Oroxylin A suppress LL-37 generated rosacea-like skin inflammation through the modulation of SIRT3-SOD2-NF-κB signaling pathway.

Rosacea is a long-term inflammatory skin disease associated with the dysfunction of vascular and immunological systems. Treatment options for rosacea are difficult to implement. Oroxylin A(OA), a traditional Chinese medicine, has anti-inflammation effects in a variety of inflammatory diseases. However, it is not known that whether OA exerts protective effects against LL-37-induced rosacea. In this study, bioinformatics analyses showed that the mechanisms of rosacea and the pharmacological targets of OA were highly overlapped. Subsequently, it was shown that the administration of OA resulted in a notable amelioration of rosacea-like skin lesions, as evidenced by a reduction in immune cell infiltration, modulation of cytokine production, and inhibition of angiogenesis. Plus, it was shown that OA effectively suppressed the generation of ROS generated by LL-37, as well as the subsequent activation of NF-κB signaling pathway. To explore further, we found that OA inhibited LL-37-induced ROS production via SIRT3-SOD2 signaling pathway in keratinocytes. Based on the aforementioned evidence, it can be inferred that OA exhibits a mitigating effect on the inflammatory response in rosacea by modulating the SIRT3-SOD2-NF-κB signaling pathway.

Dietary supplementation of n-3 PUFAs ameliorates LL37-induced rosacea-like skin inflammation via inhibition of TLR2/MyD88/NF-κB pathway.

Rosacea is a facial chronic inflammatory skin disease with dysfunction of immune and neurovascular system and treatments for rosacea are challenging. N-3 polyunsaturated fatty acids (PUFAs), one of essential fatty acids, are needed for health maintenance and exert anti-inflammation and immunomodulatory effects in a series of cutaneous diseases such as atopic dermatitis and photoaging through dietary supplementation. However, the role of n-3 PUFAs on rosacea remains to be elucidated. In this study, KEGG enrichment analysis and GO analysis indicated that the biological process and signaling pathways, including chemokine signaling pathway, regulated by n-3 PUFAs highly overlapped with those in the pathogenic biological process of rosacea, especially the erythema telangiectasia type. Next, mice were randomized to fed with a customized n-3 PUFAs diet. We showed that n-3 PUFAs ameliorated skin erythema, inhibited dermal inflammatory cell infiltration (mast cells, neutrophils, and CD4 +T cells) and suppressed elevated pro-inflammatory cytokines in LL37-induced rosacea-like mice. Besides, n-3 PUFAs were also verified to repress angiogenesis in LL37-induced mice skin. Further investigation revealed that n-3 PUFAs attenuated LL37-induced inflammation via TLR2/ MyD88/ NF-κB pathway both in mice and in keratinocytes. In conclusion, our findings underscore that dietary supplementation of n-3 PUFAs have the potential to become an efficient and safe clinical therapeutic candidate for rosacea.

Ruyi Jinhuang Powder accelerated diabetic ulcer wound healing by regulating Wnt/ß-catenin signaling pathway of fibroblasts In Vivo and In Vitro.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic ulcer is a common complication of diabetes. Therapies of diabetic ulcer are still challenging due to the complicated aetiology. Ruyi Jinhuang Powder (RJP) is gradually adopted to treat diabetic ulcer and has a significant therapeutic effect. AIM OF THE STUDY: To investigate the therapeutic potential for diabetic ulcer in vivo and in vitro, we explored whether and how RJP influences wound healing in mice and fibroblasts at the tissular, cellular and molecular levels. MATERIALS AND METHODS: The chemical composition of RJP was identified by HPLC. Streptozotocin (STZ) induced diabetic mice were used to confirm the curative effect of RJP in vivo. Besides, the impact of RJP in stimulating fibroblasts proliferation, migration and reducing inflammation was studied through CCK-8 assay, cell scratch assay, PCR, WB, etc. RESULTS: A total of 17 compounds were identified in RJP by HPLC. Our data indicated that RJP promoted fibroblasts proliferation and migration via activating Wnt/ß-catenin signaling pathway. Consistently, RNA-seq analysis of mice skin samples also showed that the shared differentially expressed genes (DEGs) between RJP group and control group were most enriched in wnt signaling pathway. These DEGs were closely related with wound repair. In addition, the anti-inflammation effect of RJP was also confirmed through downregulation of IL-1α, IL-1ß, IL-6 and IL-10 expression levels. These biological effects were reduced when the Wnt/ß-catenin signaling was blocked. The in vivo study also demonstrated the effect of RJP in improving epidermal wound closure, which was consistent with the in vitro results. CONCLUSIONS: Topical application of RJP was effective in treating diabetic ulcer. This research is helpful to provide new insights and evidence into the role of RJP in accelerating unhealing wound and reducing wound inflammation.

Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results.

BACKGROUND: Osteoporosis is a common complication in patients with rheumatoid arthritis (RA). The change of bone mineral density (BMD) in patients with RA is slow, and little data are known about the long-term change of BMD. OBJECTIVES: This study aimed to determine the frequency of osteoporosis and the long-term change on BMD in a cohort of Chinese patients with RA routinely receiving calcium and vitamin D supplementation. METHODS: A total of 304 consecutive patients with RA were recruited. Bone mineral density measurements of the forearm, lumbar spine, and total hip were performed by dual-energy x-ray absorptiometry and compared with 200 age- and sex-matched healthy controls. Risk factors were analyzed by logistic regression models. RESULTS: The prevalence of osteoporosis at all measured sites in patients with RA was statistically significantly higher than in healthy controls. A total of 107 patients of the cohort had a mean of 4 years of follow-up. More patients with BMD decrease were found without calcium and vitamin D use compared with those who continuously took calcium and vitamin D (64.3% vs 19.8% at the forearm and 28.6% vs 16.1% at the total hip, respectively). Only the use of calcium and vitamin D supplementation was associated with a decreased risk of BMD decrease both at the forearm and at the total hip. CONCLUSIONS: Osteoporosis is common in Chinese patients with RA. Routine use of calcium and vitamin D supplementation decreased the risk of BMD decrease and should be recommended for all patients with RA.