Comparative study of the chemical composition and anti-proliferative activities of the aerial parts and roots of Apium graveolens L. (celery) and their biogenic nanoparticles

Apiaceae plants are multipurpose folk remedies and bioactive foods that show a remarkable ability to biosynthesize a large number of secondary metabolites with antitumor and chemopreventive potential. Among the various members of the Apiaceae, celery (Apium graveolens L.) has long been used as a popular edible and medicinal plant owing to its plentiful health benefits and nutraceutical properties; however, the anticancer potential of this important species has been seldom studied, mostly focusing on its seeds. Therefore, this work was designed to delve into the chemical composition and anti-proliferative potential of the total ethanolic extracts of the aerial parts (TEEAGA) and roots (TEEAGR) of A. graveolens var. dulce (Mill.) Pers. as well as their green synthesized silver nanoparticles (AgNPs). In general, both TEEAGA and TEEAGR exhibited moderate to potent inhibitory activities against human liver (HepG-2), colon (Caco-2), and breast (MCF-7) cancer cell lines, with interesting IC50 profiles [(41.37 ± 0.12, 27.65 ± 0.27, and 9.48 ± 0.04 μg/mL) and (11.58 ± 0.02, 7.13 ± 0.03, and 6.58 ± 0.02 μg/mL), respectively] as compared with doxorubicin, while more pronounced anti-proliferative effects were observed for their biogenic AgNPs, which showed IC50 values ranging between 25.41 ± 0.16 and 1.37 ± 0.03 μg/mL. Moreover, HPLC‒HESI‒HRMS-based metabolomics analysis of both extracts showed the presence of a varied group of secondary metabolites, including flavonoids, phenylpropanoids, phthalides, coumarins, and sesquiterpenes that further displayed moderate to promising binding affinities to the active site of cyclin G-associated kinase (GAK), particularly graveobioside A, graveobioside B, and celeroside C, suggesting their possible contribution as GAK modulators to the anti-proliferative potential of celery. These findings can help broaden future research on the utilization of different parts of celery and their NPs as functional foods and medicines in cancer chemoprevention and therapy

Mitochondrial Targeting in an Anti-Austerity Approach Involving Bioactive Metabolites Isolated from the Marine-Derived Fungus Aspergillus sp.

The tumor microenvironment is a nutrient-deficient region that alters the cancer cell phenotype to aggravate cancer pathology. The ability of cancer cells to tolerate nutrient starvation is referred to as austerity. Compounds that preferentially target cancer cells growing under nutrient-deficient conditions are being employed in anti-austerity approaches in anticancer drug discovery. Therefore, in this study, we investigated physcion (1) and 2-(2′,3-epoxy-1′,3′,5′-heptatrienyl)-6-hydroxy-5-(3-methyl-2-butenyl) benzaldehyde (2) obtained from a culture extract of the marine-derived fungus Aspergillus species (sp.), which were isolated from an unidentified marine sponge, as anti-austerity agents. The chemical structures of 1 and 2 were determined via spectroscopic analysis and comparison with authentic spectral data. Compounds 1 and 2 exhibited selective cytotoxicity against human pancreatic carcinoma PANC-1 cells cultured under glucose-deficient conditions, with IC50 values of 6.0 and 1.7 µM, respectively. Compound 2 showed higher selective growth-inhibitory activity (505-fold higher) under glucose-deficient conditions than under general culture conditions. Further analysis of the mechanism underlying the anti-austerity activity of compounds 1 and 2 against glucose-starved PANC-1 cells suggested that they inhibited the mitochondrial electron transport chain

Hepatoprotective potential of Malvaviscus arboreus against carbon tetrachloride-induced liver injury in rats

Malvaviscus arboreus Cav. is a medicinal plant belonging to family Malvaceae with both ethnomedical and culinary value; however, its phytochemical and biological profiles have been scarcely studied. Accordingly, this work was designed to explore the chemical composition and the hepatoprotective potential of M. arboreus against carbon tetrachloride (CCl$_4$)-induced hepatotoxicity. The total extract of the aerial parts and its derived fractions (petroleum ether, dichloromethane, ethyl acetate, and aqueous) were orally administered to rats for six consecutive days, followed by injection of CCl$_4$ (1:1 v/v, in olive oil, 1.5 ml/kg, i.p.) on the next day. Results showed that the ethyl acetate and dichloromethane fractions significantly alleviated liver injury in rats as indicated by the reduced levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB), and malondialdehyde (MDA), along with enhancement of the total antioxidant capacities of their livers, with the maximum effects were recorded by the ethyl acetate fraction. Moreover, the protective actions of both fractions were comparable to those of silymarin (100 mg/kg), and have been also substantiated by histopathological evaluations. On the other hand, liquid chromatography-high resolution electrospray ionization mass spectrometry (LC‒HR‒ESI‒MS) metabolomic profiling of the crude extract of M. arboreus aerial parts showed the presence of a variety of phytochemicals, mostly phenolics, whereas the detailed chemical analysis of the most active fraction (i.e. ethyl acetate) resulted in the isolation and identification of six compounds for the first time in the genus, comprising four phenolic acids; β-resorcylic, caffeic, protocatechuic, and 4-hydroxyphenylacetic acids, in addition to two flavonoids; trifolin and astragalin. Such phenolic principles, together with their probable synergistic antioxidant and liver-protecting properties, seem to contribute to the observed hepatoprotective potential of M. arboreus

Exploring the volatile metabolites of three Chorisia species: Comparative headspace GC–MS, multivariate chemometrics, chemotaxonomic significance, and anti-SARS-CoV-2 potential

Chorisia (syn. Ceiba) species are important ornamental, economic, and medicinal plants that are endowed with a diversity of secondary metabolites; however, their volatile organic compounds (VOCs) have been scarcely studied. Therefore, this work explores and compares the headspace floral volatiles of three common Chorisia species, namely Chorisia chodatii Hassl., Chorisia speciosa A. St.-Hil, and Chorisia insignis H.B.K. for the first time. A total of 112 VOCs of varied biosynthetic origins were identified at different qualitative and quantitative ratios, encompassing isoprenoids, fatty acid derivatives, phenylpropanoids, and others. Flowers of the investigated species showed perceptibly differentiated volatile profiles, with those emitted by C. insignis being dominated by non-oxygenated compounds (56.69 %), whereas oxygenated derivatives prevailed among the volatiles of C. chodatii (66.04 %) and C. speciosa (71.53 %). The variable importance in the projection (VIP) in the partial least-squares–discriminant (PLS-DA) analysis described 25 key compounds among the studied species, of which linalool was verified as the most important aroma compound based on VIP values and significance analysis, and it could represent the most typical VOC among these Chorisia species. Furthermore, molecular docking and dynamics analyses of both the major and the key VOCs displayed their moderate to promising binding interactions with four main proteins of SARS-CoV-2, including Mpro, PLpro, RdRp, and spike S1 subunit RBD. The current results collectively cast new light on the chemical diversity of the VOCs of Chorisia plants as well as their chemotaxonomic and biological relevance

Thalassosterol, a New Cytotoxic Aromatase Inhibitor Ergosterol Derivative from the Red Sea Seagrass Thalassodendron ciliatum

Thalassodendron ciliatum (Forssk.) Den Hartog is a seagrass belonging to the plant family Cymodoceaceae with ubiquitous phytoconstituents and important pharmacological potential, including antioxidant, antiviral, and cytotoxic activities. In this work, a new ergosterol derivative named thalassosterol (1) was isolated from the methanolic extract of T. ciliatum growing in the Red Sea, along with two known first-reported sterols, namely ergosterol (2) and stigmasterol (3), using different chromatographic techniques. The structure of the new compound was established based on 1D and 2D NMR spectroscopy and high-resolution mass spectrometry (HR-MS) and by comparison with the literature data. The new ergosterol derivative showed significant in vitro antiproliferative potential against the human cervical cancer cell line (HeLa) and human breast cancer (MCF-7) cell lines, with IC$_{50}$ values of 8.12 and 14.24 µM, respectively. In addition, docking studies on the new sterol 1 explained the possible binding interactions with an aromatase enzyme; this inhibition is beneficial in both cervical and breast cancer therapy. A metabolic analysis of the crude extract of T. ciliatum using liquid chromatography combined with high-resolution electrospray ionization mass spectrometry (LC-ESI-HR-MS) revealed the presence of an array of phenolic compounds, sterols and ceramides, as well as di- and triglycerides

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially