EXCLI J EXCLI Journal 1611-2156 Leibniz Research Centre for Working Environment and Human Factors 2023-5898 10.17179/excli2022-5898 Doc315 Letter to the editor Recent studies on berberine and its biological and pharmacological activities Nadalin Priscilla 1 Kim Yong-Goo 2 Park Sang Un * 1 Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea Department of Herbal Crop Research, National Institute of Horticultural and Herbal Science, RDA, Eumseong 27709, Korea *To whom correspondence should be addressed: Sang Un Park, Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea; Tel.: +82-42-821-5730, Fax: +82-42-822-2631, E-mail: supark@cnu.ac.kr 28 02 2023 2023 22 315 328 02 02 2023 21 02 2023 Copyright © 2023 Nadalin et al. 2023

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Benzylisoquinoline alkaloids (BIAs) are a variety of plant chemicals that consist of roughly 2,500 known compounds. Many BIAs are characterized by potent pharmacological activities, notably the narcotic analgesics morphine and codeine, the antimicrobials sanguinarine and berberine, the muscle relaxants (+)-tubocurarine and papaverine, and the cough suppressant and anticancer drug noscapine. A number of medicines that have been known to humankind since ancient times are plant-derived BIAs (Hagel and Facchini, 2013[26]).

Berberine (BBR), a yellowish crystalline benzylisoquinoline alkaloid, is an active compound found in several plants. BBR has been used in traditional Chinese medicine for a long time to treat several conditions (Zhu et al., 2022[107]). BBR alkaloids are found in the leaves, bark, twigs, rhizomes, roots, and stems of plants, with bark and roots containing reasonably high amounts of BBR in comparison to other plant parts (Andola et al., 2010[7]). BBR is a tetracyclic ring system consisting of an N-benzyltetrahydroisoquinoline core with an incorporated additional C13 carbon bridge, which is formed through an oxidative step where the N-methyl group is provided by S-adenosyl methionine to an iminium ion, with a consequent cyclization into an aromatic ring through the phenolic hydroxyl. Starting from tyrosine, BBR biosynthesis consists of 13 stages in which various enzymatic reactions are involved (Singh et al., 2021[70]).

BBR has been reported to be useful for a wide range of biological and pharmacological activities, including antioxidant, anti-inflammatory, anticancer, antimicrobial, antidepressant, hepatoprotective, hypolipidemic, and hypoglycemic activities (Almatroodi et al., 2022[5]; Behl et al., 2022[8]; Cheng et al., 2022[11]; Och et al., 2022[54]; Yarmohammadi et al., 2022[93]; Mohammadian Haftcheshmeh and Momtazi‐Borojeni, 2021[48]). Interestingly, many studies have provided evidence suggesting that BBR is a valuable drug candidate with a wide range of therapeutic uses (Mujtaba et al., 2022[49]). Here, we report a summary of the current literature available on the biological and pharmacological activities of BBR (Table 1(Tab. 1); References in Table 1: Abdulredha et al., 2021[1]; Abudureyimu et al., 2020[2]; Akhzari et al., 2022[3]; Albasher et al., 2020[4]; An et al., 2022[6]; Chen et al., 2021[10], 2022[9]; Cole et al., 2021[12]; Cui et al., 2022[13]; Dai et al., 2021[14], 2022[15]; Deng and Ma, 2021[16]; Deng et al., 2022[17]; Diao et al., 2022[18]; Ding et al., 2021[19]; Duarte-Olivenza et al., 2021[20]; Ehteshamfar et al., 2020[21]; Fang et al., 2022[22]; Fu et al., 2020[23]; Ghanem et al., 2021[24]; Gu et al., 2021[25]; Han et al., 2022[27]; He et al., 2021[28]; Huang et al., 2021[30], 2022[29]; Ibrahim Fouad and Ahmed, 2021[31]; Jia et al., 2022[32]; Jiang et al., 2021[33]; Kadir et al., 2022[34]; Kang et al., 2020[35]; Li et al., 2020[38], 2021[36], 2022[37]; Liang et al., 2021[39]; Liu et al., 2022[40]; Luo et al., 2022[41]; Lv et al., 2022[42]; Ma et al., 2021[43], 2022[44]; Malekinezhad et al., 2021[45]; Man et al., 2022[46]; Mishra et al., 2020[47]; Ni et al., 2022[50][51]; Noh et al., 2022[52]; Obchoei et al., 2022[53]; Pan et al., 2022[55]; Pang et al., 2021[56]; Park et al., 2022[57]; Pu et al., 2021[58]; Qiu et al., 2021[59]; Qu et al., 2020[60]; Ren et al., 2021[61]; Rong et al., 2022[62]; Seth and Chopra, 2022[64]; Seth et al., 2021[63]; Shaker et al., 2021[65]; Shan et al., 2021[66]; Shao et al., 2021[67]; Shen et al., 2021[68]; Shu et al., 2021[69]; Sui et al., 2021[71]; Sun et al., 2022[72]; Szalak et al., 2021[73]; Tang et al., 2021[74]; Tian et al., 2021[75], 2022[76]; Vita et al., 2021[77]; Waly et al., 2022[78]; Wang et al., 2021[80], 2022[79]; Wen et al., 2022[81]; Wolf et al., 2021[82]; Wu et al., 2021[83]; Xia et al., 2022[84]; Xiang et al., 2021[85]; Xie et al., 2020[86], 2021[88], 2022[87]; Xu et al., 2021[89]; Yan et al., 2022[90]; Yang et al., 2021[92], 2022[91]; Ye et al., 2021[94], 2022[95]; Yi et al., 2021[96]; Yin et al., 2021[97]; Yu et al., 2021[98]; Zhai et al., 2020[99][100]; Zhang et al., 2022[101][102]; Zhao et al., 2021[103]; Zheng et al., 2021[104][105]; Zhu et al., 2021[106]).

Notes

Priscilla Nadalin and Yong-Goo Kim contributed equally as first author.

DeclarationConflict of interest statement

The authors have no conflicts of interest to declare.

Acknowledgments

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2022R1I1A3054240)

Abdulredha A Abosaooda M Al-Amran F Hadi NR Berberine protests the heart from ischemic reperfusion injury via interference with oxidative and inflammatory pathways Med Arch 2021 75 3 174 Abudureyimu M Yu W Cao RY Zhang Y Liu H Zheng H Berberine promotes cardiac function by upregulating PINK1/Parkin-mediated mitophagy in heart failure Front Physiol 2020 11 565751 Akhzari M Barazesh M Jalili S Farzinezhadi Zadeh MM Berberine recovered oxidative stress induced by sodium nitrite in rat erythrocytes Drug Metab Bioanal Lett 2022 15 192 201 Albasher G Alkahtani S Alarifi S Berberine mitigates oxidative damage associated with testicular impairment following mercury chloride intoxication J Food Biochem 2020 44 9 e13385 Almatroodi SA Alsahli MA Rahmani AH Berberine: An important emphasis on its anticancer effects through modulation of various cell signaling pathways Molecules 2022 27 18 5889 An C Wu Y Wu J Liu H Zhou S Ge D Berberine ameliorates pulmonary inflammation in mice with influenza viral pneumonia by inhibiting NLRP3 inflammasome activation and gasdermin D‐mediated pyroptosis Drug Dev Res 2022 83 1707 1721 Andola HC Gaira KS Rawal RS Rawat MSM Bhatt ID Habitat‐dependent variations in berberine content of Berberis asiatica Roxb. ex. DC. in Kumaon, Western Himalaya Chem Biodivers 2010 7 415 420 Behl T Singh S Sharma N Zahoor I Albarrati A Albratty M Expatiating the pharmacological and nanotechnological aspects of the alkaloidal drug berberine: current and future trends Molecules 2022 27 12 3705 Chen J Huang Y Bian X He Y Berberine ameliorates inflammation in acute lung injury via NF-κB/Nlrp3 signaling pathway Front Nutr 2022 9 851255 Chen P Li Y Xiao L Berberine ameliorates nonalcoholic fatty liver disease by decreasing the liver lipid content via reversing the abnormal expression of MTTP and LDLR Exp Ther Med 2021 22 4 1109 Cheng Z Kang C Che S Su J Sun Q Ge T Berberine: a promising treatment for neurodegenerative diseases Front Pharmacol 2022 13 845591 Cole LK Sparagna GC Vandel M Xiang B Dolinsky VW Hatch GM Berberine elevates cardiolipin in heart of offspring from mouse dams with high fat diet-induced gestational diabetes mellitus Sci Rep 2021 11 1 15770 Cui G Wang H Yang C Zhou X Wang J Wang T Berberine prevents lethal EV71 neurological infection in newborn mice Front Pharmacol 2022 13 1027566 Dai JG Huang XM Zhang C Gao JM Mechanisms of lipid metabolism promoted by berberine via peroxisome proliferator‐activated receptor gamma during in vitro maturation of porcine oocytes Anim Sci J 2021 92 1 e13582 Dai L Zhu L Ma S Liu J Zhang M Li J Berberine alleviates NLRP3 inflammasome induced endothelial junction dysfunction through Ca2+ signalling in inflammatory vascular injury Phytomedicine 2022 101 154131 Deng H Ma Z Protective effects of berberine against MPTP-induced dopaminergic neuron injury through promoting autophagy in mice Food Funct 2021 12 8366 8375 Deng J Zhao L Yuan X Li Y Shi J Zhang H Pre-administration of berberine exerts chemopreventive effects in AOM/DSS-induced colitis-associated carcinogenesis mice via modulating inflammation and intestinal microbiota Nutrients 2022 14 4 726 Diao J Chen X Mou P Ma X Wei R Potential therapeutic activity of berberine in thyroid-associated ophthalmopathy: inhibitory effects on tissue remodeling in orbital fibroblasts Invest Ophthalmol Vis Sci 2022 63 10 6 Ding L Li S Wang F Xu J Li S Wang B Berberine improves dietary-induced cardiac remodeling by upregulating Kruppel-like factor 4-dependent mitochondrial function Biol Chem 2021 402 795 803 Duarte-Olivenza C Montero JA Lorda-Diez CI Effects of berberine on the chondrogenic differentiation of embryonic limb skeletal progenitors J Inflamm Res 2021 14 5001 5011 Ehteshamfar SM Akhbari M Afshari JT Seyedi M Nikfar B Shapouri‐Moghaddam A Anti‐inflammatory and immune‐modulatory impacts of berberine on activation of autoreactive T cells in autoimmune inflammation J Cell Mol Med 2020 24 13573 13588 Fang W Huang X Wu K Zong Y Yu J Xu H Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy Front Mol Neurosci 2022 15 930599 Fu S He Z Tang Y Lan B Effects and mechanism of berberine on the dexamethasone-induced injury of human tendon cells Evid Based Complement Alternat Med 2020 2020 8832218 Ghanem HB Emam MN Mohammed ADA Nagi A-ER Impact of berberine on some epigenetic, transcription regulation and inflammatory biomarkers in a mice model of epilepsy Rep Biochem Mol Biol 2021 10 3 362 Gu L Ke Y Gan J Li X Berberine suppresses bone loss and inflammation in ligature-induced periodontitis through promotion of the G protein-coupled estrogen receptor-mediated inactivation of the p38MAPK/NF-κB pathway Arch Oral Biol 2021 122 104992 Hagel JM Facchini PJ Benzylisoquinoline alkaloid metabolism: a century of discovery and a brave new world Plant Cell Physiol 2013 54 5 647 672 Han YC Xie HZ Lu B Xiang RL Li JY Qian H Effect of berberine on global modulation of lncRNAs and mRNAs expression profiles in patients with stable coronary heart disease BMC Genomics 2022 23 1 400 He C Jia X Zhang L Gao F Jiang W Wen C Dietary berberine can ameliorate glucose metabolism disorder of Megalobrama amblycephala exposed to a high-carbohydrate diet Fish Physiol Biochem 2021 47 499 513 Huang Q He W Weng Y Wang Y Liu Y Xiang Y Berberine inhibits osteogenic differentiation of aortic valve interstitial cells by interfering Smad1/5/8 and NF-κB pathways Vascul Pharmacol 2022 144 106986 Huang S Liu H Lin Y Liu M Li Y Mao H Berberine protects against NLRP3 inflammasome via ameliorating autophagic impairment in MPTP-induced Parkinson’s disease model Front Pharmacol 2021 11 618787 Ibrahim Fouad G Ahmed KA Neuroprotective potential of berberine against doxorubicin-induced toxicity in rat’s brain Neurochem Res 2021 46 3247 3263 Jia X Shao W Tian S Berberine alleviates myocardial ischemia–reperfusion injury by inhibiting inflammatory response and oxidative stress: The key function of miR-26b-5p-mediated PTGS2/MAPK signal transduction Pharm Biol 2022 60 652 663 Jiang Y Zhao L Chen Q Zhou L Exploring the mechanism of berberine intervention in ulcerative colitis from the perspective of inflammation and immunity based on systemic pharmacology Evidence Based Complement Alternat Med 2021 2021 9970240 Kadir A Singh J Rahi V Kumar P Berberine ameliorate haloperidol and 3-Nitropropionic acid-induced neurotoxicity in rats Neurochem Res 2022 47 3285 3297 Kang H Yao Y Zhang X Mixed micelles with galactose ligands for the oral delivery of berberine to enhance its bioavailability and hypoglycemic effects J Biomed Nanotechnol 2020 16 1755 1764 Li B Niu S Geng H Yang C Zhao C Berberine attenuates neonatal sepsis in mice by inhibiting FOXA1 and NF-κB signal transduction via the induction of MiR-132-3p Inflammation 2021 44 2395 2406 Li M She J Ma L Ma L Ma X Zhai J Berberine protects against palmitate induced beta cell injury via promoting mitophagy Genes Genomics 2022 44 867 878 Li M Zhou W Dang Y Li C Ji G Zhang L Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice Biomed Pharmacother 2020 132 110953 Liang Y Ye C Chen Y Chen Y Diao S Huang M Berberine improves behavioral and cognitive deficits in a mouse model of alzheimer’s disease via regulation of β-amyloid production and endoplasmic reticulum stress ACS Chem Neurosci 2021 12 1894 1904 Liu Y Fang X Li Y Bing L Li Y Fang J Berberine suppresses the migration and invasion of colon cancer cells by inhibition of lipogenesis through modulation of promyelocytic leukemia zinc finger-mediated sterol-regulatory element binding proteins cleavage-activating protein ubiquitination J Pharm Pharmacol 2022 74 1353 1363 Luo Z Li Z Liang Z Wang L He G Wang D Berberine increases stromal production of Wnt molecules and activates Lgr5+ stem cells to promote epithelial restitution in experimental colitis BMC Biol 2022 20 1 287 Lv Y Yang H Ye P Qian Z Wang D Kong C Berberine inhibits low shear stress-induced vascular endothelial inflammation via decreasing phosphorylation of Akt and IRF3 Tissue Cell 2022 79 101946 Ma Y Yan G Guo J Li F Zheng H Wang C Berberine prolongs mouse heart allograft survival by activating T cell apoptosis via the mitochondrial pathway Front Immunol 2021 12 616074 Ma Z Zhu L Wang S Guo X Sun B Wang Q Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome Ren Fail 2022 44 1 923 932 Malekinezhad P Ellestad LE Afzali N Farhangfar SH Omidi A Mohammadi A Evaluation of berberine efficacy in reducing the effects of aflatoxin B1 and ochratoxin A added to male broiler rations Poult Sci 2021 100 797 809 Man B Hu C Yang G Xiang J Yang S Ma C Berberine attenuates diabetic atherosclerosis via enhancing the interplay between KLF16 and PPARα in ApoE−/− mice Biochem Biophys Res Commun 2022 624 59 67 Mishra R Nathani S Varshney R Sircar D Roy P Berberine reverses epithelial-mesenchymal transition and modulates histone methylation in osteosarcoma cells Mol Biol Rep 2020 47 8499 8511 Mohammadian Haftcheshmeh S Momtazi‐Borojeni AA Berberine as a promising natural compound for the treatment of periodontal disease: A focus on anti‐inflammatory properties J Cell Mol Med 2021 25 11333 11337 Mujtaba MA Akhter MH Alam M Ali MD Hussain A An updated review on therapeutic potential and recent advances in drug delivery of Berberine: Current status and future prospect Curr Pharm Biotechnol 2022 23 1 60 71 Ni L Li Z Ren H Kong L Chen X Xiong M Berberine inhibits non‐small cell lung cancer cell growth through repressing DNA repair and replication rather than through apoptosis Clin Exp Pharmacol Physiol 2022 49 1 134 144 Ni L Sun P Ai M Kong L Xu R Li J Berberine inhibited the formation of metastasis by intervening the secondary homing of colorectal cancer cells in the blood circulation to the lung and liver through HEY2 Phytomedicine 2022 104 154303 Noh JW Jun MS Yang HK Lee BC Cellular and molecular mechanisms and effects of berberine on obesity-induced inflammation Biomedicines 2022 10 7 1739 Obchoei S Detarya M Boonnate P Saranaruk P Vaeteewoottacharn K Mahalapbutr P Low dose berberine suppresses cholangiocarcinoma cell progression as a multi-kinase inhibitor Asian Pac J Cancer Prev 2022 23 3379 3386 Och A Och M Nowak R Podgórska D Podgórski R Berberine, a herbal metabolite in the metabolic syndrome: The risk factors, course, and consequences of the disease Molecules 2022 27 4 1351 Pan X Song Z Cui Y Qi M Wu G Wang M Enhancement of sensitivity to tamoxifen by berberine in breast cancer cells by inhibiting ER-α36 expression Iran J Pharm Res 2022 21 1 e126919 Pang H Zhou Y Wang J Wu H Liu X Gao F Berberine influences the survival of fat grafting by inhibiting autophagy and apoptosis of human adipose derived mesenchymal stem cells Drug Des Devel Ther 2021 15 4795 4809 Park GS Park B Lee MY Berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway Planta Med 2022 88 1116 1122 Pu Z Sun Y Jiang H Hou Q Yan H Wen H Effects of berberine on gut microbiota in patients with mild metabolic disorders induced by Olanzapine Am J Chin Med 2021 49 1949 1963 Qiu F Lu W Ye S Liu H Zeng Q Huang H Berberine promotes induction of immunological tolerance to an allograft via downregulating memory CD8+ T-cells through altering the gut microbiota Front Immunol 2021 12 646831 Qu H Song X Song Z Jiang X Gao X Bai L Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma Cancer Cell Int 2020 20 1 592 Ren S Cai Y Hu S Liu J Zhao Y Ding M Berberine exerts anti-tumor activity in diffuse large B-cell lymphoma by modulating c-myc/CD47 axis Biochem Pharmacol 2021 188 114576 Rong Q Han B Li Y Yin H Li J Hou Y Berberine reduces lipid accumulation by promoting fatty acid oxidation in renal tubular epithelial cells of the diabetic kidney Front Pharmacol 2022 12 3926 Seth E Ahsan AU Kaushal S Mehra S Chopra M Berberine affords protection against oxidative stress and apoptotic damage in F1 generation of wistar rats following lactational exposure to chlorpyrifos Pestic Biochem Physiol 2021 179 104977 Seth E Chopra M Neuroprotective efficacy of berberine following developmental exposure to chlorpyrifos in F1 generation of Wistar rats: Apoptosis-autophagy interplay Sci Total Environ 2022 834 155292 Shaker FH El-Derany MO Wahdan SA El-Demerdash E El-Mesallamy HO Berberine ameliorates doxorubicin-induced cognitive impairment (chemobrain) in rats Life Sci 2021 269 119078 Shan MY Dai Y Ren XD Zheng J Zhang KB Chen B Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis J Integr Med 2021 19 545 554 Shao J Liu S Zheng X Chen J Li L Zhu Z Berberine promotes peri‐implant osteogenesis in diabetic rats by ROS‐mediated IRS‐1 pathway Biofactors 2021 47 1 80 92 Shen HR Xu X Ye D Li XL Berberine improves the symptoms of DHEA-induced PCOS rats by regulating gut microbiotas and metabolites Gynecol Obstet Invest 2021 86 388 397 Shu X Li M Cao Y Li C Zhou W Ji G Berberine alleviates non-alcoholic steatohepatitis through modulating gut microbiota mediated intestinal FXR activation Front Pharmacol 2021 12 750826 Singh S Pathak N Fatima E Negi AS Plant isoquinoline alkaloids: Advances in the chemistry and biology of berberine Eur J Med Chem 2021 226 113839 Sui M Jiang X Sun H Liu C Fan Y Berberine ameliorates hepatic insulin resistance by regulating microRNA-146b/SIRT1 pathway Diabetes Metab Syndr Obes 2021 14 2525 2537 Sun S Yang Y Xiong R Ni Y Ma X Hou M Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut Life Sci 2022 311 121141 Szalak R Kukula-Koch W Matysek M Kruk-Słomka M Koch W Czernicka L Effect of berberine isolated from barberry species by centrifugal partition chromatography on memory and the expression of parvalbumin in the mouse hippocampus Proper Int J Mol Sci 2021 22 9 4487 Tang M Yuan D Liao P Berberine improves intestinal barrier function and reduces inflammation, immunosuppression, and oxidative stress by regulating the NF-κB/MAPK signaling pathway in deoxynivalenol-challenged piglets Environ Pollut 2021 289 117865 Tian L Ri H Qi J Fu P Berberine elevates mitochondrial membrane potential and decreases reactive oxygen species by inhibiting the Rho/ROCK pathway in rats with diabetic encephalopathy Mol Pain 2021 17 1744806921996101 Tian W Hao H Chu M Gong J Li W Fang Y Berberine suppresses lung metastasis of cancer via inhibiting endothelial transforming growth factor beta receptor 1 Front Pharmacol 2022 13 917827 Vita AA Aljobaily H Lyons DO Pullen NA Berberine delays onset of collagen-induced arthritis through T cell suppression Int J Mol Sci 2021 22 7 3522 Waly H Abd-Elkareem M Raheem S Abou Khalil NS Berberine protects against diclofenac sodium-induced testicular impairment in mice by its anti-oxidant and anti-apoptotic activities Iran J Basic Med Sci 2022 25 6 767 Wang M Geng X Li K Wang Y Duan X Hou C Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats BMC Complement Med Ther 2022 22 1 198 Wang Y Tong Q Ma SR Zhao ZX Pan LB Cong L Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota Signal Transduct Target Ther 2021 6 1 77 Wen L Han Z Li J Du Y c-MYC and HIF1α promoter G-quadruplexes dependent metabolic regulation mechanism of berberine in colon cancer J Gastrointest Oncol 2022 13 3 1152 Wolf PG Devendran S Doden HL Ly LK Moore T Takei H Berberine alters gut microbial function through modulation of bile acids BMC Microbiol 2021 21 1 24 Wu Y Chen Q Wen B Wu N He B Chen J Berberine reduces Aβ42 deposition and tau hyperphosphorylation via ameliorating endoplasmic reticulum stress Front Pharmacol 2021 12 640758 Xia S Ma L Wang G Yang J Zhang M Wang X In vitro antimicrobial activity and the mechanism of berberine against methicillin-resistant Staphylococcus aureus isolated from bloodstream infection patients Infect Drug Resist 2022 15 1933 1944 Xiang XY Liu T Wu Y Jiang XS He JL Chen XM Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress Mol Med Rep 2021 23 1 3 Xie P Ren ZK Lv J Hu YM Guan ZZ Yu WF Berberine ameliorates oxygen-glucose deprivation/ reperfusion-induced apoptosis by inhibiting endoplasmic reticulum stress and autophagy in PC12 cells Curr Med Sci 2020 40 1047 1056 Xie W Su F Wang G Peng Z Xu Y Zhang Y Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis Front Pharmacol 2022 13 4734 Xie Z Liu X Huang X Liu Q Yang M Huang D Remodelling of gut microbiota by Berberine attenuates trimethylamine N-oxide-induced platelet hyperreaction and thrombus formation Eur J Pharmacol 2021 911 174526 Xu Y Yu T Ma G Zheng L Jiang X Yang F Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway Int J Biol Sci 2021 17 12 3173 Yan S Chang J Hao X Liu J Tan X Geng Z Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora Phytomedicine 2022 102 154217 Yang KT Chao TH Wang IC Luo YP Ting PC Lin JH Berberine protects cardiac cells against ferroptosis Tzu Chi Med J 2022 34 3 310 Yang L Cao J Wei J Deng J Hou X Hao E Antiproliferative activity of berberine in HepG2 cells via inducing apoptosis and arresting cell cycle Food Funct 2021 12 12115 12126 Yarmohammadi F Hayes AW Karimi G The therapeutic effects of berberine against different diseases: A review on the involvement of the endoplasmic reticulum stress Phytother Res 2022 36 3215 3231 Ye Y Liu X Wu N Han Y Wang J Yu Y Efficacy and safety of berberine alone for several metabolic disorders: a systematic review and meta-analysis of randomized clinical trials Front Pharmacol 2021 12 653887 Ye Z Wang Q Dai S Ji X Cao P Xu C The Berberis vulgaris L. extract berberine exerts its anti-oxidant effects to ameliorate cholesterol overloading–induced cell apoptosis in the primary mice hepatocytes: an in vitro study In Vitro Cell Dev Biol Anim 2022 58 855 866 Yi J Wu S Tan S Qin Y Wang X Jiang J Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis Cell Death Discov 2021 7 1 374 Yin Z Tan R Yuan T Chen S Quan Y Hao Q Berberine prevents diabetic retinopathy through inhibiting HIF-1α/VEGF/NF-κ B pathway in db/db mice Pharmazie 2021 76 165 171 Yu M Alimujiang M Hu L Liu F Bao Y Yin J Berberine alleviates lipid metabolism disorders via inhibition of mitochondrial complex I in gut and liver Int J Biol Sci 2021 17 7 1693 Zhai J Li Z Zhang H Ma L Ma Z Zhang Y Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF‑κB signaling pathway Mol Med Rep 2020 22 4227 4235 Zhai L Huang T Xiao HT Wu PG Lin CY Ning ZW Berberine Suppresses colonic inflammation in dextran sulfate sodium–induced murine colitis through inhibition of cytosolic phospholipase A2 activity Front Pharmacol 2020 11 576496 Zhang M Liu J Yu C Tang S Jiang G Zhang J Berberine Regulation of cellular oxidative stress, apoptosis and autophagy by modulation of m6A mRNA methylation through targeting the Camk1db/ERK pathway in zebrafish-hepatocytes Antioxidants (Basel) 2022 11 12 2370 Zhang M Yang H Yang E Li J Dong L Berberine decreases intestinal GLUT2 translocation and reduces intestinal glucose absorption in mice Int J Mol Sci 2022 23 1 327 Zhao Z Zeng J Guo Q Pu K Yang Y Chen N Berberine suppresses stemness and tumorigenicity of colorectal cancer stem-like cells by inhibiting m6A methylation Front Oncol 2021 11 775418 Zheng C Wang Y Xu Y Zhou L Hassan S Xu G Berberine inhibits dendritic cells differentiation in DSS-induced colitis by promoting Bacteroides fragilis Int Immunopharmacol 2021 101 108329 Zheng Y Kou J Wang P Ye T Wang Z Gao Z Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages Aging (Albany NY) 2021 13 5 7096 Zhu C Huang K Bai Y Feng X Gong L Wei C Dietary supplementation with berberine improves growth performance and modulates the composition and function of cecal microbiota in yellow-feathered broilers Poult Sci 2021 100 1034 1048 Zhu C Li K Peng XX Yao TJ Wang ZY Hu P Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy Front Immunol 2022 13 1083788 Recent studies on the biological and pharmacological activities of berberine