Effectiveness test of Diploknema oligomera extracts to the decrease in glucose levels in alloxan-induced BALB/c male mice




Abstract. Faizah S, Eriani K, Rosnizar. 2023. Effectiveness test of Diploknema oligomera extracts to the decrease in glucose levels in alloxan-induced BALB/c male mice. Nusantara Bioscience 15: 143-148. People with diabetes mellitus usually consume chemical drugs to lower their blood glucose levels which cause side effects and require a reasonably high cost. Therefore, alternative natural medicines (phytopharmaceuticals) that are safer and more affordable are needed. Punti fruit (Diploknema oligomera H.J Lam) has the potential as an antihyperglycemic agent that can lower glucose levels in the blood because the punti fruit contains flavonoid compounds, tannins, terpenoids, and saponins. These secondary metabolites can reduce blood glucose levels. This research used an experimental method with a completely randomized design, six treatments, and four replications. This study used 24 BALB/C (Mus musculus Linnaeus, 1758) male mice grouped into six treatments, namely normal control treatment (P1), negative control by giving alloxan 150 mg/kg bw (P2), positive control by giving glibenclamide dose of 0.65 mg/kg body weight (bw) (P3), ethanol extract of punti fruit dose of 250 mg/kg bw (P4), ethanol extract of punti fruit dose of 500 mg/kg body weight (P5) and ethanol extract of punti fruit dose of 1,000 mg/kg bw (P6). The results proved that administering punti extract (P3, P4, P5) for 14 could reduce blood glucose levels in male diabetic mice with a percentage reduction of 33.6%, 37.4%, and 52.7%, and treatment-positive control decreased blood glucose by 32.6%. The conclusion showed that the ethanol extract of punti fruit at a dose of 1,000 mg/kg bw could effectively reduce blood glucose levels in diabetic mice compared to a dose of 250 mg/kg bw, 500 mg/kg bw and 0.65 mg/kg glibenclamide kg bw. Therefore, punti fruit can be used as a drug candidate to be developed as phytopharmaceuticals in treating diabetes mellitus.



Abdulgani N, Trisnawati I, Aunurohim, Hidayati D, Aisyatussoffi N, Arifiyanto A. 2014. Snakehead (Channa striata) extracts treatment towards hyperglycemic mice (Mus musculus) blood glucose levels and pancreatic histology structure. J Appl Environ Biol Sci 4: 1-6.
Adiba HMP, Arifullah M, Nazahatul AA, Sirikitputtisak T, Klaiklay S, Chumkaew P, Chewchanwuttiwong S, Norhazlini MZ, Zulhazman H. 2021. Total phenolic content and antioxidant activity of limestone endemic Araceae species, Alocasia farisii. Earth Environ Sci 842: 1-6. DOI: 10.1088/1755-1315/842/1/012064.
Azmir J, Zaidul ISM, Rahman MM, Sharif KM, Mohamed A, Sahena F, Omar AKM. 2013. Techniques for extraction of bioactive compounds from plant materials: A review. J Food Eng 117 (4) : 426-436. DOI: 0.1016/j.jfoodeng.2013.01.014.
Berraaouan A, Abderrahim Z, Hassane M, Abdelkhaleq L, Mohammed A, Mohamed B. 2015. Evaluation of protective effect of cactus pear seed oil (Opuntia ficus-indica L. Mill.) against alloxan induced diabetes in mice. Asian J Trop Med A 8: 532-537. DOI: 10.1016/j.apjtm.2015.06.013.
Campbell JE, Drucker DJ. 2013. Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metabolism 17: 819-837. DOI: 10.1016/j.cmet.2013.04.008.
Chandrika UG1, Wedage WS, Wickramasinghe SMDN1, Fernando WS. 2006. Hypoglycaemic action of
the flavonoid fraction of Artocarpus heterophyllus leaf. Afr J Tradit 3: 42-50.
Deng N, Zheng B, Li T, Liu RH. 2020. Assessment of the phenolic profiles, hypoglycemic activity, and molecular mechanism of different highland barley (Hordeum vulgare L.) varieties. Intl J Mol Sci 21: 1175. DOI: 10.3390/ijms21041175.
Dona R, Furi M, Suryani F. 2020. Determination of total phenolic, flavonoid and antioxidant activity tests of extracts and fractions of karamunting (Rhodomyrtus tomentosa (Aiton) Hassk) leaves. Indon Pharm Res J 9: 72-78. DOI: 10.51887/jpfi.v9i2.975.
Eguchi N, Vaziri ND, Dafoe DC, Ichii H. 2021. The role of oxidative stress in pancreatic ? Cell dysfunction in diabetes. Intl J Mol Sci 22: 1-18. DOI: 10.3390/ijms22041509.
Eriani K, Hasanah U, Fitriana R, Sari W, Yunita Y, Al Azhar. 2021. Antidiabetic potential of methanol extract of flamboyant (Delonix regia) flowers. Biosaintifika 13: 185-194. DOI: 10.15294/biosaintifika.v13i2.30080.
Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI, Nielsen JV, Krarup T, Saslow L, Roth KS, Vernon MC, Volek JS, Wilshire GB, Dahlqvist A, Sundberg R, Childers A, Morrison K, Manninen AH, Dashti HM, Wood RJ, Wortman J, Worm N. 2015. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 31: 1-13. DOI: 10.1016/j.nut.2014.06.011.
Furqan M, Putri NA. 2020. Isolation of phenolic compounds from punti fruit (Diploknema oligomera H.J.Lam) by FT-IR analysis. J Health Care Technol Med 6: 2615-109. DOI: 10.33143/jhtm.v6i2.1198.
Ghorbani A, Rashidia R, Nick RS. 2019. Flavonoids for preserving pancreatic beta cell survival and function: A mechanistic review. Biomed Pharm 111: 947-957. DOI: 10.1016/j.biopha.2018.12.127.
Ghosal S, Ghosal S. 2019. The side effects of metformin - a review. Diabetes Metab Disord 6: 1-7. DOI: 10.24966/DMD-201X/100030.
Golovinskaia O, Wang CK. 2023. The hypoglycemic potential of phenolics from functional foods and their mechanisms. Food Sci Human Well 12 : 986-1007. DOI: 10.1016/j.fshw.2022.10.020.
Guney MA, Lorberbaum DS. 2020. Pancreatic ? cell regeneration: To ? or not to ?. Curr Opin Physiol 14: 13-20. DOI: 10.1016/j.cophys.2019.10.019.
Hasanah U. 2016. Profil of beta pancreatic cell in rats are given kimpul (Xanthosoma sagittifolia (L.) Schott.). [Thesis]. Universitas Sebelas Maret, Surakarta, Indonesia.
Hawash ZAE, Farrag AA. Eldamaty HSE. 2020. Effect of using sweet potato powder on diabetic rats. J Home Econ 36: 1-18. DOI: 10.21608/jhe.2020.109290.
Hikmawanti NPE, Fatmawati S, Asri AW. 2021. The effect of ethanol concentrations as the extraction solvent on antioxidant activity of katuk (Sauropus androgynus (L.) Merr.) leaves extracts. IOP Conf Ser Earth Environ Sci 755 (1): 012060. DOI:10.1088/1755-1315/755/1/012060.
Hu X, Wang S, Xu J, Wang DB, Chen Y, Yang GZ. 2014. Triterpenoid saponins from Stauntonia chinensis ameliorate insulin resistance via the AMP-activated protein kinase and IR/IRS-1/PI3K/Akt pathways in insulin-resistant HepG2 cells. Intl J Mol Sci 15: 10446-10458. DOI: 10.3390/ijms150610446.
Ibrahim KG, Audu BB, Mainasara AS, Abubakar MB. 2021. Effect of Co-administration of glibenclamide and aqueous calyx extract of Hibiscus sabdariffa on oxidative stress markers in Streptozotocin-Induced diabetic rats. Niger J Physiol Sci 36: 77-84.
Ighodaro OM, Adeosun AM, Akinloye OA. 2017. Alloxan-induced diabetes, a common model for evaluating the glycemic-control potential of therapeutic compounds and plants extracts in expereimental studies. J Med 53: 365-374. DOI: 10.1016/j.medici.2018.02.001.
International Diabetes Federation (IDF). 2021. IDF Diabetes Atlas (10th edition). Diabetes Atlas, Belgium. https://diabetesatlas.org/.
Kang BB, Chiang BH. 2022. A novel phenolic formulation for treating hepatic and peripheral insulin resistance by regulating GLUT4-mediated glucose uptake. J Tradit Complement Med 12: 195-205. DOI: 10.1016/j.jtcme.2021.08.004.
Kasmawati H, Ruslin, Ihsan S, Hasnawati, Suryani, Pertama BA, Farida SA. 2019. Antidiabetic activity of ethanol extract of soni leaves (Dillenia celebica Hoogland.) on blood glucose levels and pancreatic histology of male wistar rats glucose-induced. Indo Am J Pharm Sci 6: 13649-13659. DOI: 10.5281/zenodo.3346991.
Khedher MRB, Hammami M, Arch JRS, Hislop DC, Eze D, Wargent ET, K?pczy?ska MA, Zaibi MS. 2018. Preventive effects of Salvia officinalis leaf extract on insulin resistance and inflammation in a model of high fat diet induced obesity in mice that responds to rosiglitazone. Peer J 9: 14-22. DOI: 10.7717/peerj.4166.
Kia FJ, Wibowo JP, Elachouri M, Masumi R, Jouneghani SJ, Abolhassanzadeh Z, Lorigooini Z. 2020. Battle between plants as antioxidants with free radicals in human body. J Herbmed Pharmacol 9: 191-199. DOI: 10.34172/jhp.2020.25
Latief M, Sari PM, Fatwa LT, Tarigan IL, Rupasinghe HPV. 2021. Antidiabetic activity of sungkai (Peronema canescens Jack) leaves ethanol extract on the male mice induced alloxan monohydrate. Pharmacol Clin Pharm Res 6: 64-74. DOI:10.15416/pcpr.v4i3.31666.
Liem S, Yuliet, Khumaidi A. 2015. Antidiabetic activity test of combination of glibenclamide and bay leaf extract (Syzygium polyanthum wight.) To alloxan induced mice (Mus musculus). Galenika J Pharm 1: 42-47. DOI: 10.22487/j24428744.2015.v1.i1.4831.
Lisdiani, Susanto D, Manurung, H. 2022. Phytochemical screening and antioxidant activity of methanol extract of Dillenia excelsa leaf. Biodiversitas 23: 3827-3835. DOI: 10.13057/biodiv/d230760.
Martin MA, Ramos S. 2021. Dietary flavonoids and insulin signaling in diabetes and obesity. J Cells 10: 2-22. DOI: 10.3390/cells10061474.
Matusin AHA, Ghani N IA, Ahmad N. 2021. Pancreatic islet regenerative capability of Dillenia excelsa in alloxan-induced diabetic rats. J Appl Pharm Sci 11: 121-129. DOI:10.7324/JAPS.2021.110315.
Morada NJ, Metillo EB, Uy MM, Oclarit JM. 2016. Toxicity and hypoglycemic effect of tannin-containing extract from the mangrove tree Sonneratia alba Sm. Bull Environ Pharmacol Life Sci 5: 58-64.
Nabil M, Ghaly NS, Kassem IAA, Grace MH, Melek FR. 2019. Two triterpenoid saponins with ?-glucosidase inhibitory activity from Harpullia pendula seed extract. Pharmacog J 11: 1386-1390. DOI: 10.5530/pj.2019.11.214.
Nardia L, Listerb IN, Girsang E, Fachriald E. 2020. Hypoglycemic effect of avocado seed extract (Persean americana Mill) from analysis of oral glucose tolerance test on Rattus norvegicus L. Am Sci Res J Eng Technol Sci 65: 2313-4410.
Nasution A. 2015. Clinical Pharmacokinetics. USU Press, Medan. [Indonesian]
Njogu SM, Arika WM, Machocho AK, Ngeranwa JJN, Njagi ENM. 2018. In vivo hypoglycemic effect of Kigelia africana (Lam): Studies with alloxan-induced diabetic mice. J Evid-Based Integr Med 23: 1-10. DOI: 10.1177/2515690X18768727.
Rahati S, Shahraki M, Arjomand G, Shahraki T. 2014. Food pattern, lifestyle and diabetes mellitus. Intl J High Risk Behav Addict 10: 1-5. DOI: 10.5812/ijhrba.8725.
Rahman MDS, Hossain KS, Das S, Kundu S, Adegoke EO, Rahman MDA, Hannan MDA, Uddin MDJ, Pang MG. 2021. Role of insulin in health and disease: An update. Intl J Mol Sci 22: 2-19. DOI: 10.3390/ijms22126403.
Rani M, Yadav S, Choudhary S, Sharma S, Pandey SM. 2014. Incidence of hypoglycemia and other side effects in patients of type 2 diabetes mellitus treated with glimepiride versus glibenclamide. Intl J Health Sci Res 4 : 68-72.
Seeberger KL, Anderson SJ, Ellis CE, Yeung TY, Korbutt GS. 2014. Identification and differentiation of PDX1 ?-cell progenitors within the human pancreatic epithelium. World J Diabetes 1: 59-68. DOI:10.4239/wjd.v5.i1.59.
Seidel V. 2012. Initial and bulk extraction of natural product isolation. Methods Mol Biol 864: 27-41. DOI: 10.1007/978-1-61779-624-1_2.
Sheikh Y, Chanu MB, Mondal G, Manna P, Chattoraj A, Deka DC, Talukdara NC, Borah JC. 2019. Procyanidin A2, an anti-diabetic condensed tannin extracted from Wendlandia glabrata, reduces elevated G-6-Pase and mRNA levels in diabetic mice and increases glucose uptake in CC1 hepatocytes and C1C12 myoblast cells. Royal Chem Soc 9: 17211-17219. DOI: 10.1039/c9ra02397f.
Singh JP, Kaur A, Shevkani K, Singh N. 2015. In?uence of jambolan (Syzygium cumini) and xanthan gum incorporation on the physicochemical, antioxidant and sensory properties of gluten-free eggless rice mu?ns. Intl J Food Sci Technol 50: 1190-1197. DOI: 10.1111/ijfs.12764.
Singh JP, Kaur A, Singh N, Nim L, Shevkani K, Kaur H, Arora DS. 2016. In vitro antioxidant and antimicrobial properties of jambolan (Syzygium cumini) fruit polyphenols. Food Sci Technol 65: 1025-1030. DOI:10.1016/j.lwt.2015.09.038.
Sohretoglu D, Sari S, Barut B, Özel A. 2018. Discovery of potent ?-glucosidase inhibitor flavonols: Insights into mechanism of action through inhibition kinetics and docking simulations. Bioorganic Chem 79: 257-264. DOI: 10.1016/j.bioorg.2018.05.010.
Song BR, Alam MB, Lee SH. 2022. Terpenoid-rich extract of Dillenia indica L. bark displays antidiabetic action in insulin-resistant C2C12 cells and STZ-induced diabetic mice by attenuation of oxidative stress. Antioxidants 11: 2-19. DOI: 10.3390/antiox11071227.
Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan, Bruce B. 2022. IDF diabetes atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183: 1-13. DOI: 10.1016/j.diabres.2021.109119.
Udia PM, Takem LP, Ufot UF, Antai AB, Owu DU. 2016. Insulin and alpha amylase levels in alloxan-induced diabetic rats and the effect of Rothmannia hispida (K. Schum) Fagerl leaf extract. J Phytopharmacol 1: 1-5. DOI: 10.31254/phyto.2016.5101.
Vo QV, Nam PC, Thong NM, Trung NT, Phan CTD, Mechler A. 2019. Antioxidant Motifs in Flavonoids: O?H versus C?H Bond Dissociation. ACS Omega 4: 8935-8942. DOI:10.1021/acsomega.9b00677.
Wang Y, Wang A, Alkhalidy H, Luo J, Moomaw E, Neilson AP, Liu D. 2018. Flavone hispidulin stimulates glucagon-like peptide-1 secretion and ameliorates hyperglycemia in streptozotocin-induced diabetic mice. J Mol Nutr Food Res 64: 1-12. DOI: 10.1002/mnfr.201900978.
Widastuti, Endang L, Sutyarso, Gregorius NS, Mahmud R, Mohammad K. 2017. Ameliorative properties of crude diosgenin from costus speciosus and taurine on testicular disorders in alloxan-induced diabetic mice. Biomed Pharmacol J 10: 09-17. DOI: 10.13005/bpj/1075.
Widiyanto J, and Rahayu S. 2019. Effect of diet on the incidence of diabetes mellitus at the Sidomulyo Inpatient Health Center, Pekanbaru City. Proceedings of ScienceTeKes, UMRi MIPAKes National Seminar 1: 1-7.
Xu J, Wang S, Feng T, Chen Y, Yang G. 2018. Hypoglycemic and hypolipidemic effects of total saponins from Stauntonia chinensis in diabetic db/db mice. J Cell Mol Med 22: 6026-6038. DOI: 10.1111/jcmm.13876.
Xu Y, Rashwan AK, Ge ZW, Li YT, Ge HJ, Li JX, Xie JH, Liu SY, Fang J, Cheng KJ. 2022. Identification of a novel ?-glucosidase inhibitor from Melastoma dodecandrum Lour. fruits and its effect on regulating postprandial blood glucose. Food Chem 399: 133999. DOI: 10.1016/j.foodchem.2022.133999.
Yau B, Hocking S, Andrikopoulos S, Kebede MA. 2021. Targeting the insulin granule for modulation of insulin exocytosis. Biochem Pharmacol 194 : 114821. DOI: 10.1016/j.bcp.2021.114821.
Yu Y, Fan SM, Song JK, Tashiro SI, Onodera S, Ikejima T. 2012. Hydroxyl radical (*OH) played a pivotal role in oridonin-induced apoptosis and autophagy in human epidermoid carcinoma A431 Cells. Biol Pharm Bull 35: 2148-2159. DOI: 10.1248/bpb.b12-00405.
Yuliana I, Asnawati , Ulfah M, Suhartono E. 2021. Antidiabetic potential of karamunting leaves ethanolic extract as a natural herb: Blood glucose levels and pancreatic islets histomorphology on diabetic rats model. Jurnal Kedokteran Dan Kesehatan Indonesia 12: 250-256. DOI: 10.20885/JKKI.Vol12.Iss3.art9.
Yusnawan E. 2013. The effectiveness of polar and non polar fractions of Ageratum conyzoides l. to control peanut rust disease and phytochemical screenings of secondary metabolites. Jurnal Hama dan Penyakit Tumbuhan Tropika 13: 159-166. [Indonesian]