Licorice zinc suppresses melanogenesis via inhibiting the activation of P38MAPK and JNK signaling pathway in Balb/c mice skin

Purpose: The active melanocytes in the skin were affected by hormones and ultraviolet (UV) irradiation. Licorice zinc has a whitening effect, which may have a prominent potential in the treatment of pigmented skin disease. Methods: Modeling chloasma C57BL/6J mice by daily progesterone injection (15 mg/kg) and ultraviolet B (UVB) irradiation (λ = 312 nm, 2 h/day) for 30 days. Then, mice were given 0.65, 1.3, and 2.6 (g/kg) of licorice zinc and tranexamic acid 250 mg daily by oral administration for 14 days, respectively. Hematoxylin and eosin and Fontana-Masson staining, and Western blotting (WB) were performed to test the inhibitory of melanogenesis and activation of c-Jun-N-terminal (JNK)/p38 mitogen-activated protein kinases (MAPK) for licorice zinc. Melanogenesis was induced by α-melanocyte-stimulating hormone in vitro. Cell counting kit-8, melanin content determination, and WB were performed to verify the inhibitory effect of licorice zinc on melanogenesis. Results: The present study showed that licorice zinc decreased melanin formation, cutaneous tissue injury, and the phosphorylation of JNK and P38MAPK, which was caused by UVB irradiation in vivo. In vitro, licorice zinc showed opposite effects from JNK/p38 activator. Meanwhile, tyrosinase-related protein-1, tyrosinase, and microphthalmia-associated transcription factor were decreased too. Conclusions: Licorice zinc induced a decrease in melanin synthesis by inhibiting the JNK and the P38MAPK signaling pathway, suggesting licorice zinc is a potential agent of anti-chloasma.

Effect of IL-33 on pyroptosis of macrophages in mice with sepsis via NF-κB/p38 MAPK signaling pathway

ABSTRACT Purpose To demonstrate the effect of IL-33 on the macrophage pyroptosis in mice with sepsis through the NF-kB/p38 MAPK signal pathway. Methods In total, 24 C57BL/6 mice were divided into the sham operation group (sham) and the cecal ligation and puncture group (CLP). After CLP, 24 IL-33-/- mice were divided into the IL-33-/- group and the IL-33-/- intervention group. The latter group was intraperitoneally injected with IL-33. Mouse mortality was observed after CLP. Macrophage apoptosis in peritoneal lavage fluid was detected by flow cytometry. Serum inflammatory factor level was detected by ELISA. Apoptotic protein expression and NF-κB/p38 MAKP signaling pathway protein expression were detected by qRT-PCR and Western blot. Results Knocking out IL-33 significantly reduced the mortality of CLP mice, as well as the mRNA expression of IL-33 and the levels of serum inflammatory factors, including IL-33, IL-1β, and IL-18. It also reduced the rate of macrophage apoptosis and the expression of the apoptotic protein caspase-1 p10; increased the expression of IκBα; and reduced the protein expression of NF-κB and p38 MAPK. These effects were reversed after exogenous injection of IL-33. Conclusions IL-33 can increase the level of macrophage pyroptosis in mice with sepsis (by activating the NF-kB/p38MAPK signal pathway) and the mortality of these mice.

AVALIAÇÃO DA REMODELAÇÃO CARDÍACA DE RATOS ESPONTANEAMENTE HIPERTENSOS SUBMETIDOS AO TREINAMENTO INTERVALADO DE ALTA INTENSIDADE

Avaliação da remodelação cardíaca de ratos espontaneamente hipertensos submetidos ao treinamento intervalado de alta intensidade Introdução: Hipertensão é um grave problema de saúde pública, pode levar à hipertrofia concêntrica um importante fator de risco para insuficiência cardíaca, que é considerada um preditor de maior morbimortalidade cardiovascular. O Treinamento Intervalado de Alta Intensidade (HIIT) pode ser indicado para hipertensos. Entretanto, o efeito potencial do HIIT tem mostrado resultados controversos e os aspectos moleculares remodelação cardíaca em hipertensos não foram totalmente elucidado. Objetivo: analisar os efeitos do HIIT durante a fase compensada da hipertensão arterial sobre os parâmetros estruturais, funcionais e moleculares da remodelação miocárdica em ratos espontaneamente hipertensos (SHR). Métodos: Ratos machos (12 meses de idade) foram divididos em três grupos: 1) Ratos Wistar Kyoto (WKY, n=8); 2) ratos sedentários espontaneamente hipertensos (SHR-SED, n =10) e 3) ratos espontaneamente hipertensos treinados (SHR-HIIT, n=10). Os parâmetros de pressão arterial média, capacidade máxima de exercício e perfil ecocardiográfico foram avaliados antes e após o HIIT; a remodelação cardíaca foi avaliada por meio de ecocardiografia, músculo papilar isolado e a expressão gênica em relação à via MAPK: Elk1, cJun, ATF2, MEF2. Para comparação entre os grupos foi utilizado ANOVA seguido de Tukey ou Kruskal-Wallis e Dunn (p<0.05). Resultados: HIIT diminuiu a PAS (SED-SHR: 229 ± 5.93 mmHg vs HIIT-SHR: 198.6 ± 18.3 mmHg; p = 0.001), aumentou a distância percorrida, sendo 82,7% maior no grupo SHR-HIIT (SHR-SED=183.0±88.08m vs. SHR-HIIT=1126.0±187.1m; p<0.0001) e reduziu a tensão de repouso do músculo papilar (WKY=0.77 ± 0.216; SHR-SED=1.26 ± 0.20; SHR-HITT=0.67 ± 0.23; p=0.0001). Na expressão gênica houve uma diminuição da expressão do gene ATF2 nos grupos hipertensos em relação ao grupo controle (WKY: 1.14 ± 0.62; SHR-SED: 0.39 ± 0.11; SHR-HIIT: 0.62 ± 0.21 p = 0.03) sem alterações nos demais genes. Conclusão: O HIIT aplicado ratos SHR na fase de hipertensão compensada demonstrou uma técnica adequada para diminuir a pressão arterial, melhorar a capacidade funcional, gerou um aumento da hipertrofia cardíaca, mas atenuou a disfunção diastólica miocárdica, sem prejuízos funcionais ou alteração gênica.

Evaluation of cardiac remodeling in spontaneously hypertensive rats submitted to high-intensity interval training Introduction: Hypertension, is a serious public health problem, can lead to concentric hypertrophy - an important risk factor for heart failure, which is considered a predictor of greater cardiovascular morbidity and mortality. High Intensity Interval Training (HIIT) can be indicated for hypertensive patients. However, the potential effect of HIIT has controversial results and the molecular aspects of cardiac remodeling in hypertensive patients have not been fully elucidated. Objective: to analyze the effects of HIIT during the compensated phase of arterial hypertension on the possible parameters, give and myocardial remodeling molecules in spontaneously hypertensive rats (SHR). Methods: we evaluated the influence of HIIT on blood pressure, exercise tolerance and cardiac remodeling in spontaneously hypertensive rats (SHR). Methods: Male rats (12 months old) were divided into three groups: 1) Wistar Kyoto rats (WKY, n = 8); 2) spontaneously hypertensive sedentary rats (SED-SHR, n = 10) and 3) spontaneously hypertensive trained rats (HIIT-SHR, n = 10). The parameters of mean arterial pressure, maximum exercise capacity and echocardiographic profile were taken before and after HIIT; cardiac remodeling was assessed using echocardiography, isolated papillary muscle and gene expression quantified in relation to the MAPK pathway: Elk1, cJun, ATF2, MEF2. For comparison between the groups, ANOVA was used followed by Tukey or Kruskal-Wallis and Dunns (p <0.05). Results: HIIT decreased SBP (SED-SHR: 229 ± 5,93 mmHg vs HIIT-SHR: 198,6 ± 18,3 mmHg; p = 0,001), increased the distance covered, being 82.7% greater in the SHR- HIIT (SED-SHR = 183.0 ± 88.08m vs. HIIT-SHR = 1126.0 ± 187.1m; p <0.0001) and reduced the resting period of the papillary muscle (WKY = 0.77 ± 0.216 ; SED-SHR = 1.26 ± 0.20; HIIT-SHR = 0.67 ± 0.23; p = 0.0001) and in gene expression there was a decrease in the gene encoding ATF2 protein in hypertensive groups in relation to control group (WKY: 1.14 ± 0.62; SHR-SED: 0.39 ± 0.11; HIIT-SHR: 0.62 ± 0.21 p = 0.03) Conclusion: The HIIT applied in SHR models in the compensated hypertension phase, a technique to decrease blood pressure, functional capacity, generated an increase in cardiac hypertrophy, but attenuated myocardial diastolic dysfunction, without dissipating damage or altering the gene.