Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats

Abstract Background ECa 233 is a standardized extract of C. asiatica containing the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.5):1. Anti-inflammatory activities of ECa 233 have been reported; however the immunomodulatory effects of ECa 233 on regulatory T cells,...

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Main Authors: Supannikar Tawinwung, Dhirarin Junsaeng, Supanut Utthiya, Phisit Khemawoot
Format: Article
Language:English
Published: BMC 2021-09-01
Series:BMC Complementary Medicine and Therapies
Online Access:https://doi.org/10.1186/s12906-021-03394-z
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spelling doaj-6ef282c9989a47bd8e499e0690100eef2021-09-05T11:46:31ZengBMCBMC Complementary Medicine and Therapies2662-76712021-09-0121111010.1186/s12906-021-03394-zImmunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in ratsSupannikar Tawinwung0Dhirarin Junsaeng1Supanut Utthiya2Phisit Khemawoot3Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityDepartment of Clinical Pharmacokinetics, Graduate School of Medical Sciences, Kanazawa UniversityDepartment of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn UniversityChakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol UniversityAbstract Background ECa 233 is a standardized extract of C. asiatica containing the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.5):1. Anti-inflammatory activities of ECa 233 have been reported; however the immunomodulatory effects of ECa 233 on regulatory T cells, which have a pivotal role in immune regulation, has not been elucidated. Therefore, we investigated the effects of ECa 233 on regulatory T cells that may provide benefits in autoimmune and chronic inflammatory diseases. Methods ECa 233 was prepared as oral suspension in 0.5% carboxymethylcellulose and administered to male Wistar rats via oral gavage. The pharmacokinetics and toxicity of ECa 233 were evaluated. Splenic lymphocytes were isolated and analyzed by flow cytometry and qPCR to determine the immunomodulatory effects of ECa 233 on regulatory T cells. Results All rats had good tolerability to ECa 233 and other test preparations. The pharmacokinetic study showed low oral bioavailability for both triterpenoids, with the maximum plasma concentration reached at 4 h for asiaticoside and at 0.5 h for madecassoside. Multiple oral administration of ECa 233 reduced the frequency of T cells, particularly CD8 T cells in rats. ECa 233 enhanced the percentage of regulatory T cells, characterized by high expression of CD25+ and upregulation of FoxP3 gene. Conclusions The present study demonstrated that ECa 233 possesses immunosuppressive properties by enhancing regulatory T cells. These results provide in vivo evidence for the anti-inflammatory action of ECa 233, in line with previously reports, and the potential uses of ECa 233 in the treatment of chronic inflammatory and autoimmune diseases.https://doi.org/10.1186/s12906-021-03394-z
collection DOAJ
language English
format Article
sources DOAJ
author Supannikar Tawinwung
Dhirarin Junsaeng
Supanut Utthiya
Phisit Khemawoot
spellingShingle Supannikar Tawinwung
Dhirarin Junsaeng
Supanut Utthiya
Phisit Khemawoot
Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
BMC Complementary Medicine and Therapies
author_facet Supannikar Tawinwung
Dhirarin Junsaeng
Supanut Utthiya
Phisit Khemawoot
author_sort Supannikar Tawinwung
title Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
title_short Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
title_full Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
title_fullStr Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
title_full_unstemmed Immunomodulatory effect of standardized C. asiatica extract on a promotion of regulatory T cells in rats
title_sort immunomodulatory effect of standardized c. asiatica extract on a promotion of regulatory t cells in rats
publisher BMC
series BMC Complementary Medicine and Therapies
issn 2662-7671
publishDate 2021-09-01
description Abstract Background ECa 233 is a standardized extract of C. asiatica containing the triterpenoid glycosides, madecassoside to asiaticoside in the ratio of (1.5 ± 0.5):1. Anti-inflammatory activities of ECa 233 have been reported; however the immunomodulatory effects of ECa 233 on regulatory T cells, which have a pivotal role in immune regulation, has not been elucidated. Therefore, we investigated the effects of ECa 233 on regulatory T cells that may provide benefits in autoimmune and chronic inflammatory diseases. Methods ECa 233 was prepared as oral suspension in 0.5% carboxymethylcellulose and administered to male Wistar rats via oral gavage. The pharmacokinetics and toxicity of ECa 233 were evaluated. Splenic lymphocytes were isolated and analyzed by flow cytometry and qPCR to determine the immunomodulatory effects of ECa 233 on regulatory T cells. Results All rats had good tolerability to ECa 233 and other test preparations. The pharmacokinetic study showed low oral bioavailability for both triterpenoids, with the maximum plasma concentration reached at 4 h for asiaticoside and at 0.5 h for madecassoside. Multiple oral administration of ECa 233 reduced the frequency of T cells, particularly CD8 T cells in rats. ECa 233 enhanced the percentage of regulatory T cells, characterized by high expression of CD25+ and upregulation of FoxP3 gene. Conclusions The present study demonstrated that ECa 233 possesses immunosuppressive properties by enhancing regulatory T cells. These results provide in vivo evidence for the anti-inflammatory action of ECa 233, in line with previously reports, and the potential uses of ECa 233 in the treatment of chronic inflammatory and autoimmune diseases.
url https://doi.org/10.1186/s12906-021-03394-z
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