Flavonoids are promising safe therapy against COVID-19.

Flavonoids are a class of phenolic natural products, well-identified in traditional and modern medicines in the treatment of several diseases including viral infection. Flavonoids showed potential inhibitory activity against coronaviruses including the current pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and designated as COVID-19. Here, we have collected all data related to the potential inhibitory mechanisms of flavonoids against SARS-CoV-2 infection and their significant immunomodulatory activities. The data were mapped and compared to elect major flavonoids with a promising role in the current pandemic. Further, we have linked the global existence of flavonoids in medicinal plants and their role in protection against COVID-19. Computational analysis predicted that flavonoids can exhibit potential inhibitory activity against SARS-CoV-2 by binding to essential viral targets required in virus entry and/ or replication. Flavonoids also showed excellent immunomodulatory and anti-inflammatory activities including the inhibition of various inflammatory cytokines. Further, flavonoids showed significant ability to reduce the exacerbation of COVID-19 in the case of obesity via promoting lipids metabolism. Moreover, flavonoids exhibit a high safety profile, suitable bioavailability, and no significant adverse effects. For instance, plants rich in flavonoids are globally distributed and can offer great protection from COVID-19. The data described in this study strongly highlighted that flavonoids particularly quercetin and luteolin can exhibit promising multi-target activity against SARS-CoV-2, which promote their use in the current and expected future outbreaks. Therefore, a regimen of flavonoid-rich plants can be recommended to supplement a sufficient amount of flavonoids for the protection and treatment from SARS-CoV-2 infection.

Critical discovery and synthesis of novel antibacterial and resistance-modifying agents inspired by plant phytochemical defense mechanisms.

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.

Novel betulin derivative is responsible for the anticancer folk use of Ziziphus spina-christi from the hot environmental habitat of UAE.

ETHNOPHARMACOLOGICAL RELEVANCE: Several natural products derived from plant sources are developed to remarkable medicines based on their traditional uses. Ziziphus, a worldwide known plant, is proven for potential cytotoxic activity. However, the plant growing at the unique hot environmental climate of UAE was never investigated. Different phytochemicals may be produced from the same plant genotype at different climates leading to variable pharmacological activities. AIM OF THE STUDY: The study was conducted in order to investigate phytochemicals in the UAE native Z. spina-christi plant and its anticancer activity. MATERIALS AND METHODS: Z. spina-christi plant were collected, dried and dissected into leaves, stems and thorns. The plant organs were subjected to comparative fractionation-based anticancer assay followed by spectroscopic analysis of a uniquely isolated compound. RESULTS: The results indicate that a novel betulin derivative (13-dehydrobetulin) isolated from plant stem exhibited substantial anticancer activity specifically against liver cancer and with wide therapeutic range. CONCLUSIONS: Growth of cytotoxic traditionally-known plant remedy at harsh environmental habitat advances its anticancer activity due to production of novel phytochemical with optimum activity and minimal toxicity. Furthermore, such approach may be a future to develop novel lead compounds with optimum activity.

Assessment of herbal drugs for promising anti-Candida activity.

BACKGROUND: Microbial infections are diverse and cause serious human diseases. Candida albicans infections are serious healthcare-related infections that are complicated by its morphological switching from yeast to hyphae, resistant biofilm formation and mixed infections with bacteria. Due to the increase in drug resistance to currently used antimicrobial agents and the presence of undesirable side effects, the need for safe and effective novel therapies is important. Compounds derived from plants are known for their medicinal properties including antimicrobial activities. The purpose of the study was to compare and evaluate the anti-Candida activities of several medicinal plants in order for the selection of a herbal drug for human use as effective antimicrobial. The selection was taking into considerations two important parameters; parameters related to the selected drug including activity, stability, solubility and toxicity and parameters related to the pathogen including its different dynamic growth and its accompanied secondary bacterial infections. METHODS: Seven different plants including Avicennia marina (Qurm), Fagonia indica (Shoka'a), Lawsania inermis (Henna), Portulaca oleracea (Baq'lah), Salvadora persica (Souwak), Ziziphus spina- Christi (Sidr) and Asphodelus tenuifolius (Kufer) were ground and extracted with ethanol. The ethanol extracts were evaporated and the residual extract dissolved in water prior to testing against Candida albicans in its different morphologies. The antibacterial and cytotoxic effects of the plants extracts were also tested. RESULTS: Out of the seven tested plants, L. inermis and P. oleracea showed significant anti-Candida activity with MIC ~10 µg/mL. Furthermore, both plant extracts were able to inhibit C. albicans growth at its dynamic growth phases including biofilm formation and age resistance. Accompanied secondary bacterial infections can complicate Candida pathogenesis. L. inermis and P. oleracea extracts showed effective antibacterial activities against S. aureus, P. aeruginosa, E. coli, and the multidrug resistant (MDR) A. baumannii and Klebsiella pneumoniae. Both extracts showed no toxicity when measured at their MIC on human erythrocytes. CONCLUSION: The results from this study suggested that L. inermis and P. oleracea extracts and/or their chemicals are likely to be promising drugs for human use against C. albicans and MDR bacteria.