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Anti-wound-healing effects of GSZD on MH7A cells. (A) The represented pictures of wound-healing of MH7A cells with different treatment. MH7A cells were cultured for 24 h with TNF-α (20 ng/mL, final concentration in the well), then scratch were prepared using a 200 μL pipette tips. Subsequently, MH7A cells were treated GSZD (0.4, 0.8, 1.6 mg/mL, final concentration in the well) for another 12, 24, and 36 h, and pictures were acquired using a microscope (×200). (B) The statistical chart of the would-healing results. Data were represented as Mean ± SD (n = 3), **p < 0.01, vs. Control cells (MH7A cells treated by TNF-α alone).
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Background:
Rheumatoid arthritis (RA) is a known intractable chronic inflammatory disease of synovial joints characterized by hyperplasia and consecutive inflammation with a high prevalence.Guizhi-Shaoyao-Zhimu (GSZD) is the first choice for clinical treatment of RA in Chinese traditional medicine. This study is aimed to explore the possible pharm...
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... mg/mL (which showed relative less anti-proliferative effects on MH7A cells) were selected for our following experiments. Subsequently, we determined the effects of GSZD on the cell migration ability of MH7A cells using would-healing assay. As can be seen from the Fig. 6A&B, for the normal and TNF-α stimulated MH7A cells, the scratch prepared by pipette tip was almost fully filled with MH7A cells. However, the after treated with GSZD at the concentration of 0.4, 0.8 and 1.6 mg/mL, the would-healing ratios of the TNF-α stimulated MH7A cells were significantly suppressed (p < 0.01, p < 0.01, p < 0.01, ...
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... for the normal and TNF-α stimulated MH7A cells, the scratch prepared by pipette tip was almost fully filled with MH7A cells. However, the after treated with GSZD at the concentration of 0.4, 0.8 and 1.6 mg/mL, the would-healing ratios of the TNF-α stimulated MH7A cells were significantly suppressed (p < 0.01, p < 0.01, p < 0.01, respectively, Fig. 6B) with a concentration-dependent manner, compared to the control MH7A cells (MH7A cells treated by TNF-α alone). This result above suggested that GSZD might have the potential to inhibit the cell migration in synovial ...
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... mg/mL (which showed relative less anti-proliferative effects on MH7A cells) were selected for our following experiments. Subsequently, we determined the effects of GSZD on the cell migration ability of MH7A cells using would-healing assay. As can be seen from the Fig. 6A&B, for the normal and TNF-α stimulated MH7A cells, the scratch prepared by pipette tip was almost fully filled with MH7A cells. However, the after treated with GSZD at the concentration of 0.4, 0.8 and 1.6 mg/mL, the would-healing ratios of the TNF-α stimulated MH7A cells were significantly suppressed (p < 0.01, p < 0.01, p < 0.01, ...
Context 4
... for the normal and TNF-α stimulated MH7A cells, the scratch prepared by pipette tip was almost fully filled with MH7A cells. However, the after treated with GSZD at the concentration of 0.4, 0.8 and 1.6 mg/mL, the would-healing ratios of the TNF-α stimulated MH7A cells were significantly suppressed (p < 0.01, p < 0.01, p < 0.01, respectively, Fig. 6B) with a concentration-dependent manner, compared to the control MH7A cells (MH7A cells treated by TNF-α alone). This result above suggested that GSZD might have the potential to inhibit the cell migration in synovial ...
Citations
... MH7A is a novel immortalized rheumatoid fibroblast-like synoviocyte line that was established by stably transfecting FLS cells with the SV40 T antigen gene (Miyazawa et al., 1998). It is usually used for investigating the regulation of rheumatoid FLS to develop future RA therapy (Zhang et al., 2019;Kong et al., 2020). Studies on natural compounds' anti-arthritic effects have mainly focused on their influence on antioxidant and anti-inflammatory effects (Yu et al., 2021). ...
Background: The fruit of Terminalia chebula has been widely used for a thousand years for treating diarrhea, ulcers, and arthritic diseases in Asian countries. However, the active components of this Traditional Chinese medicine and their mechanisms remain unclear, necessitating further investigation. Objectives: To perform simultaneous quantitative analysis of five polyphenols in T. chebula and evaluate their anti-arthritic effects including antioxidant and anti-inflammatory activity in vitro. Materials and methods: Water, 50% water-ethanol, and pure ethanol were used as extract solvents. Quantitative analysis of gallic acid, corilagin, chebulanin, chebulagic acid, and ellagic acid in the three extracts was performed using high-performance liquid chromatography (HPLC). Antioxidant activity was assessed by the 2,2-diphenylpicrylhydrazyl (DPPH) radical-scavenging assay, and anti-inflammatory activity was evaluated by detecting interleukin (IL)-6 and IL-8 expression in IL-1β-stimulated MH7A cells. Results: The 50% water-ethanol solvent was the optimal solvent yielding the highest total polyphenol content, and the concentrations of chebulanin and chebulagic acid were much higher than those of gallic acid, corilagin, and ellagic acid in the extracts. The DPPH radical-scavenging assay showed that gallic acid and ellagic acid were the strongest antioxidative components, while the other three components showed comparable antioxidative activity. As for the anti-inflammatory effect, chebulanin and chebulagic acid significantly inhibited IL-6 and IL-8 expression at all three concentrations; corilagin and ellagic acid significantly inhibited IL-6 and IL-8 expression at high concentration; and gallic acid could not inhibit IL-8 expression and showed weak inhibition of IL-6 expression in IL-1β-stimulated MH7A cells. Principal component analysis indicated that chebulanin and chebulagic acid were the main components responsible for the anti-arthritic effects of T. chebula. Conclusion: Our findings highlight the potential anti-arthritic role of chebulanin and chebulagic acid from T. chebula.
... Histopathology examinations were applied to analyze the inflammatory response of lung tissues in ARDS mice following the reported method with minor modifications (20). Lung tissues were collected and fixed in 4% paraformaldehyde for 24 hours, and then embedded in paraffin. ...
... Frontiers in Physiology frontiersin.org sichuan ox knee reduces the level of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17A) in serum, increases the viscosity of intra-articular knee joint fluid, and eliminates swelling and promotes blood circulation (Weng et al., 2014;Li et al., 2017;Zhang et al., 2019a). Miyajima (Miyajima et al., 2013) et al. point out that hot compress increases the temperature of local tissues and reduces the excitability of afferent nerves, and helps control swelling and reduce pain. ...
... The level of magnesium (Mg) (Zeng et al., 2015) and calcium (Ca + ) (Li et al., 2016) in the serum are significantly decreased among older adults with KOA, which reduces their functional performance, increases the risk of falls, and accelerates the deterioration of KOA (Veronese et al., 2017;Heffernan et al., 2020). Some of the Traditional Chinese Herbs, e.g., paeony root, ephedra root, atractylodes macrocephala reduce pro-inflammatory cytokines such as TNF-α and interleukins, inhibit the production of matrix metalloproteinases (Yuan et al., 2015;Malemud, 2017), thereby improve the level of Mg and Ca + in serum (Gunn et al., 2013;Zhang et al., 2019a). In addition, parsnip and anemarrhena asphodeloides reduce the expression of fibroblast-like synoviocytes and receptor activator for NF-kB ligand, inhibit the activation of osteoclasts, and reduce the destruction of cartilage, bone, and tendon (Yuan et al., 2015). ...
Background: Knee osteoarthritis (KOA) is one of the most common chronic progressive diseases with degenerative destruction of articular cartilage and bone, leading to knee pain, impaired proprioception, and reduced functional performance. This study was to investigate the effects of an 8-week Traditional Chinese herb hot compress (TCHHC) combined with therapeutic exercise (TE) on pain, proprioception, and functional performance among older adults with KOA.
Methods: Twenty-seven older adults with KOA were recruited and randomly assigned to the TCHHC + TE or TE groups. Thirteen participants received TCHHC + TE, and fourteen received TE. At pre- (week 0) and post-intervention (week 9), their pain, joint proprioception, and functional performance were measured. Two-way ANOVA with repeated measures was adopted to analyze the data.
Results: Compared with week 0, the pain score, proprioception thresholds of knee extension and ankle plantarflexion, and the times of TUG and 20-m walk tests decreased more significantly in the TCHHC + TE group than in the TE group at week 9.
Conclusion: Compared with TE, the 8-week TCHHC + TE was superior in relieving pain, recovering proprioception, and improving functional performance among older adults with KOA. It is recommended that TCHHC should be adopted prior to TE to enhance the effects of KOA rehabilitation.
... It is reported that its main pharmacological effects are related to pain relief, improvement of inflammation, regulation of immune function, protection of cartilage, reduction of pannus formation, and inhibition of synovial hyperplasia, among others. [15,16] XF, also called "cangerzi" in China, has effects of antibacterial, anti-inflammatory, analgesic, antiallergic, antioxidant, antitumor and immunomodulatory. [17] It is mainly used for treating cold, sinusitis, rheumatic arthralgia, rubella pruritus and other diseases. ...
Xanthii fructus (XF) is the dried and mature fruit of Xanthium sibiricum Patr. It has the effects of anti-inflammatory, antioxidant and anti-arthritic. Rheumatoid arthritis (RA) is the most common inflammatory disorder and often leads to disability. However, there are few studies on the treatment of RA by XF and the specific mechanism of treatment has not been clarified. This study was designed to explore the effects of proliferation and apoptosis by XF on human fibroblast-like synovial-RA (HFLS-RA) cells and investigate its mechanism. The cell proliferation ability was detected by MTS assay. Hoechst 33,342 staining was used to detect apoptosis, and the apoptosis rate was detected by flow cytometry. The expression levels of NF-κB p65 and β-catenin were detected by Western Blotting. MTS, Hoechst 33,342, flow cytometry analysis showed that the alcohol extract of XF inhibited human fibroblast-like synovial-RA cells proliferation and promoted apoptosis in a dose-dependent manner. Western Blotting experiment showed that the extract of XF could reduce the expression levels of NF-κB p65 and β-catenin. The extract of XF has a significant therapeutic effect on RA in vitro by regulating NF-κB signaling pathway and Wnt/β-catenin signaling pathway. Our research will help to clarify the potential pharmacological mechanism of XF on RA and provide experimental basis for the application of XF in clinical treatment.
... Cinnamomi Ramulus, the dried twigs of the aromatic plant Cinnamomum cassia (L.) Presl, is an important component of Guizhi-Shaoyao-Zhimu decoction (an effective antiarthritic prescription) [5]. According to phytochemistry and pharmacology researches, CR contains a variety of active substances represented by cinnamaldehyde, which have anti-inflammatory, antioxidant, antitumor, antipyretic, and analgesic effects [6]. ...
... Collagen-induced arthritis (CIA) model was prepared according to the description of previous literature [5]. Firstly, bovine type II collagen (2 mg/mL) was emulsified in an equal volume of complete Freund's adjuvant (2 mg/ mL). ...
Cinnamomi Ramulus (CR) has been extensively used as a remedy for inflammatory diseases in China. This study adopted an integrative approach of experimental research, phytochemistry, and network pharmacology to investigate its alleviative effects on rheumatoid arthritis (RA) and the underlying potential mechanisms. CR extract (50, 100, and 200 mg/kg) and methotrexate (MTX) significantly ameliorated RA symptoms in the collagen-induced arthritis (CIA) rat model. They also reduced paw volume, arthritis index, proinflammatory cytokines (TNF-α, IL-17A, IL-6, and IL-1β), and oxidative damage. Sixty-three compounds were systematically identified as the basic components of CR. Fifty-five common genes obtained from compounds and GEO databases were employed to construct the protein-protein interaction (PPI) network. Among them, 20 hub genes were identified via the cytoHubba. Enrichment analysis of the common genes indicated that the TNF signaling pathway and IL-17 signaling pathway might be the potential key pathways. Moreover, molecular docking methods confirmed the high affinity between the top 10 bioactive components of CR and the top 10 targets. In addition, in vitro results showed that CR extract (0.2, 0.4, and 0.8 mg/mL) inhibited inflammation and oxidative damage in MH7A cells stimulated by lipopolysaccharide (LPS). In summary, this study adopted multiple approaches to elucidate the protective effect and potential mechanisms of CR on RA, indicating that CR might be a promising herbal candidate for further investigation of RA treatment.
... The general information of both groups was the same (P > 0:05), which could be compared. The diagnostic criteria included fasting serum uric acid content of >420 μmol/L in men and menopausal women or >357 μmol/L in premenopausal women [20][21][22]. ...
Traditional Chinese Medicine (TCM) is a medical system with a distinctive theoretical framework and extensive experience in identification and treatment acquired by the Chinese people in long-term medical practice and life practice. It is a complete, integrated, and complex knowledge system in epistemology. This study is aimed at exploring the clinical effectiveness of TCM called the Guizhi Shaoyao Zhimu Decoction in the treatment of hyperuricemia. A total of 100 patients with hyperuricemia at the Medical College of the Second Clinical College, Shandong, China, from January 2019 to January 2022 are selected as the research subjects and divided into group A and group B according to the random table method, with 50 cases in each group. Group A is treated with oral allopurinol tablets, 100 mg, 2 times a day, and group B is treated with the modified Guizhi Shaoyao Zhimu Decoction based on group A. For observation, serum uric acid (SUA) levels, urinary uric acid (UUA) levels, levels of serum inflammatory response factors (IL-6, CRP, and TNF-α), vascular endothelial function indexes (serum malondialdehyde (MDA) content, nitric oxide (NO) content), an acute attack of gout, and the incidence of adverse reactions are measured. Results show that after 2 w and 4 w of treatment, the levels of blood uric acid in each group gradually decreased compared with those before treatment, and group B is lower than group A ( P < 0.05 ). After treatment, the vascular endothelial function indexes and inflammatory factor levels in each group are significantly improved compared with those before treatment, and the indexes in group B are better than those in group A. There is no significant difference in the incidence of related adverse reactions and acute attack of gout ( P > 0.05 ). This shows that the TCM Guizhi Shaoyao Zhimu Decoction has a significant curative effect in the treatment of patients with hyperuricemia, which is worthy of clinical reference application.
... The rats were subcutaneously injected in the tail roots with CII emulsion, followed 14 days later with secondary immunization through subcutaneous inoculation with CII emulsion of IFA (100 μL/rat) at the same location. The disease intensity was estimated using two indexes (paw oedema and arthritis rating) as previously described [14]. ...
Purpose: To study the therapeutic effect of 3-O-caffeoylquinic acid (3-O-CQA) from Periploca forrestii extract (PFE) on collagen-mediated arthritis (CIA) in rats, as well as the potential underlying mechanism of action. Methods: PFE and 3-O-CQA were successively and intragastrically administered to CIA rats. Paw swelling, arthritic scores and H & E staining were used to evaluate the therapeutic effect of 3-O-CQA. Moreover, to determine the effects of PFE and 3-O-CQA on fibroblast-resembling synoviocytes obtained from arthritic subjects (RAFLS), the viability of RAFLS cultured in vitro was measured with MMT, while apoptotic lesions were analyzed by flow cytometry. The levels of IL-6 in CIA and RAFLS were determined by enzyme-linked immunosorbent assay (ELISA), while quantitative reverse transcriptionpolymerase chain reaction (qRT-PCR) and immunoblotting were used to assess their mRNA and polypeptide levels, respectively. Results: PFE in 3-O-CQA ameliorated swelling and reduced arthritic scores in CIA rat model, and also decreased cytokine levels (p < 0.05). By decreasing mRNA and protein expressions, 3-O-CQA repressed the phosphorylation of STAT3 and JAK2 as well as the protein levels of IL-23 and RORγt (p < 0.05). Conclusion: The results of this study show that CIA and RAFLS are ameliorated in rats by 3-O-CQA in PFE through regulation of IL17/ IL23 and Th17 cells. Thus, 3-O-CQA affords a therapeutic strategy for the management of collagen-induced arthritis. Keywords: Arthriti; Periploca forrestii Schltr extract; 3-O-Caffeoylquinic acid; Interleukin (IL)-17; IL-23; Th17 cells
... Compared with radical hysterectomy, TCM treatment has positive effects on women's fertility. Cinnamomi ramulus and Paris polyphylla Sm. are commonly used in TCM [29][30][31]. e pathological basis of AM in the theory of TCM is that the blood of the meridian in the uterus is cold and stagnant. In TCM, it is believed that Cinnamomi ramulus can warm the meridian and promote blood circulation and that Paris polyphylla Sm. can remove blood stasis. ...
Objective:
To explore the molecular mechanism of the Cinnamomi ramulus and Paris polyphylla Sm. (C-P) drug pair in the treatment of adenomyosis (AM) based on network pharmacology and animal experiments.
Methods:
Via a network pharmacology strategy, a drug-component-target-disease network (D-C-T-D) and protein-protein interaction (PPI) network were constructed to explore the core components and key targets of C-P drug pair therapy for AM, and the core components and key targets were verified by molecular docking. Based on the results of network pharmacology, animal experiments were performed for further verification. The therapeutic effect of the C-P drug pair on uterine ectopic lesions was evaluated in a constructed AM rat model.
Results:
A total of 30 components and 45 corresponding targets of C-P in the treatment of AM were obtained through network pharmacology. In the D-C-T-D network and PPI network, 5 core components and 10 key targets were identified. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the PI3K signaling pathway was the most significantly enriched nontumor pathway. Molecular docking showed that most of the core components and key targets docked completely. Animal experiments showed that the C-P drug pair significantly ameliorated the pathological changes of endometriotic lesions in AM model rats and inhibited PI3K and Akt gene expression, and PI3K and Akt protein phosphorylation. In addition, treatment with the C-P drug pair promoted AM cell apoptosis; upregulated the protein expression of Bax, Caspase-3, and cleaved Caspase-9; and restrained Bcl-2 expression.
Conclusions:
We propose that the pharmacological mechanism of the C-P drug pair in the treatment of AM is related to inhibition of the PI3K/Akt pathway and promotion of apoptosis in AM ectopic lesions.
... The CIA model is recognized as the classical animal model to study human RA, which has great similarities with human RA in pathology, immunology, and clinical features (24). The wide application of this model provides more help in exploring the pathogenesis and pathological process of RA and the treatment plan for RA. ...
The liver is essential for metabolic and immune functions and has been linked to systemic inflammatory diseases. However, the role of the liver is still elusive during the development of rheumatoid arthritis (RA), although there have been indeed some reports. We used label-free quantitative proteomics and experimental verification in this study to reveal the hepatic lipid metabolism and immune function during collagen-induced arthritis (CIA) development. The proteomics results revealed that the role of the liver differs in different phases of CIA rats. In terms of specific performance, hepatic lipid metabolism, which is primarily concerned with cholesterol, triacylglycerol, and phospholipid, was significantly influenced in the CIA induction phase, whereas the immune function, which includes binding of granulocytes, adhesion of immune cells, etc., was affected considerably at the peak phase of CIA rats compared to normal rats. Finally, the hepatic dynamic changes in CIA rats were further confirmed using targeted metabolomics and ELISA. We found that most fatty acids of the liver in the CIA induction phase were significantly decreased, and proteins related to complement activation and migration or adhesion of immune cells including C3, MMP-8, CTSZ, and S100A9 were significantly increased in the liver of CIA rats in the peak phase. Our findings indicated that the lipid metabolism and immune function of the liver were influenced in CIA rats. Thus, the conditions of the liver during RA development should be considered in therapeutic and nutritional interventions.
... 10 Moreover, increasing pieces of evidence have demonstrated that TCMs, which include TCM formulas, herbal medicines, and other natural products, are precious resources for curing chronic and complex diseases. 11 Wang-Bi capsule (WB), as a TCM-based herbal formula, has been used in the treatment of RA in China for many years and has shown positive therapeutic effects. 12,13 In addition, WB is also used as a supplement to the treatment of OA. ...
Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine-threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.
