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Ephedra is one of the oldest known medicinal plants and the largest genera of the Ephedraceae family. In vivo antitumor evaluation of Ephedra foeminea revealed that ethyl acetate (EtOAc) was the most bioactive fraction. Bio-guided fractionation of EtOAc fraction afforded nine compounds isolated for the first time from the plant species. Macrocyclic spermine alkaloids (1,9), proanthocyanidins (2,4,5), quinoline alkaloids (7,8), phenolic (3), and nucleoside (6) were identified and elucidated by spectroscopic analyses including 1D and 2D NMR, ESI-MS-MS spectrometry. The tested compounds exhibited moderate anticancer activity, except for the kynurenic acid derivative (6-mKYNA) which showed significant cytotoxicity and remarkable inhibition of CA-19.9 and CA-125 tumor biomarkers. In-silico study was conducted to determine the anti-proliferative mechanism of 6-mKYNA by using the CK2 enzyme active site. Moreover, the ADME computational study suggested that 6-mKYNA is an effective candidate with a promising pharmacokinetic profile and therapeutic potential against various types of cancer.

In this study, we investigated the polyphenolic profile of Pachira macrocarpa Schltdl. & Cham. by HPLC analysis and we also isolated three compounds from the ethyl acetate leaf extract, which were identified by different spectral data as vitexin 1, luteolin 2, and ferulic acid 3. Moreover, we investigated the three isolated compounds and the plant extract for their therapeutic potential against AlCl 3 exposure-induced neurotoxicity in rats. This investigation aims to determine whether vitexin, luteolin, and ferulic acid in Pachira macrocarpa Schltdl. & Cham. extract ( P. macrocarpa ) have the ability to treat AlCl 3 -induced brain toxicity in rats. Six groups of rats were created: group 1 (normal group), group 2 treated with AlCl 3 , and groups 3, 4, 5, and 6 treated with AlCl 3 with vitexin, luteolin, ferulic acid, and P. macrocarpa extract, respectively, for 28 days. Neurotoxicity was assessed by measuring plasma IL-8 and IL-33 as well as brain superoxide dismutase (SOD), glutathione reductase (GSR), B-cell lymphoma-2 (BcL-2), B-cell lymphoma-2 associated-x (Bax), and neurogranin using the ELISA technique and c-Jun N-terminal kinase (JNK), miRNA-125b, and miRNA-132 levels using western blot and PCR. HPLC analysis identified major phenolics and flavonoids. Among the phenolics identified, chlorogenic acid was prevalent (2159.14 μg/g), and regarding flavonoids, rutin was prevalent (204.69 μg/g). A significant elevation of IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and of miRNA-125b gene expression levels was observed following AlCl 3 exposure. However, significant depletion of SOD, GSR, BcL-2, total protein, and miRNA-132 gene expression was observed in AlCl 3 -treated rats. Administration of the P. macrocarpa extract and its isolated compounds significantly increased SOD, GSR, BcL-2, total protein, and miRNA132 gene expression and decreased IL-8 and IL-33 as well as brain Bax, neurogranin, and JNK levels and brain miRNA-125b gene expression compared to AlCl 3 -treated rats. P. macrocarpa extract and its isolated compounds ameliorated AlCl 3 -induced oxidative stress and neurotoxicity in rats., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Phytochemicals have played a significant role in the discovery of many clinically anticancer medicines. Thevetia peruviana being famous as an ornamental plant, widely cultivated, and including a wide variety of secondary metabolites this motivated us to explore more about its potential medical applications. In this study, the total methanol extract of T. peruviana leaves (family Apocyanaceae) was sequentially fractionated into hexane, methylene chloride, ethyl acetate, and butanol fractions. The total phenolic content of the methanol extract of T. peruviana was determined spectrophotometrically and found to be 72.37 mg g -1 , while the total flavonoid content was found to be 12.47 mg g -1 . Fourteen polyphenolic compounds were detected by the HPLC analysis of the methanol extract, in addition to five phenolic compounds, which were isolated and identified for the first time from the EtOAc extract. They were identified as gallic acid (C1), chlorogenic acid (C2), p -coumaric acid (C3), quercetin (C4), and rutin (C5). The structures were elucidated by NMR and EI/MS spectroscopic techniques. The cytotoxic activity of the methanol extract was evaluated in vitro by cell viability assay. The cytotoxicity results showed significant anticancer activity against human colon carcinoma HCT-116 with IC 50 39.3 μg mL -1 and lesser activity against human lung carcinoma A-549 and human breast carcinoma MCF-7 cell lines with IC 50 93.4 and 110.3 μg mL -1 , respectively., Competing Interests: The authors declare there is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Saussurea costus is a plant traditionally used for the treatment of several ailments. Our study accomplished the UPLC/T-TOF-MS/MS analysis of a methanol extract of Saussurea costus roots (MESC), in addition to lipoidal matter determination and assessment of its in vivo hepatoprotective activity. In this study, we were able to identify the major metabolites in MESC rather than the previously known isolated compounds, improving our knowledge of its chemical constituents. The flavones apigenin, acacetin, baicalein, luteolin, and diosmetin, and the flavonol aglycones quercetin, kaempferol, isorhamnetin, gossypetin, and myricetin and/or their glycosides and glucuronic derivatives were the major identified compounds. The hepatoprotective activity of MESC was evaluated by measuring catalase activity using UV spectrophotometry, inflammatory cytokines and apoptotic markers using ELISA techniques, and genetic markers using PCR. Paracetamol toxicity caused a significant increase in plasma caspase 2, cytokeratin 18 (CK18), liver tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), miRNA-34a, and miRNA-223, as well as a significant decrease in liver catalase (CAT) activity and in the levels of liver nuclear factor 1α (HNF-1α), sirtuin-1, and C/ebpα. Oral pretreatment with MESC (200 mg/kg) showed a significant decrease in caspase 2, CK18, TNF-α, IL-6 and a significant increase in liver CAT activity. MESC decreased the levels of liver miRNA-34a and miRNA-223 and induced HNF-1α, sirtuin-1, and C/ebpα gene expression. The histological examination showed a significant normalization in rats pretreated with MESC. Our findings showed that Saussurea costus may exert a potent hepatoprotective activity through the modulation of the expression of cellular cytokines, miRNA-34a, and miRNA-223.

Reusing food waste is becoming popular in pharmaceutical industries. Watermelon ( Citrullus lanatus ) rind is commonly discarded as a major solid waste. Here, the in vitro cytotoxic potential of watermelon rind extracts was screened against a panel of human cancer cell lines. Cell cycle analysis was used to determine the induction of cell death, whereas annexin V-FITC binding, caspase-3, BAX, and BCL-2 mRNA expression levels were used to determine the degree of apoptosis. VEGF-promoting angiogenesis and cell migration were also evaluated. Moreover, the identification of phytoconstituents in the rind extract was achieved using UPLC/T-TOF-MS/MS, and a total of 45 bioactive compounds were detected, including phenolic acids, flavonoids aglycones, and their glycoside derivatives. The tested watermelon rind extracts suppressed cell proliferation in seven cancer cell lines in a concentration-dependent manner. The cytotoxicity of the rind aqueous extract (RAE) was higher compared with that of the other extracts. In addition to a substantial inhibitory effect on cell migration, the RAE triggered apoptosis in HCT116 and Hep2 cells by driving the accumulation of cells in the S phase and elevating the activity of caspase-3 and the BAX/BCL-2 ratio. Thus, a complete phytochemical and cytotoxic investigation of the Citrullus lanatus rind extract may identify its potential potency as an anticancer agent.

In response to the urgent need to control Coronavirus disease 19 (COVID-19), this study aims to explore potential anti-SARS-CoV-2 agents from natural sources. Moreover, cytokine immunological responses to the viral infection could lead to acute respiratory distress which is considered a critical and life-threatening complication associated with the infection. Therefore, the anti-viral and anti-inflammatory agents can be key to the management of patients with COVID-19. Four bioactive compounds, namely ferulic acid 1 , rutin 2 , gallic acid 3 , and chlorogenic acid 4 were isolated from the leaves of Pimenta dioica (L.) Merr (ethyl acetate extract) and identified using spectroscopic evidence. Furthermore, molecular docking and dynamics simulations were performed for the isolated and identified compounds ( 1 - 4 ) against SARS-CoV-2 main protease (Mpro) as a proposed mechanism of action. Furthermore, all compounds were tested for their half-maximal cytotoxicity (CC 50 ) and SARS-CoV-2 inhibitory concentrations (IC 50 ). Additionally, lung toxicity was induced in rats by mercuric chloride and the effects of treatment with P. dioca aqueous extract, ferulic acid 1 , rutin 2 , gallic acid 3 , and chlorogenic acid 4 were recorded through measuring TNF-α, IL-1β, IL-2, IL-10, G-CSF, and genetic expression of miRNA 21-3P and miRNA-155 levels to assess their anti-inflammatory effects essential for COVID-19 patients. Interestingly, rutin 2 , gallic acid 3 , and chlorogenic acid 4 showed remarkable anti-SARS-CoV-2 activities with IC 50 values of 31 µg/mL, 108 μg/mL, and 360 µg/mL, respectively. Moreover, the anti-inflammatory effects were found to be better in ferulic acid 1 and rutin 2 treatments. Our results could be promising for more advanced preclinical and clinical studies especially on rutin 2 either alone or in combination with other isolates for COVID-19 management.

Parkia roxburghii belongs to the family Mimosaceae; it has been used since ancient times as a cure for different health complications; such as inflammatory and gynecological diseases and hemiplegia. In this investigation, a reversed-phase-high-performance liquid chromatography (RP-HPLC) profile was carried out for P. roxburghii; also, the isolated bioactive compounds including quercetin, catechin, and biochaninA were individually and/or in combination investigated for their inhibitory effects on scopolamine-induced memory impairments in mice, implying that they have the ability to reduce the neurodegenerative effects of scopolamine and thus could be employed as a more effective therapeutic agent in the treatment of Alzheimer's disease (AD) in humans. The possible interactions of Parkia flavonoids with acetylcholinesterase (AChE), γ-aminobutyric acid A receptor, alpha5 (GABA A α5), glycogen synthase kinase-3 (GSK-3), p38 mitogen-activated protein kinase (p38MAP-kinase), signal-regulated kinase (ERK), and protein-serine/threonine kinase (Akt) were then determined using molecular docking., Competing Interests: The authors declare no competing financial interest., (© 2021 The Authors. Published by American Chemical Society.)

Mentha species are medicinally used worldwide and remain attractive for research due to the diversity of their phytoconstituents and large therapeutic indices for various ailments. This study used the metabolomics examination of five Mentha species ( M. suaveolens , M. sylvestris , M. piperita , M. longifolia , and M. viridis ) to justify their cytotoxicity and their anti- Helicobacter effects. The activities of species were correlated with their phytochemical profiles by orthogonal partial least square discriminant analysis (OPLS-DA). Tentatively characterized phytoconstituents using liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS) included 49 compounds: 14 flavonoids, 10 caffeic acid esters, 7 phenolic acids, and other constituents. M. piperita showed the highest cytotoxicity to HepG2 (human hepatoma), MCF-7 (human breast adenocarcinoma), and CACO2 (human colon adenocarcinoma) cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. OPLS-DA and dereplication studies predicted that the cytotoxic activity was related to benzyl glucopyranoside-sulfate, a lignin glycoside. Furthermore, M. viridis was effective in suppressing the growth of Helicobacter pylori at a concentration of 50 mg mL -1 . OPLS-DA predicted that this activity was related to a dihydroxytrimethoxyflavone. M. viridis extract was formulated with Pluronic® F127 to develop polymeric micelles as a nanocarrier that enhanced the anti- Helicobacter activity of the extract and provided minimum inhibitory concentrations and minimum bactericidal concentrations of 6.5 and 50 mg mL -1 , respectively. This activity was also correlated to tentatively identified constituents, including rosmarinic acid, catechins, carvone, and piperitone oxide., Competing Interests: The authors declare there is no conflict of interest., (This journal is © The Royal Society of Chemistry.)

Background: Citrullus colocynthis (L.) Schrad is an important medicinal plant belonging to the family Cucurbitaceae. Cucurbitacin E glucoside (1) was isolated from Citrullus colocynthis fruits. A novel mono-ester of cucurbitacin-E and cinnamyl and caffeoyl-β-D-glucoside (2 and 3) was synthesized by reaction of cucurbitacin E glucoside with cinnamic and/or caffeic acid in the presence of CHCl2 and K2CO3 with constant stirring with an ice-cooling state for 24h. Mass analyses of the isolated and purified compounds were determined., Methods: The elemental analysis (C, H, N) suggesting the molecular formulae of the compounds (1-3) to be C38H54O13, C47H60O14, and C47H60O16; respectively. I.R., 1H-NMR, and 13C-NMR analyses were recorded. The median lethal doses (LD50s) of compounds (1-3) in rats were 1262.5, 2500 and 2350 mg/kg b.w., respectively. The anti-inflammatory, total antioxidant, reducing power, anti-reactive oxygen species (ROS) and anti-reactive nitrogen species (RNS) were more pronounced in compound 3 compared to compounds (1-2). This study provides the scientific basis for the anti-inflammatory effects of the isolated cucurbitacin E glucoside (1) and its derivatives (2 and 3) in a t-BHP (tert-butyl hydrogen peroxide)-induced liver damage model., Results: Injection of rats with t-BHP (1.8 mmol/kg) showed a significant increase in plasma alanine transaminases (ALT), aspartate transaminases (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and malondialdehyde (MDA) as well as hepatic tumor Necrosis Factor-α (TNF-α), interleukin- 6 (IL-6) and interleukin-23 (IL-23) when compared with control group. Also, injection of rats with t-BHP showed a significant increase in a liver level of reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) as compared with control group. Oral administration of cucurbitacin E glucoside (1) and its derivatives (2 and 3) at a concentration of 25 and 50 mg/kg b.wt daily for 5 days showed a significant protection against-induced alteration in liver GSH, SOD, CAT and GST as well as plasma ALT, AST, ALP, LDH and MDA levels. Furthermore, Cucurbitacin E glucoside (1) and its derivatives (2 and 3) inhibited the elevation of proinflammatory cytokines (TNF-α, IL-6, and IL-23) in the livers of t-BHP-treated rat models., Conclusion: These results suggested that mechanistic-based evidence substantiating the traditional claims of cucurbitacin E glucoside (1) and its derivatives (2 and 3) to be applied for the treatment of inflammation-related disorders, such as oxidative liver damage and inflammation diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)