Andrade, L. N. | Search bioRxiv

bioRxiv2021

Cannabidiol (CBD) repurposing as antibacterial: promising therapy of CBD plus polymyxin B against superbugs

Abstract Multidrug-resistant (MDR) and extensively drug-resistant (XDR) bacteria are a major worldwide public health problem. In the last decades, resistance to last-resort antibiotics such as polymyxin B (PB) have been increasingly observed among these superbugs, compromising the effectiveness of antimicrobial therapy. The present study aimed (i) to assess the ultrapure Cannabidiol (CBD) antibacterial activity against a broad diversity of Gram-negative (GN) and Gram-positive (GP) bacteria (44 different species, 95 strains), comprising standard strains and clinical isolates, and (ii) to investigate the antibacterial activity of the combination CBD + PB against GN bacteria, including chromosomal- and plasmid-acquired PB-resistant and intrinsically PB-resistant GNB. We evaluated CBD in vitro antibacterial activity using the standard broth microdilution method, and the antibacterial activity of the combination CBD + PB was screened using the standard broth microdilution and confirmed by checkerboard assay. CBD exhibited antibacterial activity against different GP bacterial species, lipooligosaccharide (LOS)-expressing GN diplococcus (GND) (Neisseria gonorrhoeae, Neisseria meningitidis, and Moraxella catarrhalis), and Mycobacterium tuberculosis. The combination CBD + PB exhibited antibacterial activity against PB-resistant GNB (e.g., Klebsiella pneumoniae) as well as additive and/or synergistic effect against LOS-expressing GND. The antibacterial activity of the combination CBD + PB against Pseudomonas aeruginosa and plasmid-mediated colistin-resistant (MCR-1) E. coli strains could be only demonstrated in the presence of phenylalanine-arginine-{beta}-naphthylamide (PA{beta}N). In conclusion, our results show promising translational potential of the combination CBD + PB against MDR and XDR GNB, including PB-resistant K. pneumoniae, highlighting its potential as a rescue treatment for life-threatening infections caused by these superbugs. One Sentence SummaryPromising combination of cannabidiol (CBD) + polymyxin B (PB) against superbugs (e.g., PB-resistant Gram-negative bacilli): Repurposing CBD

microbiology↗

bioRxiv2018

Evaluation of the cytotoxic potential of extracts from the genus Passiflora cultived in Brazil against cancer cells

This work aimed to evaluate the cytotoxic potential against cancer cells of Passiflora genus plant species cultivated in Brazil and identify the mechanism of cytotoxicity induced by the most promising extract. Leaf extracts from 14 Passiflora (P.) species were obtained ASE and in vitro cytotoxicity evaluated against cancer cell lines using MTT assay at a single concentration of 50 g/mL. Additionally, the IC50 of the P. alata (ELPA) leaf extracts was determined against both tumor (HCT-116, SF-295, OVACAR-8, and HL-60), and non-tumor cells (PBMC). The ELPA flavonoids were identified by HPLC-DAD and UHPLC-MS/MS. The morphological analyses used light and fluorescence microscopy, and cell cycle and DNA fragmentation analyses used flow cytometry to determine the mechanism of cell death induced by ELPA in HL-60. Among the Passiflora leaf extracts evaluated; ELPA stood out with high cytotoxic activity, followed by P. capsularis and P. quadrangulares with varying high and low cytotoxic activity. ELPA presented high cytotoxic potency in HL-60 (IC50 19.37 g/mL), yet without cytotoxic activity against PBMC, suggesting selectivity for tumor cells. The cytotoxic activity of ELPA may well be linked to the presence of ten identified flavonoids. Cells treated with ELPA presented the hallmarks typical of apoptosis and necrosis, with cell cycle arrest in the G2/M phase. Conclusion: From among the studied species, ELPA presented greater cytotoxic activity, possibly a consequence of synergistic flavonoid action which induces cell death by apoptosis and necrosis.

pharmacology and toxicology↗