Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism. Issue 5 (18th June 2019)

• Record Type: Journal Article
• Authors: Qian, Ying; Huang, Rongrong; Li, Senlin; Xie, Rui; Qian, Bei; Zhang, Zijun; Li, Lei; Wang, Baotian; Tian, Cheng; Yang, Jian; Xiang, Ming
• Is Part Of: Journal of leukocyte biology. Volume 106:Issue 5(2019)
• Page Start: 1089
• Page End: 1100
• Publication Date: 2019-06-18
• Subjects: ginsenoside Rh2 -- immune deficiency -- metabolism regulation -- synergistic treatment; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1002/JLB.2A0419-117R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract: Ginsenoside Rh2 (G-Rh2) has well-established potent antitumor activity; yet, the effects of G-Rh2 on immune and metabolism regulation in cancer treatment, especially non-small cell lung cancer (NSCLC) remain unclear. We showed that G-Rh2 had a synergistic antitumor effect with cyclophosphamide (CY) on mice with NSCLC, and improved the immune deficiency caused by CY. Consistently, G-Rh2 exhibited no inhibitory effect on tumor growth of T cells-deficient nude mice. Furthermore, G-Rh2 treatment triggered the oxidative decomposition of fatty acid (FA), suppressed FA synthesis, increased ketone level, and decreased glucocorticoid (CORT) secretion. G-Rh2 significantly down-regulated the expression of fatty acid synthase ( FASN ). Of note, in liver-specific FASN knockout mice G-Rh2 failed to show the same immune enhancement effects. Further mechanistic exploration revealed that G-Rh2 suppressed the expression and nuclear translocation of sterol regulatory element binding protein 1 (SREBP-1 ), and disturbed the SREBP-1 – FASN interaction in vitro. Graphical Abstract: Ginsenoside Rh2 may enhance the anti-tumor immunology by inhibiting the transcription regulation of SREBP-1 on FASN to suppress FA synthesis, increase ketone level, and decrease CORT secretion.