Preparation and in vivo evaluation of nano sized cubosomal dispersion loaded with Ruta graveolens extracts as a novel approach to reduce asthma-mediated lung inflammation.

Asthma is a chronic disease affecting people of all ages. Asthma medications are associated with adverse effects restricting their long-term usage, demanding newer alternative therapies. This study aimed to investigate the anti-asthmatic properties of Ruta graveolens extract and its prepared nano-cubosomal dispersion (Ruta-ND). Firstly, the R. graveolens methanolic extract exhibited higher anti-inflammatory activity on Lipopolysaccharide (LPS)-activated BEAS-2B cells. To ensure best bioavailability and hence best cellular uptake, R. graveolens extract was loaded in nano-cubosomal dispersion (ND). Then, the anti-asthmatic effects of Ruta extract and ND were simultaneously evaluated in rats' model with ovalbumin-induced allergic asthma. R. graveolens extract and Ruta-ND subsided asthma score and improved lung function by restoring FEV1/FVC ratio to the expected values in control rats. Also, it showed strong antioxidant and anti-inflammatory activities manifested by lowering levels of malondialdehyde (MDA), IL-4, IL-7, TGF-ß, and Ig-E, and increasing levels of superoxide dismutase (SOD) and INF-γ in bronchoalveolar lavage fluid. Our research findings also indicate autophagy induction and apoptosis inhibition by Ruta extract and Ruta-ND. Finally, the HPLC MS/MS phytochemical profiling of R. graveolens extract evident production of various alkaloids, flavonoids, coumarins, and other phenolics with reported pharmacological properties corresponding to/emphasize our study findings. In conclusion, R. graveolens exhibited promise in managing Ova-induced allergic asthma and could be developed as an alternative anti-allergic asthma drug.

Phenolic Compounds from Populus alba L. and Salix subserrata Willd. (Salicaceae) Counteract Oxidative Stress in Caenorhabditis elegans.

Utilizing bioassay- and TLC-guided column chromatography, fifteen secondary metabolites from Populus alba and eight compounds from Salix subserrata were isolated, including a novel plant metabolite salicyl ether and characterized using ultralviolet light (UV) absorbance, mass spectrometry (MS), 1H-, 13C-NMR (nuclear magnetic resonance), heteronuclear single quantum coherence spectroscopy (HSQC) and heteronuclear multiple bond correlation (HMBC). The extracts, their sub-fractions and the isolated compounds exhibited promising antioxidant activities in vitro in DPPH and FRAP assays. Also, the extracts of P. alba leaf (PL), shoots (PS), and S. subserrata leaf (SL) demonstrated substantial antioxidant activities in vivo in the multicellular model organism Caenorhabditis elegans. For the first time, the isolated secondary metabolites, aromadendrin, tremuloidin, salicin, isorhamnetin-3-O-ß-d-rutinoside, gallocatechin, triandrin, and chrysoeriol-7-O-glucuronide were investigated. They exhibited substantial antioxidant activities in vivo. Salicin, isorhamnetin-3-O-ß-d-rutinoside and gallocatechin, in particular, protected the worms against a lethal dose of the pro-oxidant juglone (80 µM), decreased the endogenous reactive oxygen species (ROS) level to 45.34%, 47.31%, 68.09% and reduced juglone- induced hsp-16.2::GFP (green fluorescence protein) expression to 79.62%, 70.17%, 26.77%, respectively. However, only gallocatechin induced higher levels of sod-3 expression. These findings support the traditional use of Populus alba and Salix subserrata for treating inflammation especially when ROS are involved.

Dose-response relationship in Schistosoma mansoni juvenile and adult stages following limonin treatment in experimentally infected mice.

Preventive chemotherapy with praziquantel is the mainstay of schistosomiasis control. However, drug resistance is an imminent threat, particularly with large-scale administration of praziquantel, in addition to much less efficacy against young schistosomes. Several biological activities of limonin have been explored such as insecticidal, insect antifeedant, and growth-regulating activity on insects as well as antimalarial, antiviral, anticancer, cholesterol-lowering, and antioxidant activities. This study investigates limonin as an alternative antischistosomal compound using two novel, single, oral dose regimens. In the current work, the therapeutic efficacy of different limonin dosing protocols was evaluated in experimentally infected mice harboring Schistosoma mansoni (Egyptian strain) juvenile or adult stages. Oral administration of limonin in a single dose of 50 or 100 mg/kg on day 21 post-infection (p.i.) resulted in a significant worm burden reduction of 70.0 and 83.33 %, respectively. The same dose given on day 56 p.i. reduced total worm burdens by 41.09 and 60.27 %, respectively. In addition, significant reductions of 34.90 and 47.16 % in the hepatic and 46.67 and 56.1 % in the intestinal tissue egg loads, respectively, associated with significant alterations in the oogram pattern with elevated dead egg levels. Limonin produced ameliorations of hepatic pathology with reduction in dimensions and number of granulomas. Limonin also produced a variety of tegumental alterations in treated worms including tubercular disruption, edema, blebbing, and ulcerations. Results obtained by this work elucidated promising limonin bioactivity against S. mansoni juvenile and adult stages and provided a basis for subsequent experimental and clinical trials.

Chemometric discrimination of eight citrus plants utilizing chromatographic and spectroscopic techniques and insights into their biological potentials.

Citrus sinensis balady orange, C. sinensis navel orange, C. paradisi, C. limon, C. sinensis bloody orange, C. sinensis sweet orange, C. aurantium var. amara and C. reticulata were successfully discriminated using chromatographic and spectroscopic techniques coupled with chemometrics. Ultraviolet spectroscopy (UV), and nuclear magnetic resonance spectroscopy (NMR) managed to discriminate the alcohol extract samples to six and five clusters respectively on exposing the obtained data to Principle component analysis (PCA). High performance liquid chromatography (HPLC) was utilized for differentiating the different samples based upon their rutin content where C. aurantium demonstrated the highest rutin content (0.795 mg/mL). LC-ESI-MS led to the identification of 35 compounds belonging mainly to flavonoids and limonoids. In vitro biological investigations including DDPH, ABTS, FRAP and enzyme inhibitory activities revealed the promising antioxidant, neuroprotective, anti-hyperglycaemic and skin-lightning potentials of citrus samples that were correlated with the total phenol and flavonoid contents. In silico ADME/TOPKAT reflected the acceptable pharmacokinetic, pharmacodynamic and toxicity properties of the identified secondary metabolites.

Incidence of Post-Thyroidectomy Hypoparathyroidism and Associated Preoperative and Intraoperative Risk Factors.

INTRODUCTION: Thyroidectomy technique and extent are related to parathyroid injury and hypoparathyroidism. Total thyroidectomy is one of the most commonly performed endocrine surgeries, and the majority of patients recover completely without any complications. However, persistent hypoparathyroidism is the most prevalent long-term consequence following total thyroidectomy. While it is seldom deadly, it can cause severe morbidity for the patient and raise healthcare expenses. METHODS: This retrospective cohort study was conducted at King Abdulaziz Medical City, Jeddah, Saudi Arabia. We included all confirmed thyroid cancer cases that underwent thyroidectomy with or without neck dissection between July 2016 and August 2022. The data was collected from a chart review of the electronic medical record system (BEST-care), and a data collection sheet was utilized. SPSS version 26 was used to analyze the data. RESULTS: A total of 192 patients undergoing thyroid surgery were enrolled. One hundred forty-three (74.5%) were females and the mean age of participants was 45.29 ± 16.88 years. Most patients, 170 (88.5%), had a papillary histological type, and total thyroidectomy was performed in 150 (78.1%). A significant association was found between the type of surgery and postoperative hypoparathyroidism (p=<0.05*). In addition, hypocalcemia was seen in 147 (76.6%) of the patients. Postoperative hypoparathyroidism was significantly higher among patients who had asymptomatic postoperative hypocalcemia and those who received IV calcium gluconate (p=<0.05*). Moreover, postoperative hypocalcemia, hypomagnesemia, and hyperphosphatemia were significantly associated with postoperative hypoparathyroidism (p=<0.05*). CONCLUSION: The incidence of postoperative hypoparathyroidism is significantly higher among patients who underwent total thyroidectomy and had a normal level of preoperative parathyroid hormone (PTH) and magnesium (Mg) levels. Identifying these factors is a crucial step to minimize the occurrence of such complications.

Comparative metabolomics study on the secondary metabolites of the red alga, Corallina officinalis and its associated endosymbiotic fungi.

Marine endosymbionts have gained remarkable interest in the last three decades in terms of natural products (NPs) isolated thereof, emphasizing the chemical correlations with those isolated from the host marine organism. The current study aimed to conduct comparative metabolic profiling of the marine red algae Corallina officinalis, and three fungal endosymbionts isolated from its inner tissues namely, Aspergillus nidulans, A. flavipes and A. flavus. The ethyl acetate (EtOAc) extracts of the host organism as well as the isolated endosymbionts were analyzed using ultra-high performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-MS/MS)in both positive and negative ion modes, applying both full scan (FS) and all ion fragmentation (AIF) modes. Extensive interpretation of the LC-MS/MS spectra had led to the identification of 76 metabolites belonging to different phytochemical classes including alkaloids, polyketides, sesquiterpenes, butyrolactones, peptides, fatty acids, isocoumarins, quinones, among others. Metabolites were tentatively identified by comparing the accurate mass and fragmentation pattern with metabolites previously reported in the literature, as well as bioinformatics analysis using GNPS. A relationship between the host C. officinalis and its endophytes (A. flavus, A. nidulans, and A. flavipes) was discovered. C. officinalis shares common metabolites with at least one of the three endosymbiotic fungi. Some metabolites have been identified in endophytes and do not exist in their host. Multivariate analysis (MVA) revealed discrimination of A. flavipes from Corallina officinalis and other associated endophytic Aspergillus fungi (A. flavus and A. nidulans).

In vitro cytotoxicity of Withania somnifera (L.) roots and fruits on oral squamous cell carcinoma cell lines: a study supported by flow cytometry, spectral, and computational investigations.

Oral cancer is a severe health problem that accounts for an alarmingly high number of fatalities worldwide. Withania somnifera (L.) Dunal has been extensively studied against various tumor cell lines from different body organs, rarely from the oral cavity. We thus investigated the cytotoxicity of W. somnifera fruits (W-F) and roots (W-R) hydromethanolic extracts and their chromatographic fractions against oral squamous cell carcinoma (OSCC) cell lines [Ca9-22 (derived from gingiva), HSC-2, HSC-3, and HSC-4 (derived from tongue)] and three normal oral mesenchymal cells [human gingival fibroblast (HGF), human periodontal ligament fibroblast (HPLF), and human pulp cells (HPC)] in comparison to standard drugs. The root polar ethyl acetate (W-R EtOAc) and butanol (W-R BuOH) fractions exhibited the strongest cytotoxicity against the Ca9-22 cell line (CC50 = 51.8 and 40.1 µg/mL, respectively), which is relatively the same effect as 5-FU at CC50 = 69.4 µM and melphalan at CC50 = 36.3 µM on the same cancer cell line. Flow cytometric analysis revealed changes in morphology as well as in the cell cycle profile of the W-R EtOAc and W-R BuOH-treated oral cancer Ca9-22 cells compared to the untreated control. The W-R EtOAc (125 µg/mL) exerted morphological changes and induced subG1 accumulation, suggesting apoptotic cell death. A UHPLC MS/MS analysis of the extract enabled the identification of 26 compounds, mainly alkaloids, withanolides, withanosides, and flavonoids. Pharmacophore-based inverse virtual screening proposed that BRD3 and CDK2 are the cancer-relevant targets for the annotated withanolides D (18) and O (12), and the flavonoid kaempferol (11). Molecular modeling studies highlighted the BRD3 and CDK2 as the most probable oncogenic targets of anticancer activity of these molecules. These findings highlight W. somnifera's potential as an affordable source of therapeutic agents for a range of oral malignancies.

Chemical composition of the essential oils of variegated pink-fleshed lemon (Citrus x limon L. Burm. f.) and their anti-inflammatory and antimicrobial activities.

The volatile secondary metabolites of essential oils from fruit peel and leaves of variegated pink-fleshed lemon (Citrus x limon) were investigated using GLC and GLC-MS (gas-liquid chromatography-mass spectroscopy). Altogether 141 compounds were identified and quantified, accounting for 99.59% and 96.33% of the total hydrodistilled peel and leaf oil, respectively. Limonene occurred in higher amounts in fruit peel (52.73%) than in leaf oil (29.13%). Neral (12.72%), neryl acetate (8.53%), p-menth-1-en-7-al (4.63%), beta-pinene (6.35%), and nerol (4.42%) were the most abundant constituents in leaf oil, whereas gamma-terpinene (9.88%), beta-pinene (7.67%), geranial (4.44%), and neral (3.64%) dominated in the fruit peel oil. The antioxidant, anti-inflammatory, antitrypanosomal, and antimicrobial activities of the fruit peel essential oil were evaluated. The oil had a low antioxidant activity with an IC50 value of (26.66 +/- 2.07) mg/ml as compared to the efficient antioxidant ascorbic acid [IC50 (16.32 +/- 0.16) microg/ml]. The oil moderately inhibited soybean 5-lipoxygenase (5-LOX) with an IC50 value of (32.05 +/- 3.91) microg/ml and had moderate antitrypanosomal activity [IC50 (60.90 +/- 0.91) microg/ml]. In addition, moderate antimicrobial activities were detected against Gram-positive bacteria (Bacillus subtilis, Staphylococcus capitis, Micrococcus luteus), one Gram-negative bacterium (Pseudomonas fluorescens), and yeasts (Saccharomyces cerevisiae, Candida parapsilosis).

The Etiology, Diagnosis, and Management of Cerebrospinal Fluid Rhinorrhea: A Tertiary Center Experience.

Introduction The aim of the present study was to describe our institution's nine years of experience in the endoscopic endonasal management of cerebrospinal fluid (CSF) rhinorrhea and to discuss the causes, sites, and outcomes.  Methodology The medical records of patients diagnosed with CSF rhinorrhea in King Abdulaziz Medical City-Jeddah (KAMC-J) between 2014 and 2023 were retrospectively reviewed, and all relevant information including body mass index, medical and surgical history, and postoperative outcomes were obtained. Results A total of 20 cases were included in the present study, sixteen (80%) of which were females and four (20%) were males. The mean age of participants was 42.59±13.9 years. Nine cases (45%) were spontaneous CSF rhinorrhea and 11 (55%) were traumatic; within the traumatic group, six cases (54%) were iatrogenic either following previous neurosurgery or functional endoscopic sinus surgery, while the remaining five cases were related to motor vehicle accidents. The mean body mass index for the spontaneous CSF leak was 32 Kg/m2, and 33 Kg/m2 for the traumatic leaks, no statistically significant difference was noted. The cribriform plate was the most common site of leakage (65%). A multilayer surgical technique using facia lata graft with nasoseptal flap was the most common choice for reconstruction with a first-attempt success rate approximating 90%. A recurrence was observed in two patients only. No major complications were reported. The average length of stay was nine days. Conclusion The endoscopic endonasal repair of CSF leak is a safe and reliable procedure and is associated with high success rates and low risk of complications. Therefore, it should be preferred as a first-line treatment for CSF rhinorrhea.

Medical Interns' Knowledge, Attitude, and Practice Toward People Living with HIV: Multicenter Experience from Saudi Arabia.

Background: Discrimination by some healthcare providers toward people living with HIV/AIDS has been documented. Differences in cultural backgrounds make it harder for future doctors, who need a lot of knowledge and a positive attitude to treat patients. In conservative countries like Saudi Arabia, not enough is known about how much medical interns know about HIV and how they feel about people living with HIV/AIDS. Methods: From April to September 2021, this cross-sectional study use non-probability random sampling and utilized a self-administered questionnaire to collected the data from 346 medical interns who had graduated from five different medical schools. Results: Most of the subjects correctly identified the main transmission routes, such as unprotected sex (94.57%), blood and body fluid exchange (94.19%), and sharing needles or syringes (91.47%). But they did not know what the most common co-infections were for HIV patients or how to protect themselves after exposure. This paper showed that medical interns have some stigmatizing behaviors toward patients living with HIV, as 31.1% and 22.9% agreed, respectively, that they would feel more sympathetic toward people who get AIDS from blood transfusions compared to IV drug users (IDU). Conclusion: Medical interns also showed some positive attitudes, as more than half of the sample (56.2%) would not isolate beds for people living with HIV/AIDS. The study's conclusion is that HIV education and training programs should be added for medical interns, which might have a significant positive impact on their attitude.

Monoclonal antibodies for the treatment of Graves' ophthalmopathy: A systematic review and meta-analysis.

PURPOSE: The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ]). METHODS: We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials. RESULTS: Six (n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, P < 0.00001, I2 = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, P = 0.002, I2 = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, P = 0.02, I2 = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, P = 0.001, I2 = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, P = 0.03, I2 = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels. CONCLUSION: This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids.

Chemical profiling and cytotoxic potential of the n-butanol fraction of Tamarix nilotica flowers.

BACKGROUND: Cancer represents one of the biggest healthcare issues confronting humans and one of the big challenges for scientists in trials to dig into our nature for new remedies or to develop old ones with fewer side effects. Halophytes are widely distributed worldwide in areas of harsh conditions in dunes, and inland deserts, where, to cope with those conditions they synthesize important secondary metabolites highly valued in the medical field. Several Tamarix species are halophytic including T.nilotica which is native to Egypt, with a long history in its tradition, found in its papyri and in folk medicine to treat various ailments. METHODS: LC-LTQ-MS-MS analysis and 1H-NMR were used to identify the main phytoconstituents in the n- butanol fraction of T.nilotica flowers. The extract was tested  in vitro for its cytotoxic effect against breast (MCF-7) and liver cell carcinoma (Huh-7) using SRB assay. RESULTS: T.nilotica n-butanol fraction of the flowers was found to be rich in phenolic content, where, LC-LTQ-MS-MS allowed the tentative identification of thirty-nine metabolites, based on the exact mass, the observed spectra fragmentation patterns, and the literature data, varying between tannins, phenolic acids, and flavonoids. 1H-NMR confirmed the classes tentatively identified. The in-vitro evaluation of the n-butanol fraction showed lower activity on MCF-7 cell lines with IC50 > 100 µg/mL, while the higher promising effect was against Huh-7 cell lines with an IC50= 37 µg/mL. CONCLUSION: Our study suggested that T.nilotica flowers' n-butanol fraction is representing a promising cytotoxic candidate against liver cell carcinoma having potential phytoconstituents with variable targets and signaling pathways.

Coriander (Coriandrum sativum L.) essential oil and oil-loaded nano-formulations as an anti-aging potentiality via TGFß/SMAD pathway.

Aging has become a concern for many people, especially women. Given that high-quality anti-aging products are of high cost; it has imperative to search for other economical sources. Essential oils are frequently used in cosmetics products due to a wide range of biological activities as well as their pleasant odor. The current study aimed to investigate the biochemical effect of the cosmetic potential of selected Apiaceous essential oils, traditionally used for skincare, by evaluating their anti-wrinkle activity. It is worth noting that, coriander essential oil showed the highest collagenase, elastase, tyrosinase, and hyaluronidase inhibitory activities compared to other Apiaceous oils (fennel, anise, and cumin). GC-MS proved that coriander essential oil showed a very high level of oxygenated monoterpenes, with linalool (81.29%) as the most abundant constituent. Intriguingly, coriander oil cream and Coriander Essential Oil-loaded Lipid Nanoparticles (CEOLNs) formulations attenuated in vivo UV-induced skin photoaging that was manifested by significantly decreased MDA, COX-2, PGE-2, MMP-1, JNK, and AP-1 levels. Moreover, these pharmaceutical dosage forms significantly increased skin collagen content compared to UV-injured group. Also, coriander essential oil significantly increased TGFß, TGFßII, and SMAD3 protein expression levels compared to UV-injured group. In conclusion, the pharmaceutical dosage forms of coriander oil possess anti-wrinkle activities that could have an auspicious role in amending extrinsic aging.

Anticancer and Neuroprotective Activities of Ethyl Acetate Fractions from Morus macroura Miq. Plant Organs with Ultraperformance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry Profiling.

Column chromatography afforded the isolation of seven secondary metabolites (1-(2,4,6-trihydroxy phenyl)-ethanone-4-O-ß-d-glucopyranoside, naringenin-7-O-ß-d-glucopyranoside, kaempferol-3-O-α-l-rhamnoside, kaempferol-3-O-ß-d-glucopyranoside, quercetin-3-O-ß-d-glucopyranoside, quercetin-3-O-ß-d-galactopyranoside, rutin) from the ethyl acetate (ET) fractions of Morus macroura Miq. stems (S), leaves (L), and fruits (F). Their identification based on ultraviolet (UV), electron ionization (EI), electrospray ionization-mass spectrometry (ESI-MS), and 1D and 2D NMR data. In addition, profiling of ET fractions using ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) resulted in the identification of 82 compounds belonging to different classes, mainly polyphenolic constituents. Chemical profiling as well as molecular docking directed us to biological evaluation. Interestingly, the ET-L fraction exhibited a robust cytotoxic activity against HepG-2, MCF-7, and HELA cell lines. Also, it displayed a neuromodulatory activity against cisplatin neurotoxicity in rats by ameliorating the neurobehavioral dysfunction visualized in the open field and Y-maze test and modulating the neurochemical parameters such as brain amino acid levels (glutamate, aspartate, serine, and histidine), oxidative stress markers (GSH, MDA, and 8-hydroxy-2'-deoxyguanosine), and purinergic cell energy (adenosine triphosphate (ATP) and adenosine monophosphate (AMP)). In conclusion, the isolated compounds (kaempferol-3-O-ß-glucoside and quercetin-3-O-ß-glucoside) from the ET-L fraction could serve as potent anticancer agents due to their strong antioxidant, in vitro cytotoxicity, and in vivo neuroprotective activity.

Chemical profiles with cardioprotective and anti-depressive effects of Morus macroura Miq. leaves and stem branches dichloromethane fractions on isoprenaline induced post-MI depression.

This study was conducted to explore the potential cardioprotective and anti-depressive effects of dichloromethane (DCM) fractions of Morus macroura leaves (L) and stem branches (S) on post-myocardial infarction (MI) depression induced by isoprenaline (ISO) in rats in relation to their metabolites. The study was propped with a UPLC-ESI-MS/MS profiling and chromatographic isolation of the secondary metabolites. Column chromatography revealed the isolation of lupeol palmitate (6) that was isolated for the first time from nature with eight known compounds. In addition, more than forty metabolites belonging, mainly to flavonoids, and anthocyanins groups were identified. The rats were injected with ISO (85 mg kg-1, s.c) in the first two days, followed by the administration of M. macroura DCM-L and DCM-S fractions (200 mg kg-1 p.o) for 19 days. Compared with the ISO exposed rats, the treated rats displayed a reduction in cardiac biomarkers (LDH and CKMB), anxiety, and depressive-like behaviour associated with an increase in the brain defense system (SOD and GSH), neuronal cell energy, GABA, serotonin, and dopamine, confirmed by histopathological investigations. In conclusion, DCM-L and DCM-S fractions' cardioprotective and anti-depressive activities are attributed to their metabolite profile. Therefore, they could serve as a potential agent in amending post-MI depression.

Human Lung Cancer (A549) Cell Line Cytotoxicity and Anti-Leishmania major Activity of Carissa macrocarpa Leaves: A Study Supported by UPLC-ESI-MS/MS Metabolites Profiling and Molecular Docking.

Lung cancer and cutaneous leishmaniasis are critical diseases with a relatively higher incidence in developing countries. In this research, the activity of Carissa macrocarpa leaf hydromethanolic extract and its solvent-fractions (n-hexane, EtOAc, n-butanol, and MeOH) against the lung adenocarcinoma cell line (A549) and Leishmania major was investigated. The MeOH fraction exhibited higher cytotoxic activity (IC50 1.57 ± 0.04 µg/mL) than the standard drug, etoposide (IC50 50.8 ± 3.16 µg/mL). The anti-L. major results revealed strong growth inhibitory effects of the EtOAc fraction against L. major promastigotes (IC50 27.52 ± 0.7 µg/mL) and axenic amastigotes (29.33 ± 4.86% growth inhibition at 100 µg/mL), while the butanol fraction exerted moderate activity against promastigotes (IC50 73.17 ± 1.62), as compared with miltefosine against promastigotes (IC50 6.39 ± 0.29 µg/mL) and sodium stibogluconate against axenic amastigotes (IC50 22.45 ± 2.22 µg/mL). A total of 102 compounds were tentatively identified using UPLC-ESI-MS/MS analysis of the total extract and its fractions. The MeOH fraction was found to contain several flavonoids and flavan-3-ol derivatives with known cytotoxic properties, whereas the EtOAc fractions contained triterpene, hydroxycinnamoyl, sterol, and flavanol derivatives with known antileishmanial activity. Molecular docking of various polyphenolics of the MeOH fraction with HDAC6 and PDK3 enzymes demonstrates high binding affinity of the epicatechin 3-O-ß-D-glucopyranoside and catechin-7-O-ß-D-glucopyranoside toward HDAC6, and procyanidin C2, procyanidin B5 toward PDK3. These results are promising and encourage the pursuit of preclinical research using C. macrocarpa's MeOH fraction as anti-lung cancer and the EtOAc fraction as an anti-L. major drug candidates.

Secondary metabolites of ponderosa lemon (Citrus pyriformis) and their antioxidant, anti-inflammatory, and cytotoxic activities.

Column chromatography of the dichloromethane fraction from an aqueous methanolic extract of fruit peel of Citrus pyriformis Hassk. (Rutaceae) resulted in the isolation of seven compounds including one coumarin (citropten), two limonoids (limonin and deacetylnomilin), and four sterols (stigmasterol, ergosterol, sitosteryl-3-beta-D-glucoside, and sitosteryl-6'-O-acyl-3-beta-D-glucoside). From the ethyl acetate fraction naringin, hesperidin, and neohesperidin were isolated. The dichloromethane extract of the defatted seeds contained three additional compounds, nomilin, ichangin, and cholesterol. The isolated compounds were identified by MS (EI, CI, and ESI), 1H, 13C, and 2D-NMR spectral data. The limonoids were determined qualitatively by LC-ESI/MS resulting in the identification of 11 limonoid aglycones. The total methanolic extract of the peel and the petroleum ether, dichloromethane, and ethyl acetate fractions were screened for their antioxidant and anti-inflammatory activities. The ethyl acetate fraction exhibited a significant scavenging activity for DPPH free radicals (IC50 = 132.3 microg/mL). The petroleum ether fraction inhibited 5-lipoxygenase with IC50 = 30.6 microg/mL indicating potential anti-inflammatory properties. Limonin has a potent cytotoxic effect against COS7 cells [IC50 = (35.0 +/- 6.1) microM] compared with acteoside as a positive control [IC50 = (144.5 +/- 10.96) microM].

Echinops taeckholmiana Amin: Optimization of a Tissue Culture Protocol, Biological Evaluation, and Chemical Profiling Using GC and LC-MS.

There have been no reports published on the rare Echinops taeckholmiana growing wildly in Egypt. So, this study aimed to preserve it through method optimization of in vitro seed germination, besides callus formation from induced seedlings. Chemical profiling using gas chromatography-mass spectrometry (GC-MS) analysis of the n-hexane fraction afforded 29 identified components, mainly fatty acids esters, sesquiterpenes, triterpenes, one thiophene, and bis(2-ethylhexyl) phthalate. Ultra-performance liquid chromatography-electron spray ionization/tandem mass spectrometry (UPLC-ESI/MS-MS) analysis of total alcoholic root and induced calli extracts resulted in 68 metabolites. Taraxeryl acetate, ß-sitosterol, stigmasterol-3ß-d-glucoside, and 1,1,1-kestopentaose were identified from the defatted root extract, which inhibited α-amylase (IC50 54.6 µg/mL) and α-glucosidase (60.4 µg/mL) enzymes compared with acarbose (IC50 values of 30.57 and 34.71 µg/mL, respectively). Moreover, it showed moderate activity against HepG2 (IC50 31.1 ± 1.4 µg/mL) and no activity against M-NFS-60 cell lines compared to cisplatin (IC50 3.25 ± 1.4 and 8.37 ± 0.25, respectively).

Phytochemistry, Pharmacology and Medicinal Uses of Plants of the Genus Salix: An Updated Review.

The Willows (genus Salix), with more than 330-500 species and 200 hybrids, are trees, shrubs or prostrate plants that are widely distributed in Africa, North America, Europe, and Asia. The genus is traditionally used in folk medicine and represents a valuable source of biologically active compounds among them salicin, a prodrug for salicylic acid. Altogether, 322 secondary metabolites were characterized in the genus including flavonoids 94) (flavonols, flavones, flavanones, isoflavones, flavan-3-ols (catechins and procyanidins), chalcones, dihydrochalcone, anthocyanins, dihydroflavonols), phenolic glycosides (76), organic acids (28), and non-phenolic glycosides (17), sterols and terpenes (17), simple phenolics 13) and lignans 7) in addition to volatiles and fatty acids (69). Furthermore, willows exert analgesic, anti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective and hepatoprotective activities. The current review provides an updated summary of the importance of willows, their chemical composition and pharmacological activities.

Carissa macrocarpa Leaves Polar Fraction Ameliorates Doxorubicin-Induced Neurotoxicity in Rats via Downregulating the Oxidative Stress and Inflammatory Markers.

Chemotherapeutic-related toxicity exacerbates the increasing death rate among cancer patients, necessitating greater efforts to find a speedy solution. An in vivo assessment of the protective effect of the C. macrocarpa leaves polar fraction of hydromethanolic extract against doxorubicin (Dox)-induced neurotoxicity was performed. Intriguingly, this fraction ameliorated Dox-induced cognitive dysfunction; reduced serum ROS and brain TNF-α levels, upregulated the brain nerve growth factor (NGF) levels, markedly reduced caspase-3 immunoexpression, and restored the histological architecture of the brain hippocampus. The in vivo study results were corroborated with a UPLC-ESI-MS/MS profiling that revealed the presence of a high percentage of the plant polyphenolics. Molecular modeling of several identified molecules in this fraction demonstrated a strong binding affinity of flavan-3-ol derivatives with TACE enzymes, in agreement with the experimental in vivo neuroprotective activity. In conclusion, the C. macrocarpa leaves polar fraction possesses neuroprotective activity that could have a promising role in ameliorating chemotherapeutic-induced side effects.