Antimicrobial and anticancer activities of Hainan dry noni fruit alcoholic extracts and their novel compounds identification using UPLC-Q-Exactive Obitrap-MS/MS.

Morinda citrifolia Linn (noni) is an important plant in the Pacific Asian region. The fruit has been used as a food source and has shown therapeutical benefits for health. Recently, it has become a source for bioactive compounds. In this study, we investigated the antimicrobial and anticancer activities of alcoholic extracts of Hainan dry noni fruit with machinery assistance and identified their novel compounds by UPLC-Q-Exactive Obitrap-MS/MS. By IE extractor aided method, the extraction of both NFE (Noni Fruit Ethanol) and NFM (Noni Fruit Methanol) solvent crude sample extracts were obtained with recovery yields of 98.48% and 71.65%, respectively. The antimicrobial effect of the crude extracts was subjected to disc diffusion test screening against two microbial strains bacterium SA (Staphylococcus aureus) and, fungal CA (Candida albicans). The MIC values of SA and CA were 35.34 and 47.80 mg/mL for NFE, 117.40 and 108.01 mg/mL for NFM, respectively. Further on, cell viability assay showed that IC50 values of extract NFE and NFM on human UMUC-3 bladder carcinogenic cells were 865.1 and 789.1 µg/mL with less effect to human SVHUC-1 normal cell line for 72hr incubation. Using UPLC-Q-exactive Orbitrap-MS/MS, ten compounds were identified in the noni extracts and confirmed from the HMDB and FooDB. Five known bioactive compounds had been used for treatments in anti-cancer, anti-obesity, and Covid-19 patients. The remaining five compounds were found novel in noni fruit. They were Cyanidin 3-(2 G-xylosylrutinoside), Inulobiose, Clausarinol, Pectachol, and 4,7-Megastigmadien-9-ol. The potential bioactivities of these novel compounds will be studied in the near future. These findings form a basis on screening natural medicinal plant extracts for beneficial use as a food and health source.

Antiproliferative and apoptotic activity of gemcitabine-lauric acid conjugate on human bladder cancer cells.

Objectives: Gemcitabine is a first-line drug for the treatment of bladder cancer. One of the most important mechanisms of gemcitabine resistance is the low expression of cellular membrane transporter hENT1. Various derivatives containing fatty acid side chains have been developed in order to facilitate gemcitabine uptake and prolong its retention in cells, such as CP-4126. In this study, the anti-tumor effect and mechanism of a new derivative of gemcitabine named SZY-200 on bladder cancer cells were investigated. SZY-200 was assembled from the gemcitabine-lauric acid conjugate. Materials and Methods: Antiproliferative activities of SZY-200 and lauric acid were evaluated using CCK-8 assay and clonogenic survival assay. The hENT1 inhibitor NBMPR was employed to determine the role of hENT1 in the apoptotic activity of GEM, CP-4126, and SZY-200. RT-qPCR, flow cytometry, fluorescence microscope, western blotting, and wound healing assay were used to study the mechanisms of SZY-200. The target genes were predicted using the BATMAN-TCM database. Results: Our data showed that SZY-200 could inhibit the proliferation of bladder cancer cells by inducing cell cycle arrest and apoptosis. The inhibitory effects were comparable to gemcitabine and CP-4126. SZY-200 does not rely on hENT1 to help it enter bladder cancer cells. Also, we found that lauric acid could inhibit the proliferation of bladder cancer cells. SZY-200 could down-regulate the expressions of PPARG and PTGS2 which were related to the occurrence and development of bladder cancer. Conclusion: SZY-200 has the same or more advantages as CP-4126 and could be an ideal candidate drug for further in vivo investigation.