Bioassay Guided Partition of Dandang Gendis (Clinacanthus nutans L.) Monitored by Glucose Consumption Assay on Myoblast Cells and GLUT4 Molecular Docking Analysis
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Abstract
Diabetes mellitus (DM) is a prevalent global metabolic disorder, with an increasing incidence in Indonesia. Clinacanthus nutans L. has been traditionally used for its hypoglycemic properties, yet its precise mechanism of action remains unclear. This study aimed to assess the effects of C. nutans partitions on glucose consumption and to predict their potential interaction with GLUT4 through in silico analysis. A bioassay-guided partition approach was employed to partition C. nutans. Insulin resistance was induced in C2C12 myoblasts using 0.75 mM palmitic acid, followed by treatment with C. nutans partitions at concentrations of 500, 250, and 125 μg/mL. Glucose consumption was quantified using the GOD/PAP assay, with statistical significance at p<0.05. Moreover, molecular docking analysis was conducted to evaluate the binding affinity of C. nutans bioactive compounds to GLUT4. Results indicated that the insoluble partition of C. nutans significantly enhanced glucose uptake in insulin-resistant C2C12 cells at 500 µg/mL (p = 0.0021) and 250 µg/mL (p = 0.0198) compared to untreated controls. However, molecular docking analysis did not reveal direct binding interactions between C. nutans compounds and GLUT4. In conclusion, the insoluble partition of C. nutans effectively improves glucose consumption in insulin-resistant C2C12 cells, though its mechanism of action does not appear to involve direct GLUT4 modulation. These findings suggest that C. nutans holds promise as a complementary therapy for insulin resistance, aligning with Sustainable Development Goal (SDG) 3 by contributing to alternative treatments for type 2 diabetes mellitus (T2DM) and SDG 9 by fostering pharmaceutical innovation and sustainable plant-based therapies.
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References
IDF (International Diabetes Federation). IDF Diabetes Atlas 10th edition. [Online]. 2021 [cited 2024 Dec 20]. Available from: www.diabetesatlas.org.
Vijan S, Sussman JB, Yudkin JS, Hayward RA. Effect of Patients’ Risks and Preferences on Health Gains With Plasma Glucose Level Lowering in Type 2 Diabetes Mellitus. JAMA Intern Med. 2014; 174(8): 1227-1234.
Satoh T. Molecular mechanisms for the regulation of insulin-stimulated glucose uptake by small guanosine triphosphatases in skeletal muscle and adipocytes. Int. J. Mol. Sci. 2014; 15(10): 18677-18692.
Esposito DL, Li Y, Cama A, Quon MJ. Tyr612 and Tyr632 in Human Insulin Receptor Substrate-1 Are Important for Full Activation of Insulin-Stimulated Phosphatidylinositol 3-Kinase Activity and Translocation of GLUT4 in Adipose Cells. Endo. 2001; 142(7): 2833–2840.
Huang X, Liu G, Guo J, Su Z. The PI3K/AKT pathway in obesity and type 2 diabetes. Int. J. Biol. Sci. 2018; 14(11): 1483-1496.
Dewinta NR, Mukono IS, Mustika A. The Effect of Dandang Gendis (Clinacanthus nutans) Extract Administration on Blood Glucose Levels in Wistar Rats with Diabetes Mellitus Model. J. Med. Vet. 2020; 3(1): 76-81.
Abdullah N, Kasim KF. In-Vitro Antidiabetic Activity of Clinacanthus nutans Extracts. Int. J. Pharm. Phytochem. Res. 2017; 9(6): 846-852.
Vinayagam R, Xu B. Antidiabetic properties of dietary flavonoids: a cellular mechanism review. Nutr. Metab. 2015; 12(1): 60-79.
El Barky AR, Hussein SA, Eldeen AAEA, Hafez YA, Mohamed TM. Saponins and their potential role in diabetes mellitus. Diab. Manag. 2017; 7(1): 148-158.
Kumari M, Jain S. Tannins: An Antinutrient with Positive Effect to Manage Diabetes. Res. J. Recent Sci. 2012; 1(12): 1-8.
Azemia AK, Mokhtara SF, Sharif SE, Rasoola AHG. Clinacanthus nutans attenuates atherosclerosis progression in rats with type 2 diabetes by reducing vascular oxidative stress and inflammation. Pharm. Biol. 2021; 59 (1): 1430-1438.
Mustika A, Fatimah N, Safitri I, Susanti N, Noor NS. Clinacanthus nutans L Extracts Reduce the Serum Tumor Necrosis Factor-α, Malondialdehyde, and Interleukin-6 Levels and Improve the Langerhans Islet Area in Diabetic Rat Models. Clin. Med. Insights Endocrinol. Diabetes..2023; 16: 1–7.
Wahyuningsih MSH, Rakhmawati R. Penemuan dan Pengembangan Senyawa Obat dari Bahan Alam. (1st ed.). Yogyakarta: Gadjah Mada University Press; 2024. 112 p.
Wahyuningsih MSH, Ketut SSW, Regita AP, Nugrahaningsih DAA, Yuniyanti MM. Bioassay Guided Fractionation of Ciplukan (Physalis angulata L.) Monitored by Glucose Consumption Assay and Thin Layer Chromatography on Myoblast Cells. Trad. Med. J. 2023; 28(1): 22-30.
Yulianti E, Sunarti, Wahyuningsih MSH. The effect of Kappaphycus alvarezii active fraction on oxidative stress and inflammation in streptozotocin and nicotinamide-induced diabetic rats. BMC Complement. Med. Ther. 2022; 22 (1): 1-8.
Fan M, Feng Q, He M, Yang W, Peng Z, Huang Y, Wang G. Synthesis, a-glucosidase inhibition and molecular docking studies of natural product 2-(2-phenyethyl) chromone analogues. Arab. J. Chem. 2022; 15: 104301-104314.
Sabindo NH, Yatim RM, Thirumulu KP. Phytochemical composition of Clinacanthus nutans based on factors of environment, genetics and postharvest processes: A review. Biomed. 2024; 14(2): 1-11.
Anggraeni VJ, Purwaniati, Budiana W, Nurdin T. Molecular Docking Compounds in Methanol Extract of Mango Leaves (Mangifera indica L.) as Anti-Inflammatory Agent. J. Kim. Ris. 2022; 7(1): 57-65.
Wong CY, Al-Salami H, Dass CR. C2C12 cell model: its role in understanding of insulin resistance at the molecular level and pharmaceutical development at the preclinical stage. J. Pharm. Pharmacol. 2020; 72: 1667-1693.
Pratama AA, Rifai Y, Marzuki A. Molecular Docking of the Compound 5,5'-Dibromomethylsesamin. Pharmacy and Pharmacology Magazine. 2017; 21 (3):67-69.
Pantsar T, Poso A. Binding Affinity via Docking: Fact and Fiction. Mol. 2018; 23: 1899.
Novotný J, Bazzi S, Marek R, Kozelka J. Lone-pair–π interactions: analysis of the physical origin and biological implications. Phys. Chem. Chem. Phys. 2016; 18: 19472-19481.
Susanti, N. Potential of Clinacanthus Nutans as an Alternative Therapeutic Agent for Diabetes Mellitus. In: Yueniwati Y, Tchoyoson LCC, Hamid H, Arsana PM, Nakagoshi N. Proceedings of the International Conference of Medical and Life Science (ICoMELISA 2021). Netherlands: Atlantic Press; 2023. 27-36 p.
Sarega N, Imam MU, Esa NM, Zawawi N, Ismail M. Effects of phenolic-rich extracts of Clinacanthus nutans on high fat and high cholesterol diet-induced insulin resistance. BMC Complement. Altern. Med. 2016; 16(88): 1-11.
Sarega N, Imam MU, Ooi DJ, Chan KW, Esa NM, Zawawi N, Ismail M. Phenolic rich extract from Clinacanthus nutans attenuates hyperlipidemia-associated oxidative stress in rats. Oxid Med Cell Longev. 2016; 2016: 1-16.
Arullappan S, Rajamanickam P, Thevar N, Kodimani CC. In vitro screening of cytotoxic, antimicrobial and antioxidant activities of Clinacanthus nutans (Acanthaceae) leaf extracts. Trop J. Pharm Res. 2014; 13(9): 1455-1461.
Wong FC, Yong AL, Ting EPS, Khoo SC, Ong HC, Chai TT. Antioxidant, metal chelating, anti-glucosidase activities and phytochemical analysis of selected tropical medicinal plants. Iran J Pharm Res. 2014; 13(4): 1409-1415.
Yong YK, Tan JJ, Teh SS, Mah SH, Ee GCL, Chiong HS, Ahmad Z. Clinacanthus nutans extracts are antioxidant with antiproliferative effect on cultured human cancer cell lines. eCAM. 2013; 2013: 1-8.
CDC (Centers for Disease Controls and Prevention). About Insulin Resistance and Type 2 Diabetes. [Online]. 2024 [cited 2024 Dec 28]. Available from: https://www.cdc.gov/diabetes/about/insulin-resistance-type-2-diabetes.html.
Pitocco D, Tesauro M, Alessandro R, Ghirlanda G, Cardillo C. Oxidative stress in diabetes: Implications for vascular and other complications. Int. J. Mol. Sci. 2013; 14: 21525-21550.
Amine H, Benomar Y, Taouis M. Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma. Sci. Rep. 2021; 11(5427): 1-12.
Holloszy J. Regulation by exercise of skeletal muscle content of mitochondria and GLUT4. J. Physiol. Pharmacol. 2008; 59(7): 5-18.
Adawiyah R, Shabrina A, Yuliani S, Nurkhasanah. Potential Plants with Antidiabetic Activity in GLUT4 Translocation: A Narrative Review. JIFFK. 2023; 1(1): 43-52.
Van De Laar FA, Lucassen PL, Akkermans RP, Van De Lisdonk EH, Rutten GE, Van Weel C. α-Glucosidase inhibitors for patients with type 2 diabetes: Results from a cochrane systematic review and meta-analysis. Diabetes Care. 2005; 28: 154-163.
Peng X, Zhang G, Liao Y, Gong D. Inhibitory kinetics and mechanism of kaempferol on α-glucosidase. Food Chem. 2016; 190: 207-215.
Habtemariam S. α-Glucosidase Inhibitory Activity of Kaempferol-3-O-rutinoside. Nat. Prod. Commun. 2011; 6(2): 201-203.
Amin S, Ullah B, Ali M, Khan H, Rauf A, Khan SA, Sobarzo-Sánchez E. In Vitro α-glucosidase Inhibition and Computational Studies of Kaempferol Derivatives from Dryopteris cycanida. Curr Top Med Chem. 2020; 20(9): 731-737.
Oboh G, Agunloye OM, Adefegha SA, Akinyemi AJ, Ademiluyi AO. Caffeic and chlorogenic acids inhibit key enzymes linked to type 2 diabetes (in vitro): a comparative study. J Basic Clin Physiol Pharmacol. 2015; 26(2): 165-170.
Li YQ, Zhou FC, Gao F, Bian JS, Shan F. Comparative evaluation of quercetin, isoquercetin and rutin as inhibitors of alpha-glucosidase. J Agric Food Chem. 2009; 57(24): 11463-11468.
Liu H, Wang Y, Tong J, Li J, Ding H. Quercetin analogs as α-glucosidase inhibitors with antidiabetic activity. Food Biosci. 2024; 58:103713.