番茄红素对寰枢椎失稳老龄小鼠记忆的影响

Objective To observe the effect of Lycopene on the improvement of memory abilities by cumulating lactic acid for long time in atlas dentata vertebrae senile mice. Methods Totally 30% lactic acid 30μL one time every week was injected into the place between the first and the second cervical vertebrae for 3 weeks. Forty mice were randomized into five groups:young control group, model group, VitE group(50 mg/kg), control group,and two therapeutic groups of lycopene which was intragastric at the doses of 5, 2.5 mg/kg once everyday. The changes of memory in mice were observed with water-maze test and step-down avoidance test. The activities of acetylcholine esterase(AchE), and the content of acetylcholine, (Ach) in encephalon were tested. HE staining in mice brain, including the cortex and hippocampus was demonstrated. Results Compared with model group. Lycopene high dose could significantly shortened the latency period and wrong times in water-maze test (P ＜0.01 ), In stepdown avoidance test, the reaction period was shortened significantly ( P ＜ 0.01 ) and the latency period was shortened significantly. The activities of ChE decreased (P ＜0.01 ) and the content of ACh increased in the Lycopene high doses group(P＜0.01 ). The therapeutic groups of lycopene had less pathological change of cellular necrosis,neuron loss in hippocampal CAI than the model group. Conclusion Lycopene has a certain protective and improving effect on the decline of memory ability and cervical lesion induced by lactic acid in atlanto-axial joint cumulating.     

Effect of α-asarone on ethanol-induced learning and memory impairment in mice and its underlying mechanism

OBJECTIVE To investigate the effect ofα-asarone on ethanol-impaired cognitive ability and explore the underlying mechanism in mice. METHODS A mouse model of impaired learning and memory was created by ethanol(2.0 g · kg~(-1), ig). α-Asarone(7.5, 15 and 30 mg·kg~(-1), ip) was delivered 10 min prior to ethanol administration. After 40 min, the locomotor activity of mice with learning and memory impairment was evaluated by the open field test and the behavioral effect of α-asarone was evaluated using the novel object recognition test.Glutamate(Glu) and γ-aminobutyric acid(GABA) levels in the hippocampus were determined by ELISA, and the proteins expression levels of hippocampal α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA) receptor(Glu R2), N-methyl-D-aspartic acid(NMDA)receptor(NMDAR2 B), synaptophysin I(SYNΙ), glutamate transporter type 1(GLT-1) and calcium/calmodulindependent protein kinaseⅡ(Ca MKⅡ) were detected by Western blotting. RESULTS There was no significant difference in the horizontal or vertical locomotor activity between the ethanol and normal groups or the 7.5, 15 and 30 mg·kg~(-1)α-asarone groups[F(5, 48)=0.6536, P>0.05; F(5, 49)=1.995, P>0.05]. The recognition index in the ethanol group was significantly decreased as compared with that in the normal group[F(5, 46) =6.739, P<0.05]and was markedly increased in the α-asarone groups as compared with that in the ethanol group(P<0.05), with the exception of the 7.5 mg · kg~(-1)α-asarone group(P>0.05). The hippocampal Glu: GABA ratio in mice was significantly elevated in the ethanol group as compared with that in the normal group(33.42±0.8972 vs 30.79±0.2102, P<0.05) and significantly lower in the α-asarone groups(31.99±0.4986 vs. 33.42±0.8972; 30.97±0.1757 vs. 33.42±0.8972; 30.83 0.1723 vs. 33.42±0.8972, P<0.05). The expression levels of GluR2, NMDAR2B, pSYNⅠand p Ca MKII were significantly higher in the ethanol group as compared with those in the normal group(P<0.05) and obviously lower in the α-asarone groups(P<0.05), with the exception of GluR2, NMDAR2B and pCaMKⅡ in the 7.5 mg·kg~(-1)α-asarone group(P>0.05).And the expression level of GLT-1 was significantly lower in the ethanol group as compared with that in the normal group(P<0.05) and obviously higher in the α-asarone groups(P<0.05). CONCLUSION Pretreatment with α-asarone significantly improved the learning and memory impairment. A possible underlying mechanism is regulation of the calcium signaling cascade to correct functioning of related proteins, and thus, maintain the level of Glu.     

Effects of Xanthoceraside on learning and memory impairment in mice induced by i.c.v.Aβ_(1-42)

Objective To investigate the improvement of Xanthoceraside on learning and memory impairment in mice induced by intracerebroventricular injection of Aβ1-42(i.c.v.Aβ1-42)and the possible mechanisms of its protection against AD.Methods Y-maze test,water-maze test and step-down test were used to investigate the learning and memory ability of mice;Biochemical analysis was used to detect the activity of CAT,T-AOC,ATPase and the content of MDA.Results The results showed that Xanthoceraside could significantly increase the alternation behavior in Y-maze test,shorten swimming time in water maze test and increase the latency and decrease the number of errors and the total time of shock in step-down test.Xanthoceraside markedly increased the activity of CAT,T-AOC,ATPase,at the same time,decreased the content of MDA.Conclusions Xanthoceraside can improve learning and memory impairment in mice induced by i.c.v.Aβ1-42 significantly.The mechanism may be associated with the protection against damage induced by free radicals;the inhibition of membrane lipid peroxidation and the improvement of metabolism of brain.     

Effect of Tanshitone on prevention and treatment of retinoic acid-induced osteoporosis in mice

Objective To observe the prevention and therapeutic effects of tanshitone(TAN)on retinoic acid induced osteoporosis in mice.Methods The mice osteoporosis was induced by given retinoic acid intragasttrically for two weeks.The histomorphological features of bone were observed and biochemical indexes in serum(Ca,P,ALP,TRAP,E2,BGP)were determined after mice were given TAN at the dose of 40,80,160 mg·kg-1 respectively.Results Tanshitone can induce high conversion of osteoporosis.The levels of P,ALP,TRAP and BGP in the TAN groups were lower than the model group,while the E2 level was higher than the model group.Conclusions Tanshitone can prevent the loss bone in the experimental mice.The mechanism may be that it improves the level of estrogenic hormone and inhibits the high bone turnover.     

Role of TGF-β/Smad signaling pathway in pulmonary fibrosis after rheumatoid arthritis in mice北大核心CSCD

Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

corilagin protects non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet via regulating AMPK-autophagy signaling北大核心CSCD

Aim To explore the effects of corilagin on non-alcoholic fatty liver disease induced by high-fat and high-sugar diet in mice via regulating AMPK-autophagy signaling. Methods Healthy 8-week-old male C57BL/6J mice were randomly divided into control group, model group and corilagin group. The mice of model group and corilagin group were fed with a high-fat and high-sugar diet for four weeks at the age of eight weeks. The corilagin group mice were also intraperitoneally injected with corilagin (20 mg • k g - 1 ), which was given once every 2 days for 4 weeks. The mice of the control group and the model group were given equal dose of normal saline. After modeling and administration, the mice were sacrificed and the liver weight recorded. The liver pathological changes of each group mice were assessed by HE staining, oil red O staining and Masson staining. The biochemical indexes in serum and liver tissue were detected by the ELISA kit. The p-AMPK and autophagy levels were detected by Western blot. Results The results showed that compared to control group, the liver weight of the model group increased, the AST and ALT levels in serum also significantly increased, there were a large number of fat vacuoles and severe lipid deposition and mild collagen fibrosis in liver, while the liver weight and TG level in liver significantly decreased, and the liver pathological changes were significantly improved after treated with corilagin. Western blot results showed the levels of autophagy related proteins such as Atg7 and Atg5 significantly decreased in the model group, and the p-AMPK level also significantly decreased. When treated with corilagin, p-AMPK and the autophagy levels were up-regulated. Conclusion corilagin can protect non-alcoholic fatty liver disease in mice induced by high fat and high sugar diet. The mechanism may involve increasing p-AMPK level and enhancing autophagy level in liver. © 2023 Publication Centre of Anhui Medical University. All rights reserved.     

Effect of aqueous extract of Semen Cassiae on endogenous metabolomics in urine of rats北大核心CSCD

OBJECTIVE: To investigate the effect of aqueous extract of Semen Cassiae (AESC) on endogenous metabolites in urine of rats by metabolomics based on ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) to reveal the possible ways of metabolism and mechanism of action in rats caused by AESC. METHODS: Twsenty-eight male Sprague-Dawley (SD) rats were randomly equally divided into 4 groups: such normal control group, AESC 1.5, 5 and 15 g·kg-1 groups. After intragastric administration for 14 d, the urine was collected with metabolic cages. The urine metabolic profiling was analyzed using UPLC-QTOF-MS, based on which the principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were established for metabolomic analysis. Potential biomarkers were screened using variable importance in the projection (VIP) and t test. RESULTS: The results of PCA showed that samples of each group were clustered, all the groups were separated, and that the distance between AESC groups and normal control group was increased in a dose-dependent manner. The relative content of proline betaine and uric acid were 18.4±2.3 and 15.7±2.0, 16.3±4.5 and 14.7±3.0 in the AESC 5 and 15 g· kg-1 groups, significantly lower than that of the normal control group, which was 25.0±3.4 and 29.0±4.8(P<0.01), but that of AESC 1.5 g · kg-1 group did not statistically differ from that of normal control group. In AESC 1.5, 5 and 15 g·kg-1 groups, the relative content of glycine and taurine was 10.0±1.4 and 8.0±1.4, 3.6±0.7 and 66.5±7.3, 45.8±23.6 and 23.0±9.8, which was significantly lower than that of the normal control group, which was 14.6±1.9 and 102.5±25.8(P<0.01). The relative content of 1,7-dimethylguanosine was 4.5±1.2 and 4.6±0.1 in AESC 1.5 and 15 g·kg-1 groups, significantly lower than that of the normal control group, which was 6.5±0.8(P<0.05), but AESC 5 g·kg-1 group did not statistically differ from normal control group. The relative content of citric acid was 26.6±6.3 in the AESC 15 g·kg-1 group, significantly lower than that of the normal control group, which was 67±14(P< 0.01). The relative content of citric acid was 104+20 in the AESC 1.5 g·kg-1 group, significantly higher than that of the normal control group (P<0.01), but AESC 5g·kg-1 group did not statistically differ from normal control group. CONCLUSION: AESC can remarkably change endogenous metabolites and mainly affect the pathways of taurine,purine, amino acid and energy metabolism.     

Inhibitory effect of combination of tanshinone I,metformin and aspirin on malignant melanoma model mice北大核心CSCD

OBJECTIVE: To explore the antitumor effects of combined tanshinone I (Tan I), metformin (Met) and aspirin (Asp) on malignant melanoma in mice and the possible mechanisms. METHODS: C57BL/6 mice were injected with 0.1 mL B16F10 cells (2.8×109 L-1) to establish the subcutaneous transplantation tumor model at the right forelimbs axillary. Then, the mice were divided into 8 groups according to body mass, including model group, Tan I group (20 mg.kg-1 ip), Asp group (210 mg.kg-1, orally in drinking water), Met group (70 mg.kg-1, orally in drinking water), Asp+Met group, Tan I +Asp group, Tan I +Met group and Tan I +Asp+Met group, 10 mice in each group. Each mouse drank about 7 mL of water every day for a total of 18 d. The mouse body mass was measured every other day and the tumor diameter was calculated every day. The mice were sacrificed after treatment, the tumor mass was measured and the tumor inhibitory rates were counted. The histopathological changes of the liver and spleen were observed with HE staining. The percentage of lymphocytes in the tumor tissue such as CD8T, CD4+T and Treg cells was detected by flow cytometry. Inflammatory factors such as interleukin-6 (IL-6), IL-1β and tumor necrosis factor-α (TNF-α) were detected by ELISA. RESULTS: The body mass (including tumor mass) of mice in different groups increased during the experiment, but that of Tan I + Asp+Met group increased more slower than in model group (P<0.01). At the end of the experiment, no lesions were seen in any liver or spleen tissue by pathological observation, and the number of survivors was 8/10 (model group), 8/10 (Tan I group), 7/10 (Asp group), 7/10 (Met group), 8/10 (Tan I +Asp group), 8/10 (Tan I +Met group), 7/10 (Asp + Met group) and 5/10 (Tan I +Asp+ Met group), respectively. Compared with model group, there were no obvious changes in tumor volume or tumor mass in Tan I, Asp and Met groups and other two-two joint groups, but the tumor volume and tumor mass in Tan I + Asp+ Met group were significantly decreased (P<.01, P<0.05), and the tumor inhibitory rate in this group was 46.2%. Compared with the model group, the percentage of CD8+T cells increased (P<0.05) in Tan I + Asp+ Met group, but there were no significant changes in other groups. The contents of IL-6, IL-1β and TNF-α in tumor tissue of Tan I +Met group were much higher than in model group (P<0.01, P<.05, P<0.05) and the content of IL-6 increased in Tan I +Asp+Met group (P<0.01). CONCLUSION: Combination of Tan I, Asp and Met can effectively inhibit the growth of melanoma in mice, which may be related to the increasing percentage of CD8+T lymphocytes and IL-6 in tumor tissue. However there are possibly some side effects. © 2017 Chinese Journal of Pharmacology and Toxicology. All rights reserved.     

Effect of ECR on the Expression of Tau from the Brain of the Mice Induced by Overload Aluminum Salt

Aim: To study the effect of Ecdysterone (ECR) on the expression of Tau from the cerebral cortice and hippocampus and behaviors in passive avoidance reaction and spatial discrimination of the mice induced by overload aluminum salt.Methods Fourty-five NIH mice were randomly divided into five groups, the control group, the model group, the treated