Resveratrol attenuates high-fat diet-induced non-alcoholic steatohepatitis by maintaining gut barrier integrity and inhibiting gut inflammation through regulation of the endocannabinoid system

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Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.     

白藜芦醇抑制胶质瘤细胞生长与诱导细胞凋亡实验研究

目的探讨白藜芦醇(Res)对脑胶质瘤细胞(C6细胞株)和正常成纤维细胞(3T3细胞株)体外增殖的影响,进而观察Res诱导C6和3T3细胞系的凋亡作用.方法用不同浓度的Res处理C6和3T3细胞,以四甲基偶氮唑蓝(MTT)比色法检测Res对C6和3T3细胞的增殖作用,通过HE染色、扫描电子显微镜(SEM)、原位末端标记法(TUNEL)和流式细胞仪Annexin Ⅴ荧光染色,观察细胞的形态学结构改变,并定量检测细胞凋亡.结果 Res抑制了C6细胞的生长与增殖( P < 0.01 ),呈浓度依赖性反应;Res能明显诱导C6细胞凋亡,经210 μmol/L、120 μmol/L Res处理24 h后及对照组的C6细胞,其凋亡率分别为29.7%、14.6%及2.1%;相应的3T3细胞凋亡率分别为4.3%、3.5%、2.6%. 结论 Res能通过诱导C6细胞凋亡而抑制其生长与增殖,但对3T3细胞无此作用.本研究为临床应用Res治疗脑胶质细胞瘤提供了实验依据.     

白藜芦醇诱导人胃癌原代细胞裸鼠移植瘤凋亡的研究

目的：探讨白藜芦醇诱导人胃癌原代细胞裸鼠移植瘤凋亡的机制。 方法： 建立人胃癌原代细胞裸鼠移植瘤模型，采用瘤旁注射的方法，用不同剂量的白藜芦醇进行治疗，并设对照，用透射电镜和TUNEL法检测肿瘤组织细胞凋亡情况，免疫组织化学法和RT-PCR法检测肿瘤组织的凋亡相关基因bcl-2和bax的表达情况。 结果： 白藜芦醇对胃癌原代细胞移植瘤有明显的抑制作用； 透射电镜和TUNEL法发现白藜芦醇导致移植瘤内大量细胞发生凋亡；免疫组织化学法发现白藜芦醇注射组的Bcl-2蛋白阳性细胞率（3.92％±0.85％、5.70％±0.84％和11.86％±0.97％）明显低于两个对照组（P<0.05），两个对照组（27.56％±1.40％和29.48％±0.51％）之间无显著差异；Bax蛋白阳性细胞率（52.30％±1.54％、45.72％±0.88％和40.02％±1.20％）明显高于两个对照组（P<0.05），两个对照组（20.88％±0.91％和19.34％±0.35％）之间无显著差异； RT-PCR法发现白藜芦醇注射组的bcl-2 mRNA条带强度随剂量的增大而递减，并明显低于两个对照组（P<0.05），两个对照组之间无显著差异（P>0.05）；bax mRNA条带强度递增，并明显高于两个对照组（P<0.05），两个对照组之间无显著差异（P>0.05）。 结论： 白藜芦醇对胃癌原代细胞移植瘤有明显的抑制作用，通过下调bcl-2 的表达和上调bax 的表达而诱导胃癌裸鼠移植瘤细胞发生凋亡，是其抗胃癌作用的机制之一。     

白藜芦醇诱导胃癌原代细胞凋亡(英文)

目的：探讨白藜芦醇诱导胃癌原代细胞发生凋亡的可能性，揭示该凋亡发生与Bcl-2和Bax之间的关系。 方法： 在体外实验中，采用MTT比色法测定白藜芦醇对胃癌原代细胞的生长抑制率；以透射电镜和TUNEL 染色法，定性、定量地研究白藜芦醇与胃癌原代细胞凋亡的关系；通过免疫组织化学法和RT-PCR检测凋亡相关基因bcl-2和bax的表达。 结果： 白藜芦醇对胃癌原代细胞生长有明显抑制作用，随白藜芦醇浓度增加和培养时间的延长而增强；白藜芦醇诱导胃癌原代细胞出现典型的凋亡细胞形态；TUNEL 染色法可见，经白藜芦醇处理24 h、48 h、72 h、96 h后，胃癌原代细胞凋亡数明显随时间增加。免疫组化发现经白藜芦醇处理24 h、48 h、72 h、96 h后，胃癌原代细胞的Bcl-2蛋白阳性率减少，Bax蛋白阳性率增加。经白藜芦醇处理24、48、72、96 h后，RT-PCR检测发现胃癌原代细胞bcl-2和bax的mRNA表达阳性，并显示bcl-2 mRNA条带密度随时间的延长而递减，bax mRNA条带密度随时间的延长而增强。 结论： 白藜芦醇可能通过下调bcl-2的表达和上调bax的表达而诱导胃癌原代细胞发生凋亡。     

白藜芦醇通过Fas依赖途径诱导K562细胞凋亡

目的探讨白藜芦醇对K562细胞的凋亡诱导效应和可能的作用机制。方法应用噻唑蓝(MTT)比色法、WrightGiemsa染色、DNA琼脂糖凝胶电泳和细胞周期分析法检测K562细胞凋亡；采用流式细胞术(FCM)测定细胞Fas蛋白表达水平；采用RT-PCR法检测Caspase-3 mRNA表达水平，采用比色法检测Caspase-3活性。结果白藜芦醇可抑制K562细胞增殖，并呈现典型的凋亡形态改变；DNA电泳可见明显的梯状条带；细胞周期分析显示S期细胞数明显增多，出现S／G2期阻滞。40μmol／L白藜芦醇作用48h到72h后，Fas阳性率由4．1％上升到45．6％；Caspase-3 mRNA表达水平明显升高，活性明显增强。结论白藜芦醇通过Fas依赖性Caspase-3激活途径诱导K562细胞凋亡。     

白藜芦醇抑制胆囊癌细胞生长与诱导细胞凋亡的实验研究

目的:探讨白藜芦醇(Res)对胆囊癌细胞(GBC)和正常成纤维细胞(3T3)体外增殖的影响,进而观察Res对GBC和3T3细胞凋亡的影响.方法:MTT法测定肿瘤细胞生长抑制率;流式细胞术分析细胞周期,检测细胞凋亡;SABC法检测细胞bcl-2、c-myc、p53蛋白表达.结果:Res呈浓度依赖性抑制GBC细胞的生长与增殖(P＜0.01),抑制率最高可达54%.Res能明显诱导GBC细胞凋亡,凋亡率最高为30.52%;处理组较对照组G1期细胞由34.88%上升至55.47±3.95%,S期细胞减少8.41%～17.54%,呈明显的G0/G1期阻滞现象.GBC细胞的bcl-2、c-myc基因蛋白表达降低,而p53基因蛋白表达增强.结论:Res能通过诱导GBC细胞凋亡而抑制其生长与增殖,但对3T3细胞无此作用.     

Resveratrol attenuates cisplatin renal cortical cytotoxicity by modifying oxidative stress

Cisplatin, a cancer chemotherapy drug, is nephrotoxic. The aim of this study was to investigate whether resveratrol (RES) reduced cisplatin cytotoxicity and oxidative stress. Rat renal cortical slices were pre-incubated 30 min with 0 (VEH, ethanol) or 30 μg/ml RES followed by 60, 90 or 120 min co-incubation with 0, 75, or 150 μg/ml cisplatin. Lactate dehydrogenase (LDH) leakage was unchanged at 60 and 90 min by cisplatin. Cisplatin increased (p < 0.05) LDH leakage at 120 min which was protected by RES. Cisplatin induced oxidative stress prior to LDH leakage as cisplatin depressed glutathione peroxidase and superoxide dismutase (SOD) activity, increased lipid peroxidation, protein carbonyls and 4-hydroxynonenal (4-HNE) adducted proteins within 60 min. RES failed to reverse glutathione (GSH) depression by cisplatin. In order to eliminated an extracellular interaction between RES and cisplatin, additional studies (RINSE studies) allowed a 30 min RES uptake into slices, transfer of slices to buffer lacking RES, followed by 120 min cisplatin incubation. RES in the RINSE studies prevented LDH leakage by cisplatin indicating that RES protection was not via a physical interaction with cisplatin in the media. These findings indicate that RES diminished cisplatin in vitro renal toxicity and prevented the development of oxidative stress.     

Effect of resveratrol and rosuvastatin on experimental diabetic nephropathy in rats

The development of diabetic nephropathy (DN) relays mainly on control of blood glucose and restrains hyperglycemic-induced oxidative stress. Hence, the effect administration of resveratrol (RSV) (5 mg/kg) alone or in combination with rosuvastatin (RSU) (10 mg/kg) on development and progression of diabetic nephropathy (DN) was evaluated. Oral treatment of diabetic rats with RSV alone or co-administered with RSU improved renal dysfunction indicated by a significant decrease in serum creatinine, urinary protein and urinary TGF-β1 when compared with diabetic control rats. Also, a significant increase in body weight, relative kidney weight with a significant decrease in serum glucose and glycated hemoglobin in diabetic treated groups when compared with diabetic control group. Hyperglycemic-induced oxidative stress in diabetic control rats indicated by a significant decrease in renal activities of catalase, superoxide dismutase, glutathione peroxidase and reduced glutathione level with a significant increase in malondialdehyde levels. However, oral treatment of diabetic rats with RSV alone or co-administered with RSU improved the antioxidant status back to control values. Similarly, mRNA analysis of quantitative real time-PCR substantiated that RSV with RSU notably normalizes the renal expression of TGF-β1, fibronectin, NF-κB/p65, Nrf2, Sirt1 and FoxO1 in the diabetic group of rats. The histopathological observations of the combined treated diabetic rats effectively protect the kidneys from hyperglycemic-induced oxidative damage. These findings confirmed the renoprotective effects of RSV with RSU treatment through improving glycemic control and attenuating oxidative stress damage in renal tissues of diabetic rats.