Effects of berberine on learning and memory ability in vascular cognitive impairment rats / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of berberine on learning and memory ability in vascular cognitive impairment rats.@*METHODS@#Sixty-eight Wistar rats were randomly divided into control group (n=10), sham operated group (n=10) and the modeling group of vascular cognitive impairment rat (n=48), then the rats in modeling group were randomly divided into four groups (n=10): vehicle group, berberine low dose group (20 mg/kg), medium dose group (40 mg/kg) and high dose group (60 mg/kg). Bilateral common carotid arteries were occluded in rats to establish vascular cognitive impairment (VCI) model. Different doses of berberine were intraperitoneally injected into the treatment group and normal saline was intraperitoneally injected into the other groups once a day for a total of 34 days. After 28 days of administration, Morris water maze was used to test the learning and memory ability of rats. After the water maze experiment, the levels of superoxide dismutase (SOD) activity, glutathione (GSH), malondialdehyde (MDA), tumor necrosis factor alpha(TNF-α), interleukin-1 beta (IL-1β), 5-hydroxytryptamine (5-HT) and monoamine oxidase (MAO) in the forebrain cortex were detected.@*RESULTS@#Compared to sham group, the escape latency in VCI group was significantly extended (P＜0.01) and the times of passing through the platform were decreased remarkably (P＜0.01). The levels of SOD, GSH and 5-HT in the hippocampus or anterior cortex were decreased significantly (P＜0.01), while the contents of MDA, TNF-α, IL-1β and MAO were increased remarkably (P＜0.01). Compared with VCI group, the escape latency in berberine-treated groups was shortened significantly (P＜0.01, P＜0.05) and the times of passing through the platform were increased remarkably (P＜0.01, P＜0.05), the levels of SOD, GSH and 5-HT were increased significantly (P＜0.01), while the contents of TNF-α, IL-1β and MAO were decreased remarkably (P＜0.01).@*CONCLUSION@#Berberine could significantly improve the spatial learning and memory abilities of rats with vascular cognitive impairment. The mechanism may be related to the effects of berberine on the hippocampal antioxidant stress, anti-inflammatory response and the monoamine neurotransmitter system in the forebrain cortex. Berberine 60 mg/kg dose group had better effect.

Mechanism of the synergistic analgesic effect between choline and acetaminophen / 药学学报

This study was designed to investigate the synergistic analgesic effect between choline (Cho) and acetaminophen (Ace). Mice were treated with 0.6% acetic acid solution by intraperitoneal injection to build acetate writhing model. The KM mice were randomly divided into four groups:control group (n=10), Cho group (n=50), Ace group (n=50), combination group (Cho+Ace group, n=40), then the writhing times were counted respectively. OriginPro8.5 was used to calculate ED 50. The isobolographic analysis was used to test the interaction of Cho and Ace. To explore the mechanism, forty KM mice were randomly divided into control group, Cho group, Ace group and Cho + Ace group. Blood was collected for detection of TNF-α, IL-6, PGE2 and NF-κB content using ELISA kits. The result ED 50 was calculated as followings. ED50 of Cho and Ace was 19.47 mg·kg-1 and 20.56 mg·kg-1. The concentrations were 2.94 mg·kg-1 for Cho and 3.15 mg·kg-1 for Ace in the combination test. The levels of TNF-α, IL-6, PGE2 and NF-κB in Cho group and Ace group were lower than those in the control group (Pα, IL-6, PGE2, NF-κB in Cho + Ace group were reduced further (P< 0.05). The results revealed that Cho and Ace have synergistic analgesic effects, which may associate with inhibition of the NF-κB signaling pathway.

Synergistic analgesic effect of choline and parecoxib sodium in mice and the mechanism / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the synergistic analgesic effect of choline and parecoxib sodium and study its mechanism.</p><p><b>METHODS</b>In male Kunming mice with acetic acid-induced writhing, the EDof choline and parecoxib sodium (administered via the tail vein at 2 h and 30 min before modeling, respectively) and their combined use were determined. In saline (control) group, EDcholine (C) group, EDparecoxib sodium (P) group, and 1/2EDcholine and parecoxib sodium (1/2[C+P]) group, blood samples were collected from the eyeball 10 min after intraperitoneal administration of acetic acid to detect the levels of IL-1, TNF-α, PGE2, NF-κB, and I-κB levels using ELISA kits.</p><p><b>RESULTS</b>In the acetic acid-induced writhing model, the EDof choline and parecoxib sodium was 8.64 and 6.33 mg/kg, and when combined, their ED50 was 2.13 and 1.56 mg/kg, respectively. The isobolograms of parecoxib sodium and choline showed that the measured EDof the two drugs combined was below the theoretical EDvalue (P<0.05) with a combination index (CI) of <0.9. Compared with the control group, C group, P group, and 1/2 (C+P) group all showed significantly lowered IL-1 and TNF-α levels (P<0.05), especially in 1/2 (C+P) group (P<0.05). PGE2 level was significantly lower in P group and 1/2 (C+P) group compared with the control group (P<0.05). NF-κB and I-κB levels were significantly lowered in C, P, and 1/2 (C+P) groups (P<0.05), and the reduction was the most obvious in 1/2 (C+P) group (P<0.05).</p><p><b>CONCLUSION</b>Choline and parecoxib sodium has a synergistic analgesic effect, and their interactions may involve the in vivo expression of NF-κB.</p>

Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats / 中国应用生理学杂志

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.

Protective effect of anti-hypoxia shenggui tablet on cerebral ischemia injure / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To investigate the protective effects of Shengui tablet (Chinese Traditional Medicine) on experimental cerebral ischemia by acute cerebral ischemia hypoxia in mice and bilateral ligation of the carotid artery in rats.</p><p><b>METHODS</b>In the acute cerebral ischemia hypoxia model, the mice were randomly divided into control group, low-, middle- and high-dose (0.16, 0.33 and 1.00 g/kg) groups of Shengui tablet, after oral treatment for 30 d, gasping time of isolated heads of mice were observed. In bilateral ligation of the carotid artery cerebral ischemia model, the rats were randomly divided into control group, model group and low-, middle-, high-dose (0.072, 0.149 and 0.450 g/kg) groups of Shengui tablet. After oral treatment for 7 d, the cerebral index, superoxide dismutase (SOD) activity and the content of malondialdehyde (MDA) were measured.</p><p><b>RESULTS</b>Compared with the control model, Shengui tablet middle- and high-dose could significantly prolong gasping time of isolate heads of mice. Compared with model group, Shengui tablet low-, middle- and high-dose could significantly decrease the cerebral index and enhance SOD activity in brain tissue; only high-dose could reduce the content of MDA.</p><p><b>CONCLUSION</b>Shengui tablet has significant protective effect on the cerebral ischemia.</p>

Effects of iptakalim on pressure-overload induced cardiac remodeling and plasma PGI2 content in rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To study the effects of iptakalim (IPT) on pressure-overload induced cardiac remodeling in rats, and investigate correlation between this protection effects and plasma PGI2 content.</p><p><b>METHOD</b>The pressure-overload induced cardiac remodeling model was induced by abdominal aorta constriction for 6 weeks, and the rats were divided into 5 groups repectively: (1) sham group, (2) control group, (3) IPT 3 mg/kg group (IPT 3), (4) indomethacin 2 mg/kg group (Indo 2), (5) indomethacin 2 mg/kg + IPT 3 mg/kg group (Indo 2 + IPT 3). RM6000 eight channel physiological recorder was used to record haemodynamics index, heart weight was weighed and the cardiac remodeling index was calculated, HE stain and Masson's stain were employed to perform histological analysis, colorimetric method was used to detect the hydroxyproline content in cardiac tissue, radioimmunological method was used to measure the plasma PGI2 content.</p><p><b>RESULTS</b>After 42 days of aortic banding, the hyperdynamic circulation state, cardiac remodeling and decreased plasma PGI2 content were observed in the model group compared with those in the sham group, which were effectively reserved by treatment with IPT 3 mg/kg. Single-use indomethacin led to further deterioration of this pathophysiological changes, however, combination administration of IPT 3 mg/kg prevented these from worsening characteristic by ameliorating hyperdynamic circulation state and cardiac remodeling, augmnent plasma PGI2 content.</p><p><b>CONCLUSION</b>IPT can significantly reverse abdominal aorta binding/pressure-overload induced cardiac remodeling, its mechanism may contribute to binding K(ATP) channel in endothelial cells, ameliorating endothelium cells function, augmenting PGI2 synthesis and secretion.</p>