Silibinin alleviates inflammation-induced bone loss by modulating biological interaction between human gingival fibroblasts and monocytes.

BACKGROUND: Silibinin has shown various pharmacological effects that could be attributed to its antioxidant, anti-inflammatory, and immunoregulatory properties. However, the therapeutic potential of silibinin for periodontitis has not been investigated. METHODS: The therapeutic effects of silibinin in ligation-induced experimental periodontitis were investigated using biochemical, histological, and immunohistochemical methods. The effects of silibinin on the osteoclastogenesis of RAW264.7 cells were investigated using TRAP staining, quantitative polymerase chain reaction (qPCR), pit formation, and immunoblotting. Moreover, its effects on inflammatory cytokine production, RANKL expression, and oxidative stress in lipopolysaccharide (LPS)-stimulated human gingival fibroblasts (HGFs) were evaluated using qPCR and flow cytometry. A coculture system was established to elucidate the effects of silibinin on the crosstalk between LPS-stimulated HGFs and undifferentiated monocytes. RESULTS: Silibinin significantly reduced the alveolar bone loss, decreased the gingival inflammation and RANKL expression, and decreased the RANKL/osteoprotegerin ratio in gingival tissues in experimental periodontitis. The in vitro results showed that silibinin inhibited RANKL-induced osteoclast differentiation and function of RAW264.7 cells and suppressed RANKL-induced nuclear factor of activated T cells 1 (NFATc1) induction and translocation through the nuclear factor-κB and mitogen-activated protein kinase signaling pathways. Silibinin decreased the inflammatory cytokine level and oxidative stress production in LPS-stimulated HGFs; significantly suppressed membrane-bound RANKL expression on LPS-stimulated HGFs; and significantly disrupted TRAP+ cell differentiation in the coculture system. CONCLUSIONS: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators. Collectively, targeting the inflamed HGF resolution that mediates osteogenesis may use silibinin as a potential drug-repurposing candidate for modulating alveolar bone destruction in periodontitis. SUMMARY: Silibinin effectively inhibits inflammation-induced bone loss in experimental periodontitis based on the regulation of stimulated HGFs by inhibiting the expression of inflammatory and osteoclastogenic mediators.

Investigating Clinical Efficacy and Mechanism of Qingfei Paidu Decoction for Treatment of COVID-19 Based on Integrative Pharmacology / 中国实验方剂学杂志

Objective:Potential targets and pathways of Qingfei Paidu decoction（QFPD）for treating coronavirus disease-2019（COVID-19） were analyzed based on the integrative pharmacology，the efficacy and material basis was predicted.This study provide a reference for the development and clinical application of QFPD. Method:Based on the integrative pharmacology of traditional Chinese medicine（TCMIP V2.0），the key targets and pathways of the intervention of QFPD on COVID-19 were enriched，the interaction network of "formula-herb-disease-targets-pathways" was constructed to explored the molecular mechanism of QFPD for the treatment of COVID-19. Result:The research results show that key-targets such as cell tumor antigen p53（tp53），protein kinase B1（Akt1），Nuclear factor nuclear transcription factor-κB（NF-κB）p105 subunit（NFKB1），nuclear factor p65 subunit（RELA），human NF-κB inhibited protein α（NFKBIA），ect.Closely associated with lung damage.The pathways such as interleukin signaling，adrenoceptors，7 members of the family of c-type lectin domains A（CLEC7A）/inflammasome pathway，phosphoinositide-3-kinase（PI3K）/protein kinase B（Akt）inflammatory signaling pathway，tp53 regulates transcription of DNA repair ect. may be the key pathways related with QFPD's effect on the treatment of COVID-19 accompany with lung injury， fever， cough and other symptoms.The results show that QFPD has many clinical effects， such as anti-inflammatory， anti-virus， strengthening immunity， inhibit the development of pulmonary fibrosis， protecting heart and lungs， treating asthma， regulating gastrointestinal tract， etc.In addition， there is a good synergism between the original prescription and the combined prescription， and each original prescription has its own emphasiscan prevention and treatment of COVID-19. Conclusion:QFPD plays a role in balancing immunity and eliminating inflammation，and it can treat COVID-19 by multi-pathway，multi-channel，multi-target and multi-link.This study also provides a new idea for the research of prevention and treatment of modern infectious diseases by use the traditional Chinese medicine.

Effective components of traditional Chinese medicine for regulating TGF-Beta1/Smads signaling pathway in hepatic fibrosis / 中国中药杂志

Hepatic fibrosis is a liver damage healing response affected by a variety of factors; its formation is associated with multiple cytokines and a variety of signaling pathways. Transforming growth factor beta1( TGF-β1) is one of the strongest fibrosis cytokines known,and involves almost all the key links in hepatic fibrosis. TGF-β1/Smads signal pathway is the most classical pathway for TGF-β1 to play its role in promoting fibrosis as well as one of the most important signaling pathways of hepatic fibrosis formation. Studies for the signal pathway have made a series of scientific research achievements in recently years. Traditional Chinese medicine has the advantages of " multiple ingredients,multiple targets and less side effects",and is widely used in the clinical treatment of hepatic fibrosis.Effective components of traditional Chinese medicine are monomer compounds,which are extracted and purified from traditional Chinese medicine. Nowadays,the molecular biology studies of effective traditional Chinese medicine have become a hotspot. Modern advanced technology and methods can be used to directly clarify the targets and the signaling pathways,reveal the mechanism of traditional Chinese medicine in treating diseases,and promote the modernization and international development of traditional Chinese medicine industry. This review summarized the structure,function and application of TGF-β1/Smads signaling pathway in the progress of anti-hepatic fibrosis,and analyzed the action mode and possible mechanism of various effective components of traditional Chinese medicine in regulating TGF-β1/Smads signaling pathway and intervening the treatment of hepatic fibrosis in the past five years,so as to put forward new ideas for innovating new targeted traditional Chinese medicine for hepatic fibrosis.