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Nanohybrid cerasomes represent a significant advancement in the field of drug delivery systems, offering a superior alternative to traditional cerasomes and liposomes. Cerasomes are biocompatible colloidal nanoparticles characterized by an additional polyorganosiloxane network layer that enhances their stability compared to conventional liposomes. The novel hybrid liposomal cerasome, featuring a partial ceramic or silica coating, has garnered substantial interest due to its unique structure. This structure provides better morphological stability than traditional liposomes and, in comparison to silica nanoparticles, significantly reduces overall stiffness and density. By incorporating liposomal architecture, cerasomes achieve greater biocompatibility than silica nanoparticles. This unique combination leverages the benefits of both liposomes and silica nanoparticles while mitigating their respective drawbacks, positioning cerasomes as an optimal drug delivery system. Nanohybrid cerasomes offer extended circulation residence time, enabling more efficient drug delivery to disease sites and facilitating the targeting of specific disease cells. Their potential as intracellular delivery vehicles for proteins, peptides, antisense compounds, ribozymes, and DNA is particularly noteworthy. The presence of a liposomal bilayer structure in cerasomes reduces rigidity and density, enhancing their stability and effectiveness as drug and gene delivery vehicles. This article reviews the techniques for preparing cerasomes and explores their applications in targeted drug and gene delivery systems, highlighting their advantages over conventional liposomes and silica nanoparticles.

Abstract Nanoengineered chitosan functionalized titanium dioxide biohybrids (CTiO2@NPs) were prepared with Amomum subulatum Roxb extract via one-pot green method and assessed by UV–Vis spectroscopy, XRD, SEM and EDAX analyses. As revealed by XRD pattern, the nanohybrids exhibits a rutile TiO2 crystallites around 45 nm in size. The emergence of the Ti–O–Ti bond is identified by observing a peak between 400 and 800 cm−1. A wide bandgap (4.8 eV) has been observed in CTiO2@NPs, due to the quantum confinement effects and the oxygen vacancies reveal the intriguing potential of developed nanohybrids for various applications. Surface flaws were identified by observing an emission band at 382, 437, 482, 517, and 556 nm. They also exhibit better antibacterial performances using well diffusion method against Staphylococcus aureus, Bacillus substilis, Klebsiella pneumonia, and Escherichia coli. CTiO2@NPs were discovered to have free radical scavenging activity on DPPH analysis and exhibit IC50 value as 95.80 μg/mL and standard (Vitamin C) IC50 is 87.62 μg/mL. CTiO2@NPs exhibited better anticancer properties against the osteosarcoma (MG-63) cell line. All these findings suggest that there is a forum for further useful therapeutic applications. Therefore, we claim that nano-engineered carbohydrated TiO2 phytohybrid is a promising solution for bacterial infections and bone cancer.

Polyphenols have a variety of phenolic hydroxyl and carbonyl functionalities that enable them to scavenge many oxidants, thereby preserving the human redox balance and preventing a number of oxidative stress-related chronic degenerative diseases. In our ongoing investigation of polyphenol-rich plants in search of novel molecules, we resumed the investigation of Lawsonia inermis L. (Lythraceae) or henna, a popular ancient plant with aesthetic and therapeutic benefits. The leaves’ 70% aq acetone extract was fractionated on a Diaion HP-20 column with different ratios of H2O/an organic solvent. Multistep gel chromatographic fractionation and HPLC purification of the Diaion 75% aq MeOH and MeOH fractions led to a new compound (1) along with tannin-related metabolites, benzoic acid (2), benzyl 6′-O-galloyl-β-D-glucopyranoside (3), and ellagic acid (4), which are first isolated from henna. Repeating the procedures on the Diaion 50% aq MeOH eluate led to the first-time isolation of two O-glucosidic ellagitannins, heterophylliin A (5), and gemin D (6), in addition to four known C-glycosidic ellagitannins, lythracin D (7), pedunculagin (8), flosin B (9), and lagerstroemin (10). The compound structures were determined through intensive spectroscopic investigations, including HRESIMS, 1D (1H and 13C) and 2D (1H–1H COSY, HSQC, HMBC, and NOESY) NMR, UV, [α]D, and CD experiments. The new structure of 1 was determined to be a megastigmane glucoside gallate; its biosynthesis from gallic acid and a β-ionone, a degradative product of the common metabolite β-carotin, was highlighted. Cytotoxicity investigations of the abundant ellagitannins revealed that lythracin D2 (7) and pedunculagin (8) are obviously more cytotoxic (tumor specificity = 2.3 and 2.8, respectively) toward oral squamous cell carcinoma cell lines (HSC-2, HSC-4, and Ca9-22) than normal human oral cells (HGF, HPC, and HPLF). In summary, Lawsonia inermis is a rich source of anti-oral cancer ellagitannins. Also, the several discovered polyphenolics highlighted here emphasize the numerous biological benefits of henna and encourage further clinical studies to profit from their antioxidant properties against oxidative stress-related disorders.

Autism is complex and multifactorial, and is one of the fastest growing neurodevelopmental disorders. Canagliflozin (Cana) is an antidiabetic drug that exhibits neuroprotective properties in various neurodegenerative syndromes. This study investigated the possible protective effect of Cana against the valproic acid (VPA)-induced model of autism. VPA was injected subcutaneously (SC) into rat pups at a dose of 300 mg/kg, twice daily on postnatal day-2 (PD-2) and PD-3, and once on PD-4 to induce an autism-like syndrome. Graded doses of Cana were administered (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, P.O.) starting from the first day of VPA injections and continued for 21 days. At the end of the experiment, behavioral tests and histopathological alterations were assessed. In addition, the gene expression of peroxisome proliferator-activated receptor γ (PPAR γ), lactate dehydrogenase A (LDHA), pyruvate dehydrogenase kinase (PDK), cellular myeloctomatosis (c-Myc) with protein expression of glucose transporter-1 (GLUT-1), phosphatase and tensin homolog (PTEN), and level of acetylcholine (ACh) were determined. Treatment with Cana significantly counteracted histopathological changes in the cerebellum tissues of the brain induced by VPA. Cana (5 mg/kg, 7.5 mg/kg, and 10 mg/kg) improved sociability and social preference, enhanced stereotypic behaviors, and decreased hyperlocomotion activity, in addition to its significant effect on the canonical Wnt/β-catenin pathway via the downregulation of gene expression of LDHA (22%, 64%, and 73% in cerebellum tissues with 51%, 60%, and 75% in cerebrum tissues), PDK (27%, 50%, and 67% in cerebellum tissues with 34%, 66%, and 77% in cerebrum tissues), c-Myc (35%, 44%, and 72% in cerebellum tissues with 19%, 58%, and 79% in cerebrum tissues), protein expression of GLUT-1 (32%, 48%, and 49% in cerebellum tissues with 30%, 50%, and 54% in cerebrum tissues), and elevating gene expression of PPAR-γ (2, 3, and 4 folds in cerebellum tissues with 1.5, 3, and 9 folds in cerebrum tissues), protein expression of PTEN (2, 5, and 6 folds in cerebellum tissues with 6, 6, and 10 folds in cerebrum tissues), and increasing the ACh levels (4, 5, and 7 folds) in brain tissues. The current study confirmed the ameliorating effect of Cana against neurochemical and behavioral alterations in the VPA-induced model of autism in rats.

Objectives: The main objective of the present research is to provide GC–MS and LC-MS phytochemcial profiling of Corchorus olitorius along with Flow cytometry based mechanistic investigation of cytotoxic activity of its extracts against breast and lung cancer cell lines. Methods: The Soxhlet extraction method was used in the sequential extraction of C. olitorius. The phytochemical profiling was done using LC-MS and GC–MS techniques, and total phenolic and flavonoid content was determined. The cytotoxicity was studied against non-cancerous L929 cells and cancerous MCF-7 and A549 cell lines using MTT assay, followed by flow cytometry based molecular mechanisms study through anti-Bcl-2 assay, Caspase-3, and DNA fragmentation (TUNEL assay). Results: The C. olitorius methanolic extract showed the phenolic compounds and flavonoids as a major constituents with 699 µg GAE/g of dw and 1361.50 µg QE/g of dw, respectively. The GC–MS and LC-MS results confirmed the presence of active phytochemicals. Toxicity study against L929 cell line revealed that methanol extract proved to be less toxic with a higher IC50 value i.e. 227.84 µg/ml. Cell viability MTT assay for methanol extract against MCF-7 and A549 cell lines revealed significant results with IC50 values of 20 µg/ml and 12.45 µg/ml, respectively. The flow cytometry based molecular marker studies showed that the extract successively induced early and late apoptosis in tested breast and lung cancer cells through activation of Caspase-3 with inhibition of Bcl-2 protein and induced cell death through DNA damage. Conclusion: Collectively, these findings show that the methanol extract of C. olitorius inhibits breast cancer and lung cancer cell lines with significant cytotoxic activity. Thus, C. olitorius would be a promising source of chemopreventive agents that warrant further investigation to find lead compounds with cancer chemotherapeutic potential.

With more than 12 million cases worldwide, leishmaniasis is one of the top 10 neglected tropical diseases. According to the WHO, there are approximately 2 million new cases each year in foci in around 90 countries, of which 1.5 million are cutaneous leishmaniasis (CL). Cutaneous leishmaniasis (CL) is a complex cutaneous condition that is caused by a variety of Leishmania species, including L. (Leishmania) major, L. (L) tropica, L. (L) aethiopica, L. (L) mexicana, L. (Viannia) braziliensis, and L. (L) amazonensis. The disease imposes a significant burden on those who are affected since it typically results in disfiguring scars and extreme social stigma. There are no vaccines or preventive treatments available, and chemotherapeutic medications, including antimonials, amphotericin B, miltefosine, paromomycin, pentamidine, and antifungal medications, have a high price tag, a significant risk of developing drug resistance, and a variety of systemic toxicities. To work around these limitations, researchers are continuously looking for brand-new medications and other forms of therapy. To avoid toxicity with systemic medication use, high cure rates have been observed using local therapy techniques such as cryotherapy, photodynamic therapy, and thermotherapy, in addition to some forms of traditional therapies, including leech and cauterization therapies. These CL therapeutic strategies are emphasized and assessed in this review to help with the process of locating the appropriate species-specific medicines with fewer side effects, lower costs, and elevated cure rates.

There are many high-altitude plants such as Skimmia anquetilia that are unexplored for their possible medicinal values. The present study was conducted to examine the antioxidant activities of Skimmia anquetilia (SA) using in vitro and in vivo models. The SA hydro-alcoholic extracts were investigated using LC-MS for their chemical constituents. The essential oil and hydro-alcoholic extracts of SA were evaluated for pharmacological properties. The antioxidant properties were evaluated using in vitro DPPH, reducing power, cupric reducing antioxidant power, and metal chelating assays. The anti-hemolytic activity was carried out using a human blood sample. The in vivo antioxidant activities were evaluated using CCL4-induced hepatotoxicity and nephrotoxicity assay. The in vivo evaluation included histopathological examination, tissue biochemical evaluation such as the kidney function test, catalase activity, reduced glutathione activity, and lipid peroxidation estimation. The phytochemical investigation showed that the hydro-alcoholic extract contains multiple important active constituents such as L-carnosine, acacetin, linoleic acid, leucylleucyl tyrosine, esculin sesquihydrate, etc., similar to the components of SA essential oil reported in a previous study. The high amount of total phenolic content (TPC) and total flavonoid content (TFC) reflect (p < 0.001) a high level of reducing power, cupric reducing, and metal chelating properties. This significantly (p < 0.001) inhibited enlargement of the liver, with a significant reduction in ALT (p < 0.01) and AST (p < 0.001). Highly significant improvement in the functioning of the kidney was noted using the blood urea and creatinine (p < 0.001) levels. Tissue-based activities showed a major rise in catalase, reduced glutathione, and reduced lipid peroxidation activities. We conclude from this study that the occurrence of a high quantity of flavonoid and phenolic contents had strong antioxidant properties, leading to hepatoprotective and nephroprotective activity. Further active constituent-specific activities should be evaluated.

In this review, we describe and discuss the phytoconstituents present in Hedychium species and emphasize their potential as drug candidates. Though they are widely validated in vitro and in vivo models, to date, no efforts have been made to compile in a single review all the pharmacologically active phytoconstituents from Hedychium species, and their pharmacological and toxicity profile. In this study, we present a reinvestigation of the chemical constituents present in Hedychium species obtained from the essential oil and solvent extraction of the flowers, leaves and rhizomes under consideration. Key databases such as PubMed, Science Direct, Scopus, and Google Scholar amongst others were probed for a systematic search using keywords to retrieve relevant publications on this plant. An exhaustive electronic survey of the related literature on Hedychium species resulted in around 200 articles. Articles published between the years 1975–2021 were included. The studies conducted on either crude extracts, solvent fractions or isolated pure compounds from Hedychium species reported with a varied range of biological effects such as anti-inflammatory, analgesic, antidiabetic, potentially anti-asthmatic, and cytotoxic, among other related activities of the chemical constituents present in its essential oil and solvent extract deployed in this review. Traditional and herbal medication around the world that uses different parts of Hedychium species were considered for anti-inflammatory, skincare, analgesic, anti-asthmatic, anti-diabetic, antidotal uses, among others. These uses support the idea that chemical constituents obtained from solvent extraction may also exert the same action individually or in a synergistic manner. The review concluded that there is scope for computation and biological study to find out possible new targets for strengthening the potency and selectivity of the relevant compounds, and to find a commercial method for extraction of active pharmaceutical ingredients.

The plain 5-fluorouracil (5FU) formulations available in the market are associated with adverse effects such as skin irritation, pruritus, redness, blisters, allergy, and dryness on the site of application. The objective of the present study was to develop a liposomal emulgel of 5FU with increased skin permeability and efficacy using clove oil and eucalyptus oil along with pharmaceutically acceptable carriers, excipients, stabilizers, binders, and additives. A series of seven formulations were developed and evaluated for their entrapment efficiency, in vitro release profile, and cumulative drug release profile. The compatibility of drugs and excipients, as confirmed by FTIR (fourier-transform infrared spectroscopy) and DSC (differential scanning calorimetry) as well as SEM (scanning electron microscopy) and TEM (transmission electron microscopy) studies, revealed that the size and shape of liposomes are smooth and spherical, and the liposomes are non-aggregated. To understand their efficacy, the optimized formulations were evaluated for cytotoxicity using B16-F10 mouse skin melanoma cells. The eucalyptus oil and clove oil-containing preparation significantly produced a cytotoxic effect against a melanoma cell line. The addition of clove oil and eucalyptus oil increased the efficacy of the formulation by improving skin permeability and reducing the dose required for the anti-skin cancer activity.

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats.

Aim: The objective of this research is to present a phytochemical profile of Fagonia arabica and to investigate the cytotoxic potential of its extracts against breast, oral, and lung cancer cell lines using MTT assay and dual staining-based mechanistic analysis. Methods: The progressive extraction of F. arabica was carried out using the Soxhlet extraction technique. The total phenolic and flavonoid content was calculated as part of the phytochemical profiling performed using GCMS and LCMS methods. The MTT assay was utilized to assess the cytotoxicity against normal L929 cells, as well as malignant A549, MCF-7, and KB-3-1cell lines. Results: The phenolic compounds and flavonoids were the two main elements of the F. arabica methanolic extract, with 1323 µg GAE/g of dry weight and 523.07 µg QE/g of dry weight, respectively. The presence of the functional phytochemicals was verified by GCMS and LCMS analyses. Toxicity testing on the L929 cell line found that the F. arabica methanol extract was the least harmful, with the highest IC50 (296.11 µg/mL). The MTT assay for cell viability against MCF-7 and KB-3-1 yielded significant results, with IC50 values of 135.02 µg/mL and 195.21 µg/mL, respectively. The aqueous extract exhibited significant cytotoxicity against the A549 cell lines (IC50 116.06 µg/mL). The molecular marker analyses using dual staining revealed that the methanolic extract successfully triggered apoptosis in the different cancer cells tested. Conclusion: The present data suggest that the methanol extract of F. arabica has substantial cytotoxic action against lung, breast, and oral cancer cell lines. Thus, F. Arabica would be a promising source of anticancer medicines, warranting more research to identify the lead molecules with anticancer properties.

The objectives of this study are to investigate the cytotoxic effect of different Citrullus colocynthis extracts on breast and lung cancer cell lines using flow cytometry to gain mechanistic insights. C. colocynthis was extracted sequentially using the Soxhlet method. We first tested the plant extracts’ cytotoxicity on non-malignant L929 cells and cancerous breast (MCF-7) and lung (A549) cell lines. We observed that the IC50 of the methanol extract on the viability of MCF-7 and A549 cell lines was 81.08 µg/mL and 17.84 µg/mL, respectively, using the MTT assay. The aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line, with IC50 values of 235.48 µg/mL and 222.29 µg/mL, respectively. Then, using flow cytometry, we investigated the underlying molecular pathways with Annexin-V, Anti-Bcl-2, Caspase-3, and DNA fragmentation (TUNEL) assays. Flow cytometric and molecular marker analyses revealed that the methanol extract activated caspase-3 and inhibited Bcl-2 protein, causing early and late apoptosis, as well as cell death via DNA damage in breast and lung cancer cells. These findings indicate that the methanol extract of C. colocynthis is cytotoxic to breast and lung cancer cell lines. The total phenolic and flavonoid content analysis results showed the methanolic extract of C. colocynthis has a concentration of 326.25 μg GAE/g dwt and 274.61 μg QE/g dwt, respectively. GC-MS analysis of the methanol extract revealed phytochemicals relevant to its cytotoxicity.

Acute lung injury (ALI) is one of the adverse effects of the antineoplastic agent cisplatin (CIS). Oxidative stress, inflammation, and necroptosis are linked to the emergence of lung injury in various disorders. This study evaluated the effect of the macrolide antibiotic azithromycin (AZM) on oxidative stress, inflammatory response, and necroptosis in the lungs of CIS-administered rats, pinpointing the involvement of PPARγ, SIRT1, and Nrf2/HO-1 signaling. The rats received AZM for 10 days and a single dose of CIS on the 7th day. CIS provoked bronchial and alveolar injury along with increased levels of ROS, MDA, NO, MPO, NF-κB p65, TNF-α, and IL-1β, and decreased levels of GSH, SOD, GST, and IL-10, denoting oxidative and inflammatory responses. The necroptosis-related proteins RIP1, RIP3, MLKL, and caspase-8 were upregulated in CIS-treated rats. AZM effectively prevented lung tissue injury, ameliorated oxidative stress and NF-κB p65 and pro-inflammatory markers levels, boosted antioxidants and IL-10, and downregulated necroptosis-related proteins in CIS-administered rats. AZM decreased the concentration of Ang II and increased those of Ang (1-7), cytoglobin, PPARγ, SIRT1, Nrf2, and HO-1 in the lungs of CIS-treated rats. In conclusion, AZM attenuated the lung injury provoked by CIS in rats through the suppression of inflammation, oxidative stress, and necroptosis. The protective effect of AZM was associated with the upregulation of Nrf2/HO-1 signaling, cytoglobin, PPARγ, and SIRT1.

Diabetes mellitus is one of the most prevalent metabolic disorders characterized by hyperglycemia due to impaired glucose metabolism. Overproduction of free radicals due to chronic hyperglycemia may cause oxidative stress, which delays wound healing in diabetic conditions. For people with diabetes, this impeded wound healing is one of the predominant reasons for mortality and morbidity. The study aimed to develop an Ocimum sanctum leaf extract-mediated green synthesis of titanium dioxide (TiO2) nanoparticles (NPs) and further incorporate them into 2% chitosan (CS) gel for diabetic wound healing. UV-visible spectrum analysis recorded the sharp peak at 235 and 320 nm, and this was the preliminary sign for the biosynthesis of TiO2 NPs. The FTIR analysis was used to perform a qualitative validation of the biosynthesized TiO2 nanoparticles. XRD analysis indicated the crystallinity of TiO2 NPs in anatase form. Microscopic investigation revealed that TiO2 NPs were spherical and polygonal in shape, with sizes ranging from 75 to 123 nm. The EDX analysis of green synthesized NPs showed the presence of TiO2 NPs, demonstrating the peak of titanium ion and oxygen. The hydrodynamic diameter and polydispersity index (PDI) of the TiO2 NPs were found to be 130.3 nm and 0.237, respectively. The developed TiO2 NPs containing CS gel exhibited the desired thixotropic properties with pseudoplastic behavior. In vivo wound healing studies and histopathological investigations of healed wounds demonstrated the excellent wound-healing efficacy of TiO2 NPs containing CS gel in diabetic rats.

The primary objective of this research was to use flow cytometry to gain mechanistic insights into the cytotoxic effects of Tribulus terrestris extracts on breast cancer (MCF7) and lung cancer (A549) cell lines. T. terrestris was extracted using a Soxhlet apparatus in a progressive process. GC–MS was used to establish the phytochemical constituents. The amounts of phenolic compounds and flavonoids in the plant extracts were calculated using spectrophotometric analysis. The cytotoxicity of plant extracts was initially evaluated in non-malignant L929 cells, then in carcinogenic MCF-7 and A549 cell lines. Then, we performed an Annexin V assay, an anti-Bcl-2 assay, a Caspase-3 assay, and a DNA fragmentation (TUNEL) assay, using flow cytometry to investigate the underlying molecular processes. Based on the data, the methanolic extract of T. terrestris contained the highest amounts of phenolic compounds and flavonoids, with values of 169.87 µg GAE/g dwt and 160.12 µg QE/g dwt, respectively. Analysis by GC–MS revealed the presence of bioactive phytochemicals with proven cytotoxicity. Based on the MTT experiment, we determined that the IC50 values for the methanol extract’s effect on the viability of the MCF-7 and A549 cell lines were 218.19 and 179.62 µg/mL, respectively. The aqueous and methanol extracts were less cytotoxic when tested against the cancer-free L929 cell line (IC50 = 224.35 µg/mL). In both breast and lung cancer cells, the methanolic extract was found to activate caspase-3 and inhibit the Bcl-2 protein, resulting in early and late apoptosis and cell death via DNA damage. These findings point to cytotoxic effects of T. terrestris methanol extract against breast and lung cancer cell lines. Due to its potential as a source of anti-cancer chemotherapeutic medicines, T. terrestris warrants further investigation.

The objectives of this research were to carry out GC–MS and LC–MS-based phytochemical profiling of Barleria hochstetteri, as well as flow cytometry-based mechanistic investigations of the cytotoxic effect of its extracts against breast and lung cancer cell lines. This preclinical in vitro study was carried out in Saudi Arabia and India, from 11 August to 15 January 2022. Barleria hochstetteri was sequentially extracted using the Soxhlet extraction technique. Utilizing LC–MS and GC–MS methods, the phytochemical profiling was performed. Additionally, the total phenolic compounds and flavonoids were quantified in the plant extract using spectrophotometric techniques. In this study, we first examined the cytotoxicity of the plant extract on non-malignant L929 cells and on the carcinogenic MCF-7 and A549 cell lines. Then, we studied the underlying molecular pathways by means of Anti-Bcl-2, caspase-3, and DNA fragmentation (TUNEL) assays, using flow cytometry. The results revealed phenolic compounds and flavonoids to be the two major components in the methanolic extract of B. hochstetteri, with concentrations of 3210 µg GAE/g dwt and 1863 µg QE/g dwt, respectively. Results from GC–MS and LC–MS analyses revealed the presence of bioactive phytochemicals with known cytotoxicity. From the MTT assay on cell viability, the IC50 of the methanol extract for the MCF-7 and A549 cell lines were 219.67 and 144.30 µg/mL, respectively. With IC50 values of 324.24 and 266.66 µg/mL, respectively, the aqueous and methanol extracts were less toxic when tested against the non-cancerous L929 cell line. The extract caused early and late apoptosis in the tested breast and lung cancer cells by activating caspase-3 and inhibiting Bcl-2 protein, and it also caused cell death via DNA damage, based on flow cytometric and molecular marker analyses. These findings indicate that the methanol extract of B. hochstetteri was cytotoxic on breast cancer and lung cancer cell lines. To uncover cancer-fighting chemicals, there is a need for further research on B. hochstetteri, as it is a promising source of anti-cancer chemotherapeutic drugs.

In the presented study, Bacillus subtilis strain AG4 isolated from marine was identified based on morphological, physiological, phylogenetic characteristics and an examination of 16S rRNA sequences. Novel exopolysaccharide (EPSR4) was extracted and isolated from the Bacillus subtilis strain as a major fraction of exopolysaccharide (EPS). The analysis of structural characterization indicated that EPSR4 is a β-glycosidic sulphated heteropolysaccharide (48.2%) with a molecular weight (Mw) of 1.48 × 104 g/mole and has no uronic acid. Analysis of monosaccharide content revealed that EPSR4 consists of glucose, rhamnose and arabinose monosaccharide in a molar ratio of 5:1:3, respectively. Morphological analysis revealed that EPSR4 possess a high crystallinity degree with a significant degree of porosity, and its aggregation and conformation in the lipid phase might have a significant impact on the bioactivity of EPSR4. The biological activity of EPSR4 was screened and evaluated by investigating its antioxidant, cytotoxicity, anti-inflammatory, and anti-Alzheimer activities. The antioxidant activity results showed that EPSR4 has 97.6% scavenging activity toward DPPH free radicals at 1500 µg/mL, with an IC50 value of 300 µg/mL, and 64.8% at 1500 µg/mL toward hydrogen peroxide free radicals (IC50 = 1500 µg/mL, 30 min). Furthermore, EPSR4 exhibited considerable inhibitory activity towards the proliferation of T-24 (bladder carcinoma), A-549 (lung cancer) and HepG-2 (hepatocellular carcinoma) cancer cell lines with IC50 of 244 µg/mL, 148 µg/mL and 123 µg/mL, respectively. An evaluation of anti-inflammatory activity revealed that EPSR4 has potent lipoxygenase (LOX) inhibitory activity (IC50 of 54.3 µg/mL) and a considerable effect on membrane stabilization (IC50 = 112.2 ± 1.2 µg/mL), while it showed cyclooxygenase (COX2) inhibitory activity up to 125 µg/mL. Finally, EPSR4 showed considerable inhibitory activity towards acetylcholine esterase activity. Taken together, this study reveals that Bacillus subtilis strain AG4 could be considered as a potential natural source of novel EPS with potent biological activities that would be useful for the healthcare system.

Acute heart failure (AHF) is one of the most common diseases in old age that can lead to mortality. Systemic hypoperfusion is associated with hepatic ischemia–reperfusion injury, which may be irreversible. Ischemic hepatitis due to AHF has been linked to the pathogenesis of liver damage. In the present study, we extensively investigated the role of mitochondrial dynamics-related proteins and their epigenetic regulation in ischemic liver injury following AHF and explored the possible hepatoprotective role of carvedilol. The biochemical analysis revealed that the ischemic liver injury following AHF significantly elevated the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes, the level of total and direct bilirubin, and the expression of hepatic mitogen-activated protein kinase (MAPK), dynamin-1-like protein (DNM1L), and hepatic miRNA-17. At the same time, it significantly reduced the serum albumin level, the activity of hepatic superoxide dismutase (SOD), and the expression of mitochondrial peroxisome proliferator-activated receptor-1α (PGC-1α), and mitofusin 2 (Mtf2). The histological examination of the liver tissue revealed degenerated hepatocytes. Interestingly, administration of carvedilol either prior to or after isoprenaline-induced AHF significantly improved the liver function and reversed the deterioration effect of AHF-induced ischemic hepatitis, as demonstrated by biochemical, immunohistochemical, and histological analysis. Our results indicated that the hepatoprotective effect of carvedilol in ameliorating hepatic ischemic damage could be attributed to its ability to target the mitochondrial dynamics-related proteins (Mtf2, DNM1L and PGC-1α), but also their epigenetic regulator miRNA-17. To further explore the mode of action of carvedilol, we have investigated, in silico, the ability of carvedilol to target dynamin-1-like protein and mitochondrial dynamics protein (MID51). Our results revealed that carvedilol has a high binding affinity (−14.83 kcal/mol) toward the binding pocket of DNM1L protein. In conclusion, our study highlights the hepatoprotective pharmacological application of carvedilol to attenuate ischemic hepatitis associated with AHF.

Foodborne infections and antibiotic resistance pose a serious threat to public health and must be addressed urgently. Pistacia lentiscus is a wild-growing shrub and has been utilized for medicinal applications as well as for culinary purposes. The antibacterial and antioxidant activities of P. lentiscus bark in vitro, as well as the phytochemical composition, are the focus of this inquiry. The bark extract of P. lentiscus showed significant antimicrobial activity in experiments on bacteria and yeast isolated from human and food sources. The exposure time for the complete inhibition of cell viability of P. aeruginosa in the extracts was found to be 5% at 15 min. Phytochemical inquiry of the methanol extract demonstrates the existence of carbohydrates, flavonoids, tannins, coumarins, triterpenes, and alkaloids. Deep phytochemical exploration led to the identification of methyl gallate, gallic acid, kaempferol, quercetin, kaempferol 3-O-α-rhamnoside, kaempferol 3-O-β-glucoside, and Quercetin-3-O-β-glucoside. When tested using the DPPH assay, the methanol extracts of P. lentiscus bark demonstrated a high free radical scavenging efficiency. Further, we have performed a molecular modelling study which revealed that the extract of P. lentiscus bark could be a beneficial source for novel flavonoid glycosides inhibitors against SARS-CoV-2 infection. Taken together, this study highlights the Pistacia lentiscus bark methanol extract as a promising antimicrobial and antiviral agent.

Methotrexate (MTX) is one of the most commonly used chemotherapies for various types of cancer, including leukemia, breast cancer, hepatocarcinoma, and gastric cancers. However, the efficacy of MTX is frequently limited by serious side effects. Several studies have reported that the cytotoxic effect of MTX is not limited to cancer cells but can also affect normal tissues, leading to prospective damage to many organs. In the present study, we extensively investigated the molecular and microscopic basis of MTX-induced toxicity in different organs (liver, kidney, and heart) and explored the possible protective effect of pycnogenol, a polyphenolic component extracted from the bark of P. pinaster, to attenuate these effects. Biochemical analysis revealed that administration of MTX significantly reduced the function of the liver, kidney, and heart. Histological and immunohistochemical analysis indicated that MTX treatment caused damage to tissues of different organs. Interestingly, administration of pycnogenol (10, 20, and 30 mg/kg) significantly attenuated the deterioration effects of MTX on different organs in a dose-dependent manner, as demonstrated by biochemical and histological analysis. Our results reveal that pycnogenol successfully ameliorated oxidative damage and reduced toxicity, inflammatory response, and histological markers induced by methotrexate treatment. Taken together, this study provides solid evidence for the pharmacological application of pycnogenol to attenuate damage to different organs induced by MTX treatment.

Background and Objectives: Pharmacists play a major role in serving patients and delivering pharmaceutical services to the community. It is unclear whether the public fully appreciates what pharmacists can do as key health care providers. This study aims to examine public perceptions of community pharmacists and levels of satisfaction with pharmacy services. Materials and Methods: A cross-sectional study was conducted on a randomly selected sample population (n = 1000) in Saudi Arabia over a period of six months from January through June 2019. A 40-item, structured, self-administered questionnaire was used, comprised of questions on the demographics characteristics of the respondents and their satisfaction with pharmacy services. Descriptive statistics were used to analyze the data. Results: The response rate of the survey was 76.92%. Public opinions were influenced by pharmacists’ availability and knowledge, service promptness, and counseling services. Overall, 80.5% of respondents agreed that community pharmacists treat them with respect. Doctors were identified as the preferred source of drug therapy consultation by 58.7% and pharmacists by 41.29%. About 72.8% of respondents agreed that pharmacists provided them with clear instructions about medication use, and 70.2% trusted pharmacists’ opinions about medications. About 62.5% of respondents expressed satisfaction with pharmacists, and 64.8% with pharmacy services. Conclusions: Customers’ opinions were influenced by pharmacists’ availability and knowledge, pharmacy service promptness, pharmacy location, waiting area, medication knowledge, and counseling. However, the public was greatly satisfied with community pharmacists’ professionalism and pharmaceutical services. This positive perception provides an opportunity for pharmacists to extend their roles as healthcare professionals.

Anti-virulence agents are non-bacteriostatic and non-bactericidal emerging therapeutic options which hamper the production of virulence factors in pathogenic flora. In Staphylococcus aureus and Enterococcus faecalis, regulation of virulence genes’ expression occurs through the cyclic peptide-mediated accessory gene regulator (agr) and its ortholog fsr quorum sensing systems, respectively. In the present study, we screened a set of 54 actinomycetales secondary metabolites as novel anti-virulence compounds targeting quorum sensing system of the Gram-positive bacteria. The results indicated that four compounds, Phenalinolactones A–D, BU–4664LMe, 4,5-dehydrogeldamycin, and Questinomycin A, potentially inhibit the agr quorum sensing system and hemolytic activity of S. aureus. On the other hand, Decatromicin A and B, Okilactomycin, Rishirilide A, Abyssomicin I, and Rebeccamycin selectively blocked the fsr quorum sensing system and the gelatinase production in E. faecalis at sub-lethal concentrations. Interestingly, Synerazol uniquely showed the capability to inhibit both fsr and agr quorum sensing systems. Further, in silico molecular docking studies were performed which provided closer insights into the mode of action of these compounds and proposed that the inhibitory activity of these compounds could be attributed to their potential ability to bind to the ATP-active site of S. aureus AgrA. Taken together, our study highlights the potential of actinomycetales secondary metabolites with diverse structures as anti-virulence quorum sensing inhibitors.

The application of plant extracts or plant-derived compounds in the green synthesis of metal nanoparticles (NPs) was researched. Determining the exact metabolite implicated in the formation of NPs would necessitate comprehensive investigations. Copper nanoparticles (CuNPs) are gaining a lot of attention because of their unique properties and effectiveness against a wide range of bacteria and fungi, as well as their potential for usage in catalytic, optical, electrical, and microelectronics applications. In the course of this study, we aimed to formulate CuNPs utilizing pure tamarixinin A (TA) ellagitannin isolated from Tamarix aphylla galls. The main particle size of the formed CuNPs was 44 ± 1.7 nm with zeta potential equal to −23.7 mV, which emphasize the stability of the CuNPs. The X-ray diffraction spectroscopy showed a typical centered cubic crystalline structure phase of copper. Scanning electron microscopy images were found to be relatively spherical and homogeneous in shape. The antimicrobial properties of TA, as well as its mediated CuNPs, have been evaluated through well diffusion assays against four bacterial, Bacillus subtilis NCTC 10400, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853, and two fungal, Candida albicans and Aspergillus flavus, strains. The distinctive antimicrobial activities were noted against the fungal strains and the Gram-negative bacterial strains P. aeruginosa ATCC 27853, and E. coli ATCC 25922. In conclusion, CuNPs mediated by TA can be applied for combating a wide range of bacterial and fungal species especially C. albicans, Asp. flavus, and P. aeruginosa in a variety of fields.

Alcoholism is one of the most common diseases that can lead to the development of several chronic diseases including steatosis, and cognitive dysfunction. Statins are lipid-lowering drugs that are commonly prescribed for patients with fatty liver diseases; however, the exact effect of statins on cognitive function is still not fully understood. In the present study, we have investigated the molecular and microscopic basis of cognitive impairment induced by alcohol and/or Atorvastatin (ATOR) administration to male Wistar albino rats and explored the possible protective effect of acetylsalicylic acid (ASA). The biochemical analysis indicated that either alcohol or ATOR or together in combination produced a significant increase in the nucleotide-binding domain–like receptor 3 (NLRP3), interleukin-1β (IL-1β) miRNA155 expression levels in the frontal cortex of the brain tissue. The histological and morphometric analysis showed signs of degeneration in the neurons and the glial cells with aggregations of inflammatory cells and a decrease in the mean thickness of the frontal cortex. Immunohistochemical analysis showed a significant increase in the caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex. Interestingly, administration of ASA reversed the deleterious effect of the alcohol and ATOR intake and improved the cognitive function as indicated by biochemical and histological analysis. ASA significantly decreased the expression levels of miRNA155, NLRP3, and IL1B, and produced a significant decrease in caspase-8 immunoreaction in the neurons and glial cells of the frontal cortex with a reduction in the process of neuroinflammation and neuronal damage. To further investigate these findings, we have performed an extensive molecular docking study to investigate the binding affinity of ASA to the binding pockets of the NLRP3 protein. Our results indicated that ASA has high binding scores toward the active sites of the NLRP3 NACHT domain with the ability to bind to the NLRP3 pockets by a set of hydrophilic and hydrophobic interactions. Taken together, the present study highlights the protective pharmacological effect of ASA to attenuate the deleterious effect of alcohol intake and long term ATOR therapy on the cognitive function via targeting miRNA155 and NLRP3 proteins.

Wheat crops require effective nitrogen fertilization to produce high yields. Only half of chemical N2 fertilizers are absorbed into plants while the rest remains in the soil, causing environmental problems. Fungi could maximize nitrogen absorption, and from an environmental and biodiversity point of view, there is an urgent necessity for bioprospecting native fungi associated with wild plants growing in harsh environments, e.g., St. Katherine Protectorate (SKP) in the arid Sinai. Recovered taxa, either endophytic and/or rhizospheric, were screened for their plant growth-promoting (PGP) traits. Eighteen fungal isolates (15 rhizospheric and 3 endophytic) belonging to anamorphic ascomycetes were recovered from 9 different wild plants, and their PGP traits (indole-3-acetic acid [IAA] production, phosphate solubilization, siderophore production, and hydrolytic enzyme production) were measured. Rhizospheric isolate NGB-WS14 (Chaetosphaeronema achilleae) produced high levels of IAA (119.1 μg mL−1) in the presence of tryptophan, while NGB-WS 8 (Acrophialophora levis) produced high IAA levels (42.4 μg mL−1) in the absence of tryptophan. The highest phosphate-solubilizing activity (181.9 μg mL−1) was recorded by NGB-WFS2 (Penicillium chrysogenum). Endophytic isolate NGB-WFE16 (Fusarium petersiae) exhibited a high percentage level of Siderophore Unit (96.5% SU). All isolates showed variability in the secretion of extracellular hydrolytic enzymes. Remarkably, all isolates had antagonistic activity (55.6% to 87.3% suppression of pathogen growth) against the pathogenic taxon Alternaria alternata (SCUF00001378) in the dual-assay results. Out of the 18 isolates, 4 rhizospheric and 1 endophytic isolate showed significant increases in shoot dry weight and shoot nitrogen and chlorophyll content of wheat plants subjected to low inputs of chemical nitrogen (N) fertilizers (50% reduction) compared with the non-inoculated control in a pot experiment. Potent taxa were subjected to sequencing for molecular confirmation of phenotypic identification. The retrieved ITS sequences in this study have been deposited in GenBank under accession numbers from LC642736 to LC642740. This study considered the first report of endophytic fungi of Cheilanthes vellea, a wild plant with PGPF which improves wheat growth. These results recommend using PGPF as inoculants to alleviate low nitrogen fertilization.

This study was designed to investigate the effect of prenatal exposure to synthetic sex steroid on sperm quantity and quality, relative testicular and epididymal weights, and reproductive hormones level in adult Wistar rats. Forty male Wistar rats were divided into two groups: a test group (n = 20) that included mature rats that were born to dams exposed to gestational treatment with hydroxyprogesterone and a control group (n = 20) that included mature rats born to untreated dams. Compared to the control group, the test group showed a significant reduction in the sperm count, viability and motility, relative testicular and epididymal weights together with increased abnormal spermatozoa (p

Thymoquinone is a natural bioactive with significant therapeutic activity against multiple ailments including wound healing. The poor aqueous solubility and low skin permeability limit its therapeutic efficacy. The present investigation aimed to improve the biopharmaceutical attributes of thymoquinone to enhance its topical efficacy in wound healing. A nanoemulsion-based hydrogel system was designed and characterized as a nanotechnology-mediated drug delivery approach to improve the therapeutic efficacy of thymoquinone, utilizing a high-energy emulsification technique. The black seed oil, as a natural home of thymoquinone, was utilized to improve the drug loading capacity of the developed nanoemulsion system and reduced the oil droplet size to p < 0.05) influence on the mean droplet size and polydispersity index of the generated nanoemulsion. The developed nanoemulgel system of thymoquinone demonstrated the pseudoplastic behavior with thixotropic properties, and this behavior is desirable for topical application. The nanoemulgel system of thymoquinone exhibited significant enhancement (p < 0.05) in skin penetrability and deposition characteristics after topical administration compared to the conventional hydrogel system. The developed nanoemulgel system of thymoquinone exhibited quicker and early healing in wounded Wistar rats compared to the conventional hydrogel of thymoquinone, while showing comparable healing efficacy with respect to marketed silver sulfadiazine (1%) cream. Furthermore, histopathology analysis of animals treated with a developed formulation system demonstrated the formation of the thick epidermal layer, papillary dermis along with the presence of extensive and organized collagen fibers in newly healed tissues. The outcome of this investigation signifies that topical delivery of thymoquinone through nanoemulgel system is a promising candidate which accelerates the process of wound healing in preclinical study.

Clozapine is an atypical antipsychotic drug selectively effective in the treatment of refractory schizophrenia. However, myocarditis, as a serious cardiotoxic effect, has in several case reports been associated with clozapine therapy. Ani increase in the free radical production and ischemia, probably induced by clozapine-induced release of catecholamines, have been hypothesized to trigger an inflammatory response that leads to the clinically observed cardiomyopathy and sudden death even in young patients. The aim of this work is to study the role of oxidative stress in clozapine-induced myocarditis and myocardial DNA damage in a rat model. Methods: Male Wistar rats, age ∼6 weeks, were administered 5, 10 or 25 mg/kg clozapine daily for 21 days; saline-treated rats served as the control. Heart sections were stained with hematoxylin and eosin for histopathological examination. Plasma CK-MB, LDH and TNF-α concentrations were determined. Myocardial oxidative stress (MDA and NO), antioxidant (GSH and GSH-Px) parameters, and the marker of oxidative DNA damage (8-OHdG) were determined. Results: Clozapine treatment resulted in significant dose-related increases in myocardial inflammation with increased plasma TNF-α, CK-MB and LDH levels. Myocardial MDA, NO and serum and cardiac 8-OHdG levels increased while GSH level and GSH-Px activity decreased with the highest significance seen with the largest tested dose (25 mg/kg) of clozapine. Conclusions: Clozapine, in relatively large doses induced myocarditis consistently with increased myocardial oxidative stress, DNA damage and inflammatory cytokines in rat a model.

Clozapine, an ideal antipsychotic drug for the treatment of resistant schizophrenia, is considered the most underutilised treatment for schizophrenia. However, safety concerns have been raised about clozapine-induced cardiotoxicity, which may lead to sudden death, particularly in young patients. The exact mechanism of clozapine cardiotoxicity has not yet been thoroughly studied. This study aimed to investigate the possible mechanisms of clozapine-induced cardiotoxicity in a rat model. Young male Wistar rats were treated with clozapine (10, 15 and 25 mg/kg/day, i.p.) for 21 days. Haemodynamic and echocardiographic studies were performed for assessment of cardiac functions. Heart sections were studied histopathologically and immunohistochemically. Serum and cardiac markers of cardiotoxicity, oxidative stress, inflammation and apoptosis were evaluated. Heart sections of CLZ-treated animals showed increased cardiac inflammation that correlated with the clozapine dose. Serum levels of CK-MB and LDH levels increased, as did cardiac levels of TNF-α, MDA, NO, myeloperoxidase (MPO), 8-OHdG, caspase-3 and NF-κB p65. In contrast, GSH levels and GSH-Px activity decreased. Furthermore, immunohistochemical examination of the heart sections showed positive immunostaining for both 3-nitrotyrosine and caspase-3 in all clozapine-treated groups. Clozapine, particularly in relatively high doses, has a clear cardiotoxic effect. This cardiotoxicity is accompanied by increased myocardial oxidative stress, inflammatory cytokines, DNA damage and apoptosis with attenuation in antioxidant defences, thus explaining the previously reported myocarditis and pericarditis during clozapine therapy in clinical studies.