Accelerated and severe lupus nephritis benefits from M1, an active metabolite of ginsenoside, by regulating NLRP3 inflammasome and T cell functions in mice
Journal
Frontiers in Immunology
Journal Volume
10
Journal Issue
AUG
Date Issued
2019-01-01
Author(s)
Lin, Tsai Jung
Wu, Chung Yao
Tsai, Pei Yi
Hsu, Wan Han
Hua, Kuo Feng
Lee, Yu Chieh
Chen, Ann
Lee, Sheau Long
Lin, Yi Jin
Hsieh, Chih Yu
Yang, Shin Ruen
Liu, Feng Cheng
Ka, Shuk Man
Abstract
© 2019 Lin, Wu, Tsai, Hsu, Hua, Chu, Lee, Chen, Lee, Lin, Hsieh, Yang, Liu and Ka. Chinese herbal medicines used in combination have long-term been shown to be mild remedies with “integrated effects.” However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.
Subjects
Active metabolite of ginsenoside | Autophagy | Lupus nephritis | NLRP3 inflammasome | Regulatory T cell
SDGs
Publisher
FRONTIERS MEDIA SA
Type
journal article