| In vitro: |
| BIOTECHNOLOGY LETTERS, 2014, 36(4):685. | | Reversing P-glycoprotein-mediated multidrug resistance in vitro by α-asarone and β-asarone, bioactive cis–trans isomers from Acorus tatarinowii.[Reference: WebLink] | P-Glycoprotein (P-gp), an ATP-binding cassette transporter, plays an important role in multidrug resistance (MDR).
METHODS AND RESULTS:
alpha-Asarone
and β-asarone, bioactive cis–trans isomers found in Acorus tatarinowii Schott, were tested for their potential ability to modulate the expression and function of P-gp in Caco-2 cells. MTT assays revealed that both alpha-Asarone and β-asarone significantly enhanced the vincristine-induced cytotoxicity to cells. β-Asarone was the most potent. Flow cytometry showed that alpha-Asarone
and β-asarone increased Rhodamine 123 (Rh123) uptake and inhibited Rh123 efflux in Caco-2 cells in a concentration-dependent manner. Furthermore, P-gp expression and P-gp mRNA in cells were decreased by exposure to alpha-Asarone and β-asarone. In addition, β-asarone increased the inhibition of P-gp activity in cells more than α-asarone.
CONCLUSIONS:
Thus, alpha-Asarone and β-asarone effectively reversed MDR by inhibiting P-gp function and expression. | | Evidence-Based Complementary and Alternative Medicine, 2014, 2014:1-7. | | Alpha-Asarone Protects Endothelial Cells from Injury by Angiotensin II.[Pubmed: 24757494 ] | alpha-Asarone is the major therapeutical constituent of Acorus tatarinowii Schott.
METHODS AND RESULTS:
In this study, the potential protective effects of alpha-Asarone
against endothelial cell injury induced by angiotensin II were investigated in vitro. The EA.hy926 cell line derived from human umbilical vein endothelial cells was pretreated with alpha-Asarone
(10, 50, 100 µmol/L) for 1 h, followed by coincubation with Ang II (0.1 µmol/L) for 24 h. Intracellular nitric oxide (NO) and reactive oxygen species (ROS) were detected by fluorescent dyes, and phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177 was determined by Western blotting. alpha-Asarone
dose-dependently mitigated the Ang II-induced intracellular NO reduction (P < 0.01 versus model) and ROS production (P < 0.01 versus model). Furthermore, eNOS phosphorylation (Ser1177) by acetylcholine was significantly inhibited by Ang II, while pretreatment for 1 h with alpha-Asarone partially prevented this effect (P < 0.05 versus model). Additionally, cell viability determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay (105~114.5% versus control, P > 0.05) was not affected after 24 h of incubation with α-asarone at 1–100 µmol/L.
CONCLUSIONS:
Therefore, alpha-Asarone protects against Ang II-mediated damage of endothelial cells and may be developed to prevent injury to cardiovascular tissues. |
|
| In vivo: |
| Journal of Pharmacy & Pharmacology, 2010, 58(10):1343-1349. | | Hypolipidaemic and antiplatelet activity of phenoxyacetic acid derivatives related to α-asarone.[Reference: WebLink] | The phenoxyacetic acid derivatives 1-6 [2-methoxy-4-(2-propenyl)phenoxyacetic acid (1); 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetic acid (2); methyl 2-methoxy-4-(2-propenyl)phenoxyacetate (3); ethyl 2-methoxy-4-(2-propenyl)phenoxyacetate (4); methyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (5); ethyl 2-methoxy-5-nitro-4-(2-propenyl)phenoxyacetate (6)] related to alpha-asarone have been reported previously as hypolipidaemic agents in diet-induced hyperlipidaemic mice. We have aimed to expand the pharmacological profile of these derivatives by investigating their hypolipidaemic activity in rats and mice under different experimental conditions. The antiplatelet activity was tested also in-vitro from blood derived from consenting healthy volunteers.
METHODS AND RESULTS:
In normolipidaemic rats, compounds 2, 3 and 5 at oral doses of 40 and 80 mg kg(-1) significantly decreased total cholesterol and LDL-cholesterol levels. Moreover, analogues 3 and 5 administered to hypercholesterolaemic rats at the same doses for seven days also produced a reduction in the content of these same lipoproteins. In neither case were the high-density lipoprotein cholesterol and triglyceride concentrations affected. However, practically all tested compounds were found to be hypocholesterolaemic agents, and were shown to effectively lower low-density lipoprotein cholesterol and triglyceride levels in Triton-induced hyperlipidaemic mice at oral doses of 50 and 100 mg kg(-1).
CONCLUSIONS:
In all tests, all animals appeared to be healthy throughout the experimental period in their therapeutic ranges. Triton-induced hypercholesterolaemic mice appeared to be a desirable model for this class of hypolipidaemic drugs. On the other hand, compounds 1, 2, 4 and 5 significantly inhibited ADP-induced aggregation in-vitro. These findings indicated that all of these compounds appeared to be promising for the treatment of human hyperlipidaemia and thrombotic diseases. |
|
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