Evaluation of the alpha-amylase inhibitory activity of Nepalese medicinal plants used in the treatment of diabetes mellitus

Karan Khadayat1, Bishnu P. Marasini1, Hira Gautam1, Sajani Ghaju1, Niranjan Parajuli2
1Department of Biotechnology, National College, Tribhuvan University, Naya Bazar, Kathmandu, Nepal
2Central Department of Chemistry, Tribhuvan University, Kirtipur, Kathmandu, Nepal

Tóm tắt

AbstractBackground

α-Amylase catalyses the hydrolysis of starch and ultimately producing glucose. Controlling the catalytic activity of this enzyme reduces glucose production in the postprandial stage, which could be a therapeutic benefit for people with diabetes. This study was conducted to evaluate α-amylase inhibition for utilizing the crude extracts of some medicinal plants traditionally used in Nepal for the treatment of diabetes and its related complications.

Methods

Microtiter plate approach has been used to assess inhibitory activities of in vitro α-amylase of methanolic extracts of thirty-two medicinal plants. A starch tolerance test was used in rats to investigate the in vivo study of the methanolic extract concerning glibenclamide as the positive control.

Results

Acacia catechu,Dioscorea bulbifera, andSwertia chirataexhibited inhibitory activity against α-amylase and with IC50values; 49.9, 296.1, and 413.5 μg/mL, respectively. Kinetics study revealed that all the extracts displayed a mixed type of inhibition pattern, with Kivalues ranging from 26.6–204.2 μg/mL. Free radical scavenging activity was again re-examined and found prominent in extracts ofA. catechu. Likewise,A. catechuandS. chiratashowed significant reduction of blood glucose concentration up to 30 min after oral dose of 250 mg/kg (F (4, 20) = 4.1,p = .048), and (F (4, 20) = 4.1,p = .036), respectively.

Conclusions

Enzymatic assay for α-amylase inhibition using extracts was successfully evaluated. Also, the in-vitro and in-vivo study model revealed that medicinal plants could be a potent source of α-amylase inhibition. So, they could serve as potential candidates for future drug development strategies for curing diabetes with minimal or no adverse side effects.

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Tài liệu tham khảo

International Diabetes Federation. IDF diabetes atlas. 9th ed; 2019.

World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia: report of a WHO/IDF consultation; 2006.

American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2014;37(Supplement 1):S81–90.

World Health Organization. Global report on diabetes, vol. 978; 2016. p. 88.

Imam SK. Diabetes: a new horizon and approach to management. In: Glucose intake and utilization in pre-diabetes and diabetes UK: Elsevier Academic press; 2015. p. 29–44.

Anitha Gopal B, Muralikrishna G. Porcine pancreatic α-amylase and its isoforms: purification and kinetic studies. Int J Food Prop. 2009;12(3):571–86.

Janeček Š, Baláž Š. α-Amylases and approaches leading to their enhanced stability. FEBS Lett. 1992;304(1):1–3.

Pasero L, Mazzéi-Pierron Y, Abadie B, Chicheportiche Y, Marchis-Mouren G. Complete amino acid sequence and location of the five disulfide bridges in porcine pancreatic α-amylase. Biochim Biophys Acta (BBA)-Protein Struct Molec Enzym. 1986;869(2):147–57.

Kazeem MI, Adamson JO, Ogunwande IA. Modes of inhibition of α-amylase and α-glucosidase by aqueous extract of Morinda lucida Benth leaf. Biomed Res Int. 2013;2013:1.

Chaudhury A, Duvoor C, Dendi R, Sena V, Kraleti S, Chada A, et al. Clinical review of antidiabetic drugs: implications for type 2 diabetes mellitus management. Front Endocrinol. 2017;8:6.

Kumar S, Narwal S, Kumar V, Prakash O. α-Glucosidase inhibitors from plants: a natural approach to treat diabetes. Pharmacogn Rev. 2011;5(9):19.

Hsieh SH, Shih KC, Chou CW, Chu CH. Evaluation of the efficacy and tolerability of miglitol in Chinese patients with type 2 diabetes mellitus inadequately controlled by diet and sulfonylureas. Acta Diabetol. 2011;48(1):71–7.

Ali H, Houghton PJ, Soumyanath A. α-Amylase inhibitory activity of some Malaysian plants used to treat diabetes; with particular reference to Phyllanthus amarus. J Ethnopharmacol. 2006;107(3):449–55.

Subhedar S, Goswami P. Ethnobotany and literature survey of herbal anti-diabetic drugs. Int J Drug Discov Herbal Res. 2011;1(3):177–84.

Mojica L, Meyer A, Berhow MA, de Mejía EG. Bean cultivars (Phaseolus vulgaris L.) have similar high antioxidant capacity, in vitro inhibition of α-amylase and α-glucosidase while diverse phenolic composition and concentration. Food Res Int. 2015;69:38–48.

Udani J, Hardy M, Madsen DC. Blocking carbohydrate absorption and weight loss: a clinical trial using phase 2™ brand proprietary fractionated white bean extract. Altern Med Rev. 2004;9(1):63–9.

Kunwar RM, Shrestha KP, Bussmann RW. Traditional herbal medicine in far-West Nepal: a pharmacological appraisal. J Ethnobiol Ethnomed. 2010;6(1):35.

Adhikari M, Thapa R, Kunwar RM, Devkota HP, Poudel P. Ethnomedicinal uses of plant resources in the Machhapuchchhre rural municipality of Kaski District, Nepal. Medicines. 2019;6(2):69.

American Diabetes Association. Classification and diagnosis of diabetes. Sec. 2. In standards of medical care in diabetes −2015. Diabetes Care. 2015;38:S8–16.

Brand-Williams W, Cuvelier ME, Berset CL. Use of a free radical method to evaluate antioxidant activity. LWT-Food Sci Technol. 1995;28(1):25–30.

Senger MR, Gomes LD, Ferreira SB, Kaiser CR, Ferreira VF, Silva FP Jr. Kinetics studies on the inhibition mechanism of pancreatic α-amylase by Glycoconjugated 1H-1, 2, 3-Triazoles: a new class of inhibitors with Hypoglycemiant activity. ChemBioChem. 2012;13(11):1584–93.

Marasini BP, Rahim F, Perveen S, Karim A, Khan KM, Choudhary MI. Synthesis, structure-activity relationships studies of benzoxazinone derivatives as α-chymotrypsin inhibitors. Bioorg Chem. 2017;70:210–21.

Lineweaver H, Burk D. The determination of enzyme dissociation constants. J Am Chem Soc. 1934;56(3):658–66.

Dixon M. The determination of enzyme inhibitor constants. Biochem J. 1953;55(1):170.

Segel IH. Enzyme kinetics: behavior and analysis of rapid equilibrium and steady state enzyme systems. Hoboken: Wiley; 1993.

Ali RB, Atangwho IJ, Kuar N, Ahmad M, Mahmud R, Asmawi MZ. In vitro and in vivo effects of standardized extract and fractions of Phaleria macrocarpa fruits pericarp on lead carbohydrate digesting enzymes. BMC Complement Altern Med. 2013;13(1):39.

Joshi K. Ethnobotanical study of plants used for the treament of diabetes mellitus in the mountainous regions of Nepal. J Non-timber For Prod. 2011;18(1):19–26.

Shrestha P, Jamarkattel-Pandit N. Survey on medicinal plants used for anti-diabetic activity in Kaski District, Nepal. JHAS. 2018;7(1):1–7.

Singh AG. 9. Ethnomedicinally important plants used as spices and condiments in the rupandehi district, West Nepal by Anant gopal singh. Life Sci Leaflets. 2017;85:64–71.

Kunwar RM, Uprety Y, Burlakoti C, Chowdhary CL, Bussmann RW. Indigenous use and ethnopharmacology of medicinal plants in far-West Nepal. Ethnobot Res Appl. 2009;7:005–28.

Rai SK. Medicinal plants used by Meche people of Jhapa district, eastern Nepal. Nature. 2004;2(1):27–32.

Singh AG, Kumar A. Ethnomedicinal aspects of climbing plants of Palpa district, Nepal. Trop Plant Res. 2017;4(2):307–13.

Ghosh S, More P, Derle A, Patil AB, Markad P, Asok A, et al. Diosgenin from Dioscorea bulbifera: novel hit for treatment of type II diabetes mellitus with inhibitory activity against α-amylase and α-glucosidase. PLoS One. 2014;9(9):e106039.

Kunwar RM, Bussmann RW. Ficus (fig) species in Nepal: a review of diversity and indigenous uses. Lyonia. 2006;11(1):85–97.

Malla B, Gauchan DP, Chhetri RB. Medico-ethnobotanical investigations in Parbat district of Western Nepal. J Med Plant Res. 2014;8(2):95–108.

Medicinal plants of Nepal. Bulletin of Department of Plant Resources (DPR): Thapathali, Kathmandu, Nepal. 2nd ed; 2016.

Singh AG, Kumar A, Tewari DD, Bharati KA. New ethnomedicinal claims from Magar community of Palpa district. Nepal Indian J Tradit Knowl. 2018;17(3):499–511.

Rai MB. Medicinal plants of Tehrathum district, eastern Nepal. Nature. 2003;1(1):42–8.

Oliveira HM, Pinheiro AQ, Fonseca AJ, Cabrita AR, Maia MR. Flexible and expeditious assay for quantitative monitoring of alpha-amylase and amyloglucosidase activities. MethodsX. 2019;6:246–58.

Xiao Z, Storms R, Tsang A. A quantitative starch iodine method for measuring alpha-amylase and glucoamylase activities. Anal Biochem. 2006;351(1):146–8.

Pimstone NR. A study of the starch-iodine complex: a modified colorimetric micro determination of amylase in biologic fluids. Clin Chem. 1964;10(10):891–906.

Cybulski RL, inventor; Dade International Inc, assignee. Method for eliminating hemolysis interference in an amylase analysis. United States patent US 5,766,872. 1998 Jun 16.

Lakshmi T, Ramasamy R, Thirumalaikumaran R. Preliminary phytochemical analysis and In vitro antioxidant, FTIR spectroscopy, anti-diabetic activity of Acacia catechu ethanolic seed extract. Phcog J. 2015;7:6.

Roy P, Abdulsalam FI, Pandey DK, Bhattacharjee A, Eruvaram NR, Malik T. Evaluation of antioxidant, antibacterial, and antidiabetic potential of two traditional medicinal plants of India: Swertia cordata and Swertia chirayita. Pharm Res. 2015;7(Suppl 1):S57.

Manach C, Scalbert A, Morand C, Rémésy C, Jiménez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;79(5):727–47.

Go HK, Rahman M, Kim GB, Na CS, Song CH, Kim JS, et al. Antidiabetic effects of yam (Dioscorea batatas) and its active constituent, allantoin, in a rat model of streptozotocin-induced diabetes. Nutrients. 2015;7(10):8532–44.

Duval A, Averous L. Characterization and physicochemical properties of condensed tannins from Acacia catechu. J Agric Food Chem. 2016;64(8):1751–60.

Shen D, Wu Q, Wang M, Yang Y, Lavoie EJ, Simon JE. Determination of the predominant catechins in Acacia catechu by liquid chromatography/electrospray ionization− mass spectrometry. J Agric Food Chem. 2006;54(9):3219–24.

Hara Y, Honda M. The inhibition of α-amylase by tea polyphenols. Agric Biol Chem. 1990;54(8):1939–45.

Yilmazer-Musa M, Griffith AM, Michels AJ, Schneider E, Frei B. Inhibition of α-amylase and α-glucosidase activity by tea and grape seed extracts and their constituent catechins. J Agric Food Chem. 2012;60(36):8924.

Ghosal S, Sharma PV, Chaudhuri RK, Bhattacharya SK. Chemical constituents of the gentianaceae V: Tetraoxygenated xanthones of Swertia chirata buch.-ham. J Pharm Sci. 1973;62(6):926–30.

Bajpai MB, Asthana RK, Sharma NK, Chatterjee SK, Mukherjee SK. Hypoglycemic effect of swerchirin from the hexane fraction of Swertia chirayita. Planta Med. 1991;57(02):102–4.

Choudhary DK, Mishra A. In vitro and in silico interaction of porcine α-amylase with Vicia faba crude seed extract and evaluation of antidiabetic activity. Bioengineered. 2017;8(4):393–403.

Cornish-Bowden A. A simple graphical method for determining the inhibition constants of mixed, uncompetitive and non-competitive inhibitors. Biochem J. 1974;137(1):143.

Nielsen MM, Seo ES, Bozonnet S, Aghajari N, Robert X, Haser R, et al. Multi-site substrate binding and interplay in barley α-amylase 1. FEBS Lett. 2008;582(17):2567–71.

Nielsen MM, Bozonnet S, Seo ES, Mótyán JA, Andersen JM, Dilokpimol A, et al. Two secondary carbohydrate binding sites on the surface of barley α-amylase 1 have distinct functions and display synergy in hydrolysis of starch granules. Biochemistry. 2009;48(32):7686–97.

Tomai F, Crea F, Gaspardone A, Versaci F, De Paulis R. Penta de Peppo a, Chiariello L, Gioffrè PA. Ischemic preconditioning during coronary angioplasty is prevented by glibenclamide, a selective ATP-sensitive K+ channel blocker. Circulation. 1994;90(2):700–5.

Doyle ME, Egan JM. Pharmacological agents that directly modulate insulin secretion. Pharmacol Rev. 2003;55(1):105–31.

Niu CS, Chen W, Wu HT, Cheng KC, Wen YJ, Lin KC, et al. Decrease of plasma glucose by allantoin, an active principle of yam (Dioscorea spp.), in streptozotocin-induced diabetic rats. J Agric Food Chem. 2010;58(22):12031–5.

Kato A, Miura T, Fukunaga T. Effects of steroidal glycosides on blood glucose in normal and diabetic mice. Biol Pharm Bull. 1995;18(1):167–8.

Baynes JW, Thorpe SR. Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999;48(1):1–9.

Son SM, Whalin MK, Harrison DG, Taylor WR, Griendling KK. Oxidative stress and diabetic vascular complications. Curr Diab Rep. 2004;4(4):247–52.

Modak M, Dixit P, Londhe J, Ghaskadbi S, Devasagayam TP. Recent advances in Indian herbal drug research guest editor: Thomas Paul Asir Devasagayam Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr. 2007;40(3):163–73.

Sakurai K, Katoh M, Someno K, Fujimoto Y. Apoptosis and mitochondrial damage in INS-1 cells treated with alloxan. Biol Pharm Bull. 2001;24(8):876–82.

Van Doan H, Riyajan S, Iyara R, Chudapongse N. Antidiabetic activity, glucose uptake stimulation and α-glucosidase inhibitory effect of Chrysophyllum cainito L. stem bark extract. BMC Complement Altern Med. 2018;18(1):1–10.

Jha P, Mandal RA. Assessment of growth performance of Acacia catechu. IJARB. 2019;5(1):34–8.

Thapa HB. Growth of five fast growing tree species in the Terai of eastern Nepal. Banko Janakari. 1998;8(2):14–22.

Rajendra KC. Contribution of NWFPs in National Economy. Banko Janakari. 2018;28(2):1–2.

Olsen CS, Helles F. Medicinal plants, markets, and margins in the Nepal Himalaya: trouble in paradise. Mt Res Dev. 1997;17(4):363–74.

Bhandari MR, Kasai T, Kawabata J. Nutritional evaluation of wild yam (Dioscorea spp.) tubers of Nepal. Food Chem. 2003;82(4):619–23.