The Attenuation of TNF-α-mediated Inflammatory Responses in Human Lung Adenocarcinoma Cell Line by Perilla Seed and Seed Meal Extract

Thai perilla (Perilla frutescens) extracts, which contain a substantial quantity of bioactive substances including phenolics and flavonoids, have shown marked anti-inflammatory activities in several investigated models. In the present study, the effect of perilla seed extract (PSE) and seed meal extract (PSME) on TNF-α-induced inflammatory response in human lung adenocarcinoma A549 cells was investigated. The total phenolic and flavonoid contents in PSME was lower than PSE. Markedly, rosmarinic acid was identified as the main constituent in both extracts. However, the DPPH and ABTS assays indicated that the antioxidant capacity of PSME was equal to PSE. Moreover, the iron-binding activity of PSE and PSME were exhibited by complex formation with Fe3+-NTA, indicating that the extracts may inhibit hydroxyl radical production via Fenton reaction. In vitro cytotoxicity analysis showed that both PSE or PSME co-treated with TNF-α, at 24 h exposure, were not toxic to the A549 cells. Interestingly, PSE and PSME dramatically exhibited an anti-inflammatory activity by inhibiting the mRNA expression of pro-inflammatory cytokines, IL-1β, IL-6, IL-8, and TNF-α, but did not influence iNOS and COX-2 mRNA expressions. Moreover, both extracts significantly reduced reactive oxygen species (ROS) production in TNF-α-induced A549 cells. The findings presented in this paper suggest that PSE and PSME could mitigate TNF-α-mediated inflammatory responses via limiting pro-inflammatory cytokine expressions and decreasing ROS production. Thus, perilla seed and seed meal, the by-product of a perilla seed oil cold-pressed extraction process, could be developed as food supplements or functional foods for the prevention of inflammation-induced lung carcinogenesis development. Keywords: Human lung adenocarcinoma cell line, Inflammation, Perilla seed, Perilla seed meal, Tumor necrosis factor-alpha (TNF-α)

Cytotoxic Activity against A549 Human Lung Cancer Cells and ADMET Analysis of New Pyrazole Derivatives

Two new pyrazole derivatives, namely compound 1 and compound 2, have been synthesized, and their biological activity has been evaluated. Monocrystals of the obtained compounds were thoroughly investigated using single-crystal X-ray diffraction analysis, FTIR spectroscopy, and NMR spectroscopy. The results gathered from all three techniques are in good agreement, provide complete information about the structures of 1 and 2, and confirm their high purity. Thermal properties were studied using thermogravimetric analysis; both 1 and 2 are stable at room temperature. In order to better characterize 1 and 2, some physicochemical and biological properties have been evaluated using ADMET analysis. The cytotoxic activity of both compounds was determined using the MTT assay on the A549 cell line in comparison with etoposide. It was determined that compound 2 was effective in the inhibition of human lung adenocarcinoma cell growth and may be a promising compound for the treatment of lung cancer.