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Background: Fibroblast-like synoviocytes (FLS) have cancer cell-like characteristics, such as abnormal proliferation and resistance to apoptosis, and play a pathogenic role in rheumatoid arthritis (RA). Hyperproliferation of RA-FLS that can be triggered by the activation of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling destructs cartilage and bone in RA patients. Chrysoeriol is a flavone found in medicinal herbs such as Chrysanthemi Indici Flos (the dried capitulum of Chrysanthemum indicum L.). These herbs are commonly used in treating RA. Chrysoeriol has been shown to exert anti-inflammatory effects and inhibit STAT3 signaling in our previous studies. This study aimed to determine whether chrysoeriol inhibits hyperproliferation of RA-FLS, and whether inhibiting STAT3 signaling is one of the underlying mechanisms. Methods: IL-6/soluble IL-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS were used to evaluate the effects of chrysoeriol. CCK-8 assay and crystal violet staining were used to examine cell proliferation. Annexin V-FITC/PI double staining was used to detect cell apoptosis. Western blotting was employed to determine protein levels. Results: Chrysoeriol suppressed hyperproliferation of, and evoked apoptosis in, IL-6/sIL-6R-stimulated RA-FLS. The apoptotic effect of chrysoeriol was verified by its ability to cleave caspase-3 and caspase-9. Mechanistic studies revealed that chrysoeriol inhibited activation/phosphorylation of Janus kinase 2 (JAK2, Tyr1007/1008) and STAT3 (Tyr705); decreased STAT3 nuclear level and down-regulated protein levels of Bcl-2 and Mcl-1 that are transcriptionally regulated by STAT3. Over-activation of STAT3 significantly diminished anti-proliferative effects of chrysoeriol in IL-6/sIL-6R-stimulated RA-FLS. Conclusions: We for the first time demonstrated that chrysoeriol suppresses hyperproliferation of RA-FLS, and suppression of JAK2/STAT3 signaling contributes to the underlying mechanisms. This study provides pharmacological and chemical justifications for the traditional use of chrysoeriol-containing herbs in treating RA, and provides a pharmacological basis for developing chrysoeriol into a novel anti-RA agent. [ABSTRACT FROM AUTHOR]

Tea is a rich source of pharmacologically active molecules that has been suggested to provide a variety of health benefits. However, its mechanism of action in aging-related intestinal flora dysbiosis mediated neuroinflammation is still unclear. This study aimed to explore whether tea polyphenols (TP) can improve memory by regulating intestinal flora mediated neuroinflammation in aging model rats. Ovariectomy (OVX) combined with D-galactose injection was used to establish aging rats related to menopause. The rats were divided into Sham control group, Aging model group, TP 75 mg/kg, 150 mg/kg, 300 mg/kg groups and VE group. After 12 weeks of intervention, the shuttle box test and Y maze test were used to check the memory of rats. The composition of intestinal flora was assessed by 16S rRNA sequencing technology. HE staining and ELISA were used to detect intestinal epithelial morphology and permeability, respectively. TLR4/NF-κB inflammation pathway related indicators were investigated by western blot, and the microglia activation in rat hippocampal tissue was checked by immunofluorescence. In the shuttle box test and the Y maze test, compared with the Sham control group, the memory of Aging model rats was significantly declined. It was observed that the intestinal flora of Aging model rats was dysbiosis, the permeability of the intestinal epithelium was increased. Further experimental results showed that the expression of TLR4/NF-κB inflammatory pathway related proteins in the hippocampus were increased, and the excessive activation of microglia was observed. The beneficial effects of TP intervention have been found to prevent memory decline and significantly improve brain inflammation induced by intestinal flora dysbiosis, and TP 300 mg/kg showed a more obvious advantage than TP 75 mg/kg. TP 300 mg/kg can significantly improve the behavior of rats, improve the composition and diversity of the intestinal flora, and the shape and function of the intestinal epithelium. By reversing the increased expression levels of TLR4, IRAK, p-IκBα and nuclear NF-κB p65 proteins in the hippocampus of Aging model rats, the activation of microglia in the CA1, CA3 and Dentate gyrus (DG) sub-regions of the hippocampus can be inhibited. TP inhibits the brain TLR4/NF-κB inflammatory signal pathway caused by the dysbiosis of intestinal flora, which may be one of the mechanisms to improve the memory decline in aging model rats. [Display omitted] • In this study, ovariectomy and D-galactose injection were used to establish aging model rats related to menopause. • The composition of the intestinal flora of aging rats was dysbiosis, which in turn triggered inflammation in the brain. • This study can provide laboratory evidence for the prevention of menopause-related memory decline. [ABSTRACT FROM AUTHOR]

Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb's anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats. To investigate the anti-gastritis activities of Am-EE and explore the mode of action. Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGE 2 ELISA kit was employed to detect prostaglandin E 2 (PGE 2). Enzyme activities and protein contents were examined by immunoblotting. Luciferase reporter gene assays (LRA) were employed to observe nuclear transcription factor (NF)-κB activity. The SPSS (SPSS Inc., Chicago, Illinois, United States) application was used for statistical examination. HPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin E 2 (PGE 2) production. The mRNA and protein synthesis of inducible cyclooxygenase (COX)-2 and NO synthase (iNOS) was down-regulated following treatment in RAW cells. Am-EE decreased NF-κB (p50) nuclear protein levels and inhibited NF-κB-stimulated LRA activity in RAW cells. Lastly, Am-EE decreased the up-regulated levels of phosphorylated IκBα and Akt proteins in rat stomach lysates and in LPS challenged RAW cell samples. Our study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer. [Display omitted] [ABSTRACT FROM AUTHOR]