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The Possible Potency of Ocimum basilicum New Constituent on Glucosestimulated Insulin Secretion In Vitro and β-cell Function In Vivo

[ Vol. 15 , Issue. 9 ]

Author(s):

Huma Aslam Bhatti*, Kiran Maryam, Rizwana S. Waraich, Abdul Hameed and Rahman M. Hafizur   Pages 969 - 978 ( 10 )

Abstract:


Objects: Three compounds, 2-phenyl-2,3-dihydrochromen-4-one (1), 2-4-(benzyloxy-3- methoxyphenyl)-2-3-dihydrochromen-4-one (2), basilmoside 24-ethyl-25-methylcholesta-5,22- dien-3-β-O-D-glucoside (3) along with Compound 4 formed by the acetylation of Compound 3 from Ocimum basilicum were isolated and structures were elucidated through spectroscopic methods including EI-Mass, 1D and 2D NMR followed by biological evaluation for the modulatory effect on insulin secretion and β-cell function.

Design: An in vitro and in vivo pharmacology study.

Subjects and Study Interventions: For in vitro, freshly isolated islets from Balb/c mice were incubated for 60 min with glucose supplemented with Compound(s) 1-4. For in vivo, overnight fasted Wistar rats were orally challenged with glucose (3 g/kg) 60 min after administration of compound 1 (30 mg/kg). cAMP content was measured with ELISA kit. βTC-6, MIN6 and 3T3 cells were cultured for toxicity study.

Outcome Measurements: Glucose-stimulated insulin secretion, fasting blood glucose, fasting plasma insulin, insulinogenic index, immunohistochemistry and cell viability.

Results: Compounds 1, 2 and 3 induced glucose-stimulated insulin secretion from mice islets and maximum stimulation was found by compound 1 comparable to standard drug tolbutamide (12.3 ± 0.375 ng/islet/hr vs. 9.99 ± 1.005 ng/islet/hr; p < 0.001). Compound 1 induced insulin secretion which was significantly inhibited by verapamil, Ca2+ channels blocker (1.59 ± 0.29 ng/islet/hr vs. 14.26 ± 1.48 ng/islet/hr). Compound 1 also enhanced significantly the intracellular cAMP contents. Compound 1 reduced blood glucose (7.13 ± 0.47 mM vs. 9.25 ± 0.67 mM; p < 0.05) and enhanced glucose-stimulated plasma insulin compared to vehicle (443.76 ± 44.72 pM vs. 304.44 ± 29.24 pM; p < 0.01). Insulinogenic index, a frequently used index of beta-cell function, was 3-fold higher (p <0.01) in compound 1-treated group compared to vehicle. Immunohistochemistry of rat pancreas revealed that compound 1 has insulin degranulation role. Fluorescence intensity analysis showed less fluorescence in compound 1-treated rat pancreas.

Conclusion: Among Compounds 1-3, compound 1 modulates glucose-stimulated insulin secretion in vitro and lowers the blood glucose, enhances plasma insulin in vivo which suggests Ocimum basilicum as an effectual source of anti-diabetic management for traditional use.

Keywords:

Ocimum basilicum, 2-phenyl-2, 3-dihydrochromen-4-one, mice islets, insulin secretion, insulinogenic index.

Affiliation:

HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences (ICCBS), University of Karachi, Karachi-75270

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