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Abstract

PROTECTIVE EFFECTS OF PIPER BETEL PHENOL, HYDROXYCHAVICOL AND ITS DERIVATIVES AGAINST ROTENONE INDUCED NEUROTOXICITY: SYNTHESIS, IN VITRO AND IN VIVO EFFICACY STUDIES

Venkata Rao Ghanta, Aparna Pasula, Sai Kiran S. S. Pindiprolu, Praveen T. Krishnamurthy*, Ravi Chandran J. K. and Balamurali Raman*

ABSTRACT

Hydroxychavicol or 4-Allylpyrocatechol (4-APC) is a Piper betel phenol, reported to modulate vital pathways involved in inflammation and oxidative stress. However, the potential neuro protective benefits of 4APC against neurodegeneration, where similar pathways are involved was not reported and hence 4APC and its derivatives (3a – 3j) were evaluated for their possible neuroprotective activity against rotenone induced neurotoxicity. In the present study 4-allyl pyrocatechol (APC) and its derivatives (3a – 3j) were synthesized via heck coupling with aryl bromides and evaluated for their possible in vitro and in vivo neuroprotective activity against rotenone induced neurotoxicity in SH-SY5Y cell lines and in Swiss albino mice, respectively. In the in vitro studies, among the tested compounds, the 4APC and its derivative, 3c, have shown significant protection against rotenone induced cytotoxicity. In mice, these 2 molecules significantly prevent the rotenone (3 mg/kg, s.c.) induced changes in grip strength, locomotor activity and oxidative & inflammatory stress markers at a tested oral dose of 20/mg/kg.

Keywords: 4-allylpyrocatachol, Heck coupling, SH-SY5Y cell lines, rotenone induced neurotoxicity.


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