Eliciting Callus Cultures for the Production of Cytotoxic Polyphenolics from Maesa indica Roxb. Sweet.

Maesa indica Roxb. Sweet is a shrub known for its richness in secondary metabolites. A callus culture protocol was established to enhance its chemical profile. Sixteen elicitation culture treatments were evaluated, and we confirmed that the treatment of 200 mg/L polyethylene glycol (4000) coupled with exposure to 30 W UV irradiation for 60 min (PEG4) resulted in the highest total phenolic and total flavonoid contents, which were 4.1 and 4.9 times those of the plant ethanolic extract and 4.9 and 4.8 times those of a control sample, respectively. The phenolic compounds in the different treatments were identified qualitatively and quantitatively using the LC-ESI-MS/MS-MRM technique. Molecular docking studies of the phenolic compounds were conducted using MOE software and revealed that rutin showed the highest binding affinity toward the anti-cancer target (p38α MAPK). The cytotoxicity of the ME and PEG 4 treatment was tested against colon, breast, prostate, lung, and liver cell lines using an MTT assay. The highest cytotoxic effect of PEG4 was against prostate cancer with an IC50 value of 25.5 µg/mL. Hence, this study showed enhanced secondary metabolite accumulation and identified the phenolic compounds in the 16 treatments. The cytotoxicity assay highlighted the possible cytotoxic effect of the PEG4 treatment, and we recommend further investigations into its activity.

Comparative metabolomics analysis of Citrus medica var. sarcodactylis Swingle and Limonia acidissima Linn. Fruits and leaves cultivated in Egypt in context to their antiviral effects.

A comprehensive study of fruits and leaves extracts of Citrus medica var. sarcodactylis Swingle and Limonia acidissima L. family Rutaceae was accomplished to investigate their antiviral activity along with their zinc oxide nanoparticles formulation (ZnONPs) against the avian influenza H5N1 virus. A thorough comparative phytochemical investigation of C. medica and L.acidissima leaves and fruits was performed using UPLC-QTOF-MS-MS. Antiviral effects further aided by molecular docking proved the highly significant potential of using C. medica and L.acidissima extracts as medicinal agents. Antiviral potency is ascendingly arranged as L. acidissima leaves (LAL) > L. acidissima fruits (LAF) > C. medica leaves (CML) at 160 µg. Nano formulation of LAF has the most splendid antiviral upshot. The metabolomic profiling of CMF and LAL revealed the detection of 48 & 74 chromatographic peaks respectively. Docking simulation against five essential proteins in survival and replication of the influenza virus revealed that flavonoid di-glycosides (hesperidin, kaempferol-3-O-rutinoside, and kaempferol-7-neohesperidoside) have shown great affinity toward the five investigated proteins and achieved docking scores which approached or even exceeded that achieved by the native ligands. Hesperidin has demonstrated the best binding affinity toward neuraminidase (NA), haemagglutinin (HA), and polymerase protein PB2 (-10.675, -8.131, and -10.046 kcal/mol respectively. We propose using prepared crude methanol extracts of both plants as an antiviral agent.

The gastroprotective effect of Yucca filamentosa standardized crude leaves extract versus its nano-cubosomal formulation in ethanol-induced gastric injury.

Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway. The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed. Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats. Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.

Metabolomic profiling of Medicago sativa-derived fungal endophytes and evaluation of their biological activities.

This study aimed to discover the potential of Medicago sativa-derived fungal endophytes as a prospective source of bioactive metabolites. In the present study, three different strains of fungal endophyte Aspergillus terreus were isolated from leaves L, roots T and stems St of Medicago sativa to explore their biological and chemical diversity. These isolated fungi were exposed to different fermentation conditions by adding various chemical elicitors to their solid fermentation media. According to LC-HRESIMS-based metabolomics and multivariate analysis, each chemical treatment had a different effect on the chemical profiles of the fungi. Orthogonal Projections to Latent Structures Discriminant Analysis (OPLS-DA) proposed several compounds with anticancer action against MCF-7 (a human breast cancer cell line) and MDA-MB-231 (a human epithelial breast cancer cell line).

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies.

Introduction: In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. Methods: The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Results and Discussion: The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

Phytochemical Elucidation and Effect of Maesa indica (Roxb.) Sweet on Alleviation of Potassium Dichromate-Induced Pulmonary Damage in Rats.

Maesa indica (Roxb.) Sweet is one of the well-known traditionally-used Indian plants. This plant is rich in secondary metabolites like phenolic acids, flavonoids, alkaloids, glycosides, saponins, and carbohydrates. It contains numerous therapeutically active compounds like palmitic acid, chrysophanol, glyceryl palmitate, stigmasterol, ß-sitosterol, dodecane, maesaquinone, quercetin 3-rhaminoside, rutin, chlorogenic acid, catechin, quercetin, nitrendipine, 2,3-dihydroxypropyl octadeca-9,12-dienoate, kiritiquinon, and ß-thujone. The Maesa indica plant has been reported to have many biological properties including antidiabetic, anticancer, anti-angiogenic, anti-leishmanial, antioxidant, radical scavenging, antibacterial, antiviral, and anti-coronavirus effects. One purpose of the current study was to investigate the leaves' metabolome via Triple-Time-of-Flight-Liquid-Chromatography-Mass Spectrometry (T-TOF LC/MS/MS) to identify the chemical constituents of the Maesa indica ethanolic extract (ME). Another purpose of this study was to explore the protective effect of ME against potassium dichromate (PD)-induced pulmonary damage in rats. Rats were assigned randomly into four experimental groups. Two different doses of the plant extract, (25 and 50 mg/kg), were administered orally for seven consecutive days before PD instillation injection. Results of our study revealed that ME enhanced cellular redox status as it decreased lipid peroxidation marker, MDA and elevated reduced glutathione (GSH). In addition, ME upregulated the cytoprotective signaling pathway PI3K/AKT. Moreover, ME administration ameliorated histopathological anomalies induced by PD. Several identified metabolites, such as chlorogenic acid, quercetin, apigenin, kaempferol, luteolin, and rutin, had previously indicated lung-protective effects, possibly through an antioxidant effect and inhibition of oxidative stress and inflammatory mediators. In conclusion, our results indicated that ME possesses lung-protective effects, which may be the result of its antioxidant and anti-inflammatory properties.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) kunth. Ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats.

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

LC-HRMS Profiling and Cytotoxic Potential of Actinomycetes Associated with the Red Sea Soft Coral Sarcophyton glaucum: In vitro and In silico Studies.

In the current study, the actinomycetes associated with the red sea-derived soft coral Sarcophyton glaucum were investigated in terms of biological and chemical diversity. Four different media, M1, ISP2, Marine Agar (MA), and Actinomycete isolation agar (AIA) were used for the isolation of three strains of actinomycetes that were identified as Streptomyces sp. UR 25, Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. LC-HRMS analysis was used to investigate the chemical diversity of the isolated actinobacteria. The LC-HRMS data were statistically processed using MetaboAnalyst 5.0 viz to differentiate the extract groups and determine the optimal growth culturing conditions. Multivariate data statistical analysis revealed that the Micromonospora sp. extract cultured on (MA) medium is the most distinctive extract in terms of chemical composition. While, the Streptomyces sp. UR 25 extracts are differ significantly from Micromonospora sp. UR32 and Saccharomonospora sp. UR 19. Biological investigation using in vitro cytotoxic assay for actinobacteria extracts revealed the prominent potentiality of the Streptomyces sp. UR 25 cultured on oligotrophic medium against human hepatoma (HepG2), human breast adenocarcinoma (MCF-7) and human colon adenocarcinoma (CACO2) cell lines (IC50 =3.3, 4.2 and 6.8 µg/mL, respectively). SwissTarget Prediction speculated that among the identified compounds, 16-deethyl, indanomycin (8) could have reasonable affinity on HDM2 active site. In this respect, molecular docking study was performed for compound (8) to reveal a substantial affinity on HDM2 active site. In addition, molecular dynamics simulations were carried out at 200 ns for the most active compound (8) compared to the co-crystallized inhibitor DIZ giving deeper information regarding their thermodynamic and dynamic properties as well.

Effect of Phenolics from Aeonium arboreum on Alpha Glucosidase, Pancreatic Lipase, and Oxidative Stress; a Bio-Guided Approach.

Metabolic syndrome (MetS) is a global issue affecting over a billion people, raising the risk of diabetes, cardiovascular disorders, and other ailments. It is often characterized by hypertension, dyslipidemia and/or obesity, and hyperglycemia. Chemical investigation of Aeonium arboreum (L.) Webb & Berthel led to the isolation of six compounds, viz. ß-sitosterol, ß-sitosterol glucoside, myricetin galactoside, quercetin rhamnoside, kaempferol rhamnoside, and myricetin glucoside. Interestingly, A. arboreum's dichloromethane (DCM), 100 and 50% MeOH Diaion fractions and the isolated compound (quercetin-3-rhamnoside) revealed potent α-glucosidase inhibitory activity, especially 50% Diaion fraction. In addition, they also showed very potent antioxidant potential, especially the polar fractions, using DPPH, ABTS, FRAP, ORAC, and metal chelation assays. Notably, the 50% Diaion fraction had the highest antioxidant potential using DPPH and ORAC assays, while the 100% Diaion fraction and quercetin-3-rhamnoside showed the highest activity using ABTS, FRAP, and metal chelation assays. Also, quercetin-3-rhamnoside showed a good docking score of -5.82 kcal/mol in comparison to acarbose. In addition, molecular dynamic stimulation studies illustrated high stability of compound binding to pocket of protein. Such potent activities present A. arboreum as a complementary safe approach for the management of diabetes mellitus as well as MetS.

UPLC-MS-Based Metabolomics Profiling and Chemometric Analysis for Hypericum sinaicum Boiss and the Endophytic Aspergillus foetidus in Comparison to Hypericum perforatum L.

One of the endangered plant species in Saint Catherine protectorate is Hypericum sinaicum Boiss which is endemic to Egypt, Jordan, and Saudi Arabia. The fungus-host relationship can assist in the investigation of bioactive compounds produced by H. sinaicum paving the way for economic and medicinal implications. Therefore, a comprehensive metabolic approach via MS and chemical analysis was used to track and compare metabolites from H. sinaicum and Aspergillus foetidus var. pallidus, the endophytic fungus, with Hypericum perforatum. Metabolomics analysis revealed the presence of 25 metabolites distributed among samples and the discovery of new chemotaxonomic compounds, i. e., phloroglucinols and xanthones, allowing the discrimination between species. A. foetidus extract is considered a reliable source of furohyperforin and naphthodianthrone derivatives. In conclusion, using A. foetidus as an in vitro technique for producing potential phytoconstituents was cost effective, having easier optimization conditions and faster growth with fewer contamination rates than other in vitro methods.

Metabolomics analysis of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima Linn. fruits and leaves in perspective to their antimicrobial potential.

Antimicrobial potential of Citrus medica var. sarcodactylis (Siebold ex Hoola van Nooten) Swingle and Limonia acidissima L. fruits and leaves extracts CMF, CML, LAF and LAL, respectively were evaluated. Gas chromatography-mass spectrometry (GC-MS) analysis for lipoidal matters revealed a high percentage of non-oxygenated compounds. Phytol was the major in LAL. Palmitic and linoleic acid were the major in CML and LAL, respectively. Rutin and P-hydroxy benzoic acid were the main compounds identified by High-performance liquid chromatography (HPLC) analysis. The antibacterial and antifungal activities of the plants extract were determined by the well diffusion method. Antimicrobial investigation for different successive fractions of active methanol extracts of CML, LAL, LAF and CMF showed the highest activity (CML), whereas the petroleum ether (CML PE) and MeOH (CML) fractions exhibit a significant antifungal activity against Candida albicans minimum inhibitory concentration (MIC) 12 and 15 µg/mL, respectively. The antifungal activity prevailed by C. medica leaves may be attributed to its polyphenolics (rutin, chlorogenic and rosmarinic acid) in addition to phenylated hydrocarbon.

Phytochemical Profiling and Antiviral Activity of Green Sustainable Nanoparticles Derived from Maesa indica (Roxb.) Sweet against Human Coronavirus 229E.

Plant secondary metabolites are key components for new, safe and effective drugs. Ethanolic extract of Maesa indica Roxb. Sweet (ME) aerial parts were used for biosynthesis of sustainable green zinc oxide nanoparticles (ZnO NPs) with an average particle size 6.80 ± 1.47 nm and zeta potential -19.7 mV. Both transmission electron microscopy and X-ray diffraction assay confirmed the hexagonal shape of ZnO NPs. Phenolic ingredients in ME were identified using LC-ESI-MS/MS-MRM revealing the identification of chlorogenic acid, gallic acid, caffeic acid, rutin, coumaric acid, vanillin, naringenin, quercetin, ellagic acid, 3.4-dihydroxybenzoic acid, methyl gallate, kaempferol, ferulic acid, syringic acid, and luteolin. The major compound was chlorogenic acid at concentration of 1803.84 µg/g. The antiviral activity of ME, ZnO NPs, and combination of ME with ZnO NPs against coronavirus 229E were investigated. ZnO NPs had superior antiviral effect against coronavirus 229E than ME while their combination showed the highest anti-coronavirus 229E effect, with 50% inhibition concentration (IC50) of 5.23 ± 0.18 µg/mL and 50% cytotoxic concentration (CC50) of 138.49 ± 0.26 µg/mL while the selectivity index (SI) was 26.47. The current study highlighted the possible novel anti-coronavirus 229E activity of green ZnO NPs synthesized from Maesa indica. More studies are needed to further investigate this antiviral activity to be utilized in future biomedical and environmental applications.

Pectin Nanoparticle-Loaded Soft Coral Nephthea sp. Extract as In Situ Gel Enhances Chronic Wound Healing: In Vitro, In Vivo, and In Silico Studies.

This study shed light for the first time on the in vivo diabetic wound healing potential activity of natural marine soft coral polymeric nanoparticle in situ gel using an excision wound model. A Nephthea sp. methanol-methylene chloride extract loaded with pectin nanoparticles (LPNs) was created. For the preparation of in situ gel, ion-gelation techniques, the entrapment efficiency, the particle size, the polydispersity index, the zeta potential, the in-vitro drug release, and a transmission electron microscope were used and the best formula was selected. Using (UPLC-Q/TOF-MS), 27 secondary metabolites responsible for extract biological activity were identified. Isolation and identification of arachidic acid, oleic acid, nervonic acid, and bis-(2-ethylhexyl)-phthalate (DEHP) of Nephthea sp. was firstly reported here using NMR and mass spectral analyses. Moreover, LPN in situ gel has the best effects on regulating the proinflammatory cytokines (NF-κB, TNF-α, IL-6, and IL-1ß) that were detected on days 7 and 15. The results were confirmed with an in vitro enzymatic inhibitory effect of the extract against glycogen synthase kinase (GSK-3) and matrix metalloproteinase-1 (MMP-1), with IC50 values of 0.178 ± 0.009 and 0.258 ± 0.011 µg/mL, respectively. The molecular docking study showed a free binding energy of -9.6 kcal/mol for chabrolosteroid E, with the highest binding affinity for the enzyme (GSK-3), while isogosterone B had -7.8 kcal/mol for the enzyme (MMP-1). A pharmacokinetics study for chabrolohydroxybenzoquinone F and isogosterone B was performed, and it predicted the mode of action of wound healing activity.

Promising Cytotoxic butenolides from the Soybean endophytic fungus Aspergillus terreus: a combined molecular docking and in-vitro studies.

AIM: This study aimed to use one strain many compounds approach (OSMAC) to investigate the cytotoxic potential of Aspergillus terreus associated with soybean versus several cancer cell lines, by means of in-silico and in vitro approaches. METHODS AND RESULTS: Fermentation of the isolated strain was done on five media. The derived extracts were investigated for their inhibitory activities against three human cancer cell lines; mammary gland breast cancer (MCF-7), colorectal adenocarcinoma (Caco-2), and hepatocellular carcinoma (HepG2) using MTT Assay. The fungal mycelia fermented in Modified Potato Dextrose Broth (MPDB) was the most cytotoxic extract against HepG2, MCF-7, and Caco-2 cell lines with IC50 4.2 ± 0.13, 5.9 ± 0.013 and 7.3 ± 0.004 µg mL-1, respectively. MPDB extract was scaled up resulting in the isolation of six metabolites; three fatty acids (1, 2, and 4), one sterol (3) and two butenolides (5 and 6) by column chromatography. The isolated compounds (1-6) were screened through a molecular docking approach for their binding aptitude to various active sites. butyrolactone-I (5) revealed a significant interaction within the CDK2 active site, while aspulvinone E (6) showed promising binding affinity to FLT3 and EGFR active sites that was confirmed by in vitro CDK2, FLT3 and EGFR inhibitory activity. Finally, the in vitro cytotoxic activities of butyrolactone-I (5) and aspulvinone E (6) revealed the antiproliferative activity of butyrolactone-I (5), against HepG2 cell line (IC50 = 17.85 ± 0.32 µM). CONCLUSION: Molecular docking analysis and in vitro assays suggested the CDK2/A2 inhibitory potential of butyrolactone-I (5) in addition to the promising interaction abilities of aspulvinone E (6) with EGFR and FLT3 active sites as a possible mechanism of their biological activities.

Vetiver aerial parts and roots ameliorate rheumatoid arthritis in complete Freund's adjuvant rat model, a phytochemical profiling and mechanistic study.

ETHNOPHARMACOLOGICAL RELEVANCE: Vetiver (Chrysopogon zizanioides) is indigenous to India where it is traditionally used to relief rheumatisms, lumbagos and sprains. Vetiver anti-inflammatory activity has not been previously investigated, and its specific interactions with body inflammation cascade remain largely unknown. AIM OF THE STUDY: The present work was performed to validate the ethnobotanical use of the plant and compare the anti-inflammatory activities of the ethanolic extracts of the most traditionally used part (aerial part) to that of the root. Furthermore, we attempt to reveal the molecular mechanism of this anti-inflammatory activity in correlation to the chemical composition of C. zizanioides aerial (CA) and root parts (CR). MATERIALS AND METHODS: Ultraperformance liquid chromatography coupled to high resolution mass spectrometry (UHPLC/HRMS) was used for comprehensive analysis of both CA and CR. The anti-inflammatory effect of both extracts was evaluated in complete Freund's adjuvant (CFA)-induced RA model in Wistar rats. RESULTS: Phenolic metabolites were predominant in CA and 42 were identified for the first time, while only 13 were identified in CR. Meanwhile, triterpenes and sesquiterpenes were confined to the root extract. In CFA arthritis model, CA showed better anti-inflammatory activity than CR marked by an increase in serum level of IL-10 with simultaneous decrease in pro-inflammatory markers; IL-6, ACPA and TNF-α and was evident in histopathological examination. This anti-inflammatory effect was accompanied by down-regulation of JAK2/STAT3/SOCs3, ERK1/ERK2, TRAF6/c-FOS/NFATC1, TRAF6/NF-κB/NFATC1 and RANKL pathways which were all upregulated after CFA injection. These pathways were modulated to larger extent by CA, except for ERK1/ERK2 which was downregulated more effectively by CR. This differential effect between CA and CR can be explained by the variability in their phytoconstituents profile. CONCLUSION: In agreement with the ethnobotanical preference, CA extract was more effective than CR extract in reducing the symptoms of RA probably due to its enrichment with flavonoids, lignans, and flavolignans. Both CA and CR reduced the production of inflammatory cytokines through modulating various biological signaling pathways. These findings support the traditional use of vetiver leaves as a remedy for RA and suggest that the use of the whole plant may offer advantage by synergistically affecting more inflammatory pathways.

ESI-LC-MS/MS based comparative multivariate metabolomic and biological profiling with dynamic molecular docking of Gmelina arborea Roxb different organs.

A comprehensive study of leaves, flowers, fruits, bark, and seeds' extracts of Gmelina arborea Roxb was performed for first time to investigate their anti-inflammatory, anti-Alzheimer, and antidiabetic activities. A thorough comparative phytochemical investigation of the five organs was performed using Tandem ESI-LC-MS. The biological investigation, further aided by multivariate data analysis and molecular docking proved the highly significant potential of using G.arborea organs' extracts as medicinal agents. Chemometric analysis of the obtained data revealed 4 distinct clusters among different samples of the 5 G.arborea (GA)organs and also confirmed that each organ was chemically distinct from the others, except for fruits and seeds which were closely correlated. Compounds anticipated to be responsible for activity were identified by LC-MS/MS. To clarify the differential chemical biomarkers of G. arborea organs, an orthogonal partial least squares discriminant analysis (OPLS-DA) was constructed. Bark exhibited it's in vitro anti-inflammatory activity through down regulation of COX-1 pro-inflammatory markers while fruits and leaves affected mainly DPP4 the marker for diabetes, and flowers were the most potent against Alzheimer maker acetylcholine (ACE) esterase. The metabolomic profiling of the 5 extracts lead to the identification of 27 compounds in negative ion mode and the differences in chemical composition were correlated to difference in activity. Iridoid glycosides were the major class of identified compounds. Molecular docking proved the different affinities of our metabolite towards different targets. Gmelina arborea Roxb. is a very important plant both economically and medicinally.

Metabolic profiling and biological activity of two Livistona species: L. chinensis and L. australis.

Livistona is a genus of family Arecaceae and widely grown in tropical areas. The phytochemical analysis of the leaves and fruits of two Livistona species, L. chinensis and L. australis were carried out using UPLC/MS and determination of the total phenolic and total flavonoid contents, in addition to the isolation and identification of five phenolic compounds and one fatty acid from L. australis fruits. The total phenolic compounds varied from 19.72 to 78.87 mg GAE g-1 dry plant, while the total flavonoid contents were in the range of 4.82-17.75 mg RE g-1 dry plant. The UPLC/MS analysis of the two species led to the characterization of forty-four metabolites belonging mainly to the different classes of flavonoids and phenolic acids, while the compounds isolated from L. australis fruits were identified as gallic acid, vanillic acid, protocatechuic acid, hyperoside, quercetin 3-O-α-d-arabinopyranoside and dodecanoic acid. The in vitro biological evaluation of L. australis leaves and fruits were estimated as anticholinesterase, telomerase reverse transcriptase (TERT) potentiation and anti-diabetic through measuring the capacity of the extracts to inhibit dipeptidyl peptidase (DPP-IV). The results revealed that the leaves showed remarkable anticholinesterase and antidiabetic activity compared to fruits with IC50 values of 65.55 ± 3.75 ng mL-1 and 90.8 ± 4.48 ng mL-1, respectively. In the TERT enzyme assay, the leaves extract triggered a 1.49-fold increase in telomerase activity. This work showed that the Livistona species are a good source for flavonoids and phenolics, which play an important role in anti-aging and the treatment of chronic diseases, such as diabetes and Alzheimer's.

Network pharmacology and molecular docking study for biological pathway detection of cytotoxicity of the yellow jasmine flowers.

BACKGROUND: The yellow jasmine flower (Jasminum humile L.) is a fragrant plant belonging to the Oleaceae family with promising phytoconstituents and interesting medicinal uses. The purpose of this study was to characterize the plant metabolome to identify the potential bioactive agents with cytotoxic effects and the underlying mechanism of cytotoxic activity. METHODS: First, HPLC-PDA-MS/MS was used to identify the potential bioactive compounds in the flowers. Furthermore, we assessed the cytotoxic activity of the flower extract against breast cancer (MCF-7) cell line using MTT assay followed by the cell cycle, DNA-flow cytometry, and Annexin V-FITC analyses alongside the effect on reactive oxygen species (ROS). Finally, Network pharmacology followed by a molecular docking study was performed to predict the pathways involved in anti-breast cancer activity. RESULTS: HPLC-PDA-MS/MS tentatively identified 33 compounds, mainly secoiridoids. J. humile extract showed a cytotoxic effect on MCF-7 breast cancer cell line with IC50 value of 9.3 ± 1.2 µg/mL. Studying the apoptotic effect of J. humile extract revealed that it disrupts G2/M phase in the cell cycle, increases the percentage of early and late apoptosis in Annexin V-FTIC, and affects the oxidative stress markers (CAT, SOD, and GSH-R). Network analysis revealed that out of 33 compounds, 24 displayed interaction with 52 human target genes. Relationship between compounds, target genes, and pathways revealed that J. humile exerts its effect on breast cancer by altering, Estrogen signaling pathway, HER2, and EGFR overexpression. To further verify the results of network pharmacology, molecular docking was performed with the five key compounds and the topmost target, EGFR. The results of molecular docking were consistent with those of network pharmacology. CONCLUSION: Our findings suggest that J. humile suppresses breast cancer proliferation and induces cell cycle arrest and apoptosis partly by EGFR signaling pathway, highlighting J. humile as a potential therapeutic candidate against breast cancer.

Elicitation for activation of the actinomycete genome's cryptic secondary metabolite gene clusters.

This review summarizes the recent advances in the elicitation approaches used to activate the actinomycete genome's cryptic secondary metabolite gene clusters and shows the diversity of natural products obtained by various elicitation methods up to June 2022, such as co-cultivation of actinomycetes with actinomycetes, other non-actinomycete bacteria, fungi, cell-derived components, and/or algae. Chemical elicitation and molecular elicitation as transcription factor decoys, engineering regulatory genes, the promoter replacement strategy, global regulatory genes, and reporter-guided mutant selection were also reported. For researchers interested in this field, this review serves as a valuable resource for the latest studies and references.