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 (CC₅₀) and SARS-CoV-2 inhibitory concentrations (IC₅₀). 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 IC₅₀ 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.

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.

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.

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 IC₅₀ 39.3 μg mL⁻¹ and lesser activity against human lung carcinoma A-549 and human breast carcinoma MCF-7 cell lines with IC₅₀ 93.4 and 110.3 μg mL⁻¹, respectively.

HPLC profile, antimicrobial, cytotoxic, and anti-inflammatory activities of carob (Ceratonia siliqua L.) pulp and seeds extracts were investigated. Gallic acid was the main identified phenolic. Ellagic acid, rutin, quercetin, and kaempferol were also tentatively identified. Carob seeds extract exhibited antimicrobial activity against Pseudomonas aeruginosa (6.25 and 25 mg mL-1 for minimum inhibitory concentration and minimum bactericidal concentration: respectively). Carob extracts showed a weak dose-response inhibition of the lipopolysaccharide induced nitric oxide release in RAW macrophages. Carob extracts even in the high dose did not inhibit the cell growth either against MCF-7 or HT-29 cell lines. Carob pods could be used as a functional food or food additive based on these findings.

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 AlCl₃ 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 AlCl₃-induced brain toxicity in rats. Six groups of rats were created: group 1 (normal group), group 2 treated with AlCl₃, and groups 3, 4, 5, and 6 treated with AlCl₃ 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 AlCl₃ exposure. However, significant depletion of SOD, GSR, BcL-2, total protein, and miRNA-132 gene expression was observed in AlCl₃-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 AlCl₃-treated rats. P. macrocarpa extract and its isolated compounds ameliorated AlCl₃-induced oxidative stress and neurotoxicity in rats.