Antimicrobial and cytotoxic activities of flavonoid and phenolics extracted from Sepia pharaonis ink (Mollusca: Cephalopoda).

BACKGROUND: Several studies have been reported previously on the bioactivities of different extracts of marine molluscs. Therefore, we decided to evaluate the cytotoxic and antimicrobial activities of S. pharaonis ink as a highly populated species in the Red Sea. We extracted the flavonoids from the ink and analyzed their composition. Then we evaluated systematically the cytotoxic and antimicrobial properties of this extract. A pharmacokinetic study was also conducted using SwissADME to assess the potential of the identified flavonoids and phenolic compounds from the ink extract to be orally active drug candidates. RESULTS: Cytotoxic activity was evaluated against 5 cell lines (MCF7, Hep G2, A549, and Caco2) at different concentrations (0.4 µg/mL, 1.6 µg/mL, 6.3 µg/mL, 25 µg/mL, 100 µg/mL). The viability of examined cells was reduced by the extract in a concentration-dependent manner. The highest cytotoxic effect of the extract was recorded against A549 and Hep G2 cancer cell lines cells with IC50 = 2.873 and 7.1 µg/mL respectively. The mechanistic analysis by flow cytometry of this extract on cell cycle progression and apoptosis induction indicated that the extract arrests the cell cycle at the S phase in Hep G2 and MCF7, while in A549 cell arrest was recorded at G1 phase. However, it causes G1 and S phase arrest in Caco2 cancer cell line. Our data showed that the extract has significant antimicrobial activity against all tested human microbial pathogens. However, the best inhibitory effect was observed against Candida albicans ATCC 10,221 with a minimum inhibitory concentration (MIC) of 1.95 µg/mL. Pharmacokinetic analysis using SwissADME showed that most flavonoids and phenolics compounds have high drug similarity as they satisfy Lipinski's criteria and have WLOGP values below 5.88 and TPSA below 131.6 Å2. CONCLUSION: S. pharaonis ink ethanolic extract showed a promising cytotoxic potency against various cell lines and a remarkable antimicrobial action against different pathogenic microbial strains. S. pharaonis ink is a novel source of important flavonoids that could be used in the future in different applications as a naturally safe and feasible alternative of synthetic drugs.

Combating the causative agent of amoebic keratitis, Acanthamoeba castellanii, using Padina pavonica alcoholic extract: toxicokinetic and molecular docking approaches.

Natural products play a significant role in providing the current demand as antiparasitic agents, which offer an attractive approach for the discovery of novel drugs. The present study aimed to evaluate in vitro the potential impact of seaweed Padina pavonica (P. pavonica) extract in combating Acanthamoeba castellanii (A. castellanii). The phytochemical constituents of the extract were characterized by Gas chromatography-mass spectrometry. Six concentrations of the algal extract were used to evaluate its antiprotozoal activity at various incubation periods. Our results showed that the extract has significant inhibition against trophozoites and cysts viability, with complete inhibition at the high concentrations. The IC50 of P. pavonica extract was 4.56 and 4.89 µg/mL for trophozoites and cysts, respectively, at 24 h. Morphological alterations of A. castellanii trophozoites/cysts treated with the extract were assessed using inverted and scanning electron microscopes and showed severe damage features upon treatment with the extract at different concentrations. Molecular Docking of extracted compounds against Acanthamoeba cytochrome P450 monooxygenase (AcCYP51) was performed using Autodock vina1.5.6. A pharmacokinetic study using SwissADME was also conducted to investigate the potentiality of the identified bioactive compounds from Padina extract to be orally active drug candidates. In conclusion, this study highlights the in vitro amoebicidal activity of P. pavonica extract against A. castellanii adults and cysts and suggests potential AcCYP51 inhibition.

In silico assessment of diterpenes as potential inhibitors of SARS-COV-2 main protease.

Aim: We aimed to investigate the potential inhibitory effects of diterpenes on SARS-CoV-2 main protease (Mpro). Materials & methods: We performed a virtual screening of diterpenoids against Mpro using molecular docking, molecular dynamics simulation and absorption, distribution, metabolism and excretion) analysis. Results: Some tested compounds followed Lipinski's rule and showed drug-like properties. Some diterpenoids possessed remarkable binding affinities with SARS-CoV-2 Mpro and drug-like pharmacokinetic properties. Three derivatives exhibited structural deviations lower than 1 Å. Conclusion: The findings of the study suggest that some of the diterpenes could be candidates as potential inhibitors for Mpro of SARS-CoV-2.

In vitro and In silico assessment of antischistosomal activities of ethanolic extract of Cornulacamonacantha.

Schistosomiasis is the second most prevailing parasitic disease worldwide. Although praziquantel is considered an effective drug in the treatment against schistosomiasis to some extent, there is an emerging drug resistance that widely recorded. Therefore, there is an urgent need to develop effective and safe anti-schistosomal drugs. In this study, Cornulaca monacantha (C. monacantha), a sub-saharan plant, was extracted using aqueous ethanol and characterized by High-Performance Liquid Chromatography (HPLC). Major constituents of the extract are belonging to flavonoids, tannins and phenolic glycosides. Worms' viability and surface morphology of Schistosoma mansoni (S. mansoni) adult worms treated with the extract were assessed using in vitro viability assay, Scanning Electron Microscopy (SEM), and histological examination. The extract (80-350 µg/ml) reduced viability percentage of worms by 40-60% and caused degeneration of both oral and ventral suckers, tegumental, sub-tegumental and muscular damage. Molecular docking approach was utilized to assess the binding affinities of the extracted compounds with S. mansoni alpha-carbonic anhydrase (SmCA), an essential tegument protein. Pharmacokinetic analysis using SwissADME showed that 7 compounds have high drug similarity. This study confirms the in vitro schistomicidal activity of C. monacantha extract against S. mansoni adult worms and suggests potential SmCA inhibition.

Flavonoids-mediated TLR4 Inhibition as a Promising Therapy for Renal Diseases.

Toll-like receptors (TLRs) control both innate and adaptive immunity with a wide expression on renal epithelial cells and leukocytes. Activation of TLRs results in the production of cytokines, chemokines and interferons along with activation of the transcription factor NF-κB, resulting in inflammatory perturbations. TLR4 signaling pathway is the most extensively studied of TLRs. TLR4 is expressed on renal microvascular endothelial and tubular epithelial cells. So, targeting TLR4 modulation could be a therapeutic approach to attenuate kidney diseases that are underlined by inflammatory cascade. Medicinal plants with anti-inflammatory activities display valuable effects and are employed as alternative sources to alleviate renal disease linked with inflammation. Flavonoids and other phytochemicals derived from traditional medicines possess promising pharmacological activities owing to their relatively cheap and high safety profile. Our review focuses on the potent anti-inflammatory activities of twenty phytochemicals to verify if their potential promising renoprotective effects are related to suppression of TLR4 signaling in different renal diseases, including sepsis-induced acute kidney injury, renal fibrosis, chemotherapy-induced nephrotoxicity, diabetic nephropathy and renal ischemia/reperfusion injury. Additionally, molecular docking simulations were employed to explore the potential binding affinity of these phytochemicals to TLR4 as a strategy to attenuate renal diseases associated with activated TLR4 signaling.

The antimicrobial, antibiofilm, and wound healing properties of ethyl acetate crude extract of an endophytic fungus Paecilomyces sp. (AUMC 15510) in earthworm model.

The endophytic fungus Paecilomyces sp. (AUMC 15510) was isolated from healthy stem samples of the Egyptian medicinal plant Cornulaca monacantha. We used GC-MS and HPLC analysis to identify the bioactive constituents of ethyl acetate crude extract of Paecilomyces sp. (PsEAE). Six human microbial pathogens have been selected to evaluate the antimicrobial activity of PsEAE. Our data showed that the extract has significant antimicrobial activity against all tested pathogens. However, the best inhibitory effect was observed against Bacillus subtilis ATCC 6633 and Pseudomonas aeruginosa ATCC 90274 with a minimum inhibitory concentration (MIC) of 3.9 µg/ml and minimum bactericidal concentration (MBC) of 15.6 µg/ml, for both pathogens. Also, PsEAE exerts a significant inhibition on the biofilm formation of the previously mentioned pathogenic strains. In addition, we evaluated the wound healing efficiency of PsEAE on earthworms (Lumbricus castaneus) as a feasible and plausible model that mimics human skin. Interestingly, PsEAE exhibited a promising wound healing activity and enhanced wound closure. In conclusion, Paecilomyces sp. (AUMC 15510) could be a sustainable source of antimicrobial agents and a potential therapeutic target for wound management.

Flavonoids-mediated SIRT1 signaling activation in hepatic disorders.

The prevalence of various hepatic diseases increases dramatically worldwide and regarded as a serious health problem. Sirtuins are one of the main strategic controllers of different cellular processes, including cell cycle, mitochondrial biogenesis, insulin secretion, redox balance, inflammation, and apoptosis. SIRT1 is the most prominent and broadly studied member of sirtuins that implicated in health status and longevity. Therefore, targeting the SIRT1 signaling pathways may be a reasonable therapeutic approach to treat different diseases, including hepatic disorders. Flavonoids are polyphenolic compounds widely present in different plants and possess beneficial effects against diverse diseases. In this review, we focused on the flavonoids, (-)-epicatechin, ampelopsin, baicalin, delphinidin, fisetin, epigallocatechin-3-gallate, luteolin, pinocembrin, quercetin, silibinin, trans-chalcone and xanthohumol, to verify whether their potential promising hepatoprotective effects are related to activation of SIRT1. Additionally, molecular modeling simulations were applied to explore the potential binding mode of these flavonoids to SIRT1. The complied information and molecular docking simulations suggested that SIRT1 signaling is involved in the beneficial pharmacologic activities of flavonoids in different hepatic diseases.