Invivo and invitro evaluation of antitumor effects of iron oxide and folate core shell-iron oxide nanoparticles / Avaliação in vivo e in vitro dos efeitos antitumorais de nanopartículas de óxido de ferro e óxido de ferro com núcleo de folato

Abstract Nanoparticles are considered viable options in the treatment of cancer. This study was conducted to investigate the effect of magnetite nanoparticles (MNPs) and magnetite folate core shell (MFCS) on leukemic and hepatocarcinoma cell cultures as well as their effect on the animal model of acute myelocytic leukemia (AML). Through current study nanoparticles were synthesized, characterized by various techniques, and their properties were studied to confirm their nanostructure. Invivo study, nanoparticles were evaluated to inspect their cytotoxic activity against SNU-182 (human hepatocellular carcinoma), K562 (human leukemia), and THLE2 (human normal epithelial liver) cells via MTT test. Apoptotic signaling proteins Bcl-2 and Caspase-3 expression were inspected through RT-PCR method. A cytotoxic effect of MNPs and MFCS was detected in previous cell cultures. Moreover, the apoptosis was identified through significant up-regulation of caspase-3, with Bcl-2 down-regulation. Invitro study, AML was induced in rats by N-methyl-N-nitrosourea followed by oral treatment with MNPS and MFCS. Biochemical indices such as aspartate and alanine amino transferases, and lactate dehydrogenase activities, uric acid, complete blood count, and Beta -2-microglubulin were assessed in serum. Immunophenotyping for CD34 and CD38 detection was performed. Liver, kidney, and bone marrow were microscopically examined. Bcl-2 promoter methylation, and mRNA levels were examined. Although, both MNPs and MFCS depict amelioration in biochemical parameters, MFCS alleviated them toward normal control. Anticancer activity of MNPs and MFCS was approved especially for AML. Whenever, administration of MFCS was more effective than MNPs. The present work is one of few studies used MFCS as anticancer agent.

Resumo Nanopartículas são consideradas opções viáveis ​​no tratamento do câncer. Este estudo foi conduzido para investigar o efeito de nanopartículas de magnetita (MNPs) e núcleo de folato de magnetita (MFCS) em culturas de células leucêmicas e de hepatocarcinoma, bem como seu efeito no modelo animal de leucemia mielocítica aguda (LMA). Através do atual estudo, nanopartículas foram sintetizadas, caracterizadas por várias técnicas, e suas propriedades foram estudadas para confirmar sua nanoestrutura. No estudo in vivo, as nanopartículas foram avaliadas para inspecionar sua atividade citotóxica contra células SNU-182 (carcinoma hepatocelular humano), K562 (leucemia humana) e THLE2 (fígado epitelial humano normal) por meio do teste MTT. A expressão das proteínas sinalizadoras apoptóticas Bcl-2 e Caspase-3 foram inspecionadas através do método RT-PCR. Um efeito citotóxico de MNPs e MFCS foi detectado em culturas de células anteriores. Além disso, a apoptose foi identificada por meio de regulação positiva significativa da Caspase-3, com regulação negativa de Bcl-2. No estudo in vitro, a AML foi induzida em ratos por N-metil-N-nitrosoureia seguida por tratamento oral com MNPS e MFCS. Índices bioquímicos como aspartato e alanina aminotransferases e atividades de lactato desidrogenase, ácido úrico, hemograma completo e Beta-2-microglubulina foram avaliados no soro. A imunofenotipagem para detecção de CD34 e CD38 foi realizada. Fígado, rim e medula óssea foram examinados microscopicamente. A metilação do promotor Bcl-2 e os níveis de mRNA foram examinados. Embora tanto os MNPs quanto os MFCS representem uma melhora nos parâmetros bioquímicos, o MFCS os aliviou em direção ao controle normal. A atividade anticâncer de MNPs e MFCS foi aprovada especialmente para AML. Sempre, a administração de MFCS foi mais eficaz do que MNPs. O presente trabalho é um dos poucos estudos que utilizou o MFCS como agente anticâncer.

Chemical characterization and effects of volatile oil of Alpinia zerumbet on the quality of collagen deposition and caveolin-1 expression in a muscular fibrosis murine model / Caracterização química e efeitos do óleo volátil de Alpinia zerumbet na qualidade da deposição do colágeno e expressão da caveolina-1 em modelo murino de fibrose muscular

Abstract This study evaluated the effect of the volatile oil of Alpinia zerumbet (VOAz) on caveolin-1 gene expression and muscular fibrosis. The rats were immobilized to induce fibrosis of the gastrocnemius muscle, and they were treated with VOAz. Collagen quality was assessed by histology and the expression of the caveolin-1 (CAV-1) gene was evaluated using qPCR. Histomorphological analysis indicated a significant reduction in the perimeter, width, and intensity of collagen in the treated groups, thus showing that the oil was effective in regulating the quality of collagen at the three concentrations. The results of expression levels suggested a decrease in the lesioned group and in two treatment groups (0.0115 µg/g and 0.009 µg/g). However, with the lowest concentration (0.0065 µg/g), no significant difference was observed, with levels similar to those found in healthy tissue. Therefore, the results showed that VOAz has the potential to be a non-invasive and low-cost alternative to aid in the treatment of muscular fibrosis.

Resumo Este estudo avaliou o efeito do óleo volátil de Alpinia zerumbet (OVAz) na expressão do gene da caveolina-1 e na fibrose muscular. Os ratos foram imobilizados para induzir a fibrose do músculo gastrocnêmio, e foram tratados com OVAz. A qualidade do colágeno foi avaliada com histologia e à expressão do gene caveolina-1 (CAV-1) foi avaliada usando qPCR. A análise histomorfológica indicou uma redução significativa no perímetro, largura e intensidade do colágeno nos grupos tratados. Os resultados dos níveis de expressão sugeriram diminuição nos grupos de lesão e em dois grupos de tratamento (0,0115 µg/g e 0,009 µg/g). No entanto, com a menor concentração (0,0065 µg/g), não foi observada diferença significativa, apresentando níveis semelhantes aos encontrados em tecido saudável. O uso do OVAz foi eficaz para reverter as alterações do colágeno causadas pela fibrose, e sua menor concentração apresentou uma possível tendência de aumento na expressão do CAV-1. Portanto, os resultados mostraram que o OVAz tem potencial para ser uma alternativa não invasiva e de baixo custo para auxiliar no tratamento da fibrose muscular.

Effects of Solanum lycopersicum L. (tomato) against isoniazid and rifampicin induced hepatotoxicity in wistar albino rats / Efeitos de Solanum lycopersicum L. (tomate) contra hepatotoxicidade induzida por isoniazida e rifampicina em ratos albinos wistar

Anti-tuberculosis drugs are reported to cause hepatotoxicity, which varies from asymptomatic rise of the hepatic enzymes. Hepatoprotective plants plays important role to protect liver. This study investigated the hepatoprotective potential of the Solanum lycopersicum in rats intoxicated with Isoniazid and Rifampicin (INH+RIF) to induce hepatotoxicity. Thirty wistar albino rats were divided into five groups of six animals each. Group 1 rats were kept control while groups II, III, IV and V were administered with INH+RIF (75+150 mg/kg) orally, for seven consecutive days. For treatment, rats in group III received silymarin while animals in group IV and V were provided with 40 mg/kg and 80 mg/kg of Solanum lycopersicum extract, respectively. On day 0 and 8th blood samples were collected for the analysis of hepatic biomarkers. The data were subjected to one-way ANOVA and Bonferroni's post hoc test for statistical analysis. Hepatotoxicity induced by INH+RIF resulted in significant elevation of serum hepatic enzymes including Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and total bilirubin while decreased the albumin level. The Solanum lycopersicum at dose of 80 mg/kg significantly reduced the hepatic enzymes AST, ALT, ALP and bilirubin while the albumin level was significantly increased. The treatment had non-significant effect on body and liver weight. Drug induced hepatotoxicity can be effectively treated with Solanum lycopersicum at 80 mg/kg dose.

As drogas antituberculose são relatadas como causadoras de hepatotoxicidade, ocasionando o aumento assintomático das enzimas hepáticas. As plantas hepatoprotetoras desempenham um papel importante na proteção do fígado. Este estudo investigou o potencial hepatoprotetor de Solanum lycopersicum em ratos que foram intoxicados com isoniazida e rifampicina (INH + RIF) para induzir hepatotoxicidade. Trinta ratos wistar albinos foram divididos em cinco grupos de seis animais cada. Os ratos do grupo 1 representaram o grupo controle, enquanto os ratos dos grupos II, III, IV e V receberam INH + RIF (75 + 150 mg/kg) por via oral, por sete dias consecutivos. Para o tratamento, os ratos do grupo III receberam silimarina, enquanto os animais do grupo IV e V receberam 40 mg/kg e 80 mg/kg de extrato de S. lycopersicum, respectivamente. Nos dias 0 e 8, foram coletadas amostras de sangue para análise de biomarcadores hepáticos. Os dados foram submetidos a teste unilateral (ANOVA) e post hoc de Bonferroni para análise estatística. A hepatotoxicidade induzida por INH + RIF resultou em elevação significativa das enzimas hepáticas séricas, incluindo aspartato aminotransferase (AST), alanina aminotransferase (ALT), fosfatase alcalina (ALP) e bilirrubina total, enquanto houve a diminuição do nível de albumina. O S. lycopersicum, na dose de 80 mg / kg, reduziu significativamente as enzimas hepáticas AST, ALT, ALP e bilirrubina, enquanto o nível de albumina aumentou de forma significativa. O tratamento não teve efeito significativo no peso corporal e hepático. A hepatotoxicidade induzida por drogas pode ser tratada de forma eficaz com S. lycopersicum na dose de 80 mg/kg.

Alterations of serum biochemical parameters and tyrosine phosphorylation in kidney and liver of chronic stress-induced rats / Alterações dos parâmetros bioquímicos séricos e fosforilação da tirosina em rim e fígado de ratos induzidos por estresse crônico

Chronic stress (CS) can contribute to dysfunction in several organs including liver and kidney. This study was performed to investigate the changes in serum biochemistry, histological structure, as well as in localization of tyrosine phosphorylated proteins (TyrPho) and Heat shock protein 70 (Hsp-70) in liver and kidney tissues of CS rats induced by two stressors (restrained and force swimming) for 60 consecutive days. Samples of blood, liver, and kidney were collected from adult male Sprague-Dawley rats in each group. Our results showed that serum biochemical parameters including corticosterone, blood sugar, urea nitrogen, creatinine, cholesterol, triglyceride, HDL-C, LDL-C, ALT, AST, alkaline phosphatase in CS group were significantly different from that in normal group in both liver and kidney tissues. Although histological structure was not changed. TyrPho expression was significantly increased in liver lysate but significantly decreased in kidney. Hsp-70 expression in liver increased whereas in kidney decreased. In conclusion, CS can induce changes in liver and kidney functions.

O estresse crônico (SC) pode contribuir para a disfunção em vários órgãos, incluindo fígado e rim. Este estudo foi realizado para investigar as alterações na bioquímica sérica, estrutura histológica, bem como na localização de proteínas tirosina fosforiladas (TyrPho) e proteína de choque térmico 70 (Hsp-70) em tecidos hepáticos e renais de ratos CS induzidas por dois estressores (restrito e natação forçada) por 60 dias consecutivos. Amostras de sangue, fígado e rim foram coletadas de ratos Sprague-Dawley machos adultos em cada grupo. Nossos resultados mostraram que os parâmetros bioquímicos séricos, incluindo corticosterona, glicemia, nitrogênio ureico, creatinina, colesterol, triglicerídeos, HDL-C, LDL-C, ALT, AST, fosfatase alcalina no grupo CS foram significativamente diferentes do grupo normal em ambos os fígados e tecidos renais. Embora a estrutura histológica não tenha sido alterada, a expressão de TyrPho aumentou significativamente no lisado hepático, mas diminuiu significativamente no rim. A expressão de Hsp-70 no fígado aumentou, enquanto que no rim diminuiu. Em conclusão, a CS pode induzir alterações nas funções hepáticas e renais.

The bioprotective role of irradiated hibiscus against harmful effects of using repeatedly frying edible oil / O papel bioprotetor do hibisco irradiado contra os efeitos nocivos do uso de óleo comestível para fritar

Abstract Repeatedly frying process of dietary edible oil has a potential role in the generation of free radicals. Therefore, questions have always been raised as to whether, there is an efficient and economical method to reduce the harmful effects of repeated use of frying edible oil. Since hibiscus has been stated to have a wide variety of therapeutic effects, it was important to investigate its properties against harmful effects of free radicals. The current study aspires to find out whether irradiated powder of hibiscus has a protective role against adverse effects of repeated use of frying edible oil. Thirty-five adult male albino rats were equally assigned into five groups. First group"G1" was fed with normal diet as control group, meanwhile, group"G2" the diet mixed with fresh oil, "G3" diet mixed with repeatedly frying oil only, "G4" diet mixed with frying oil treated with hibiscus and "G5" diet mixed with frying oil treated with irradiated hibiscus. Feeding duration was six weeks. Fatty acid analyses of oil as well as peroxide values were determined. Blood and liver samples were collected for biochemical analyses as well as histological study. Repeatedly heated cooked oil has significant increases in peroxide value, acid value, free fatty acid and both conjugated diene and triene compared with repeatedly frying oil treated with hibiscus. Also there are significant increases in cholesterol and triglyceride and impaired in liver functions in "G3"compared with others. In addition, relative to the hibiscus groups, there is a substantial reduction in oxygen consumption in "G3". Both hibiscus as well as irradiated hibiscus attract attention in order to play a vital and economical role against harmful effects of frequent use of frying edible oil on some biological functions but, irradiated hibiscus was more effective.

Resumo O processo de fritura repetida de óleo comestível da dieta tem papel potencial na geração de radicais livres que podem ter efeitos prejudiciais em algumas funções biológicas. Portanto, sempre se questionou se existe uma maneira eficiente e econômica de prevenir ou pelo menos reduzir os efeitos nocivos do uso repetido de óleo comestível para fritar. Como o hibisco tem ampla variedade de efeitos terapêuticos, foi importante investigar suas propriedades como agente antioxidante contra os efeitos nocivos dos radicais livres. O presente estudo pretende descobrir se o pó irradiado de hibisco tem papel protetor contra os efeitos adversos do uso repetido de óleo comestível para fritar. Trinta e cinco ratos albinos machos adultos foram divididos igualmente em cinco grupos. O primeiro grupo "G1" foi alimentado com dieta normal como grupo controle, enquanto o grupo "G2" dieta misturada com óleo fresco, dieta "G3" misturada com óleo de fritura repetida, dieta "G4" misturada com óleo de fritura tratada com hibisco e dieta "G5" misturada com óleo de fritura tratada com hibisco irradiado. A duração da alimentação foi de seis semanas. Foram determinadas as análises de ácidos graxos de óleo, bem como os valores de peróxidos. Amostras de sangue e fígado foram coletadas para análises bioquímicas e estudo histológico. O óleo cozido repetidamente aquecido tem aumentos significativos no valor de peróxido, valor de ácido, ácido graxo livre e dieno e trieno conjugados em comparação com óleo de fritura repetidamente tratado com hibisco. Também há aumentos significativos no colesterol e triglicérides e comprometimento das funções hepáticas no "G3" em comparação com outros. Além disso, em relação aos grupos de hibiscos, há uma redução substancial no consumo de oxigênio no "G3". Tanto o hibisco como o hibisco irradiado chamam atenção por desempenhar papel vital e econômico contra os efeitos nocivos do uso frequente de óleo comestível para fritar em algumas funções biológicas, mas o hibisco irradiado foi mais eficaz.

Oral glutamine dipeptide or oral glutamine free amino acid reduces burned injury progression in rats / O dipeptídeo de glutamina oral ou aminoácido livre de glutamina oral reduz a progressão da lesão por queimadura em ratos

Abstract This study was carried out to evaluate the effect of Glutamine, as a dipeptide or a free amino acid form, on the progression of burn injuries in rats. Thirty male Wistar rats were burned with a comb metal plate heated in boiling water (98 °C) for three minutes, creating four rectangular full-thickness burn areas separated by three unburned interspaces (zone of stasis) in both dorsum sides. The animals were randomized into three groups (n=10): saline solution (G1-Control) and treated groups that orally received Glutamine as dipeptide (G2-Dip) or free amino acid (G3-FreeAA). Two and seven days after burn injury, lesions were photographed for unburned interspaces necrosis evolution assessment. Seven days after injury, glutathione seric was measured and histopathological analysis was performed. By photographs, there was a significant reduction in necrosis progression in G3-Free-AA between days two and seven. Histopathological analysis at day 7 showed a significantly higher stasis zone without necrosis and a higher number of fibroblasts in G2-Dip and G3-FreeAA compared with G1-Control. Also, glutathione serum dosage was higher in G2-Dip. The plasmatic glutathione levels were higher in the G2-Dip than the G1-Control, and there was a trend to higher levels in G3-FreeAA. The reduction in histological lesions, greater production of fibroblasts, and greater amounts of glutathione may have benefited the evolution of burn necrosis, which showed greater preservation of interspaces.

Resumo Este estudo foi realizado para avaliar o efeito da Glutamina, como um dipeptídeo ou forma de aminoácido livre, na progressão de queimaduras em ratos. Trinta ratos Wistar machos foram queimados com um pente de metal aquecido em água fervente (98 °C) por três minutos, criando quatro áreas retangulares queimadas separadas por três interesespaços não queimados (zona de estase) em ambos os lados do dorso. Os animais foram randomizados em três grupos (n = 10): solução salina (G1-Controle) e grupos tratados que receberam glutamina via oral como dipeptídeo (G2-Dip) ou aminoácido livre (G3-FreeAA). Dois e sete dias após a queimadura, as lesões foram fotografadas para avaliação da evolução da necrose entre os espaços não queimados. Sete dias após a lesão, foi dosada a glutationa sérica e realizada análise histopatológica. Pelas fotografias, houve uma redução significativa na progressão da necrose no G3-Free-AA entre os dias dois e sete. A análise histopatológica no dia 7 mostrou uma zona de estase significativamente maior sem necrose e número mais elevado de fibroblastos em G2-Dip e G3-FreeAA em comparação com G1-Controle. Os níveis plasmáticos de glutationa foram maiores no G2-Dip em relação ao G1-Controle, e houve tendência a níveis mais elevados no G3-FreeAA. A redução das lesões histológicas, maior produção de fibroblastos, maior quantidade de glutationa podem ter beneficiado a evolução da necrose da queimadura, que mostrou maior preservação dos interespaços.

Synthesis and evaluation of 2-phenylamino-1, 4-naphthoquinones derivatives as potential hypoglycaemic agents / Síntese e avaliação de derivados de 2-fenilamino-1, 4-naftoquinonas como potenciais agentes hipoglicemiantes

Due to the severe side effects revealed by most of the currently used antidiabetic medicines, search for finding new and safe drugs to manage diabetes is continued. Naphthoquinones possessing strong antioxidant properties have been employed as candidates for diabetes therapy. Present study is aimed at finding the antioxidant and hypoglycaemic potential of some novel derivatives of 2-phenylamino-1,4-naphthoquinones (PAN) including chloro, nitro, methyl and bromo (5a-d) derivatives synthesized by single pot experiment. Product crystals were purified by TLC and characterized by FT-IR. The antioxidant potential of the compounds was assayed through DPPH radical scavenging and reducing power activities noted as UV-vis. absorbance. The DPPH assay has showed the powerful antioxidant activity of nitro and bromo derivatives, while the nitro derivative showed the significant reduction potential towards FRAP assay. Hypoglycaemic potential of the compounds was studied in rat animal model. All synthesized compounds revealed better hypoglycaemic activity; however, the chloro-derivative exhibited the more potent hypoglycaemic activity showing about 43% reduction in the mean blood glucose levels of the treated animals. As the bioreduction of naphthoquinones may be influenced by changing its redox properties, it has been noticed that the e-donating resonance effect (+R) of 'chloro' group has shown the significant effects on biological activity through stabalization of its imine form which limits the potential of generation of free radicals during bioreduction of quinones and thus has been proposed as the reason of its hypoglycaemic activity. Future studies employing the properties of e-donating groups of PAN may optimize the drug-receptor interaction for better drug designing and drug development strategies against diabetes and also for the clinical trials.

Em razão dos graves efeitos colaterais causados pela maioria dos medicamentos antidiabéticos atualmente utilizados, continua a busca por novos medicamentos seguros para o controle do diabetes. As naftoquinonas, que possuem fortes propriedades antioxidantes, têm sido empregadas como candidatas à terapia do diabetes. O presente estudo visa encontrar o potencial antioxidante e hipoglicemiante de alguns novos derivados de 2-fenilamino-1,4-naftoquinonas (PAN), incluindo derivados de cloro, nitro, metil e bromo (5a-d) sintetizados por experimento em pote único. Os cristais do produto foram purificados por TLC e caracterizados por FT-IR. O potencial antioxidante dos compostos foi testado por meio de atividades de sequestro de radicais DPPH e redução de energia observada como absorção no UV-vis. O ensaio DPPH mostrou a poderosa atividade antioxidante dos derivados nitro e bromo, enquanto o derivado nitro mostrou o potencial de redução significativo para o ensaio FRAP. O potencial hipoglicêmico dos compostos foi estudado em modelo animal de rato. Todos os compostos sintetizados revelaram melhor atividade hipoglicemiante; no entanto, o derivado cloro apresentou atividade hipoglicêmica mais potente, com redução de 43% nos níveis médios de glicose no sangue dos animais tratados. Como a biorredução de naftoquinonas pode ser influenciada pela alteração de suas propriedades redox, notou-se que o efeito da doação eletrônica por ressonância (+R) do grupo "cloro" tem sido significativo na atividade biológica por meio da estabilização de sua forma imina, que limita o potencial de geração de radicais livres durante a biorredução de quinonas, e, portanto, tem sido proposto como a razão de sua atividade hipoglicemiante. Estudos futuros empregando as propriedades de grupos de doação eletrônica de PAN podem otimizar a interação droga-receptor para melhor planejamento de medicamentos e estratégias de desenvolvimento de medicamentos contra o diabetes e também para os ensaios clínicos.

Therapeutic potential of stem cell and melatonin on the reduction of CCl4-induced liver fibrosis in experimental mice model / Potencial terapêutico de células-tronco e melatonina na redução da fibrose hepática induzida por CCl4 no modelo de ratos experimentais

Liver fibrosis is initial stage of any chronic liver disease and its end stage is develops into cirrhosis. Chronic liver diseases are a crucial global health issue and the cause of approximately 2 million deaths per year worldwide. Cirrhosis is currently the 11th most common cause of death globally. Mesenchymal stem cell (MSCs) treatment is the best way to treat acute and chronic liver disease. The aim of this study is to improve the therapeutic potential of MSCs combined with melatonin (MLT) to overcome CCl4-induced liver fibrosis and also investigate the individual impact of melatonin and MSCs against CCl4-induced liver impairment in animal model. Female BALB/c mice were used as CCL4-induced liver fibrotic animal model. Five groups of animal model were made; negative control, Positive control, CCl4+MSCs treated group, CCl4+MLT treated group and CCl4+MSCs+MLT treated group. Cultured MSCs from mice bone marrow were transplanted to CCl4-induced liver injured mice model, individually as well as together with melatonin. Two weeks after MSCs and MLT administration, all groups of mice were sacrificed for examination. Morphological and Histopathological results showed that combined therapy of MSCs+MLT showed substantial beneficial impact on CCl4-induced liver injured model, compared with MSCs and MLT individually. Biochemically, considerable reduction was observed in serum bilirubin and ALT levels of MLT+MSC treated mice, compared to other groups. PCR results shown down-regulation of Bax and up-regulation of Bcl-xl and Albumin, confirm a significant therapeutic effect of MSCs+MLT on CCI4-induced liver fibrosis. From the results, it is concluded that combined therapy of MSCs and MLT show strong therapeutic effect on CCL4-induced liver fibrosis, compared with MSCs and MLT individually.

A fibrose hepática é a fase inicial de qualquer doença hepática crônica, e em sua fase final desenvolve-se para cirrose. As doenças hepáticas crônicas são uma questão de saúde global crucial e a causa de aproximadamente 2 milhões de mortes por ano em todo o mundo. A cirrose, hoje em dia, é a 11ª causa mais comum de morte globalmente. O tratamento da célula-tronco mesenquimal (MSCs) é uma maneira eletiva de tratar a doença hepática aguda e crônica. O objetivo deste estudo é melhorar o potencial terapêutico dos MSCs combinados com a melatonina (MLT) para superar a fibrose hepática induzida por CCl4 e também investigar o impacto individual da melatonina e MSCs contra o comprometimento do fígado induzido por CCl4 no modelo animal. Os ratos BALB / C fêmeas foram usados ​​como modelo de animal fibrótico de fígado induzido por CCl4. Cinco grupos de modelo animal foram feitos: Controle Negativo, Controle Positivo, CCl4 + MSCs Tratados Grupo, Grupo Tratado CCl4 + MLT e Grupo Tratado CCl4 + MSCs + MLT. MSCs cultivados da medula óssea dos ratos foram transplantados para o modelo de camundongos de fígado induzido por CCl4, individualmente, bem como em conjunto com a melatonina. Duas semanas após a administração MSCs e MLT, todos os grupos de camundongos foram sacrificados para o exame. Os resultados morfológicos e histopatológicos mostraram que a terapia combinada do MSCs + MLT mostrou impacto benéfico substancial no modelo ferido no fígado induzido pelo CCl4, em comparação com o MSCs e o MLT individualmente. A redução bioquimicamente considerável foi observada em bilirrubina sérica e níveis ALT de ratinhos tratados com MLT + MSCs, em comparação com outros grupos. Os resultados de PCR mostraram regulação negativa do BAX e regulação positiva do BCL-XL e da albumina, confirmando um efeito terapêutico significativo do MSCs + MLT na fibrose hepática induzida por CCl4. Dos resultados, conclui-se que a terapia combinada de MSCs e MLT mostram um forte efeito terapêutico na fibrose hepática induzida por CCl4, em comparação com MSCs e MLT individualmente.

Antiulcerogenic and antioxidant activities of Plantago ovata ethanolic extract in rats / Atividade antiulcerogênica e antioxidante do extrato etanólico de Plantago ovata em ratos

This study aimed to determine the antiulcerogenic and antioxidant activities of Psyllium (Plantago ovata Forssk) seed ethanolic extract in rats. We assessed the antioxidant potential using free radical scavenging on DPPH, ß-carotene bleaching activity, ferric reducing power, and hydroxyl radical scavenging activity. In the antiulcerogenic study, pre-treatment with Plantago ovata seeds ethanolic extract (POE) (400 mg/kg b.wt) significantly protected against ethanol-induced gastric ulcer in rats by decreasing the ulcer index value and preserving the integrity of the gastric mucosa. The oxidative stress status in the stomach tissues showed a significant increase in the antioxidant enzyme levels of superoxide dismutase, catalase, and glutathione peroxidase with a significant decrease in lipid peroxidation during pre-treatment with POE. In conclusion, the POE protects against gastric ulcer due to its antioxidant potential and presence of bioactive molecules.

O presente estudo teve como objetivo determinar as atividades antiulcerogênica e antioxidante das sementes de Psyllium (Plantago ovata Forssk) em ratos. O potencial antioxidante foi avaliado utilizando o método do sequestro do radical livre DPPH, autooxidação do ß-caroteno, poder redutor de ferro e atividade de sequestro do radical hidroxila. No estudo antiulcerogênico, o pré-tratamento com o extrato etanólico das sementes de Plantago ovata (POE) (400 mg/Kg b.wt) reduziu a úlcera gástrica induzida pelo etanol em ratos, diminuindo o valor do índice de úlcera e preservando a integridade da mucosa gástrica. O estudo do estresse oxidativo nos tecidos estomacais mostrou um aumento significativo dos níveis das enzimas antioxidantes superóxido dismutase, catalase e glutationa peroxidase, com uma diminuição significativa da peroxidação lipídica enquanto pré-tratamento com POE. Em conclusão, o POE protege contra úlcera gástrica devido aos seus potenciais antioxidantes e à presença de moléculas bioativas.

Fasten the analysis of metal-binding proteins with GE-ICP-MS via increasing the electrolyte concentration of the running buffer.

The coupled system of column gel electrophoresis and inductively coupled plasma mass spectrometry (GE-ICP-MS) is a highly effective technique for detecting metal-binding proteins. However, it takes a long time for this method to test a single sample, which greatly limits its application. In this study, GE-ICP-MS system was optimized by adjusting the analytical conditions, including the concentration and pH of running buffer and the proportion of polyacrylamide gel. The results of the experiment showed that the migration speed of proteins in GE was enhanced by increasing the electrolyte concentration in the running buffer solution. Additionally, the ICP-MS response, which was dramatically decreased because of the change in running buffer solution, can be stabilized by adjusting pH of running buffer. Meanwhile, the optimization of polyacrylamide gel ratio allows GE-ICP-MS to maintain high resolution for proteins of similar molecular weight with increased detection speed. After increasing the concentration of running buffer by 10 times, four iodine labeled proteins were successfully separated at baseline by the GE-ICP-MS system at pH 8.0 in 40 min using a resolving gel (8%, 7 cm) and a stacking gel (4%, 1 cm), which was three times faster than the original one. Finally, the optimized method was proved by detecting a silver-binding protein in rat plasma samples. The above method provided an effective and rapid detection for metal-binding proteins in organism.

Illustrate the distribution and metabolic regulatory effects of pterostilbene in cerebral ischemia-reperfusion rat brain by mass spectrometry imaging and spatial metabolomics.

Pterostilbene is a promising molecule with superior pharmacological activities and pharmacokinetic characteristics compared to its structural analogue resveratrol, which could be used to treat ischemic stroke. However, its mechanism is still unclear. The cutting-edge air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and spatial metabolomics analysis were applied to investigate the distribution of pterostilbene in ischemic rat brain and the changes of related small molecule metabolic pathways to further explore the potential mechanisms of pterostilbene against cerebral ischemia-reperfusion injury. This research found that pterostilbene could significantly restore cerebral microcirculation blood flow, reduce infarct volume, improve neurological function and ameliorate neuronal damage in ischemic rats. Moreover, pterostilbene was widely and abundantly distributed in ischemic brain tissue, laying a solid foundation for the rescue of ischemic penumbra. Further study revealed that pterostilbene played a therapeutic role in restoring energy supply, rebalancing neurotransmitters, reducing abnormal polyamine accumulation and phospholipid metabolism. These findings offer an opportunity to illustrate novel mechanisms of pterostilbene in the treatment of cerebral ischemia/reperfusion injury resulting from ischemic stroke.

Genetic and Immunohistochemistry Tools to Visualize Rat Macrophages In Situ.

Macrophages contribute to many aspects of development and homeostasis, innate and acquired immunity, immunopathology, and tissue repair. Every tissue contains an abundant resident macrophage population. Inflammatory stimuli promote the recruitment of monocytes from the blood and their adaptation promotes the removal of the stimulus and subsequent restoration of normal tissue architecture. Dysregulation of this response leads to chronic inflammation and tissue injury. In many tissues, their differentiation and survival are dependent on the colony stimulating factor 1 receptor (CSF1R) signalling axis, which is highly conserved across all vertebrates. Complete loss of either CSF1R or its cognate ligands, colony stimulating factor 1 (CSF1), and interleukin 34 (IL-34), results in the loss of many tissue-resident macrophage populations. This provides a useful paradigm to study macrophages.There are many tools used to visualize tissue-resident macrophages and their precursors, monocytes, in mice and humans. Particularly in mice there are genetic tools available to delete, enhance and manipulate monocytes and macrophages and their gene products to gain insight into phenotype and function. The laboratory rat has many advantages as an experimental model for the understanding of human disease, but the analytical resources are currently more limited than in mice. Here, we describe available genetic models, antibodies, and immunohistochemistry (IHC) methods that may be used to visualize tissue-resident macrophages in rats.

Antidepressant effect of Perilla frutescens essential oil through monoamine neurotransmitters and BDNF/TrkB signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine posits that affect-mind ill-being is the primary cause of depression, with Qi movement stagnation as its pathogenesis. As such, clinical treatment for depression should prioritize regulating Qi and relieving depressive symptoms. The pharmacological properties of traditional Chinese medicine indicate that Perilla frutescens may have potential therapeutic effects on depression and other neuropsychiatric diseases due to its ability to regulate Qi and alleviate depressive symptoms. Although previous studies have reported the antidepressant effects of Perilla frutescens, the mechanism underlying PFEO inhalation-mediated antidepressant effect remains unclear. AIM OF THE STUDY: The aim of this investigation is to elucidate the antidepressant mechanisms of PFEO by examining its effects on monoamine neurotransmitters and the BDNF/TrkB signaling pathway. MATERIALS AND METHODS: The CUMS rat model of depression was established, and the depressive state of the animals was assessed through sucrose preference and forced swim tests. ELISA assays were conducted to determine monoamine neurotransmitter levels in the hippocampus and cerebral cortex of rats. Immunohistochemistry, western blotting, and RT-PCR experiments were employed to investigate the BDNF/TrkB signaling pathway's regulation of depression via PFEO inhalation. RESULTS: It has been observed that inhalation administration of PFEO can significantly enhance the preference for sugar water in CUMS rats and reduce their immobility time during forced swimming. Additionally, there was an increase in the levels of monoamine transmitters in both the hippocampus and cerebral cortex of these rats. Furthermore, there was an upregulation in the expression levels of BDNF and TrkB positive cells as well as BDNF and TrkB proteins within both regions, along with increased BDNF mRNA and TrkB mRNA expression levels. CONCLUSION: The antidepressant effect of PFEO via inhalation administration is speculated to be mediated through the monoamine neurotransmitters and BDNF/TrkB signaling pathway.

Qinzhizhudan formula dampens inflammation in microglia polarization of vascular dementia rats by blocking MyD88/NF-κB signaling pathway: Through integrating network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinzhizhudan Formula (QZZD) is composed of Scutellaria baicalensis Georgi (Huang Qin) extract, Gardenia jasminoides (Zhizi) extract and Suis Fellis Pulvis (Zhudanfen) (ratio of 4:5:6). This formula is optimized from Qingkailing (QKL) injection. Regarding brain injury, QZZD is protective. However, the mechanism by which QZZD treats vascular dementia (VD) has not been elucidated. AIM OF THE STUDY: To ascertain QZZD's effect on the treatment of VD and further investigate the molecular mechanisms. MATERIALS AND METHODS: In this study, we screened the possible components and targets of QZZD against VD and microglia polarization using network pharmacology (NP), then an animal model of bilateral common carotid artery ligation method (2VO) was induced. Afterward, The Morris water maze was employed to evaluate cognitive ability, and pathological alterations in the CA1 area of the hippocampus were detected using HE and Nissl staining. To confirm the affect of QZZD on VD and its molecular mechanism, the contents of inflammatory factors IL-1ß, TNF-α, IL-4, and IL-10 were performed to detect by ELISA, the phenotype polarization of microglia cells was detected by immunofluorescence staining, and the expressions of MyD88, p-IκBα and p-NF-κB p65 in brain tissue were detected by western blot. RESULTS: A total of 112 active compounds and 363 common targets of QZZD, microglia polarization, and VD were identified, according to the NP analysis. 38 hub targets were screened out from the PPI network. GO analysis and KEGG pathway analysis showed that QZZD may regulate microglia polarization through anti-inflammatory mechanism such as Toll-like receptor signaling pathway and NF-κB signaling pathway. The further results showed that QZZD can alleviate the memory impairment induced by 2VO. QZZD profoundly rescued brain hippocampus neuronal damage and increased the number of neurons. These advantageous outcomes were linked to the control of microglia polarization. QZZD decreased M1 phenotypic marker expression while increasing M2 phenotypic marker expression. QZZD may controll the polarization of the M1 microglia by blocking the core part of Toll-like receptor signaling pathway, that is the MyD88/NF-κB signaling pathway, which reduced the neurotoxic effects of the microglia. CONCLUSION: Here, we explored the anti-VD microglial polarization characteristic of QZZD for the first time and clarified its mechanisms. These findings will provide valuable clues for the discovery of anti-VD agents.

Astragalus saponins protect against extrahepatic and intrahepatic cholestatic liver fibrosis models by activation of farnesoid X receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic Liver Fibrosis (CLF) is a hepatobiliary disease that typically arises as a late-stage complication of cholestasis, which can have multiple underlying causes. There are no satisfactory chemical or biological drugs for CLF. Total Astragalus saponins (TAS) are considered to be the main active constituents of the traditional Chinese herb Astragali Radix (AR), which has the obvious improvement effects for treating CLF. However, the mechanism of anti-CLF effects of TAS is still unclear. AIM OF THE STUDY: The present study was undertaken to investigate the therapeutic effects of TAS against bile duct ligation (BDL) and 3, 5-diethoxycarbonyl-1,4-dihydroxychollidine (DDC) -induced CLF models and to reveal the potential mechanism to support its clinic use with scientific evidence. MATERIALS AND METHODS: In this study, BDL-induced CLF rats were treated with TAS (20 mg/kg, 40 mg/kg) and DDC-induced CLF mice were treated with 56 mg/kg TAS. The therapeutic effects of TAS on extrahepatic and intrahepatic CLF models were evaluated by serum biochemical analysis, liver histopathology and hydroxyproline (Hyp). Thirty-nine individual bile acids (BAs) in serum and liver were quantified by using UHPLC-Q-Exactive Orbitrap HRMS. qRT-PCR, Western blot and immunohistochemistry analysis were used to measure the expression of liver fibrosis and ductular reaction markers, inflammatory factors and BAs related metabolic transporters, along with nuclear receptor farnesoid X receptor (FXR). RESULTS: The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBiL), direct bilirubin (DBiL) and contents of liver Hyp were dose-dependently improved after treatment for TAS in BDL and DDC- induced CLF models. And the increased levels of ALT and AST were significantly improved by total extract from Astragali radix (ASE) in BDL model. The liver fibrosis and ductular reaction markers, α-smooth muscle actin (α-SMA) and cytokeratin 19 (CK19), were significantly ameliorated in TAS group. And the liver expression of inflammatory factors: interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin 1ß (IL-1ß) were significantly decreased after TAS treatment. In addition, TAS significantly ameliorated taurine-conjugated BAs (tau-BAs) levels, particularly α-TMCA, ß-TMCA and TCA contents in serum and liver, which correlated with induced expressions of hepatic FXR and BAs secretion transporters. Furthermore, TAS significantly improved short heterodimer partner (SHP), cholesterol 7α-hydroxylase (Cyp7a1), Na+ taurocholate cotransport peptide (NTCP) and bile-salt export pump (BSEP) mRNA and protein expression. CONCLUSIONS: TAS exerted a hepatoprotective effect against CLF by ameliorating liver injury, inflammation and restoring the altered tau-BAs metabolism to produce a positive regulatory effect on FXR-related receptors and transporters.

Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-ß/NF-κb signaling pathway: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. AIM OF THE STUDY: This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. MATERIALS AND METHODS: The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. RESULTS: We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-ß, and NF-κB proteins in the liver of hyperlipidemic rats. CONCLUSION: QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-ß/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance.

Therapeutic potential of elema-1,3,7(11),8-tetraen-8,12-lactam from Curcuma wenyujin on diabetic retinopathy via anti-inflammatory and anti-angiogenic pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, the causes of diabetic retinopathy (DR) are blood stasis and heat. Curcuma wenyujin Y. H. Chen & C. Ling and its extracts have the effects of promoting blood circulation to remove blood stasis, clearing the heart, and cooling the blood, and have been used in the treatment of DR. Elema-1,3,7 (11),8-tetraen-8,12-lactam (Ele), an N-containing sesquiterpene isolated from this plant. However, the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR are still unknown. AIM OF THE STUDY: To evaluate the anti-inflammatory and anti-angiogenic effects of Ele and its therapeutic potential in DR. MATERIALS AND METHODS: In vitro, anti-inflammatory and anti-angiogenic effects were assessed using TNF-α or VEGF-stimulated HUVECs. Protein expression was analyzed using Western blotting. ICAM-1 and TNF-α mRNA expressions were analyzed using real-time quantitative RT-PCR. The therapeutic potential in DR was assessed using both animal models of STZ-induced diabetes and oxygen-induced retinopathy. The retinal vascular permeability was measured using Evans blue, and the quantitation of retinal leukostasis using FITC-coupled Con A. The retinal neovascular tufts were analyzed using fluorescein angiography and counting pre-retinal vascular lumens. RESULTS: Ele inhibited NF-κB pathway, and ICAM-1, TNF-α mRNA expression in TNF-α- stimulated HUVECs. It also inhibits the multistep process of angiogenesis by inhibiting the phosphorylation of VEGFR2 and its downstream signaling kinases Src, Erk1/2, Akt, and mTOR in VEGF-stimulated HUVECs. Intravitreal injection of Ele can significantly reduce retinal microvascular leakage, leukostasis, and expression of ICAM-1, TNF-α in diabetic rats and inhibits oxygen-induced retinal neovascularization and VEGFR2 phosphorylation in OIR mice. CONCLUSIONS: Ele has anti-inflammatory and anti-angiogenic effects through inhibiting NF-κB and VEGFR2 signaling pathways, and it may be a potential drug candidate for DR.

Quality control assessment, toxicity profiling, and experimental validation of network pharmacology-predicted anti-inflammatory potential of Natsiatum herpeticum Buch.-Ham. Ex Arn.

ETHNOPHARMACOLOGICAL RELEVANCE: Natsiatum herpticum Buch.-Ham. Ex Arn., a least-explored plant, is being considered a wild edible plant by the Bankariya community of Nepal and the Mishing, Sonowal Kachari, and several ethnic groups in the north-east region of India. It is also used as a traditional remedy for the treatment of pain and inflammation-associated conditions like cuts and wounds, stomach ache, backache, and headache as a practice of a folkloristic system of medicine. In spite of several previous publications suggesting its use by different tribes, no documentation or scientific approaches have been made hitherto to validate its ethnopharmacological claims. AIM OF STUDY: The study aimed at the botanical quality control assessment, toxicity profiling, and network pharmacology-assisted experimental validation of the anti-inflammatory potential of the aqueous extract of N. herpeticum to fill the lacunae in the current knowledge. MATERIAL AND METHOD: Plant material was authenticated using a classical taxonomical approach and DNA barcoding. The quality control methods, acute toxicity study, and repeated dose 28-day oral toxicity study were performed as per standard guidelines. QToF-MS analysis, drug-likeness properties, network pharmacology-based anti-inflammatory prediction, and in vitro assays were carried out. RESULTS: Quality control assessment was done for the plant. Toxicity studies revealed the aqueous extract to be non-toxic when consumed for short periods at low doses. Alterations in food and water intake, biochemical parameters, and alterations in liver histology (n = 2 female rats) implicate repeated exposure to high doses (2000 mg/kg) that may possess deleterious effects, particularly in hepatic tissues. 21 representative compounds (14 drug-like molecules) were detected by QToF-MS analysis and then subjected to network pharmacology to predict anti-inflammatory effects. It was found that an anti-inflammatory effect may be exerted by modulating inflammatory pathways involving genes such as TNF, PTGS2, EGFR, STAT3, PPARG, PTGER4, PPARA, NOS2, TRPV1, and JAK2. Further, in vitro studies demonstrated plant extract to possess a good anti-inflammatory effect with IC50 values of 98.76, 85.73, and 96.16 µg/ml in protein denaturation, proteinase inhibition, and haemolysis inhibition assays, respectively. CONCLUSION: The plant extract was found to be safer at acute dose but may cause potential liver toxicity on prolonged use. The anti-inflammatory property predicted by network pharmacology was further supported by the positive results of in vitro experiments. In summary, to further establish the toxicity profile of this edible plant and its anti-inflammatory properties, chronic toxicity study and in vivo experiments are required.

Toxicological safety evaluation of zengye granule through acute and 30-day toxicity studies in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Zengye granule (ZYG), a traditional Chinese medicine formula composed of Radix Scrophulariae, Radix Ophiopogonis, and Radix Rehmanniae in the ratio of 1.0:0.8:0.8, is listed in the Chinese Pharmacopoeia for treating diseases associated with yin deficiency, such as inner heat, dry mouth and pharynx, and dry bound stool. However, little information is available on its toxicological safety. AIM OF THE STUDY: To evaluate the acute and subacute toxicity of ZYG after oral administration in rats. MATERIALS AND METHODS: In the acute toxicity study, ZYG was orally administered to rats at a single dose of 10 g/kg/day. In the subacute toxicity study, ZYG was administered orally to rats at repeated daily doses of 2.5, 5.0, or 10 g/kg/day for 30 days. The toxicological effects were evaluated by assessing the rats' general behavior, body weight, food intake, water consumption, blood biochemical and hematological parameters, organ coefficients, and organ histopathology. RESULTS: No obvious adverse reactions were found in the rats in the acute toxicity study, indicating that ZYG was non-toxic. In the subacute toxicity study, ZYG had no toxic effect on the rats at a dose of 2.5 g/kg/day but showed slight toxicity in the kidneys, and spleens of the rats at doses of 5 and 10 g/kg/day. Significant drug toxicity was observed in male and female rats at 5 and 10/kg/day; however, elevated WBCs counts, ALT, and LYMs levels were found in female rats. CONCLUSIONS: The oral administration of ZYG at a dose of less than 10 g/kg/day for 1 day or 2.5 g/kg/day for 30 consecutive days can be considered safe, as these doses showed no distinct toxicity or side effects in the rats in this study. Therefore, the dosage should be set according to the clinically recommended dosage to ensure its safety.

Urtica cannabina L. water extract exhibits anti-inflammatory activity by regulating inflammatory cytokines: In vitro and in vivo evidence.

ETHNOPHARMACOLOGICAL RELEVANCE: Urtica cannabina L. (U. cannabina) is a medicinal plant used in traditional Chinese and Kazakh medicine for treatment of various ailments such as rheumatoid arthritis, rheumatic pain, high blood pressure, and snake bites. However, very few studies have focused on the anti-inflammatory effects of U. cannabina and the mechanisms underlying these effects. AIM OF THE STUDY: This study to investigate the in vitro and in vivo anti-inflammatory effect of U. cannabina, the underlying mechanisms, and its phytochemical profile. MATERIALS AND METHODS: We investigated the anti-inflammatory effects of the U. cannabina water extract on lipopolysaccharide-stimulated RAW264.7 macrophages and paw edema in rats and analyzed its chemical components using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). RESULTS: U. cannabina water extract effectively inhibited the secretion of multiple inflammatory factors, and its corresponding mRNA expression in LPS-induced RAW264.7 cells (p < 0.05). Tincture of U. cannabina water extract significantly reduced carrageenan-induced rat paw edema and levels of inflammatory factors (p < 0.05). A total of 31 compounds, which mainly include organic acids, were tentatively identified based on the comparison of their mass spectrum profiles with those recorded in a mass spectra database. CONCLUSIONS: The results of this study elucidated the anti-inflammatory effect of U. cannabina water extract in vitro and in vivo and showed that the extract elicits the anti-inflammatory effects by regulating the activity of inflammatory cytokines. The results prove that U. cannabina is a valuable source of active compounds with anti-inflammatory activity.