Generic placeholder image

Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Alkaloids as Promising Agents for the Management of Insulin Resistance: A Review

Author(s): Ayoub Amssayef and Mohamed Eddouks*

Volume 29, Issue 39, 2023

Published on: 30 November, 2023

Page: [3123 - 3136] Pages: 14

DOI: 10.2174/0113816128270340231121043038

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Insulin resistance is one of the main factors that lead to the development of type 2 diabetes mellitus (T2DM). The effect of alkaloids on insulin resistance has been extensively examined according to multiple scientific researches.

Objective: In this work, we aimed to summarize the interesting results from preclinical and clinical studies that assessed the effects of natural alkaloids (berberine, nigelladine A, piperine, trigonelline, capsaicin, nuciferine, evodiamine, mahanine, and magnoflorine) on impaired insulin sensitivity and worsened insulin resistance, which play a pivotal role in the pathogenesis of type 2 diabetes.

Methods: In the current review, PubMed, ScienceDirect, Springer, and Google Scholar databases were used. The inclusion criteria were based on the following keywords and phrases: insulin sensitivity, insulin resistance, alkaloids and insulin resistance, alkaloids and type 2 diabetes, mechanisms of action, and alkaloids.

Results: The outcomes reported in this review demonstrated that the selected alkaloids increased insulin sensitivity and reduced insulin resistance in vitro and in vivo evidence, as well as in clinical trials, through improving insulin-signaling transduction mainly in hepatocytes, myocytes, and adipocytes, both at cellular and molecular levels. Insulin signaling components (InsR, IRS-1, PI3K, Akt, etc.), protein kinases and phosphatases, receptors, ion channels, cytokines, adipokines, and microRNAs, are influenced by alkaloids at transcriptional and translational levels, also in terms of function (activity and/or phosphorylation). Multiple perturbations associated with insulin resistance, such as ectopic lipid accumulation, inflammation, ER stress, oxidative stress, mitochondrial dysfunction, gut microbiota dysbiosis, and β-cell failure, are reversed after treatment with alkaloids. Furthermore, various indices and tests are employed to assess insulin resistance, including the Matsuda index, insulin sensitivity index (ISI), oral glucose tolerance test (OGTT), and insulin tolerance test (ITT), which are all enhanced by alkaloids. These improvements extend to fasting blood glucose, fasting insulin, and HbA1c levels as well. Additionally, the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and the Homeostasis Model Assessment of β-cell function (HOMA-β) are recognized as robust markers of insulin sensitivity and β-cell function, and it is noteworthy that alkaloids also lead to improvements in these two markers.

Conclusion: Based on the findings of the current review, alkaloids may serve as both preventive and curative agents for metabolic disorders, specifically type 2 diabetes. Nonetheless, there is an urgent need for additional clinical trials to explore the potential benefits of alkaloids in both healthy individuals and those with type 2 diabetes. Additionally, it is crucial to assess any possible side effects and interactions with antidiabetic drugs.

Keywords: Insulin resistance, diabetes, medicinal plants, alkaloids, insulin sensitivity, mechanism of action.

[1]
Zimmet P, Alberti KGMM, Shaw J. Global and societal implications of the diabetes epidemic. Nature 2001; 414(6865): 782-7.
[http://dx.doi.org/10.1038/414782a] [PMID: 11742409]
[2]
Kahn SE. The relative contributions of insulin resistance and beta- cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003; 46(1): 3-19.
[http://dx.doi.org/10.1007/s00125-002-1009-0] [PMID: 12637977]
[3]
Patel DK, Kumar R, Laloo D, Hemalatha S. Evaluation of phytochemical and antioxidant activities of the different fractions of Hybanthus enneaspermus (Linn.) F. Muell. (Violaceae). Asian Pac J Trop Med 2011; 4(5): 391-6.
[http://dx.doi.org/10.1016/S1995-7645(11)60110-7] [PMID: 21771683]
[4]
Dumasia R, Eagle K, Kline-Rogers E, May N, Cho L, Mukherjee D. Role of PPAR- gamma agonist thiazolidinediones in treatment of pre-diabetic and diabetic individuals: A cardiovascular perspective. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5(5): 377-86.
[http://dx.doi.org/10.2174/156800605774370362] [PMID: 16248830]
[5]
Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001; 108(8): 1167-74.
[http://dx.doi.org/10.1172/JCI13505] [PMID: 11602624]
[6]
Ajibesin KK. Herbal medicine: Evidential, experiential, and circumstantial. Niger Med J 2017; 1(2): 40-62.
[7]
Balaraman R, Parmar G, Maheshwari RA, Anuj SD. A review on the biological effects of some natural products. J Nat Remed 2020; 20(3): 117-27.
[http://dx.doi.org/10.18311/jnr/2020/25581]
[8]
Kumar A, Aswal S, Semwal RB, Chauhan A, Joshi SK, Semwal DK. Role of plant-derived alkaloids against diabetes and diabetes-related complications: A mechanism-based approach. Phytochem Rev 2019; 18(5): 1277-98.
[http://dx.doi.org/10.1007/s11101-019-09648-6]
[9]
Ajebli M, Khan H, Eddouks M. Natural alkaloids and diabetes mellitus: A review. Endocr Metab Immune Disord Drug Targets 2021; 21(1): 111-30.
[http://dx.doi.org/10.2174/1871530320666200821124817] [PMID: 32955004]
[10]
Christodoulou MI, Tchoumtchoua J, Skaltsounis AL, Scorilas A, Halabalaki M. Natural alkaloids intervening the insulin pathway: New hopes for anti-diabetic agents? Curr Med Chem 2019; 26(32): 5982-6015.
[http://dx.doi.org/10.2174/0929867325666180430152618] [PMID: 29714135]
[11]
Rasouli H, Yarani R, Pociot F, Popović-Djordjević J. Anti-diabetic potential of plant alkaloids: Revisiting current findings and future perspectives. Pharmacol Res 2020; 155: 104723.
[http://dx.doi.org/10.1016/j.phrs.2020.104723] [PMID: 32105756]
[12]
Koeppen BM, Stanton BA. Berne and levy physiology e-book. Amsterdam: Elsevier Health Sciences 2017.
[13]
Weiss M, Steiner DF, Philipson LH. Insulin Biosynthesis, Secretion, Structure, and Structure-Activity Relationships. Endotext. Feingold, KR 2014.
[14]
Rutter GA, Pullen TJ, Hodson DJ, Martinez-Sanchez A. Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem J 2015; 466(2): 203-18.
[http://dx.doi.org/10.1042/BJ20141384] [PMID: 25697093]
[15]
Alessi DR, Andjelkovic M, Caudwell B, et al. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J 1996; 15(23): 6541-51.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb01045.x] [PMID: 8978681]
[16]
Stephens L, Anderson K, Stokoe D, et al. Protein kinase B kinases that mediate phosphatidylinositol 3,4,5-trisphosphate-dependent activation of protein kinase B. Science 1998; 279(5351): 710-4.
[http://dx.doi.org/10.1126/science.279.5351.710] [PMID: 9445477]
[17]
Sarbassov DD, Guertin DA, Ali SM, Sabatini DM. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 2005; 307(5712): 1098-101.
[http://dx.doi.org/10.1126/science.1106148] [PMID: 15718470]
[18]
Lee SH, Park SY, Choi CS. Insulin resistance: From mechanisms to therapeutic strategies. Diabetes Metab J 2022; 46(1): 15-37.
[http://dx.doi.org/10.4093/dmj.2021.0280] [PMID: 34965646]
[19]
Horton JD, Goldstein JL, Brown MS. SREBPs: Activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002; 109(9): 1125-31.
[http://dx.doi.org/10.1172/JCI0215593] [PMID: 11994399]
[20]
Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep 2001; 2(4): 282-6.
[http://dx.doi.org/10.1093/embo-reports/kve071] [PMID: 11306547]
[21]
Rieusset J, Andreelli F, Auboeuf D, et al. Insulin acutely regulates the expression of the peroxisome proliferator-activated receptor-gamma in human adipocytes. Diabetes 1999; 48(4): 699-705.
[http://dx.doi.org/10.2337/diabetes.48.4.699] [PMID: 10102684]
[22]
Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: Insights into insulin action. Nat Rev Mol Cell Biol 2006; 7(2): 85-96.
[http://dx.doi.org/10.1038/nrm1837] [PMID: 16493415]
[23]
Gutiérrez-Rodelo C, Roura-Guiberna A, Olivares-Reyes JA. Molecular mechanisms of insulin resistance: An update. Gac Med Mex 2017; 153(2): 214-28.
[PMID: 28474708]
[24]
Boucher J, Kleinridders A, Kahn CR. Insulin receptor signaling in normal and insulin-resistant states. Cold Spring Harb Perspect Biol 2014; 6(1): a009191.
[http://dx.doi.org/10.1101/cshperspect.a009191] [PMID: 24384568]
[25]
Elchebly M, Payette P, Michaliszyn E, et al. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 1999; 283(5407): 1544-8.
[http://dx.doi.org/10.1126/science.283.5407.1544] [PMID: 10066179]
[26]
Khalid M, Alkaabi J, Khan MAB, Adem A. Insulin signal transduction perturbations in insulin resistance. Int J Mol Sci 2021; 22(16): 8590.
[http://dx.doi.org/10.3390/ijms22168590] [PMID: 34445300]
[27]
Alonso A, Sasin J, Bottini N, et al. Protein tyrosine phosphatases in the human genome. Cell 2004; 117(6): 699-711.
[http://dx.doi.org/10.1016/j.cell.2004.05.018] [PMID: 15186772]
[28]
Koren S, Fantus IG. Inhibition of the protein tyrosine phosphatase PTP1B: Potential therapy for obesity, insulin resistance and type-2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab 2007; 21(4): 621-40.
[http://dx.doi.org/10.1016/j.beem.2007.08.004] [PMID: 18054739]
[29]
Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cell Physiol 2019; 234(6): 8152-61.
[http://dx.doi.org/10.1002/jcp.27603] [PMID: 30317615]
[30]
Hawley JA. Exercise as a therapeutic intervention for the prevention and treatment of insulin resistance. Diabetes Metab Res Rev 2004; 20(5): 383-93.
[http://dx.doi.org/10.1002/dmrr.505] [PMID: 15343584]
[31]
Lee JO, Lee SK, Kim JH, et al. Metformin regulates glucose transporter 4 (GLUT4) translocation through AMP-activated protein kinase (AMPK)-mediated Cbl/CAP signaling in 3T3-L1 preadipocyte cells. J Biol Chem 2012; 287(53): 44121-9.
[http://dx.doi.org/10.1074/jbc.M112.361386] [PMID: 23135276]
[32]
Saltiel AR, Olefsky JM. Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 1996; 45(12): 1661-9.
[http://dx.doi.org/10.2337/diab.45.12.1661] [PMID: 8922349]
[33]
Li M, Chi X, Wang Y, Setrerrahmane S, Xie W, Xu H. Trends in insulin resistance: Insights into mechanisms and therapeutic strategy. Signal Transduct Target Ther 2022; 7(1): 216.
[http://dx.doi.org/10.1038/s41392-022-01073-0] [PMID: 35794109]
[34]
Chaudhury A, Duvoor C, Reddy Dendi VS, et al. Clinical review of antidiabetic drugs: Implications for type 2 diabetes mellitus management. Front Endocrinol 2017; 8: 6.
[http://dx.doi.org/10.3389/fendo.2017.00006] [PMID: 28167928]
[35]
Goedeke L, Perry RJ, Shulman GI. Emerging pharmacological targets for the treatment of nonalcoholic fatty liver disease, insulin resistance, and type 2 diabetes. Annu Rev Pharmacol Toxicol 2019; 59(1): 65-87.
[http://dx.doi.org/10.1146/annurev-pharmtox-010716-104727] [PMID: 30625285]
[36]
Eddouks M, Bidi A, El Bouhali B, Hajji L, Zeggwagh NA. Antidiabetic plants improving insulin sensitivity. J Pharm Pharmacol 2014; 66(9): 1197-214.
[http://dx.doi.org/10.1111/jphp.12243] [PMID: 24730446]
[37]
Shehadeh MB, Suaifan GARY, Abu-Odeh AM. Plants secondary metabolites as blood glucose-lowering molecules. Molecules 2021; 26(14): 4333.
[http://dx.doi.org/10.3390/molecules26144333] [PMID: 34299610]
[38]
Chauhan DS, Gupta P, Pottoo FH, Amir M. Secondary metabolites in the treatment of diabetes mellitus: A paradigm shift. Curr Drug Metab 2020; 21(7): 493-511.
[http://dx.doi.org/10.2174/1389200221666200514081947] [PMID: 32407267]
[39]
Li J, Bai L, Wei F, et al. Therapeutic mechanisms of herbal medicines against insulin resistance: A review. Front Pharmacol 2019; 10: 661.
[http://dx.doi.org/10.3389/fphar.2019.00661] [PMID: 31258478]
[40]
Bhambhani S, Kondhare KR, Giri AP. Diversity in chemical structures and biological properties of plant alkaloids. Molecules 2021; 26(11): 3374.
[http://dx.doi.org/10.3390/molecules26113374] [PMID: 34204857]
[41]
Kohnen-Johannsen K, Kayser O. Tropane alkaloids: Chemistry, pharmacology, biosynthesis and production. Molecules 2019; 24(4): 796.
[http://dx.doi.org/10.3390/molecules24040796] [PMID: 30813289]
[42]
Matsuura HN, Fett-Neto AG. Plant alkaloids: Main features, toxicity, and mechanisms of action. Plant toxins 2015; 2(7): 1-5.
[43]
Moreira R, Pereira D, Valentão P, Andrade P. Pyrrolizidine alkaloids: Chemistry, pharmacology, toxicology and food safety. Int J Mol Sci 2018; 19(6): 1668.
[http://dx.doi.org/10.3390/ijms19061668] [PMID: 29874826]
[44]
Dey P, Kundu A, Kumar A, et al. Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids). Recent Adv Nat Prod Anal 2020; 505-67.
[45]
Buckingham J, Baggaley KH, Roberts AD, Szabo LF. Dictionary of alkaloids, with CD-ROM. Boca Raton, FL: CRC Press 2010.
[http://dx.doi.org/10.1201/EBK1420077698]
[46]
Gutiérrez-Grijalva EP, López-Martínez LX, Contreras-Angulo LA, Elizalde-Romero CA, Heredia JB. Plant alkaloids: Structures and bioactive properties. Plant-derived bioactives. Singapore: Springer 2020; pp. 85-117.
[http://dx.doi.org/10.1007/978-981-15-2361-8_5]
[47]
Ranjitha D, Sudha K. Alkaloids in foods. Int J Pharm Chem Biol Sci 2015; 5(4).
[48]
Hussain G, Rasul A, Anwar H, et al. Role of plant derived alkaloids and their mechanism in neurodegenerative disorders. Int J Biol Sci 2018; 14(3): 341-57.
[http://dx.doi.org/10.7150/ijbs.23247] [PMID: 29559851]
[49]
Aniszewski T. Alkaloids: chemistry, biology, ecology, and applications. Pacific Grove, CA: Elsevier 2015; p. 496.
[50]
Goyal S. Ecological role of alkaloids. SpringerLink 2013; pp. 149-71.
[http://dx.doi.org/10.1007/978-3-642-22144-6_98]
[51]
Bribi N. Pharmacological activity of alkaloids: A review. Asian J Botany 2018; 1(1): 1-6.
[52]
Dey A, Mukherjee A. Plant-derived alkaloids: A promising window for neuroprotective drug discovery. Discovery and development of neuroprotective agents from natural products. Elsevier 2018; pp. 237-320.
[http://dx.doi.org/10.1016/B978-0-12-809593-5.00006-9]
[53]
Liu LZ, Cheung SCK, Lan LL, et al. Berberine modulates insulin signaling transduction in insulin-resistant cells. Mol Cell Endocrinol 2010; 317(1-2): 148-53.
[http://dx.doi.org/10.1016/j.mce.2009.12.027] [PMID: 20036710]
[54]
Chen C, Zhang Y, Huang C. Berberine inhibits PTP1B activity and mimics insulin action. Biochem Biophys Res Commun 2010; 397(3): 543-7.
[http://dx.doi.org/10.1016/j.bbrc.2010.05.153] [PMID: 20515652]
[55]
Wang Y, Gong W, Lv S, Qu H, He Y. Berberine improves insulin resistance in adipocyte models by regulating the methylation of hypoxia-inducible factor-3α. Biosci Rep 2019; 39(10): BSR20192059.
[http://dx.doi.org/10.1042/BSR20192059]
[56]
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: 2525-37.
[http://dx.doi.org/10.2147/DMSO.S313068] [PMID: 34113144]
[57]
Wei S, Zhang M, Yu Y, et al. Berberine attenuates development of the hepatic gluconeogenesis and lipid metabolism disorder in type 2 diabetic mice and in palmitate-incubated HepG2 cells through suppression of the HNF-4α miR122 pathway. PLoS One 2016; 11(3): e0152097.
[http://dx.doi.org/10.1371/journal.pone.0152097] [PMID: 27011261]
[58]
Lou T, Zhang Z, Xi Z, et al. Berberine inhibits inflammatory response and ameliorates insulin resistance in hepatocytes. Inflammation 2011; 34(6): 659-67.
[http://dx.doi.org/10.1007/s10753-010-9276-2] [PMID: 21110076]
[59]
Choi BH, Ahn IS, Kim YH, et al. Berberine reduces the expression of adipogenic enzymes and inflammatory molecules of 3T3-L1 adipocyte. Exp Mol Med 2006; 38(6): 599-605.
[http://dx.doi.org/10.1038/emm.2006.71] [PMID: 17202835]
[60]
Wang Z, Lu F, Xu L, Dong H. Berberine reduces endoplasmic reticulum stress and improves insulin signal transduction in Hep G2 cells. Acta Pharmacol Sin 2010; 31(5): 578-84.
[http://dx.doi.org/10.1038/aps.2010.30] [PMID: 20383171]
[61]
Tang D, Chen QB, Xin XL, Aisa HA. Anti-diabetic effect of three new norditerpenoid alkaloids in vitro and potential mechanism via PI3K/Akt signaling pathway. Biomed Pharmacother 2017; 87: 145-52.
[http://dx.doi.org/10.1016/j.biopha.2016.12.058] [PMID: 28049096]
[62]
Wan CP, Wei YG, Li XX, Zhang LJ, Yang R, Bao ZR. Piperine regulates glucose metabolism disorder in HepG2 cells of insulin resistance models via targeting upstream target of AMPK signaling pathway. Zhongguo Zhongyao Zazhi 2017; 42(3): 542-7.
[PMID: 28952262]
[63]
Jung HJ, Bang E, Jeong SH, Kim BM, Chung HY. Effects of piperine on insulin resistance and lipid accumulation in palmitate-treated HepG2 cells. J Life Sci 2019; 29(9): 964-71.
[64]
Zhang W, Ho CT, Lu M. Piperine improves lipid dysregulation by modulating circadian genes Bmal1 and Clock in HepG2 cells. Int J Mol Sci 2022; 23(10): 5611.
[http://dx.doi.org/10.3390/ijms23105611] [PMID: 35628429]
[65]
Liu LH, Xie JY, Guo WW, et al. Evodiamine activates AMPK and promotes adiponectin multimerization in 3T3-L1 adipocytes. J Asian Nat Prod Res 2014; 16(11): 1074-83.
[http://dx.doi.org/10.1080/10286020.2014.939071] [PMID: 25082563]
[66]
Pajvani UB, Hawkins M, Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279(13): 12152-62.
[http://dx.doi.org/10.1074/jbc.M311113200] [PMID: 14699128]
[67]
Wang T, Kusudo T, Takeuchi T, et al. Evodiamine inhibits insulin-stimulated mTOR-S6K activation and IRS1 serine phosphorylation in adipocytes and improves glucose tolerance in obese/diabetic mice. PLoS One 2013; 8(12): e83264.
[http://dx.doi.org/10.1371/journal.pone.0083264] [PMID: 24391749]
[68]
Um SH, Frigerio F, Watanabe M, et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 2004; 431(7005): 200-5.
[http://dx.doi.org/10.1038/nature02866] [PMID: 15306821]
[69]
Ma C, Li G, He Y, et al. Pronuciferine and nuciferine inhibit lipogenesis in 3T3-L1 adipocytes by activating the AMPK signaling pathway. Life Sci 2015; 136: 120-5.
[http://dx.doi.org/10.1016/j.lfs.2015.07.001] [PMID: 26164185]
[70]
Du X, Di Malta C, Fang Z, et al. Nuciferine protects against high- fat diet-induced hepatic steatosis and insulin resistance via activating TFEB-mediated autophagy–lysosomal pathway. Acta Pharm Sin B 2022; 12(6): 2869-86.
[http://dx.doi.org/10.1016/j.apsb.2021.12.012] [PMID: 35755273]
[71]
Biswas A, Bhattacharya S, Dasgupta S, et al. Insulin resistance due to lipid-induced signaling defects could be prevented by mahanine. Mol Cell Biochem 2010; 336(1-2): 97-107.
[http://dx.doi.org/10.1007/s11010-009-0257-4] [PMID: 19826769]
[72]
Nooron N, Athipornchai A, Suksamrarn A, Chiabchalard A. Mahanine enhances the glucose-lowering mechanisms in skeletal muscle and adipocyte cells. Biochem Biophys Res Commun 2017; 494(1-2): 101-6.
[http://dx.doi.org/10.1016/j.bbrc.2017.10.075] [PMID: 29050941]
[73]
Kim SH, Hwang JT, Park HS, Kwon DY, Kim MS. Capsaicin stimulates glucose uptake in C2C12 muscle cells via the reactive oxygen species (ROS)/AMPK/p38 MAPK pathway. Biochem Biophys Res Commun 2013; 439(1): 66-70.
[http://dx.doi.org/10.1016/j.bbrc.2013.08.027] [PMID: 23958300]
[74]
Ojeda-Montes MJ, Ardid-Ruiz A, Tomás-Hernández S, et al. Ephedrine as a lead compound for the development of new DPP-IV inhibitors. Future Med Chem 2017; 9(18): 2129-46.
[http://dx.doi.org/10.4155/fmc-2017-0080] [PMID: 29172693]
[75]
Opinto G, Natalicchio A, Marchetti P. Physiology of incretins and loss of incretin effect in type 2 diabetes and obesity. Arch Physiol Biochem 2013; 119(4): 170-8.
[http://dx.doi.org/10.3109/13813455.2013.812664] [PMID: 23859800]
[76]
Zhang N, Liu X, Zhuang L, et al. Berberine decreases insulin resistance in a PCOS rats by improving GLUT4: Dual regulation of the PI3K/AKT and MAPK pathways. Regul Toxicol Pharmacol 2020; 110: 104544.
[http://dx.doi.org/10.1016/j.yrtph.2019.104544] [PMID: 31778716]
[77]
Xia Q, Wu F, Wu W, et al. Berberine reduces hepatic ceramide levels to improve insulin resistance in HFD-fed mice by inhibiting HIF-2α. Biomed Pharmacother 2022; 150: 112955.
[http://dx.doi.org/10.1016/j.biopha.2022.112955] [PMID: 35429745]
[78]
Xu J, Zhang Y, Yu Z, et al. Berberine mitigates hepatic insulin resistance by enhancing mitochondrial architecture via the SIRT1/Opa1 signalling pathway. Acta Biochim Biophys Sin 2021; 54(10): 1464-75.
[79]
Liu D, Zhang Y, Liu Y, et al. Berberine modulates gut microbiota and reduces insulin resistance via the TLR4 signaling pathway. Exp Clin Endocrinol Diabetes 2018; 126(8): 513-20.
[http://dx.doi.org/10.1055/s-0043-125066] [PMID: 29365334]
[80]
Zhang DS, Bai XH, Yao YJ, Mu DZ, Chen J. Effect of berberine on the insulin resistance and TLR4/βNF-κB signaling pathways in skeletal muscle of obese rats with insulin resistance. Sichuan Da Xue Xue Bao Yi Xue Ban 2015; 46(6): 827-31.
[PMID: 26867315]
[81]
Jwa H, Choi Y, Park UH, Um SJ, Yoon SK, Park T. Piperine, an LXRα antagonist, protects against hepatic steatosis and improves insulin signaling in mice fed a high-fat diet. Biochem Pharmacol 2012; 84(11): 1501-10.
[http://dx.doi.org/10.1016/j.bcp.2012.09.009] [PMID: 23000915]
[82]
Liu C, Yuan Y, Zhou J, Hu R, Ji L, Jiang G. Piperine ameliorates insulin resistance via inhibiting metabolic inflammation in monosodium glutamate-treated obese mice. BMC Endocr Disord 2020; 20(1): 152.
[http://dx.doi.org/10.1186/s12902-020-00617-1] [PMID: 33028294]
[83]
Aldakinah AAA, Al-Shorbagy MY, Abdallah DM, El-Abhar HS. Trigonelline and vildagliptin antidiabetic effect: Improvement of insulin signalling pathway. J Pharm Pharmacol 2017; 69(7): 856-64.
[http://dx.doi.org/10.1111/jphp.12713] [PMID: 28271502]
[84]
Kang JH, Tsuyoshi G, Han IS, Kawada T, Kim YM, Yu R. Dietary capsaicin reduces obesity-induced insulin resistance and hepatic steatosis in obese mice fed a high-fat diet. Obesity 2010; 18(4): 780-7.
[http://dx.doi.org/10.1038/oby.2009.301] [PMID: 19798065]
[85]
Yamashita H, Kusudo T, Takeuchi T, et al. Dietary supplementation with evodiamine prevents obesity and improves insulin resistance in ageing mice. J Funct Foods 2015; 19: 320-9.
[http://dx.doi.org/10.1016/j.jff.2015.09.032]
[86]
Yadav A, Singh A, Phogat J, Dahuja A, Dabur R. Magnoflorine prevent the skeletal muscle atrophy via Akt/mTOR/FoxO signal pathway and increase slow-MyHC production in streptozotocin-induced diabetic rats. J Ethnopharmacol 2021; 267: 113510.
[http://dx.doi.org/10.1016/j.jep.2020.113510] [PMID: 33141056]
[87]
Ko BS, Choi SB, Park SK, Jang JS, Kim YE, Park S. Insulin sensitizing and insulinotropic action of berberine from Cortidis rhizoma. Biol Pharm Bull 2005; 28(8): 1431-7.
[http://dx.doi.org/10.1248/bpb.28.1431] [PMID: 16079488]
[88]
Lv X, Zhao Y, Yang X, et al. Berberine potentiates insulin secretion and prevents β-cell dysfunction through the miR-204/SIRT1 signaling pathway. Front Pharmacol 2021; 12: 720866.
[http://dx.doi.org/10.3389/fphar.2021.720866] [PMID: 34630099]
[89]
Li M, She J, Ma L, Ma L, Ma X, Zhai J. Berberine protects against palmitate induced beta cell injury via promoting mitophagy. Genes Genomi 2022; pp. 1-2.
[90]
Gao N, Zhao TY, Li XJ. The protective effect of berberine on β- cell lipoapoptosis. J Endocrinol Invest 2011; 34(2): 124-30.
[http://dx.doi.org/10.1007/BF03347042] [PMID: 20414047]
[91]
Wang ZQ, Lu FE, Leng SH, et al. Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity. World J Gastroenterol 2008; 14(39): 6004-11.
[http://dx.doi.org/10.3748/wjg.14.6004] [PMID: 18932278]
[92]
Zhao MM, Lu J, Li S, et al. Author Correction: Berberine is an insulin secretagogue targeting the KCNH6 potassium channel. Nat Commun 2021; 12(1): 6342.
[http://dx.doi.org/10.1038/s41467-021-26635-8] [PMID: 33397941]
[93]
Zhou J, Zhou S, Tang J, et al. Protective effect of berberine on beta cells in streptozotocin- and high-carbohydrate/high-fat diet-induced diabetic rats. Eur J Pharmacol 2009; 606(1-3): 262-8.
[http://dx.doi.org/10.1016/j.ejphar.2008.12.056] [PMID: 19374872]
[94]
Lu SS, Yu YL, Zhu HJ, et al. Berberine promotes glucagon-like peptide-1 (7–36) amide secretion in streptozotocin-induced diabetic rats. J Endocrinol 2009; 200(2): 159-65.
[http://dx.doi.org/10.1677/JOE-08-0419] [PMID: 18996945]
[95]
Zhang Q, Xiao X, Li M, et al. Berberine moderates glucose metabolism through the GnRH-GLP-1 and MAPK pathways in the intestine. BMC Complement Altern Med 2014; 14(1): 188.
[http://dx.doi.org/10.1186/1472-6882-14-188] [PMID: 24912407]
[96]
Wang P, Yan Z, Zhong J, et al. Transient receptor potential vanilloid 1 activation enhances gut glucagon-like peptide-1 secretion and improves glucose homeostasis. Diabetes 2012; 61(8): 2155-65.
[http://dx.doi.org/10.2337/db11-1503] [PMID: 22664955]
[97]
He Q, Xu JY, Gu J, et al. Piperine is capable of improving pancreatic β-cell apoptosis in high fat diet and streptozotocin induced diabetic mice. J Funct Foods 2022; 88: 104890.
[http://dx.doi.org/10.1016/j.jff.2021.104890]
[98]
Tharaheswari M, Jayachandra Reddy N, Kumar R, Varshney KC, Kannan M, Sudha Rani S. Trigonelline and diosgenin attenuate ER stress, oxidative stress-mediated damage in pancreas and enhance adipose tissue PPARγ activity in type 2 diabetic rats. Mol Cell Biochem 2014; 396(1-2): 161-74.
[http://dx.doi.org/10.1007/s11010-014-2152-x] [PMID: 25070833]
[99]
Yang J, Yin J, Gao H, et al. Berberine improves insulin sensitivity by inhibiting fat store and adjusting adipokines profile in human preadipocytes and metabolic syndrome patients. Evid-based Complement Altern Med 2012; 2012.
[100]
Zhang H, Wei J, Xue R, et al. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression. Metabolism 2010; 59(2): 285-92.
[http://dx.doi.org/10.1016/j.metabol.2009.07.029] [PMID: 19800084]
[101]
Cao C, Su M. Effects of berberine on glucose-lipid metabolism, inflammatory factors and insulin resistance in patients with metabolic syndrome. Exp Ther Med 2019; 17(4): 3009-14.
[http://dx.doi.org/10.3892/etm.2019.7295] [PMID: 30936971]
[102]
Memon M, Khan R, Riaz S, Ain Q, Ahmed M, Kumar N. Methylglyoxal and insulin resistance in berberine-treated type 2 diabetic patients. J Res Med Sci 2018; 23(1): 110.
[http://dx.doi.org/10.4103/jrms.JRMS_1078_17] [PMID: 30693045]
[103]
Yuan LJ, Qin Y, Wang L, et al. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns. Clin Nutr 2016; 35(2): 388-93.
[http://dx.doi.org/10.1016/j.clnu.2015.02.011] [PMID: 25771490]
[104]
Rondanelli M, Opizzi A, Perna S, et al. Improvement in insulin resistance and favourable changes in plasma inflammatory adipokines after weight loss associated with two months’ consumption of a combination of bioactive food ingredients in overweight subjects. Endocrine 2013; 44(2): 391-401.
[http://dx.doi.org/10.1007/s12020-012-9863-0] [PMID: 23271695]
[105]
Neta JFF, Veras VS, Sousa DF, et al. Effectiveness of the piperine-supplemented Curcuma longa L. in metabolic control of patients with type 2 diabetes: A randomised double-blind placebo- controlled clinical trial. Int J Food Sci Nutr 2021; 72(7): 968-77.
[http://dx.doi.org/10.1080/09637486.2021.1885015] [PMID: 33586583]
[106]
van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care 2009; 32(6): 1023-5.
[http://dx.doi.org/10.2337/dc09-0207] [PMID: 19324944]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy