Astragalus adscendens extract shows antidiabetic effects through controlling oxidative stress, inflammation and apoptosis in streptozotocin-induced diabetic rats

Abstract

Objective: To assess the effect of oral treatment of methanolic extract of the aerial parts of Astragalus adscendens in streptozotocin-induced diabetic rats. Methods: In order to induce diabetes, rats intraperitoneally received streptozotocin at 65 mg/kg. Sixty adult male Wistar rats were allocated into six groups (10 rats per each) including the healthy control group, the diabetic group as well as the diabetic group treated with Astragalus adscendens methanolic extract at 50, 100, and 200 mg/kg per day or glibenclamide (0.6 mg/kg/day) for 28 d. The effects of Astragalus adscendens methanolic extract on the levels of glucose, insulin, alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, creatinine, urea, uric acid, total protein, albumin, triglyceride, cholesterol, α-amylase, oxidant/antioxidant enzymes, and inflammatory cytokines were evaluated. Real time-PCR was also used for measuring the gene expression of caspase-3, Bcl2, and Bax. Results: The levels of glucose, cholesterol, triglyceride, creatinine, urea, uric acid, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, bilirubin, and malondialdehyde considerably declined (P<0.001) in diabetic rats after treatment with Astragalus adscendens methanolic extract especially at a dose of 200 mg/kg. In addition, treatment with Astragalus adscendens methanolic extract noticeably increased the level of insulin, total protein, and albumin as well as improved the activities of catalase, glutathione peroxidase, and superoxide dismutase, as well as the expression levels of TNF-α, IL-1β, caspase-3, Bcl2 and Bax (P<0.001) compared to the diabetic control group. The extract also inhibited α-amylase in a dose-dependent manner with an IC₅₀ value of 19.6 µg/mL. Conclusions: Astragalus adscendens methanolic extract shows potent antidiabetic, anti-inflammatory, anti-apoptotic, and antioxidant effects in diabetic rats. However, more studies are needed to verify the underlying mechanism of the effect of this plant extract and test its efficacy in clinical trials.

Keywords

Herbal medicines / Astragalus adscendens / Diabetes / Antioxidant / Antidiabetes / Streptozotocin / Antiinflammation

Acknowledgments

The authors would like to thank the staff of Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran, for their help in this work.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

Authors received no extramural funding for this study.

Authors’ contributions

YR designed the study. KK, HRM, and MNM performed experiments and collected data. HM and JGY drafted the manuscript. MNM and JGY discussed the results and strategy. MNM and JGY supervised, directed, and managed the study. All authors approved the final version to be published.

References

[1] Edelman SV, Polonsky WH. Type 2 diabetes in the real world: The elusive nature of glycemic control. Diabetes Care 2017; 40(11): 1425-1432.

[2] Yaribeygi H, Farrokhi FR, Butler AE, Sahebkar A. Insulin resistance: Review of the underlying molecular mechanisms. J Cellul Physiol 2019; 234(6): 8152-8161.

[3] Bagheri S, Khorramabadi RM, Assadollahi V, Khosravi P, Cheraghi Venol A, Veiskerami S, et al. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Arch Physiol Biochem 2021; 18: 1-9.

[4] Raza SA, Chaudhary AR, Mumtaz MW, Adnan A, Mukhtar H, Akhtar MT. Metabolite profiling and antidiabetic attributes of ultrasonicated leaf extracts of Conocarpus lancifolius. Asian Pac J Trop Biomed 2020; 10(8): 353-360.

[5] Joshi R, Laddha AP, Kulkarni YA, Wairkar S. Improved performance of naringenin herbosomes over naringenin in streptozotocin-induced diabetic rats: In vitro and in vivo evaluation. Asian Pac J Trop Biomed 2021; 11(9): 385-393.

[6] Stolar M. Glycemic control and complications in type 2 diabetes mellitus. American J Med 2010; 123(3): S3-S11.

[7] Oguntibeju OO. Type 2 diabetes mellitus, oxidative stress and inflammation: Examining the links. Int J Physiol Pathophysiol Pharmacol 2019; 11(3): 45.

[8] Jacob B, Narendhirakannan RT. Role of medicinal plants in the management of diabetes mellitus: A review. 3 Biotech 2019; 9(1): 4.

[9] Li X, Qu L, Dong Y, Han L, Liu E, Fang S, et al. A review of recent research progress on the Astragalus genus. Molecules 2014; 19(11): 18850-18880.

[10] Mahmoudvand H, Al-Abodi HR, Zolfagharkhani P, Ghasemian Yadegari J. Anti-helminthic effects and cellular mechanisms of Astragalus ecbatanus extract against Echinococcus granulosus protoscoleces. J Parasitic Dis 2022; 46(4): 1047-1054.

[11] Rios JL, Waterman PG. A review of the pharmacology and toxicology of Astragalus. Phytother Res 1997; 11(6): 411-418.

[12] Ghasemian Yadegari J, Fazeli Moghadam E, Golmohammadi H, Dastyarhaghighi S, Ghoulami M, Mahmoudvand H. Effect of oral administration of Astragalus ecbatanus chloroform extract on acute and chronic pain in Balb/C mice. Res J Pharmacog 2023; 6: 21-25.

[13] Yadegari JG, Khalaf AK, Saadatmand M, Mahmoudvand H. Antiparasitic activity of Astragalus brachycalyx subsp. brachycalyx extract against hydatid cyst protoscoleces and its effect on induction of apoptosis: An in vitro and ex vivo study. J Herbmed Pharmacol 2022; 11(3): 428-434.

[14] Ghasemian Yadegari J, Khudair Khalaf A, Darabi R, Mahmoudvand H. Antiparasitic effects and cellular mechanism of Astragalus maximus chloroform extract against clinical isolates of Giardia lamblia. Res J Pharmacog 2022; 9(3): 5-13.

[15] Singleton VL, Orthofer R, Lamuela-Raventós RM. Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods Enzymol 1999; 299: 152-178.

[16] Phuyal N, Jha PK, Raturi PP, Rajbhandary S. Total phenolic, flavonoid contents, and antioxidant activities of fruit, seed, and bark extracts of Zanthoxylum armatum DC. Sci World J 2020; 2020. doi: 10.1155/2020/8780704.

[17] Markossian S, Coussens NP, Dahlin JL, Sittampalam GS. Assay guidance manual for drug discovery: Robust or go bust. SLAS Discover 2021; 26(10): 1241-1242.

[18] Clark JD, Gebhart GF, Gonder JC, Keeling ME, Kohn DF. The 1996 guide for the care and use of laboratory animals. ILAR J 1997; 38(1): 41-48.

[19] Junod A, Lambert AE, Stauffacher W, Renold AE. Diabetogenic action of streptozotocin: Relationship of dose to metabolic response. J Clin Invest 1969; 48(11): 2129-2139.

[20] Hsu CY, Lin GM, Chang ST. Hypoglycemic activity of extracts of Chamaecyparis obtusa var. formosana leaf in rats with hyperglycemia induced by high-fat diets and streptozotocin. J Trad Com Med 2020; 10(4): 389-395.

[21] Pullen RA, Lindsay DG, Wood SP. Receptor-binding region of insulin. Nature 1976; 259(5542): 369-373.

[22] Kumar S, Mittal A, Babu D, Mittal A. Herbal medicines for diabetes management and its secondary complications. Curr Diab Rev 2021; 17(4): 437-456.

[23] Navarro MC, Montilla MP, Martín A, Jiménez J, Utrilla MP. Free radical scavenger and antihepatotoxic activity of Rosmarinus tomentosus. Planta Medica 1993; 59(4): 312-314.

[24] Salehi B, Ata AV, Anil Kumar N, Sharopov F, Ramirez-Alarcon K, Ruiz-Ortega A, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecules 2019; 9(10): 551.

[25] Khodzhaieva RS, Gladkov ES, Kyrychenko A, Roshal AD. Progress and achievements in glycosylation of flavonoids. Front Chem 2021; 9: 637994.

[26] Santilli F, Lapenna D, La Barba S, Davi G. Oxidative stress-related mechanisms affecting response to aspirin in diabetes mellitus. Free Radic Biol Med 2015; 80: 101-110.

[27] Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, et al. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud 2010; 7(1): 15-25.

[28] Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin nicotinamide induced diabetic rats. Life Sci 2009; 85(23-26): 830-834.

[29] Vincent AM, Russell JW, Low P, Feldman EL. Oxidative stress in the pathogenesis of diabetic neuropathy. Endocr Rev 2004; 25(4): 612-628.

[30] Chang YC, Chuang LM. The role of oxidative stress in the pathogenesis of type 2 diabetes: From molecular mechanism to clinical implication. Am J Transl Res 2010; 2(3): 316-331.

[31] Mahomoodally MF, Subratty AH, Gurib-Fakim A, Choudhary MI, Nahar Khan S. Traditional medicinal herbs and food plants have the potential to inhibit key carbohydrate hydrolyzing enzymes in vitro and reduce postprandial blood glucose peaks in vivo. Sci World J 2012; 2012. doi: 10.1100/2012/285284.

[32] Picot C, Subratty AH, Mahomoodally MF. Inhibitory potential of five traditionally used native antidiabetic medicinal plants on α-amylase, α-glucosidase, glucose entrapment, and amylolysis kinetics in vitro. Adv Pharmacol Sci 2014; 2014. doi: 10.1155/2014/739834.

[33] Duncan BB, Schmidt MI, Pankow JS, Ballantyne CM, Couper D, Vigo A, et al. Low-grade systemic inflammation and the development of type 2 diabetes: The atherosclerosis risk in communities study. Diabetes 2003; 52: 1799-1805.

[34] Köhler C, Orrenius S, Zhivotovsky B. Evaluation of caspase activity in apoptotic cells. J Immunol Method 2002; 265(1-2): 97-110.

[35] Wang J, Song Y, Wang Q, Kralik PM, Epstein PN. Causes and characteristics of diabetic cardiomyopathy. Rev Diabet Stud 2006; 3(3): 108.

[36] Marzetti E, Privitera G, Simili V, Wohlgemuth SE, Aulisa L, Pahor M, et al. Multiple pathways to the same end: Mechanisms of myonuclear apoptosis in sarcopenia of aging. Sci World J 2010; 10: 340-349.