Qingda Granule Attenuates Hypertension-Induced Cardiac Damage via Regulating Renin-Angiotensin System Pathway.

OBJECTIVE: To assess the efficacy of Qingda Granule (QDG) in ameliorating hypertension-induced cardiac damage and investigate the underlying mechanisms involved. METHODS: Twenty spontaneously hypertensive rats (SHRs) were used to develope a hypertension-induced cardiac damage model. Another 10 Wistar Kyoto (WKY) rats were used as normotension group. Rats were administrated intragastrically QDG [0.9 g/(kg•d)] or an equivalent volume of pure water for 8 weeks. Blood pressure, histopathological changes, cardiac function, levels of oxidative stress and inflammatory response markers were measured. Furthermore, to gain insights into the potential mechanisms underlying the protective effects of QDG against hypertension-induced cardiac injury, a network pharmacology study was conducted. Predicted results were validated by Western blot, radioimmunoassay immunohistochemistry and quantitative polymerase chain reaction, respectively. RESULTS: The administration of QDG resulted in a significant decrease in blood pressure levels in SHRs (P<0.01). Histological examinations, including hematoxylin-eosin staining and Masson trichrome staining revealed that QDG effectively attenuated hypertension-induced cardiac damage. Furthermore, echocardiography demonstrated that QDG improved hypertension-associated cardiac dysfunction. Enzyme-linked immunosorbent assay and colorimetric method indicated that QDG significantly reduced oxidative stress and inflammatory response levels in both myocardial tissue and serum (P<0.01). CONCLUSIONS: Both network pharmacology and experimental investigations confirmed that QDG exerted its beneficial effects in decreasing hypertension-induced cardiac damage by regulating the angiotensin converting enzyme (ACE)/angiotensin II (Ang II)/Ang II receptor type 1 axis and ACE/Ang II/Ang II receptor type 2 axis.

The neurovascular protective effect of alogliptin in murine MCAO model and brain endothelial cells.

Endothelial damage and blood brain barrier disruption contribute to ischemic stroke and brain injury. Gliptins are a novel class of treatment agents for diabetes, and recent studies have linked the use of gliptins to neuroprotection. Alogliptin is a type of orally available gliptin that was approved for clinical use by the FDA in 2013. In this study, we investigated the neurovascular protective effects of alogliptin both in vivo and in vitro. In a murine middle cerebral artery occlusion (MCAO) stroke model, administration of alogliptin ameliorated cerebral infarction and disruption of brain vascular permeability, and restored expression of the endothelial tight junction proteins occludin and zona occludens 1 (ZO-1). In brain vascular endothelial cells exposed to oxygen and glucose deprivation/reperfusion (OGD/R), alogliptin prevented OGD/R-induced high permeability of the endothelial monolayer. Alogliptin treatment recovered the reduction in occludin and ZO-1 induced by OGD/R. Moreover, alogliptin treatment prevented OGD/R-induced induction of metalloproteinase (MMP)-2 and MMP-9, and restored expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2. Collectively, our data indicate that alogliptin can improve neurovascular integrity and exerts neuroprotective effects.

Correlation between Calpain-10 single-nucleotide polymorphisms and obstructive sleep apnea/hypopnoea syndrome with ischemic stroke in a Chinese population: A population-based study.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is a common chronic disorder which is followed by various complications. Calpain-10 belongs to a commonly expressed member of the Calpain-like cysteine protease family, which acts as risk marker for some diseases. The purpose of this study is to elucidate correlation between Calpain-10 single-nucleotide polymorphisms (SNPs) and the incidence of OSAHS followed by ischemic stroke (IS). METHODS: OSAHS patients were divided as OSAHS + IS, OSAHS, and control groups, respectively. Immunohistochemistry was performed for Calpain-10 protein expression, polymerase chain reaction (PCR)-restriction fragment length polymorphism for detection of gene polymorphisms of SNP 43 and SNP 19, and PCR-allele specific amplification for SNP 44. Polysomnography was conducted to check the nocturnal polysomnography indicators, and also Montreal Cognitive Assessment (MoCA), Scientific Data System scores cognition and anxiety of patients, respectively. Logistic analysis was used for the risky factors for OSAHS. RESULTS: Calpain-10 protein expression was significantly increased in the OSAHS + IS and OSAHS groups compared with the control group. Significant differences in SNP 43 and SNP 44 genotype, and also allele frequency were observed in 3 groups, among which the OSAHS + IS group had higher SNP 43 and SNP 44 allele frequency than the control and OSAHS groups. There were differences regarding apnea-hypopnea index, minimum fingertip blood oxygen saturation (LSaO2 [%]), oxygen reduction index (ODI) between patients with different genotypes of SNP 43 and SNP 44 in OSAHS patients, and also GC and AT frequency in the OSAHS + IS and OSAHS groups. As compared with the OSAHS group, the MoCA scores and MoCA subitems in the OSAHS + IS group were declined, whereas the Scientific Data System scores were elevated. Additionally, GG 43 genotype, high apnea-hypopnea index, and body mass index were detected as the risk factors of OSAHS. CONCLUSION: These findings indicate that the Calpain-10 SNP 43 may be related to OSAHS with IS, with SNP 43 GG genotype as a risk factor for OSAHS with IS.

[Determination of schisandrin in shengmaiyin by HPLC].

OBJECTIVE: To determine the concentration of schisandrin in Shengmaiyin with HPLC. METHOD: The sample was extracted with ethyl acetate through supersonic wave. The solution was filtrated and evaporated. The residue was resolved with methanol and determined by HPLC using PHENOMENEX C18 (4.6 mm x 250 mm, 5 microns) chromatographic column, methanol-acetonitrile-water (15:15:10) as mobile phase. The wavelength for detection was 254 nm. RESULT: The peak of schizandrin appears on about 7.10 minutes. The standard curves of schizandrin were linear in the concentration range of 0.2-2.0 micrograms, r = 0.9996. The average recovery of schizandrin were 100.5% (RSD 2.84%). CONCLUSION: This method was found to be sensitive, quick and accurate for the measurement of schizandrin concentrations in Shengmaiyin.