Improvement of the Thermal Stability and Aqueous Solubility of Three Matrine Salts Assembled by the Similar Structure Salt Formers.

Matrine (MAT), a natural Chinese herbal medicine, has a unique advantage in the treatment of various chronic diseases. However, its low melting point, low bioavailability, and high dosage restrict its subsequent development into new drugs. In this study, three kinds of MAT salts, namely, MAT-2,5-dihydroxybenzoic acid (MAT-25DHB), MAT-2,6-dihydroxybenzoic acid (MAT-26DHB), and MAT-salicylic acid-hydrate (MAT-SAL-H2O), were designed and synthesized to improve the drugability of MAT. The three salts were characterized by using various analytical techniques, including single-crystal X-ray diffractometry, powder X-ray diffractometry, differential scanning calorimetry, thermogravimetry, and infrared spectroscopy. The results of the thermal stability evaluation showed that the formation of salts improved the stability of MAT; MAT-25DHB is the most stable salt reported at present. The results of aqueous solubility showed that the solubility of MAT-25DHB was higher than that of MAT, while that of MAT-26DHB and MAT-SAL-H2O were less. Given that the MAT-25DHB salt further improved the solubility of MAT, it is expected to be subjected to further research as an optimized salt. Lattice energy and solvation free energy are important factors affecting the solubility of salts; the reasons for the changes of solubility and stability of three kinds of salts are explained by calculating them.

Berberine ameliorates erectile dysfunction in rats with streptozotocin-induced diabetes mellitus through the attenuation of apoptosis by inhibiting the SPHK1/S1P/S1PR2 and MAPK pathways.

BACKGROUND: The population with diabetes mellitus-induced erectile dysfunction is increasing rapidly, but current drugs are not effective in treating erectile dysfunction. Studies of the traditional Chinese medicine extract berberine on diabetes and its complications provide us with new ideas. OBJECTIVES: To evaluate the therapeutic effect and potential mechanism of berberine on the erectile function of diabetic rats. MATERIALS AND METHODS: Fifty male Sprague-Dawley rats were randomly grouped, and 42 rats were injected intraperitoneally with streptozotocin to establish a diabetes model. Erectile dysfunction rats were screened out through the apomorphine test and randomly divided into the diabetes mellitus and berberine groups, and these animals were administered berberine (200 mg/kg/day) and normal saline by gavage for 4 weeks. Primary corpus cavernous smooth muscle cells from healthy rats were cultured and treated with berberine. RESULTS: Fasting blood glucose in the diabetes mellitus group was significantly increased, while berberine showed no significant effect on glucose. Erectile function was obviously impaired in the diabetes mellitus group, and berberine administration partially rescued this impairment. The expression of sphingosine kinase 1, S1PR2, and sphingosine-1-phosphate in the diabetes mellitus group was increased. Berberine partially inhibited the expression of sphingosine kinase 1 and S1PR2, but the decrease in sphingosine-1-phosphate was not significant. Moreover, mitogen-activated protein kinase pathway factor expression was upregulated and eNOS activity was decreased in the diabetes mellitus group. Berberine treatment could partially reverse these alterations. Severe fibrosis and apoptosis were detected in diabetic rats, accompanied by higher expression of TGFß1, collagen I/IV, Bax/Bcl-2, and caspase 3 than in the other groups. However, supplementation with berberine inhibited the expression of these proteins and attenuated fibrosis and apoptosis. CONCLUSIONS: Berberine ameliorated erectile dysfunction in rats with diabetes mellitus, possibly by improving endothelial function and inhibiting apoptosis and fibrosis by suppressing the sphingosine kinase 1/sphingosine-1-phosphate/S1PR2 and mitogen-activated protein kinase pathways.

Systematic Review and Meta-Analysis of the Association between Vitamin D Status and Lower Urinary Tract Symptoms.

PURPOSE: Cumulative studies have shown that vitamin D may be associated with lower urinary tract symptoms but the findings have been inconsistent. The aim of this study was to systematically evaluate the relationship between vitamin D and lower urinary tract symptoms. MATERIALS AND METHODS: The PubMed®, Scopus® and Embase™ databases were searched for articles up to June 2020. A meta-analysis was conducted to evaluate the effects of vitamin D insufficiency or intake on lower urinary tract symptoms. A qualitative description summarized vitamin D intervention for treating lower urinary tract symptoms. Sensitivity analysis was conducted to examine heterogeneity and the robustness of the results. RESULTS: A total of 23 studies including 86,332 participants were analyzed in our study. Vitamin D insufficiency was associated with a 1.37-fold to 2.06-fold increased likelihood of having lower urinary tract symptoms, and patients with lower urinary tract symptoms had significantly lower levels of vitamin D. Furthermore, vitamin D intake was significantly associated with an 11% reduction in the risk of lower urinary tract symptoms. In the subgroup analysis, the effects of vitamin D insufficiency on the risk of lower urinary tract symptoms were notably observed in nonAsians, females and patients with urinary incontinence. CONCLUSIONS: Consistent results indicated that vitamin D insufficiency was a crucial risk factor for lower urinary tract symptoms and that vitamin D supplementation showed promising effects on these symptoms. It would be of great guiding significance to consider vitamin D status when treating lower urinary tract symptoms.

Liraglutide Ameliorates Erectile Dysfunction via Regulating Oxidative Stress, the RhoA/ROCK Pathway and Autophagy in Diabetes Mellitus.

BACKGROUND: Erectile dysfunction (ED) occurs more frequently and causes a worse response to the first-line therapies in diabetics compared with nondiabetic men. Corpus cavernosum vascular dysfunction plays a pivotal role in the occurrence of diabetes mellitus ED (DMED). The aim of this study was to investigate the protective effects of glucagon-like peptide-1 (GLP-1) analog liraglutide on ED and explore the underlying mechanisms in vivo and in vitro. METHODS: Type 1 diabetes was induced in rats by streptozotocin, and the apomorphine test was for screening the DMED model in diabetic rats. Then they were randomly treated with subcutaneous injections of liraglutide (0.3 mg/kg/12 h) for 4 weeks. Erectile function was assessed by cavernous nerve electrostimulation. The corpus cavernosum was used for further study. In vitro, effects of liraglutide were evaluated by primary corpus cavernosum smooth muscle cells (CCSMCs) exposed to low or high glucose (HG)-containing medium with or without liraglutide and GLP-1 receptor (GLP-1R) inhibitor. Western blotting, fluorescent probe, immunohistochemistry, and relevant assay kits were performed to measure the levels of target proteins. RESULTS: Administration of liraglutide did not significantly affect plasma glucose and body weights in diabetic rats, but improved erectile function, reduced levels of NADPH oxidases and ROS production, downregulated expression of Ras homolog gene family (RhoA) and Rho-associated protein kinase (ROCK) 2 in the DMED group dramatically. The liraglutide treatment promoted autophagy further and restored expression of GLP-1R in the DMED group. Besides, cultured CCSMCs with liraglutide exhibited a lower level of oxidative stress accompanied by inhibition of the RhoA/ROCK pathway and a higher level of autophagy compared with HG treatment. These beneficial effects of liraglutide effectively reversed by GLP-1R inhibitor. CONCLUSION: Liraglutide exerts protective effects on ED associated with the regulation of smooth muscle dysfunction, oxidative stress and autophagy, independently of a glucose- lowering effect. It provides new insight into the extrapancreatic actions of liraglutide and preclinical evidence for a potential treatment for DMED.