chikusetsu-saponin-iva and Neoplasms

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

The activation of IL6/STAT3 signaling is associated with the pathogenesis of many cancers. Agents that suppress IL6/STAT3 signaling have cancer-therapeutic potential. In this study, we found that chikusetsusaponin IVa butyl ester (CS-IVa-Be), a triterpenoid saponin extracted from Acanthopanas gracilistylus W.W.Smith, induced cancer cell apoptosis. CS-IVa-Be inhibited constitutive and IL6-induced STAT3 activation, repressed STAT3 DNA-binding activity, STAT3 nuclear translocation, IL6-induced STAT3 luciferase reporter activity, IL6-induced STAT3-regulated antiapoptosis gene expression in MDA-MB-231 cells, and IL6-induced TF-1 cell proliferation. Surprisingly, CS-IVa-Be inhibited IL6 family cytokines rather than other cytokines induced STAT3 activation. Further studies indicated that CS-IVa-Be is an antagonist of IL6 receptor via directly binding to the IL6Rα with a Kd of 663 ± 74 nmol/L and the GP130 (IL6Rβ) with a Kd of 1,660 ± 243 nmol/L, interfering with the binding of IL6 to IL6R (IL6Rα and GP130) in vitro and in cancer cells. The inhibitory effect of CS-IVa-Be on the IL6-IL6Rα-GP130 interaction was relatively specific as CS-IVa-Be showed higher affinity to IL6Rα than to LIFR (Kd: 4,910 ± 1,240 nmol/L) and LeptinR (Kd: 4,990 ± 915 nmol/L). We next demonstrated that CS-IVa-Be not only directly induced cancer cell apoptosis but also sensitized MDA-MB-231 cells to TRAIL-induced apoptosis via upregulating DR5. Our findings suggest that CS-IVa-Be as a novel IL6R antagonist inhibits IL6/STAT3 signaling pathway and sensitizes the MDA-MB-231 cells to TRAIL-induced cell death. Mol Cancer Ther; 15(6); 1190-200. ©2016 AACR.

Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cell Survival; Drug Synergism; Gene Expression Regulation, Neoplastic; Hep G2 Cells; Humans; Interleukin-6; MCF-7 Cells; Neoplasms; Oleanolic Acid; Receptors, Interleukin-6; Saponins; Signal Transduction; STAT3 Transcription Factor; TNF-Related Apoptosis-Inducing Ligand