Gualou Xiebai Decoction prevents myocardial fibrosis by blocking TGF-beta/Smad signalling.

OBJECTIVES: The present study is aimed to investigate the effect of Gualou Xiebai Decoction (GXD) ethanol extract on myocardial fibrosis and clarify the possible mechanism. METHODS: Rats with ligated left anterior descending coronary artery were treated with GXD ethanol extract (1.14 g/kg, 2.27 g/kg, 4.53 g/kg) daily via gavage for 4 weeks. Histopathological changes and collagen distribution were evaluated by haematoxylin and eosin and Masson staining. The mRNA levels of Collagen I and Collagen III were detected by real-time PCR. The expressions of TGF-ß1, TGFß receptor (TGFßR)I, TGFßRII, P-Smad2/3 and Smad7 were determined by Western blot. RESULTS: GXD treatment was significantly reduced the heart weight/body weight ratio (P < 0.05) as well as the left ventricle weight/body weight ratio (P < 0.05). It also significantly alleviated the degree of inflammation, decreased myocardial collagen volume fraction (P < 0.05 ∼ 0.01), together with markedly prevented the upregulations of Collagen I and Collagen III (P < 0.05 ∼ 0.01). Moreover, GXD downregulated expressions of TGF-ß1, TGFßRI, TGFßRII, Smad2/3 whereas improved Smad7 expression in the myocardial fibrosis rats. CONCLUSIONS: GXD ameliorates myocardial fibrosis induced by cardiac infarction with ligated left anterior descending coronary artery, the mechanism maybe involve in inhibiting the TGF-ß1 signalling pathway.

Effect of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome.

OBJECTIVE: To investigate the effects of Liangxuehuayu Recipe on hemorheology in rats with blood stasis syndrome induced by mutifactor stimuli. METHODS: SD rats were divided into control, model, Liangxuehuayu Recipe (high, middle and low dose, 18, 9, 4.5 g/kg accordingly). Except the control group, blood stasis model was established in the rest groups. The hemorheological parameters were measured and compared. RESULTS: Blood viscosity at high, moderate and low level in rats with blood stasis significantly increased (P<0.05), but blood viscosity at high level and plasma viscosity was significantly decreased in rats induced by some stimuli after Liangxuehuayu Recipe were intra-gastrically administered for 1 weeks (P<0.01, P<0.05). CONCLUSIONS: Liangxuehuayu Recipe is effective in improving hemorheology, and has important application value in the prevention of occurrence and development of ischemic stroke.

[Effect of electroacupuncture combined with intragastric administration of borneol on the permeability of blood-brain barrier in the mouse].

OBJECTIVE: To observe the effect of electroacupuncture (EA) combined with gavage of borneol on the permeability and ultrastructure of the blood-brain barrier (BBB) in mice, so as to reveal its mechanism underlying improving permeability of BBB. METHODS: For assaying Evans blue (EB) content in the brain, 60 Kunming mice were evenly divided into control, EA, borneol (0.2 g/kg, borneol-0.2), borneol (0.4 g/kg, borneol-0.4), borneol (0.2 g/kg, borneol-0.2) + EA and borneol (0.4 g/kg, borneol-0.4) + EA groups. For determination of P-glycoprotein [P-gp, a member of the superfamily of ATP-binding cassette (ABC) transporters which transport various molecules across extra- and intra-cellular membranes] function and the ultrastructure of BBB, other 84 mice were randomized into control, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups (n=10 for P-gp. function analysis, and n 2 for electron microscopic observation). EA (2 Hz, 1 mA) was applied to "Baihui" (GV 20) and "Yamen"(GV 15) for 20 ml once daily for 14 days. EB (2.5%, 0.2 mL/kg) and rhodamine (Rh) 123 (0.2 mg/kg) were injected intravenously first through the tail vein, and their contents in the brain and Rh 123 in the plasma were detected after EA by using an ultraviolet fluorescence microplate reader. At the same time, the permeation index (Kp) was calculated by the ratio of Rh 123brain/Rh 123blood. RESULTS: Compared with the control group, the cerebral EB and Rh 123 contents and Kp of BBB in the EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups were increased significantly (P < 0.05, P < 0.01). The cerebral EB content was significantly higher in the borneol-0.2 + EA group than in the borneol-0.2 group (P < 0.05), suggesting a synergistic effect of EA and borneol. No significant differences were found among the EA, borneol-0.2 and borneol-0.4 groups in cerebral EB levels, among the control, EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups in plasma Rh 123 contents, and among the EA, borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA and verapamil groups in cerebral Rh 123 contents and Kp of BBB (P > 0.05). Results of the electron transmission microscope showed that the compact degree of the tight junction of BBB was decreased in the borneol-0.2, borneol-0.4, borneol-0.2 + EA, borneol-0.4 + EA groups but not in the EA group. CONCLUSION: EA and gavage of borneol treatments may enhance the permeability of BBB for EB and Rh 123 and have a certain synergistic effect in mice. The effect of borneol may be closely with the inhibition of P-glycoprotein and the decrease of tight junction of BBB while the effect of EA treatment is probably related to the inhibition of P-glycoprotein only.

[Influence of electroacupuncture plus intragastric administration of extract of hypericum perforatum L on ethology and brain microcirculation in depression rats].

OBJECTIVE: To observe the effect of combined administration of intragastric perfusion of extract of Hypericum Perforatum L (HP-L) and electroacupuncture (EA) of "Baihui" (GV 20) and "Yamen" (GV 15) on behavior and brain microcirculation in depression rats. METHODS: Female SD rats were randomized into control, model, lower-dose of HP-L (lower-dose in short, 10 mg/kg), lower-dose+ EA, higher-dose (20 mg/kg) and higher-dose+ EA groups (n = 10/group). Depression model was established by lonely raising and chronic unpredictable mild stress (tail cramping, water-deprivation, fasting, electrical shock stimulation, etc. ) for 21 days. EA (2 Hz, 1 mA) was applied to "Baihui"(GV 20) and "Yamen"(GV 15) for 20 min, once daily for 14 days. Changes of ethology including glucose-consumption during 1 h, crossing and rearing scores of open-field test during 3 min (for assessing the rats' locomoto)and laser Doppler flowmetry values of cortical regional cerebral bloodflow (r CBF) were detected, and Morris water maze test (for assessing the rats' learning-memory ability) was conducted. RESULTS: In comparison with the control group, the sucrose consumption, crossing and rearing scores of open-field test, the average swimming velocity (ASV). the ratios of path length and swimming duration near the hidden-platform and the path length and swimming duration far from the platform of Morris water maze test during 70 seconds, and the cortical r CBF value in the model group were decreased significantly (P < 0.01), while the total swimming distance and escape latency in the model group increased apparently (P < 0.01). Compared to the model group, the average sucrose consumption, crossing and rearing scores of open-field test, the ASV, and the ratios of path length and swimming duration near the platform and those far from the platform in the lower-dose. lower-dose + EA, higher-dose and higher-dose + EA groups, and the cortical r CBF in the lower-dose + EA and higher-dose + EA groups were increased considerably (P < 0.05, P < 0.01). The total swimming distances and escape latencies of lower-dose, lower-dose + EA, higher-dose and higher-dose + EA groups were significantly shortened in comparison with the model group (P < 0.05, P < 0.01). The sucrose consumption and crossing score were significantly higher in the higher-dose + EA group than the lower-dose group (P < 0.05). The escape latency was significantly shorter in the higher-dose + EA group than in the lower-dose group (P < 0.05). No significant differences were found among the lower-dose, lower-dose + EA and higher-dose groups the sucrose consumption, crossing score and escape latency: among the lower-dose, lower-dose + EA, higher-dose and higher-dose + EA groups in the rearing score and ASV; among the lower-dose, higher-dose and model groups in the cortical r CBF (P > 0.05). CONCLUSION: EA can enhance the effect of extract of HP-L in increasing sucrose consumption, crossing score and cerebral blood flow, and in shortening escape latency in depression rats, which may contribute to their effect in improving depression. But HP-L itself has no effect on cortical microcirculation.

Beneficial effect of Cyclovirobuxine D on heart failure rats following myocardial infarction.

The effect of Cyclovirobuxine D, an active ingredient from Buxus microphylla, was investigated in the potential prevention of cardiac dysfunction in rats with congestive heart failure. Heart failure was induced by left coronary artery occlusion and verified using echocardiography. Cyclovirobuxine D was administered for 30 days (0.5, 1.0 and 2.0mg/kg, ig) and mortality, cardiac function, hemodynamics, microcirculation, histology and ultrastructure assessments were observed. Results from the present study suggest that Cyclovirobuxine D is beneficial for heart failure induced by myocardial infarction and supports the potential for Cyclovirobuxine D as a new therapy for heart failure.

[Effects of CVB-D on hemodynamic in anaesthetized dogs in vivo].

OBJECTIVE: To investigate hemodynamic in anaesthetized dogs after the intravenous injection of cyclovirobuxine D (CVB-D). METHODS: The hemodynamic of anaesthetized dogs were observed after intravenous injection of CVB-D at doses of 0.1, 0.2, 0.4 mg/kg. RESULTS: CVB-D of 0.2 and 0.4 mg/kg could decrease HR, TPVR and increase CBF. In addition, CVB-D of 0.4 mg/kg could increase SAP and SV. Yet MAP and CO of dogs showed no remarkable changes with the treatment of CVB-D. CONCLUSION: CVB-D has effect of improving cardiac function, which may be the mechanism of anti-myocardial ischemia effect of CVB-D.

Echinacoside elicits endothelium-dependent relaxation in rat aortic rings via an NO-cGMP pathway.

The aim of this study was to identify and elucidate the vasorelaxant activity of echinacoside, a phenylethanoid glycoside isolated from the medicinal herb Cistanche tubulosa, and its possible underlying mechanism on isolated rat thoracic aortic rings pre-contracted with phenylephrine (PE, 1 microM) and KCl (60 mM). Echinacoside (30-300 microM) exhibited an acute relaxation in endothelium-intact rings in a concentration-dependent manner, while this relaxation was significantly inhibited in endothelium-denuded condition and in the presence of the endothelial nitric oxide synthase (eNOS) inhibitor, N(W)-nitro-L-arginine methyl ester (L-NNA, 100 microM), an unselective soluble guanylate cyclase blocker, methylene blue (10 microM), the selective sGC inhibitor 1 H-[1, 2, 4]oxadiazolo[4,3- A]quinoxalin-1-one (ODQ, 1 microM); in addition, atropine (1 microM), a selective muscarinic receptor antagonist, partially affected the relaxation. However, the cyclooxygenase inhibitor indomethacin (5 microM) had no influence on the action. Echinacoside enhanced the cyclic guanosine monophosphate (cGMP) production in aortic rings contracted with PE. These results indicate for the first time that echinacoside mediates the endothelium-dependent vasodilator action in rat thoracic aortic rings through nitric oxide (NO)-cGMP pathway.