Polysaccharide extract from Isatidis Radix inhibits multiple inflammasomes activation and alleviate gouty arthritis

Abstract

The polysaccharide extract from Isatidis Radix exhibits potent antiinflammatory and antiviral activities, but the mechanism of Isatidis Radix polysaccharide (IRP) remains obscure. Herein, we reported that IRP blocked the activation of nod‐like receptor pyrin domain‐containing 3 (NLRP3) inflammasome, leading to the inhibiting of caspase‐1 cleavage and IL‐1β secretion. Mechanistically, IRP did not inhibit NLRP3 inflammasome through suppressing mitochondrial reactive oxygen species (mtROS) production. However, IRP can significantly suppress the oligomerization of apoptosis‐associated speck‐like protein (ASC) and subsequently block the formation of inflammasome. Next, we evaluate the role of IRP in monosodium urate (MSU)‐induced gout in vivo which is a NLRP3‐associated disease. We also observed that oral administration of IRP can reduce the increased ankle thickness and the secretion of IL‐1β, IL‐18, IL‐6, TNF‐α and MPO of the mouse ankle joints caused by MSU crystals. Furthermore, flow cytometry analysis highlighted a significant modulation of T helper 17 cells (Th17)/regulatory T cells (Treg) following IRP treatment in MSU induced gout. Overall, our findings suggest that IRP has comprehensive and potent antiinflammatory effects and provide a reasonable therapeutic strategy in preventing inflammasome‐associated diseases, such as inflammatory gouty arthritis.

Effects and Mechanisms of Traditional Chinese Medicine and Related Active Constituents Treating Gout

“…Under in vitro conditions, IRP can inhibit caspase-1 cleavage and IL-1β secretion by blocking NLRP3 inflammasome activation. Under in vivo conditions, IRP can alleviate joint swelling caused by MSU crystals in mice and reduce the secretion of MPO, IL-6, IL-18, and IL-1β in the swollen joints [77].…”

Role of NLRP3 in the pathogenesis and treatment of gout arthritis

“…The experimental study showed that Madecassoside alleviated MSU-triggered pad swelling, joint 99mTc uptake, and joint inflammation, which was accompanied with decreased expression of caspase-1, IL-1β and NLRP3 ( 100 ). The polysaccharide, extracted from Isatidis Radix , has a positive effect on alleviating GA. Mechanistically, polysaccharide suppressed the oligomerization of ASC and subsequently blocked the formation of NLRP3 inflammasome, which probably lead to the decreased ankle thickness and IL-1β, IL-18, IL-6, TNF-α and MPO secretion ( 101 ). Dioscin, an active ingredient, has been reported to have a protective effect against MSU-mediated inflammatory response in GA mouse model through inhibiting NLRP3 inflammasome and TLR4/NF-κB signaling pathway activation ( 102 ).…”

TCM and related active compounds in the treatment of gout: the regulation of signaling pathway and urate transporter

“…This modulation aids in alleviating symptoms linked to MSU-induced gouty arthritis, such as neutrophil infiltration in knee joints, joint circumference and the production of TNF-α, IL-1β, IL-6, and IL-18. This effective inhibition of the NLRP3 signaling pathway is facilitated by this approach ( Ren et al, 2022 ). Furthermore, palmatine ( Cheng et al, 2022 ), rhein ( Chang et al, 2019 ), berberine ( Zheng et al, 2023 ), dihydroberberine ( Xu et al, 2021 ), celastrol ( Yan et al, 2021 ), tanshinone IIA ( Xu et al, 2022b ), total saponin of Dioscorea polystachya Turcz.…”

“…Through its modulation of the NLRP3 signaling pathway, scutellarin can enhance renal damage caused by UA (Li et al, 2020b). Tetrahydropalmatine, a primary bioactive compound with analgesic, anti-addictive, anti-inflammatory, neuroprotection, and anticancer activities (Du et al, 2022) approach (Ren et al, 2022). Furthermore, palmatine (Cheng et al, 2022), rhein (Chang et al, 2019), berberine (Zheng et al, 2023), dihydroberberine (Xu et al, 2021), celastrol (Yan et al, 2021), tanshinone IIA (Xu et al, 2022b), total saponin of Dioscorea polystachya Turcz.…”