Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats

Nurlaili Susanti; Arifa Mustika; Junaidi Khotib

doi:10.29228/jrp.885

Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats

Abstract

Preserving pancreatic β-cell mass and function provides a potentially effective approach for mitigating the development and aggravation of diabetes. This study aimed to prove the effect of Clinacanthus nutans on pancreatic β cell mass and function in rat models of diabetes. The study involved grouping male Wistar rats into six different groups: normal control, diabetes control, diabetes treated with Glibenclamide, and diabetes treated with C. nutans doses of 100, 200, and 400 mg/kg body weight. Body weight, food intake, and fasting blood glucose levels were documented periodically during the study. Serum insulin levels were determined by the Enzyme-linked immunosorbent assay method. The Homeostatic model assessment of β-cell function (HOMA-β) value was calculated based on the given formula. Histopathological examination of pancreatic tissue was performed by Hematoxylin Eosin and Aldehyde Fuchsin staining. The results showed that administration of C. nutans extracts in diabetic rats for twenty-eight days significantly decreased fasting blood glucose levels. Additionally, there was an observed increase in serum insulin levels and HOMA-β values. Similarly, the morphometric analysis findings demonstrated enhancements in the area and number of islets, along with an increase in β-cells count and density. The findings suggest that C. nutans exhibits promising antidiabetic properties through its ability to enhance pancreatic β-cells mass and function.

Keywords

References

[1] Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbaya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WH, Zhang P, Bommer C, Kuo S, Boyko EJ, Magliano DJ. IDF Diabetes Atlas : Global , regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022;183:1–13. https://dx.doi.org/10.1016/j.diabres.2021.109119.
[2] American Diabetes Assosiation. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes 2021. Diabetes Care. 2021;44(1):S15–33. https://dx.doi.org/10.2337/dc21-S002.
[3] Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: A review of current evidence. Diabetologia. 2019;62:3–16. https://dx.doi.org/10.1007/s00125-018-4711-2.
[4] Chen C, Cohrs CM, Stertmann J, Bozsak R, Speier S. Human beta-cell mass and function in diabetes: recent advances in knowledge and technologies to understand disease pathogenesis. Mol Metab. 2017;6:943–957. https://dx.doi.org/10.1016/j.molmet.2017.06.019.
[5] Xavier GDS. The cells of the islets of langerhans. J Clin Med. 2018;7(54):1–17. https://dx.doi.org/10.3390/jcm7030054.
[6] Fu Z, R. Gilbert E, Liu D. Regulation of ınsulin synthesis and secretion and pancreatic beta-cell dysfunction in diabetes. Curr Diabetes Rev. 2013;9(1):25–53. https://dx.doi.org/10.2174/15733998130104.
[7] Gerber PA, Rutter GA. The role of oxidative stress and hypoxia in pancreatic beta-cell dysfunction in diabetes mellitus. Antioxidants Redox Signal. 2017;26(10):501–518. https://dx.doi.org/10.1089/ars.2016.6755.
[8] Cohrs CM, Panzer JK, Drotar DM, Enos SJ, Kipke N, Chen C, Bozsak R, Schöniger E, Ehehalt F, Distler M, Brennand A, Bornstein SR, Weitz J, Solimena M, Speier S. Dysfunction of persisting β-cells ıs a key feature of early type 2 diabetes pathogenesis. Cell Rep. 2020;31:1–9. https://dx.doi.org/10.1016/j.celrep.2020.03.033.

[9] Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature. 2004;429(6987):41–46. https://dx.doi.org/10.1038/nature02520.
[10] Zhou Q, Melton DA. Pancreas regeneration. Nature. 2018;557:351–358. https://dx.doi.org/10.1038/s41586-018 0088-0.
[11] Boughton CK, Munro N, Whyte M. Targeting beta-cell preservation in the management of type 2 diabetes. Br J Diabetes. 2017;17(4):134–143. https://dx.doi.org/10.15277/bjd.2017.148.
[12] Wickramasinghe ASD, Kalansuriya P, Attanayake AP. Herbal medicines targeting the ımproved β-cell functions and β-cell regeneration for the management of diabetes mellitus. Evid-Based Complement Altern Med. 2021;2021 :2920530. https://dx.doi.org/10.1155/2021/2920530.
[13] Chia TY, Gan CY, Murugaiyah V, Hashmi SF, Fatima T, Ibrahim L, Abdulla MH, Alswailmi FK, Johns EJ, Ahmad A. A narrative review on the phytochemistry, pharmacology and therapeutic potentials of Clinacanthus nutans (Burm. f.) Lindau leaves as an alternative source of future medicine. Molecules. 2022;27(1):139. https://dx.doi.org/10.3390/molecules27010139.
[14] Zulkipli IN, Rajabalaya R, Idris A, Sulaiman NA, David SR. Clinacanthus nutans: a review on ethnomedicinal uses, chemical constituents and pharmacological properties. Pharm Biol. 2017;55(1):1093–1113. https://dx.doi.org/10.1080/13880209.2017.1288749.
[15] Khoo LW, Audrey KS, Lee MT, Tan CP, Shaari K, Tham CL, Abas F. A comprehensive review on phytochemistry and pharmacological activities of Clinacanthus nutans (Burm.f.) Lindau. Evid-Based Complement Altern Med. 2018;2018: 9276260. https://dx.doi.org/10.1155/2018/9276260.
[16] 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. https://dx.doi.org/10.1186/s12906-016-1049-5.
[17] Azemi AK, Mokhtar SS, Rasool AHG. Clinacanthus nutans leaves extract reverts endothelial dysfunction in type 2 diabetes rats by ımproving protein expression of eNOS. Oxid Med Cell Longev. 2020;2020: 7572892. https://dx.doi.org/10.1155/2020/7572892.
[18] Umar-Imam M, Ismail M, George A, Chinnappan SM, Yusof A. Aqueous leaf extract of Clinacanthus nutans improved metabolic indices and sorbitol-related complications in type II diabetic rats (T2D). Food Sci Nutr. 2019;7(4):1482–1493. https://dx.doi.org/10.1002/fsn3.988.
[19] Butler AE, Janson J, Soeller WC, Butler PC. Increased β-cell apoptosis prevents adaptive increase in β-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes. 2003;52:2304–2314. https://dx.doi.org/10.2337/diabetes.52.9.2304.
[20] Cerf ME. Beta-cell dysfunction and insulin resistance. Front Endocrinol (Lausanne). 2013;4:37. https://dx.doi.org/10.2337/10.3389/fendo.2013.00037.
[21] El-Abhar HS, Schaalan MF. Phytotherapy in diabetes: Review on potential mechanistic perspectives. World J Diabetes. 2014;5(2):176–97. https://dx.doi.org/10.4239/wjd.v5.i2.176.
[22] Zhong F, Jiang Y. Endogenous pancreatic β cell regeneration: A potential strategy for the recovery of β-cell deficiency in diabetes. Front Endocrinol (Lausanne). 2019;10:101. https://dx.doi.org/10.3389/fendo.2019.00101.
[23] Bayramoglu G, Senturk H, Bayramoglu A, Uyanoglu M, Colak S, Ozmen A, Kolankaya D. Carvacrol partially reverses symptoms of diabetes in STZ-induced diabetic rats. Cytotechnology. 2014;66:251–257. https://dx.doi.org/10.1007/s10616-013-9563-5.
[24] Nahdi AMTA, John A, Raza H. Elucidation of molecular mechanisms of streptozotocin-ınduced oxidative stress, apoptosis, and mitochondrial dysfunction in Rin-5F pancreatic β-cells. Oxid Med Cell Longev. 2017;2017: 7054272. https://dx.doi.org/10.1155/2017/7054272.
[25] Goyal SN, Reddy NM, Patil KR, Nakhate KT, Ojha S, Patil CR, Agrawal YO. Challenges and issues with streptozotocin-induced diabetes - a clinically relevant animal model to understand the diabetes pathogenesis and evaluate therapeutics. Chem Biol Interact. 2016;244(2016):49–63. https://dx.doi.org/10.1016/j.cbi.2015.11.032.
[26] Rashid K, Sil PC. Curcumin enhances recovery of pancreatic islets from cellular stress induced inflammation and apoptosis in diabetic rats. Toxicol Appl Pharmacol. 2015;282:297–310. https://dx.doi.org/10.1016/j.taap.2014.12.003.
[27] Aydemir O, Polat EB, Aljesri K, Taskin T, Bitis L, Elcioglu HK. The effects of Origanum onites in streptozotocin induced diabetes mellitus in rats. J Res Pharm. 2022;26(6):1884–1892. https://dx.doi.org/10.29228/jrp.278.
[28] Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, Ostolaza H, Martín C. Pathophysiology of type 2 diabetes mellitus. Int J Mol Sci. 2020;21(17):6275. https://dx.doi.org/10.3390/ijms21176275.
[29] Eleazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12(1):60. https://dx.doi.org/10.1186/2251-6581-12-60.
[30] Tokarz VL, MacDonald PE, Klip A. The cell biology of systemic insulin function. J Cell Biol. 2018;17(7): 2273-2289 . https://dx.doi.org/10.1083/jcb.201802095.
[31] Madsbad S, Holst JJ. Assessment of ıslet alpha- and beta- cell function. In: Krentz AJ, Weyer C, Hompesch M. (eds). Translational research methods in diabetes, obesity, and nonalcoholic fatty liver disease. Springer Nature, Switzerland, 2019, pp. 37-74.
[32] Ortega-Camarillo C. Dysfunction and death of pancreatic beta-cells in type 2 diabetes. In: Rodriguez-Saldana J. (ed). The diabetes textbook. Springer Nature, Switzerland, 2019, pp. 169-184.
[33] Zhu Y, Liu Q, Zhou Z, Ikeda Y. Pdx1, Neurogenin-3, and MAFA: Critical transcription regulators for beta-cell development and regeneration. Stem Cell Res Ther. 2017;8(1):240. https://dx.doi.org/10.1186/s13287-017-0694-z.
[34] Kitamura T. The role of FOXO1 in β-cell failure and type 2 diabetes mellitus. Nat Rev Endocrinol. 2013;9(10):615 623. https://dx.doi.org/10.1038/nrendo.2013.157.
[35] Baumel-Alterzon S, Scott DK. Regulation of Pdx1 by oxidative stress and Nrf2 in pancreatic beta-cells. Front Endocrinol (Lausanne). 2022;13: 1011187. https://dx.doi.org/10.3389/fendo.2022.1011187.
[36] Kaneto H, Nakatani Y, Kawamori D, Miyatsuka T, Matsuoka TA, Matsuhisa M, Yamasaki Y. Role of oxidative stress, endoplasmic reticulum stress, and c-Jun N-terminal kinase in pancreatic β-cell dysfunction and insulin resistance. Int J Biochem Cell Biol. 2005;37:1595–1608. https://dx.doi.org/10.1016/j.biocel.2005.04.003.
[37] Noh JR, Hwang JH, Kim YH, Kim KS, Gang GT, Kim SW, Kim DK, Shong M, Lee IK, Choi HS, Lee CH. The orphan nuclear receptor small heterodimer partner negativelyregulates pancreatic beta-cell survival and hyperglycemia in multiplelow-dose streptozotocin-induced type 1 diabetic mice. Int J Biochem Cell Biol. 2013;45:1538–1545. https://dx.doi.org/10.1016/j.biocel.2013.05.004.
[38] Zhang Y, Ren C, Lu G, Mu Z, Cui W, Gao H, Wang Y. Anti-diabetic effect of mulberry leaf polysaccharide by inhibiting pancreatic islet-cell apoptosis and ameliorating insulin secretory capacity in diabetic rats. Int Immunopharmacol. 2014;22:248–257. https://dx.doi.org/10.1016/j.intimp.2014.06.039.
[39] An L, Wang Y, Wang C, Fan M, Han X, Xu G, Yuan G, Li H, Sheng Y, Wang M, Sun J, Zhan J, Sun H, Li N, Ding F, Du P. Protective effect of Schisandrae chinensis oil on pancreatic β-cells in diabetic rats. Endocrine. 2015;48:818–825. https://dx.doi.org/10.1007/s12020-014-0375-y.
[40] Tomita T. Apoptosis in pancreatic β-islet cells in Type 2 diabetes. Bosn J Basic Med Sci. 2016;16(3):162–179. https://dx.doi.org/10.17305/bjbms.2016.919.
[41] Hudish LI, Reusch JEB, Sussel L. β-cell dysfunction during progression of metabolic syndrome to type 2 diabetes. J Clin Invest. 2019;129(10):4001–4008. https://dx.doi.org/10.1172/JCI129188.
[42] Marrano N, Biondi G, Cignarelli A, Perrini S, Laviola L, Giorgino F, Natalicchio A. Functional loss of pancreatic islets in type 2 diabetes: how can we halt it? Metabolism. 2020;110:154304. https://dx.doi.org/10.1016/j.metabol.2020.154304.
[43] Chelyn JL, Omar MH, Mohd Yousof NSA, Ranggasamy R, Wasiman MI, Ismail Z. Analysis of flavone C-glycosides in the leaves of Clinacanthus nutans (Burm. f.) Lindau by HPTLC and HPLC-UV/DAD. Sci World J. 2014;2014:724267. https://dx.doi.org/10.1155/2014/724267.
[44] Khoo LW, Mediani A, Zolkeflee NKZ, Leong SW, Ismail IS, Khatib A, Shaari K, Abas F. Phytochemical diversity of Clinacanthus nutans extracts and their bioactivity correlations elucidated by NMR based metabolomics. Phytochem Lett. 2015;14:123–133. https://dx.doi.org/10.1016/j.phytol.2015.09.015.
[45] Susanti N, Mustika A, Khotib J, Muti’ah R, Rochmanti M. Phytochemical, metabolite compound, and antioxidant activity of Clinacanthus nutans leaf extract from Indonesia. Sci Technol Indones. 2023;8(1):38–44. https://dx.doi.org/10.26554/sti.2023.8.1.38-44.
[46] Ghorbani A, Rashidi R, Shafiee-Nick R. Flavonoids for preserving pancreatic beta-cell survival and function: a mechanistic review. Biomed Pharmacother. 2019;111:947–957. https://dx.doi.org/10.1016/j.biopha.2018.12.127.
[47] Tabatabaie PS, Yazdanparast R. Teucrium polium extract reverses symptoms of streptozotocin-induced diabetes in rats via rebalancing the Pdx1 and FoxO1 expressions. Biomed Pharmacother. 2017;93:1033–1039. https://dx.doi.org/10.1016/j.biopha.2017.06.082.
[48] Zakaria ZA, Rahim MHA, Mohtarrudin N, Kadir AA, Cheema MS, Ahmad Z, Mooi CS, Tohid SF. Acute and sub chronic oral toxicity studies of methanol extract of Clinacanthus nutans in mice. Afr J Tradit Complement Altern Med. 2016;13(2):210–222. https://dx.doi.org/10.4314/ajtcam.v13i2.25.
[49] Aliyu A, Shaari MR, Sayuti NSA, Reduan MFH, Sithambaram S, Noordin MM, Shaari K, Hamzah H. Subacute oral administration of Clinacanthus nutans ethanolic leaf extract induced liver and kidney toxicities in ICR mice. Molecules. 2020;25(11):2631. https://dx.doi.org/10.3390/molecules25112631.
[50] Erukainure OL, Ijomone OM, Chukwuma CI, Xiao X, Salau VF, Islam MS. Dacryodes edulis (G. Don) H. J. Lam modulates glucose metabolism, cholinergic activities and Nrf2 expression, while suppressing oxidative stress and dyslipidemia in diabetic rats. J Ethnopharmacol. 2020;255:112744. https://dx.doi.org/10.1016/j.jep.2020.112744.
[51] Majd NE, Tabandeh MR, Shahriari A, Soleimani Z. Okra (Abelmoscus esculentus) improved islets structure, and down-regulated PPARs gene expression in pancreas of high-fat diet and streptozotocin-induced diabetic rats. Cell J. 2018;20(1):31–40. https://dx.doi.org/10.22074/cellj.2018.4819.
[52] Arokoyo DS, Oyeyipo IP, Du Plessis SS, Chegou NN, Aboua YG. Modulation of inflammatory cytokines and islet morphology as therapeutic mechanisms of Basella alba in streptozotocin-induced diabetic rats. Toxicol Res. 2018;34(4):325–332. https://dx.doi.org/10.5487/TR.2018.34.4.325.

Details

Primary Language

English

Subjects

Medical Pharmacology

Journal Section

Research Article

Authors

Nurlaili Susanti This is me
0000-0002-3799-2440
Indonesia

Arifa Mustika ^* This is me
0000-0001-6461-5782
Indonesia

Junaidi Khotib This is me
0000-0002-8468-8441
Indonesia

Publication Date

June 28, 2025

Submission Date

November 28, 2023

Acceptance Date

February 2, 2024

Published in Issue

Year 2024 Volume: 28 Number: 6

DOI

https://doi.org/10.29228/jrp.885

IZ

https://izlik.org/JA59FA74GM

Cite

RIS / Bibtex

APA

Susanti, N., Mustika, A., & Khotib, J. (2025). Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats. Journal of Research in Pharmacy, 28(6), 2104-2113. https://doi.org/10.29228/jrp.885

AMA

1.Susanti N, Mustika A, Khotib J. Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats. J. Res. Pharm. 2025;28(6):2104-2113. doi:10.29228/jrp.885

Chicago

Susanti, Nurlaili, Arifa Mustika, and Junaidi Khotib. 2025. “Protective Effect of Clinacanthus Nutans on Pancreatic β Cell Mass and Function in Diabetic Rats”. Journal of Research in Pharmacy 28 (6): 2104-13. https://doi.org/10.29228/jrp.885.

EndNote

Susanti N, Mustika A, Khotib J (July 1, 2025) Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats. Journal of Research in Pharmacy 28 6 2104–2113.

IEEE

[1]N. Susanti, A. Mustika, and J. Khotib, “Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats”, J. Res. Pharm., vol. 28, no. 6, pp. 2104–2113, July 2025, doi: 10.29228/jrp.885.

ISNAD

Susanti, Nurlaili - Mustika, Arifa - Khotib, Junaidi. “Protective Effect of Clinacanthus Nutans on Pancreatic β Cell Mass and Function in Diabetic Rats”. Journal of Research in Pharmacy 28/6 (July 1, 2025): 2104-2113. https://doi.org/10.29228/jrp.885.

JAMA

1.Susanti N, Mustika A, Khotib J. Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats. J. Res. Pharm. 2025;28:2104–2113.

MLA

Susanti, Nurlaili, et al. “Protective Effect of Clinacanthus Nutans on Pancreatic β Cell Mass and Function in Diabetic Rats”. Journal of Research in Pharmacy, vol. 28, no. 6, July 2025, pp. 2104-13, doi:10.29228/jrp.885.

Vancouver

1.Nurlaili Susanti, Arifa Mustika, Junaidi Khotib. Protective effect of Clinacanthus nutans on pancreatic β cell mass and function in diabetic rats. J. Res. Pharm. 2025 Jul. 1;28(6):2104-13. doi:10.29228/jrp.885