中国临床药理学与治疗学 ›› 2026, Vol. 31 ›› Issue (7): 965-974.doi: 10.12092/j.issn.1009-2501.2026.07.013
徐茜茜1(
), 汪清2, 史元元3, 王巧雪1, 龙桓1,*()
收稿日期:2025-02-28
修回日期:2025-04-17
出版日期:2026-07-26
发布日期:2026-08-04
通讯作者:
龙桓
E-mail:xxx_ciccy@163.com;longh10@seu.edu.cn
作者简介:徐茜茜，女，硕士，药师，研究方向：中药抗类风湿关节炎作用机理研究。E-mail：基金资助:
Xixi XU1(), Qing WANG2, Yuanyuan SHI3, Qiaoxue WANG1, Huan LONG1,*()
Received:2025-02-28
Revised:2025-04-17
Online:2026-07-26
Published:2026-08-04
Contact:
Huan LONG
E-mail:xxx_ciccy@163.com;longh10@seu.edu.cn
摘要：
类风湿关节炎是一种慢性、进行性自身免疫性疾病，疾病发展后期可导致关节肿胀、畸形及功能丧失，严重影响患者生活质量。近年研究表明，细胞焦亡在类风湿关节炎的发病机制中发挥关键作用。细胞焦亡由炎症小体激活引发，通过调控促炎因子释放和免疫细胞活化，参与类风湿关节炎的免疫炎性反应。中医药以其多靶点、多途径的作用特点，可有效调节类风湿关节炎相关的细胞焦亡过程。本文系统综述了细胞焦亡在类风湿关节炎发生发展中的重要作用、研究进展，以及中药对类风湿关节炎疾病相关细胞焦亡的调控机制，旨在为深入阐明类风湿关节炎发病机制和开发中药新型治疗靶点提供理论依据。
中图分类号:
徐茜茜, 汪清, 史元元, 王巧雪, 龙桓. 中药调控细胞焦亡治疗类风湿关节炎研究进展[J]. 中国临床药理学与治疗学, 2026, 31(7): 965-974.
Xixi XU, Qing WANG, Yuanyuan SHI, Qiaoxue WANG, Huan LONG. Research progress in traditional Chinese medicine regulating pyroptosis for treating rheumatoid arthritis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2026, 31(7): 965-974.
图 1
Fig.1 Primary molecular mechanisms by which traditional Chinese medicine (TCM) alleviates rheumatoid arthritis by regulating pyroptosis. In the schematic diagram, TCM1 that targets TLR4 includes the monomer derivative of paeoniflorin, mangiferin, cinnamic acid, Baihu-Guizhi decoction and Gancao-Fuzi decoction. TCM2 that inhibits the phosphorylation of NF-κB represents isochlorogenic acid A. TCM3 that targets NLRP3 includes punicalagin, berberine, wogonin, luteolin, icariin, Duanteng Yimu decoction, Qingre Huoxue formula, Duhuo Jisheng decoction, Bitongqing decoction, Sishen decoction, Xinfeng capsule and Wanbiqing pills. TCM4 that decreases the expression of Caspase-1, 4, 5 represents Jinwujiangu capsule. TCM1, TCM2 and TCM3 regulate pyroptosis through the classical pyroptosis pathway, while TCM4 regulates pyroptosisthrough both the classical and non-classical pyroptosis pathway.
| No. | Compounds | Description | Model | Treatment | Mechanism | References |
| 1 | Punicalagin | Pomegranate peel | CIA mice | 10 and 20 mg·kg?1·d?1, i.p. | (1) Downregulate the expression of NLRP3 and caspase-1, (2) Decrease the expression of iNOS and proinflammatory cytokines released by M1 macrophages, and increase the expression of Arg-1 and IL-10 released by M2 macrophages. | [ |
| 2 | The monomer derivative of paeoniflorin | Paeoniflorin | AIA rats | 50 mg·kg?1·d?1, i.g. | Decrease the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage, down-regulate the cytokine levels of IL-18 and IL-1β, and regulate the M1/M2 ratio. | [ |
| 3 | Mangiferin and cinnamic acid | Baihu-Guizhi decoction | AIA-M rats, RAW264.7 cells, MH7A cells | Animal assay: mangiferin 600.912 mg·kg?1·d?1, i.g. cinnamic acid 46.652 mg·kg?1·d?1, i.g. Cell assay: mangiferin 1.69 ng/mL and cinnamic acid 0.13 ng/mL for 24 h | Inhibit NF-kB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream Caspase-1, the reduced release of IL-1β and IL-18. | [ |
| 4 | Berberine | Coptis chinensis | CIArats, MH7A cells | Animal assay: 200 mg·kg?1·d?1, i.g. Cell assay: 10 μmol/L | (1) Inhibit RA-FLS pyroptosis by downregulating of NLRP3 and Caspase-1, (2) ease the pro-inflammatory activities via activating the Hippo signaling pathway. | [ |
| 5 | Wogonin | Scutellaria baicalensis | CIA rats | 50, 100 and 200 mg·kg?1·d?1, i.g. | Reduce the expression of NLRP3, pro-Caspase-1, Caspase-1 protein, and reduce the levels of IL-1β, TNF-α and IL-18. | [ |
| 6 | Luteolin | Honeysuckle and selfheal, et al. | CIA rats | 100 mg·kg?1·d?1, i.g. | Decrease the expression of NLRP3, Caspase-1, RANKL, VEGF, HIF-1α protein in voix pedis and enhance the expression of OPG protein in bone tissue. | [ |
| 7 | Isochlorogenic acid A | Honeysuckle et al. | CIA rats | 50 and 100 mg·kg?1·d?1, i.g. | Decrease the phosphorylation of NF-κB to reduce the expression of NLRP3 and Caspase-1, and reduce the levels of IL-1β, TNF-α and IL-18. | [ |
| 8 | Icariin | Epimedium | CIA mice | 10, 20 and 40 mg·kg?1·d?1, i.g. | Decrease the expression of NLRP3, Caspase-1, and inhibit the activation of NLRP3 inflammasomes, while inhibiting the expression of IL-1β and IL-18. | [ |
表 1
Table 1 Chinese herbal compounds for improving RA by regulating pyroptosis
| No. | Compounds | Description | Model | Treatment | Mechanism | References |
| 1 | Punicalagin | Pomegranate peel | CIA mice | 10 and 20 mg·kg?1·d?1, i.p. | (1) Downregulate the expression of NLRP3 and caspase-1, (2) Decrease the expression of iNOS and proinflammatory cytokines released by M1 macrophages, and increase the expression of Arg-1 and IL-10 released by M2 macrophages. | [ |
| 2 | The monomer derivative of paeoniflorin | Paeoniflorin | AIA rats | 50 mg·kg?1·d?1, i.g. | Decrease the expressions of TLR4, MyD88, NLRP3, Caspase-1, ASC, and GSDMD-N in macrophage, down-regulate the cytokine levels of IL-18 and IL-1β, and regulate the M1/M2 ratio. | [ |
| 3 | Mangiferin and cinnamic acid | Baihu-Guizhi decoction | AIA-M rats, RAW264.7 cells, MH7A cells | Animal assay: mangiferin 600.912 mg·kg?1·d?1, i.g. cinnamic acid 46.652 mg·kg?1·d?1, i.g. Cell assay: mangiferin 1.69 ng/mL and cinnamic acid 0.13 ng/mL for 24 h | Inhibit NF-kB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream Caspase-1, the reduced release of IL-1β and IL-18. | [ |
| 4 | Berberine | Coptis chinensis | CIArats, MH7A cells | Animal assay: 200 mg·kg?1·d?1, i.g. Cell assay: 10 μmol/L | (1) Inhibit RA-FLS pyroptosis by downregulating of NLRP3 and Caspase-1, (2) ease the pro-inflammatory activities via activating the Hippo signaling pathway. | [ |
| 5 | Wogonin | Scutellaria baicalensis | CIA rats | 50, 100 and 200 mg·kg?1·d?1, i.g. | Reduce the expression of NLRP3, pro-Caspase-1, Caspase-1 protein, and reduce the levels of IL-1β, TNF-α and IL-18. | [ |
| 6 | Luteolin | Honeysuckle and selfheal, et al. | CIA rats | 100 mg·kg?1·d?1, i.g. | Decrease the expression of NLRP3, Caspase-1, RANKL, VEGF, HIF-1α protein in voix pedis and enhance the expression of OPG protein in bone tissue. | [ |
| 7 | Isochlorogenic acid A | Honeysuckle et al. | CIA rats | 50 and 100 mg·kg?1·d?1, i.g. | Decrease the phosphorylation of NF-κB to reduce the expression of NLRP3 and Caspase-1, and reduce the levels of IL-1β, TNF-α and IL-18. | [ |
| 8 | Icariin | Epimedium | CIA mice | 10, 20 and 40 mg·kg?1·d?1, i.g. | Decrease the expression of NLRP3, Caspase-1, and inhibit the activation of NLRP3 inflammasomes, while inhibiting the expression of IL-1β and IL-18. | [ |
| NO. | Chinese herbal formulas | Model | Treatment | Mechanism | References |
| 1 | Baihu-Guizhi decoction | AIA-M rats, RAW264.7 cells, MH7A cells | Animal assay: 21.4 g·kg?1·d?1, i.g. Cell assay: 28.54 mg/mL for 24 h | Inhibit NF-kB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream Caspase-1, the reduced release of IL-1β and IL-18. | [ |
| 2 | Duanteng Yimu decoction | RA mice chondrocyte | 6, 12 and 24 μg/mL for 24 h | Decrease the expression of HMGB1 and NLRP3 in RA chondrocytes, and decrease mRNA expressions of Caspase-1, IL-1β and IL-18. | [ |
| 3 | Gancao-Fuzi decoction | CIA rats | 4, 8 and 16 g·kg?1·d?1, i.g. | Inhibit the protein expression of TLR4, cleaved Caspase-1, NLRP3, GSDMD-N, IL-1β, IL-6 in CIA rats, and increase the expression of IL-10. | [ |
| 4 | Qingre Huoxue formula | CIA rats | 8.5, 17 and 34 g·kg?1·d?1, i.g. | Down-regulate the expression of NLRP3/Caspase-1/GSDMD mRNA in the cell pyroptosis pathway and reduce the release of IL-1β and IL-18 inflammatory factors. | [ |
| 5 | Sidaxue | MH7A cells | 5, 10, 20 and 40 mg/L for 24 h | Down-regulate the expressions of TNF-α, IL-1β and IL-18, up-regulate the expressions of Bax, Fas, and FasL, and inhibit Bcl-2 and caspase-1 protein expressions. | [ |
| 6 | Duhuo Jisheng decoction | AIA rats chondrocyte | Drug serum | Down-regulate the mRNA and protein level of NLRP3, Caspase-1, ASC, IL-1β and IL-18 in RA model chondrocyte cells via NLRP3/Caspase-1 signaling. | [ |
| 7 | Bitongqing decoction | CIA rats, RAW264.7 cells | Animal assay: 9.68, 19.35 and 38.7 g·kg?1·d?1, i.g. Cell assay: 5, 10 and 15% drug serum | Suppress the expression of proteins in the NLRP3/Caspase-1/GSDMD pathway, and reduce the levels of IL-1β and IL-18. | [ |
| 8 | Sishen decoction | AIA rats | 4.5, 9 and 18 g·kg?1·d?1, i.g. | Inhibit ASIC1a/NLRP3 pathway activation, and decrease the expression of NLRP3, ASC and Caspase-1. | [ |
| 9 | Xinfeng capsule | RA-FLS | 20% drug serum | Alleviate inflammatory response of joints in RA by inhibiting pyroptosis of the FLS through inhibition of the NLRP3/GSDMD pathway. | [ |
| 10 | Wanbiqing pills | RA patients with damp-heat obstruction syndrome | 12 g/d for 4 weeks, p.o. | Inhibit the expression of NLRP3, Caspase-1, IL-1β and IL-18 mRNA, and reduce the inflammatory response. | [ |
| 11 | Jinwujiangu capsule | New Zealand White rabbits; RA-FLS cells | Animal assay: 7.29 g?1·kg·d?1, i.g. Cell assay：5%, 15% and 20% drug serum | Down-regulate the expression of Caspase-1, 3, 4, 5, GSDMD, NLRP3, ASC, IL-1β, IL-18, and downregulate the number of double-positive FITC anti-caspase-1 and PI. | [ |
表 2
Table 2 Chinese herbal formulas for improving RA by regulating pyroptosis
| NO. | Chinese herbal formulas | Model | Treatment | Mechanism | References |
| 1 | Baihu-Guizhi decoction | AIA-M rats, RAW264.7 cells, MH7A cells | Animal assay: 21.4 g·kg?1·d?1, i.g. Cell assay: 28.54 mg/mL for 24 h | Inhibit NF-kB via TLR4/PI3K/AKT signaling to suppress the activation of the NLRP3 inflammasome, leading to the downregulation of downstream Caspase-1, the reduced release of IL-1β and IL-18. | [ |
| 2 | Duanteng Yimu decoction | RA mice chondrocyte | 6, 12 and 24 μg/mL for 24 h | Decrease the expression of HMGB1 and NLRP3 in RA chondrocytes, and decrease mRNA expressions of Caspase-1, IL-1β and IL-18. | [ |
| 3 | Gancao-Fuzi decoction | CIA rats | 4, 8 and 16 g·kg?1·d?1, i.g. | Inhibit the protein expression of TLR4, cleaved Caspase-1, NLRP3, GSDMD-N, IL-1β, IL-6 in CIA rats, and increase the expression of IL-10. | [ |
| 4 | Qingre Huoxue formula | CIA rats | 8.5, 17 and 34 g·kg?1·d?1, i.g. | Down-regulate the expression of NLRP3/Caspase-1/GSDMD mRNA in the cell pyroptosis pathway and reduce the release of IL-1β and IL-18 inflammatory factors. | [ |
| 5 | Sidaxue | MH7A cells | 5, 10, 20 and 40 mg/L for 24 h | Down-regulate the expressions of TNF-α, IL-1β and IL-18, up-regulate the expressions of Bax, Fas, and FasL, and inhibit Bcl-2 and caspase-1 protein expressions. | [ |
| 6 | Duhuo Jisheng decoction | AIA rats chondrocyte | Drug serum | Down-regulate the mRNA and protein level of NLRP3, Caspase-1, ASC, IL-1β and IL-18 in RA model chondrocyte cells via NLRP3/Caspase-1 signaling. | [ |
| 7 | Bitongqing decoction | CIA rats, RAW264.7 cells | Animal assay: 9.68, 19.35 and 38.7 g·kg?1·d?1, i.g. Cell assay: 5, 10 and 15% drug serum | Suppress the expression of proteins in the NLRP3/Caspase-1/GSDMD pathway, and reduce the levels of IL-1β and IL-18. | [ |
| 8 | Sishen decoction | AIA rats | 4.5, 9 and 18 g·kg?1·d?1, i.g. | Inhibit ASIC1a/NLRP3 pathway activation, and decrease the expression of NLRP3, ASC and Caspase-1. | [ |
| 9 | Xinfeng capsule | RA-FLS | 20% drug serum | Alleviate inflammatory response of joints in RA by inhibiting pyroptosis of the FLS through inhibition of the NLRP3/GSDMD pathway. | [ |
| 10 | Wanbiqing pills | RA patients with damp-heat obstruction syndrome | 12 g/d for 4 weeks, p.o. | Inhibit the expression of NLRP3, Caspase-1, IL-1β and IL-18 mRNA, and reduce the inflammatory response. | [ |
| 11 | Jinwujiangu capsule | New Zealand White rabbits; RA-FLS cells | Animal assay: 7.29 g?1·kg·d?1, i.g. Cell assay：5%, 15% and 20% drug serum | Down-regulate the expression of Caspase-1, 3, 4, 5, GSDMD, NLRP3, ASC, IL-1β, IL-18, and downregulate the number of double-positive FITC anti-caspase-1 and PI. | [ |
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