Potential Surviving Effect of Cleome droserifolia Extract against Systemic Staphylococcus aureus Infection: Investigation of the Chemical Content of the Plant.

The increasing rates of morbidity and mortality owing to bacterial infections, particularly Staphylococcus aureus have necessitated finding solutions to face this issue. Thus, we elucidated the phytochemical constituents and antibacterial potential of Cleome droserifolia extract (CDE). Using LC-ESI-MS/MS, the main phytoconstituents of CDE were explored, which were kaempferol-3,7-O-bis-alpha-L-rhamnoside, isorhamnetin, cyanidin-3-glucoside, kaempferide, kaempferol-3-O-alpha-L-rhamnoside, caffeic acid, isoquercitrin, quinic acid, isocitrate, mannitol, apigenin, acacetin, and naringenin. The CDE exerted an antibacterial action on S. aureus isolates with minimum inhibitory concentrations ranging from 128 to 512 µg/mL. Also, CDE exhibited antibiofilm action using a crystal violet assay. A scanning electron microscope was employed to illuminate the effect of CDE on biofilm formation, and it considerably diminished S. aureus cell number in the biofilm. Moreover, qRT-PCR was performed to study the effect of CDE on biofilm gene expression (cna, fnbA, and icaA). The CDE revealed a downregulating effect on the studied biofilm genes in 43.48% of S. aureus isolates. Regarding the in vivo model, CDE significantly decreased the S. aureus burden in the liver and spleen of CDE-treated mice. Also, it significantly improved the mice's survival and substantially decreased the inflammatory markers (interleukin one beta and interleukin six) in the studied tissues. Furthermore, CDE has improved the histology and tumor necrosis factor alpha immunohistochemistry in the liver and spleen of the CDE-treated group. Thus, CDE could be considered a promising candidate for future antimicrobial drug discovery studies.

The effects of cholesterol and statins on Parkinson's neuropathology: a narrative review.

Parkinson disease (PD) is chronic and progressive neurodegenerative disease of the brain characterized by motor symptoms including tremors, rigidity, postural instability, and bradykinesia. PD neuropathology is due to the progressive degeneration of dopaminergic neurons in the substantia nigra and accumulation of Lewy bodies in the survival neurons. The brain contains a largest amount of cholesterol which is mainly synthesized from astrocytes and glial cells. Cholesterol is intricate in the pathogenesis of PD and may be beneficial or deleterious. Therefore, there are controversial points concerning the role of cholesterol in PD neuropathology. In addition, cholesterol-lowering agents' statins can affect brain cholesterol. Different studies highlighted that statins, via inhibition of brain HMG-CoA, can affect neuronal integrity through suppression of neuronal cholesterol, which regulates synaptic plasticity and neurotransmitter release. Furthermore, statins affect the development and progression of different neurodegenerative diseases in bidirectional ways that could be beneficial or detrimental. Therefore, the objective of the present review was to clarify the double-sward effects of cholesterol and statins on PD neuropathology.

Outlining the Phytoconstituents of Greek Clover Herb Extract and Assessment of Its Effect against Foodborne Infections Caused by Salmonella typhimurium.

Owing to the spread of resistance between pathogenic bacteria, searching for novel compounds with antibacterial activity is essential. Here, we investigated the potential antibacterial activity of Greek clover or Trigonella foenum-graecum herb extract on Salmonella typhimurium clinical isolates. The chemical profile of the herb was initially determined using LC-ESI-MS/MS, which explored 36 different compounds. Interestingly, the fenugreek extract possessed antibacterial action in vitro with minimum inhibitory concentrations of 64 to 512 µg/mL. The potential mechanism of action was studied by elucidating the effect of the fenugreek extract on the membrane properties of S. typhimurium bacteria, including the inner and outer membrane permeability and membrane integrity. Remarkably, the fenugreek extract had detrimental effects on the membrane properties in 40-60% of the isolates. Moreover, the in vivo antibacterial action was studied using a gastrointestinal infection model with S. typhimurium bacteria. Interestingly, the fenugreek extract (200 mg/kg) improved the infection outcomes in the tested mice. This was represented by the noteworthy decrease (p < 0.05) in the bacterial count in the small intestine and caecum tissues. The survival rate of the fenugreek-extract-treated mice significantly increased compared to the S. typhimurium-infected group. Additionally, there was an improvement in the histological and immunohistochemical features of tumor necrosis factor-alpha. In addition, using an ELISA and qRT-PCR, there was an improvement in the proinflammatory and oxidative stress markers in the fenugreek-extract-treated group. Consequently, fenugreek extract should be investigated further on other food pathogens.

In Vitro Antiviral Effect and Potential Neuroprotection of Salvadora persica L. Stem Bark Extract against Lipopolysaccharides-Induced Neuroinflammation in Mice: LC-ESI-MS/MS Analysis of the Methanol Extract.

Neuroinflammation is a serious immunomodulatory complex disorder that causes neurological and somatic ailments. The treatment of brain inflammation with new drugs derived from natural sources is a significant therapeutic goal. Utilizing LC-ESI-MS/MS analysis, the active constituents of Salvadora persica extract (SPE) were identified tentatively as exerting antioxidant and anti-inflammatory effects in natural medicine. Herein, we determined the antiviral potential of SPE against herpes simplex virus type 2 (HSV-2) using the plaque assay. HSV-2 is a neurotropic virus that can cause neurological diseases. SPE exhibited promising antiviral potential with a half-maximal cytotoxic concentration (CC50) of 185.960 ± 0.1 µg/mL and a half-maximal inhibitory concentration (IC50) of 8.946 ± 0.02 µg/mL. The in vivo study of the SPE impact against lipopolysaccharide (LPS)-induced neuroinflammation was performed using 42 mice divided into seven groups. All groups were administered LPS (0.25 mg/kg) intraperitoneally, except for the normal and SPE groups 1 and 2. Groups 5, 6, and 7 received 100, 200, and 300 mg/kg SPE. It was revealed that SPE inhibited acetylcholinesterase in the brain. It increased superoxide dismutase and catalase while decreasing malondialdehyde, which explains its antioxidative stress activity. SPE downregulated the gene expression of the inducible nitric oxide synthase, as well as the apoptotic markers (caspase-3 and c-Jun). In addition, it decreased the expression of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor-alpha). Mice administered SPE (300 mg/kg) with LPS exhibited normal neurons in the cerebral cortices, hippocampus pyramidal layer, and cerebellum, as determined by the histopathological analysis. Therefore, using S. persica to prevent and treat neurodegeneration could be a promising new therapeutic strategy to be explored.

Elucidation of Natural Components of Gardenia thunbergia Thunb. Leaves: Effect of Methanol Extract and Rutin on Non-Alcoholic Fatty Liver Disease.

The rising prevalence of non-alcoholic fatty liver disease NAFLD has strained the healthcare system. Natural products could solve this problem, so the current study focused on the impact of G. thunbergia Thunb. against this ailment. LC-ESI-MS/MS revealed the phytochemical profile of the methanol extract from Gardenia thunbergia leaves (GME). Forty-eight compounds were tentatively identified, and stigmasterol, fucosterol, ursolic acid, and rutin were isolated. The separation of the last three compounds from this plant had not before been achieved. The anti-NAFLD effect of the methanol extract of the leaves of G. thunbergia, and its major metabolite, rutin, was assessed in mice against high-fructose diet (HFD)-induced obesity. Male mice were allocated into nine groups: (1) saline (control), (2) 30% fructose (diseased group), (3) HFD, and 10 mg/kg of simvastatin. Groups 4-6 were administered HFD and rutin 50, 75, and 100 mg/kg. Groups (7-9) were administered HFD and methanol extract of leaves 100, 200, and 300 mg/kg. Methanol extract of G. thunbergia leaves at 200 mg/kg, and rutin at 75 mg/kg significantly reduced HFD-induced increments in mice weight and hepatic damage indicators (AST and ALT), steatosis, and hypertrophy. The levels of total cholesterol, LDL-C, and triglycerides in the blood decreased. In addition, the expressions of CYP2E1, JNK1, and iNOS in the diseased mice were downregulated. This study found that GME and rutin could ameliorate NAFLD in HFD-fed mice, with results comparable to simvastatin, validating G. thunbergia's hepatoprotective effects.

A perspective study of the possible impact of obeticholic acid against SARS-CoV-2 infection.

The causative agent of CoV disease 2019 is a new coronavirus CoV type 2, affecting the respiratory tract with severe manifestations (SARS-CoV-2). Covid-19 is mainly symptomless, with slight indications in about 85% of the affected cases. Many efforts were done to face this pandemic by testing different drugs and agents to make treatment protocols in different countries. However, the use of these proposed drugs is associated with the development of adverse events. Remarkably, the successive development of SARS-CoV-2 variants which could affect persons even they were vaccinated, prerequisite wide search to find efficient and safe agents to face SARS-CoV-2 infection. Obeticholic acid (OCA), which has anti-inflammatory effects, may efficiently treat Covid-19. Thus, the goal of this perspective study is to focus on the possible medicinal effectiveness in managing Covid-19. OCA is a powerful farnesoid X receptor (FXR) agonist possessing marked antiviral and anti-inflammatory effects. FXR is dysregulated in Covid-19 resulting in hyper-inflammation with concurrent occurrence of hypercytokinemia. Interestingly, OCA inhibits the reaction between this virus and angiotensin-converting enzyme type 2 (ACE2) receptors. FXR agonists control the expression of ACE2 and the inflammatory signaling pathways in this respiratory syndrome, which weakens the effects of Covid-19 disease and accompanied complications. Taken together, FXR agonists like OCA may reveal both direct and indirect impacts in the modulation of immune reaction in SARS-CoV-2 conditions. It is highly recommended to perform many investigations regarding different phases of the discovery of new drugs.

Bilosomes as Nanoplatform for Oral Delivery and Modulated In Vivo Antimicrobial Activity of Lycopene.

Owing to the disseminating resistance among pathogenic bacteria, especially Klebsiella pneumoniae, there is a high need for alternate compounds with antibacterial activity. Herein, lycopene was isolated from Lycopersicon esculentum L. Molecular docking approach was employed to explore lycopene binding affinity to selected vital proteins of K. pneumoniae with the binding mechanisms being investigated. This proposed a promising antibacterial activity of lycopene. However, the pharmacological use of lycopene is hampered by its poor solubility and limited oral bioavailability. Accordingly, bilosomes were fabricated for oral lycopene delivery. The computed entrapment efficiency, mean vesicular size, and zeta potential values for the optimized formulation were 93.2 ± 0.6%, 485.8 ± 35.3 nm, and -38.3 ± 4, respectively. In vitro drug release studies revealed controlled lycopene release from constructed bilosomes, with the drug liberation being based on the Higuchi kinetics model. Transmission electron microscopic evaluation of bilosomes revealed spherical nanovesicles free from aggregates. Moreover, the in vitro and in vivo antibacterial activity of lycopene and its constructed formulations against multidrug-resistant K. pneumoniae isolates were explored. The optimized bilosomes exhibited the lowest minimum inhibitory concentrations ranging from 8 to 32 µg/mL. In addition, scanning electron microscopy revealed remarkable deformation and lysis of the bilosomes-treated bacterial cells. Regarding in vivo investigation, a lung infection model in mice was employed. The tested bilosomes reduced the inflammation and congestion in the treated mice's lung tissues, resulting in normal-sized bronchioles and alveoli with very few congested vessels. In addition, it resulted in a significant reduction in pulmonary fibrosis. In conclusion, this study investigated the potential activity of the naturally isolated lycopene in controlling infections triggered by multidrug-resistant K. pneumoniae isolates. Furthermore, it introduced bilosomes as a promising biocompatible nanocarrier for modulation of oral lycopene delivery and in vivo antimicrobial activity.

Assessment of drugs administered in the Middle East as part of the COVID-19 management protocols.

The pandemic spread of coronavirus (COVID-19) has been reported first at the end of 2019. It continues disturbing various human aspects with multiple pandemic waves showing more fatal novel variants. Now Egypt faces the sixth wave of the pandemic with controlled governmental measures. COVID-19 is an infectious respiratory disease-causing mild to moderate illness that can be progressed into life-threatening complications based on patients- and variant type-related factors. The symptoms vary from dry cough, fever to difficulty in breathing that required urgent hospitalization. Most countries have authorized their national protocols for managing manifested symptoms and thus lowering the rate of patients' hospitalization and boosting the healthcare systems. These protocols are still in use even with the development and approval of several vaccines. These protocols were instructed to aid home isolation, bed rest, dietary supplements, and additionally the administration of antipyretic, steroids, and antiviral drugs. The current review aimed to highlight the administered protocols in the Middle East, namely in Egypt and the Kingdom of Saudi Arabia demonstrating how these protocols have shown potential effectiveness in treating patients and saving many soles.

Combination Treatment of Omega-3 Fatty Acids and Vitamin C Exhibited Promising Therapeutic Effect against Oxidative Impairment of the Liver in Methotrexate-Intoxicated Mice.

Drug-induced liver injury (DILI) is the main cause of liver damage mediated by the excretion of toxic active drug metabolites. Omega-3 fatty acids and vitamin C have potent antioxidant, anti-inflammatory, and antiapoptotic effects that could offer protection against oxidative stress and liver damage. This study evaluated the hepatoprotective effect of omega-3 and vitamin C alone as well as in a combined form in methotrexate- (MTX-) induced acute liver injury in mice. Male ICR mice of seven groups (7 mice per group) were used. Groups 1 (control group) and 2 (MTX) received 0.9% saline/day (po) for 9 days. Groups 3 and 4 received 100 and 200 mg/kg bw/day omega-3 (po), respectively, for 9 days. Groups 5 and 6 received 100 and 200 mg/kg bw/day vitamin C (po), respectively, for 9 days, while group 7 received omega-3 (100 mg/kg bw/day) and vitamin C (100 mg/kg bw/day) (po) for 9 days. All animals in groups 2 to 7 received 20 mg/kg/day MTX (I.P.) once on the 10th day. Our results revealed that MTX significantly induced the elevation of transaminases, alkaline phosphates (ALP), lactate dehydrogenase (LDH), and malonaldehyde (MDA) while depleting the levels of superoxide dismutase (SOD) and glutathione (GSH) when compared to the control group. Treatment with omega-3 fatty acids or vitamin C significantly attenuated the antioxidants and biochemical alterations in a dose-independent manner. Our molecular docking study of ligand-receptor interaction revealed that both ascorbic acid and omega-3 docked well to the binding cavity of LDH with high binding affinities of -5.20 and -4.50 kcal/mol, respectively. The histopathological features were also improved by treatment with omega-3 and vitamin C. The combined form of omega-3 and vitamin C showed a remarkable improvement in the liver enzymes, oxidative stress biomarkers, and the histopathological architecture of the mice. Conclusively, the combination of omega-3 and vitamin C demonstrated a synergistic therapeutic effect against MTX-intoxicated mice, hence representing a potential novel strategy for the management of drug-induced liver disorders.

Elucidation of the Metabolite Profile of Yucca gigantea and Assessment of Its Cytotoxic, Antimicrobial, and Anti-Inflammatory Activities.

The acute inflammation process is explained by numerous hypotheses, including oxidative stress, enzyme stimulation, and the generation of pro-inflammatory cytokines. The anti-inflammatory activity of Yucca gigantea methanol extract (YGME) against carrageenan-induced acute inflammation and possible underlying mechanisms was investigated. The phytochemical profile, cytotoxic, and antimicrobial activities were also explored. LC-MS/MS was utilized to investigate the chemical composition of YGME, and 29 compounds were tentatively identified. In addition, the isolation of luteolin-7-O-ß-d-glucoside, apigenin-7-O-ß-d-glucoside, and kaempferol-3-O-α-l-rhamnoside was performed for the first time from the studied plant. Inflammation was induced by subcutaneous injection of 100 µL of 1% carrageenan sodium. Rats were treated orally with YGME 100, 200 mg/kg, celecoxib (50 mg/kg), and saline, respectively, one hour before carrageenan injection. The average volume of paws edema and weight were measured at several time intervals. Levels of NO, GSH, TNF-α, PGE-2, serum IL-1ß, IL-6 were measured. In additionally, COX-2 immunostaining and histopathological examination of paw tissue were performed. YGME displayed a potent anti-inflammatory influence by reducing paws edema, PGE-2, TNF-α, NO production, serum IL-6, IL-1ß, and COX-2 immunostaining. Furthermore, it replenished the diminished paw GSH contents and improved the histopathological findings. The best cytotoxic effect of YGME was against human melanoma cell line (A365) and osteosarcoma cell line (MG-63). Moreover, the antimicrobial potential of the extract was evaluated against bacterial and fungal isolates. It showed potent activity against Gram-negative, Gram-positive, and fungal Candida albicans isolates. The promoting multiple effects of YGME could be beneficial in the treatment of different ailments based on its anti-inflammatory, antimicrobial, and cytotoxic effects.

Antidiarrheal and Antibacterial Activities of Monterey Cypress Phytochemicals: In Vivo and In Vitro Approach.

Monterey cypress (Cupressus macrocarpa) is a decorative plant; however, it possesses various pharmacological activities. Therefore, we explored the phytochemical profile of C. macrocarpa root methanol extract (CRME) for the first time. Moreover, we investigated its antidiarrheal (in vivo), antibacterial, and antibiofilm (in vitro) activities against Salmonella enterica clinical isolates. The LC-ESI-MS/MS analysis of CRME detected the presence of 39 compounds, besides isolation of 2,3,2″,3″-tetrahydro-4'-O-methyl amentoflavone, amentoflavone, and dihydrokaempferol-3-O-α-l-rhamnoside for the first time. Dihydrokaempferol-3-O-α-l-rhamnoside presented the highest antimicrobial activity and the range of values of MICs against S. enterica isolates was from 64 to 256 µg/mL. The antidiarrheal activity of CRME was investigated by induction of diarrhea using castor oil, and exhibited a significant reduction in diarrhea and defecation frequency at all doses, enteropooling (at 400 mg/kg), and gastrointestinal motility (at 200, 400 mg/kg) in mice. The antidiarrheal index of CRME increased in a dose-dependent manner. The effect of CRME on various membrane characters of S. enterica was studied after typing the isolates by ERIC-PCR. Its impact on efflux and its antibiofilm activity were inspected. The biofilm morphology was observed using light and scanning electron microscopes. The effect on efflux activity and biofilm formation was further elucidated using qRT-PCR. A significant increase in inner and outer membrane permeability and a significant decrease in integrity and depolarization (using flow cytometry) were detected with variable percentages. Furthermore, a significant reduction in efflux and biofilm formation was observed. Therefore, CRME could be a promising source for treatment of gastrointestinal tract diseases.

Antibacterial, Immunomodulatory, and Lung Protective Effects of Boswelliadalzielii Oleoresin Ethanol Extract in Pulmonary Diseases: In Vitro and In Vivo Studies.

Lung diseases such as asthma, chronic obstructive pulmonary diseases, and pneumonia are causing many global health problems. The COVID-19 pandemic has directed the scientific community's attention toward performing more research to explore novel therapeutic drugs for pulmonary diseases. Herein, gas chromatography coupled with mass spectrometry tentatively identified 44 compounds in frankincense ethanol extract (FEE). We investigated the antibacterial and antibiofilm effects of FEE against Pseudomonas aeruginosa bacteria, isolated from patients with respiratory infections. In addition, its in vitro immunomodulatory activity was explored by the detection of the gene expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), nitric oxide synthase (iNOS), cycloxygenase-2 (COX-2), and nuclear factor kappa-B (NF-κB) in lipopolysaccharide (LPS)-induced peripheral blood mononuclear cells (PBMC). In addition, its anticancer activity against the A549 lung cancer cell line and human skin fibroblast (HSF) normal cell line was studied. Moreover, the in vivo lung protective potential of FEE was explored histologically and immunohistochemically in mice using a benzo(a)pyrene induced lung damage model. FEE exhibited antibacterial and antibiofilm activities besides the significant inhibition of gene expression of TNFα, IL-6, and NF-κB. FEE also exerted a cytotoxic effect against A549 cell line. Histological and immunohistochemical investigations with morphometric analysis of the mean area percentage and color intensity of positive TNF-α, COX-2, and NF-κB and Bcl-2 reactions revealed the lung protective activity of FEE. This study outlined the promising therapeutic activity of oleoresin obtained from B. dalzielii in the treatment of different pulmonary diseases.

Elucidation of Phytochemical Content of Cupressus macrocarpa Leaves: In Vitro and In Vivo Antibacterial Effect against Methicillin-Resistant Staphylococcus aureus Clinical Isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important human pathogen that causes various infections. The increasing resistance of MRSA to different antibiotics is widely spreading; therefore, plant extracts may be novel therapeutic alternatives. The phytochemical profiling of Cupressus macrocarpa Hartw. ex Gordon leaves in vitro, and in vivo, antimicrobial potential of its extracts against MRSA clinical isolates were explored. A phytochemical tentative identification of 49 compounds was performed in the leaves using LC-ESI-MS/MS; in addition, isolation, and structure elucidation of hesperidin and eriocitrin were achieved for the first time. The diethyl ether extract (DEEL) exhibited the best antibacterial effect with MIC values ranging from 2 to 8 µg/mL, which significantly reduced the growth and efflux activity in 48.78% and 29.26% of isolates, respectively. qRT-PCR showed a significant down expression of norA and norB genes, which significantly affected the bacterial cell morphology and had a non-significant effect on membrane depolarization (using flow cytometry). In a rat model, four groups were wounded and treated with normal saline or DEEL, or infected with MRSA, or infected and treated with DEEL. The regeneration of the epidermis, maturation of granulation tissue, and reduction of inflammatory cell infiltration were observed after treatment with DEEL. Thus, C. macrocarpa leaves may be a promising source for new antimicrobials against MRSA.