Anti-hyperglycemic fraction from Alternanthera sessilis L. leaves gets elucidated following bioassay-guided isolation and mass spectrometry

Authors

  • Richelle Ann Mallapre Manalo Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines SCImago image Institute of Pharmaceutical Sciences, National Institutes of Health, University of the Philippines Manila, Manila, Philippines http://orcid.org/0000-0001-5440-3102
  • fmheralde1@up.edu.ph Department of Biochemistry and Molecular Biology, College of Medicine, University of the Philippines Manila, Manila, Philippines

DOI:

https://doi.org/10.1590/s2175-97902023e21283

Keywords:

Alternanthera sessilis, Anti-hyperglycemic, Apigenin, Luteolin, Bioassay-guided isolation

Abstract

The anecdotal use of Alternanthera sessilis L. as a relief for diabetes has been known in the Philippines for generations, and antidiabetic activity of similar varieties in other countries is likewise documented. However, the compounds responsible for this activity remain unclear. This study aims to isolate the anti-hyperglycemic fraction of local A. sessilis leaves and identify the compounds in this fraction. Methanol extract of A. sessilis leaves and its hexane, ethyl acetate (ASE), and water fractions were administered to alloxan-induced diabetic mice. ASE (250mg/kg) had the highest anti-hyperglycemic activity at 6-h post-treatment (25.81%±12.72%), with almost similar blood glucose reduction rate as metformin (30.13±3.75%, p=0.767). Repeated fractionation employing chromatographic separation techniques followed by in vivo anti-hyperglycemic assay yielded partially purified subfractions. A. sessilis ethyl acetate subfraction 4-2 (100mg/kg) displayed remarkable suppression of blood glucose rise in diabetic mice at 6-h post-treatment (26.45±3.75%, p<0.0001), with comparable activity with metformin (100mg/kg, 27.87±5.65%, p=0.652). Liquid chromatography/mass spectrometry showed eight distinct peaks, with four peaks annotated via the Traditional Chinese Medicine library and custom library for A. sessilis. Among these, luteolin, apigenin, ononin, and sophorabioside were identified as putative compounds responsible for the anti-hyperglycemic activity. This result provided basis for the reported anecdotal claims and potential utility of the local variety of A. sessilis leaves as sources of anti-hyperglycemic agents.

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References

Abdallah HM, Al-Abd AM, Asaad GF, Abdel-Naim AB, El-halawany AM. Isolation of antiosteoporotic compounds from seeds of Sophora japonica. PLoS One. 2014;9(6):e98559.

Arcellana AE, Jimeno C. Challenges and opportunities for diabetes care in the Philippines in the time of the COVID-19 pandemic. JAFES. 2020;35(1):55-57.

Benedé-Ubieto R, Estévez-Vázquez O, Ramadori P, Cubero FJ, Nevzorova YA. Guidelines and considerations for metabolic tolerance tests in mice. Diabetes Metab Syndr Obes. 2020;13:439-450.

Chai TT, Khoo CS, Tee CS, Wong FC. Alpha-glucosidase inhibitory and antioxidant potential of antidiabetic herb Alternanthera sessilis: comparative analyses of leaf and callus solvent fractions. Pharmacogn Mag. 2016;12(48):253-258.

Das M, Ashok Kumar D, Mastanaiah K, Das A. Evaluation of anti-diabetic activity of ethanolic extract of Alternanthera sessilis L. in streptozotocin-induced diabetic rats. IJSPR. 2015;6(7):1027-1032.

Ding L, Jin D, Chen X. Luteolin enhances insulin sensitivity via activation of PPARγ transcriptional activity in adipocytes. J Nutr Biochem. 2010;21(10):941-947.

Flora & Fauna Web. Alternanthera sessilis ‘Red’ [Internet], 2020. [cited 2021 Feb 27]. Available from: Available from: https://www.nparks.gov.sg/florafaunaweb/flora/3/4/3433

» https://www.nparks.gov.sg/florafaunaweb/flora/3/4/3433

Guo Guang W, Xiao HL, Wei L, Xue Z, Cui Z. Protective effects of luteolin on diabetic nephropathy in STZ-induced diabetic rats. Evid Based Complement Alternat Med. 2011;323171.

Hoo RLC, Wong JYL, Qiao CF, Xu A, Xu HX, Lam KSL. The effective fraction isolated from Radix astragali alleviates glucose intolerance, insulin resistance and hypertriglyceridemia in db/db diabetic mice through its anti-inflammatory activity. Nutr Metab. 2010;7:67.

Hossain AI, Faisal M, Rahman S, Jahan R, Rahmatullah M. A preliminary evaluation of antihyperglycemic and analgesic activity of A. sessilis aerial parts. BMC Complement Altern Med. 2014;14:169.

Huang M, Deng S, Han Q, Zhao P, Zhou Q, Zheng S, Ma X, Xu C, Yang J, Yang X. Hypoglycemic activity and the potential mechanism of the flavonoid rich extract from Sophora tonkinensis Gagnep. in KK-Ay mice. Front Pharmacol. 2016;7:288.

India Biodiversity Portal. Alternanthera sessilis [Internet], 2018. [cited 2021 Feb 27]. Available from: Available from: https://indiabiodiversity.org/species/show/32910

» https://indiabiodiversity.org/species/show/32910

International Diabetes Federation. International Diabetes Atlas 9th edition [Internet], 2019. [cited 2021 Mar 29]. Available from: Available from: https://www.diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf

» https://www.diabetesatlas.org/upload/resources/material/20200302_133351_IDFATLAS9e-final-web.pdf

Jia H, Jian L, Xiaoxia L, Yanxia L, Jingya R, Yongzhe D, et al. Aromatic constituents from the stems of Astragalus membranaceus (Fisch.) Bge. var. Mongholicus (Bge.) Hsiao. Molecules. 2016;21(3):354.

Jung UJ, Cho YY, Choi MS. Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high fat diet-induced obese mice. Nutrients. 2016;8(5):305-321.

Khatun H, Rahman A, Biswas M, Ul Islam A. Water-soluble fraction of Abelmoschus esculentus L interacts with glucose and metformin hydrochloride and alters their absorption kinetics after coadministration in rats. ISRN Pharm. 2011;2011:260537.

Kim JS, Kwon CS, Son KH. Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. Biosci Biotechnol Biochem. 2000;64(11):2458-2461.

Luna B, Feinglos MN. Intra-gastric agents in the management of type 2 diabetes mellitus. Am Fam Physician. 2001;63(9):1747-1757.

Monroy AEM, Limsiaco CL. Phytochemical and antimicrobial analysis of “Lupo” (Alternanthera sessilis L.R.Br.). WVSU Res J. 2016;5(2):21-34.

Moses RG. Combination therapy for patients with type 2 diabetes: repaglinide in combination with metformin. Expert Rev Endocrinol Metabol. 2010;5(3):331-342.

Organization for Economic Cooperation and Development. OECD Guidelines for Testing of Chemicals. Acute oral toxicity test [Internet], 2008. [cited 2021 June 28]. Available from: Available from: http://www.oecd-ilibrary.org/environment/test-no-425-acute-oral-toxicity-up-and-down-procedure_9789264071049-en

» http://www.oecd-ilibrary.org/environment/test-no-425-acute-oral-toxicity-up-and-down-procedure_9789264071049-en

Sisa M, Bonnet SL, Ferreira D, Van der Westhuizen JH. Phytochemistry of flavonoids. Molecules . 2010;15(8):5196-5245.

Tan KK, Kim KH. Alternanthera sessilis Red ethyl acetate fractions exhibit antidiabetic potential on obese type 2 diabetic rats. Evid Based Complement Alternat Med . 2013;845172.

Yap A, Nishiumi S, Yoshida K, Ashida H. Rat L6 myotubes as an in vitro model system to study GLUT4-dependent glucose uptake stimulated by inositol derivatives. Cytotechnology. 2007;55(2-3):103-108.

Zang Y, Igarashi K, Li Y. Anti-diabetic effects of luteolin and luteolin-7-O-glucoside on KK-Ay mice. Biosci Biotechnol Biochem . 2016;80(8):1580-6.

Zhang BW, Li X, Sun WL, Xing Y, Xiu ZL, Zhuang CL, et al. Dietary flavonoids and acarbose synergistically inhibit α-glucosidase and lower postprandial blood glucose. J Agric Food Chem. 2017;65(38):8319-8330.

Zhao T, Mao G, Zhang M, Li F, Zou Y, Zheng W, et al. Anti-diabetic effects of polysaccharides from ethanol-insoluble residue of Schisandra chinensis (Turcz.) Baill on alloxan-induced diabetic mice. Chem Res Chin Univ. 2013;29(1):99-102.

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Published

2023-05-08

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Original Article

How to Cite

Anti-hyperglycemic fraction from Alternanthera sessilis L. leaves gets elucidated following bioassay-guided isolation and mass spectrometry. (2023). Brazilian Journal of Pharmaceutical Sciences, 59, e21283. https://doi.org/10.1590/s2175-97902023e21283