Essential Safety Pharmacology and safety evaluation of bioactive fraction of Xylocarpus moluccensis: an antidyslipidaemic agent

Abstract

Background & objectives - Mangrove plants are used in folklore medicine and proven their medicated
significance for humans. The present study showed the essential safety pharmacology (ESP) and toxicity
profile of new patented (US 7959954 from CSIR-CDRI) bioactive fraction of mangrove Xylocarpus
moluccensis for antidyslipidaemic activity (fraction code is CDR267F018). The effective dose (ED) of
CDR267F018 is 50mg / kg in rodents.
Methods – Essential safety pharmacology (ESP) studies were performed to investigate the effect of
CDR267F018 on central nervous system (CNS) and cardiovascular system (CVS). To explore the adverse
effects of CDR267F018 on biochemistry, hematology and different organs of rodents and rhesus monkey,
the toxicity studies were performed as per regulatory guidelines.
Results - Administration of CDR267F018 did not cause significant alteration CNS and CVS of animals as
observed by ESP studies. No significant alteration in general behavior, body weight and urinalysis
parameters were observed. Few biochemical parameters were altered significantly though the value remains
with in range of normalcy. No significant change in organ weight was observed except the increase in liver
weight of few animals of 10 day DRF study. CDR267F018 administration did not cause any significant
histological changes in animals except few incidental findings of focal mononuclear cell collection (FMCC)
in liver and bronchus associated lymphoid tissue (BALT) in lung and calcification in adrenal medulla.
Interpretation & conclusions - The maximum tolerated dose of CDR267F018 was 500 mg / kg and 250 mg /
kg in rodents and primates respectively. Findings suggested that fraction is safe to be use as candidate drug
for the treatment of dyslipidaemic disorder and should proceed for clinical trials.