Intestinal interleukin-10 mobilization as a contributor to the anti-arthritis effect of orally administered madecassoside: A unique action mode of saponin compounds with poor bioavailability

被引：23

作者：

Wang, Ting ^{[1
]}

Wei, Zhifeng ^{[1
]}

Dou, Yannong ^{[1
]}

Yang, Yan ^{[1
]}

Leng, Dandan ^{[1
]}

Kong, Lingyi ^{[2
]}

Dai, Yue ^{[1
]}

Xia, Yufeng ^{[1
]}

机构：

[1] China Pharmaceut Univ, Dept Pharmacol Chinese Mat Med, Jiangsu Key Lab Drug Discovery Metab Dis, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Dept Nat Med Chem, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2015年 / 94卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Madecassoside; Rheumatoid arthritis; Pharmacokinetics-pharmacodynamics discrepancy; Small intestine; Interleukin-10; COLLAGEN-INDUCED ARTHRITIS; REGULATORY T-CELLS; RHEUMATOID-ARTHRITIS; HERBAL MEDICINES; RATS; DISEASE; MICE; PHARMACOKINETICS; MECHANISMS; IL-10;

D O I：

10.1016/j.bcp.2015.01.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Madecassoside, a triterpenoid saponin present in Centella asiatica herbs with extremely low bioavailability, possesses excellent anti-rheumatoid arthritis property after oral administration. Such a disconnection between poor pharmacokinetic property and undoubted bioactivity also exists in many other herbal medicines. However, there is no reasonable explanation for this phenomenon to date. Here we showed that orally administered madecassoside displayed marked therapeutic effect on collagen-induced arthritis (CIA) in rats, which was accompanied by a systemic downregulation of inflammatory cytokines and an upregulation of anti-inflammatory cytokine IL-10. In vitro assays demonstrated that neither madecassoside nor its main metabolite madecassic acid could directly interfere with the secretion of inflammatory cytokines and IL-10. Intraperitoneal injection of madecassoside or madecassic acid was absent of significant effects on CIA progression, which further excluded the possibility of systemic action and highlighted the indispensable role of intestinal tracts. Notably, madecassoside could dramatically enhance the secretion of IL-10 from the small intestine of CIA rats probably through increasing the number of Foxp3(+) T lymphocytes in the lamina propria. In conclusion, madecassoside displays anti-arthritis property not by absorption into blood or by its metabolite, but through an intestine-dependent manner. The action can be mediated by, at least partially, the mobilization of IL-10 that originates from small intestines. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：30 / 38

页数：9