Aqueous and n-Hexane Fractions of Eruca sativa Differentially Target Glycemic Control and Pancreatic Islet Protection in Diabetic Rats
Abstract
BACKGROUND: The search for novel antidiabetic agents that simultaneously lower blood glucose and protect pancreatic β-cells is crucial. While Eruca sativa is known for its antidiabetic properties, the specific contribution of its solvent fractions to different therapeutic targets remains poorly understood. Therefore, this study was conducted to identify how different fractions selectively target glycemic control or pancreatic islet integrity.
METHODS: Twenty-five male Wistar rats were rendered diabetic by a single intraperitoneal injection of 45 mg/kg streptozotocin. Diabetic animals were divided into five groups (n=5): diabetic control, positive control (0.45 mg/kg glibenclamide), and three treatment groups receiving n-hexane, ethyl acetate, or aqueous fractions of 400 mg/kgBW E. sativa for 14 days. Phytochemical screening was performed to identify bioactive profiles. Blood glucose was monitored periodically, and pancreatic tissues were assessed using a histopathological scoring system (0–4) and islet area measurement.
RESULTS: Aqueous fraction showed the most potent antihyperglycemic activity, significantly reducing blood glucose (208.8±36.02 mg/dL) compared to the diabetic control (419.6± 117.11 mg/dL). Conversely, the n-hexane fraction provided superior pancreatic protection, maintaining the highest islet area (19,109.81±7,549.98 µm²) and the best histopathological score (2.8±0.8) among all treatment groups. Phytochemical screening revealed a distinct distribution of compounds, with flavonoids concentrated in the aqueous fraction and terpenoids in the n-hexane fraction.
CONCLUSION: This study demonstrates that therapeutic efficacy of E. sativa is fraction-specific, driven by its distinct phytochemical profiles. The aqueous fraction is the most effective for rapid glycemic control, significantly reducing blood glucose levels. Conversely, the n-hexane fraction provides superior pancreatic protection, as evidenced by the highest islet area and improved histopathological scores. These findings suggest that E. sativa possesses a dual-target potential; while the aqueous fraction excels in antihyperglycemic action, the n-hexane fraction is more potent for pancreatic islet preservation.
KEYWORDS: Eruca sativa, diabetes mellitus, histopathology, pancreatoprotective, solvent fractions, antihyperglycemic
References
Dilmurodovna TD. Diabetes mellitus in central Asia: Problems and solutions. Best Intellectual Research. 2024; 12(4): 204-13, article.
Alam S, Hasan MK, Neaz S, Hussain N, Hossain MF, Rahman T. Diabetes mellitus: Insights from epidemiology, biochemistry, risk factors, diagnosis, complications and comprehensive management. Diabetology. 2021; 2(2): 36-50, CrossRef.
Suryasa IW, Rodríguez-Gámez M, Koldoris T. Health and treatment of diabetes mellitus. Int J Health Sci. 2021; 5(1): I-V, CrossRef.
Yang JJ, Yu D, Wen W, Saito E, Rahman S, Shu XO, et al. Association of diabetes with all-cause and cause-specific mortality in Asia: A pooled analysis of more than 1 million participants. JAMA Netw Open. 2019; 2(4): e192696, CrossRef.
Arifah FH, Nugroho AE, Rohman A, Sujarwo W. A review of medicinal plants for the treatment of diabetes mellitus: The case of Indonesia. South African J Bot. 2022; 149: 537-58, CrossRef.
Grami D, Selmi S, Rtibi K, Sebai H, De Toni L. Emerging role of Eruca sativa Mill. in male reproductive health. Nutrients. 2024; 16(2): 253, CrossRef.
Teixeira AF, de Souza J, Dophine DD, de Souza Filho JD, Saúde-Guimarães DA. Chemical analysis of Eruca sativa ethanolic extract and its effects on hyperuricaemia. Molecules. 2022; 27(5): 1506, CrossRef.
Awadelkareem AM, Al-Shammari E, Elkhalifa AEO, Adnan M, Siddiqui AJ, Snoussi M, et al. Phytochemical and in silico ADME/tox analysis of Eruca sativa extract with antioxidant, antibacterial and anticancer potential against Caco-2 and HCT-116 colorectal carcinoma cell lines. Molecules. 2022; 27(4): 1409, 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.
Aligita W, Susilawati E, Sukmawati IK, Holidayanti L, Riswanti J. Antidiabetic activities of Muntingia calabura L. leaves water extract in type 2 diabetes mellitus animal models. Indones Biomed J. 2018; 10(2): 165-70, CrossRef.
Alwahaibi N, Budin SB, Hamid ZA, Mohamed J, Latip J, Ismail NB, et al. Tocotrienol rich fraction from palm oil reduces plasma and erythrocyte membrane lipid alteration in diabetic rats: Tocotrienols reduce dyslipidemia in plasma and erythrocytes. Indones Biomed J. 2019; 11(3): 247-56, CrossRef.
Elisa N, Anggoro AB, Indriyanti E. Aktivitas antihipertensi ekstrak dan fraksi-fraksi daun avokad (Persea americana Mill) pada tikus jantan dengan parameter sistolik dan diastolik. J Ilm Sains. 2021; 21(2): 145-54, CrossRef.
Sunarti S, Octavini P. Efek antidiabetes fraksi N-heksana, etil asetat, dan air dari bunga telang (Clitoria ternatea L.) pada tikus jantan yang diinduksi streptozotocin-nikotinamid. J Pharm Sci. 2023; 6(2): 400-8, CrossRef.
Abubakar AR, Haque M. Preparation of medicinal plants: Basic extraction and fractionation procedures for experimental purposes. J Pharm Bioallied Sci. 2020; 12(1): 1-10, CrossRef.
Tandi J, Muttaqin HK, Handayani KR, Mulyani S, Patala R. Potential test of secondary metabolites extract of petai fruit peel (Parkia speciosa Hassk) on creatine. KOVALEN J Ris Kim. 2020; 6(2): 143-51, CrossRef.
Damayanti A, Kusuma IY, Febrina D. Kombinasi ekstrak etanol mesokarp semangka (Citrullus lanatus (Thunb.)) dan bawang putih (Allium sativum L.) terhadap kadar glukosa darah dengan metode GOD-PAP pada tikus diabetes. Pharm Genius. 2023; 02(01): 60-73, CrossRef.
Mahlani M, Hadi RS, Arifandi F, Mustofa S. The effects of honey fermentation (Apis mellifera) on pancreas histology of cisplatin-induced rats and the review according to islamic perspective. Jr Med J. 2023; 2(1): 17-29, CrossRef.
Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013; 50(6): 1007-15, CrossRef.
Ukratalo AM, Amahoru G, Manery DE, Zuneldi T, Pangemanan VO, Loilatu MF. Perubahan berat badan mencit (Mus musculus) model diabetes melitus tipe 1 yang diterapi ekstrak alga coklat sargassum sp. J Anestesi. 2024; 2(3): 39-47, CrossRef.
Rufino AT, Costa VM, Carvalho F, Fernandes E. Flavonoids as antiobesity agents: A review. Med Res Rev. 2021; 41(1): 556-85, CrossRef.
Ra K, Rudnicka J, Krakowska A, Maru A, Narkute M. Effect of solvent and extraction technique on composition and biological activity of Lepidium sativum extracts. Food Chem. 2019; 289: 16-25, CrossRef.
Wakeel A, Jan SA, Ullah I, Shinwari ZK. Solvent polarity mediates phytochemical yield and antioxidant capacity of Isatis tinctoria. PeerJ. 2019: 7: e7857, CrossRef.
Kotecha JL, Ram VR. Extraction and identification of phytochemicals in N-hexane and methanol extracts of Cocos nucifera L. leaves. Adv Zool Bot. 2023; 11(3): 213-9, CrossRef.
Jannah M, Nafis A, Septiarini AD, Irma A. In vitro anti-diabetic activity test of guava (Psidium guajava L.) leaf extract and fraction using α-amylase. J Kesehat Poltekkes Kemenkes RI Pangkalpinang. 2024; 12(1): 8-18, CrossRef.
Sida NA, Mahmudah, Rifa'atul Trinovitasari N, Nada S, Parawansah, Nuralifah, Rafid A, et al. Tectona grandis Linn.: Antidiabetic activity of the fractions using an in vivo approach. Med Sains J Ilm Kefarmasian. 2024; 9(1): 155-64, CrossRef.
Suharyanisa, Enjelina S E, Natanael P. Uji aktivitas ekstrak etil asetat buah luwingan (Ficus hispida L. F) terhadap penurunan kadar glukosa darah pada tikus putih jantan galur Wistar. Farmanesia. 2024; 11(1): 39-48, CrossRef.
Siregar RP, Nasution MA, Lubis MS. Asetat dan n heksan daun kupu-kupu (Bauhinia purpurea L.) terhadap mencit yang diinduksi aloksan. J Kesehat Tambusai. 2024; 5(4): 13569-82, CrossRef.
Shehadeh MB, Suaifan GARY, Abu-Odeh AM. Plants secondary metabolites as blood glucose-lowering molecules. Molecules. 2021; 26(14): 4333, 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.
Hetta MH, Owis AI, Haddad PS, Eid HM. The fatty acid-rich fraction of Eruca sativa ( rocket salad ) leaf extract exerts antidiabetic effects in cultured skeletal muscle, adipocytes and liver cells. Pharm Biol. 2017; 55(1): 810-8, CrossRef.
Purnamayanti A, Budipramana K, Gondokesumo ME. The potential application of Clitoria ternatea for cancer treatment. Pharm Sci Res. 2022; 9(3): 109-24, CrossRef.
Suharti N, Armenia A, Abdillah R, Ramadan CM. Roselle calyx (Hibiscus sabdariffa. L) as an anti-diabetic: Ethyl acetate fraction reduce fasting blood glucose total cholesterol and repair pancreas function on diabetic model. Int J Appl Pharm. 2024; 16(Special Issue 1): 105-10, CrossRef.
Mai Nguyen PT, van Ngo Q, Hong Nguyen MT, Quach LT, Pyne SG. Hypoglycemic activity of the ethyl acetate extract from Smilax glabra Roxb in mice: Biochemical and histopathological studies. Iran J Basic Med Sci. 2020; 23(12): 1558-64, CrossRef.
Kakisina P, Rehiara R. Langerhans islet cells regeneration in type-1 DM mice (Mus musculus) treated with methanol extract of gayam (Inocarpus edulis forst) stem bark. Int J Health Med Curr Res. 2017; 2(03): 528-33, article.
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: 11795514231196462, CrossRef.
Lee MS, Chyau CC, Wang CP, Wang TH, Chen JH, Lin HH. Flavonoids identification and pancreatic beta-cell protective effect of lotus seedpod. Antioxidants. 2020; 9(658): 1-23, CrossRef.
Gondokesumo ME, Kusuma HSW, Widowati W. α-/β-glucosidase and α-amylase inhibitory activities of roselle (Hibiscus sabdariffa L.) ethanol extract. Mol Cell Biomed Sci. 2017; 1(1): 34-40, CrossRef.
Ahmad MF, Haidar MA, Naseem N, Ahsan H, Siddiqui WA. Hypoglycaemic, hypolipidaemic and antioxidant properties of Celastrus paniculatus seed extract in STZ-induced diabetic rats. Mol Cell Biomed Sci. 2023; 7(1): 10-7, CrossRef.
Romatua Aruan DG, Barus T, Haro G, Siburian R, Simanjuntak P. Phytochemical screening and antidiabetic activity of N-hexane, ethyl acetate and water extract from durian leaves (Durio zibethinus L.). Orient J Chem. 2019; 35(1): 487-90, CrossRef.
Rumidatul A, Fadilah TI, Rahayu A, Mawangi NWL, Sandy PS, Kodariah L, et al. Combination of Gmelina arborea and Falcataria moluccana extracts in reducing glucose and improving histology in hyperglycemic mice. Indones J Pharm Sci Technol. 2025; 12(3): 378-86, CrossRef.
DOI: https://doi.org/10.18585/inabj.v18i1.3994
Copyright (c) 2026 The Prodia Education and Research Institute
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Indexed by:
The Prodia Education and Research Institute
