Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats / 中国中药杂志

This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats. The rat model of arthritis was established by injecting Freund's complete adjuvant, and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) in the positive ion multiple reaction monitoring(MRM) mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmiao Pills, respectively. The differences in pharmacokinetics and tissue distribution of the four active components were compared, and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored. This study established an UPLC-MS/MS for simultaneous determination of four alkaloids, and the specificity, linearity, accuracy, precision, and stability of this method all met the requirements. Pharmacokinetics study found that as compared with normal rats, the AUC and C_(max) of phellodendrine, magnoflorine, berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills, the clearance rate CL/F was significantly increased, and the distribution and tissue/plasma concentration ratio of the four alkaloids in the liver, kidney, and joint were significantly reduced. Achyranthis Bidentatae Radix increased the AUC of phellodendrine, berberine, and palmatine, reduced the clearance rate, and significantly increased the distribution of the four alkaloids in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distribution of the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding role in meridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

Application value of psTg combined with lymph node ratio in prognosis of papillary thyroid cancer patients treated with 131I / 中华核医学与分子影像杂志

Objective:To explore the value of pre-ablation stimulated thyroglobulin (psTg) before 131I treatment combined with lymph node ratio (LNR) in predicting 131I treatment response in patients with papillary thyroid cancer (PTC). Methods:From January 2016 to December 2018, 178 PTC patients (47 males, 131 females; age (43.2±12.6) years) treated with 131I in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. According to 131I treatment response, patients were divided into excellent response (ER) group and non-ER group. The clinical data of the two groups were compared by χ2 test, independent-sample t test and Mann-Whitney U test. The cut-off values and AUCs of psTg and LNR to predict treatment response were calculated according to the ROC curve. Factors affecting 131I treatment response were analyzed by logistic multivariate regression analysis. Results:There were 118 patients (66.3%, 118/178) in ER group and 60 patients (33.7%, 60/178) in non-ER group, and there were significant differences in N stage ( χ2=11.15, P=0.004), 131I treatment dose ( χ2=12.65, P<0.001), American Thyroid Association (ATA) initial risk stratification ( χ2=15.25, P<0.001), number of metastatic lymph nodes ( χ2=22.63, P<0.001), LNR ( U=1 506.00, P<0.001) and psTg ( U=919.00, P<0.001) between the two groups. The cut-off values of psTg and LNR predicting ER were 3.97 μg/L and 0.29, with the AUC of 0.870 and 0.787 respectively. PsTg (odds ratio ( OR)=10.88, 95% CI: 4.67-25.36, P<0.001) and LNR ( OR=5.30, 95% CI: 1.85-15.23, P=0.002) were independent factors to predict 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR ( OR=9.40, 95% CI: 2.06-42.92, P=0.004) was an independent factor affecting 131I treatment response in PTC patients. Conclusions:PsTg and LNR are independent factors affecting 131I treatment response in PTC patients. When psTg≥3.97 μg/L, LNR can be used as a supplementary factor to predict 131I treatment response. The combination of psTg and LNR can better predict 131I treatment response in PTC patients.

Metabolomics analysis reveals the renal protective effect of Panax ginseng C. A. Mey in type 1 diabetic rats / 中国天然药物

The dry root and rhizome of Panax ginseng C. A. Mey has garnered much interest owing to its medicinal properties against diabetes and cardiovascular diseases. In this study, an ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS)-based metabolomics approach was used to illustrate the therapeutic mechanisms of ginseng extract on the serum and urinary metabolic profiles in streptozotocin-induced type 1 diabetes mellitus (T1DM) rats. Pharmacological and renal parameters in response to the administration of ginseng were also evaluated. In total, 16 serum endogenous metabolites and 14 urine endogenous metabolites, including pyruvic acid, indoleacetic acid, and phenylacetylglycine, were identified as potential biomarkers for diabetes. Pathway enrichment and network analysis revealed that the biomarkers modulated by ginseng were primarily involved in phenylalanine and pyruvate metabolism, as well as in arginine biosynthesis. Moreover, the levels of several renal injury-related biomarkers in T1DM rats were significantly restored following treatment with ginseng. The administration of the extract helped maintain tissue structure integrity and ameliorated renal injury. The findings suggest that the regulatory effect of ginseng extract on T1DM involves metabolic management of diabetic rats, which subsequently attenuates T1DM-induced early renal dysfunction.

Efficacy of Liuwei Nengxiao Capsule Combined With Fecal Bacteria Transplantation on Patients with Chronic Spleen Deficiency and Chronic Functional Constipation / 中国实验方剂学杂志

Objective:To explore the efficacy of Liuwei Nengxiao capsule combined with fecal bacteria transplantation on chronic functional constipation with spleen Qi deficiency. Method:A total of 129 patients with chronic functional constipation of spleen Qi deficiency treated in Affiliated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into three groups by the computer numerical table method： fecal bacteria transplantation group， Liuwei Nengxiao capsule group， and Liuwei Nengxiao capsule combined with fecal bacteria transplantation group， with 43 cases in each group. Fecal bacteria transplantation group was treated with fecal bacteria， Liuwei Nengxiao capsule group was treated with Liuwei Nengxiao capsule， and Liuwei Nengxiao capsule combined with fecal bacteria transplanted group was treated with Liuwei Nengxiao capsule combined with fecal bacteria. The efficacy of the 3 groups was compared. Result:After treatment， the frequency and amplitude of intestinal electricity increased significantly in three parts， with statistically significant differences from before treatment （P<0.05）. After treatment， the frequency and amplitude of the transverse colon， sigmoid colon， and descending colon of patients in Liuwei Nengxiao capsule combined with faecal transplantation group were higher than those in faecal transplantation group and Liuwei Nengxiao capsule group （P<0.05）. After treatment， substance P （SP） and motilin （MTL） of Liuwei Nengxiao capsule combined with faecal transplantation group were higher than those of faecal transplantation group and Liuwei Nengxiao capsule group， while nitric oxide （NO） and vasoactive intestinal peptide （VIP） were lower than those of faecal transplantation group and Liuwei Nengxiao capsule group （P<0.05）. The number of bifidobacteria and lactobacillus after treatment was higher in three groups than before treatment （P<0.05）. The numbers of yeast and enterobacteria were lower than before treatment （P<0.05）. After treatment， the number of bifidobacteria and lactobacillus in Liuwei Nengxiao capsule combined with faecal transplantation group was higher than that in faecal transplantation group and Liuwei Nengxiao capsule group， whereas the numbers of yeast， and enterobacteria were all lower than those in bacterial transplantation group and Liuwei Nengxiao capsule group （P<0.05）. After treatment， the BSFS scores of three groups were higher than before the treatment， while Wexner continence grading scale （Wexner） constipation score and patient assessment of constipation quality of life questionnaire （PAC-QOL） score were lower than before treatment （P<0.05）. Bristol stool form scale （BSFS） score of Liuwei Nengxiao capsule combined with fecal bacteria transplantation group was higher than that of fecal bacteria transplantation group and Liuwei Nengxiao capsule group. Wexner constipation score and PAC-QOL score were lower than those of fecal bacteria transplantation group and Liuwei Nengxiao capsule group （P<0.05）. Conclusion:Fecal bacteria transplantation combined with Liuwei Nengxiao capsule can effectively promote the recovery of intestinal electrical function， improve the intestinal flora balance， reduce the intestinal oxidative stress response， and promote the disappearance of patients' symptoms in the treatment of elderly chronic functional constipation， and thus is worth further promotion in clinic application.

An extract of Perilla stem inhibits Src homology phosphatase-1 (SHP)-1 and influences insulin signaling.

Protein tyrosine phosphatases (PTPs) are enzymes that catalyze protein tyrosine dephosphorylation of which Src homology phosphatase-1 (SHP-1) is one of the best-validated, a widely distributed intracellular tyrosine phosphatase that contains two SH2 domains. Down regulation of SHP-1 tyrosine phosphatases was significantly increased sensitivity to insulin in insulin signaling pathway. Through in vitro enzymatic reaction kinetics experiment, we found that the extract of Perilla stem was a potential inhibitor to δSHP-1, the catalytic domain of SHP-1 protein tyrosine phosphatase, and its IC(50) was 4ug/ml, and was more sensitive towards SHP-1than other PTPs, which indicated that SHP-1 might be a target of the extract of Perilla stem. It can strengthened the level of tyrosine phosphorylation of insulin receptor (IR) and extracellular signal-regulated protein kinase (ERK) in HepG2 cells, and then activated the insulin signaling pathway through inhibiting the protein phosphorylation of SHP-1. These results demonstrated that the extract of Perilla stem could play an important role for diabetes treatment through inhibiting the level of SHP-1 in insulin signaling pathway.

Discussing of influence mechanism of Chinese herbal monomer on physical stability of cream / 中国中药杂志

This study left flavonoids and alkaloids Chinese herbal monomer with common parent nucleus as cream base carriages drug respectively, cream base were prepared with stable span 60-tween 80 emulsification system. The near-infrared stability analysis technology was performed to quantitatively characterize the physical stability of cream. Base on the theory of gel network structure, theory of emulsification, theory of solubility parameter and theory of double layer, the influence mechanism of Chinese herbal monomer on physical stability of cream was discussed. The results showed that tetrahydropalmatine, matrine and naringenin had similar solubility parameter value with cream base material, creams prepared with those Chinese herbal monomer have higher Zeta potential value and stronger physical stability, and that those creams had similar microstructure information with cream base. However, a larger solubility parameter difference exists between baicalin, baicalein, berberine, palmatine and cream base material. Creams prepared with those Chinese herbal monomers had lower Zeta potential value and poorer physical stability, and that those creams had great different microstructure information with cream base.

Effect of ethanol extract of Rhodiola rosea on the early nephropathy in type 2 diabetic rats / 华中科技大学学报（医学）（英德文版）

This study aimed to investigate the therapeutical effects of Rhodiola rosea extract on rats with type 2 diabetic nephropathy (DN). The rat type 2 DN model was established by high fat and high calorie feeding and intravenous injection of streptozocin (STZ). Wistar rats were randomly divided into normal group, control group, low dose Rhodiola rosea group, high dose Rhodiola rosea group and Captopril group. Oral glucose tolerance test (OGTT) was performed to determine the impairment of glucose tolerance in the established animal model. A series of parameters including fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), creatinine clearance rate (Ccr), 24-h urinary albumin (UA), the ratio of kidney mass/body weight (renal index) and glomerular area were examined after 8 weeks. Moreover, the expression of transforming growth factor (TGF)-β1 in renal tissues was detected by using immunohistochemisty. At the end of the eighth week, FBG, TC, TG, Ccr, 24-h urinary albumin, the ratio of kidney mass/body weight and glomerular area were significantly reduced in Rhodiola rosea extract treatment groups as compared with those in control group. TGF-β1 expression in renal tissues of Rhodiola rosea extract treatment groups was also significantly decreased as compared with that of control group. These results indicate that Rhodiola rosea extract may have a protective effect on early nephropathy in diabetic rats, which might be related to the decrease of the renal expression of TGF-β1.

Study on solubility of Chinese herbal compound by solubility parameter / 中国中药杂志

<p><b>OBJECTIVE</b>To demonstrate the solubility of Chinese herbal compound with solubility parameters.</p><p><b>METHOD</b>The solubility parameters of Liangfu effective components and Liangfu compound were determined by inverse gas chromatograph (IGC) and group contribution. Hansen ball was plotting by HSPiP, which could be used to investigate the solubility of Liangfu effective components and Liangfu compound in different solvents. And the results were verified by approximate solubility.</p><p><b>RESULT</b>Liangfu effective components and Liangfu compound could be dissolved in chloroform, ethyl acetate, acetone, octanol and ether, and were slightly soluble in glycerol, methanol, ethanol and propanediol, but could not be dissolved in water. They were all liposoluble, and the results were the same as the test results of the approximate solubility.</p><p><b>CONCLUSION</b>The solubility of Chinese herbal compound can be expressed by solubility parameters, and it is accurate, convenient and visual.</p>

Dermatopharmacokinetic studies of liangfu cream in mice skin / 中国中药杂志

<p><b>OBJECTIVE</b>To study the relationship between deposition content and time of the active ingredients in rat skin, and investigate the dermatopharmacokinetics of Liangfu Cream.</p><p><b>METHOD</b>The contents of paeonol, dictamnine, fraxinellone and glycyrrhetinic acid in rat skin were determined by HPLC. The dermatopharmacokinetics parameters were calculated by DAS software.</p><p><b>RESULT</b>The dermatopharmacokinetics of paeonol and glycyrrhetinic acid were two compartment model, while that of dictamnine and fraxinellone were one compartment model: T(1/2Ka) of four active ingredients were 0.307, 0.112, 0.146, 0.216 h, respectively; T(lag) of them were 0.006, 0.123, 0.136, 0.109 h, respectively; all the Tmax of them was 0.5 h; the Cmax, were 40.163, 1.607, 6.725, 100.553 microg x cm(-3), respectively; the t(1/2beta), were 14.719, 1.262, 0.838, 234.807 h, respectively; the AUC(0-infinity), were 16.987, 2.713, 9.345, 697.000 microg x cm(-3) x h(-1), respectively; and the MRT(0-infinity) were 3.662, 1.67, 1.585, 10.897, respectively.</p><p><b>CONCLUSION</b>The skin pharmacokinetics characteristic of four ingredients in Liangfu cream is lined with the cataplasm long time.</p>

Effects of penetration enhancers on in vitro percutaneous absorption and amount retained in skin of paeonol, dictamnine, fraxinellone and glycyrrhetinic acid in Liangfu cream / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of different penetration enhancers on the in vitro percutaneous absorption and amount retained in skin of active ingredients in Liangfu cream and to screen out the effective accelerator.</p><p><b>METHOD</b>Using improved Franz-type difusion cell and excised small mouse skin in vitro as transdermal barrier, the amount retained in skin and kinetics parameters of active ingredients such as cumulative permeation quantity, permeation rate and permeation lagged time were determined by HPLC. The enhancement ability of four different enhancers such as azone, oleic acid, transcutol P and isopropyl myristate were investigated.</p><p><b>RESULT</b>3% IPM enhanced the cumulative permeation quantity better than other penetration enhancers. The enhancive permeation multiples of paeonol, dictamnine, fraxinellone and glycyrrhetinic acid were 1.52, 1.24, 1.73 and 3.21 times (P < 0.05). The enhancive amount retained in skin multiple of glycyrrhetinic acid was 1.96 times (P < 0.05), but for other components there were no significant impacts.</p><p><b>CONCLUSION</b>The effects of penetration enhancers on the in vitro percutaneous absorption and amount retained in skin of components in Liangfu cream are different. 3% IPM which can enhance the cumulative permeation quantity of four components and amount retained in skin of glycyrrhetinic acid is the most suitable penetration enhancer for Liangfu cream.</p>

Studies on characteristics of absorption and separation of traditional Chinese medicine compound prescription by macroporous resin / 中国中药杂志

<p><b>OBJECTIVE</b>Study the characteristics of absorption and separation of traditional Chinese medicine compound prescription using macroporous resin.</p><p><b>METHOD</b>Study the techniquecs and characteristics of absorption and separation of a sample by macroporous resin, which is composed of coptis root, rhubarb and common anemarrhena rhizome, containing alkaloid, anthraquinone and saponin.</p><p><b>RESULT</b>It is proved by qualitative and quantitative researches studies that after absorbed and separated by optimized technics process, most prime effective components or section fractions in traditional Chinese medicine compound prescription can be reserved maintained.</p><p><b>CONCLUSION</b>If the techniquecs of separation is properly designed, the same kind of macropore resin can absorbd and separate various effective components or section in traditional Chinese medicine compound prescription which have with different chemical structures efficiently.</p>

The preparation of the polylacticacid nanoparticles of cucurbitacin and their drug loading / 中国中药杂志

This paper introduced an experimental study of the preparation of polylacticacid (PLA) nanoparticles of cucurbitacin (CuC) using a precipitation method. The residual acetone, ratio of CuC PLA precipitates, and the relationships between the ratios of two precipitates and drug incorporation rates were measured. It appeared that the nanoparticles with 60% of PLA incorporated with 5.5% of CuC were formed when acetone was injected into the aqueous phase. As the acetone gradually evaporated, drug incorporation/encapsulation continued, with most of CuC (about 70%) formed new crystalline cores and suspended in the form of microcrystals in the medium, resulting a suspension containing both nanoparticles and microcrystals. We also concluded that this system may not necessarily be suitable for all lipophilic drugs to be prepared to PLA nanoparticles with good incorporation rate. The drug incorporation depended on the interactions among drug, PLA, and organic solvents, in addition to the solubility of the drug.