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Objective To observe the effect of aralia saponins on the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) in the kidney of diabetic nephropathy mice.Methods After 10 days of adaptive feeding,90 clean Kunming mice were randomly divided into the normal group (n =10) and 5 model groups (model group,positive drug benazepril intervention group,aralia saponins low,middle and high doses treatment groups).Excepted the normal group,the kidney damage model of type 2 diabetes mellitus in mice was induced by high-fat and high-sugar diet for one month plus disposable streptozotocin (STZ).The model was successfully constructed and killed after 6 weeks of treatment.A total of 25 mice failed to establish the model.And totally 55 mice were randomly divided into 5 groups with 11 mice in each group.The serum changes of blood urea nitrogen (BUN),serum creatinine (SCr),insulin,inflammatory factors interleukin-1α (IL-1α),interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in each group were detected.The expression of vascular endothelial growth factor and MMP-9 protein in renal tissue were detected by immunohistochemistry and Western blot.Results Compared with the normal group,the levels of blood glucose,insulin,BUN,SCr,IL-1α,IL-6 and TNF-α in the model group were significantly increased (P ＜ 0.05).The above indexes were decreased in positive drug group and aralia saponins treatment groups.The contents of insulin,BUN and SCr in the high dose of aralia saponins group were significantly lower than those parameters in benazepril group (P ＜ 0.05).In addition,the contents of blood glucose,IL-1α,IL-6 and TNF-α in the three dose aralia saponins groups were significantly lower than those parameters in the benazepril group (P ＜ 0.05).Compared with the normal group,the expression level of VEGF protein in the model group was significantly higher (P ＜ 0.05),and the expression level of MMP-9 protein was significantly lower (P ＜ 0.05).Compared with the model group,both benazepril and aralia saponins can reduce VEGF (P ＜ 0.05),increase MMP-9 (P ＜ 0.05).In addition for VEGF and MMP-9,the high dose of aralia saponins group and benazepril group was basically same.Conclusions Aralia saponins can significantly reduce blood glucose,insulin and serum inflammatory factors,while downregnlate VEGF and increase MMP-9 protein levels,thereby protecting the kidneys of diabetic nephropathy mice.
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OBJECTIVE: To develop a highly sensitive and specific LC-MS/MS method to explore the pharmacokinetic properties of araloside A. METHODS: Araloside A was administered in a dose of 50 mg•kg-1 via gastric in fusion and 5 mg•kg-1 by intravenous injection in rats. Araloside A was analyzed by a validated LC-MS /MS method in plasma after intravenous and intragastric administration. The pharmacokinetic parameters were evaluated by software DAS 3.0. RESULTS: The results of pharmacokinetic study showed that the linear range of araloside A was good in 1.0 - 10 000.0 μg•L-1 (r > 0.994 8). The specificity, precision and accuracy, matrix effect and extraction recovery rate and stability all meet the requirements. The main pharmacokinetic parameters for intragastric administration with araloside A 50 mg•kg-1 and intravenous injection of araloside A 5 mg•kg-1 were as follows: t1/2 was (8.65 ± 3.22 ) and (2.00 ± 0.21) h, AUC0-t was (277.14 ± 101.00) and (21 194.59 ± 4 385.13) ng•h•L-1, MRT0-t was (7.88 ± 0.64) and (1.21 ± 0.11) h, Vd/F was (2 229.99 ± 1 013.97) and (0.71 ± 0.20) L•kg-1, CL/F was (149.11 ± 62.28) and (0.24 ± 0.05) L•h-1•kg-1, respectively; ρmax was (32.68 ± 10.74) μg•L-1 for intragastric administration and tmax reached(1.21 ± 0.70) h, oral bioavailability of araloside A was about 0.14%. CONCLUSION: The LC-MS/MS method established is specific and sensitive, and can be successfully applied in basic pharmacokinetic study of araloside A in rat plasma.
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Objective To explore the inhibition role of araloside on cervical cancer HeLa cell proliferation and migration to reveal the molecular mechanism of NF-κB in HeLa cell in the process of tumor suppression.Methods The in vitro cultured cervical cancer HeLa cell line served as the research object.The experiment was divided into the control group and araloside(200 μg/mL) treatment group(observation group).The change of proliferation and migration ability after 48 h were observed in the two groups.Western blot was used to detect the expression of NF-κB molecule and change of autophagy involved protein Beclin 1 and LC3B.Results Araloside could significantly inhibit the proliferation and migration of HeLa cells and the NF-κB signaling pathway,and promoted the expression of autophagy related molecule Beclin 1,Atg 5 and LC3B.Conclusion Araloside could inhibit the NF-κB signaling pathways,thus induces autophagy occurrence and influences the proliferation and migration of cervical cancer HeLa cells.
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Araloside A is one of the main active ingredients of Aralia taibaiensis. In this study, HPLC-MS/MS analysis method of araloside A in the main organs of SD rats was established. At the same time, the content of araloside A in the main organs (heart, liver, spleen, lung, kidney, brain) after oral administration with araloside A (50 mg•kg⁻¹) were determined to explore the tissue distribution characteristics of araloside A in vivo. The results showed that the methodological study of araloside A in the main organs of SD rats met the requirements, araloside A distributed in heart, liver, spleen, lung, kidney and brain tissues reached peak at 1 h or 2 h after oral administration with 50 mg•kg-1.The distributions of araloside A at different time points after administration were distinct as follows： the content of araloside A at 20 min：liver>heart>spleen>lung>kidney>brain; the content of araloside A at 1 h： liver>spleen>kidney>lung>heart>brain; the content of araloside A at 2 h： liver>kidney>heart>spleen>lung>brain; the content of araloside A at 4 h： kidney>liver>spleen>heart>lung>brain; the content of araloside A at 8 h： spleen>heart>liver>kidney>lung>brain. Therefore, araloside A was mainly distributed in liver tissue, which had a certain correlation with the common use of Aralia taibaiensis in the treatment of hepatic disease. In addition, araloside A shows a low content but an obvious distribution in brain tissues, which indicates that the drug can pass through blood-brain barrier, and provides the basis for the study of araloside A in brain tissue.
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Objective To explore the effect of araloside on the proliferation and apoptosis of HeLa cells.Methods Human cervical cancer cell line HeLa was cultured in vitro,the experiment was divided into 4 groups as follows:blank group,araloside trea-ted groups(50,100,200 μg/mL).Normal saline and araloside (50,100,200 μg/mL)were gave,respectively.24,48 and 72 hours lat-er,the cells were collected.Cell proliferation was detected by MTT,cell apoptosis was determined by flow cytometry,the expression of pAkt1,pIкBα,NF-κB (p65),Bcl-2 and Caspase-3 were evaluated by western blot.Results Araloside obviously inhibited the pro-liferation and increased the apoptosis level of HeLa cells in a time-dose dependent manner.Moreover,Araloside significantly de-creased the phosphorylation of Akt1 and IκBα,reduced the expression of NF-κB(p65)and Bcl-2,whereas obviously increased Caspase-3 content.Conclusion Araloside could inhibit the proliferation and promote the apoptosis of HeLa cells via suppressing Akt/NF-кB signaling pathway.
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Objective: To explore the optimal separation of the araloside A from Aralia chinensis by selecting appropriate macroporous resins and to systematically study the factors which affect the separation. Methods: Static and dynamic adsoption-desorption methods were adopted and evaluated for separating efficiency by measuring the concentration of araloside A in A. chinensis with HPLC. Results: Macroporous resin AB-8 had the best separating efficiency when the content in A. chinensis liquid was 0.1 g/mL equivalent to raw material. The volume of drug is 6 BV (resin bed volume) with the adsorption-power 2.5 BV/h and the volume of 50% ethanol as eluant 4 BV with desorption-power 2 BV/h. After the treatment of AB-8 resin, the purity of araloside A could reach 30% and total araloside to 80%. Conclusion: This method is simple and feasible with good effect of separation, which can meet the industrial requirements.
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Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression.