Anti-Obesity Therapeutic Targets Studied In Silico and In Vivo: A Systematic Review.

In the age of information technology and the additional computational search tools and software available, this systematic review aimed to identify potential therapeutic targets for obesity, evaluated in silico and subsequently validated in vivo. The systematic review was initially guided by the research question "What therapeutic targets have been used in in silico analysis for the treatment of obesity?" and structured based on the acronym PECo (P, problem; E, exposure; Co, context). The systematic review protocol was formulated and registered in PROSPERO (CRD42022353808) in accordance with the Preferred Reporting Items Checklist for Systematic Review and Meta-Analysis Protocols (PRISMA-P), and the PRISMA was followed for the systematic review. The studies were selected according to the eligibility criteria, aligned with PECo, in the following databases: PubMed, ScienceDirect, Scopus, Web of Science, BVS, and EMBASE. The search strategy yielded 1142 articles, from which, based on the evaluation criteria, 12 were included in the systematic review. Only seven these articles allowed the identification of both in silico and in vivo reassessed therapeutic targets. Among these targets, five were exclusively experimental, one was exclusively theoretical, and one of the targets presented an experimental portion and a portion obtained by modeling. The predominant methodology used was molecular docking and the most studied target was Human Pancreatic Lipase (HPL) (n = 4). The lack of methodological details resulted in more than 50% of the papers being categorized with an "unclear risk of bias" across eight out of the eleven evaluated criteria. From the current systematic review, it seems evident that integrating in silico methodologies into studies of potential drug targets for the exploration of new therapeutic agents provides an important tool, given the ongoing challenges in controlling obesity.

Jaboticaba (Myrciaria jaboticaba) peel extracts induce reticulum stress and apoptosis in breast cancer cells.

Jaboticaba peel (Myrciaria jaboticaba) is a source of bioactive compounds. We investigated the anticancer activity of ethyl acetate extract (JE1) and hydroethanolic extract (JE2) of Jaboticaba peel against breast cancer. Both JE1 and JE2 inhibited clonogenic potential of MDA-MB-231 cells while JE1 was particularly effective in MCF7 cells. Anchorage-independent growth and cell viability was also inhibited by JE1 and JE2. In addition to growth inhibition, JE1 and JE2 could also inhibit migration and invasion of cells. Interestingly, JE1 and JE2 show selective inhibition towards certain breast cancer cells and biological processes. Mechanistic evaluations showed that JE1 induced PARP cleavage, BAX and BIP indicating apoptotic induction. An elevation of phosphorylated ERK was observed in MCF7 cells in response to JE1 and JE2 along with increased IRE-α and CHOP expression indicating increased endoplasmic stress. Therefore, Jaboticaba peel extracts could be potentially considered for further development for breast cancer inhibition.

Culture matters: A systematic review of antioxidant potential of tree legumes in the semiarid region of Brazil and local processing techniques as a driver of bioaccessibility.

Ethnobotanical studies report that human populations from the Brazilian Caatinga biome use tree legumes (Fabaceae) with medicinal and food purposes. Our study provides a systematic review of the available published information concerning the antioxidant potential of Hymenaea courbaril L. (jatobá), Libidibia ferrea (Mart. Ex Tul.) L.P.Queiroz (jucá), and Dioclea grandiflora Mart. Ex Benth. (mucunã). Furthermore, in this paper, we infer the possible effects of local processing techniques applied to these plants on their antioxidant potential. In order to achieve these goals, we reviewed 52 articles, including studies from ethnobiology (n = 17), chemistry (n = 32), and food studies testing antioxidant activity (n = 17), excluding 14 repetitions. We found that these legume species can inhibit the formation of free radicals and this potential action varies among different parts of the plant. Probably, the presence of phenolic compounds such as phenolic acids and flavonoids, which are not uniformly distributed in the plants, explain their antioxidant activity. Local processing techniques (i.e., roasting, milling) affect the bioaccessibility of antioxidant components of tree legumes, inducing both positive and negative effects. However, studies about the antioxidant potential did not consider local processing techniques in their analyses. Our study highlights that culture is a fundamental driver of nutritional and pharmacological outcomes related to edible resources since it determines which parts of the plant people consume and how they prepare them. Hence, ignoring cultural variables in the analysis of antioxidant activity will produce inaccurate or wrong scientific conclusions.

Can polyphenols improve the gut health status in pre-clinical study with diet-induced obesity?: A protocol for systematic review and/or meta-analysis.

INTRODUCTION: Obesity is characterized as a low-grade inflammation that impairs physiological functions, including intestinal functioning and gut microbiota balance. Dietary polyphenols can be a strategy for obesity management, collaborating to preserve or recover gut health through antioxidant and anti-inflammatory actions, as well as modulators of the microbiota. This study describes a systematic review protocol to elucidate effects of polyphenols on intestinal health of pre-clinical models with diet-induced obesity. AIM: Our aim is to evaluate evidence about polyphenols' effects in the gut microbiota composition and diversity, parameters of the physical and molecular status of the gut barrier in obese models, additionally, understand the possible involved mechanisms. METHODOLOGY: A protocol was developed and published on PROSPERO (Registration No: CRD42021262445). Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols is used to outline the protocol. The articles will be selected according to the PICOS strategy (population, interventions, control, outcome, and study design) in the following databases: PubMed, Science Direct, Scopus, Web of Science, and EMBASE. Experimental studies performed on rats and mice with a control group that describes treatment with polyphenols (from food matrix or crude extracts or isolated compounds) at any frequency, time, and dose will be included. Two reviewers will, independently, select the papers, extract data, and evaluate the data quality. The Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) tool will be used to assess the risk of bias. EXPECTED RESULTS: Results will be showed through of native synthesis and, if possible, a metanalysis will be conducted. The review produced with this protocol can show the scientific evidence level about polyphenols' effects in intestinal health in obesity status.

Nutritional status, diet and viral respiratory infections: perspectives for severe acute respiratory syndrome coronavirus 2.

COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was recognised by the WHO as a pandemic in 2020. Host preparation to combat the virus is an important strategy to avoid COVID-19 severity. Thus, the relationship between eating habits, nutritional status and their effects on the immune response and further implications in viral respiratory infections is an important topic discussed in this review. Malnutrition causes the most diverse alterations in the immune system, suppressing of the immune response and increasing the susceptibility to infections such as SARS-CoV-2. On the other hand, obesity induces low-grade chronic inflammation caused by excess adiposity, which increases angiotensin-converting enzyme 2. It decreases the immune response favouring SARS-CoV-2 virulence and promoting respiratory distress syndrome. The present review highlights the importance of food choices considering their inflammatory effects, consequently increasing the viral susceptibility observed in malnutrition and obesity. Healthy eating habits, micronutrients, bioactive compounds and probiotics are strategies for COVID-19 prevention. Therefore, a diversified and balanced diet can contribute to the improvement of the immune response to viral infections such as COVID-19.

Obesity and the increased risk for COVID-19: mechanisms and nutritional management.

The global COVID-19 (coronavirus disease 2019) pandemic has become a complex problem that overlaps with a growing public health problem, obesity. Obesity alters different components of the innate and adaptive immune responses, creating a chronic and low-grade state of inflammation. Nutritional status is closely related to a better or worse prognosis of viral infections. Excess weight has been recognised as a risk factor for COVID-19 complications. In addition to the direct risk, obesity triggers other diseases such as diabetes and hypertension, increasing the risk of severe COVID-19. The present review explains the diets that induce obesity and the importance of different foods in this process. We also review tissue disruption in obesity, leading to impaired immune responses and the possible mechanisms by which obesity and its co-morbidities increase COVID-19 morbidity and mortality. Nutritional strategies that support the immune system in patients with obesity and with COVID-19 are also discussed in light of the available data, considering the severity of the infection. The discussions held may contribute to combating this global emergency and planning specific public health policy.

Aqueous Extract of Brazilian Berry (Myrciaria jaboticaba) Peel Improves Inflammatory Parameters and Modulates Lactobacillus and Bifidobacterium in Rats with Induced-Colitis.

Natural compounds could be a complementary alternative to inflammatory bowel disease (IBD) management. This study determined the effects of an aqueous extract of Myrciaria jaboticaba peel (EJP) (50 g L-1) on 2,4,6-trinitrobenzenesulfonic acid-induced colitis. Wistar rats were randomized into five groups: HC-healthy control, CC-colitis control, DC-drug control, SJ-short-term treatment with EJP, and LJ-long-term treatment with EJP. The EJP treatments reduced body weight loss, stool consistency score, and spleen enlargement. Gut microbiota was modulated through increased Lactobacillus and Bifidobacterium counts after EJP treatment. Short-chain fatty acids were also higher in the EJP treatment groups. The antioxidant enzyme activities were greater than CC or DC controls. Myeloperoxidase activity (LJ), inducible nitric oxide synthase (LJ/SJ), and intercellular adhesion molecule (SJ) levels were lower than in the CC group. EJP decreased histological scoring, mucosal thickness, and preserved the crypts and histological structure. Therefore, EJP showed beneficial effects and could be potentially used as an adjuvant in IBD treatment.

Aqueous extract of berry (Plinia jaboticaba) byproduct modulates gut microbiota and maintains the balance on antioxidant defense system in rats.

Previous studies have assessed the properties of aqueous extracts, using byproducts such as jaboticaba peel. We have assessed potential antioxidant effects of jaboticaba extract (Plinia jaboticaba) (JAE = 50 g/L) in vitro and in vivo. Healthy Wistar rats received ad libitum JAE for either 15 or 49 days in vivo. Cyanidin-3-O-glucoside, delphinidin-3-O-glucoside, gallic acid, rutin, myricetin, and quercetin were identified as the main polyphenols in JAE. Lipid peroxidation values in the serum and colon were similar throughout the groups. In addition, JAE did not disturb the antioxidant systems. JAE also altered gut microbiota, increasing since Lactobacillus, Bifidobacterium and Enterobacteriaceae counts. Bacterial metabolites were higher in the colon content of rats fed with JAE than in the control group. Given these results, under healthy conditions, JAE dietary supplementation could perform in vivo modulation of gut microbiota, without disturbing the antioxidant system. PRACTICAL APPLICATION: Jaboticaba (Plinia jaboticaba) peel is a rich and often-wasted source of bioactive compounds, such as polyphenols. Previous studies have shown that physiological benefits of this berry. The jaboticaba peel could contribute to antioxidant defense systems; it may also have an effect over gut microbiota related to polyphenols contents. Aqueous extraction may be a practical way of employing the bioactive compounds of jaboticaba peel; these compounds can be consumed daily and safely, and thus have attracted particular attention. This work showed positive impacts of jaboticaba peel treatments on microbiota and antioxidant defense systems, and could guide future clinical studies.