Browse > Article
http://dx.doi.org/10.3831/KPI.2022.25.2.130

Artemisia annua L. Extracts Improved Insulin Resistance via Changing Adiponectin, Leptin and Resistin Production in HFD/STZ Diabetic Mice  

Ghanbari, Mahshid (Department of Toxicology and Pharmacology, Faculty of Pharmacy, Manzandaran University of Medical Sciences)
Lamuki, Mohammad Shokrzadeh (Department of Toxicology and Pharmacology, Faculty of Pharmacy, Manzandaran University of Medical Sciences)
Habibi, Emran (Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences)
Sadeghimahalli, Forouzan (Pharmaceutical Science Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences)
Publication Information
Journal of Pharmacopuncture / v.25, no.2, 2022 , pp. 130-137 More about this Journal
Abstract
Objectives: Insulin resistance (IR) is major cause of type 2 diabetes (T2D), and adipokines (e.g., adiponectin, leptin, and resistin) play an important role in insulin sensitivity. Medicinal plants are frequently used for T2D treatment. This study investigates the effect of Artemisia annua L. (AA) extracts on adipokines in mice with high-fat-diet (HFD)/streptozotocin (STZ)-induced T2D. Methods: We divided 60 mice into 12 groups (n = 5 per group): control, untreated T2D, treated T2D, and 9 other groups. T2D was induced in all groups, except controls, by 8 weeks of HFD and STZ injection. The treated T2D group was administered 250 mg/kg of metformin (MTF), while the nine other groups were treated with 100, 200, and 400 mg/kg of hot-water extract (HWE), cold-water extract (CWE), and alcoholic extract (ALE) of AA (daily oral gavage) along with 250 mg/kg of MTF for 4 weeks. The intraperitoneal glucose tolerance test (IPGTT) was performed, and the homeostasis model assessment of adiponectin (HOMA-AD) index and blood glucose and serum insulin, leptin, adiponectin, and resistin levels were measured. Results: Similar to MTF, all three types of AA extracts (HWEs, CWEs, and ALEs) significantly (p < 0.0001) decreased the area under the curve (AUC) of glucose during the IPGTT, the HOMA-AD index, blood glucose levels, and serum insulin, leptin, and resistin levels and increased serum adiponectin levels in the MTF group compared to the T2D group (p < 0.0001). The HWEs affected adipokine release, while the CWEs and ALEs decreased leptin and resistin production. Conclusion: Water and alcoholic AA extracts have an antihyperglycemic and antihyperinsulinemic effect on HFD/STZ diabetic mice. In addition, they decrease IR by reducing leptin and resistin production and increasing adiponectin secretion from adipocytes.
Keywords
adiponectin; leptin; resistin; artemisia anuua l.; diabetes;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
연도 인용수 순위
1 Ogbonna CIC, Ogbonna AI, Onyimba IA, Itelima JU, Umar AF, Onyezili N, et al. Combined anti-diabetic effects of extracts of Artemisia annua var. chiknensis (CBGE/CHNA/09/LTNGS/G) and each of three other plants (Momordica charantia Linn. Vernonia amygdalina Del. and Aegle marmelos Correa) traditionally used in Nigeria for the treatment of diabetes. J Sci Res Rep. 2017;16(2):1-12.
2 Sadeghimahalli F, Khaleghzadeh-Ahangar H, Baluchnejadmojarad T. Role of prostaglandins in the vasodilator effect of the aqueous extract from artemisia annua plant in streptozotocininduced diabetic rats. Annu Res Rev Biol. 2019;31(6):1-10.
3 Helal EGE, Abou-Aouf N, Khattab AM, Zoair MA. Antidiabetic effect of artemisia annua (Kaysom) in alloxan-induced diabetic rats. Egypt J Hosp Med. 2014;57:422-30.   DOI
4 Albasher G, Alwahaibi M, Abdel-Daim MM, Alkahtani S, Almeer R. Protective effects of Artemisia judaica extract compared to metformin against hepatorenal injury in high-fat diet/streptozotocine-induced diabetic rats. Environ Sci Pollut Res Int. 2020;27(32):40525-36.   DOI
5 Honmore V, Kandhare A, Zanwar AA, Rojatkar S, Bodhankar S, Natu A. Artemisia pallens alleviates acetaminophen induced toxicity via modulation of endogenous biomarkers. Pharm Biol. 2015;53(4):571-81.   DOI
6 Gao J, Cheng Y, Hao H, Yin Y, Xue J, Zhang Q, et al. Decitabine assists umbilical cord-derived mesenchymal stem cells in improving glucose homeostasis by modulating macrophage polarization in type 2 diabetic mice. Stem Cell Res Ther. 2019;10(1):259.   DOI
7 Liu M, Zhang K, Wang L, Yang H, Yan K, Pan H, et al. Serum ZAG and adiponectin levels were closely related to obesity and the metabolically abnormal phenotype in Chinese population. Diabetes Metab Syndr Obes. 2020;13:3099-112.   DOI
8 Guo Y, Fu W, Xin Y, Bai J, Peng H, Fu L, et al. Antidiabetic and antiobesity effects of artemether in db/db Mice. Biomed Res Int. 2018;2018:8639523.
9 Vilela BS, Vasques AC, Cassani RS, Forti AC, Pareja JC, Tambascia MA, et al. The HOMA-Adiponectin (HOMA-AD) closely mirrors the HOMA-IR index in the screening of insulin resistance in the Brazilian Metabolic Syndrome Study (BRAMS). PLoS One. 2016;11(8):e0158751.   DOI
10 Jung UJ, Baek NI, Chung HG, Bang MH, Yoo JS, Jeong TS, et al. The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ-db/db mice. Food Chem Toxicol. 2007;45(10):2022-9.   DOI
11 Matsuhisa M, Yamasaki Y, Emoto M, Shimabukuro M, Ueda S, Funahashi T, et al. A novel index of insulin resistance determined from the homeostasis model assessment index and adiponectin levels in Japanese subjects. Diabetes Res Clin Pract. 2007;77(1):151-4.   DOI
12 Pittas AG, Joseph NA, Greenberg AS. Adipocytokines and insulin resistance. J Clin Endocrinol Metab. 2004;89(2):447-52.   DOI
13 Goldstein BJ. Insulin resistance as the core defect in type 2 diabetes mellitus. Am J Cardiol. 2002;90(5A):3G-10G.   DOI
14 El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: review on potential mechanistic perspectives. World J Diabetes. 2014;5(2):176-97.   DOI
15 Kang YJ, Jung UJ, Lee MK, Kim HJ, Jeon SM, Park YB, et al. Eupatilin, isolated from Artemisia princeps Pampanini, enhances hepatic glucose metabolism and pancreatic beta-cell function in type 2 diabetic mice. Diabetes Res Clin Pract. 2008;82(1):25-32.   DOI
16 Richard AJ, Burris TP, Sanchez-Infantes D, Wang Y, Ribnicky DM, Stephens JM. Artemisia extracts activate PPARγ, promote adipogenesis, and enhance insulin sensitivity in adipose tissue of obese mice. Nutrition. 2014;30(7-8 Suppl):S31-6.   DOI
17 Das S. Artemisia annua (Qinghao): a pharmacological review. Int J Pharm Sci Res. 2012;3(12):4573-7.
18 Melillo de Magalhaes P, Dupont I, Hendrickx A, Joly A, Raas T, Dessy S, et al. Anti-inflammatory effect and modulation of cytochrome P450 activities by Artemisia annua tea infusions in human intestinal Caco-2 cells. Food Chem. 2012;134(2):864-71.   DOI
19 Kadi I, Ouinten M, Gourine N, Yousfi M. Synergistic antinociceptive activity of combined aqueous extracts of Artemisia campestris and Artemisia herba-alba in several acute pain models. Nat Prod Res. 2019;33(6):875-8.   DOI
20 Kim YH, Park CM, Yoon G. Amelioration of metabolic disturbances and adipokine dysregulation by mugwort (Artemisia princeps P.) extract in high-fat diet-induced obese rats. J Nutr Health. 2016;49(6):411-9.   DOI
21 Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature. 1999;401(6748):73-6.   DOI
22 Morton GJ, Gelling RW, Niswender KD, Morrison CD, Rhodes CJ, Schwartz MW. Leptin regulates insulin sensitivity via phosphatidylinositol-3-OH kinase signaling in mediobasal hypothalamic neurons. Cell Metab. 2005;2(6):411-20.   DOI
23 Eddouks M, Bidi A, El Bouhali B, Hajji L, Zeggwagh NA. Antidiabetic plants improving insulin sensitivity. J Pharm Pharmacol. 2014;66(9):1197-214.   DOI
24 Aba PE, Asuzu IU. Mechanisms of actions of some bioactive anti-diabetic principles from phytochemicals of medicinal plants: a review. Indian J Nat Prod Resour. 2018;9(2):85-96.
25 Gao CL, Zhao DY, Qiu J, Zhang CM, Ji CB, Chen XH, et al. Resistin induces rat insulinoma cell RINm5F apoptosis. Mol Biol Rep. 2009;36(7):1703-8.   DOI
26 Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab. 2002;13(1):18-23.   DOI
27 Fathy SM, Mahmoud MS. Moringa oleifera Lam. leaf extract mitigates carbon tetrachloride-mediated hepatic inflammation and apoptosis via targeting oxidative stress and toll-like receptor 4/nuclear factor kappa B pathway in mice. Food Sci Hum Wellness. 2021;10(3):383-91.   DOI
28 Hassan M, El Yazidi C, Landrier JF, Lairon D, Margotat A, Amiot MJ. Phloretin enhances adipocyte differentiation and adiponectin expression in 3T3-L1 cells. Biochem Biophys Res Commun. 2007;361(1):208-13.   DOI
29 Xu A, Wang H, Hoo RL, Sweeney G, Vanhoutte PM, Wang Y, et al. Selective elevation of adiponectin production by the natural compounds derived from a medicinal herb alleviates insulin resistance and glucose intolerance in obese mice. Endocrinology. 2009;150(2):625-33.   DOI
30 Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: review of the underlying molecular mechanisms. J Cell Physiol. 2019;234(6):8152-61.   DOI
31 Balland E, Cowley MA. New insights in leptin resistance mechanisms in mice. Front Neuroendocrinol. 2015;39:59-65.   DOI
32 Ebrahimi E, Shirali S, Afrisham R. Effect and mechanism of herbal ingredients in improving diabetes mellitus complications. Jundishapur J Nat Pharm Prod. 2017;12(1):e31657.
33 Ribnicky DM, Poulev A, Watford M, Cefalu WT, Raskin I. Antihyperglycemic activity of Tarralin, an ethanolic extract of Artemisia dracunculus L. Phytomedicine. 2006;13(8):550-7.   DOI
34 Kim KE, Ko KH, Heo RW, Yi CO, Shin HJ, Kim JY, et al. Artemisia annua leaf extract attenuates hepatic steatosis and inflammation in high-fat diet-fed mice. J Med Food. 2016;19(3):290-9.   DOI
35 Al-Waili NS. Treatment of diabetes mellitus by Artemisia herbaalba extract: preliminary study. Clin Exp Pharmacol Physiol. 1986;13(7):569-73.   DOI
36 Korkmaz H, Gurdal A. Effect of Artemisia santonicum L. on blood glucose in normal and alloxan-induced diabetic rabbits. Phytother Res. 2002;16(7):675-6.   DOI
37 Li YJ, Guo Y, Yang Q, Weng XG, Yang L, Wang YJ, et al. Flavonoids casticin and chrysosplenol D from Artemisia annua L. inhibit inflammation in vitro and in vivo. Toxicol Appl Pharmacol. 2015;286(3):151-8.   DOI