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Aim. Hyperuricemia (HUA) has received increased attention in the last few decades due to its global prevalence. Our previous study found that administration of a macroporous resin extract of Dendrobium officinale leaves (DoMRE) to rats with HUA that was induced by exposure to potassium oxazine combined with fructose and a high-purine diet led to a significant reduction in serum uric acid (SUA) levels. The aim of this study was to explore the effects of DoMRE on hyperuricemia induced by anthropomorphic unhealthy lifestyle and to elucidate its possible mechanisms of action. Methods. Dosages (5.0 and 10.0 g/kg/day) of DoMRE were administered to rats daily after induction of HUA by anthropomorphic unhealthy lifestyle for 12 weeks. The levels of UA in the serum, urine, and feces; the levels of creatinine (Cr) in the serum and urine; and the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were all measured using an automatic biochemical analyzer. The activities of xanthine oxidase (XOD) and adenosine deaminase (ADA) in the serum, liver, and intestine tissue supernatant were measured using appropriate kits for each biological target. The expressions levels of UA transporters (ABCG2 and GLUT9), tight junction (TJ) proteins (ZO-1 and occludin), and inflammatory factors (IL-6, IL-8, and TNF-α) in the intestine were assayed by immunohistochemical (IHC) staining. Hematoxylin and eosin (H&E) staining was used to assess histological changes in the renal and intestinal tissues. Results. DoMRE treatment significantly reduced SUA levels and concomitantly increased fecal UA (FUA) levels and the fractional excretion of UA (FEUA) in HUA rats. Furthermore, DoMRE significantly reduced both the XOD activity in the serum, liver, and intestine and the ADA activity in the liver and intestine. DoMRE also effectively regulated the expression of GLUT9 and ABCG2 in the intestine, and it significantly upregulated the expression of the intestinal TJ proteins ZO-1 and occludin. Therefore, DoMRE reduced the damage to the intestinal barrier function caused by the increased production of inflammatory factors due to HUA to ensure normal intestinal UA excretion. Conclusion. DoMRE demonstrated anti-HUA effects in the HUA rat model induced by an anthropomorphic unhealthy lifestyle, and the molecular mechanism appeared to involve the regulation of urate transport-related transporters (ABCG2 and GLUT9) in the intestine, protection of the intestinal barrier function to promote UA excretion, and inhibition of XOD and ADA activity in the liver and intestine to inhibit UA production in the HUA-induced rats. [ABSTRACT FROM AUTHOR]

Shenmai injection (SMI) has been widely used for the treatment of cardiovascular diseases in China. Cardiovascular disorders are often related to excessive catecholamine (CA) secretion. Here, we report the effects of SMI on CA secretion and synthesis in cultured bovine adrenal medullary cells. We found that SMI significantly reduced CA secretion induced by 300 μM acetylcholine (ACh). Cotreatment with SMI (10 μL/mL) and either of the ACh receptor α-subunit inhibitors, HEX (α3) or DhβE (α4β2), did not produce any further inhibition, indicating that SMI may play a role through α3 and α4β2 channels. Furthermore, SMI reduced tyrosine hydroxylase (TH) activity induced by ACh by inhibiting the phosphorylation of TH at Ser19 and Ser40. TH is phosphorylated at Ser19 by Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and at Ser40 by protein kinase A (PKA). KN-93 and H89, the antagonists of CaM kinase II and PKA, respectively, inhibited the ACh-induced phosphorylation at Ser19 and Ser40, and the addition of SMI did not augment the inhibitory effect. Taken together, our results show that SMI likely inhibits CA secretion by blocking TH activity at its Ser19 and Ser40 sites. [ABSTRACT FROM AUTHOR]

SangQiQingXuan (SQQX) decoction is a pharmaceutical preparation exerting good therapeutic efficacy on high blood pressure (BP) and has widely been accepted in primarily hypertensive patients as a herbal formula prescribed by Professor Li Huang from China-Japan Friendship Hospital according to her 30-year clinical experience. A previous study showed that SQQX could reduce BP by decreasing levels of many inflammatory factors such as transforming growth factor beta (TGFβ) and elevating peroxisome proliferator activated receptor (PPAR) expression. However, a research focusing on SQQX's protection against HTN from a metabolomic perspective has never been done before. This study aimed to figure out the metabolic profiling variations due to oral administration of SQQX in spontaneous hypertensive rat (SHR) models and to find out the optimal dosage of SQQX. SHR in the intervention group orally received SQQX extract of three doses, namely, the low- (5.25 g/kg/d), middle- (10.5 g/kg/d), and high-dosage groups (21 g/kg/d) for 90 days. Rats were sacrificed at the end of the experiment, and their serum was collected for further examination. Serum metabolic profiling variations were analyzed using ultraperformance liquid chromatography coupled with tandem mass spectrometry (UPLC/MS). Results showed that dealing with SQQX remarkably decreased systolic blood pressure (SBP) of SHRs and the high-dosage group was with the best therapeutic effect where a total of 11 metabolites were markedly changed in contrast to the model group. Orthogonal partial least square discriminant analysis (OPLS-DA) score plot showed that the 5 groups of serum samples were divided into 5 categories, and the metabolic trajectory of the high-dosage SQQX group was inclined to move to the control group. Glycochenodeoxycholic acid, nicotinamide-N-oxide, and tryptophan betaine might be biomarkers that specifically marked the protective effects of SQQX against high BP mainly involving in cholesterol metabolism, primary bile acid biosynthesis, bile secretion, and nicotinate and nicotinamide metabolism. To conclude, SQQX has a protective effect on SHR, which may be partially correlated to restoration of perturbed metabolism in serum. [ABSTRACT FROM AUTHOR]

To investigate the potential cardioprotective effects of Shuang Shen Ning Xin on myocardial ischemia/reperfusion injury. Wistar rats were treated with trimetazidine (10mg/kg/day, ig), Shuang Shen Ning Xin (22.5, 45mg/kg/day, ig), or saline for 5 consecutive days. Myocardial ischemia/reperfusion injury was induced by ligation of the left anterior descending coronary artery for 40 min and reperfusion for 120 min on the last day of administration. It is found that Shuang Shen Ning Xin pretreatment markedly decreased infarct size and serum LDH levels, and this observed protection was associated with reducedmyocardial oxidative stress and cardiomyocyte apoptosis after myocardial ischemia/reperfusion injury. In addition, further studies on mitochondrial function showed that rats treated with Shuang Shen Ning Xin displayed decreased mitochondrial swelling and cytosolic cytochrome c levels, which were accompanied by a preservation of complex I activities and inhibition of mitochondrial permeability transition. In conclusion, the mitochondrial protective effect of Shuang Shen Ning Xin could be a new mechanism, by which Shuang Shen Ning Xin attenuates myocardial ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]