Gynura procumbens Leaf Extract Ameliorates Hyperglycemia, Oxidative Stress, and Pancreatic Islet Damage in Diabetic Rats

Evelyn Angie, Ermi Girsang, Refi Ikhtiari

Abstract


BACKGROUND: Conventional antidiabetic drugs, while effective, are often associated with adverse effects, secondary failure, and high costs, particularly in developing countries. This has driven interest in complementary plant‑based therapies. Gynura procumbens is a medicinal plant traditionally used in Southeast Asia for diabetes and metabolic disorders, however scientific evidences supporting this use have not been elucidated well. In this study, G. procumbens leaf extract (GPLE) was assessed whether it could lower glucose, restore antioxidant enzymes including superoxide dismutase (SOD) and glutathione peroxidase (GPx), reduce the oxidative marker malondialdehyde (MDA), suppress pro‑inflammatory cytokines such as interleukin (IL)‑6, IL‑8, tumor necrosis factor (TNF)‑α, and improve pancreatic structure in diabetic rats.

METHODS: Twenty eight male Wistar rats were divided into four groups: normal rats, untreated diabetic rats, and diabetic rats given 500 or 1000 mg/kg of GPLE orally for 14 days. Blood glucose, SOD, GPx, and MDA were measured by spectrophotometry, while IL‑6, IL‑8, and TNF‑α were measured by enzyme‑linked immunosorbent assay (ELISA). Pancreas sections were stained with H&E.

RESULTS: Administration of both extract doses significantly lowered fasting blood glucose by approximately 66% relative to the untreated diabetic control group (p<0.05). The administration of 1000 mg/kg GPLE increased SOD activity by 107% and GPx activity by 488%, while reducing MDA by 95% (p<0.05). Proinflammatory cytokines were markedly suppressed IL‑6 by 76%, IL‑8 by 76%, and TNF‑α by 79% at the high dose. Histological examination showed that treated rats had nearly normal islet morphology, reduced vascular congestion, and almost no lymphocytic infiltration.

CONCLUSION: GPLE demonstrates promising antihyperglycemic, antioxidant, and anti-inflammatory activities alongside structural pancreatic preservation in a preclinical model. These findings suggest its potential as a candidate for further exploration in complementary metabolic therapies.

KEYWORDS: antioxidants, diabetes mellitus, Gynura procumbens, histopathology, inflammation, oxidative stress


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Rahayu RF, Zahrah FA, Anugrah TS, Yudhani RD, Yueniwati Y, Irawan AT, et al. Vitamin D and magnesium combination lowers high-sensitivity C-reactive protein, interleukin-12, renin, and carotid vessel in diabetic rats. Indones Biomed J. 2026; 18(2): 193-200, CrossRef.

Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, et al. IDF Diabetes Atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract. 2022; 183: 109119, CrossRef.

Siddiqui MNI. Global epidemic of diabetes, growing burden of young-onset diabetes, and regional perspective. J Assoc Clin Endocrinol Diabetol Bangladesh. 2025; 4(1): 1-3, CrossRef.

Saberi S, Askaripour M, Khaksari M, Amin Rajizadeh M, Abbas Bejeshk M, Akhbari M, et al. Exercise training improves diabetic renal injury by reducing fetuin-A, oxidative stress and inflammation in type 2 diabetic rats. Heliyon. 2024; 10(6): e27749, CrossRef.

González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: An integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023; 24(11): 9352, CrossRef.

Shkurat MA, Mashkina EV, Milyutina NP, Shkurat TP. The role of polymorphism of redox-sensitive genes in the mechanisms of oxidative stress in obesity and metabolic diseases. Ecol Genet. 2023; 21(3): 261-87, CrossRef.

Shabalala SC, Johnson R, Basson AK, Ziqubu K, Hlengwa N, Mthembu SXH, et al. Detrimental effects of lipid peroxidation in type 2 diabetes: exploring the neutralizing influence of antioxidants. Antioxidants. 2022; 11(10): 2071, CrossRef.

Saxena P, Selvaraj K, Khare SK, Chaudhary N. Superoxide dismutase as multipotent therapeutic antioxidant enzyme: Role in human diseases. Biotechnol Lett. 2022; 44(1): 1-22, CrossRef.

Pei J, Pan X, Wei G, Hua Y. Research progress of glutathione peroxidase family (GPX) in redoxidation. Front Pharmacol. 2023; 14: 1147414, CrossRef.

Singh H, Singh R, Singh A, Singh H, Singh G, Kaur S, et al. Role of oxidative stress in diabetes-induced complications and their management with antioxidants. Arch Physiol Biochem. 2024; 130(6): 616-41, CrossRef.

Krawczyk M, Burzynska-Pedziwiatr I, Wozniak LA, Bukowiecka-Matusiak M. Impact of polyphenols on inflammatory and oxidative stress factors in diabetes mellitus: nutritional antioxidants and their application in improving antidiabetic therapy. Biomolecules. 2023; 13(9): 1402, CrossRef.

Rahayu RF, Prayitno A, Purwanto B, Soewondo W, Nurwati I, Pamungkasari EP, et al. Combination of metformin and magnesium citrate reduces TNF-α, NF-κB p65, IL-6, CD4, and MMP-9 expressions in diabetic model rats. Indones Biomed J. 2024; 16(6): 546-52, CrossRef.

Szukiewicz D. Molecular mechanisms for the vicious cycle between insulin resistance and the inflammatory response in obesity. Int J Mol Sci. 2023; 24(12): 9818, CrossRef.

Varthaliti A, Lygizos V, Fanaki M, Pergialiotis V, Papapanagiotou A, Pappa K, et al. The role of IL-6 and TNF-α as early biomarkers in the prediction and diagnosis of gestational diabetes mellitus. Biomedicines. 2025; 13(7): 1627, CrossRef.

Todingan M, Muhiddin R, Kurniawan LB. IL-6 levels analysis controlled in type 2 diabetes mellitus patients and uncontrolled. Indones J Clin Pathol Med Lab. 2023; 29(2): 175-9, CrossRef.

Zhao L, Hu H, Zhang L, Liu Z, Huang Y, Liu Q, et al. Inflammation in diabetes complications: molecular mechanisms and therapeutic interventions. MedComm. 2024; 5(4): e516, CrossRef.

Dinić S, Arambašić Jovanović J, Uskoković A, Mihailović M, Grdović N, Tolić A, et al. Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. Front Endocrinol. 2022; 13: 1006376, CrossRef.

Majety P, Lozada Orquera FA, Edem D, Hamdy O. Pharmacological approaches to the prevention of type 2 diabetes mellitus. Front Endocrinol. 2023; 14: 1118848, CrossRef.

Rais N, Ved A, Ahmad R, Parveen K, Gautam GK, Bari DG, et al. Model of streptozotocin-nicotinamide induced type 2 diabetes: a comparative review. Curr Diabetes Rev. 2022; 18(8): e171121198001, CrossRef.

Sariyanti M, Andita TA, Erlinawati ND, Yunita E, Nasution AA, Sari K, et al. Probiotic Lactobacillus acidophilus FNCC 0051 improves pancreatic histopathology in streptozotocin-induced type-1 diabetes mellitus rats. Indones Biomed J. 2022; 14(4): 410-5, CrossRef.

Odeyemi S, Bradley G. Medicinal plants used for the traditional management of diabetes in the Eastern Cape, South Africa: pharmacology and toxicology. Molecules. 2018; 23(11): 2759, CrossRef.

Bose PA, Sohag MMH, Rabbee MF, Zamee TM, Kona JN, Elora B, et al. Pharmacological overview of bioactive natural products from Gynura procumbens (Lour.) Merr. Plants. 2025; 14(17): 2714, CrossRef.

Jeong T, Hong S, Sung J, Jeong H, Lee H, Lee J. Effect of post-harvest ultrasound treatment on phytochemical enhancement in Gynura procumbens leaves and their protection against oxidative stress-induced muscle atrophy. J Sci Food Agric. 2026; 106(4): 2270-9, CrossRef.

Kashtoh H, Baek KH. Recent updates on phytoconstituent alpha-glucosidase inhibitors: an approach towards the treatment of type two diabetes. Plants. 2022; 11(20): 2722, CrossRef.

Husak V, Shvadchak V, Sheremeta L, Abrat O. Therapeutic potential of Gynura procumbens in obesity, metabolic syndrome, and diabetes. J Vasyl Stefanyk Precarpathian Natl Univ Biol. 2024; 11: 20-32, CrossRef.

Rosiana V, Taurhesia S, Djamil R. Synergistic effect on tyrosinase inhibition of Cassia fistula flower with Gynura procumbens leaf extracts. S Afr J Bot. 2024; 170: 172-6, CrossRef.

Nagori M, Rajput D, Choudhary G, Khabiya R. Qualitative and quantitative methods of phytochemical analysis. In: Odoh UE, Gurav SS, Chukwuma MO. Pharmacognosy and Phytochemistry. Hoboken: Wiley; 2025. p.143-66, CrossRef.

Gusti AMT, Qusti SY, Alshammari EM, Toraih EA, Fawzy MS. Antioxidants-related superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) gene variants analysis in an obese population: a preliminary case-control study. Antioxidants. 2021; 10(4): 595, CrossRef.

Ahmed OM, Fahim HI, Ahmed HY, Al-Muzafar HM, Ahmed RR, Amin KA, et al. The preventive effects and the mechanisms of action of navel orange peel hydroethanolic extract, naringin, and naringenin in N-acetyl-p-aminophenol-induced liver injury in Wistar rats. Oxid Med Cell Longev. 2019; 2019: 2745352, CrossRef.

Angie E, Girsang E, Ikhtiari R. Linking MDA levels and blood glucose in streptozotocin-induced rat diabetes: implications for diabetic complications and therapeutic strategies. J Penelit Pendidik IPA. 2024; 10(6): 2898-905, CrossRef.

Kim SS, Suvarna K, Layton C, Bancroft JD. Bancroft's theory and practice of histological techniques. 8th ed. Amsterdam: Elsevier; 2020.

Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013; 50(6): 1007-15, CrossRef.

Widowati W, Rani AP, Hamzah RA, Arumwardana S, Afifah E, Kusuma HSW, et al. Antioxidant and antiaging assays of Hibiscus sabdariffa extract and its compounds. Nat Prod Sci. 2017; 23(3): 192-9, CrossRef.

Sun B, Chen H, Xue J, Li P, Fu X. The role of GLUT2 in glucose metabolism in multiple organs and tissues. Mol Biol Rep. 2023; 50(8): 6963-74, CrossRef.

Sugiharto, Winarni D, Wibowo AT, Islamatasya U, Bhakti IN, Nisa N, et al. Gynura procumbens adventitious root extract altered expression of antioxidant genes and exert hepatoprotective effects against cadmium-induced oxidative stress in mice. HAYATI J Biosci. 2022; 29(4): 479-86, CrossRef.

Valgimigli L. Lipid peroxidation and antioxidant protection. Biomolecules. 2023; 13(9): 1291, CrossRef.

Al-Ishaq RK, Abotaleb M, Kubatka P, Kajo K, Büsselberg D. Flavonoids and their anti-diabetic effects: cellular mechanisms and effects to improve blood sugar levels. Biomolecules. 2019; 9(9): 430, CrossRef.

Panda P, Nayak S, Panigrahi K, Sahu PK, Panda JK. Adipose tissue-derived TNF-alpha as a mediator of insulin resistance in obese and non-obese type 2 diabetes mellitus. SSR Inst Int J Life Sci. 2025; 11(4): 7955-62, CrossRef.




DOI: https://doi.org/10.18585/inabj.v18i3.4134

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