Mechanisms of the ethanol extract of Gelidium amansii for slow aging in high-fat male Drosophila by metabolomic analysis.

Gelidium amansii (GA) is a kind of red alga homologous to medicine and food and is distributed all over the world. Studies on GA are mainly focused on its polysaccharides, with little research on the ethanol extract. The ethanol extract of Gelidium amansii (GAE) was subjected to a reverse-phase column to obtain 7 components. Among them, 100% methanol solution (GAM), enriched with phytene-1,2-diol, exhibited the strongest DPPH free radical scavenging activity (IC50 = 0.17 mg mL-1). Subsequently, high-fat male flies (HMFs) were used as a model to explore the antioxidant and anti-aging effects of GAM in vivo. Studies showed that GAM can effectively prolong the lifespan of HMFs. When GAM concentrations were 0.2 and 1.0 mg mL-1, the average lifespan of HMFs was increased by 28.7 and 40.7%, respectively, while the longest lifespan of HMFs was increased by 20.55% and 32.88%, respectively. Further research revealed that GAM can significantly downregulate the levels of malondialdehyde (MDA) and protein carbonyl (PCO), and can significantly upregulate the levels of catalase (CAT) and total superoxide dismutase (T-SOD). In addition, by analyzing differential metabolites, we found that GAM relieves aging caused by oxidative stress by regulating amino acid, lipid, sugar, and energy metabolism. The GAM group significantly regulated the levels of adenine, cholic acid, glutamate, L-proline, niacin, and stachyose which tend to recover to the levels of the normal diet male fly (NMF) group. In general, our research provides ideas for the high-value utilization of GA and provides a lead compound for the research and development of anti-aging food or medicine.

Antioxidants (selenium and garlic) alleviated the adverse effects of tramadol on the reproductive system and oxidative stress markers in male rabbits.

Tramadol has been used by millions of patients as an analgesic drug to relief the severe pain caused by cancers and other diseases. The current study aimed to investigate the protective effects of antioxidants (garlic and selenium) against the toxic effects of tramadol on semen characteristics, steroid hormones, the protein expressions of different cytochrome P450 isozymes [CYP 21A2, CYP 19, and 11A1], and on antioxidant enzyme activities in testes of rabbits. Western immunoblotting, spectrophotometric, and histological methods were used in this study. Tramadol (1.5 mg/kg body weight) was administered orally to male rabbits for up to three months (three times/week), and after pretreatment of rabbits with garlic (800 mg/kg) and/or selenium (1 mg/kg body weight) by 2 h. The present study showed that motilities, semen volumes, morphologies, sperm counts, testosterone, and estrogen levels were significantly decreased after 4, 8, and 12 weeks of tramadol treatment. In addition, the protein expressions of CYP 21A2, CYP 19, and 11A1 were down-regulated in the testes of the tramadol-treated rabbits. On the other hand, pretreatment of rabbits with garlic, selenium, and/or garlic-selenium for 2 h before administration of tramadol restored the downregulated CYP 21A2 and 11A1 to their normal levels after 12 weeks of tramadol treatment. Activities of antioxidant enzymes including glutathione reductase, glutathione peroxidase, glutathione S-transferase, catalase, superoxide dismutase, and levels of glutathione were inhibited in the testes of tramadol-treated rabbits. On the other hand, free radical levels were significantly increased in the testes of tramadol-treated rabbits for 12 weeks. Interestingly, such changes in the activities of antioxidant enzymes as well as free radical levels caused by tramadol were restored to their normal levels in the rabbits pretreated with either selenium, garlic, and/or their combination. Histopathological investigations showed that tramadol caused substantial vacuolization with the presence of damaged immature spermatozoid in the testes. However, selenium and garlic treatments showed an increase in healthy sperm production with normal mitotic and meiotic divisions. The present study illustrated for the first time the mechanisms of low steroid hormone levels in the testes of tramadol-treated rabbits which could be due to the downregulation of CYPs proteins, induction of oxidative stress, and inhibition of antioxidant enzyme activities. In addition, the present data showed that such toxic effects of tramadol were attenuated and restored to their normal levels after pretreatment of rabbits with garlic, selenium, and/or their combination. This finding may pave the way for a new approach to reducing the toxicity of tramadol.

Network pharmacology, molecular docking and in vivo and in vitro experiments to explore the molecular mechanism of licorice green tea beverage to scavenge oxygen free radicals.

Excessive oxygen free radicals can lead to aging, cancer, and other diseases. Therefore, searching for effective antioxidants to scavenge oxygen free radicals has become the focus of modern medicine. In this study, the molecular mechanism of Licorice Green Tea Beverage (LGTB) in scavenging oxygen free radicals was investigated by means of network pharmacology, molecular docking and experimental verification. Network pharmacology studies have shown that paeonol, eugenol, cinnamaldehyde, swertisin, rutin, glycyrrhetinic acid, oleic, pelargonidin-3-O-glucoside and quercetin, kaferempol were the main active components of LGTB, and SOD and CAT are important targets for LGTB in scavenging oxygen free radicals. The results of molecular docking showed that these representative compounds had good affinity to SOD and CAT target proteins. In vitro free radical scavenging experiments showed that LTGB had significant scavenging effects on both DPPH and ABTS radicals, and had strong total reducing power. In vitro cell experiments showed that LGTB could protect HaCaT cells from oxidative stress induced by H2 O2 . The mechanism of LGTB was related to the increase of SOD and CAT activity. Western blotting showed that LGTB could inhibit PI3K/AKT/HIF-1 signaling pathway and improve the antioxidant capacity of HaCaT cells. In vivo experiments showed that LGTB could significantly increase mouse visceral index, increase serum SOD and GSH-Px activity, decrease the content of MDA, and improve liver and kidney pathological state. This study reported the molecular mechanism of LTGB scavenging oxygen free radicals, which provided scientific basis for the treatment and clinical research of aging and other diseases caused by excessive free radicals. PRACTICAL APPLICATIONS: Free radicals are produced by the normal response of cells during aerobic respiration and perform various functions, such as signaling and providing protection against infection. However, excessive free radicals can lead to aging, cancer, and other diseases. The antioxidant can overcome the harm caused by excessive free radicals. In this study, we investigated the molecular mechanism of scavenging oxygen free radicals of Licorice Green Tea Beverage (LGTB) through network pharmacology and molecular docking, and its efficacy was verified by free radical scavenging experiment in vitro, HaCaT cell oxidative stress injury induced by H2 O2 , D-galactose to establish an aging model in mice and Western blotting experiment. It not only elucidates its mechanism at the system level, but also proves its validity at the biological level. It provides the theoretical basis and experimental evidence for the follow-up research and promotion of the product.

Preclinical and Clinical Role of Coenzyme Q10 Supplementation in Various Pathological States.

Coenzyme Q10 (CoQ10) is an efficient antioxidant produced endogenously in a living organism. It acts as an important cofactor in the electron transport system of mitochondria and reported as a safe supplement in humans and animals with minimal adverse effect. CoQ10 is found naturally, as a trans configuration, chemical nomenclature of which is 2,3- dimethoxy-5- methyl-6-decaprenyle -1,4-benzoquinone. It is found in the body in two forms. In quinone form (oxidized form), it serves as an electron transporter that transfers the electrons in the electron transport chain between various complexes, and in ubiquinol form (reduced form), it serves as potent antioxidants by scavenging free radicals or by tocopherol regeneration in the living organism. Its primary roles include synthesis of adenosine triphosphate (ATP), stabilizes lipid membrane, antioxidant activity, cell growth stimulation, and cell death inhibition. CoQ10 has shown a variety of pharmacological and clinical effects including neuroprotective, hepatoprotective, anti-atherosclerotic, anticonvulsant, antidepressant, anti-inflammatory, antinociceptive, cardiovascular, antimicrobial, immunomodulatory, and various effects on the central nervous system. Present review has set about to bring updated information regarding to clinical and preclinical activities of CoQ10, which may be helpful to researchers to explore a new bioactive molecules for various therapeutic application.

Phytochemical: a treatment option for heavy metal induced neurotoxicity.

Heavy metals are known to be carcinogenic, mutagenic, and teratogenic. Some heavy metals are necessary while present in the growing medium in moderate concentrations known to be essential heavy metals as they required for the body functioning as a nutrient. But there are some unwanted metals and are also toxic to the environment and create a harmful impact on the body, which termed to be non-essential heavy metals. Upon exposure, the heavy metals decrease the major antioxidants of cells and enzymes with the thiol group and affect cell division, proliferation, and apoptosis. It interacts with the DNA repair mechanism and initiates the production of reactive oxygen species (ROS). It subsequently binds to the mitochondria and may inhibit respiratory and oxidative phosphorylation in even low concentrations. This mechanism leads to damage antioxidant repair mechanism of neuronal cells and turns into neurotoxicity. Now, phytochemicals have led to good practices in the health system. Phytochemicals that are present in the fruits and herbs can preserve upon free radical damage. Thus, this review paper summarized various phytochemicals which can be utilized as a treatment option to reverse the effect of the toxicity caused by the ingestion of heavy metals in our body through various environmental or lifestyles ways.

Evaluating anti-obesity potential, active components, and antioxidant mechanisms of Moringa peregrina seeds extract on high-fat diet-induced obesity.

There are no medical drugs that provide an acceptable weight loss with minimal adverse effects. This study evaluated the Moringa peregrina (MP) seed extract's anti-obesity effect. Twenty-four (6/each group) male Sprague Dawley rats were divided into group Ι (control), group ΙΙ (high-fat diet [HFD]), group ΙΙΙ (HFD+ MP [250 mg/kg b.wt]), and group ΙV (HFD+ MP [500 mg/kg b.wt]). MP administration significantly ameliorated body weight gains and HFD induced elevation in cholesterol, triglycerides, LDL, and reduced HDL. Moreover, MP seed oil showed high free radical-scavenging activity, delayed ß-carotene bleaching and inhibited lipoprotein and pancreatic lipase enzymes. High-performance liquid chromatography (HPLC) revealed three major active components: crypto-chlorogenic acid, isoquercetin, and astragalin. Both quantitative Real-time PCR (RT-PCR) and western blotting revealed that MP seeds oil significantly decreased the expression of lipogenesis-associated genes such as peroxisome proliferator-activated receptors gamma (PPARγ) and fatty acid synthase (FAS) and significantly elevated the expression of lipolysis-associated genes (acetyl-CoA carboxylase1, ACCl). The oil also enhanced phosphorylation of AMP-activated protein kinase alpha (AMPK-α) and suppressed CCAAT/enhancer-binding protein ß (C/EBPß). In conclusion, administration of M. peregrina seeds oil has anti-obesity potential in HFD-induced obesity in rats. PRACTICAL APPLICATIONS: M. peregrina seeds oil had a potential anti-obesity activity that may be attributed to different mechanisms. These included decreasing body weight, and body mass index and improving lipid levels by decreasing total cholesterol, triglycerides and LDL-C, and increasing HDL-C. Also, M. peregrina seeds oil regulated adipogenesis-associated genes, such as downregulating the expression of (PPARγ, C/EBPα, and FAS) and improving and upregulating the expression and phosphorylation of AMPKα and ACCl. Despite that M. peregrina extract has reported clear anti-obesity potential through animal and laboratory studies, the available evidence-based on human clinical trials are very limited. Therefore, further studies are needed that could focus on clinical trials investigating anti-obesity potential different mechanisms of M. peregrina extract in humans.

Aspergillus awamori attenuates ochratoxin A-induced renal and cardiac injuries in rabbits by activating the Nrf2/HO-1 signaling pathway and downregulating IL1ß, TNFα, and iNOS gene expressions.

Ochratoxin A (OTA) is one of the most dangerous and that pollute agricultural products, inducing a variety of toxic effects in humans and animals. The current study explored the protective effect of different concentrations of Aspergillus awamori (A. awamori) against OTA (0.3 mg/kg diet) induced renal and cardiac damage by exploring its mechanism of action in 60 New Zealand white male rabbits. Dietary supplementation of A. awamori at the selected doses of 50, 100, and 150 mg/kg diet, respectively, for 2 months significantly improved the rabbit's growth performance; modulated the suppressed immune response and restored the altered hematological parameters; reduced the elevated levels of renal injury biomarkers such as urea, creatinine, and alkaline phosphatase; and increased serum total proteins concentrations. Moreover, it also declined enzymatic activities of cardiac injury biomarkers, including AST, LDH, and CK-MB. A. awamori alleviated OTA-induced degenerative and necrotic changes in the kidney and heart of rabbits. Interestingly, A. awamori upregulated Nrf2/OH-1 signaling pathway. Therefore enhanced TAC, CAT, and SOD enzyme activities and reduced OTA-induced oxidative and nitrosative stress by declining iNOS gene expression and consequently lowered MDA and NO levels. In addition to attenuating renal and cardiac inflammation via reducing IL-1ß, TNF-α gene expressions in a dose-dependent response. In conclusion,this is the first report to pinpoint that dietary incorporation of A. awamori counteracted OTA-induced renal and cardiac damage by potentiating the rabbit's antioxidant defense system through its potent antioxidant, free radical scavenging, and anti-inflammatory properties in a dose-dependent response. Based on our observations, A. awamori could be utilized as a natural protective agent against ochratoxicosis in rabbits.

The role of plant-derived natural antioxidants in reduction of oxidative stress.

Free radicals are a group of damaging molecules produced during the normal metabolism of cells in the human body. Exposure to ultraviolet radiation, cigarette smoking, and other environmental pollutants enhances free radicals in the human body. The destructive effects of free radicals may also cause harm to membranes, enzymes, and DNA, leading to several human diseases such as cancer, atherosclerosis, malaria, coronavirus disease (COVID-19), rheumatoid arthritis, and neurodegenerative illnesses. This process occurs when there is an imbalance between free radicals and antioxidant defenses. Since antioxidants scavenge free radicals and repair damaged cells, increasing the consumption of fruits and vegetables containing high antioxidant values is recommended to slow down oxidative stress in the body. Additionally, natural products demonstrated a wide range of biological impacts such as anti-inflammatory, anti-aging, anti-atherosclerosis, and anti-cancer properties. Hence, in this review article, our goal is to explore the role of natural therapeutic antioxidant effects to reduce oxidative stress in the diseases.

Haskap Berry Phenolic Subclasses Differentially Impact Cellular Stress Sensing in Primary and Immortalized Dermal Fibroblasts.

It is generally accepted that dietary phenolics from fruits are of significant importance to human health. Unfortunately, there is minimal published data on how differences in phenolic structure(s) impact biological pathways at cellular and molecular levels. We observed that haskap berry extracts isolated with ethanol:formic acid:water or phenolic subclass fractions separated using different concentrations of ethanol (40% and 100%) impacted cell growth in a positive manner. All fractions and extracts significantly increased population doubling times. All extracts and fractions reduced intracellular free radicals; however, there were differences in these effects, indicating different abilities to scavenge free radicals. The extracts and fractions also exhibited differing impacts on transcripts encoding the antioxidant enzymes (CAT, SOD1, GPX1, GSS and HMOX1) and the phosphorylation state of nuclear factor-κB (NF-κB). We further observed that extracts and fractions containing different phenolic structures had divergent impacts on the mammalian target of rapamycin (mTOR) and sirtuin 1 (SIRT1). siRNA-mediated knockdown of SIRT1 transcripts demonstrated that this enzyme is key to eliciting haskap phenolic(s) impact on cells. We postulate that phenolic synergism is of significant importance when evaluating their dietary impact.

Oxyresveratrol-Loaded PLGA Nanoparticles Inhibit Oxygen Free Radical Production by Human Monocytes: Role in Nanoparticle Biocompatibility.

Oxyresveratrol, a polyphenol extracted from the plant Artocarpus lakoocha Roxb, has been reported to be an antioxidant and an oxygen-free radical scavenger. We investigated whether oxyresveratrol affects the generation of superoxide anion (O2-) by human monocytes, which are powerful reactive oxygen species (ROS) producers. We found that oxyresveratrol inhibited the O2- production induced upon stimulation of monocytes with ß-glucan, a well known fungal immune cell activator. We then investigated whether the inclusion of oxyresveratrol into nanoparticles could modulate its effects on O2- release. We synthesized poly(lactic-co-glycolic acid) (PLGA) nanoparticles, and we assessed their effects on monocytes. We found that empty PLGA nanoparticles induced O2- production by resting monocytes and enhanced the formation of this radical in ß-glucan-stimulated monocytes. Interestingly, the insertion of oxyresveratrol into PLGA nanoparticles significantly inhibited the O2- production elicited by unloaded nanoparticles in resting monocytes as well as the synergistic effect of nanoparticles and ß-glucan. Our results indicate that oxyresveratrol is able to inhibit ROS production by activated monocytes, and its inclusion into PLGA nanoparticles mitigates the oxidative effects due to the interaction between these nanoparticles and resting monocytes. Moreover, oxyresveratrol can contrast the synergistic effects of nanoparticles with fungal agents that could be present in the patient tissues. Therefore, oxyresveratrol is a natural compound able to make PLGA nanoparticles more biocompatible.

Lysosome-targetable selenium-doped carbon nanodots for in situ scavenging free radicals in living cells and mice.

Lysosome-targetable selenium-doped carbon nanodots (Lyso-Se-CDs) that can efficiently scavenge lysosomal •OH in living cells and mice were designed in this research. Se-CDs with redox-responsive fluorescence (λex = 379 nm, λem = 471 nm, quantum yield = 7.1%) were initially synthesized from selenocystine by a facile hydrothermal method, followed by the surface modification with morpholine, a lysosome targeting moiety. The as-synthesized Lyso-Se-CDs exhibited excellent colloidal stability, efficient scavenging abilities towards •OH, low biotoxicity, as well as good biocompatibility and lysosome targetability. Due to these desirable properties, Lyso-Se-CDs had been successfully utilized for rescuing cells from elevated lysosomal •OH levels. More importantly, Lyso-Se-CDs efficiently relieved phorbol 12-myristate 13-acetate (PMA) triggered ear inflammation in live mice. These findings reveal that Lyso-Se-CDs are potent candidates for treating •OH-related inflammation.

Antioxidant enzyme activities and immune responses in rainbow trout (Onchorhynchus mykiss) juveniles fed diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts.

In the present study, antioxidant activity, immune responses, and growth performance of rainbow trout (Onchorhynchus mykiss) juveniles fed with diets supplemented with dandelion (Taraxacum officinalis) and lichen (Usnea barbata) extracts were assessed. Four different concentrations of aqueous methanolic extract of the plants (0% (control), 0.1%, 0.5%, and 1% (D, dandelion; L, lichen) were added to the diets, and fish were fed for 75 days. On the 15th, 45th, and 75th day of the study, liver antioxidant enzyme activities were determined, and immune responses were determined every 15th day. The results showed that SOD activity increased in the fish group of 0.1% D on the 15th and 45th day compared to control; however, it was lower in all the lichen extract-treated groups than in control at almost all sampling times, except on the 15th day in the 0.1% L group. CAT activity showed an increased value (P < 0.05) in 0.5% L and 1% L treated fish groups on the 15th day, in fish of 1% D and 1% L groups on 45th and on 75th day in 0.1% D group. GPX activity increased on the 15th day of the study in fish of 0.1% D group, on the 45th day in 1% D and 1% L groups and on the 75th day in fish of 0.5% D, 0.1% D, and 0.5% L groups (P < 0.05). G6PDH enhanced in all treatment groups compared to control on the 15th day, except in 0.1% L and 0.5% L groups. An elevated G6PDH activity was also observed on the 75th day of the study in 0.5% D, 1% D, and 0.5% L fish groups. An increase on lipid peroxidation (LP) was observed in all L groups on the 45th day of the study. Lysozyme activity was determined to be the highest in 0.5% and 1% L on the 45th day, in 0.1% L on the 60th day and in the 0.5% L fish group on the 75th day compared to control (P < 0.05). Myeloperoxidase was found to be the highest at the end of the study in 1% L fish group compared to the control (P < 0.05). In conclusion, we suggest the use of dandelion to combat oxidative stress and to lower FCR and the use of lichen to modulate the immune response in rainbow trout. The use of such products will be economical for aquaculture and harmless for the environment.

Green Coffea robusta (Coffea canephora) from Lampung province effect toward free radicals in chickens infected with Salmonella enteritidis bacteria.

Background: Foodborne diseases are caused by acquired pathogenic bacteria such as Salmonella enteritidis. It causes an intestinal imbalance and the microbial toxins found in the gastrointestinal tract induce symptoms such as diarrhea. Coffee contains active ingredients such as antioxidants and is used as an anti-inflammatory agent by reducing pro-inflammatory cytokine levels in the body. Aim: The purpose of this study was to determine the interaction between Lampung's robusta coffee and tissue damage in chickens infected by S. enteritidis. Methods: This study used first-day-old Isa brown layer chickens (n = 60), which were divided into five treatment groups. The negative control group consisted of healthy and normal chickens, whereas the positive control group consisted of chickens infected with S. enteritidis bacteria at a concentration of 108 CFU/ml. Groups T1, T2, and T3 were given coffee extract with doses of 500 mg/kg BW (low dose), 1,000 mg/kg BW (moderate dose), and 1,500 mg/kg BW (high dose), respectively, and then infected with S. enteritidis bacteria at a concentration of 108 CFU/ml. The coffee extract and bacteria were given orally via a feeding tube at a volume of 0.5 ml per chick. The extract was given for 14 days (from day 3 to day 16), and the bacteria were given on days 16 and 17. On day 18, the chickens were necropsied. The malondialdehyde (MDA) level was analyzed using one-way analysis of variance test with the GLM procedure (<0.05), while the tissue histopath was analyzed using a descriptive qualitative study to examine the ileal damage. Results: The results showed that the MDA levels (nmol/l) decreased in treatment groups T1, T2, and T3 compared to the positive control. On the contrary, we found improvements in the ileum histopathology of group T1 and T2 in the form of normal and regular intestinal epithelium arrangement of the ileum, long intestinal villi, and decreased total leukocytes. Conclusion: Green coffee robusta has the potential to increase antioxidants and reduce inflammation in the small intestine of chickens infected with S. enteritidis.

Molecular Mechanism of Vitamin K2 Protection against Amyloid-ß-Induced Cytotoxicity.

The pathological role of vitamin K2 in Alzheimer's disease (AD) involves a definite link between impaired cognitive functions and decreased serum vitamin K levels. Vitamin K2 supplementation may have a protective effect on AD. However, the mechanism underlying vitamin K2 protection has not been elucidated. With the amyloid-ß (Aß) cascade hypothesis, we constructed a clone containing the C-terminal fragment of amyloid precursor protein (ß-CTF/APP), transfected in astroglioma C6 cells and used this cell model (ß-CTF/C6) to study the protective effect of vitamin K2 against Aß cytotoxicity. Both cellular and biochemical assays, including cell viability and reactive oxygen species (ROS), assays assay, and Western blot and caspase activity analyses, were used to characterize and unveil the protective role and mechanism of vitamin K2 protecting against Aß-induced cytotoxicity. Vitamin K2 treatment dose-dependently decreased the death of neural cells. The protective effect of vitamin K2 could be abolished by adding warfarin, a vitamin K2 antagonist. The addition of vitamin K2 reduced the ROS formation and inhibited the caspase-3 mediated apoptosis induced by Aß peptides, indicating that the mechanism underlying the vitamin K2 protection is likely against Aß-mediated apoptosis. Inhibitor assay and Western blot analyses revealed that the possible mechanism of vitamin K2 protection against Aß-mediated apoptosis might be via regulating phosphatidylinositol 3-kinase (PI3K) associated-signaling pathway and inhibiting caspase-3-mediated apoptosis. Our study demonstrates that vitamin K2 can protect neural cells against Aß toxicity.

Multidirectional effects of saponin fraction isolated from the leaves of sea buckthorn Elaeagnus rhamnoides (L.) A. Nelson.

Many studies show that saponins isolated from various plants have a cytotoxic effect on cancer cells inducing apoptosis and autophagy. On the other hand, saponins also exhibit a number of beneficial properties, such as antioxidant properties. Thus, saponins can be considered both in terms of their therapeutic and protective effects during anticancer treatment. In this study, we investigated the effect of the saponin fraction isolated from sea buckthorn (Elaeagnus rhamnoides (L.) A. Nelson) leaves on the viability of HL-60 cancer cells using resazurin assay and its ability to induction of apoptosis with Annexin V-FITC and propidium iodide (PI) double staining. Moreover, we studied its effect on the oxidative stress induced by H2O2, and anti-platelet and anticoagulant potential in whole blood using T-TAS, a microchip-based flow chamber system. We observed that the saponin fraction significantly decreased the viability of HL-60 cells at the concentration above 50 µg/mL and induced apoptosis at the concentration of 100 µg/mL. Moreover, we observed that saponin fraction used at lower concentrations, such as 0.5 and 1 µg/mL, stimulated HL-60 cells and increased their viability. The saponin fraction also decreased the level of free radicals and reduced oxidative DNA damage measured by the comet assay. However, at high concentration of oxidant H2O2 equal 5 mM, we noticed that the saponin fraction at 50 µg/mL increased the level of free radicals in HL-60 cells. We also demonstrated anticoagulant potential of the saponin fraction at the concentration of 50 µg/mL. Our results indicate that the saponin fraction obtained from sea buckthorn leaves can show both chemotherapeutic and chemoprotective potential.

The mechanism and prevention of mitochondrial injury after exercise.

With the development of society, physical activity has come to be an effective means by which people pursue good health to improve the quality of life. However, with the increase of intensity and the passage of time, exercise injury has become a hazard that can no longer be ignored. It is imperative to find effective ways to inhibit or reduce the negative effects of exercise. Mitochondria are important organelles involved in exercise and play an important role in exercise injury and prevention. Studies have found that exercise preconditioning and increased mitochondrial nutrition can effectively decrease mitochondrial damage after exercise. Against this background, some of the newest developments in this important field are reviewed here. The results discussed indicate that exercise preconditioning and supplement mitochondrial nutrition need to be increased to prevent exercise-related injuries.

Grape polyphenols supplementation for exercise-induced oxidative stress.

Exercise induces free radicals' overproduction and therefore, an enhancement of oxidative stress, defined as an imbalance between the production of reactive species and the intrinsic antioxidant defense. Redox activity of reactive species plays an important and a positive role on exercise adaptation, but these species at very high concentrations have detrimental effects. As a result, the use of antioxidant supplements for reducing oxidative stress can be an effective health strategy to maintain an optimal antioxidant status. In this sense, grapes are an important source of natural antioxidants due to their high content in polyphenols. They have shown antioxidant potential benefits for the reduction of intense exercise effect in athletes of different sport disciplines. Consequently, it is plausible to hypothesize that a strategic supplementation with grape based products may be a good approach to mitigate the exercise induced oxidative stress. The goal of this review is to present the state of the art of supplementation effects with grape beverages and grape extracts on the oxidative stress markers in athletes. The data of polyphenolic dosages, participant characteristics and exercise protocols are reported.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50 °C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe = 866.0 ppm), 125Te{1H} (δTe = 422.0 ppm) and 31P{1H} (δP = -1.0, -13.0 and -15.0 ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened in vitro and ex vivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

Free Radicals as a Double-Edged Sword: The Cancer Preventive and Therapeutic Roles of Curcumin.

Free radicals, generally composed of reactive oxygen species (ROS) and reactive nitrogen species (RNS), are generated in the body by various endogenous and exogenous systems. The overproduction of free radicals is known to cause several chronic diseases including cancer. However, increased production of free radicals by chemotherapeutic drugs is also associated with apoptosis in cancer cells, indicating the dual nature of free radicals. Among various natural compounds, curcumin manifests as an antioxidant in normal cells that helps in the prevention of carcinogenesis. It also acts as a prooxidant in cancer cells and is associated with inducing apoptosis. Curcumin quenches free radicals, induces antioxidant enzymes (catalase, superoxide dismutase, glutathione peroxidase), and upregulates antioxidative protein markers-Nrf2 and HO-1 that lead to the suppression of cellular oxidative stress. In cancer cells, curcumin aggressively increases ROS that results in DNA damage and subsequently cancer cell death. It also sensitizes drug-resistant cancer cells and increases the anticancer effects of chemotherapeutic drugs. Thus, curcumin shows beneficial effects in prevention, treatment and chemosensitization of cancer cells. In this review, we will discuss the dual role of free radicals as well as the chemopreventive and chemotherapeutic effects of curcumin and its analogues against cancer.

Do free radical NETwork and oxidative stress disparities in African Americans enhance their vulnerability to SARS-CoV-2 infection and COVID-19 severity?

This review focuses on the hypothetical mechanisms for enhanced vulnerability of African Americans to SARS-CoV-2 infection, COVID-19 severity, and increased deaths. A disproportionately higher number of African Americans are afflicted with autoimmune and inflammatory diseases (e.g., diabetes, hypertension, obesity), and SARS-CoV-2 has helped expose these health disparities. Several factors including socioeconomic status, inferior health care, and work circumstances contribute to these disparities. Identifying potential inflammatory biomarkers and decreasing basal levels in high-risk individuals with comorbidities through preventive measures is critical. Immune cells, particularly neutrophils, protect us against pathogens (bacteria, fungi, and viruses) through increased generation of free radicals or oxidants and neutrophil extracellular traps (NETs) that ensnare pathogens, killing them extracellularly. However, continued generation of NETs coupled with the lack of prompt removal pose danger to host cells. NET levels are increased during pro-inflammatory diseases. COVID-19 patients exhibit elevated NET levels, depending upon disease severity. Conceivably, high-risk individuals with elevated basal NET levels would exhibit hyper-inflammation when infected with SARS-CoV-2, amplifying disease severity and deaths. Drugs inhibiting oxidant formation and vitamin supplements decreased NET formation in mice models of inflammation. Thus, it is conceivable that preventive treatments lowering NET levels and inflammation in high-risk individuals could mitigate SARS-CoV-2-induced complications and decrease mortality.