Tomato lipidic extract plus selenium decrease prostatic hyperplasia, dihydrotestosterone and androgen receptor expression versus finasteride in rats.

PURPOSE: Evaluate the therapeutic effect of a tomato lipidic extract (STE) in combination with selenium (Se) on rats with prostatic hyperplasia (PH) and to observe its possible mechanisms of action and synergism versus finasteride. MATERIALS AND METHODS: 54 male Wistar rats of nine weeks old were divided in Control (C), PH, Finasteride (F), STE, Se, F + STE, F + Se, STE + Se and F + STE + Se with testosterone enanthate (except C). After 4 weeks of treatment administration, prostate weight, bladder weight, diuresis, prooxidant and antioxidant activity, dihydrotestosterone (DHT), androgen receptor (AR) expression and anatomopathological analysis were determined. RESULTS: STE + Se decreased prostate weight 53.8% versus 28% in F group, also STE + Se decreased significatively glandular hyperplasia, prooxidant activity, DHT and AR expression and increased diuresis and antioxidant activity versus finasteride which increased MDA in prostate. CONCLUSIONS: These results demonstrate a greater therapeutic and beneficial effect of tomato lipidic extract in combination with Se in young rats with PH with respect to finasteride without increase prooxidant activity.

α-Mangostin induces oxidative damage, mitochondrial dysfunction, and apoptosis in a triple-negative breast cancer model.

Triple-negative breast cancer (TNBC) does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor; therefore, TNBC lacks targeted therapy, and chemotherapy is the only available treatment for this illness but causes side effects. A putative strategy for the treatment of TNBC could be the use of the polyphenols such as α-Mangostin (α-M), which has shown anticancerogenic effects in different cancer models and can modulate the inflammatory and prooxidant state in several pathological models. The redox state, oxidative stress (OS), and oxidative damage are highly related to cancer development and its treatment. Thus, this study aimed to evaluate the effects of α-M on redox state, mitochondrial metabolism, and apoptosis in 4T1 mammary carcinoma cells. We found that α-M decreases both protein levels and enzymatic activity of catalase, and increases reactive oxygen species, oxidized proteins and glutathione disulfide, which demonstrates that α-M induces oxidative damage. We also found that α-M promotes mitochondrial dysfunction by abating basal respiration, the respiration ligated to oxidative phosphorylation (OXPHOS), and the rate control of whole 4T1 cells. Additionally, α-M also decreases the levels of OXPHOS subunits of mitochondrial complexes I, II, III, and adenosine triphosphate synthase, the activity of mitochondrial complex I as well as the levels of peroxisome proliferator-activated receptor-gamma co-activator 1α, showing a mitochondrial mass reduction. Then, oxidative damage and mitochondrial dysfunction induced by α-M induce apoptosis of 4T1 cells, which is evidenced by B cell lymphoma 2 decrease and caspase 3 cleavage. Taken together, our results suggest that α-M induces OS and mitochondrial dysfunction, resulting in 4T1 cell death through apoptotic mechanisms.

The Protective Role of Ozone Therapy in Kidney Disease: A Review.

Ozone (O3) is a reactive oxygen species (ROS) that can interact with cellular components and cause oxidative stress. Following said logic, if O3 induces such a stressful milieu, how does it exert antioxidant functions? This is mediated by controlled toxicity produced by low concentrations of O3, which enhance the cell's suppliance of antioxidant properties without causing any further damage. Therapeutic concentrations vary extensively, although 50 µg/mL is commonly used in experimental and clinical procedures, given that augmented concentrations might work as germicides or cause endogenous damage. O3 therapy has been shown to be effective when applied before or after traumatic renal procedures, whether caused by ischemia, xenobiotics, chronic damage, or other models. In this review, we focus on discussing the role of O3 therapy in different models of kidney damage associated with fibrosis, apoptosis, oxidative stress, and inflammation. We integrate and report knowledge about O3 in renal therapy, debunking skepticism towards unconventional medicine, explaining its proven therapeutic properties, and thus providing background for its use in further research as well as in clinical settings.

Nutriepigenomics in Environmental-Associated Oxidative Stress.

Complex molecular mechanisms define our responses to environmental stimuli. Beyond the DNA sequence itself, epigenetic machinery orchestrates changes in gene expression induced by diet, physical activity, stress and pollution, among others. Importantly, nutrition has a strong impact on epigenetic players and, consequently, sustains a promising role in the regulation of cellular responses such as oxidative stress. As oxidative stress is a natural physiological process where the presence of reactive oxygen-derived species and nitrogen-derived species overcomes the uptake strategy of antioxidant defenses, it plays an essential role in epigenetic changes induced by environmental pollutants and culminates in signaling the disruption of redox control. In this review, we present an update on epigenetic mechanisms induced by environmental factors that lead to oxidative stress and potentially to pathogenesis and disease progression in humans. In addition, we introduce the microenvironment factors (physical contacts, nutrients, extracellular vesicle-mediated communication) that influence the epigenetic regulation of cellular responses. Understanding the mechanisms by which nutrients influence the epigenome, and thus global transcription, is crucial for future early diagnostic and therapeutic efforts in the field of environmental medicine.

Antimicrobial Activity of Spices Popularly Used in Mexico against Urinary Tract Infections.

Urinary tract infections (UTIs) are the most common infectious diseases worldwide. These infections are common in all people; however, they are more prevalent in women than in men. The main microorganism that causes 80-90% of UTIs is Escherichia coli. However, other bacteria such as Staphylococcus aureus, Enterococcus faecalis, Pseudomonas aeruginosa, Proteus mirabilis, and Klebsiella pneumoniae cause UTIs, and antibiotics are required to treat them. However, UTI treatment can be complicated by antibiotic resistance and biofilm formation. Therefore, medicinal plants, such as spices generally added to foods, can be a therapeutic alternative due to the variety of phytochemicals such as polyphenols, saponins, alkaloids, and terpenes present in their extracts that exert antimicrobial activity. Essential oils extracted from spices have been used to demonstrate their antimicrobial efficacy against strains of pathogens isolated from UTI patients and their synergistic effect with antibiotics. This article summarizes relevant findings on the antimicrobial activity of cinnamon, clove, cumin, oregano, pepper, and rosemary, spices popularly used in Mexico against the uropathogens responsible for UTIs.

Therapeutic Effect of Curcumin on 5/6Nx Hypertriglyceridemia: Association with the Improvement of Renal Mitochondrial ß-Oxidation and Lipid Metabolism in Kidney and Liver.

Chronic kidney disease (CKD) prevalence is constantly increasing, and dyslipidemia in this disease is characteristic, favoring cardiovascular events. However, the mechanisms of CKD dyslipidemia are not fully understood. The use of curcumin (CUR) in CKD models such as 5/6 nephrectomy (5/6Nx) has shown multiple beneficial effects, so it has been proposed to correct dyslipidemia without side effects. This work aimed to characterize CUR's potential therapeutic effect on dyslipidemia and alterations in lipid metabolism and mitochondrial ß-oxidation in the liver and kidney in 5/6Nx. Male Wistar rats were subjected to 5/6Nx and progressed by 4 weeks; meanwhile, CUR (120 mg/kg) was administered for weeks 5 to 8. Our results showed that CUR reversed the increase in liver and kidney damage and hypertriglyceridemia induced by 5/6Nx. CUR also reversed mitochondrial membrane depolarization and ß-oxidation disorders in the kidney and the increased lipid uptake and the high levels of proteins involved in fatty acid synthesis in the liver and kidney. CUR also decreased lipogenesis and increased mitochondrial biogenesis markers in the liver. Therefore, we concluded that the therapeutic effect of curcumin on 5/6Nx hypertriglyceridemia is associated with the restoration of renal mitochondrial ß-oxidation and the reduction in lipid synthesis and uptake in the kidneys and liver.

Antioxidant/anti-inflammatory effect of Mg2+ in coronavirus disease 2019 (COVID-19).

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), characterised by high levels of inflammation and oxidative stress (OS). Oxidative stress induces oxidative damage to lipids, proteins, and DNA, causing tissue damage. Both inflammation and OS contribute to multi-organ failure in severe cases. Magnesium (Mg2+ ) regulates many processes, including antioxidant and anti-inflammatory responses, as well as the proper functioning of other micronutrients such as vitamin D. In addition, Mg2+ participates as a second signalling messenger in the activation of T cells. Therefore, Mg2+ deficiency can cause immunodeficiency, exaggerated acute inflammatory response, decreased antioxidant response, and OS. Supplementation with Mg2+ has an anti-inflammatory response by reducing the levels of nuclear factor kappa B (NF-κB), interleukin (IL) -6, and tumor necrosis factor alpha. Furthermore, Mg2+ supplementation improves mitochondrial function and increases the antioxidant glutathione (GSH) content, reducing OS. Therefore, Mg2+ supplementation is a potential way to reduce inflammation and OS, strengthening the immune system to manage COVID-19. This narrative review will address Mg2+ deficiency associated with a worse disease prognosis, Mg2+ supplementation as a potent antioxidant and anti-inflammatory therapy during and after COVID-19 disease, and suggest that randomised controlled trials are indicated.

Characterization of Mitochondrial Proteome and Function in Luminal A and Basal-like Breast Cancer Subtypes Reveals Alteration in Mitochondrial Dynamics and Bioenergetics Relevant to Their Diagnosis.

Breast cancer (BC) is the most prevalent cancer and the one with the highest mortality among women worldwide. Although the molecular classification of BC has been a helpful tool for diagnosing and predicting the treatment of BC, developments are still being made to improve the diagnosis and find new therapeutic targets. Mitochondrial dysfunction is a crucial feature of cancer, which can be associated with cancer aggressiveness. Although the importance of mitochondrial dynamics in cancer is well recognized, its involvement in the mitochondrial function and bioenergetics context in BC molecular subtypes has been scantly explored. In this study, we combined mitochondrial function and bioenergetics experiments in MCF7 and MDA-MB-231 cell lines with statistical and bioinformatics analyses of the mitochondrial proteome of luminal A and basal-like tumors. We demonstrate that basal-like tumors exhibit a vicious cycle between mitochondrial fusion and fission; impaired but not completely inactive mitochondrial function; and the Warburg effect, associated with decreased oxidative phosphorylation (OXPHOS) complexes I and III. Together with the results obtained in the cell lines and the mitochondrial proteome analysis, two mitochondrial signatures were proposed: one signature reflecting alterations in mitochondrial functions and a second signature exclusively of OXPHOS, which allow us to distinguish between luminal A and basal-like tumors.

Antinociceptive effect of garlic, garlic preparations and derivative compounds.

BACKGROUND AND OBJECTIVE: The antinociceptive effects of garlic have shown promise in treating different chronic diseases in humans, such as knee osteoarthritis, rheumatoid arthritis and peripheral arterial occlusive disease stage II. The most common garlic products are garlic powder (dried garlic), steam distilled garlic oils, garlic oil macerate and aged garlic extract. These commercial products contain organosulphur compounds (OSCs) that have been extensively evaluated in preclinical models and some clinical assays to treat different diseases against pain. In this review, we describe the importance of some bioactive compounds found in garlic and their role in treating pain. MATERIALS & METHODS: A systematic search of the literature in Dimensions, PubMed, Scopus, and Web of Science was performed. Terms and preselected keywords relating to garlic, its derivatives and organusulphure compounds in acute, chronic and neuropathic pain, were used to perform a systematic literature search. Two independent reviewers screened the papers for inclusion and assessed the methodological quality. RESULTS & DISCUSSION: The antinociceptive activity of garlic and its OSC is related to its antioxidant and anti-inflammatory properties, which may be explained by the ability to block the synthesis of PGs, pro-inflammatory cytokines and interferon-γ, by the reduction COX-2 activity and increasing the levels of anti-inflammatory cytokines. Besides, garlic extract is an activator of TRPA1 and TRPV1, where the principal responsible for this activation are OSC. CONCLUSION: The relationship between these pathways allows a better understanding how garlic and its derivates could be carrying out its pharmacological action over the management of acute and chronic pain and provide a base by further investigations. SIGNIFICANCE: Antinociceptive effect of garlic and its OSCs has been extensively evaluated in preclinical models and clinical assays to treat different diseases, contributing to the modulation of inflammation as an essential factor in reducing pain. The current review emphasizes the potential therapeutic effect of garlic and its derivatives in treatment of pain and related mechanisms of action. Moreover, it provides information about the potential clinical use in patients with painful conditions.

Effect of Dietary Magnesium Content on Intestinal Microbiota of Rats.

BACKGROUND: Magnesium is a mineral that modulates several physiological processes. However, its relationship with intestinal microbiota has been scarcely studied. Therefore, this study aimed to assess the role of dietary magnesium content to modulate the intestinal microbiota of Wistar male rats. METHODS: Rats were randomly assigned one of three diets: a control diet (C-Mg; 1000 mg/kg), a low magnesium content diet (L-Mg; 60 mg/kg), and a high magnesium content diet (H-Mg; 6000 mg/kg), for two weeks. After treatment, fecal samples were collected. Microbiota composition was assessed by sequencing the V3-V4 hypervariable region. RESULTS: The C-Mg and L-Mg groups had more diversity than H-Mg group. CF231, SMB53, Dorea, Lactobacillus and Turibacter were enriched in the L-Mg group. In contrast, the phyla Proteobacteria, Parabacteroides, Butyricimonas, and Victivallis were overrepresented in the H-Mg group. PICRUSt analysis indicated that fecal microbiota of the L-Mg group were encoded with an increased abundance of metabolic pathways involving carbohydrate metabolism and butanoate metabolism. CONCLUSION: Dietary magnesium supplementation can result in intestinal dysbiosis development in a situation where there is no magnesium deficiency. Conversely, low dietary magnesium consumption is associated with microbiota with a higher capacity to harvest energy from the diet.

Chronic impairment of mitochondrial bioenergetics and ß-oxidation promotes experimental AKI-to-CKD transition induced by folic acid.

Recent studies suggest that mitochondrial bioenergetics and oxidative stress alterations may be common mechanisms involved in the progression of renal damage. However, the evolution of the mitochondrial alterations over time and the possible effects that their prevention could have in the progression of renal damage are not clear. Folic acid (FA)-induced kidney damage is a widely used experimental model to induce acute kidney injury (AKI), which can evolve to chronic kidney disease (CKD). Therefore, it has been extensively applied to study the mechanisms involved in AKI-to-CKD transition. We previously demonstrated that one day after FA administration, N-acetyl-cysteine (NAC) pre-administration prevented the development of AKI induced by FA. Such therapeutic effect was related to mitochondrial preservation. In the present study, we characterized the temporal course of mitochondrial bioenergetics and redox state alterations along the progression of renal damage induced by FA. Mitochondrial function was studied at different time points and showed a sustained impairment in oxidative phosphorylation capacity and a decrease in ß-oxidation, decoupling, mitochondrial membrane potential depolarization and a pro-oxidative state, attributed to the reduction in activity of complexes I and III and mitochondrial cristae effacement, thus favoring the transition from AKI to CKD. Furthermore, the mitochondrial protection by NAC administration before AKI prevented not only the long-term deterioration of mitochondrial function at the chronic stage, but also CKD development. Taken together, our results support the idea that the prevention of mitochondrial dysfunction during an AKI event can be a useful strategy to prevent the transition to CKD.

Antioxidant Properties and Protective Effects of Some Species of the Annonaceae, Lamiaceae, and Geraniaceae Families against Neuronal Damage Induced by Excitotoxicity and Cerebral Ischemia.

This study aimed to compare the antioxidant activities of extracts obtained from three plant families and evaluate their therapeutic effect on strokes. Ethanol extracts were obtained from either the leaf or the aerial parts of plants of the families Annonaceae (Annona cherimola, A. diversifolia, A. muricata, A. purpurea, and A. reticulata), Lamiaceae (Salvia amaríssima and S. polystachya), and Geraniaceae (Geranium niveum and G. mexicanum). Extracts were analyzed in terms of hydroxyl radical (OH•), peroxyl radical (ROO•), and superoxide anion (O2•-). The efficiency of the extracts to prevent neuronal death induced by excitotoxicity was tested with the tetrazolium assay, the O2•- scavenging capacity was evaluated with the dihydroethidium dye, and the protective effect of the extracts with the highest antioxidant activity was tested on a stroke experimental model. The extracts' IC50 values (µg/mL) of scavenging varied from 98.9 to 155.04, 4.5 to 102.4, and 20.2 to 118.97 for OH•, ROO•, and O2•-, respectively. In the excitotoxicity model, Annonaceae extracts were highly cytotoxic while Lamiaceae and Geraniaceae reduced intracellular O2•- production and protect neurons against oxidative stress. Salvia polystachya reduced cerebral damage, as well as improved survival and behavior after ischemia. Our results encouraged the use of plant extracts as natural antioxidants to minimize neuronal injury following stroke.

Nordihydroguaiaretic Acid: From Herbal Medicine to Clinical Development for Cancer and Chronic Diseases.

Nordihydroguaiaretic acid (NDGA) is a phenolic lignan obtained from Larrea tridentata, the creosote bush found in Mexico and USA deserts, that has been used in traditional medicine for the treatment of numerous diseases such as cancer, renal, cardiovascular, immunological, and neurological disorders, and even aging. NDGA presents two catechol rings that confer a very potent antioxidant activity by scavenging oxygen free radicals and this may explain part of its therapeutic action. Additional effects include inhibition of lipoxygenases (LOXs) and activation of signaling pathways that impinge on the transcription factor Nuclear Factor Erythroid 2-related Factor (NRF2). On the other hand, the oxidation of the catechols to the corresponding quinones my elicit alterations in proteins and DNA that raise safety concerns. This review describes the current knowledge on NDGA, its targets and side effects, and its synthetic analogs as promising therapeutic agents, highlighting their mechanism of action and clinical projection towards therapy of neurodegenerative, liver, and kidney disease, as well as cancer.

Ethnobotanical, nutritional and medicinal properties of Mexican drylands Cactaceae Fruits: Recent findings and research opportunities.

The Mexican drylands possess enormous biotic and cultural wealth, representing 65% of the national territory. Approximately 50% of Mexican dryland flora is endemic and accompanied by ample local and traditional knowledge. There are certain types of cactus fruits that are being technologically produced. However, there are other cactus fruit that are underutilized and understudied that could be promoted for their sustainable use. Evidence indicates that the genera of Escontria, Myrtilocactus, Hylocereus, and Stenocereus contain bioactive compounds such as betalains and phenols. Opuntia, the most abundant cactus in Mexico, produces fruit known as prickly pears with bioactive compounds that are associated with health benefits. The purpose of this review is to compile the nutritional and functional properties of selected cactus fruits from the Mexican drylands, as well as their use in the health, food, cosmetic, and agricultural industries in order to establish knowledge gaps and well-supported future research directions.

Ergosterol Peroxide Isolated from Oyster Medicinal Mushroom, Pleurotus ostreatus (Agaricomycetes), Potentially Induces Radiosensitivity in Cervical Cancer.

Every year, more than 500,000 new cases of cervical cancer are reported, making it the fourth leading cause of cancer globally. Although human papillomavirus (HPV) vaccines show promise as a protective measure, HPV-related cancers remain a public health problem since the vaccines, which are only specific to certain viral types, are unavailable for mass distribution. Furthermore, the effects of toxicity following ionizing radiation therapy have reoriented views toward the search for radiosensitizers that can reduce toxicity as a consequence of decreased radiation doses. Here, we isolated ergosterol peroxide (EP) from Pleurotus ostreatus and purified it to test its potential effects in vitro. We thus observed that a gradual increase in EP dose correlates with a loss of viability in HeLa and CaSki cervical cell lines. Dose/response curves were constructed using cervical cancer cell lines, as well as normal human peripheral blood mononuclear cells. The selectivity of EP in human lymphocytes and cervical cancer cell lines was tested, and no toxicity was found in normal cells. A combination of treatments revealed a radiosensitizer effect in HeLa cells, when measuring the exposure to EP followed by irradiation with 137Cs. Our findings suggest that EP may be effective as a radiosensitizer in treating cervical cancer.

The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes.

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels.

Goats' Feeding Supplementation with Acacia farnesiana Pods and Their Relationship with Milk Composition: Fatty Acids, Polyphenols, and Antioxidant Activity.

BACKGROUND: Research efforts have focused on the evaluation of the bioactive quality of animal products (milk, cheese, meat, and other by-products) contrasting various feeding strategies coming from different ecological zones. The study aimed to describe the fatty acids (FA), polyphenols (P), bioactive compounds (BC), and antioxidant activity (AA) of goat's milk. METHODS: Dairy goats were fed with five systems: (1) Grazing; (2) conventional diet (CD); (3) CD + 10% of Acacia farnesiana (AF) pods; (4) CD + 20% AF; and (5) CD + 30% AF. The fatty acid profile, health promoting and thrombogenic indexes were calculated. Milk extracts were evaluated by HPLC to determent phenolic compounds (gallic, caffeic, chlorogenic, and ferulic acids, catechin, epicatechin, and quercetin). Antioxidant activity of goat's milk extract was evaluated using 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•), oxygen radical absorbance capacity (ORAC), and the ferric reducing antioxidant power (FRAP) assays. RESULTS: Conventional diet showed the highest content of polyunsaturated fatty acids while grazing showed the best n-6:n-3 and the linoleic:alpha linolenic acid ratio. Similarly, grazing and AF boosted the polyphenol content. CONCLUSIONS: Acacia farnesiana inclusion in the goats' diets increased the presence of bioactive compounds and the antioxidant activity while diminishing the cholesterol content of goat's milk.

The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus.

Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of 64 ± 1 years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline 8.9 ± 0.2 vs. posttreatment 8.6 ± 0.3) and the PG (baseline 8.8 ± 0.2 vs. posttreatment 8.4 ± 0.3) compared to the CG (baseline 8.8 ± 0.3 vs. six months 9.1 ± 0.3) although the difference was not statistically significant (p < 0.05). There was a statistically significant decrease (p < 0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline 100 ± 3 vs. posttreatment 57 ± 3, PG: baseline 106 ± 7 vs. posttreatment 77 ± 5, and CG: baseline 94 ± 10 vs. six months 107 ± 11 pg/mL). Likewise, a statistically significant decrease (p < 0.05) in the concentration of the RAGE was found in the EG (baseline 1636 ± 88 vs. posttreatment 1144 ± 68) and the PG (baseline 1506 ± 97 vs. posttreatment 1016 ± 82) compared to CG (baseline 1407 ± 112 vs. six months 1506 ± 128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration number ISRCTN13159380.

Antimicrobial, Antioxidant Activities, and HPLC Determination of the Major Components of Verbena carolina (Verbenaceae).

Verbena carolina L. (Verbenaceae) is used as a decoction in Mexican folk medicine with applications against digestive problems and for dermatological infections. The present work firstly reported HPLC analysis, as well as the free radical scavenging capacity of the extracts and isolated compounds. Antimicrobial analyses of these substances against the bacteria Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Salmonella typhi and the fungi Candida albicans, Trichophyton mentagrophytes and T. rubrum were also tested, as well as the acute oral toxicity in mice of aqueous extracts. Major secondary metabolites in V. carolina extracts were isolated by conventional phytochemical methods which consisted of three terpenoids ((1), (3) and (4)) and four phenolic compounds ((2), (4)-(6)). Their contents were determined by HPLC in six different samples from different locations. The results indicated that ursolic acid (1), hispidulin (2), verbenaline (3), hastatoside (4), verbascoside (5), hispidulin 7-O-ß-d-glucuronopyranoside (6) and pectolinaringenin-7-O-α-d-glucuronopyranoside (7) were the main constituents and ranged from 0.17 to 3.37 mg/g of dried plant, with verbascoside being the most abundant and with a significant antioxidant activity in reactive oxygen species (ROS). Hispidulin was the only active compound against T. mentagrophytes and T. rubrum. The aqueous extract showed no significant toxicity (LD50: > 5000 mg/mL). To our knowledge, this is the first comprehensive report of the chemical characterization of V. carolina and also of the activity of its constituents towards reactive oxygen species and dermatophytes, and its safety for consumption.

Alpha-mangostin: Anti-inflammatory and antioxidant effects on established collagen-induced arthritis in DBA/1J mice.

Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.