Novel human STING activation by hydrated-prenylated xanthones from Garcinia cowa.

OBJECTIVES: We investigate the anticancer activity and human stimulator of interferon genes pathway activation by a new hydrated-prenylated tetraoxygenated xanthone, garcicowanone I (1) and two known xanthones (2 and 3) that were isolated from the root bark of Garcinia cowa Roxb. ex Choisy. METHODS: The anticancer activity of each compound was evaluated by sulforhodamine B assay in immortalized cancer cell lines. Stimulator of interferon genes pathway activation was assessed by western blot analysis using human THP-1-derived macrophages. The production of pro-inflammatory cytokines from these macrophages was also evaluated via enzyme-linked immunosorbent assay. KEY FINDINGS: Both compounds 1 and 3 displayed moderate inhibitory effects on the cancer cells, including a cisplatin-resistant cell line, with IC50 values in the range of 10-20 µM. All three xanthones activated the stimulator of interferon genes, as evidenced by phosphorylation of tank-binding kinase 1, the stimulator of interferon genes protein and interferon regulatory factor 3. Furthermore, treatment of these macrophages with compounds 1-3 led to the production of pro-inflammatory cytokines, including interleukin 6, tumour necrosis factor α and interleukin 1ß. CONCLUSIONS: In conclusion, the isolated xanthones, including the novel garcicowanone I, displayed promising anticancer and immunomodulatory activity that warrants further research.

Six New Polyoxygenated Xanthones from Garcinia cowa and Their Neuroprotective Effects on Glutamate-Mediated Hippocampal Neuronal HT22 Cell Death.

Six new polyoxygenated xanthones, garcicowanones F-H (1-3), norcowanol A-B (4-5), and garcinone F (6) along with twelve known compounds 7-18 were obtained from the latex of Garcinia cowa Roxb. ex Choisy. All new compounds have a 1,3,7-trioxygenated or 1,3,6,7-tetraoxygenated xanthone nucleus and differ from majority of xanthones from G. cowa by hydrated side chains. Compounds 1, 7, 8 and 18 exhibited significant neuroprotective effects on glutamate-mediated hippocampal neuronal HT22 cell death. In particular, compound 1 exhibited the most potent neuroprotective effect with >80 % cell viability in the concentration range of 2.9-115 µM. Further studies on compound 1 showed that it decreased cellular Ca2+ influx and inhibits cellular reactive oxygen species generation in HT22 cells. A Western blot analysis showed that MAPK phosphorylation, Bax, and AIF translocation dramatically increased upon treatment with 5 mM glutamate and decreased upon a co-treatment with compound 1.