Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

https://www.mdpi.com/2218-273X/9/12/795/pdf

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

A new steroidal saponin, furotrilliumoside from Trillium tschonoskii inhibits lipopolysaccharide-induced inflammation in Raw264.7 cells by targeting PI3K/Akt, MARK and Nrf2/HO-1 pathways

Anti-inflammatory effect of Calycosin glycoside on lipopolysaccharide-induced inflammatory responses in RAW 264.7 cells.

Imperatorin (IMT) is a furanocoumarin from the root of Phlomis younghusbandii (Lamiaceae) with various activities. In the present study, the anti-inflammatory effects of IMT were evaluated by examining dimethylbenzene-induced ear edema, acetic acid-induced vascular permeability and by performing cotton pellet granuloma assessments in mice. In addition, the expression of pro-inflammatory cytokines, including tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β, were detected using enzyme-linked immunosorbent assay kits in mice and using reverse transcription polymerase chain reaction analysis in RAW 264.7 cells. The expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear p65, cytosolic p65 and inhibitor of nuclear factor (NF)-κB (IκB) in RAW 264.7 cells were determined using western blot analysis. The results showed that the oral administration of IMT significantly inhibited the inflammatory reactions and reduced the release of TNF-α, IL-6 and IL-1β reactions and reduced and suppressed the mRNA expression of TNF-A expressionact1o, and the protein expression of iNOS and COX-2 in the RAW 264.7 cells. The results also indicated that IMT suppressed the activity of NF-κB via upregulating p65 and IκB in the cytoplasm and downregulating p65 in the nucleus. In conclusion, IMT possessed notable anti-inflammatory activities in vitro and in vivo through inhibiting the NF-κB pathway.

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Imperatorin possesses notable anti-inflammatory activity in vitro and in vivo through inhibition of the NF-κB pathway

Sarsasapogenin-AA13 (AA13) is a novel synthetic derivative of sarsasapogenin extracted from the Chinese herb Rhizoma Anemarrhenae. In this study we investigated the effects of AA13 on lipopolysaccharide (LPS)-induced production of inflammatory factors in macrophage cells and the anti-inflammatory activity of AA13 in an inflammatory model of dimethylbenzene-induced ear edema. Macrophage cells (RAW264.7 cells and mouse peritoneal macrophages) were exposed to LPS (1 μg/mL); pretreatment with AA13 (5-20 μmol/L) dose-dependently inhibited LPS-induced production of NO, TNF-α and PGE2, and LPS-stimulated expression levels of COX-2 and iNOS. Furthermore, pretreatment with AA13 dose-dependently suppressed LPS-stimulated phosphorylation of p38 and JNK, but had no effect on ERK in RAW264.7 cells. Moreover, pretreatment with AA13 inhibited LPS-induced activation of the nuclear factor (NF)-κB in RAW264.7 cells. The in vivo anti-inflammatory activity of AA13 was demonstrated in a mouse inflammatory model: pre-treatment with either AA13 (20 mg·kg-1·d-1, ig) or a positive control antifani (10 mg·kg-1·d-1, ig) for 3 d significantly relieved dimethylbenzene-induced ear edema. Our results demonstrate that AA13 effectively inhibit LPS-induced inflammatory responses in macrophage cells in vitro and relieve dimethylbenzene-induced ear edema in vivo.

/pdf/sarsasapogenin-aa13-inhibits-lps-induced-inflammatory-2e57r37k9h.pdf

Qingzhong Li

Papers

Anti-inflammatory activity of phlomisoside F isolated from Phlomis younghusbandii Mukerjee.