γ-aminobutyric acid (GABA) has been reported to improve stress resistance in plants. Nonetheless, little is known about the effects of GABA on the nutritional quality and regulatory mechanisms of edamame. Therefore, we analyzed the flavonoid and amino acid (AA) metabolism and the effects of GABA on the nutrient content of edamame seeds through physiological and metabolomic analyses. Exogenous GABA increased endogenous GABA metabolism and GABA transaminase activity and enhanced the oxoglutarate content, which entered into nitrogen metabolism and increased the activity and expression of nitrogen metabolism-related enzymes, to accumulate AAs and bioactive peptides. Meanwhile, exogenous GABA induced the metabolism of flavonoids, including total flavonoids, anthocyanins, 6\'\'-o-malonyglycitin, glycitin, ononin, cyanin, and ginkgetin, by increasing the activity and expression of flavonoid biosynthetic enzymes. This is the first study to reveal that GABA effectively improves the nutritional quality of edamame through the accumulation of AAs, bioactive peptides, isoflavones, anthocyanins, sugars, and organic acids.

Crinum jagus (C. jagus; J. Thomps.) Dandy (Liliaceae) is a pantropical plant known for its medicinal values and pharmacological properties. The study assessed the protective effects and changes in oxidative stress indices due to C. jagus leaf extracts on the toluene-induced liver and kidney injuries in rats. The study was conducted on 8-week-old male Wistar rats (n = 80), weighing 243.3 ± 1.42 g. Group I, 1 ml/kg distilled water for 7 days; Group II, 4.5 ml/kg toluene once, 1 ml/kg distilled water for 7 days; Group III, 4.5 ml/kg toluene once, 500 mg/kg methanolic extract for 7 days; Group IV, 4.5 ml/kg toluene once, 500 mg/kg aqueous extract for 7 days; Group V, 500 mg/kg methanolic extract for 7 days; Group VI, 500 mg/kg aqueous extract for 7 days; Group VII, 500 mg/kg of vitamin C for 7 days; Group, VIII, 4.5 ml/kg toluene once, 500 mg/kg vitamin C for 7 days, all administrations were given by oral gavage. The phytochemical contents, absolute and relative organ weights of liver and kidneys, liver and kidney function tests, antioxidant status, as well as histological tests were analyzed using standard protocols. The tannins, flavonoids, and polyphenols were in highest concentration in both extracts, content in methanol extract (57.04 ± 1.51 mgg-1, 35.43 ± 1.03 mgg-1, 28.2 ± 0.34 mgg-1 respectively) > aqueous extract (18.74 ± 1.01 mgg-1, 13.43 ± 0.47 mgg-1, 19.65 ± 0.21 mgg-1 respectively). In the negative control group (II), bodyweights significantly (P < 0.05) reduced by 22%, liver weight and kidney weight significantly (P < 0.05) increased by 42% and 83% respectively, liver-to-bodyweight and kidney-to-bodyweight ratios increased significantly (P < 0.05); serum liver function tests (LFTs) i.e., bilirubin, alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Gamma-glutamyl transferase (GGT), and serum kidney function tests (creatinine and urea) were significantly (P < 0.05) elevated; oxidant status (tissue malondialdehyde; MDA) was significantly (P < 0.05) elevated, antioxidant status i.e., tissue superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) levels was significantly (P < 0.05) reduced; with markedly visible renal and hepatic histopathological findings, compared to the normal control group. In C. jagus extract test groups (III and IV), the parameters were significantly (P < 0.05) alleviated and reversed to normal/near normal compared to the negative control. The LFTs, kidney function tests, and antioxidant status were significantly (P < 0.05) more improved with the methanol extract test and standard control groups compared to the aqueous extract test group; Also, the methanol extract test group showed better histological features than the aqueous extract test and standard control groups. The methanolic extract shows better antioxidant potential due to the availability of more nonenzymatic antioxidants (tannins, flavonoids, and polyphenols). The findings showed that toluene is a very aggressive xenobiotic due to the promotion of oxidative stress and peroxidation of cellular lipids, but C. jagus leaves provide significant protection through the reducing power of nonenzymatic antioxidants and their ability to induce endogenous antioxidant enzymes (SOD, CAT, and glutathione reductase or GR) causing reduced cellular lipid peroxidation and tissue damages, quickened tissue repair, and improved cell biology of liver and kidneys during toluene toxicity. The methanol leaf extract provides better protection and should be advanced for more experimental and clinical studies to confirm its efficacy in alleviating oxidative stress tissue injuries, specifically due to toluene.

The purpose of this work was to investigate the protective effect of five essential oils (EOs); Rosmarinus officinalis, Thymus vulgaris, Origanum compactum Benth., Eucalyptus globulus Labill. and Ocimum basilicum L.; against oxidative stress induced by hydrogen peroxide in Saccharomyces cerevisiae. The chemical composition of the EOs was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC/MS). The in vitro antioxidant activity was evaluated and the protective effect of EOs was investigated. Yeast cells were pretreated with different concentrations of EOs (6.25-25 µg/ml) for an hour then incubated with H2O2 (2 mM) for an additional hour. Cell viability, antioxidants (Catalase, Superoxide dismutase and Glutathione reductase) and metabolic (Succinate dehydrogenase) enzymes, as well as the level of lipid peroxidation (LPO) and protein carbonyl content (PCO) were evaluated. The chemical composition of EOs has shown the difference qualitatively and quantitatively. Indeed, O. compactum mainly contained Carvacrol, O. basilicum was mainly composed of Linalool, T. vulgaris was rich in thymol, R. officinalis had high α-Pinene amount and for E. globulus, eucalyptol was the major compound. The EOs of basil, oregano and thyme were found to possess the highest amount of total phenolic compounds. Moreover, they have shown the best protective effect on yeast cells against oxidative stress induced by H2O2. In addition, in a dose dependent manner of EOs in yeast medium, treated cells had lower levels of LPO, lower antioxidant and metabolic enzymes activity than cells exposed to H2O2 only. The cell viability was also improved. It seems that the studied EOs are efficient natural antioxidants, which can be exploited to protect against damages and serious diseases related to oxidative stress.

The purpose of the study was to determine the effects of a tea from the leaves and flowers of Crataegus oxyacantha in rats with colitis. Colitis was induced by administration of 2,4,6-trinitrobenzene sulfonic acid. Hawthorn tea (HT) (100 mg/kg) was given via gavage for 21 days and the mesalamine drug (100 mg/kg) was administrated during the period of disease onset. HT was rich in total phenolic compounds (16.5%), flavonoids (1.8%), and proanthocyanidins (1.5%); vitexin-2-O-rhamnoside was the main compound detected. Mesalamine and the HT diminished the length of the lesions formed in the colon, in addition to reducing the levels of myeloperoxidase and interleukin-1β. Mesalamine was able to significantly reverse the body weight loss, while HT improved the activity of glutathione reductase and catalase. Histological scoring was not changed by the interventions, but it was highly correlated with the necrotic area. HT given at 100 mg/kg can be effective against colitis.

Anti-tumour efficacy of doxorubicin is hindered by the cumulative dose-dependent cardiotoxicity induced by reactive oxygen species during its metabolism. As Cinnamomum zeylanicum has proven antioxidant potential, objective of this study was to investigate the cardioprotective activity of Cinnamomum bark extract against doxorubicin induced cardiotoxicity in Wistar rats. Physicochemical and phytochemical analysis was carried out and dose response effect and the cardioprotective activity of Cinnamomum were determined in vivo. 180 mg/kg dexrazoxane was used as the positive control. Plant extracts were free of heavy metals and toxic phytoconstituents. In vivo study carried out in Wistar rats revealed a significant increase (p < 0.05) in cardiac troponin I, NT-pro brain natriuretic peptide, AST and LDH concentrations in the doxorubicin control group (18 mg/kg) compared to the normal control. Rats pre-treated with the optimum dosage of Cinnmamomum (2.0 g/kg) showed a significant reduction (p < 0.05) in all above parameters compared to the doxorubicin control. A significant reduction was observed in the total antioxidant capacity, reduced glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase and catalase activity while the lipid peroxidation and myeloperoxidase activity were significantly increased in the doxorubicin control group compared to the normal control (p < 0.05). Pre-treatment with Cinnamomum bark showed a significant decrease in lipid peroxidation, myeloperoxidase activity and significant increase in rest of the parameters compared to the doxorubicin control (p < 0.05). Histopathological analysis revealed a preserved appearance of the myocardium and lesser degree of cellular changes of necrosis in rats pre-treated with Cinnamomum extract. In conclusion, Cinnamomum bark extract has the potential to significantly reduce doxorubicin induced oxidative stress and inflammation in Wistar rats.

Phenylhydrazine (PHZ), an intermediate in the synthesis of fine chemicals is toxic for human health and environment. Despite of having severe detrimental effects on different physiological systems, exposure of erythrocytes to PHZ cause destruction of haemoglobin and membrane proteins leading to iron release and complete haemolysis of red blood cells (RBC). Involvement of oxidative stress behind such action triggers the urge for searching a potent antioxidant. The benefits of consuming olive oil is attributed to its 75% oleic acid (OA) content in average. Olive oil is the basic component of Mediterranean diet. Hence, OA has been chosen in our present in vitro study to explore its efficacy against PHZ (1 mM) induced alterations in erythrocytes. Four different concentrations of OA (0.01 nM, 0.02 nM, 0.04 nM and 0.06 nM) were primarily experimented with, among which 0.06 nM OA has shown to give maximal protection. This study demonstrates the capability of OA in preserving the morphology, intracellular antioxidant status and the activities of metabolic enzymes of RBCs that have been diminished by PHZ, through its antioxidant mechanisms. The results of the present study firmly establish OA as a promising antioxidant for conserving the health of erythrocyte from PHZ toxicity which indicate toward future possible use of OA either singly or in combination with other dietary components for protection of erythrocytes against PHZ induced toxic cellular changes.

Acetaminophen (APAP) is used as a primary drug due to its antipyretic and analgesic activity. The mechanism of action of APAP toxicity in the liver is due to the depletion of glutathione which elicited free radicals generation. Therefore, the objective of our work is to investigate the APAP induced liver damage and its repair by free radical scavenging activity of cinnamon oil (CO) in male Wistar rats. To investigate the effects of CO at different doses (50, 100 and 200 mg/kg b.w.), animals were given a single oral dose of CO per day for 14 days between 12:00-1:00 PM. The biochemical changes, imbalance in oxidative markers, interleukins, caspases and histopathological studies were determined for quantifying the hepatoprotective effect of CO. One dose of APAP (2 g/kg b.w.) results in significant hepatotoxicity and marked increase the serum markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, albumin, total protein, content of lipid peroxidation (LPO), interleukins (IL-1β, IL-6), caspase-3, -9 expression, DNA fragmentation and histopathological changes were observed. Significant decrease in the levels of LPO, interleukins IL-1β, IL-6, caspase-3, -9 expressions, qualitative as well as quantitative determination of DNA fragments and histopathological changes were reversed by the administration of CO dose dependently. Furthermore, it also restores the depleted activity of antioxidative enzymes. Our study shows that an imbalance in the oxidative parameter in the liver by APAP is restored by treating the animals with CO.

Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.

Hypothyroidism is the most frequent consequence of the interaction of a large variety of drugs, environmental pollutants and industrial chemicals with the thyroid gland. It is associated with diminished endocrine function which may lead to hyperlipidemia, diabetes, Alzheimer\'s disease, weight gain, and other metabolic disorders. The present study evaluates the pro-thyroid activity of a bioactive fraction from a polyherbal teabag in rats with hypothyroidism induced by propylthiouracil. The teabag was formulated to stimulate synthesis and/or release of T4 and affectthe conversion of T4 to T3. Phytoconstituents of the polyherbal teabag are potent antioxidants that may be responsible for the pro-thyroid activity. The tea-extract (1000 mg) was found to contain 1076 μg of gallic acid and 1131 μg of rutin from HPTLC analysis. Rats received propylthiouracil (8 mg/kg) for the first 15days followed by the polyherbal tea-extract (500, 1000 and 1500 mg/kg), the standard drug levothyroxine (0.1 mg/kg), aerobic exercise, and a combination of tea-extract (1000 mg/kg) and aerobic exercise daily along with propylthiouracil for the next 30 days. Finally, rats received their respective treatments alone without propylthiouracil for 15 more days. Lipid profile and levels of glucose, insulin, T3, T4, TSH, cortisol, homocysteine, creatinine, uric acid, malondialdehyde, glucose-6 phosphatase, and endogenous antioxidants were determined. All treatments attenuated significantly the propylthiouracil-elevated TSH, homocysteine, creatinine, uric acid, glucose-6-phosphatase, insulin, and malondialdehyde levels, and restored favorably the propylthiouracil-altered lipid profile, T3, T4, and endogenous antioxidant levels. The polyherbal tea-extract (1000 and 1500 mg/kg) treatment and thecombination treatment of tea-extract (1000 mg/kg) with aerobic exercise displayed significant restoration of the suboptimalthyroid function. This may be due to a favorablemodulation ofthe hypothalamic-pituitary-thyroid and the hypothalamic-pituitary-adrenal axes.

BACKGROUND: Vanadium (V) is an element with a wide range of effects on the mammalian organism. The ability of this metal to form organometallic compounds has contributed to the increase in the number of studies on the multidirectional biological activity of its various organic complexes in view of their application in medicine.
OBJECTIVE: This review aims at summarizing the current state of knowledge of the pharmacological potential of V and the mechanisms underlying its anti-viral, anti-bacterial, anti-parasitic, anti-fungal, anti-cancer, anti-diabetic, anti-hypercholesterolemic, cardioprotective, and neuroprotective activity as well as the mechanisms of appetite regulation related to the possibility of using this element in the treatment of obesity. The toxicological potential of V and the mechanisms of its toxic action, which have not been sufficiently recognized yet, as well as key information about the essentiality of this metal, its physiological role, and metabolism with certain aspects on the timeline is collected as well. The report also aims to review the use of V in the implantology and industrial sectors emphasizing the human health hazard as well as collect data on the directions of further research on V and its interactions with Mg along with their character.
CONCLUSIONS: Multidirectional studies on V have shown that further analyses are still required for this element to be used as a metallodrug in the fight against certain life-threatening diseases. Studies on interactions of V with Mg, which showed that both elements are able to modulate the response in an interactive manner are needed as well, as the results of such investigations may help not only in recognizing new markers of V toxicity and clarify the underlying interactive mechanism between them, thus improving the medical application of the metals against modern-age diseases, but also they may help in development of principles of effective protection of humans against environmental/occupational V exposure.