Aqueous extract of clove inhibits tumor growth by inducing autophagy through AMPK/ULK pathway

Cloves (Syzygium aromaticum), a traditional Chinese medicinal herb, displays broad biological activity. In the present study, the aqueous extract of clove (AEC) was prepared, and its anticancer affects were studied. 3‐(4,5‐Dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetra‐zolium (MTS) analysis revealed that AEC was able to inhibit cancer cell growth in vitro on several cancer cell lines; the IC₅₀ is around 150 μg/ml for human pancreatic ASPC‐1 and human colon HT‐29 cancer cells. Treatment of the cancer cells with AEC also diminished the colony formation significantly in both human pancreatic ASPC‐1 cancer cells and human colon HT‐29 cancer cells. In vivo study revealed that AEC inhibited the tumor growth significantly in HT‐29 xenograft mice model. Transmission electron microscope, flow cytometry assay, and fluorescence microscope analysis confirmed that AEC is capable of inducing cell autophagy. Further study showed that AMPK/ULK pathway plays an important role in AEC‐induced autophagy in cancer cells. Analysis of AEC components was performed by liquid chromatograph mass spectrometer approach, and more than nine constitutes were identified in AEC fraction. The study provides evidence that AEC has potential to be developed as a novel anticancer agent or as an adjuvant in cancer chemotherapy.     

迷迭香酸通过AMPK/mTOR通路减轻新生大鼠缺血缺氧性脑损伤研究

目的 探讨迷迭香酸对新生大鼠缺血缺氧脑损伤（hypoxic-ischemic encephalopathy,HIE）的影响,及其对单磷酸腺苷活化蛋白激酶（adenosine monophosphate activated protein kinase,AMPK）/雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）通路的调控作用,初步探讨其脑保护机制。方法 取7 d龄SD新生大鼠,随机分为对照组、模型组、迷迭香酸（300 mg/kg）组、AMPK/mTOR激动剂MT6378（10 mg/kg）组、AMPK抑制剂GSK-690693（30 mg/kg）组和迷迭香酸（300 mg/kg）+MT6378（10 mg/kg）组,每组20只。建立HIE模型,给予相应药物进行干预,采用TTC染色法检测大鼠脑梗死情况;透射电镜（TEM）观察大鼠海马神经元结构损伤及自噬状况;免疫荧光法检测大鼠海马神经元自噬标记物微管相关蛋白1轻链3B（microtubule-associated protein 1 light chain 3B,LC3B）阳性表达;TUNEL法检测大鼠海马神经元凋亡率;免疫组化法检测大鼠海马神经元磷酸化AMPK（p-AMPK）阳性表达;Western blotting检测大鼠海马组织活化的半胱氨酸蛋白酶3（cleaved Caspase-3）、mTOR及其磷酸化蛋白（p-mTOR）、Unc-51样自噬激活激酶1（uncoordinated-51 like autophagy activating kinase 1,Ulk1）及其磷酸化蛋白（p-Ulk1）、LC3B表达。结果 与对照组相比,模型组大鼠脑梗死严重,海马神经元结构损伤及自噬空泡形成较多,细胞自噬及凋亡水平升高,AMPK/mTOR通路活化（P<0.05）。与模型组相比,迷迭香酸组及GSK-690693组大鼠脑梗死、海马神经元结构损伤、凋亡及自噬减弱,AMPK/mTOR通路被抑制（P<0.05）;MT6378组海马组织AMPK/mTOR通路进一步激活,大鼠脑梗死、海马神经元结构损伤、凋亡及自噬进一步加重（P<0.05）;MT6378可逆转迷迭香酸的上述作用（P<0.05）。结论 迷迭香酸可能通过抑制AMPK/mTOR通路激活,降低海马神经元自噬及凋亡进程,发挥抗HIE脑损伤作用。     

基于AMPK/mTOR自噬通路研究甘草酸二铵对柯萨奇病毒B3病毒性心肌炎小鼠的保护作用

目的 基于单磷酸腺苷活化蛋白激酶（adenosine monophosphate-activated protein kinase,AMPK）/哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,m TOR）自噬通路探究甘草酸二铵（diammonium glycyrrhizinate,DG）对病毒性心肌炎（viral myocarditis,VMC）小鼠心肌的保护作用及机制。方法 50只BALB/c小鼠随机分为对照组、模型组、DG(19.5mg/kg)组、DG(19.5 mg/kg)+Compound C(20 mg/kg)组和DG(19.5 mg/kg)+Compound C(20 mg/kg)+雷帕霉素（2.0 mg/kg）组,每组10只。采用试剂盒检测血清中肌酸激酶同工酶（creatine kinase-MB,CK-MB）活性、心肌钙蛋白Ⅰ（cardiac troponinⅠ,c TnⅠ）水平及心肌组织中白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)水平;...     

金匮肾气丸通过AMPK/mTOR途径抑制肺组织细胞凋亡和自噬在大鼠慢性阻塞性肺疾病中的作用

[目的] 探究金匮肾气丸对慢性阻塞性肺疾病（COPD）的作用及其可能的作用机制。[方法] 40只SD大鼠随机分为空白对照组、COPD组、金匮肾气丸3.7 g/kg组、金匮肾气丸7.4 g/kg组和地塞米松组,每组各8只。除空白对照组外,其余组大鼠采用烟熏联合气管内滴注脂多糖（LPS）法建立COPD大鼠模型。各组给予相应药处理AniRes2005动物肺功能分析系统检测大鼠肺功能;酶联免疫吸附（ELISA）试剂盒检测白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-17（IL-17）水平;苏木精-伊红（HE）染色检测肺组织病理学变化;TUNEL染色检测肺组织细胞凋亡;蛋白质免疫印迹（Western blot）检测自噬及磷酸腺苷活化蛋白激酶（AMPK）/哺乳动物雷帕霉素靶蛋白（mTOR）途径相关蛋白的表达。[结果] 与空白对照组相比,COPD组大鼠肺功能降低,IL-1β、TNF-α、IL-6和IL-17水平明显升高（P<0.05）,炎症评分、细胞凋亡率和LC3Ⅱ/LC3Ⅰ、Beclin1、p-AMPK/AMPK蛋白表达水平明显升高（P<0.05）,p62和p-mTOR/mTOR蛋白表达水平明显降低（P<0.05）;与COPD组相比,金匮肾气丸3.7 g/kg组、金匮肾气丸7.4 g/kg组和地塞米松组大鼠肺功能升高,IL-1β、TNF-α、IL-6和IL-17水平明显降低（P<0.05）,炎症评分、细胞凋亡率和LC3Ⅱ/LC3Ⅰ、Beclin1、p-AMPK/AMPK蛋白表达水平明显降低（P<0.05）,p62和p-mTOR/mTOR蛋白表达水平明显升高（P<0.05）。[结论] 金匮肾气丸可能通过AMPK/mTOR途径抑制肺组织细胞凋亡和自噬,延缓大鼠慢性阻塞性肺疾病进展。     

Jian-Gan-Xiao-Zhi decoction ameliorates high-fat high-carbohydrate diet-induced non-alcoholic fatty liver disease and insulin resistance by regulating the AMPK/JNK pathway

Background:Non-alcoholic fatty liver disease(NAFLD)can cause insulin resistance(IR)and diabetes.Our previous studies have demonstrated that Jian-Gan-Xiao-Zhi decoction(JGXZ)could be effective for the treatment of NAFLD and IR.However,the possible mechanism underlying the effects of JGXZ on NAFLD and IR remains unknown.Methods:Fifty rats received a high-fat high-carbohydrate(HFHC)diet for 12 weeks to induce NAFLD.After 4 weeks of HFHC treatment,rats were orally treated with JGXZ(8,16,and 32 g/kg weight)for 8 weeks.Ten rats in the control group received standard chow.In the positive control group,rats were orally treated with metformin(90 mg/kg weight)for 8 weeks.After JGXZ and metformin treatment,H&E staining was conducted on rat livers and serum biochemical markers,including alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),and total cholesterol(TC),were measured using test kits.Moreover,a fasting blood glucose test and an oral glucose tolerance test(OGTT)were conducted.Serum levels of insulin were determined using ELISA kit,and the homeostatic model assessment of insulin resistance(HOMA-IR)was calculated.The levels of total insulin receptor substrate-1(IRS1),AMP-activated protein kinase-α(AMPKα)and c-Jun N-terminal kinase(JNK)as well as the levels of phosphorylation of IRS1(p-IRS1),phosphorylation of AMPK(p-AMPK)and phosphorylation of JNK(p-JNK)were measured using western blotting.Results:The body weights in JGXZ low-,middle-,and high-dose groups were lower than those in the model group(P<0.05,P<0.01,P<0.01,respectively).The serum levels of AST(P<0.05 in JGXZ middle-and high-dose groups),ALT(P<0.01 in JGXZ middle-dose group and P<0.05 in JGXZ high-dose group),TG(P<0.01 in JGXZ middle-and high-dose groups),and TC(P<0.01)upon JGXZ treatment were lower those than in NAFLD model rats.H&E staining showed that JGXZ treatment reduced steatosis of the hepatocytes in NAFLD model rats.JGXZ decreased the levels of fasting blood glucose(P<0.01),HOMA-IR(P<0.01),AUC(area under the curve)of the OGTT(P<0.05)and p-IRS1(P<0.01 in JGXZ middle-and high-dose groups,P<0.05 in JGXZ low-dose groups).Moreover,JGXZ regulated the hepatic AMPKα/JNK pathway in NAFLD model rats,which reflected the induction of p-AMPKαand inhibition of p-JNK.Conclusion:This study showed that JGXZ improved liver function and reduced steatosis of the hepatocytes in NAFLD model rats.Moreover,JGXZ improved IR in NAFLD model rats.The possible mechanism underlying the effects of JGXZ on NAFLD and IR involves the modulation of the AMPK/JNK pathway.     

中医分期论治非酒精性脂肪性肝病探微

论述中医分期辨治非酒精性脂肪性肝病经验。认为早期以肝郁脾虚为主,治宜疏肝健脾、理气化痰;中期以湿热蕴结为主,治宜清热利湿、软坚化痰;晚期以毒瘀阻络为主,治宜化痰解毒通络、兼顾扶正。     

Quercetin improves nonalcoholic fatty liver by ameliorating inflammation,oxidative stress,and lipid metabolism in db/db mice

Multiphase pathological processes involve in Type 2 diabetes (T2DM)‐induced nonalcoholic fatty liver disease (NAFLD). However, the therapies are quite limited. In the present study, the hepatoprotective effects and underlying mechanisms of quercetin in T2DM‐induced NAFLD were investigated. T2DM‐induced NAFLD and quercetin treatment models were established in vivo and in vitro. The results revealed that quercetin alleviated serum transaminase levels and markedly reduced T2DM‐induced histological alterations of livers. Additionally, quercetin restored superoxide dismutase, catalase, and glutathione content in livers. Not only that, quercetin markedly attenuated T2DM‐induced production of interleukin 1 beta, interleukin 6, and TNF‐α. Accompanied by the restoration of the increased serum total bile acid (p = .0001) and the decreased liver total bile acid (p = .0005), quercetin could reduce lipid accumulation in the liver of db/db mice. Further mechanism studies showed that farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathways was involved in quercetin regulation of lipid metabolism in T2DM‐induced NAFLD. In high D‐glucose and free fatty acid cocultured HepG2 cells model, quercetin eliminated lipid droplets and restored the upregulated total cholesterol and triglyceride levels. Similar to the findings in mice, quercetin could also activate farnesoid X receptor 1/Takeda G‐protein‐coupled receptor 5 signaling pathway. These findings suggested that quercetin might be a potentially effective drug for the treatment of T2DM‐induced NAFLD.     

Scutellarin,a modulator of mTOR,attenuates hepatic insulin resistance by regulating hepatocyte lipid metabolism via SREBP‐1c suppression

High levels of consumption of saturated lipids have been largely associated with the increasing prevalence of metabolic diseases. In particular, saturated fatty acids such as palmitic acid (PA) have been implicated in the development of insulin resistance (IR). Scutellarin (Scu) is one of the effective traditional Chinese medicines considered beneficial for liver diseases and diabetes. In this study, we investigated the effect of Scu on IR and lipid metabolism disorders in vitro and in high fat diet (HFD)‐fed mice. In vitro, we found that Scu decreased insulin‐dependent lipid accumulation and the mRNA expression of CD36, Fasn, and ACC in PA‐treated HepG2 cells. Additionally, Scu upregulated Akt phosphorylation and improved the insulin signalling pathway. Moreover, Scu downregulated mammalian target of rapamycin (mTOR) phosphorylation and the n‐SREBP‐1c protein level and also reduced lipid accumulation via the mTOR‐dependent pathway, as confirmed by the molecular docking of Scu to mTOR. In HFD‐fed C57BL/6 mice, Scu improved oral glucose tolerance, pyruvate tolerance and the IR index and also increased the Akt phosphorylation level. Moreover, Scu reduced hepatocyte steatosis, decreased lipid accumulation and triglyceride levels, inhibited mTOR phosphorylation, and decreased the SREBP‐1c level in the liver. Taken together, these findings suggest that Scu ameliorates hepatic IR by regulating hepatocyte lipid metabolism via the mTOR‐dependent pathway through SREBP‐1c suppression.     

九味肝泰胶囊对高脂饮食诱导大鼠非酒精性脂肪肝的治疗作用

目的研究九味肝泰胶囊对高脂饮食诱导的大鼠非酒精性脂肪性肝病(NAFLD)的治疗作用和可能机制。方法采用高脂饮食诱导大鼠NAFLD动物模型。设对照组,模型组,水飞蓟素阳性对照组(0.05 g/kg),九味肝泰胶囊高、中、低剂量(1.80、0.90、0.45g/kg)组。除对照组给予普通饲料饲养外,其他各组以高脂饲料喂养,饲养10周。从第5周开始,4个给药组分别ig给予相应药物,共给药6周。观察和检测大鼠体质量、肝湿质量、肝脏指数和肝脏形态学变化;检测血清中的高密度脂蛋白-胆固醇(HDL-C)、游离脂肪酸(FFA)、天冬氨酸转氨酶(AST)、丙氨酸转氨酶(ALT)水平;检测肝脏组织中总胆固醇(TC)、三酰甘油(TG)、超氧化物歧化酶(SOD)、丙二醛(MDA)水平。结果与模型组比较,九味肝泰胶囊高、中剂量组能显著降低NAFLD大鼠血清中的FFA、AST、ALT水平(P0.05),升高HDL-C水平(P0.05);显著降低NAFLD大鼠肝脏组织中的TC、TG、MDA水平(P0.05),升高SOD的活性(P0.05);NAFLD大鼠的肝组织病理学形态均得到不同程度改善,大鼠肝组织脂肪变程度减轻。结论九味肝泰胶囊对NAFLD大鼠具有调节脂质和保护肝脏的作用,其作用机制可能与减少脂质在肝脏的沉积、减轻过氧化损伤有关。     

化滞柔肝颗粒治疗非酒精性脂肪性肝病疗效观察

目的观察化滞柔肝颗粒治疗非酒精性脂肪性肝病（NAFLD）的临床疗效。方法将60例NAFLD患者随机分为2组,对照组30例口服水飞蓟宾葡甲胺片,治疗组30例口服化滞柔肝颗粒,2组均治疗12周。比较2组患者治疗前后症状积分、血清肝酶、血脂、体质量指数和肝脏B超分度情况。结果治疗组总有效率为87％,对照组为67％,2组比较差异有统计学意义（P〈0．05）;治疗组症状积分、体质量指数、血脂和肝脏B超分度改善情况均明显优于对照组（P均〈0．05）;2组治疗后肝功能均有改善,但组间比较差异无统计学意义（P〉0．05）。结论化滞柔肝颗粒治疗NAFLD疗效较好,其疗效机制有待进一步探讨。     

健肝降脂汤治疗非酒精性脂肪肝的疗效观察

[目的]观察健肝降脂汤治疗非酒精性脂肪肝的临床疗效.[方法]将确诊为非酒精性脂肪肝的120例患者,随机分为两组,治疗组给予健肝降脂汤1剂/d,水煎服300mL,早晚分服.对照组给予多稀磷酸酰胆碱胶囊2粒,3次/d,口服.两组疗程均为3个月,观察治疗前后患者症状变化、肝功能、血脂、肝脏彩超变化.[结果]治疗组达到临床基本治愈者39例,好转14例,无效6例,总有效率为88.3%.对照组分别为17例,23例,20例,总有效率为68.3%.两组总有效率比较有显著性差异(P＜0.01).[结论]健肝降旨汤能有效地降低血脂,改善肝功能,改善肝脏影像学变化,对非酒精性脂肪肝有确切疗效.     

罗格列酮对高脂饮食诱导非酒精性脂肪肝大鼠脂肪因子的影响

目的观察罗格列酮对高脂饮食诱导的非酒精性脂肪肝大鼠血清中脂肪因子的影响及肝脏保护作用。方法将40只SD大鼠分为对照组、模型组和治疗组。对照组予基础饲料,其余2组予高脂饲料喂养,其中治疗组从第9周开始予罗格列酮5 mg/(kg.d)灌胃,各组均喂养16周。于16周末处死大鼠,称肝脏及脂肪质量,计算肝指数;肝脏组织制作石蜡切片行HE染色;用ELISA法检测各组大鼠血清中抵抗素、瘦素、脂联素水平。结果模型组与对照组相比,肝指数增高,血清中瘦素及抵抗素水平显著升高,光镜下肝脏出现明显脂肪变性及纤维化;治疗组与模型组比较,肝指数降低,光镜下的肝脏脂肪变性及纤维化明显改善,血清中脂联素水平明显上升;但与对照组比较,肝指数仍然显著升高,肝组织中仍有脂肪变性及纤维化,瘦素及抵抗素水平仍有所升高。结论罗格列酮可以显著改善高脂饮食诱导的肝脏脂肪变性,并且对脂肪因子有显著影响。     

中药活性成分治疗非酒精性脂肪肝作用靶点的研究进展

非酒精性脂肪肝是一种与胰岛素抵抗和遗传易感密切相关的代谢应激性肝脏损伤。近年来中药治疗非酒精性脂肪肝的研究越来越多,研究结果表明中药活性成分治疗非酒精性脂肪肝的作用机制与其激活AMPK信号通路,改善胰岛素抵抗,调节PPARγ活性和表达,抗氧化应激,抗炎,调节肠道菌群等有关。该文将归纳总结近年来中药治疗非酒精性脂肪肝的作用靶点,为今后非酒精性脂肪肝的中医药治疗提供新的思路。     

Ginkgo biloba extract protects against diabetic cardiomyopathy by restoring autophagy via adenosine monophosphate-activated protein kinase/mammalian target of the rapamycin pathway modulation

Studies demonstrated that Ginkgo biloba extract (GBE) played a cardioprotective role in diabetic conditions. Impaired autophagy is one of the mechanisms underlying diabetic cardiomyopathy (DCM). The effect of GBE on autophagy has been observed in several diseases; however, whether GBE can ameliorate DCM by regulating autophagy remains unclear. Here, we investigated the effect of GBE on DCM and the potential mechanisms regarding autophagy using a streptozotocin (STZ)-induced diabetic rat model and a high-glucose (HG)-stimulated H9C2 cell model. We demonstrated that GBE attenuated metabolic disturbances, improved cardiac function, and reduced myocardial pathological changes in diabetic rats. Impaired autophagy as well as dysregulation of the adenosine monophosphate-activated protein kinase/ mammalian target of the rapamycin (AMPK/mTOR) signaling pathway were observed in diabetic hearts, as evidenced by the reduced conversion of LC3B-I to LC3B-II along with excessive p62 accumulation, decreased AMPK phosphorylation, and increased mTOR phosphorylation, which could be reversed by GBE treatment. In vitro, GBE reduced the apoptosis induced by HG in H9C2 cells by activating AMPK and inhibiting mTOR to restore autophagy. However, this effect was inhibited by the AMPK inhibitor Compound C. In conclusion, the ameliorative effect of GBE on DCM might be dependent on the restoration of autophagy through modulation of the AMPK/mTOR pathway.     

健脾导滞汤治疗脾虚气滞型非酒精性脂肪肝

目的观察健脾导滞汤治疗脾虚气滞型非酒精性脂肪肝(非酒精性脂肪性肝病)的临床疗效。方法将108例临床确诊为非酒精性脂肪性肝病的患者随机分为治疗组和对照组,各54例,治疗组采用健脾导滞汤加减(砂仁、干姜、炙甘草、山楂等,1剂/d)治疗,对照组采用脂必妥片(脂必妥片3片/次,2次/d)治疗,疗程均为3个月。对比观察2组治疗的综合疗效和治疗前后中医症状积分、体质量指数、血脂指标、肝功能指标、肝脾影像指标变化。结果治疗组治疗后总有效率为96.30%,对照组为75.93%,2组比较,差异有统计学意义(P<0.05);2组患者治疗后中医症状积分、体质量指数、血脂指标(TC、TG)、肝功能指标(AST、ALT)及肝脾影像指标(肝脾CT比值)均较治疗前明显改善,差异有统计学意义(P<0.05或P<0.01);治疗组治疗后中医症状积分、TC及肝/脾CT比值改善明显优于对照组,差异有统计学意义(P<0.05)。结论健脾导滞汤治疗脾虚气滞型非酒精性脂肪肝可有效恢复患者肝功能、降低血脂,减轻脂肪肝病情程度,延缓病情发展。     

血清纤溶酶原激活物抑制剂1水平对非酒精性脂肪性肝病的诊断价值

目的评价血清纤溶酶原激活物抑制剂1(PAI-1)水平对非酒精性脂肪性肝病(NAFLD)特别是非酒精性脂肪性肝炎(NASH)的诊断价值。方法选择2013年7月—2017年8月在上海交通大学医学院附属第九人民医院就诊的NAFLD患者82例作为NAFLD组,然后根据肝脏组织病理学检查结果将患者分为NASH组32例和非NASH组50例(其中单纯性脂肪肝患者20例,临界NASH患者30例);选择同期参加体检的健康志愿者25例作为健康组。比较各组性别、年龄、体质量指数(BMI)、血清PAI-1水平、肝功能指标[丙氨酸转氨酶(ALT)、谷氨酸转氨酶(AST)、碱性磷酸酶(ALP)、γ-谷氨酰转肽酶(GGT)、AST/ALT]、血脂指标[总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)]、空腹血糖(FPG),分析血清PAI-1水平与各指标的相关性,应用ROC曲线评价PAI-1对NAFLD特别是NASH的诊断价值。结果NAFLD组的性别、年龄、血清ALP水平与健康组比较差异均无统计学意义(P均>0.05),BMI及血清ALT、AST、AST/ALT、GGT、TG、TC、HDL-C、LDL-C、FPG、PAI-1水平均显著高于健康组(P均<0.05)。NASH组的性别、年龄及血清ALT、AST、AST/ALT、ALP、GGT、TC、HDL-C、LDL-C、FPG水平与非NASH组比较差异均无统计学意义(P均>0.05),BMI及血清TG、PAI-1水平均明显高于非NASH组(P均<0.05)。血清PAI-1水平与BMI、ALT、GGT、TC、TG、LDL-C、FPG均呈正相关(r=0.726,0.214,0.319,0.434,0.331,0.311,0.218,P均<0.05),与AST/ALT呈负相关(r=-0.316,P<0.05)。血清PAI-1水平诊断NAFLD和NASH的AUC值分别为0.812[95%CI(0.725,0.881)]、0.954[95%CI(0.884,0.988)],差异均有统计学意义(Z=7.766,17.901,P均<0.05)。血清PAI-1>9.71 ng/mL对预测NAFLD的敏感度为70.73%,特异度为100%。血清PAI-1>11.60 ng/mL对预测NASH的敏感度为100%,特异度为90%。结论血清PAI-1水平对NAFLD特别是NASH具有较高的诊断价值。     

Hesperidin improves hepatic steatosis,hepatic enzymes,and metabolic and inflammatory parameters in patients with nonalcoholic fatty liver disease: A randomized,placebo‐controlled,double‐blind clinical trial

This study aimed to evaluate the effects of hesperidin on nonalcoholic fatty liver disease (NAFLD) characteristics. In this randomized, double‐blind, controlled clinical trial, 50 NAFLD patients were supplemented with either 1‐g hesperidin capsule or identical placebo capsule for 12 weeks. During the intervention, both groups were advised to follow healthy lifestyle habits including dietary and physical activity recommendations. At the end of the study, hesperidin supplementation, compared with placebo, was associated with a significant reduction in alanine aminotransferase (p = .005), γ‐glutamyltransferase (p = .004), total cholesterol (p = .016), triglyceride (p = .049), hepatic steatosis (p = .041), high‐sensitivity C‐reactive protein (p = .029), tumor necrosis factor‐α, and nuclear factor‐κB (NF‐κB). In conclusion, our results indicate that hesperidin supplementation accompanied with lifestyle modification is superior to lifestyle modification alone in management of NAFLD at least partially through inhibiting NF‐κB activation and improving lipid profile. Further studies with higher dose of hesperidin are required to find the optimal dose.     

黄连素对新诊断2型糖尿病患者非酒精性脂肪肝及血液流变学的影响

目的:探讨黄连素对诊断2型糖尿病(T2DM)伴非酒精性脂肪肝及血流变的治疗效果.方法:选取2009年3月至2010年3月就诊的60例新诊断T2DM伴非酒精性脂肪肝患者,随机分为2组,分别给予黄连素及血脂康治疗,疗程12周.检测2组患者治疗前后肝脏B超、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、丙氨酸氨基转移酶(ALT)、门冬氨酸氨基转移酶(AST)、血流变等指标并进行比较.结果:黄连素组治疗后复查肝脏B超显效及有效共21例,有效率70.0％,血脂康组有效共22例,有效率73.3％,2组疗效无差异.黄连素组治疗后ALT,AST,TC,TG,LDL-L,血流变(包括全血粘度、全血高切还原粘度、全血低切还原粘度、血浆粘度、血沉、红细胞压积、纤维蛋白原)水平均较治疗前明显降低,HDL-L水平明显升高(P＜0.05);血脂康组亦显示出相同的结果(P＜0.05);2组各指标治疗前后的差值均无明显差异.结论:黄连素能明显改善新诊断T2DM伴非酒精性脂肪肝患者肝脏病变,有效降低血流变相关指标,具有良好的应用前景.     

Alpinetin alleviates osteoporosis by promoting osteogenic differentiation in BMSCs by triggering autophagy via PKA/mTOR/ULK1 signaling

Osteoporosis, a systemic bone disease that is characterized by a reduction in bone mass and destruction of bone microstructure, is becoming a serious problem worldwide. Bone marrow mesenchymal stem cells (BMSCs) can differentiate into bone-forming osteoblasts, and play an important role in maintaining homeostasis of bone metabolism, thus being a potential therapeutic target for osteoporosis. Although the phytochemical alpinetin (APT) has been reported to possess a variety of pharmacological activities, it is still unclear whether APT can influence the osteogenic differentiation of on BMSCs and if it can improve osteoporosis. In this study, we found that APT treatment was able to enhance osteogenic differentiation levels of human BMSCs in vitro and mouse ones in vivo as revealed by multiple osteogenic markers including increased alkaline phosphatase activity and osteocalcin expression. Mechanistically, the protein kinase A (PKA)/mTOR/ULK1 signaling was involved in the action of APT to enhance the osteogenic differentiation of BMSCs. In addition, oral administration of APT significantly mitigated the bone loss in a dexamethasone-induced mouse model of osteoporosis through strengthening PKA signaling and autophagy. Altogether, these data demonstrate that APT promotes osteogenic differentiation in BMSCs by augmenting the PKA/mTOR/ULK1 autophagy signaling, highlighting its potential therapeutic application for treating osteoporotic diseases.