Antihypertensive Effects of Gynura divaricata (L.) DC in Rats with Renovascular Hypertension.

Gynura divaricata (L.) DC (Compositae) (GD) could be found in various parts of Asia. It has been used as a traditional medicine to treat diabetes, high blood pressure, and other diseases, but its effects have not yet been scientifically confirmed. Therefore, we aimed at determining whether GD could affect renal function regulation, blood pressure, and the renin-angiotensin-aldosterone system (RAAS). Cardio-renal syndrome (CRS) is a disease caused by the interaction between the kidney and the cardiovascular system, where the acute or chronic dysfunction in one organ might induce acute or chronic dysfunction of the other. This study investigated whether GD could improve cardio-renal mutual in CRS type 4 model animals, two-kidney one-clip (2K1C) renal hypertensive rats. The experiments were performed on the following six experimental groups: control rats (CONT); 2K1C rats (negative control); OMT (Olmetec, 10 mg/kg/day)-treated 2K1C rats (positive control); and 2K1C rats treated with GD extracts in three different doses (50, 100, and 200 mg/kg/day) for three weeks by oral intake. Each group consisted of 10 rats. We measured the systolic blood pressure weekly using the tail-cuff method. Urine was also individually collected from the metabolic cage to investigate the effect of GD on the kidney function, monitoring urine volume, electrolyte, osmotic pressure, and creatinine levels from the collected urine. We observed that kidney weight and urine volume, which would both display typically increased values in non-treated 2K1C animals, significantly decreased following the GD treatment (###p < 0.001 vs. 2K1C). Osmolality and electrolytes were measured in the urine to determine how renal excretory function, which is reduced in 2K1C rats, could be affected. We found that the GD treatment improved renal excretory function. Moreover, using periodic acid-Schiff staining, we confirmed that the GD treatment significantly reduced fibrosis, which is typically increased in 2K1C rats. Thus, we confirmed that the GD treatment improved kidney function in 2K1C rats. Meanwhile, we conducted blood pressure and vascular relaxation studies to determine if the GD treatment could improve cardiovascular function in 2K1C rats. The heart weight percentages of the left atrium and ventricle were significantly lower in GD-treated 2K1C rats than in non-treated 2K1C rats. These results showed that GD treatment reduced cardiac hypertrophy in 2K1C rats. Furthermore, the acetylcholine-, sodium nitroprusside-, and atrial natriuretic peptide-mediated reduction of vasodilation in 2K1C rat aortic rings was also ameliorated by GD treatment (GD 200 mg/kg/day; p < 0.01, p < 0.05, and p < 0.05 vs. 2K1C for vasodilation percentage in case of each compound). The mRNA expression in the 2K1C rat heart tissue showed that the GD treatment reduced brain-type natriuretic peptide and troponin T levels (p < 0.001 and p < 0.001 vs. 2K1C). In conclusion, this study showed that GD improved the cardiovascular and renal dysfunction observed in an innovative hypertension model, highlighting the potential of GD as a therapeutic agent for hypertension. These findings indicate that GD shows beneficial effects against high blood pressure by modulating the RAAS in the cardio-renal syndrome. Thus, it should be considered an effective traditional medicine in hypertension treatment.

Hwangryunhaedoktang exerts anti-inflammation on LPS-induced NO production by suppressing MAPK and NF- κB activation in RAW264.7 macrophages.

OBJECTIVE: This study aimed to evaluate whether Hwangryunhaedoktang (HHT), a herbal compound, has an inhibitory effect on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages. METHODS: The effects of HHT were evaluated by confirming nitric oxide (NO) production and expression of inducible NO synthase (iNOS) and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW264.7 macrophages via the Griess assay, Western blotting, and real-time reverse transcription quantitative polymerase chain reaction. Western blot analyses and luciferase assays were used to evaluate whether HHT has an effect on the phosphorylation and translocation of nuclear factor-κB (NF-κB). The secretion and expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined via enzyme-linked immunosorbent assay and Western blot analyses. RESULTS: HHT suppressed LPS-induced NO production and expression of iNOS in a dose-dependent manner. Additionally, MAPKs activation was also attenuated via inhibition of phosphorylation of extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinase and p38 which were related to inflammatory pathway. Furthermore, HHT also effectively attenuated NF-κB activation and its translocation to the nucleus, a process that is closely linked to inflammation. LPS normally induced the expression of inflammatory cytokines such as TNF-α and IL-6, but the secretion and expression of TNF-α and IL-6 were significantly attenuated by pretreating the cells with HHT. CONCLUSION: HHT suppressed LPS-induced NO production by blocking the activation of NF-κB and MAPK signaling pathways in RAW264.7 macrophages. Furthermore, HHT may have an anti-inflammatory effect by suppressing the LPS-induced secretion of TNF-α and IL-6. Therefore, the traditional herbal formula HHT might be a useful potential therapeutic agent for inflammation.

Copper-Catalyzed Tandem Reactions for Synthesis of Pyrazolo[5,1-a]isoquinolines with Heterocyclic Ketene Aminals as Ligands.

A CuI-catalyzed tandem reaction of 5-(2-bromoaryl)-N-aryl-1H-pyrazol-3-amines with active acetonitrile derivatives to prepare pyrazolo[5,1-a]isoquinolines in good to excellent yields has been successfully developed under mild conditions with heterocyclic ketene aminals (HKAs) as new ligands. This is the first time HKAs have been used as ligands for copper-catalyzed coupling reactions.