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| 1 | Berberine inhibits hepatic gluconeogenesis via the LKB1-AMPK-TORC2 signaling pathway in streptozotocin-induced diabetic rats显示文摘AIM: To investigate the molecular mechanisms of berberine inhibition of hepatic gluconeogenesis in a diabetic rat model.METHODS: The 40 rats were randomly divided into five groups. One group was selected as the normal group. In the remaining groups(n = 8 each), the rats were fed on a high-fat diet for 1 mo and received intravenous injection of streptozotocin for induction of the diabetic models. Berberine(156 mg/kg per day)(berberine group) or metformin(184 mg/kg per day)(metformin group) was intragastrically administered to the diabetic rats and 5-aminoimidazole-4-carboxamide1-β-D-ribofuranoside(AICAR)(0.5 mg/kg per day)(AICAR group) was subcutaneously injected to the diabetic rats for 12 wk. The remaining eight diabetic rats served as the model group. Fasting plasma glucose and insulin levels as well as lipid profile were tested.The expressions of proteins were examined by western blotting. The nuclear translocation of CREB-regulated transcription co-activator(TORC)2 was observed by immunohistochemical staining. RESULTS: Berberine improved impaired glucose tolerance and decreased plasma hyperlipidemia. Moreover, berberine decreased fasting plasma insulin and homeostasis model assessment of insulin resistance(HOMA-IR). Berberine upregulated protein expression of liver kinase(LK)B1, AMP-activated protein kinase(AMPK) and phosphorylated AMPK(p-AMPK). The level of phophorylated TORC2(p-TORC2) protein in the cytoplasm was higher in the berberine group than in the model group, and no significant difference in total TORC2 protein level was observed. Immunohistochemical staining revealed that more TORC2 was localized in the cytoplasm of the berberine group than in the model group. Moreover, berberine treatment downregulated protein expression of the key gluconeogenic enzymes(phosphoenolpyruvate carboxykinase and glucose-6-phosphatase) in the liver tissues. CONCLUSION: Our findings revealed that berberine inhibited hepatic gluconeogenesis via the regulation of the LKB1-AMPK-TORC2 signaling pathway. | Shu-Jun Jiang Hui Dong Jing-Bin Li Li-Jun Xu Xin Zou Kai-Fu Wang Fu-Er Lu Ping Yi | 2015 | World Journal of Gastroenterology2015，21，25： | 33 |
| 2 | Biological properties and clinical applications of berberine显示文摘Berberine,an isoquinoline alkaloid isolated from the Chinese herb Coptis chinens is and other Berber is plants,has a wide range of pharmacological properties.Berberine can be used to treat many diseases,such as cancer and digestive,metabolic,cardiovascular,and neurological diseases.Berberine has protective capacities in digestive diseases.It can inhibit toxins and bacteria,including Helicobac terpylo riprotect the intestinal epithelial barrier from injury,and ameliorate liver injury.Berberine also inhibits the proliferation of various types of cancer cells and impedes invasion and metastasis.Recent evidence has confirmed that berberine improves the efficacy and safety of chemoradiotherapies.In addition,berberine regulates glycometabolism and lipid metabolism,improves energy expenditure,reduces body weight,and alleviates nonalcoholic fatty liver disease.Berberine also improves cardiovascular hemodynamics,suppresses ischemic arrhythmias,attenuates the development of atherosclerosis,and reduces hypertension.Berberine shows potent neuroprotective effects,including antioxidative,antiapoptotic,and anti-ischemic.Furthermore,berberine exerts protective effects against other diseases.The mechanisms of its functions have been extensively explored,but much remains to be clarified.This article summarizes the main pharmacological actions of berberine and its mechanisms in cancer and digestive,metabolic,cardiovascular,and neurological diseases. | Danyang Song Jianyu Hao Daiming Fan | 2020 | Frontiers of Medicine2020，14，5： | 30 |
| 3 | Antidiabetic Effects of Gegen Qinlian Decoction via the Gut Microbiota Are Attributable to Its Key Ingredient Berberine显示文摘Gegen Qinlian Decoction(GQD),a traditional Chinese medicine(TCM)formula,has long been used for the treatment of common metabolic diseases,including type 2 diabetes mellitus.However,the main limitation of its wider application is ingredient complexity of this formula.Thus,it is critically important to identify the major active ingredients of GQD and to illustrate mechanisms underlying its action.Here,we compared the effects of GQD and berberine,a hypothetical key active pharmaceutical ingredient of GQD,on a diabetic rat model by comprehensive analyses of gut microbiota,short-chain fatty acids,proinflammatory cytokines,and ileum transcriptomics.Our results show that berberine and GQD had similar effects on lowering blood glucose levels,modulating gut microbiota,inducing ileal gene expression,as well as relieving systemic and local inflammation.As expected,both berberine and GQD treatment significantly altered the overall gut microbiota structure and enriched many butyrate-producing bacteria,including Faecalibacterium and Roseburia,thereby attenuating intestinal inflammation and lowering glucose.Levels of short-chain fatty acids in rat feces were also significantly elevated after treatment with berberine or GQD.Moreover,concentration of serum proinflammatory cytokines and expression of immune-related genes,including Nfkb1,Stat1,and Ifnrg1,in pancreatic islets were significantly reduced after treatment.Our study demonstrates that the main effects of GQD can be attributed to berberine via modulating gut microbiota.The strategy employed would facilitate further standardization and widespread application of TCM in many diseases. | Xizhan Xu Zezheng Gao Fuquan Yang Yingying Yang Liang Chen Lin Han Na Zhao Jiayue Xu Xinmiao Wang Yue Ma Lian Shu Xiaoxi Hu Na Lyu Yuanlong Pan Baoli Zhu Linhua Zhao Xiaolin Tong Jun Wang | 2020 | Genomics, Proteomics & Bioinformatics2020，18，6： | 29 |
| 4 | Microcalorimetric investigation of the effect of berberine alkaloids from Coptis chinensis Franch on Staphylococcus aureus growth显示文摘The inhibitory effects of three berberine alkaloids (BAs) from rhizome of Coptis chinensis Franch, a traditional Chinese medicinal (TCM) herb, on Staphylococcus aureus growth were investigated by mi- crocalorimetry. The power–time curves of S. aureus with and without BAs were acquired; meanwhile the extent and duration of inhibitory effects on the metabolism were evaluated by studying the growth rate constant (k), half inhibitory ratio (IC50), maximum heat-output power (Pmax), peak time of maximum heat-output power (tp) and total heat production (Qt). The value of k of S. aureus in the presence of the three BAs decreased with the increasing concentrations of BAs. Moreover, Pmax was reduced and the value of tp increased with increasing concentrations of the three drugs. The inhibitory activity varied with different drugs. The values of IC50 of the three BAs are respectively, 101.4 μg/mL for berberine, 241.0 μg/mL for palmatine and 792.3 μg/mL for jateorrhizine. The sequence of antimicrobial activity of the three BAs is: berberine > palmatine > jateorrhizine. It is suggested that the functional group me- thylenedioxy or methoxyl at C2 on the phenyl ring could possibly improve antimicrobial activity more strongly than hydroxyl at C2 on the phenyl ring. | YAN Dan XIAO XiaoHe JIN Cheng DONG XiaoPing | 2008 | Science China Chemistry2008，51，7： | 27 |
| 5 | Berberine Ameliorates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Rats via Activation of SIRT3/AMPK/ACC Pathway显示文摘This study aimed to verify the effects of berberine(BBR)on the fat metabolism proteins involved in the sirtuin 3(SIRT3)/adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)pathway in the liver tissues of rats with high-fat diet(HFD)-induced non-alcoholic fatty liver disease(NAFLD).Forty-eight rats were randomly divided into the normal control(NC)group,HFD group or BBR group,with 16 rats in each group.After 8 and 16 weeks of treatment,serum and liver samples were collected.Subsequently,body parameters,biochemical parameters and liver pathology were examined.The expression levels of proteins involved in the SIRT3/AMPK/ACC pathway in the liver were detected by Western blotting.After 8 and 16 weeks of a HFD,the successful establishment of rat models with different degrees of NAFLD was confirmed by hematoxylin and eosin(H&E)and Oil Red O staining.NAFLD rat models exhibited obesity and hyperlipidemia,and the protein expression levels of SIRT3,p-AMPK.p-ACC,and CPT-1A in the liver were significantly decreased compared to those in the NC group.The concurrent administration of BBR with the HFD effectively improved serum and liver lipid profiles and ameliorated liver injury.Furthermore,the protein expression levels of SIRT3,p-AMPK,p-ACC,and CPT-1 A in the liver were significantly increased in the BBR group as compared with those in the HFD group.In conclusion,our data suggest that the mechanism by which BBR ameliorates HFD-induced hepatic steatosis may be related to the activation of the SIRT3/AMPK/ACC pathway in the liver. | Yu-pei ZHANG Yuan-jun DENG Kai-rui TANG Run-sen CHEN Shu LIANG Yin-ji LIANG Li HAN Ling JIN Zi-en LIANG Yan-ning CHEN Qin-he YANG | 2019 | Current Medical Science2019，39，1： | 21 |
| 6 | Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota显示文摘The phenylalanine-tyrosine-dopa-dopamine pathway provides dopamine to the brain.Iin this process,tyrosine hydroxylase(TH)isthe rate-limiting enzyme that hydroxylates tyrosine and generates levodopa(L-dopa)with tetranydrobiopterin(BH_(4))as a coenzyme.Here,we show that oral berberine(BBR)might supply H^(·) through dihydroberberine(reduced BBR produced by bacterial nitroreductase)and promote the production of BHl from dihydrobiopterin;the increased BH,enhances TH activity,which accelerates the production of L-dopa by the gut bacteria.Oral BBR acts in a way similar to vitamins.The L-dopa produced by theintestinal bacteria enters the brain through the circulation and is transformed to dopamine.To verify the gut-brain dialog activatedby BBR's effect,Enterococcus foecalis or Enterococcus faecium was transplanted into Parkinson's disease(PD)mice.The bacteriasignificantly increased brain dopamine and ameliorated PD manifestation in mice;additionally,combination of BBR with bacteriashowed better therapeutic effect than that with bacteria alone.Moreover,2,4,6-trimethy-pyranylium tetrafluoroborate(TMP-TFB)-derivatized matrix-assisted laser desorption mass spectrometry(MALDI-MS)imaging of dopamine identihed elevated striataldopamine levels in mouse brains with oral Enterococcus,and BBR strengthened the imaging intensity of brain dopamine.Theseresults demonstrated that BBR was an agonist of TH in Enterococcus and could lead to the production of L-dopa in the gut.Furthermore,a study of 28 patients with hyperlipidemia conhrmed that oral BBR increased bloodfecal L-dopa by the intestinalbacteria.Hence,BBR might improve the brain function by upregulating the biosynthesis of-dopa in the gut microbiota through avitamin-like effect. | Yan Wang Qian Tong Shu-Rong Ma Zhen-Xiong Zhao Li-Bin Pan Lin Cong Pei Han Ran Peng Hang Yu Yuan Lin Tian-Le Gao Jia-Wen Shou Xiao-Yang Li Xian-Feng Zhang Zheng-Wei Zhang Jie Fu Bao-Ying Wen Jin-Bo Yu Xuetao Cao Jian-Dong Jiang | 2021 | Signal Transduction and Targeted Therapy2021，6，3： | 16 |
| 7 | Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells显示文摘 | Zeng-si WANG Fu-er LU Li-jun XU Hui DONG | 2010 | Acta Pharmacologica Sinica2010，31，5： | 16 |
| 8 | Potential antibacterial activity of berberine against multi drug resistant enterovirulent Escherichia coli isolated from yaks(Poephagus grunniens) with haemorrhagic diarrhoea显示文摘Objective:To evaluate the antimicrobial efficacy of berberine,a plant alkaloid.Methods:Five multi-drug resistant(MDR) STEC/EPEC and five MDR ETEC isolates from yaks with haemorrhagic diarrhoea were selected for the study.Antibacterial activity of berberine was evaluated by broth dilution and disc diffusion methods.The binding kinetics of berberine to DNA and protein was also enumerated.Results:For both categories of enterovirulent Escherichia coli(E.roli) isolates, berberine displayed the antibaclerial effect in a dose dependent manner.The MIC50 of berberine chloride for STEC/EPEC isolates varied from 2.07μM to 3.6μM with a mean of(2.95±0.33)μM where as for ETEC strains it varied from 1.75 to 1.96μM with a mean of(1.87±0.03)μM. Berberine bind more tightly with double helix DNA with Bmax and Kd of(24.68±2.62) and(357.8±57.8),respectively.Berberine reacted with protein in comparatively loose manner with Bmax and Kd of(18.9±3.83) and <286.2±113.6),respectively.Conclusions:The results indicate clearly that berberine may serve as a good antibacterial against multi drug resistant E.coli. | Samiran Bandyopadhyay Pabitra H Patra Achintya Mahanti Dipak K Mondal Premanshu Dandapat Subhasis Bandyopadhyay Indranil Samanta Chandan Lodh Asit K Bera Debasish Bhattacharyya Mihir Sarkar Kishore K Baruah | 2013 | Asian Pacific Journal of Tropical Medicine2013，6，4： | 11 |
| 9 | Antibacterial Mechanisms of Berberine and Reasons for Little Resistance of Bacteria显示文摘Objective To study the antibacterial mechanisms of berberine and try to understand the reasons why bacteria cells difficultly resisted to it.Methods Detecting the minimal inhibitory concentration(MIC) of bacterial cultures incubated under sub-MIC concentration of berberine,Huanglian,and Neomycin for more than 200 generations,in order to analyze the bacteria resistance.Detecting the binding kinetics of berberine to DNA,RNA,and proteins.Observing the changes in bacterial cell surface structure with scanning electron microscopy.Detecting the Ca2 +and K +released from berberine-treated bacterial cells with atomic absorption spectrum.Detection the absorption of methyl-3H-thymine (3 H-dT),3 H-uridine(3 H-U),and 3 H-tyrosine(3 H-Tyr)into berberine-treated bacterial cells.Results MICs of bacterial cultures,growing more than 200 generations in MH medium with 1/2 MIC of berberine(BA200) or Huanglian(HA200),did not increase compared to the control,while remarkably increased in MH medium with 1/2 MIC of Neomycin (NA200).In addition,from the culture NA200 it was easy to isolate resistant mutant strains which could grow in MH medium with more than four times MIC Neomycin,but from the culture BA200 and HA200 it was difficult to isolate berberine or Huanglian mutant strains could grow in MH medium with more than four times MIC berberine or Huanglian.The binding kinetics of berberine to DNA,RNA,and proteins illustrated that berberine could easily and tightly bind to DNA and RNA,and hardly dis-bind from DNA-and RNA-berberine complexes.Berberine could easily bind to protein too,but also easily dis-bind from berberine-protein complex.The bacterial cells treated with berberine sharply decreased the absorption of 3 H-dT,3 H-U,and 3 H-Tyr,as the radioactive precursors of DNA,RNA,and protein biosynthesis.Berberine could damage bacterial cell surface structure,especially for Gram-negative bacteria.Ca2 +and K + released from berberine-treated cells increased significantly compared to the control.Conclusion All of above results indicate that bacterial cells could not easily become resistant mutants to berberine.The mechanisms for the bactericidal effect of berberine include:inhibiting DNA duplication,RNA transcription,and protein biosynthesis;influencing or inhibiting enzyme activities;destructing the bacterial cell surface structure and resulting in Ca2 +and K +released from cells.All of the berberine bactericidal mechanisms are the most essential physiological functions for a live cell,if influenced any one such function,the mutation would be lethal mutation,so that it is difficult to get berberine resistant cells.The results in this paper also prefigure that berberine and its related Chinese medicines would provide a feasible way to control antibiotic resistance problem. | JIN Jian-ling,HUA Guo-qiang,MENG Zhen,GAO Pei-ji State Key Laboratory of Microbial Technology,School of Life Sciences,Shandong University,Jinan 250100,China | 2011 | Chinese Herbal Medicines2011，3，1： | 11 |
| 10 | The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation显示文摘Long non-coding RNAs(lncRNAs)have been identified as essential mediators in neurological dysfunction.Our previous study shows that berberine(BBR)hampers the nuclear-to-cytosolic translocation of high-mobility group box 1(HMGB1)in the process of poststroke inflammation.In this study,we explored the role of lncRNA metastasis‐associated lung adenocarcinoma transcript 1(Malat1)in the process of BBR-induced inhibition of HMGB1 in ischemic brain.Before the 60-min MCAO surgery,the mice were pretreated with BBR(50 mg·kg−1 per day,ig)for 14 days or ICV injected with specific lentiviral vector or shRNA.We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex,which was significantly attenuated by pretreatment with BBR.Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia,whereas overexpression of Malat1 exacerbated ischemic brain inflammation.Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines.The above results suggested a potential correlation between Malat1 and stroke inflammation.Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p,whereas Malat1 acted as a competitive endogenous RNA(ceRNA)for miR-181c-5p targeted the 3′-UTR of HMGB1 to promote inflammation after ischemic stroke.Knockdown of Malat1 significantly decreased HMGB1 level,which could be abrogated by transfection with miR-181c-5p inhibitors.Taken together,our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke,and they may provide a novel avenue for targeted therapy. | Ding-wen Cao Man-man Liu Rui Duan Yi-fu Tao Jun-shan Zhou Wei-rong Fang Jun-rong Zhu Li Niu Jian-guo Sun | 2020 | Acta Pharmacologica Sinica2020，41，1： | 11 |
| 11 | Berberine prevents stress-induced gut inflammation and visceral hypersensitivity and reduces intestinal motility in rats显示文摘BACKGROUND Irritable bowel syndrome (IBS) is a common chronic non-organic disease of the digestive system. Berberine (BBR) has been used to treat patients with IBS, but the underlying therapeutic mechanism is little understood. We believe that BBR achieves its therapeutic effect on IBS by preventing stress intestinal inflammation and visceral hypersensitivity and reducing bowel motility. AIM To test the hypothesis that BBR achieves its therapeutic effect on IBS by preventing subclinical inflammation of the intestinal mucosa and reducing visceral hypersensitivity and intestinal motility. METHODS IBS was induced in rats via water avoidance stress (WAS). qRT-PCR and histological analyses were used to evaluate the levels of cytokines and mucosal inflammation, respectively. Modified ELISA and qRT-PCR were used to evaluate the nuclear factor kappa-B (NF-κB) signal transduction pathway. Colorectal distention test, gastrointestinal transit measurement, Western blot, and qRT-PCR were used to analyze visceral sensitivity, intestinal motility, the expression of Ckit (marker of Cajal mesenchymal cells), and the expression of brain derived neurotrophic factor (BDNF) and its receptor TrkB.RESULTS WAS led to mucosal inflammation, visceral hyperalgesia, and high intestinal motility. Oral administration of BBR inhibited the NF-κB signal transduction pathway, reduced the expression of pro-inflammatory cytokines [interleukin (IL)- 1β, IL-6, interferon-γ, and tumor necrosis factor-α], promoted the expression of anti-inflammatory cytokines (IL-10 and transforming growth factor-β), and improved the terminal ileum tissue inflammation. BBR inhibited the expression of BDNF, TrkB, and C-kit in IBS rats, leading to the reduction of intestinal motility and visceral hypersensitivity. The therapeutic effect of BBR at a high dose (100 mg/kg) was superior to than that of the low-dose (25 mg/kg) group. CONCLUSION BBR reduces intestinal mucosal inflammation by inhibiting the intestinal NF-κB signal pathway in the IBS rats. BBR reduces the expression of BDNF, its receptor TrkB, and C-kit. BBR also reduces intestinal motility and visceral sensitivity to achieve its therapeutic effect on IBS. | Zhi-Chao Yu Yong-Xin Cen Ben-Hua Wu Cheng Wei Feng Xiong De-Feng Li Ting-Ting Liu Ming-Han Luo Li-Liangzi Guo Ying-Xue Li Li-Sheng Wang Jian-Yao Wang Jun Yao | 2019 | World Journal of Gastroenterology2019，25，29： | 11 |
| 12 | Cardiovascular and metabolic effects of Berberine显示文摘Berberine(BBR) is a natural alkaloid isolated from the Coptis Chinensis.While this plant has been used in Ay-urvedic and Chinese medicine for more than 2500 years,interest in its effects in metabolic and cardiovascular disease has been growing in the Western world in the last decade.Many papers have been published in these years reporting beneficial effects in carbohydrate and lip-id metabolism,endothelial function and the cardiovascu-lar system.In this review,we report a detailed analysis of the scientific literature regarding this topic,describing the effects and the underlying mechanisms of BBR on carbohydrate and lipid metabolism,endothelial function and the cardiovascular system. | Flora Affuso Valentina Mercurio Valeria Fazio Serafino Fazio | 2010 | World Journal of Cardiology2010，2，4： | 10 |
| 13 | In vitro assessment of the glucose-lowering effects of berberrubine-9-O-β-D-glucuronide, an active metabolite of berberrubine显示文摘Berberrubine (BRB ) 是在 vivo 比 BBR 显示出更强壮的葡萄糖阴沉的效果的 berberine (BBR ) 的主要代谢物。在另一方面, BRB 快速并且广泛地被使产生代射变化进 berberrubine-9-O -- 在在口头的管理以后的老鼠的 D-glucuronide (BRBG ) 。在这研究,我们在老鼠比较了 BRB 和 BRBG 的 pharmacokinetic 性质,并且探索了位于他们的葡萄糖阴沉的活动下面的机制。有导致 HFD 的多糖症的 C57BL/6 老鼠被管理 BRB (50 mg 吗?? | Na YANG Run-bin SUN Xing-long CHEN Le ZHEN Chun GE Yu-qing ZHAO Jun HE Jian-liang GENG Jia-hua GUO Xiao-yi YU Fei FEI Si-qi FENG Xuan-xuan ZHU Hong-bo WANG Feng-hua FU Ji-ye AA Guang-ji WANG | 2017 | Acta Pharmacologica Sinica2017，38，3： | 9 |
| 14 | Antinociceptive effect of berberine on visceral hypersensitivity in rats显示文摘AIM: To assess the protective effect of berberine administration and the role of nitric oxide (NO) in visceral hypersensitivity. METHODS: Fifty male Sprague-Dawley rats were randomly assigned to five groups. An inflammatory bowel disease model was induced in rats by intracolonic instillation of 1 mL 4% acetic acid at 8 cm proximal to the anus for 30 s and restraint stress. After subsidence of inflammation on day 7 of the experiment, the rats were subjected to rectal distension, performed by a balloon (6-Fr, 2 mm external diameter, disposable silicon balloon-urethral catheter for pediatric use) which was rapidly inflated with increasing volumes of prewarmed (37 ℃) water (0.1, 0.2, 0.3, 0.4, 0.6, 0.8 and 1 mL) for 30 s at four-minute intervals, and then the abdominal withdrawal reflex (AWR) and the level of fecal output were measured, respectively. AWR scores either 0, 1, 2, 3 or 4 were obtained by blinded observers. Rats had been pretreated with berberine or aminoguanidine (NO synthetase inhibitor) or berberine + aminoguanidine before measurement. RESULTS: The rats in the placebo group showed a hypersensitive response to rectal distension (2.69 ± 0.08 vs 1.52 ± 0.08, P = 0.000) and defecated more frequently than those in the control group (5.0 ± 0.16 vs 0.44 ± 0.16, P = 0.000). Comparing the berberine with placebo group, the AWR scores were reduced for all distension volumes and were significant at 0.2-1 mL (1.90 ± 0.08 vs 2.69 ± 0.08, P = 0.000), while the numbers of hard pellets, soft pellets, formless stools, and total fecal output in the placebo group were significantly larger than in the berberine group (5.0 ± 0.16 vs 2.56 ± 0.16, P = 0.000). Administration of aminoguanidine or berberine + aminoguanidine before VH score measurement reversed the antinociceptive effect of berberine (2.52 ± 0.08 vs 1.90 ± 0.08, P = 0.000; 2.50 ± 0.08 vs 1.90 ± 0.08, P = 0.000). The numbers of hard pellets, soft pellets, formless stool, and total of fecal output in aminoguanidine group were significantly larger than the corresponding values in control group, berberine group, and berberine + aminoguanidine group (4.81 ± 0.16 vs 0.44 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 2.56 ± 0.16, P = 0.000; 4.81 ± 0.16 vs 3.75 ± 0.16, P = 0.000). The berberine and berberine + aminoguanidine groups showed reduced defecation, but aminoguanidine alone did not reduce defecation (2.56 ± 0.16 vs 4.81 ± 0.16, P = 0.000; 3.75 ± 0.16 vs 4.81 ± 0.16, P = 0.000). CONCLUSION: Berberine had an antinociceptive effect on visceral hypersensitivity, and NO might play a role in this effect. | Qing-Lin Tang Min-Ling Lai Yuan-Fu Zhong Ai-Min Wang Jun-Kai Su Ming-Qing Zhang | 2013 | World Journal of Gastroenterology2013，19，28： | 9 |
| 15 | Berberine displays antitumor activity in esophageal cancer cells in vitro显示文摘AIM To investigate the effects of berberine on esophageal cancer(EC) cells and its molecular mechanisms.METHODS Human esophageal squamous cell carcinoma cell line KYSE-70 and esophageal adenocarcinoma cell line SKGT4 were used. The effects of berberine on cell proliferation were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assay. For cell cycle progression, KYSE-70 cells were stained with propidium iodide(PI) staining buffer(10 mg/m L PI and 100 mg/m L RNase A) for 30 min and cell cycle was analyzed using a BD FACSCalibur flow cytometer. For apoptosis assay, cells were stained with an Annexin V-FITC/PI apoptosis detection kit. The rate of apoptotic cells was analyzed using a dual laser flow cytometer and estimated using BD Mod Fit software. Levels of proteins related to cell cycle and apoptosis were examined by western blotting.RESULTS Berberine treatment resulted in growth inhibition of KYSE-70 and SKGT4 cells in a dose-dependent and time-dependent manner. KYSE-70 cells were more susceptible to the inhibitory activities of berberine than SKGT4 cells were. In KYSE-70 cells treated with 50 μmol/L berberine for 48 h, the number of cells in G2/M phase(25.94% ± 5.01%) was significantly higher than that in the control group(9.77% ± 1.28%, P < 0.01), and berberine treatment resulted in p21 upregulation in KYSE-70 cells. Flow cytometric analyses showed that berberine significantly augmented the KYSE-70 apoptotic population at 12 and 24 h posttreatment, when compared with control cells(0.83% vs 43.78% at 12 h, P < 0.05; 0.15% vs 81.86% at 24 h, P < 0.01), and berberine-induced apoptotic effect was stronger at 24 h compared with 12 h. Western blotting showed that berberine inhibited the phosphorylation of Akt, mammalian target of rapamycin and p70S6 K, and enhanced AMP-activated protein kinase phosphorylation in a sustained manner.CONCLUSION Berberine is an inhibitor of human EC cell growth and could be considered as a potential drug for the treatment of EC patients. | shu-xian jiang bo qi wen-jian yao cheng-wei gu xiu-feng wei yi zhao yu-zhen liu bao-sheng zhao | 2017 | World Journal of Gastroenterology2017，23，14： | 9 |
| 16 | Podoplanin mediates the renoprotective effect of berberine on diabetic kidney disease in mice显示文摘Hyperglycemia-caused podocyte injury plays a crucial role in the progress of diabetic kidney disease.Podoplanin,one of the podocyte-associated molecules,is closely related to the integrity of the glomerular filtration barrier.A number of studies demonstrate that berberine could ameliorate renal dysfunction in diabetic mice with nephropathy,but the molecular mechanisms have not been fully elucidated.In this study,we explored the relationship between the renoprotective effect of berberine and podoplanin expression in streptozotocin(STZ)-induced diabetic mice as well as mouse podocytes(MPC5 cells)cultured in high glucose(HG,30 mM)medium.We found that the expression levels of podoplanin were significantly decreased both in the renal glomerulus of STZ-induced diabetic mice and HG-cultured MPC5 cells.We also demonstrated that NF-κB signaling pathway was activated in MPC5 cells under HG condition,which downregulated the expression level of podoplanin,thus leading to increased podocyte apoptosis.Administration of berberine(100,200 mg/kg every day,ig;for 8 weeks)significantly improved hyperglycemia and the renal function of STZ-induced diabetic mice and restored the expression level of podoplanin in renal glomerulus.In high glucose-cultured MPC5 cells,treatment with berberine(30-120μM)dose-dependently decreased the apoptosis rate,increased the expression of podoplanin,and inhibited the activation of NF-κB signaling pathway.When podoplanin expression was silenced with shRNA,berberine treatment still inhibited the NF-κB signaling pathway,but its antiapoptotic effect on podocytes almost disappeared.Our results suggest that berberine inhibits the activation of NF-κB signaling pathway,thus increasing the podoplanin expression to exert renoprotective effects. | Jing Yu Guan-nan Zong Hao Wu Ke-qin Zhang | 2019 | Acta Pharmacologica Sinica2019，40，12： | 8 |
| 17 | Mechanism underlying berberine's effects on HSP70/TNFα under heat stress:Correlation with the TATA boxes显示文摘Heat stress can stimulate an increase in body temperature,which is correlated with increased expression of heat shock protein 70(HSP70) and tumor necrosis factor α(TNFα).The exact mechanism underlying the HSP70 and TNFα induction is unclear.Berberine(BBR) can significantly inhibit the temperature rise caused by heat stress,but the mechanism responsible for the BBR effect on HSP70 and TNFα signaling has not been investigated.The aim of the present study was to explore the relationship between the expression of HSP70 and TNFα and the effects of BBR under heat conditions,using in vivo and in vitro models.The expression levels of HSP70 and TNFα were determined using RT-PCR and Western blotting analyses.The results showed that the levels of HSP70 and TNFα were up-regulated under heat conditions(40 °C).HSP70 acted as a chaperone to maintain TNFα homeostasis with rising the temperature,but knockdown of HSP70 could not down-regulate the level of TNFα.Furthermore,TNFα could not influence the expression of HSP70 under normal and heat conditions.BBR targeted both HSP70 and TNFα by suppressing their gene transcription,thereby decreasing body temperature under heat conditions.In conclusion,BBR has a potential to be developed as a therapeutic strategy for suppressing the thermal effects in hot environments. | JIANG Jing-Fei LEI Fan YUAN Zhi-Yi WANG Yu-Gang WANG Xin-Pei YAN Xiao-Jin YU Xuan XING Dong-Ming DU Li-Jun | 2017 | Chinese Journal of Natural Medicines2017，15，3： | 8 |
| 18 | 小檗碱通过Ezrin蛋白抑制鼻咽癌细胞迁移和伪足形成显示文摘目的观察小檗碱(Berberine,BBR)对鼻咽癌细胞埃兹蛋白(Ezrin)和磷酸化埃兹蛋白(phos-Ezrin)表达的影响以及其对细胞伪足形成和迁移的抑制作用,探讨BBR抗鼻咽癌转移可能的分子机制。方法以体外培养的鼻咽癌细胞株(CNE1)为研究对象,用MTr法分析BBR对CNE1细胞生长的影响,选用BBR细胞无毒性浓度(non-cytotoxic concentration,NCC)进行实验。免疫印迹(Western-blotting)分析CNE1Ezrin和phos-Ezrin的表达。用光镜CNE1观察细胞迁移能力,电子显微镜观察细胞伪足形成。Ezrin小干扰RNA(Ezrin-siRNA)转染阻断Ezrin蛋白表达,进一步确证BBR通过Ezrin抑制细胞伪足形成。结果MTT结果显示,BBR在5μM以上明显抑制CNE1增殖(P〈0.05),浓度(0—5)州对CNE1细胞生长增殖抑制作用不明显,为BBR对CNE1的细胞无毒性浓度(NCC)。BBR在NCC能明显抑制CNE1细胞phos-Ezfin表达,且呈浓度依赖性。光镜观察显示BBR对CNE1细胞迁移有明显的抑制作用。电镜观察结果显示,BBR抑制CNE1细胞伪足形成。结论BBR可能通过抑制Ezfin磷酸化而抑制鼻咽癌CNE1迁移。 | 陈宇 王巍巍 华建江 王雷 谢春蕾 孟菁菁 黄大毛 伍斌 唐发清 | 2008 | 中国耳鼻咽喉颅底外科杂志2008，14，6： | 8 |
| 19 | Microbiota transplantation reveals beneficial impact of berberine on hepatotoxicity by improving gut homeostasis显示文摘Berberine has been shown to reduce acute liver injury although the underlying mechanism is not fully understood. Because of the anatomic connection, the liver is constantly exposed to gut-derived bacterial products and metabolites. In this study, we showed that berberine has beneficial effects on both hepatotoxicity and intestinal damage in a rat model of chronic or acute liver injury. Microbiota transplantation from the rats with chronic hepatotoxicity could aggravate acute hepatotoxicity in mice treated with diethylnitrosamine(DEN). In rat models with gut homeostasis disruption induced by penicillin or dextran sulfate sodium(DSS), their fecal microbiota could also cause an enhanced hepatotoxicity of recipient mice. When treated with berberine,the DSS-induced enteric dysbacteriosis could be mitigated and their fecal bacteria were able to reduce acute hepatotoxicity in recipient mice. This study indicates that berberine could improve intestinal dysbacteriosis, which reduces the hepatotoxicity caused by pathological or pharmacological intervention. Fecal microbiota transplantation might be a useful method to directly explore homeostatic alteration in gut microbiota. | Chenjie Qin Huilu Zhang Linghao Zhao Min Zeng Weijian Huang Gongbo Fu Weiping Zhou Hongyang Wang Hexin Yan | 2018 | Science China(Life Sciences)2018，61，12： | 8 |
| 20 | A nutraceutical combination improves insulin sensitivity in patients with metabolic syndrome显示文摘AIM:To test the efficacy of a proprietary nutraceutical combination in reducing insulin resistance associated with the metabolic syndrome(MetS).METHODS:Sixty-four patients with MetS followed at a tertiary outpatient clinic were randomly assigned to receive either placebo or a proprietary nutraceutical combination(AP)consisting of berberine,policosanol and red yeast rice,in a prospective,double-blind,placebo-controlled study.Evaluations were performed at baseline and after 18 wk of treatment.The homeostasis model assessment of insulin resistance(HOMAIR)index was the primary outcome measure.Secondary endpoints included lipid panel,blood glucose and insulin fasting,after a standard mixed meal and after an oral glucose tolerance test(OGTT),ow-mediated dilation(FMD),and waist circumference.RESULTS:Fifty nine patients completed the study,2 withdrew because of adverse effects.After 18 wk there was a signif icant reduction in the HOMA-IR index in the AP group compared with placebo(ΔHOMA respectively-0.6 ± 1.2 vs 0.4 ± 1.9;P < 0.05).Total and low density lipoprotein cholesterol also significantly decreased in the treatment arm compared with placebo(Δlow density lipoprotein cholesterol-0.82 ± 0.68 vs-0.13 ± 0.55 mmol/L;P < 0.001),while triglycerides,high density lipoprotein cholesterol,and the OGTT were not affected.In addition,there were significant reductions in blood glucose and insulin after the standard mixed meal,as well as an increase in FMD(ΔFMD 1.9 ± 4.2 vs 0 ± 1.9 %;P < 0.05)and a significant reduction in arterial systolic blood pressure in the AP arm.CONCLUSION:This short-term study shows that AP has relevant beneficial effects on insulin resistance and many other components of MetS. | Flora Affuso Valentina Mercurio Antonio Ruvolo Concetta Pirozzi Filomena Micillo Guido Carlomagno Fabrizia Grieco Serafino Fazio | 2012 | World Journal of Cardiology2012，4，3： | 7 |
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