Antimicrobial and Antibiofilm Activity of Monolaurin against Methicillin-Resistant Staphylococcus aureus Isolated from Wound Infections.

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is one of the major pathogens associated with life-threatening infections, showing resistance to various antibiotics. This study aimed to assess the influence of monolaurin on biofilm-forming MRSA. Methods: The agar dilution method determined the minimum inhibitory concentration (MIC) of monolaurin against MRSA isolates and explored its impact on the resistance profile of selected antibiotics. The assessment of combined therapy involving monolaurin and antibiotics was conducted using fractional inhibitory concentration (FIC). The tissue culture plate strategy appraised monolaurin's antibiofilm activity and its inhibitory concentration (IC50), with assessment via scanning electron microscopy. Reverse transcription polymerase chain reaction (RT-PCR) discerned a monolaurin effect on the expression of the icaD gene. Results: Monolaurin exhibited MIC values ranging from 500 to 2000 µg/mL. FIC index showed a synergistic effect of monolaurin with ß-lactam antibiotics ranging from 0.0039 to 0.25 (p < 0.001). Among the 103 investigated MRSA isolates, 44 (44.7%) displayed moderate biofilm formation, while 59 (55.3%) were strong biofilm producers. Antibiofilm activity demonstrated concentration dependence, confirming monolaurin's capacity to inhibit biofilm formation and exhibited strong eradicating effects against preformed MRSA biofilms with IC50 values of 203.6 µg/mL and 379.3 µg/mL, respectively. Scanning electron microscope analysis revealed reduced cell attachments and diminished biofilm formation compared to the control. The expression levels of the icaD gene were remarkably reduced at monolaurin concentrations of 250 and 500 µg/mL. Conclusion: Monolaurin had significant inhibitory effects on MRSA pre-existing biofilms as well as biofilm development. So, it can be employed in the treatment of severe infections, particularly those associated with biofilm formation including catheter-associated infections.

Investigating the superiority of chitosan/D-alpha-tocopheryl polyethylene glycol succinate binary coated bilosomes in promoting the cellular uptake and anti-SARS-CoV-2 activity of polyphenolic herbal drug candidate.

The evolution of a safe and effective therapeutic system to conquer SAR-CoV-2 infection deemed to be a crucial worldwide demand. Curcumin (CUR) is a phytomedicinal polyphenolic drug that exhibited a well-reported anti-SAR-CoV-2. However, the therapeutic activity of CUR is hindered by its poor intestinal permeability and diminished aqueous solubility. Therefore, this study strived to develop D-alpha-tocopheryl polyethylene glycol succinate (TPGS) bilosomes (TPGS-Bs) adopting 23 full factorial designs to improve solubility and intestinal permeability of CUR, hence boosting its anti-SARS-CoV-2 activity. Eight experimental runs were attained considering three independent variables: soybean phosphatidylcholine amount (mg) (SPC amount), bile salt amount (mg) (BS amount), and TPGS amount (mg). The optimum formula (F4) exhibited EE % (88.5 ± 2.4 %), PS (181.5 ± 21.6 nm), and ZP (-34.5 ± 3.7 mV) with desirability value = 0.739 was picked as an optimum formula. Furthermore, the optimum formula (F4) was extra coated with chitosan (CS) to improve permeability and anti-SAR-CoV-2 activity. Caco-2 cell uptake after 2 hr revealed the superiority of CS-F4 and F4 by 6 and 5 folds relative to CUR dispersion, respectively. Furthermore, CS-F4 exhibited a significantly higher anti-SARS-CoV-2 activity with IC50 (0.24 µg/ml) by 8.3 times than F4 (1.99 µg/ml). Besides, the mechanistic study demonstrated that the two formulae imparted antiviral activity by inhibiting the spike protein by virucidal potentialities. In addition, the conducted molecular docking and MD simulations towards the SARS-CoV-2 Mpro enzyme confirmed the interaction of CUR with key residues of the virus enzymes. Based on the preceded, CS-F4 could be assumed to be used to effectively eradicate SARS-CoV-2 infection.

Gypsogenin Battling for a Front Position in the Pentacyclic Triterpenes Game of Thrones on Anti-Cancer Therapy: A Critical Review-Dedicated to the Memory of Professor Hanaa M. Rady.

In the last decade, gypsogenin has attracted widespread attention from medicinal chemists by virtue of its prominent anti-cancer potential. Despite its late identification, gypsogenin has proved itself as a new anti-proliferative player battling for a frontline position among other classic pentacyclic triterpenes such as oleanolic acid, glycyrrhetinic acid, ursolic acid, betulinic acid, and celastrol. Herein, we present the most important reactions of gypsogenin via modification of its four functional groups. Furthermore, we demonstrate insights into the anti-cancer activity of gypsogenin and its semisynthetic derivatives and go further by introducing our perspective to judiciously guide the prospective rational design. The present article opens a new venue for a better exploitation of gypsogenin chemical entity as a lead compound in cancer chemotherapy. To the best of our knowledge, this is the first review article exploring the anti-cancer activity of gypsogenin derivatives.

Ameliorative impact of cold-pressed Rosmarinus officinalis oil against liver toxicity and genotoxic effects in streptozotocin-induced diabetic rats and their offspring.

Diabetes mellitus (DM) is a chronic, lifelong condition threatening human health. Rosmarinus officinalis oil (RO) could have a future role in DM therapy. This study evaluated the composition and antioxidative potential of RO. Antidiabetic traits of RO in streptozotocin (STZ)-induced diabetic rats was also studied considering the ameliorative impact against embryogenesis defects using in vitro and in vivo biochemical, histological, and genetic assays. RO was investigated for fatty acids and bioactive compounds (tocols and total phenolic compounds), and antiradical potential against DPPH• radicals. The genetic effects were investigated using comet assay and DNA fragmentation test. DM was induced to albino rats by injecting 60 mg/kg of STZ, while RO (100 mg/kg b.w.) was administered. The pregnant animals were divided into four groups; control (C), RO-treated (RO), diabetic (D), and combined diabetic with RO-treated (D-RO). The study was conducted for 180 days. In RO, the contents of polyunsaturated fatty acids, monounsaturated fatty acids, and saturated fatty acids were 42.3%, 41.7%, and 15.8%, respectively. The levels of α-, ß-, γ-, and δ-tocopherols were 280, 20, 1,025, and 35 mg/100 g RO, respectively. RO contained 7.2 mg GAE/g of total phenolic compounds (TPC), while RO quenched 70% of DPPH• radicals. While glucose levels reached the highest in DM rats, treating STZ-induced diabetic animals with RO-resoluted serum glucose levels. RO reduced the highest levels of serum chemistry parameters were recorded in DM animals. Histological photographs of maternal and fetus liver exhibited degenerated hepatic cells and congestion central vein. Comet cells and DNA fragments were significantly decreased in D-RO group comparing to the DM group. RO exhibited antidiabetic capabilities, and thus, it could be utilized as a functional ingredient in novel foods, nutraceuticals, and dietary supplements for diabetic patients. PRACTICAL APPLICATIONS: RO is rich in bioactive phytochemicals (tocols and phenolic compounds) with antiradical and antihyperglycemic capabilities. Tocols and phenolics are active in radical scavenging of reactive nitrogen species (i.e., peroxynitrite and nitrogen dioxide), and in the prevention of DNA bases nitration. Our results demonstrated that RO could improve the disturbed metabolism of carbohydrate in STZ-diabetic animals. The potential mode of action of bioactive compounds in RO most likely encompasses the intracellular pathway involved in glucose homeostasis or insulin signaling. In addition, the suppression of oxidative stress by phenolic compounds could provide to the antidiabetic impacts of RO. Our data supported that RO could be utilized to ameliorate DM. Protection with RO directed high protection of the maternal organs and offspring against the oxidative stress of diabetes due to the antihyperlipidemic effects and the antioxidant capabilities of RO.

Ameliorative impact of Morus alba leaves' aqueous extract against embryonic ophthalmic tissue malformation in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus (DM) is becoming a serious threat to human health. Morus alba var. multicaulis (Perr.) Loudon (Moraceae) showed a bright future in DM therapy. OBJECTIVE: The study evaluates the antioxidant activity of Morus alba leaves aqueous extract (MLAE) and antidiabetic properties of MLAE in streptozotocin-induced diabetic rats focusing on the ameliorative effects against embryogenesis defects. MATERIALS AND METHODS: MLAE was assayed for bioactive compounds, and antiradical potential. MLAE (100mg/kg body weight) was orally administered to albino rats. DM was induced by intraperitoneal injection of STZ (60mg/kg). The pregnant rats were arranged into 4 groups including control pregnant (C), MLAE-treated group (M), experimental diabetic group (D), and combined diabetic with MLAE-treated group (D-MLAE). The experiment performed in about six months. RESULTS: TPC in MLAE accounted for 11mg GAE/g dry weight (dw) while vitamin C and ß-carotene amounts were 144 and 0.1mg/100g, respectively. MLAE exhibited DPPH, NO and O-2 radical scavenging activities. Treatment of diseased-rats with MLAE resoluted serum glucose levels (378mg/dL), wherein glucose recorded the highest level (830mg/dL) in DM mothers. DM rats recorded the highest level of TC, TG, HDLc, LDLc, and CK, while MLAE treatment reduced those levels. DM rats recorded the highest level of MDA, H2O2, SOD, CAT, GST, GSPase, GSH, GOT, GPT, albumin, bilirubin, arginase, and α-l-fucosidase, while MLAE reduced those levels. Histological photomicrographs of maternal retina showed degenerated ganglionic cells, and neovascularization of nerve fiber layer with edematous inner plexiform layer, and partial loss outer plexiform layer in DM rats. CONCLUSION: MLAE could be used to ameliorate DM. Thus, it might be considered as useful dietary supplements in diabetic patients.