Aspirin,a non-steroidal anti-inflammatory drug,is widely used in clinics with definite therapeutic effects and a few adverse drug reactions.Recent studies demonstrated that other effects besides antipyretic,analgesic,and anti-inflammatory effects have been discovered,such as anti-cancer,anti-cardiovascular diseases,anti-skeletal muscle diseases,and anti-nervous system diseases.This paper reviewed the therapeutic effects and possible mechanisms of aspirin on cancer,cardiovascular disease,muscle-skeletal disease,and nervous system disease based on the related research status at home and abroad.It will provide clues and a theoretical basis for clinical rational drug use and discover novel pharmacological effects of aspirin in the future.

OBJECTIVE To investigate the effect of icariin(ICA)on the ubiquitination modification of β-amy-loid precursor protein(APP)in Alzheimer's disease mice.METHODS In vitro,① HEK 293 cells stably overex-pressing human APP695(OE-hAPP)were treated with different concentrations of ICA(10-100 μmol·L-1)for 24 h and the cell viability was detected by MTT assay.②CHX(50 mg·L-1)was used to block protein synthesis and MG132(20 μmol·L-1)inhibits proteasome activity,then the level of APP in different time(0,0.5,1,2,3 and 4 h)and the ubiquitination were tested by Western blotting.③ E3 ubiquitin ligases HMG-CoA reductase degradation pro-tein 1(HRD1)protein expression in OE-hAPP was tested by Western blotting,as well as the level and ubiquitination of APP were tested under HRD1 silent condition by Co-IP and Western blotting.In vivo,① male APP/PS1 mice and wild type(WT)mice were randomly divided into 5 groups:WT,WT+ICA,APP/PS1,APP/PS1+ICA,and APP/PS1+donepezil(DPZ)groups.ICA(60 mg·kg-1·d-1)and DPZ(1 mg·kg-1·d-1)were treated for 3 months by gavage from 6 months of age,and WT mice were given equal volume of distilled water.②Morris water maze and Y-maze experiments were used to detect the alteration of spatial learning memory function.③ After then,the brain tissues were collected,total proteins were extracted,APP antibodies were subjected to Co-IP,and total ubiqui-tination(Ub),K48-linked polyubiquitination(UbK48)and K63-linked polyubiquitination of APP level,APP and HRD1 proteins were detected by Western blotting.RESULTS In vitro results showed that ICA significantly enhanced APP degradation(vs control,P＜0.01),up-reg-ulated HRD1 expression(vs control,P＜0.05;vs OE-hAPP,P＜0.05),elevated the level Ub and UbK48 of APP,as well as increased APP degradation.Moreover,silenced HRD1 gene abolished abovementioned effects of ICA(vs control-siRNA,P＜0.05;vs HRD1-siRNA,P＜0.05).In vivo results showed that ICA improved the spa-tial learning and memory function APP/PS1 mice by Mor-ris water maze and Y-maze tests,increased HRD1 expres-sion(vs APP/PS1 + vehicle,P＜0.05),enhanced APP ubiquitination and reduced APP protein level(vs APP/PS1 + vehicle,P＜0.01).CONCLUSION ICA promotes the ubiquitination and proteasome-dependent degrada-tion of APP by up-regulating HRD1,thereby improving the spatial learning and memory function of Alzheimer disease mice.

Objective: Sweet Tea (ST), derived from the leaves of Lithocarpus polystachyus, is a Chinese folk medicine with wide pharmacological activities. However, the promotive effects of ST water extract on hepatocytes proliferation and its underlying mechanism remains still unknown. In the present study, the beneficial effects of ST water extract on human hepatocytes and its possible mechanism were investigated. Methods: MTT assay was used to detect the safety range of ST; HL7702 cells were divided into four groups: control group, ST low- (50 μg/mL), medium- (200 μg/mL) and high-concentration (800 μg/mL) groups; BrdU ELISA and EDU staining were used to observe DNA content and cell proliferation; Moreover, flow cytometry was applied to analyze the distribution of cell cycle. Furthermore, the expression of cyclin D1, CDK4, HGF/c-Met, Akt, Erk1/2 were detected by Western blot. Results: It was found that ST water extract concentration-dependent promoted human hepatocytes HL7702 cell proliferation within 72 h through accumulating the cells in S phase and G2/M phase. Furthermore, ST water extract up-regulated expression of Cyclin D1 and CDK4 proteins. Moreover, ST water extract not only increased HGF expression and phosphorylation of c-Met level, but also activated the phosphorylation levels of AKT, ERK1/2. Interestingly, both of AKT inhibitor A6730 and ERK1/2 inhibitor U0126 reversed the promotive effects of ST water extract, which further confirmed that activation of AKT and ERK1/2 were involved. Conclusion: The findings reveal that ST water extract promoted HL7702 cells proliferation through the stimulation of cell cycle mediated by activating the AKT- and ERK1/2-related pathway.

Objective:To investigate the changes of advanced glycosylation end product(AGEs)/sodium-glucose cotransporter-1(SGLT-1) in intestinal and renal tissues and intestinal flora of mice with diabetes kidney disease.Methods:Twenty KKay mice were divided into diabetic group(DM group, n=10) and diabetic kidney disease group(DKD group, n=10). The concentrations of serum AGEs, lipopolysaccharide(LPS), tumor necrosis factor-α(TNF-α), and intereukin-6(IL-6) were measured. Western blot technique was used to detect the protein expression of AGEs and SGLT-1 in kidney and intestinal tissue, and high-throughput sequencing was used to analyze the difference of intestinal flora. Results:The levels of inflammatory markers TNF-α, IL-6, and serum endotoxin in DKD group were significantly higher than those in DM group( P<0.05). The contents of AGEs in serum and intestine and kidney were increased, and the contents of SGLT-1 in intestine and kidney were increased( P<0.05). Metastats test showed that the abundance of Verrucomicrobia decreased and the abundance of Proteobacteria increased in DKD group( P<0.05). G - bacteria such as Aeromonas, Enterobacter, Morgan, Klebsiella, Serratia, and Burkholderia were relatively dominant, and the abundance of Akkermansia was significantly lower than that in DM group( P<0.05). Conclusion:The increase of AGEs in intestinal tract of DKD mice may induce intestinal dysbacteriosis, especially the increase of Proteobacteria, the decrease of Verrucosa and Wilhelm Ackermann, and the leakage of G-bacteria into the blood to produce intestinal endotoxemia and cause inflammatory reaction, this may be an important factor in the development of DKD. SGLT-1 is elevated in intestinal tissue, which may be involved in the development of DKD.

Objective To observe the effect of IcarisideⅡ (ICSⅡ) on spatial learning and memory impairments and axonal regeneration induced by chronic cerebral hypoperfusion (CCH) in rats.Methods 90 male SD rats were randomly divided into normal group,sham operation group,CCH group and ICS Ⅱ low,middle and high-dose treatment groups.The chronic cerebral hypoperfusion model was established by permanent bilateral common carotid artery occlusion.Then these rats in ICS Ⅱ low,middle and high-dose treatment groups were given ICS Ⅱ4,8 and 16 mg/(kg · d) by gavage on the 1st day after modeling.There were 5 rats in every group at each observing time(4,8 and 12 week).Morris water maze experiment was utilized to assess the escape latency and the target quadrant residence time while HE and immunohistochemistry analysis were applied to test the morphology change and expressions of GAP-43,MAP-2 and Nogo-A in hippocampal CA 1.Results Compared with those of sham operation groups at 4,8 and 12 week respectively,the escape latency in CCH group were significantly prolonged(40.02±4.95) s,(42.29±5.75) s,(53.68±6.14) s vs (26.43±2.68) s,(26.84±2.06) s,(31.53±4.12) s,P＜0.05;the target quadrant residence time were significantly reduced(28.53±2.40) s,(28.02±4.28) s,(22.60±4.03) s vs (33.34±2.89) s,(33.31 ±4.14) s,(31.63±2.20)s,P＜0.05);the expressions of GAP-43 and Nogo-A were increased with that of MAP-2 reduced(P＜0.05).Meanwhile,the neuropathological changes with more denatured neurons and less normal neurons were found in hippocampal CA1.However,compared with those of CCH group,the escape latency of ICS Ⅱ middle and high-dose groups (30.58±3.03) s,(29.19±4.23) s,(38.77±5.80) s;(28.90±2.98) s,(26.91 ±6.63) s,(36.51 ±3.98) s) were shortened (P＜0.05);the target quadrant residence time (32.54± 3.41) s,(32.69±3.47) s,(28.27±3.57) s;(32.69±3.54) s,(33.20±4.29) s,(28.07±4.04) s) were increased (P＜ 0.05);the expression of Nogo-A was decreased while those of GAP-43 and MAP-2 were conversely increased (P＜0.05).Moreover,few denatured neurons were observed in hippocampal CA1.But there were no differences for those indexs between CCH group and ICS Ⅱ low-dose treatment groups (P＞0.05).Compared with those in 8 week and 4 week,the escape latency and the target quadrant residence time were prolonged and reduced with the expression of Nogo-A increased in all groups except normal group and sham operation group(P＜0.05),the expressions of GAP-43 and MAP-2 were decreased in CCH group and ICS Ⅱ low-dose treatment group(P＜0.05),but there were no significant differences in ICS Ⅱ middle and high-dose treatment groups at 12 week(P＞0.05).However,there were no statistical significance of all indexes between 8 week and 4 week(P＞0.05).Conclusion ICS Ⅱ can improve the spatial learning and memory in chronic cerebral hypoperfusion rats,which may be achieved by neuroprotective effects and reducing the expression of Nogo-A consequently promotes the regeneration of axons.

In recent years,the role of phosphodiesterase 5(PDE5)has been highlighted in the development and progression of neurological disease.PDE5 inhibitors show significant effect of neruoprotection,which may be related with some effects such as resistance to stroke,anti-oxidation,inhibition of neuroinflammation and amelioration of cognitive deficits.Based on the domestic and overseas researches about PDE5,this review systematically summarized the neuroprotection of PDE5 and their related mechanisms.

Aim To investigate the protective effect of noble dendrobium polysaccharides ( NDP ) on lipopo-lysaccharide ( LPS)-induced neuron injuries in newborn rat cerebral cortex glial cells and neuron mixed cul-tures.Methods The primary cultures of newborn rat cortical neurons and glial cells were established and the existence of the neurons , astrocytes and microglia was verified respectively .NDP was given to LPS-induced mixed cultures , the mRNA levels of IL-1β, TNF-αand COX-2 were assayed by real time PCR .Results NDP reduced the glial cell activation and neuron dam-age after it was given to LPS-induced mixed cultures . The mRNA levels of IL-1β, TNF-α, COX-2 were re-duced .Conclusion NDP protects against LPS-in-duced neuron-inflammation in neurons and glial cells cultures.

Objective To observe the effects of icarisid Ⅱ (ICS Ⅱ)on cognitive deficits and expression of synaptophysin(SYN)in chronic cerebral hypoperfusion(CCH)rat models.Methods 40 male SD rats were randomly divided into four groups:normal group,sham operation group,model group and ICSⅡgroup.The model was established by permanent bilateral common carotid artery occlusion(BCCAO).ICS Ⅱ group was administered ICS Ⅱ at a dose of 8mg·kg -1 ·d -1 by gavage on 1st day after modeling.Sham group and CCH group were injected double -distilled water.The escape latency(s)and spatial probe times were measured by water maze test.Then,the morphology change and expression of SYN in hippocampal were assayed by HE and immunohistochemistry analysis.Results At the 1st month and 2nd month,the escape latency in the model group[(40.02 ±4.95)s,(42.29 ±5.75)s]were significantly prolonged compared with the sham operation group[(26.43 ±2.68)s,(26.84 ±2.06)s](t =4.89,5.06,all P <0.05).And those in the ICS Ⅱ group[(30.58 ±3.03)s,(29.19 ±4.23)s]were significantly decreased compared with the model group(t =3.63,4.10,all P <0.05).The space probe times in the model group[(2.6 ±0.89)times, (2.40 ±1.14)times]were significantly reduced compared with the sham operation group[(6.00 ±2.16)times, (5.75 ±2.16)times](t =3.23,4.18,P <0.05).And those in the ICS Ⅱ group[(4.40 ±1.34)times,(5.00 ± 1.58)times]were significantly increased compared with the model group (t =2.49,2.98,all P <0.05).The average optical density of SYN in hippocampal in the model group[CA1:(0.121 ±0.009),(0.122 ±0.008);CA3:(0.172 ± 0.028),(0.173 ±0.021 )]were significantly reduced compared with the sham operation group[CA1:(0.131 ± 0.006),(0.136 ±0.007);CA3:(0.218 ±0.035),(0.204 ±0.018)](t =2.43,2.53,3.12,2.34,P <0.05). Those in the ICS Ⅱ group[CA1:(0.131 ±0.006),(0.132 ±0.006);(0.212 ±0.02),(0.208 ±0.022)]were significantly increased compared with model group(t =2.41,2.41,2.31,2.77,all P <0.05).However,there was no statistically significant difference of those index between the normal group and sham operation group(P >0.05 ). Conclusion ICS Ⅱ can improve the cognitive deficits in CCH rat models and this effect may be associated with increased expressions of SYN in hippocampal.

Objective To investigate optimal extraction process of Piper puberulum ( Benth.) Maxim.and qualitative analyze the chemical component of the extracts.Methods Method of solvent heating reflux was used for extraction.On the basis of single factor experiment, L9 (34 ) orthogonal experiment was designed with the variants of extraction frequency, time, material-liquid ratio, and immersion time.Extraction rate as index, extraction processes were optimized to achieve best extraction.The extracts, including total extract, water elution, and ethanol elution, were physiochemically analysed to achieve an initial qualitative result.Results The optimal extraction process was: extractions 3 times for 2 hours, with an 1︰30 material -liquid ratio and 2 hours of immersion, Initial qualitative analyzed the total extracts containing amino acids, polypeptides, proteins, alkaloids, steroids or triterpenes, flavones, saponins, polysaccharides, reducing sugars or glucosides, cumarins, terpene lactones, phenols, and tannins.The water elution containing: amino acids, polypeptides, proteins, saponins, polysaccharides, reducing sugars or glucosides, cumarins, and terpene lactones.The ethanol elution containing: amino acids, polypeptides, proteins, alkaloids, steroids or triterpenes, flavones, polysaccharides, reducing sugars or glucosides, phenols, and tanins.Conclusion The experiments show that optimal extraction process can achieve high extraction yield, stable and practical.

Aim To investigate the effect of icariin ( ICA) on renal interstitial fibrosis in SHR and explore its mechanism. Methods Fourteen male SHR of 13-week-old were randomly divided into model group( n=7 ) and ICA group ( n=7 ) , and WKY as control group (n=7). One week after adaptive breeding,the rats in the ICA group were given ICA 40 mg·kg-1,ig,bid to 26-week-old. The other rats in the model group and control group were given the same amount of normal sa-line. Then, the morphological changes of the kidney were observed by HE and Masson staining,respective-ly. The contents of plasma aldosterone andⅢcollagen were measured by double antibody sandwich method. The mRNA expressions of TGF-β1 , Smad2 , CTGF and FN were examined by real time RT-PCR. Results Compared with the normal control group, the kidney structures of model group were disordered,the mesang-ial matrix and the tubular interstitial fibrosis were in-creased. The contents of plasma aldosterone and Ⅲcollagen were increased in model group ( P <0. 01 ) . And the mRNA expressions of TGF-β1 , Smad2 , CTGF and FN in kidney tissues were up-regulated in model group( P <0. 01 or P <0. 05 ) . Compared with the model group,the kidney structures were improved and the contents of plasma aldosterone and Ⅲ collagen were reduced, as well as the mRNA expressions of TGF-β1,Smad2,CTGF and FN in kidney tissues were down-regulated(P<0. 01 or P<0. 05)in ICA group. Conclusion ICA may have anti-renal interstitial fi-brosis effect on SHR,and the mechanism might be re-lated to the reduced plasma aldosterone levels and the down-regulated expression of TGF-β1 and Smad2 .