Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence, severity and progression of autoimmune diseases (e.g. scleroderma, multiple sclerosis, rheumatoid arthritis) and certain inflammatory diseases (e.g. asthma) are sex-biased where these pathologies dominate in women. However, other immune disorders such as sepsis, post-surgery infections and gout display higher incidence and severity in men. The molecular and cellular basis underlying this sex dimorphism remains incompletely elucidated but may provide important insights for sex-specific pharmacotherapy. Nevertheless, the sex as a variable in biochemical and preclinical research on inflammation is often neglected. Thus, respective animal studies are routinely performed with males, and experiments with isolated cells rarely report the sex of the donor. However, sex differences on the cellular level do exist, in particular related to inflammatory processes that prompt for sex-specific appreciation of inflammation research. For instance, the biosynthesis of pro-inflammatory eicosanoids is sex-biased where leukotriene (LT) formation is under control of testosterone that regulates the subcellular localization of the key enzyme 5-lipoxygenase, with possible implications for gender-tailored pharmacotherapy of LT-related disorders (i.e. asthma). Moreover, prostaglandin (PG) production is sex-biased, and sex-dependent efficacy of aspirin was evident in several clinical trials. Here, we highlight the sex bias in eicosanoid biology possibly underlying the obvious sex disparities in inflammation, stimulating scientists to take sex into account when studying the pathophysiology and pharmacotherapy of inflammatory diseases.
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PMID:Sex-biased eicosanoid biology: Impact for sex differences in inflammation and consequences for pharmacotherapy. 2864 90

The Chinese herbal medicine, Huzhen Tongfeng Formula (HZTF), derived from traditional Chinese medicine (TCM) practice, has recognized therapeutic benefits for gouty arthritis (GA). HZTF is currently in the late stage of approval process as a new anti-GA drug application. However, the underlying mechanism of HZTF as an antigout medication is unclear. In this study, we combined network pharmacology and experimental validation approaches to elucidate the mechanism of action of HZTF. First, the relative drug-disease target networks were constructed and analyzed for pathway enrichment. Potential pathways were then validated by in vitro and in vivo experiments. We found that 34 compounds from HZTF matched 181 potential drug targets. Topology analysis revealed 77 core targets of HZTF, which were highly related to gout, following screening of KEGG pathway enrichment. Further analysis demonstrated that the arachidonic acid metabolic pathway was the most relevant pathway involved in the mechanism of HZTF. Validation experiments showed that HZTF significantly inhibited the inflammatory cell infiltration into gouty joints, improved the swelling of affected joints, and increased the pain threshold. HZTF significantly reduced the transcription and production of various cytokines and inflammatory mediators in vitro. In particular, cyclooxygenase (COX)-1, COX-2, and 5-lipoxygenase were simultaneously downregulated. In conclusion, our study suggests that the antigout mechanism of HZTF is associated with the inhibition of the arachidonic acid pathway, resulting in the suppression of inflammatory cytokines and mediators. These findings extend our understanding of the pharmacological action of HZTF, rationalizing the application HZTF as an effective herbal therapy for GA.
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PMID:Chinese Medicine Huzhen Tongfeng Formula Effectively Attenuates Gouty Arthritis by Inhibiting Arachidonic Acid Metabolism and Inflammatory Mediators. 3313 56