Anti-obesity effect of combined treatment of hyperforin and amlexanox on ob/ob mice / 中华内分泌代谢杂志

Objective:To investigate the effect of combined treatment of hyperforin(HPF) and amlexanox(AM) on obesity and metabolic disorders.Methods:ob/ob mice were used as an obese mice model and treated with HPF alone(2.5 mg/kg intraperitoneal injection) or combined with AM(50 mg/kg, gavage administration) for 4 weeks. Their body weight and food intake were monitored, glucose tolerance test and insulin tolerance test were performed, serum alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels were detected. Nuclear magnetic resonance was used to detect the body composition and metabolic cage was used to detect the energy consumption. After sampling, HE staining was used to observed the pathological change of fat and liver tissues, Western blotting and enzyme-linked immunosorbent assay(ELISA) were used to detect the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA) signaling pathway.Results:Compared to the vehicle-treated mice(54.07 g), HPF-treated mice showed attenuated body weight gain(51.33 g, P=0.042) and reduced total fat mass( P=0.011); while administration of HPF in combination with AM(HPF/AM) further reduced the body weight(47.61 g, P=0.041). HE staining analysis showed that HPF alone or HPF/AM treatment both decreased the diameters of adipocytes and infiltration of white fat( P=0.014, P=0.032) in brown adipose tissues, which resulted in a trend of browning. However, HPF/AM-treatment didn′t further diminish adipocytes or reduce lipid accumulation in brown adipose tissues compared to HPF-treated mice. In addition, the basal oxygen consumption rate(VO 2, P<0.001) and(VCO 2, P=0.002) of HPF-treated mice were mainly elevated in the light phase relative to that of control mice; while HPF/AM-treatment further promote the energy consumption both in the dark phase and light phase. Notably, cAMP-PKA signaling pathway was obviously activated under HPF/AM-treatment in inguinal white adipose tissue. Moreover, HPF/AM-treatment showed beneficial effects on glucose metabolism and fatty liver, as indicated by improved insulin resistance, reduced liver steatosis( P=0.049) and the serum ALT levels( P=0.008). Conclusion:Combined administration of HPF and AM is an effective strategy in the treatment of obesity, improvement of metabolic disorders and alleviation of catecholamine resistance.

Effect of hyperforin on learning and memory abilities and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of Alzheimer's disease model mice / 中国中药杂志

To investigate the effect of the hyperforin (HF) on learning and memory function and Aβ₁₋₄₂, βAPP and BACE1 protein expressions in hippocampus of five-month-old APP/PS1 double transgenic mice, and discuss the underlying mechanism of HF. The five-month-old APP/PS1 double transgenic mice were randomly divided into the model group, rosiglitazone group (12 mg•kg⁻¹•d⁻¹) and HF high dose, middle dose and low dose groups (600, 300 and 150 mg•kg⁻¹•d⁻¹) in each group; in addition, 15C57BL/6J mice with the same months and background were selected as normal group. Drugs were diluted in the same volume before using, and then administrated by ig for 7 months, 1 time a day; the mice in normal group and model group received the same volume of distilled water. The learning and memory ability was tested by Morris water maze; Aβ₁₋₄₂, βAPP and BACE1proteinexpressionlevelswere tested by immunohistochemistry and Western blot. The Morris water maze results showed that as compared with the normal group, the learning and memory ability was significantly impaired in mice of model group (P<0.01); as compared with the model group, the learning and memory ability was improved in mice of rosiglitazone group and HF high, middle and low dose groups(P<0.01 or P<0.05). Immunohistochemistry and western blot results showed thatas compared with the normal group, the Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were significantly increased in mice of model group (P<0.01);as compared with the model group, Aβ₁₋₄₂, βAPP and BACE1 protein expression levels in hippocampus were decreased in mice of rosiglitazone group and HF high, middle and low dose groups (P<0.01 or P<0.05). HF may improve the learning and memory ability of AD model mice via inhibition of βAPP and BACE1 protein expressions, thus reduced the generation of Aβ₁₋₄₂ proteins and amyloid plaque deposits in the brain.

Aspectos botânicos, químicos, farmacológicos e terapêuticos do Hypericum perforatum L / Botanical, chemical, pharmacological and therapeutic aspects of Hypericum perforatum L

Estima-se que aproximadamente 25% das drogas prescritas em todo o mundo são oriundas de espécies vegetais. Dentre as plantas com alto potencial medicinal, se destaca o Hypericum perforatum L. (HP), planta herbácea perene, pertencente à família Hypericaceae. Extratos orgânicos e aquosos de HP têm sido utilizados na medicina popular e em testes pré-clínicos para o tratamento e prevenção de diversas doenças através de efeitos nefroprotetores, atividades antioxidante, antifúngica, ansiolítica, antiviral e cicatrizante. Estudos clínicos indicaram que esta espécie pode ser útil no tratamento de desordens originadas do sistema nervoso central, especialmente na depressão unipolar. HP contém, ao menos, dez classes de compostos biologicamente ativos, dentre eles antraquinonas/naftodiantronas, derivados de floroglucinol, flavonoides, biflavonas, xantonas, óleos voláteis, aminoácidos, vitamina C, cumarinas, taninos e carotenoides. Ao mesmo tempo em que os constituintes possuem relevantes efeitos farmacológicos, os mesmos podem prejudicar, por antagonismo farmacocinético (interação com algumas enzimas do citocromo), a eficácia de outros fármacos. Devido a relevante importância do HP como agente terapêutico, ressalta-se a importância do desenvolvimento de novos estudos com o intuito de elucidar questões ainda controversas acerca do extrato de HP, e.g., dose, melhor horário para colheita, padronização dos extratos, e possíveis efeitos tóxicos, podendo assim, definir claramente os riscos e benefícios da utilização desta planta.

It is estimated that approximately 25% of prescribed drugs are derived from plant species. Among the plants with high medicinal potential, it highlights the Hypericum perforatum L. (HP), perennial herbaceous plant belonging to the family Hypericaceae. Organic and aqueous extracts of HP have been used in folk medicine and in pre-clinical testing for the treatment and prevention of several diseases through effects nefroprotetores, antioxidant, antifungal, anxiolytic, wound healing and antiviral activities. Clinical studies indicated that this specie can be useful in the treatment of central nervous system disorders, especially to unipolar depression. HP contains at least ten classes of biologically active compounds, including anthraquinones/naftodiantronas, phloroglucinol derivatives, flavonoids, biflavones, xanthones, volatile oils, amino acids, vitamin C, coumarins, carotenoids and tannins. At the same time that the secondary metabolites have important pharmacological effects, they can impair the effectiveness of other drugs by pharmacokinetic antagonism.

Effects of herbal compatibility on hyperforin in Hypericum perforatum L / 中成药

AIM:To explore the effect on stability of hyperforin with different medicinal herbs and the changes of hyperforin content in herb combinations with Hypericum perforatum L.(HP).METHODS:Several common antidepressant medicinal herbs were selected separately to match with HP.The herbal samples consisted of HP group,HP with Curcuma wenyujin Y.H.Chen et C.Ling group,HP with Curcuma longa.L.group,HP with Epimedium brevicornum Maxim group and HP with Wuling powder(WY)group.The contents of hyperforin with each group were determined by reverse phase HPLC.RESULTS:The rates of extraction and retention of hyperforin in HP with Curcuma wenyujin Y.H.Chen et C.Ling group and HP with Curcuma longa.L.group were significantly lower than that of HP group.There were no obvious differences in the extraction rates of the HP group,HP with Epimedium brevicornum Maxim group and HP with WY group.The retention rate of hyperforin in HP group with WY powder was higher than that of HP group.The retention rate of hyperforin in HP with Curcuma wenyujin Y.H.Chen et C.Ling group,was lower than that of HP group.CONCLUSION:The results show that compatibility of HP with traditional Chinese medicine have effects on the stability of active herbal component.