Enhancing effect and mechanism of muscone on transdermal penetration of traditional Chinese medicine ingredients with different log P value / 中国中药杂志

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action. The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values. The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC. Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR) was employed to explore the effect of muscone on the molecular structure of SC. The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs, and the enhancement ratio(ER) increased with the decrease in the log P. Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing, which improved skin permeability and promoted transdermal absorption of drugs. This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.

Preparation of compound liquorice microemulsion gel and its pharmacodynamics evaluation / 中国中药杂志

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.

Combined detection of interleukin-6 and γ-glutamyltranspeptidase facilitates evaluation of therapeutic efficacy and prognosis of AFP-negative TACE-treated hepatocellular carcinoma patients / 解放军医学杂志

Objective To analyze the clinical value of combined detection of several serum markers in the treatment and prognosis of patients with alpha-fetoprotein (AFP)-negative hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). Methods A total of 120 patients (from September 2016 to March 2018) diagnosed with HCC followed by TACE are recruited in this study. Serum samples were collected and dynamic markers, serum AFP, carcinoembryonic antigen (CEA), carbohydrate antigen-199 (CA199), CA125, gamma-glutamyltranspeptidase (GGT), interleukin (IL)-2, IL-4, IL-6, IL-10, γ-interferon (IFN-γ), and tumor necrosis factor α (TNF-α) levels were detected in 44 AFP-negative patients and 76 AFP-positive patients prior, 1 and 3 months after TACE. During the follow-up period, the tumor activity of patients was monitored and the clinical value of different marker combinations on the efficacy and prognosis of AFP-negative HCC patients after TACE was analyzed until July 2018. Results There was no statistically significant difference in the pre-operative indicator levels between AFP-negative and AFP-positive patients (P>0.05). The sensitivity, specificity, negative predictive value, and positive predictive value of IL-6 combined with GGT in detecting the efficacy and prognosis of AFP-negative and AFP-positive patients were 95.2%, 87.0%, 87.0%, 95.2% and 85.7%, 59.6%, 70.1%, and 79.1%, respectively. The area under the ROC curve of IL-6 for the prognosis of AFP-negative and AFP-positive HCC patients was 0.839 and 0.666. Conclusion Serum IL-6 combined with GGT can be used as an effective indicator for predicting the efficacy and tumor activity of AFP-negative HCC patients after TACE.

Comparison of essential oil from Mentha haplocalyx and menthol used as penetration enhancers / 中国中药杂志

The aim of this paper was to investigate and compare the penetration-enhancing characteristics of menthol and essential oil from Mentha haplocalyx(M.haplocalyx oil) on the transdermal absorption of the complex traditional Chinese medicine(TCM) components. A series of TCM components were selected as model drugs based on their lipophilicity (logP value), namely osthole(OT, logP=3.85), tetramethylpyrazine(TMP, logP=2.34), ferulic acid(FA, logP=1.26), puerarin(PR, logP=-0.35) and geniposide(GP, logP=-1.01), in order to simply and characterize the TCM complex components system. Transdermal experiment in vitro was employed to investigate and compare the penetration-enhancing characteristics of menthol and M.haplocalyx oil on the transdermal absorption of these model drugs. Meanwhile, Fourier transform infrared spectroscopy(FTIR) was used to further compare the effect of menthol and M. haplocalyx oil on the molecular structure of stratum corneum(SC). The results showed that both of menthol and M.haplocalyx oil at proper concentration could promote the transdermal absorption of the selected model drugs. After application of menthol, the drug logP values gradually tended to have negative linear relationship with the logarithm of penetration enhancement ratio(ER); while after application of M.haplocalyx oil, the logP values tended to have parabolic relationship with the logarithm of ER. However, both menthol and M.haplocalyx oil exhibited higher efficiency for the drugs with relative low lgP value(ie hydrophilic drugs), with similar penetration-enhancing characteristics between these two. Infrared spectroscopy results showed that menthol and M.haplocalyx oil could affect the skin barrier functions mainly via stratum corneum lipids, with similar effect intensity, and this was consistent with the results of transdermal experiment in vitro. Thus, Menthol had similar penetration-enhancing characteristics with M.haplocalyx oil, and had same effect on the SC molecular structure. Therefore, as transdermal penetration enhancer, the menthol with single composition could be considered to replace M.haplocalyx oil with complex compositions.

Matrix formulation of chaizhi cataplasma optimized by D-optimal mixture design combined with multiple mechanical indicators and its in vitro evaluation / 中国中药杂志

To optimize the matrix formulation of Chaizhi cataplasma (CC) and investigate its release and transdermal absorption properties in vitro. The optimized matrix formulation of cataplasma containing liquid herbal extract is determined by using D-optimal mixture design, with initial bonding strength, endurance bonding strength and gel strength as the evaluating indicators. Modified Franz diffusion cells were used to study the in vitro release and transdermal absorption of geniposide in CC. The optimized matrix formulation of CC contained NP700, aluminum glycinate, tartaric acid, glycerin, PVPK90 and water (9∶0.7∶0.8∶30∶5∶30.5). Cumulative release rate of geniposide in CC was (77.02±3.73)% in 24 h. The percutaneous penetration rate of geniposide was 7.25 μg•cm⁻²•h⁻¹ and the 24 h permeated amount was (156.22±4.90) μg•cm⁻². The optimized CC prepared by the D-optimal mixture design showed a good adhesion and formability. The in vitro release of the geniposide in CC was in accordance with the first order equation, while its in vitro transdermal absorption was close to the zero order equation.

Effect of terpene penetration enhancer and its mechanisms on membrane fluidity and potential of HaCaT keratinocytes / 中国中药杂志

The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well-established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption.

Biological evaluation of Radix Isatidis based on neuraminidase activity assay / 药学学报

Radix Isatidis (Banlangen in Chinese) is a traditional Chinese medicinal (TCM) herb, and is frequently used for treating influenza. However, the current quality control method for Radix Isatidis should be developed since it has little correlation to the pharmacodynamic action. In this paper, the in vitro inhibitory action of Radix Isatidis on neuraminidase (NA) was investigated by fluorometric assay with 4-methylumbelliferyl-D-N-acetylneuraminate (FL-MU-NANA) method. Based on the method, the experimental condition was optimized and a bioassay statistic method was established according to the reaction type and the regularity of "parallel lines of qualitative effect". Then the bioassay method of Radix Isatidis was established. This study indicated that Radix Isatidis had obvious in vitro inhibitory activity on NA with IC50 = (0.90 +/- 0.20) mg x mL(-1) (herb). The correlation between logarithmic dose and reaction rate showed an "S" shape--is quite similar to Tamiflu's reaction curve, which hinted that Radix Isatidis had the same inhibitory function on NA as Tamiflu. The established bioassay method of "parallel lines of qualitative effect" had a good reproducibility (RSD = 5.78%). The results of potency determination of Radix Isatidis were reliable (reliability test: deviation from straight line P > 0.05, deviation from parallel line P > 0.05) and well regular. As a conclusion, this bioassay method is suitable to control and evaluate the quality of Radix Isatidis.

A clinical trial on the treatment of compression fracture of osteoporotic vertebral body by self-made spinal expander / 中国骨伤

<p><b>OBJECTIVE</b>To observe the effects of self-made spinal expander in treatment of compression fracture of osteoporotic vertebral body.</p><p><b>METHODS</b>Ninty-six patients were randomly divided into two groups, treatment group included 42 cases with 56 centrums, 14 males and 28 females, aged from 50 to 69 years, and control group included 54 cases with 68 centrums, 19 males and 35 females, aged from 51 to 75 years. All cases were examined by X-ray and CT. MRI was taken in 27 patients to make sure the diagnosis which was compression fracture of vertebral body due to osteoporosis. The degree of osteoporosis was judged by X-ray of L3 bone trabecula. Fifty-six centrums in treatment group were treated with self-made spinal expander and bone cement. Sixty-eight centrums in control group were treated with PVP. Compression rate and recovery rate of vertebral height, and leakage rate of bone cement were measured according to the Lee standard.</p><p><b>RESULTS</b>(1) VAS between treatment group and control group had significant statistically difference (P<0.05). (2) In treatment group, compression rate of anterior and middle vertebal height were statistical difference before and after operation (P<0.05). In control group, the compression rate of pre-and post-operative vertebal height had no significant difference (P>0.05). (3) The recovery rate of kyphosis between treatment group (71.8%) and control group (37.8%) was significant statistically difference (P<0.05). (4) There was no cement leakage in the treatment group, however the leakage rate in control group was 47%. (5) The curative effect was assessed based on the standard of WHO. In treatment group, 36 cases was completely relieved, 4 cases was partially relieved and the relief rate was 95.24%. In control group, 43 cases was completely relieved, 3 cases was partially relieved and the relief rate was 84.19%. There was no statistically significant difference between two groups (P<0.05).</p><p><b>CONCLUSION</b>The self-made spinal expander is a minimal invasive technique, which can substitute the imported balloon. This technique can alleviate pain rapidly and recover the height of vertebral body.</p>

Expression of type I inositol 1,4,5-triphosphate receptor on rat glomerular and afferent arterioles in a model of liver cirrhosis / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To study the expression of type I inositol 1,4,5-triphosphate receptor in rat glomerular and afferent arterioles in a model of liver cirrhosis and study the role of cross-membrane message transduction in the pathogenesis of hepatorenal syndrome.</p><p><b>METHODS</b>In a rat model of carbontetrachloride liver cirrhosis, the expression of type I inositol 1,4,5-triphosphate receptor (IP3R) on glomerular and afferent arterioles was measured by immunohistochemical method.</p><p><b>RESULTS</b>In the experimental group, 30 rats were used to make a model of liver cirrhosis. 11 rats survived during the experiment. The expression of type I IP3R on glomerular and afferent arterioles was 4.97+/-1.34 and 4.09+/-1.14 in the liver cirrhosis group, and it was 2.43+/-1.67 and 1.83+/-1.32 in the normal control rats. The differences between these two groups are statistically significant (t = 2.28, P = 0.0458).</p><p><b>CONCLUSION</b>Expression of type I IP3 receptor on rat glomerular and afferent arterioles in a model of liver cirrhosis indicated that the mechanism of cross-membrane message transduction plays a very important role in the pathogenesis of hepatorenal syndrome.</p>

Tumor necrosis factor-alpha enhances the effect of endothelin on renal vasoconstriction in isolated perfused rat kidney / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To explore the role of tumor necrosis factor-alpha (TNF-alpha) in the pathogenesis of hepatorenal syndrome.</p><p><b>METHODS</b>By isolated perfused kidney technique, rat kidneys were perfused at a constant flow. Changes in perfusion pressure (mmHg) were consecutively measured with multi-functional physiology recorder. After TNF-alpha or heparin treated 90 minutes, the perfusion pressure stimulated by endothelin-1 (ET-1) was detected.</p><p><b>RESULTS</b>TNF-alpha and heparin didn't modify the baseline perfusion pressure. When ET-1 was added at 2 nmol/L, the perfusion pressures increased to (47+/-9) mmHg, (97+/-36) mm Hg and (11+/-6) mm Hg in control, TNF-alpha and heparin (10mg/L) treated group, respectively, which were different among the three groups (t>or=3.811, P<0.01). No pathological damages were found in kidney tissues from all the groups after being stained with hematoxylin/eosin.</p><p><b>CONCLUSION</b>TNF-alpha plays an important role in the pathogenesis of hepatorenal syndrome by promoting renal vasoconstriction.</p>