ATIVIDADES FARMACOLÓGICAS DE BERGININA E DERIVADOS: UMA REVISÃO SISTEMÁTICA

Diana Mendes do Nascimento Veloso; Patrícia Danielle Oliveira de Almeida; Emersom Silva Lima

doi:10.47820/recima21.v4i1.2615

Authors

Diana Mendes do Nascimento Veloso Universidade Federal do Amazonas https://orcid.org/0000-0001-6395-1434
Patrícia Danielle Oliveira de Almeida Universidade Federal do Amazonas https://orcid.org/0000-0002-2620-8251
Emersom Silva Lima Universidade Federal do Amazonas https://orcid.org/0000-0002-9367-2812

DOI:

https://doi.org/10.47820/recima21.v4i1.2615

Keywords:

Bergenine, pharmacological activity, synthesis, anti-inflammatory, antioxidant

Abstract

Bergenine is a C-glycoside of 4-O-methyl-gallic acid, characterized as a crystalline and colorless polyphenol. It has been reported to have been isolated from medicinal plants such as Flueggea leucopyrus, Bergenia crassifolia, Mallotus philippensis, Corylopsis spicata, Caesalpinia digyna, Mallotus japonicus and Sacoglottis gabonensis. In the Amazon region specifically, bergenine is listed as one of the main bioactive compounds present in the species Endopleura uchi, popularly known as yellow uchi. It is a substance that has multiple pharmacological properties such as anti-inflammatory, antitumor, cytoprotective, antiarrhythmic, antimicrobial, antidiabetic, among others. Through a bibliographic survey in the PubMed and Science Direct databases, between 2016 and 2022, using the descriptors “bergenin”, “pharmacological activity”, “synthesis” and “antioxidant”, after applying the inclusion and exclusion criteria, a total of 35 articles on bergenine and derivatives were evaluated. The results showed that the most recurrent pharmacological properties attributed to bergenine were those related to anti-inflammatory activities (8 publications), followed by antitumor (5 publications), cytoprotection (5 publications), action on bone metabolism (3 publications), immunomodulatory (3 publications), antiparasitic (2 publications) and antioxidant activity (2 publications). Of the 35 articles studied, six were productions related to bergenine derivatives, which studied anti-inflammatory and antitumor properties. This review presents a comprehensive literature search of different studies and provides information on the potential of bergenine and its derivatives for the use and development of new drugs.

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Author Biographies

Diana Mendes do Nascimento Veloso, Universidade Federal do Amazonas

Laboratório de Atividade Biológica, Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas

Patrícia Danielle Oliveira de Almeida, Universidade Federal do Amazonas

Laboratório de Atividade Biológica, Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas.

Emersom Silva Lima, Universidade Federal do Amazonas

Laboratório de Atividade Biológica, Faculdade de Ciências Farmacêuticas, Universidade Federal do Amazonas.

References

Aggarwal D, Gautam D, Sharma M, Singla SK. Bergenin attenuates renal injury by reversing mitochondrial dysfunction in ethylene glycol induced hyperoxaluric rat model. Eur J Pharmacol [Internet]. 2016;791(September):611–21. Available from: http://dx.doi.org/10.1016/j.ejphar.2016.10.002. 2. Kaur R, Kaur S. Evaluation of in vitro and in vivo antileishmanial potential of bergenin rich Bergenia

ligulata (Wall.) Engl. root extract against visceral leishmaniasis in inbred BALB/c mice through immunomodulation. J Tradit Complement Med [Internet]. 2018;8(1):251–60. Available from: http://dx.doi.org/10.1016/j.jtcme.2017.06.006 3. Jayakody RS, Wijewardhane P, Herath C, Perera S. Bergenin: a computationally proven promising scaffold for novel galectin-3 inhibitors. J Mol Model. 2018;24(10). 4. Li G, Lou HX. Strategies to diversify natural products for drug discovery. Med Res Rev. 2018;4(38):1255–94. 5. Chen Y, Garcia De Lomana M, Friedrich NO, Kirchmair J. Characterization of the Chemical Space of Known and Readily Obtainable Natural Products. J Chem Inf Model. 2018;58(8):1518–32. 6. Hay JE, Haynes LJ. 453. Bergenin, a C-glycopyranosyl derivative of 4-O-methylgallic acid. J Chem Soc. 1958;1958:2231–8. 7. Barai P, Raval N, Acharya S, Borisa A, Bhatt H, Acharya N. Neuroprotective effects of bergenin in Alzheimer’s disease: Investigation through molecular docking, in vitro and in vivo studies. Behav Brain Res [Internet]. 2019;356:18–40. Available from: https://doi.org/10.1016/j.bbr.2018.08.010 8. Shakeel F, Mothana RA, Haq N, Siddiqui NA, Al-Oqail MM, Al-Rehaily AJ. Solubility and thermodynamic function of bergenin in different (DMSO + water) mixtures at different temperatures. J Mol Liq [Internet]. 2016;220:823–8. Available from: http://dx.doi.org/10.1016/j.molliq.2016.05.015 9. Liang C, Pei S, Ju W, Jia M, Tian D, Tang Y, et al. Synthesis and in vitro and in vivo antitumour activity study of 11-hydroxyl esterified bergenin/cinnamic acid hybrids. Eur J Med Chem [Internet]. 2017;133:319–28. Available from: http://dx.doi.org/10.1016/j.ejmech.2017.03.053. 10. Whittemore R, Knaf K. The integrative review: updated methodology. J Adv Nurs. 2005;52(5):546–53. 11. Patel DK, Patel K, Kumar R, Gadewar M, Tahilyani V. Pharmacological and analytical aspects of bergenin: A concise report. Asian Pacific J Trop Dis [Internet]. 2012;2(2):163–7. Available from: http://dx.doi.org/10.1016/S2222-1808(12)60037-. 12. Bajracharya GB. Diversity, pharmacology and synthesis of bergenin and its derivatives: Potential materials for therapeutic usages. Fitoterapia [Internet]. 2015;101:133–52. Available from: http://dx.doi.org/10.1016/j.fitote.2015.01.001. 13. Gao X jiao, Guo M yao, Zhang Z cai, Wang T cheng, Cao Y guo, Zhang N sheng. Bergenin Plays an Anti-Inflammatory Role via the Modulation of MAPK and NF-κB Signaling Pathways in a Mouse Model of LPS-Induced Mastitis. Inflammation. 2015;38(3):1142–50. 14. El-Hawary SS, Mohammed R, Abouzid S, Ali ZY, Elwekeel A. Anti-arthritic activity of 11-O-(4′-O-methyl galloyl)-bergenin and Crassula capitella extract in rats. J Pharm Pharmacol. 2016;68(6):834–44. 15. Zhang C, Zhao B, Zhang C, Qiu M, Ma S, Jin X, et al. Mechanisms of bergenin treatment on chronic bronchitis analyzed by liquid chromatography-tandem mass spectrometry based on metabolomics. Biomed Pharmacother [Internet]. 2019;109(November 2018):2270–7. Available from: https://doi.org/10.1016/j.biopha.2018.11.119. 16. Yu KY, Wu W, Li SZ, Dou LL, Liu L Le, Li P, et al. A new compound, methylbergenin along with eight known compounds with cytotoxicity and anti-inflammatory activity from Ardisia japonica. Nat Prod Res [Internet]. 2017;31(22):2581–6. Available from: http://dx.doi.org/10.1080/14786419.2017.1283495. 17. Lopes de Oliveira GA, Alarcón de la Lastra C, Rosillo MÁ, Castejon Martinez ML, Sánchez-Hidalgo M, Rolim Medeiros JV, et al. Preventive effect of bergenin against the development of TNBS-induced acute colitis in rats is associated with inflammatory mediators inhibition and NLRP3/ASC inflammasome signaling pathways. Chem Biol Interact [Internet]. 2019;297:25–33. Available from: https://doi.org/10.1016/j.cbi.2018.10.020. 18. Wang K, Li YF, Lv Q, Li XM, Dai Y, Wei ZF. Bergenin, acting as an agonist of PPARγ, ameliorates experimental colitis in mice through improving expression of SIRT1, and therefore inhibiting NF-κB-mediated macrophage activation. Front Pharmacol. 2018;8(JAN):1–20. 19. Yang S, Yu Z, Wang L, Yuan T, Wang X, Zhang X, et al. The natural product bergenin ameliorates lipopolysaccharide-induced acute lung injury by inhibiting NF-kappaB activition. J Ethnopharmacol [Internet]. 2017;200:147–55. Available from: http://dx.doi.org/10.1016/j.jep.2017.02.013. 20. Ren X, Ma S, Wang J, Tian S, Fu X, Liu X, et al. Comparative effects of dexamethasone and bergenin on chronic bronchitis and their anti-inflammatory mechanisms based on NMR metabolomics. Mol Biosyst [Internet]. 2016;12(6):1938–47. Available from: http://dx.doi.org/10.1039/c6mb00041j. 21. Yang J, Kan M, Wu GY. Bergenin ameliorates diabetic nephropathy in rats via suppressing renal inflammation and TGF-β1-Smads pathway. Immunopharmacol Immunotoxicol. 2016;38(2):145–52. 22. Xiang S, Chen K, Xu L, Wang T, Guo C. Bergenin exerts hepatoprotective effects by inhibiting the release of inflammatory factors, apoptosis and autophagy via the PPAR-γ pathway. Drug Des Devel Ther. 2020;14:129–43. 23. Lee KH, Choi EM. Effects of bergenin on methylglyoxal-induced damage in osteoblastic MC3T3-E1 cells. J Appl Toxicol. 2018;38(4):585–93. 24. Shal B, Khan A, Khan AU, Ullah R, Ali G, Islam SU, et al. Alleviation of memory deficit by bergenin via the regulation of reelin and Nrf-2/NF-κB pathway in transgenic mouse model. Vol. 22, International Journal of Molecular Sciences. 2021. 25. Suh KS, Chon S, Jung WW, Choi EM. Effect of bergenin on RANKL-induced osteoclast differentiation in the presence of methylglyoxal. Toxicol Vitr. 2019;61(January). 26. Hou W, Ye C, Chen M, Li W, Gao X, He R, et al. Bergenin activates SIRT1 as a novel therapeutic agent for osteogenesis of bone mesenchymal stem cells. Front Pharmacol. 2019;10(JUN):1–9. 27. Suh KS, Chon S, Choi EM. Bergenin increases osteogenic differentiation and prevents methylglyoxal-induced cytotoxicity in MC3T3-E1 osteoblasts. Cytotechnology. 2018;70(1):215–24. 28. Khan H, Amin H, Ullah A, Saba S, Rafique J, Khan K, et al. Antioxidant and Antiplasmodial Activities of Bergenin and 11- O -Galloylbergenin Isolated from Mallotus philippensis. Oxid Med Cell Longev. 2016;2016. 29. Singh R, Kumar V, Bharate SS, Vishwakarma RA. Synthesis, pH dependent, plasma and enzymatic stability of bergenin prodrugs for potential use against rheumatoid arthritis. Bioorganic Med Chem [Internet]. 2017;25(20):5513–21. Available from: https://doi.org/10.1016/j.bmc.2017.08.011. 30. Ambika S, Saravanan R. Effect of bergenin on hepatic glucose metabolism and insulin signaling in C57BL/6J mice with high fat-diet induced type 2 diabetes. J Appl Biomed [Internet]. 2016;14(3):221–7. Available from: http://dx.doi.org/10.1016/j.jab.2016.04.002. 31. Qiao S, Liu R, Lv C, Miao Y, Yue M, Tao Y, et al. Bergenin impedes the generation of extracellular matrix in glomerular mesangial cells and ameliorates diabetic nephropathy in mice by inhibiting oxidative stress via the mTOR/β-TrcP/Nrf2 pathway. Free Radic Biol Med [Internet]. 2019;145:118–35. Available from: https://www.sciencedirect.com/science/article/pii/S0891584919310548. 32. Rajput SA, Mirza MR, Choudhary MI. Bergenin protects pancreatic beta cells against cytokine-induced apoptosis in INS-1E cells. PLoS One [Internet]. 2021;15(12 December):1–16. Available from: http://dx.doi.org/10.1371/journal.pone.0241349. 33. Dong G, Zhou Y, Song X. In vitro inhibitory effects of bergenin on human liver cytochrome p450 enzymes. Pharm Biol [Internet]. 2018;56(1):620–5. Available from: https://doi.org/10.1080/13880209.2018.1525413. 34. Richardson ET, Shukla S, Sweet DR, Wearsch PA, Tsichlis PN, Henry Boom W, et al. Toll-like receptor 2-dependent extracellular signal-regulated kinase signaling in Mycobacterium tuberculosis-infected macrophages drives anti-inflammatory responses and inhibits Th1 polarization of responding T cells. Infect Immun. 2015;83(6):2242–54. 35. Dwivedi VP, Bhattacharya D, Yadav V, Singh DK, Kumar S, Singh M, et al. The phytochemical bergenin enhances T helper 1 responses and anti-mycobacterial immunity by activating the MAP kinase pathway in macrophages. Front Cell Infect Microbiol. 2017;7(MAY):1–9. 36. Kumar S, Sharma C, Kaushik SR, Kulshreshtha A, Chaturvedi S, Nanda RK, et al. The phytochemical bergenin as an adjunct immunotherapy for tuberculosis in mice. J Biol Chem. 2019;294(21):8555–63. 37. Qi Q, Dong Z, Sun Y, Li S, Zhao Z. Protective effect of bergenin against cyclophosphamide-induced immunosuppression by immunomodulatory effect and antioxidation in balb/c mice. Molecules. 2018;23(10). 38. Shi X, Xu M, Luo K, Huang W, Yu H, Zhou T. Anticancer activity of bergenin against cervical cancer cells involves apoptosis, cell cycle arrest, inhibition of cell migration and the STAT3 signalling pathway. Exp Ther Med. 2019;3525–9. 39. Pavan Kumar P, Siva B, Venkateswara Rao B, Dileep Kumar G, Lakshma Nayak V, Nishant Jain S, et al. Synthesis and biological evaluation of bergenin-1,2,3-triazole hybrids as novel class of anti-mitotic agents. Bioorg Chem [Internet]. 2019;91(April):103161. Available from: https://doi.org/10.1016/j.bioorg.2019.103161. 40. Shen M, Li H, Yuan M, Jiang L, Zheng X, Zhang S, et al. Preparation of bergenin - Poly (lactic acid) polymers and in vitro controlled release studies. Int J Biol Macromol [Internet]. 2018;116:354–63. Available from: https://doi.org/10.1016/j.ijbiomac.2018.04.118. 41. de Oliveira GAL, da Silva Oliveira GL, Nicolau LAD, Mafud AC, Batista LF, Mascarenhas YP, et al. Bergenin from Peltophorum dubium: Isolation, Characterization, and Antioxidant Activities in Non-Biological Systems and Erythrocytes. Med Chem (Los Angeles). 2017;13(6):592–603. 42. Yun J, Lee Y, Yun K, Oh S. Bergenin decreases the morphine-induced physical dependence via antioxidative activity in mice. Arch Pharm Res. 2015;38(6):1248–54. 43. Rashid K, Sil PC. Curcumin ameliorates testicular damage in diabetic rats by suppressing cellular stress-mediated mitochondria and endoplasmic reticulum-dependent apoptotic death. Biochim Biophys Acta - Mol Basis Dis [Internet]. 2015;1852(1):70–82. Available from: http://dx.doi.org/10.1016/j.bbadis.2014.11.007. 44. Sanjeev S, Murthy MK, Sunita Devi M, Khushboo M, Renthlei Z, Ibrahim KS, et al. Isolation, characterization, and therapeutic activity of bergenin from marlberry (Ardisia colorata Roxb.) leaf on diabetic testicular complications in Wistar albino rats. Environ Sci Pollut Res. 2019;26(7):7082–101. 45. Ji Y, Wang D, Zhang B, Lu H. Bergenin Ameliorates MPTP-Induced Parkinson’s Disease by Activating PI3K/Akt Signaling Pathway. J Alzheimer’s Dis. 2019;72(3):823–33.