Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer׳s patches of rats with adjuvant induced arthritis

Xiong, Ying; Ma, Yan; Han, Wei; Kodithuwakku, Nandani Darshika; Liu, Lifang; Li, Fengwen; Fang, Weirong; Li, Yunman

doi:10.1016/j.jep.2014.07.028

Cited by 19 publications

(10 citation statements)

References 43 publications

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“…C-AR suppressed TGF-β1 and α-SMA induction, and thus prevented ECM deposits in the synovium. C-AR is documented to exert anti-inflammatory activity in RA rats (22, 23); the present work further showed that C-AR reduced ECM deposits via suppression of myofibroblast activation, elucidating the special role of C-AR in anti-fibrosis.…”

Section: Discussionsupporting

confidence: 72%

“…C-AR reduced succinate accumulation and inhibited HIF-1α induction, thereby preventing NLRP3 inflammasome activation in the synovium of RA rats. Previous works demonstrated the anti-inflammatory effects of C-AR on RA rats (22, 23), and our work indicated that suppression of inflammasome activation should be the unifying mechanism for the same action.…”

Section: Discussionsupporting

confidence: 71%

“…After that, rats were administrated with C-AR (50 mg/kg, by gavage) or digoxin (100 μg/kg, by intraperitoneal injection) once a day for 2 weeks. The choice of dosage value for C-AR was based on the published reports (22, 23). Normal and model rats were orally given an equal volume of distilled water in parallel.…”

Section: Methodsmentioning

confidence: 99%

“…(Wei Ling Xian) has been used for the treatment of arthritis in traditional Chinese medicine with a prevalent clinical practice in many formulae defined in the Chinese Pharmacopoeia (2015 edition) and C-AR is considered the effective component for the treatment of RA (21). Previous study showed that C-AR exerts anti-inflammatory and immunosuppressive properties and ameliorate collagen-induced arthritis (CIA) in rats (22, 23). But up to now, little is known about its molecular targets and working pathways in the prevention of fibrosis.…”

Section: Introductionmentioning

confidence: 99%

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Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

Zheng

Liu

et al. 2016

Front. Immunol.

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Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppression of fibroblast activation. Low oxygen tension and transforming growth factor-β (TGF-β1) induction in the synovium contribute to fibrosis in arthritis. This study was designed to investigate the effect of C-AR on synovial fibrosis from the aspects of hypoxic TGF-β1 and hypoxia-inducible transcription factor-1α (HIF-1α) induction. In the synovium of rheumatoid arthritis (RA) rats, hypoxic TGF-β1 induction increased succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation and induced NLRP3 inflammasome activation in a manner dependent on HIF-1α induction. In response to NLRP3 inflammasome activation, the released IL-1β further increased TGF-β1 induction, suggesting the forward cycle between inflammation and fibrosis in myofibroblast activation. In the synovium of RA rats, C-AR inhibited hypoxic TGF-β1 induction and suppressed succinate-associated NLRP3 inflammasome activation by inhibiting SDH activity, and thereby prevented myofibroblast activation by blocking the cross-talk between inflammation and fibrosis. Taken together, these results showed that succinate worked as a metabolic signaling, linking inflammation with fibrosis through NLRP3 inflammasome activation. These findings suggested that synovial succinate accumulation and HIF-1α induction might be therapeutical targets for the prevention of fibrosis in arthritis.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionsupporting

confidence: 71%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

Zheng

Liu

et al. 2016

Front. Immunol.

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“…As a bacterial cell membrane component, LPS administration in mice is known to induce the production of numerous proinflammatory cytokines [9,10] and mimic the pathological conditions of ALI. Traditional Chinese medicine has been used by almost one-fifth of the world's population since ancient times, and it is an important source of pharmaceutical remedies [11,12]. Bleomycin (BLE) is a drug for the treatment of a variety of human malignancies [13].…”

Section: Contents Lists Available At Sciencedirectmentioning

confidence: 99%

Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro

Tao

Wang

et al. 2015

International Immunopharmacology

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Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

Zhang

2019

Phytotherapy Research

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Rheumatoid arthritis (RA) is a systemic disease characterized by autoimmunity, joint inflammation, and cartilage destruction, which affects 0.5–1% of the population. Many compounds from herbal medicines show the potentials to treat RA. On this basis, the compounds with good pharmacokinetic behaviors and drug‐likeness properties will be further studied and developed. Therefore, the herbal compounds with anti‐RA activities were reviewed in this paper, and the cheminformatics tools were used to predict their drug‐likeness properties and pharmacokinetic parameters. A total of 90 herbal compounds were analyzed, which were reported to be effective on RA models through anti‐inflammation, chondroprotection, immunoregulation, antiangiogenesis, and antioxidation. Most of the herbal compounds have good drug‐likeness properties. Most of the compounds can be an alternative and valuable source for anti‐RA drug discovery.

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Clematichinenoside AR induces immunosuppression involving Treg cells in Peyer׳s patches of rats with adjuvant induced arthritis

Cited by 19 publications

References 43 publications

Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects of Clematichinenoside AR on Arthritis

Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro

Herbal compounds for rheumatoid arthritis: Literatures review and cheminformatics prediction

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