Characterization of α-Glucosidase Inhibitor  Streptomyces  sp. IPBCC.a.29.1556 Aqueous Extract: An Endophyte of Indonesian  Ficus deltoidea

Isra Janatiningrum; Yulin Lestari; Dedy Duryadi Solihin; Anja Meryandini

doi:10.22146/ijc.72433

Characterization of α-Glucosidase Inhibitor Streptomyces sp. IPBCC.a.29.1556 Aqueous Extract: An Endophyte of Indonesian Ficus deltoidea

https://doi.org/10.22146/ijc.72433

Isra Janatiningrum^(1*), Yulin Lestari⁽²⁾, Dedy Duryadi Solihin⁽³⁾, Anja Meryandini⁽⁴⁾

(1) Pharmacy Study Program, Faculty of Health Sciences, UIN Syarif Hidayatullah Jakarta, South Tangerang 15419, Indonesia
(2) Department of Biology, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Agatis, Dramaga, Bogor 16680, West Java, Indonesia; Tropical Biopharmaca Research Center, IPB University, Jl. Taman Kencana No. 3, Bogor 16128, West Java, Indonesia
(3) Department of Biology, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Agatis, Dramaga, Bogor 16680, West Java, Indonesia
(4) Department of Biology, Faculty of Mathematics and Natural Sciences, IPB University, Jl. Agatis, Dramaga, Bogor 16680, West Java, Indonesia
(*) Corresponding Author

Abstract

Filamentous bacteria have been known as actinobacteria which could produce various secondary metabolites, including an α-glucosidase inhibitor. The α-glucosidase inhibitor has been identified to be potentially valuable for the treatment of diabetes mellitus. Endophytic actinobacteria are able to produce bioactive compounds that are similar to their hosts. Indonesian Ficus deltoidea is one of the medicinal plants which has the activity of the α-glucosidase inhibitor. The α-glucosidase inhibitor has been characterized by optimizing compound production, fractionation, analysis using TLC and LC-MS, and identifying inhibitor mechanisms. The α-glucosidase inhibitor substance is present in Streptomyces sp. IPBCC.a.29.1556 aqueous extract. The aqueous extract was separated and fraction 1 had an IC₅₀ value of 58.8 μg/mL, which is better than acarbose (IC₅₀ = 90.4 μg/mL). Kinetic studies revealed that this fraction inhibited the enzyme through a non-competitive mechanism. Chemical profile based on LC-MS, fraction 1 showed the presence of Phenylpropynal, Butyric acid, 2-(2-Ethoxyethoxy)ethanolate, 1,1-Diethoxyethane acetate, N,N-dimethyl-3-oxide-1H-Benzotriazole-1-propanamine, p-coumaric acid, and isoquinolinium which might contribute individually or synergistically to the observed α-glucosidase inhibitor activity. These results suggest that fraction 1 from the aqueous extract of Streptomyces sp. IPBCC.a.29.1556 is the potential source to produce an α-glucosidase inhibitor for the management of postprandial hyperglycemia.

Keywords

α-glucosidase inhibitor; diabetes mellitus; endophytes; Ficus deltoidei; Streptomyces

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References

[1] Jose, P.A., Maharshi, A., and Jha, B., 2021, Actinobacteria in natural products research: Progress and prospects, Microbiol. Res., 246, 126708.

[2] Golinska, P., Wypij, M., Agarkar, G., Rathod, D., Dahm, H., and Rai, M., 2015, Endophytic actinobacteria of medicinal plants: Diversity and bioactivity, Antonie van Leeuwenhoek, 108 (2), 267–289.

[3] Xu, M., and Wright, G.D., 2018, Heterologous expression-facilitated natural products discovery in actinomycetes, J. Ind. Microbiol. Biotechnol., 46 (3), 415–431.

[4] Barka, E.A., Vatsa, P., Sanchez, L., Gaveau-Vaillant, N., Jacquard, C., Klenk, H.P., Clément, C., Ouhdouch, Y., and van Wezel, G.P., 2016, Taxonomy, physiology, and natural products of the actinobacteria, Microbiol. Mol. Biol. Rev., 80 (1), 1–43.

[5] Manivasagan, P., Kang, K.H., Sivakumar, K., Li-Chan, E.C.Y., Oh, H.M., and Kim, S.K., 2014, Marine actinobacteria: An important source of bioactive natural products, Environ. Toxicol. Pharmacol., 38 (1), 172–188.

[6] Schmidt, D.D., Frommer, W., Junge, B., Müller, L., Wingender, W., Truscheit, E., and Schäfer, D., 1977, Alpha-glucosidase inhibitor. New complex oligosaccharides of microbial origin, Naturwissenschaften, 64 (10), 535–536.

[7] Rengasamy, K.R.R., Aderogba, M.A., Amoo, S.O., Stirk, W.A., and Van Staden, J., 2013, Potential antiradical and alpha-glucosidase inhibitor from Ecklonia maxima (Osbeck) Papenfuss, Food Chem., 141 (2), 1412–1415.

[8] Lordan, S., Smyth, T.J., Soler-Vila, A., Stanton, C., and Ross, R.P., 2013, The α-amylase and α-glucosidase inhibitory effects of Irish seaweed extracts, Food Chem., 141 (3), 2170–2176.

[9] Mengistu, A.A., 2020, Endophytes: Colonization, behaviour, and their role in defense mechanism, Int. J. Microbiol., 2020, 6927219.

[10] Pujiyanto, S., Lestari, Y., Suwanto, A., Budiarti, S., and Darusman, L.K., 2012, Alpha-glucosidase inhibitor activity and characterization of endophytic actinomycetes isolated from some Indonesia diabetic medicinal plants, Int. J. Pharm. Pharm. Sci., 4, 327–333.

[11] Akshatha, V.J., Nalini, M.S., D’Souza, C., and Prakash, H.S., 2015, Streptomycete endophytes from anti-diabetic medicinal plants of the Western Ghats inhibit alpha-amylase and promote glucose uptake, Lett. Appl. Microbiol., 58 (5), 433–439.

[12] Ashraf, K., Halim, H., Lim, S.M., Ramasamy, K., and Sultan, S., 2020, In vitro antioxidant, antimicrobial and antiproliferative studies of four different extracts of Orthosiphon stamineus, Gynura procumbens and Ficus deltoideia, Saudi J. Biol. Sci., 27 (1), 417–432.

[13] Nurdiana, S., Goh, Y.M., Hafandi, A., Dom, S.M., Nur Syimal’ain, A., and Noor Syaffinaz, N.M., 2018, Improvement of spatial learning and memory, cortical gyrification patterns and brain oxidative stress markers in diabetic rats treated with Ficus deltoidea leaf extract and vitexin, J. Tradit. Complementary Med., 8 (1), 190–202.

[14] Draman, S., Aris, M.A.M., Akter, S.F.U., Azlina, H., Nor Azlina, A., Muzaffar, R., Norazlanshah, H., and Azian, A., 2012, Mas cotek (Ficus deltoidea): A possible supplement for type II diabetes: (A pilot study), Pertanika J. Trop. Agric. Sci., 35 (1), 93–102.

[15] Kalman, D.S., Schwartz, H.I., Feldman, S., and Krieger, D.R., 2013, Efficacy and safety of Elaeis guineensis and Ficus deltoidea leaf extracts in adults with pre-diabetes, Nutr. J., 12 (1), 36.

[16] Janatiningrum, I., Solihin, D.D., Meryandini, A., and Lestari, Y., 2018, Comparative study on the diversity of endophytic actinobacteria communities from Ficus deltoidea using metagenomic and culture dependent approaches, Biodiversitas, 19 (4), 1514–1520.

[17] Janatiningrum, I., Solihin, D.D., Meryandini, A., and Lestari, Y., 2020, Rat alpha glucosidase inhibitor and phytochemicals activities of endophytic actinobacteria from Ficus deltoideia, Pak. J. Pharm. Sci., 33 (3), 969–975.

[18] Mohamed Sham Shihabudeen, H., Hansi Priscilla, D., and Thirumurugan, K., 2011, Cinnamon extract inhibits α-glucosidase activity and dampers postprandial glucose excursion in diabetic rats, Nutr. Metab., 8 (1), 46–57.

[19] Kim, S.D., and Nho, H.J., 2004, Isolation and characterization of α-glucosidase inhibitor from the fungus Ganoderma lucidum, J. Microbiol., 42 (3), 223–227.

[20] Adisakwattana, S., Charoenlertkul, P., and Yibchok-Anun, S., 2009, α-Glucosidase inhibitory activity of cyanidin-3-galactoside and synergistic effect with acarbose, J. Enzyme Inhib. Med. Chem., 24 (1), 65–69.

[21] Narayana, K.J.P., and Vijayalakshmi, M., 2008, Optimization of antimicrobial metabolites production by Streptomyces albidoflavus, Res. J. Pharmacol., 2 (1), 4–7.

[22] Augustine, S.K., Bhavsar, S.P., and Kapadnis, B.P., 2005, Production of a growth dependent metabolite active against dermatophytes by Streptomyces rochei AK 39, Indian J. Med. Res., 121 (3), 164–170.

[23] Manteca, Á., and Yagüe, P., 2018, Streptomyces differentiation in liquid cultures as a trigger of secondary metabolism, Antibiotics, 7 (2), 41.

[24] Al-Ansari, M., Kalaiyarasi, M., Almalki, M.A., and Vijayaraghavan, P., 2020, Optimization of medium components for the production of antimicrobial and anticancer secondary metabolites from Streptomyces sp. AS11 isolated from the marine environment, J. King Saud Univ., Sci., 32 (3), 1993–1998.

[25] Karimi, E., and Sadeghi, A., 2015, Study on optimum growth condition and designing formulation for increasing shelf life of Streptomyces rimosus Strain C-2012 as biocontrol agent, Biol. J. Microorg., 4 (15), 109–122.

[26] Damsud, T., Adisakwattana, S., and Phuwapraisirisan, P., 2013, Three new phenylpropanoyl amides from the leaves of Piper sarmentosum and their a-glucosidase inhibitory activities, Phytochem. Lett., 6 (3), 350–354.

[27] Gupta, A., and Pandey, A.K., 2020, “Antibacterial Lead Compounds and Their Targets for Drug Development” in Phytochemicals as Lead Compounds for New Drug Discovery, Eds. Egbuna, C., Kumar, S., Ifemeje, J.C., Ezzat, S.M., and Kaliyaperumal, S., Elsevier, Cambridge, US, 275–292.

[28] Chen, R., Xu, Y., Wu, P., Zhou, H., Lasanajak, Y., Fang, Y., Tang, L., Ye, L., Li, X., Cai, Z., and Zhao, J., 2019, Transplantation of fecal microbiota rich in short chain fatty acids and butyric acid treat cerebral ischemic stroke by regulating gut microbiota, Pharmacol. Res., 148, 104403.

[29] Mahalak, K.K., Bobokalonov, J., Firrman, J., Williams, R., Evans, B., Fanelli, B., Soares, J.W., Kobori, M., and Liu, L.S., 2022, Analysis of the ability of capsaicin to modulate the human gut microbiota in vitro, Nutrients, 14 (6), 1283.

[30] Quagliariello, V., Masarone, M., Armenia, E., Giudice, A., Barbarisi, M., Caraglia, M., Barbarisi, A., and Persico, M., 2018, Chitosan-coated liposomes loaded with butyric acid demonstrate anticancer and anti-inflammatory activity in human hepatoma HepG2 cells, Oncol. Rep., 41 (3), 1476–1486.

[31] Allsopp, P., Possemiers, S., Campbell, D., Oyarzábal, I.S., Gill, C., and Rowland, I., 2013, An exploratory study into the putative prebiotic activity of fructans isolated from Agave angustifolia and the associated anticancer activity, Anaerobe, 22, 38–44.

[32] Yang, Y., Huang, J., Li, J., Yang, H., and Yin, Y., 2020, The effects of butyric acid on the differentiation, proliferation, apoptosis, and autophagy of IPEC-J2 cells, Curr. Mol. Med., 20 (4), 307–317.

[33] Balan, K., Perumal, P., Sundarabaalaji, N., and Palvannan, T., 2015, Synthesis, molecular modeling and biological evaluation of novel 2-allyl amino 4-methyl sulfanyl butyric acid as α-amylase and α-glucosidase inhibitor, J. Mol. Struct., 1081, 62–68.

[34] Evren, A.E., Yurttas, L., and Yılmaz-Cankilic, M., 2020, Synthesis of novel N-(naphthalen-1-yl)propanamide derivatives and evaluation their antimicrobial activity, Phosphorus Sulfur Silicon Relat. Elem., 195 (2), 158–164.

[35] Ugwuja, D.I., Okoro, U.C., Soman, S.S., Soni, R., Okafor, S.N., and Ugwu, D.I., 2019, New peptide derived antimalaria and antimicrobial agents bearing sulphonamide moiety, J. Enzyme Inhib. Med. Chem., 34 (1), 1388–1399.

[36] Nobre, P.C., Borges, E.L., Silva, C.M., Casaril, A.M., Martinez, D.M., Lenardão, E.J., Alves, D., Savegnago, L., and Perin, G., 2014, Organochalcogen compounds from glycerol: synthesis of new antioxidants, ‎Bioorg. Med. Chem., 22 (21), 6242–6249.

[37] Dulić, M., Ciganović, P., Vujić, L., and Končić, M.Z., 2019, Antidiabetic and cosmeceutical potential of common barbery (Berberis vulgaris L.) root bark extracts obtained by optimization of ‘green’ ultrasound-assisted extraction, Molecules, 24 (19), 3613.

[38] Saber, F.R., Ashour, R.M., El-Halawany, A.M., Mahomoodally, M.G., Gunes, A.K., and Zengin, G., 2020, Phytochemical profile, enzyme inhibition activity and molecular docking analysis of Feijoa sellowiana O. Berg, J. Enzyme Inhib. Med. Chem., 36 (1), 618–626.

[39] Wang, Z.W., Wang, J.S., Luo, J., and Kong, L.Y., 2013, α-Glucosidase inhibitory triterpenoids from the stem barks of Uncaria laevigata, Fitoterapia, 90, 30–37.

[40] Trifonova, D., Stoilova, I., Marchev, A., Denev, P., Angelova, G., Lante, A., and Krastanov, A., 2021, Phytochemical constituents of pressurized liquid extract from Ziziphus jujubа Mill. (Rhamnaceae) fruits and in vitro inhibitory activity on α-glucosidase, pancreatic α-amylase and lipase, Bulg. J. Agric. Sci., 27 (2), 391–402.

[41] Assefa, S.T., Yang, E.Y., Chae, S.Y., Song, M., Lee, J., Cho, M.C., and Jang, S., 2020, Alpha glucosidase inhibitory activities of plants with focus on common vegetables, Plants, 9 (1), 2.

[42] Wongsa, P., Chaiwarit, J., and Zamaludien, A., 2012, In vitro screening of phenolic compounds, potential inhibition against α-amylase and α-glucosidase of culinary herbs in Thailand, Food Chem., 131 (3), 964–971.

[43] Dong, Y., Zhang, B., Sun, W., and Xing, Y., 2019, “Intervention of Prediabetes by Flavonoids from Oroxylum indicum” in Bioactive Food as Dietary Interventions for Diabetes, 2^nd Ed., Eds. Watson, R.R., and Preedy, V.R., Academic Press, Cambridge, US, 559–575.

[44] Sun, W., Sun, J., Zhang, B., Xing, Y., Yu, X., Li, X., Xiu, Z., and Dong, Y., 2017, Baicalein improves insulin resistance via regulating SOCS3 and enhances the effect of acarbose on diabetes prevention, J. Funct. Foods, 37, 339–353.

[45] Boath, A.S., Stewart, D., and McDougall, G.J., 2012, Berry components inhibit α-glucosidase in vitro: Synergies between acarbose and polyphenols from black currant and rowanberry, Food Chem., 135 (3), 929–936.

DOI: https://doi.org/10.22146/ijc.72433