Egyptian mandarin peel oil's anti-scabies potential via downregulation-of-inflammatory/immune-cross-talk: GC-MS and PPI network studies.

The current study investigated the scabicidal potential of Egyptian mandarin peel oil (Citrus reticulata Blanco, F. Rutaceae) against sarcoptic mange-in-rabbits. Analysis of the oil's GC-MS identified a total of 20 compounds, accounting for 98.91% of all compounds found. Mandarin peel oil topical application improved all signs of infection, causing a scabicidal effect three days later, whereas in vitro application caused complete mite mortality one day later. In comparison to ivermectin, histopathological analysis showed that the epidermis' inflammatory-infiltration/hyperkeratosis-had disappeared. In addition to TIMP-1, the results of the mRNA gene expression analysis showed upregulation of I-CAM-1-and-KGF and downregulation of ILs-1, 6, 10, VEGF, MMP-9, and MCP-1. The scabies network was constructed and subjected to a comprehensive bioinformatic evaluation. TNF-, IL-1B, and IL-6, the top three hub protein-coding genes, have been identified as key therapeutic targets for scabies. From molecular docking data, compounds 15 and 16 acquired sufficient affinity towards the three screened proteins, particularly both possessing higher affinity towards the IL-6 receptor. Interestingly, it achieved a higher binding energy score than the ligand of the docked protein rather than displaying proper binding interactions like those of the ligand. Meanwhile, geraniol (15) showed the highest affinity towards the GST protein, suggesting its contribution to the acaricidal effect of the extract. The subsequent, MD simulations revealed that geraniol can achieve stable binding inside the binding site of both GST and IL-6. Our findings collectively revealed the scabicidal ability of mandarin peel extract for the first time, paving the way for an efficient, economical, and environmentally friendly herbal alternative for treating rabbits with Sarcoptes mange.

Vitis vinifera leaf extract liposomal Carbopol gel preparation's potential wound healing and antibacterial benefits: in vivo, phytochemical, and computational investigation.

Vitis vinifera Egyptian edible leaf extract loaded on a soybean lecithin, cholesterol, and Carbopol gel preparation (VVL-liposomal gel) was prepared to maximize the in vivo wound healing and anti-MRSA activities for the crude extract, using an excision wound model and focusing on TLR-2, MCP-1, CXCL-1, CXCL-2, IL-6 and IL-1ß, and MRSA (wound infection model, and peritonitis infection model). VVL-liposomal gel was stable with significant drug entrapment efficiency reaching 88% ± 3, zeta potential value ranging from -50 to -63, and a size range of 50-200 µm nm in diameter. The in vivo evaluation proved the ability of VVL-liposomal gel to gradually release the drugs in a sustained manner with greater complete wound healing effect and tissue repair after 7 days of administration, with a significant decrease in bacterial count compared with the crude extract. Phytochemical investigation of the crude extract of the leaves yielded fourteen compounds: two new stilbenes (1, 2), along with twelve known ones (3-14). Furthermore, a computational study was conducted to identify the genes and possible pathways responsible for the anti-MRSA activity of the isolated compounds, and inverse docking was used to identify the most likely molecular targets that could mediate the extract's antibacterial activity. Gyr-B was discovered to be the best target for compounds 1 and 2. Hence, VVL-liposomal gel can be used as a novel anti-dermatophytic agent with potent wound healing and anti-MRSA capacity, paving the way for future clinical research.

The Potential of Corchorus olitorius Seeds Buccal Films for Treatment of Recurrent Minor Aphthous Ulcerations in Human Volunteers.

Aphthous ulcers are very common disorders among different age groups and are very noxious and painful. The incidence of aphthous ulcer recurrence is very high and it may even last for a maximum of 6 days and usually, patients cannot stand its pain. This study aims to prepare a buccoadhesive fast dissolving film containing Corchorus olitorius seed extract to treat recurrent minor aphthous ulceration (RMAU) in addition to clinical experiments on human volunteers. An excision wound model was used to assess the in vivo wound healing potential of Corchorus olitorius L. seed extract, with a focus on wound healing molecular targets such as TGF-, TNF-, and IL-1. In addition, metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds was explored. Moreover, molecular docking experiments were performed to elucidate the binding confirmation of the isolated compounds with three molecular targets (TNF-α, IL-1ß, and GSK3). Additionally, the in vitro antioxidant potential of C. olitorius seed extract using both H2O2 and superoxide radical scavenging activity was examined. Clinical experiments on human volunteers revealed the efficiency of the prepared C. olitorius seeds buccal fast dissolving film (CoBFDF) in relieving pain and wound healing of RMAU. Moreover, the wound healing results revealed that C. olitorius seed extract enhanced wound closure rates (p ≤ 0.001), elevated TGF-ß levels and significantly downregulated TNF-α and IL-1ß in comparison to the Mebo-treated group. The phenotypical results were supported by biochemical and histopathological findings, while metabolomic profiling using HR-LCMS for the crude extract of Corchorus olitorius seeds yielded a total of 21 compounds belonging to diverse chemical classes. Finally, this study highlights the potential of C. olitorius seed extract in wound repair uncovering the most probable mechanisms of action using in silico analysis.

Bioactives and functional food ingredients with promising potential for the management of cerebral and myocardial ischemia: a comprehensive mechanistic review.

Ischemia is a deadly disease featured by restricted perfusion to different organs in the body. An increase in the accumulation of reactive oxygen species and cell debris is the driving force for inducing many oxidative, inflammatory and apoptotic signaling pathways. However, the number of therapeutics existing for ischemic stroke patients is limited and there is insufficient data on their efficiency, which warrants the search for novel therapeutic candidates from natural sources. Herein, a comprehensive survey was done on the reported functional food bioactives (ca. 152 compounds) to manage or protect against health consequences of myocardial and cerebral ischemia. Furthermore, we reviewed the reported mechanistic studies for their anti-ischemic potential. Subsequently, network pharmacology- and in silico-based studies were conducted using the reported myocardial and cerebral ischemia-relevant molecular targets to study their complex interactions and highlight key targets in disease pathogenesis. Subsequently, the most prominent 20 compounds in the literature were used in a comprehensive in silico-based analysis (inverse docking, ΔG calculation and molecular dynamics simulation) to determine other potential targets for these compounds and their probable interactions with different signaling pathways relevant to this disease. Many functional food bioactives, belonging to different chemical classes, i.e., flavonoids, saponins, phenolics, alkaloids, iridoids and carotenoids, were proven to exhibit multifactorial effects in targeting the complex pathophysiology of ischemic conditions. These merits make them valuable therapeutic agents that can outperform the conventional drugs, and hence they can be utilized as add-ons to the conventional therapy for the management of different ischemic conditions; however, their rigorous clinical assessment is necessary.

Hyphaene thebaica (doum)-derived extract alleviates hyperglycemia in diabetic rats: a comprehensive in silico, in vitro and in vivo study.

In the present study, we investigated the hypoglycemic effect of different extracts (i.e. organic and aqueous) derived from the fruits of Hyphaene thebaica (doum) on male streptozotocin-induced diabetic rats. Blood glucose levels as well as the relative gene expression of insulin, TNF-α, and TGF-ß were determined in the pancreatic tissue of the experimental animals. Treatment of STZ-induced diabetic rats with aqueous extracts of the plant fruit over 7 weeks significantly reduced the elevated blood glucose and increased the relative expression of insulin, while the relative expression of inflammatory mediators (i.e. TNF-α and TGF-ß) was significantly reduced. Histopathological investigation also revealed that the aqueous extract treatment effectively reversed the ß-cell necrosis induced by STZ and restored its normal morphology. Furthermore, liquid chromatography high resolution mass spectrometry (LC-HRMS) and in silico chemical investigation of the aqueous extract elucidated its major bioactive phytochemicals (i.e. flavonoids) and putatively determined the pancreatic KATP channel as a target for these bioactive components. In vitro insulin secretion assay revealed that myricetin, luteolin, and apigenin were able to induce insulin secretion by human pancreatic cells (insulin production = 20.9 ± 1.3, 13.74 ± 1.8, and 11.33 ± 1.1 ng mL-1, respectively). Using molecular docking and dynamics simulations, we were able to shed the light on the insulin secretagogue's mode of action through these identified bioactive compounds and to determine the main structural elements required for its bioactivity. This comprehensive investigation of this native fruit will encourage future clinical studies to recommend edible and widely available fruits like doum to be a part of DM treatment plans.

Anti-Alzheimer chemical constituents of Morus macroura Miq.: chemical profiling, in silico and in vitro investigations.

Herein, we investigated both fruits and leaves of Morus macroura Miq. as a potential source of bioactive compounds against Alzheimer's disease (AD). LC-HRMS-assisted chemical profiling of its extracts showed that they are a rich source of diverse phytochemicals. Among the 29 identified compounds in both the fruit and leaf extracts, moracin D, chrysin, resveratrol, and ferulic acid were predicted to pass the human blood-brain barrier (BBB), and hence, reach their therapeutic targets in the brain. Subsequently, these compounds were subjected to a comprehensive pharmacophore-based screening for their protein targets relevant to AD using two independent software programs (i.e. Swiss Target Prediction and PharmMapper). The results of this initial virtual screening were further refined by a number of docking and molecular dynamic simulation experiments to suggest a number of crucial AD-related proteins (e.g. acetylcholine esterase, ß-secretase, and monoamine oxidase) as potential targets for these compounds. Finally, in vitro testing was performed to validate the in silico investigation's results, where chrysin, resveratrol, and ferulic acid were found to inhibit the predicted AD-related enzymes with IC50 values comparable with those of the reference inhibitors. Additionally, they were able to inhibit the aggregation of amyloid-beta, one of the hallmarks in AD pathogenesis, and to exhibit considerable antioxidant capacity. Our results highlighted Morus macroura compounds as future anti-Alzheimer chemical leads.