Er Miao San, a traditional Chinese herbal formula, attenuates complete Freund’s adjuvant-induced arthritis in rats by regulating Th17/Treg cells

Dai, Xing; Yang, Dongpeng; Bao, Jianchun; Zhang, Qiying; Ding, Jiemin; Liu, Min; Ding, Meihuizi; Liu, Mengli; Liang, Juan Boo; Jia, Xiaoyi

doi:10.1080/13880209.2020.1720745

“…In the current study, the compound decoction added more 2 kinds of Chinese herbs on the basis of the above formula including Cortex phellodendri and Rhizoma Atractylodis to strengthen its power of dispelling wind, removing dampness, and clearing heat. Previous studies have proved that the combination of Cortex phellodendri and Rhizoma Atractylodis (Er-Miao-San) exhibits antiarthritic activity via regulating the balance of cytokines [ 32 , 33 ]. The major finding of our study was that Shentong Zhuyu Decoction can inhibit the inflammatory response, migration, and invasion and promote apoptosis of rheumatoid arthritis fibroblast-like synoviocytes via the MAPK p38/PPAR γ /CTGF pathway.…”

Section: Discussionmentioning

confidence: 99%

Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway

Han

¹

,

Wang

²

,

Meng

³

et al. 2021

BioMed Research International

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Introduction. The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. Materials and Methods. The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. Results. After treatment with Shentong Zhuyu Decoction medicated serum, the OD570 value, migrative and invasive abilities, and the secretion of IL-1β, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). Conclusions. Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.

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“…RA is the most prevalent chronic and long-term autoimmune inflammatory disease (Wang et al, 2017a;Li et al, 2019a;Saleem et al, 2020;Zhu et al, 2020). Although there are many anti-RA drugs in clinic, such as immunosuppressants, biological agents, DMARDs, steroidal drugs, and NSAIDs, most of them are associated with long-term adverse effects and costs (Li et al, 2019b;Dai et al, 2020;Zhu et al, 2020). In addition, the CFA-induced arthritis (AIA) model and the collagen-induced arthritis model are two typical preclinical experimental animal models of RA, and the former is a classic, easy-to-measure, short duration, reliable and reproducible test animal model, which is extensively used for the preclinical evaluation of anti-RA drugs since its pathological and morphological characteristics were similar to those of human RA Pan et al, 2017;Voon et al, 2017;Zhang et al, 2019;Saleem et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, the serum levels of these inflammatory mediators were determined by enzyme-linked immunosorbent assay (ELISA) kits (Lin et al, 2013;Wang et al, 2017a). Currently, immunosuppressants, biological agents and disease-modifying anti-rheumatic drugs (DMARDs), and steroidal and non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for the treatment of RA, but most of them display long-term adverse effects, toxicity and comorbidities (Dai et al, 2020;Li et al, 2019a, Li et al, 2019bRui et al, 2019). As a result of this, exploring effective and safe anti-RA drug candidates from natural products, especially traditional folk medicines, could be a momentous breakthrough.…”

Section: Introductionmentioning

confidence: 99%

Chemical Composition of Pterospermum heterophyllum Root and its Anti-Arthritis Effect on Adjuvant-Induced Arthritis in Rats via Modulation of Inflammatory Responses

Yang

¹

,

Liu

²

,

Fan

³

et al. 2020

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease without effective and beneficial drugs. Many traditional folk medicines have been proven to be effective in treating RA. Among these, the root of Pterospermum heterophyllum Hance has been widely used as a traditional remedy against RA in China, but there is no scientific basis yet. The aim of this study was to investigate for the first time the chemical compositions and therapeutic effect of P. heterophyllum on adjuvant-induced arthritis (AIA) model in rats. 73 compounds were identified from P. heterophyllum based on ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-qTOF-MS/MS), and flavonoids may be partly responsible for the major anti-arthritic effect. In parallel, the P. heterophyllum extract at 160, 320, and 640 mg/kg/day were orally administered to rats for 22 days after post-administration adjuvant. The results showed that P. heterophyllum remarkably ameliorated histological lesions of the knee joint, increased body weight growth, decreased arthritis score, reduced thymus and spleen indices in model rats. Moreover, P. heterophyllum treatment persuasively downregulated the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2), and observably upregulated IL-4 and IL-10 levels in model rats. These findings suggest that P. heterophyllum has a prominent anti-RA effect on AIA rats by modulating the inflammatory responses, and supports the traditional folk use of this plant.

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“…Previous research has shown that EMS water extract has a therapeutic effect on AA rats, significantly reducing the pathological index and paw swelling in rats with arthritis [12]. In order to further study the effective antiarthritis parts of EMS, these were extracted using different organic solvents, such as dichloromethane, ethyl acetate, chloroform, and petroleum ether.…”

Section: Discussionmentioning

confidence: 99%

The Protective Effects of the Ethyl Acetate Part of Er MiaoSan on Adjuvant Arthritis Rats by Regulating the Function of Bone Marrow‐Derived Dendritic Cells

Ding

¹

,

Liu

²

,

Xuan

³

et al. 2020

Evidence-Based Complementary and Alternative Medicine

Self Cite

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Aims. The aim of this study was to evaluate the protective effects of Er Miao San (EMS) and the regulative function of bone marrow-derived dendritic cells (BMDCs) on adjuvant arthritis (AA) in rats. Methods. The ethyl acetate part of EMS (3 g/kg, 1.5 g/kg, and 0.75 g/kg) was orally administered from day 15 after immunization to day 29. The polyarthritis index and paw swelling were measured, the ankle joint pathological changes were observed using hematoxylin-eosin (HE) staining, and the spleen and thymus index were determined. Moreover, T and B cell proliferation were determined using the CCK-8 assay. The expression of BMDC surface costimulatory molecules and inflammatory factors were determined using flow cytometry and ELISA kits, respectively. Results. Compared with the AA model rats, the ethyl acetate fraction of EMS obviously reduced paw swelling (from 1.0 to 0.7) and the polyarthritis index (from 12 to 9) P < 0.01 and improved the severity of histopathology P < 0.01 . The treatment using ethyl acetate fraction of EMS significantly reduced the spleen and thymus index P < 0.01 and inhibited T and B cell proliferation P < 0.01 . Moreover, EMS significantly modulated the expression of surface costimulatory molecules in BMDCs, including CD40, CD80, CD86, and major histocompatibility complex class II (MHC-II) P < 0.01 . The results also showed that the ethyl acetate part of EMS significant inhibited the levels of proinflammatory cytokines interleukin- (IL-) 23 tumor necrosis factor- (TNF-) α and inflammatory factor prostaglandin (PG) E2 in the supernatant of BMDCs. However, the level of anti-inflammatory cytokine IL-10 was significantly increased P < 0.01 . Conclusion. These results suggest that the ethyl acetate part of EMS has better protective effects on AA rats, probably by regulating the function of BMDCs and modulating the balance of cytokines.

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Er Miao San, a traditional Chinese herbal formula, attenuates complete Freund’s adjuvant-induced arthritis in rats by regulating Th17/Treg cells

Cited by 25 publications

References 24 publications

Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway

Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway

Chemical Composition of Pterospermum heterophyllum Root and its Anti-Arthritis Effect on Adjuvant-Induced Arthritis in Rats via Modulation of Inflammatory Responses

The Protective Effects of the Ethyl Acetate Part of Er MiaoSan on Adjuvant Arthritis Rats by Regulating the Function of Bone Marrow‐Derived Dendritic Cells

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