Applicability of Isolates and Fractions of Plant Extracts in Murine Models in Type II Diabetes: A Systematic Review

Type II diabetes mellitus is one of the most common public health problems worldwide. Its increasing prevalence in several countries and the difficult metabolic control of individuals with the disease justify studying strategies for primary prevention. The population has sought alternative and cheaper ways to treat the disease, including the use of plants considered medicinal by the population. In this study, we carried out a systematic review on the applicability of isolates and fractions of plant extracts in animal models in type II diabetes. A literature search was performed in MEDLINE/PubMed and Scopus databases. Studies using other experimental animals (horses, rabbits, and monkeys) and humans as well as articles in Chinese, German, and Russian were excluded. We assessed the quality of the studies included by using the criteria described in the ARRIVE guidelines. In general, the animals that received fractions or isolates presented reduced blood glucose levels, normalization of body weight and plasma insulin levels, and reduced total triglycerides and cholesterol. In addition, we observed wide variation among the analyzed parameters, which hindered comparison between the studies found. In further studies, standardized reports and experimental design would help to establish comparable study groups and advance the overall knowledge, thus facilitating translatability from animal data to human clinical conditions

Evaluation of the healing effect of the extract of cabbage (Brassica oleracea var captata) in Wistar rats

O objetivo deste trabalho foi investigar os efeitos cicatrizantes do extrato de Brassica oleracea var. capitata a 10% nas formulações pomada e bálsamo, analisando histológicamente as feridas induzidas em modelo animal. Foram feitas cinco feridas cirúrgicas por animal com o auxilio de um bisturi em local demarcado com a boca de um tubo de ensaio de 10 mm umedecida em fucsina. Os animais foram agrupados aleatoriamente. Foram avaliados quatro tratamentos com seis repetições: pomada a base de brassica sp. 10%, bálsamo a base de brassica sp. a 10%, Dersani® e salina 0,9%; A cada 4 dias os animais foram pesados, as feridas foram medidas, e os fragmentos retirados para análise histológica. Os dados de fechamento da ferida foram analisados estatisticamente pelo teste de Tukey (p>0,05); os fragmentos foram incluídos em parafina e as lâminas analisada em microscópio de polarização. Os resultados demonstraram que o uso do bálsamo promoveu melhor taxa de cicatrização, seguido pela pomada, Dersani® e salina 0,9%, obteve uma maior quantidade de fibras colágenas tipo I e melhor organização dessas fibras.The objective of this work was to investigate the healing effects of the extract of Brassica oleracea var. capitata to 10% in the formulations ointment and balsam, analyzing histologically the wounds induced in animal model. They were made five surgical wounds by animal, with the aid of a bistoury, in place demarcated through the opening of a test tube of 10 mm humidified in fucsina. The animals were aleatorily separate. They were appraised four treatments with six repetitions: ointment to the base of brassica sp. to 10%, balsam to the base of brassica sp. to 10%, Dersani® and saline 0,9%. Of 4 in 4 days the animals were heavy, the wounds were measured and the fragments retired for histological analysis. The data of closing of the wound were analyzed statistically by the Tukey test (p>0,05). The fragments were included in paraffin and the glass slides analyzed in polarization microscope. The results demonstrated that the balsam presented better cicatrization rate, followed for the ointment, Dersani® and saline 0,9%, and it obtained a larger amount of type I collagen fibers and better organization of those fibers

Action of plant extracts in the repair of skin wounds in diabetic rats

Objetivo: Investigar o efeito da aplicação tópica da pomada à base de Strycnos pseudoquina nas concentrações 5 e 10% na cicatrização de feridas cutâneas em ratos diabéticos. Material e Método: Amostras de S. pseudoquina foram coletadas no Município de Rio Verde, Goiás, Brasil e em seguida submetido a prospecção fitoquímica. O extrato foi emulsificado em lanolina nas concetrações 5% e 10%. Foram utilizados trinta ratos Wistar que após a indução do diabetes com estreptozotocina, foram divididos em 5 grupos de 6 animais: Sal: feridas tratadas com 0,9% de solução salina; VH (veículo da pomada): feridas tratadas com 0,6 g de creme de lanolina; SS (Sulfadiazina de Prata): feridas tratadas com 0,6 g de creme de Sulfadiazina de Prata (0,01%); ES5: feridas tratadas com pomada a base de S. pseudoquina (5%); ES10: feridas tratadas com pomada a base de S. pseudoquina (10%). Três feridas circulares de 12 mm de diâmetro foram realizadas no dorso dos animais e fragmentos das feridas foram retirados para análises histológicas e bioquímicas a cada 7 dias durante 21 dias. Resultados: Os grupos que receberam o extrato de S. pseudoquina nas concentrações 5 e 10% apresentaram maior taxa de fechamento das feridas, maior quantidade de células, vasos sanguíneos e aumento do colágeno III e I. Os marcadores de estresse oxidativo foram menores nos grupos ES5 e ES10, e os níveis de enzimas antioxidantes foram maiores nestes mesmos grupos. Conclusão: Os resultados deste trabalho demonstraram que a aplicação tópica de pomada à base de S. pseudoquina promove um reparo cutâneo rápido e eficaz em ratos diabéticosObjective: Investigate the effect of topical application of the ointment of Strychnos pseudoquina in concentrations of 5 to 10% in the skin wound healing in diabetic rats. Material and Methods: Samples of S. pseudoquina were collected in Rio Verde, Goiás, Brazil, and then submitted to phytochemical prospection. The extract was emulsified in lanolin at concentrations of 5% and 10%. Thirty rats were used which after diabetes induction with streptozotocin, were divided into 5 groups of 6 animals: Sal: wounds treated with 0.9% saline solution; VH (Ointment vehicle): wounds treated with 0.6 g of lanolin cream; SS (Silver Sulfadiazine): wounds treated with 0.6 g of silver sulfadiazine cream (1%); ES5: wounds treated with ointment base S. pseudoquina (5%); ES10: wounds treated with ointment base S. pseudoquina (10%). Three circular wounds of 12mm in diameter were made on the animal‟s back and fragments of the wounds were removed for histological and biochemical analysis each 7 days for 21 days. Results: The groups that received concentrations of 5 and 10% of S. pseudoquina extract had higher closing rate of wounds and increase of cells, blood vessels, collagen III and I. The oxidative stress markers were lower in the groups ES5 and ES10 and levels of antioxidant enzymes were higher in the same groups. Conclusion: The results of this work have shown that topical application of S. pseudoquina ointment promotes fast and effective skin repair in diabetic rats.Fundação de Amparo à Pesquisa do Estado de Minas Gerai

Cutaneous Redox Senescence

Our current understanding of skin cell senescence involves the role of environmental stressors (UV, O3, cigarette smoke, particulate matter, etc.), lifestyle (diet, exercise, etc.) as well as genetic factors (metabolic changes, hormonal, etc.). The common mechanism of action of these stressors is the disturbance of cellular redox balance characterized by increased free radicals and reactive oxygen species (ROS), and when these overload the intrinsic antioxidant defense system, it can lead to an oxidative stress cellular condition. The main redox mechanisms that activate cellular senescence in the skin involve (1) the oxidative damage of telomeres causing their shortening; (2) the oxidation of proteomes and DNA damage; (3) an a in lysosomal mass through the increased activity of resident enzymes such as senescence-associated β-galactosidase (SA-β-gal) as well as other proteins that are products of lysosomal activity; (4) and the increased expression of SASP, in particular pro-inflammatory cytokines transcriptionally regulated by NF-κB. However, the main targets of ROS on the skin are the proteome (oxi-proteome), followed by telomeres, nucleic acids (DNAs), lipids, proteins, and cytoplasmic organelles. As a result, cell cycle arrest pathways, lipid peroxidation, increased lysosomal content and dysfunctional mitochondria, and SASP synthesis occur. Furthermore, oxidative stress in skin cells increases the activity of p16INK4A and p53 as inhibitors of Rb and CDks, which are important for maintaining the cell cycle. p53 also promotes the inactivation of mTOR-mediated autophagic and apoptotic pathways, leading to senescence. However, these markers alone cannot establish the state of cellular senescence, and multiple analyses are encouraged for confirmation. An updated and more comprehensive approach to investigating skin senescence should include further assays of ox-inflammatory molecular pathways that can consolidate the understanding of cutaneous redox senescence

OxInflammatory Responses in the Wound Healing Process: A Systematic Review

Significant sums are spent every year to find effective treatments to control inflammation and speed up the repair of damaged skin. This study investigated the main mechanisms involved in the skin wound cure. Consequently, it offered guidance to develop new therapies to control OxInflammation and infection and decrease functional loss and cost issues. This systematic review was conducted using the PRISMA guidelines, with a structured search in the MEDLINE (PubMed), Scopus, and Web of Science databases, analyzing 23 original studies. Bias analysis and study quality were assessed using the SYRCLE tool (Prospero number is CRD262 936). Our results highlight the activation of membrane receptors (IFN-δ, TNF-α, toll-like) in phagocytes, especially macrophages, during early wound healing. The STAT1, IP3, and NF-kβ pathways are positively regulated, while Ca2+ mobilization correlates with ROS production and NLRP3 inflammasome activation. This pathway activation leads to the proteolytic cleavage of caspase-1, releasing IL-1β and IL-18, which are responsible for immune modulation and vasodilation. Mediators such as IL-1, iNOS, TNF-α, and TGF-β are released, influencing pro- and anti-inflammatory cascades, increasing ROS levels, and inducing the oxidation of lipids, proteins, and DNA. During healing, the respiratory burst depletes antioxidant defenses (SOD, CAT, GST), creating a pro-oxidative environment. The IFN-δ pathway, ROS production, and inflammatory markers establish a positive feedback loop, recruiting more polymorphonuclear cells and reinforcing the positive interaction between oxidative stress and inflammation. This process is crucial because, in the immune system, the vicious positive cycle between ROS, the oxidative environment, and, above all, the activation of the NLRP3 inflammasome inappropriately triggers hypoxia, increases ROS levels, activates pro-inflammatory cytokines and inhibits the antioxidant action and resolution of anti-inflammatory cytokines, contributing to the evolution of chronic inflammation and tissue damage

Anti-Inflammatory, Antioxidant, and Skin Regenerative Potential of Secondary Metabolites from Plants of the Brassicaceae Family: A Systematic Review of In Vitro and In Vivo Preclinical Evidence (Biological Activities Brassicaceae Skin Diseases)

The Brassicaceae family constitutes some of the most well-studied natural products in the world, due to their anti-inflammatory, anti-oxidative, and pro-regenerative properties as well as their ubiquitous distribution across the world. To evaluate the potential efficacy of the Brassicaceae family in the treatment of inflammatory skin disorders and wounds, based on preclinical evidence from in vivo and in vitro studies. This systematic review was performed according to the PRISMA guidelines, using a structured search on the PubMed-Medline, Scopus, and Web of Science platforms. The studies included were those that used murine models and in vitro studies to investigate the effect of Brassicaceae on skin disorders. Bias analysis and methodological quality assessments were examined through SYRCLE’s RoB tool. Brassicaceae have shown positive impacts on inflammatory regulation of the skin, accelerating the wound healing process, and inhibiting the development of edema. The studies showed that the Brassicaceae family has antioxidant activity and effects on the modulation of cyclooxygenase 2 and the nuclear factor kappa β (NFκβ) pathway. The secondary metabolites present in Brassicas are polyphenols (68.75%; n = 11), terpenes/carotenoids (31.25%; n = 5), and glycosylates (25%; n = 4), which are responsible for their anti-inflammatory, healing, and antioxidant effects. In addition, the current evidence is reliable because the bias analysis showed a low risk of bias. Our review indicates that compounds derived from Brassicaceae present exceptional potential to treat inflammatory skin diseases and accelerate cutaneous wound healing. We hope that our critical analysis can help to expedite clinical research and to reduce methodological bias, thereby improving the quality of evidence in future research. The registration number on the Prospero platform is CRD42021262953

Ozone Exposure Controls Oxidative Stress and the Inflammatory Process of Hepatocytes in Murine Models

(1) Background: Ozone exposure is a promising tool for treating liver damage since it is known to control the release of free radicals and increase the expression of antioxidant enzymes. The objective is to investigate the main intracellular pathways activated after exposure to ozone, considering the dosage of antioxidant enzymes and markers of oxidative stress. (2) Methods: This systematic review was performed based on the PRISMA guidelines and using a structured search in MEDLINE (PubMed), Scopus, and Web of Science. Bias analysis and methodological quality assessments were examined using the SYRCLE Risk of Bias tool. (3) Results: Nineteen studies were selected. The results showed that the exposure to ozone has a protective effect on liver tissue, promoting a decrease in inflammatory markers and a reduction in oxidative stress in liver tissue. In addition, ozone exposure also promoted an increase in antioxidant enzymes. The morphological consequences of controlling these intracellular pathways were reducing the tissue inflammatory process and reducing areas of degeneration and necrosis. (4) Conclusions: Ozone exposure has a beneficial effect on models of liver injury through the decrease in oxidative stress in tissue and inflammatory markers. In addition, it regulates the Nrf2/ARE antioxidant pathway and blocks the NF-κB inflammatory pathway

Does antibiotic use accelerate or retard cutaneous repair? A systematic review in animal models.

BackgroundThe presence of infections is one of the main factors that leads to delays in healing or non-closure of cutaneous wounds. Although the goal of antibiotic use is to treat or prevent infection, there is currently no agreement on the effectiveness of these products.AimThe aim of this study was to evaluate the efficacy of antibiotic use during the healing process of skin wounds in animal models not intentionally infected, as well as to analyze the advances and limitations of the studies carried out in this field.Main methodsThis systematic review was performed according to the PRISMA guidelines, using a structured search on the MedLine (PubMed) and Scopus platforms to retrieve studies published until August 29, 2018, 13:35p.m. The studies included were limited to those that used excision or incision wound models and that were not intentionally infected. The data for the animal models, antibiotic used, and the main results of the studies were extracted, and compared where possible. Bias analysis and methodological quality assessments were examined through the SYRCLE's Risk of Bias tool.Key findingsTwenty-seven studies were selected. Overall, the effects of the antibiotic on the wound decreased inflammatory cell infiltration and promoted an increased number of fibroblasts, extracellular matrix constituents, re-epithelialization and tissue strength. A great deal of important information about the methodology was not presented, such as: the statistical analysis used, the animal model (sex and age), antibiotic dosage, blinding and randomization of the animals chosen.SignificanceBased on the results found, we believe that antibiotic therapy can be considered a viable alternative for the treatment of cutaneous wounds. However, current evidence obtained from the methodological quality analysis points towards a high risk of bias. This is due to the incomplete characterization of the experimental design and treatment protocol, which compromises the reproducibility of the studies

What Is the Impact of Depletion of Immunoregulatory Genes on Wound Healing? A Systematic Review of Preclinical Evidence

Cytokines and growth factors are known to play an important role in the skin wound closure process; however, in knockout organisms, the levels of these molecules can undergo changes that result in the delay or acceleration of this process. Therefore, we systematically reviewed evidence from preclinical studies about the main immunoregulatory molecules involved in skin repair through the analysis of the main mechanisms involved in the depletion of immunoregulatory genes, and we carried out a critical analysis of the methodological quality of these studies. We searched biomedical databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to those which used knockout animals and excision or incision wound models without intervention. A total of 27 studies were selected; data for animal models, gene depletion, wound characteristics, and immunoregulatory molecules were evaluated and compared whenever possible. Methodological quality assessments were examined using the ARRIVE and SYRCLE’s bias of risk tool. In our review, the extracellular molecules act more negatively in the wound healing process when silenced and the metabolic pathway most affected involved in these processes was TGF-β/Smad, and emphasis was given to the importance of the participation of macrophages in TGF-β signaling. Besides that, proinflammatory molecules were more evaluated than anti-inflammatory ones, and the main molecules evaluated were, respectively, TGF-β1, followed by VEGF, IL-6, TNF-α, and IL-1β. Overall, most gene depletions delayed wound healing, negatively influenced the concentrations of proinflammatory cytokines, and consequently promoted a decrease of inflammatory cell infiltration, angiogenesis, and collagen deposition, compromising the formation of granulation tissue. The studies presented heterogeneous data and exhibited methodological limitations; therefore, mechanistic and highly controlled studies are required to improve the quality of the evidence