阿尔采末病神经元凋亡发生机制的研究及四氢小檗碱的抗凋亡作用

本研究用免疫组织化学、细胞培养和膜片钳技术研究阿尔采末病 (AD)脑中的细胞凋亡 ,以及β 淀粉样肽 ( β AP)诱导离体培养海马神经元的凋亡及其离子机制。结果表明AD脑内存在细胞凋亡 ,β AP可以通过抑制神经元的电压依赖性K+和Na+通道促进神经元凋亡 ,一氧化氮与其有一定的协同作用。同时发现四氢小檗碱可通过降低细胞内Ca2 +而减轻β AP引起的神经元凋亡。

HPLC法测定复方炎消颗粒中盐酸小檗碱的含量

【目的】建立测定复方炎消颗粒中盐酸小檗碱含量的高效液相色谱法。【方法】采用Diamonsil C18柱，以乙腈-水（含0．05％磷酸和0．1％三乙胺）（42：58）为流动相，检测波长266nm。【结果】该色谱条件下盐酸小檗碱在4．08～81．6mg／L浓度范围内呈良好的线性关系。平均回收率为98．5％，相对标准偏差（RSD）为1．16％。【结论】本法简便可行、重复性好，可用于该制剂中盐酸小檗碱的含量测定。

盐酸小檗碱的新用途

盐酸小檗碱（黄连素）是异喹啉类抗菌药的典型代表，它为由黄连、黄柏或三颗针中提取的有效成份，也可人工合成。常用于治疗菌痢、急性肠胃炎、慢性胆囊炎以及眼结膜炎、化脓性中耳炎等疾病，均有显著疗效，深受人们青睐。近几年来，随着医学科学的不断发展和药理研究的不断深入，又开拓了一些新的用途。主要的新用途如下。

盐酸小檗碱片含量测定样品溶液配制方法改进

目的:建立盐酸小檗碱片含量测定的样品溶解处理的方法——流动相溶解法。方法:盐酸小檗碱片含量测定的样品溶解处理的方法中用流动相代替沸水溶解。结果:检测结果平均提高2.0%。该法样品处理简单,结果稳定、准确,可作为盐酸小檗碱片含量测定的样品溶解处理的方法。

小檗碱对糖尿病脑病大鼠海马组织氧化应激及BDNF表达的影响

目的:观察糖尿病脑病大鼠海马组织氧化应激水平及脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)的表达,初步探讨小檗碱治疗糖尿病脑病的机制。方法:除空白组给予普通饲料外,其余大鼠高糖高脂饲料喂养60d,腹腔注射40mg/kg链脲佐菌素(Streptozocin,STZ)制备糖尿病模型,模型成功后随机分为模型组、小檗碱低(50mg/kg)、中(100mg/kg)、高(200mg/kg)剂量组,罗格列酮组(5mg/kg)。给药30d后处死大鼠取血,检测血糖,部分动物取海马组织测定过氧化氢酶(CAT)、过氧化脂质(LPO)、还原型谷胱甘肽(GSH)。其余动物取脑进行BDNF免疫组化染色。结果:较空白组,模型大鼠体重明显降低,血糖显著升高(P<0.05,P<0.01),小檗碱中、高剂量及罗格列酮可显著降低模型大鼠血糖(P<0.01,P<0.05),升高CAT活性、GSH水平(P<0.01),降低LPO水平(P<0.01),提高海马CA1区BDNF的表达。结论:糖尿病脑病与氧化应激水平及海马组织BDNF表达降低相关,小檗碱可通过降血糖,抗氧化,增强神经营养因子表达而发挥脑保护作用。

稀土小檗碱配合物杀菌乳剂的制备及药效研究

研究开发了两种新型稀土配合物杀菌悬浮乳剂,分别是Sm(NO3)3,Nd(NO3)3(B)3。使用差热热重和红外表征了配合物,说明配合物是不同于稀土和小檗碱的一种新物质。对稀土小檗碱配合物乳剂的乳液稳定性、低温稳定性、抗冻性和热贮稳定性等理化性质进行了测定,并考察了其对番茄溃疡病菌、向日葵菌核病菌、尖孢镰刀菌和胡萝卜黑斑病菌抑菌活性。结果表明:两种悬浮乳剂符合国家农药乳剂的标准,且对四种农作物病菌有较好的抑菌效果。

小檗碱与苦参总碱不同配比对DNCB致大鼠UC模型的影响

目的:探讨小檗碱与苦参总碱不同配比对溃疡性结肠炎大鼠模型的治疗作用。方法:采用2,4-二硝基氯苯复制大鼠溃疡性结肠炎模型,检测大鼠粪便常规、隐血试验、长度8cm病变结肠的粘连指数和重量,并进行结肠黏膜组织病理学检查,测定黏膜组织肿瘤坏死因子、环氧合酶-2的表达。结果:小檗碱180mg/kg、小檗碱120mg/kg+苦参总碱60mg/kg给药3天后能明显改善溃疡性结肠炎大鼠粪常规,隐血试验大部分呈阴性;给药7天后结肠腺体多数完整,改善结肠组织病理学检查;结肠黏膜肿瘤坏死因子及环氧合酶-2平均灰度较模型组有显著性差异。结论:小檗碱180mg/kg、小檗碱120mg/kg+苦参总碱60mg/kg对2,4-二硝基氯代苯致溃疡性结肠炎大鼠治疗效果显著。

小檗碱通过抑制巨噬细胞炎症反应改善脂肪细胞糖代谢异常

目的:研究小檗碱(berberine,BBR)抑制巨噬细胞炎症反应及与脂肪细胞糖代谢的关系。方法:体外培养RAW264.7巨噬细胞,运用MTT法检测不同浓度小檗碱对巨噬细胞增殖的影响;单独加入100ng/L脂多糖(LPS)或者合并加入1.86mg/L小檗碱孵育24小时,分别留取细胞上清,抽提蛋白和mRNA进行检测炎症因子的表达、分泌和炎症信号通路,并收集巨噬细胞上清,加入3T3-L1脂肪细胞中孵育24小时,检测脂肪细胞上清葡萄糖含量和提取蛋白检测炎症信号通路。结果:与正常组细胞比较,0.37mg/L和1.86mg/L的小檗碱对巨噬细胞活性未产生显著影响,而3.72、18.59、37.18mg/L的小檗碱显示出明显的抑制作用;小檗碱(1.86mg/L)能够明显抑制LPS刺激下巨噬细胞肿瘤坏死因子(TNF-α),白介素6(IL-6)和单核细胞趋化蛋白(MCP-1)表达量的上调,减少上清MCP-1、IL-6的含量,并且抑制巨噬细胞炎症信号通路JNK和IKKβ的磷酸化激活,下调NF-κB的p65亚基的表达量;LPS刺激后的巨噬细胞上清能够减少脂肪细胞胰岛素刺激下的葡萄糖消耗,而小檗碱能够促使下降的葡萄糖消耗恢复,同时减轻脂肪细胞JNK和IKKβ的磷酸化激活。结论:小檗碱通过抑制巨噬细胞的炎症反应改善脂肪细胞的糖代谢异常。

盐酸小檗碱体外抗单纯疱疹病毒1型的作用及机制研究

目的:探讨盐酸小檗碱体外抗单纯疱疹病毒1型(HSV-1)的作用及作用机制。方法:MTT法检测盐酸小檗碱对Vero细胞的毒性作用,观察HSV-1感染Vero细胞后所致的细胞病变效应(Cytopathologic effects,CPE),实时荧光定量PCR法检测盐酸小檗碱对病毒蛋白gD的mRNA表达水平,免疫印迹(Western blot)法检测盐酸小檗碱对病毒蛋白ICP27和ICP8表达的影响。结果:盐酸小檗碱半数中毒浓度(TC50)为392.5μmol/L,病毒半数抑制浓度(IC50)为66.49μmol/L,选择性指数(SI)为5.9。实时荧光定量PCR结果显示盐酸小檗碱可降低HSV-1 gD的mRNA表达水平。Western blot显示盐酸小檗碱可明显抑制病毒蛋白ICP27和ICP8的表达。结论:盐酸小檗碱具有抗HSV-1的作用,可能与抑制病毒蛋白ICP27的表达进而影响ICP8和gD的表达有关。

胡椒碱与小檗碱改善脂肪细胞胰岛素抵抗的比较研究

目的:胡椒碱和小檗碱分别是温里药荜茇和清热药黄连的主要成分,二者均可以改善胰岛素抵抗。本研究通过建立3T3-L1脂肪细胞胰岛素抵抗模型[1,2],观察胡椒碱和小檗碱对该细胞模型的糖代谢紊乱的干预作用,意在探讨药效相似、药性相反的胡椒碱是否同小檗碱一样可以通过调节腺苷酸活化蛋白激酶AMPK而改善胰岛素抵抗。方法:诱导3T3-L1脂肪细胞分化为成熟的脂肪细胞后,采用1μM地塞米松作用48h建立脂肪细胞胰岛素抵抗模型,以AMPK激活剂AICAR和罗格列酮为阳性药,观察不同浓度的胡椒碱和小檗碱作用该模型48h后对糖代谢紊乱的调节作用,继而采用Western blot检测药物作用不同时间后细胞中AMPKα的水平变化。结果:胡椒碱、小檗碱同阳性药AICAR、罗格列酮一样在作用该脂肪细胞胰岛素抵抗模型48h后均可改善糖代谢紊乱。Western blot检测结果:与模型组比较,40u M胡椒碱、5u M小檗碱同阳性AICAR一样在作用脂肪细胞胰岛素抵抗模型6h,12h和24h后,P-AMPKα的蛋白表达明显提高。结论:胡椒碱同小檗碱一样能够改善糖代谢紊乱,其机理有可能是通过调节AMPK信号通路中的AMPKα的活性而改善胰岛素抵抗的。

人参茎叶皂苷联合盐酸小檗碱在抑制乳腺癌术后复发及转移中的临床疗效分析

目的:研究人参茎叶皂苷与盐酸小檗碱联合用药对乳腺癌术后肿瘤复发和转移的临床抑制效果。方法:选取我科室2005年1月至2007年12月收治疗的确诊为乳腺癌并行手术治疗的患者共100例,按随机数字表发分为治疗组和对照组各50例,治疗组在常规化疗的基础上给予人参茎叶皂苷与盐酸小檗碱辅助治疗,对照组术后给予西药常规化疗,在治疗后12月、治疗后24月、治疗后36月、治疗后48月和治疗后60月随访并记录两组患者的KPS日常功能状态评分及两组患者肿瘤复发及转移情况,采用统计学方法对数据进行分析。结果:两组患者KPS功能状态评分:治疗组治疗后12月、24月、36月、48月、60月KPS评分分别为(72.05±2.0、76.25±2.5、79.89±1.9、82.56±2.3、86.14±2.7)分,均高于对照组(65.32±2.1、69.55±1.8、73.44±2.2、77.55±2.4、80.55±2.6)分,且差异均有显著性。治疗组治疗后12月、24月、36月癌胚抗原(CEA)水平分别为(77.21±2.01、10.56±2.11、10.18±1.98)ng/ml均优于对照组(9.32±1.91、14.89±2.33、13.55±2.19)ng/ml,且差异均有显著性。治疗组治疗后12月、24月、36月癌抗原125(CA125)水平分别为(47.33±5.01、59.62±6.79、61.38±7.41)u/ml均优于对照组(9.32±1.91、14.89±2.33、13.55±2.19)u/ml,且差异均有显著性。(4)5年后治疗组共9例患者出现肿瘤复发和转移低于对照组(19例),且差异有显著性。(5)治疗60个月后治疗组无复发生存率与总生存率分别为(82%、94%)均高于对照组(62%、80%),且差异均有显著性。治疗组中位生存时间为(71.2±3.01)月,高于对照组中位生存时间(65.7±2.13)月,且差异有显著性。(6)治疗组副反应发生情况为(恶心呕吐5例、腹泻3例、厌食7例、白细胞降低8例),对照组为(恶性呕吐6例、腹泻3例、厌食6例、白细胞降低7例),无明显差异性。结论:人参茎叶皂苷与盐酸小檗碱联合应用能提高乳癌患者术后生存质量,能明显提高患者的五年生存率降低乳癌手术复发及转移的几率,与常规西药化疗相比无明显副反应,值得临床进一步研究和应用。

如意金黄巴布剂透皮吸收研究

采用改良Franz扩散池法，研究了如意金黄散及其剂改新制剂如意金黄巴布剂中小檗碱的透皮吸收特性，HPLC法检测透过的小檗碱。结果表明：散剂改为巴布剂后能显著提高其透皮吸收效果，如意金黄巴布剂透皮吸收过程符合Higuchi方程，具有一定的缓释效果。

Effect of Berberine Chloride on Experimental Murine Colitis Induced by Dextran Sulfate Sodium

Aim To investigate the effect in berberine chloride （BER） on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium （DSS） solution or distilled water freely with different doses of BER （15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1） or sallcylazosulfapyridine （SASP, 520 mg·kg^-1）, and solvent （0. 2 mL/10 mg Wt） once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index （DAI）. Myeloperoxidase （MPO） and superoxide dismutase （SOD） activities and malondialdehyde （MDA） content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 （ ICAM-1 ） proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.

Simultaneous Determination of Baicalin, Berberine and Rhein by HPLC in Traditional Chinese Patent Medicine Sanhuang Tablets

Aim To establish a reversed phase liquid chromatographic method forsimultaneous determination of three main medicinal constituents, baicalin, berberine and rhein, inSanhuang tablets. Methods The separation was performed on a Kromasil C_(18) column with TEA-adjusted0.02 mol·L^(-1) H_3PO_4 (pH 6.78)-acetonitrile-methanol (40 : 9 : 7) as mobile phase at aflow-rate of 1.0 mL·min^(-1), with detection at 254 ran. Considering interaction between acidic andalkaline compounds, three standard markers were added respectively and the volume of samplesolution was doubled in recovery experiments. Results Three regression equations revealed excellentlinear relationship between the peak areas and concentrations and the correlation coefficients allsurpassed 0.999 8. The average recovery was 96.1% (RSD = 2.1%) baicalin, 98.5% (RSD = 2.4%) forberberine, and 101.5% (RSD =1.3%) for rhein. Conclusion The method developed can be used to controlthe quality of Sanhuang tablets comprehensively.

Effect of berberine on glucolipid metabolization in diabetic skeletal muscle and its mechanism

Aim To investigate the effect of berberine on damaged morphology and glucolipid metabolization in skeletal muscle of diabetic rat and the relationship between peroxisome proliferator-activated receptor （PPARs） α/γ/δ protein expression. Methods Type 2 diabetes mellitus rats were induced by an injection of 35 mg.kg^-1 streptozotocin （STZ） and a high-carbohydrate/ high-fat diet for 16 weeks. From week 17 to 32, diabetic rats were given low-, middle-, high-dose berberine （75, 150, 300 mg.kg^-1）, fenofibrate （100 mg.kg^-1） and rosiglitazone （4 mg.kg^-1） by oral administration, respectively. The skeletal muscle structure was observed with hematoxylin-eosin （HE） staining, glycogen and triglyceride contents were measured by spectrophotometry and PPAR α/γ/δ protein expressions were detected by immunohistochemistry. Results Fiber distribution remained normal in skeletal muscles of all the groups, middle-, high-dose berberine partly improved diabetic fibre atrophy, increased glycogen and decreased triglyceride levels in diabetic muscle （P〈 0.01）. Middle-, high-dose berberine and rosiglitazone all significantly reduced PPARy protein level in diabetic skeletal muscle （P 〈 0.01）; middle-, high-dose berberine and fenofibrate strikingly increased both PPARu and PPAR8 expression （P〈 0.01）. Conclusion Berberine modulates PPAR α/γ/δ protein expression in diabetic skeletal muscle which may contribute to ameliorate fibre damage and glucolipid metabolization.

Effects of Berberine on TXB 2 and 6 Keto PGF 1α Plasma Levels in Rabbits with Uncomplete Cerebral Ischemia

Effects of berberine (Ber) on platelet aggregation and TXB2 and 6 keto PGF1a plasma levels were studied in rabbits with uncomplete cerebral ischemia. Ber inhibited uncomplete cerebral ischemic rabbit platelet aggregation triggered by collagen, ADP, and arachidonic acid (AA) with the IC 50 of 0.15, 0.46, and 0.51 mg·ml 1 , respectively. In rabbits, Ber 25, or 50 mg·kg 1 iv 30 min after uncomplete cerebral ischemia, restrained the collagen ADP and AA induced platelet aggregation determined 90 min later. With radioimmunoassay, we measured the thromboxane B2 (TXB 2) and 6 ketoprostaglandin F 1α (6 keto PGF 1α ) contents in rabbit plasma. The results indicated that the TXB 2 level in rabbit 120 min after uncomplete cerebral ischemia (921±539 pg·ml 1 ) was higher than that (230±71 pg·ml 1 ) in normal rabbits ( P < 0.01), but 6 keto PGF 1α level after ischemia (73±23pg·ml 1 ) was lower than that (262±988pg·ml 1 ) in normal rabbit. Ber (5, 25 or 50 mg·kg 1 ) reduced obviously the plasma TXB 2 level in rabbit with uncomplete cerebral ischemia (504±196, 386±174, or 272±183 vs 921±539 pg·ml 1 , respectively, P < 0.01). We conclude that the decrease of TXB 2 content is one of the possible mechanisms of Ber anti cerebral ischemic effect.

Berberine promotes the development of atherosclerosis and foam cell formation by inducing scavenger receptor A expression in macrophage

Berberine is identified to lower the serum cholesterol level in human and hamster through the induction of low density lipoproteins （LDL） receptor in hepatic cells. To evaluate its potential in preventing atherosclerosis, the effect of berberine on atherosclerosis development in apolipoprotcin E-deficient （apoE^-/-） mice was investigated. In apoE^-/- mice, berberine induced in rivo foam cell formation and promoted atheroselerosis development. The foam cell formation induced by berberinc was also observed in mouse RAW264.7 cells, as well as in mouse and human primary macrophages. By inducing scavenger receptor A （SR-A） expression in macrophages, berberine increased the uptake of modified LDL （DiO-Ac-LDL）. Bcrberine-induced SR-A expression was also observed in macrophage foam cells in vivo and in the cells at atherosclerotic lesion. Analysis in RAW264.7 cells indicated that berberine induced SR-A expression by suppressing PTEN expression, which led to sustained Akt activation. Our results suggest that to evaluate the potential of a cholesterol-reducing compound in alleviating atherosclerosis, its effect on the ceils involved in atherosclerosis development, such as macrophages, should also be considered. Promotion of foam cell formation could counter-balance the beneficial effect of lowering serum cholesterol.

Antifungal susceptibility analysis of berberine,baicalin,eugenol and curcumin on Candida albicans

Objective:To analyze the antifungal effects of Chinese herb monomers,i.e.berberine,baicalin,eugenol and curcumin,on Candida albicans.Methods:After Candida albicans strain Y01-09 was incubated for 48 h in YEPD broth which contained different concentrations of Chinese herb components,the cell cycle,fluorescent intensity and the size of cell volume were detected by flow cytometry.Results:The 4 Chinese herb monomers could affect the cell cycle of Candida albicans in different ranges.The ratio of cells in S-G2-M period decreased as the agents concentration increased,indicating that the cell division was inhibited.The fluorescent intensity of Candida albicans cells became weaker after being incubated,which reflected the loss of DNA fragments.The higher the concentration was,the weaker the fluorescent intensity became.The cell size,cell diopter and particle size changed much as the agents concentration increased.Conclusion:Chinese herb monomers play the antifungal role in inhibiting cell division.FCM could be used to determine the susceptibility of antifungal agents.

Systematic Investigation of Berberine for Treating Hepatocellular Carcinoma Based on Network Pharmacology

Objective Liver cancer is the 4th leading cause of cancer death worldwide,and hepatocellular carcinoma(HCC)accounts for the largest proportion of these deaths.Berberine is a quaternary amine compound extracted from plants such as Coptidis Rhizoma(Huang Lian,黄连)and Phellodendri Chinensis Cortex(Huang Bo,黄柏)and is considered as a potential candidate for treating HCC.This study used network pharmacology methods,reveal the core mechanism of action of berberine in the treatment of HCC,clarify its medicinal value,and locate the anti-tumor mechanism of berberine.Methods Structural information of Berberine(PubChem CID:2353)was obtained from the NCBI PubChem;ADME parameter were obtained from the Traditional Chinese Medicine Systems Pharmacology(TCMSP)database;Berberine prediction targets were collected from symmap,stitch and targetnet databases;HCC significant targets were retrieved from OncoDB.HCC and Liverome;A PPI network was established at STRING,Prediction target of berberine therapy for HCC are collected by gene mapping;The core target,pathway,biological process(BP),cellular component(CC),and molecular function(MF)of berberine in the treatment of HCC were predicted by topological analysis and enrichment analysis;the visualized"target pathway"network diagram of berberine in the treatment of HCC was established by the software of Cytoscape.Results Through PubChem and tcmsp databases,the good drugforming properties of berberine were identified;32 prediction targets of berberine were collected in symmap,stitch and targetnet databases;566 related targets of HCC were collected in oncodb.hcc and liverome databases;10 targets of berberine treatment for HCC were predicted by gene mapping,and a PPI with 10 nodes and 34 edges was established Through topological analysis and enrichment analysis,6 topologically important targets,6 related pathways and 16 BP,6 cc and 7 MF involved in Berberine treatment of HCC were obtained.Conclusions The anticancer effect of berberine is mainly involved in the regulation of cells of hepatoma cells through complex interactions between the TB52,MAPK1,CCND1,PTGS2,ESR1 that act on Hub nodes and their associated 6 pathways.The cycle is related to the immune inflammatory response,including biological processes such as proliferation and apoptosis of liver cancer cells.

Regulatory effects of the combination of berberine and ginsenoside Rb1 on high-fat diet-induced nonalcoholic fatty liver disease via AMPK pathway and improved pharmacokinetics

Objective： We evaluated the protective effects of berberine （BBR） combined with ginsenoside Rb1 （G-Rb1） on high-fatdiet （HFD）-induced nonalcoholic fatty liver disease （NAFLD） in rats and futher investigated the underlying mechanisms.Methods： Rats were fed an HFD for 6 weeks and then randomly divided into four groups and treated with BBR （50mg/kg）, G-Rb1 （100 mg/kg）, BBR （50 mg/kg） ＋ G-Rb1 （100 mg/kg）, or fenofibrate （40 mg/kg）. Histological examinationof liver tissue was performed. In human hepatocellular carcinoma cells HepG2, protein expression of AMP-activatedprotein kinase （AMPK） and acetyl-CoA carboxylase was detected by western blotting, and the mRNA expression ofcarnitine palmitoyl transferase 1 and 3-hydroxy-3-methyl glutaryl coenzyme A reductase was detected by quantitativePCR. Pharmacokinetic assessments included analysis of bioavailability of BBR and G-Rb1 in vivo and G-Rb1 metabolismby intestinal bacteria in vitro. Results： Compared to the single-use group, BBR combined with G-Rb1 significantlyameliorated hepatic fat accumulation in HFD-induced obese rats, as demonstrated by reduced hepatic triglyceridecontent, and histological evaluation of liver sections. Activation of hepatic AMPK and phosphorylation of acetyl-CoAcarboxylase were significantly elevated in hepatocytes treated with both BBR and G-Rb1. Consistent with the activationof AMPK, the mRNA expression of carnitine palmitoyl transferase 1 was stimulated, while the mRNA expression of3-hydroxy-3-methyl glutaryl coenzyme A reductase was suppressed. Pharmacokinetic analysis revealed that BBRincreased the bioavailability of G-Rb1 in Sprague-Dawley rats. Additionally, BBR prevented degradation of G-Rb1 infecal solution in vitro. Conclusion： BBR combined with G-Rb1 improved NAFLD through the AMPK signaling pathway,and BBR enhanced G-Rb1 bioavailability via promoting the intestinal absorption of G-Rb1. This combination may be auseful therapeutic agent for NAFLD.