isobavachalcone and Arthritis--Rheumatoid

Inflammation is a biological function which triggered after the mechanical tissue disruption or from the responses by the incidence of physical, chemical or biological negotiator in body. These responses are essential act provided by the immune system during infection and tissue injury to maintain normal tissue homeostasis. Inflammation is a quite complicated process at molecular level with the involvement of several proinflammatory expressions. Several health problems are associated with prolonged inflammation, which effects nearly all major to minor diseases. The molecular and epidemiological studies jagged that the inflammation is closely associated with several disorders with their specific targets. It would be great achievement for human health around the world to overcome on inflammation. Mostly used anti-inflammatory drugs are at high risk of side effects and also expensive. Hence, the plant-based formulations gained a wide acceptance by the public and medical experts to treat it. Due to extensive dispersal, chemical diversity and systematically established biological potentials of natural products have induced renewed awareness as a gifted source for medications. However, today's urgent need to search for cheaper, more potent and safe anti-inflammatory medications to overcome on current situation. The goal of this review to compile an update on inflammation, associated diseases, molecular targets, inflammatory mediators and role of natural products. The entire text concise the involvement of various cytokines in pathogenesis of various human disorders. This assignment discussed about 321 natural products with their promising anti-inflammatory potential discovered during January 2009 to December 2018 with 262 citations.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Products; Cardiovascular Diseases; Humans; Inflammation; Neoplasms; Skin Diseases

Isobavachalcone (IBC) is a natural chalcone compound widely distributed in traditional Chinese medicine Psoralea corylifolia L., and Tibetan medicine Abelmoschus manihot (L.) Medik. Etc.. Among them, Psoralea corylifolia has the effect of tonifying the kidney and strengthening Yang, and it is recorded in the Medicinal theory that it can be used in managing rheumatism and arthralgia. In addition, It has been included in many prescriptions in traditional Chinese medicine as the main herb for managing rheumatoid arthritis (RA). Similarly, Abelmoschus manihot is a common Tibetan medicinal herb and is a common medicinal material in Tibetan medicine and reported in ancient medicinal books such as Jing Zhu Ben Cao and Si Bu Yi Dian to possess the effect of Ganhuangshui and thus can be used in treating Huangshui diseases (such as RA). Previous research has demonstrated IBC to possess numerous biological activities, including anti-cancer, anti-inflammatory, antibacterial and immunomodulatory. Nevertheless, its efficacy and potential mechanism in treating rheumatoid arthritis are yet to be investigated.. This study aimed at investigating the therapeutic efficacy and mechanism of IBC in treating RA through a combined strategy of network pharmacology, in vitro, and in vivo evaluation.. The Swiss Target Prediction and GeneCards databases were consulted to predict the potential targets of IBC and RA. Additionally, the potential targets for IBC in treating RA were predicted by consulting databases such as String, Cytoscape, MCODE, and Cytohubba. R software was utilized for enrichment analysis of GO and KEGG pathways, followed by in vitro experimentation using cell lines and in vivo experimentation using animals to explore the potential mechanism of IBC in RA treatment.. By integrating the results of network pharmacological analysis, 17 genes were found to be strongly associated with RA, such as TNF, MAPK13, EGFR, PTGS2, MMP3, etc. The enrichment analysis indicated that IBC possessed tremendous therapeutic efficacy in managing RA through PI3K-AKT, rheumatoid arthritis, and TNF signaling pathways. The in vitro experimentation indicated that IBC inhibited the proliferation, migration, and invasion, and promoted apoptosis and inhibition of inflammation of MH7A cell lines stimulated with TNF-α. The IBC might also have an increasing effect on the intracellular ROS and reducing effect on the mitochondrial membrane potential. The western blotting results indicated that IBC markedly inhibited the expression of p-PI3K, p-AKT, p-JAK1, p-STAT3 and SOCS3 proteins in TNF-α stimulated MH7A cells. Furthermore, we found that IBC also significantly reduced paw swelling and arthritis severity in CIA model rats through in vivo animal studies.. In short, this study explored the effect of IBC by combining network pharmacology prediction with in vitro and in vivo experimentation. The results indicated that IBC exerts its anti-rheumatoid arthritis effect by regulating cell proliferation and survival via PI3K/AKT and JAK/STAT signaling pathways. This may open a new horizon and provide a theoretical foundation for further development and utilization of IBC in RA management.

Topics: Animals; Arthritis, Rheumatoid; Chalcones; Drugs, Chinese Herbal; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Tumor Necrosis Factor-alpha