NRF-2 and nonalcoholic fatty liver disease.

Currently, chronic liver diseases have conditioned morbidity and mortality, many of these with a metabolic, toxicologic, immunologic, viral, or other etiology. Thus, a transcription factor that has been of huge importance for biomedical research is NRF-2. The latter is considered a principal component of the antioxidant mechanism, and it has been acknowledged that it impairs the function of NRF-2 in many liver diseases and that it forms an essential part of the pathologic changes that occur in the liver to contain inflammation and damage. Within the investigations and experiments carried out, there are isolated drugs, many of them related to plants and natural extracts that possess antioxidant properties through the NRF-2 signaling pathway, or even involving the stimulation of the transcription target proteins of NRF-2. Notwithstanding all of these experimental findings, to date there is not sufficient clinical evidence to justify the use of NRF-2 in medical practice.

Effect of Silymarin Supplementation on Physical Performance, Muscle and Myocardium Histological Changes, Bodyweight, and Food Consumption in Rats Subjected to Regular Exercise Training.

(1) Background: Regular exercise induces physiological and morphological changes in the organisms, but excessive training loads may induce damage and impair recovery or muscle growth. The purpose of the study was to evaluate the impact of Silymarin (SM) consumption on endurance capacity, muscle/cardiac histological changes, bodyweight, and food intake in rats subjected to 60 min of regular exercise training (RET) five days per week. (2) Methods: Male Wistar rats were subjected to an eight-week RET treadmill program and were previously administered SM and vitamin C. Bodyweight and food consumption were measured and registered. The maximal endurance capacity (MEC) test was performed at weeks one and eight. After the last training session, the animals were sacrificed, and samples of quadriceps/gastrocnemius and cardiac tissue were obtained and process for histological analyzes. (3) Results: SM consumption improved muscle recovery, inflammation, and damaged tissue, and promoted hypertrophy, vascularization, and muscle fiber shape/appearance. MEC increased after eight weeks of RET in all trained groups; moreover, the SM-treated group was enhanced more than the group with vitamin C. There were no significant changes in bodyweight and in food and nutrient consumption along the study. (5) Conclusion: SM supplementation may enhance physical performance, recovery, and muscle hypertrophy during the eight-week RET program.

Asthma: New Integrative Treatment Strategies for the Next Decades.

Asthma is a chronic disease whose main anatomical-functional alterations are grouped into obstruction, nonspecific bronchial hyperreactivity, inflammation and airway remodeling. Currently, the Global Initiative of Asthma 2020 (GINA 2020) suggests classifying it into intermittent cases, slightly persistent, moderately persistent and severely persistent, thus determining the correct guidelines for its therapy. In general, the drugs used for its management are divided into two groups, those with a potential bronchodilator and the controlling agents of inflammation. However, asthmatic treatments continue to evolve, and notable advances have been made possible in biological therapy with monoclonal antibodies and in the relationship between this disease and oxidative stress. This opens a new path to dietary and herbal strategies and the use of antioxidants as a possible therapy that supports conventional pharmacological treatments and reduces their doses and/or adverse effects. This review compiles information from different published research on risk factors, pathophysiology, classification, diagnosis and the main treatments; likewise, it synthesizes the current evidence of herbal medicine for its control. Studies on integrative medicine (IM) therapies for asthmatic control are critically reviewed. An integrative approach to the prevention and management of asthma warrants consideration in clinical practice. The intention is to encourage health professionals and scientists to expand the horizons of basic and clinical research (preclinical, clinical and integrative medicine) on asthma control.

Genotoxic Evaluation of Duloxetine II. The Effect on the Number of Sister Chromatid Exchanges, the Mitotic Index, and the Proliferation Kinetics in Mouse Bone Marrow.

Duloxetine is an antidepressant which has showed valuable results, particularly in patients with major depression. This type of drugs is known to require genotoxic studies as part of their preclinical safety evaluation. In the case of duloxetine, however, there have been controversial results. Therefore, we considered it worthwhile to extend studies on the matter in an attempt to reach a conclusion. The present assay was made in mouse bone marrow to evaluate the capacity of the drug to induce sister chromatid exchanges (SCE), as well as to modify the proliferation kinetics and the mitotic index. Three doses of the antidepressant were tested (2, 20, and 200 mg/kg), besides the control mice were administered with purified water, and the positive treated animals administered with 1 mg/kg of doxorubicin. The results indicated a moderate but significant increase of SCE with the three tested doses, no effect regarding the mitotic index and a small reduction in the proliferation kinetics. Although in our assay the drug showed a lower effect, the present study agreed with a previous report that analyzed the amount of micronuclei in mouse peripheral blood, and it confirmed the relevance of evaluating the genotoxic effect of antidepressants, specifically duloxetine by applying diverse tests.

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse.

Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

Cytotoxic and antiproliferative effect of tepary bean lectins on C33-A, MCF-7, SKNSH, and SW480 cell lines.

For many years, several studies have been employing lectin from vegetables in order to prove its toxic effect on various cell lines. In this work, we analyzed the cytotoxic, antiproliferative, and post-incubatory effect of pure tepary bean lectins on four lines of malignant cells: C33-A; MCF-7; SKNSH, and SW480. The tests were carried out employing MTT and 3[H]-thymidine assays. The results showed that after 24 h of lectin exposure, the cells lines showed a dose-dependent cytotoxic effect, the effect being higher on MCF-7, while C33-A showed the highest resistance. Cell proliferation studies showed that the toxic effect induced by lectins is higher even when lectins are removed, and in fact, the inhibition of proliferation continues after 48 h. Due to the use of two techniques to analyze the cytotoxic and antiproliferative effect, differences were observed in the results, which can be explained by the fact that one technique is based on metabolic reactions, while the other is based on the 3[H]-thymidine incorporated in DNA by cells under division. These results allow concluding that lectins exert a cytotoxic effect after 24 h of exposure, exhibiting a dose-dependent effect. In some cases, the cytotoxic effect is higher even when the lectins are eliminated, however, in other cases, the cells showed a proliferative effect.

Evaluation of the Antigenotoxic Potential of Two Types of Chayote (Sechium edule) Juices.

Sechium edule (Jacq.) Swartz is a perennial herbaceous climbing plant with tendrils and tuberous roots belonging to the Cucurbitaceae family. Its fruits ("chayote"), stems, roots, and leaves are edible and are commonly ingested by humans. It has shown medicinal properties attributed to its bioactive compounds (vitamins, phenolic acids, flavonoids, carotenoids, triterpenoids, polyphenolic compounds, phytosterols, and cucurbitacins), which together have been associated with the control and prevention of chronic and infectious diseases, highlighting its antibacterial, anti-cardiovascular/antihypertensive, antiepileptic, anti-inflammatory, hepatoprotective, antiproliferative, and antioxidant activities. The objective of the study was to determine the antigenotoxic potential of two types of fresh chayote juice (filtered (FChJ) and unfiltered (UFChJ)) against DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay (MN). The juices were consumed freely for 2 weeks. A negative control, a control group of each juice, a positive batch [B[a]P], and two combined batches (B[a]P plus FChJ or UFChJ) were included. Blood smears were stained and observed under a microscope to quantify the number of micronucleated normochromic erythrocytes (MNNEs). The results indicate: (a) B[a]P increased the frequency of MNNEs and reduced the rate of PEs; and (b) no juice produced toxic effects or induced MN. On the contrary, both juices were genoprotective. However, the most significant effect was presented by UFChJ at the end of the experiment (70%). It is suggested that UFChJ has a greater amount of fiber and/or phytochemicals that favor the therapeutic effect. Possibly, the genoprotection is also related to its antioxidant capacity.

Phytochemicals and Their Usefulness in the Maintenance of Health.

Inflammation is the immune system's first biological response to infection, injury, or irritation. Evidence suggests that the anti-inflammatory effect is mediated by the regulation of various inflammatory cytokines, such as nitric oxide, interleukins, tumor necrosis factor alpha-α, interferon gamma-γ, as well as the non-cytokine mediator, prostaglandin E2. Currently, the mechanism of action and clinical usefulness of phytochemicals is known; their action on the activity of cytokines, free radicals, and oxidative stress. The latter are of great relevance in the development of diseases, such that the evidence collected demonstrates the beneficial effects of phytochemicals in maintaining health. Epidemiological evidence indicates that regular consumption of fruits and vegetables is related to a low risk of developing cancer and other chronic diseases.

In vitro effect of sodium fluoride on malondialdehyde concentration and on superoxide dismutase, catalase, and glutathione peroxidase in human erythrocytes.

The aim of this paper was to describe the in vitro effect of sodium fluoride (NaF) on the specific activity of the major erythrocyte antioxidant enzymes, as well as on the membrane malondialdehyde concentration, as indicators of oxidative stress. For this purpose, human erythrocytes were incubated with NaF (0, 7, 28, 56, and 100 µg/mL) or NaF (100 µg/mL) + vitamin E (1, 2.5, 5 and 10 µg/mL). The malondialdehyde (MDA) concentration on the surface of the erythrocytes was determined, as were the enzymatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GlPx). Our results demonstrated that erythrocytes incubated with increasing NaF concentrations had an increased MDA concentration, along with decreased activity of antioxidant enzymes. The presence of vitamin E partially reversed the toxic effects of NaF on erythrocytes. These findings suggest that NaF induces oxidative stress in erythrocytes in vitro, and this stress is partially reversed by the presence of vitamin E.

Antioxidant Activity and Anticarcinogenic Effect of Extracts from Bouvardia ternifolia (Cav.) Schltdl.

According to the available ethnobotanical data, the Bouvardia ternifolia plant has long been used in Mexican traditional medicine to relieve the symptoms of inflammation. In the present study, the cytotoxic effect of extracts obtained from the flowers, leaves and stems of B. ternifolia using hexane, ethyl acetate (AcOEt) and methanol (MeOH) was evaluated by applying them to the SiHa and MDA-MB-231 cancer cell lines. An MTT reduction assay was carried out along with = biological activity assessments, and the content of total phenols, tannins, anthocyanins, betalains and saponins was quantified. According to the obtained results, nine extracts exhibited a cytotoxic effect against both the SiHa and MDA lines. The highest cytotoxicity was measured for leaves treated with the AcOEt (ID50 of 75 µg/mL was obtained for MDA and 58.75 µg/mL for SiHa) as well as inhibition on ABTS•+ against DPPH• radical, while MeOH treatment of stems and AcOEt of flowers yielded the most significant antioxidant capacity (90.29% and 90.11% ABTS•+ radical trapping). Moreover, the highest phenolic compound content was measured in the stems (134.971 ± 0.294 mg EAG/g), while tannins were more abundant in the leaves (257.646 mg eq cat/g) and saponins were most prevalent in the flowers (20 ± 0 HU/mg). Screening tests indicated the presence of flavonoids, steroids, terpenes and coumarins, as well as ursolic acid, in all the studied extracts. These results demonstrate the biological potential of B. ternifolia.

Effects of Spirulina maxima on a Model of Sexual Dysfunction in Streptozotocin-Induced Diabetic Male Rats.

Arthrospira (Spirulina) maxima (SM) is a cyanobacterium that has a long history of being used as human food. In recent years, several investigations have shown its beneficial biological effects, among which its antioxidant capacity has been highlighted. The purpose of this study was to evaluate the effects of SM on body weight, glycemia, sexual behavior, sperm quality, testosterone levels, sex organ weights, and the activity of antioxidant enzymes in diabetic male rats (a disease characterized by an increase in reactive oxygen species). The experiment consisted of six groups of sexually expert adult males (n = 6): (1) control (vehicle); (2) streptozotocin (STZ)-65 mg/kg; (3) SM-400 mg/kg; (4) STZ + SM-100 mg/kg; (5) STZ + SM-200 mg/kg; and (6) STZ + SM-400 mg/kg. Sexual behavior tests were performed during the first 3 h of the dark period under dim red illumination. Our results showed that SM significantly improved sexual behavior and sperm quality vs. diabetic animals. Likewise, while the enzymatic activities of SOD and GPx increased, TBARS lipoperoxidation decreased and testosterone levels increased. In view of the findings, it is suggested that SM may potentially be used as a nutraceutical for the treatment of diabetic male sexual dysfunction due to its antioxidant property.

Investigation on the protective effects of cranberry against the DNA damage induced by benzo[a]pyrene.

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.

Prognostic impact of the preoperatory neutrophil/lymphocyte index on early surgical complications of patients with colorectal cancer.

Colorectal cancer (CRC) is found among those with greatest frequency and exponential increase worldwide, with high mortality rates, which are observed as increasing due to the postsurgical complications that come to present. Systemic inflammation participates in the development and progression of cancer; therefore, inflammatory and/or immunological response markers such as the neutrophil/lymphocyte index (NLI) can aid us in predicting the poor results of our interventions. The purpose of our study was to determine the impact of an NLI of ≥2.6 as a predictor of early postsurgical complications. By means of a prospective cohort, we analyzed 158 patients with CRC who were submitted to elective surgery with a later 30-day follow-up. We found that the preoperatory NLI of ≥2.6 obtained an odds ratio (OR) = 2.24 (95% confidence interval [CI], 1.15-4.36) as a prognostic factor of early postsurgical complications according to the Clavien-Dindo classification scale, which represents a low prognostic impact due to its predictive yield with low accuracy, which is the opposite of what other reports have previously published. The use of chemotherapy before the surgical procedure was also determined to be a risk factor for post-surgical complications.

Effects of Germination and Popping on the Anti-Nutritional Compounds and the Digestibility of Amaranthus hypochondriacus Seeds.

Amaranth seeds, although a valuable food in Mexico, contain anti-nutritional compounds that can affect food quality. As a part of this work, the proximate composition, fatty acid profile, protein digestibility, and the effect of germination and popping of Amaranthus hypochondriacus seeds was analyzed with the aim of eliminating anti-nutritional compounds. Untreated seeds comprised of 11.35-18.8% protein and 0.27-13.39% lipids, including omega 3, 6, and 9 fatty acids such as oleic, linoleic, linolenic, and arachidonic acid. The main minerals detected were Ca+2, K+1, and Mg+2. Nevertheless in vitro studies indicate that germination significantly improved digestibility, whereby treatments aimed at reducing anti-nutritional compounds decreased lectin concentration, while significantly increasing tannins and completely eliminating trypsins and saponins.

A Complete Review of Mexican Plants with Teratogenic Effects.

In Mexico, the use of medicinal plants is the first alternative to treat the diseases of the most economically vulnerable population. Therefore, this review offers a list of Mexican plants (native and introduced) with teratogenic effects and describes their main alterations, teratogenic compounds, and the models and doses used. Our results identified 63 species with teratogenic effects (19 native) and the main alterations that were found in the nervous system and axial skeleton, induced by compounds such as alkaloids, terpenes, and flavonoids. Additionally, a group of hallucinogenic plants rich in alkaloids employed by indigenous groups without teratogenic studies were identified. Our conclusion shows that several of the identified species are employed in Mexican traditional medicine and that the teratogenic species most distributed in Mexico are Astragalus mollissimus, Astragalus lentiginosus, and Lupinus formosus. Considering the total number of plants in Mexico (≈29,000 total vascular plants), to date, existing research in the area shows that Mexican plants with teratogenic effects represent ≈0.22% of the total species of these in the country. This indicates a clear need to intensify the evaluation of the teratogenic effect of Mexican plants.

Potential protective effect of beta-caryophyllene against cadmium chloride-induced damage to the male reproductive system in mouse.

Cadmium is a metal that can affect the male reproductive process, possibly leading to infertility. In contrast, beta-caryophyllene (BC) is a sesquiterpene that has shown antigenotoxic, anticancer, and antioxidant properties. Therefore, the aim of the present study was to determine the protective effect of BC against the deleterious effects of cadmium chloride (CC) on various mouse testicular and sperm parameters. We tested three doses of BC (20, 200, and 400 mg/kg) given before and during exposure to 3 mg/kg CC (six days after a single administration). Our results show significant alleviation of the damage induced by CC after the three doses of BC. Regarding the sperm concentration and morphology, the protection with the high dose was complete, and regarding sperm mobility and viability, the protection was more than 74%. In the comet assay, the highest dose showed a reduction of 92.5% in the damage induced by CC, and regarding the number of micronuclei in the spermatids, the reduction was 83.3%. In the oxidative evaluation, regarding sperm lipoperoxidation, the improvement was complete with the high dose, and in the ABTS.+ test, the improvement in the response to the BC high dose was 26.3%. Regarding testicular lipoperoxidation and protein oxidation, the protective effects of the high BC dose were 87.6% and 89.9%, respectively. We also found that BC protected against the histological and morphometric alterations induced by CC. Therefore, our study clearly demonstrates the beneficial, chemopreventive effect of BC against the mouse sperm and testicular alterations induced by CC.

Polyphenols as potential enhancers of stem cell therapy against neurodegeneration.

The potential of polyphenols for treating chronic-degenerative diseases (particularly neurodegenerative diseases) is attractive. However, the selection of the best polyphenol for each treatment, the mechanisms by which they act, and their efficacy are frequently discussed. In this review, the basics and the advances in the field, as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays, are compiled and discussed. Thus, stem cells exhibit several responses when polyphenols are added to their environment, which could provide us with knowledge for advancing the elucidation of the origin of neurodegeneration. But also, polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to neurodegeneration. In this regard, flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects; but increasing reports are involving other polyphenols. Even if some facts limiting bioactivity prevent them from conventional use, some natural polyphenols and derivatives hold the promise for being improved compounds, judged by their induced effects. The current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

Phytochemicals in Skeletal Muscle Health: Effects of Curcumin (from Curcuma longa Linn) and Sulforaphane (from Brassicaceae) on Muscle Function, Recovery and Therapy of Muscle Atrophy.

The mobility of the human body depends on, among other things, muscle health, which can be affected by several situations, such as aging, increased oxidative stress, malnutrition, cancer, and the lack or excess of physical exercise, among others. Genetic, metabolic, hormonal, and nutritional factors are intricately involved in maintaining the balance that allows proper muscle function and fiber recovery; therefore, the breakdown of the balance among these elements can trigger muscle atrophy. The study from the nutrigenomic perspective of nutritional factors has drawn wide attention recently; one of these is the use of certain compounds derived from foods and plants known as phytochemicals, to which various biological activities have been described and attributed in terms of benefiting health in many respects. This work addresses the effect that the phytochemicals curcumin from Curcuma longa Linn and sulforaphane from Brassicaceae species have shown to exert on muscle function, recovery, and the prevention of muscle atrophy, and describes the impact on muscle health in general. In the same manner, there are future perspectives in research on novel compounds as potential agents in the prevention or treatment of medical conditions that affect muscle health.

Opuntia spp. in Human Health: A Comprehensive Summary on Its Pharmacological, Therapeutic and Preventive Properties. Part 2.

Plants of the genus Opuntia spp are widely distributed in Africa, Asia, Australia and America. Specifically, Mexico has the largest number of wild species; mainly O. streptacantha, O. hyptiacantha, O. albicarpa, O. megacantha and O. ficus-indica. The latter being the most cultivated and domesticated species. Its main bioactive compounds include pigments (carotenoids, betalains and betacyanins), vitamins, flavonoids (isorhamnetin, kaempferol, quercetin) and phenolic compounds. Together, they favor the different plant parts and are considered phytochemically important and associated with control, progression and prevention of some chronic and infectious diseases. Part 1 collected information on its preventive actions against atherosclerotic cardiovascular diseases, diabetes and obesity, hepatoprotection, effects on human infertility and chemopreventive capacity. Now, this second review (Part 2), compiles the data from published research (in vitro, in vivo, and clinical studies) on its neuroprotective, anti-inflammatory, antiulcerative, antimicrobial, antiviral potential and in the treatment of skin wounds. The aim of both reviews is to provide scientific evidences of its beneficial properties and to encourage health professionals and researchers to expand studies on the pharmacological and therapeutic effects of Opuntia spp.

Phytochemicals and modulation of exercise-induced oxidative stress: a novel overview of antioxidants.

The practice of physical exercise induces a series of physiological changes in the body at different levels, either acutely or chronically. During exercise, the increase in oxygen consumption promotes the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are necessary to maintain homeostasis. ROS/RNS activate cellular signaling pathways, such as the antioxidant cytoprotective systems, inflammation, and cell proliferation, which are crucial for cell survival. However, in exhaustive-extended physical exercise, workloads can exceed the endogenous antioxidant defenses, which may be related to impairment of muscle contraction, fatigue, and a decrease in athletic performance. This review addresses the role of some antioxidants from plant-derived extracts called phytochemicals that can mediate the response to oxidative stress induced by physical exercise by activating signaling pathways, such as Nrf2/Keap1/ARE, responsible for the endogenous antioxidant response and possibly having an impact on sports performance.