Tanshinone IIA alleviates monocrotaline-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of tanshinone IIA in the treatment of pulmonary arterial hypertension (PAH) in rats.@*METHODS@#A total of 100 male SD rats were randomized into 5 groups (n=20), and except for those in the control group with saline injection, all the rats were injected with monocrotaline (MCT) on the back of the neck to establish models of pulmonary hypertension. Two weeks after the injection, the rat models received intraperitoneal injections of tanshinone IIA (10 mg/kg), phosphatidylinositol 3 kinase (PI3K) inhibitor (1 mg/kg), both tanshinone IIA and PI3K inhibitor, or saline (model group) on a daily basis. After 2 weeks of treatment, HE staining and α-SMA immunofluorescence staining were used to evaluate the morphology of the pulmonary vessels of the rats. The phosphorylation levels of PI3K, protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS) in the lung tissue were determined with Western blotting; the levels of eNOS and NO were measured using enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The results of HE staining and α-SMA immunofluorescence staining showed that tanshinone IIA effectively inhibited MCT-induced pulmonary artery intimamedia thickening and muscularization of the pulmonary arterioles (P < 0.01). The results of Western blotting showed that treatment with tanshinone IIA significantly increased the phosphorylation levels of PI3K, Akt and eNOS proteins in the lung tissue of PAH rats; ELISA results showed that the levels of eNOS and NO were significantly decreased in the rat models after tanshinone IIA treatment (P < 0.01).@*CONCLUSION@#Treatment with tanshinone IIA can improve MCT-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway.

Inhibition effect of 6-gingerol on hair growth / 中华整形外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of 6-gingerol, the main active component of ginger, on hair shaft elongation in vitro and hair growth in vivo.</p><p><b>METHODS</b>Firstly, Hair follicles were co-cultured with 3 different concentration of 6-gingerol for 5 days and hair elongation in three groups was measured. Secondly, The proliferative effect of 6-gingerol on DPCs was measured using MTT assay. Thirdly, the expression of Bcl-2 and Bax in DPCs were measured using Western blotting. In vivo study, the influence of 6-gingerol on hair growth in C57BL/6 rats was measured through topical application of 6-gingerol on the dorsal skin of each animal.</p><p><b>RESULTS</b>The length of hair shaft in 20 microg/ml 6-Gingerol group (0.50 +/- 0.08 mm) is less than 0 microg/ml (0.66 +/- 0.19) mm and 10 microg/ml (0.64 +/- 0.03) mm 6-Gingerol group (P < 0.05). In cell culture, compared to 0 microg/ml and 5 microg/ml 6-Gingerol, 10 microg/ml 6-Gingerol can significantly inhibited the proliferation of DPCs (P < 0.05). Along with the growth inhibition of DPCs by 6-gingerol, the Bax/Bcl-2 ratio increased obviously. In vivo study, the hair length and density decreased a lot after using 1 mg/ml 6-gingerol.</p><p><b>CONCLUSIONS</b>6-Gingerol can suppress human hair shaft elongation because it has pro-apoptotic effects on DPCs via increasing Bax/Bcl-2 ratio. It might inhibit hair growth by prolonging the telogen stage in vivo.</p>

Modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui / 药学学报

To investigate the modulation on the P-glycoprotein in the jejunum by combined use of Glycyrrhiza inflata and Kansui with ussing chamber and rt-pcr, Rhodamine 123 (R123), a P-gp substrate and fluorescein sodium (CF), a model drug of non-P-gp substrate transported by a passive diffusion were taken as investigational drugs. Because these two drugs can be easily assayed and widely used in various research fields. The permeability of R123 or CF via Wistar rat jejunum membranes was evaluated by in vitro ussing chamber after oral administration of four different decoctions of Glycyrrhiza inflata and Kansui for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry in the receiving solution. Meanwhile the expression of mdr1a in P-glycoprotein was detected by real-time fluorescent quantitative PCR. After oral administration of combined decoction of the single drug, the absorptive directed permeability of R123 increased significantly (P < 0.01). On the other hand, Kansui and combine decoction of the two drugs also decrease the permeability of secretory directed transport (P < 0.05). No action of Glycyrrhiza inflata was found on the secretory transport of R123 [Papp = (2.56 +/- 0.38) x 10(-5), cm x s(-1)] across the jejunum tissues, while Papp of control group was found [Papp = (2.35 +/- 0.27) x 10(-5), cm x s(-1)]. After oral administration of Kansui decoction for 1 week and 2 weeks, the levels of mdr1a expression in Wistar rats were lower than that of the control group, but there were no significant difference in the results. Meanwhile, Glycyrrhiza inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group. Kansui may slightly inhibit P-glycoprotein function in the intestinal membrane. For another, some compositions in Kansui inhibit P-glycoprotein function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-glycoprotein was enhanced by combination of Glycyrrhiza inflata and Kansui, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of Glycyrrhiza inflata and Kansui.

Effect of liquorice decoction on rat intestinal P-glycoprotein / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effect of liquorice in functional modulation of intestinal P-glycoprotein (P-gp) in rats.</p><p><b>METHODS</b>An in vitro diffusion chamber system (Ussing chamber) was used to examine the direct effect of liquorice decoction on rhodamine 123 (a subtrate of P-gp) transport and evaluate the permeability of rhodamine 123 or fluorescein sodium through rat jejunum membranes after oral administration of liquorice decoction.</p><p><b>RESULTS</b>Direct application of liquorice decoction did not obviously affect rhodamine 123 transport across the intestinal mucosa. Oral administration of liquorice decoction (10 g/kg, twice daily for a week) significantly increased the absorption of rhodamine 123 and also enhanced rhodamine 123 secretion across the jejunum mucosa. Liquorice had no obvious effect on the transport of CF across the jejunum mucosa.</p><p><b>CONCLUSION</b>Liquorice may slightly inhibit P-gp function in the intestinal mucosa to increase the intestinal absorption of rhodamine 123.</p>

Effect of Glycyrrhiza inflata and Daphne genkwa on permeabilities of rhodamine 123, a P-glycoprotein substrate across rat jejunum membranes in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the modulation of Glycyrrhiza inflata and Daphne genkwa on the permeability characteristics of rhodamine 123 (R123), one P-glycoprotein (P-gp) substrate, across the jejunum membranes. And then approach the possible permeability mechanism of the drugs after co-administration of G. inflata and D. genkwa in gastrointestinal tract.</p><p><b>METHOD</b>The permeability of R123 or fluorescein sodium (CF) via Wistar rat jejunum membranes was evaluated by in vitro diffusion chamber system after oral administration of four different decoctions and 0.9% sodium chloride (20 mL x kg(-1)) for 1 week. And the concentration of R123 or CF was determined by the fluorospectrophotometry. The apparent permeability coefficient (P(app)) was calculated by the equation P(app) = dQ/d(t) x (1/A x C0), where P(app) was expressed in cm/s, dQ/dT was the slope of the linear portion of the permeation curves, A was the diffusion area, and C0 was the initial concentration of rebamipide in the donor side, and then compare their differences were compared with control group.</p><p><b>RESULT</b>After oral administration of G. inflata decoction, D. genkwa decoction and decoction of the combination of the previous decoctions, the absorptive directed transport of R123 was significantly increased (P < 0.05, compared with control group). On the other hand, D. genkwa could also decrease the permeability of secretory directed transport (P(app) = 2.98 +/- 0.59), while no action of G. inflata was found on the secretory transport of R123 ( P(app) = 5.24 +/- 3.98) across the jejunum tissues, while P(app) of control group was 4.38 +/- 1.18. Meanwhile, G. inflata had no effect on transport of CF across the jejunum tissues, though the other three groups could decrease the permeability of CF, as compared with control group.</p><p><b>CONCLUSION</b>G. inflata may slightly inhibit P-glycoprotein function in the intestinal membrane, while D. genkwa may be a relatively strong inhibitor of P-gp. For another, some compositions in D. genkwa inhibit P-gp function, and some others strengthen the tight junction between cells in the intestinal membrane to decrease permeability of CF. As the inhibitory action to P-gp was enhanced by combination of G. inflata and D. genkwa, based on the results, it may be one of the mechanisms of creating toxicity once co-administration of G. inflata and D. genkwa.</p>