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

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

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

Author: Sandip B BHARATE ¹ ; Vikas KUMAR ² ; Sonali S BHARATE ² ; Bikarma SINGH ³ ; Gurdarshan SINGH ² ; Amarinder SINGH ² ; Mehak GUPTA ² ; Deepika SINGH ⁴ ; Ajay KUMAR ² ; Surjeet SINGH ² ; Ram A VISHWAKARMA ⁵
Author Information

1. Medicinal Chemistry Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu 180001, India. Electronic address: sbharate@iiim.ac.in.
2. PK-PD Toxicology & Formulation Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu 180001, India.
3. Biodiversity and Applied Botany Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu 180001, India.
4. Quality Control and Quality Assurance Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu 180001, India.
5. Medicinal Chemistry Division, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Jammu 180001, India.
Publication Type:Journal Article
Keywords: Arthritis; Bergenia ciliata; Bergenin; Botanical preclinical candidate; Gastroretentive sustained release formulation; IIIM-160
From: Journal of Integrative Medicine 2019;17(3):192-204
CountryChina
Language:English
Abstract: 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.