| Kinase Assay: |
| Cell Physiol Biochem. 2012;29(3-4):431-42. | | Comparative effects of liensinine and neferine on the human ether-a-go-go-related gene potassium channel and pharmacological activity analysis.[Pubmed: 22508050] | Liensinine and neferine, a kind of isoquinoline alkaloid, can antagonize the ventricular arrhythmias. The human ether-a-go-go-related gene (hERG) is involved in repolarization of cardiac action potential. We investigated the effects of Liensinine and neferine on the biophysical properties of hERG channel and the underlying structure-activity relationships.
METHODS AND RESULTS:
The effects of Liensinine and neferine were examined on the hERG channels in the stable transfected HEK293 cells using a whole-cell patch clamp technique, western blot analysis and immunofluorescence experiment. The pharmacokinetics and tissue distribution determination of Liensinine and neferine in rats were determined by a validated RP-HPLC method. Liensinine and neferine induced decrease of current amplitude in dose-dependent. Liensinine reduced hERG tail current from 70.3±6.3 pA/pF in control group to 56.7±2.8 pA/pF in the 1 μM group, 53.0±2.3 pA/pF (3 μM) and 17.8±0.7 pA/pF (30 μM); the corresponding current densities of neferine-treated cells were 41.9±3.1 pA/pF, 32.3±3.1 pA/pF and 16.2±0.6 pA/pF, respectively. Neferine had binding affinity for the open and inactivated state of hERG channel, Liensinine only bound to the open state. The inhibitory effects of Liensinine and neferine on hERG current were attenuated in the F656V or Y652A mutant channels. Neferine distributed more quickly than Liensinine in rats, which was found to be in higher concentration than Liensinine. Both Liensinine and neferine had no effect on the generation and expression of hERG channels. I
CONCLUSIONS:
n conclusion, neferine is a more potent blocker of hERG channels than Liensinine at low concentration (<10 μM), which may be due to higher hydrophobic nature of neferine compared with Liensinine. Neferine may be safety even for long-term treatment as an antiarrhythmic drug. |
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| Cell Research: |
| J Ethnopharmacol. 2013 Nov 25;150(2):485-91. | | In vitro characterization of ABC transporters involved in the absorption and distribution of liensinine and its analogs.[Pubmed: 24036064] | Lotus plumule, the dried young cotyledon and radicle of the Nelumbo nucifera Gaertn. (Fam. Nymphaeaceae) ripe seed, is a famous Traditional Chinese Medicine to remove heat from the heart, anchor the mind, improve seminal emission, and arrest bleeding for centuries in China. Liensinine and its analogs neferine and isoLiensinine are the major active components in lotus plumule. Aim of the study is to investigate the association of Liensinine, neferine, and isoLiensinine with efflux transporters.
METHODS AND RESULTS:
Caco-2, MDCK, MDCK-MDR1, and MDCK-MRP2 were used as cell models for the transcellular transport and accumulation studies.
The results obtained in Caco-2 cells suggested that P-glycoprotein (P-gp) might be involved in transcellular transport. Cellular accumulation and transport experiments were further performed in MDCK-MDR1 cells. GF120918 and cyclosporine A were found to completely inhibit the efflux, and the net efflux ratios of these alkaloids exhibited saturation over the concentration range. No significant differences in Liensinine accumulation and transport were observed between MDCK and MDCK-MRP2 cells.
CONCLUSIONS:
These results demonstrated that Liensinine, neferine, and isoLiensinine are substrates of P-gp, whereas MRP2 is not involved in the transport process, suggesting that P-gp might be responsible for the absorption and distribution of the 3 alkaloids. |
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| Animal Research: |
| Chinese Pharmacological Bulletin, 2010, 26(6):768-72. | | Effects of liensinine on platelet aggregation and coagulability and thrombotic activity[Reference: WebLink] | To investigate the effects of Liensinine on platelet aggregation and coagulation function in rats,as well as the effect on experimental thrombosis.
METHODS AND RESULTS:
Inhibition rates of platelet aggregation for Liensinine in vivo were determined by the model of platelet aggregation induced by adenosine diphosphate.Coagulation time of mice was measured by capillary vessel method,and bleeding time of mice was measured by tail-cutting method.The effects of Liensinine were also evaluated on prothrombin time(PT),activated partial thromboplastin time(APTT)and thrombin time(TT).The model of artery-vein bypass thrombosis and Chandler's model were established to observe the effect of Liensinine. The result showed that Liensinine 5 and 10 mg·kg-1 had significant effect on inhibition of platelet aggregation and markedly prolonged bleeding time,coagulation time,PT,APTT and TT.Liensinine 5 and 10 mg·kg-1 inhibited the artery-vein bypass and Chandler's thrombus in different degree,reduced the thrombus weight significantly (either wet ordry).
CONCLUSIONS:
Liensinine exerts remarkable effect against thrombosis and possesses strong effect against platelet aggregation and coagulation. |
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