Norma Paniagua-Castro

Obesity contributes to an increase in the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and is diagnosed when hepatic steatosis is accompanied by at least one of the following factors: obesity or overweight, diabetes mellitus, or signs of metabolic abnormalities. MAFLD is a term that encompasses a wide range of liver disorders, ranging from simple steatosis to metabolic steatohepatitis, which can progress to cirrhosis and eventually, hepatocellular carcinoma (HCC). Lipotoxicity generated by a high-fat diet causes liver inflammation, therefore, blocking inflammatory pathways is considered a promising strategy to prevent MAFLD progression. Inflammatory responses and oxidative stress are linked to endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR) pathway. Although drugs such as resmetirom and semaglutide have recently been approved for the treatment of MAFLD, there is still a need to identify complementary therapies with different mechanisms of action. In this context, the present study evaluated the hepatoprotective effect of ellagic acid through the modulation of mRNAs of proteins in the UPR-Perk pathway in a murine model fed a high-calorie diet. This study revealed that the high-calorie diet activated the UPR pathway in response to stress, increasing the expression of the Grp78, Eif2ak3, Eif2α, Ddit3, Atf4, and Nfe2l2 genes in the liver and epididymal adipose tissue. Ellagic acid modulated the pathway genes and reduced levels of glucose, total cholesterol, HDL and VLDL, triglycerides, insulin, and glycated hemoglobin, and could therefore be considered a hepatoprotective agent.

Background/Objectives: Obesity is the primary risk factor for the development of chronic degenerative diseases. Multidisciplinary treatments target multiple pathologies associated with obesity. In this study, a potential adjuvant therapy was evaluated by combining extracts from Hibiscus sabdariffa and Zingiber officinale. These extracts were used in both a simple and liposomal suspension, the latter aimed at enhancing the activity of phenolic compounds and determining various metabolic benefits. Methods: In this research, the use of biotechnological approaches for the development of a liposomal suspension formulation with appropriate characteristics of stability, particle size, polydispersity index, concentration, and zeta potential induced an effective reduction in body weight and epididymal fat in a murine obesity model over 8 and 45 days. Results: Treatment with the liposomal suspension reduced variables in the lipid profile, aspartate aminotransferase activity, and energy expenditure, while also promoting an increase in locomotor activity. Conclusions: Therefore, it is suggested that the liposomal suspension represents an alternative for obesity treatment and the reduction of cardiovascular risks.

Mycetoma is currently considered as a neglected tropical disease. The incidence of mycetoma is unknown but most of the worldwide cases are present in the “mycetoma belt” including countries like Mexico, India, Senegal, and others. The treatment of mycetoma depends on the etiological agent responsible for the case. Treatment success reaches 60 to 90%; however, common treatment has been reported to be ineffective in some cases, due in part to resistance to the prescribed antibiotics. Therefore, it is necessary to develop new therapeutic options. In the past two decades, quinoxaline derivatives have shown relevance as antibacterial agents. Therefore, in this work, esters of quinoxaline 1,4-di-N-oxide derivatives were evaluated in vitro against the reference strain CECT-3052 from N. brasiliensis, six clinical isolates, and macrophages J774A.1 to determine their cytotoxicity and security index. Additionally, nine reference drugs were evaluated as controls. The results show that nine esters of quinoxaline 1,4-di-N-oxide derivatives had a minimum inhibitory concentration (MIC) < 1 µg/mL against the reference strain and four of them (N-05, N-09, N-11, and N-13) had an MIC < 1 µg/mL against the clinical isolates. Therefore, the scaffold quinoxaline 1,4-di-N-oxide could be used to develop new and more potent antinocardial agents.

Chronic kidney disease (CKD) is a burden in low- and middle-income countries, and a late diagnosis with systemic arterial hypertension (SAH) is the major complication of CKD. C-phycoerythrin (CPE) is a bioactive compound derived from Phormidium persicinum that presents anti-inflammatory and antioxidant effects in vitro and nephroprotective effects in vivo. In the current study, we determine the antihypertensive effect of CPE in a 5/6 nephrectomy-induced CKD model using twenty normotensives male Wistar rats, grouped into four groups (n = 5): sham; sham + CPE; 5/6 nephrectomy (NFx); and NFx + CPE. Treatment started a week post-surgery and continued for five weeks, with weekly hemodynamic evaluations. Following treatment, renal function, oxidative stress, and the expression of vascular dysfunction markers were assessed. The renal function analysis revealed CKD hyperfiltration, and the hemodynamic evaluation showed that SAH developed at the third week. AT₁R upregulation and AT₂R downregulation together with Mas1/p-Akt/p-eNOS axis were also observed. CPE treatment mitigated renal damage, preserved renal function, and prevented SAH with the modulation of the vasodilative AT₁R, AT₂R, and Mas1/pAKT/peNOS axis. This result reveals that CPE prevented CKD progression to SAH by avoiding oxidative stress and vascular dysfunction in the kidneys.

Las enfermedades metabólicas, incluyendo la obesidad y la diabetes mellitus tipo 2, representan un grave problema de salud y mortalidad, en México. La Organización Mundial de la Salud (OMS) y otras asociaciones como la Federación internacional de la Diabetes (IDF) y el Programa Nacional de Educación para el Colesterol-Panel de Tratamiento para el Adulto III (NCEP-ATP III) definen el Síndrome Metabólico (SM), como la agrupación de alteraciones metabólicas que conllevan al desarrollo de obesidad, hipertensión y diabetes mellitus. El objetivo de este estudio fue desarrollar un modelo de SM en roedores CD1 utilizando una dieta hipercalórica y determinar las ventajas y/o desventajas comparado con otros modelos murinos. Se utilizaron ratones CD1 hembras y machos se dividieron en 2 grupos por género, un grupo control y otro grupo con dieta hipercalórica durante 10 semanas. Los resultados obtenidos mostraron que la dieta hipercalórica es eficiente para desarrollar las alteraciones metabólicas presentes en el SM, se observaron mejores resultados en los ratones macho, por lo que se sugiere la utilización en este género para evitar los cambios hormonales presentes en las hembras adultas

Background. Little is known about the effects of cocoa and its main flavanols on the prothrombotic state associated with the development of hypertension in diet-induced obesity models. Purpose. To evaluate the effects of cocoa powder, cocoa extract and their main flavanols on plasma biomarkers related to impaired coagulation and fibrinolysis and its association with hypertension and obesity-related metabolic disorders in rats fed a hypercaloric diet. Methods. Male Wistar rats were randomly assigned to 7 treatment groups (n = 7): normal diet (ND); hypercaloric diet control group (HCD); HCD + cocoa powder (CO); HCD + cocoa extract (CO-EX); HCD + (−)-epicatechin (EPI); HCD + (+)-catechin (CAT); and HCD + procyanidin B2 (PB2). Blood pressure was measured using the tail-cuff method (week 7). At the end of the experimental period (week 8), rats were sacrificed and blood samples were collected immediately for coagulation and biochemical analyses. Results. Oral administration of CO, CO-EX and their main flavanols significantly decreased plasma biomarkers related to impaired coagulation and fibrinolysis (vWF, FVIII, fibrinogen and PAI-1) in rats fed a hypercaloric diet. These effects were associated with decreased systolic and diastolic blood pressure, aortic oxidative stress (MDA levels) and improvement of dyslipidemia, insulin resistance and circulating markers of inflammation (TNF-α, IL-6 and CRP) compared to the HCD group. Conclusion. Our results showed that cocoa and its main flavanols may improve endothelial dysfunction and exert their antihypertensive effects by decreasing the prothrombotic state in rats fed a hypercaloric diet. Moreover, improvement of obesity-related metabolic disorders may also contribute to their BP-lowering effect.

Brown algae and its carotenoids have been shown to have a positive influence on obesity and its comorbidities. This study evaluated the effect of Undaria pinnatifida and fucoxanthin on biochemical, physiological and inflammation markers related to obesity and on the expression of genes engaged on white adipose tissue lipid metabolism in a murine model of diet-induced obesity. The treatments improved energy expenditure, β-oxidation and adipogenesis by upregulating PPARα, PGC1α, PPARγ and UCP-1. Adipogenesis was also confirmed by image analysis of the retroperitoneal adipose tissue, by measuring cell area, perimeter and cellular density. Additionally, the treatments, ameliorated adipose tissue accumulation, insulin resistance, blood pressure, cholesterol and triglycerides concentration in serum, and reduced lipogenesis and inflammation by downregulating acetyl-CoA carboxylase (ACC) gene expression, increasing serum concentration and expression of adiponectin as well as downregulating IL-6 expression. Both fucoxanthin and Undaria pinnatifida may be considered for treating obesity and other diseases related.

Quercus sideroxyla is a wood species whose bark has phenolic compound and should be considered to be bioactive; the hypoglycemic and genotoxic properties of Q. sideroxyla bark were evaluated in this study. Total phenolic compound was determined in crude extract (CE) and organic extract (OE). The OE has the highest amount of phenols (724.1 ± 12.0 GAE/g). Besides, both CE and OE demonstrated effect over the inhibition of α‐amylase in vitro. Hypoglycemic activity was assessed by glucose tolerance curve and the area under curve (UAC); OE showed the highest hypoglycemic activity. In addition, diabetes was induced by streptozotocin (65 mg/kg) and the extracts (50 mg/kg) were administered for 10 days; OE showed hypoglycemic effect compared with diabetic control and decreased hepatic lipid peroxidation. Acute toxicity and genotoxicity were evaluated in CE; results of acute toxicity did not show any mortality. Besides, the comet assay showed that CE at a dose of 100 mg/kg did not show any genotoxic effect when evaluated at 24 h, whereas it induced slight damage at 200 mg/kg, with the formation of type 1 comets.

Evaluation of the phenolic compounds and antioxidant activity ofCedrela odorataL. andJuglans regiaL. bark extracts was performedin vitro.Juglans regiashowed greater extract concentration and higher antioxidant activity. Hypoglycemic activity in rats was assessed by generating a glucose tolerance curve and determining the area under the curve (AUC). Diabetes was later induced by an injection with streptozotocin (65 mg/kg of b.w.) and confirmed after 24 hours. The extract was administered (200 mg/kg b.w.) over 10 days, and blood glucose was monitored and compared with a control group. The glucose AUC showed a hypoglycemic effect ofJ. regiaandC. odoratain normal rats. Both extracts reduced hepatic lipid peroxidation in diabetic rats. Polyphenolic extracts reduced cholesterol levels in a hypercholesterolemic mouse model and decreased hepatic lipid peroxidation. Polyphenolic extract doses of 100 and 200 mg/kg b.w. were administered alone or with cyclophosphamide (CPA) 50 mg/kg ip, which was used as a positive control. Analyses were performed using leukocytes in a comet assay after 4 and 24 h of treatment. Genotoxic effects were evaluated by the comet assay, which showed that whileJ. regiaextract had no effect,C. odorataextract induced slight damage at 200 mg/kg, with the formation of type 0 and 1 comets.