Electronic Theses and Dissertations

Date of Award

1-1-2019

Document Type

Dissertation

Degree Name

Ph.D. in Pharmaceutical Sciences

First Advisor

Ikhlas A. Khan

Second Advisor

Robert J. Doerksen

School

University of Mississippi

Relational Format

dissertation/thesis

Abstract

Tinospora crispa Miers ex Hook.f. & Thomson and Tinospora sinensis (Lour.) Merr. (Menispermaceae) are two species that have morphological similarities which makes distinction between the two of critical importance because T. crispa has been reported to cause hepatotoxicity. Comparative morpho-anatomy of the leaves and stems of Tinospora species indigenous to south and southeast Asia was undertaken to elaborate their distinguishing pharmacognostic features. Chemical characterization of the secondary metabolites of the two species may aid in elucidating their chemical diversity and hence help to resolve safety and quality issues. Phytochemical investigation of the stems led to the isolation of nineteen compounds including one new compound and three new source compounds from T. crispa and fifteen phytoconstituents from T. sinensis including two new compounds and five new source compounds. Chemical structures were elucidated by 1D and 2D NMR spectroscopy and confirmed by HRESIMS. The role of Tinospora plants and borapetosides B C and F on livers was assessed in a 21-day short term and acute study in normal and LPS induced health compromised mice. No hepatotoxicity was observed for any of the crude extracts (1 g/kg b.wt./day oral) or pure compounds (500 mg/kg b. wt./day oral) in either the 21 day or acute study. The hepatoprotective effect was assessed using the monocrotaline-LPS induced hepatotoxicity model. Pretreatment with the crude methanolic extracts of T. crispa T. sinensis (500 mg/kg b.wt./day oral) or combination BCF (250 mg/kg/day) for seven days did not counter the monocrotaline-LPS induced hepatotoxic insult. Elevated ALT levels and alteration in liver histological morphology was observed. A rapid sensitive and reproducible method was established using ultra-high-performance liquid chromatography coupled with photodiode array and single quadrupole electrospray mass spectrometry detectors to achieve decisiveness in not only identifying but also differentiating T. crispa from T. sinensis and other closely related Tinospora species. A chemical fingerprint was developed with a flavonoid two alkaloids an amide and six diterpenoids. Thirty-four Tinospora plant samples and dietary supplements claiming to contain T. crispa T. sinensis and T. cordifolia were analyzed. The newly developed and validated method successfully resulted in the conclusive identification of two dietary supplements that were mislabeled.

Available for download on Wednesday, February 16, 2022

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