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.

Ceiba pentandra ethyl acetate extract improves doxorubicin antitumor outcomes against chemically induced liver cancer in rat model: a study supported by UHPLC-Q-TOF-MS/MS identification of the bioactive phytomolecules.

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.

Sodium alginate-based smart gastro-retentive drug delivery system of revaprazan loaded SLNs; Formulation and characterization.

Revaprazan (REV), a novel reversible Proton Pump Inhibitor (PPI) used to treat peptic ulcers, faces challenges in therapeutic efficacy due to its poor dissolution properties and a short half-life. Solid lipid nanoparticles (SLNs) have emerged as a drug delivery system capable of enhancing dissolution and bioavailability of lipid soluble drugs. Here, we report on the development and optimization of a smart gastro-retentive raft system of REV-loaded SLNs (GRS/REV-SLNs) to enhance drug bioavailability and gastric retention. The optimized REV-SLNs had a particle size of 120 nm, a Polydispersity Index (PDI) of 0.313, a zeta potential of -20.7 mV, and efficient drug incorporation of 88 %. Transmission Electron Microscopy (TEM) affirmed the spherical morphology of these REV-SLNs, while Fourier Transform Infrared Spectroscopy (FTIR) revealed no chemical interactions among components. In-vitro assessment of the final GRS/REV-SLNs demonstrated sustained gelation and buoyancy for over 12 h, which would significantly enhance REV retention and its release within the stomach. Further assessments in rats confirmed successful gel transformation within the stomach, resulting in the improved bioavailability of REV. Thus, the development of GRS/REV-SLNs significantly improved the delivery and bioavailability of REV within the stomach, and offers a potentially improved method of treating peptic ulcers.

Phenolic Profile, Antioxidant, Antidiabetic, and Antigout Potential of Stem Extracts of Four Sweet Cherry Cultivars.

In order to highlight the activities of bioactive compounds present in the stem of sweet cherries, four different cultivars (Van, Burlat, Napoleon, and Cœur pigeon) were collected in Sefrou city in Morocco and were studied. Several assays were performed for this purpose, such as the quantification of phenolic compounds (TPC, TFC, and CTC) and the evaluation of the antioxidant activity using DPPH, ABTS, and FRAP assays. The phenolic profile of each extract was characterized by UHPLC-DAD/MS analysis. The antidiabetic (α-amylase inhibition) and antigout (xanthine oxidase inhibition) activities were also investigated. The results showed high levels of phenolic compounds, with the values of 340 ± 12.06, 244 ± 10.20, 232 ± 5.07, and 19 ± 3.10 mg gallic acid equivalent/g extract for the cultivars Napoleon, Coeur de pigeon, Van, and Burlat, respectively. According to the same order, the flavonoids showed amounts of 34.31 ± 2.08, 23.75 ± 1.02, 24.37 ± 1.20, and 23.31 ± 0.90 mg (rutin equivalent) RE/g extract. These values were correlated with the results of the antioxidant assays, where the Napoleon cultivar proved to be the most potent using the DPPH (IC50 = 2.51 µg/mL) and ABTS (IC50 = 55.38 µg/mL) assays. The phenolic profile of each extract resulted in the identification of twenty-two compounds belonging to five distinct groups. The major phenolic compounds identified were sakuranetin and dihydrowgonin with their glucosides. Antidiabetic activity assays showed that only stem extracts from Burlat and Napoleon cultivars were able to inhibit the α-amylase enzyme with values of 85.57 ± 1.09% and 68.01 ± 3.52%, respectively. All stem extracts proved their ability to inhibit the xanthine oxidase enzyme which is directly linked to the gout disease, with a high value for Van cultivar (40.63 ± 2.37%). These new findings could provide new opportunities for the valorization of cherry stems for the pharmaceutical application of their active phytochemicals.

Evaluation of the Wound Healing Potential of Cynara humilis Extracts in the Treatment of Skin Burns.

Cynara humilis is traditionally used to treat skin burns and microbial infections. However, experimental studies on this plant are rare. Furthermore, the aim of this study was to investigate the effects of Cynara humilis, a Moroccan herbal remedy, on the healing of deep second-degree burns in rats with a silver sulfadiazine group. This research was also carried out to confirm if C. humilis had antibacterial capabilities. Under typical burn procedures, each rat received a deep second-degree burn on the upper back. The burns were treated regularly with control groups (control and control VH), silver sulfadiazine (SDD) in group 3, C. humilis ethanolic extract (CHEE) in group 4, and C. humilis aqueous extract (CHAE) in group 5. Throughout the treatment, digital photography was used to measure rat responses to the treatment until day 18. After the scar biopsy at the end of the study, histological parameters (inflammatory cells, collagen, epithelialization, fibrosis, and granulation tissue) were assessed. Using the well technique, the antibacterial activity of the extracts was tested against Staphylococcus aureus CIP 483, Bacillus subtilis CIP 5262, Escherichia coli CIP 53126, Pseudomonas aeruginosa CIP 82118, and Salmonella enterica CIP 8039, and the results showed important activities of the ethanolic and aqueous extracts against the five species tested with MICs of 2 and 4 mg/mL, respectively. In the aqueous extract group, the wound healed faster. In addition, the healing rate in the C. humilis extracts (CHEA and CHEE) group was faster than in the silver sulfadiazine and control groups. In the C. humilis group, maximum wound surface recovery was observed at the same time, as it was not noted in the silver sulfadiazine group. Pathologically, epithelialization was more marked in wounds treated with C. humilis extracts (CHE). Angiogenesis and inflammatory cells were considerably lower in the CHE group than in the silver and other control groups. However, elastic fibers were considerable in the CHE-treated group. In histological examination, the C. humilis group had a low incidence of angiogenesis and inflammation, indicating that this group had less wound scarring. Collagen and burn wound healing were both faster in the C. humilis group. The findings of this study suggest that C. humilis, as indicated by traditional medicine, is a promising natural source for the management of wound healing.

Computational insight into structural basis of human ELOVL1 inhibition.

Very long-chain fatty acids (VLCFAs) play a direct role in the development of a neurological disorder, X-linked adrenoleukodystrophy (X-ALD). Since ELOVL1 catalyzes the rate-limiting step of the synthesis of VLCFAs, it has emerged as an attractive target for the treatment of X-ALD. Recently two potent inhibitors, compound 22 (C22) and compound 27 (C27) have been reported to specifically inhibit human ELOVL1 but their structural basis of inhibition has not been explored. In the present study, we have used a homology model of human ELOVL1 to deduce the binding site and binding modes of C22 and C27. We have employed computational approaches to characterize the binding of C22 and C27. Initially, binding of hexacosanoyl-CoA (C26:0-CoA) to ELOVL1 was modelled and further validated by molecular dynamics (MD) simulation. We observed that the fatty acid tail of C26: CoA protrudes from a unique opening located at the occluded end of ELOVL1. Structural comparison of ELOVL1 with the crystal structure of ELOVL7 revealed that the unique opening was not present in human ELOVL7. Combined blind and focused molecular docking approaches revealed that C22 and C27 exhibit favourable binding in the same unique opening. Further, MD simulations and free binding energy calculations confirmed that C22 and C27 maintain the favourable binding in the unique opening of ELOVL1. Overall, our findings suggest that selective human ELOVL1 inhibitors block the binding of long tails of VLCFAs near the occluded end of ELOVL1. Present study will be helpful in the discovery and design of novel, selective and potent inhibitors of human ELOVL1.

Epidemiological Trends of Acute Chemical Poisoning among Children over a Recent Three-Year Period in Saudi Arabia.

Acute intoxication from chemicals is a major medical emergency that can result in illness and mortality. This retrospective study aims to evaluate acute chemical poisoning incidents among children in Saudi Arabia from 2019 to 2021. A total of 3009 children were recorded as being chemically intoxicated. The SPSS/PC statistics package was used for the statistical analysis. The acute chemical poisoning incidents that occurred in the age groups were <1 year: 237 (7.8%), 1-5 years: 2301 (76.4%), 6-12 years: 214 (7.1%), and 13-19 years: 257 (8.5%). The mean rate of acute chemical poisoning in the northern region was 40.1%. The most common poisonous agents were organic solvents (20.4%) and disinfection agents (22.7%). Interestingly, there is a significant relationship between the different types of acute chemical poisoning and various factors, including gender, age, the location where acute chemical intoxication occurred, the type of exposure, and whether these were intentional or unintentional events. The data suggest that the northern region of Saudi Arabia has had the highest number of recorded incidents of acute chemical poisoning over the last three years (2019-2021). Individuals between 1-5 years old were the worst hit. Organic solvents and detergents were to blame for the acute unintentional chemical poisonings that took place in homes. Therefore, educating the public about chemical poisoning and reducing children's exposure to toxic chemicals requires educational programs, which may help to reduce chemical poisoning occurrence.

Meta-Analysis and Systematic Review of HLA DQ2/DQ8 in Adults with Celiac Disease.

Although people with human leukocyte antigens (HLA) DQ2 and/or DQ8 are more likely to develop celiac disease (CD), the condition cannot be fully explained by this genetic predisposition alone. Multiple, as yet unidentified, factors contribute to the genesis of CD, including genetics, the environment, and the immune system. In order to provide insight into a prospective possibility and an expanded screening technique, we aim to undertake a comprehensive and meta-analytical study of the assessment and distribution of HLA class II (HLA-DQ2/DQ8) in adult CD patients. A systematic review was conducted using an electronic search of databases (PubMed, Google Scholar, Embase, and Direct Science) from January 2004 to February 2022. DQ2/DQ2 homozygotes have the highest risk of developing CD. DQ2/DQ8 typing is an effective test to exclude CD from the differential diagnosis of a patient with CD symptoms. Although other non-HLA genes have been associated with CD, they are rarely considered at diagnosis because they account for only a small proportion of the heritability of CD. This finding, together with the information gathered previously, may be useful in considering widely available and economically feasible screening options for celiac disease in young people.

Comparative Investigation of Chemical Constituents of Kernels, Leaves, Husk, and Bark of Juglans regia L., Using HPLC-DAD-ESI-MS/MS Analysis and Evaluation of Their Antioxidant, Antidiabetic, and Anti-Inflammatory Activities.

Leaves, husk, kernels, and bark methanolic extracts of Juglans regia L. were tested for their in vitro antidiabetic, anti-inflammatory, and antioxidant activities. For these purposes, α-amylase and α-glucosidase were used as the main enzymes to evaluate antidiabetic activities. Moreover, lipoxidase and tyrosinase activities were tested to estimate anti-inflammatory properties. Antioxidant properties of Juglans regia L., extracts were determined using three different assays. Leaves extract has an important radical scavenging activity and a-amylase inhibition. Similarly, husk extracts showed high total phenolic content (306.36 ± 4.74 mg gallic acid equivalent/g dry extract) with an important α-amylase inhibition (IC50 = 75.42 ± 0.99 µg/mL). Kernels exhibit significant tyrosinase (IC50 = 51.38 ± 0.81 µg/mL) correlated with antioxidant activities (p < 0.05). Husk and bark extracts also showed strong anti-lipoxidase activities with IC50 equal to 29.48 ± 0.28 and 28.58 ± 0.35 µg/mL, respectively. HPLC-DAD-ESI-MS/MS analysis highlights the phenolic profile of methanolic extracts of Juglans regia L. plant parts. The identified polyphenols were known for their antioxidant, antidiabetic (dicaffeoyl-quinic acid glycoside in kernels), and anti-inflammatory (3,4-dihydroxybenzoic acid in leaves) activities. Further investigations are needed to determine molecular mechanisms involved in these effects as well as to study the properties of the main identified compounds.

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.

Variations in Antioxidant Capacity, Oxidative Stability, and Physicochemical Quality Parameters of Walnut (Juglans regia) Oil with Roasting and Accelerated Storage Conditions.

Walnut oil, like all vegetable oils, is chemically unstable because of the sensitivity of its unsaturated fatty acids to the oxidation phenomenon. This phenomenon is based on a succession of chemical reactions, under the influence of temperature or storage conditions, that always lead to a considerable change in the quality of the oil by promoting the oxidation of unsaturated fatty acids through the degradation of their C-C double bonds, leading to the formation of secondary oxidation products that reduce the nutritional values of the oil. This research examines the oxidative stability of roasted and unroasted cold-pressed walnut oils under accelerated storage conditions. The oxidative stability of both oils was evaluated using physicochemical parameters: chemical composition (fatty acids, phytosterols, and tocopherols), pigment content (chlorophyll and carotenoids), specific extinction coefficients (K232 and K270), and quality indicators (acid and peroxide value) as well as the evaluation of radical scavenging activity by the DPPH method. The changes in these parameters were evaluated within 60 days at 60 ± 2 °C. The results showed that the levels of total phytosterols, the parameters of the acid and peroxide value, K232 and K270, increased slightly for both oils as well as the total tocopherol content and the antioxidant activity affected by the roasting process. In contrast, the fatty acid profiles did not change considerably during the 60 days of our study. After two months of oil treatment at 60 °C, the studied oils still showed an excellent physicochemical profile, which allows us to conclude that these oils are stable and can withstand such conditions. This may be due to the considerable content of tocopherols (vitamin E), which acts as an antioxidant.

Effects of Extraction Methods on the Bioactivities and Nutritional Value of Virginia and Valencia-Type Peanut Oil.

This study aimed to evaluate the effects of peanut varieties cultivated in Morocco (Virginia and Valencia) and extraction methods (cold press, CP; Soxhlet, Sox and maceration, and Mac) on the fatty acid profile, phytosterol, and tocopherol contents, quality characteristics, and antioxidant potential of peanut seed oil. The DPPH method was used to determine the antioxidant activity of the oils. The results revealed that fatty acid content was slightly affected by the extraction technique. However, the CP method was shown to be an excellent approach for extracting oil with desirable quality features compared to the Sox and Mac methods. Furthermore, the peanut oil extracted via CP carried a higher amount of bioactive compounds and exhibited remarkable antioxidant activities. The findings also revealed higher oleic acid levels from the Virginia oil, ranging from 56.46% to 56.99%. Besides, a higher total phytosterol and tocopherol content and DPPH scavenging capacity were obtained from the Valencia oil. Analyzing the study, it can be inferred that extraction method and variety both affect the composition of the peanut oil's bioactive compounds and antioxidant activity. This information is relevant for extracting peanut oil with a greater level of compounds of industrial interest.

Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.

The mammalian target of rapamycin (mTOR) is a highly conserved serine/threonine-protein kinase, which regulates many biological processes related to metabolism, cancer, immune function, and aging. It is an essential protein kinase that belongs to the phosphoinositide-3-kinase (PI3K) family and has two known signaling complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Even though mTOR signaling plays a critical role in promoting mitochondria-related protein synthesis, suppressing the catabolic process of autophagy, contributing to lipid metabolism, engaging in ribosome formation, and acting as a critical regulator of mRNA translation, it remains one of the significant signaling systems involved in the tumor process, particularly in apoptosis, cell cycle, and cancer cell proliferation. Therefore, the mTOR signaling system could be suggested as a cancer biomarker, and its targeting is important in anti-tumor therapy research. Indeed, its dysregulation is involved in different types of cancers such as colon, neck, cervical, head, lung, breast, reproductive, and bone cancers, as well as nasopharyngeal carcinoma. Moreover, recent investigations showed that targeting mTOR could be considered as cancer therapy. Accordingly, this review presents an overview of recent developments associated with the mTOR signaling pathway and its molecular involvement in various human cancer types. It also summarizes the research progress of different mTOR inhibitors, including natural and synthetised compounds and their main mechanisms, as well as the rational combinations with immunotherapies.

Chemical Composition and Antioxidant, Antimicrobial, and Anti-Inflammatory Properties of Origanum compactum Benth Essential Oils from Two Regions: In Vitro and In Vivo Evidence and In Silico Molecular Investigations.

The purposes of this investigatory study were to determine the chemical composition of the essential oils (EOs) of Origanum compactum from two Moroccan regions (Boulemane and Taounate), as well as the evaluation of their biological effects. Determining EOs' chemical composition was performed by a gas chromatography-mass spectrophotometer (GC-MS). The antioxidant activity of EOs was evaluated using free radical scavenging ability (DPPH method), fluorescence recovery after photobleaching (FRAP), and lipid peroxidation inhibition assays. The anti-inflammatory effect was assessed in vitro using the 5-lipoxygenase (5-LOX) inhibition test and in vivo using the carrageenan-induced paw edema model. Finally, the antibacterial effect was evaluated against several strains using the disk-diffusion assay and the micro-dilution method. The chemical constituent of O. compactum EO (OCEO) from the Boulemane zone is dominated by carvacrol (45.80%), thymol (18.86%), and α-pinene (13.43%). However, OCEO from the Taounate zone is rich in 3-carene (19.56%), thymol (12.98%), and o-cymene (11.16%). OCEO from Taounate showed higher antioxidant activity than EO from Boulemane. Nevertheless, EO from Boulemane considerably inhibited 5-LOX (IC50 = 0.68 ± 0.02 µg/mL) compared to EO from Taounate (IC50 = 1.33 ± 0.01 µg/mL). A similar result was obtained for tyrosinase inhibition with Boulemane EO and Taounate EO, which gave IC50s of 27.51 ± 0.03 µg/mL and 41.83 ± 0.01 µg/mL, respectively. The in vivo anti-inflammatory test showed promising effects; both EOs inhibit and reduce inflammation in mice. For antibacterial activity, both EOs were found to be significantly active against all strains tested in the disk-diffusion test, but O. compactum EO from the Boulemane region showed the highest activity. Minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for O. compactum EO from the Boulemane region ranged from 0.06 to 0.25% (v/v) and from 0.15 to 0.21% (v/v) for O. compactum from the Taounate region. The MBC/MIC index revealed that both EOs exhibited remarkable bactericidal effects.

Mineral and Phenolic Composition of Erodium guttatum Extracts and Investigation of Their Antioxidant Properties in Diabetic Mice.

Erodium guttatum is widely used in folk medicine in many countries to treat various ailments such as urinary inflammation, diabetes, constipation, and eczema. The aim of this study is the determination of mineral and phenolic compounds of E. guttatum extracts as well as the investigation of their antidiabetic and antioxidant properties. The mineral composition was determined by the methods of inductively coupled plasma atomic emission spectroscopy analysis. Phytochemical contents of total polyphenols, total flavonoids, and catechic tannins were estimated by colorimetric dosages. The phenolic composition was identified by high-resolution mass spectrometry (HRMS) analysis. The antioxidant activity of E. guttatum extracts was measured in vitro by five methods (DPPH, ABTS, FRAP, H2O2, and xanthine oxidase) and in vivo by assaying the malondialdehyde marker (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). The obtained results showed that the root plant material is rich in minerals such as k, Ca, and Mg. The methanolic extract of E. guttatum is the richest in polyphenols (389.20 ± 1.55 mg EAG/gE), tannins (289.70 ± 3.57 mg EC/gE), and flavonoids (432.5 ± 3.21 mg ER/gE). Concerning the ESI-HRMS analysis, it showed the presence of numerous bioactive compounds, including shikimic acid, rottlerine, gallic acid, and vanillic acid. Moreover, the aqueous and alcoholic extracts of E. guttatum exhibited antiradical and antioxidant activity in five tests used, with the best effect of the methanolic extract. Moreover, findings showed that in vivo investigations confirmed those obtained in vitro. On the other hand, E. guttatum showed important antidiabetic effects in vivo. Indeed, diabetic mice treated with extracts of E. guttatum were able to significantly reduce MDA levels and increase the secretion of enzymatic and nonenzymatic antioxidants (SOD, CAT, and GSH, respectively). However, the antioxidant activity of the extracts might be attributed to the abundance of bioactive molecules; as results, this work serves as a foundation for additional pharmacological research.

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review.

Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.

Cardioprotective Potential of Aqueous Extract of Fumaria indica on Isoproterenol-Induced Myocardial Infarction in SD Rats.

Ischemic heart disease (IHD) treatments and preventions by using plant extract and its phytochemical constituents have achieved considerable attention globally due to its cardioprotective effects. This study is aimed at investigating the cardioprotective and vascular effects of Fumaria indica (F. indica) crude extract on isoproterenol- (ISO-) induced myocardial infarction (MI) in Sprague-Dawley (SD) rats. Rats treated with isoproterenol (85 mg/kg, s.c), administered. Twice at an interval of 24 h showed a significant ST-segment elevation in ECG, edema, and necrosis in histopathology and also in troponin I (cTnI), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), and aspartate aminotransferase (AST). Pretreatment with F. indica (10, 30, and 100 mg/kg, p.o) for 21 days significantly reversed the effects of isoproterenol-induced ischemic changes in the ECG, levels of cTnI, CPK, LDH, and AST, and histopathological changes. In isolated rat atrial strips, F. indica induced negative chronotropic and inotropic effects which were not affected by pretreatment with atropine, excluding role of cardiac muscarinic receptors. Cumulative addition of the extract induced a vasorelaxant effect on phenylephrine-evoked contractions in isolated rat aortic rings, which remained unchanged when challenged with L-NAME, excluding role of endothelial NO. However, extract of F. indica concentration dependently reversed contractions evoked with high K+, indicating calcium entry blocking effect. In conclusion, the F. indica extract is a cardioprotective remedy that ameliorates the isoproterenol-induced cardiotoxic effects and reverses cardiac ischemia, and the calcium antagonistic effect might be of useful in the treatment of MI.

Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach.

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (-10.1 kcal/mol), kuwanon S (-9.6 kcal/mol), manuifolin H (-9.5 kcal/mol), and kuwanon F (-9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.