whether oridonin could exert chemo-sensitization activity on cisplatin-resistant ovarian carcinoma cells.
METHODS: Firstly, A2780CP cells and SKOV3/DDP cells were exposed to cisplatin and/or oridonin treatment. Cell counting kit-8 (CCK-8) kit and Dead Cell Apoptosis Kit with Annexin V-FITC and PI were carried out to test cell viability and apoptosis, respectively. Then, pBeclin-1 was transfected to overexpress Beclin-1. 3-Methyladenine (3-MA) acted as autophagy inhibitor, while rapamycin acted as autophagy activator. Finally, the influence of cisplatin and/or oridonin treatment on human normal ovarian epithelial IOSE 364 cell viability and apoptosis were also detected.
RESULTS: Oridonin incubation notably elevated the cisplatin-caused reduction of A2780CP and SKOV3/DDP cell viabilities and enhancement of cell apoptosis. Cisplatin-caused A2780CP and SKOV3/DDP cell autophagy was dramatically inhibited by oridonin. Overexpression of Beclin-1 mitigated the influence of oridonin on cisplatin-caused A2780CP and SKOV3/DDP cell autophagy. Inhibition of cell autophagy by 3-MA promoted the oridonin + cisplatin-caused A2780CP and SKOV3/DDP cell apoptosis, while activation of cell autophagy by rapamycin had opposite effects. Oridonin and cisplatin co-treatment had no significant effects on IOSE 364 cell viability and apoptosis.
CONCLUSION: The chemo-sensitization activity of oridonin on cisplatin-resistant ovarian carcinoma cells was verified in this study. Oridonin elevated sensitivity of ovarian carcinoma cells to cisplatin via suppressing cisplatin-mediated autophagy.


greenmedinfo--2020-08-29--The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance.

Chemotherapy remains a primary treatment method for advanced pancreatic cancer .
However , chemotherapy resistance can influence the therapeutic effect of pancreatic cancer .
The resistance mechanism of chemotherapeutic agents such as gemcitabine , which is an agent typically used to treat pancreatic cancer , is complicated and can be influenced by genes and the environment .
Oridonin is a tetracyclic diterpenoid compound extracted from the traditional Chinese herb .
Oridonin may overcome drug resistance in pancreatic cancer , but researching pancreatic cancer drug resistance of chemotherapy by oridonin is not completely understood.The present study aimed to assess the impact @ @ @ @ @ @ @ apoptosis-associated proteins and energy metabolism in gemcitabine-resistant PANC-1 ( PANC-1/Gem ) pancreatic cancer cells.Gemcitabine resistance in PANC-1/Gem cells was induced using a concentration gradient of gemcitabine .
Cell Counting Kit-8 assays were used to detect the impact of gemcitabine and oridonin on the proliferation of PANC-1 and PANC-1/Gem cells .
Western blot analysis and immunofluorescence were used to detect the expression of multidrug resistance proteins , apoptosis-associated proteins and low-density lipoprotein receptor protein 1 ( LRP1 ) proteins in PANC-1/Gem cells .
The effects of gemcitabine and oridonin on PANC-1/Gem cells apoptosis were @ @ @ @ @ @ @ tumor assays were used to detect the effect of gemcitabine and oridonin on pancreatic cancer in vivo .
Furthermore , the ATP Assay kit was used to determine the effects of gemcitabine and oridonin on ATP levels in PANC-1/Gem cells .
Immunofluorescence assays were used to detect the effects of gemcitabine and oridonin on the expression of low-density lipoprotein receptor protein 1 ( LRP1 ) in PANC-1/Gem cells .
In addition , LRP1 expression was knocked down in PANC-1/Gem cells via lentiviral vector-mediated RNA silencing .
Clone formation assays and Western blot analysis @ @ @ @ @ @ @ LRP1 knockdown on the proliferation of PANC-1/Gem cells.The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance by regulating GST pi and LRP1/ERK/JNK signaling.In conclusion , the present study indicated that oridonin could overcome gemcitabine resistance in PANC-1/Gem cells by regulating GST pi and LRP1/ ERK/JNK signaling , inducing cell apoptosis .
Therefore , oridonin with gemcitabine may be a promising preoperative treatment for patients who suffer from pancreatic cancer .

Chemotherapy remains a primary treatment method for advanced pancreatic cancer. However, chemotherapy resistance can influence the therapeutic effect of pancreatic cancer. The resistance mechanism of chemotherapeutic agents such as gemcitabine, which is an agent typically used to treat pancreatic cancer, is complicated and can be influenced by genes and the environment. Oridonin is a tetracyclic diterpenoid compound extracted from the traditional Chinese herb. Oridonin may overcome drug resistance in pancreatic cancer, but researching pancreatic cancer drug resistance of chemotherapy by oridonin is not completely understood.The present study aimed to assess the impact of oridonin on multidrug resistance proteins, apoptosis-associated proteins and energy metabolism in gemcitabine-resistant PANC-1 (PANC-1/Gem) pancreatic cancer cells.Gemcitabine resistance in PANC-1/Gem cells was induced using a concentration gradient of gemcitabine. Cell Counting Kit-8 assays were used to detect the impact of gemcitabine and oridonin on the proliferation of PANC-1 and PANC-1/Gem cells. Western blot analysis and immunofluorescence were used to detect the expression of multidrug resistance proteins, apoptosis-associated proteins and low-density lipoprotein receptor protein 1 (LRP1) proteins in PANC-1/Gem cells. The effects of gemcitabine and oridonin on PANC-1/Gem cells apoptosis were detected using flow cytometry. Animal xenograft tumor assays were used to detect the effect of gemcitabine and oridonin on pancreatic cancer in vivo. Furthermore, the ATP Assay kit was used to determine the effects of gemcitabine and oridonin on ATP levels in PANC-1/Gem cells. Immunofluorescence assays were used to detect the effects of gemcitabine and oridonin on the expression of low-density lipoprotein receptor protein 1 (LRP1) in PANC-1/Gem cells. In addition, LRP1 expression was knocked down in PANC-1/Gem cells via lentiviral vector-mediated RNA silencing. Clone formation assays and Western blot analysis were used to detect the effect of LRP1 knockdown on the proliferation of PANC-1/Gem cells.The present results demonstrate that oridonin overcomes PANC-1/Gem cells gemcitabine reistance by regulating GST pi and LRP1/ERK/JNK signaling.In conclusion, the present study indicated that oridonin could overcome gemcitabine resistance in PANC-1/Gem cells by regulating GST pi and LRP1/ ERK/JNK signaling, inducing cell apoptosis. Therefore, oridonin with gemcitabine may be a promising preoperative treatment for patients who suffer from pancreatic cancer.


greenmedinfo--2020-08-29--Oridonin inhibits the proliferation, migration and invasion of human osteosarcoma cells.

PURPOSE : Oridonin , a diterpenoid , has been reported to exhibit anticancer activity against a wide range of cancer types.In this study , the effect Oridonin was examined against human osteosarcoma cells .
METHODS : The human osteosarcoma cells U2OS were treated with various concentrations of Oridonin from 0-200μM for 24 h. The anti-proliferative effects of Oridonin were measured by cell viability assay .
DAPI and annexin V/propidium iodide ( PI ) assays were employed to examine the induction of apoptosis .
Transwell assay was performed to examine the cell migration and invasion .
Expression analysis was performed by @ @ @ @ @ @ @ the proliferation of U2OScells and exhibited an IC50 of 30µM .
The antiproliferative effects were mainly found to be due to induction of apoptosis as indicated by DAPI staining .
Moreover , the annexin V/PI staining showed that the percentage of the apoptotic cells increased with increase in the concentration of Oridonin .
The induction of apoptosis was alsorelated with upregulation of Bax , Caspase 3 and 9 expression and downregulation of Bcl-2 .
Oridonin was also found to cause significant decrease in the expression of MMP-2 , 3 and 9 concentration-dependently .
@ @ @ @ @ @ @ migration and invasion of the U2OS cells .
CONCLUSION : It is concluded that Oridonin exhibits significant antiproliferative effects on the osteosarcoma cells and may prove essential in the development of systemic therapy for osteosarcoma .

PURPOSE: Oridonin, a diterpenoid, has been reported to exhibit anticancer activity against a wide range of cancer types.In this study, the effect Oridonin was examined against human osteosarcoma cells.
METHODS: The human osteosarcoma cells U2OS were treated with various concentrations of Oridonin from 0-200μM for 24 h. The anti-proliferative effects of Oridonin were measured by cell viability assay. DAPI and annexin V/propidium iodide (PI) assays were employed to examine the induction of apoptosis. Transwell assay was performed to examine the cell migration and invasion. Expression analysis was performed by western blot.
RESULTS: Oridonin inhibited the proliferation of U2OScells and exhibited an IC50 of 30µM. The antiproliferative effects were mainly found to be due to induction of apoptosis as indicated by DAPI staining. Moreover, the annexin V/PI staining showed that the percentage of the apoptotic cells increased with increase in the concentration of Oridonin. The induction of apoptosis was alsorelated with upregulation of Bax, Caspase 3 and 9 expression and downregulation of Bcl-2. Oridonin was also found to cause significant decrease in the expression of MMP-2, 3 and 9 concentration-dependently. Transwell assay showed that Oridonin inhibited the migration and invasion of the U2OS cells.
CONCLUSION: It is concluded that Oridonin exhibits significant antiproliferative effects on the osteosarcoma cells and may prove essential in the development of systemic therapy for osteosarcoma.


greenmedinfo--2020-08-29--Oridonin sensitizes cisplatin-induced apoptosis via AMPK/Akt/mTOR-dependent autophagosome accumulati

Oridonin sensitizes cisplatin-induced apoptosis via AMPK/Akt/mTOR-dependent autophagosome accumulation in A549 cells.

AMPK-mediated autophagy and Akt/mTOR pathways play important roles in current cancer treatments .
Oridonin ( Ori ) , an ent-kaurane diterpenoid isolated from Isodon rubescens , exerts extensive anti-tumor potential and controversial effects on autophagy .
In this study , we investigated the effect of Ori on the autophagy , apoptosis , and AMPK/Akt/mTOR pathways and determined whether Ori was related to the increased cisplatin sensitivity observed in A549 cells .
First , we found that Ori suppressed Akt/mTOR , Bcl2 and autophagy flux with enhanced levels of Atg3 , P62 , and LC3II , which was also shown as @ @ @ @ @ @ @ pro-apoptotic proteins ( caspase3 , Bax , and PARP ) were activated in Ori-treated cells .
With the pretreatment of compound c ( AMPK inhibitor ) , the activation of autophagosomes , apoptosis and the inhibition of Akt/mTOR pathways induced by Ori were all reversed .
The Ori-activated apoptosis-related markers mentioned previously and the cell-killing effect were restrained by 3-MA ( inhibitor of autophagosomes ) treatment .
Therefore , we hypothesized that the Ori-induced pro-apoptotic effect was mediated by AMPK/Akt/mTOR-dependent accumulation of impaired autophagosomes .
Furthermore , Ori could increase the sensitivity of @ @ @ @ @ @ @ and apoptosis-inducing activities .
In addition to sensitizing cisplatin , Ori also alleviated cisplatin-induced acute renal injury , manifested as depleted BUN , CRE , kidney index , and weight loss compared to the cisplatin group .
In summary , apart from its protective effect on cisplatin-induced nephrotoxicity , Ori enhanced cisplatin sensitivity via its pro-apoptotic activity mediated by AMPK/Akt/mTOR-dependent autophagosome activation , which may be a potential therapeutic target for non-small cell lung cancer .

AMPK-mediated autophagy and Akt/mTOR pathways play important roles in current cancer treatments. Oridonin (Ori), an ent-kaurane diterpenoid isolated from Isodon rubescens, exerts extensive anti-tumor potential and controversial effects on autophagy. In this study, we investigated the effect of Ori on the autophagy, apoptosis, and AMPK/Akt/mTOR pathways and determined whether Ori was related to the increased cisplatin sensitivity observed in A549 cells. First, we found that Ori suppressed Akt/mTOR, Bcl2 and autophagy flux with enhanced levels of Atg3, P62, and LC3II, which was also shown as the accumulation of autophagosomes. AMPK and pro-apoptotic proteins (caspase3, Bax, and PARP) were activated in Ori-treated cells. With the pretreatment of compound c (AMPK inhibitor), the activation of autophagosomes, apoptosis and the inhibition of Akt/mTOR pathways induced by Ori were all reversed. The Ori-activated apoptosis-related markers mentioned previously and the cell-killing effect were restrained by 3-MA (inhibitor of autophagosomes) treatment. Therefore, we hypothesized that the Ori-induced pro-apoptotic effect was mediated by AMPK/Akt/mTOR-dependent accumulation of impaired autophagosomes. Furthermore, Ori could increase the sensitivity of cisplatin through its increased cell-killing, autophagy-suppressing and apoptosis-inducing activities. In addition to sensitizing cisplatin, Ori also alleviated cisplatin-induced acute renal injury, manifested as depleted BUN, CRE, kidney index, and weight loss compared to the cisplatin group. In summary, apart from its protective effect on cisplatin-induced nephrotoxicity, Ori enhanced cisplatin sensitivity via its pro-apoptotic activity mediated by AMPK/Akt/mTOR-dependent autophagosome activation, which may be a potential therapeutic target for non-small cell lung cancer.


greenmedinfo--2020-08-29--Oridonin inhibits hypoxia-induced epithelial-mesenchymal transition and cell migration in gallbladde

Oridonin inhibits hypoxia-induced epithelial-mesenchymal transition and cell migration in gallbladder cancer.

Hypoxia has crucial roles in cancer development and progression .
Our previous study indicated that cell migration was increased in a hypoxic microenvironment in GBC-SD gallbladder cancer ( GBC ) cells .
Oridonin , a bioactive diterpenoid compound that is isolated from the plant Rabdosia rubescens , has been identified as an anticancer agent in various types of cancer .
However , its roles in cell proliferation , apoptosis , and migration in a hypoxic microenvironment and the associated regulatory mechanisms have not yet to be fully elucidated in GBC .
The present study investigated the effect of oridonin on @ @ @ @ @ @ @ cycle and cell migration in GBC in vitro and in vivo .
Furthermore , the role of oridonin in hypoxia-induced cell migration and its underlying mechanisms were explored in GBC .
The results indicated that treatment with oridonin significantly suppressed cell proliferation and the metastatic ability of GBC-SD cells in a dose-dependent manner , increased the level of cell apoptosis and induced cell cycle arrest at the G0/G1 phase .
Further experiments demonstrated that oridonin could inhibit hypoxia-induced epithelial-mesenchymal transition and cell migration by downregulating the expression levels of hypoxia-inducible factor ( HIF @ @ @ @ @ @ @ .
In addition , oridonin suppressed GBC cell growth and downregulated the expression levels of HIF-1α and MMP-9 in a GBC-SD cell xenograft model .
Taken together , these results suggest that oridonin possesses anticancer properties in GBC .
Notably , oridonin can suppress tumor epithelial-mesenchymal transition and cell migration by targeting the HIF-1α/MMP-9 signaling pathway .

Hypoxia has crucial roles in cancer development and progression. Our previous study indicated that cell migration was increased in a hypoxic microenvironment in GBC-SD gallbladder cancer (GBC) cells. Oridonin, a bioactive diterpenoid compound that is isolated from the plant Rabdosia rubescens, has been identified as an anticancer agent in various types of cancer. However, its roles in cell proliferation, apoptosis, and migration in a hypoxic microenvironment and the associated regulatory mechanisms have not yet to be fully elucidated in GBC. The present study investigated the effect of oridonin on cell proliferation, apoptosis, the cell cycle and cell migration in GBC in vitro and in vivo. Furthermore, the role of oridonin in hypoxia-induced cell migration and its underlying mechanisms were explored in GBC. The results indicated that treatment with oridonin significantly suppressed cell proliferation and the metastatic ability of GBC-SD cells in a dose-dependent manner, increased the level of cell apoptosis and induced cell cycle arrest at the G0/G1 phase. Further experiments demonstrated that oridonin could inhibit hypoxia-induced epithelial-mesenchymal transition and cell migration by downregulating the expression levels of hypoxia-inducible factor (HIF)-1α/matrix metallopeptidase (MMP)-9. In addition, oridonin suppressed GBC cell growth and downregulated the expression levels of HIF-1α and MMP-9 in a GBC-SD cell xenograft model. Taken together, these results suggest that oridonin possesses anticancer properties in GBC. Notably, oridonin can suppress tumor epithelial-mesenchymal transition and cell migration by targeting the HIF-1α/MMP-9 signaling pathway.


greenmedinfo--2020-08-29--Oridonin attenuates carrageenan-induced pleurisy.

The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases , such as pleurisy .
Because oridonin ( Ori ) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity , we herein aimed to assess the effects of Ori in a mouse model of carrageenan ( CAR ) -induced pleurisy .
The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors ( TNF-α , IL-6 and IL-1β ) , effects that were significantly reduced by treatment with Ori .
In addition , increased neutrophil infiltration @ @ @ @ @ @ @ in the exudates of the CAR group , and these phenomena were suppressed by Ori treatment .
Regarding cellular pathways , Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways .
Additionally , oxidative stress was shown to be involved in the pathogenesis of pleurisy , but possible mechanisms remain to be explored .
Herein , Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS , MPO and MDA levels .
Furthermore , Ori inhibited NOX-4 levels , initiated the dissociation of KEAP-1 from Nrf2 , activated @ @ @ @ @ @ @ effects on CAR-induced pleurisy .
In conclusion , Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties .

The classic NLRP3 inflammasome and NF-κB molecular pathways are activated in many inflammatory-related diseases, such as pleurisy. Because oridonin (Ori) has been indicated as a covalent NLRP3 inhibitor with strong anti-inflammasome activity, we herein aimed to assess the effects of Ori in a mouse model of carrageenan (CAR)-induced pleurisy. The results showed that CAR caused hemorrhaging and exudation of lung tissues and the release of inflammatory factors (TNF-α, IL-6 and IL-1β), effects that were significantly reduced by treatment with Ori. In addition, increased neutrophil infiltration, protein concentrations and volumes were found in the exudates of the CAR group, and these phenomena were suppressed by Ori treatment. Regarding cellular pathways, Ori could alleviate the CAR-activated NF-κB and TXNIP/NLRP3 pathways. Additionally, oxidative stress was shown to be involved in the pathogenesis of pleurisy, but possible mechanisms remain to be explored. Herein, Ori reversed the CAR-induced depletion of GSH and SOD and the CAR-induced increases in ROS, MPO and MDA levels. Furthermore, Ori inhibited NOX-4 levels, initiated the dissociation of KEAP-1 from Nrf2, activated the downstream genes HO-1 and exerted antioxidative effects on CAR-induced pleurisy. In conclusion, Ori conferred protection against CAR-induced pleurisy via Nrf2-dependent antioxidative and NLRP3-dependent anti-inflammatory properties.


greenmedinfo--2020-08-29--Oridonin displays therapeutic efficacy towards memory deficits via improvement of insulin resistance

Oridonin displays therapeutic efficacy towards memory deficits via improvement of insulin resistance in minimal hepatic encephalopathy.

Minimal hepatic encephalopathy ( MHE ) was characterized for cognitive dysfunction .
Insulin resistance ( IR ) has been identified @ @ @ @ @ pathogenesis of MHE .
Oridonin ( Ori ) is an active terpenoid , which has @ @ @ @ @ loss and restore insulin sensitivity .
In this study , we found that intraperitoneal injection @ @ @ @ @ reduced the autophagosome formation and synaptic loss and improved cognitive dysfunction in MHE rats .
@ @ @ @ @ cells and N2a cells , we found that Ori blocked IR-induced synaptic deficits via the @ @ @ @ @ phosphorylation of Akt and the inhibition of autophagy .
Taken together , these results suggested @ @ @ @ @ towards memory deficits via improvement of IR in MHE and represents a novel bioactive therapeutic @ @ @ @ @

Minimal hepatic encephalopathy (MHE) was characterized for cognitive dysfunction. Insulin resistance (IR) has been identified to be correlated with the pathogenesis of MHE. Oridonin (Ori) is an active terpenoid, which has been reported to rescue synaptic loss and restore insulin sensitivity. In this study, we found that intraperitoneal injection of Ori rescued IR, reduced the autophagosome formation and synaptic loss and improved cognitive dysfunction in MHE rats. Moreover, in insulin-resistant PC12 cells and N2a cells, we found that Ori blocked IR-induced synaptic deficits via the down-regulation of PTEN, the phosphorylation of Akt and the inhibition of autophagy. Taken together, these results suggested that Ori displays therapeutic efficacy towards memory deficits via improvement of IR in MHE and represents a novel bioactive therapeutic agent for treating MHE.


greenmedinfo--2020-08-29--Protective effects of oridonin on acute liver injury.

Objective : Recent researches have demonstrated that inflammation-related diseases are effectively regulated by posttranslational modifications ( PTMs ) including phosphorylation and acetylation .
Our previous study found a new acetyltransferase inhibitor , oridonin , which had a protective effect on acute liver injury ( ALI ) .
In the present study , we further investigated its protective mechanism against D-galactosamine ( D-Gal ) combined with lipopolysaccharide- ( LPS- ) induced ALI in mice .
Methods : Intraperitoneal injections of LPS ( 40 g/mouse ) /D-Gal ( 5 mg/mouse ) were given to the mice , and the experimental group was @ @ @ @ @ @ @ 0.2 mg/mouse ) .
To elucidate the protective mechanism of oridonin , we collected liver specimens and used RNA-sequencing ( RNA-Seq ) analysis .
We focused on the genes that were upregulated by LPS/D-Gal and downregulated after pretreatment with oridonin .
The downregulated genes examined by Gene Ontology ( GO ) and Kyoto Encyclopedia of Genes and Genomes ( KEGG ) pathway analysis were further verified by real-time polymerase chain reaction ( PCR ) and western blot .
Results : GO analysis showed that genes that were downregulated after pretreatment with oridonin were @ @ @ @ @ @ @ , and inflammatory response .
Real-time PCR confirmed that the expression of these genes was upregulated by LPS/D-Gal induction and reduced after treatment with oridonin , which was consistent with RNA-Seq results .
KEGG pathway analysis showed a significantly enriched downregulated gene that was present in the Toll-like receptor ( TLR ) 4 signaling cascade .
Our results manifested that phosphorylation levels of upstream signaling molecules in the TLR4 signaling cascade , including extracellular signal-regulated kinase ( ERK ) , P38 , and IB , were significantly inhibited by oridonin .
Furthermore , @ @ @ @ @ @ @ gene loci in the TLR4 signaling pathway , including phosphorylation of IL-1 receptor-associated kinase 4 ( IRAK4 T345/S346 ) and acetylation of IRAK4 ( K34 ) .
However , after treatment with oridonin , the modification pattern of IRAK4 expression stimulated by LPS/D-Gal was suggestively attenuated .
Conclusion : Our study revealed that the protective effects of oridonin on LPS/D-Gal-induced ALI mediated by inhibition of the PTMs of IRAK4 , including phosphorylation of T345/S346 and acetylation of K34 .

Objective: Recent researches have demonstrated that inflammation-related diseases are effectively regulated by posttranslational modifications (PTMs) including phosphorylation and acetylation. Our previous study found a new acetyltransferase inhibitor, oridonin, which had a protective effect on acute liver injury (ALI). In the present study, we further investigated its protective mechanism against D-galactosamine (D-Gal) combined with lipopolysaccharide- (LPS-) induced ALI in mice.
Methods: Intraperitoneal injections of LPS (40 g/mouse)/D-Gal (5 mg/mouse) were given to the mice, and the experimental group was pretreated with intraperitoneal injection of oridonin (0.2 mg/mouse). To elucidate the protective mechanism of oridonin, we collected liver specimens and used RNA-sequencing (RNA-Seq) analysis. We focused on the genes that were upregulated by LPS/D-Gal and downregulated after pretreatment with oridonin. The downregulated genes examined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were further verified by real-time polymerase chain reaction (PCR) and western blot.
Results: GO analysis showed that genes that were downregulated after pretreatment with oridonin were extremely concentrated in immune response, chemotaxis, and inflammatory response. Real-time PCR confirmed that the expression of these genes was upregulated by LPS/D-Gal induction and reduced after treatment with oridonin, which was consistent with RNA-Seq results. KEGG pathway analysis showed a significantly enriched downregulated gene that was present in the Toll-like receptor (TLR) 4 signaling cascade. Our results manifested that phosphorylation levels of upstream signaling molecules in the TLR4 signaling cascade, including extracellular signal-regulated kinase (ERK), P38, and IB, were significantly inhibited by oridonin. Furthermore, LPS/D-Gal stimulation triggered posttranslational modifications of related gene loci in the TLR4 signaling pathway, including phosphorylation of IL-1 receptor-associated kinase 4 (IRAK4 T345/S346) and acetylation of IRAK4 (K34). However, after treatment with oridonin, the modification pattern of IRAK4 expression stimulated by LPS/D-Gal was suggestively attenuated.
Conclusion: Our study revealed that the protective effects of oridonin on LPS/D-Gal-induced ALI mediated by inhibition of the PTMs of IRAK4, including phosphorylation of T345/S346 and acetylation of K34.


greenmedinfo--2020-08-29--The antibacterial mechanism of oridonin against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant ( MRSA ) is a very harmful bacterium .
Oridonin , a component in ( Hemsl . )
Hara ( Lamiaceae ) , is widely used against bacterial infections in China.We evaluated oridonin effects on MRSA cell membrane and wall , protein metabolism , lactate dehydrogenase ( LDH ) , DNA and microscopic structure.Broth microdilution and flat colony counting methods were used to measure oridonin minimal inhibitory concentration ( MIC ) and minimum bactericidal concentration ( MBC ) against USA300 strain .
Electrical conductivity and DNA exosmosis were analysed to study oridonin effects ( 128 μg/mL ) on cell @ @ @ @ @ @ @ , 2 , 4 and 6 h. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to detect effects on soluble protein synthesis after 6 , 10 and 16 h. LDH activity was examined with an enzyme-linked immunosorbent assay .
Effects of oridonin on USA300DNA were investigated with DAPI staining .
Morphological changes in MRSA following oridonin treatment were determined with scanning electron microscopy ( SEM ) and transmission electron microscopy ( TEM ) .Oridonin MIC and MBC values against USA300 were 64 and 512 μg/mL , respectively .
The conductivity and DNA exosmosis @ @ @ @ @ @ @ % and increased by 58.63 ± 1.78 μg/mL , respectively .
LDH and soluble protein levels decreased by 30.85±7.69 % and 27.51 ± 1.39 % , respectively .
A decrease in fluorescence intensity was reported with time .
Oridonin affected the morphology of USA300.Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability , disturbance in protein and DNA metabolism , and influence on bacterial morphology .
Thus , oridonin may help in treating MRSA infection .

Methicillin-resistant(MRSA) is a very harmful bacterium. Oridonin, a component in(Hemsl.) Hara (Lamiaceae), is widely used against bacterial infections in China.We evaluated oridonin effects on MRSA cell membrane and wall, protein metabolism, lactate dehydrogenase (LDH), DNA and microscopic structure.Broth microdilution and flat colony counting methods were used to measure oridonin minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against USA300 strain. Electrical conductivity and DNA exosmosis were analysed to study oridonin effects (128 μg/mL) on cell membrane and wall for 0, 1, 2, 4 and 6 h. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to detect effects on soluble protein synthesis after 6, 10 and 16 h. LDH activity was examined with an enzyme-linked immunosorbent assay. Effects of oridonin on USA300DNA were investigated with DAPI staining. Morphological changes in MRSA following oridonin treatment were determined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM).Oridonin MIC and MBC values against USA300 were 64 and 512 μg/mL, respectively. The conductivity and DNA exosmosis level of oridonin-treated USA300 improved by 3.20±0.84% and increased by 58.63 ± 1.78 μg/mL, respectively. LDH and soluble protein levels decreased by 30.85±7.69% and 27.51 ± 1.39%, respectively. A decrease in fluorescence intensity was reported with time. Oridonin affected the morphology of USA300.Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability, disturbance in protein and DNA metabolism, and influence on bacterial morphology. Thus, oridonin may help in treating MRSA infection.


greenmedinfo--2020-08-29--Recent progress of oridonin and its derivatives for the treatment of acute myelogenous leukemia.

First stage human clinical trial ( CTR20150246 ) for HAO472 , the L-alanine- ( 14-oridonin ) ester trifluoroacetate , was @ @ @ @ @ , Hengrui Medicine Co. Ltd , to develop a new treatment for acute myelogenous leukemia @ @ @ @ @ and CN201410047904.X , covered the development of the I-type crystal , stability experiment , conversion @ @ @ @ @ , safety assessment , and solubility study .
HAO472 hewed out new avenues to explore @ @ @ @ @ derivatives and develop promising treatment of cancer originated from naturally derived drug candidates .
Herein @ @ @ @ @ recent progress of the synthetic , physiological , and pharmacological investigations of oridonin and its @ @ @ @ @ the therapeutic potentials and broaden the platform for the discovery of new anticancer drugs .

First stage human clinical trial (CTR20150246) for HAO472, the L-alanine-(14-oridonin) ester trifluoroacetate, was conducted by a Chinese company, Hengrui Medicine Co. Ltd, to develop a new treatment for acute myelogenous leukemia. Two patents, WO2015180549A1 and CN201410047904.X, covered the development of the I-type crystal, stability experiment, conversion rate research, bioavailability experiment, safety assessment, and solubility study. HAO472 hewed out new avenues to explore the therapeutic properties of oridonin derivatives and develop promising treatment of cancer originated from naturally derived drug candidates. Herein, we sought to overview recent progress of the synthetic, physiological, and pharmacological investigations of oridonin and its derivatives, aiming to disclose the therapeutic potentials and broaden the platform for the discovery of new anticancer drugs.


greenmedinfo--2020-08-29--The inhibitory effect of oridonin on colon cancer was mediated by deactivation of TGF-β1/Smads-PAI-1

The inhibitory effect of oridonin on colon cancer was mediated by deactivation of TGF-β1/Smads-PAI-1 signaling pathway in vitro and vivo.

Background : Oridonin , the main active component of Rabdosia rubescens , has been demonstrated to have anti-tumor effect on all kinds of cancer cells through various mechanisms and it has shown antitumor activity in some tumors partially via the suppression of TGF-β/Smads signaling pathway .
The aim of this study was to explore the anticancer effect of oridonin on human colon carcinoma and underlying mechanism in vitro and vivo .
Methods : CCK-8 assay was employed to assess cell viability .
The key target genes and proteins involved in TGF-β/Smads pathway was detected by RT-PCR , Western blotting and @ @ @ @ @ @ @ of colon cance LOVO cell was introduced to detect anti-cancer effects in vivo .
Results : Oridonin inhibited the proliferation of colon cancer LOVO cells in a concentration and time dependent manner .
In addition , oridonin reduced the levels of Smad2 , Smad3 , Smad4 , PAI-1 and the phosphorylation of Smad2 and Smad3 induced by TGF-β1 in vitro .
Subsequently , we established an orthotopically implanted tumor model in nude mice and found that oridonin treatment significantly suppressed tumor growth , and which was accompanied by the down-regulation of Smad2 , @ @ @ @ @ @ @ , p-Smad3 expression levels .
Conclusion : Our present study demonstrated that the growth inhibition of colon cancer by oridonin could be partially mediated through discontinuing TGF-β1/Smads-PAI-1 signaling pathway , suggesting it as a promising agent in treating colorectal cancer .

Background: Oridonin, the main active component of Rabdosia rubescens, has been demonstrated to have anti-tumor effect on all kinds of cancer cells through various mechanisms and it has shown antitumor activity in some tumors partially via the suppression of TGF-β/Smads signaling pathway. The aim of this study was to explore the anticancer effect of oridonin on human colon carcinoma and underlying mechanism in vitro and vivo.
Methods: CCK-8 assay was employed to assess cell viability. The key target genes and proteins involved in TGF-β/Smads pathway was detected by RT-PCR, Western blotting and immunohistochemistry. The orthotopic transplantation tumor model of colon cance LOVO cell was introduced to detect anti-cancer effects in vivo.
Results: Oridonin inhibited the proliferation of colon cancer LOVO cells in a concentration and time dependent manner. In addition, oridonin reduced the levels of Smad2, Smad3, Smad4, PAI-1 and the phosphorylation of Smad2 and Smad3 induced by TGF-β1 in vitro. Subsequently, we established an orthotopically implanted tumor model in nude mice and found that oridonin treatment significantly suppressed tumor growth, and which was accompanied by the down-regulation of Smad2, Smad3, Smad4, PAI-1 and p-Smad2, p-Smad3 expression levels.
Conclusion: Our present study demonstrated that the growth inhibition of colon cancer by oridonin could be partially mediated through discontinuing TGF-β1/Smads-PAI-1 signaling pathway, suggesting it as a promising agent in treating colorectal cancer.


greenmedinfo--2020-08-29--Oridonin induces apoptosis in HGC-27 cells by activating the JNK signaling pathway.

Gastric cancer ( GC ) is a very common type of cancer .
Although current treatment modalities include surgical resection @ @ @ @ @ are either not eligible for radical resection or have a poor response to chemotherapy .
@ @ @ @ @ of the disease , there is a need for complementary therapy .
In the present @ @ @ @ @ oridonin on cell proliferation , invasion and apoptosis were assessed in the HGC-27 cell line @ @ @ @ @ assay , real-time cell analysis , and an Annexin V-FITC/propidium iodide ( PI ) detection @ @ @ @ @ effect of oridonin on apoptosis , through the JNK pathway , was also investigated using @ @ @ @ @ study demonstrated that oridonin can suppress cell viability and inhibit cell proliferation by inducing G/M @ @ @ @ @ caspase-dependent apoptosis in cells by activating the phosphorylated-JNK/C-JUN pathway .
These results demonstrate the potential @ @ @ @ @ therapeutic compound for the treatment of GC .

Gastric cancer (GC) is a very common type of cancer. Although current treatment modalities include surgical resection and chemotherapy, many patients are either not eligible for radical resection or have a poor response to chemotherapy. Due to the complex features of the disease, there is a need for complementary therapy. In the present study, the effects of oridonin on cell proliferation, invasion and apoptosis were assessed in the HGC-27 cell line using the Cell Counting Kit-8 assay, real-time cell analysis, and an Annexin V-FITC/propidium iodide (PI) detection kit, respectively. The effect of oridonin on apoptosis, through the JNK pathway, was also investigated using western blotting. The present study demonstrated that oridonin can suppress cell viability and inhibit cell proliferation by inducing G/M arrest. Oridonin also induced caspase-dependent apoptosis in cells by activating the phosphorylated-JNK/C-JUN pathway. These results demonstrate the potential of oridonin as a potential therapeutic compound for the treatment of GC.


greenmedinfo--2020-08-29--Oridonin suppresses autophagy and survival in rheumatoid arthritis fibroblast-like synoviocytes.

Oridonin exhibits various pharmacological and physiological activities , including antioxidant , antibacterial , anti-inflammatory , pro-apoptotic , anticancer and neurological @ @ @ @ @ role in rheumatoid arthritis ( RA ) is yet to be revealed.We evaluated the effects @ @ @ @ @ and autophagy of RA-fibroblast-like synoviocytes ( FLSs ) .RA-FLSs were treated with oridonin at serial @ @ @ @ @ , 4 , 6 , 8 and 10 µg/mL for 24 , 48 and 72 @ @ @ @ @ and apoptosis were measured .
A GFP-LC3 plasmid was transfected into the cells to determine @ @ @ @ @ a dose-dependent manner .
The half maximal inhibitory concentrations ( IC ) of oridonin at @ @ @ @ @ h were 8.28 , 7.88 and 8.35 µg/mL , respectively .
Treatment with oridonin for @ @ @ @ @ 4.1 % , and increased the protein levels of Bax and cleaved caspase-3 but significantly @ @ @ @ @ in the culture supernatant (

Oridonin exhibits various pharmacological and physiological activities, including antioxidant, antibacterial, anti-inflammatory, pro-apoptotic, anticancer and neurological effects. However, its role in rheumatoid arthritis (RA) is yet to be revealed.We evaluated the effects of oridonin on the survival and autophagy of RA-fibroblast-like synoviocytes (FLSs).RA-FLSs were treated with oridonin at serial concentrations of 0, 2, 4, 6, 8 and 10 µg/mL for 24, 48 and 72 h. Then, cell proliferation and apoptosis were measured. A GFP-LC3 plasmid was transfected into the cells to determine autophagy.Oridonin suppressed RA-FLS proliferation in a dose-dependent manner. The half maximal inhibitory concentrations (IC) of oridonin at 24, 48 and 72 h were 8.28, 7.88 and 8.35 µg/mL, respectively. Treatment with oridonin for 24 h increased apoptosis by 4.1%, and increased the protein levels of Bax and cleaved caspase-3 but significantly decreased the levels of IL-1β in the culture supernatant ( < 0.05). In addition, 6 h of oridonin treatment significantly decreased the number of GFP-LC3 punctate dots and inhibited the protein levels of ATG5 and Beclin1 by 80.01% and 42.12%, respectively. Chloroquine (CQ) significantly reinforced the effects of oridonin on inhibition of autophagy, suppression of proliferation, and induction of apoptosis in RA-FLSs ( < 0.05).Our results indicate that treatment with oridonin in combination with CQ inhibits autophagy and cell proliferation and induces apoptosis in RA-FLSs more effectively than treatment oridonin alone. This finding indicates that oridonin is a potential therapeutic agent for RA.


greenmedinfo--2020-08-29--Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer c

Oridonin inhibits the migration and epithelial-to-mesenchymal transition of small cell lung cancer cells.

Small cell lung cancer ( SCLC ) is a severe malignant with high morbidity ; however , few effective and secure therapeutic strategy is used in current clinical practice .
Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens .
This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688 , a kind of small cell lung cancer cells from human .
Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment ( 20 μmol/L ) .
Meanwhile , cell migration was suppressed by oridonin ( @ @ @ @ @ @ @ not affect cell proliferation and apoptosis .
The expression level of E-cadherin was significantly increased , and the expression of vimentin , snail and slug was reduced after administration of oridonin .
These expression changes were associated with the suppressed integrin β1 , phosphorylation of focal adhesion kinase ( FAK ) and ERK1/2 .
In addition , oridonin ( 5 and 10 mg/kg ) inhibited tumour growth in a nude mouse model ; however , HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin ( 10 mg/kg ) @ @ @ @ @ @ @ aminotransferase ( ALP ) was significantly increased and lactate dehydrogenase ( LDH ) was reduced after oridonin treatment ( 10 mg/kg ) .
Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo .
These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition ( EMT ) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway .
Thus , oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety .

Small cell lung cancer (SCLC) is a severe malignant with high morbidity; however, few effective and secure therapeutic strategy is used in current clinical practice. Oridonin is a small molecule from the traditional Chinese herb Rabdosia rubescens. This study mainly aimed to investigate the role of oridonin on inhibiting the process of H1688, a kind of small cell lung cancer cells from human. Oridonin could suppress H1688 cell proliferation and induce their apoptosis in a high dosage treatment (20 μmol/L). Meanwhile, cell migration was suppressed by oridonin (5 and 10 μmol/L) that did not affect cell proliferation and apoptosis. The expression level of E-cadherin was significantly increased, and the expression of vimentin, snail and slug was reduced after administration of oridonin. These expression changes were associated with the suppressed integrin β1, phosphorylation of focal adhesion kinase (FAK) and ERK1/2. In addition, oridonin (5 and 10 mg/kg) inhibited tumour growth in a nude mouse model; however, HE staining revealed a certain degree of cytotoxicity in hepatic tissue after treatment oridonin (10 mg/kg). Furthermore, the concentration of alanine aminotransferase (ALP) was significantly increased and lactate dehydrogenase (LDH) was reduced after oridonin treatment (10 mg/kg). Immunohistochemical analysis further revealed that oridonin increased E-cadherin expression and reduced vimentin and phospho-FAK levels in vivo. These findings indicated that oridonin can inhibit the migration and epithelial-to-mesenchymal transition (EMT) of SCLC cells by suppressing the FAK-ERK1/2 signalling pathway. Thus, oridonin may be a new drug candidate to offer an effect of anti-SCLC with relative safety.


greenmedinfo--2020-08-29--Oridonin attenuates lipopolysaccharide-induced ROS accumulation and inflammation in HK-2 cells.

Renal tubulointerstitial inflammation plays an important role in chronic kidney disease ( CKD ) .
Inflammation reduction is a good strategy to combat CKD .
Oridonin , an ent-kaurane diterpenoid isolated from ( Donglingcao ) , is considered as an effective natural candidate for the treatment of anti-inflammatory , antiviral , and antibacterial activities , including liver fibrosis and many tumors ; however , no study has demonstrated its effect on lipopolysaccharide- ( LPS- ) induced renal inflammation .
To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells ( HK-2 cells ) , the expression @ @ @ @ @ @ @ ) and reactive oxygen species ( ROS ) were evaluated by Western blot analysis and 2',7'-dichlorofluorescein diacetate ( DCF-DA ) staining , respectively .
The level of intracellular ROS increased in a dose-dependent manner following LPS treatment , whereas oridonin inhibited this effect , suggestive of its ability to prevent ROS accumulation .
As the mitogen-activated protein kinase ( MAPK ) family of enzymes plays an important role in physiological responses , we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation .
Oridonin also attenuated @ @ @ @ @ @ @ cells .
Taken together , oridonin protected against LPS-induced inflammation including ROS accumulation , JNK activation , NF-B nuclear translocation in HK-2 cells , and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells .
Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells .

Renal tubulointerstitial inflammation plays an important role in chronic kidney disease (CKD). Inflammation reduction is a good strategy to combat CKD. Oridonin, an ent-kaurane diterpenoid isolated from(Donglingcao), is considered as an effective natural candidate for the treatment of anti-inflammatory, antiviral, and antibacterial activities, including liver fibrosis and many tumors; however, no study has demonstrated its effect on lipopolysaccharide- (LPS-) induced renal inflammation. To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells (HK-2 cells), the expression levels of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) were evaluated by Western blot analysis and 2',7'-dichlorofluorescein diacetate (DCF-DA) staining, respectively. The level of intracellular ROS increased in a dose-dependent manner following LPS treatment, whereas oridonin inhibited this effect, suggestive of its ability to prevent ROS accumulation. As the mitogen-activated protein kinase (MAPK) family of enzymes plays an important role in physiological responses, we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation. Oridonin also attenuated RAW 264.7 cell chemotaxis towards LPS-treated HK-2 cells. Taken together, oridonin protected against LPS-induced inflammation including ROS accumulation, JNK activation, NF-B nuclear translocation in HK-2 cells, and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells. Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells.


greenmedinfo--2020-08-29--Oridonin ameliorates carbon tetrachloride-induced liver fibrosis.

Liver fibrosis is characterized by the activation of hepatic stellate cells ( HSCs ) and accumulation of the extracellular matrix @ @ @ @ @ the current therapies for liver fibrosis .
Recently , oridonin was shown to induce apoptosis @ @ @ @ @ we aimed to determine the roles of oridonin in chronic liver injury and fibrosis .
@ @ @ @ @ CClin mice injected intraperitoneally with oridonin for 6 weeks .
The administration of oridonin significantly @ @ @ @ @ ALT levels .
In addition , Sirius Red staining and the expression of α-smooth muscle @ @ @ @ @ significantly reduced by oridonin in murine livers with fibrosis .
The expression of NLRP3 , @ @ @ @ @ with the oridonin treatment .
Furthermore , the expression of F4/80 in liver tissues was @ @ @ @ @ .
These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis .
Mechanically , @ @ @ @ @ of the NLRP3 inflammasome and inflammation in the liver .
These results highlight the potential @ @ @ @ @ agent for liver fibrosis .

Liver fibrosis is characterized by the activation of hepatic stellate cells (HSCs) and accumulation of the extracellular matrix. There are limitations in the current therapies for liver fibrosis. Recently, oridonin was shown to induce apoptosis in HSCs. Thus, we aimed to determine the roles of oridonin in chronic liver injury and fibrosis. Liver fibrosis was induced by CClin mice injected intraperitoneally with oridonin for 6 weeks. The administration of oridonin significantly attenuated liver injury and reduced ALT levels. In addition, Sirius Red staining and the expression of α-smooth muscle actin (α-SMA) were significantly reduced by oridonin in murine livers with fibrosis. The expression of NLRP3, caspase-1, andIL-1β was downregulated with the oridonin treatment. Furthermore, the expression of F4/80 in liver tissues was also decreased by oridonin treatment. These results demonstrate that oridonin ameliorates chronic liver injury and fibrosis. Mechanically, oridonin may inhibit the activity of the NLRP3 inflammasome and inflammation in the liver. These results highlight the potential of oridonin as a therapeutic agent for liver fibrosis.


greenmedinfo--2020-08-29--Oridonin alleviates IRI-induced kidney injury by inhibiting inflammatory response of macrophages.

BACKGROUND Acute kidney injury ( AKI ) is one of the most common complications in clinic , but there is still no effective treatment .
Oridonin , extracted from Rabdosia rubescens , has been identified to promote inhibitory effects on tumor , inflammatory and fibrosis by previous study .
This study aimed to assess the kidney-protective role of Oridonin in AKI and the underlying mechanism by which Oridonin improves AKI in vivo and inhibits inflammation in LPS-induced bone marrow-derived macrophages ( BMDM ) in vitro .
MATERIAL AND METHODS SPF C57BL/6J male mice ( 8 - 10 weeks old , @ @ @ @ @ @ @ were divided into 3 groups - sham group , AKI group , and Oridonin-treated AKI group - with 6 mice in each group .
In the in vitro study , LPS-induced inflammatory BMDM cells were treated with Oridonin and agonist of AKT .
The expression and secretion levels of inflammation-related indicators and AKT-related signaling molecules were detected by real-time PCR , ELISA , Western blot , and immunofluorescence .
Also , various methods are used to assess renal function and pathological changes .
RESULTS The results showed that Oridonin treatment significantly improved the @ @ @ @ @ @ @ mice .
Interestingly , treatment with Oridonin also resulted in decreased the infiltration of macrophages in renal tissues of AKI mice , which was associated with decreased expression and activation of AKT and its related signaling pathways , such as NF-kappaB and STAT3 , suggesting that Oridonin attenuates AKI kidney injury via a mechanism associated with reducing the inflammatory response of macrophages in the AKI kidney .
This was investigated in vitro in macrophages , and the results showed that Oridonin reduced the LPS-stimulated inflammatory response in macrophages .
Mechanistically , the addition @ @ @ @ @ @ @ , NF-kappaB , and STAT3 expression and inflammatory response in macrophages , suggesting that Oridonin has a protective role , via the AKT-related signaling pathways , in reducing the inflammatory response of macrophages in AKI mice .
This was further confirmed by adding agonist of AKT of IGF-1 to block the inhibitory effect of Oridonin on inflammatory response in vitro .
CONCLUSIONS Oridonin ameliorates AKI kidney injuries by suppressing AKT-mediated inflammatory response of macrophages .

BACKGROUND Acute kidney injury (AKI) is one of the most common complications in clinic, but there is still no effective treatment. Oridonin, extracted from Rabdosia rubescens, has been identified to promote inhibitory effects on tumor, inflammatory and fibrosis by previous study. This study aimed to assess the kidney-protective role of Oridonin in AKI and the underlying mechanism by which Oridonin improves AKI in vivo and inhibits inflammation in LPS-induced bone marrow-derived macrophages (BMDM) in vitro. MATERIAL AND METHODS SPF C57BL/6J male mice (8 - 10 weeks old, body weight 20 - 25 g) were divided into 3 groups - sham group, AKI group, and Oridonin-treated AKI group - with 6 mice in each group. In the in vitro study, LPS-induced inflammatory BMDM cells were treated with Oridonin and agonist of AKT. The expression and secretion levels of inflammation-related indicators and AKT-related signaling molecules were detected by real-time PCR, ELISA, Western blot, and immunofluorescence. Also, various methods are used to assess renal function and pathological changes. RESULTS The results showed that Oridonin treatment significantly improved the serum creatinine and BUN levels in AKI mice. Interestingly, treatment with Oridonin also resulted in decreased the infiltration of macrophages in renal tissues of AKI mice, which was associated with decreased expression and activation of AKT and its related signaling pathways, such as NF-kappaB and STAT3, suggesting that Oridonin attenuates AKI kidney injury via a mechanism associated with reducing the inflammatory response of macrophages in the AKI kidney. This was investigated in vitro in macrophages, and the results showed that Oridonin reduced the LPS-stimulated inflammatory response in macrophages. Mechanistically, the addition of Oridonin reversed LPS-induced downregulation of AKT, NF-kappaB, and STAT3 expression and inflammatory response in macrophages, suggesting that Oridonin has a protective role, via the AKT-related signaling pathways, in reducing the inflammatory response of macrophages in AKI mice. This was further confirmed by adding agonist of AKT of IGF-1 to block the inhibitory effect of Oridonin on inflammatory response in vitro. CONCLUSIONS Oridonin ameliorates AKI kidney injuries by suppressing AKT-mediated inflammatory response of macrophages.


greenmedinfo--2020-08-29--Cetuximab enhances oridonin-induced apoptosis through mitochondrial pathway and endoplasmic reticulu

Cetuximab enhances oridonin-induced apoptosis through mitochondrial pathway and endoplasmic reticulum stress in laryngeal squamous cell carcinoma cells.

Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell carcinoma ( LSCC ) , as been reported @ @ @ @ @ further mechanistically extended action of the synergistic effects of combination treatment .
Firstly , two @ @ @ @ @ to oridonin , whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells @ @ @ @ @ .
Next , cetuximab/oridonin significantly enhanced the mitochondrial apoptosis through NF-κB .
Meanwhile , PI3K/Akt @ @ @ @ @ with the nucleus translocation of NF-κB by combination treatment .
Additionally , cetuximab enhanced oridonin-promoted @ @ @ @ @ , both ER stress and mitochondrial apoptosis by combination treatment are abrogated by ROS scavenger @ @ @ @ @ ROS production after 1.5 h , followed by G2/M arrest and apoptosis , indicating that @ @ @ @ @ early and key event .
Taken together , cetuximab enhances oridonin-induced ER stress and mitochondrial @ @ @ @ @ to the synergistic antitumor effects of cetuximab/oridonin .

Cetuximab plus oridonin showed a synergistic way to kill laryngeal squamous cell carcinoma (LSCC), as been reported previously. The present work further mechanistically extended action of the synergistic effects of combination treatment. Firstly, two LSCC cells displayed higher sensitivity to oridonin, whereas both low EGFR expression tumor cells and EGFR knockdown LSCC cells were less sensitive to oridonin. Next, cetuximab/oridonin significantly enhanced the mitochondrial apoptosis through NF-κB. Meanwhile, PI3K/Akt and JAK2/STAT3 pathways are associated with the nucleus translocation of NF-κB by combination treatment. Additionally, cetuximab enhanced oridonin-promoted ER stress-related apoptosis. Interestingly, both ER stress and mitochondrial apoptosis by combination treatment are abrogated by ROS scavenger. Furthermore, oridonin/cetuximab induced ROS production after 1.5 h, followed by G2/M arrest and apoptosis, indicating that ROS generation might be an early and key event. Taken together, cetuximab enhances oridonin-induced ER stress and mitochondrial apoptotic pathway, which contributes to the synergistic antitumor effects of cetuximab/oridonin.


greenmedinfo--2020-08-29--Oridonin induces the apoptosis of mucoepidermoid carcinoma cell lines in a myeloid cell leukemia‑1‑d

Oridonin induces the apoptosis of mucoepidermoid carcinoma cell lines in a myeloid cell leukemia‑1‑dependent manner.

Oridonin , an active diterpenoid isolated from Rabdosia rubescens , has been reported to exhibit anticancer activities in several tumors @ @ @ @ @ present study was to investigate the anticancer effects and molecular mechanisms of oridonin in mucoepidermoid @ @ @ @ @ Treatment with oridonin induced the apoptosis of MC‑3 and YD‑15 cell and inhibited the expression @ @ @ @ @ MCL‑1 ) through the regulation of the protein level through post‑translational regulation in these cell @ @ @ @ @ the expression level of truncated Bid ( t‑Bid ) as a downstream target of MCL‑1 @ @ @ @ @ membrane potential .
The ectopic expression of MCL‑1 protein was sufficient to reverse the induction @ @ @ @ @ t‑Bid expression induced by oridonin in both cell lines .
Taken together , these results @ @ @ @ @ apoptotic effect through the modulation of MCL‑1 and t‑Bid in human MEC cell lines and @ @ @ @ @ anticancer drug candidate for the treatment of human MEC .

Oridonin, an active diterpenoid isolated from Rabdosia rubescens, has been reported to exhibit anticancer activities in several tumors. The aim of the present study was to investigate the anticancer effects and molecular mechanisms of oridonin in mucoepidermoid carcinoma (MEC). Treatment with oridonin induced the apoptosis of MC‑3 and YD‑15 cell and inhibited the expression of myeloid cell leukemia‑1 (MCL‑1) through the regulation of the protein level through post‑translational regulation in these cell lines. Oridonin significantly increased the expression level of truncated Bid (t‑Bid) as a downstream target of MCL‑1 and subsequently decreased the mitochondrial membrane potential. The ectopic expression of MCL‑1 protein was sufficient to reverse the induction of apoptosis and the increased t‑Bid expression induced by oridonin in both cell lines. Taken together, these results suggest that oridonin exerts an apoptotic effect through the modulation of MCL‑1 and t‑Bid in human MEC cell lines and may thus be a potential anticancer drug candidate for the treatment of human MEC.


greenmedinfo--2020-08-30--Top Six Benefits of Selenium

Top Six Benefits of Selenium

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greenmedinfo--2020-08-30--Oridonin induces apoptosis in oral squamous cell carcinoma.

The anti-inflammatory effects of oridonin ( Ordn ) have been well established in previous studies .
However , the apoptotic effects of Ordn on oral cancer cells have not yet been evaluated , at least to the best of our knowledge .
The aim of this study was to examine the apoptotic activity of Ordn in oral squamous cell carcinoma cells and to eluciudate the underlying mechanisms .
For this purpose , we employed experimental techniques , such as MTT assay , DAPI staining , soft agar assay , flow cytometry and western blot analysis .
Our results revealed that @ @ @ @ @ @ @ soft agar colony formation , while it induced reactive oxygen species ( ROS ) -dependent apoptosis in a dose or time-dependent manner .
The generation of ROS was detected in HN22 and HSC4 cells treated with Ordn and the use of the free radical scavenger , N-acetyl-L-cysteine , almost blocked Ordn-induced apoptosis .
The phosphorylation of JNK and p38 mitogen-activated protein kinase ( MAPK ) was manifested in the Ordn-treated cells .
Furthermore , Ordn induced the apoptosis of oral cancer cells through the mitochondrial-dependent pathway , involving the loss of mitochondrial membrane @ @ @ @ @ @ @ , the induction of poly ( ADP-Ribose ) polymerase ( PARP ) cleavage , alterations in the ratios of apoptotic proteins and the activation of the caspase cascade .
Taken together , these findings indicate that Ordn induces the apoptosis of oral cancer cells probably via ROS-mediated JNK/p38 MAPK and mitochondrial pathways ; thus , Ordn may have potential for use in the treatment of oral cancer .

The anti-inflammatory effects of oridonin (Ordn) have been well established in previous studies. However, the apoptotic effects of Ordn on oral cancer cells have not yet been evaluated, at least to the best of our knowledge. The aim of this study was to examine the apoptotic activity of Ordn in oral squamous cell carcinoma cells and to eluciudate the underlying mechanisms. For this purpose, we employed experimental techniques, such as MTT assay, DAPI staining, soft agar assay, flow cytometry and western blot analysis. Our results revealed that Ordn suppressed oral cancer cell proliferation and soft agar colony formation, while it induced reactive oxygen species (ROS)-dependent apoptosis in a dose or time-dependent manner. The generation of ROS was detected in HN22 and HSC4 cells treated with Ordn and the use of the free radical scavenger, N-acetyl-L-cysteine, almost blocked Ordn-induced apoptosis. The phosphorylation of JNK and p38 mitogen-activated protein kinase (MAPK) was manifested in the Ordn-treated cells. Furthermore, Ordn induced the apoptosis of oral cancer cells through the mitochondrial-dependent pathway, involving the loss of mitochondrial membrane potential, the release of cytochrome c, the induction of poly(ADP-Ribose) polymerase (PARP) cleavage, alterations in the ratios of apoptotic proteins and the activation of the caspase cascade. Taken together, these findings indicate that Ordn induces the apoptosis of oral cancer cells probably via ROS-mediated JNK/p38 MAPK and mitochondrial pathways; thus,Ordn may have potential for use in the treatment of oral cancer.