Abstract
Adenosine 5’-monophosphate-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase involved in the homeostasis of cellular energy. AMPK has developed as an appealing clinical target for the diagnosis of multiple metabolic diseases such as diabetes mellitus, obesity, inflammation, and cancer. Genetic and pharmacological studies indicate that AMPK is needed in response to glucose deficiency, dietary restriction, and increased physical activity for preserving glucose homeostasis. After activation, AMPK influences metabolic mechanisms contributing to enhanced ATP production, thus growing processes that absorb ATP simultaneously. In this review, several natural products have been discussed which enhance the sensitivity of AMPK and alleviate sub complications or different pathways by which such AMPK triggers can be addressed. AMPK Natural products as potential AMPK activators can be developed as alternate pharmacological intervention to reverse metabolic disorders including type 2 diabetes.
Similar content being viewed by others
References
Riddle MC, Cefalu WT, Evans PH, Gerstein HC, Nauck MA, Oh WK, Rothberg AE, Le Roux CW, Rubino F, Schauer P, Taylor R, Twenefour D. Consensus report: Definition and interpretation of remission in type 2 diabetes. Diabetes Care. 2021;44(10):2438–44. https://doi.org/10.2337/dci21-0034.
Jangra A, Datusalia AK, Sharma SS. Reversal of neurobehavioral and neurochemical alterations in STZ-induced diabetic rats by FeTMPyP, a peroxynitrite decomposition catalyst and 1,5-Isoquinolinediol a poly(ADP-ribose) polymerase inhibitor. Neurol Res. 2014;36(7):619–26. https://doi.org/10.1179/1743132813Y.0000000301.
Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444(7121):847–53. https://doi.org/10.1038/nature05483.
Taylor EB, An D, Kramer HF, Yu H, Fujii NL, Roeckl KSC, Bowles N, Hirshman MF, Xie J, Feener EP, Goodyear LJ. Discovery of TBC1D1 as an insulin-, AICAR-, and contraction-stimulated signaling nexus in mouse skeletal muscle. J Biol Chem. 2008;283(15):9787–96. https://doi.org/10.1074/jbc.M708839200.
Tanida M, Yamamoto N, Shibamoto T, Rahmouni K. Involvement of hypothalamic AMP-activated protein kinase in leptin-induced sympathetic nerve activation. PLoS One. 2013;8(2). https://doi.org/10.1371/journal.pone.0056660.
Timmers S, Konings E, Bilet L, Houtkooper RH, Van De Weijer T, Goossens GH, Hoeks J, Van Der Krieken S, Ryu D, Kersten S, Moonen-Kornips E, Hesselink MKC, Kunz I, Schrauwen-Hinderling VB, Blaak EE, Auwerx J, Schrauwen P. Calorie restriction-like effects of 30 days of resveratrol supplementation on energy metabolism and metabolic profile in obese humans. Cell Metab. 2011;14(5):612–22. https://doi.org/10.1016/j.cmet.2011.10.002.
Thakur A, Dan N, Bhakat S, Jayaprakash V, Banerjee S. 5’ adenosine monophosphate-activated protein kinase modulators as anticancer agents. Anticancer Agents Med Chem. 2016;16(8):961–72. https://doi.org/10.2174/1871520616666160211124240.
Babu PVA, Liu D, Gilbert ER. Recent advances in understanding the anti-diabetic actions of dietary flavonoids. J Nutr Biochem. 2013;24(11):1777–89. https://doi.org/10.1016/j.jnutbio.2013.06.003.
Messina G, Palmieri F, Monda V, Messina A, Dalia C, Viggiano A, Tafuri D, Messina A, Moscatelli F, Valenzano A, Cibelli G, Chieffi S, Monda M. Exercise causes muscle GLUT4 translocation in an insulin-independent manner. Biol Med. 2015;7(Specialissue3). https://doi.org/10.4172/0974-8369.1000S3007.
Shepherd PR, Withers DJ, Siddle K. Phosphoinositide 3-kinase: The key switch mechanism in insulin signalling. Biochem J. 1998;333(3):471–90. https://doi.org/10.1042/bj3330471.
Zhu S, Sun F, Li W, Cao Y, Wang C, Wang Y, Liang D, Zhang R, Zhang S, Wang H, Cao F. Apelin stimulates glucose uptake through the PI3K/Akt pathway and improves insulin resistance in 3T3-L1 adipocytes. Mol Cell Biochem. 2011;353(1–2):305–13. https://doi.org/10.1007/s11010-011-0799-0.
Kim YB, Kotani K, Ciaraldi TP, Henry RR, Kahn BB. Insulin-stimulated protein kinase C λ/ζ activity is reduced in skeletal muscle of humans with obesity and type 2 diabetes: Reversal with weight reduction. Diabetes. 2003;52(8):1935–42. https://doi.org/10.2337/diabetes.52.8.1935.
Khan A, Pessin J. Insulin regulation of glucose uptake: A complex interplay of intracellular signalling pathways. Diabetologia. 2002;45(11):1475–83. https://doi.org/10.1007/s00125-002-0974-7.
Russell RR, Bergeron R, Shulman GI, Young LH. Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR. Am J Physiol - Hear Circ Physiol. 1999;277(2 46–2):643–9. https://doi.org/10.1152/ajpheart.1999.277.2.h643.
Tan MJ, Ye JM, Turner N, Hohnen-Behrens C, Ke CQ, Tang CP, Chen T, Weiss HC, Gesing ER, Rowland A, James DE, Ye Y. Antidiabetic activities of triterpenoids isolated from bitter melon associated with activation of the AMPK pathway. Chem Biol. 2008;15(3):263–73. https://doi.org/10.1016/j.chembiol.2008.01.013.
Ceddia RB, Somwar R, Maida A, Fang X, Bikopoulos G, Sweeney G. Globular adiponectin increases GLUT4 translocation and glucose uptake but reduces glycogen synthesis in rat skeletal muscle cells. Diabetologia. 2005;48(1):132–9. https://doi.org/10.1007/s00125-004-1609-y.
Viollet B, Lantier L, Devin-Leclerc J, Hebrard S, Amouyal C, Mounier R, Foretz M, Andreelli F. Targeting the AMPK pathway for the treatment of Type 2 diabetes. Front Biosci (Landmark Ed). 2009;14:3380–400. https://doi.org/10.2741/3460.
Jung DY, Kim JH, Lee H, Jung MH. Antidiabetic effect of gomisin N via activation of AMP-activated protein kinase. Biochem Biophys Res Commun. 2017;494(3–4):587–93. https://doi.org/10.1016/j.bbrc.2017.10.120.
Liu L, Yasen M, Tang D, Ye J, Aisa HA, Xin X. Polyphenol-enriched extract of Rosa rugosa Thunb regulates lipid metabolism in diabetic rats by activation of AMPK pathway. Biomed Pharmacother. 2018;100(January):29–35. https://doi.org/10.1016/j.biopha.2018.01.143.
Xiong H, Zhang S, Zhao Z, Zhao P, Chen L, Mei Z. Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. J Ethnopharmacol. 2018;211:366–74. https://doi.org/10.1016/j.jep.2017.10.004.
Abdou HM, Hamaad FA, Ali EY, Ghoneum MH. Antidiabetic efficacy of Trifolium alexandrinum extracts hesperetin and quercetin in ameliorating carbohydrate metabolism and activating IR and AMPK signaling in the pancreatic tissues of diabetic rats. Biomed Pharmacother. 2022;149. https://doi.org/10.1016/j.biopha.2022.112838.
Entezari M, Hashemi D, Taheriazam A, Zabolian A, Mohammadi S, Fakhri F, Hashemi M, Hushmandi K, Ashrafizadeh M, Zarrabi A, Ertas YN, Mirzaei S, Samarghandian S. AMPK signaling in diabetes mellitus, insulin resistance and diabetic complications: A pre-clinical and clinical investigation. Biomed Pharmacother. 2022;146. https://doi.org/10.1016/j.biopha.2021.112563.
Garcia D, Shaw RJ. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell. 2017;66(6):789–800. https://doi.org/10.1016/j.molcel.2017.05.032.
Flores K, Siques P, Brito J, Arribas SM. AMPK and the challenge of treating hypoxic pulmonary hypertension. Int J Mol Sci. 2022;23(11):6205. https://doi.org/10.3390/ijms23116205.
Grahame Hardie D. Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharm Sin B. 2016;6(1):1–19. https://doi.org/10.1016/j.apsb.2015.06.002.
Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48(7):e245. https://doi.org/10.1038/emm.2016.81.
Kgopa AH, Makhubela SD, Mogale MA, Shai LJ. Effect of cinnamomum cassia stem-bark extracts on the synthesis and secretion of insulin in RIN-m5F cells. Online J Biol Sci. 2022;22(2):177–90. https://doi.org/10.3844/ojbsci.2022.177.190.
Wang QY, Tong AH, Pan YY, Zhang XD, Ding WY, Xiong W. The effect of cassia seed extract on the regulation of the LKB1-AMPK-GLUT4 signaling pathway in the skeletal muscle of diabetic rats to improve the insulin sensitivity of the skeletal muscle. Diabetol Metab Syndr. 2019;11(1):1–10. https://doi.org/10.1186/s13098-019-0504-0.
Shen Y, Honma N, Kobayashi K, Jia LN, Hosono T, Shindo K, Ariga T, Seki T. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling. PLoS One. 2014;9(2):1–9. https://doi.org/10.1371/journal.pone.0087894.
Kannappan S, Jayaraman T, Rajasekar P, Ravichandran MK, Anuradha CV. Cinnamon bark extract improves glucose metabolism and lipid profile in the fructose-fed rat. Singap Med J. 2006;47(10):858–63.
Nishikai-Shen T, Hosono-Fukao T, Ariga T, et al. Cinnamon extract improves abnormalities in glucose tolerance by decreasing Acyl-CoA synthetase long-chain family 1 expression in adipocytes. Sci Rep. 2022;12:12574. https://doi.org/10.1038/s41598-022-13421-9.
Park JH, Kho MC, Kim HY, Ahn YM, Lee YJ, Kang DG, Lee HS. Blackcurrant suppresses metabolic syndrome induced by high-fructose diet in rats. Evid Based Complement Alternat Med. 2015;2015:385976. https://doi.org/10.1155/2015/385976.
Iizuka Y, Ozeki A, Tani T, Tsuda T. Blackcurrant extract ameliorates hyperglycemia in type 2 diabetic mice in association with increased basal secretion of glucagon-like peptide-1 and activation of AMP-activated protein kinase. J Nutr Sci Vitaminol (Tokyo). 2018;64(4):258–64. https://doi.org/10.3177/jnsv.64.258.
Shih CC, Shlau MT, Lin CH, Wu JB. Momordica charantia ameliorates insulin resistance and dyslipidemia with altered hepatic glucose production and fatty acid synthesis and AMPK phosphorylation in high-fat-fed mice. Phytother Res. 2014;28(3):363–71. https://doi.org/10.1002/ptr.5003.
Guan Y, Cui ZJ, Sun B, Han LP, Li CJ, Chen LM. Celastrol attenuates oxidative stress in the skeletal muscle of diabetic rats by regulating the AMPK-PGC1α-SIRT3 signaling pathway. Int J Mol Med. 2016;37(5):1229–38. https://doi.org/10.3892/ijmm.2016.2549.
Liu H, Qi X, Yu K, Lu A, Lin K, Zhu J, Zhang M, Sun Z. AMPK activation is involved in hypoglycemic and hypolipidemic activities of mogroside-rich extract from Siraitia grosvenorii (Swingle) fruits on high-fat diet/streptozotocin-induced diabetic mice. Food Funct. 2019;10(1):151–162. https://doi.org/10.1039/c8fo01486h.
Chen XB, Zhuang JJ, Liu JH, Lei M, Ma L, Chen J, Shen X, Hu LH. Potential AMPK activators of cucurbitane triterpenoids from Siraitia grosvenorii Swingle. Bioorg Med Chem. 2011;19(19):5776–81. https://doi.org/10.1016/j.bmc.2011.08.030.
Xue W, Mao J, Chen Q, Ling W, Sun Y. Mogroside IIIE. Alleviates high glucose-induced inflammation, oxidative stress and apoptosis of podocytes by the activation of AMPK/SIRT1 signaling pathway. Diabetes Metab Syndr Obes. 2020;13:3821–3830. https://doi.org/10.2147/DMSO.S276184.
Wang DS, Wang JM, Zhang FR, Lei FJ, Wen X, Song J, Sun GZ, Liu Z. Ameliorative effects of malonyl ginsenoside from Panax ginseng on glucose-lipid metabolism and insulin resistance via IRS1/PI3K/Akt and AMPK signaling pathways in type 2 diabetic mice. Am J Chin Med. 2022;50(3):863–82. https://doi.org/10.1142/S0192415X22500367.
Kang OH, Shon MY, Kong R, Seo YS, Zhou T, Kim DY, Kim YS, Kwon DY. Anti-diabetic effect of black ginseng extract by augmentation of AMPK protein activity and upregulation of GLUT2 and GLUT4 expression in db/db mice. BMC Complement Altern Med. 2017;17(1):341. https://doi.org/10.1186/s12906-017-1839-4.
Lee MS, Hwang JT, Kim SH, Yoon S, Kim MS, Yang HJ, Kwon DY. Ginsenoside Rc, an active component of Panax ginseng, stimulates glucose uptake in C2C12 myotubes through an AMPK-dependent mechanism. J Ethnopharmacol. 2010;127(3):771–6. https://doi.org/10.1016/j.jep.2009.11.022.
Jin MN, Shi GR, Tang SA, Nan-Qin, Qiao W, Duan HQ. Flavonoids from Tetrastigma obtectum enhancing glucose consumption in insulin-resistance HepG2 cells via activating AMPK. Fitoterapia. 2013;90:240–6. https://doi.org/10.1016/j.fitote.2013.07.024.
Han J, Yi J, Liang F, Jiang B, Xiao Y, Gao S, Yang N, Hu H, Xie WF, Chen W. X-3, a mangiferin derivative, stimulates AMP-activated protein kinase and reduces hyperglycemia and obesity in db/db mice. Mol Cell Endocrinol. 2015;405:63–73. https://doi.org/10.1016/j.mce.2015.02.008.
Wang X, Gao L, Lin H, Song J, Wang J, Yin Y, Zhao J, Xu X, Li Z, Li L. Mangiferin prevents diabetic nephropathy progression and protects podocyte function via autophagy in diabetic rat glomeruli. Eur J Pharmacol. 2018;824:170–178. https://doi.org/10.1016/j.ejphar.2018.02.009.
Zhang Y, Liu X, Han L, Gao X, Liu E, Wang T. Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/AKT signaling pathways. Food Chem. 2013;141(3):2896–905. https://doi.org/10.1016/j.foodchem.2013.05.121.
Naimi M, Tsakiridis T, Stamatatos TC, Alexandropoulos DI, Tsiani E. Increased skeletal muscle glucose uptake by rosemary extract through AMPK activation. Appl Physiol Nutr Metab. 2015;40(4):407–13. https://doi.org/10.1139/apnm-2014-0430.
Tu Z, Moss-Pierce T, Ford P, Jiang TA. Rosemary (Rosmarinus officinalis L.) extract regulates glucose and lipid metabolism by activating AMPK and PPAR pathways in HepG2 cells. J Agric Food Chem. 2013;61(11):2803–10. https://doi.org/10.1021/jf400298c.
Shamshoum H, Vlavcheski F, MacPherson REK, Tsiani E. Rosemary extract activates AMPK, inhibits mTOR and attenuates the high glucose and high insulin-induced muscle cell insulin resistance. Appl Physiol Nutr Metab. 2021;46(7):819–827. https://doi.org/10.1139/apnm-2020-0592.
Vlavcheski F, Naimi M, Murphy B, Hudlicky T, Tsiani E. Rosmarinic acid, a rosemary extract polyphenol, increases skeletal muscle cell glucose uptake and activates AMPK. Molecules. 2017;22(10):14–8. https://doi.org/10.3390/molecules22101669.
Shen Y, Honma N, Kobayashi K, Jia LN, Hosono T, Shindo K, Ariga T, Seki T. Cinnamon extract enhances glucose uptake in 3T3-L1 adipocytes and C2C12 myocytes by inducing LKB1-AMP-activated protein kinase signaling. PLoS One. 2014;9(2):e87894. https://doi.org/10.1371/journal.pone.0087894.
Absalan A, Mohiti-Ardakani J, Hadinedoushan H, Khalili MA. Hydro-alcoholic cinnamon extract, enhances glucose transporter isotype-4 translocation from intracellular compartments into the cytoplasmic membrane of C2C12 myotubes. Indian J Clin Biochem. 2012;27(4):351–6. https://doi.org/10.1007/s12291-012-0214-y.
Edoga CO, Njoku OO, Amadi EN, Okeke JJ. Blood sugar lowering effect of Moringa oleifera lam in albino rats. Int J Sci Technol. 2013;3(1):88–90.
Bao Y, Xiao J, Weng Z, Lu X, Shen X, Wang F. A phenolic glycoside from Moringa oleifera Lam. improves the carbohydrate and lipid metabolisms through AMPK in db/db mice. Food Chem. 2020;311:125948. https://doi.org/10.1016/j.foodchem.2019.125948.
Joung H, Kim B, Park H, Lee K, Kim HH, Sim HC, Do HJ, Hyun CK, Do MS. Fermented Moringa oleifera decreases hepatic adiposity and ameliorates glucose intolerance in high-fat diet-induced obese mice. J Med Food. 2017;20(5):439–47. https://doi.org/10.1089/jmf.2016.3860.
Hwang SL, Jeong YT, Hye Yang J, Li X, Lu Y, Son JK, Chang HW. Pinusolide improves high glucose-induced insulin resistance via activation of AMP-activated protein kinase. Biochem Biophys Res Commun. 2013;437(3):374–9. https://doi.org/10.1016/j.bbrc.2013.06.084.
Kim T, Davis J, Zhang AJ, He X, Mathews ST. Curcumin activates AMPK and suppresses gluconeogenic gene expression in hepatoma cells. Biochem Biophys Res Commun. 2009;388(2):377–82. https://doi.org/10.1016/j.bbrc.2009.08.018.
Lakshmanan AP, Watanabe K, Thandavarayan RA, Sari FR, Meilei H, Soetikno V, Arumugam S, Giridharan VV, Suzuki K, Kodama M. Curcumin attenuates hyperglycaemia-mediated AMPK activation and oxidative stress in cerebrum of streptozotocin-induced diabetic rat. Free Radic Res. 2011;45(7):788–95. https://doi.org/10.3109/10715762.2011.579121.
Lv J, Cao L, Zhang R, Bai F, Wei P. A curcumin derivative J147 ameliorates diabetic peripheral neuropathy in streptozotocin (STZ)-induced DPN rat models through negative regulation AMPK on TRPA1. Acta Cir Bras. 2018;33(6):533–41. https://doi.org/10.1590/s0102-865020180060000008.
Zhao L, Zou T, Gomez NA, Wang B, Zhu MJ, Du M. Raspberry alleviates obesity-induced inflammation and insulin resistance in skeletal muscle through activation of AMP-activated protein kinase (AMPK) α1. Nutr Diabetes. 2018;8(1):39. https://doi.org/10.1038/s41387-018-0049-6.
Xiong H, Zhang S, Zhao Z, Zhao P, Chen L, Mei Z. Antidiabetic activities of entagenic acid in type 2 diabetic db/db mice and L6 myotubes via AMPK/GLUT4 pathway. J Ethnopharmacol. 2018;211:366–374. https://doi.org/10.1016/j.jep.2017.10.004.
Zheng T, Hao X, Wang Q, Chen L, Jin S, Bian F. Entada phaseoloides extract suppresses hepatic gluconeogenesis via activation of the AMPK signaling pathway. J Ethnopharmacol. 2016;193:691–9. https://doi.org/10.1016/j.jep.2016.10.039.
Hashiesh HM, Meeran MFN, Sharma C, Sadek B, Kaabi JA, Ojha SK. Therapeutic potential of β-caryophyllene: A dietary cannabinoid in diabetes and associated complications. Nutrients. 2020;12(10):2963. https://doi.org/10.3390/nu12102963.
Esposito D, Damsud T, Wilson M, Grace MH, Strauch R, Li X, Lila MA, Komarnytsky S. Black currant anthocyanins attenuate weight gain and improve glucose metabolism in diet-induced obese mice with intact, but not disrupted, gut microbiome. J Agric Food Chem. 2015;63(27):6172–80. https://doi.org/10.1021/acs.jafc.5b00963.
Joseph B, Jini D. Antidiabetic effects of Momordica charantia (bitter melon) and its medicinal potency. Asian Pac J Trop Dis. 2013;3(2):93–102. https://doi.org/10.1016/S2222-1808(13)60052-3.
Chung MY, Choi HK, Hwang JT. AMPK activity: A primary target for diabetes prevention with therapeutic phytochemicals. Nutrients. 2021;13(11):4050. https://doi.org/10.3390/nu13114050.
Jin D, Yu M, Li X, Wang X. Efficacy of Tripterygium wilfordii Hook F on animal model of Diabetic Kidney Diseases: A systematic review and meta-analysis. J Ethnopharmacol. 2021;281:114536. https://doi.org/10.1016/j.jep.2021.114536.
Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, Kim HW, Cha JJ, Hyun YY, Han SY, Han KH, Han JY, Cha DR. Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLoS One. 2013;26(4):e62068. https://doi.org/10.1371/journal.pone.0062068.
Gong P, Cui D, Guo Y, Wang M, Wang Z, Huang Z, Yang W, Chen F, Chen X. A novel polysaccharide obtained from Siraitia grosvenorii alleviates inflammatory responses in a diabetic nephropathy mouse model via the TLR4-NF-κB pathway. Food Funct. 2021;12(19):9054–9065. https://doi.org/10.1039/d1fo01182k.
Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, Cho JY. Pharmacological potential of ginseng and its major component ginsenosides. J Ginseng Res. 2021;45(2):199–210. https://doi.org/10.1016/j.jgr.2020.02.004.
Naseri K, Saadati S, Sadeghi A, Asbaghi O, Ghaemi F, Zafarani F, Li H, Bin, Gan RY. The efficacy of ginseng (Panax) on human prediabetes and type 2 diabetes mellitus: A systematic review and meta-analysis. Nutrients. 2022;14(12). https://doi.org/10.3390/nu14122401.
Park EY, Kim HJ, Kim YK, Park SU, Choi JE, Cha JY, Jun HS. Increase in insulin secretion induced by Panax ginseng berry extracts contributes to the amelioration of hyperglycemia in streptozotocininduced diabetic mice. J Ginseng Res. 2012;36(2):153–60. https://doi.org/10.5142/jgr.2012.36.2.153.
Zhang L, Li B, Wang M, Lin H, Peng Y, Zhou X, Peng C, Zhan J, Wang W. Genus Tetrastigma: A review of its folk uses, phytochemistry and pharmacology. Chin Herb Med. 2022;14(2):210–33. https://doi.org/10.1016/j.chmed.2022.03.003.
Sharma H, Kumar S. Natural AMPK activators: An alternative approach for the treatment and management of metabolic syndrome. Curr Med Chem. 2017;24(10):1007–47. https://doi.org/10.2174/0929867323666160406120814.
Ru Y, Chen X, Wang J, Guo L, Lin Z, Peng X, Qiu B, Wong WL. Structural characterization, hypoglycemic effects and mechanism of a novel polysaccharide from Tetrastigma hemsleyanum Diels et Gilg. Int J Biol Macromol. 2019;123:775–783. https://doi.org/10.1016/j.ijbiomac.2018.
Kasbe P, Jangra A, Lahkar M. Mangiferin ameliorates aluminium chloride-induced cognitive dysfunction via alleviation of hippocampal oxido-nitrosative stress, proinflammatory cytokines and acetylcholinesterase level. J Trace Elem Med Biol. 2015;31:107–12. https://doi.org/10.1016/j.jtemb.2015.04.002.
Arora MK, Kisku A, Jangra A. Mangiferin ameliorates intracerebroventricular-quinolinic acid-induced cognitive deficits, oxidative stress, and neuroinflammation in Wistar rats. Indian J Pharmacol. 2020;52(4):296–305. https://doi.org/10.4103/ijp.IJP_699_19.
Jangra A, Arora MK, Kisku A, Sharma S. The multifaceted role of mangiferin in health and diseases: a review. Adv Tradit Med (ADTM). 2021;21:619–43. https://doi.org/10.1007/s13596-020-00471-5.
Saleh S, El-Maraghy N, Reda E, Barakat W. Modulation of diabetes and dyslipidemia in diabetic insulin-resistant rats by mangiferin: role of adiponectin and TNF-α An. Acad Bras Cienc. 2014;86(4):1935–48. https://doi.org/10.1590/0001-3765201420140212.
Wang F, Yan J, Niu Y, Li Y, Lin H, Liu X, Liu J, Li L. Mangiferin and its aglycone, norathyriol, improve glucose metabolism by activation of AMP-activated protein kinase. Pharm Biol. 2014;52(1):68–73. https://doi.org/10.3109/13880209.2013.814691.
Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int J Biol Sci. 2018;14(11):1483–1496. https://doi.org/10.7150/ijbs.27173.
Vlavcheski F, Baron D, Vlachogiannis IA, MacPherson REK, Tsiani E. Carnosol increases skeletal muscle cell glucose uptake via AMPK-dependent GLUT4 glucose transporter translocation. Int J Mol Sci. 2018;19(5):1321. https://doi.org/10.3390/ijms19051321.
Qusti S, El Rabey HA, Balashram SA. The hypoglycemic and antioxidant activity of cress seed and cinnamon on streptozotocin induced diabetes in male rats. Evid Based Complement Alternat Med. 2016;2016:5614564. https://doi.org/10.1155/2016/5614564.
Vijayakumar K, Rengarajan RL, Suganthi N, Prasanna B, Velayuthaprabhu S, Shenbagam M, Vijaya Anand A. Acute toxicity studies and protective effects of Cinnamon cassia bark extract in streptozotocin-induced diabetic rats. Drug Chem Toxicol. 2021:1–11. https://doi.org/10.1080/01480545.2021.
Farazandeh M, Mahmoudabady M, Asghari AA, Niazmand S. Diabetic cardiomyopathy was attenuated by cinnamon treatment through the inhibition of fibro-inflammatory response and ventricular hypertrophy in diabetic rats. J Food Biochem. 2022;46(8):e14206. https://doi.org/10.1111/jfbc.14206.
Gannon NP, Schnuck JK, Mermier CM, Conn CA, Vaughan RA. trans-Cinnamaldehyde stimulates mitochondrial biogenesis through PGC-1α and PPARβ/δ leading to enhanced GLUT4 expression. Biochimie. 2015;119:45–51. https://doi.org/10.1016/j.biochi.2015.10.001.
Paikra BK, Dhongade HKJ, Gidwani B. Phytochemistry and pharmacology of Moringa oleifera Lam. J Pharmacopunct. 2017;20(3):194–200. https://doi.org/10.3831/KPI.2017.20.022.
Jangra A, Kwatra M, Singh T, Pant R, Kushwah P, Sharma Y, Saroha B, Datusalia AK, Bezbaruah BK. Piperine augments the protective effect of curcumin against lipopolysaccharide-induced neurobehavioral and neurochemical deficits in mice. Inflammation. 2016;39(3):1025–38. https://doi.org/10.1007/s10753-016-0332-4.
Ahmad RS, Hussain MB, Sultan MT, Arshad MS, Waheed M, Shariati MA, Plygun S, Hashempur MH, Biochemistry. Safety, pharmacological activities, and clinical applications of turmeric: A mechanistic review. Evid Based Complement Alternat Med. 2020;10:7656919. https://doi.org/10.1155/2020/7656919.
Na LX, Zhang YL, Li Y, Liu LY, Li R, Kong T, Sun CH. Curcumin improves insulin resistance in skeletal muscle of rats. Nutr Metab Cardiovasc Dis. 2011;21(7):526–33. https://doi.org/10.1016/j.numecd.2009.11.009.
Lu X, Wu F, Jiang M, Sun X, Tian G. Curcumin ameliorates gestational diabetes in mice partly through activating AMPK. Pharm Biol. 2019;57(1):250–4. https://doi.org/10.1080/13880209.2019.1594311.
Soetikno V, Sari FR, Sukumaran V, Lakshmanan AP, Harima M, Suzuki K, Kawachi H, Watanabe K. Curcumin decreases renal triglyceride accumulation through AMPK-SREBP signaling pathway in streptozotocin-induced type 1 diabetic rats. J Nutr Biochem. 2013;24(5):796–802. https://doi.org/10.1016/j.jnutbio.2012.04.013.
Yao Q, Ke ZQ, Guo S, Yang XS, Zhang FX, Liu XF, Chen X, Chen HG, Ke HY, Liu C. Curcumin protects against diabetic cardiomyopathy by promoting autophagy and alleviating apoptosis. J Mol Cell Cardiol. 2018;124:26–34. https://doi.org/10.1016/j.yjmcc.2018.10.004.
Burton-Freeman BM, Sandhu AK, Edirisinghe I. Red raspberries and their bioactive polyphenols: Cardiometabolic and neuronal health links. Adv Nutr. 2016;7(1):44–65. https://doi.org/10.3945/an.115.009639.
Haizhaoa S, Xinchuna S, Qiangb C, Xiaodong Z. Red raspberry (poly)phenolic extract improves diet-induced obesity, hepatic steatosis and insulin resistance in obese mice. J Berry Res. 2021;11:349–62.
Zheng T, Shu G, Yang Z, Mo S, Zhao Y, Mei Z. Antidiabetic effect of total saponins from Entada phaseoloides (L.) Merr. in type 2 diabetic rats. J Ethnopharmacol. 2012;139(3):814–21. https://doi.org/10.1016/j.jep.2011.12.025.
Acknowledgements
The authors express sincere thanks to the Director, Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra for providing facilities for this work.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
There is no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Chauhan, S., Singh, A.P., Rana, A.C. et al. Natural activators of AMPK signaling: potential role in the management of type-2 diabetes. J Diabetes Metab Disord 22, 47–59 (2023). https://doi.org/10.1007/s40200-022-01155-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40200-022-01155-4