Xinmai 'an extract enhances the efficacy of sildenafil in the treatment of pulmonary arterial hypertension via inhibiting MAPK signalling pathway.

CONTEXT: Xinmai 'an tablet has been used to improve myocardial blood supply. Recently, some compounds from its formula have shown that they can treat pulmonary arterial hypertension (PAH). OBJECTIVE: This study investigates the effects of Xinmai 'an extract (XMA) on PAH and further tests the co-therapeutic enhancement with sildenafil (SIL). MATERIALS AND METHODS: Pulmonary artery smooth muscle cells were subjected to stimulation with SIL (12.5 µM) and XMA (250 µg/mL) for 48 h. Sprague-Dawley rats were randomly grouped into eight groups (n = 8 per group): (I) control group received saline; (II) MCT group received MCT (60 mg/kg); (III) SIL-Low group received MCT + SIL at 10 mg/kg/day; (IV) SIL-high group received MCT + SIL at 30 mg/kg/day; (V) XMA-High group received MCT + XMA at 251.6 mg/kg/day; (VI) SIL (Low)+XMA (Low) group received SIL (10 mg/kg) + XMA at 62.9 mg/kg/day; (VII) SIL (Low)+XMA (Medium) group received SIL (10 mg/kg) + XMA at 125.8 mg/kg/day; (VIII) SIL (Low)+XMA (High) group received SIL (10 mg/kg) + XMA at 251.6 mg/kg/day. Both XMA and SIL were given by gavage and were maintained daily for 2 weeks. RESULTS: XMA could improve SIL's efficacy in the treatment of PAH by decreasing cell viability more effectively at non-cytotoxic concentrations (250 µg/mL) and reducing Right Ventricular Systolic Pressure (RVSP) in PAH rat. Potential mechanisms might at least in part be through activating the MAPK signalling pathway. DISCUSSION AND CONCLUSIONS: The combination of XMA and SIL can improve the efficacy of pulmonary hypertension and reduce the dosage of SIL.

[Preparation of evodiamine-glycyrrhizic acid micelles with glycyrrhizic acid as carrier and their anti-hepatic fibrosis activity].

This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.