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.

Impact of microplastics on the intestinal microbiota: A systematic review of preclinical evidence.

AIMS: We systematically review the in vivo preclinical evidence on the impact of microplastics (MPs) on the intestinal microbiota and morphofunctional changes involving the intestinal mucosa. METHODS: By using a comprehensive and structured search in electronic databases 28 original studies were recovered and analyzed. KEY FINDINGS: Zebrafish and mice were the main animal models, while the dose and shape of MPs used were quite heterogeneous. Studies show that MPs are potential triggers of intestinal dysbiosis, which has been characterized by enrichment of Firmicutes, Proteobacteria and Chlamydia. Conversely, there was a reduction in Bacteroidetes phylum abundance. By trapping and stimulating intestinal inflammatory infiltrate, exposure to MPs increased intestinal permeability and the expression of immune signatures associated with inflammation, such as IL-1α, IL-1ß, TNF-α, IFN-γ and IL-6. SIGNIFICANCE: Thus, current evidence supports potential inflammatory and dysbiotic properties of MPs. In addition, the data indicate that MPs can display structural changes secondary to exposure to MPs. Analysis of methodological quality indicated that current preclinical evidence is at high risk of bias. We hope that controlling that bias sources described in this systematic review will be useful to improve the quality of reports.

New Insights Into Blue Light Phototherapy in Experimental Trypanosoma cruzi Infection.

The search for an effective etiologic treatment to eliminate Trypanosoma cruzi, the causative agent of Chagas disease, has continued for decades and yielded controversial results. In the 1970s, nifurtimox and benznidazole were introduced for clinical assessment, but factors such as parasite resistance, high cellular toxicity, and efficacy in acute and chronic phases of the infection have been debated even today. This study proposes an innovative strategy to support the controlling of the T. cruzi using blue light phototherapy or blue light-emitting diode (LED) intervention. In in vitro assays, axenic cultures of Y and CL strains of T. cruzi were exposed to 460 nm and 40 µW/cm2 of blue light for 5 days (6 h/day), and parasite replication was evaluated daily. For in vivo experiments, C57BL6 mice were infected with the Y strain of T. cruzi and exposed to 460 nm and 7 µW/cm2 of blue light for 9 days (12 h/day). Parasite count in the blood and cardiac tissue was determined, and plasma interleukin (IL-6), tumoral necrosis factor (TNF), chemokine ligand 2 (CCL2), and IL-10 levels and the morphometry of the cardiac tissue were evaluated. Blue light induced a 50% reduction in T. cruzi (epimastigote forms) replication in vitro after 5 days of exposure. This blue light-mediated parasite control was also observed by the T. cruzi reduction in the blood (trypomastigote forms) and in the cardiac tissue (parasite DNA and amastigote nests) of infected mice. Phototherapy reduced plasma IL-6, TNF and IL-10, but not CCL2, levels in infected animals. This non-chemical therapy reduced the volume density of the heart stroma in the cardiac connective tissue but did not ameliorate the mouse myocarditis, maintaining a predominance of pericellular and perivascular mononuclear inflammatory infiltration with an increase in polymorphonuclear cells. Together, these data highlight, for the first time, the use of blue light therapy to control circulating and tissue forms of T. cruzi. Further investigation would demonstrate the application of this promising and potential complementary strategy for the treatment of Chagas disease.

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.

Preclinical study of methotrexate-based hydrogels versus surfactant based liquid crystal systems on psoriasis treatment.

Psoriasis is an autoimmune, inflammatory and chronic skin disease in which cell growth and proliferation are increased, causing erythema, lesions and skin's peeling. Oral methotrexate (MTX) is the first-choice drug when phototherapy or retinoid treatment are not effective. Topical administration can be advantageous to better orientate the drug's delivery; however, the stratum corneum performs as a barrier for hydrofilic drugs penetration. This study sought to evaluate two different types of vehicles for MTX on the psoriasis treatment - hydrogel and liquid crystal systems (LCs). Lamellar and hexagonal liquid crystalline phases were selected from a ternary phase diagram based on polysorbate 80, isopropyl miristate and water. The hydrogel was based on alkylated carbomer (ACH). Rheological analysis showed ACH was more elastic than lamellar and hexagonal phases. ACH interacted better with pig skin than LCs in bioadhesion assay. Preclinical study revealed the ACH decreased inflammation in mice with induced psoriasis, being as effective as dexamethasone to regulate epidermis thickness, COX-2 and myeloperoxidase activity and TNF-α level, while LCs demonstrated inflammatory effect. Therefore, MTX-loaded hydrogel based platforms are indicated for local treatment of psoriasis and present great potential for further studies.

Ellagitannins from jabuticaba (Myrciaria jaboticaba) seeds attenuated inflammation, oxidative stress, aberrant crypt foci, and modulated gut microbiota in rats with 1,2 dimethyl hydrazine-induced colon carcinogenesis.

Since dietary factors are thought to be responsible for high colon cancer risk, we investigated the chemopreventive effect of jabuticaba seed extract (LJE) by administering yogurt with or without LJE against 1,2 dimethyl hydrazine (DMH)-induced colon carcinogenesis in rats. Results showed that LJE contained a total phenolic content of 57.16 g/100 g of seed extract in which 7.67 and 10.09 g/100 g represented total flavonoids and ellagitannins, respectively. LJE protected DNA and human LDL against induced in vitro oxidation, which was associated with the ellagitannin content and with the free-radical scavenging and reducing capacities. LJE alone had a non-clastogenicity/aneugenicity property, but in combination with cisplatin, it enhanced the chromosome aberrations in cancer cells. In colon cancer-induced rats, yogurt with or without LJE caused a reduction in pro-inflammatory parameters, decreased the RNA expression of antiapoptotic cytokines and increased the expression of proapoptotic cytokines. Moreover, LJE attenuated colon cancer initiation and progression by decreasing aberrant crypt foci and LJE recovered the gut microbiome. Together, this evidence suggests that LJE provides chemopreventive protection against colon cancer development by reducing inflammation and increasing proapoptotic pathways.

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.

Tagitinin F has anti-inflammatory, anti-nociceptive and anti-matrix metalloproteinase properties: An in silico, in vitro and in vivo study.

Sesquiterpene lactones (SL) are natural bioactive molecules indicated as potential scaffolds for anti-inflammatory and analgesic drug design. However, their anti-inflammatory applicability remains underestimated since the impact of SL on inflammatory nociception and tissue repair are overlooked. Thus, we used an integrated in silico, in vitro and in vivo framework to investigate the impact of tagitinin F (TAG-F) on lipopolysaccharide (LPS)-challenged macrophages, excisional skin wounds, and carrageenan-induced paw edema and mechanical hyperalgesia in mice. RAW 264.7 macrophages in culture were challenged with LPS and treated with TAG-F (5, 10, 50 and 100 µM). The paw of BALB/c mice was injected with carrageenan and treated with 0.5% and 1% TAG-F. Excisional wounds were also produced in BALB/c mice and treated with 0.5% and 1% TAG-F. Our results indicated a consistent concentration-dependent downregulation in 5-lipoxygenase, cyclooxygenase 1 and 2 (COX-1 and COX-2), matrix metalloproteinase 1 and 2 (MMP-1 and MMP-2) activities; as well as attenuation in prostaglandin E2 (PGE2), leukotriene B4 (LTB4) and tumor necrosis factor-α (TNF-α) production in both in vitro and in vivo models. In vivo, TAG-F also attenuated carrageenan-induced paw edema and mechanical hyperalgesia in mice. From the excisional skin wound, TAG-F was still effective in reducing neutrophils and macrophages infiltration and stimulating collagen deposition in the scar tissue, accelerating tissue maturation. Together, our findings indicate that the anti-inflammatory effect of TAG-F is more comprehensive than previously suggested, exerting a significant impact on the control of edema, inflammatory pain and modulating central metabolic processes linked to skin wound healing.

Antioxidant and Anti-Inflammatory Effects of Anacardium occidentale L. and Anacardium microcarpum D. Extracts on the Liver of IL-10 Knockout Mice.

BACKGROUND: The Anacardium occidentale L. (cashew) and Anacardium microcarpum D. (cajuí) are plants commonly found in Brazil. They present phytochemical compounds with antioxidant and anti-inflammatory action. Therefore, the objective of this study was to analyze the antioxidant and anti-inflammatory activities of ethanolic extracts from leaves of A. occidentale and A. microcarpum and its effect on the hepatic tissue in experimental knockout models after they received Paracetamol®. METHODS: Ethanol extracts from A. occidentale and A. microcarpum leaves were prepared. Total phenolics were determined by Folin-Ciocalteau reagent, and flavonoids are based on the complexation reaction with the aluminum metal, forming a colored complex. Fingerprint HPLC was performed to detect phenolic compounds. Knockout IL-10 mice randomly divided into six groups were used and received the following treatments: G1, only water; G2, A. occidentale extract; G3, A. microcarpum extract; G4, Paracetamol®; G5, Paracetamol® + A. occidentale extract (400 mg/kg); G6, Paracetamol® + A. microcarpum extract (400 mg/kg). Biochemical parameters of the blood and differential count of leukocytes were done. Oxidative markers and histopathological analyses were performed on their liver tissue. RESULTS: Phenolic compounds and total flavonoids were detected in both two extracts analyzed. The HPLC fingerprint detected phenolic acid, gallic acid, and catechin flavonoid in the two extracts. Histopathological analyses of the hepatic tissue permitted evaluation of nuclear increase, sinusoid congestion, and inflammatory infiltrate. A. microcarpum presented more antioxidant activity increasing antioxidant enzyme levels and reducing TBARS and carbonyl protein when compared to the other treatments after exposure to Paracetamol®. Histopathological analyses showed a decrease in the inflammatory infiltrate after treatment with extracts. CONCLUSION: Our findings indicate that both extracts, especially A. microcarpum, can reduce hepatic damage in knockout mice exposed to paracetamol, indicating the curative power of these extracts reducing lipid peroxidation and in the morphofunctional damage to the liver parenchyma.

Acidic Phospholipase A2-Peptide Derivative Modulates Oxidative Status and Microstructural Reorganization of Scar Tissue after Cutaneous Injury.

From in vitro and in vivo models, the proliferative and healing potential of an acidic phospholipase A2 (LAPLA2) from Lachesis muta venom was investigated. The LAPLA2 proliferative activity was evaluated on fibroblasts and keratinocytes cultured, and the antioxidant and regenerative potential of LAPLA2 was analyzed in a murine model. The animal study consisted of four groups: C (negative control): 0.9% NaCl; SS (positive control): 1% silver sulfadiazine; L1 group: 0.5% LAPLA2; and L2 group: 0.25% LAPLA2. Wounds were topically treated daily for 12 days, and scar tissue samples were collected every 4 days. In vitro, LAPLA2 stimulated marked time-dependent cell proliferation. In vivo, it increased the antioxidant activity of superoxide dismutase (SOD) and catalase (CAT) and decreased malondialdehyde (MDA) and carbonyl protein (CP) levels in scar tissue treated with LAPLA2 at 0.5%. This peptide was effective in stimulating cellular proliferation, neoangiogenesis, type I and III collagen deposition, and maturation in a time-dependent-way, reducing the time required for wound closure. Our results indicated that LAPLA2 presented a remarkable potential in improving the oxidative status and microstructural reorganization of the scar tissue by stimulation of cellularity, angiogenesis, colagenogenesis, and wound contraction, suggesting that the peptide could be a potential candidate for a new healing drug.

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.

The photobiomodulation (658, 830 and 904nm) on wound healing in histomorphometric analysis / A fotobiomodulação (658, 830 e 904nm) na cicatrização de feridas na análise histomorfométrica / La fotobiomodulación (658, 830 y 904nm) en la cicatrización de heridas en el análisis histomorfométrico

Abstract Introduction: Photobiomodulation (PBM) assists in the processes of angiogenesis and cellular mitosis after skin lesion, contributing to tissue repair. Objective: to investigate the effects of photobiomodulation (during the proliferative phase) of 658 nm, 830 nm and 904 nm in the repair of skin lesions in an animal model. Method: 658 nm (G658), 830 nm (G830), 904 nm (G904) PBM, and control group (CG) integrated the research. We submitted the animals to an excisional wound and treatment at different wavelengths for 14 days. On the seventh and 14-1485004059th postoperative days, we calculated the area and percentage of lesion contraction. The animals were sacrificed on the 14-1485004056th postoperative day and cutaneous section of the injured region was collected for histomorphometric evaluation of the cellularity, neovascularization, thickness of the epidermis and volume density of collagen fibers colored with H&E and Picross Sirius respectively. For the statistical analysis, we applied the ANOVA test. Results: the G658 presented higher cellularity than GC (p = 0.03). The animals in the G658 group showed a significant increase in the neovascularization in relation to the CG (p = 0.01). Type III collagen significantly increased in G904 compared to G830 (p < 0.0001) and CG (p < 0.0001). The G658 had a significant increase in type III collagen fibers compared to G830 (p < 0.0001) and GC (p < 0.0001). We found no significant difference in the thickness of the epidermis, wound area, and in the percentage wound of contraction between the analyzed groups. Conclusion: PBM was effective to stimulate the tissue repair process, with better results for the 658 nm wavelength.

Resumo Introdução: A Fotobiomodulação (FBM) auxilia nos processos de angiogênese e mitose celular após lesão cutânea, contribuindo para reparo do tecido. Objetivo: investigar os efeitos da fotobiomodulação (durante a fase proliferativa) com comprimento de onda de 658 nm, 830 nm e 904 nm no reparo de lesões cutâneas em modelo animal. Método: FBM 658 nm (G658), 830 nm (G830), 904 nm (G904) e controle (GC) integraram a pesquisa. Os animais foram submetidos a uma ferida excisional e receberam tratamento em diferentes comprimentos de por 14 dias. No 7º e 14º dia pós-operatório, calculou-se a área e a porcentagem de contração da lesão. Os animais foram sacrificados no 14º dia pós-operatório e a secção cutânea da região lesada foi coletada para avaliação histomorfométrica da celularidade, neovascularização, espessura da epiderme e densidade volumétrica das fibras colágenas, corados com H&E e Picross Sirius respectivamente. Para a análise estatística, foi aplicado o teste ANOVA. Resultados: o G658 apresentou maior celularidade que GC (p = 0,03). Os animais do grupo G658 apresentaram aumento significativo da neovascularização em relação ao GC (p = 0,01). Houve aumento significativo do colágeno tipo III no G904 em relação ao G830 (p < 0,0001) e GC (p < 0,0001). O G658 teve um aumento significativo nas fibras colágenas tipo III em comparação ao G830 (p < 0,0001) e GC (p < 0,0001). Nenhuma diferença significativa foi encontrada na espessura da epiderme, área da ferida e na porcentagem de contração da ferida entre os grupos analisados. Conclusão: a PBM foi efetiva para estimular o processo de reparo tecidual, com melhores resultados para o comprimento de onda de 658 nm.

Resumen Introducción: La fotobiomodulación (FBM) auxilia en los procesos de angiogénesis y mitosa celular después de lesión cutánea, contribuyendo para la reparación. Objetivo: investigar los efectos de la fotobiomodulación (durante la fase proliferativa) con longitud de onda de 658 nm, 830 nm y 904 nm en la reparación de lesiones cutáneas en modelo animal. Método: grupos de FBM 658 nm (G658), 830 nm (G830), 904 nm (G904) y control (GC) integraron la investigación. Los animales fueron sometidos a una herida excisional y recibieron tratamiento 14 días. En el 7º y 14º día postoperatorio, se calculó el área y el porcentaje de contracción de la lesión. Los animales fueron sacrificados en el 14º día postoperatorio y la sección cutánea de la región lesada fue recolectada para evaluación histomorfométrica de la celularidad, neovascularización, espesor de la epidermis y densidad volumétrica de las fibras colágenas, colorados con H & E y Picross Sirius respectivamente. Para el análisis estadístico, se aplicó la prueba ANOVA. Resultados: G658 presentó mayor celularidad que GC (p = 0,03). G658 presentaron un aumento significativo de la neovascularización en relación al GC (p = 0,01). Se observó un aumento significativo del colágeno tipo III en el G904 con respecto al G830 (p < 0,0001) y GC (p < 0,0001). El G658 tuvo un aumento significativo en las fibras colágenas tipo III en comparación con el G830 (p < 0,0001) y GC (p < 0,0001). Ninguna diferencia significativa se encontró en el espesor de la epidermis, área de la herida entre los grupos. Conclusión: la PBM fue efectiva para estimular el proceso de reparación del tejido, con mejores resultados para grupo 658 nm.

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.

Hepatoprotective and Antioxidant Activities of Oil from Baru Almonds (Dipteryx alata Vog.) in a Preclinical Model of Lipotoxicity and Dyslipidemia.

The oil obtained from baru (Dipteryx alata Vog.) almonds exhibits high energy value and is reported in popular medicine for the treatment of rheumatic diseases and reproductive disturbances. Although baru oil is used in domestic cuisine, the chemical characterization of this oil and its effects on lipid metabolism are still poorly understood. Therefore, this study evaluated the fatty acid (FA) profile and the effects of baru oil on liver and aorta in a murine model of dyslipidemia. The chromatographic profile of baru oil showed high levels of unsaturated FAs, especially oleic acid. Saturated FAs, such as palmitic and lignoceric acids, were found in lower amounts. Hypercholesterolemia was induced in male Wistar rats by daily administration of a lipid emulsion by gavage for 15 weeks. Biochemical and histopathological analysis were performed on serum, aorta, and liver. The results demonstrated that animals developed marked hypercholesterolemia, liver steatosis, and increased lipid peroxidation in the aorta. Treatment with baru oil attenuated lipid peroxidation and drastically reduced liver damage, especially ballooning degeneration and steatosis. By restricting vascular and hepatic injury, this oil showed potential applicability as a functional food, reinforcing its use in popular medicine and domestic cuisine.

Applicability of Plant Extracts in Preclinical Studies of Melanoma: A Systematic Review.

Melanoma is the most aggressive form of skin cancer and arises from melanocyte gene mutation. This disease is multifactorial, but its main cause is the excessive exposure to ultraviolet radiation. Currently, available chemotherapy has shown little expressive results, which may justify the high use of natural products to treat this cancer. We performed a systematic review to compile the results of studies carried out in murine models and investigated the effect of plant extracts on melanoma treatment. Papers were selected in MEDLINE/Pubmed and Scopus according to the PRISM statement. Search filters were developed using three parameters: plant extract, melanoma, and animal model. The 35 identified studies were all submitted to the criteria described in the ARRIVE guidelines. The different extracts showed antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activity, and also proved to be effective in cell cycle modulation and apoptosis evasion. Bias analysis evidenced the absence of standardized experimental designs, as well as failures in statistical tests and in the presentation of results. The analysis of the studies suggests that the use of plant extracts is effective for the treatment of melanoma in murine models.

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.

Flavonoids Effects on Hepatocellular Carcinoma in Murine Models: A Systematic Review.

The hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. It occurs primarily as manifestation of other pathological processes, such as viral hepatitis, cirrhosis, and toxin exposure that affect directly the cellular process. Studies were selected from PubMed and Scopus databases according to the PRISMA statement. The research filters were constructed using three parameters: flavonoids, hepatocellular carcinoma, and animal model. The bias analysis of the 34 selected works was done using the ARRIVE guidelines. The most widely used flavonoid in the studies was epigallocatechin gallate extracted from green tea. In general, the treatment with different flavonoids presented inhibition of tumor growth and antiangiogenic, antimetastatic, antioxidant, and anti-inflammatory activities. The bias analysis evidenced the absence of methodological processes in all studies, such as the age or weight of the animals, the method of flavonoids' extraction, or the experimental designs, analytical methods, and outcome measures. It has been known that flavonoids have a protective effect against HCC. However, the absence or incomplete characterization of the animal models, treatment protocols, and phytochemical and toxicity analyses impaired the internal validity of the individual studies, making it difficult to determine the effectiveness of plant-derived products in the treatment of HCC.

Could diet composition modulate pathological outcomes in schistosomiasis mansoni? A systematic review of in vivo preclinical evidence.

Schistosomiasis and malnutrition are often overlapped in poor communities, resulting in disproportionately high mortality rates. Currently, fragmented data make it difficult to define the relationship between diet and schistosomiasis. Thus, we systematically review the preclinical evidence on the impact of diet in Schistosoma mansoni infection. From a structured search, we recovered 27 original articles. All studies used mice and most of them investigated hypoproteic (70.37%), hyperlipidic (22.22%) or vitamin-deficient (7.41%) diets. Diets based on carbohydrate, zinc or milk supplementation were investigated at a reduced frequency (3.70% each). Hypoproteic diets attenuated parasitic load and granulomatous inflammation, but also reduced host resistance to S. mansoni infection, determining higher mortality rates. By stimulating steatohepatitis, parasitic load and granulomatous inflammation, hyperlipidic diets increase organ damage and mortality in infected animals. Although a high-sugar diet and vitamin restriction potentiate and zinc supplementation attenuates S. mansoni infection, the current evidence for these diets remains inconclusive. Analysis of methodological quality indicated that the current evidence is at high risk of bias due to incomplete characterization of the experimental design, diet composition and treatment protocols. From the bias analysis, we report methodological limitations that should be considered to avoid systematic reproduction of inconsistent and poorly reproducible experimental designs.

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.