姜黄素激活Nrf2抗氧化系统缓解百草枯诱导的胰岛素抵抗

目的：观察姜黄素是否具有改善百草枯（ paraquat,PQ）所致氧化应激诱导的胰岛素抵抗作用并探讨其改善胰岛素抵抗的效应机理。方法将实验小鼠随机分成对照组（ Control组）,百草枯组（ PQ组）以及PQ加姜黄素组（ Cur组）。 PQ和Cur组连续腹腔注射百草枯7天造模成功后。 Cur组继续Cur灌胃干预。7天后,取胰岛素敏感组织肌肉,用蛋白免疫印迹方法（ Western blot,WB）检测蛋白水平和磷酸化变化,并检测脂质过氧化指标MDA。结果在PQ诱导的小鼠胰岛素抵抗模型中,姜黄素可改善小鼠葡萄糖耐量并对抗 PQ 所致的胰岛素信号蛋白 PKB－Ser473磷酸化损害;姜黄素还可明显降低肌肉MDA水平,激活小鼠Nrf2系统,促进Nrf2核转位和NQO－1的表达,同时能增强IкBα的水平,缓解氧化应激及炎症反应。结论姜黄素通过增强内源性Nrf2系统功能和胰岛素信号水平,对抗PQ诱导的氧化应激,是其缓解胰岛素抵抗的重要机理。     

姜黄素促进骨骼肌GLUT4转位改善糖尿病大鼠胰岛素抵抗

目的研究姜黄素对STZ诱导糖尿病大鼠骨骼肌胰岛素抵抗的影响及其机制。方法雄性SD大鼠腹腔注射STZ诱导糖尿病大鼠模型。成模大鼠分为糖尿病组(DM),糖尿病+姜黄素组(DM+Cur),糖尿病+缓冲液对照组(DM+NC)。以正常SD大鼠为正常对照组(NC)。DM+Cur组予姜黄素灌胃治疗,DM+NC组给予等体积缓冲液灌胃。连续给药12周。12周后检测血糖变化,高胰岛素-正葡萄糖钳夹试验检测外周胰岛素抵抗。实验结束处死大鼠,取骨骼肌提取总蛋白及细胞膜蛋白,Western blot法检测骨骼肌磷酸化PI3K及AKT和总PI3K及AKT水平,检测骨骼肌总GLUT4及细胞膜上GLUT4水平,免疫荧光检测骨骼肌细胞膜上GLUT4水平。多组间的比较采用单因素方差分析,评估PI3K、AKT磷酸化程度及GLUT4向细胞膜转位的变化。结果姜黄素治疗组血糖水平低于糖尿病组[(18.67±1.99对24.38±2.88)mmol/L,P<0.05],胰岛素抵抗较糖尿病组减轻[平均GIR(14.69±0.29对10.25±0.30)mg·kg-1·min-1,P<0.01],胰岛素信号通路中p-PI3K、p-AKT水平升高,GLUT4向细胞膜转位增多。结论姜黄素通过激活PI3K/AKT通路,促进GLUT4向细胞膜转位,增加骨骼肌葡萄糖摄取,最终改善胰岛素抵抗。     

姜黄素下调miR-155抑制缺血性脑卒中炎性应答的实验研究

目的分析姜黄素对缺血性脑卒中的抗炎作用,并探讨miR-155、Toll样受体4(TLR4信号通路是否参与该抗炎机制。方法线栓法建立Sprague Dawley大鼠大脑中动脉闭塞模型(MCAO),将大鼠分为假手术组(8例)、MCAO模型组(8例)、姜黄素治疗组(8例),检测大鼠梗死体积、miR-155 mRNA相对表达量以及TLR4蛋白表达情况,ELISA法检测大鼠肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)、白介素-1β(IL-1β)表达。结果姜黄素显著改善MCAO大鼠脑梗死体积、神经系统功能评分以及运动功能(P<0.05),可显著降低MCAO大鼠miR-155mRNA、TLR4蛋白以及炎性因子TNF-α、IL-6、IL-1β的表达(均P<0.05)。结论姜黄素主要通过下调miR-155/TLR4信号通路抑制缺血性脑卒中的炎性应答。     

姜黄素对肝星状细胞增殖与凋亡的影响

目的　观察姜黄素对体外培养肝星状细胞 (HSC)增殖与凋亡的影响。方法　不同浓度姜黄素处理HSC株HSC T6 ,MTT法检测细胞增殖 ,流式细胞仪、透射电镜和琼脂糖凝胶电泳法检测细胞凋亡。结果　在 2 0～ 10 0 μmol/L浓度范围内 ,姜黄素可剂量依赖性地抑制HSC增殖 (P <0 .0 1)。 2 0、4 0、6 0 μmol/L姜黄素处理HSC 2 4h后 ,细胞周期分析发现S期细胞减少 ,G2 /M期细胞显著增加 (P <0 .0 1) ;流式细胞术检测到明显的亚G1峰 ,各组的凋亡指数 (% )分别是 15 .3± 1.9,2 6 .7± 2 .8,37.6± 4 .4 ,与对照组 (1.9± 0 .6 )相比 ,差异有显著性 (P <0 .0 1) ;4 0 μmol/L姜黄素作用 12、2 4、36、4 8h ,凋亡指数 (% )分别是 12 .0± 2 .4、2 6 .7± 3.5、33.8± 1.8和 4 9.3± 1.6 ,与对照组相比 ,差异有显著性 (P <0 .0 1) ;透射电镜观察到细胞皱缩、核染色质浓缩沿核膜排列和凋亡小体形成等 ;琼脂糖凝胶电泳可见到明显的DNA梯带形成。结论　姜黄素可显著抑制HSC增殖 ,使细胞周期停滞于G2 /M期 ,并诱导其凋亡 ,其作用具有时间和剂量依赖性     

Selective phytochemicals targeting pancreatic stellate cells as new anti-fibrotic agents for chronic pancreatitis and pancreatic cancer

Activated pancreatic stellate cells (PSCs) have been widely accepted as a key precursor of excessive pancreatic fibrosis, which is a crucial hallmark of chronic pancreatitis (CP) and its formidable associated disease, pancreatic cancer (PC). Hence, anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs. Most of the anti-fibrotic agents have been limited to phase I/II clinical trials involving vitamin analogs, which are abundant in medicinal plants and have proved to be promising for clinical application. The use of phytomedicines, as new anti-fibrotic agents, has been applied to a variety of complementary and alternative approaches. The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents, including curcumin, resveratrol, rhein, emodin, green tea catechin derivatives, metformin, eruberin A, and ellagic acid, in combating PSC in CP and PC models. It aimed to describe the mechanism(s) of the phytochemicals used, either alone or in combination, and the associated molecular targets. Most of them were tested in PC models with similar mechanism of actions, and curcumin was tested intensively. Future research may explore the issues of bioavailability, drug design, and nano-formulation, in order to achieve successful clinical outcomes with promising activity and tolerability.     

The efficacy of high- and low-dose curcumin in knee osteoarthritis: A systematic review and meta-analysis

ObjectivesThe aim of this study was to critically appraise and evaluate effects of low- and high-dose curcuminoids on pain and functional improvement in patients with knee osteoarthritis (OA) and to compare adverse events (AEs) between curcuminoids and non-steroid anti-inflammatory drugs (NSAIDs).MethodsWe systematically reviewed all randomized controlled trials (RCTs) on curcuminoids in knee osteoarthritis from the PubMed, Embase, Cochrane Library, AMED, Cinahl, ISI Web of Science, Chinese medical database, and Indian Scientific databases from inception to June 21, 2021.ResultsWe included eleven studies with a total of 1258 participants with primary knee OA. The meta-analysis results showed that curcuminoids were significantly more effective than comparators regarding visual analogue scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scores. However, no significant difference in pain relief or AEs between the high-dose (daily dose ≥1000 mg or total dose ≥42 gm) and low-dose (daily dose <1000 mg or total dose <42 gm) curcuminoid treatments was observed. When comparing curcumininoids versus NSAIDs, a significant difference in VAS pain was found. For AE analysis, three of our included studies used NSAIDs as comparators, with all reporting higher AE rates in the NSAID group, though significance was reached in only one study.ConclusionsThe results of our meta-analysis suggest that low- and high-dose curcuminoids have similar pain relief effects and AEs in knee OA. Curcuminoids are also associated with better pain relief than NSAIDs; therefore, using curcuminoids as an adjunctive treatment in knee OA is recommended.     

Immunomodulatory Effects of Curcumin

Curcumin (diferuloylmethane), found in the spice turmeric, exhibits anti-inflammatory, antioxidant, and chemopreventive activities. However, the effect of curcumin on the immunological responses largely remains unknown. In this study we have investigated the effect of curcumin on mitogen (phytohaemagglutinin; PHA) stimulated T-cell proliferation, natural killer (NK) cell cytotoxicity, production of cytokines by human peripheral blood mononuclear cells (PBMCs), nitric oxide (NO) production in mouse macrophage cells, RAW-264.7. Furthermore, we have carried out an electromobility shift assay to elucidate the mechanism of action of curcumin at DNA protein interaction level. We observed that curcumin inhibits PHA-induced T-cell proliferation, interleukin-2 production, NO generation, and lipopolysachharide-induced nuclear factor-κB (NF-κB) and augments NK cell cytotoxicity. Our results suggest that curcumin most likely inhibits cell proliferation and cytokine production by inhibiting NF-κB target genes involved in the induction of these immune parameters.     

Photodynamic inactivation of Streptococcus mutans by curcumin in combination with EDTA

ObjectiveThis study aimed to test the efficacy of photodynamic inactivation (PDI) mediated by curcumin with EDTA against Streptococcus mutans in planktonic suspension using blue LED light.MethodsAntibacterial activity of curcumin and EDTA was evaluated by determination of their minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The fractional inhibitory concentration index (FICI) was used to estimate the synergistic effect of various combination ratios of curcumin and EDTA against S. mutans. Cultures of S. mutans (18 h, 37 °C, 5% C0₂) were prepared to test the effect of curcumin-mediated PDI (50 μM and 500 μM) with or without 0.4% EDTA and 40 s of light-activation with blue light. EDTA and each concentration of curcumin were also tested individually. Chlorhexidine (0.2%), was used as positive control. Planktonic suspensions were also analyzed by viable colony counts (VCC), confocal laser scanning microscopy (CLSM), transmission electron microscopy (TEM), and polymerase chain reaction (PCR).ResultsThe MIC values of curcumin and EDTA were 5 mM and 0.125% respectively. FICI showed a synergistic interaction between curcumin and EDTA. All the combinations with curcumin and blue LED light resulted in a complete inactivation of the S. mutans and CLSM confirms these results, TEM showed morphological changes produced by the PDI. No damage on DNA structure was detected by PCR.SignificanceCurcumin-mediated PDI with EDTA using a blue light, shows a strong inhibitory effect against S. mutans in planktonic culture. Because of the unspecific target mechanism, it could be a promising technique for disinfection of dental tissues.