Assessment of Antidiabetic and Cyto-Regenerative Activity of Ficus carica through Gene Expression Analysis in Diabetic Rat Model


  • Makkia Saleem National Institute of Food Science and Technology, Faculty of Food Nutrition and Home Sciences, University of Agriculture Faisalabad, Pakistan
  • Mian Kamran Sharif National Institute of Food Science and Technology, Faculty of Food Nutrition and Home Sciences, University of Agriculture Faisalabad, Pakistan
  • Masood Sadiq Butt National Institute of Food Science and Technology, Faculty of Food Nutrition and Home Sciences, University of Agriculture Faisalabad, Pakistan
  • Muhammad Naeem Faisal Institute of Pharmacy, Physiology, and Pharmacology, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan



Diabetes Mellitus, Pancreases, Regeneration, Ficus carica, Genes, Extract, Histopathology


Diabetes mellitus is a metabolic disease of the endocrine system, characterized by chronic hyperglycemia resulting from insulin resistance or defective insulin production. Among the complementary and alternative medicines, diet-based approaches are gaining popularity worldwide for the management of it. Ficus carica, one of the oldest plants cultivated on the earth, is rich in phytochemicals including anthocyanins, phenolics, flavonoids, and organic acids. The present study was designed to analyze the therapeutic potential of dried fig and extract for their potential against hyperglycemia and related complication in the diabetic rat model. Diabetes was induced by using alloxan monohydrate and divided into five groups including Negative-, Positive-, standard drug- group, treated-I (given extract), and treated-II (given 10% dried figs). Fig extract was administered through the intragastric tube, and fig paste was mixed in the feed of the experimental group, and then rats were decapitated after 6 weeks to collect the blood and serum. At the end of the study, biochemical analysis such as fasting blood glucose (FBG), serum glucose, and insulin was performed. Histopathological study of the pancreas showed cell deformation in the positive control group whereas damage was reversed in treated groups. The pancreas was also saved for gene expression analysis. The results revealed that the positive control group has lower expression of INS-1, INS-2, Pdx-1, amylin, and GLUT-2 genes. Results revealed that serum glucose and FBG started to normalize after the administration of treatment (Glibenclamide, dry fig, and fig fruit extract), and insulin concentration also started to improve. 10% dried fig was more effective to control hyperglycemic conditions, which might be due to the presence of fiber. However, the gene expression was more modulated in the group treated with fig extract.  The findings of current research suggested the utilization of fig and fig-based products because of their potential to reverse the damage induced by the alloxan or stressors of daily life.


R.A. DeFronzo, E. Ferrannini, P. Zimmet, and G. Alberti. International Textbook of Diabetes Mellitus, 2 Volume Set, 4th Edition. Wiley-Blackwell. (2015).

A. Basit, A. Fawwad, H. Qureshi, and A.S. Shera. Prevalence of diabetes, pre-diabetes and associated risk factors: Second National Diabetes Survey of Pakistan (NDSP), 2016-2017. BMJ Open 8: 1-10 (2018).

IDF (International Diabetes Federation). IDF Diabetes Atlas, 10th ed. International Diabetes Federation, Brussels, Belgium (2021).

J.K. Grover, V. Vats, S.S. Rathi, and R. Dawar. Traditional Indian anti-diabetic plants attenuate progression of renal damage in streptozotocin-induced diabetic mice. Journal of Ethnopharmacology 76: 233-238 (2001).

M.S. Iqbal, M.Z. Iqbal, M.W. Iqbal, and M.B. Bahari. Complementary and alternative medicines (CAM) among diabetes patients: A prospective study from Pakistan. Value Health 18:620 (2015).

S. Ercisli, M. Tosun, H. Karlidag, A. Dzubur, S. Hadziabulic, and Y. Aliman. Color and antioxidant characteristics of some fresh fig (Ficus carica L.) genotype from Northeastern Turkey. Plant Foods for Human Nutrition 67: 271-276 (2012).

GOP (Government of Pakistan). Food Composition Table of Pakistan. Ministry of Planning, Development & Reform, Islamabad, Pakistan (2001).

R. Veberic, and M. Mikulic-Petkovsek. Phytochemical composition of common fig (Ficus carica L.) cultivars. In: Nutritional Composition of Fruit Cultivars. Preedy, V.R. and M. Simmonds (Eds.), Academic Press, London, UK.(2016).

M.F. Mendes, and I.D.L. Bogle. Evaluation of the effects and mechanisms of bioactive components present in hypoglycemic plants. International Journal of Chemical and Biomolecular Science 1:167-178 (2015).

S. Mawa, K. Husain, and I. Jantan. Ficus carica L. (Moraceae): Phytochemistry, traditional uses and biological activities. Evidence-Based Complementary and Alternative Medicine 2013:1-8 (2013).

S.B. Badgujar, V.V. Patel, A.H. Bandivdekar, and R.T. Mahajan. Traditional uses, phytochemistry and pharmacology of Ficus carica: A review. Pharmaceutical Biology 52:1487-1503 (2014).

H. Crisosto, L. Ferguson, and V. Bremer, U. 2011, Fig (Ficus carica L.) In: Postharvest biology and technology of tropical and subtropical fruits. Vol.3 Yahia, E.M. Woodhead Publishing, Philadelphia, USA.

A., Chawla, R. Kaur, and A.K. Sharma. Ficus carica Linn.: A review on its pharmacogenetic, phytochemical and pharmacological aspects. International Journal of Pharmaceutical and Phytopharmacological Research 1:215-232 (2012).

O. Belguith-Hadriche, S. Ammar, M.M. Contreras, M. Turki1, A. Segura-Carretero, A. El Feki, F. Makni-Ayedi, and M. Bouaziz. Antihyperlipidemic and antioxidant activities of edible Tunisian Ficus carica L. fruits in high fat diet-induced hyperlipidemic rats. Plant Foods for Human Nutrition 71: 183-189 (2016).

H. Guo, M. Xia, T. Zou, W. Ling, R. Zhong, and W. Zhang. Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor Foxo1. The Journal of Nutritional Biochemistry 23: 349-60 (2012).

A. Bucić-Kojić, M. Planinić, S. Tomas, S. Jokić, I. Mujić, M. Bilić, and D. Velić. Effect of extraction conditions on the extractability of phenolic compounds from lyophilised fig fruits (Ficus carica L). Polish Journal of Food and Nutrition Sciences 61: 195-199. (2011).

S. Nurdiana, Y.M. Goh, H. Ahmad, S.M. Dom, N.S. Azmi, N. Syaffinaz N., M. Zin, and M. Ebrahimi. Changes in pancreatic histology, insulin secretion and oxidative status in diabetic rats following treatment with Ficus deltoidea and vitexin. Complementary and Alternative Medicine 17: 290-306 (2017).

J. Eberwine, C. Spencer, K. Miyashiro, S. Mackler, and R. Finnell. Complementary DNA synthesis in situ: Methods and applications. Methods in Enzymology 216: 80-100 (1992).

D.C. Montgomery. Design and Analysis of Experiments, 7th ed. John Wiley & Sons. Inc. Hoboken, NJ, USA. pp. 162-264 (2008).

E.A. Arafa, W. Hassan, G. Murtaza, and M.A. Buabeid. Ficus carica and Sizigium cumini regulate glucose and lipid parameters in high-fat diet and streptozocin-induced rats. Hindawi Journal of Diabetes Research 2020: 1-9 (2020).

F.S. Atkinson, A. Villar, A. Mulà, A. Zangara, E. Risco, C.R. Smidt, R. Hontecillas, A. Leber, and J. Bassaganya-Riera. Abscisic acid standardized fig (Ficus carica) extracts ameliorate postprandial glycemic and insulinemic responses in healthy adults. Nutrients 11: 1757-1765 (2019).

R. Mopuri, M. Ganjayi, B. Meriga, N.A. Koorbanally, and S. Islam. The effects of Ficus carica on the activity of enzymes related to metabolic syndrome. Journal of Food and Drug Analysis 26:201-210 (2018).

S.S. Irudayaraj, S. Christudas, S. Antony, V. Duraipandiyan, A.N. Abdullah, and S. Ignacimuthu. Protective effects of Ficus carica leaves on glucose and lipids levels, carbohydrate metabolism enzymes and b-cells in type 2 diabetic rats. Pharmaceutical Biology 55: 1074-1081 (2017).

S.S. Irudayaraj, A. Stalin, C. Sunil, V. Duraipandiyan, N.A. Al-Dhabi, and S. Ignacimuthu. Antioxidant, antilipidemic and antidiabetic effects of ficusin with their effects on GLUT4 translocation and PPARγ expression in type 2 diabetic rats. Chemico-Biological Interactions 25: 85-93 (2016).

Y. Sheikh, B.C. Maibam, D. Biswas, S. Laisharm, L. Deb, N.C. Talukdar, and J.C. Borah. Anti-diabetic potential of selected ethnomedicinal plants of northeast India. Journal of Ethnopharmacology 171: 37-41 (2015).

C.B. Breneman, and L. Tucker. Dietary fiber consumption and insulin resistance - The role of body fat and physical activity. British Journal of Nutrition 110: 375-383 (2013).

D.K. Patel, S.K. Prasad, R. Kumar, and S. Hemalatha. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pacific Journal of Tropical Biomedicine 2:320-330 (2012).

F.A. El-Shobaki, A.M. El-Bahay, R.S.A. Esmail, A.A.A. El-Megeid, and N.S. Esmail. Effect of figs fruit (Ficus carica L.) and its leaves on hyperglycemia in alloxan diabetic rats. World Journal of Dairy & Food Sciences 5: 47-57 (2010).

C.F. Eliakim-Ikechukwu, and A.I. Obri. Histological changes in the pancreas following administration of ethanolic extract of Alchornea Cordifolia leaf in alloxan-induced diabetic Wistar rats. Nigerian Journal of Physiological Sciences 24: 153-155 (2009).

M. Abdul-Hamid, and N. Moustafa. Protective effect of curcumin on histopathology and ultrastructure of pancreas in the alloxan treated rats for induction of diabetes. The Journal of Basic and Applied Zoology 66: 169-179 (2013).

C.O. Okoli, A.F. Ibiam, A.C. Ezike, P.A. Akah, and T.C. Okoye. Evaluation of antidiabetic potentials of Phyllanthus niruri in alloxan diabetic rats. African Journal of Biotechnology 9: 248-259 (2010).

N.A. Shah, and M.R. Khan. Antidiabetic effect of sida cordata in alloxan induced diabetic rats. BioMed Research International 2014:1-15 (2014).

B.F. Hasan. Effect of water extract of Ficus carica leaves on hematological, biochemical parameters and on histology of pancreas, liver and kidney of dexamethasone induced diabetic male rabbits. Life Science Archives 2: 798-806 (2016).

L. Leroux, B. Durel, V. Autier, L. Deltour, D. Bucchini, J. Jami, and R.L. Joshi. Ins1 gene up-regulated in a beta-cell line derived from Ins2 knockout mice. International Journal of Experimental Diabesity Research 4: 7-12 (2003).

T. Siddique, and F.R. Awan. Effects of Reg3 Delta bioactive peptide on blood glucose levels and pancreatic gene expression in an alloxan-induced mouse model of diabetes. Canadian Journal of Diabetes 40:198-203 (2016).

E.P. Cai, and J.K. Lin. Epigallocatechin gallate (EGCG) and rutin suppress the glucotoxicity through activating IRS2 and AMPK signaling in rat pancreatic β cells. Journal of Agricultural and Food Chemistry 57: 9817 (2009).

W. Gisela. Insulin and insulin resistance. The Clinical Biochemist Review 26(2):19-39 (2005).

L. Vetterli, T. Brun, L. Giovannoni, D. Bosco, and P. Maechler. Resveratrol potentiates glucose-stimulated insulin secretion in INS-1E beta-cells and human islets through a SIRT1-dependent mechanism. Journal of Biological Chemistry 286:6049-6060 (2011).

Y. Liu, X. Ge1, X. Dou, L. Guo, Y. Liu, S. Zhou, X. Wei, S. Qian, H. Huang, C. Xu, W. Jia, Y. Dang, X. Li, and Q. Tang. Protein inhibitor of activated STAT 1 (PIAS1) protects against obesity-induced insulin resistance by inhibiting inflammation cascade in adipose tissue. Diabetes 64:4061-4074 (2015).

J. Cheng, L. Tang, Q. Hong, H. Ye, X. Xu, L. Xu, S. Bu, Q. Wang, D. Dai, D. Jiang, and S. Duan. Investigation into the promoter DNA methylation of three genes (CAMK1D, CRY2 and CALM2) in the peripheral blood of patients with type 2 diabetes. Experimental and Therapeutic Medicine 8: 579-584 (2014).

E. Lucas, M. Jurado-Pueyo, M.A. Fortuño, S. Fernández-Veledo, R. Vila-Bedmar, L.J. Jiménez-Borreguero, J.J. Lazcano, E. Gao, J. Gómez-Ambrosi, G. Frühbeck, W.J. Koch, J. Díez, F. Mayor Jr, and C. Murga. Downregulation of G protein-coupled receptor kinase 2 levels enhances cardiac insulin sensitivity and switches on cardioprotective gene expression patterns. Biochimica et Biophysica Acta 1842:2448-2456 (2014).

Z. Laron. Insulin-like growth factor 1 (IGF-1): A growth hormone. Journal of Molecular Pathology 54: 311-316 (2011).

B.A. Sullivan, J. Hollister-Lock, S. Bonner-Weir, and G.C. Weir. Reduced Ki67 staining in the postmortem state calls into question past conclusions about the lack of turnover of adult human β-cells. Diabetes 64:1698-1702 (2015).

P. Delafontaine, Y. Song, and Y. Li. Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. Arteriosclerosis, Thrombosis, and Vascular Biology 24: 435-444 (2004).

S. Wang, V.L. DeGroff, and S.K. Clinton. Tomato and soy polyphenols reduce insulin-like growth factor-i–stimulated rat prostate cancer cell proliferation and apoptotic resistance in vitro via inhibition of intracellular signaling pathways involving tyrosine kinase. Journal of Nutrition 133:2367-2376 (2003).

X. Zhang, Y. Pan, Y. Huang, and H. Zhao. Neuroendocrine hormone amylin in diabetes. World Journal of Diabetes 7:189-197 (2016).




How to Cite

Saleem, M., Sharif, M. K., Butt, M. S., & Faisal, M. N. (2023). Assessment of Antidiabetic and Cyto-Regenerative Activity of Ficus carica through Gene Expression Analysis in Diabetic Rat Model. Proceedings of the Pakistan Academy of Sciences: B. Life and Environmental Sciences, 60(3), 443–454.



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