Comparison in vitro permeation of curcumin from topical gels by liquid chromatography tandem mass spectrometry

Objective： To fred a more effective method of topical transdermal delivery of curcumin. Methods： We prepared curcumin carbopol （CRB） 974P and hydroxypropylcellulose （HPC） gel formulations containing menthol or Azone as permeation enhancers In this study, negative mode electrospray ionization and a triple quadruple LC/MS/MS instrument operated in multiple reaction mode was used for curcumin detection. The assay was linear over a concentration range of 10 ng/mL to 400 ng/mL for curcumin （average R2 = 0.997 2）. Excised nude mouse dorsal side skin was used in an in vitro skirt permeation study performed using the method of Franz. Results： Our results showed that all of the topical gel formulations we developed were free from skin irritation. The percutaneous flux and enhancement ratio of curcumin across nude mouse epidermis were enhanced markedly by the addition of menthol or Azone to both types of gel formulations. We found that the HPC gels containing quantities of Azone showed an enhanced permeation effect as compared to gels containing menthol. In the case of HPC gels containing Azone, the increase in permeability was significant （P〈0.05） as compared to the gels containing menthol. Conclusion： Azone shows a significantly more remarkable permeation effect than menthol. As such, this novel delivery strategy offers significant promise and is worthy of further exploration in attempts to enhance the medicinal application of curcumin

Effects of different transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids,HSL and HMG-CoA reductase in hyperlipidemia rabbits

Objective:To observe the effects of laurocapram and borneol as transdermal penetration enhancers applied to herbal cake-partitioned moxibustion on liver lipids,hormone-sensitive lipase(HSL)and hydroxymethylglutaryl CoA(HMG-CoA)reductase in hyperlipidemia rabbits.Methods:Forty New-Zealand rabbits were randomly divided into 5 groups using the random number table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with a normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not given any intervention.After the model was prepared successfully,rabbits in the non-transdermal penetration enhancer group received herbal cake-partitioned moxibustion without transdermal penetration enhancers;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,the serum was isolated and enzyme-linked immunosorbent assay(ELISA)was applied for the detection of HSL and HMG-CoA reductase.The liver tissues were isolated,and total cholesterol(TC)and triglycerides(TG)were measured by enzymatic methods.One-step method was applied for high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C)detection,and transmission turbidimetry was for apolipoprotein A1(Apo-A1)and apolipoprotein B(Apo-B)detection.Results:The serum concentrations of the drugs in the laurocapram and the borneol groups were significantly higher than those in the non-transdermal penetration enhancer group(both P<0.05);all drug penetrations in the borneol group were significantly higher than those in the laurocapram group(both P<0.05),except for tanshinoneⅡA.Compared with the non-transdermal penetration enhancer group,the HSL was significantly increased while the HMG-CoA reductase was significantly decreased in the laurocapram and the borneol groups(both P<0.05);between groups,the HSL in the borneol group was significantly higher than that in the laurocapram group(P<0.05).Compared with the blank group,the levels of LDL-C,TG,TC and Apo-B in rabbit liver were significantly increased in the model group(P<0.05);compared with the model group,the levels of LDL-C,TG,TC and Apo-B in the non-transdermal penetration enhancer,the laurocapram,and the borneol groups were significantly decreased(all P<0.05);between groups,the TG and TC in the laurocapram group and the LDL-C,TG,TC and Apo-B in the borneol group were significantly lower than those in the non-transdermal penetration enhancer group(all P<0.05),and the TG,LDL-C and Apo-B in the borneol group were significantly lower than those in the laurocapram group(all P<0.05).Compared with the blank group,the HDL-C and Apo-A1 were significantly decreased in the model group(both P<0.05),while compared with the model group,the HDL-C and Apo-A1 were significantly increased in the non-transdermal penetration enhancer,the laurocapram,and the borneol groups(all P<0.05).Between groups,the Apo-A1 in the laurocapram group,the HDL-C and Apo-A1 in the borneol group were significantly higher than those in the non-transdermal penetration enhancer group(all P<0.05).Conclusion:The application of laurocapram and borneol,as transdermal penetration enhancers,in herbal cake-partitioned moxibustion can promote the penetration of the drugs in the herbal cake,increase the levels of HDL-C and Apo-A1,improve the metabolism of HSL and HMG-CoA reductase,and also simultaneously reduce the levels of TC,TG,LDL-C and Apo-B in the liver.The transdermal penetration enhancement effect of borneol is slightly better than or equivalent to that of laurocapram.

Effect of herbal cake-partitioned moxibustion on Leptin/JAK#STAT3 in lipid-lowering pathway of hyperlipidemia rabbits

Objective:To observe the lipid-lowering effect of different transdermal absorption enhancers applied to the herbal cake-partitioned moxibustion in hyperlipidemia model rabbits,and to explore the possible mechanism.Methods:Forty New-Zea I a nd rabbits were ran domly divided into 5 groups using the ran dom nu mber table method,with 8 rats in each group.Rabbits in the blank group were fed routinely with normal diet;rabbits in the other groups were fed with high-fat diet for 12 weeks to establish the hyperlipidemia model.Rabbits in the blank and the model groups were not treated.After the model was prepared,rabbits in the non-transdermal absorption enhancer group received herbal cake-partitioned moxibustion without transdermal absorption enhancer;rabbits in the laurocapram group and the borneol group received herbal cake-partitioned moxibustion with laurocapram or borneol respectively.After 4 weeks of treatment,serum was collected for enzyme-linked immunosorbent assay(ELISA),and the liver tissues were isolated for imm uno histochemistry,qua ntitative polymerase chain reactio n(qPCR)and Western-blotting(WB)detecti on.Results:Serum ELISA results showed that leptin was significantly decreased in the model group compared with the blank group(P<0.05);compared with the model group,lepti n was significa ntly in creased in the non-tran sdermal absorpti on enhanee。the laurocapram and the borneol groups(all P<0.05);compared with the non-transdermal absorption enhancer group,leptin was significantly increased in the laurocapram group and the borneol group(both P<0.05);there was no significant differenee in leptin between the laurocapram and the borneol groups(P>0.05).The qPCR results of rabbit liver tissues showed that the mRNA expressions of leptin,Janus kinase 2(JAK2)and signal transducer and activator of transcription 3(STOT3)in the model group were significantly lower than those in the blank group(all P<0.05);compared with the model group,the mRNA expressions of leptin,leptin receptor(LR),JAK2 and S1AT3 in the non-transdermal absorptio n enhan cer,the laurocapram and the born eol groups were significantly in creased(all P<0.05);compared with the non-transdermal absorption enhancer group,the mRNA expressions of leptin,LR,JAK2 and S77VT3 in the laurocapram and the bor neol groups were sign ificantly in creased(all P<0.05);compared with the laurocapram group,the mRNA expressi ons of lepti n,LR,JAK2 and SW3 in the bor neol group were significa ntly in creased(P<0.05).The trend of immun ohistochemistry and WB detecti on results was basically con siste nt with the qPCR assay results.The immuno histochemistry and WB detection results of phosphorylated JAK2(phospho-JAK2)and phosphorylated S7AT3(phospho-STAT3)were basically consistent with those of JAK2 and S7AT3.Conclusion:The molecular expression of Leptin/JAK"S7AT3 pathway in the hyperlipidemia model rabbits was decreased.The molecular expression of Leptin/JAK0STCT3 pathway was significantly increased after the herbal cake-partitioned moxibustion.The application of laurocapram and borneol,as transdermal absorption enhancers,in the herbal cake-partitioned moxibustion could more obviously up-regulate the factors of the Leptin/JAK^SIAT3 lipid-regulating pathway than the herbal cake-partitioned moxibustion alone.