greenmedinfo--2020-09-12--Tanshinone IIA elevates serum soluble klotho levels and decreases cardiovascular events in patients

Tanshinone IIA elevates serum soluble klotho levels and decreases cardiovascular events in patients on maintenance hemodialysis.

BACKGROUND : Cardiovascular disease ( CVD ) is the most common adverse event of maintenance hemodialysis ( MHD ) , in which serum soluble klotho plays a vital role .
Tanshinone IIA ( tan ) has been used to protect the cardiovascular system for hundreds of years .
This study was performed to investigate the effects of tan on klotho level and cardiovascular events of MHD patients .
METHODS : Totally 112 patients were enrolled in this study , and their demographic , clinical , and laboratory characteristics were collected at admission .
Serum soluble klotho , carotid intima-media thickness @ @ @ @ @ @ @ calcification ( AAC ) level were measured to determine their relationship .
Seventy-one patients were given sodium tan sulfonate injection according to their willingness , while 41 patients were not given any specific treatment .
The endpoint events were recorded , including cardiovascular mortality , nonfatal cardiovascular events , and all-cause mortality .
RESULTS : All patients were divided into two groups on whether the level of serum soluble klotho was more than medium or not .
CIMT and AAC grade showed significant differences between 2 groups ( group of low level of @ @ @ @ @ @ @ klotho , CIMT : 1.03±0.22 vs. 0.85±0.20 mm , P < 0.001 ; AAC grade : 5.04±3.93 vs. 1.69±2.30 points , P < 0.001 ) .
All patients were followed up for at least one year .
The results revealed that using tan improved the level of serum soluble klotho ( 490.23±153.97 pg/mL after using tan versus 444.49±143.32 pg/mL before using tan , P=0.042 ) .
Kaplan-Meier curves showed that cardiovascular event-free survival was significantly higher in patients given tan ( P=0.040 ) compared with patients not given tan .
CONCLUSIONS : Tan @ @ @ @ @ @ @ klotho and further reduces the incidence of cardiovascular events in MHD patients .

BACKGROUND: Cardiovascular disease (CVD) is the most common adverse event of maintenance hemodialysis (MHD), in which serum soluble klotho plays a vital role. Tanshinone IIA (tan) has been used to protect the cardiovascular system for hundreds of years. This study was performed to investigate the effects of tan on klotho level and cardiovascular events of MHD patients.
METHODS: Totally 112 patients were enrolled in this study, and their demographic, clinical, and laboratory characteristics were collected at admission. Serum soluble klotho, carotid intima-media thickness (CIMT), and abdominal aorta calcification (AAC) level were measured to determine their relationship. Seventy-one patients were given sodium tan sulfonate injection according to their willingness, while 41 patients were not given any specific treatment. The endpoint events were recorded, including cardiovascular mortality, nonfatal cardiovascular events, and all-cause mortality.
RESULTS: All patients were divided into two groups on whether the level of serum soluble klotho was more than medium or not. CIMT and AAC grade showed significant differences between 2 groups (group of low level of klotho versus group of high level of klotho, CIMT: 1.03±0.22 vs. 0.85±0.20 mm, P<0.001; AAC grade: 5.04±3.93 vs. 1.69±2.30 points, P<0.001). All patients were followed up for at least one year. The results revealed that using tan improved the level of serum soluble klotho (490.23±153.97 pg/mL after using tan versus 444.49±143.32 pg/mL before using tan, P=0.042). Kaplan-Meier curves showed that cardiovascular event-free survival was significantly higher in patients given tan (P=0.040) compared with patients not given tan.
CONCLUSIONS: Tan effectively increases the level of serum soluble klotho and further reduces the incidence of cardiovascular events in MHD patients.


greenmedinfo--2020-09-12--Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model

Tanshinone IIA alleviates the damage of neurocytes by targeting GLUT1 in ischaemia reperfusion model.

Stroke is partial or complete brain dysfunction combined with acute cerebral circulatory disorders , and it affects millions of individuals around the world each year .
A total of 70-80 % of patients experience ischaemic stroke caused by disturbances in cerebral circulation , leading to cerebral ischaemia , neuronal apoptosis , and necrosis .
Tanshinone IIA is a natural compound extracted from Salvia miltiorrhiza and has been proven to assist in recovery from cerebralischaemia reperfusion injury .
GLUT1 is ubiquitously expressed in all types of tissues in the human body and has important physiological functions due to its glucose uptake @ @ @ @ @ @ @ detect the effect of GLUT1 in promoting the therapeutic effect of tanshinone IIA .
Here , we found that tanshinone IIA treatment increased the viability of neurons and promoted the recovery of brain function , and that the concentration of glucose in serum and cultured medium was also increased .
We noticed that these effects might be mediated by an increased glucose uptake ability .
In addition , we further found that the PI3K/mTOR/HER3 signalling pathway played an important role in regulating these effects .
Thus , we thought that overexpression of GLUT1 @ @ @ @ @ @ @ treatment of cerebral ischaemia-reperfusion .

Stroke is partial or complete brain dysfunction combined with acute cerebral circulatory disorders, and it affects millions of individuals around the world each year. A total of 70-80% of patients experience ischaemic stroke caused by disturbances in cerebral circulation, leading to cerebral ischaemia, neuronal apoptosis, and necrosis. Tanshinone IIA is a natural compound extracted from Salvia miltiorrhiza and has been proven to assist in recovery from cerebralischaemia reperfusion injury. GLUT1 is ubiquitously expressed in all types of tissues in the human body and has important physiological functions due to its glucose uptake ability. This experiment was performed to detect the effect of GLUT1 in promoting the therapeutic effect of tanshinone IIA. Here, we found that tanshinone IIA treatment increased the viability of neurons and promoted the recovery of brain function, and that the concentration of glucose in serum and cultured medium was also increased. We noticed that these effects might be mediated by an increased glucose uptake ability. In addition, we further found that the PI3K/mTOR/HER3 signalling pathway played an important role in regulating these effects. Thus, we thought that overexpression of GLUT1 might be an important target in the treatment of cerebral ischaemia-reperfusion.


greenmedinfo--2020-09-12--Tanshinone IIA promotes axonal regeneration in rats with focal cerebral ischemia.

Purpose : The aim of this study was to evaluate the neuroprotective effect of tanshinone IIA ( TSA ) on focal cerebral ischemia in rats and to investigate whether it was associated with Nogo-A/NgR1/RhoA/Rho-associated protein kinase 2 ( ROCKII ) /myosin light chain ( MLC ) signaling .
Methods : In this study , focal cerebral ischemia animal model was used .
Neurological deficit scores and infarction volume were investigated to evaluate the neuroprotection of TSA .
Hematoxylin-eosin staining , Nissl staining , and immunofluorescence staining were conducted to detect ischemic changes in brain tissue and changes in neurofilament protein @ @ @ @ @ @ @ ( GAP-43 ) expression , respectively .
Western blotting and qRT-PCR analyses were used to detect the expression levels of NF200 , GAP-43 and Nogo-A/NgR1/RhoA/ROCKII/MLC pathway-related signaling molecules .
Results : TSA treatment can improve the survival rate of rats , reduce the neurological score and infarct volume , and reduce neuron damage .
In addition , TSA also increased axon length and enhanced expression of NF200 and GAP-43 .
Importantly , TSA significantly attenuated the expression of Nogo-A , NgR1 , RhoA , ROCKII , and p-MLC , and thus inhibiting the @ @ @ @ @ @ @ : TSA promoted axonal regeneration by inhibiting the Nogo-A/NgR1/RhoA/ROCKII/MLC signaling pathway , thereby exerting neuroprotective effects in cerebral ischemia rats , which provided support for the clinical application of TSA in stroke treatment .

Purpose: The aim of this study was to evaluate the neuroprotective effect of tanshinone IIA (TSA) on focal cerebral ischemia in rats and to investigate whether it was associated with Nogo-A/NgR1/RhoA/Rho-associated protein kinase 2 (ROCKII)/myosin light chain (MLC) signaling.
Methods: In this study, focal cerebral ischemia animal model was used. Neurological deficit scores and infarction volume were investigated to evaluate the neuroprotection of TSA. Hematoxylin-eosin staining, Nissl staining, and immunofluorescence staining were conducted to detect ischemic changes in brain tissue and changes in neurofilament protein 200 (NF200) and growth-associated protein-43 (GAP-43) expression, respectively. Western blotting and qRT-PCR analyses were used to detect the expression levels of NF200, GAP-43 and Nogo-A/NgR1/RhoA/ROCKII/MLC pathway-related signaling molecules.
Results: TSA treatment can improve the survival rate of rats, reduce the neurological score and infarct volume, and reduce neuron damage. In addition, TSA also increased axon length and enhanced expression of NF200 and GAP-43. Importantly, TSA significantly attenuated the expression of Nogo-A, NgR1, RhoA, ROCKII, and p-MLC, and thus inhibiting the activation of this signaling pathway.
Conclusion: TSA promoted axonal regeneration by inhibiting the Nogo-A/NgR1/RhoA/ROCKII/MLC signaling pathway, thereby exerting neuroprotective effects in cerebral ischemia rats, which provided support for the clinical application of TSA in stroke treatment.


greenmedinfo--2020-09-12--Tanshinone IIA ameliorates the progression of coronary artery disease.

Background : Coronary artery disease ( CAD ) leads to the highest mortality worldwide , seriously threatening human health .
Tanshinone IIA ( Tan IIA ) , which could be extracted from Danshen , is applied in the treatment of cardiovascular and cerebrovascular diseases .
MicroRNAs ( miRNAs , miRs ) play pivotal roles in cell proliferation and cell apoptosis of the cardiovascular system .
The aim of the present study was to explore the role of Tan IIA in CAD in vitro and the underlying molecular mechanism .
Methods : Real-time polymerase chain reaction ( RT-PCR ) and Western @ @ @ @ @ @ @ miRNA/mRNA and protein , respectively .
Target genes of miR-133a-3p were searched in TargetScan , and the targeting relationship was verified by dual-luciferase reporter assay .
Cell proliferation was determined using a Cell Counting Kit-8 ( CCK-8 ) and EdU labeling .
Cell apoptosis was detected by flow cytometry and TUNEL staining .
Results : In the present study , lower miR-133a-3p level and higher epidermal growth factor receptor ( EGFR ; the target of miR-133a-3p ) level were found in HO-induced H9c2 cells .
In addition , Tan IIA upregulated miR-133a-3p and @ @ @ @ @ @ @ IIA promoted cell proliferation and suppressed apoptosis and enhanced G0/G1 , which was reversed by miR-133a-3p inhibitor , while siRNA-EGFR abolished the effects induced by miR-133a-3p in HO-induced H9c2 cells .
Conclusion : Tan IIA reversed HO-induced cell proliferation reduction , cell apoptosis induction , and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis .
The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD .

Background: Coronary artery disease (CAD) leads to the highest mortality worldwide, seriously threatening human health. Tanshinone IIA (Tan IIA), which could be extracted from Danshen, is applied in the treatment of cardiovascular and cerebrovascular diseases. MicroRNAs (miRNAs, miRs) play pivotal roles in cell proliferation and cell apoptosis of the cardiovascular system. The aim of the present study was to explore the role of Tan IIA in CAD in vitro and the underlying molecular mechanism.
Methods: Real-time polymerase chain reaction (RT-PCR) and Western blot were used for the detection of miRNA/mRNA and protein, respectively. Target genes of miR-133a-3p were searched in TargetScan, and the targeting relationship was verified by dual-luciferase reporter assay. Cell proliferation was determined using a Cell Counting Kit-8 (CCK-8) and EdU labeling. Cell apoptosis was detected by flow cytometry and TUNEL staining.
Results: In the present study, lower miR-133a-3p level and higher epidermal growth factor receptor (EGFR; the target of miR-133a-3p) level were found in HO-induced H9c2 cells. In addition, Tan IIA upregulated miR-133a-3p and downregulated EGFR expression. Moreover, Tan IIA promoted cell proliferation and suppressed apoptosis and enhanced G0/G1, which was reversed by miR-133a-3p inhibitor, while siRNA-EGFR abolished the effects induced by miR-133a-3p in HO-induced H9c2 cells.
Conclusion: Tan IIA reversed HO-induced cell proliferation reduction, cell apoptosis induction, and G0/G1 arrest reduction in H9c2 cells by miR-133a-3p/EGFR axis. The findings suggested a potential molecular basis of Tan IIA in treating patients with CAD.


greenmedinfo--2020-09-12--Tanshinone IIA induces ferroptosis in gastric cancer cells.

Gastric cancer represents a malignant type of cancer worldwide .
Tanshinone IIA ( Tan IIA ) , a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge ( Danshen ) , has been reported to possess an anti-cancer effect in gastric cancer .
However , its mechanisms are still not fully understood .
In the present study , we found that Tan IIA induced ferroptosis in BGC-823 and NCI-H87 gastric cancer cells .
Tan IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression , two markers of ferroptosis .
Ferrostatin-1 ( Fer-1 ) , @ @ @ @ @ @ @ Tan IIA caused-lipid peroxidation and Ptgs2 and Chac1 expression .
In addition , Tan IIA also up-regulated p53 expression and down-regulated xCT expression .
Tan IIA caused decreased intracellular glutathione ( GSH ) level and cysteine level and increased intracellular reactive oxygen species ( ROS ) level .
p53 knockdown attenuated Tan IIA-induced lipid peroxidation and ferroptosis .
Tan IIA also induced lipid peroxidation and ferroptosis in BGC-823 xenograft model , and the anti-cancer effect of Tan IIA was attenuated by Fer-1 in vivo .
Therefore , Tan IIA could suppress the proliferation @ @ @ @ @ @ @ ferroptosis .
Our study have identified a novel mechanism of Tan IIA against gastric cancer , and might provide a critical insight into the application of Tan IIA in gastric cancer intervention .

Gastric cancer represents a malignant type of cancer worldwide. Tanshinone IIA (Tan IIA), a pharmacologically active component isolated from the rhizome of the Chinese herb Salvia miltiorrhiza Bunge (Danshen), has been reported to possess an anti-cancer effect in gastric cancer. However, its mechanisms are still not fully understood. In the present study, we found that Tan IIA induced ferroptosis in BGC-823 and NCI-H87 gastric cancer cells. Tan IIA increased lipid peroxidation and up-regulated Ptgs2 and Chac1 expression, two markers of ferroptosis. Ferrostatin-1 (Fer-1), an inhibitor of lipid peroxidation, inhibited Tan IIA caused-lipid peroxidation and Ptgs2 and Chac1 expression. In addition, Tan IIA also up-regulated p53 expression and down-regulated xCT expression. Tan IIA caused decreased intracellular glutathione (GSH) level and cysteine level and increased intracellular reactive oxygen species (ROS) level. p53 knockdown attenuated Tan IIA-induced lipid peroxidation and ferroptosis. Tan IIA also induced lipid peroxidation and ferroptosis in BGC-823 xenograft model, and the anti-cancer effect of Tan IIA was attenuated by Fer-1 in vivo. Therefore, Tan IIA could suppress the proliferation of gastric cancer via inducing p53 upregulation-mediated ferroptosis. Our study have identified a novel mechanism of Tan IIA against gastric cancer, and might provide a critical insight into the application of Tan IIA in gastric cancer intervention.


greenmedinfo--2020-09-12--Why You Should Eat Two Apples a Day

Why You Should Eat Two Apples a Day

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greenmedinfo--2020-09-12--Tanshinone IIA attenuates acetaminophen-induced hepatotoxicity.

Tanshinone IIA ( Tan IIA ) , an active component in S. miltiorrhiza , has been reported to have excellent antioxidant and detoxifying activity .
Here , we prove that Tan IIA attenuates acetaminophen-induced hepatotoxicity from a pharmacokinetic perspective .
Compared with acetaminophen ( APAP , 200 mg/kg ) treated mice , Tan IIA pretreatment ( 30 mg/kg/d ) not only reduced the plasma level of the toxic metabolite N-acetyl-p-benzoquinone imine ( NAPQI ) but also increased its bile level .
After Tan IIA pretreatment , significant induction of nuclear factor E2-related factor 2 ( Nrf2 ) , multidrug resistance-associated @ @ @ @ @ @ @ multidrug resistance-associated protein 4 ( Mrp4 ) mRNA and protein expression was detected in Nrf2mouse liver , however , much lower increase of Mrp2 and Mrp4 mRNA and protein expression was observed in Nrf2mouse liver .
Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Nrf2 bounds to antioxidant responsive elements ( AREs ) of the MRP2 and MRP4 promoter , thus regulating the expression of MRP2 and MRP4 .
in vitro experiments revealed that Tan IIA increase Nrf2 , MRP2 , and MRP4 expression through a mechanism of inhibiting the expression of HOX @ @ @ @ @ @ @ belongs to long non-coding RNAs .
Collectively , the present results demonstrated that Tan IIA could protect against APAP-induced hepatotoxicity by altering the pharmacokinetic characteristics of APAP and its metabolites via HOTAIR-Nrf2-MRP2/4 signaling pathway , and HOTAIR plays a pivotal role in the MRP2 and MRP4 expression regulated by Nrf2 .

Tanshinone IIA (Tan IIA), an active component in S. miltiorrhiza, has been reported to have excellent antioxidant and detoxifying activity. Here, we prove that Tan IIA attenuates acetaminophen-induced hepatotoxicity from a pharmacokinetic perspective. Compared with acetaminophen (APAP, 200 mg/kg) treated mice, Tan IIA pretreatment (30 mg/kg/d) not only reduced the plasma level of the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI) but also increased its bile level. After Tan IIA pretreatment, significant induction of nuclear factor E2-related factor 2 (Nrf2), multidrug resistance-associated protein 2 (Mrp2), and multidrug resistance-associated protein 4 (Mrp4) mRNA and protein expression was detected in Nrf2mouse liver, however, much lower increase of Mrp2 and Mrp4 mRNA and protein expression was observed in Nrf2mouse liver. Luciferase reporter and chromatin immunoprecipitation assays demonstrated that Nrf2 bounds to antioxidant responsive elements (AREs) of the MRP2 and MRP4 promoter, thus regulating the expression of MRP2 and MRP4. in vitro experiments revealed that Tan IIA increase Nrf2, MRP2, and MRP4 expression through a mechanism of inhibiting the expression of HOX transcript antisense RNA (HOTAIR) which belongs to long non-coding RNAs. Collectively, the present results demonstrated that Tan IIA could protect against APAP-induced hepatotoxicity by altering the pharmacokinetic characteristics of APAP and its metabolites via HOTAIR-Nrf2-MRP2/4 signaling pathway, and HOTAIR plays a pivotal role in the MRP2 and MRP4 expression regulated by Nrf2.


greenmedinfo--2020-09-12--Tanshinone IIA regulates human AML cell proliferation, cell cycle, and apoptosis.

Background : The roots ofare used in traditional Chinese medicine ( TCM ) and have high medicinal value .
Tanshinone IIA ( Tan IIA ) is the active ingredient ofwhich can inhibit the growth of acute leukemia cell lines in vitro , although the mechanism remains unclear .
Methods : CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability .
Western blot analysis was used to detect protein expression .
miR-497-5p expression level was detected by using qRT-PCR , and Annexin V-FITC/propidium iodide ( PI ) was used to detect cell apoptosis .
Results : Here we @ @ @ @ @ @ @ proliferation , induce cell cycle arrest , and promote cell apoptosis in acute myeloid leukemia ( AML ) cells .
Thus , Tan IIA had the anti-cancer activity in AML cell lines , which was likely mediated by up-regulation of miR-497-5p expression .
Our data further showed that in AML cells , the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic .
We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p .
We subsequently identified that AKT3 was the direct target @ @ @ @ @ @ @ Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions .
In turn , PCNA expression was increased and cleaved Caspase-3 was suppressed , which contributed to the growth of AML cells .
Conclusions : Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway .

Background: The roots ofare used in traditional Chinese medicine (TCM) and have high medicinal value. Tanshinone IIA (Tan IIA) is the active ingredient ofwhich can inhibit the growth of acute leukemia cell lines in vitro, although the mechanism remains unclear.
Methods: CCK-8 assays and BrdU stain were used to evaluate cell proliferation ability. Western blot analysis was used to detect protein expression. miR-497-5p expression level was detected by using qRT-PCR, and Annexin V-FITC/propidium iodide (PI) was used to detect cell apoptosis.
Results: Here we reported that Tan IIA could inhibit cell proliferation, induce cell cycle arrest, and promote cell apoptosis in acute myeloid leukemia (AML) cells. Thus, Tan IIA had the anti-cancer activity in AML cell lines, which was likely mediated by up-regulation of miR-497-5p expression. Our data further showed that in AML cells, the same effects were observed with overexpression of miR-497-5p by a miR-497-5p mimic. We demonstrated that Tan IIA could inhibit the expression of AKT3 by up-regulating the expression of miR-497-5p. We subsequently identified that AKT3 was the direct target of miR-497-5p, and that treatment with Tan IIA obviously reversed the effect of treatment with an miR-497-5p inhibitor under harsh conditions. In turn, PCNA expression was increased and cleaved Caspase-3 was suppressed, which contributed to the growth of AML cells.
Conclusions: Our results showed that Tan IIA could inhibit cell proliferation in AML cells through miR-497-5p-mediated AKT3 downregulation pathway.


greenmedinfo--2020-09-12--Tanshinone Inhibits NSCLC by Downregulating AURKA Through Let-7a-5p.

Lung cancer is the most deadly malignancy in the last decade , accounting for about 1.6 million deaths every year globally .
Tanshinone is the constituent of ; it has been found that they influence tumorigenesis .
However , the role of tanshinones on lung cancer is still not clear .
Let-7a-5p , a short non-coding RNA , is regarded as a suppressor gene in tumorigenesis .
Herein , we verified that let-7a-5p is significantly downregulated in non-small-cell lung cancer ( NSCLC ) tissues and cell lines .
Tanshinone suppressed the expression of aurora kinase A ( AURKA ) , @ @ @ @ @ @ @ cycle progression .
Our results showed that tanshinones suppressed NSCLC by upregulating the expressions of let-7a-5p via directly targeting AURKA .
Besides , the data reveal that the knockdown of AURKA can also inhibit cell proliferation , arrest cell cycle , and promote cell apoptosis .
Furthermore , this study demonstrates that AURKA was negatively correlated with let-7a-5p in NSCLC patient tissues .
Taken together , our findings suggest that tanshinone inhibits NSCLC by downregulating AURKA through let-7a-5p .
Tanshinones and let-7a-5p have the potential to be candidates for drug development of NSCLC @ @ @ @ @ @ @ that tanshinones with miRNA linking lead to partial mechanism in NSCLC .

Lung cancer is the most deadly malignancy in the last decade, accounting for about 1.6 million deaths every year globally. Tanshinone is the constituent of; it has been found that they influence tumorigenesis. However, the role of tanshinones on lung cancer is still not clear. Let-7a-5p, a short non-coding RNA, is regarded as a suppressor gene in tumorigenesis. Herein, we verified that let-7a-5p is significantly downregulated in non-small-cell lung cancer (NSCLC) tissues and cell lines. Tanshinone suppressed the expression of aurora kinase A (AURKA), inhibited cell proliferation, and arrested cell cycle progression. Our results showed that tanshinones suppressed NSCLC by upregulating the expressions of let-7a-5p via directly targeting AURKA. Besides, the data reveal that the knockdown of AURKA can also inhibit cell proliferation, arrest cell cycle, and promote cell apoptosis. Furthermore, this study demonstrates that AURKA was negatively correlated with let-7a-5p in NSCLC patient tissues. Taken together, our findings suggest that tanshinone inhibits NSCLC by downregulating AURKA through let-7a-5p. Tanshinones and let-7a-5p have the potential to be candidates for drug development of NSCLC. In conclusion, this study revealed that tanshinones with miRNA linking lead to partial mechanism in NSCLC.


greenmedinfo--2020-09-12--Tanshinone IIA suppresses lipopolysaccharide-induced neuroinflammatory responses.

Tanshinone IIA ( tan IIA ) , a key component of Salvia miltiorrhiza Bunge ( Danshen ) , has been proven to play a significant role in suppressing inflammation .
However , the molecular mechanisms underlying the anti-inflammatory properties of tan IIA against lipopolysaccharide ( LPS ) -induced neuroinflammation and neurotoxicity in human U87 astrocytoma cells have not been well justified .
Therefore , in this study , U87 cells were pretreated with tan IIA ( 1 , 5 and 10μM ) for 30 min , followed by stimulation with LPS for 24 h. Immunofluorescence , reverse transcription-polymerase chain reaction @ @ @ @ @ @ @ ( ELISA ) , and western blotting were performed to investigate the effects of tan IIA on neuroinflammatory responses .
The findingsdemonstrated that tan IIA prevented LPS-induced cell viability decrease , inhibited U87 cells activation , and suppressed the expression of glial fibrillary acidic protein ( GFAP ) .
Furthermore , tan IIA significantly reduced the mRNA expression of interleukin-1β ( IL-1β ) , tumor necrosis factor-α ( TNF-α ) , and interleukin-6 ( IL-6 ) in LPS-stimulated U87 cells .
Meanwhile , the increased protein levels of IL-1β , TNF-α , and @ @ @ @ @ @ @ markedly inhibited by tan IIA .
Moreover , tan IIA significantly alleviated the phosphorylation of IκBα , nuclear factor-kappa B ( NF-κB ) , p38 , and JNK induced by LPS .
Additionally , tan IIA suppressed the upstream signaling adaptor molecules toll-like receptor 4 ( TLR4 ) , myeloid differentiation primary response protein 88 ( MyD88 ) , and tumor necrosis factor receptor-associated factor 6 ( TRAF6 ) .
Blockade of NF-κB , p38 , and JNK obviously attenuated IL-1β , TNF-α , and IL-6 in U87 cells .
In conclusion , @ @ @ @ @ @ @ can attenuate LPS-induced neurotoxicity and neuroinflammation partly by inhibiting TLR4/NF-κB/MAPKs signaling pathways in U87 cells .

Tanshinone IIA (tan IIA), a key component of Salvia miltiorrhiza Bunge (Danshen), has been proven to play a significant role in suppressing inflammation. However, the molecular mechanisms underlying the anti-inflammatory properties of tan IIA against lipopolysaccharide (LPS)-induced neuroinflammation and neurotoxicity in human U87 astrocytoma cells have not been well justified. Therefore, in this study, U87 cells were pretreated with tan IIA (1, 5 and 10μM) for 30 min, followed by stimulation with LPS for 24 h. Immunofluorescence, reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blotting were performed to investigate the effects of tan IIA on neuroinflammatory responses. The findingsdemonstrated that tan IIA prevented LPS-induced cell viability decrease, inhibited U87 cells activation, and suppressed the expression of glial fibrillary acidic protein (GFAP). Furthermore, tan IIA significantly reduced the mRNA expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) in LPS-stimulated U87 cells. Meanwhile, the increased protein levels of IL-1β, TNF-α, and IL-6 in cell culture supernatants were also markedly inhibited by tan IIA. Moreover, tan IIA significantly alleviated the phosphorylation of IκBα, nuclear factor-kappa B (NF-κB), p38, and JNK induced by LPS. Additionally, tan IIA suppressed the upstream signaling adaptor molecules toll-like receptor 4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and tumor necrosis factor receptor-associated factor 6 (TRAF6). Blockade of NF-κB, p38, and JNK obviously attenuated IL-1β, TNF-α, and IL-6 in U87 cells. In conclusion, the present results suggested that tan IIA can attenuate LPS-induced neurotoxicity and neuroinflammation partly by inhibiting TLR4/NF-κB/MAPKs signaling pathways in U87 cells.


greenmedinfo--2020-09-12--Tanshinone II A improves the chemosensitivity of breast cancer cells to doxorubicin.

Numerous evidence link aberrant nuclear β-catenin accumulation to the development of breast cancer resistance , therefore , targeted inhibition of β-catenin nuclear translocation may effectively improve the chemosensitivity of breast cancer .
Doxorubicin ( Dox ) is the most commonly used chemotherapeutic drug for breast cancer .
Here , we determined that tanshinone II A ( Tan II A ) could improve the sensitivity of Dox-resistant breast cancer MCF-7/dox cells to Dox , and evaluated whether the sensitization effect of Tan II A on Dox was targeted to inhibit β-catenin nuclear translocation .
The results showed that Tan II Anot @ @ @ @ @ @ @ β-catenin in MCF-7/dox cells treated by Dox but also inhibited the nuclear translocation of β-catenin in MCF-7 cells treated by Dox to a certain degree .
Furthermore , when the above two cells treated by Dox combined with Tan II A were intervened with β-catenin agonist WAY-262611 , with the re-nuclear translocation of β-catenin in the cells , the sensitization effect of Tan II A on Dox was greatly reduced .
These results indicated that Tan II A could improve the chemosensitivity of breast cancer cells to Dox by inhibiting β-cateninnuclear translocation .
@ @ @ @ @ @ @ used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy .

Numerous evidence link aberrant nuclear β-catenin accumulation to the development of breast cancer resistance, therefore, targeted inhibition of β-catenin nuclear translocation may effectively improve the chemosensitivity of breast cancer. Doxorubicin (Dox) is the most commonly used chemotherapeutic drug for breast cancer. Here, we determined that tanshinone II A (Tan II A) could improve the sensitivity of Dox-resistant breast cancer MCF-7/dox cells to Dox, and evaluated whether the sensitization effect of Tan II A on Dox was targeted to inhibit β-catenin nuclear translocation. The results showed that Tan II Anot only significantly inhibited the nuclear translocation of β-catenin in MCF-7/dox cells treated by Dox but also inhibited the nuclear translocation of β-catenin in MCF-7 cells treated by Dox to a certain degree. Furthermore, when the above two cells treated by Dox combined with Tan II A were intervened with β-catenin agonist WAY-262611, with the re-nuclear translocation of β-catenin in the cells, the sensitization effect of Tan II A on Dox was greatly reduced. These results indicated that Tan II A could improve the chemosensitivity of breast cancer cells to Dox by inhibiting β-cateninnuclear translocation. Therefore, Tan II A could be used as a potential chemosensitizer in combination with Dox for breast cancer chemotherapy.


greenmedinfo--2020-09-12--Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505

Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells.

Anaplastic thyroid cancer ( ATC ) is the most aggressive thyroid cancer .
Current approaches including surgery , chemotherapy and therapeutic drugs provide limited benefits for ATC patients .
Diallyl trisulfide ( DATS ) has been documented as a promising anti-cancer agent for various carcinomas .
However , its role in ATC tumorigenesis remained unclear .
Our results showed that DATS treatment at 12.5 , 25 and 50μM decreased the viability of 8505C cells both in a time- and dose-dependent manner .
The phosphorylation of H2A.X , which is a DNA damage marker , was induced by DATS both in @ @ @ @ @ @ @ , DATS mediated the DNA damage through the phosphorylation of ATM but not ATR .
DATSalso induced G2/M cell-cycle arrest followed by the translocation of Cdc25C from the nucleus to the cytoplasm .
Further results showed that DATS induced mitochondrial apoptosis in 8505C cells , evidenced by Hoechst/PI double staining , PI-Annexin V assay and western blot .
Taken altogether , our findings demonstrated that DATS induced G2/M cell-cycle arrest and mitochondrial apoptosis by triggering DNA damage in ATC 8505C cells , which shed light on a novel therapeutic approach for ATC treatment @

Anaplastic thyroid cancer (ATC) is the most aggressive thyroid cancer. Current approaches including surgery, chemotherapy and therapeutic drugs provide limited benefits for ATC patients. Diallyl trisulfide (DATS) has been documented as a promising anti-cancer agent for various carcinomas. However, its role in ATC tumorigenesis remained unclear. Our results showed that DATS treatment at 12.5, 25 and 50μM decreased the viability of 8505C cells both in a time- and dose-dependent manner. The phosphorylation of H2A.X, which is a DNA damage marker, was induced by DATS both in a dose- and time-dependent manner. Moreover, DATS mediated the DNA damage through the phosphorylation of ATM but not ATR. DATSalso induced G2/M cell-cycle arrest followed by the translocation of Cdc25C from the nucleus to the cytoplasm. Further results showed that DATS induced mitochondrial apoptosis in 8505C cells, evidenced by Hoechst/PI double staining, PI-Annexin V assay and western blot. Taken altogether, our findings demonstrated that DATS induced G2/M cell-cycle arrest and mitochondrial apoptosis by triggering DNA damage in ATC 8505C cells, which shed light on a novel therapeutic approach for ATC treatment.


greenmedinfo--2020-09-12--Diallyl trisulfide inhibits cell growth of human papillary thyroid carcinoma KTC-1 cells.

Diallyl trisulfide ( DATS ) , derived from garlic , is a well-known hydrogen sulfide ( HS ) donor .
HS has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression .
The present study demonstrated that DATS along with other two HS donors , NaHS and GYY4137 , significantly inhibited papillary thyroid carcinoma KTC-1 cells growth .
DATS treatment triggered a rapid HS generation within 5 min in KTC-1 cells .
Iodoacetamide , a potent thiol blocker reagent , partially rescued the cell membrane damage and ultimate cell death induced by DATS , indicating HS @ @ @ @ @ @ @ on thyroid cancer cells .
Specifically , DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma-lyase ( CTH ) , one of HS-producing enzymes , which was responsible for endogenous HS generation .
After DATS treatment , HS quickly permeated cell membranes and activated NF-κΒ/p65 signaling pathway in KTC-1 cells .
Nuclear translocated NF-κB bound to the promoter of CTH to enhance its transcription .
These evidences proved that exogenous HS elevated CTH expression .
CTH , in turn , catalytically generated a much higher level of endogenous HS .
@ @ @ @ @ @ @ , which resulted in PTC cells growth inhibition .
These findings may shed light on the development of novel HS-based antitumor agents .

Diallyl trisulfide (DATS), derived from garlic, is a well-known hydrogen sulfide (HS) donor. HS has recently emerged as a novel gasotransmitter involved in the regulation of cancer progression. The present study demonstrated that DATS along with other two HS donors, NaHS and GYY4137, significantly inhibited papillary thyroid carcinoma KTC-1 cells growth. DATS treatment triggered a rapid HS generation within 5 min in KTC-1 cells. Iodoacetamide, a potent thiol blocker reagent, partially rescued the cell membrane damage and ultimate cell death induced by DATS, indicating HS contributed to the apoptosis-inducing efficacy of DATS on thyroid cancer cells. Specifically, DATS treatment significantly upregulated the expression and enzymatic activity of cystathionine gamma-lyase (CTH), one of HS-producing enzymes, which was responsible for endogenous HS generation. After DATS treatment, HS quickly permeated cell membranes and activated NF-κΒ/p65 signaling pathway in KTC-1 cells. Nuclear translocated NF-κB bound to the promoter of CTH to enhance its transcription. These evidences proved that exogenous HS elevated CTH expression. CTH, in turn, catalytically generated a much higher level of endogenous HS. This positive feedback sustained excess HS production, which resulted in PTC cells growth inhibition. These findings may shed light on the development of novel HS-based antitumor agents.


greenmedinfo--2020-09-12--Diallyl trisulfide inhibits leptin-induced oncogenic signalling in human breast cancer cells.

Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide ( DATS ) on growth of breast cancer cells in vitro and in vivo .
This study investigated the effect of DATS on oncogenic signaling regulated by leptin , which plays an important role in breast carcinogenesis .
Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in the presence of DATS in MCF-7 ( a luminal-type human breast cancer cell line ) and MDA-MB-231 ( a basal-like human breast cancer cell line ) .
Leptin-stimulated cell proliferation , clonogenic cell survival , and migration and/or invasion ability @ @ @ @ @ @ @ suppressed by DATS treatment .
DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2 , Bcl-xL , Cyclin D1 , vascular endothelial growth factor , and matrix metalloproteinase-2 .
Western blotting revealed a decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when compared to controls in vivo .
However , the incidence of-methyl -- nitrosourea-induced luminal-type breast cancer development in rats was not affected by oral administration of 5 mg/kg or 25 mg/kg DATS .
The present study reveals that oncogenic @ @ @ @ @ @ @ the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity .

Previous studies have demonstrated inhibitory effect of garlic component diallyl trisulfide (DATS) on growth of breast cancer cells in vitro and in vivo. This study investigated the effect of DATS on oncogenic signaling regulated by leptin, which plays an important role in breast carcinogenesis. Leptin-induced phosphorylation and nuclear translocation of STAT3 was inhibited significantly in the presence of DATS in MCF-7 (a luminal-type human breast cancer cell line) and MDA-MB-231 (a basal-like human breast cancer cell line). Leptin-stimulated cell proliferation, clonogenic cell survival, and migration and/or invasion ability in MCF-7 and/or MDA-MB-231 cells were also suppressed by DATS treatment. DATS exposure resulted in inhibition of leptin-stimulated expression of protein and/or mRNA levels of Bcl-2, Bcl-xL, Cyclin D1, vascular endothelial growth factor, and matrix metalloproteinase-2. Western blotting revealed a decrease in protein levels of phosphorylated STAT3 in breast cancer xenografts from DATS-treated mice when compared to controls in vivo. However, the incidence of-methyl--nitrosourea-induced luminal-type breast cancer development in rats was not affected by oral administration of 5 mg/kg or 25 mg/kg DATS. The present study reveals that oncogenic signaling induced by leptin is inhibited in the presence of DATS but higher doses of this phytochemical may be required to achieve chemopreventive activity.


greenmedinfo--2020-09-12--Diallyl trisulfide suppresses AGE-induced cardiomyocyte apoptosis.

Chronic high-glucose exposure results in the production of advanced glycation end-products ( AGEs ) leading to reactive oxygen species ( ROS ) generation , which contributes to the development of diabetic cardiomyopathy .
PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study .
Diallyl trisulfide ( DATS ) is a natural cytoprotective compound under various stress conditions .
In this study , the cardioprotective effect of DATSagainst rat streptozotocin ( STZ ) -induced diabetic mellitus ( DM ) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte ( NRVM ) @ @ @ @ @ @ @ DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS , inhibition of PKCδ activation , and recuded apoptosis-related proteins .
Most importantly , DATS reduced PKCδ mitochondrial translocation induced by AGE .
However , apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type ( WT ) .
Inhibition of PKCδ by PKCδ-kinase-deficient ( KD ) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis .
Interestingly , overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ @ @ @ @ @ @ @ to AGE , indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation .
Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration .
Taken together , our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling , suggesting that DATShas potential in diabetic cardiomyopathy ( DCM ) treatment .

Chronic high-glucose exposure results in the production of advanced glycation end-products (AGEs) leading to reactive oxygen species (ROS) generation, which contributes to the development of diabetic cardiomyopathy. PKCδ activation leading to ROS production and mitochondrial dysfunction involved in AGE-induced cardiomyocyte apoptosis was reported in our previous study. Diallyl trisulfide (DATS) is a natural cytoprotective compound under various stress conditions. In this study, the cardioprotective effect of DATSagainst rat streptozotocin (STZ)-induced diabetic mellitus (DM) and AGE-induced H9c2 cardiomyoblast cell/neonatal rat ventricular myocyte (NRVM) damage was assessed. We observed that DATS treatment led to a dose-dependent increase in cell viability and decreased levels of ROS, inhibition of PKCδ activation, and recuded apoptosis-related proteins. Most importantly, DATS reduced PKCδ mitochondrial translocation induced by AGE. However, apoptosis was not inhibited by DATS in cells transfected with PKCδ-wild type (WT). Inhibition of PKCδ by PKCδ-kinase-deficient (KD) or rottlerin not only inhibited cardiac PKCδ activation but also attenuated cardiac cell apoptosis. Interestingly, overexpression of PKCδ-WT plasmids reversed the inhibitory effects of DATS on PKCδ activation and apoptosis in cardiac cells exposed to AGE, indicating that DATS may inhibit AGE-induced apoptosis by downregulating PKCδ activation. Similar results were observed in AGE-induced NRVM cells and STZ-treated DM rats following DATS administration. Taken together, our results suggested that DATS reduced AGE-induced cardiomyocyte apoptosis by eliminating ROS and downstream PKCδ signaling, suggesting that DATShas potential in diabetic cardiomyopathy (DCM) treatment.


greenmedinfo--2020-09-12--This study indicated that Allium sativum powder ameliorated MSG-induced neurotoxicity.

This study evaluated the neuroprotective potential ofagainst monosodium glutamate ( MSG ) -induced neurotoxicity with respect to its impact on short-term memory in rats .
Forty male Wistar albino rats were assigned into four groups .
The control group received distilled water .
The second group was administeredpowder ( 200 mg/kg of body weight ) orally for 7 successive days , then was left without treatment until the 30th day .
The third group was injected intraperitoneally with MSG ( 4 g/kg of body weight ) for 7 successive days , then left without treatment until the 30th day .
@ @ @ @ @ @ @ in the same manner as the third group and was treated withpowder in the same manner as the second group , simultaneously .
Phytochemical analysis ofpowder identified the presence of diallyl disulphide , carvone , diallyl trisulfide , and allyl tetrasulfide .
MSG-induced excitotoxicity and cognitive deficit were represented by decreased distance moved and taking a long time to start moving from the center in the open field , as well as lack of curiosity in investigating the novel object and novel arm .
Moreover , MSG altered hippocampus structure and increased MDA @ @ @ @ @ @ @ acidic protein ( GFAP ) , calretinin , and caspase-3 , whereas it decreased superoxide dismutase ( SOD ) activity and protein expression of Ki-67 in brain tissue .
However , powder prevented MSG-induced neurotoxicity and improved short-term memory through enhancing antioxidant activity and reducing lipid peroxidation .
In addition , it decreased protein expression of GFAP , calretinin , and caspase-3 and increased protein expression of Ki-67 in brain tissues and retained brain tissue architecture .
This study indicated thatpowder ameliorated MSG-induced neurotoxicity through preventing oxidative stress-induced gliosis and apoptosis of brain @ @ @ @

This study evaluated the neuroprotective potential ofagainst monosodium glutamate (MSG)-induced neurotoxicity with respect to its impact on short-term memory in rats. Forty male Wistar albino rats were assigned into four groups. The control group received distilled water. The second group was administeredpowder (200 mg/kg of body weight) orally for 7 successive days, then was left without treatment until the 30th day. The third group was injected intraperitoneally with MSG (4 g/kg of body weight) for 7 successive days, then left without treatment until the 30th day. The fourth group was injected with MSG in the same manner as the third group and was treated withpowder in the same manner as the second group, simultaneously. Phytochemical analysis ofpowder identified the presence of diallyl disulphide, carvone, diallyl trisulfide, and allyl tetrasulfide. MSG-induced excitotoxicity and cognitive deficit were represented by decreased distance moved and taking a long time to start moving from the center in the open field, as well as lack of curiosity in investigating the novel object and novel arm. Moreover, MSG altered hippocampus structure and increased MDA concentration and protein expression of glial fibrillary acidic protein (GFAP), calretinin, and caspase-3, whereas it decreased superoxide dismutase (SOD) activity and protein expression of Ki-67 in brain tissue. However,powder prevented MSG-induced neurotoxicity and improved short-term memory through enhancing antioxidant activity and reducing lipid peroxidation. In addition, it decreased protein expression of GFAP, calretinin, and caspase-3 and increased protein expression of Ki-67 in brain tissues and retained brain tissue architecture. This study indicated thatpowder ameliorated MSG-induced neurotoxicity through preventing oxidative stress-induced gliosis and apoptosis of brain tissue in rats.


greenmedinfo--2020-09-12--Diallyl trisulfide suppresses angiotensin II-induced vascular remodelling Via inhibition of mitochon

Diallyl trisulfide suppresses angiotensin II-induced vascular remodelling Via inhibition of mitochondrial fission.

OBJECTIVE : We have shown previously that diallyl trisulfide ( DATS ) ameliorates mitochondrial fission and oxidative stress in a hyperglycemia-induced endothelial apoptosis and diabetic mouse model .
The aim of this study was to investigate whether DATS mitigates Ang II-induced vascular smooth muscle cell ( VSMC ) phenotypic switching and vascular remodeling , and if so , to determine the underlying molecular events .
METHODS : Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 2-week Ang II infusion using a subcutaneous osmotic pump .
Animals were intraperitoneally injected with DATS or vehicle .
Physiological @ @ @ @ @ @ @ markers were assessed .
For in vitro studies , VSMCs were pretreated with or without DATS for 1 h , then were stimulated with Ang II , and mitochondrial morphology and phenotypic switching of VSMCs were also measured .
RESULTS : In primary mouse VSMCs , we found that Drp1-dependent mitochondrial fission regulated mitochondrial reactive oxygen species ( mtROS ) generation , which eventually promoted Ang II-induced VSMC proliferation , migration , and phenotypic switching .
Moreover , Ang II was found to up-regulate the Rho-associated coiled coil-containing protein kinase 1 ( ROCK1 @ @ @ @ @ @ @ VSMC phenotypic switching by phosphorylating Drp1 .
However , the biological effect of Ang II was abrogated by DATS .
Consistent with the effects in VSMCs , we found that DATS markedly alleviated mitochondrial fission , VSMC differentiation , and vessel wall thickening in an animal model of Ang II-induced vascular remodeling , which was regulated by the ROCK1/Drp1 signal .
CONCLUSIONS : Our findings showed that DATS mitigated Ang II-induced vascular remodeling by suppressing Drp1-mediated mitochondrial fission in an ROCK1-dependent manner .

OBJECTIVE: We have shown previously that diallyl trisulfide (DATS) ameliorates mitochondrial fission and oxidative stress in a hyperglycemia-induced endothelial apoptosis and diabetic mouse model. The aim of this study was to investigate whether DATS mitigates Ang II-induced vascular smooth muscle cell (VSMC) phenotypic switching and vascular remodeling, and if so, to determine the underlying molecular events.
METHODS: Male C57BL/6 mice were used to establish a vascular remodeling model by continuous 2-week Ang II infusion using a subcutaneous osmotic pump. Animals were intraperitoneally injected with DATS or vehicle. Physiological parameters, vascular morphology, and molecular markers were assessed. For in vitro studies, VSMCs were pretreated with or without DATS for 1 h, then were stimulated with Ang II, and mitochondrial morphology and phenotypic switching of VSMCs were also measured.
RESULTS: In primary mouse VSMCs, we found that Drp1-dependent mitochondrial fission regulated mitochondrial reactive oxygen species (mtROS) generation, which eventually promoted Ang II-induced VSMC proliferation, migration, and phenotypic switching. Moreover, Ang II was found to up-regulate the Rho-associated coiled coil-containing protein kinase 1 (ROCK1), which regulated mitochondrial fission and VSMC phenotypic switching by phosphorylating Drp1. However, the biological effect of Ang II was abrogated by DATS. Consistent with the effects in VSMCs, we found that DATS markedly alleviated mitochondrial fission, VSMC differentiation, and vessel wall thickening in an animal model of Ang II-induced vascular remodeling, which was regulated by the ROCK1/Drp1 signal.
CONCLUSIONS: Our findings showed that DATS mitigated Ang II-induced vascular remodeling by suppressing Drp1-mediated mitochondrial fission in an ROCK1-dependent manner.


greenmedinfo--2020-09-12--Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain.

Background : Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide .
There have been studies showing the neuroprotective actions of these organosulfur compounds .
However , the potential of these organosulfur compounds in neuropathic pain has not been explored .
The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury ( CCI ) -induced neuropathic pain in rats .
The study also explored their pain-attenuating mechanisms through modulation of HS , brain-derived neurotrophin factor ( BDNF ) and nuclear factor erythroid 2-related @ @ @ @ @ @ @ : The rats were subjected to CCI injury by ligating the sciatic nerve in four places .
The development of neuropathic pain was measured by assessing mechanical hyperalgesia ( Randall-Selittotest ) , mechanical allodynia ( Von Frey test ) , and cold allodynia ( acetone drop test ) on 14th day after surgery .
Results : Administration of diallyl disulfide ( 25 and 50 mg/kg ) and diallyl trisulfide ( 20 and 40 mg/kg ) for 14 days led to a significant reduction in pain in CCI-subjected rats .
Moreover , treatment with @ @ @ @ @ @ @ of HS , BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia .
Coadministration of ANA-12 ( BDNF blocker ) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide , without modulating HS levels .
Conclusions : Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of HS-BDNF-Nrf2 signaling pathway .

Background: Garlic oil is a rich source of organosulfur compounds including diallyl disulfide and diallyl trisulfide. There have been studies showing the neuroprotective actions of these organosulfur compounds. However, the potential of these organosulfur compounds in neuropathic pain has not been explored. The present study was aimed at investigating the pain attenuating potential of diallyl disulfide and diallyl trisulfide in chronic constriction injury (CCI)-induced neuropathic pain in rats. The study also explored their pain-attenuating mechanisms through modulation of HS, brain-derived neurotrophin factor (BDNF) and nuclear factor erythroid 2-related factor 2 (Nrf2).
Methods: The rats were subjected to CCI injury by ligating the sciatic nerve in four places. The development of neuropathic pain was measured by assessing mechanical hyperalgesia (Randall-Selittotest), mechanical allodynia (Von Frey test), and cold allodynia (acetone drop test) on 14th day after surgery.
Results: Administration of diallyl disulfide (25 and 50 mg/kg) and diallyl trisulfide (20 and 40 mg/kg) for 14 days led to a significant reduction in pain in CCI-subjected rats. Moreover, treatment with these organosulfur compounds led to the restoration of HS, BDNF and Nrf2 levels in the sciatic nerve and dorsal root ganglia. Coadministration of ANA-12 (BDNF blocker) abolished pain attenuating actions as well as BDNF and the Nrf2 restorative actions of diallyl disulfide and diallyl trisulfide, without modulating HS levels.
Conclusions: Diallyl disulfide and diallyl trisulfide have the potential to attenuate neuropathic pain in CCI-subjected rats possibly through activation of HS-BDNF-Nrf2 signaling pathway.


greenmedinfo--2020-09-12--Diallyl trisulfide potentiates chemotherapeutic efficacy of doxorubicin in experimentally induced ma

Diallyl trisulfide potentiates chemotherapeutic efficacy of doxorubicin in experimentally induced mammary carcinoma.

The prevalence of breast cancer is remarkably increasing worldwide .
Therefore , introduction of new approaches along with improvement of the existing ones in cancer treatment field is of great demand .
The present study was designated to investigate the anti-proliferative role of Diallyl trisulfide ( DATS ) alone or in combination with Doxorubicin ( Doxo ) in Ehrlich solid carcinoma ( ESC ) -bearing mice .
ESC was induced in female albino mice as an experimental model for breast cancer .
The anti-tumorigenic effect of DATS was mediated by suppression of Notch signaling proteins ( Notch 1 , JAG @ @ @ @ @ @ @ of tumor inflammation ( NFκB , TNF-α , IL-6 , IL-1β ) and proliferation ( cyclin D1 , Ki67 ) and enhancement of apoptosis ( caspase 3 , p53 ) .
DATS and Doxo mono-treatments displayed opposing effect regarding expression of Notch signaling proteins and cyclin D1 gene expression .
However , DATS and Doxo co-treatment markedly decreasedtumor volume and weight , increased animals ' survival rate , and attenuated Doxo-induced tumor inflammation .
In parallel , microscopic investigation displayed that ESC tumor tissues from animals treated with DATS and/or DOX showed shrinkage @ @ @ @ @ @ @ apoptosis .
In conclusion , DATS acts via multiple molecular targets to elicit anti-proliferative activity .
Combination of DATS with Doxo -which exhibit different mechanisms of action- might be a potential novel strategy to augment Doxo-antitumor effect .

The prevalence of breast cancer is remarkably increasing worldwide. Therefore, introduction of new approaches along with improvement of the existing ones in cancer treatment field is of great demand. The present study was designated to investigate the anti-proliferative role of Diallyl trisulfide (DATS) alone or in combination with Doxorubicin (Doxo) in Ehrlich solid carcinoma (ESC)-bearing mice. ESC was induced in female albino mice as an experimental model for breast cancer. The anti-tumorigenic effect of DATS was mediated by suppression of Notch signaling proteins (Notch 1, JAG 1 and HES 1), attenuation of tumor inflammation (NFκB, TNF-α, IL-6, IL-1β) and proliferation (cyclin D1, Ki67) and enhancement of apoptosis (caspase 3, p53). DATS and Doxo mono-treatments displayed opposing effect regarding expression of Notch signaling proteins and cyclin D1 gene expression. However, DATS and Doxo co-treatment markedly decreasedtumor volume and weight, increased animals' survival rate, and attenuated Doxo-induced tumor inflammation. In parallel, microscopic investigation displayed that ESC tumor tissues from animals treated with DATS and/or DOX showed shrinkage of tumor lesions and wider zones of apoptosis. In conclusion,DATS acts via multiple molecular targets to elicit anti-proliferative activity. Combination of DATS with Doxo -which exhibit different mechanisms of action- might be a potential novel strategy to augment Doxo-antitumor effect.


greenmedinfo--2020-09-12--Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced inflammation and oxidati

Protective effects of diallyl trisulfide (DATS) against doxorubicin-induced inflammation and oxidative stress in the brain.

Doxorubicin ( DOX ) is a widely used antitumor drug that causes severe neurotoxicity in patients .
Diallyl trisulfide ( DATS ) is an organosulfur compound with established potent antioxidant and anti-inflammatory properties .
Herein , we investigated the neuroprotective efficacy of DATS in preventing DOX-induced neurotoxicity in a rat model .
Specifically , DATS ( 40 mg/kg ) was administered to rats 24 h after DOX treatment , once a week for 8 weeks .
Our results showed that DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha ( TNF-α ) induced by DOX .
@ @ @ @ @ @ @ architecture and neuronal loss .
Immunohistochemical staining indicated that DATS decreased the expression of glial fibrillar acidic protein ( GFAP ) in DOX treated rats .
Components of stress-related inflammatory proteins ( TNF-α , phospho nuclear factor kappa B ( NF-κB ) , inducible nitricoxide synthase ( iNOS ) and cyclooxygenase-2 ( COX-2 ) ) were all significantly increased in the DOX group , in comparison with the control group , whereas they were decreased after DATS treatment .
In addition , the mRNA of antioxidant enzymes ( superoxide dismutase 2 ( SOD2 @ @ @ @ @ @ @ , 4 ( GPx1 and GPx4 ) ) and antioxidant proteins ( heme oxygenase-1 ( HO-1 ) , superoxide dismutase 1 , 2 ( SOD1 and SOD2 ) , Γ-glutamylcysteine synthase ( Γ-GCSc ) ) were markedly increased in DOX group compared with the control group , which were significantly attenuated by DATS treatment .
The upregulation of antioxidants enzymes in DOX groupwas probably a compensatory effect against elevated oxidative stress induced by DOX .
DATS treatment could ameliorate this oxidative stress in brain .
Our results suggested that DATS has potential clinical @ @ @ @ @ @ @ by ameliorating inflammatory insults and oxidative stress .

Doxorubicin (DOX) is a widely used antitumor drug that causes severe neurotoxicity in patients. Diallyl trisulfide (DATS) is an organosulfur compound with established potent antioxidant and anti-inflammatory properties. Herein, we investigated the neuroprotective efficacy of DATS in preventing DOX-induced neurotoxicity in a rat model. Specifically, DATS (40 mg/kg) was administered to rats 24 h after DOX treatment, once a week for 8 weeks. Our results showed that DATS treatment led to a decrease in plasma levels of tumor necrosis factor-alpha (TNF-α) induced by DOX. DATS restored cerebral cortex and hippocampus histopathological architecture and neuronal loss. Immunohistochemical staining indicated that DATS decreased the expression of glial fibrillar acidic protein (GFAP) in DOX treated rats. Components of stress-related inflammatory proteins (TNF-α, phospho nuclear factor kappa B (NF-κB), inducible nitricoxide synthase (iNOS) and cyclooxygenase-2 (COX-2)) were all significantly increased in the DOX group, in comparison with the control group, whereas they were decreased after DATS treatment. In addition, the mRNA of antioxidant enzymes (superoxide dismutase 2 (SOD2), catalase, glutathione peroxidase 1, 4 (GPx1 and GPx4)) and antioxidant proteins (heme oxygenase-1 (HO-1), superoxide dismutase 1, 2 (SOD1 and SOD2), Γ-glutamylcysteine synthase (Γ-GCSc)) were markedly increased in DOX group compared with the control group, which were significantly attenuated by DATS treatment. The upregulation of antioxidants enzymes in DOX groupwas probably a compensatory effect against elevated oxidative stress induced by DOX. DATS treatment could ameliorate this oxidative stress in brain. Our results suggested that DATS has potential clinical applications in the prevention of DOX-induced neurotoxicity by ameliorating inflammatory insults and oxidative stress.


greenmedinfo--2020-09-12--Topical applications of thiosulfinate-enriched Allium sativum extract accelerates acute cutaneous wo

Topical applications of thiosulfinate-enriched Allium sativum extract accelerates acute cutaneous wound healing.

OBJECTIVE : To determine whether topical applications of thiosulfinate-enriched Allium sativum extract ( TASE ) can accelerate acute cutaneous wound healing ( WH ) in a murine model .
METHODS : Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures .
Effects of topical TASE ( 0.5μg/mL of allicin in 97 % ethanol ) on acute cutaneous WH were determined in a murine model of acute cutaneous wound .
Twelve mice were alternately assigned to the vehicle- and TASE-treated groups ( n=6 per group ) .
Expression levels of mRNA for keratinocyte differentiation marker-related proteins ( filaggrin @ @ @ @ @ @ @ synthetic enzymes ( elongation of very long chain fatty acids protein 4 ( ELOVL4 ) , fatty acid synthase ( FA2H ) , 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase ( HMGCoA ) , and serine palmitoyltransferase ( SPT ) ) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding , while transepidermal water loss ( TEWL ) rates were measured in wounded areas .
RESULTS : TASE accelerated WH both in vivo ( 40 % vs. 22 % reduction in wound area , P < 0.01 ) and in @ @ @ @ @ @ @ reduction in wound area , P < 0.01 ) .
Moreover , topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4 , HMGCoA , SPT , filaggrin , loricrin and involucrin ( P < 0.05 vs. vehicle-treated controls ) on day 3 after wounding .
Likewise , TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 ( 33.06±2.09 g/ ( m·h ) vs. 24.60±2.04 g/ ( m·h ) , P < 0.01 ) .
CONCLUSIONS : Topical applications of TASE stimulated keratinocyte proliferation and formation @ @ @ @ @ @ @ to acceleration of acute cutaneous WH .
Topical products containing TASE could be used to manage acute cutaneous WH .

OBJECTIVE: To determine whether topical applications of thiosulfinate-enriched Allium sativum extract (TASE) can accelerate acute cutaneous wound healing (WH) in a murine model.
METHODS: Keratinocyte viability and in vitro wound closure were assessed in keratinocyte cultures. Effects of topical TASE (0.5μg/mL of allicin in 97% ethanol) on acute cutaneous WH were determined in a murine model of acute cutaneous wound. Twelve mice were alternately assigned to the vehicle- and TASE-treated groups (n=6 per group). Expression levels of mRNA for keratinocyte differentiation marker-related proteins (filaggrin, loricrin and involucrin) and lipid synthetic enzymes (elongation of very long chain fatty acids protein 4 (ELOVL4), fatty acid synthase (FA2H), 3-hydroxy- 3-methyl-glutaryl-coenzyme A reductase (HMGCoA), and serine palmitoyltransferase (SPT)) were assessed using real-time quantitative polymerase chain reaction on day 3 and 8 after wounding, while transepidermal water loss (TEWL) rates were measured in wounded areas.
RESULTS: TASE accelerated WH both in vivo (40% vs. 22% reduction in wound area, P<0.01) and in vitro (90% vs. 65% reduction in wound area, P<0.01). Moreover, topical applications of TASE upregulated the expression levels of epidermal mRNA for ELOVL4, HMGCoA, SPT, filaggrin, loricrin and involucrin (P<0.05 vs. vehicle-treated controls) on day 3 after wounding. Likewise, TASE significantly lowered TEWL rates in comparison with vehicle alone on day 8 (33.06±2.09 g/(m·h) vs. 24.60±2.04 g/(m·h), P<0.01).
CONCLUSIONS: Topical applications of TASE stimulated keratinocyte proliferation and formation of epidermal permeability barrier function, leading to acceleration of acute cutaneous WH. Topical products containing TASE could be used to manage acute cutaneous WH.


greenmedinfo--2020-09-12--Allicin inhibited proliferation of glioblastoma cells in vitro.

Purpose : Allicin , an extract of garlic , has antitumor effects in multiple tumor types .
However , the efficacy of allicin for treating glioblastoma has not yet been examined .
This study examined the antitumor effect of allicin on human cytomegalovirus ( HCMV ) -infected glioblastoma multiforme ( GBM ) and its role in cytokine signaling .
Materials and Methods : HCMV-infected glioblastoma was modeled by transfection of U87MG glioblastoma cells with HMCV proteins .
MTT assay was used to assess the effect of allicin on the proliferation of glioma cells .
Western blot analysis was used to @ @ @ @ @ @ @ expression of intermediate-early gene 2 ( IE2 ) and p53 .
Reverse transcription-quantitative polymerase chain reaction was used to assess and the levels of interleukin ( IL ) -6 and interferon ( IFN ) -β .
Single cell gel electrophoresis was used to analyze changes in radiotherapy-induced DNA damage .
Results : Transfection of the IE2 protein led to decreased p53 expression and increased glioblastoma cell proliferation .
Allicin inhibited this proliferation in a dose- and time-dependent manner .
An inhibitory effect on cytokine release was observed in GBM cells treated with allicin @ @ @ @ @ @ @ levels increased significantly , whereas expression of the inflammatory factors such as IL-6 and IFN-β decreased .
U87MG cells treated with allicin and 10 Gy irradiation had increased intracellular DNA damage compared to either treatment alone .
Conclusion : Allicin inhibited proliferation of glioblastoma cells in vitro .
Allicin also inhibited cytokine release , upregulated p53 activity , and increased the sensitivity of glioblastoma to radiotherapy .
These results suggest that allicin is effective against HCMV-infected glioblastomas .

Purpose: Allicin, an extract of garlic, has antitumor effects in multiple tumor types. However, the efficacy of allicin for treating glioblastoma has not yet been examined. This study examined the antitumor effect of allicin on human cytomegalovirus (HCMV)-infected glioblastoma multiforme (GBM) and its role in cytokine signaling.
Materials and Methods: HCMV-infected glioblastoma was modeled by transfection of U87MG glioblastoma cells with HMCV proteins. MTT assay was used to assess the effect of allicin on the proliferation of glioma cells. Western blot analysis was used to detect the effect of allicin on the expression of intermediate-early gene 2 (IE2) and p53. Reverse transcription-quantitative polymerase chain reaction was used to assess and the levels of interleukin (IL)-6 and interferon (IFN)-β. Single cell gel electrophoresis was used to analyze changes in radiotherapy-induced DNA damage.
Results: Transfection of the IE2 protein led to decreased p53 expression and increased glioblastoma cell proliferation. Allicin inhibited this proliferation in a dose- and time-dependent manner. An inhibitory effect on cytokine release was observed in GBM cells treated with allicin. After treatment with allicin, p53 levels increased significantly, whereas expression of the inflammatory factors such as IL-6 and IFN-β decreased. U87MG cells treated with allicin and 10 Gy irradiation had increased intracellular DNA damage compared to either treatment alone.
Conclusion: Allicin inhibited proliferation of glioblastoma cells in vitro. Allicin also inhibited cytokine release, upregulated p53 activity, and increased the sensitivity of glioblastoma to radiotherapy. These results suggest that allicin is effective against HCMV-infected glioblastomas.


greenmedinfo--2020-09-12--Organosulphur compounds induce apoptosis and cell cycle arrest in cervical cancer cells.

BACKGROUND : The quest for strong , safe and cost-effective natural antiproliferative agents that could reduce cancer have been focused now a day .
In this regard , the organosulfur compounds from garlic ( AlliumsativumL . )
, like diallyl sulfide ( DAS ) and diallyl disulfide ( DADS ) , have been shown to exhibit potent antiproliferative and anticancer properties in many studies .
However , the potential of these compounds against viral oncoproteins in cervical cancer has not been fully elucidated yet .
OBJECTIVE : The objective of this study was to analyze the antiproliferative and apoptotic properties @ @ @ @ @ @ @ cervical cancer Caski cell line .
METHODS : Caski ( cervical cancer cells ) were cultured and followed by the treatment of various concentrations of organosulphur compounds ( DADS and DAS ) , cell viability was measured by MTT assay .
The apoptotic assay was performed by DAPI and Hoechst3342 staining .
Reactive Oxygen Species ( ROS ) was estimated by DCFDA staining protocol .
The distributions of cell cycle and apoptosis ( FITC-Annexin V assay ) were analyzed by flow cytometry .
Finally , gene expression analysis was performed via quantitative real @ @ @ @ @ @ @ showed that DAS and DADS exerted significant antiproliferative effect on Caski cells by reducing the cell viability and inducing a dose-related increment in intracellular ROS production along with apoptosis in Caski cells .
DAS and DADS also induced cellcycle arrest in G0/G1 phase , which was supported by the downregulation of cyclin D1 and CDK4 and upregulation of CDK inhibitors p21WAF1/CIP1 and p27KIP1 in Caski cells .
Additionally , DAS and DADS lead to downregulation of viral oncogene E6 and E7 and restoration of p53 function .
CONCLUSION : Thus , this study @ @ @ @ @ @ @ compounds DADS and DAS against cervical cancer cells .

BACKGROUND: The quest for strong, safe and cost-effective natural antiproliferative agents that could reduce cancer have been focused now a day. In this regard, the organosulfur compounds from garlic (AlliumsativumL.), like diallyl sulfide (DAS) and diallyl disulfide (DADS), have been shown to exhibit potent antiproliferative and anticancer properties in many studies. However, the potential of these compounds against viral oncoproteins in cervical cancer has not been fully elucidated yet.
OBJECTIVE: The objective of this study was to analyze the antiproliferative and apoptotic properties of DADS and DAS in HPV16+ human cervical cancer Caski cell line.
METHODS: Caski (cervical cancer cells) were cultured and followed by the treatment of various concentrations of organosulphur compounds (DADS and DAS), cell viability was measured by MTT assay. The apoptotic assay was performed by DAPI and Hoechst3342 staining. Reactive Oxygen Species (ROS) was estimated by DCFDA staining protocol. The distributions of cell cycle and apoptosis (FITC-Annexin V assay) were analyzed by flow cytometry. Finally, gene expression analysis was performed via quantitative real time PCR.
RESULTS: Our results showed that DAS and DADS exerted significant antiproliferative effect on Caski cells by reducing the cell viability and inducing a dose-related increment in intracellular ROS production along with apoptosis in Caski cells. DAS and DADS also induced cellcycle arrest in G0/G1 phase, which was supported by the downregulation of cyclin D1 and CDK4 and upregulation of CDK inhibitors p21WAF1/CIP1 and p27KIP1 in Caski cells. Additionally, DAS and DADS lead to downregulation of viral oncogene E6 and E7 and restoration of p53 function.
CONCLUSION: Thus, this study confirms the efficacy of both the organosulfur compounds DADS and DAS against cervical cancer cells.


greenmedinfo--2020-09-12--Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis

Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures.

Using primary rat hepatocyte cultures , the potency of several garlic-derived organosulfur compounds to inhibit cholesterol biosynthesis in toto as well as at early and late steps of this metabolic pathway was compared .
Concerning early steps , allicin significantly inhibited incorporation of [ 14C ] acetate into nonsaponifiable neutral lipids already at concentrations as low as 10 microM , while diallyl disulfide and allyl mercaptan were effective above 100 microM only .
Likewise , inhibition in response to the two vinyl-dithiins started at 500 microM .
If [ 14C ] acetate was replaced by [ 14C ] mevalonate , @ @ @ @ @ @ @ , and allyl mercaptan disappeared suggesting that HMGCoA-reductase was the target of inhibition .
In contrast , for the vinyl-dithiins a stimulation of mevalonate incorporation was found .
Concerning the late step , the potency to exert accumulation of lanosterol presumably by inhibiting lanosterol 14 alpha-demethylase decreased in the order allicin > diallyl disulfide > allyl mercaptan = 1,3-vinyl-dithiin > 1,2-vinyldithiin , the effect of the latter compound being close to zero .
With respect to the total inhibition of [ 14C ] acetate labeling of cholesterol , the half-maximal effective concentration-value of @ @ @ @ @ @ @ 2 microM compared to 64 +/- 7 microM for diallyl disulfide and to 450 +/- 20 microM for allyl mercaptan .
Cytotoxicity as determined by the lactate dehydrogenase leakage assay was slightly higher for the two vinyl-dithiins than for diallyl disulfide and allyl mercaptan , but was apparent only at concentrations higher than 10 mM and , consequently , was irrelevant for the effects described .
These results demonstrate that different garlic-derived organosulfur compounds interfere differently with cholesterol biosynthesis and , thus , may provoke multiple inhibition of this metabolic pathway in response @ @ @ @ @ @ @ allicin was the most effective inhibitor argues against the possibility that its degradation products , namely diallyl disulfide or allyl mercapatan , might mediate its effects , a possibility that might be true , however , in the case of the vinyl-dithiins .

Using primary rat hepatocyte cultures, the potency of several garlic-derived organosulfur compounds to inhibit cholesterol biosynthesis in toto as well as at early and late steps of this metabolic pathway was compared. Concerning early steps, allicin significantly inhibited incorporation of [14C]acetate into nonsaponifiable neutral lipids already at concentrations as low as 10 microM, while diallyl disulfide and allyl mercaptan were effective above 100 microM only. Likewise, inhibition in response to the two vinyl-dithiins started at 500 microM. If [14C]acetate was replaced by [14C]mevalonate, inhibition due to allicin, diallyl disulfide, and allyl mercaptan disappeared suggesting that HMGCoA-reductase was the target of inhibition. In contrast, for the vinyl-dithiins a stimulation of mevalonate incorporation was found. Concerning the late step, the potency to exert accumulation of lanosterol presumably by inhibiting lanosterol 14 alpha-demethylase decreased in the order allicin>diallyl disulfide>allyl mercaptan = 1,3-vinyl-dithiin>1,2-vinyldithiin, the effect of the latter compound being close to zero. With respect to the total inhibition of [14C]acetate labeling of cholesterol, the half-maximal effective concentration-value of allicin was determined to be 17 +/- 2 microM compared to 64 +/- 7 microM for diallyl disulfide and to 450 +/- 20 microM for allyl mercaptan. Cytotoxicity as determined by the lactate dehydrogenase leakage assay was slightly higher for the two vinyl-dithiins than for diallyl disulfide and allyl mercaptan, but was apparent only at concentrations higher than 10 mM and, consequently, was irrelevant for the effects described. These results demonstrate that different garlic-derived organosulfur compounds interfere differently with cholesterol biosynthesis and, thus, may provoke multiple inhibition of this metabolic pathway in response to garlic consumption. The fact that allicin was the most effective inhibitor argues against the possibility that its degradation products, namely diallyl disulfide or allyl mercapatan, might mediate its effects, a possibility that might be true, however, in the case of the vinyl-dithiins.


greenmedinfo--2020-09-12--Red Clover Beats Inflammation and Oxidative Stress

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greenmedinfo--2020-09-12--Naringin attenuates Bisphenol-A mediated neurotoxicity in hypertensive rats.

We examined whether active fruit naringin can reduce the risk of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats and whether the modulation could be linked to improvement of brain NO signaling .
Male albino rats were randomly distributed into eight ( n = 7 ) groups .
Group I was control animals , Group II was orally-treated with L-NAME , Group III was orally treated with 100 mg/kg BPA , Group IV was orally-treated with L-NAME +100 mg/kg BPA .
Group V was orally-administered with L-NAME +80 mg/kg NAR .
Group VI was orally-administered with 100 mg/kg BPA +80 mg/kg @ @ @ @ @ @ @ L-NAME+100 mg/kg BPA +80 mg/kg NAR .
Lastly , group VIII was orally-treated with 80 mg/kg NAR .
The treatment lasted for 14 days .
Sub-acute exposure to L-NAME and BPA induced hypertension and mediated-neuroinflammation at CA-2 and CA-4 of hippocampus cells .
It was evident by increase in PDE-5and enzymes of ATP hydrolysis ( ATPase , ADPase and AMPase ) with corresponding upsurge in cholinergic ( AChE and BuChE ) , dopaminergic ( MAO-A ) and adenosinergic ( ADA ) enzymes as well as movement disorder .
The hypertensive-mediated neurotoxicity was related @ @ @ @ @ @ @ release of pro-inflammatory cytokines ( TNF-α and IL-1β ) , apoptotic proteins ( P53 and caspace-9 ) and facilitated entry of T-lymphocytes ( CD43 ) into CNS through blood brain barrier potentiated by antigen presenting cells .
Hence , these features of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats were prohibited by co-administration of NAR through production of neuro-inflammatory mediators , stabilizing neurotransmitter enzymes , normalizing NO signaling and improving brain histology .

We examined whether active fruit naringin can reduce the risk of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats and whether the modulation could be linked to improvement of brain NO signaling. Male albino rats were randomly distributed into eight (n = 7) groups. Group I was control animals, Group II was orally-treated with L-NAME, Group III was orally treated with 100 mg/kg BPA, Group IV was orally-treated with L-NAME +100 mg/kg BPA. Group V was orally-administered with L-NAME +80 mg/kg NAR. Group VI was orally-administered with 100 mg/kg BPA +80 mg/kg NAR. Group VII was orally-administered with L-NAME+100 mg/kg BPA +80 mg/kg NAR. Lastly, group VIII was orally-treated with 80 mg/kg NAR. The treatment lasted for 14 days. Sub-acute exposure to L-NAME and BPA induced hypertension and mediated-neuroinflammation at CA-2 and CA-4 of hippocampus cells. It was evident by increase in PDE-5and enzymes of ATP hydrolysis (ATPase, ADPase and AMPase) with corresponding upsurge in cholinergic (AChE and BuChE), dopaminergic (MAO-A) and adenosinergic (ADA) enzymes as well as movement disorder. The hypertensive-mediated neurotoxicity was related to alteration of NO signaling and higher release of pro-inflammatory cytokines (TNF-α and IL-1β), apoptotic proteins (P53 and caspace-9) and facilitated entry of T-lymphocytes (CD43) into CNS through blood brain barrier potentiated by antigen presenting cells. Hence, these features of BPA-mediated neurotoxicity in L-NAME induced hypertensive rats were prohibited by co-administration of NAR through production of neuro-inflammatory mediators, stabilizing neurotransmitter enzymes, normalizing NO signaling and improving brain histology.


greenmedinfo--2020-09-12--These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity.

Bisphenol-A-glycidyldimethacrylate ( BisGMA ) is a resin monomer frequently used in dentin restorative treatments .
The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages .
Rutin has various beneficial bioeffects , including antioxidation and antiinflammation .
In this study , we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner .
BisGMA-induced apoptosis , which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1 , and genotoxicity , which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays @ @ @ @ @ @ @ concentration-dependent manner .
Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8 .
Rutin inhibited the activation of the mitochondrial apoptotic pathway , including cytochrome C release and mitochondria disruption , after macrophages were treated with BisGMA .
Finally , BisGMA-induced reactive oxygen species ( ROS ) generation and antioxidant enzyme ( AOE ) deactivation could be reversed by rutin .
Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation , caspase-3 activity , mitochondrial apoptotic pathway activation , and genotoxicity .
These results @ @ @ @ @ @ @ genotoxicity , the mitochondrial apoptotic pathway , and relatively upstream factors , including reduction of ROS generation and induction of AOE .

Bisphenol-A-glycidyldimethacrylate (BisGMA) is a resin monomer frequently used in dentin restorative treatments. The leakage of BisGMA monomer from BisGMA-based polymeric resins can lead to cytotoxicity in macrophages. Rutin has various beneficial bioeffects, including antioxidation and antiinflammation. In this study, we found that pretreatment of RAW264.7 macrophages with rutin-inhibited cytotoxicity induced by BisGMA in a concentration-dependent manner. BisGMA-induced apoptosis, which was detected by levels of phosphatidylserine from the internal to the external membrane and formation of sub-G1, and genotoxicity, which was detected by cytokinesis-blocked micronucleus and single-cell gel electrophoresis assays, were inhibited by rutin in a concentration-dependent manner. Rutin suppressed the BisGMA-induced activation of caspase-3 and -9 rather than caspase-8. Rutin inhibited the activation of the mitochondrial apoptotic pathway, including cytochrome C release and mitochondria disruption, after macrophages were treated with BisGMA. Finally, BisGMA-induced reactive oxygen species (ROS) generation and antioxidant enzyme (AOE) deactivation could be reversed by rutin. Parallel trends were observed in the elevation of AOE activation and inhibition of ROS generation, caspase-3 activity, mitochondrial apoptotic pathway activation, and genotoxicity. These results suggested that rutin suppressed BisGMA-induced cytotoxicity through genotoxicity, the mitochondrial apoptotic pathway, and relatively upstream factors, including reduction of ROS generation and induction of AOE.


greenmedinfo--2020-09-12--Bisphenol A-induced epigenetic changes and its effects on the male reproductive system.

Bisphenol A ( BPA ) is a widespread chemical agent which can exert detrimental effects on the male reproductive system @ @ @ @ @ been shown to induce several epigenetic modifications in both animal and human cells .
Specifically @ @ @ @ @ modify the methylation pattern of multiple genes encoding proteins related to reproductive physiology but also @ @ @ @ @ for DNA methylation .
BPA effects include hormonal alterations , microscopic and macroscopic alteration of @ @ @ @ @ inheritable epigenetic changes involving human reproduction .
BPA exposure was also linked to prostate cancer @ @ @ @ @ show the current scenario of BPA-induced epigenetic changes and its effects on the male reproductive @ @ @ @ @ counter the toxic effect of BPA were also addressed .

Bisphenol A (BPA) is a widespread chemical agent which can exert detrimental effects on the male reproductive system. Exposure to BPA has been shown to induce several epigenetic modifications in both animal and human cells. Specifically, BPA could not only modify the methylation pattern of multiple genes encoding proteins related to reproductive physiology but also directly influence the genes responsible for DNA methylation. BPA effects include hormonal alterations, microscopic and macroscopic alteration of male reproductive organs, and inheritable epigenetic changes involving human reproduction. BPA exposure was also linked to prostate cancer. This review aims to show the current scenario of BPA-induced epigenetic changes and its effects on the male reproductive system. Possible strategies to counter the toxic effect of BPA were also addressed.


greenmedinfo--2020-09-13--Influence of resveratrol on the cardiovascular health effects of chronic kidney disease.

Cardiovascular disease ( CVD ) is closely related to chronic kidney disease ( CKD ) , and patients with CKD have a high risk of CVD-related mortality .
Traditional CVD risk factors can not account for the higher cardiovascular risk of patients with CKD , and standard CVD interventions can not reduce the mortality rates among patients with CKD .
Nontraditional factors related to mineral and vitamin-D metabolic disorders provide some explanation for the increased CVD risk .
Non-dialyzable toxins , indoxyl sulfate ( IS ) and-cresol sulfate ( PCS ) -produced in the liver by colonic microorganisms-cause kidney and @ @ @ @ @ @ @ ) -a gut microbe-dependent metabolite of dietary L-carnitine and choline-is elevated in CKD and related to vascular disease , resulting in poorer long-term survival .
Therefore , the modulation of colonic flora can improve prospects for patients with CKD .
Managing metabolic syndrome , anemia , and abnormal mineral metabolism is recommended for the prevention of CVD in patients with CKD .
Considering nontraditional risk factors , the use of resveratrol ( RSV ) , a nutraceutical , can be helpful for patients with CVD and CKD .
This paper discusses the beneficial @ @ @ @ @ @ @ and clinical responses , including improvements in intestinal epithelial integrity , modulation of the intestinal microbiota and reduction in hepatic synthesis of IS , PCS and TMAO in patients with CVD and CKD .

Cardiovascular disease (CVD) is closely related to chronic kidney disease (CKD), and patients with CKD have a high risk of CVD-related mortality. Traditional CVD risk factors cannot account for the higher cardiovascular risk of patients with CKD, and standard CVD interventions cannot reduce the mortality rates among patients with CKD. Nontraditional factors related to mineral and vitamin-D metabolic disorders provide some explanation for the increased CVD risk. Non-dialyzable toxins, indoxyl sulfate (IS) and-cresol sulfate (PCS)-produced in the liver by colonic microorganisms-cause kidney and vascular dysfunction. Plasma trimethylamine-N-oxide (TMAO)-a gut microbe-dependent metabolite of dietary L-carnitine and choline-is elevated in CKD and related to vascular disease, resulting in poorer long-term survival. Therefore, the modulation of colonic flora can improve prospects for patients with CKD. Managing metabolic syndrome, anemia, and abnormal mineral metabolism is recommended for the prevention of CVD in patients with CKD. Considering nontraditional risk factors, the use of resveratrol (RSV), a nutraceutical, can be helpful for patients with CVD and CKD. This paper discusses the beneficial effects of RSV on biologic, pathophysiological and clinical responses, including improvements in intestinal epithelial integrity, modulation of the intestinal microbiota and reduction in hepatic synthesis of IS, PCS and TMAO in patients with CVD and CKD.


greenmedinfo--2020-09-13--Preventive role of L-carnitine and balanced diet in Alzheimer's disease.

The prevention or alleviation of neurodegenerative diseases , including Alzheimer 's disease ( AD ) , is a challenge for contemporary health services .
The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet , dietary carnitine supplements and the MIND ( Mediterranean-DASH Intervention for Neurodegenerative Delay ) diet , which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension ( DASH ) diet .
L-carnitine ( LC ) plays a crucial role in the energetic metabolism of the cell .
A properly @ @ @ @ @ @ @ LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis .
In healthy people , carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency .
In persons with dysfunction of mitochondria , e.g.
, with AD connected with extensive degeneration of the brain structures , there are often serious disturbances in the functioning of the whole organism .
The Mediterranean diet is characterized by a high consumption of fruits and vegetables , cereals , nuts , olive oil , and seeds as the major source of @ @ @ @ @ @ @ poultry , low to moderate consumption of dairy products and alcohol , and low intake of red and processed meat .
The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life .

The prevention or alleviation of neurodegenerative diseases, including Alzheimer's disease (AD), is a challenge for contemporary health services. The aim of this study was to review the literature on the prevention or alleviation of AD by introducing an appropriate carnitine-rich diet, dietary carnitine supplements and the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which contains elements of the Mediterranean diet and the Dietary Approaches to Stop Hypertension (DASH) diet. L-carnitine (LC) plays a crucial role in the energetic metabolism of the cell. A properly balanced diet contains a substantial amount of LC as well as essential amino acids and microelements taking part in endogenous carnitine synthesis. In healthy people, carnitine biosynthesis is sufficient to prevent the symptoms of carnitine deficiency. In persons with dysfunction of mitochondria, e.g., with AD connected with extensive degeneration of the brain structures, there are often serious disturbances in the functioning of the whole organism. The Mediterranean diet is characterized by a high consumption of fruits and vegetables, cereals, nuts, olive oil, and seeds as the major source of fats, moderate consumption of fish and poultry, low to moderate consumption of dairy products and alcohol, and low intake of red and processed meat. The introduction of foodstuffs rich in carnitine and the MIND diet or carnitine supplementation of the AD patients may improve their functioning in everyday life.


greenmedinfo--2020-09-13--Nut intake may yield a modulatory effect on the gut microbiota.

There is increasing evidence linking the gut microbiota to various aspects of human health .
Nuts are a food rich in prebiotic fibre and polyphenols , food components which have been shown to have beneficial effects on the gut microbiota .
This systematic review aimed to synthesise the evidence regarding the effect of nut consumption on the human gut microbiota .
A systematic search of the databases MEDLINE , PubMed , Cochrane CENTRAL and CINAHL was performed until 28 November 2019 .
Eligible studies were those that investigated the effects of nut consumption in humans ( aged over 3 years @ @ @ @ @ @ @ .
Primary outcome measures were between-group differences inα- and β-diversity metrics and gut microbial composition .
A total of eight studies were included in the review .
Included studies assessed the effects of either almonds , walnuts , hazelnuts or pistachios on the gut microbiota .
Overall , nut consumption had a modest impact on gut microbiota diversity , with two studies reporting a significant shift in α-diversity and four reporting a significant shift in β-diversity .
Walnuts , in particular , appeared to more frequently explain shifts in β-diversity , which may @ @ @ @ @ @ @ composition .
Some shifts in bacterial composition ( including an increase in genera capable of producing SCFA : Clostridium , Roseburia , Lachnospira and Dialister ) were reported following the consumption of nuts .
Nut intake may yield a modulatory effect on the gut microbiota ; however , results were inconsistent across studies , which may be explained by variations in trial design , methodological limitations and inter-individual microbiota .

There is increasing evidence linking the gut microbiota to various aspects of human health. Nuts are a food rich in prebiotic fibre and polyphenols, food components which have been shown to have beneficial effects on the gut microbiota. This systematic review aimed to synthesise the evidence regarding the effect of nut consumption on the human gut microbiota. A systematic search of the databases MEDLINE, PubMed, Cochrane CENTRAL and CINAHL was performed until 28 November 2019. Eligible studies were those that investigated the effects of nut consumption in humans (aged over 3 years old), utilising next-generation sequencing technology. Primary outcome measures were between-group differences inα- and β-diversity metrics and gut microbial composition. A total of eight studies were included in the review. Included studies assessed the effects of either almonds, walnuts, hazelnuts or pistachios on the gut microbiota. Overall, nut consumption had a modest impact on gut microbiota diversity,with two studies reporting a significant shift in α-diversity and four reporting a significant shift in β-diversity. Walnuts, in particular, appeared to more frequently explain shifts in β-diversity, which may be a result of their unique nutritional composition. Some shifts in bacterial composition (including an increase in genera capable of producing SCFA: Clostridium, Roseburia, Lachnospira and Dialister) were reported following the consumption of nuts. Nut intake may yield a modulatory effect on the gut microbiota; however, results were inconsistent across studies, which may be explained by variations in trial design, methodological limitations and inter-individual microbiota.