RESUMO
Alzheimer's disease (AD) is a neurodegenerative brain disorder that progressively impairs long-term and working memory. The function and mechanism of PA(Patchouli alcohol) in improving AD in the external treatment of encephalopathy remain unclear. This study aimed to investigate the therapeutic effect of PA on AD using an Aß1-42 induced AD mouse model with LPS(Lipopolysaccharide) stimulation of BV2 microglial cells. Additionally, we aimed to explore the potential mechanism of PA in enhancing autophagy and reducing neuroinflammation through the AMPK (AMP-activated protein kinase)/mTOR (Mammaliam target of rapamycin) signaling pathway. The Morris water maze was used to assess cognitive function, and cortical and hippocampal tissues were collected for further analysis of the corresponding signaling pathways and inflammatory changes through biological experiments. Our research findings demonstrate that PA has a significant positive impact on cognitive and memory impairments in mice that have been induced with Aß1-42-induced AD. Additionally, PA was also found to revert the activation of microglia induced by LPS. These effects may be attributed to the reduction of neuroinflammation and enhancement of the AMPK/mTOR autophagy pathway. Therefore, PA may serve as an effective therapeutic option to prevent or delay the progression of AD-associated memory dysfunction.
Assuntos
Proteínas Quinases Ativadas por AMP , Doença de Alzheimer , Peptídeos beta-Amiloides , Disfunção Cognitiva , Microglia , Fragmentos de Peptídeos , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Peptídeos beta-Amiloides/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Camundongos , Doença de Alzheimer/metabolismo , Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Fragmentos de Peptídeos/metabolismo , Fragmentos de Peptídeos/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais de DoençasRESUMO
INTRODUCTION: The polarization of T helper (Th) cells plays an important role in the inflammatory response, pathogen removal, and tissue damage processes of infectious acute lung injury (ALI). However, Th cell polarization in viral- or bacterial-mediated ALI is not well defined. Herein, an influenza virus (A/FM/1/47, H1N1) and lipopolysaccharide (LPS) were chosen to induce ALI in mice, and the resultant diversity of Th-cell polarization was explored. METHODOLOGY: BALB/c mice were challenged intranasally with the influenza virus or LPS. Edema of the lung, infiltration of inflammatory cells (macrophages, neutrophils, and lymphocytes), oxidative stress, and signature cytokines of Th1 and Th2 cells were detected at 2 days post virus or LPS challenge. RESULTS: The mice exhibited increased capillary permeability accompanied by lung edema and protein-rich alveolar exudation after virus or LPS challenge. Additionally, excessive infiltration of inflammatory cells, robust oxidative stress, and cytokine production were observed in both mouse groups. However, there was conspicuous disparity in the inflammatory cell infiltration and cytokines between the virus- and LPS-challenged mice, where the infiltration in virus-challenged mice was mainly of macrophages and accompanied by robust Th1 cytokine elevation, whereas the infiltration in LPS-challenged mice was primarily of neutrophils and accompanied by robust Th2 cytokine elevation. CONCLUSIONS: The Th cell polarization was skewed depending on whether ALI was induced by the influenza virus or LPS. The polarization in the virus-challenged mice was primarily toward a Th1 response, whereas that in the LPS-challenged mice was mainly toward Th2.
Assuntos
Lesão Pulmonar Aguda/patologia , Imunidade Celular , Vírus da Influenza A Subtipo H1N1/crescimento & desenvolvimento , Lipopolissacarídeos/toxicidade , Infecções por Orthomyxoviridae/patologia , Células Th1/imunologia , Células Th2/imunologia , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos BALB CRESUMO
Rosmarinic acid-4-O-ß-D-glucoside (RAG) is a dicaffeoyl phenolic compound isolated from Sarcandra glabra (Thunb.) Nakai. Preliminary studies show that RAG has significant anti-inflammatory properties and can alleviate ear swelling in mice and the paw swelling in rats. Here, the anti-influenza effects of RAG were investigated in mice infected with A/FM/1/47 H1N1 virus. The survival rate and body weight were observed, the lung edema, virus copies, inflammatory cytokines (including IL-4, IL-5, TNF-α and IFN-γ) and oxidative damage indexes (including SOD, MDA, NO, and CAT) were measured. Moreover, immune cell recruitment in alveoli was measured with white blood cells and differential counts. Therapeutic RAG concentrations substantially improve the symptoms, mitigate body weight loss and alleviate lung edema induced by virus, thus improve survival protection effects. Furthermore, RAG was shown to regulate influenza virus-induced inflammatory cytokine expression, specifically by downregulating the Th1 cell cytokines IFN-γ, TNF-α and upregulating the Th2 cell cytokines IL-4, IL-5. Cell migration and infiltration were also diminished after RAG administration.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios não Esteroides/administração & dosagem , Cinamatos/administração & dosagem , Depsídeos/administração & dosagem , Glucosídeos/administração & dosagem , Infecções por Orthomyxoviridae/complicações , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios não Esteroides/química , Peso Corporal , Cinamatos/química , Citocinas/análise , Depsídeos/química , Modelos Animais de Doenças , Glucosídeos/química , Pulmão/patologia , Pulmão/virologia , Camundongos , Infecções por Orthomyxoviridae/patologia , Análise de Sobrevida , Carga Viral , Ácido RosmarínicoRESUMO
OBJECTIVE: To establish the diagnostic quantitative criteria for fire-heat syndrome (FHS) of Chinese medicine (CM) based on the receiver operating characteristic (ROC) curve and principal component analysis (PCA). METHODS: The symptoms and signs of FHS cases and healthy subjects from Guangzhou, Henan and Hunan of China were collected through questionnaire, and the diagnostic quantitative score tables were established for the three regions, respectively, with the method of maximum likelihood analysis. The homogeneity test was then performed on the diagnostic score tables for the three regions with ROC curve, and the diagnostic efficiency of diagnostic score tables for the three regions was compared with the prospective test and retrospective test. The method of PCA was adopted to obtain the analysis matrix for classifying the tapes of FHS. RESULTS: Twenty-seven elements of FHS were confirmed through Chi-square test, and the diagnostic score tables for the three regions were established with the method of maximum likelihood analysis on the basis of the collected case data. According to the ROC curve test, the areas under ROC curve of Guangzhou diagnostic score table assessment with candidates in Guangzhou, Henan and Hunan were 0.998, 0.961 and 0.956, respectively. It showed that the diagnostic efficiency of Guangzhou diagnostic score tables was the highest one. With the prospective test, the area under ROC of Guangzhou diagnostic score table was 0.949, and more than any other diagnostic score table. By PCA, FHS was classified into excess fire and deficiency fire, and then classified into syndrome of flaring up of Heart (Xin) fire, syndrome of Lung (Fei)-Stomach (Wei) excess fire, syndrome of deficiency of Liver (Gan)-yin and Kidney (Shen)-yin, and syndrome of deficiency of Lung-yin from the view of viscera. In the retrospective test, the consistency with clinicians' diagnosis was 69.4%, and in the prospective test, it was 70.1%. CONCLUSIONS: The Guangzhou diagnostic score table could be used as the recommended criteria for the diagnosis of FHS. The classification of FHS was basically in conformity with the clinical situation.
Assuntos
Medicina Tradicional Chinesa/métodos , Análise de Componente Principal , Curva ROC , Adulto , Feminino , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos , SíndromeRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Many traditional Chinese medicines (TCM) have been used for hundreds of years for hair blackening and hair nourishing, and now many of them are commonly used in Chinese herbal shampoo to nourish the hair and promote hair growth. AIMS OF THE STUDY: The present study was performed to screen 5α-reductase (5αR) inhibitors from traditional Chinese medicines, evaluate its hair growth promoting activity in vivo, and further investigate its effects on androgen metabolism and the expression of 5αR II in hair follicles. MATERIALS AND METHODS: Nine TCM which were dried, ground and extracted by maceration with 75% ethanol or distilled water were used for screening 5αR inhibitors, and enzymes were extracted from the rat epididymis. The leaves of Platycladus orientalis (L.) Franco was used to evaluate the in vivo anti-androgenic activity. Skin color was observed daily and the hair re-growth was assessed by assigning the hair growth score. The longitudinal sections of hair follicles were used for observing follicle morphology, classifying of distinct stages of hair follicle morphogenesis and calculate the average score. The transverse sections were used for determination of hair follicle counts. Testosterone (T), Dihydrotestosterone (DHT) and Estradiol (E2) levels in serum and skin tissue were detected by ELISA kits. The immunofluorescence assay was used to detect the influence of CP-ext on 5αR expression in dorsal skin. RESULTS: We found the extract of Ganoderma lucidum (GL-ext), Polygonum multiflori (PM-ext), Cacumen platycladi (CP-ext) and Cynomorium songaricum (CS-ext) showed stronger 5αR inhibitory activity. CP-ext (5mg and 2mg/mouse/day) could significantly shorten the time of the dorsal skin darkening and got longhaired (P<0.01), and showed high hair re-growth promoting activity. Furthermore the histological data of hair follicles in each group showed that CP-ext could promote the growth of hair follicle and slowed down hair follicles enter the telogen. What's more CP-ext significantly reduced DHT levels and down-regulated the expression of 5αRâ ¡in skin (P<0.01). CONCLUSIONS: GL-ext, PM-ext, CP-ext and CS-ext showed strong 5αR inhibitory activity. CP-ext possesses high hair growth promoting activity in the in vivo androgen-sensitive mouse model via inhibiting the 5αR activity, decreasing the DHT levels and in turn suppressing the expression of 5αR. Our study may contribute to the development of a new generation of herbal supplements with clearer material basis of pharmacodynamic for treating androgenic alopecia (AGA).
Assuntos
3-Oxo-5-alfa-Esteroide 4-Desidrogenase/metabolismo , Alopecia/induzido quimicamente , Cupressaceae/química , Medicamentos de Ervas Chinesas/farmacologia , Cabelo/efeitos dos fármacos , Testosterona/toxicidade , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase/genética , Animais , Medicamentos de Ervas Chinesas/química , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect of moxibustion on alleviating menstrual pain and relieving the symptoms of dysmenorrhea in a cohort of young nursing students in China. METHODS: A randomized double blind clinical trial of crossover design was used. In the two-phase study, a total of 56 nursing students with menstrual pain in Guangzhou University of Chinese Medicine in China was randomly allocated into two groups. In the first treatment phase, the participants in Group A (n=28) received moxibustion therapy from five days before the menstrual period to the onset through a specific heating box in which burning moxa stick was fixed, the participants in Group B (n=28) received the same heating box but with a paper-wrapped stick incense fixed inside (placebo therapy) during the same intervention period. The acupoints Guanyuan(CV4) and Shenque(CV8) were selected for treatment. After the first treatment phase for two menstrual cycles, the intervention was stopped for three menstrual cycles during a wash period. In the second treatment phase, the intervention of two groups were switched. Group A received the placebo therapy and Group B received moxibustion therapy. NRS, VRS, PRI, VAS and BRS-6 were evaluated at the baseline and after each treatment phase. RESULTS: There was no statistically significant difference in age, history of dysmenorrhea, length of menstrual cycle, age at menarche, duration of menstrual flow, PRI score, VAS score, BRS score and RSS score between Group A and Group B (p>0.05). After the first treatment phase, the score of BRS-6 has significant differences between two groups at the first menstrual cycle (p<0.05). At the second menstrual cycle, the score of VAS, BRS-6,sensory of PRI, affective dimension of PR and total score of PRI in Group A were much lower than Group B (p<0.05). NRS and VRS had significant differences between two groups with Wilcoxon Mann-Whitney test after the first treatment phase (p<0.05). The frequency rating of weakness, loss of appetite, diarrhea, and the total score had significant differences between two groups at the first menstrual cycle (p<0.05). And the frequency rating of weakness, backache, facial blemishes, loss of appetite, diarrhea, and the total score had significant differences between two groups at the second menstrual cycle (p<0.05). The severity rating of backaches, loss of appetite, sleeplessness, and the total score had significant differences between two groups after the second menstrual cycle (p<0.05). After three months' wash period, the score of VAS, BRS-6, sensory of PRI, affective of PR, total score of PRI and VRS had significant differences between two groups after the second treatment phase (p<0.01). And the frequency rating of leg aches, dizziness, nervousness and the total score had significant differences between two groups after the second treatment phase (p<0.05). And the severity rating of abdominal pain, weakness, leg aches, dizziness, nervousness and the total score had significant differences between two groups after the second treatment phase (p<0.05). CONCLUSIONS: The results suggested that moxibustion therapy with a heating box was effective for alleviating menstrual pain and symptoms of young female university students in China. The effect of moxibustion might not only due to heat stimulation, but also from the burning of moxa stick. Boxing moxibustion could be recommended as a nonpharmacological pain relief intervention for university students for its cost effectiveness, practical design and relative safety, and it is easy for the university students themselves to self-administer at home.