Impact of plant extracts on hepatic redox metabolism upon lead exposure: a systematic review of preclinical in vivo evidence.

The liver is a central target organ of heavy metals toxicity, and secondary metabolites of several plant species are suggested to attenuate lead (Pb)-induced hepatotoxicity through antioxidant and anti-inflammatory mechanisms. We used a systematic review framework to map the impact of plant extracts and bioactive secondary metabolites on immunological markers and liver redox metabolism in preclinical models of Pb exposure. This is a systematic review performed according to PRISMA guidelines. The structured research of publications was done through PubMed, Scopus, Web of Science, and Embase databases, selecting and analyzing 41 original studies included via the eligibility criteria. Evidence indicates that Pb-exposure increases reactive oxygen/nitrogen species (ROS/RNS) production by δ-aminolevulinic acid auto-oxidation, xanthine dehydrogenase, and xanthine oxidase upregulation. Pb exposure also inhibits antioxidant enzymes, potentiating ROS/NOS levels and reactive cell damage. Plant extracts rich in flavonoids, tannins, alkaloids, anthocyanins, and vitamins exerted hepatoprotective effects by chelating and decreasing Pb bioaccumulation. In addition, plant extracts reinforce exogenous and endogenous antioxidant defenses, attenuating liver oxidative stress and cell death. The lack of blinded evaluators and randomized experimental groups were the main sources of bias identified, which need to be controlled in toxicological studies aimed at identifying natural products applied to the prevention or treatment of Pb poisoning.

The relevance of the use of plant extracts on testicular cells: A systematic review.

This review aims to establish an association between traditional and scientific knowledge to allow the evaluation of the effectiveness of medicinal plants, as well as their risks based on the testicular microenvironment. A systematic search was performed using PRISMA guidelines. The descriptors were structured based on search filters built for three domains: Animals, Plants, and Testis. The filters on the PubMed/Medline platform were constructed using a hierarchical distribution of the MeSH Terms. Methodological quality assessments were performed using the SYRCLE risk bias tool. Data on testicular cells, hormones and biochemistry, sperm, and sexual behavior were evaluated and compared. The search came out with 2644 articles, and 36 articles met the inclusion criteria and were used in this review. The included studies analyzed testicular cells from murine models treated with crude plant extracts. Plant extracts act directly on the hypothalamic-pituitary axis and/or directly on testicular cells, inhibiting and stimulating the reproductive process, thus causing alterations in fertility rates. Apiaceae and the Cucurbitaceae families are the most used in male reproductive biology experiments, being Apiaceae described as sexual stimulants, while Cucurbitaceae are the main sources of deleterious effects on the male reproductive system.

Hydroalcoholic extract of Remijia ferruginea accelerates the closure of skin wounds by modulating tissue morphology and antioxidant profile: An in vitro and in vivo study.

ETHNOPHARMACOLOGICAL RELEVANCE: Remijia ferruginea DC. (Rubiaceae) (syn. Cinchona ferruginea A.St.-Hil.) is used in traditional medicine for the treatment of wounds, fever and malaria. AIM: This study investigated in vitro the proliferative and antioxidant effects of hydroalcoholic extract of leaves of R. ferruginea (HERF) and in vivo the healing effect of ointment based on HERF. MATERIALS AND METHODS: The plant extract was characterized by liquid chromatography/mass spectrometry. Cell proliferation assays and in vitro antioxidant activity were performed. In in vivo assays, wound contraction ax was evaluated, as well as histological analyzes such as cellularity, proportion of blood vessels and collagen type I and III index. In addition, analyzes of the antioxidant enzymes SOD, CAT and GST were performed. RESULTS: Our results showed in the chromatographic analysis that catechin, rutin and quercetin were the main phenolic compounds in the plant extract and may be responsible for the antioxidant and proliferative effects (p < 0.05). In addition, these compounds were found in higher concentration in leaves collected in spring. The ointment containing HERF was able to modulate tissue morphology, increasing cell proliferation, blood vessels, being able to stimulate the production of collagen fibers type I and III, (p < 0.05) contributing to scar tissue maturation and resistance. CONCLUSION: Our findings indicated that the three doses of HERF tested (1%, 3% and 5%) can modulate the skin repair process, but the best effects were observed after exposure to the highest dose.

Effects of Curcumin Supplementation on Inflammatory Markers, Muscle Damage, and Sports Performance during Acute Physical Exercise in Sedentary Individuals.

Exhaustive and acute unusual physical exercise leads to muscle damage. Curcumin has been widely studied due to the variety of its biological activities, attributed to its antioxidant and anti-inflammatory properties. Furthermore, it has shown positive effects on physical exercise practitioners. However, there is no literature consensus on the beneficial effects of curcumin in acute physical activities performed by sedentary individuals. Therefore, we systematically reviewed evidence from clinical trials on the main effects of curcumin supplementation on inflammatory markers, sports performance, and muscle damage during acute physical exercises in these individuals. We searched PubMed/MEDLINE, Scopus, Web of Science, and Embase databases, and only original studies were analyzed according to the PRISMA guidelines. The included studies were limited to supplementation of curcumin during acute exercise. A total of 5 studies were selected. Methodological quality assessments were examined using the SYRCLE's risk-of-bias tool. Most studies have shown positive effects of curcumin supplementation in sedentary individuals undergoing acute physical exercise. Overall, participants supplemented with curcumin showed less muscle damage, reduced inflammation, and better muscle performance. The studies showed heterogeneous data and exhibited methodological limitations; therefore, further research is necessary to ensure curcumin supplementation benefits during acute and high-intensity physical exercises. Additionally, mechanistic and highly controlled studies are required to improve the quality of the evidence and to elucidate other possible mechanisms. This study is registered with Prospero number CRD42021262718.

Evaluation of the efficacy of probiotic VSL#3 and synbiotic VSL#3 and yacon-based product in reducing oxidative stress and intestinal permeability in mice induced to colorectal carcinogenesis.

The objective of the present study was to evaluate the effect of probiotic VSL#3 isolated or associated with a yacon-based product (synbiotic) on oxidative stress modulation and intestinal permeability in an experimental model of colorectal carcinogenesis. Forty-five C57BL/6J mice were divided into three groups: control (standard diet AIN-93 M); probiotic (standard diet AIN-93 M and multispecies probiotic VSL#3, 2.25 × 109 CFU), and synbiotic (standard diet AIN-93 M with yacon-based product, 6% fructooligosaccharides and inulin, and probiotic VSL#3, 2.25 × 109 CFU). The experimental diets were provided for 13 weeks. The probiotic and the yacon-based product showed antioxidant activity, with the percentage of DPPH radical scavenging equal to 69.7 ± 0.4% and 74.3 ± 0.1%, respectively. These findings contributed to reduce hepatic oxidative stress: the control group showed higher concentration of malondialdehyde (1.8-fold, p = 0.007 and 1.5-fold, p = 0.035) and carbonylated protein (2-fold, p = 0.008 and 5.6-fold, p = 0.000) compared to the probiotic and synbiotic groups, respectively. Catalase enzyme activity increased 1.43-fold (p = 0.014) in synbiotic group. The crypt depth increased 1.2-fold and 1.4-fold with the use of probiotic and synbiotic, respectively, compared to the control diet (p = 0.000). These findings corroborate the reduction in intestinal permeability in the probiotic and synbiotic groups, as measured by the percentage of urinary lactulose excretion (CON: 0.93 ± 0.62% × PRO: 0.44 ± 0.05%, p = 0.048; and CON: 0.93 ± 0.62% × SYN: 0.41 ± 0.12%, p = 0.043). In conclusion, the probiotic and synbiotic showed antioxidant activity, which contributed to the reduction of oxidative stress markers. In addition, they protected the mucosa from damage caused by chemical carcinogen and reduced intestinal permeability. PRACTICAL APPLICATION: The relationship between intestinal health and the occurrence of various organic disorders has been demonstrated in many studies. The use of probiotics and prebiotics is currently one of the main targets for modulation of intestinal health. We demonstrated that the use of a commercial mix of probiotic bacteria (VSL#3) isolated or associated with a yacon-based prebiotic, rich in fructooligosaccharides and inulin, is able to reduce the oxidative stress and intestinal permeability in a colorectal carcinogenesis model. These compounds have great potential to be used as a food supplement, or as ingredients in the development of food products.

Relevance of the Isoflavone Absorption and Testicular Function: A Systematic Review of Preclinical Evidence.

Isoflavone is a phytoestrogen found in different types of food that can act as endocrine disrupters leading to testicular dysfunction. Currently, fragmented data on the action of this compound in the testicles make it difficult to assess its effects to define a safe dose. Thus, we systematically reviewed the preclinical evidence of the impact of isoflavone on testicular function. We also determined which form (aglycones or glycosylated) was the most used, which allowed us to understand the main biological processes involved in testicular function after isoflavone exposure. This systematic review was carried out according to the PRISMA guidelines using a structured search on the biomedical databases MEDLINE (PubMed), Scopus, and Web of Science, recovering and analyzing 22 original studies. The bias analysis and the quality of the studies were assessed by the criteria described in the risk of bias tool developed by SYRCLE (Systematic Review Centre for Laboratory Animal Experimentation). The aglycones and glycosylated isoflavones proved to be harmful to the reproductive health, and the glycosylates at doses of 50, 100, 146, 200, 300, 500, and 600 mg/kg, in addition to 190 and 1000 mg/L, appear to be even more harmful. The main testicular pathologies resulting from the use of isoflavones are associated with Leydig cells resulting from changes in molecular functions and cellular components. The most used isoflavone to evaluate testicular changes was the genistein/daidzein conjugate. The consumption of high doses of isoflavones promotes changes in the functioning of Leydig cells, inducing testicular changes and leading to infertility in murine models.

Croton urucurana Baillon stem bark ointment accelerates the closure of cutaneous wounds in knockout IL-10 mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Croton urucurana Baill. (Euphorbiaceae) is a plant used in Brazilian popular medicine for the treatment of wound healing, inflammatory diseases, gastritis, infections, and hemorrhoids. AIM: The present study aimed to evaluate the in vivo wound healing activity of an ointment based on ethanolic extract of C. urucurana stem bark, at concentrations of 5% and 10%, and to relate it with compounds that could be associated with this activity. MATERIALS AND METHODS: Analyses by FIA-ESI-IT-MSn were carried out to investigate the chemical composition of C. urucurana. Knockout IL-10 (n = 60) mice and wild type C57 (n = 12) mice were separated into 6 groups to evaluate the wound healing activity. Knockout IL-10 mice: SAL (0.9% saline); BAS (ointment base); SS (1% silver sulfadiazine); CR1 (ointment with extract of C. urucurana 5%); CR2 (ointment with extract of C. urucurana 10%); and wild mice C57: SALC57 (Saline 0.9%). A circular wound with 10 mm in diameter was generated on the dorsal of the animals. Tissue specimen of the wounds were removed on days 7 and 14 of the treatment for histopathological, oxidative status and analyses of pro-and anti-inflammatory cytokines in scar tissue. RESULTS: In the phytochemical profile, twelve proanthocyanidins were identified (in the form of monomers, dimers, trimers, and tetramers), based on (epi)catechin and (epi)gallocatechin. Furthermore, two quercetin derivatives and two alkaloids were detected. The groups treated with CR1 and CR2 ointments presented higher rate of wound closure, increased total number of cells, mast cells, blood vessels and higher deposition of type III and I collagen. In addition, they showed increased amount of pro-inflammatory cytokines (IL- 2 and IFN-γ), and anti-inflmatory cytokines (IL-4), on the 7th day of treatment. CONCLUSION: The results presented support the popular use of preparations based on the bark of C. urucurana as a healing compound.

Plant Extracts in the Bone Repair Process: A Systematic Review.

Bone lesions are an important public health problem, with high socioeconomic costs. Bone tissue repair is coordinated by an inflammatory dynamic process mediated by osteoprogenitor cells of the periosteum and endosteum, responsible for the formation of a new bone matrix. Studies using antioxidant products from plants for bone lesion treatment have been growing worldwide. We developed a systematic review to compile the results of works with animal models investigating the anti-inflammatory activity of plant extracts in the treatment of bone lesions and analyze the methodological quality of the studies on this subject. Studies were selected in the PubMed/MEDLINE, Scopus, and Web of Science databases according to the PRISMA statement. The research filters were constructed using three parameters: animal model, bone repair, and plant extracts. 31 full-text articles were recovered from 10 countries. Phytochemical prospecting was reported in 15 studies (48.39%). The most common secondary metabolites were flavonoids, cited in 32.26% studies (n = 10). Essential criteria to in vivo animal studies were frequently underreported, suggesting publication bias. The animals treated with plant extracts presented positive results in the osteoblastic proliferation, and consequently, this treatment accelerated osteogenic differentiation and bone callus formation, as well as bone fracture repair. Possibly, these results are associated with antioxidant, regenerative, and anti-inflammatory power of the extracts. The absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impairs the internal validity of the evidence, making it difficult to determine the effectiveness and safety of plant-derived products in bone repair.

Strychnos pseudoquina modulates the morphological reorganization of the scar tissue of second intention cutaneous wounds in rats.

Natural substances are used in folk medicines to treat injuries. Strychnos pseudoquina has scarring, antipyretic, and antimalarial actions. The present study aimed to analyze the effect of S. pseudoquina on cutaneous wound healing in rats. The S. pseudoquina extract was submitted to phytochemical prospection. The levels of flavonoids and total phenolic compounds in the extract were 50.7 mg/g and 2.59 mg/g, respectively. Thirty Wistar rats were individualized in cages with food and water ad libitum (registration no. 730/2014). After anesthesia, three circular wounds (12mm diameter) were made in the animals, which were randomly separated into five treatments: Sal, saline; VO, ointment vehicles (lanolin and Vaseline); SS, positive control (silver sulfadiazine 1%); LE 5, freeze-dried extract 5%; and LE 10, lyophilized extract 10%. The animals were treated with the ointment daily for 21 days. Every seven days, the area and the rate of wound contraction were evaluated. Tissue samples were removed for histopathological analysis of the number of mast cells, elastic and collagen fibers, and biochemical analyses, quantification of malondialdehyde (MDA), carbonylated proteins (PCN), superoxide dismutase (SOD), catalase (CAT), transforming growth factor ß (TGF-ß), Interleukin 10 (IL-10) and tumor necrosis factor (TNF). The number of mast cells, collagen and elastic fibers in the rat wounds were higher in the treatments with the plant. The extract also stimulated the activity of antioxidant enzymes, particularly SOD, presenting high levels, and maintained low levels of PCN. The TGF-ß and IL-10 concentration was higher in the LE5 and LE10 treatment of the extract than in the Sal, OV and SS treatments on day 7. The ointment based on S. pseudoquina closed the wound faster and accelerated wound healing in animals.

Effect of Topical Administration of Fractions and Isolated Molecules from Plant Extracts on Skin Wound Healing: A Systematic Review of Murine Experimental Models.

Background and Purpose. Skin wound healing is a dynamic process driven by molecular events responsible for the morphofunctional repair of the injured tissue. In a systematic review, we analyzed the relevance of plant fractions and isolates on skin wound healing. By revising preclinical investigations with murine models, we investigated if the current evidence could support clinical trials. Methods. Studies were selected in the MEDLINE/PubMed and Scopus databases according to the PRISMA statement. All 32 identified studies were submitted to data extraction and the methodological bias was investigated according to ARRIVE strategy. Results. The studies demonstrated that plant fractions and isolates are able to modulate the inflammatory process during skin wound healing, being also effective in attenuating the oxidative tissue damage in the scar tissue and stimulating cell proliferation, neoangiogenesis, collagen synthesis, granulation tissue expansion, reepithelialization, and the wound closure rate. However, we identified serious methodological flaws in all studies, such as the high level of reporting bias and absence of standardized experimental designs, analytical methods, and outcome measures. Conclusion. Considering these limitations, the current evidence generated from flawed methodological animal studies makes it difficult to determine the relevance of herbal medicines to treat skin wounds and derails conducting clinical studies.

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.

Ointment of Brassica oleracea var. capitata Matures the Extracellular Matrix in Skin Wounds of Wistar Rats.

Wound healing is a complex process that aims to restore damaged tissue. Phytotherapeutics, such as cabbage, Brassica oleracea var. capitata (Brassicaceae), and sunflower, Helianthus annuus L. (Asteraceae) oil, are used as wound healers. Five circular wounds, each 12 mm in diameter, were made in the dorsolateral region of each rat. The animals were divided into four groups: balsam (B. oleracea); ointment (B. oleracea); sunflower oil (Helianthus annuus); control (saline solution 0.9%). These products were applied daily for 20 days and every four days the tissues of different wounds were removed. The wound contraction area, total collagen, types I and III collagen, glycosaminoglycans, and tissue cellularity were analyzed. In the groups that received ointment and balsam there was reduction in the wound area on days 4, 8, 12, and 20. Throughout the trial period, the balsam and ointment groups showed a higher amount of total collagen, type I collagen, and glycosaminoglycan compared to the others groups. The rats in the groups treated with B. oleracea var. capitata showed a higher number of cells on days 8, 16, and 20. B. oleracea was effective in stimulating the maturation of collagen and increasing the cellularity, as also in improving the mechanical resistance of the newly formed tissue.

Comparative study of the effects of laser photobiomodulation and extract of Brassica oleracea on skin wounds in wistar rats: A histomorphometric study.

The objective of this study was to investigate the effect of a photobiomodulation laser and Brassica oleracea on tissue morphology in skin wounds. The parameters analyzed were type I and III collagen fibers, and thickness and surface density of the epithelial tissue, as well as how quickly the wound closed. Five skin wounds 12mm in diameter were made on the backs of the animals, which were randomized into four groups (8 animals each). Saline Group: 0.9% saline solution; Ointment Group (extract of Cabbage, B. oleracea, 10% lanolin); Balsam Group (10% glycolic extract of B. oleracea emulsion oil); L60 Group (laser GaAsAl 60J/cm(2)). The applications were made daily during a 20-day treatment, and every 4 days tissue from different wounds was removed. The reduction in the size of the wounds on the 4th, 8th, 12th and 16th days was significantly greater in the treated groups compared to the control group. At all the time points analyzed, there was a greater proportion of collagen in the Balsam and L60 groups (p<0.05). There was also a greater proliferation of epithelial cells in the L60 and Balsam groups after 20 days of treatment (p<0.05). The healing extract and laser 60j/cm(2) exerted a great effect on collagen proliferation in stimulating scar tissue maturation.