ISOLATION OF CUCURBITACIN-B FROM CUCUMIS CALLOSUS AND ITS HYPOGLYCEMIC EFFECT IN ISOLATED RAT ENTEROCYTES

Authors

  • Siva Prasad Panda Associate professor, KL College of Pharmacy, KLEF Deemed to be University, Vaddeswaram, Guntur, India
  • Asit Kumar Sarangi Assistant professor, College of Pharmaceutical Sciences, Puri, Odisha, India
  • Uttam Prasad Panigrahy Assistant professor, KL College of Pharmacy, KLEF Deemed to be University, Vaddeswaram, Guntur, India

DOI:

https://doi.org/10.22159/ijpps.2018v10i5.25788

Keywords:

Cucumis callosus, Cucurbitacin-B, CYP450, Metformin

Abstract

Objective: The pericarp of fruits of Cucumis callous (Rottl.) Cogn. (Cucurbitaceae) is traditionally used for curing diabetes, epilepsy, and diarrhea. It has an active compound include Cucurbitacin-B (CuB), which acts as a potent inducer of CYP450 of rat enterocytes. This study was conducted with the aim of elaborating and reconciling our previous finding on the glucose-lowering effect of Cucumis callosus (Rottl.) Cogn. fruits.

Methods: In vivo hypoglycemic potential for methanolic pericarp extracts from C callosus (MPCC, 350 mg/kg b.w. p. o), methanolic seed extract of C callosus (MSCC, 250 mg/kg b.w. p. o) and CuB (80 µg/kg b.w. p. o) were studied in streptozotocin (STZ, 55 mg/kg b.w. i. p) induced diabetic rats. Metformin (25 mg/kg b.w. p. o) served as reference drug. Ex vivo model of intestinal tissue preparation of Swiss albino rats named Single Pass Intestinal Perfusion (SPIP) technique was performed for ex vivo hypoglycemic study. The glucose levels in the serosal fluid were determined by commercially available glucose oxidase kit and compared with the standard drug metformin (0.1 mg/kg).

Results: In vivo results showed that administration of MPCC (350 mg/kg b.w. p. o) and Cucurbitacin-B (80 µg/kg b.w. p. o) produced the hypoglycemic effect. The MPCC (1.4 mg/kg) and CuB (0.4 µg/kg) produced hypoglycemic effect in ex vivo technique. These effects are due to induction of 0.53 mµmoles of CYP450 proteins with maximum absorption at 454 mµ in rat enterocytes.

Conclusion: The present investigation gave evidence that bitter pericarp of C callosus fruit has a hypoglycemic effect due to the presence of Cucurbitacin B as phytoconstituent but seeds did not have such effects.

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References

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini Ele, Nauck M, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position statement of the American diabetes association (ADA) and the European association for the study of diabetes (EASD). Diabetes Care 2012;35:1364-79.

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;6:943-57.

Huang THW, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, et al. The anti-diabetic action of Punica granatum flower extract: activation of PPAR-c and identification of an active component. Toxicol Appl Pharmacol 2005;207:160-9.

Neyenwe EA, Jerkins TW, Umpierrez GE, Kitabchi AE. Management of type 2 diabetes: evolving strategies for the treatment of patients with type 2 diabetes. Metabolism 2011;60:1–23.

Malviya N, Jain S, Malviya S. Antidiabetic potential of medicinal plants. Acta Pol Pharm Drug Res 2010;67:113-8.

Lorenzati B, Zucco C, Miglietta S, Lamberti F, Bruno G. Oral hypoglycemic drugs: Pathophysiological basis of their mechanism of action. Pharmaceuticals (Basel) 2010;3:3005–20.

Kumar R, Arora V, Verma R, Bhandari A, Vyas P. Hypoglycemic and hypolipidemic effect of Allopolyherbal formulations in streptozotocin-induced diabetes mellitus in rats. Int J Diabetes Mellitus 2015;3:45-50.

Hui H, Tang G, Go VL. Hypoglycemic herbs and their action mechanisms. Chinese Med 2009;4:1-11.

Chen H, Guo J, Pang B, Zhao L, Tong X. Application of herbal medicines with a bitter flavor and cold property on treating diabetes mellitus. J Evidence-Based Complementary Altern Med 2015:1-7. http://dx.doi.org/10.1155/2015/529491

Cao H, Sethumadhavan K, Grimm CC, Ullah AHJ. Characterization of a soluble phosphatidic acid phosphatase in bitter melon (Momordica charantia). PLoS One 2014;9:1-10.

Rathore M. Nutrient content of important fruit trees from arid zone of Rajasthan. J Horticulture Forestry 2009;1:103-8.

Raut M. Glimpses of nature series (No.4) our monsoon plants, Bombay Natural History, Society. Bombay, India; 1959.

Singh DK. Cucurbits. In: Underutilized and underexploited horticulture crops; 2007. p. 175-93.

Kirtikar KR, Basu BD. Indian medicinal plants. M/S Periodical Experts; New Delhi; 1984. p. 1585-8.

Seliya AR, Patel NK. Ethnomedicinal uses of climbers from saraswati river region of patan district, North Gujarat. Ethnobotanical Leaflets 2009;13:865-72.

Rahman AHMM. Ethno-medicinal investigation on the ethnic community in the northern region of Bangladesh. Am J Life Sci 2013;2:77-81.

Patil DA, Patil PS, Ahirrao YA, Aher UP, Dushing YA. Ethnobotany of buldhana district (Maharashtra: India): Plants used in veterinary medicine. J Phytol 2010;12:22-34.

Panda SP, Chakraborty M, Majumder P, Mazumder S, Das S, Haldar PK. The antidiabetic, antioxidant and anti-hyperlipidemic activity of Cucumis callosus in streptozotocin-induced diabetic rats. Int J Pharm Sci Res 2016;7:1978-84.

Trivedi PC. Medicinal plants: traditional knowledge. In: Sharma UK, Gogoi J. eds. Ethno-Medico-Botany of some sacred plants of Dhemaji district of Assam, IK International Pvt. Ltd., New Delhi; 2006. p. 102.

Issa RM, Khedr AM, Rizk HF. UV-vis, IR and H NMR spectroscopic studies of some schiff bases derivatives of 4-aminoantipyrine. Spectrochim Acta Part A 2005;62:621-9.

Thangaraj P. Preliminary phytochemical studies. In: Pharmacological assays of plant-based natural products. Prog Drug Res 2016;71:15-9.

Iszard MB, Curtis JL, Klaassen D. Effet of several metallothionein inducers on oxidative stress defense mechanisms in rats. Toxicology 1995;104:325-33.

Kumar A, Sutharson L, Shrivastava TP, Bhattacharya S, Haldar PK. Hypoglycemic activity of Erythrina variegata leaf in streptozotocin-induced diabetic rats. Pharm Biol 2011;49:577-82.

Franco M, Lopedota A, Trapani A, Cutrignelli A, Meleleo D, Micelli S, et al. Rat intestinal sac as an in vitro method for the assessment of intestinal permeability in humans: application to carrier transported drugs. Int J Pharm 2008;352:182–8.

Bert NLaDu, George H, Mandel E, Leong Way. Fundamentals of drug metabolism and drug disposition. In: Mazel P. ed. Laboratory experiments in the study of drug metabolism and drug disposition, Hyderabad, India: PharmaMed Press; 2010. p. 560-75.

Cherksey BD, Altszuler N. On the mechanism of potentiation by morphine of thiopental sleeping time. Pharmacology 1974;12:362-71.

Varma MV, Panchagnula R. Enhanced oral paclitaxel absorption with vitamin E-TPGS: effect on solubility and permeability in vitro, in situ and in vivo. Eur J Pharm Sci 2005;25:445–53.

Patel M, Mishra S. A kinetic study for in vitro intestinal uptake of monosaccharide across rat everted gut sacs in the presence of some antidiabetic medicinal plants. Int J Altern Med 2009;7:1-7.

Theresa SV, Thirumalai T, Tamilselvan N, David E. In vivo and ex-vivo inhibition of intestinal glucose uptake: a scope for antihyperglycemic. J Acute Disease 2014;3:36-40.

Afifi MS, Ross SA, ElSohly MA, Naeem ZE, Halaweish FT. Cucurbitacins of Cucumis prophetarum. J Chem Ecol 1999;25:847–59.

Sankaram AVB, Reddy VVN. Structure of ebenone, a possible biogenetic precursor of elliptinone, from Diospyros ebenum. Phytochemistry 1984;23:2039-42.

Panda SP, Haldar PK, Das S. In vitro hypoglycemic and antimicrobial activity of Cucumis callosus (Rottl.) Cogn. fruit. Asian J Pharm Clin Res 2016;9:77-81.

Yerasi N, Vurimindi H, Devarakonda K. Rat intestinal perfusion to evaluate drug permeability: application to p-gp and cyp3a4 substrates. Front Pharmacol 2015;141:1-8.

Nebert DW, Dalton TP. The role of cytochrome P450 enzymes in endogenous signaling pathways and environmental carcinogenesis. Nat Rev Cancer 2006;12:947-60.

Pelkonen O, Turpeinen M, Hakkola J, Honkakoski P, Hukkanen J, Raunio H. Inhibition and induction of human cytochrome P450 enzymes: current status. Arch Toxicol 2008;82:667-715.

Guengerich FP, Cheng Q. Orphans in the human cytochrome P450 superfamily: approaches to discovering functions and relevance in pharmacology. Pharmacol Rev 2011;63:684-99.

Guengerich FP. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem Res Toxicol 2001;14:611-50.

Errico ID, Salvatore L, Murzilli S, Sasso GL, Latorre D, Martelli N, et al. Peroxisome proliferator-activated receptor-γ coactivator 1-α (PGC1α) is a metabolic regulator of intestinal epithelial cell fate. Proc Natl Acad Sci 2011;108:6603–8.

Obi BC, Okoye TC, Okpashi VE, Igwe CN, Alumanah EO. Comparative study of the antioxidant effects of metformin, glibenclamide, and repaglinide in alloxan-induced diabetic rats. J Diabetes Res 2016. Doi:10.1155/2016/1635361

Bailey CJ, Mynett KJ, Page T. Importance of the intestine as a site of metformin-stimulated glucose utilization. Br J Pharmacol 1994;112:671–5.

Song R. Mechanism of metformin: a tale of two sites. Diabetes Care 2016;39:187-9.

Yajima K, Shimada A, Hirose H, Kasuga A, Saruta T. Low dose metformin improves hyperglycemia better than Acarbose in type 2 diabetics. Rev Diabet Stud 2004;1:89–94.

Watkins PB, Wrighton SA, Schuetz EG, Molowa DT, Guzelian PS. Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest 1987;80:1029–36.

Ondieki G, Nyagblordzro M, Kikwete S, Liang R, Wang L, He X. Cytochrome P450 and P-glycoprotein-mediated interactions involving African herbs indicated for common noncommunicable diseases. J Evidence Based Complementary Altern Med 2017:18. Doi:10.1155/2017/2582463

Greene JR, Harri DN. Endocrine system. In: Pathophysiology and therapeutics for pharmacists. 3rd edn. Great Britain: RPS Publisher; 2008. p. 582.

Sinko PJ, Leesman GD, Amidon GL. Predicting fraction dose absorbed in humans using a macroscopic mass balance approach. Pharm Res 1991;8:979-88.

Published

01-05-2018

How to Cite

Panda, S. P., A. K. Sarangi, and U. P. Panigrahy. “ISOLATION OF CUCURBITACIN-B FROM CUCUMIS CALLOSUS AND ITS HYPOGLYCEMIC EFFECT IN ISOLATED RAT ENTEROCYTES”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 10, no. 5, May 2018, pp. 123-9, doi:10.22159/ijpps.2018v10i5.25788.

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