cajanine 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

Natural killer (NK) cells play important roles in immune responses and have been wildly used in immunotherapy. Nevertheless, some limitations remain. It is urgent to explore novel and safe strategies to enhance NK cell activity.. The aim of this study was to investigate the immuno-stimulatory effects and to reveal the molecular mechanism of LJ101019C, a derivative of a natural small-molecule compounds cajanine, on NK cells.. Cell proliferation was examined by CCK8 assay, then we used the cytotoxicity detection kit to detect the cytotoxicity of NK cells. The change of cell cycle, intracellular reactive oxygen species (ROS) level and mitochondrial mass were evaluated by FACS and Operetta high-content image analysis, respectively. Furthermore, the IFN-γ secretion of NK cells were measured by ELISA. The Kv1.3 protein expression and function were detected by western blot and patch-clamp technique, respectively. The role of Kv1.3 in AKT/mTOR pathway activation was determined by western blot.. The results showed that LJ101019C at relatively low concentrations (0.05-0.1 µM) significantly increased the proliferation of NK cells. And 1 µM LJ101019C could elevate the proportion of NK cells in the S-phase of the cell cycle (*p < 0.1). Furthermore, the cytotoxic effects of NK cells targeting MIA PaCa-2 cells were significantly enhanced by 0.1 and 1 µM LJ101019C, and were associated with the enhanced secretion of IFN-γ by NK cells (*p < 0.1; **p < 0.05). 0.1 and 1 µM LJ101019C increased intracellular levels of ROS (**p < 0.05), and 0.1 µM LJ101019C elevated mitochondrial mass (*p < 0.1). Electrophysiological recordings indicated that LJ101019C led to a remarkably increase the Kv1.3 current density. Moreover, western blot results indicated that LJ101019C elevated Kv1.3 protein expression and activated AKT/mTOR signaling via increasing the expression of Kv1.3 in NK cells.. LJ101019C increases the proliferation and the cytotoxicity of NK cells at relatively low concentrations. The mechanism is the activation of AKT/mTOR signaling pathway driven by up-regulation of Kv1.3 in NK cells. These suggest LJ101019C is a promising candidate for improving the efficacy of NK cell-based immunotherapies.

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Diethylstilbestrol; Female; Humans; Immunotherapy; Killer Cells, Natural; Kv1.3 Potassium Channel; Mice; Mice, Inbred BALB C; Neoplasms; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction; TOR Serine-Threonine Kinases; Up-Regulation