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]).
Table 1. Recent studies on the biological and pharmacological activities of berberine.
Notes
Priscilla Nadalin and Yong-Goo Kim contributed equally as first author.
Declaration
Conflict 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)
References
- 1.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. doi: 10.5455/medarh.2021.75.174-179. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.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. doi: 10.3389/fphys.2020.565751. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.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. doi: 10.2174/2949681015666220902114519. [DOI] [PubMed] [Google Scholar]
- 4.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. doi: 10.1111/jfbc.13385. [DOI] [PubMed] [Google Scholar]
- 5.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. doi: 10.3390/molecules27185889. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.An C, Wu Y, Wu J, Liu H, Zhou S, Ge D, et al. 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. doi: 10.1002/ddr.21995. [DOI] [PubMed] [Google Scholar]
- 7.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. doi: 10.1002/cbdv.200900041. [DOI] [PubMed] [Google Scholar]
- 8.Behl T, Singh S, Sharma N, Zahoor I, Albarrati A, Albratty M, et al. Expatiating the pharmacological and nanotechnological aspects of the alkaloidal drug berberine: current and future trends. Molecules. 2022;27(12):3705. doi: 10.3390/molecules27123705. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.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. doi: 10.3389/fnut.2022.851255. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.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. doi: 10.3892/etm.2021.10543. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Cheng Z, Kang C, Che S, Su J, Sun Q, Ge T, et al. Berberine: a promising treatment for neurodegenerative diseases. Front Pharmacol. 2022;13:845591. doi: 10.3389/fphar.2022.845591. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.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. doi: 10.1038/s41598-021-95353-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Cui G, Wang H, Yang C, Zhou X, Wang J, Wang T, et al. Berberine prevents lethal EV71 neurological infection in newborn mice. Front Pharmacol. 2022;13:1027566. doi: 10.3389/fphar.2022.1027566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.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. doi: 10.1111/asj.13582. [DOI] [PubMed] [Google Scholar]
- 15.Dai L, Zhu L, Ma S, Liu J, Zhang M, Li J, et al. Berberine alleviates NLRP3 inflammasome induced endothelial junction dysfunction through Ca2+ signalling in inflammatory vascular injury. Phytomedicine. 2022;101:154131. doi: 10.1016/j.phymed.2022.154131. [DOI] [PubMed] [Google Scholar]
- 16.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. doi: 10.1039/d1fo01360b. [DOI] [PubMed] [Google Scholar]
- 17.Deng J, Zhao L, Yuan X, Li Y, Shi J, Zhang H, et al. 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. doi: 10.3390/nu14040726. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18.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. doi: 10.1167/iovs.63.10.6. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Ding L, Li S, Wang F, Xu J, Li S, Wang B, et al. Berberine improves dietary-induced cardiac remodeling by upregulating Kruppel-like factor 4-dependent mitochondrial function. Biol Chem. 2021;402:795–803. doi: 10.1515/hsz-2020-0267. [DOI] [PubMed] [Google Scholar]
- 20.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. doi: 10.2147/JIR.S324292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Ehteshamfar SM, Akhbari M, Afshari JT, Seyedi M, Nikfar B, Shapouri‐Moghaddam A, et al. 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. doi: 10.1111/jcmm.16049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Fang W, Huang X, Wu K, Zong Y, Yu J, Xu H, et al. Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy. Front Mol Neurosci. 2022;15:930599. doi: 10.3389/fnmol.2022.930599. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.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. doi: 10.1155/2020/8832218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.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. doi: 10.52547/rbmb.10.3.362. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.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. doi: 10.1016/j.archoralbio.2020.104992. [DOI] [PubMed] [Google Scholar]
- 26.Hagel JM, Facchini PJ. Benzylisoquinoline alkaloid metabolism: a century of discovery and a brave new world. Plant Cell Physiol. 2013;54(5):647–672. doi: 10.1093/pcp/pct020. [DOI] [PubMed] [Google Scholar]
- 27.Han YC, Xie HZ, Lu B, Xiang RL, Li JY, Qian H, et al. 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. doi: 10.1186/s12864-022-08641-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.He C, Jia X, Zhang L, Gao F, Jiang W, Wen C, et al. Dietary berberine can ameliorate glucose metabolism disorder of Megalobrama amblycephala exposed to a high-carbohydrate diet. Fish Physiol Biochem. 2021;47:499–513. doi: 10.1007/s10695-021-00927-8. [DOI] [PubMed] [Google Scholar]
- 29.Huang Q, He W, Weng Y, Wang Y, Liu Y, Xiang Y, et al. Berberine inhibits osteogenic differentiation of aortic valve interstitial cells by interfering Smad1/5/8 and NF-κB pathways. Vascul Pharmacol. 2022;144:106986. doi: 10.1016/j.vph.2022.106986. [DOI] [PubMed] [Google Scholar]
- 30.Huang S, Liu H, Lin Y, Liu M, Li Y, Mao H, et al. Berberine protects against NLRP3 inflammasome via ameliorating autophagic impairment in MPTP-induced Parkinson’s disease model. Front Pharmacol. 2021;11:618787. doi: 10.3389/fphar.2020.618787. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Ibrahim Fouad G, Ahmed KA. Neuroprotective potential of berberine against doxorubicin-induced toxicity in rat’s brain. Neurochem Res. 2021;46:3247–3263. doi: 10.1007/s11064-021-03428-5. [DOI] [PubMed] [Google Scholar]
- 32.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. doi: 10.1080/13880209.2022.2048029. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.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. doi: 10.1155/2021/9970240. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 34.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. doi: 10.1007/s11064-022-03677-y. [DOI] [PubMed] [Google Scholar]
- 35.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. doi: 10.1166/jbn.2020.30041755. [DOI] [PubMed] [Google Scholar]
- 36.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. doi: 10.1007/s10753-021-01510-2. [DOI] [PubMed] [Google Scholar]
- 37.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. doi: 10.1007/s13258-022-01250-z. [DOI] [PubMed] [Google Scholar]
- 38.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. doi: 10.1016/j.biopha.2020.110953. [DOI] [PubMed] [Google Scholar]
- 39.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. doi: 10.1021/acschemneuro.0c00808. [DOI] [PubMed] [Google Scholar]
- 40.Liu Y, Fang X, Li Y, Bing L, Li Y, Fang J, et al. 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. doi: 10.1093/jpp/rgac026. [DOI] [PubMed] [Google Scholar]
- 41.Luo Z, Li Z, Liang Z, Wang L, He G, Wang D, et al. 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. doi: 10.1186/s12915-022-01492-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 42.Lv Y, Yang H, Ye P, Qian Z, Wang D, Kong C, et al. Berberine inhibits low shear stress-induced vascular endothelial inflammation via decreasing phosphorylation of Akt and IRF3. Tissue Cell. 2022;79:101946. doi: 10.1016/j.tice.2022.101946. [DOI] [PubMed] [Google Scholar]
- 43.Ma Y, Yan G, Guo J, Li F, Zheng H, Wang C, et al. Berberine prolongs mouse heart allograft survival by activating T cell apoptosis via the mitochondrial pathway. Front Immunol. 2021;12:616074. doi: 10.3389/fimmu.2021.616074. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Ma Z, Zhu L, Wang S, Guo X, Sun B, Wang Q, et al. Berberine protects diabetic nephropathy by suppressing epithelial-to-mesenchymal transition involving the inactivation of the NLRP3 inflammasome. Ren Fail. 2022;44(1):923–932. doi: 10.1080/0886022X.2022.2079525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.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. doi: 10.1016/j.psj.2020.10.040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 46.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. doi: 10.1016/j.bbrc.2022.07.072. [DOI] [PubMed] [Google Scholar]
- 47.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. doi: 10.1007/s11033-020-05892-8. [DOI] [PubMed] [Google Scholar]
- 48.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. doi: 10.1111/jcmm.17019. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.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. doi: 10.2174/1389201022666210208152113. [DOI] [PubMed] [Google Scholar]
- 50.Ni L, Li Z, Ren H, Kong L, Chen X, Xiong M, et al. 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. doi: 10.1111/1440-1681.13582. [DOI] [PubMed] [Google Scholar]
- 51.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. doi: 10.1016/j.phymed.2022.154303. [DOI] [PubMed] [Google Scholar]
- 52.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. doi: 10.3390/biomedicines10071739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 53.Obchoei S, Detarya M, Boonnate P, Saranaruk P, Vaeteewoottacharn K, Mahalapbutr P, et al. Low dose berberine suppresses cholangiocarcinoma cell progression as a multi-kinase inhibitor. Asian Pac J Cancer Prev. 2022;23:3379–3386. doi: 10.31557/APJCP.2022.23.10.3379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 54.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. doi: 10.3390/molecules27041351. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 55.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. doi: 10.5812/ijpr-126919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Pang H, Zhou Y, Wang J, Wu H, Liu X, Gao F, et al. 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. doi: 10.2147/DDDT.S337215. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 57.Park GS, Park B, Lee MY. Berberine induces autophagic cell death by inactivating the Akt/mTOR signaling pathway. Planta Med. 2022;88:1116–1122. doi: 10.1055/a-1752-0311. [DOI] [PubMed] [Google Scholar]
- 58.Pu Z, Sun Y, Jiang H, Hou Q, Yan H, Wen H, et al. Effects of berberine on gut microbiota in patients with mild metabolic disorders induced by Olanzapine. Am J Chin Med. 2021;49:1949–1963. doi: 10.1142/S0192415X21500920. [DOI] [PubMed] [Google Scholar]
- 59.Qiu F, Lu W, Ye S, Liu H, Zeng Q, Huang H, et al. 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. doi: 10.3389/fimmu.2021.646831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Qu H, Song X, Song Z, Jiang X, Gao X, Bai L, et al. Berberine reduces temozolomide resistance by inducing autophagy via the ERK1/2 signaling pathway in glioblastoma. Cancer Cell Int. 2020;20(1):592. doi: 10.1186/s12935-020-01693-y. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 61.Ren S, Cai Y, Hu S, Liu J, Zhao Y, Ding M, et al. Berberine exerts anti-tumor activity in diffuse large B-cell lymphoma by modulating c-myc/CD47 axis. Biochem Pharmacol. 2021;188:114576. doi: 10.1016/j.bcp.2021.114576. [DOI] [PubMed] [Google Scholar]
- 62.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. doi: 10.3389/fphar.2021.729384. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 63.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. doi: 10.1016/j.pestbp.2021.104977. [DOI] [PubMed] [Google Scholar]
- 64.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. doi: 10.1016/j.scitotenv.2022.155292. [DOI] [PubMed] [Google Scholar]
- 65.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. doi: 10.1016/j.lfs.2021.119078. [DOI] [PubMed] [Google Scholar]
- 66.Shan MY, Dai Y, Ren XD, Zheng J, Zhang KB, Chen B, et al. Berberine mitigates nonalcoholic hepatic steatosis by downregulating SIRT1-FoxO1-SREBP2 pathway for cholesterol synthesis. J Integr Med. 2021;19:545–554. doi: 10.1016/j.joim.2021.09.003. [DOI] [PubMed] [Google Scholar]
- 67.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. doi: 10.1002/biof.1692. [DOI] [PubMed] [Google Scholar]
- 68.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. doi: 10.1159/000518040. [DOI] [PubMed] [Google Scholar]
- 69.Shu X, Li M, Cao Y, Li C, Zhou W, Ji G, et al. Berberine alleviates non-alcoholic steatohepatitis through modulating gut microbiota mediated intestinal FXR activation. Front Pharmacol. 2021;12:750826. doi: 10.3389/fphar.2021.750826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 70.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. doi: 10.1016/j.ejmech.2021.113839. [DOI] [PubMed] [Google Scholar]
- 71.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. doi: 10.2147/DMSO.S313068. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 72.Sun S, Yang Y, Xiong R, Ni Y, Ma X, Hou M, et al. Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut. Life Sci. 2022;311:121141. doi: 10.1016/j.lfs.2022.121141. [DOI] [PubMed] [Google Scholar]
- 73.Szalak R, Kukula-Koch W, Matysek M, Kruk-Słomka M, Koch W, Czernicka L, et al. 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. doi: 10.3390/ijms22094487. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 74.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. doi: 10.1016/j.envpol.2021.117865. [DOI] [PubMed] [Google Scholar]
- 75.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. doi: 10.1177/1744806921996101. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 76.Tian W, Hao H, Chu M, Gong J, Li W, Fang Y, et al. Berberine suppresses lung metastasis of cancer via inhibiting endothelial transforming growth factor beta receptor 1. Front Pharmacol. 2022;13:917827. doi: 10.3389/fphar.2022.917827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 77.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. doi: 10.3390/ijms22073522. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 78.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. doi: 10.22038/IJBMS.2022.62811.13895. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 79.Wang M, Geng X, Li K, Wang Y, Duan X, Hou C, et al. Berberine ameliorates mesenteric vascular dysfunction by modulating perivascular adipose tissue in diet-induced obese in rats. BMC Complement Med Ther. 2022;22(1):198. doi: 10.1186/s12906-022-03667-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 80.Wang Y, Tong Q, Ma SR, Zhao ZX, Pan LB, Cong L, et al. Oral berberine improves brain dopa/dopamine levels to ameliorate Parkinson’s disease by regulating gut microbiota. Signal Transduct Target Ther. 2021;6(1):77. doi: 10.1038/s41392-020-00456-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 81.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. doi: 10.21037/jgo-22-389. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 82.Wolf PG, Devendran S, Doden HL, Ly LK, Moore T, Takei H, et al. Berberine alters gut microbial function through modulation of bile acids. BMC Microbiol. 2021;21(1):24. doi: 10.1186/s12866-020-02020-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 83.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. doi: 10.3389/fphar.2021.640758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 84.Xia S, Ma L, Wang G, Yang J, Zhang M, Wang X, et al. 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. doi: 10.2147/IDR.S357077. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 85.Xiang XY, Liu T, Wu Y, Jiang XS, He JL, Chen XM, et al. Berberine alleviates palmitic acid‑induced podocyte apoptosis by reducing reactive oxygen species‑mediated endoplasmic reticulum stress. Mol Med Rep. 2021;23(1):3. doi: 10.3892/mmr.2020.11641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 86.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. doi: 10.1007/s11596-020-2286-x. [DOI] [PubMed] [Google Scholar]
- 87.Xie W, Su F, Wang G, Peng Z, Xu Y, Zhang Y, et al. Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front Pharmacol. 2022;13:4734. doi: 10.3389/fphar.2022.1015045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 88.Xie Z, Liu X, Huang X, Liu Q, Yang M, Huang D, et al. Remodelling of gut microbiota by Berberine attenuates trimethylamine N-oxide-induced platelet hyperreaction and thrombus formation. Eur J Pharmacol. 2021;911:174526. doi: 10.1016/j.ejphar.2021.174526. [DOI] [PubMed] [Google Scholar]
- 89.Xu Y, Yu T, Ma G, Zheng L, Jiang X, Yang F, et al. Berberine modulates deacetylation of PPARγ to promote adipose tissue remodeling and thermogenesis via AMPK/SIRT1 pathway. Int J Biol Sci. 2021;17(12):3173. doi: 10.7150/ijbs.62556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 90.Yan S, Chang J, Hao X, Liu J, Tan X, Geng Z, et al. Berberine regulates short-chain fatty acid metabolism and alleviates the colitis-associated colorectal tumorigenesis through remodeling intestinal flora. Phytomedicine. 2022;102:154217. doi: 10.1016/j.phymed.2022.154217. [DOI] [PubMed] [Google Scholar]
- 91.Yang KT, Chao TH, Wang IC, Luo YP, Ting PC, Lin JH, et al. Berberine protects cardiac cells against ferroptosis. Tzu Chi Med J. 2022;34(3):310. doi: 10.4103/tcmj.tcmj_236_21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 92.Yang L, Cao J, Wei J, Deng J, Hou X, Hao E, et al. Antiproliferative activity of berberine in HepG2 cells via inducing apoptosis and arresting cell cycle. Food Funct. 2021;12:12115–12126. doi: 10.1039/d1fo02783b. [DOI] [PubMed] [Google Scholar]
- 93.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. doi: 10.1002/ptr.7539. [DOI] [PubMed] [Google Scholar]
- 94.Ye Y, Liu X, Wu N, Han Y, Wang J, Yu Y, et al. 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. doi: 10.3389/fphar.2021.653887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 95.Ye Z, Wang Q, Dai S, Ji X, Cao P, Xu C, et al. 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. doi: 10.1007/s11626-022-00737-z. [DOI] [PubMed] [Google Scholar]
- 96.Yi J, Wu S, Tan S, Qin Y, Wang X, Jiang J, et al. Berberine alleviates liver fibrosis through inducing ferrous redox to activate ROS-mediated hepatic stellate cells ferroptosis. Cell Death Discov. 2021;7(1):374. doi: 10.1038/s41420-021-00768-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 97.Yin Z, Tan R, Yuan T, Chen S, Quan Y, Hao Q, et al. Berberine prevents diabetic retinopathy through inhibiting HIF-1α/VEGF/NF-κ B pathway in db/db mice. Pharmazie. 2021;76:165–171. doi: 10.1691/ph.2021.01012. [DOI] [PubMed] [Google Scholar]
- 98.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. doi: 10.7150/ijbs.54604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 99.Zhai J, Li Z, Zhang H, Ma L, Ma Z, Zhang Y, et al. Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF‑κB signaling pathway. Mol Med Rep. 2020;22:4227–4235. doi: 10.3892/mmr.2020.11505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 100.Zhai L, Huang T, Xiao HT, Wu PG, Lin CY, Ning ZW, et al. Berberine Suppresses colonic inflammation in dextran sulfate sodium–induced murine colitis through inhibition of cytosolic phospholipase A2 activity. Front Pharmacol. 2020;11:576496. doi: 10.3389/fphar.2020.576496. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 101.Zhang M, Liu J, Yu C, Tang S, Jiang G, Zhang J, et al. 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. doi: 10.3390/antiox11122370. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 102.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. doi: 10.3390/ijms23010327. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 103.Zhao Z, Zeng J, Guo Q, Pu K, Yang Y, Chen N, et al. Berberine suppresses stemness and tumorigenicity of colorectal cancer stem-like cells by inhibiting m6A methylation. Front Oncol. 2021;11:775418. doi: 10.3389/fonc.2021.775418. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
- 104.Zheng C, Wang Y, Xu Y, Zhou L, Hassan S, Xu G, et al. Berberine inhibits dendritic cells differentiation in DSS-induced colitis by promoting Bacteroides fragilis. Int Immunopharmacol. 2021;101:108329. doi: 10.1016/j.intimp.2021.108329. [DOI] [PubMed] [Google Scholar]
- 105.Zheng Y, Kou J, Wang P, Ye T, Wang Z, Gao Z, et al. Berberine-induced TFEB deacetylation by SIRT1 promotes autophagy in peritoneal macrophages. Aging (Albany NY) 2021;13(5):7096. doi: 10.18632/aging.202566. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 106.Zhu C, Huang K, Bai Y, Feng X, Gong L, Wei C, et al. 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. doi: 10.1016/j.psj.2020.10.071. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 107.Zhu C, Li K, Peng XX, Yao TJ, Wang ZY, Hu P, et al. Berberine a traditional Chinese drug repurposing: Its actions in inflammation-associated ulcerative colitis and cancer therapy. Front Immunol. 2022;13:1083788. doi: 10.3389/fimmu.2022.1083788. [DOI] [PMC free article] [PubMed] [Google Scholar]

