Arsenic (As) is a highly toxic metalloid adversely affecting the environment, human health, and crop productivity. The present study assessed the synergistic effects of salinity and As on photosynthetic attributes, stomatal regulations, and metabolomics responses of the xero-halophyte Salvadora persica to decipher the As-salinity cross-tolerance mechanisms and to identify the potential metabolites/metabolic pathways involved in cross-tolerance of As with salinity. Salinity and As stress-induced significant stomatal closure in S. persica suggests an adaptive response to decrease water loss through transpiration. NaCl supplementation improved the net photosynthetic rate (by +39%), stomatal conductance (by +190%), water use efficiency (by +55%), photochemical quenching (by +37%), and electron transfer rate (54%) under As stress as compared to solitary As treatment. Our results imply that both stomatal and non-stomatal factors account for a reduction in photosynthesis under high salinity and As stress conditions. A total of 64 metabolites were identified in S. persica under salinity and/or As stress, and up-regulation of various metabolites support early As-salinity stress tolerance in S. persica by improving antioxidative defense and ROS detoxification. The primary metabolites such as polyphenols (caffeic acid, catechin, gallic acid, coumaric acid, rosmarinic acid, and cinnamic acid), amino acids (glutamic acid, cysteine, glycine, lysine, phenylalanine, and tyrosine), citrate cycle intermediates (malic acid, oxalic acid, and α-ketoglutaric acid), and most of the phytohormones accumulated at higher levels under combined treatment of As + NaCl compared to solitary treatment of As. Moreover, exogenous salinity increased glutamate, glycine, and cysteine, which may induce higher synthesis of GSH-PCs in S. persica. The metabolic pathways that were significantly affected in response to salinity and/or As include inositol phosphate metabolism, citrate cycle, glyoxylate and dicarboxylate metabolism, amino acid metabolism, and glutathione metabolism. Our findings indicate that inflections of various metabolites and metabolic pathways facilitate S. persica to withstand and grow optimally even under high salinity and As conditions. Moreover, the addition of salt enhanced the arsenic tolerance proficiency of this halophyte.

The increase in ambient fine dust particles (FDP) due to urbanization and industrialization has been identified as a major contributor to air pollution. It has become a serious issue that threatens human health because it causes respiratory diseases and skin aging. In the present study, the protective effect of the green tea catechin, (−)-epigallocatechin gallate (EGCG), against FDP (ERM-CZ100)-stimulated skin aging in human dermal fibroblasts (HDFs) was investigated. The results demonstrate that EGCG significantly and dose-dependently scavenged intracellular reactive oxygen species (ROS) in and increased the viability of FDP-stimulated HDFs. In addition, EGCG dose-dependently recovered collagen synthesis and inhibited intracellular elastase and collagenase activities. Moreover, EGCG decreased the expression of human matrix metalloproteinases (MMPs) via regulation of nuclear factor kappa B (NF-κB), activator protein 1 (AP-1), and mitogen-activated protein kinases (MAPKs) signaling pathways in FDP-stimulated HDFs. This study suggests that EGCG is a potential anti-aging candidate that can be used for FDP-induced skin aging as a therapeutic agent itself or as an ingredient in pharmaceutical and cosmeceutical products.

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.

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.

Mercury (Hg) is a highly toxic heavy metal for all organisms. In the present study, the mitigative role of 190 mg/L and 380 mg/L doses of green tea extract (GTex) against mercury(II) chloride (HgCI₂)-induced toxicity was evaluated in Allium cepa L. For this aim, selected physiological, genotoxicity, and biochemical parameters as well as meristematic cell injuries in the roots were investigated. Ratios of catechin and caffeine in GTex were determined by HPLC analysis. Also, free radical scavenging activity of GTex was tested against superoxide and hydrogen peroxide radicals. As a result of HgCI₂ application, germination percentage, root elongation, weight gain, and mitotic index (MI) declined, while the frequency of micronucleus (MN), chromosomal abnormalities (CAs), and meristematic cell damages increased. HgCI₂ administration also led to a significant increase in malondialdehyde content, superoxide dismutase, and catalase activities which are signs of oxidative stress. On contrary, applications of GTex together with HgCI₂ reduced HgCI₂-induced adverse effects in all parameters in a dose-dependent manner. Antioxidant components in GTex were listed as caffeine, epigallocatechin gallate, epigallocatechin, epicatechin gallate, and catechin according to their abundance. GTex exhibited a strong scavenging ability in the presence of superoxide and hydrogen peroxide radicals. The present study revealed the strong protective capacity of GTex against HgCI₂-induced toxicity in A. cepa owing to its high antioxidant content with a multifaceted perspective. With this study, a reliable starting point was established for future studies investigating the more common and diverse use of GTex against toxic substances.

This study was conducted to identify the bioactive phytochemicals in Salvia officinalis essential oil, to determine the polyphenols in the aqueous extract (SOE), and to evaluate their protective role against cadmium (Cd)-induced oxidative damage and genotoxicity in rats. Six groups of female rats were treated orally for 2 weeks including the control group, CdCl₂-treated group, SOE-treated groups at low or high dose (100 and 200 mg/kg b.w), and CdCl₂ plus SOE-treated groups at the two doses. The GC-MS analysis identified 39 compounds; the main compounds were 9-octadecenamide, eucalyptol, palmitic acid, and oleic acid. However, the HPLC analysis showed 12 polyphenolic compounds and the majority were coumaric acid, chlorogenic acid, coffeic acid, catechin, vanillin, gallic acid, ellagic acid, and rutin. In the biological study, rats received CdCl₂ displayed severe disturbances in liver and kidney indices alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin (Alb), total protein (TP), total bilirubin (T. Bil), direct bilirubin (D. Bil), creatinine, uric acid, and urea, lipid profile, tumor necrosis factor-alpha (TNF-α), alpha-fetoprotein (AFP) and CEA), glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA), nitric oxide (NO), gene expressions, DNA fragmentation, and histological alterations in the liver and kidney tissue. SOE showed a potent antioxidant and mitigated these alterations in serum and tissue. Moreover, the high dose succeeded to normalize most of the tested parameters and histological features. It could be concluded that S. officinalis is a promising source for bioactive compounds with therapeutic benefits against environmental toxicants.

The present study investigated the antimutagenic, antioxidant, and antiproliferative properties of extracts of Cassia fistula prepared by sequentially fractionation of 80% methanolic (CaLM extract) extract of C. fistula leaves, namely CaLH (hexane), CaLC (chloroform), CaLE (ethyl acetate), CaLB (n-butanol), and CaLA (aqueous) fractions. The antimutagenicity of the fractions was tested against mutagens viz. S9-independent, namely 4-nitro-o-phenylenediamine (TA98) and sodium azide (TA100) and S9-dependent, 2-AF (2-aminofluorene). Among the tested fractions, CaLE fraction showed a potent efficacy with an inhibition percentage of 85.57% (TA98) and 89.93% (TA100) against the mutagenicity induced by 2-aminofluorene. The CaLE fraction could significantly scavenge free radicals in various assays, namely DPPH, lipid peroxidation inhibition, and superoxide anion radical scavenging assays with an IC₅₀ of 12.80, 144, and 257.3 μg/ml respectively. The antiproliferative potential of the effective CaLE fraction was assessed using MTT assay against HeLa and MCF-7 cancer cells with GI₅₀ value of 243.4 and 324.6 μg/ml respectively. The fraction exhibited remarkable apoptosis-inducing effects through the externalization of phosphatidylserine in HeLa cells as analyzed by annexin V-FITC/PI double staining assay. The HPLC analysis of CaLE revealed the presence of catechin, epiafzelechin, and chlorogenic acid which are responsible for its antimutagenic and antiproliferative efficacy. Graphical abstract

Cardiovascular diseases are key complications primarily associated with hyperthyroidism disorders. The present study sought to ameliorate hyperthyroidism-mediated cardiovascular inflammations and related oxidative stress paradigms in experimental rats using the broadly distributed green seaweed Ulva fasciata. Forty-eight adult male albino rats were recruited and randomly classified into six groups. Hyperthyroidism was stimulated using L-thyroxine sodium at a dose of 100 μg/kg i.p. for 3 weeks daily. Further, 200 mg/kg b.wt. concentration of the U. fasciata methanolic (U. fasciata-MeOH) extract was the recommended dose and administrated orally to the hyperthyroid rats. The standard commercial drug “propranolol hydrochloride” was also tested at a dose of 10 mg/kg i.p. to compare the findings obtained from the seaweed extract. A combined treatment with the U. fasciata-MeOH extract and propranolol hydrochloride was also assessed. Our results implied that the treatment of hyperthyroid rats with the U. fasciata-MeOH extract significantly reduced serum levels of the thyroid hormones T3 and T4, proinflammatory cytokines (TNF-α, MPO, and CRP), triglycerides and total cholesterol, as well as the cardiac biomarkers CK-MB, LDH, and troponin to thresholds close to those of the standard drug. In addition, levels of high-density lipoprotein cholesterol (HDL-C) and interleukin 10 (IL-10) were significantly upregulated. Hyperthyroid rats only treated with propranolol hydrochloride, or with a combination of the drug and the seaweed extract, conferred the same observations. Histopathological architecture boosted our interesting findings where the myocardium tissues in hyperthyroid rats, administrated the U. fasciata-MeOH extract or/and propranolol hydrochloride, exhibited more or less a normal structure as the control, reflecting the potential cardiovascular recovery exerted by this seaweed extract. In vitro DPPH, ABTS, and FRAP antioxidant assays of the U. fasciata-MeOH extract showed an outstanding ROS-scavenging potential. HPLC analysis of the U. fasciata-MeOH extract unraveled an inestimable valuable array of phenolics (mainly p-coumaric, gallic, ferulic, chlorogenic, and syringic acids) and flavonoids (hesperidin, kaempferol, catechin, quercetin, and rutin). Conclusively, the seaweed U. fasciata is a profitable source of antioxidant polyphenolics characterized by having a pharmaceutical potential against hyperthyroidism-linked cardiovascular inflammations and oxidative stress patterns due to their substantial free radical quenching properties, and also via regulating the signalling pathways of the proinflammatory, lipid profile, and cardiac biomarkers.

Pentachlorophenol (PCP) is an organochlorine compound that is used as pesticide, biocide, and wood preservative. PCP is highly toxic and carcinogenic. It has been detected in food and several consumable products. The toxicity of PCP is thought to be due to generation of oxidative stress in cells. We examined whether the dietary antioxidant catechin can attenuate or protect human erythrocytes and lymphocytes against PCP-induced cytotoxicity and genotoxicity, respectively. Human erythrocytes were treated with increasing concentrations of catechin (0.05–2.5 mM) for 30 min followed by addition of 0.75 mM PCP and further incubation for 4 h at 37 °C. Hemolysates were prepared and assayed for various biochemical parameters. Treatment with PCP alone increased the generation of reactive oxygen and nitrogen species, lipid and protein oxidation, and damaged the plasma membrane, when compared to PCP untreated (control) cells. It significantly decreased glutathione level, total sulfhydryl content, and cellular antioxidant power. PCP treatment lowered the activity of antioxidant enzymes and inhibited enzymes of glucose metabolism. However, prior incubation with catechin attenuated the PCP-induced changes in all these parameters in a catechin concentration-dependent manner. Scanning electron microscopy of erythrocytes confirmed these biochemical results. PCP treatment converted the normal discoidal erythrocytes to irregularly contracted cells, acanthocytes, and echinocytes but the presence of catechin inhibited these morphological changes and erythrocytes retained their biconcave shape to a large extent. Genotoxicity was studied in human lymphocytes by single-cell gel electrophoresis (comet assay). It showed strand breaks and longer comet tail length in PCP alone treated cells. The comet tail length was reduced in the catechin +PCP-treated lymphocytes showing that catechin protected cells from PCP-induced DNA damage. These results show that catechin protects human blood cells against PCP-induced oxidative damage.

The present study investigates the phenolic profile of exudates and extracts of the green algae Dunaliella tertiolecta, harvested in natural seawater in the absence (control) and in the presence of Cu(II) (315 and 790 nmol L⁻¹) and Fe(III) (900 nmol L⁻¹) in order to identify and quantify the phenolic compounds produced under metallic stress conditions. The presence of metal ions modifies the growth of cells and changes cell metabolism by producing phenolic compounds adapted to the solution. The use of reversed-phase high-performance liquid chromatography (RP-HPLC) permitted the identification of 14 phenolic constituents. The concentration and type of polyphenols detected in cell extracts and in solution are directly related with the metal and its concentration during growth cultures, achieving 1.4 times higher levels of polyphenols under 790 nmol Cu(II) L⁻¹ with respect to the control experiments. Microalga excretes polyphenols to be adapted to the environmental conditions. Gentisic acid, (+) catechin and (−) epicatechin, the most prominent phenolic compounds detected in the algae extracts, showed high antioxidant activity in inhibiting 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. This potent activity may be related to its presence in cells and exudates in high concentrations.