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).

The impact of seasonal variation on the composition of the volatile oil of Polyalthia suberosa (Roxb.) Thwaites leaves and evaluation of its acetylcholinesterase inhibitory activity.

BACKGROUND: Polyalthia suberosa (Roxb.) Thwaites (Annonaceae) is a medicinal plant that has been reported for its various pharmacological potentials, such as its anti-inflammatory, analgesic, antioxidant, and neuropharmacological activities. This study aimed to analyze the leaf essential oils of P. suberosa (PSLO) collected in different seasons, to evaluate the acetylcholinesterase inhibitory activity, and to corroborate the obtained results via in-silico molecular docking studies. METHODS: The leaf essential oils of P. suberosa collected in different seasons were analyzed separately by GC/MS. The acetylcholinesterase inhibitory activity of the leaves oil was assessed via colorimetric assay. In-silico molecular docking studies were elucidated by virtual docking of the main compounds identified in P. suberosa leaf essential oil to the active sites in human acetylcholinesterase crystal structure. RESULTS: A total of 125 compounds were identified where D-limonene (0.07 - 24.7%), α-copaene (2.25 - 15.49%), E-ß-caryophyllene (5.17 - 14.42%), 24-noroleana-3,12-diene (12.92%), ß-pinene (0.14 - 8.59%), and α-humulene (2.49-6.9%) were the most abundant components. Results showed a noteworthy influence of the collection season on the chemical composition and yield of the volatile oils. The tested oil adequately inhibited acetylcholinesterase enzyme with an IC50 value of 91.94 µg/mL. Additionally, in-silico molecular docking unveiled that palmitic acid, phytol, p-cymene, and caryophyllene oxide demonstrated the highest fitting scores within the active sites of human acetylcholinesterase enzyme. CONCLUSIONS: From these findings, it is concluded that P. suberosa leaf oil should be evaluated as a food supplement for enhancing memory.

Role of Nutraceuticals in Obesity Management: A Mechanism and Prospective Supported by Molecular Docking Studies.

Obesity and its comorbidities represent a major health problem worldwide. Treatment by reducing food intake and physical activity interventions has limited success especially with elderly people with chronic diseases. Nutraceuticals are naturally originated and successfully used for their physiological and nutritional benefit in health care. They might be alternative means to help lose weight and reduce obesity-associated metabolic disorders with the improvement of health, delay the aging process, prevention of chronic diseases, increase of life expectancy, or support to the structure or function of the body. The current study enumerates the inherent role of nutraceuticals in the management of obesity and its related comorbidities. The study is supported with the molecular docking studies discussing the mechanism of action. An attempt to optimize the role of nutraceuticals is made in this article in addition to widen the scope of its use in this chronic worldwide disease.

Unveiling the Antimicrobial and Larvicidal Potential of Butyrolactones and Orsellinic Acid Derivatives from the Morus alba-derived Fungus Aspergillus terreus via Integrated In vitro and In silico Approaches.

The emergence of multi-drug-resistant microbial strains spurred the search for antimicrobial agents; as a result, two distinct approaches were combined: four in vitro studies and four corresponding molecular docking investigations. Antituberculosis, anti-methicillin-resistant Staphylococcus aureus (anti-MRSA), antifungal, and larvicidal activities of the crude extract, two fractions, and seven isolated compounds from Aspergillus terreus derived from Morus alba roots were explored. The isolated compounds (5 butyrolactones and 2 orsellinic acid derivatives) showed potent to moderate antitubercular activity with MIC values ranging from 1.95 to 62.5 µg/mL (compared to isoniazid, 0.24 µg/mL) and promising anti-MRSA potential with inhibition zone diameters ranging from 8 to 25 mm. Additionally, the in silico study proved that the isolated compounds bind to the two corresponding proteins' active sites with high to moderate -(C-Docker interaction energies) and stable interactions. The isolated compounds displayed antifungal activities against different fungal strains at diverse degrees of activity, among them compound (8"S,9")-dihydroxy-dihydrobutyrolactone I eliciting the best antifungal activity. Meanwhile, all isolated compounds, fractions, and the crude extract demonstrated extremely selective potent to moderate activity against Cryptococcus neoformans. The isolated five butyrolactone derivatives could develop potential mosquito larvicidal agents as a result of promising docking outcomes in the larval enzyme carboxylesterase.

Genus Curcuma: chemical and ethnopharmacological role in aging process.

Aging or senescence is part of human life development with many effects on the physical, mental, and physiological aspects which may lead to age-related deterioration in many organs. Genus Curcuma family Zingieraceae represents one of the well-studied and medically important genera with more than eighty species. The genus is reported to contain different classes of biologically active compounds that are mainly presented in diphenylheptanoids, diphenylpentanoids, diphenylalkanoids, phenylpropene derivatives, alkaloids, flavonoids, chromones, terpenoids, phenolic acids and volatile constituents. Rhizomes and roots of such species are rich with main phytoconstituents viz. curcumin, demethoxycurcumin and bis-demethoxycurcumin. A wide variety of biological activities were demonstrated for different extracts and essential oils of genus Curcuma members including antioxidant, anti-inflammatory, cytotoxic and neuroprotective. Thus, making them as an excellent safe source for nutraceutical products and as a continuous promising area of research on lead compounds that may help in the slowing down of the aging process especially the neurologic and mental deterioration that are usually experienced upon aging. In this review different species of the genus Curcuma were summarized with their phytochemical and biological activities highlighting their role as antiaging agents. The data were collected from different search engines viz. Pubmed®, Google Scholar®, Scopus® and Web of Science® limiting the search to the period between 2003 up till now.

Comparative metabolic study of the chloroform fraction of three Cystoseira species based on UPLC/ESI/MS analysis and biological activities.

This study aims to investigate the phytoconstituents of the chloroform fraction of three Cystoseira spp. namely C. myrica, C. trinodis, and C. tamariscifolia using UPLC/ESI/MS technique. The results revealed the identification of 19, 20 and 11 metabolites in C. myrica, C. trinodis, and C. tamariscifolia, respectively mainly terpenoids, flavonoids, phenolic acids and fatty acids. Also, an in vitro antioxidant study using FRAP and DPPH assays was conducted where the chloroform fraction of C. trinodis displayed the highest antioxidant activity in both assays, which would be attributed to its highest total phenolics and total flavonoids. Besides, the investigation of COX-1, α-glucosidase and α-amylase inhibitory activities were performed. Regarding C. trinodis, it showed the strongest inhibitory activity towards COX-1. Moreover, it showed potent inhibitory activity towards α-glucosidase and α-amylase enzymes. According to the molecular docking studies, the major compounds characterised showed efficient binding to the active sites of the target enzymes.

Eremophila purpurascens: Anti-oxidant, Anti-hyperglycemic, and Hepatoprotective Potential of Its Polyphenolic Rich Leaf Extract and Its LC-ESI-MS/MS Chemical Characterization and Standardization.

The genus Eremophila, despite comprising more than 250 species, has scarce literature studies that could be traced concerning the chemical profile and bioactivity of Eremophila purpurascens. The current study targets the investigation of the in vitro and in vivo anti-oxidant, anti-hyperglycemic, and hepatoprotective potential of the polyphenol-rich leaf extract of E. purpurascens (EP). EP showed promising total anti-oxidant capacity with IC50 values of 106 and 114 µg/mL in 2,2'-azinobis [3-ethylbenzothiazoline-6-sulfonic acid]-diammonium salt (ABTS) and diphenyl-1-picrylhydrazyl (DPPH) assays, respectively, with total anti-oxidant capacities of 331, 245, and 1767 µmol/g in ABTS, DPPH, and ferric reducing anti-oxidant power assays, respectively. In HepG2 cells, pre-treated with CCl4, a dose of 100 µg/mL EP ameliorated the reduced superoxide dismutase and glutathione levels and total anti-oxidant capacity with values of 312.5 U/mL, 15.47 mg/dL, and 1.03 nmol/mL, respectively. In vitro anti-diabetic evaluation using 3T3-L1 adipocyte culture showed that at a dose of 30 µg/mL, the EP extract elicited a 6.3% decrease in the concentration of glucose (22.4 mmol/L), showing significant amelioration with regard to pioglitazone and insulin. EP also demonstrated elevated serum insulin by 77.78% with a marked reduction in fasting blood glucose level by 64.55% relative to the streptozotocin diabetic rats in vivo. EP also relieved the liver stress markers both in vitro in CCl4 and in vivo in tamoxifen (TAM) models. EP markedly decreased TAM toxicity, as demonstrated by the decline in the liver stress markers, ALT and AST, by 36.1 and 51.1%, respectively. It also relieved the oxidative stress triggered by TAM, as revealed by the reduction in the levels of TBARs and TNF-α by 21.4 and 40%, respectively. Liquid chromatography electrospray ionization mass spectrometry of EP revealed a total of twelve peaks belonging to phenylpropanoids, lignans, and phenolics, where verbascoside and pinoresinol-4-O-ß-d-glucoside represented the most abundant secondary metabolites. The docking experiment showed that tri-O-galloyl-hexoside had the best fitting within the NADPH oxidase active sites with binding energy (ΔG = -81.12 kcal/mol). Thus, the plant can be of beneficial value in the control of hyperglycemia in diabetic patients, besides its prophylactic potential against hepatic complications.

Antimicrobial activities of metabolites isolated from endophytic Aspergillus flavus of Sarcophyton ehrenbergi supported by in-silico study and NMR spectroscopy.

BACKGROUND: Endophytic Aspergillus species produce countless valuable bioactive secondary metabolites. In the current study, Aspergillus flavus an endophyte from the soft coral Sarcophyton ehrenbergi was chemically explored and the extracted phytoconstituents were subsequently evaluated for antimicrobial activity. This is accomplished by employing nuclear magnetic resonance (NMR) spectroscopy and computational techniques. Additionally, An in vitro anticancer analysis of A. flavus total extract against breast cancer cells (MCF-7) was investigated. RESULT: Six compounds were separated from the crude alcohol extract of the endophytic Aspergillus flavus out of which anhydro-mevalonolactone was reported for the first time. The anti-fungal and anti-Helicobacter pylori properties of two distinct compounds (Scopularides A and B) were assessed. Additionally, computational research was done to identify the binding mechanisms for all compounds. Both the compounds were found to be active against H. pylori with minimum inhibitory concentration (MIC) values ranging from 7.81 to 15.63 µg/ mL as compared with clarithromycin 1.95 µg/ mL. Scopularides A was potent against both Candida albicans and Aspergillus niger with MIC values ranging from 3.9 to 31.25 µg/ mL, while scopularides B only inhibits Candida albicans with MIC value of 15.63 µg/ mL and weak inhibitory activity against A. niger (MIC = 125 µg/ mL). Furthermore, cytotoxic activity showed a significant effect (IC50: 30.46 mg/mL) against MCF-7 cells. CONCLUSION: Our findings report that cytotoxic activity and molecular docking support the antimicrobial activity of Aspergillus flavus, which could be a promising alternative source as a potential antimicrobial agent.

Insights into the Role of Erythrina corallodendron L. in Alzheimer's Disease: in Vitro and in Silico Approach.

Alzheimer's disease (AD) is a major health problem. Cholinergic transmission is greatly affected in AD. Phytochemical investigation of the alkaloid rich fraction (AF) of Erythrina corallodendron L leaves resulted in isolation of five known alkaloids: erysodine, erythrinine, 8-oxoerythrinine, erysovine N-oxide and erythrinine N-oxide. In this study, eysovine N-oxide was reported for the second time in nature. AF was assayed for cholinesterase inhibition at the concentration of 100 µg mL-1 . AF showed a higher percent inhibition for butyrylcholinesterase enzyme (BuChE) (83.28 %) compared to acetylcholinesterase enzyme (AChE) (64.64 %). The isolated alkaloids were also assayed for their anti-BuChE effect. In-silico docking study was done for the isolated compounds at the binding sites of AChE and BuChE to determine their binding pattern and interactions, also molecular dynamics were estimated for the compound displaying the best fit for AChE and BuChE. In addition, ADME parameters and toxicity were predicted for the isolated alkaloids compared to donepezil.

Austalide derivative from marine-derived Aspergillus sp. and evaluation of its cytotoxic and ADME/TOPKAT properties.

In-depth chemical investigation of an ethyl acetate extract of Aspergillus sp. isolated from the soft coral Sinularia species resulted in the isolation of one new meroterpenoid, austalide Z (1), one known austalide W (2), six known prenylated indole diketopiperazine alkaloids (3-8), and phthalic acid and its ethyl derivative (9-10). The structures were established by means of 1D and 2D NMR (one- and two-dimensional nuclear magnetic resonance) experiments supported by UV analysis and ESI-MS (electrospray ionization mass spectrometry). In vitro cytotoxic evaluation was performed against the Caco-2 cancer cell line using the MTT assay, which showed that the examined compounds had weak to moderate activities, with the new meroterpenoid austalide Z (1) displaying an IC50 value of 51.6 µg mL-1. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) predication performed in silico showed that most of the isolated compounds possessed reasonable pharmacokinetic, pharmacodynamic, and toxicity properties. Thus, it can be concluded that Aspergillus sp. could act as a source of drug leads for cancer prevention with promising pharmacokinetic and pharmacodynamic properties and thus could be incorporated in pharmaceutical dosage forms.

Analyses of Elaeocarpus sphaericus Extract for Antioxidant, Antiproliferative and Gene Repression Activities against HIF-1α and VEGF.

The study presents antioxidant, phytochemical, anti-proliferative, and gene repression activities against Hypoxia-inducible factor (HIF-1) alpha and Vascular endothelial growth factor (VEGF) of Elaeocarpus sphaericus extract. Elaeocarpus sphaericus dried and crushed plant leaves were extracted using water and methanol by ASE (Accelerated Solvent Extraction) method. Total phenolic content (TPC) and total flavonoid content (TFC) were used to measure the extracts' phytochemical activity (TFC). Antioxidant potential of the extracts was measured through DPPH, ABTS, FRAP, and TRP. Methanolic extract of the leaves of E. sphaericus has shown a higher amount of TPC (94.666±4.040 mg/gm GAE) and TFC value (172.33±3.21 mg/gm RE). The antioxidant properties of extracts in the yeast model (Drug Rescue assay) showed promising results. Ascorbic acid, gallic acid, hesperidin, and quercetin were found in the aqueous and methanolic extracts of E. sphaericus at varying amounts, according to a densiometric chromatogram generated by HPTLC analysis. Methanolic extract of E. sphaericus (10 mg/ml) has shown good antimicrobial potential against all bacterial strains used in the study except E. coli. The anticancer activity of the extract in HeLa cell lines ranged from 77.94±1.03 % to 66.85±1.95 %, while it ranged from 52.83±2.57 % to 5.44 % in Vero cell lines at varying concentration (1000 µg/ml-31.2 µg/ml). A promising effect of extract was observed on the expression activity of HIF-1 and VEGF gene through RT-PCR assay.

A comprehensive review on the medicinally valuable endosymbiotic fungi Penicillium chrysogenum.

Recently, it has been shown that metabolites derived from endosymbiotic fungi attracted high attention, since plenty of them have promising pharmaceutical applications. The variation of metabolic pathways in fungi is considered an optimistic source for lead compounds. Among these classes are terpenoids, alkaloids, polyketides, and steroids, which have proved several pharmacological activities, including antitumor, antimicrobial, anti-inflammatory, and antiviral actions. This review concludes the major isolated compounds from different strains of Penicillium chrysogenum during the period 2013-2023, together with their reported pharmacological activities. From literature surveys, 277 compounds have been identified from P. chrysogenum, which has been isolated as an endosymbiotic fungus from different host organisms, with specific attention paid to those showing marked biological activities that could be useful in the pharmaceutical industry in the future. This review represents documentation for a valuable reference for promising pharmaceutical applications or further needed studies on P. chrysogenum.

Metabolic profiling, antioxidant, and enzyme inhibition potential of Iris pseudacorus L. from Egypt and Japan: A comparative study.

Genus Iris comprises numerous and diverse phytoconstituents displaying marked biological activities. The rhizomes, and aerial parts of Iris pseudacorus L. cultivars from Egypt and Japan were subjected to comparative metabolic profiling using UPLC-ESI-MS/MS. The antioxidant capacity was determined using DPPH assay. In vitro enzyme inhibition potential against α-glucosidase, tyrosinase and lipase was evaluated. In silico molecular docking was conducted on the active sites of human α-glucosidase and human pancreatic lipase. Forty-three compounds were tentatively identified including flavonoids, isoflavonoids, phenolics and xanthones. I. pseudacorus rhizomes extracts (IPR-J and IPR-E) exhibited the highest radical scavenging activity with IC50 values of 40.89 µg/mL and 97.97 µg/mL, respectively (Trolox IC50 value was 14.59 µg/mL). Moreover, IPR-J and IPR-E exhibited promising α-glucosidase inhibitory activity displaying IC50 values of 18.52 µg/mL, 57.89 µg/mL, respectively being more potent as compared to acarbose with IC50 value of 362.088 µg/mL. All extracts exerted significant lipase inhibitory activity exhibiting IC50 values of 2.35, 4.81, 2.22 and 0.42 µg/mL, respectively compared to cetilistat with IC50 value of 7.47 µg/mL. However, no tyrosinase inhibitory activity was observed for all I. pseudacorus extracts up to 500 µg/mL. In silico molecular modelling revealed that quercetin, galloyl glucose, and irilin D exhibited the highest fitting scores within the active sites of human α-glucosidase and pancreatic lipase. ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that most of the phytoconstituents exhibited promising pharmacokinetic, pharmacodynamics and tolerable toxicity properties. According to our findings, I. pseudacorus might be considered as a valuable source for designing novel phytopharmaceuticals.

Unearthing the fungal endophyte Aspergillus terreus for chemodiversity and medicinal prospects: a comprehensive review.

Aspergillus terreus microorganism represents a promising prospective source for drug discovery since it is rich in diverse kinds of bioactive secondary metabolites. It contributed to many biotechnological applications and its metabolites are used in the synthesis of certain pharmaceuticals and food products, in addition to its useful uses in fermentation processes. There are about 346 compounds identified from marine and terrestrial-derived A. terreus from 1987 until 2022, 172 compounds of them proved a vast array of bioactivity. This review aimed to create an up-to-date comprehensive literature data of A. terreus's secondary metabolites classes supported by its different bioactivity data to be a scientific record for the next work in drug discovery.

Chemical and Biological Review of Endophytic Fungi Associated with Morus sp. (Moraceae) and In Silico Study of Their Antidiabetic Potential.

The chronic nature of diabetes mellitus motivates the quest for novel agents to improve its management. The scarcity and prior uncontrolled utilization of medicinal plants have encouraged researchers to seek new sources of promising compounds. Recently, endophytes have presented as eco-friendly leading sources for bioactive metabolites. This article reviewed the endophytic fungi associated with Morus species and their isolated compounds, in addition to the biological activities tested on their extracts and chemical constituents. The relevant literature was collected from the years 2008-2022 from PubMed and Web of Science databases. Notably, no antidiabetic activity was reported for any of the Morus-associated endophytic fungal extracts or their twenty-one previously isolated compounds. This encouraged us to perform an in silico study on the previously isolated compounds to explore their possible antidiabetic potential. Furthermore, pharmacokinetic and dynamic stability studies were performed on these compounds. Upon molecular docking, Colletotrichalactone A (14) showed a promising antidiabetic activity due to the inhibition of the α-amylase local target and the human sodium-glucose cotransporter 2 (hSGT2) systemic target with safe pharmacokinetic features. These results provide an in silico interpretation of the possible anti-diabetic potential of Morus endophytic metabolites, yet further study is required.

Phytochemical Investigation of Three Cystoseira Species and Their Larvicidal Activity Supported with In Silico Studies.

Culex pipiens mosquitoes are transmitters of many viruses and are associated with the transmission of many diseases, such as filariasis and avian malaria, that have a high rate of mortality. The current study draws attention to the larvicidal efficacy of three methanolic algal extracts, Cystoseira myrica, C. trinodis, and C. tamariscifolia, against the third larval instar of Cx. pipiens. The UPLC-ESI-MS analysis of three methanol fractions of algal samples led to the tentative characterization of twelve compounds with different percentages among the three samples belonging to phenolics and terpenoids. Probit analysis was used to calculate the lethal concentrations (LC50 and LC90). The highest level of toxicity was attained after treatment with C. myrica extract using a lethal concentration 50 (LC50) of 105.06 ppm, followed by C. trinodis (135.08 ppm), and the lowest level of toxicity was achieved by C. tamariscifolia (138.71 ppm) after 24 h. The elevation of glutathione-S-transferase (GST) and reduction of acetylcholine esterase (AChE) enzymes confirm the larvicidal activity of the three algal extracts. When compared to untreated larvae, all evaluated extracts revealed a significant reduction in protein, lipid, and carbohydrate contents, verifying their larvicidal effectiveness. To further support the observed activity, an in silico study for the identified compounds was carried out on the two tested enzymes. Results showed that the identified compounds and the tested enzymes had excellent binding affinities for each other. Overall, the current work suggests that the three algal extractions are a prospective source for the development of innovative, environmentally friendly larvicides.

Phytoecdysteroids and Anabolic Effect of Atriplex dimorphostegia: UPLC-PDA-MS/MS Profiling, In Silico and In Vivo Models.

Atriplex dimorphostegia (Saltbush) is an annual halophytic shrub that is widely distributed across various parts of Asia. The current study is the first to report the metabolites profile of the total ethanol extract of the aerial parts of A. dimorphostegia (TEAD), and its anabolic activity together with the isolated 20-hydroxyecdysone (20-HE) in orchidectomized male rats. TEAD was analyzed and standardized utilizing UPLC-PDA-ESI−MS/MS and UPLC-PDA-UV techniques, resulting in tentative identification of fifty compounds including polyphenols, steroids and triterpenoids. In addition, 20-HE was quantified, representing 26.79 µg/mg of the extract. Phytochemical investigation of TEAD resulted in the isolation of 20-HE from the ethyl acetate fraction (EFAD) and was identified by conventional spectroscopic methods of analysis. Furthermore, the anabolic effect of the isolated 20-HE and TEAD was then evaluated using in silico and in vivo models. Molecular docking experiments revealed in vitro selectivity of 20-HE towards estrogen receptors (ERs), specifically ERß over ERα and androgenic receptor (AR). The anabolic efficacy of TEAD and 20-HE was studied in orchidectomized immature male Wistar rats using the weight of gastrocnemius and soleus muscles. The weights of ventral prostate and seminal vesicles were used as indicators for androgenic activity. Rats administered 20-HE and TEAD showed a significant increase (p = 0.0006 and p < 0.0001) in the net muscle mass compared to the negative control, while the group receiving TEAD showed the highest percentage among all groups at p < 0.0001. Histopathological investigation of skeletal muscle fibers showed normal morphological structures, and the group administered 20-HE showed an increase in cross sectional area of muscle fibers comparable to methandienone and testosterone groups at p > 0.99. A. dimorphostegia exhibited promising anabolic activity with minimal androgenic side effects.

Protective effect of acrocarpus fraxinifolius extract against hepatic fibrosis induced by Gamma irradiation and carbon tetrachloride in albino rats.

PURPOSE: Liver fibrosis is considered as one of the ultimate outcomes of chronic liver disorders, characterized by outrageous cell proliferation and abnormal deposition of extracellular matrix, resulting in sever pathological distortions in the architecture and performance of liver tissues. The present study aimed to investigate the protective properties of aqueous methanol extract of Acrocarpus fraxinifolius leaves (AFL) against liver fibrosis induced by dual toxicity of γ-irradiation and carbon tetrachloride (CCl4) in rats. METHODS: The animals were exposed to 2 Gy irradiation once/week concurrently with intraperitoneal administration of CCl4 (0.2 mL/100 g body weight) for seven weeks. Afterwards, liver toxicity and fibrosis were assessed biochemically at cellular and molecular as well as histopathological levels. RESULTS: The livers of intoxicated rats showed distinct structural and functional changes, compared with the normal rats. The administration of AFL (500 mg/kg, p.o) significantly ameliorated the histopathological manifestations of fibrotic liver evidenced by mitigated steatosis progression, necrosis, fibrotic septa, apoptotic bodies, and immunochistochemical studies of alpha-smooth muscle actin. Also, AFL increased the final body weight, total protein, albumin levels and albumin/globulin ratio. While, the absolute liver weight, liver enzymes, total cholesterol and triglycerides were reduced. A significant modulation was observed in hydroxyproline, transforming growth factor-ß and collagen-1expression. Furthermore, AFL exerted a direct effect on liver fibrosis by promoting extracellular matrix degradation via overexpression of the tissue inhibitor metalloproteinase-1, coupled with decease of metalloproteinase-9 activity. CONCLUSIONS: Our findings suggested that AFL effectively improved the architecture of fibrotic liver and modified the biochemical markers of liver fibrosis.

Phytochemical analysis of Pithecellobium dulce (Roxb) Benth Bark via UPLC-ESI-MS/MS and evaluation of its biological activity.

The metabolites profile of Egyptian P. dulce bark was investigated using UPLC-ESI-MS/MS analysis with subsequent analysis of its cytotoxicity, antimicrobial, and antioxidant activities. Asides, in silico molecular docking study was performed for validation of cytotoxicity. P. dulce bark showed richness in polyphenolics and flavonoids, displaying 575.5 mg GAE/g extract (total phenolic content) and 310.82 mg CE/g extract (flavonoid content). A total of 29 compounds were tentatively identified. Proanthocyanidins and phenolic acids were the major classes observed. P. dulce bark possessed promising antioxidant and cytotoxic activities, however, it exhibited a weak antimicrobial activity. No antifungal activity was observed. In silico molecular docking revealed that daidzein compound achieved the best interaction energy score on the 5II2 of Gibbs free energy of -6.911 kcal/mol. This study revealed that P. dulce bark can be introduced as a potential source for valuable bioactive compounds that supporting its usage in food and pharmaceutical industries.