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Dioscin showed various pharmacological effects in our previous studies; however, the effects and mechanisms against lung ischemia/reperfusion injury (LI/RI) have not been reported. Hypoxia/reoxygenation (H/R) models were established using A549 and primary AEC-II cells, while LI/RI models were established in rats and mice. The effects of dioscin on oxidative stress, inflammation and apoptosis in vivo and in vitro were investigated. The mechanisms were investigated focus on dioscin regulating FXR/LKB1 signaling pathway. Dioscin improved cell viability and mitochondrial membrane potential, reduced reactive oxygen species level, and inhibited H/R-mediated cell apoptosis. It also significantly decreased the lung wet/dry weight ratio, ameliorated levels of oxidative stress indicators, and enhanced the mitochondrial membrane potential and inhibited cell apoptosis in vivo. The results of mechanism research showed that dioscin activated FXR/LKB1 signals by increasing the expression of p-LKB1 and p-AMPKα, promoting the nuclear translocation of Nrf2, up-regulating the levels of HO-1, NQO1 and GCLC, expressed against oxidative stress. Furthermore, dioscin reduced Cyt C released, decreased the expression levels of Caspase-9 and Caspase-3 during apoptosis. Dioscin suppressed inflammation by inhibiting NF-κB translocation, reducing the expression levels of NF-κB, HMGB1, COX-2, IL-1β, IL-6 and TNF-α. The transfection of FXR or LKB1 siRNA further confirmed that the protective effect of dioscin against LI/RI was attributable to the regulation of FXR/LKB1 signaling pathway. Our research showed that dioscin exhibited potent activity against LI/RI, by adjusting the levels of FXR/LKB1-mediated oxidative stress, apoptosis, and inflammation, and should be considered as a new candidate for treating LI/RI., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent researches have shown that estrogen receptor-β (ERβ) activator may be a potent anticancer agent for prostate cancer (PCa), and our previous study also indicated that dioscin can upregulate the expression of ERβ in MC3T3-E1 cell. In the present work, the activity and mechanism of dioscin, a natural product, against PCa were investigated. The results showed that dioscin markedly inhibited cell viability, colony formation, motility and induced apoptosis in PC3 cells. Moreover, dioscin disrupted the formation of PC3 cell-derived mammospheres and reduced aldehyde dehydrogenase (ALDH) level and the CD133 + /CD44 + cells, indicating that dioscin had a potent inhibitory activity on prostate cancer stem cells (PCSCs). In vivo results also showed that dioscin significantly suppressed the tumor growth of PC3 cell xenografts in nude mice. Furthermore, mechanism investigation showed that dioscin markedly upregulated ERβ expression level, subsequently increased prolyl hydroxylase 2 level, decreased the levels of hypoxia-inducible factor-1α, vascular endothelial growth factor A and BMI-1, and thus induced cell apoptosis by regulating the expression levels of caspase-3 and Bcl-2 family proteins. In addition, transfection experiment of ERβ-siRNA further indicated that diosicn showed excellent activity against PCa in vitro and in vivo by increasing ERβ expression level. The co-immunoprecipitation (Co-IP) results further suggested that dioscin promoted the interaction of c-ABL and ERβ, but did not change c-ABL expression. Moreover, the molecular docking assay showed that dioscin processed powerful affinity toward to ERβ mainly through the strong hydrogen bonding and hydrophobic effects, and the actions of dioscin on ERβ activation and tumor cells inhibition were significantly weakened in the mutational (Phe-336, Phe-468) PC3 cells. Collectively, these findings proved that dioscin exerted efficient anti-PCa activity via activation of ERβ, which should be developed as an efficient candidate in clinical for treating this cancer in the future.

In our previous study, the effects of dioscin against alcohol-, carbon tetrachloride- and acetaminophen-induced liver damage have been found. However, the activity of it against dimethylnitrosamine (DMN)-induced acute liver injury remained unknown. In the present study, dioscin markedly decreased serum ALT and AST levels, significantly increased the levels of SOD, GSH-Px, GSH, and decreased the levels of MDA, iNOS and NO. Mechanism study showed that dioscin significantly decreased the expression levels of IL-1β, IL-6, TNF-α, IκBα, p50 and p65 through regulating TLR4/MyD88 pathway to rehabilitate inflammation. In addition, dioscin markedly up-regulated the expression levels of SIRT1, HO-1, NQO1, GST and GCLM through increasing nuclear translocation of Nrf2 against oxidative stress. Furthermore, dioscin significantly decreased the expression levels of FasL, Fas, p53, Bak, Caspase-3/9, and upregulated Bcl-2 level through decreasing IRF9 level against apoptosis. In conclusion, dioscin showed protective effect against DMN-induced acute liver injury via ameliorating apoptosis, oxidative stress and inflammation, which should be developed as a new candidate for the treatment of acute liver injury in the future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Dioscin, a natural product, has activity against glioblastoma multiforme, lung cancer and colon cancer. In this study, the effects of dioscin against human cervical carcinoma HeLa and SiHa cells were further confirmed, and the possible mechanism(s) were investigated. A transmission electron microscopy (TEM) assay and DAPI staining were used to detect the cellular morphology. Flow cytometry was used to assay cell apoptosis, ROS and Ca(2+) levels. Single cell gel electrophoresis and immunofluorescence assays were used to test DNA damage and cytochrome C release. The results showed that dioscin significantly inhibited cell proliferation and caused DNA damage in HeLa and SiHa cells. The mechanistic investigation showed that dioscin caused the release of cytochrome C from mitochondria into the cytosol. In addition, dioscin significantly up-regulated the protein levels of Bak, Bax, Bid, p53, caspase-3, caspase-9, and down-regulated the protein levels of Bcl-2 and Bcl-xl. Our work thus demonstrated that dioscin notably induces apoptosis in HeLa and SiHa cells through adjusting ROS-mediated DNA damage and the mitochondrial signaling pathway.

The anti-cancer effects of dioscin have been widely reported. However, its effect on laryngeal cancer remains unknown. In the present paper, our results showed that dioscin markedly caused cell apoptosis and DNA damage, increased reactive oxygen species (ROS) level, induced S-phase arrest, and inhibited invasion of human laryngeal cancer HEp-2 and TU212 cells. Mechanism investigation showed that dioscin markedly up-regulated p53 level, and down-regulated cyclin-dependent kinase 2 (CDK2) and Cyclin A levels. In addition, dioscin significantly down-regulated the levels of p-ERK, Bcl-2, up-regulated the levels of p-JNK, p-p38, Bax, cleaved caspase-3/-9, and caused Cytochrome c release. Furthermore, U0126, an ERK1/2 inhibitor, markedly down-regulated Bcl-2 level, up-regulated the levels of Bax, cleaved caspase-3/9, and enhanced Cytochrome c release inducted by dioscin. While, SP600125 (one JNK inhibitor) and SB203580 (one p38 inhibitor) markedly up-regulated Bcl-2 level, down-regulated the levels of Bax, cleaved caspase-3/9, and obviously boosted Cytochrome c release induced by dioscin. Interestingly, dioscin also markedly down-regulated the levels of MMP2 and MMP9 associated with tumor invasion. Taken together, our study indicated that dioscin suppressed laryngeal cancer cells growth via inducting cell-cycle arrest, MAPK-mediated mitochondrial- derived apoptosis and inhibiting tumor invasion, which could be used as one potential candidate for the treatment of laryngeal cancer in the future., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Dioscin shows potent effects against liver damage in our previous studies; however, the action of it on hepatic ischemia-reperfusion (I/R) injury is still unknown. In the present article, the effects and possible mechanisms of dioscin against hepatic I/R injury were investigated., Methods: Seventy percent partial hepatic warm ischemia was induced in Wistar rats for 60 min followed by succedent reperfusion. In the prophylactic test, dioscin was administered intragastrically to the rats at doses of 20, 40, and 60 mg/kg once daily for seven consecutive days before I/R. In the therapeutic test, the rats received dioscin intragastrically at a dose of 60 mg/kg once 2 hr before I/R., Results: We found that dioscin significantly decreased serum alanine aminotransferase and aspartate aminotransferase activities, increased survival rate of rats, and improved I/R-induced hepatocyte abnormality. In addition, dioscin obviously increased the levels of SOD, CAT, GSH-Px, GSH, decreased the levels of MDA, TNOS, iNOS, NO, and prevented DNA fragmentation caused by I/R injury. Further research indicated that dioscin markedly decreased the gene expressions of interleukin-1β, interleukin-6, tumor necrosis factor-α, intercellular adhesion molecule-1, MIP-1α, MIP-2, Fas, FasL, decreased the protein expressions of NF-κB, AP-1, COX-2, HMGB-1, CYP2E1, Bak, caspase-3, p53, PARP, Caspase-9, decreased the levels of JNK, ERK and p38 MAPKs phosphorylation, and upregulated the levels of Bcl-2 and Bcl-x., Conclusion: Our results suggest that dioscin has potent actions against hepatic I/R injury through suppression of inflammation, oxidative-nitrative stress, and apoptosis, which should be developed as a new drug to treat hepatic I/R injury in the future.

Oxidative stress-induced neuronal death has an important role in the pathogenesis of neurodegenerative disorders. The effects and mechanisms of action of the total flavonoids (TFs) from Rosa laevigata Michx fruit against hydrogen peroxide (H2O2)-induced oxidative injury in PC12 cells were investigated in this study. The results demonstrated that the TFs protected against cell apoptosis, DNA and mitochondrial damage caused by H2O2 based on single cell gel electrophoresis, in situ terminal deoxynucleotidyltransferase dUTP nick end labeling (TUNEL), flow cytometry and transmission electron microscope (TEM) assays. In addition, the TFs notably decreased cytochrome C release from mitochondria into the cytosol and intracellular Ca2+ levels, and diminished intracellular generation of reactive oxygen species (ROS). Furthermore, the TFs inhibited the phosphorylation levels of JNK, ERK and p38 MAPK as well as down-regulated the expressions of IL-1, IL-6, TNF-α, Fas, FasL, CYP2E1, Bak, caspase-3, caspase-9, p53, COX-2, NF-κB, AP-1, and up-regulated the expressions of Bcl-2 and Bcl-xl. In conclusion, these results suggest that the TFs from R. laevigata Michx fruit show good effects against H2O2-induced oxidative injury in PC12 cells by adjusting oxidative stress, and suppression of apoptosis and inflammation, and could be developed as a potential candidate to prevent oxidative stress in the future.

Dioscin shows various pharmacological effects. However, its activity on colorectal cancer is still unknown. The present work showed that dioscin significantly inhibited cell proliferation on human HCT-116 colon cancer cells, and affected Ca(2+) release and ROS generation. The content of nitric oxide (NO) and its producer inducible NO synthase (iNOS) associated with DNA damage and aberrant cell signaling were assayed using the kits. DNA damage and cell apoptosis caused by dioscin were also analyzed through single-cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. The results showed that dioscin increased the levels of NO and inducible NO synthase. The comet length in dioscin-treated groups was much longer than that of the control group, and the number of terminal deoxynucleotidyl transferase dUTP nick-end labeling positive cells (apoptotic cells) was significantly increased by the compound (p < 0.01). Furthermore, dioscin caused mitochondrial damage and G2/M cell cycle arrest through transmission electron microscopy and flow cytometry analysis, respectively. To study the cytotoxic mechanism of dioscin, an iTRAQ-based proteomics approach was used. There were 288 significantly different proteins expressed in response to dioscin, which were connected with each other and were involved in different Kyoto Encyclopedia of Genes and Genomes pathways. Then, some differentially expressed proteins involved in oxidative phosphorylation, Wnt, p53, and calcium signaling pathways were validated by Western blotting and quantitative real-time PCR assays. Our work elucidates the molecular mechanism of dioscin-induced cytotoxicity in colon cancer cells, and the identified targets may be useful for treatment of colorectal cancer in future., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

The neuroprotective effect and mechanism of the flavonoid-rich extract (FRE) from Rosa laevigata Michx fruit on cerebral ischemia-reperfusion (I/R) injury were investigated. The contents of flavonoids, saponins and tannin were determined, and ten chemicals including chlorogenic acid, 4-hydroxy-3-methoxybenzoic acid, apigenin, luteolin, kaempferol, querce-tin, kaempferide-3-O-glucoside, quercetin-3-rhamnoside, rutin and isorhamnetin-3-O-β-rutinoside from the crude extract were separated. Oral administration of FRE obviously improved the survival rate and prevented I/R-induced disability and histological damage. Further works showed that the natural product had excellent antioxidant activity, significantly decreased DNA fragmentation, up-regulated the expression of Bcl-2, and down-regulated the expressions of p53, Apaf1, Fas, FasL, Bax, Bid, cytochrome C and active Caspase-3, -9 and -8. Moreover, the FRE decreased the expressions of NF-κB, iNOS, MMP-9, COX-2, TNF-α, IL-1β, IL-4, IL-6, and down-regulated the levels of p-JNK, p-ERK and p-p38 in MAPK pathways. Therefore, the flavonoid-rich extract from R. laevigata Michx fruit has the potential actions for treatment of ischemic stroke due to its anti-oxidant, anti-apoptosis and anti-inflammatory properties., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Dioscin, a natural steroid saponin, has been widely investigated. However, its anti-cancer activities on human lung cancer cells are still unknown. In the present paper, the inhibitory effects of dioscin were investigated, and the results showed that dioscin inhibited the proliferation of human A549, NCI-H446 and NCI-H460 cancer cells. DNA damage and cell apoptosis in dioscin-treated cells were found through single cell gel electrophoresis and in situ terminal deoxynucleotidyl transferase dUTP nick-end labeling assays. Furthermore, dioscin caused mitochondrial structure changes and blocked cell cycle at S phase based on transmission electron microscope and flow cytometry analysis. In addition, dioscin treatment caused the release of cytochrome c from mitochondria into cytosol. The activities of Caspase-3 and -9 in dioscin-treated groups were significantly increased compared with control group. Western blotting analysis showed that dioscin significantly down-regulated the expressions of Bcl-2 and Bcl-xl, and up-regulated the expressions of Bax, Bak and Bid. Our results indicate that dioscin has anticancer activities against human lung cancer cells through inducing cell cycle arrest, DNA damage and activating mitochondrial signal pathway., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Dioscin, a natural product obtained from medicinal plants shows lipid-lowering, anti-cancer and hepatoprotective effects. However, the effect of it on glioblastoma is unclear. In this study, dioscin significantly inhibited proliferation of C6 glioma cells and caused reactive oxygen species (ROS) generation and Ca²⁺ release. ROS accumulation affected levels of malondialdehyde, nitric oxide, glutathione disulfide and glutathione, and caused cell apoptosis. In addition, ROS generation caused mitochondrial damage including structural changes, increased mitochondrial permeability transition and decreased mitochondria membrane potential, which led to the release of cytochrome C, nuclear translation of programmed cell death-5 and increased activities of caspase-3,9. Simultaneously, dioscin down-regulated protein expression of Bcl-2, Bcl-xl, up-regulated expression of Bak, Bax, Bid and cleaved poly (ADP-ribose) polymerase. Also, oxygen stress induced S-phase arrest of cancer cells by way of regulating expression of DNA Topo I, p53, CDK2 and Cyclin A and caused DNA damage. In a rat allograft model, dioscin significantly inhibited tumor size and extended the life cycle of the rats. In conclusion, dioscin shows noteworthy anti-cancer activity on glioblastoma cells by promoting ROS accumulation, inducing DNA damage and activating mitochondrial signal pathways. Ultimately, we believe dioscin has promise as a new therapy for the treatment of glioblastoma., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background and Purpose: The microRNA miR-29b-3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR-29b-3p on II/R injury on order to find drug targets to treat the injury.Experimental Approach: Two models - in vitro hypoxia/reoxygenation (H/R) of IEC-6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual-luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR-29b-3p on II/R injury via targeting TNF receptor-associated factor 3 (TRAF3).Key Results: The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC-6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR-29b-3p were decreased in H/R-induced cells and II/R-induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR-29b-3p level markedly increased TRAF3 expression via activating TGF-α-activated kinase 1 phosphorylation, increasing NF-κB (p65) levels to promote inflammation, up-regulating Bcl2-associated X expression, and down-regulating Bcl-2 expression to trigger apoptosis. In addition, the miR-29b-3p mimetic and TRAF3 siRNA in IEC-6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg.Conclusions and Implications: The miR-29b-3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease. [ABSTRACT FROM AUTHOR]

Background and Purpose: Dioscin shows potent effects against cancers. We aimed to elucidate its pharmacological effects and mechanisms of action on hepatocellular carcinoma (HCC) in vivo and in vitro.Experimental Approach: Effects of dioscin were investigated in SMMC7721 and HepG2 cells, diethylnitrosamine-induced primary liver cancer in rats, and cell xenografts in nude mice. Isobaric tags for relative and absolution quantitation (iTRAQ)-based proteomics was used to find dioscin's targets and investigate its mechanism.Key Results: In SMMC7721 and HepG2 cells dioscin markedly inhibited cell proliferation and migration, induced apoptosis, autophagy, and DNA damage. It inhibited DEN-induced primary liver cancer in rats, markedly changed body weights and restored levels of α fetoprotein, alanine transaminase, aspartate transaminase, γ-glutamyltransferase, alkaline phosphatase, and Ki67. It also inhibited growth of xenografts in mice. In SMMC7721 cells, 191 differentially expressed proteins were found after dioscin, based on iTRAQ-based assay. TP53-inducible glycolysis and apoptosis regulator (TIGAR) was identified as being significantly down-regulated by dioscin. Dioscin induced cell apoptosis, autophagy, and DNA damage via increasing expression levels of p53, cleaved PARP, Bax, cleaved caspase-3/9, Beclin-1, and LC3 and suppressing those of Bcl-2, p-Akt, p-mammalian target of rapamycin (mTOR), CDK5, p-ataxia telangiectasia-mutated gene (ATM). The transfection of TIGAR siRNA into SMMC7721 cells and xenografts in nude mice further confirmed that the potent activity of dioscin against HCC is evoked by adjusting TIGAR-mediated inhibition of p53, Akt/mTOR, and CDK5/ATM pathways.Conclusions and Implications: The data suggest that dioscin has potential as a therapeutic, and TIGAR as a drug target for treating HCC. [ABSTRACT FROM AUTHOR]

Background and Purpose: The aim of the present study was to investigate the effects and possible underlying mechanisms of dioscin against pancreatic cancer in vitro and in vivo.Experimental Approach: In vitro actions of dioscin on viability of ASPC-1 and PANC-1 cells, and in vivo effects to suppress the tumour growth of cell xenografts in nude mice were assessed. In addition, microRNA microarray analysis determined which microRNAs were affected by dioscin. The mechanisms underlying the actions of dioscin against pancreatic cancer were elucidated in terms of Akt1 and other proteins related to aopoptosis.Key Results: Dioscin markedly induced apoptosis and significantly suppressed the tumour growth of ASPC-1 and PANC-1 cell xenografts, in nude mice. Total of 107 microRNAs with differential changes were found, in which miR-149-3P targeted with Akt1 was markedly up-regulated by dioscin. Further studies showed that dioscin significantly down-regulated Akt1 levels, and thus induced cell apoptosis by increasing the levels of Bax, Apaf-1, cleaved caspase-3/9, cleaved PARP, suppressing Bcl-2 levels, and causing cytochrome c release. The effects of an inhibitor of miR-149-3P and of siRNA of testicular Akt1 suggested that dioscin showed excellent activity against pancreatic cancer via miR- 149-3P-mediated inhibition of Akt1 signalling pathway.Conclusions and Implications: Collectively, these findings confirmed the potent effects of dioscin against pancreatic cancer and also provided novel insights into the mechanisms of the compound as a potential candidate for the treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: We previously reported the effect of dioscin on human gastric carcinoma SGC-7901 cells, but its effects on other gastric cancers are still unknown.Purpose: The present paper aimed to demonstrate the activity of dioscin against human gastric carcinoma MGC-803 and MKN-45.Study Design: In our study, MGC-803 and MKN-45 cells were used to examine the effects of dioscin on human gastric carcinoma in vitro. The effects of dioscin against human gastric carcinoma in vivo were accomplished by the xenografts of MGC-803 cells in BALB/c nude mice.Methods: AO/EB and DAPI staining, TEM, single cell gel electrophoresis and flow cytometry assays were used in cell experiments. Then, an iTRAQ-based proteomics approach, DNA and siRNA transfection experiments were carried out for mechanism investigation.Results: In MGC-803 cells, dioscin caused DNA damage and mitochondrial change, induced ROS generation, Ca(2+) release and cell apoptosis, and blocked cell cycle at S phase. In vivo results showed that dioscin significantly suppressed the tumor growth of MGC-803 cell xenografts in nude mice. In addition, dioscin markedly inhibited cell migration, caused Cytochrome c release and adjusted mitochondrial signal pathway. Then, an iTRAQ-based proteomics approach was carried out and 121 differentially expressed proteins were found, in which five biomarkers associated with cell cycle, apoptosis and migration were evaluated. Dioscin significantly up-regulated the levels of GALR-2 and RBM-3, and down-regulated CAP-1, Tribbles-2 and CliC-3. Furthermore, overexpressed DNA transfection of CAP-1 enhanced cell migration and invasion, which was decreased by dioscin. SiRNA to Tribbles-2 affected the protein levels of Bcl-2, Bax and MAPKs, suggesting that dioscin decreased Tribbles-2 level leading to cell apoptosis.Conclusion: Our works confirmed the activity of dioscin against gastric cancer. In addition, this work also provided that dioscin is a new potent candidate for treating gastric cancer in the future. [ABSTRACT FROM AUTHOR]

ABSTRACT In the present study, the antiproliferative effect of dioscin on human gastric carcinoma SGC-7901 cells was confirmed by 3-(4, 5-dimethylthiahiazo-zyl)-2, 5-dip-henytetrazolium bromide and flow cytometry assays. Through acridine orange-ethidium bromide double fluorescent staining, apoptotic morphology of the cells was observed. Radioimmunoassays showed that the tumor necrosis factor (TNF)- α concentration in cells treated with dioscin significantly increased compared with untreated cells. Several proteins and mRNA related to the mitochondrial and death receptor pathways were investigated. We found that the expression of Bid, bcl-2 and bcl-xl was markedly downregulated, and the expression of Bak and Bax was upregulated. In addition, cytochrome c was released from the mitochondria into the cytosol, which indicates activation of the mitrochondrial pathway by dioscin. Furthermore, upregulation of Fas, FasL (Fas ligand), TNF- α, TNF receptor-1, TNF receptor-associated factor 1 and Fas-associated protein with death domain demonstrated involvement of the death receptor pathway. Increased mRNA expression of p53 was also found in dioscin-treated SGC-7901 cells, and the activation of caspase-3 and −8 was also observed. Consequently, this study clarifies the mechanism underlying the anticancer effect of dioscin, and also indicates that dioscin may be a potential drug treatment for human gastric cancer. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Dioscin Induces the Apoptosis of Human Cervical Carcinoma HeLa and SiHa Cells Through ROS-mediated DNA Damage, Cell Cycle Arrest and Mitochondrial Signaling Pathways. This error affects the flow cytometry data presented in Figure 8. Graph: Figure 8 (A) Dioscin-caused apoptosis in HeLa cells by flow cytometric analysis with Annexin V-FITC and PI-staining; (B) Dioscin-caused apoptosis in SiHa cells by flow cytometric analysis with Annexin V-FITC and PI-staining. [Extracted from the article]

Potent Effects of Flavonoid-Rich Extract from Rosa laevigata Michx Fruit against Hydrogen Peroxide-Induced Damage in PC12 Cells via Attenuation of Oxidative Stress, Inflammation and Apoptosis. This error affects the flow cytometry data for the model group presented in Figure 2A. We provide the correct figure below. 1 Liu M., Xu Y., Han X., Liang C., Yin L., Xu L., Qi Y., Zhao Y., Peng J., Sun C. Potent Effects of Flavonoid-Rich Extract from Rosa laevigata Michx Fruit against Hydrogen Peroxide-Induced Damage in PC12 Cells via Attenuation of Oxidative Stress, Inflammation and Apoptosis. [Extracted from the article]

We previously reported the promising effects of dioscin against liver injury, but its effect on liver fibrosis remains unknown. The present work investigated the activities of dioscin against liver fibrosis and the underlying molecular mechanisms. Dioscin effectively inhibited the cell viabilities of HSC-T6, LX-2 and primary rat hepatic stellate cells (HSCs), but not hepatocytes. Furthermore, dioscin markedly increased peroxisome proliferator activated receptor-γ (PPAR-γ) expression and significantly reduced a-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), collagen α1 (I) (COL1A1) and collagen α1 (III) (COL3A1) levels in vitro. Notably, dioscin inhibited HSCs activation and induced apoptosis in activated HSCs. In vivo, dioscin significantly improved body weight and hydroxylproline, laminin, α-SMA, TGF-β1, COL1A1 and COL3A1 levels, which were confirmed by histopathological assays. Dioscin facilitated matrix degradation, and exhibited hepatoprotective effects through the attenuation of oxidative stress and inflammation, in addition to exerting anti-fibrotic effects through the modulation of the TGF-β1/Smad, Wnt/β-catenin, mitogen-activated protein kinase (MAPK) and mitochondrial signaling pathways, which triggered the senescence of activated HSCs. In conclusion, dioscin exhibited potent effects against liver fibrosis through the modulation of multiple targets and signaling pathways and should be developed as a novel candidate for the treatment of liver fibrosis in the future. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Inflammatory reaction and cell apoptosis are two important processes in intestinal ischemia/reperfusion (II/R) injury, and exploration of effective lead compounds against II/R injury via regulating inflammation and apoptosis is critical important. In this paper, the results indicated that dioscin significantly increased cell viability, and inhibited inflammation and apoptosis caused by hypoxia-reoxygenation (H/R) injury in IEC-6 cells. in vivo II/R injury, dioscin markedly suppressed inflamma- tion and apoptosis, improved pathological changes, and depressed chiu' score in rats. Mechanistic studies indicated that dioscin notably up-regulated the expression level of MAPK13 through decreasing miR-351-5p level, and thereby decreased the expression levels of p-PKD1, NF-κB, Apaf-1, cleaved Caspase-3 and cleaved Caspase-9. Furthermore, miR-351-5p mimic and inhibitor experiments in IEC-6 cells further proved that dioscin up-regulated MAPK13 expression by decreasing miR-351-5p level to inhibit inflammation and apoptosis. Therefore, dioscin showed protective effect against II/R injury via adjusting miR-351-5/MAPK13-mediated inflammation and apoptosis. Dioscin should be considered as one potent candidate and miR-351-5/ MAPK13 should be one effective drug target for the treatment of II/R injury. [ABSTRACT FROM AUTHOR]

Abstract: The present study was to investigate the effects and possible mechanisms of the total saponins from Dioscorea nipponica Makino (TSDN) against CCl4-induced hepato-toxicity in mice. The mice were orally administrated with TSDN for seven days and then given CCl4 (0.3%, 10ml/kg i.p.). The results showed that TSDN significantly attenuated the activities of ALT and AST, consistent with hematoxylin–eosin staining. The ALP levels and relative liver weight were significantly decreased by TSDN compared with model group. Moreover, TSDN dramatically decreased MDA, iNOS and NO levels, while the levels of GSH, GSH-Px and SOD were increased. Further investigations showed that TSDN inhibited CCl4-induced metabolic activation and CYP2E1 expression, down-regulated the levels of MAPKs phosphorylation, NF-κB, HMGB1, COX-2 as well as effectively suppressed the expressions of Caspase-3, Caspase-9, PARP and Bak. Quantitative real-time PCR assay demonstrated that TSDN obviously decreased the gene expressions of TNF-a, IL-1β, IL-6, IL-10, Fas, FasL, Bax as well as modulated Bcl-2 mRNA level. This is the first time to report the protective actions of the TSDN against CCl4-induced liver damage in mice through suppression of inflammation and apoptosis. This natural product should be developed as a new drug for treatment of liver injury in future. [Copyright &y& Elsevier]