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Qianjinba is primarily cultivated in the southern regions of China and finds extensive use in traditional Chinese medicine (TCM) for conditions such as rheumatism, arthralgia, and gynecological ailments. It has been officially recognized as a protected variety of TCM by the state. The aim of this study was to investigate the therapeutic potential of Qianjinba polysaccharide (QJBDT) in treating rheumatoid arthritis (RA) in mice, along with a preliminary exploration of its mechanisms for inhibiting RA in these animals. Kunming mice (KM) were randomly divided into several groups, including a normal group, a model group (LPS group), low-dose, medium-dose, and high-dose QJBDT groups, as well as a positive control group (TGP group), each consisting of 10 mice. To induce inflammation and create an RA model, type II collagen was injected into the right hind foot joint. Following a 7-day modeling period, various concentrations of QJBDT and the positive control drug total glycoside of peony were administered via gavage once a day for 21 consecutive days. Throughout the study, we monitored and recorded the mice's weight, measured foot swelling, and assessed the arthritis index on a weekly basis. We also conducted pathological examinations of joint tissues and analyzed the signal pathway of p38 mitogen-activated protein kinase (MAPK) as well as the protein expression of nuclear factor NF-κB in the mice's right foot joint tissues. Additionally, we employed ELISA to detect the levels of interleukin-β (IL-β), IL-17, and tumor necrosis factor-α (TNF-α) in the mice's serum. The results of this study revealed that QJBDT effectively reduced the degree of foot swelling and the arthritis index in collagen-induced arthritis mice while improving their weight loss (P < 0.05). Furthermore, it alleviated the pathological damage observed in the mice's joints. Notably, the expression of transcription factors p38 and NF-κB proteins was down-regulated (P < 0.05), and the levels of inflammatory cytokines IL-β, IL-17, and TNF-α in the mice's serum were decreased (P < 0.05). In conclusion, this study demonstrated that polysaccharides could inhibit the expression of transcription factors p38 and NF-κB, reduce the production of inflammatory factors, and alleviate the progression of RA to a certain extent. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects the body. Periploca forrestii was a miao ethnic drug in China that was used to treat arthritis for hundreds of years. But, the therapeutic mechanism is so far unknown. Therefore, the chemical component and effect of Periploca forrestii on arthritis in rats were studied using HPLC-QTOF MS, micro-CT, and other experiments in this paper. Method: Male Sprague-Dawley rats were used to assess the in vivo activity. HPLC QTOF-MS was used to analyze the chemical profile of the P. forrestii (PF). Bovine type II collagen and Complete Freund's Adjuvant were used to stimulate and construct the collagen-induced arthritis (CIA) model. Three dosages of PF (100 mg/kg, 200 mg/kg, 400 mg/kg) were used to evaluate in vivo activity. Methotrexate was used as the positive drug. H/E staining and micro-CT methods were used to monitor the pathological changes of CIA rats. ELISA method was used to assess the serum level of immune- and inflammationrelated cytokines. Immunohistochemical experiments were used to test the gene expression in JAK and Nf-B pathways. Results: 42 compounds were identified from PF. PF administration lowered the increased spleen index compared with that of control and MTX groups, and partially restored body weight, reduced paw swelling, and arthritis score compared with the model group. Macroscopic assessment indicated inflamed paw with significant swelling in the model group, while the extent of inflammation and swelling was attenuated by both MTX and PF. H/E staining experiments demonstrated that pathological changes of synovial cells and infiltration of inflammatory cells were observed in the model group. In contrast, the MTX and PF treatment partially reversed these pathological changes. Micro-CT examination showed severe injuries and scars caused by inflammation for the model group, and in the high-dosage group (400 mg/kg) the inflammationcaused injuries and scars were dramatically ameliorated. Mechanism study showed that PF restored Nf-B phosphorylation and JAK2 expression compared with the model group. Conclusion: P. forrestii possesses a potent effect on CIA rats. Nf-B and JAK2 pathways are involved in its protective effect on CIA. [ABSTRACT FROM AUTHOR]

Background: Fufang Xiaohuoluo pill (FFXHL) is a commonly used prescription in clinical practice for treating rheumatoid arthritis in China, yet its specific mechanism remains unclear. This study aims to elucidate the pharmacological mechanisms of FFXHL using both in vivo and in vitro experiments. Methods: The collagen-induced arthritis (CIA) rat model was established to evaluate FFXHL's therapeutic impact. Parameters that include paw swelling, arthritis scores, and inflammatory markers were examined to assess the antiinflammatory and analgesic effects of FFXHL. Human fibroblast-like synoviocytes (MH7A cells) is activated by tumour necrosis factor-alpha (TNF-α) were used to explore the anti-inflammatory mechanism on FFXHL. Results: Our findings indicate that FFXHL effectively reduced paw swelling, joint pain, arthritis scores, and synovial pannus hyperplasia. It also lowered serum levels of TNF-α, interleukin-1β (IL1β), and interleukin-6 (IL-6). Immunohistochemical analysis revealed decreased expression of nuclear factor-kappa B (NF-κB) p65 in FFXHL-treated CIA rat joints. In vitro experiments demonstrated FFXHL's ability to decrease protein secretion of IL-1β and IL-6, suppress mRNAexpression of matrix metalloproteinases (MMP) -3, -9, and -13, reduce reactive oxygen species (ROS) levels, and inhibit NF-κB p65translocation in TNF-α stimulated MH7Acells. FFXHL also suppressed protein levels of extracellular signal-regulated kinase (ERK), c-Jun Nterminal kinase (JNK), p38 MAP kinase (p38), protein kinase B (Akt), p65, inhibitor of kappa B kinase α/β (IKKα/β), Toll-like receptor 4 (TLR4), and myeloid differentiation primary response 88 (MyD88) induced by TNF-α in MH7A cells. Conclusion: The findings imply that FFXHL exhibits significant anti-inflammatory and antiarthritic effects in both CIA rat models and TNF-α-induced MH7A cells. The potential mechanism involves the inactivation of TLR4/MyD88, mitogen-activated protein kinases (MAPKs), NF-κB, and Akt pathways by FFXHL. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by synovial inflammation and joint damage with complex pathological mechanisms. In recent years, many studies have shown that the dysregulation of intestinal mucosal immunity and the damage of the epithelial barrier are closely related to the occurrence of RA. Total glucosides of paeony (TGP) have been used clinically for the treatment of RA in China for decades, while the pharmacological mechanism is still uncertain. The purpose of this study was to investigate the regulatory effect and mechanism of TGP on intestinal immunity and epithelial barrier in RA model rats. The results showed that TGP alleviated immune hyperfunction by regulating the ratio of CD3+, CD4+ and CD8+ in different lymphocyte synthesis sites of the small intestine, including Peyer's patches (PPs), intraepithelial lymphocytes (IELs), and lamina propria lymphocytes (LPLs). Specially, TGP first exhibited immunomodulatory effects on sites close to the intestinal lumen (IELs and LPLs), and then on PPs far away from the intestinal lumen as the administration time prolonged. Meanwhile, TGP restores the intestinal epithelial barrier by upregulating the ratio of villi height (V)/crypt depth (C) and expression of tight junction proteins (ZO-1, occludin). Finally, the integrated analysis of metabolomics-network pharmacology was also used to explore the possible regulation mechanism of TGP on the intestinal tract. Metabolomics analysis revealed that TGP reversed the intestinal metabolic profile disturbance in CIA rats, and identified 32 biomarkers and 163 corresponding targets; network pharmacology analysis identified 111 potential targets for TGP to treat RA. By intersecting the results of the two, three key targets such as ADA, PNP and TYR were determined. Pharmacological verification experiments showed that the levels of ADA and PNP in the small intestine of CIA rats were significantly increased, while TGP significantly decreased their ADA and PNP levels. In conclusion, purine metabolism may play an important role in the process of TGP improving RA-induced intestinal immune imbalance and impaired epithelial barrier. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis (RA) is an autoimmune disease that seriously affects the patient's quality of life. Total glucosides of peony (TGP) have long been used to treat RA in China despite the need for long-term administration. The main active ingredients in TGP are paeoniflorin (PF) and albiflorin (AF). This study aimed to clarify the effective mechanism of TGP only after long-term administration, and the pharmacokinetics of PF and AF following single and chronic oral TGP administration in collagen-induced arthritic (CIA) and normal rats. Materials and Methods: Comparative pharmacokinetic studies of TGP were conducted in male Sprague Dawley rats. Plasma concentrations of PF and AF were determined with ultra-high performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). DAS software was used to estimate pharmacokinetic parameters. Results: Bimodal phenomenon was observed. After a single TGP dose, the absorption of AF and PF were both lower in CIA rats compared to control rats. Compared with single-dose groups, the absorption of AF and PF in CIA rats increased after long-term administration of TGP. No significant differences were seen between the groups after chronic administration in low-dose groups in normal rats. Conclusion: We found that after long-term administration of TGP, the absorption of PF and AF are promoted in CIA rats. These results, combined with the existing literature, may help substantiate the TGP-related changes in gut microbiota. [ABSTRACT FROM AUTHOR]

Background: Wutou Decoction (WTD), as a classic prescription, has been generally used to treat rheumatoid arthritis (RA) for two thousand years in China. However, the potential protective effects of WTD on rheumatoid arthritis and its possible mechanism have rarely been reported. Purpose: The aim of this study was to explore the possible mechanism of WTD against RA and a promising alternative candidate for RA therapy. Methods: A model of collagen-induced arthritis (CIA) was constructed in rats to assess the therapeutic effects of WTD. Histopathological staining, immunofluorescence, and western blotting of synovial sections were conducted to detect the antiangiogenic effects of WTD. Then, cell viability assays, flow cytometry, scratch healing assays, and invasion assays were conducted to explore the effects of WTD on MH7A human fibroblast-like synoviocyte (FLS) cell proliferation, apoptosis, migration, and invasion in vitro. The ability of WTD to induce blood vessel formation after MH7A cell and human umbilical vein endothelial cell line (HUVEC) coculture with WTD intervention was detected by a tube formation assay. The mechanisms of WTD were screened by network pharmacology and confirmed by in vivo and in vitro experiments. Results: WTD ameliorated the symptoms and synovial pannus hyperplasia of CIA rats. Treatment with WTD inhibited MH7A cell proliferation, migration, and invasion and promoted MH7A apoptosis. WTD could inhibit MH7A cell expression of proangiogenic factors, including VEGF and ANGI, to induce HUVEC tube formation. Furthermore, the PI3K-AKT-mTOR-HIF-1α pathway was enriched as a potential target of WTD for the treatment of RA through network pharmacology enrichment analysis. Finally, it was confirmed in vitro and in vivo that WTD inhibits angiogenesis in RA by interrupting the PI3K-AKT-mTOR-HIF-1α pathway. Conclusion: WTD can inhibit synovial hyperplasia and angiogenesis, presumably by inhibiting the migration and invasion of MH7A cells and blocking the production of proangiogenic effectors in MH7A cells. The possible underlying mechanism by which WTD ameliorates angiogenesis in RA is the PI3K-AKT-mTOR-HIF-1α pathway. [ABSTRACT FROM AUTHOR]

Background: The bark of Securidaca inappendiculata Hassk. is traditionally used for treating inflammatory diseases and bone fractures in China. We have previously validated the xanthone-enriched fraction (XRF) of S. inappendiculata with anti-rheumatic potentials, but mechanism underlying the joints protective effects is still largely unknown. Materials and Methods: The male rats with collagen-induced arthritis (CIA) were treated with XRF. The therapeutic efficacy of XRF was evaluated by arthritis score changes, morphological observation of paws, histological examinations and serological analyses. Protein expression in tissues and cells was investigated by either immunohistochemical or immunoblotting methods, while levels of mRNA expression were investigated by RT-qPCR. Metabolites in serum were detected by LC-MS approach. The joints homogenates were used for analyzing possible targeted genes by genome microarray analyses. Results: Treatment with XRF and methotrexate (MTX) led to significant decrease in arthritis scores, and alleviated deformation of paws in CIA rats. In addition, XRF and MTX reduced circulating TNF-α, IL-1β and IL-17α in the serum and down-regulated TLR4/NF-κB and JNK pathways in joints of CIA rats. Compared to MTX, XRF-loading microemulsion significantly protected joints, which was accompanied by dramatic decrease in MMP3. Differential genes-based KEGG enrichment and metabolomics analysis suggested that XRF reduced fatty acids biosynthesis by regulating PPAR-γ signaling. S inappendiculata-derived 1,7-dihydroxy-3,4-dimethoxyxanthone (XAN) up-regulated PPAR-γ expression in macrophages, but suppressed it in pre-adipocytes in vitro, which was synchronized with SIRT1 changes. Adiponectin production and SCD-1 expression in pre-adipocytes were also decreased. Aside the direct inhibition on MMP3 expression in synovioblast, the presence of XAN in macrophages-pre-adipocytes co-culture system further reinforced this effect. Conclusion: This study revealed the joint protective  advantages of the bioactive fraction from S. inappendiculata in CIA rats over MTX, and demonstrated that S. inappendiculata-derived xanthones suppressed the erosive nature of synovioblast acquired under inflammatory circumstances by regulating PPAR-γ signaling-controlled metabolism-immunity feedback. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Munziq Balgam (MBm) is a classic preparation of a traditional Uyghur medicine used for many years to treat abnormal body fluid diseases. The formula, as an in-hospital preparation, has already been used in the Hospital of Xinjiang Traditional Uyghur Medicine to treat rheumatoid arthritis (RA) with significant clinical effects., Aim of the Study: This study intends to reveal the intervention effect of MBm on collagen-induced arthritis (CIA) rats, discover the potential biomarkers with efficacy, and explore the mechanisms of metabolic regulation by using metabolomics method., Material and Methods: Sprague Dawley (SD) rats were randomly divided into five groups: blank group, CIA model group, Munziq Balgam nomal-dosage, Munziq Balgam high-dosage group and control group. Body weight, paw swelling, arthritis index, immune indices and histopathological experiments were carried out. Plasma from rats were detected by UPLC-MS/MS. Metabolomics of plasma was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of MBm for CIA rats. The main metabolic result of Uyghur medicine MBm was compared with that of Zhuang medicine Longzuantongbi granules (LZTBG) to explore the characteristics of two ethnic medicines from different regions for RA., Results: MBm could significantly alleviate symptoms of CIA rats by relieving arthritis symptoms on paw redness and swelling, inflammatory cell infiltration, synovial hyperplasia, pannus, cartilage and bone tissue destruction, as well as inhibiting the expression of IL-1β, IL-6, TNF-α, UA and ALP. Linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, sphingolipid metabolism, primary bile acid biosynthesis, porphyrin and chlorophyll metabolism and fatty acid degradation served as the main nine pathways of the interventional effect of MBm on CIA rats. Twenty-three different metabolites were screened out and strongly associated with the indicator makes of RA. Eight potential efficacy-related biomarkers were finally discovered in metabolic pathway network (phosphatidylcholine, bilirubin, sphinganine 1-phosphate, phytosphingosine, SM (d18:1/16:0), pantothenic acid, l-palmitoylcarnitine, chenodeoxycholate). Three metabolites (chenodeoxycholate, hyodeoxycholic acid and O-palmitoleoylcarnitine) were changed in both the metabolic study of MBm and LZTBG intervention effects on CIA rats. Additionally, MBm and LZTBG shared the same 6 metabolic pathways including linoleic acid, alpha-linolenic acid, pantothenate and CoA biosynthesis, achidonic acid, gycerophospholipid, and primary bile acid biosynthesis., Conclusion: The study suggested that MBm may effectively alleviate RA by regulating inflammation, immunity-related pathways and multiple targets. Metabolomics analysis showed that MBm (Xinjiang, the north of China) and LZTBG (Guangxi, the south of China), two ethnic medicines from different regions in China, share common metabolites and pathways but also have distinct differences in their interventions for RA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To study the effect of Wenhua Juanbi Recipe (温化蠲痹方, WJR) on proliferation and apoptosis of synoviocytes in rats with collagen-inducing arthritis (CIA). Methods: A CIA model was induced by intradermal injection of bovine collagen type II emulsion at the base of rat tails. Thirty modeled healthy Wistar rats were randomly assigned to one of three groups (10 per group): the model group, the methotrexate (MTX)-treated group (0.78 mg/kg) and the WJR-treated group (22.9 g/kg). A group of 10 healthy rats was used as normal control. Treatments or normal saline for the control group were administered by oral gavage once daily. Rats were sacrificed after 30-day treatment and subjected to the following examinations: arthritis index (AI) was estimated, inflammatory cell infiltration and proliferation in synovial membrane were evaluated by microscopy, the synoviocyte apoptosis was determined by TUNEL assay, and the cell apoptosis index was calculated. Results: AI was lowered significantly in the WJR group compared to the model group ( P<0.01). The pathological findings observed in the model group were reversed in the WJR group, including increase in inflammatory cell infiltration and synoviocyte proliferation in synovial membrane and reduction in cell apoptosis index (all P<0.01). Conclusions: Synoviocyte proliferation and apoptosis reduction were present in CIA rats. WJR was effective in treating the rat model of CIA. The therapeutic effect might be exerted through inducing apoptosis and suppressing proliferation of synoviocytes. [ABSTRACT FROM AUTHOR]

Ethnopharmacological Relevance: Rheumatoid arthritis (RA) is known as "Fawang" in Zhuang medical theory. Longzuantongbi granules (LZTBG) is an in-hospital preparation used at the First Affiliated Hospital of the Guangxi University of Chinese Medicine. This medicine is based on traditional Zhuang medicine theory for the treatment of "Fawang", and has an effectiveness of over 86.67%. It comprises eight medicinal materials, including the main drug Toddalia asiatica (L.) Lam. and Kadsura coccinea (Lem.) A.C. Smith, the assisting drugs Alangium chinense (Lour.) Harms, Zanthoxylum nitidum (Roxb.) DC., Sinomenium acutum (Thunb.) Rehd.et Wils., Bauhinia championii (Benth.) Benth., Spatholobus suberectus Dunn, and Ficus hirta Vahl. All of these herbs are commonly used in Zhuang medicine., Aim of the Study: This study aims to reveal the effect of LZTBG on collagen-induced arthritis (CIA) rats, to discover the potential efficacy-related biomarkers and explore the intervention mechanism of LZTBG from a molecular level, based on metabolomics., Materials and Methods: Sprague-Dawley (SD) rats were randomly assigned into a normal group, a CIA model group, a positive control (MTX) group and two different LZTBG treatment groups (5.4 g/kg/d and 2.7 g/kg/d). Body weight, arthritis index (AI), paw swelling, and hematoxylin and eosin (HE) staining experiments were used to evaluate the efficacy of the established model. A metabolomics method based on an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was established to analyze plasma taken from the rats, and to explore the interventional mechanism of LZTBG., Results: LZTBG showed a positive effect on the CIA model rats. Thirty-one differential metabolites were screened out, and combined with pathway analysis, 11 potential efficacy-related biomarkers were then mapped in the pathway. These included linoleic acid (LA), phosphatidylcholine (PC), lysophosphatidylcholine (LPC), arachidonic acid (AA), 12-HETE, alpha-linolenic acid (ALA), 13(S)-HOT, 2-oxobutanoate, 3-hydroxybutyric acid, L-Valine, and acetylcholine. Furthermore, it was found that these metabolites may exhibit an intervention effect by means of modulating pathways related to both lipid metabolism and amino acid metabolism to associated with inflammation., Conclusion: LZTBG can effectively alleviate symptoms of RA, an effect that can primarily be attributed to the regulation of multiple pathways and multiple targets These results demonstrate that LC-MS/MS-based metabolomics is an advantageous technique for the investigation of the intervention effect and molecular mechanism of traditional compound medicine., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Abstract: Aim of this study: To confirm the anti-arthritic effect and explore the potential mechanism of the dried heartwood of Caesalpinia sappan L. (HCS) on collagen-induced arthritis (CIA) in rats, an animal model of rheumatoid arthritis. Materials and methods: CIA was induced in male Wistar rats by intradermal injection of bovine collagen-II in Freund''s incomplete adjuvant (IFA). The rats in the onset of arthritis were treated daily with oral administration of an ethanol extract from HCS (EHCS) at different doses (1.2, 2.4 and 3.6g/kg) or olive oil-vehicle for 10 days. Paw swelling, arthritis index, radiographic and histopathologic changes were evaluated to confirm the anti-arthritic effect of EHCS on CIA in rats. Levels of proinflammatory cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α) as well as prostaglandin E2 (PGE2) in blood and expression of cyclooxygenase-2 (COX-2) and transcription factor NF-κB p65 in paw cartilage were detected to further study the molecular mechanism of the anti-arthritic effects of EHCS on CIA in rats. In addition, the adverse effects of EHCS on liver and kidney of rats were also evaluated. Results: The results showed that the EHCS markedly attenuated collagen-induced arthritis and reduced the levels of IL-1β, IL-6, TNF-α and PGE2 in serum and the expression of COX-2 and transcription factor NF-κB p65 in paw cartilage of CIA rats. EHCS (3.6g/kg) induced slight hepatotoxicity and body weight loss. Conclusion: These results indicate that EHCS significantly attenuates CIA in rats by decreasing the levels of IL-1β, IL-6, TNF-α and PGE2 in serum and the expression of COX-2 and transcription factor NF-κB in paw cartilage. [Copyright &y& Elsevier]

Abstract: Aim of the study: To investigate the expression of β-arrestins in fibroblast-like synoviocytes (FLS) from collagen-induced arthritis (CIA) rats and the effect of total glucosides of paeony (TGP). Materials and methods: TGP and glucosides of tripterygium wilfordii (GTW) were intragastriclly administrated to collagen-induced arthritis (CIA) rats after immunization. The secondary inflammatory reaction was evaluated by hind paw swelling, polyarthritis index and histopathological changes. Antibodies to type II collagen (CII) were determined by enzyme-linked immunosorbent assay (ELISA). Synoviocyte proliferations were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The expression of β-arrestins in synoviocytes from CIA rats was measured by western blot. Results: The administration of TGP (25, 50, 100mg/kg) depressed hind paw swelling and decreased the arthritis scores of CIA rats. TGP improved the pathologic manifestations of CIA. Serum anti-CII antibodies level increased significantly in CIA rats, while TGP had no effect on it. Fibroblast-like synoviocytes (FLS) proliferation was inhibited by TGP (50, 100mg/kg). On d14, d28 after immunization, β-arrestins expression greatly up-regulated in synoviocytes from CIA rats and then returned to baseline levels on d42 after immunization. TGP (50, 100mg/kg) significantly reduced the expression of β-arrestins. Conclusion: An inflammatory process in vivo induces an up-regulation of β-arrestins in synoviocytes from CIA rats while TGP can inhibit this change, which might be one of the important mechanisms for TGP to produce a marked therapeutic effect on RA. [Copyright &y& Elsevier]

Bone destruction plays a key role in damaging the joint function of rheumatoid arthritis (RA). Fengshi Qutong capsule (FSQTC) consisting of 19 traditional Chinese medicines has been used for treating RA in China for many years. Preliminary studies show that FSQTC has analgesic activity and inhibits synovial angiogenesis of collagen-induced arthritis (CIA), but its role on bone destruction of RA is still unclear. To explore the effect of FSQTC on bone destruction of RA and the possible mechanism of osteoclastogenesis in vivo and in vitro. LC-MS system was used to detect the quality control components of FSQTC. The anti-arthritic effect of FSQTC on CIA rats was evaluated by arthritis score, arthritis incidence and histopathology evaluation of inflamed joints. The effect of treatment with FSQTC on bone destruction of joint tissues was determined with X-ray and micro-CT quantification, and on bone resorption marker CTX-I and formation marker osteocalcin in sera were detected by ELISA. Then, osteoclast differentiation and mature were evaluated by TRAP staining, actin ring immunofluorescence and bone resorption assay both in joints and RANKL-induced RAW264.7 cells. In addition, RANKL, OPG, IL-1β and TNFα in sera were evaluated by ELISA. The molecular mechanisms of the inhibitions were elucidated by analyzing the protein and gene expression of osteoclastic markers CTSK, MMP-9 and β3-Integrin, transcriptional factors c-Fos and NFATc1, as well as phosphorylation of ERK1/2, JNK and P38 in joints and in RANKL-induced RAW264.7 cells using western blot and/or qPCR. In this study, 12 major quality control components were identified. Our data showed that FSQTC significantly increased bone mineral density, volume fraction, trabecular thickness, and decreased trabecular separation of inflamed joints both at periarticular and extra-articular locations in CIA rats. FSQTC also diminished the level of CTX-I and simultaneously increased osteocalcin in sera of CIA rats. The effects were accompanied by reductions of osteoclast differentiation, bone resorption, and expression of osteoclastic markers (CTSK, MMP-9 and β3-Integrin) in joints. Interestingly, FSQTC treatment could reduce the protein level of RANKL, increase the expression of OPG, and decrease the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. In addition, FSQTC inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as IL-1β and TNFα in sera. When RAW264.7 cells were treated with RANKL, FSQTC inhibited the formation of TRAP + multinucleated cells, actin ring and the bone-resorbing activity in dose-dependent manners. Furthermore, FSQTC reduced the RANKL-induced expression of osteoclastic genes and proteins and transcriptional factors (c-Fos and NFATc1), as well as phosphorylation of mitogen-activated protein kinases (MAPKs). FSQTC may inhibit bone destruction of RA by its anti-osteoclastogenic activity both in vivo and in vitro. [Display omitted] [ABSTRACT FROM AUTHOR]

Callicarpalongissima has been used as a Yao folk medicine to treat arthritis for years in China, although its active anti-arthritic moieties have not been clarified so far. In this study, two natural phenolic diterpenoids with anti-rheumatoid arthritis (RA) effects, rosmanol and carnosol, isolated from the medicinal plant were reported on for the first time. In type II collagen-induced arthritis DBA/1 mice, both rosmanol (40 mg/kg/d) and carnosol (40 mg/kg/d) alone alleviated the RA symptoms, such as swelling, redness, and synovitis; decreased the arthritis index score; and downregulated the serum pro-inflammatory cytokine levels of interleukin 6 (IL-6), monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor α (TNF-α). Additionally, they blocked the activation of the Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)/c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) pathways. Of particular interest was that when they were used in combination (20 mg/kg/d each), the anti-RA effect and inhibitory activity on the TLR4/NF-κB/MAPK pathway were significantly enhanced. The results demonstrated that rosmanol and carnosol synergistically alleviated RA by inhibiting inflammation through regulating the TLR4/NF-κB/MAPK pathway, meaning they have the potential to be developed into novel, safe natural combinations for the treatment of RA. [ABSTRACT FROM AUTHOR]

Abstract: Madecassoside is the highest amount of triterpene constituent in Centella asiatica herbs, a frequently prescribed crude drug in southeastern Asian and China for wound healing and scar management. The present study aimed to investigate the therapeutic potential and underlying mechanisms of madecassoside on collagen II (CII)-induced arthritis (CIA) in mice. Madecassoside (10, 20 and 40mg/kg), orally administered from the day of the antigen challenge for twenty consecutive days, dose-dependently alleviated the severity of the disease based on the reduced clinical scores, and elevated the body weights of mice. Histopathological examination indicated that madecassoside alleviated infiltration of inflammatory cells and synovial hyperplasia as well as protected joint destruction. Moreover, madecassoside reduced the serum level of anti-CII IgG, suppressed the delayed type hypersensitivity against CII in ears, and moderately suppress CII-stimulated proliferation of lymphocytes from popliteal lymph nodes in CIA mice. In vitro, madecassoside was ineffective in the activation of macrophages caused by lipopolysaccharide. It was concluded that madecassoside substantially prevented mouse CIA, and might be the major active constituent of C. asiatica herbs responsible for clinical uses for rheumatoid arthritis. The underlying mechanisms of action may be mainly through regulating the abnormal humoral and cellular immunity as well as protecting joint destruction. [Copyright &y& Elsevier]