Discovery and preclinical development of IIIM-160,a Bergenia ciliatabased anti-inflammatory and anti-arthritic botanical drug candidate

摘要

Objective:Bergenia ciliata(Haw.)Sternb.is used in the Indian traditional system of medicine to treat various ailments including rheumatism and to heal wounds.The objective of the present study was to perform a preclinical characterization of the B.ci/iata-based botanical extract HIM-160.Methods:IUM-160 was chemically standardized and analyzed for heavy metal content,aflatoxins,pesticides and microbial load.The in vitro and in vivo efficacies were determined in suitable models of inflammation,arthritis and nociception.An acute oral toxicity study was performed in Swiss albino mice.A suitable oral formulation was developed and characterized.Results:Bergeni n was found to be the major comp on ent(9.1%w/w)of IIIM-160.The botanical lead displayed inhibitio n of lipopolysaccharide-induced productio n of proinflammatory cytokines in TH P-1 cells,with selectivity toward interleukin-6(IL-6)and had an excellent safety-window.It showed anti-i nflammatory,an ti-arthritic and anti no ciceptive activity in an imal models and was not toxic at oral doses up to 2 g/kg in Swiss-albino mice.The gastroretentive,sustained-release capsule formulation showed sustained-「elease of the bergenin over the period of 24 h,resulting in improved plasma-exposure of bergenin in Sprague-Dawley rats.Conclusion:The dual-activity of IL-6 inhibition and antinociception marks the suitability of IIIM-160 for treating rheumatoid arthritis.This study will serve as the benchmark for further research on this botanical formulation.