Dahuang-Wumei decoction protects against hepatic encephalopathy in mice: Behavioural, biochemical, and molecular evidence.

BACKGROUND: Disturbance of the blood‒brain barrier (BBB) and associated inflammatory responses are observed in patients with hepatic encephalopathy (HE) and can cause long-term complications. Dahuang-Wumei decoction (DWD) is a renowned traditional Chinese herbal medicine with a long history of clinical use and has been widely employed as an effective treatment for hepatic encephalopathy (HE). Despite its established efficacy, the precise mechanisms underlying the therapeutic effects of DWD have not been fully elucidated. PURPOSE: The present study aimed to comprehensively explore the potential effects and underlying molecular mechanisms of DWD on HE through an integrated investigation that included both in vivo and in vitro experiments. METHODS: In the present study, carbon tetrachloride (CCl4) and thioacetamide (TAA) were used to establish an HE model in mice. The therapeutic effects of DWD on liver injury, fibrosis, brain injury, behaviour, and consciousness disorders were evaluated in vivo. C8-D1A and bEnd.3 cells were used to construct a BBB model in vitro. The effects of DWD on proinflammatory factor expression, BBB damage and the Wnt/ß-catenin pathway were detected in vivo and in vitro. RESULTS: Our results showed that DWD can improve liver injury and fibrosis and brain damage and inhibit neurofunctional and behavioural disorders in mice with HE. Afterwards, we found that DWD decreased the levels of proinflammatory factors and suppressed BBB disruption by increasing the levels of junction proteins in vivo and vitro. Further studies verified that the Wnt/ß-catenin pathway may play a pivotal role in mediating the inhibitory effect of DWD on HE. CONCLUSION: These results demonstrated that DWD can treat HE by preventing BBB disruption, and the underlying mechanisms involved were associated with the activation of the Wnt/ß-catenin pathway and the inhibition of inflammatory responses.

Mechanisms of NLRP3 inflammasome in rheumatoid arthritis and osteoarthritis and the effects of traditional Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: It has been widely reported that various anti-rheumatic traditional Chinese medicines (TCMs) ameliorate rheumatoid arthritis (RA) and osteoarthritis (OA) through regulating the abnormal production, assembly, and activation of the NOD-like receptor thermal protein domain-associated protein 3 (NLRP3) inflammasome. These TCMs include monomers isolated from Chinese herbs, extracts of Chinese herbs, and Chinese medical formulae with a lengthy application history. AIM OF THE STUDY: This review aimed to summarize and analyze the published articles about the NLRP3 inflammasome and its role in the pathogenesis of RA and OA. We also reviewed existing knowledge on the therapeutic mechanism of TCMs in RA and OA via the regulation of the NLRP3 inflammasome. MATERIALS AND METHODS: We searched for relevant articles with the keywords "NLRP3 inflammasome", "traditional Chinese medicine," "Chinese herbal drugs," "rheumatoid arthritis," and "osteoarthritis." The information retrieval was conducted in medical Chinese and English databases from the date of construction to April 19, 2023, including PubMed, MEDLINE, Web of Science, Scopus, Ovid, China National Knowledge Infrastructure (CNKI), Chinese Biomedicine Literature Database (CBM), Chinese Science and Technology Periodicals Database (VIP), and China Online Journals (COJ). RESULTS: According to retrieval results, 35 TCMs have been demonstrated to relieve RA by targeting the NLRP3 inflammasome, including six traditional Chinese prescriptions, seven extracts of Chinese herbs, and 22 monomers extracted from traditional Chinese herbs and formulae. Additionally, 23 TCMs have shown anti-OA effects with abilities to modulate the NLRP3 inflammasome, including five traditional Chinese prescriptions, one extract of Chinese herbs, and 17 monomers from Chinese herbs. CONCLUSIONS: We summarized mechanism research about the pivotal roles of the NLRP3 inflammasome in the pathogenesis of RA and OA. Moreover, a review of TCMs with targets of the NLRP3 inflammasome in RA and OA treatment was also conducted. Our work is conducive to a better application of TCMs in complementary and alternative therapies in RA and OA.

Interaction of gut microbiota with the tumor microenvironment: A new strategy for antitumor treatment and traditional Chinese medicine in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignancies worldwide and the second leading cause of cancer-related death. In recent years, the relationship between gut microbiota and CRC has attracted increasing attention from researchers. Studies reported that changes in the composition of gut microbiota, such as increase in the number of Fusobacterium nucleatum and Helicobacter hepaticus, impair the immune surveillance by affecting the intestinal mucosal immunity and increase the risk of tumor initiation and progression. The tumor microenvironment is the soil for tumor survival. Close contacts between gut microbiota and the tumor microenvironment may directly affect the progression of tumors and efficacy of antitumor drugs, thus influencing the prognosis of patients with CRC. Recently, many studies have shown that traditional Chinese medicine can safely and effectively improve the efficacy of antitumor drugs, potentially through remodeling of the tumor microenvironment by regulated gut microbiota. This article describes the effect of gut microbiota on the tumor microenvironment and possible mechanisms concerning the initiation and progression of CRC, and summarizes the potential role of traditional Chinese medicine.

Simiao pill attenuates collagen-induced arthritis and bleomycin-induced pulmonary fibrosis in mice by suppressing the JAK2/STAT3 and TGF-ß/Smad2/3 signalling pathway.

ETHNOPHAMACOLOGICAL RELEVANCE: Simiao Pill (SM) as a classic prescription of traditional Chinese medicine treatment of damp-heat arthralgia, the earliest from 'Cheng Fan Bian Du ', written by the Qing Dynasty doctor Zhang Bingcheng. Previous studies have shown that SM has obvious curative effect on rheumatoid arthritis, which provides a basis for the application of SM in rheumatoid arthritis related complications. AIM OF THE STUDY: Interstitial lung disease (ILD), as the most severe complication of rheumatoid arthritis (RA), lacks effective clinical treatments and a corresponding animal model. Simiao pill (SM) is a traditional Chinese medicine prescription extensively used as a complementary and alternative treatment for RA. However, the effect and mechanism of SM on RA-ILD have not yet been reported. This study aimed to investigate an appropriate animal model that can simulate RA-ILD, and the efficacy, safety, and mechanism of SM on RA-ILD. METHODS: Collagen-induced arthritis (CIA) and bleomycin-induced pulmonary fibrosis model were combined to construct the CIA-BLM model. After the intervention of SM, the protective effects of SM on RA-ILD were determined by detecting the CIA mouse arthritis index (AI), Spleen index, and the extent of pulmonary fibrosis. The joint inflammation and pulmonary fibrosis were detected by immunohistochemistry, H&E staining, safranin- O fast green Sirius red staining, trap staining, and Masson staining. Finally, the mechanism was verified by Western blot and immunohistochemistry. RESULTS: Our work showed that SM significantly reduced joint swelling, arthritis index, pulmonary fibrosis score, and spleen index in CIA mice. The pathological examination results indicated Si-Miao Pill suppressed inflammation, pulmonary fibrosis, bone erosion, and cartilage degradation of the ankle joint. Besides, SM up-regulated expressions of E-cadherin, whereas down-regulated expressions of α-SMA. Further studies confirmed that SM regulated JAK2/STAT3 and TGF-ß/SMAD2/3. CONCLUSION: SM can not only effectively improve joint inflammation by JAK2/STAT3 Pathway but also inhibit pulmonary fibrosis by TGF-ß/SMAD2/3. The fibrosis induced by CIA-BLM model was more stable and obvious than that induced by CIA model alone.

Wutou decoction attenuates the synovial inflammation of collagen-induced arthritis rats via regulating macrophage M1/M2 type polarization.

ETHNOPHARMACOLOGICAL RELEVANCE: Thousands of years of clinical practice in the treatment of joint-related diseases support the efficacy and safety of Wutou decoction (WTD). Nevertheless, the lack of pharmacological evidence and unclear mechanisms make it difficult for WTD to become a recognized complementary therapy for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: This study aimed to investigate the effect of WTD against synovial inflammation in RA and whether this effect depends on the regulation of macrophage polarization. MATERIALS AND METHODS: Sprague-Dawley rats were used to establish the collagen-induced arthritis (CIA) model. WTD with low and high doses was administered for 45 days. RAW264.7 cells were stimulated by lipopolysaccharide (LPS) or interleukin (IL)-4 to polarize M1 and M2 macrophages, which were pre-treated with WTD extract for 4 h. The anti-arthritic and anti-inflammatory effects of WTD were studied using arthritis score, histopathological staining, immunostaining, and enzyme-linked immunosorbent assay (ELISA). The polarization state of RAW264.7 cells and related pro/anti-inflammatory cytokines was detected by ELISA, reverse transcription quantitative polymerase chain reaction and western blotting. Western blotting and immunofluorescence were used to investigate the effect of WTD on nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and peroxisome proliferator-activated receptors γ (PPARγ) activation both in vivo and in vitro. RESULTS: WTD significantly reduced the arthritis score and the pathological damage of the knee joint and decreased the expression of tumor necrosis factor alpha (TNF-α), IL-6 in serum, TNF-α, IL-1ß, monocyte chemoattractant protein-1 (MCP-1), and matrix metalloproteinase-3 (MMP3) in the knee synovium. WTD inhibited M1 type polarization and promoted M2 type polarization, both in vitro and in vivo, and reduced the expression of pro-inflammatory cytokines while increasing the expression of anti-inflammatory cytokines. Experiments showed that WTD inhibited the phosphorylation of NF-κB and downstream p38 in the synovium of CIA rats and LPS-induced M1 type polarized RAW264.7 cells. In addition, PPARγ expression in the synovium of CIA rats was mainly located in the cytoplasm, and WTD treatment increased the nuclear translocation of PPARγ, which was further verified in RAW264.7 cells. CONCLUSIONS: NF-κB and PPARγ regulating M1 and M2 macrophage polarization and subsequent secretion of pro-inflammatory and anti-inflammatory cytokines are the underlying mechanisms of WTD that ameliorate RA synovial inflammation.

Dexamethasone and potassium canrenoate alleviate hyperalgesia by competitively regulating IL-6/JAK2/STAT3 signaling pathway during inflammatory pain in vivo and in vitro.

BACKGROUND: Dexamethasone (Dexa) and potassium canrenoate (Cane) modulate nociceptive behavior via glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by two mechanisms (genomic and nongenomic pathways). This study was designed to investigate the Dexa- or Cane-mediated nongenomic and genomic effects on mechanical nociception and inflammation-induced changes in interleukin-6 (IL-6) mediated signaling pathway in rats. METHODS: Freund's complete adjuvant (FCA) was used to trigger an inflammation of the right hind paw in male Sprague-Dawley rats. First, the mechanical nociceptive behavioral changes were examined following intraplantar administration of GR agonist Dexa and/or MR antagonist Cane in vivo. Subsequently, the protein levels of IL-6, IL-6Rα, JAK2, pJAK2, STAT3, pSTAT3Ser727 , migration inhibitory factor, and cyclooxygenase-2 were assessed by Western blot following intraplantar injection of Dexa or Cane or the combination. Moreover, the molecular docking studies determined the interaction between Dexa, Cane, and IL-6. The competition binding assay was carried out using enzyme-linked immunosorbent assays (ELISA). RESULTS: Administration of Dexa and Cane dose-dependently attenuated FCA-induced inflammatory pain. The sub-additive effect of Dexa/Cane combination was elucidated by isobologram analysis, accompanied by decrease in the spinal levels of IL-6, pJAK2, and pSTAT3Ser727 . The molecular docking study demonstrated that both Dexa and Cane displayed a firm interaction with THR138 binding site of IL-6 via a strong hydrogen bond. ELISA revealed that Dexa has a higher affinity to IL-6 than Cane. CONCLUSIONS: There was no additive or negative effect of Dexa and Cane, and they modulate the IL-6/JAK2/STAT3 signaling pathway through competitive binding with IL-6 and relieves hypersensitivity during inflammatory pain.

Ginkgo biloba L. extract prevents steroid-induced necrosis of the femoral head by rescuing apoptosis and dysfunction in vascular endothelial cells via the PI3K/AKT/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. extract (EGb) is one of the world's most extensively used herbal medicines. Due to the diverse pharmacological properties of EGb, it has been used in the treatment of neurological illnesses, as well as cardiovascular and cerebrovascular ailments. However, the effect and pharmacological mechanism of EGb on steroid-induced necrosis of the femoral head (SINFH) are still unclear. AIM OF THE STUDY: SINFH remains a challenging problem in orthopedics. Previous investigations have shown that EGb has the potential to reduce the occurrence of SINFH. The goal was to determine the effect and mechanism of EGb in preventing SINFH by inhibiting apoptosis and improving vascular endothelial cells (VECs) functions. MATERIALS AND METHODS: CCK-8, nitric oxide (NO) production and flow cytometry were used to determine the cell apoptosis and function. The scratch and angiogenesis tests assessed migration and tube formation. Western blot analysis detected the expressions of apoptosis-related proteins and PI3K/AKT/eNOS pathway-related proteins. Apoptosis and angiogenesis were also detected treated with the inhibitors. A mouse model of SINFH was established. Paraffin section was used to determine the necrotic pathology and apoptosis. Vessels in the femoral heads were assessed by immunofluorescence staining. RESULTS: When stimulated by methylprednisolone (MPS), cell viability, NO generation and tube formation were decreased, the apoptotic rate increased. Simultaneously, MPS decreased the expression levels of p-PI3K, p-AKT, and p-eNOS. EGb increased the expression levels of these proteins, restrained apoptosis, and restored cell functions. The addition of the inhibitors decreased anti-apoptotic effect and angiogenesis. In addition, when compared to the model mice, there were fewer empty lacunae and normal trabecular arrangement after taking different doses of EGb. The protective effect was also confirmed by the vascular quantitative analysis in vivo. CONCLUSION: This study established that EGb increased endothelial cell activity and inhibited apoptosis and function loss induced by MPS, elucidating the effect and molecular mechanism of EGb on early SINFH.

Potential Implications of Quercetin in Autoimmune Diseases.

Autoimmune diseases are a worldwide health problem with growing rates of morbidity, and are characterized by breakdown and dysregulation of the immune system. Although their etiology and pathogenesis remain unclear, the application of dietary supplements is gradually increasing in patients with autoimmune diseases, mainly due to their positive effects, relatively safety, and low cost. Quercetin is a natural flavonoid that is widely present in fruits, herbs, and vegetables. It has been shown to have a wide range of beneficial effects and biological activities, including anti-inflammation, anti-oxidation, and neuroprotection. In several recent studies quercetin has reportedly attenuated rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, and systemic lupus erythematosus in humans or animal models. This review summarizes the evidence for the pharmacological application of quercetin for autoimmune diseases, which supports the view that quercetin may be useful for their prevention and treatment.

Quercetin-mediated SIRT1 activation attenuates collagen-induced mice arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Herba taxilli (HT, Sangjisheng in Chinese), which is composed of the dried stems and leaves of Taxillus chinensis (DC.) Danser, has been commonly used to treat inflammation and arthritis in traditional Chinese medicine (TCM). Quercetin (Que) is a major active flavonoid component isolated from HT and is one of the quality control indexes of HT. In the clinical practice of TCM, formulas containing HT are commonly used to treat rheumatoid arthritis (RA). Recent studies have shown that Que exerts antiarthritic effects. However, the mechanism by which Que treatment affects RA is not fully understood. AIM OF THE STUDY: This study aimed to explore the antiarthritic activity of Que in a collagen-induced arthritis (CIA) mouse model and investigate the underlying mechanisms. MATERIALS AND METHODS: The antiarthritic activity of Que was evaluated in a CIA mouse model by determining the paw clinical arthritis scores and left ankle thicknesses and by conducting micro-PET imaging and histopathological analysis of ankle joint tissues. The proinflammatory cytokine (IL-6, TNF-α, IL-1ß, IL-8, IL-13, IL-17) levels in the serum and ankle joint tissues were measured by ELISA. Mitochondrial oxidative stress was assessed by biochemical methods. Mitochondrial biogenesis was analysed by RT-qPCR. The protein levels of silent information regulator 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), high-mobility group box 1 (HMGB1), Toll-like receptor 4 (TLR4), p38, phospho-p38, extracellular signal-regulated kinases (ERK)-1/2, phospho-ERK1/2, p65, and phospho-p65 in ankle joint tissues were detected by Western blot analysis. A total of 30 RA patients were recruited to investigate the relationship between the disease activity score (DAS28) and the SIRT1, PGC-1α, NRF1, and HMGB1 plasma levels. RESULTS: Que treatment decreased the clinical score and left ankle thickness of CIA mice, attenuated the synovial inflammation and hyperplasia and bone/cartilage destruction in ankle joints, and decreased the secretion of IL-6, TNF-α, IL-1ß, IL-8, IL-13, and IL-17. Mechanistically, Que treatment improved impaired mitochondrial biogenesis and mitochondrial function by regulating the SIRT1/PGC-1α/NRF1/TFAM pathway and inhibited inflammation via the HMGB1/TLR4/p38/ERK1/2/NF-κB p65 pathway. Notably, epidemiological data revealed correlations between abnormal circulating levels of SIRT1, PGC-1α, NRF1, HMGB1 and RA disease activity in patients. CONCLUSIONS: Our data suggested a potential role of Que as a dietary therapeutic drug for RA treatment that may act through SIRT1 to target mitochondrial biogenesis. Additionally, the role of impaired mitochondrial biogenesis in RA was evaluated.

Si Miao San Attenuates Inflammation and Oxidative Stress in Rats with CIA via the Modulation of the Nrf2/ARE/PTEN Pathway.

OBJECTIVE: Si Miao San (SMS) is a traditional Chinese formula used in China to treat rheumatic diseases. To date, its mechanism in rheumatoid arthritis (RA) treatment is uncertain. Our study aims to assess the antiarthritic effects of SMS in experimental arthritic rats. MATERIALS AND METHODS: SMS (8.63, 4.31, and 2.16 g/kg/day) was orally administered after the first immunization from day 14 to day 53. The effects of SMS on rats with collagen-induced arthritis (CIA) were evaluated by arthritis score and histological assessment. The levels of cytokines and anti-CII antibodies in rat serum were measured by ELISAs. The expression of oxidative stress parameters was detected by biochemical assay kits. The levels of Nrf2, HO-1, NQO1, and PTEN were determined by western blotting. RESULTS: Medium- and high-dose SMS treatment significantly decreased arthritis scores and alleviated ankle joint histopathology in the rats with CIA. It inhibited the production of IL-6, TNF-α, COX-2, and PGE2 in rat serum. SMS also suppressed the expression of anti-CII antibodies IgG1 and IgG2a. Moreover, SMS significantly suppressed the levels of MDA and MPO in the synovial tissues while increasing the levels of SOD and CAT in the rats with CIA. The levels of Nrf2, HO-1, NQO1, and PTEN were upregulated by SMS in rat synovial tissues. CONCLUSIONS: This study demonstrated that SMS effectively alleviated the disease progression of CIA by decreasing the levels of proinflammatory cytokines and reducing oxidative stress damage, as indicated by IL-6, TNF-α, COX-2, and PGE2 levels; inhibiting the overproduction of MDA and MPO; and enhancing antioxidant enzymes by upregulating the Nrf2/ARE/PTEN signalling pathway.

Modified Si-Miao Pill for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this review and meta-analysis was to assess the effects and safety of modified Si-Miao pill (mSMP) in treatment of rheumatoid arthritis. DESIGN: A systematic literature search was carried out in eight databases from their available dates of inception to April 2020. After screening, fifteen randomized, controlled trials (RCTs) comparing the effects and safety of mSMP in combination with western medicine (including disease-modifying antirheumatic drugs (DMARDs) and nonsteroidal anti-inflammatory drugs (NSAIDs)) in treating rheumatoid arthritis patients were included after screening. RESULTS: In comparison with DMARDs, or coadministration of DMARDs and NSAIDs, mSMP in combination with western medicine significantly lowered erythrocyte sedimentation rate (mean difference (MD) = -10.61, 95% confidence interval (CI) [-12.19, -9.03]), C-reactive protein (MD = -6.50, 95% CI [-8.43, -4.56]), rheumatoid factors (MD = -17.31, 95% CI [-24.34, -10.27]), swollen joint count (MD = -1.63, 95% CI [-2.29, -0.97]), tender joint count (MD = -1.98, 95% CI [-2.34, -1.62]), and morning stiffness time (MD = -24.37, 95% CI [-29.41, 19.33]) and ameliorated the condition of patients (odds ratio (OR) = 3.69, 95% CI [2.64, 5.14]). Additionally, mSMP in combination with western medicine seemed safer (OR = 0.49, 95% CI [0.30, 0.81]). CONCLUSION: The results of the meta-analysis study have shown that mSMP in combination with western medicine therapies appears to be more effective and safer than western medicine alone in the treatment of rheumatoid arthritis including reducing inflammatory markers and adverse events and improving symptoms. Howbeit, more high-grade, large-scale RCTs of mSMP in various countries and regions are still needed.

Berberine Modulates LPA Function to Inhibit the Proliferation and Inflammation of FLS-RA via p38/ERK MAPK Pathway Mediated by LPA1.

OBJECTIVE: This study aimed to investigate whether berberine exerted anti-inflammatory and antiproliferative effects on the fibroblast-like synoviocytes of rheumatoid arthritis (FLS-RA) through regulating the lysophosphatidic acid (LPA) function. METHODS: Firstly, the expression levels of LPA and lysophosphatidic acid receptor 1 (LPA1) in RA patients, osteoarthritis (OA) patients, and healthy controls were detected. Moreover, molecular docking was employed to characterize the binding sites of berberine in the predicted protein targets. Later, FLS-RA were stimulated using berberine, LPA, and the specific inhibitor (Ki16425) of LPA1, thereafter, the effects on the proliferation, apoptosis, the release of inflammatory mediators of FLS-RA, and the MAPK pathway were observed. RESULTS: Compared with healthy controls (n = 25), the plasma LPA level (n = 28) and synovial fluid (n = 10) were markedly higher in RA patients. LPA1 was highly expressed in RA patients (n = 4) relative to that in OA patients (n = 4). Berberine remarkably inhibited the proliferation and the excessive production of IL-6 and TNF-α in FLS-RA, whereas suppressing the expression of K-ras, c-Raf, and p-38/ERK-phosphorylation. In addition, berberine inhibited the LPA-induced p-38/ERK-phosphorylation through binding to LPA1. CONCLUSIONS: LPA plays a certain role in promoting the proliferation and inflammation of FLS-RA. Berberine potentially modulates LPA function to suppress the proliferation and inflammation of FLS-RA through blocking the p38/ERK MAPK pathway mediated by LPA1. These findings suggest that, berberine possesses potential lipid-regulating, antiarthritis, and synovial hyperplasia inhibition activities against RA, which may provide a promising therapeutic target for the clinical drug development for RA patients with dyslipidemia and high CVD risk.

Efficacy and safety of total glucosides of paeony combined with methotrexate and leflunomide for active rheumatoid arthritis: a meta-analysis.

Purpose: Total glucosides of paeony (TGP) have been confirmed to reduce hepatotoxicity caused by methotrexate (MTX) and leflunomide (LEF) in rheumatoid arthritis (RA). Nevertheless, high-quality evidence-based meta-analysis data on the issue are unavailable. This study aimed to evaluate the efficacy and safety of this combination treatment for RA. Materials and methods: PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials, Chinese Biomedical Literature database, China National Knowledge Internet, Wan Fang, and VIP were searched up to February 2019. Randomized controlled trials (RCTs) on the efficacy and safety of TGP combined MTX and LEF for RA were included. Results: Eight RCTs were included in the final meta-analysis. Pooled results showed better therapeutic effects against RA in the TGP-treated group (RR =1.10, 95% CI: 1.04 -1.16). The TGP+MTX+LEF group showed a reduced erythrocyte sedimentation rate (MD = -2.80 mm/h, 95% CI: -5.08 - -0.52), C-reactive protein level (MD = -4.17 mg/L, 95% CI: -7.84 - -0.51), and rheumatoid factor (MD = -12.09 IU/mL, 95% CI: -14.05 - -10.14). Besides, the combination treatment tended to benefit lipid profiles (total cholesterol: 95% CI: -1.27-0.06; triglycerides: 95% CI: -0.49 - -0.08; high-density lipoprotein cholesterol: 95% CI: 0.15-0.83; and low-density lipoprotein cholesterol: 95% CI: -0.54 - -0.02). Adverse events, hepatotoxicity in particular, significantly decreased (RR =0.55, 95% CI: 0.38-0.80) in the TGP group. Conclusion: Compared to MTX and LEF therapy, TGP combination treatment may be a more effective and safer strategy. It is advisable to apply TGP as an adjuvant given its hepatoprotective and possible lipid-regulating effect. However, further large-scale and high-quality clinical trials are warranted, and the efficacy of TGP in terms of its effect on lipid profiles should be further confirmed.

Synergistic and Hepatoprotective Effect of Total Glucosides of Paeony on Ankylosing Spondylitis: A Systematic Review and Meta-Analysis.

The objective of this systematic review was to conduct a meta-analysis of the efficacy and safety of total glucosides of paeony (TGP) for the treatment of ankylosing spondylitis (AS). TGP is commonly applied as a complementary medicine, especially in combination with disease-modifying antirheumatic drugs (DMARDs) and/or non-steroidal anti-inflammatory drugs (NSAIDs) to treat AS in China. Nevertheless, the efficacy and safety of TGP combination treatment still needs more validation. A systematic literature search was conducted using PubMed, EMBASE, Web of Science, the Cochrane library, ClinicalTrials, the Chinese Biomedical Literature database (CBM), the China National Knowledge Internet (CNKI), the Wan Fang Medical Database and the VIP Database for available randomized controlled trials (RCTs) investigating the efficacy and safety of TGP on AS up to November 2018. Review Manager 5.3 software and Stata 12.0 software were used to analyze all included studies according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement protocol. The pooled results of 23 RCTs exhibited better symptoms improvement (SI) (95% CI 1.16 to 1.36), lower erythrocyte sedimentation rate (ESR) (95% CI -5.89 to -1.32), lower levels of C-reactive protein (CRP) (95% CI -5.01 to -1.49), morning stiffness (MS) time (95% CI -3.46 to -1.86), finger to floor distance (FFD) (95% CI -4.80 to -0.86), peripheral joint pain index (PJPI) (95% CI -3.48 to -0.69), and higher level of thoracic expansion (TE) (95% CI 0.18-0.40) in TGP group. While Schober's test (Schober) showed no significant difference between the two groups. Adverse events (AEs) were significantly decreased (95% CI 0.48-0.79) with the usage of TGP. It is worthwhile to apply TGP as an auxiliary medicine on AS for better efficacy and less side effects, especially when considering the impact of traditional treatment on the liver. Still, further clinical trials with larger sample and better methodological quality are warranted to ascertain the potential benefits of TGP on AS.

Simiao Pill Attenuates Collagen-Induced Arthritis in Rats through Suppressing the ATX-LPA and MAPK Signalling Pathways.

OBJECTIVE: Simiao pill (SM), a traditional Chinese formula, has been used as an antirheumatic drug in clinical practice for hundreds of years. Rheumatoid arthritis (RA) is characterized by chronic synovial inflammation and hyperplasia, cartilage destruction, and joint damage. This study was designed to investigate the protective effects of SM on collagen-induced arthritis (CIA) in rats. It also aimed to explore whether this protective effect of SM was related to the inhibition of the ATX-LPA and MAPK signalling pathways. MATERIALS AND METHODS: Rats were injected with a collagen II emulsion at the end of the tail and on the back to induce arthritis. Treatment with different doses of SM was conducted by intragastric administration. Then, body weights and arthritis scores were measured. The serum levels of tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, C-reactive protein (CRP), osteoprotegerin (OPG), autotaxin (ATX), and lysophosphatidic acid (LPA) were determined by ELISA. Pathological changes in the joints were measured by micro-CT and assessed via haematoxylin-eosin (H&E) staining. The expression of ATX, LPA receptor 1 (LPA1) was detected by immunohistochemical staining, and the expression of mitogen-activated protein kinase (MAPK) was detected by Western blotting. RESULTS: SM significantly alleviated arthritis symptoms, inhibited bone erosion, and decreased the levels of TNF-α, IL-1ß, CRP, ATX, and LPA in the sera of CIA rats. Importantly, SM clearly reduced the protein expression of LPA1 and ATX. The activation of the MAPK signalling pathway was also inhibited by SM in the synovial tissues of CIA rats. CONCLUSIONS: The antirheumatic effects of SM were associated with the regulation of the ATX-LPA and MAPK pathways, the suppression of proinflammatory cytokine production, and the alleviation of cartilage and bone injury. These findings suggest that SM might be a promising alternative candidate for RA therapy.

Preventive effect of Ibrolipim on suppressing lipid accumulation and increasing lipoprotein lipase in the kidneys of diet-induced diabetic minipigs.

BACKGROUND: The role of renal lipoprotein lipase (LPL) per se in kidney diseases is still controversial and obscure. The purpose of this study was to observe the preventive effects of Ibrolipim, a LPL activator, on lipid accumulation and LPL expression in the kidneys of minipigs fed a high-sucrose and high-fat diet (HSFD). METHODS: Male Chinese Bama minipigs were fed a control diet or HSFD with or without 0.1 g/kg/day Ibrolipim for 5 months. Body weight, plasma glucose, insulin, lipids, LPL activity, and urinary microalbumin were measured. Renal tissue was obtained for detecting LPL activity and contents of triglyceride and cholesterol, observing the renal lipid accumulation by Oil Red O staining, and examining the mRNA and protein expression of LPL by real time PCR, Western Blot and immunohistochemistry. RESULTS: Feeding HSFD to minipigs caused weight gain, hyperglycemia, hyperinsulinemia, hyperlipidemia and microalbuminuria. HSFD increased plasma LPL activity while it decreased the mRNA and protein expression and activity of LPL in the kidney. The increases in renal triglyceride and cholesterol contents were associated with the decrease in renal LPL activity of HSFD-fed minipigs. In contrast, supplementing Ibrolipim into HSFD lowered body weight, plasma glucose, insulin, triglyceride and urinary albumin concentrations while it increased plasma total cholesterol and HDL-C. Ibrolipim suppressed the renal accumulation of triglyceride and cholesterol, and stimulated the diet-induced down-regulation of LPL expression and activity in the kidney. CONCLUSIONS: Ibrolipim exerts renoprotective and hypolipidemic effects via the increase in renal LPL activity and expression, and thus the increased expression and activity of renal LPL play a vital role in suppressing renal lipid accumulation and ameliorating proteinuria in diet-induced diabetic minipigs.

Effect of electrochemical treatment on high-flow vascular malformations in the maxillofacial region.

We explored the effect of electrochemical therapy for the treatment of high-flow venous malformations in the maxillofacial region in 32 patients. We used a method of anaesthesia that was suitable to the site and size of the lesion, and then inserted platinum needles into the lesion in a sterile environment. We protected the normal skin by inserting the cannulas into plastic sheaths, and connected the needles to an electrochemical machine. The common voltage, electric current, and amount of electricity were 6-8 V, 80-100 mA, and 10-20 C/cm(2), respectively. During a follow up period of two months to three years, 18 (56%) patients had a complete response, and 14 a partial response (44%). Electrochemical treatment is a simple, relatively atraumatic method of dealing with high-flow venous malformations that leaves no scars.

[A new approach for exploring the essence of meridian].

The paper includes a brief review and evaluation of the progress in the research of the essence of meridian in China in the last two decades, in which the author suggests that more effort at all levels involving multiple disciplines needs to be investigated in the pursuit of this issue after the failure of prolonged research in the fields of histological anatomy. Microcosmic investigation, in particular, should be pursued making full use of the available achievement in molecular cell biology, genome research, biophysics and biochemistry and so forth, so as to build a solid plateform for making a breakthrough. The author urges the importance of research in the information carrier that regulates the meridian physiological network of the body. Based on the theories in cellular signal transduction and relevant experimental data, the author points out that the signal amplitude and frequency of intracellular Ca(2+) oscillations and intercellular Ca(2) wave elicited by specific acupuncture may contain information of the meridian routes and physiological function regulations. Through its binding proteins, Ca(2+) participates in almost all the physiological processes such as reproduction, metabolism, muscle contraction to cognition and memory. It is therefore hypothetically believed that Ca(2+) and inositol trisphosphate (IP(3), which is required for the propagation of intercellular Ca(2+) waves) can be the long-quested information carriers of the meridian physiological network, and they in conjunction with the gap-junction protein (connexon) build the material bases of the meridian. The author also specifies some possible directions of further study and experimental methods.