An emerging stress of pesticides in plant and soil is closely watched as it affects crop antioxidant systems, nutritional quality, and flavor. Although selenium (Se) can enhance the resistance of plants, the protective mechanism of nanoselenium is still not known under the long-term pesticide stress in tea trees. In this study, we investigated the potential effects of foliar application of nanoselenium for a two-year field experiment on tea plants under pesticide-induced oxidative stress. Compared to control, nano-Se (10 mg/L) markedly enhanced the protein, soluble sugar, carotenoid, tea polyphenols, and catechins contents. High levels of theanine, glutamic acid, proline, and arginine were found to be induced most likely by adjusting the GS-GOGAT cycle. Se-supplementation may promote tea leaves’ secondary metabolism, thus increasing the accumulation of total phenols and flavonoids (apigenin, kaempferol, quercetin, myricetin, and rutin). It also minimized the accumulation of malondialdehyde, hydrogen peroxide, and superoxide anion by activating the antioxidants enzymes including in the AsA-GSH cycle. Selenium-rich tea also showed better fragrance and flavor. In summary, nano-Se can ameliorate the nutrients quality and abiotic stresses resistance of crops.

Narcissus tazetta (Amaryllidaceae) is a medicinal plant widely used for cut flowers and potted ornamental plant in Tunisia flora. The current study evaluated the phenolic composition and antioxidant properties of its flower extracts and investigated its potential protective activity against cadmium chloride (CdCl₂)–induced hepatotoxicity in mice. Mice were divided into six groups of six each: group 1, serving as negative controls, received by intraperitoneal way only distilled water; group 2 received by intraperitoneal way CdCl₂ (0.16 mg/kg bw); groups 3 and 4 received CdCl₂ at the same dose of group 2 and 100 or 200 mg/kg bw of Narcissus tazetta flower extracts via oral route; groups 5 and 6, serving as positive controls, received only Narcissus tazetta flower extracts. Polyphenolic compounds of the extract were analyzed by colorimetric and high-performance liquid chromatography-mass spectrometry (HPLC-MS) methods. Total antioxidant activity and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging potential of the extract were estimated using colorimetric method. Results indicated that ethanolic flower extract contained high levels of total phenolic and flavonoid along with a strong total antioxidant and DPPH free radical scavenging activities. HPLC-MS analysis identified eight phenolic compounds, including rutin, kaempferol glycosides, and chlorogenic acids. The extract also exhibited marked hepatoprotective effects against CdCl₂ toxicity by reducing hepatic levels of malondialdehyde, advanced oxidation protein products, hydrogen peroxide, metallothioneins, and DNA degradation. Additionally, co-administration of Narcissus tazetta flower extracts lowered the plasma activities of transaminases, gamma glutamyl transpeptidase, and lactate dehydrogenase and increased hepatic levels of reduced glutathione, nonprotein thiols, vitamin C, and catalase activity. The hepatoprotective effects of the extract were demonstrated by histopathological improvement of liver disorders. The current study provided ethnopharmacological application of Narcissus tazetta flower extracts against CdCl₂-induced oxidative stress, suggesting its chemoprevention role of its phenolic compounds as a natural antioxidant.

Pergularia tomentosa L. (P. tomentosa) has been largely used in Tunisian folk medicine as remedies against skin diseases, asthma, and bronchitis. The main objectives of this study were to identify phytochemical compounds that have antioxidant and antimicrobial properties from the stem, leaves, and fruit crude methanolic extracts of P. tomentosa, and to search for tyrosyl-tRNA synthetase (TyrRS), topoisomerase type IIA, and Candidapepsin-1 (SAP1) enzyme inhibitors through molecular docking study. Phytochemical quantification revealed that fruit and leaves extracts displayed the highest total flavonoids (582 mg QE/g Ex; 219 mg QE/g Ex) and tannins content (375 mg TAE/g Ex; 216 mg TAE/g Ex), also exhibiting significant scavenging activity to decrease free radicals for ABTS, DPPH, β-carotene, and FRAP assay with IC₅₀ values (> 1 mg/mL). Additionally, promising antimicrobial activities towards different organs have been observed against several bacteria and Candida strains. From the liquid chromatography-mass spectrometry (LC-MS) analysis, five polyphenolic compounds, namely digitoxigenin, digitonin glycoside and calactina in the leaves, kaempferol in the fruit, and calotropagenin in the stems, were identified. They were also analyzed for their drug likeliness, based on computational methods. Molecular docking study affirmed that the binding affinity of calactin and actodigin to the active site of TyrRS, topoisomerase type IIA, and SAP1 target virulence proteins was the highest among the examined dominant compounds. Therefore, this study indicated that P. tomentosa methanolic extracts displayed great potential to become a potent antimicrobial agent and might be a promising source for therapeutic and nutritional functions. These phytocompounds could be further promoted as a candidate for drug discovery and development.

Date was considered a high nutritional value fruit due to its high content of active ingredients. Frequent exposure to cosmetic radiations including UVC caused deleterious effects and tissue damage and organ affection. This study investigated the efficacy of Ajwa date extract (ADE) in protection against UVC-induced kidney injury in rats. Five groups of rats were included in this study. Group I: Rats were exposed to UVC radiation at a dose 5 kJ (1 h/day) for 28 days. Group II: Rats were pretreated orally with ADE (10 mg/kg/day) 1 h before exposure to UVC radiation with dose 5 kJ. Group III: Rats were pretreated with ADE (15 mg/kg) 1 h before exposure to UVC radiation. Group IV: Rats were exposed to UVC radiation then treated with ADE (10 mg/kg). Group V: Rats exposed to UV radiation then treated with ADE (15 mg/kg) after 1 h from exposure. Analyzing the active constituents of ADE by GC/MS showed that, quercetin, myricetin kaempferol, thymine, and catechol are the most active ingredients. Biochemical markers obtained showed that, serum 8-oxoguanine as marker for DNA damage was increased, and total antioxidant activity and glutathione reduced were decreased (p < 0.01), while neutrophil (p < 0.001), conjugated diene (p < 0.05), and interferon-γ (p < 0.01) were increased after exposure to UVC. However, all the parameters changed were reversed by ADE-treated rats compared with untreated; the higher dose was more effective and protective effect was better than treated effect. Kidney total proteins and reduced glutathione and procollagen levels were decreased while malondialdehyde was increased after exposure to UVC (p < 0.01). These abnormalities were normalized by ADE treatment and protected. It was concluded that, flavonoids from Ajwa extract protected against deleterious effects of UVC by enhancing antioxidant activities and reducing infiltration of neutrophils that caused kidney injury.

This study evaluated the protective effect of kaempferol, a natural flavonoid, against cadmium chloride (CdCl₂)-induced liver damage and examined the possible anti-inflammatory and antioxidant mechanisms of protection. Adult male rats were divided into 4 groups (each of 8 rats) as control, kaempferol (50 mg/kg/day orally), CdCl₂ (15 ppm/day), and CdCl₂ (15 ppm/day) + kaempferol (50 mg/kg/day). All treatments were given for 30 days. With no effect on attenuating the reduced food intake, kaempferol significantly increased body weight and lowered serum levels of liver injury markers including bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase 1 (γ-GTT1) in the CdCl₂-treated rats. It also restored normal liver architectures, prevented hepatocyte, loss, and swelling and reduced inflammatory cell infiltration. These effects were associated with a reduction in mitochondrial permeability transition pore, as well as in the expression of cytochrome-c and cleaved caspase-3, markers of mitochondrial damage, and intrinsic cell death. In both the control positive and CdCl₂-treated rats, kaempferol significantly lowered the hepatic levels of reactive oxygen species, malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), Interleukine-6 (IL-6), and the nuclear activity and localization of NF-κB p65. Besides, kaempferol significantly increased the hepatic total and nuclear levels of the nuclear factor erythroid 2–related factor 2 (Nrf2) and heme oxygenase-1, as well as levels of superoxide dismutase (SOD) and reduced glutathione (GSH) but reduced the cytoplasmic protein levels of keap1. In conclusion, the protective effect of kaempferol against CdCl₂-induced hepatic damage is mediated by antioxidant and anti-inflammatory effects driven by upregulating Nrf2/HO-1 axis and suppressing the NF-κB p65 and keap1.

Pathogenesis of Parkinson’s disease (PD) specifically involves the degeneration of dopaminergic neurons in the substantia nigra region, which mainly begun with the overwhelmed oxidative stress and neuroinflammation. Considering the antioxidant and other pharmacological properties, Eclipta alba needs to be exploited for its possible neuroprotective efficacy against PD and other neurological disorders. Therefore, the current study was conducted to exemplify the remedial effects of hydro-alcoholic extract of E. alba (EA-MEx) against MPP⁺-elicited in vitro and in vivo PD models. SH-SY5Y, a neuroblastoma cell culture and male Wistar rats were used to impersonate the hallmarks of PD. Qualitative and quantitative analyses of EA-MEx revealed the presence of quercetin, ellagic acid, catechin, kaempferol, and epicatechin at varying concentrations. EA-MEx was found to deliver considerable protection against MPP⁺-induced oxidative damages in SH-SY5Y cells. Furthermore, in vivo study also supported the neuroprotective efficacy of EA-MEx, with significant mitigation of behavioral deficits induced by intrastriatal injection of MPP⁺. Furthermore, the disturbed levels of cellular antioxidant machinery have been significantly improved with the pre-treatment of EA-MEx. Mechanistically, the expression of α-synuclein, tyrosine hydroxylase, and mortalin were also found to be improved with the prior treatment of EA-MEx. Hence, the study suggests Eclipta alba as a suitable candidate for the development of better neuropathological therapeutics.

A multi-herbal combination (MHC) of five herbs, namely Punica granatum L., Putranjiva roxburghii Wall., Swertia chirata Buch.-Ham., Tinospora cordifolia (Willd.) Miers and Trigonella corniculata L. was assessed against the paracetamol-induced acute hepatotoxicity in female Wistar rats. The animals were randomly assorted into seven groups with six animals in each group. The rats were pre-treated with MHC (50, 100, and 200 mg/kg bw) and silymarin (50 mg/kg bw) once daily for seven consecutive days via oral route followed by administration of paracetamol (3 g/kg bw) on day 7, an hour after the last administration of MHC and silymarin. It was observed that MHC administration significantly (p ≤ 0.05) overturned the paracetamol-induced increase in serum liver function biomarkers (serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, alkaline phosphatase, and total bilirubin), phase I reaction enzymes (NADPH-cytochrome P450 reductase and NADH-cytochrome b5 reductase), and oxidant biomarkers (lactate dehydrogenase, lipid peroxidation, lipid hydroperoxides, and protein content). MHC administration also reinstated the paracetamol-induced significant decrease (p ≤ 0.05) in haematological indices (haematocrit, haemoglobin, red and white blood cells, and platelets), phase II reaction enzymes (glutathione-S-transferase and DT-diaphorase), membrane-bound enzymes (Na⁺/K⁺-ATPase, Ca²⁺-ATPase, and Mg²⁺-ATPase), and antioxidant biomarkers (reduced glutathione, superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). Overall, MHC at 200 mg/kg bw dose significantly (p ≤ 0.05) sheltered the red blood cells from the assault of free radicals, stabilized the structural and functional integrity of hepatocytes, hindered acetaminophen (APAP) biotransformation to its toxic metabolites, and endorsed conjugating abilities to detoxify toxic entities. Furthermore, MHC significantly (p ≤ 0.05) activated enzymatic machinery to scavenge/inhibit the formation of reactive oxygen species, regulated nucleic acid metabolism, surface potential, and membrane fluidity, attenuated tissue breakdown, quenched peroxyl radicals, and provided protection against tissue injury. The necroinflammatory scores revealed strong evidence of MHC (200 mg/kg bw) effectiveness against the paracetamol-induced hepatotoxicity in rats at p ≤ 0.05. The synergistic effect of major inherent phytoconstituents (kaempferol, ellagic acid, and gallic acid), detected by HPLC-PDA, in MHC might have overturned the paracetamol-induced biochemical toxic alterations in rat liver.

Onosma bracteata Wall. (Boraginaceae), commonly known as “gaozaban” is a highly valuable medicinal herb, useful in the treatment of body swellings, abdominal pain, eye-related problems, fever, and urinary calculi. The present study was performed to investigate the antioxidant properties of extract/fractions, viz. ethanol (Obeth) extract, hexane (Obhex) fraction, chloroform (Obcl) fraction, ethyl acetate (Obea) fraction, butanol (Obbu) fraction, and aqueous (Obaq) fraction isolated from O. bracteata. Obea fraction showed stronger free radical quenching ability in various antioxidant assays, as compared to the other fractions. Obea fraction with effective free radical-scavenging properties was further evaluated for the antiproliferative activity against human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay. Obea fraction showed strong cytotoxicity with GI₅₀ value of 88.56, 101.61, and 112.7 μg/ml towards MG-63, IMR-32, and A549 cells respectively. Mechanistic studies revealed that Obea fraction in osteosarcoma MG-63 cells increased reactive oxygen species (ROS) level and reduced mitochondrial membrane potential. In the presence of Obea, the cells were found to be arrested in the G₀/G₁ phase in a dose-dependent manner which is also confirmed by the enhancement in the early apoptotic cell population in flow cytometer analysis. Western blotting demonstrated the decrease in expression of p-NFκB, COX-2, p-Akt, and Bcl-xL, whereas upregulation was observed in the expression of GSK-3β, p53, caspase-3, and caspase-9 proteins. RT-qPCR studies revealed downregulation of Bcl-2, cyclin E, CDK2, and mortalin gene expression and upregulation in the expression of p53 genes. The antioxidant and cytotoxic potential of Obea was attributed to the presence of catechin, kaempferol, onosmin A, and epicatechin, as revealed by HPLC analysis. This is the first report regarding the antiproliferative potential of O. bracteata against osteosarcoma.

After the early advent of the Coronavirus Disease 2019 (COVID-19) pandemic, myriads of FDA-approved drugs have been massively repurposed for COVID-19 treatment based on molecular docking against selected protein targets that play fundamental roles in the replication cycle of the novel coronavirus. Honeybee products are well known of their nutritional values and medicinal effects. Bee products contain bioactive compounds in the form of a collection of phenolic acids, flavonoids, and terpenes of natural origin that display wide spectrum antiviral effects. We revealed by molecular docking the profound binding affinity of 14 selected phenolics and terpenes present in honey and propolis (bees glue) against the main protease (Mᵖʳᵒ) and RNA-dependent RNA polymerase (RdRp) enzymes of the novel SARS-CoV-2 virus (the causative agent of COVID-19) using AutoDock Vina software. Of these compounds, p-coumaric acid, ellagic acid, kaempferol, and quercetin have the strongest interaction with the SARS-CoV-2 target enzymes, and it may be considered an effective COVID-19 inhibitor.

Acacia jacquemontii possess has numerous traditional therapeutic uses. The rationale of this study was to investigate the role of Acacia jacquemontii ethyl acetate extract (AJEAE) in the downregulation of hyperglycemia. The current study was performed in two parts, in vitro, through characterization (high-performance liquid chromatography), estimation of total phenolic content, total flavonoid content, antioxidant (2,2-diphenyl-1-picrylhydrazylassay), and α-amylase inhibitory activities of the studied extract, and in vivo using Wistar rats in which animals were divided into five groups NC, DC, GL, AJEAE 250 mg/kg, and AJEAE 500 mg/kg. The effects of AJEAE on fasting plasma glucose, plasma insulin, HOMA-IR, oral glucose tolerance test, glycated hemoglobin (HBA1c), lipid profile, inflammatory cytokines (Interleukin-6, tumor necrosis factor-alpha), and oxidative stress markers (lipid peroxidation, nitic oxide, superoxide dismutase, catalase, glutathione peroxidase) were evaluated. Our findings confirmed the presence of quercetin, kaempferol, gallic acid, vanillic acid, syringic acid, M-coumaric acid, sinapic acid, chlorogenic acid, cinnamic acid, and ferulic acid in AJEAE. Total flavonoid and phenolic contents in AJEAE were 83.83 mg GAE/g and 77.06 mg QE/g, respectively. Significant inhibition of DPPH (69.470%/1 mg/ml) and α-amylase (71.8%/1 mg/ml) activities were exhibited by AJEAE. Alloxan-injected rats showed marked hyperglycemia and hypoinsulinemia, and increased inflammatory marker levels as compared to normal control (p < 0.001). Additionally, raised levels of triglyceride (139.7 ± 2.771), total cholesterol (198.7 ± 1.856), very low-density lipoprotein (33.43 ± 0.2728), low-density lipoprotein (155.5 ± 2.754), lipid peroxidation, and nitric oxide (p < 0.001) and decreased levels of high-density lipoprotein (17.20 ± 0.1732), superoxide dismutase, catalase, and glutathione peroxidase were observed in diabetic rats (p < 0.001). AJEAE significantly (p < 0.05) improved the aforementioned parameters and the protective efficacy was comparable to glibenclamide. Histopathological findings also evidenced the anti-hyperglycemic properties of AJEAE through regeneration of pancreatic β cells. Conclusively, our findings demonstrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and pancreatic beta β cell regenerative properties of AJEAE against alloxan-induced diabetes.