Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antio... more Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antioxidant, anticancer and antimutagenic properties. Its low aqueous solubility and permeability in GIT, permanent binding to DNA and proteins of cells and first pass metabolism are considered as the reasons for its low oral bioavailability and consequently its low therapeutic potential. Cyclodextrin-based nanosponges (NS) have been utilized to improve the solubilization efficiency of Ellagic acid and to control its release. The scope of the work was to prepare EA nanosponges (EA-NS) using cyclodextrin (β-CD) and cross-linked by dimethyl carbonate (DMC). It was found that the particle size of the prepared EA-NS was 423.2 nm with low polydispersity index (0.409) and high zeta potential (-34 mV) which manifests the construction of a stabilized colloidal nanoformulation. Moreover, high solubilization efficiency of the loaded EA-NS (49.79μg/ml) compared with the free EA (9.73μg/ml) was spotted. The prepared EA-NS was characterized by XRD, FTIR, and DSC studies and it elucidated a definite interaction of EA with NS. EA-NS successively improved its solubility and provided a controlled in vitro release for 24 hours. EA-NS produced about 69.17% drug content which indicates a good drug loading of the prepared nanosponges. Dissolution of EA-NS was higher than the drug alone. Animal study displayed an improvement in the oral bioavailability of EA indicated by an increase in AUC (1345.49 ng.hr.ml-1) of the EA -NS compared with (598.94 ng.hr.ml-1) for EA.
Background: Natural products display a remarkable role not only in the synthesis, design, and dis... more Background: Natural products display a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of innovative drugs and bioactive substances. Genus Pulicaria (Asteraceae) includes about 100 species that are widely distributed in Europe, Asia, and Africa. Objective: In this work, the chemical investigation of Pulicaria undulata aerial parts was performed. In addition, the cytotoxic activity of the isolated metabolites was estimated toward various cell lines. Materials and Methods: Plant extract was subjected to fractionation and different column chromatography to isolate the biometabolites. Their structures were verified using nuclear magnetic resonance, infrared, ultraviolet, and high-resolution mass spectrometry, as well as compared with the literature. The cytotoxic effect was evaluated in vitro toward various cell lines: HCT-116 (colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), and A549 (lung carcinoma). Results: A new triterpene fatty acid ester, undulaterpene A (1) (3β,16β-dihydroxylup-20 (29)-ene 3-decanoate) and four known metabolites: 3-O-acetyl-pseudotaraxasterol (2), pseudotaraxasterol (3), stigmasterol (4), and tomentosin (5) were separated. Compound 1 displayed cytotoxic potential toward hormone-dependent breast carcinoma cell line (MCF7), colon carcinoma cell line (HCT116), and lung carcinoma cell line (A549) cell lines with half maximal inhibitory concentrations (IC50s) 8.2, 6.9, and 12.4 μM, respectively in comparison to doxorubicin (IC50s 0.14, 0.39, and 1.15 μM, respectively). However, 2, 3, and 4 displayed activity toward HCT-116 with IC50s 13.2, 23.1, and 16.4 μM, respectively. Conclusion: This work led to the identification of a new triterpene fatty acid ester (1) and four known metabolites (2–5) from P. undulata growing in Saudi Arabia. The new compound showed moderate cytotoxic potential against hormone-dependent breast carcinoma cell line (MCF7), colon carcinoma cell line (HCT116), and lung carcinoma cell line (A549) cancer cell lines.
Background: Endophytic fungi attracted attention as a prolific source of bioactive natural produc... more Background: Endophytic fungi attracted attention as a prolific source of bioactive natural products with a potent pharmaceutical activity and unique structure. Objective: The main goal of the study is to separate and identify the bioactive constituents from the endophytic fungus Fusarium sp. as well as to evaluate the antimicrobial of the new metabolites. Materials and Methods: The fungus was cultured on a rice medium, and then, the cultures were extracted with ethyl acetate (EtOAc). The EtOAc extract was chromatographed utilizing different chromatographic methods to give five metabolites. The structural determination of these metabolites was carried out by the analyses of various spectroscopic data, in addition to comparison with the formerly reported data. The antifungal and antibacterial potentials were evaluated toward various microbial strains using disc diffusion assay. Results: A new aminobenzamide derivative, namely fusaribenzamide A (2), and four known metabolites: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), adenosine (3), p-hydroxyacetophenone (4), and tyrosol (5) were isolated. Fusaribenzamide A (2) possessed significant antifungal activity toward Candida albicans with minimum inhibitory concentration (MIC) value 11.9 μg/disc compared to nystatin (MIC 4.9 μg/disc). Conclusion: The endophytic fungus Fusarium sp. could be considered as a wealthy pool for the isolation of aminobenzamide derivatives. Fusaribenzamide A may be a candidate for the discovery of a promising antifungal agent. Abbreviations Used: CC: Column chromatography; CHCl3: Chloroform; COSY: Correlations spectroscopy; DBE: double bond equivalent; EtOAc: Ethyl acetate; DMSO: Dimethyl sulfoxide; H2SO4: Sulfuric acid; HMBC: Heteronuclear multiple bond correlation experiment; HRMS: High-resolution mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single quantum correlation; IR: Infrared; IZD: Inhibition zone diameter; KBr: Potassium bromide; LTQ: Linear trap quadrupole; MeOH; Methanol; MIC: Minimum inhibitory concentration; NMR: Nuclear magnetic resonance; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.
ETHNOPHARMACOLOGICAL RELEVANCE Cucurbitacins are highly oxygenated tetracyclic triterpenoids, tha... more ETHNOPHARMACOLOGICAL RELEVANCE Cucurbitacins are highly oxygenated tetracyclic triterpenoids, that represent the major metabolites reported from C. colocynthis (L.) Schrad.. Cucurbitacin E glucoside (CuE) is a tetracyclic triterpene glycoside separated from Cucurbitaceae plants. CuE has potent anti-inflammatory, immunomodulatory, and anti-tumor properties. AIM OF THE STUDY The current study aimed at examining the hepatoprotective effect of CuE against concanavalin A (Con A)-produced hepatitis. MATERIALS AND METHODS Mice were intravenously administered Con A (15 mg/kg) to induce AIH. CuE was orally administered at two different doses for five days preceding Con A injection. RESULTS The results revealed that CuE pretreatment markedly attenuated the serum indices of hepatotoxicity and the severity of hepatic lesions. CuE depressed Con A-provoked increment in CD4+ T-cells in hepatic tissue. The antioxidant activity of CuE was evident through its ability to decrease markers of Con A-induced oxidative stress (malondialdehyde, 4-hydroxyenonanal, and protein carbonyl) and intensified the antioxidants in the hepatic tissue (SOD, GSH, and TAC). CuE increased mRNA expression of SIRT1 and Nrf2 as well as its binding capacity. Subsequently, CuE augmented mRNA expression of Nrf2 targeted genes as NQO1, GCL, and HO-1 and recovered its normal level. CuE inhibited the activation of NF-κB/downstream pro-inflammatory mediators signaling. Furthermore, CuE attenuated the mRNA expression of NLRP3 and its associated genes. CONCLUSION Collectively, these results demonstrated the remarkable hepatoprotective potential of CuE towards Con A-induced AIH which was mediated via suppression of oxidative stress, enhancing SIRT1/Nrf2/HO-1, and prohibition of the NF-κB/NLRP3 signaling. CuE could be a candidate for hepatitis patients.
Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antio... more Ellagic acid (EA) is a polyphenolic compound, naturally occurring in various fruits. It has antioxidant, anticancer and antimutagenic properties. Its low aqueous solubility and permeability in GIT, permanent binding to DNA and proteins of cells and first pass metabolism are considered as the reasons for its low oral bioavailability and consequently its low therapeutic potential. Cyclodextrin-based nanosponges (NS) have been utilized to improve the solubilization efficiency of Ellagic acid and to control its release. The scope of the work was to prepare EA nanosponges (EA-NS) using cyclodextrin (β-CD) and cross-linked by dimethyl carbonate (DMC). It was found that the particle size of the prepared EA-NS was 423.2 nm with low polydispersity index (0.409) and high zeta potential (-34 mV) which manifests the construction of a stabilized colloidal nanoformulation. Moreover, high solubilization efficiency of the loaded EA-NS (49.79μg/ml) compared with the free EA (9.73μg/ml) was spotted. The prepared EA-NS was characterized by XRD, FTIR, and DSC studies and it elucidated a definite interaction of EA with NS. EA-NS successively improved its solubility and provided a controlled in vitro release for 24 hours. EA-NS produced about 69.17% drug content which indicates a good drug loading of the prepared nanosponges. Dissolution of EA-NS was higher than the drug alone. Animal study displayed an improvement in the oral bioavailability of EA indicated by an increase in AUC (1345.49 ng.hr.ml-1) of the EA -NS compared with (598.94 ng.hr.ml-1) for EA.
Background: Natural products display a remarkable role not only in the synthesis, design, and dis... more Background: Natural products display a remarkable role not only in the synthesis, design, and discovery of new drugs but also as the most prominent source of innovative drugs and bioactive substances. Genus Pulicaria (Asteraceae) includes about 100 species that are widely distributed in Europe, Asia, and Africa. Objective: In this work, the chemical investigation of Pulicaria undulata aerial parts was performed. In addition, the cytotoxic activity of the isolated metabolites was estimated toward various cell lines. Materials and Methods: Plant extract was subjected to fractionation and different column chromatography to isolate the biometabolites. Their structures were verified using nuclear magnetic resonance, infrared, ultraviolet, and high-resolution mass spectrometry, as well as compared with the literature. The cytotoxic effect was evaluated in vitro toward various cell lines: HCT-116 (colorectal adenocarcinoma), MCF-7 (human breast adenocarcinoma), and A549 (lung carcinoma). Results: A new triterpene fatty acid ester, undulaterpene A (1) (3β,16β-dihydroxylup-20 (29)-ene 3-decanoate) and four known metabolites: 3-O-acetyl-pseudotaraxasterol (2), pseudotaraxasterol (3), stigmasterol (4), and tomentosin (5) were separated. Compound 1 displayed cytotoxic potential toward hormone-dependent breast carcinoma cell line (MCF7), colon carcinoma cell line (HCT116), and lung carcinoma cell line (A549) cell lines with half maximal inhibitory concentrations (IC50s) 8.2, 6.9, and 12.4 μM, respectively in comparison to doxorubicin (IC50s 0.14, 0.39, and 1.15 μM, respectively). However, 2, 3, and 4 displayed activity toward HCT-116 with IC50s 13.2, 23.1, and 16.4 μM, respectively. Conclusion: This work led to the identification of a new triterpene fatty acid ester (1) and four known metabolites (2–5) from P. undulata growing in Saudi Arabia. The new compound showed moderate cytotoxic potential against hormone-dependent breast carcinoma cell line (MCF7), colon carcinoma cell line (HCT116), and lung carcinoma cell line (A549) cancer cell lines.
Background: Endophytic fungi attracted attention as a prolific source of bioactive natural produc... more Background: Endophytic fungi attracted attention as a prolific source of bioactive natural products with a potent pharmaceutical activity and unique structure. Objective: The main goal of the study is to separate and identify the bioactive constituents from the endophytic fungus Fusarium sp. as well as to evaluate the antimicrobial of the new metabolites. Materials and Methods: The fungus was cultured on a rice medium, and then, the cultures were extracted with ethyl acetate (EtOAc). The EtOAc extract was chromatographed utilizing different chromatographic methods to give five metabolites. The structural determination of these metabolites was carried out by the analyses of various spectroscopic data, in addition to comparison with the formerly reported data. The antifungal and antibacterial potentials were evaluated toward various microbial strains using disc diffusion assay. Results: A new aminobenzamide derivative, namely fusaribenzamide A (2), and four known metabolites: (22E,24R)-stigmasta-5,7,22-trien-3-β-ol (1), adenosine (3), p-hydroxyacetophenone (4), and tyrosol (5) were isolated. Fusaribenzamide A (2) possessed significant antifungal activity toward Candida albicans with minimum inhibitory concentration (MIC) value 11.9 μg/disc compared to nystatin (MIC 4.9 μg/disc). Conclusion: The endophytic fungus Fusarium sp. could be considered as a wealthy pool for the isolation of aminobenzamide derivatives. Fusaribenzamide A may be a candidate for the discovery of a promising antifungal agent. Abbreviations Used: CC: Column chromatography; CHCl3: Chloroform; COSY: Correlations spectroscopy; DBE: double bond equivalent; EtOAc: Ethyl acetate; DMSO: Dimethyl sulfoxide; H2SO4: Sulfuric acid; HMBC: Heteronuclear multiple bond correlation experiment; HRMS: High-resolution mass spectrometry; HRESIMS: High-resolution electrospray ionization mass spectrometry; HSQC: Heteronuclear single quantum correlation; IR: Infrared; IZD: Inhibition zone diameter; KBr: Potassium bromide; LTQ: Linear trap quadrupole; MeOH; Methanol; MIC: Minimum inhibitory concentration; NMR: Nuclear magnetic resonance; RP: Reversed phase; SiO2: Silica gel; TLC: Thin-layer chromatography; UV: Ultraviolet; VLC: Vacuum liquid chromatography.
ETHNOPHARMACOLOGICAL RELEVANCE Cucurbitacins are highly oxygenated tetracyclic triterpenoids, tha... more ETHNOPHARMACOLOGICAL RELEVANCE Cucurbitacins are highly oxygenated tetracyclic triterpenoids, that represent the major metabolites reported from C. colocynthis (L.) Schrad.. Cucurbitacin E glucoside (CuE) is a tetracyclic triterpene glycoside separated from Cucurbitaceae plants. CuE has potent anti-inflammatory, immunomodulatory, and anti-tumor properties. AIM OF THE STUDY The current study aimed at examining the hepatoprotective effect of CuE against concanavalin A (Con A)-produced hepatitis. MATERIALS AND METHODS Mice were intravenously administered Con A (15 mg/kg) to induce AIH. CuE was orally administered at two different doses for five days preceding Con A injection. RESULTS The results revealed that CuE pretreatment markedly attenuated the serum indices of hepatotoxicity and the severity of hepatic lesions. CuE depressed Con A-provoked increment in CD4+ T-cells in hepatic tissue. The antioxidant activity of CuE was evident through its ability to decrease markers of Con A-induced oxidative stress (malondialdehyde, 4-hydroxyenonanal, and protein carbonyl) and intensified the antioxidants in the hepatic tissue (SOD, GSH, and TAC). CuE increased mRNA expression of SIRT1 and Nrf2 as well as its binding capacity. Subsequently, CuE augmented mRNA expression of Nrf2 targeted genes as NQO1, GCL, and HO-1 and recovered its normal level. CuE inhibited the activation of NF-κB/downstream pro-inflammatory mediators signaling. Furthermore, CuE attenuated the mRNA expression of NLRP3 and its associated genes. CONCLUSION Collectively, these results demonstrated the remarkable hepatoprotective potential of CuE towards Con A-induced AIH which was mediated via suppression of oxidative stress, enhancing SIRT1/Nrf2/HO-1, and prohibition of the NF-κB/NLRP3 signaling. CuE could be a candidate for hepatitis patients.
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