Sains Malaysiana 51(10)(2022): 3359-3370

http://doi.org/10.17576/jsm-2022-5110-20

Antihyperglycemic, Antihyperlipidemic, and Antioxidant Effects of Eclipta prostrata L. Aqueous Extract in Streptozotocin-Induced Diabetic Rats

(Kesan Antihiperglisemik, Antihiperlipidemik dan Antioksidan Ekstrak Akueus Eclipta prostrata L. pada Tikus Diabetik Aruhan Streptozotocin)

LINGMING ZHANG¹†, CHAO ZHENG²†, TONGDAO XU³ & LIANG DU^4,*

¹Department of Endocrinology, Qinghai Provincial People's Hospital, Xining, Qinghai, 810000, P.R. China

²Department of Endocrinology, Punan Hospital, Pudong New Area, Shanghai, Shanghai, 200125, P.R. China

³Department of Endocrinology, The Second People's Hospital of Lianyungang, Lianyungang, Jiangsu, 222000, P.R. China

⁴Department of endocrinology and metabolism, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan, Hubei, 442008, P.R. China

Received: 27 November 2021/Accepted: 31 May 2022

†Equally contributed

Abstract

With the rising prevalence of diabetes mellitus around the world, researchers have been searching for a new treatment option that is both more effective and safer than chemotherapy. This study evaluated the antidiabetic activities of aqueous extracts of Eclipta prostrataL. in streptozotocin (STZ)-induced diabetic rats.  The rats were randomized into six groups: Normal control, STZ-induced diabetic rats (50 mg/kg), STZ + EPE (100 mg/kg), STZ + EPE (200 mg/kg), STZ+glibenclamide (600 µg/kg) and EPE alone (200 mg/kg).  The STZ-induced diabetic rats showed significantly (p<0.05) elevated glucose, HbA1c, lipid profile, hepatic, and kidney markers, while significantly (p<0.05) decreased insulin levels. The changes in activities of carbohydrate metabolizing enzymes such as glucose-6-phosphatase, fructose-1,6–bisphosphatase were significantly (p<0.05) increased in diabetic rats, while the activity of glucokinase and glucose-6-phosphate dehydrogenase were significantly (p<0.05) reduced. Oral treatment of STZ-induced diabetic rats with E. prostrata(100 and 200 mg/kg) and glibenclamide (600 µg/kg) prevented the alteration as mentioned earlier and brought back them to near normalcy. The current findings in experimental diabetic rats suggest that oral treatment with E. prostrate ameliorated carbohydrate metabolizing enzymes, showed total cholesterol-lowering effects, improved serum high-density lipoprotein (HDL) cholesterol levels and exhibited intriguing antioxidant activities.

Keywords: Diabetes mellitus; Eclipta prostrata; glucose; insulin

Abstrak

Dengan peningkatan kelaziman diabetes mellitus di seluruh dunia, penyelidik telah mencari pilihan rawatan baharu yang lebih berkesan dan selamat daripada kemoterapi. Kajian ini menilai aktiviti antidiabetik ekstrak akueus Eclipta prostrataL. pada tikus diabetes yang disebabkan oleh streptozotocin (STZ). Tikus telah dibahagikan secara rawak kepada enam kumpulan: Kawalan, tikus diabetes aruhan-STZ (50 mg/kg), STZ + EPE (100 mg/kg), STZ + EPE (200 mg/kg), STZ+glibenclamide (600 µg/ kg) dan EPE sahaja (200 mg/kg). Tikus diabetes aruhan-STZ menunjukkan peningkatan secara signifikan (p<0.05) glukosa, HbA1c, profil lipid, penanda hepar dan buah pinggang, manakala secara signifikan (p<0.05) menurunkan tahap insulin. Perubahan dalam aktiviti enzim metabolisme karbohidrat seperti glukosa-6-fosfatase, fruktosa-1,6-bisphosphatase meningkat dengan ketara (p<0.05) pada tikus diabetes, manakala aktiviti glukokinase dan glukosa-6-fosfat dehidrogenase adalah ketara (p<0.05) berkurangan. Rawatan oral tikus diabetes aruhan-STZ dengan E. prostrata (100 dan 200 mg/kg) dan glibenclamide (600 µg/kg) menghalang pengubahan seperti yang dinyatakan sebelum ini dan membawanya kembali kepada tahap normal. Penemuan dalam uji kaji tikus diabetik ini menunjukkan bahawa rawatan oral dengan E. prostrate memperbaiki enzim metabolisme karbohidrat, menunjukkan kesan penurunan kolesterol secara keseluruhan, meningkatkan paras serum kolesterol lipoprotein berketumpatan tinggi (HDL) dan menunjukkan aktiviti antioksidan yang menarik.

Kata kunci: Diabetes mellitus; Eclipta prostrata; glukosa; insulin

REFERENCES

Aebi, H. 1984. Catalase in vitro. Methods Enzymol. 105: 121-6.

Babaei-Balderlou, F. & Zare, S. 2012. Melatonin improves spatial navigation memory in male diabetic rats. Veterinary Research Forum: An International Quarterly Journal 3: 187-192.

Bakar, M.H.A., Sarmidi, M.R., Cheng, K.K., Khan, A.A., Suan, C.L., Huri, H.Z. & Yaakob, H.  2015. Metabolomics - The complementary field in systems biology: A review on obesity and type 2 diabetes. Molecular BioSystems 11: 1742-1774.

Canfora, E.E., Jocken, J.W. & Blaak, E.E. 2015. Short-chain fatty acids in control of body weight and insulin sensitivity. Nature Reviews Endocrinology 11: 577-591.

Catignani, G.L. & Bieri, J.G. 1983. Simultaneous determination of retinol and alpha-tocopherol in serum or plasma by liquid chromatography. Clinical Chemistry 29: 708-712.

Chung, I.M., Rajakumar, G., Lee, J.H., Kim, S.H. & Thiruvengadam, M. 2017. Ethnopharmacological uses, phytochemistry, biological activities, and biotechnological applications of Eclipta prostrata. Appl. Microbiol. Biotechnol. 101: 5247-5257.

Czech, M.P.  2017. Insulin action and resistance in obesity and type 2 diabetes. Nature Medicine 23: 804-814.

Dardevet, D., Sornet, C., Savary, I., Debras, E., Patureau-Mirand, P. & Grizard, J. 1998. Glucocorticoid effects on insulin-and IGF-I-regulated muscle protein metabolism during aging. Journal of Endocrinology 156: 83-89.

Daryabor, G., Atashzar, M.R., Kabelitz, D., Meri, S. & Kalantar, K. 2020. The effects of Type 2 diabetes mellitus on organ metabolism and the immune system. Frontiers in Immunology 11: 1582.

Hall, K.D., Heymsfield, S.B., Kemnitz, J.W., Klein, S., Schoeller, D.A. & Speakman, J.R. 2012. Energy balance and its components: Implications for body weight regulation. The American Journal of Clinical Nutrition 95: 989-994.

Han, H.S., Kang, G., Kim, J.S., Choi, B.H. & Koo, S.H. 2016. Regulation of glucose metabolism from a liver-centric perspective. Experimental & Molecular Medicine 48: e218-e218.

Hayashi, H., Mizuguchi, H., Miyahara, I., Nakajima, Y., Hirotsu, K. & Kagamiyama, H. 2003. Conformational change in aspartate aminotransferase on substrate binding induces strain in the catalytic group and enhances catalysis. Journal of Biological Chemistry 278(11): 9481-9488.

Henry, N.L. 1974. Knowledge management: A new concern for public administration. Public Administration Review 34: 189-196.

Home, P.D. 2015. Plasma insulin profiles after subcutaneous injection: How close can we get to physiology in people with diabetes? Diabetes, Obesity and Metabolism 17: 1011-1020.

Huang, X.J., Choi, Y.K., Im, H.S., Yarimaga, O., Yoon, E. & Kim, H.S. 2006. Aspartate aminotransferase (AST/GOT) and alanine aminotransferase (ALT/GPT) detection techniques. Sensors (Basel, Switzerland) 6: 756-782.

Iqbal, M.O., Sial, A.S., Akhtar, I., Naeem, M., Hazafa, A., Ansari, R.A. & Rizvi, S.A.A. 2021. The nephroprotective effects of Daucus carota and Eclipta prostrata against cisplatin-induced nephrotoxicity in rats. Bioengineered 12: 12702-12721.

Jahan, R., Al-Nahain, A., Majumder, S. & Rahmatullah, M. 2014. Ethnopharmacological significance of <i>Eclipta alba</i> (L.) Hassk. (Asteraceae). International Scholarly Research Notices 2014: 385969.

Jaiswal, Y.S., Tatke, P.A., Gabhe, S.Y. & Vaidya, A.B. 2017. Antidiabetic activity of extracts of Anacardium occidentale Linn. leaves on n-streptozotocin diabetic rats. Journal of Traditional and Complementary Medicine 7: 421-427.

Kemboi, D., Peter, X., Langat, M. & Tembu, J. 2020. A review of the ethnomedicinal uses, biological activities, and triterpenoids of Euphorbia species. Molecules 25(17): 4019.

Khan, J., Ikbal, A.M.A.I., Debnath, B., Rajkhowa, A., Choudhury, P.D., Sen, S., Paul, K., Choudhury, D., Debsarkar, S. & Jamatia, K. 2021. Management of diabetes mellitus by nano based drug delivery with special reference to phytosomes. Pharmaceutical and Biosciences Journal 9(6): 11-28.

Kim, D.I., Lee, S.H., Choi, J.H., Lillehoj, H.S., Yu, M.H. & Lee, G.S. 2008. The butanol fraction of Eclipta prostrata  Linn. effectively reduces serum lipid levels and improves antioxidant activities in CD rats. Nutrition Research 28: 550-554.

Lobo, V., Patil, A., Phatak, A. & Chandra, N. 2010. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacognosy Reviews 4: 118.

Loria, P., Lonardo, A. & Anania, F. 2013. Liver and diabetes. A vicious circle. Hepatology Research 43: 51-64.

Luna, B. & Feinglos, M.N. 2001. Oral agents in the management of type 2 diabetes mellitus. American Family Physician 63: 1747.

MacDonald, M.J. & Gapinski, J.P. 1989. A rapid ELISA for measuring insulin in a large number of research samples. Metabolism 38: 450-452.

Manimegalai, S., Mahboob, S., Al-Ghanim, K.A., Al-Misned, F., Govindarajan, M., Anbarasu, K., & Rajeswari, V.D. 2020. Down-regulation of hepatic G-6-Pase expression in hyperglycemic rats: Intervention with biogenic gold nanoconjugate. Saudi Journal of Biological Sciences 27: 3334-3341.

Marklund, S. & Marklund, G. 1974. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European Journal of Biochemistry 47: 469-474.

Matschinsky, F.M. & Wilson, D.F. 2019. The central role of glucokinase in glucose homeostasis: A perspective 50 years after demonstrating the presence of the enzyme in islets of Langerhans. Frontiers in Physiology 10: 148.

Mora‐Fernández, C., Domínguez‐Pimentel, V., de Fuentes, M.M., Górriz, J.L., Martínez‐Castelao, A. & Navarro‐González, J.F. 2014. Diabetic kidney disease: From physiology to therapeutics. The Journal of Physiology 592: 3997-4012.

Murray, A.J., Lygate, C.A., Cole, M.A., Carr, C.A., Radda, G.K., Neubauer, S. & Clarke, K.  2006. Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart. Cardiovascular Research 71: 149-157.

Nilsson, A.C., Johansson-Boll, E.V. & Björck, I.M.E.  2015. Increased gut hormones and insulin sensitivity index following a 3-D intervention with a barley kernel-based product: A randomised cross-over study in healthy middle-aged subjects. British Journal of Nutrition 114: 899-907.

Omisore, O.M., Ojokoh, B.A., Babalola, A.E., Igbe, T., Folajimi, Y., Nie, Z. & Wang, L. 2021. An affective learning-based system for diagnosis and personalized management of diabetes mellitus. Future Generation Computer Systems 117: 273-290.

Paglia, D.E. & Valentine, W.N. 1967. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. Journal of Laboratory and Clinical Medicine 70: 158-169.

Pranata, R., Henrina, J., Raffaello, W.M., Lawrensia, S. & Huang, I. 2021. Diabetes and COVID-19: The past, the present, and the future. Metabolism 121: 154814.

Rahman, M.S., Rahman, M.Z., Begum, B., Chowdhury, R., Islam, S.N. & Rashid, M.A. 2011. Antidiabetic principle from Eclipta prostrata. Latin American Journal of Pharmacy 30: 1656-1660.

Ramachandran, V. & Saravanan, R. 2013. Efficacy of asiatic acid, a pentacyclic triterpene on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin-induced diabetic rats. Phytomedicine 20: 230-236.

Sasidharan, S., Sumathi, V., Jegathambigai, N.R. & Latha, L.Y. 2011. Antihyperglycaemic effects of ethanol extracts of Carica papaya and Pandanus amaryfollius leaf in streptozotocin-induced diabetic mice. Natural Product Research 25: 1982-1987.

Stefaniak, A.A., Krajewski, P.K., Bednarska-Chabowska, D., Bolanowski, M., Mazur, G. & Szepietowski, J.C. 2021. Itch in adult population with Type 2 diabetes mellitus: Clinical profile, pathogenesis and disease-related burden in a cross-sectional study. Biology 10: 1332.

Teo, Z.L., Tham, Y.C., Yu, M., Chee, M.L., Rim, T.H., Cheung, N., Bikbov, M.M., Wang, Y.X., Tang, Y. & Lu, Y. 2021. Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis. Ophthalmology 128: 1580-1591.

Tewtrakul, S., Subhadhirasakul, S., Tansakul, P., Cheenpracha, S. & Karalai, C. 2011. Antiinflammatory constituents from Eclipta prostrata using RAW264.7 macrophage cells. Phytotheraphy Research 25: 1313-1316.

Vijayakumar, S., Vinayagam, R., Anand, M.A.V., Venkatachalam, K., Saravanakumar, K., Wang, M.H., Sangeetha Casimeer, C., Gothandam, KM. & David, E. 2020. Green synthesis of gold nanoparticle using Eclipta alba and its antidiabetic activities through regulation of Bcl-2 expression in pancreatic cell line. Journal of Drug Delivery Science and Technology 58: 101786.

Wang-Fischer, Y. & Garyantes, T. 2018. Improving the reliability and utility of streptozotocin-induced rat diabetic model. Journal of Diabetes Research 2018: 8054073.

Wybenga, D.R., Di Giorgio, J. & Pileggi, V.J. 1971. Manual and automated methods for urea nitrogen measurement in whole serum. Clinical Chemistry 17: 891-895.

Yadav, N.K., Arya, R.K., Dev, K., Sharma, C., Hossain, Z., Meena, S., Arya, K.R., Gayen, J.R., Datta, D. & Singh, R.K. 2017. Alcoholic extract of eclipta alba shows in vitro antioxidant and anticancer activity without exhibiting toxicological effects. Oxidative Medicine and Cellular Longevity 2017: 9094641.

^*Corresponding author; email: duliangdf120@sina.com