AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.
MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.
RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.
CONCLUSION: Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.
AIMS OF THE REVIEW: To critically anayze the literature for the botany, traditional uses, phytochemistry, pharmacology, toxicity, and clinical trials of P. sarmentosum in order to provide a scientific consensus for further research and discovery of potential candidate drugs.
MATERIALS AND METHODS: The contents of this review were sourced from electronic databases including PubMed, SciFinder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wanfang, Chinese Scientific and Technological Periodical Database (VIP), Chinese Biomedical Database (CBM), Cochrane Controlled register of Clinical Trials, Clinical Trials. gov, and Chinese Clinical Trial Registry. Chinese medicine books published over the years were used to elucidate the traditional uses of P. sarmentosum and additional information was also collected from Yao Zhi website (https://db.yaozh.com/).
RESULTS: Phytochemical analyses of the chemical constituents of P. sarmentosum include essential oil, alkaloids, flavonoids, lignans, and steroids. The literature supports the ethnomedicinal uses of P. sarmentosum for the treatment of cold, gastritis, and rheumatoid joint pain, and further confirms its relatively new pharmacological activities, including anti-inflammatory, antineoplastic, and antipyretic activities. Other biological roles such as anti-osteoporosis, antibacterial, antidepressant, anti-atherosclerotic, and hypoglycemic activities have also been reported. However, the methodologies employed in individual studies are limited.
CONCLUSIONS: There is convincing evidence from both in vitro and in vivo studies supporting the traditional use of P. sarmentosum and it is imperative that natural bioactive compounds are examined further. More efforts should be focused on the pharmacodynamic constituents of P. sarmentosum to provide practical basis for quality control, and additional studies are needed to understand the mechanism of their action. Further studies on the comprehensive evaluation of medicinal quality and understandings of serum chemistry, multi-target network pharmacology, and molecular docking technology of P. sarmentosum are of great importance and should be considered.
METHODS: MTT assay, DNA fragmentation, ELISA and cell cycle analysis were carried out.
RESULTS: Nordamnacanthal and damnacanthal at IC50 values of 1.7 μg/mL and10 μg/mL, respectively. At the molecular level, these compounds caused internucleosomal DNA cleavage producing multiple 180-200 bp fragments that are visible as a "ladder" on the agarose gel. This was due to the activation of the Mg2+/Ca2+-dependent endonuclease. The induction of apoptosis by nordamnacanthal was different from the one induced by damnacanthal, in a way that it occurs independently of ongoing transcription process. Nevertheless, in both cases, the process of dephosphorylation of protein phosphates 1 and 2A, the ongoing protein synthesis and the elevations of the cytosolic Ca2+ concentration were not needed for apoptosis to take place. Nordamnacanthal was found to have a cytotoxic effect by inducing apoptosis, while damnacanthal caused arrest at the G0/G1 phase of the cell cycle.
CONCLUSION: Damnacanthal and nordamnacanthal have anticancer properties, and could act as potential treatment for T-lymphoblastic leukemia.