Macrophage M1/M2 polarization and rheumatoid arthritis: A systematic review.

Pathological pain can be initiated after inflammation and/or peripheral nerve injury. It is a consequence of the pathological functioning of the nervous system rather than only a symptom. In fact, pain is a significant social, health, and economic burden worldwide. Flavonoids are plant derivative compounds easily found in several fruits and vegetables and consumed in the daily food intake. Flavonoids vary in terms of classes, and while structurally unique, they share a basic structure formed by three rings, known as the flavan nucleus. Structural differences can be found in the pattern of substitution in one of these rings. The hydroxyl group (-OH) position in one of the rings determines the mechanisms of action of the flavonoids and reveals a complex multifunctional activity. Flavonoids have been widely used for their antioxidant, analgesic, and anti-inflammatory effects along with safe preclinical and clinical profiles. In this review, we discuss the preclinical and clinical evidence on the analgesic and anti-inflammatory proprieties of flavonoids. We also focus on how the development of formulations containing flavonoids, along with the understanding of their structure-activity relationship, can be harnessed to identify novel flavonoid-based therapies to treat pathological pain and inflammation.

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Therapeutic Potential of Flavonoids in Pain and Inflammation: Mechanisms of Action, Pre-Clinical and Clinical Data, and Pharmaceutical Development.

Traditional herbal medicine: Therapeutic potential in rheumatoid arthritis.

Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms

Rheumatoid arthritis (RA) is a chronic prototypic immune-mediated inflammatory disease which is characterized by persistent synovial inflammation, leading to progressive joint destruction. Whilst the introduction of targeted biological drugs has led to a step change in the management of RA, 30-40% of patients do not respond adequately to these treatments, regardless of the mechanism of action of the drug used (ceiling of therapeutic response). In addition, many patients who acheive clinical remission, quickly relapse following the withdrawal of treatment. These observations suggest the existence of additional pathways of disease persistence that remain to be identified and targeted therapeutically. A major barrier for the identification of therapeutic targets and successful clinical translation is the limited understanding of the cellular mechanisms that operate within the synovial microenvironment to sustain joint inflammation. Recent insights into the heterogeneity of tissue resident synovial cells, including macropahges and fibroblasts has revealed distinct subsets of these cells that differentially regulate specific aspects of inflammatory joint pathology, paving the way for targeted interventions to specifically modulate the behaviour of these cells. In this review, we will discuss the phenotypic and functional heterogeneity of tissue resident synovial cells and how this cellular diversity contributes to joint inflammation. We discuss how critical interactions between tissue resident cell types regulate the disease state by establishing critical cellular checkpoints within the synovium designed to suppress inflammation and restore joint homeostasis. We propose that failure of these cellular checkpoints leads to the emergence of imprinted pathogenic fibroblast cell states that drive the persistence of joint inflammation. Finally, we discuss therapeutic strategies that could be employed to specifically target pathogenic subsets of fibroblasts in RA.

/pdf/critical-role-of-synovial-tissue-resident-macrophage-and-261bo2vqte.pdf

Critical Role of Synovial Tissue–Resident Macrophage and Fibroblast Subsets in the Persistence of Joint Inflammation

Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K/AKT pathway in complete Freund's adjuvant-induced arthritis in mice.

In this study, we using the in vivo destabilization of the medial meniscus (DMM) mouse model to investigate the role of bone morphogenetic protein 5 (BMP5) in osteoarthritis (OA) progression mediated via chondrocyte senescence and apoptosis. BMP5 expression was significantly higher in knee articular cartilage tissues of OA patients and DMM model mice than the corresponding controls. The Osteoarthritis Research Society International scores based on histological staining of knee articular cartilage sections were lower in DMM mice where BMP5 was knocked down in chondrocytes than the corresponding controls 4 weeks after DMM surgery. DMM mice with BMP5-deficient chondrocytes showed reduced levels of matrix-degrading enzymes such as MMP13 and ADAMTS5 as well as reduced cartilage destruction. BMP5 knockdown also decreased chondrocyte apoptosis and senescence by suppressing the activation of p38 and ERK MAP kinases. These findings demonstrate that BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as OA progression by downregulating activity in the p38/ERK signaling pathway.

Fan Kai

Papers

Hesperidin inhibits synovial cell inflammation and macrophage polarization through suppression of the PI3K/AKT pathway in complete Freund's adjuvant-induced arthritis in mice.

BMP5 silencing inhibits chondrocyte senescence and apoptosis as well as osteoarthritis progression in mice.