Comparative Assessment of the Antioxidant and Anticancer Activities of Plicosepalus acacia and Plicosepalus curviflorus: Metabolomic Profiling and In Silico Studies

This study presents a comparison between two mistletoe plants—P. acacia and P. curviflorus—regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC50 = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe+2/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC50 = 25.83 μg/mL) than P. acacia (IC50 = 34.12 μg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics—chiefly flavonoid derivatives, beside some triterpenes and sterols—in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer

Anti-Blastocystis Activity In Vitro of Egyptian Herbal Extracts (Family: Asteraceae) with Emphasis on Artemisia judaica

Achillea fragrantissima (Forssk.) Sch. Bip. (known as Qaysoom), Echinops spinosus L. (known as Shoak Elgamal) and Artemisia judaica L. (known Shih Baladi) are members of the Asteraceae family known for their traditional medical use in Egypt. The ethanol extracts of these plants were evaluated for their efficacy against a protozoan parasite (Blastocystis). Two different molecular subtypes of Blastocystis were used (ST1 and ST3). Significant growth inhibition of Blastocystis was observed when exposed to both A. judaica (99.3%) and A. fragrantissima (95.6%) with minimal inhibitory concentration (MIC90) at 2000 mu g/mL. Under the effect of the extracts, changes in Blastocystis morphology were noted, with the complete destruction of Blastocystis forms after 72 h with the dose of 4000 mu g/mL. Different subtypes displayed different responses to the herbal extracts tested. ST1 exhibited significantly different responses to the herbal extracts compared to ST3. A. judaica was selected as the herb of choice considering all of its variables and because of its effective action against Blastocystis. It was then exposed to further fractionation and observation of its effect on ST1 and ST3. Solvent portioned fractions (dichloromethane (DCM), ethyl acetate (EtOAc) and n-hexane) in A. judaica were found to be the potent active fractions against both of the Blastocystis subtypes used

New antibacterial xanthone from the marine sponge-derived Micrococcus sp. EG45

Microluside A [4 (19-para-hydroxy benzoyloxy-O-β-d-cellobiosyl), 5 (30-para-hydroxy benzoyloxy-O-β-d-glucopyranosyl) xanthone (1)] is a unique O-glycosylated disubstituted xanthone isolated from the broth culture of Micrococcus sp. EG45 cultivated from the Red Sea sponge Spheciospongia vagabunda. The structure of microluside A was determined by 1D- and 2D-NMR techniques as well as high resolution tandem mass spectrometry. The antimicrobial activity evaluation showed that 1 exhibited antibacterial potential against Enterococcus faecalis JH212 and Staphylococcus aureus NCTC 8325 with MIC values of 10 and 13 μM, respectively

Chemical Profiling, Antioxidant, Cytotoxic Activities and Molecular Docking Simulation of Carrichtera annua DC. (Cruciferae)

Our investigation intended to analyze the chemical composition and the antioxidant activity of Carrichtera annua and to evaluate the antiproliferative effect of C. annua crude and phenolics extracts by MTT assay on a panel of cancerous and non-cancerous breast and liver cell lines. The total flavonoid and phenolic contents of C. annua were 47.3 ± 17.9 mg RE/g and 83.8 ± 5.3 mg respectively. C. annua extract exhibited remarkable antioxidant capacity (50.92 ± 5.64 mg GAE/g) in comparison with BHT (74.86 ± 3.92 mg GAE/g). Moreover, the extract exhibited promising reduction ability (1.17 mMol Fe+2/g) in comparison to the positive control (ascorbic acid with 2.75 ± 0.91) and it displayed some definite radical scavenging effect on DPPH (IC50 values of 211.9 ± 3.7 µg/mL). Chemical profiling of C. annua extract was achieved by LC-ESI-TOF-MS/MS analysis. Forty-nine hits mainly polyphenols were detected. Flavonoid fraction of C. annua was more active than the crude extract. It demonstrated selective cytotoxicity against the MCF-7 and HepG2 cells (IC50 = 13.04 and 19.3 µg/mL respectively), induced cell cycle arrest at pre-G1 and G2/M-phases and displayed apoptotic effect. Molecular docking studies supported our findings and revealed that kaempferol-3,7-O-bis-α-L-rhamnoside and kaempferol-3-rutinoside were the most active inhibitors of Bcl-2. Therefore, C. annua herb seems to be a promising candidate to further advance anticancer research. In extrapolation, the intake of C. annua phenolics might be adventitious for alleviating breast and liver malignancies and tumoral proliferation in humans

In Vitro and In Vivo Studies of Anti-Lung Cancer Activity of Artemesia judaica L. Crude Extract Combined with LC-MS/MS Metabolic Profiling, Docking Simulation and HPLC-DAD Quantification

Artemisia judaica L. (Family: Asteraceae) exhibited antioxidant, anti-inflammatory, and antiapoptotic effects. The in vitro cytotoxic activity of A. judaica ethanolic extract was screened against a panel of cancer cell lines. The results revealed its cytotoxic activity against a lung cancer (A549) cell line with a promising IC50 of 14.2 μg/mL compared to doxorubicin as a standard. This was confirmed through the downregulation of antiapoptotic genes, the upregulation of proapoptotic genes, and the cell cycle arrest at the G2/M phase. Further in vivo study showed that a solid tumor mass was significantly reduced, with a tumor inhibition ratio of 54% relative to doxorubicin therapy in a Xenograft model. From a chemical point of view, various classes of natural products have been identified by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS). The docking study of the detected metabolites approved their cytotoxic activity through their virtual binding affinity towards the cyclin-dependent kinase 2 (CDK-2) and epidermal growth factor receptor (EGFR) active sites. Finally, A. judaica is a fruitful source of polyphenols that are well-known for their antioxidant and cytotoxic activities. As such, the previously reported polyphenols with anti-lung cancer activity were quantified by high-performance liquid chromatography coupled with a diode array detector (HPLC-DAD). Rutin, quercetin, kaempferol, and apigenin were detected at concentrations of 6 mg/gm, 0.4 mg/gm, 0.36 mg/gm, and 3.9 mg/gm of plant dry extract, respectively. It is worth noting that kaempferol and rutin are reported for the first time. Herein, A. judaica L. may serve as an adjuvant therapy or a promising source of leading structures in drug discovery for lung cancer treatment

The Antioxidant <i>Carrichtera annua</i> DC. Ethanolic Extract Counteracts Cisplatin Triggered Hepatic and Renal Toxicities

Cisplatin is a powerful anti-neoplastic drug that displays multi-organ toxicity, especially to the liver and kidneys. Consumption of phytomedicines is a promising strategy to overcome the side effects of chemotherapy. Carrichtera annua extract proved to possess potent antioxidant activity. Its protective potential against cisplatin-induced hepato–nephrotoxicity was scrutinized. Moreover, a phytochemical study was conducted on C. annua ethyl acetate fraction which led to the isolation of five known phenolic compounds. Structure determination was achieved utilizing 1H- and 13C-NMR spectral analyses. The isolated phytochemicals were trans-ferulic acid (1), kaempferol (2), p-coumaric acid (3), luteolin (4) and quercetin (5). Regarding our biological study, C. annua has improved liver and kidney deteriorated functions caused by cisplatin administration and attenuated the histopathological injury in their tissues. Serum levels of ALT, AST, blood urea nitrogen and creatinine were significantly decreased. C. annua has modulated the oxidative stress mediated by cisplatin as it lowered MDA levels while enhanced reduced-GSH concentrations. More importantly, the plant has alleviated cisplatin triggered inflammation, apoptosis via reduction of INFγ, IL-1β and caspase-3 production. Moreover, mitochondrial injury has been ameliorated as remarkable increase of mtDNA was noted. Furthermore, the MTT assay proved the combination of cisplatin—C. annua extract led to growth inhibition of MCF-7 cells in a notable additive way. Additionally, we have investigated the binding affinity of C. annua constituents with caspase-3 and IFN-γ proteins using molecular simulation. All the isolated compounds exhibited good binding affinities toward the target proteins where quercetin possessed the most auspicious caspase-3 and IFN-γ inhibition activities. Our results put forward that C. annua is a promising candidate to counteract chemotherapy side effects and the observed activity could be attributed to the synergism between its phytochemicals

Comparative Assessment of the Antioxidant and Anticancer Activities of <i>Plicosepalus acacia</i> and <i>Plicosepalus curviflorus</i>: Metabolomic Profiling and In Silico Studies

This study presents a comparison between two mistletoe plants—P. acacia and P. curviflorus—regarding their total phenolic contents and antioxidant and anticancer activities. P. curviflorus exhibited a higher total phenolics content (340.62 ± 19.46 mg GAE/g extract), and demonstrated higher DPPH free radical scavenging activity (IC50 = 48.28 ± 3.41µg/mL), stronger reducing power (1.43 ± 0.54 mMol Fe+2/g) for ferric ions, and a greater total antioxidant capacity (41.89 ± 3.15 mg GAE/g) compared to P. acacia. The cytotoxic effects of P. acacia and P. curviflorus methanol extracts were examined on lung (A549), prostate (PC-3), ovarian (A2780) and breast (MDA-MB-231) cancer cells. The highest anticancer potential for the two extracts was observed on PC-3 prostate cancer cells, where P. curviflorus exhibited more pronounced antiproliferative activity (IC50 = 25.83 μg/mL) than P. acacia (IC50 = 34.12 μg/mL). In addition, both of the tested extracts arrested the cell cycle at the Pre-G1 and G1 phases, and induced apoptosis. However, P. curviflorus extract possessed the highest apoptotic effect, mediated by the upregulation of p53, Bax, and caspase-3, 8 and 9, and the downregulation of Bcl-2 expression. In the pursuit to link the chemical diversity of P. curviflorus with the exhibited bioactivities, its metabolomic profiling was achieved by the LC-ESI-TOF-MS/MS technique. This permitted the tentative identification of several phenolics—chiefly flavonoid derivatives, beside some triterpenes and sterols—in the P. curviflorus extract. Furthermore, all of the metabolites in P. curviflorus and P. acacia were inspected for their binding modes towards both CDK-2 and EGFR proteins using molecular docking studies in an attempt to understand the superiority of P. curviflorus over P. acacia regarding their antiproliferative effect on PC-3 cancer cells. Docking studies supported our experimental results; with all of this taken together, P. curviflorus could be regarded as a potential prospect for the development of chemotherapeutics for prostate cancer

Chemical Composition of the Red Sea Green Algae <i>Ulva lactuca</i>: Isolation and In Silico Studies of New Anti-COVID-19 Ceramides

Coronavirus disease 2019 (COVID-19) is the disease caused by the virus SARS-CoV-2 responsible for the ongoing pandemic which has claimed the lives of millions of people. This has prompted the scientific research community to act to find treatments against the SARS-CoV-2 virus that include safe antiviral medicinal compounds. The edible green algae U. lactuca. is known to exhibit diverse biological activities such as anti-influenza virus, anti-Japanese encephalitis virus, immunomodulatory, anticoagulant, antioxidant and antibacterial activities. Herein, four new ceramides in addition to two known ones were isolated from Ulva lactuca. The isolated ceramides, including Cer-1, Cer-2, Cer-3, Cer-4, Cer-5 and Cer-6 showed promising antiviral activity against SARS-CoV-2 when investigated using in silico approaches by preventing its attachment to human cells and/or inhibiting its viral replication. Cer-4 and Cer-5 were the most effective in inhibiting the human angiotensin converting enzyme (hACE)–spike protein complex which is essential for the virus to enter the human host. In addition to this, Cer-4 also showed an inhibition of the SARS-CoV-2 protease (Mpro) that is responsible for its viral replication and transcription. In this study, we also used liquid chromatography coupled to electrospray ionization high-resolution mass spectroscopy (LC-ESI-HRMS) to identify several metabolites of U. lactuca, including metabolites such as fatty acids, their glyceride derivatives, terpenoids, sterols and oxysterols from the organic extract. Some of these metabolites also possessed promising antiviral activity, as previously reported

Comparative Cytotoxic Evaluation of Zygophyllum album Root and Aerial Parts of Different Extracts and Their Biosynthesized Silver Nanoparticles on Lung A549 and Prostate PC-3 Cancer Cell Lines

The current work demonstrates a comparative study between aerial and root parts of Zygophyllum album L. The total phenolic (TPC) and flavonoid content (TFC), in addition to the antioxidant activity, of the crude extracts were investigated, where the aerial parts revealed a higher value overall. By means of UV&ndash;VIS and HPLC, rutin and caffeic acid were detected and then quantified as 5.91 and 0.97 mg/g of the plant extract, respectively. Moreover, the biosynthesis of AgNPs utilizing the crude extract of the arial parts and root of Z. album L. and the phenolic extracts was achieved in an attempt to enhance the cytotoxicity of the different plant extracts. The prepared AgNPs formulations were characterized by TEM and zeta potential measurements, which revealed that all of the formulated AgNPs were of a small particle diameter and were highly stable. The mean hydrodynamic particle size ranged from 67.11 to 80.04 nm, while the zeta potential ranged from 29.1 to 38.6 mV. Upon biosynthesis of the AgNPs using the extracts, the cytotoxicity of the tested samples was improved, so the polyphenolics AgNPs of the aerial parts exhibited a potent cytotoxicity against lung A549 and prostate PC-3 cancer cells with IC50 values of 6.1 and 4.36 &micro;g/mL, respectively, compared with Doxorubicin (IC50 values of 6.19 and 5.13 &micro;g/mL, respectively). Regarding the apoptotic activity, polyphenolics AgNPs of the aerial parts induced apoptotic cell death by 4.2-fold in PC-3 and 4.7-fold in A549 cells compared with the untreated control. The mechanism of apoptosis in both cancerous cells appeared to be via the upregulation proapoptotic genes; p53, Bax, caspase 3, 8, and 9, and the downregulation of antiapoptotic gene, Bcl-2. Hence, this formula may serve as a good source for anticancer agents against PC-3 and A549 cells