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

作　　者：Sandip B.Bharate Vikas Kumar Sonali S.Bharate Bikarma Singh Gurdarshan Singh Amarinder Singh Mehak Gupta Deepika Singh Ajay Kumar Surjeet Singh Ram A.Vishwakarma 

机构地区：[1]Medicinal Chemistry Division,Indian Institute of Integrative Medicine Council of Scientific and Industrial Research [2]PK-PD Toxicology & Formulation Division,Indian Institute of Integrative Medicine Council of Scientific and Industrial Research [3]Biodiversity and Applied Botany Division,Indian Institute of Integrative Medicine Council of Scientific and Industrial Research [4]Quality Control and Quality Assurance Division,Indian Institute of Integrative Medicine Council of Scientific and Industrial Research

出　　处：《Journal of Integrative Medicine》2019年第3期192-204,共13页结合医学学报（英文版）

基　　金：financially supported by CSIR 12th Five Year Plan project BSC-0205;CSIR-Phytopharmaceutical Mission Project HCP010;CSIR-YSA (Young Scientist Award,P90807) Research Grant;the fellowship from Department of Biotechnology,India (GAP-2158).IIIM publication number: ⅢM/2222/2018

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. ciliata-based botanical extract IIIM-160.Methods: ⅢM-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: Bergenin was found to be the major component(9.1% w/w) of ⅢM-160. The botanical lead displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6(IL-6) and had an excellent safety-window. It showed anti-inflammatory, anti-arthritic and antinociceptive activity in animal 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-release 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.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. ciliata-based botanical extract IIIM-160.Methods: ⅢM-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: Bergenin was found to be the major component(9.1% w/w) of ⅢM-160. The botanical lead displayed inhibition of lipopolysaccharide-induced production of proinflammatory cytokines in THP-1 cells, with selectivity toward interleukin-6(IL-6) and had an excellent safety-window. It showed anti-inflammatory, anti-arthritic and antinociceptive activity in animal 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-release 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.

关 键 词：BOTANICAL PRECLINICAL candidate UIM-160 Bergenia ciliata Arthritis GASTRORETENTIVE sustained release formulation BERGENIN 

分 类 号：R[医药卫生]