Principle active metabolites of Pinus morrisonicola Hayata synergistically inhibit cell proliferation and autophagy to elevate apoptosis in hepatocellular carcinoma cells.

Hepatocellular carcinoma (HCC), a common primary tumor of liver is a leading cause of cancer-associated deaths. Improving cellular apoptosis and enhancing autophagic clearance is been considered to improve treatment outcomes of HCC. Polyphenols from Pinus morrisonicola (Hayata) have shown various physiological and therapeutic benefits and the flavonoid chrysin is been known for their anticancer effects. However, the main bioactive principle and the mechanism underlying the antitumor activity of pine needle extract are not clear yet. In this study, the effects of ethanol extract from pine needle on HCC cells were determined. The results show that when compared with administration of chrysin alone, a fraction containing pinocembrin, chrysin, and tiliroside significantly reduced autophagy and increased apoptosis. The results also correlated with decrease in cell cycle regulators and the autophagic proteins like LC3-II. Collectively, the results imply the fraction containing pinocembrin, chrysin, and tiliroside as an ideal complementary medicine for an effective antitumor activity.

Essential Oil from Glossogyne tenuifolia Inhibits Lipopolysaccharide-Induced Inflammation-Associated Genes in Macro-Phage Cells via Suppression of NF-κB Signaling Pathway.

Glossogyne tenuifolia Cassini (Hsiang-Ju in Chinese) is a perennial herb native to Taiwan. It was used in traditional Chinese medicine (TCM) as an antipyretic, anti-inflammatory, and hepatoprotective agent. Recent studies have shown that extracts of G. tenuifolia possess various bioactivities, including anti-oxidant, anti-inflammatory, immunomodulation, and anti-cancer properties. However, the pharmacological activities of G. tenuifolia essential oils have not been studied. In this study, we extracted essential oil from air-dried G. tenuifolia plants, then investigated the anti-inflammatory potential of G. tenuifolia essential oil (GTEO) on lipopolysaccharide (LPS)-induced inflammation in murine macrophage cells (RAW 264.7) in vitro. Treatment with GTEO (25, 50, and 100 µg/mL) significantly as well as dose-dependently inhibited LPS-induced pro-inflammatory molecules, such as nitric oxide (NO) and prostaglandin E2 (PGE2) production, without causing cytotoxicity. Q-PCR and immunoblotting analysis revealed that the inhibition of NO and PGE2 was caused by downregulation of their corresponding mediator genes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), respectively. Immunofluorescence and luciferase reporter assays revealed that the inhibition of iNOS and COX-2 genes by GTEO was associated with the suppression of nuclear export and transcriptional activation of the redox-sensitive transcription factor, nuclear factor -κB (NF-κB). In addition, GTEO treatment significantly inhibited phosphorylation and proteosomal degradation of the inhibitor of NF-κB (I-κBα), an endogenous repressor of NF-κB. Moreover, treatment with GTEO significantly blocked the LPS-mediated activation of inhibitory κB kinase α (IKKα), an upstream kinase of the I-κBα. Furthermore, p-cymene, ß-myrcene, ß-cedrene, cis-ß-ocimene, α-pinene, and D-limonene were represented as major components of GTEO. We found that treatment with p-cymene, α-pinene, and D-limonene were significantly inhibiting LPS-induced NO production in RAW 264.7 cells. Taken together, these results strongly suggest that GTEO inhibits inflammation through the downregulation of NF-κB-mediated inflammatory genes and pro-inflammatory molecules in macrophage cells.