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Objective: To investigate the effect and the potential mechanism of Senegenin (Sen) against injury induced by hypoxia/reoxygenation (H/R) in highly differentiated PC12 cells., Methods: The cultured PC12 cells were treated with H/R in the presence or absence of Sen (60 μmol/L). Four groups were included in the experiment: control group, H/R group, H/R+Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase (LDH) in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential (△Ψm), reactive oxygen species (ROS) and intracellular free calcium ([Ca(2+)]i) were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase (NOX) were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively., Results: Sen significantly elevated cell viability (P<0.05), decreased the leakage of LDH (P<0.05) and apoptosis rate (P<0.05) in H/R-injured PC12 cells. Sen maintained the value of △Ψm (P<0.05) and suppressed the activity of caspase-3 (P<0.05). Moreover, Sen reduced ROS accumulation P<0.05) and [Ca(2+)]i increment (P<0.05) by inhibiting the activity of NOX (P<0.05)., Conclusion: Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca(2+)]i, thereby suppressing the mitochondrial pathway of cellular apoptosis.

Aim: To investigate the mechanisms responsible for the protective action of berberine (Ber) against gut damage in endotoxemic mice., Methods: Male BALB/c mice were administered intragastrically with distilled water (0.1 mL/10 g), Ber (50 mg/kg) alone, yohimbine (2 mg/kg) alone, or Ber (50 mg/kg) in combination with yohimbine (2 mg/kg) for 3 d. On the third day, lipopolysaccharide (LPS, 18 mg/kg) or normal saline was intraperitoneally injected one hour after the intragastric administration. Following the treatment, intestinal injury in the ileum was histopathologically accessed; enterocyte apoptosis was examined using TUNEL method; Toll-like receptor 4 (TLR4) mRNA expression was measured using RT-PCR assay; inhibitor protein-κBα (I-κBα) phosphorylation and myeloperoxidase content were examined using Western blloting. The macrophage inflammatory protein-2 (MIP-2) production was measured using ELISA assay., Results: Mice challenged with LPS caused extensive ileum injury, including a significantly increased injury score, decreased intestinal villus height, reduced gut mucosal weight and increased intestinal permeability. Furthermore, LPS significantly induced enterocyte apoptosis, increased TLR4 mRNA expression, I-κBα phosphorylation, MIP-2 production and myeloperoxidase content in the ileum. Pretreatment with Ber significantly alleviated all the alterations in the ileum in the endotoxemic mice. Pretreatment with the α2-adrenoceptor antagonist yohimbine did not block the protective action of Ber against LPS-induced intestinal injury. In addition, treatment with yohimbine alone did not prevent LPS-induced intestinal injury., Conclusion: Pretreatment with Ber provides significant protection against LPS-induced intestinal injury in mice, via reducing enterocyte apoptosis, inhibiting the TLR4-nuclear factor κB-MIP-2 pathway and decreasing neutrophil infiltration that are independent of α2-adrenoceptors.

Objective: To evaluate the improvement of Kangshuai Yizhi Formula I ( I, KYF I) on: the learning and memory dysfunction in mice, and on the mechanism of the hippocampal cholinergic system and the nervous system of monoamine which are closely related to learning and memory function., Methods: Mice: in the low-, middle-, and high-dose KYF I groups were given low-, middle-, and high-dose KYF, respectively, by gastrogavage for 35 successive days. Animals in the control group and the model group were treated with distilled water. The acute learning and memory dysfunction model was established by injection of scopolamine from day 31, and Morris water maze was used to assess the behavior performance of scopolamine-induced model mice for five days. The activities of acetylcholinesterase (AChE), choline acetyl transferase (ChaT) and the content of monoamine neurotransmitters in hippocampus were measured. The activity of monoamine oxidase (MAO) in hippocampus and serum was also detected., Results: (1) Compared with the control group, the: mean escape latency was shortened, and the frequency across the platform and the staying time at the platform area on the 5th day were decreased in the model group by Morris water maze test. The activities of AChE and MAO were increased, and the ChaT activity and monoamine neurotransmitter content were decreased as well. (2) The escape latency for 4 days in the low-, middle-, and high-dose KYF I groups was significantly shortened than that in the model group, with the shortest latency in the high-dose KYF I group (P<0.05, P<0.01). The frequency across the platform was significantly increased and the staying time at the platform was significantly prolonged in the middle- and high-dose KYF I groups (P<0.05, P<0.01). (3) As compared with the model group, the activity of ChaT and the content of monoamine neurotransmitters in the hippocampus were significantly increased, and the activities of AchE and MAO were significantly decreased in the hippocampus in the high-dose KYF I group (P<0.01)., Conclusions: High-dose KYF I can significantly improve the learning and memory dysfunction: induced by scopolamine in mice. Its mechanism may be related to improving the central cholinergic system and regulating the hippocampal monoamine neurotransmitters.

Aim: To study the antipyretic effect and mechanism of Daqingye injection (DQYI)., Methods: The IL-1beta-induced febrile New Zealand rabbits were chosen as experimental models and the antipyretic effect of DQYI was observed. The expression of EP3 mRNA was investigated by using in situ hybridization (ISH) in POAH., Results: First, the colonic temperature went up gradually after intravenous(i.v) IL-1beta. The peak value of temperature(deltaT) and thermal response index (TRI(1)) in IL-1beta-treated group were higher than those in control group (P<0.01). The DeltaT and TRI(1) of in DQYI and IL-1beta- treated group were lower than those in IL-1beta-treated group (P<0.05). The temperature of DQYI-treated group showed no distinguished difference compared with that in control group (P>0.05). Second, the expression of EP3 mRNA in the POAH of IL- 1beta-treated group increased markedly compared with that in control group (P<0.01). The expression of EP3 mRNA treated by IL-1beta+DQYI in the POAH decreased strikingly compared with that in IL-1beta group(P<0.05)., Conclusion: DQYI has distinct antipyretic effect on IL-1beta-induced fever. The mechanism might be the inhibition of EP3 mRNA expression in POAH from rabbits.

Objective: To observe the efficacy and safety of Yigu capsule (YGC), a Chinese herbal compound preparation, in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism., Methods: The clinical study was conducted in a prospective, randomized, double blinded method lasting for 6 months with placebo and positive control. Two hundred and ten PMO patients with confirmed diagnosis were assigned into the YGC group, the calciferol group and the placebo group. Besides being administered element calcium, they were treated with YGC, calciferol capsule and placebo capsule respectively. And such symptoms as newly found fracture and ostealgia, bone mineral density (BMD) of the 2nd-4th lumbar vertebrae (L(2-4)) and upper femur, blood and urinary indexes for bone metabolism, sex hormone level and adverse reaction that occurred in patients were observed., Results: In the YGC group, the total effective rate was 95.50%, with no new occurrence of fractures, which was significantly better than that in the other two groups (P < 0.05). Moreover, in the YGC group, the increase rate of BMD was 9.83% in L(2-4), 4.09% in femoral neck, 4.60% in Wards triangle, 3.00% in greater trochanter, which was also better than that in the placebo group (P < 0.05, P < 0.01). As compared with the placebo group, levels in the YGC group of urinary oxyproline hydroxyproline/creatinine, urinary calcium/creatinine were significantly lower, serum and bone alkaline phosphatase, osteocalcin, estradiol and estradiol/testosterone were significantly higher, but no difference was shown in the comparison of testosterone level. In the observation period, no abnormality in blood or urine routine, liver or renal function was found. Only mild, transient gastro-intestinal response occurred in individual patients, but it did not affect the treatment., Conclusion: YGC could treat PMO effectively, as it could obviously increase the BMD of lumbar vertebrae and coxafemoral bone, elevate the alleviating rate of ostealgia and incessant motion time, yet causing no newly found compressive fracture of vertebrae, or and any related adverse reaction. YGC could not only promote the formation, but also inhibit the absorption of bone as well as increase the sex hormone level. Therefore, it is a pure Chinese herbal compound preparation worthy of further research and development.

Objective: To observe the efficacy and safety of Yigu capsule (YGC, a Chinese herbal compound preparation) in treating postmenopausal osteoporosis (PMO) and to explore its possible mechanism., Methods: The clinical study was conducted adopting prospective, randomized, double blinded method for 6 months with placebo and positive controls. Two hundred and ten PMO patients with confirmed diagnosis were divided into the YGC group, the osteocalcin group and the placebo group, they were treated with YGC, osteocalcin capsule and placebo capsule, respectively. The symptoms, as new fracture and ostealgia, bone mineral density (BMD) of the 2nd to the 4th lumbar vertebrae (L24) and upper segment of femur, blood and urinary indexes for bone metabolism, sex hormone level and adverse reaction were observed., Results: In the YGC group, the total effective rate was 95.50%, no new fracture occurred, which was significantly better than that in the other two groups (P < 0.05). The increase of BMD was 9.83% in L2-4, 4.09% in femoral neck, 4.60% in Wards triangle, 3.00% in greater trochanter, which were better than those in the placebo group (P < 0.05, P < 0.01). As compared with the placebo group, in the YGC group, levels of urinary oxyproline hydroxyproline/creatinine, urinary calcium/creatinine were lower, serum and bone alkaline phosphatase, osteocalcin, estradiol, and estradiol/testosterone were higher, but with no difference in level of testosterone. In the observation period, no abnormal findings in blood and urine routine examination as well as in liver and renal function were found. Mild, transient gastro-intestinal response occurred in individual patients but it didn't affect the treatment., Conclusion: YGC could treat PMO effectively, it could obviously increase the BMD of lumbar vertebrae and hip, elevate the alleviating rate of ostealgia and incessant motion time, without new compressive fracture of vertebrae, and without any related adverse reaction. YGC could not only promote the formation, but also inhibit the absorption of bone, and increase the sex hormone level, therefore, it is a pure Chinese herbal compound preparation that worths further deep research and development.