Investigation of the pharmacokinetics of paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments by the skin-blood synchronous microdialysis coupled with LC/MS is reported in this study. The microdialysis systems were established by linear probes and concentric circles probes. In vivo recovery of paeonol in skin is (69.7 +/- 4.8) % and in blood is (51.6 +/- 7.2)%. The paeonol microemulsion, microemulsion-based gels and marketed paeonol ointments were administered to rats. PBS (pH 7.4) served as perfused solution. The perfusion rate was 5 microL x mL(-1) and the microdialysis samples were collected every 20 min intervals. The paeonol concentration in perfused solution was determined by LC/MS. The results showed that paeonol microemulsion and microemulsion-based gels significantly raised the drug concentrations in skin more than that of paeonol ointments. The paeonol microemulsion-based gels has similar bioavailability as the paeonol ointments in blood, but its blood drug concentrations were steadier. The paeonol microemulsion-based gels may be developed into a new preparation for dermis eczema. The skin-blood synchronous microdialysis technique proved to be a new method for the pharmacokinetics study of transdermal delivery systems.

Objective To study the benzofuran compounds from roots and rhizomes of Ligularia caloxantha, which is a folk medicine used in the Naxi Nationality in Yunnan Province. Methods Compounds were separated and purified by silica gel and Sephadex LH-20 column chromatography. Their structures were elucidated by physicochemical properties and spectral analysis. Results Eighit compounds are isolated from ethanolic extracts of the roots and rhizomes. They were identified as euparin (Ⅰ), 6-methoxy-euparin (Ⅱ), 4, 5-dimethoxy-2-hydroxybenzaldehyde (Ⅲ), 2-acetyl-5, 6-dimethyoxybenzofuran (Ⅳ), 4-hydroxyacetophenone (Ⅴ), 2-isopropenyl-5, 6-dimethoxy-2, 3-hydrocumaran (Ⅵ), 8?-hydroxy-7(11)-eremophilen-12, 8?-olide (Ⅶ), lupeol (Ⅷ). Conclusion All the eight compounds were obtained from L. caloxantha for the first time as benzofurans. Compounds Ⅰ and Ⅱ are two major ones with insecticide and insect food refusal-induced activities. That is the relative reason of L. caloxantha used for folk anti-insect.

Metabolic profile of bile acids was used to evaluate hepatotoxicity of mice caused by ethanol extraction of Dioscorea bulbifera L. (ethanol extraction, ET) and diosbulbin B (DB), separately. Ultra-performance liquid chromatography coupled with quadrupole mass spectrometry (UPLC-MS) was applied to determine the contents of all kinds of endogenous bile acids including free bile acids, taurine conjugates and glycine conjugates. Obvious liver injuries could be observed in mice after administrated with ET and DB. Based on the analysis using principle components analysis (PCA), toxic groups could be distinguished from their control groups, which suggested that the variance of the contents of bile acids could evaluate hepatotoxicity caused by ET and DB. Meanwhile, ET and DB toxic groups were classified in the same trends comparing to control groups in the loading plot, and difference between the two toxic groups could also be observed. DB proved to be one of the toxic components in Dioscorea bulbifera L. Bile acids of tauroursodeoxycholic acid (TUDCA), taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), taurodeoxycholic acid (TDCA), cholic acid (CA) and others proved to be important corresponds to ET and DB induced liver injury according to analysis of partial least square-discriminant analysis (PLS-DA) and the statistical analysis showed that there were significant differences between the control groups and toxic groups (P < 0.01). Furthermore, good correlation could be revealed between the foregoing bile acids and ALT, AST. It indicated that taurine conjugated bile acids as TUDCA, TCDCA, TCA and TDCA along with CA could be considered as sensitive biomarkers of ET and DB induced liver injury. This work can provide the base for the further research on the evaluation and mechanism of hepatotoxicity caused by Dioscorea bulbifera L.

OBJECTIVETo investigate the alkaloids from Senecio scandens.

METHODCompounds were isolated with silica gel and Sephadex LH-20 column chromatography and their structures were determined by spectral analysis and chemical evidence. The hepatic cytotoxicity of isolated compounds was tested by MTT method in vitro.

RESULTSix alkaloids were obtained and identified as adonifoline (1), 7-angeloylturneforcidine (2), hordenine (3), 1, 3, 6, 6-tetramethyl-5, 6, 7, 8-tetrahydro-isoquinolin-8-one (4), 4-(pyrrolidin-2-one) -phenyl acetic acid (5), (4-pyrrolidinophenyl) acetic acid (6).

CONCLUSIONCompound 6 is a new natural product, compounds 3, 4 were obtained from the genus Senecio for the first time, compounds 2, 5 were obtained from this plant for the first time. Compound 1 showed significant growth inhibitory effect against hepatocyte at 100 micromol x L(-1).

Acetic Acid ; chemistry ; Alkaloids ; chemistry ; isolation & purification ; pharmacology ; Animals ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chromatography, High Pressure Liquid ; methods ; Dextrans ; chemistry ; Hepatocytes ; Lactones ; isolation & purification ; metabolism ; pharmacology ; Mice ; Mice, Inbred ICR ; Pyrrolizidine Alkaloids ; isolation & purification ; metabolism ; pharmacology ; Senecio ; chemistry ; Silica Gel ; Tyramine ; analogs & derivatives ; isolation & purification ; pharmacology

OBJECTIVETo develop a RP-HPLC method for quantitative determination of norisoboldine in Radix Linderae and to provide valuable data for quality control of Radix Linderae.

METHODThe separation was performed on a Phenomenex Gemini C18 column (4.6 mm x 250 mm, 5 microm) at 25 degrees C using a gradient elution of mobile phase A (0.5% formic acid, adjusted pH 2.25 with triethylamine) and mobile phase B (acetonitrile). The detection wavelength was 280 nm.

RESULTThe calibration curve showed a good linearity (r = 0.999 9) within test ranges of 0.015-1.509 microg. The average recovery was 99.58% with RSD 1.4%.

CONCLUSIONThe developed method is simple, accurate and reliable with good repeatability. It is suitable for quality evaluation of Radix Linderae.

Alkaloids ; analysis ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; analysis ; Lindera ; chemistry

To improve the quality control specification of Perillae Fructus, the identification methods and assay were developed. Rosmarinic acid, luteolin and apigenin in the sample were identified by TLC. The content of rosmarinic acid was determined by HPLC. The linear calibration curve of rosmarinic acid was obtained in the ranges of 19.4-194.2 g x L(-1) (R2 = 0.9999). The arerage coveriy (n=9) for the assay was 99.8% (RSD 3.6%). The established methods are accuracy, sensitivity and reproducible, and can be used for the quality control of Perillae Fructus.
Apigenin ; analysis ; Chromatography, High Pressure Liquid ; Chromatography, Thin Layer ; Cinnamates ; analysis ; Depsides ; analysis ; Luteolin ; analysis ; Perilla frutescens ; chemistry ; Reproducibility of Results

Bile acids(BAs)are synthesized by the liver from cholesterol through several complementary pathways and aberrant cholesterol metabolism plays pivotal roles in the pathogeneses of cholesterol gallbladder polyps(CGP)and cholesterol gallstones(CGS).To date,there is neither systematic study on BAs profile of CGP or CGS,nor the relationship between them.To explore the metabolomics profile of plasma BAs in healthy volunteers,CGP and CGS patients,an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)method was developed and validated for simultaneous determination of 42 free and conjugated BAs in human plasma.The developed method was sensitive and reproducible to be applied for the quantification of BAs in the investigation of plasma samples.The results show that,compared to healthy volunteers,CGP and CGS were both characterized by the significant decrease in plasma BAs pool size,furthermore CGP and CGS shared aberrant BAs metabolic characteristics.Cheno-deoxycholic acid,glycochenodeoxycholic acid,λ-muricholic acid,deoxycholic acid,and 7-ketolithocholic acid were shared potential markers of these two cholesterol gallbladder diseases.Subsequent analysis showed that clinical characteristics including cysteine,ornithine and body mass index might be closely related to metabolisms of certain BA modules.This work provides metabolomic information for the study of gallbladder diseases and analytical methodologies for clinical target analysis and efficacy evaluation related to BAs in medical institutions.

Diabetic nephropathy （DN） is one of the serious and common microvascular complications of diabetes mellitus （DM） and the main cause of end-stage renal disease （ESRD）. Endoplasmic reticulum stress （ERS） is a common stress defense mechanism in eukaryotic cells. In the ERS state， cells activate the unfolded protein response （UPR） to enhance the folding of unfolded proteins and the degradation of misfolded proteins， so as to restore the normal physiological function of the endoplasmic reticulum and avoid cell damage. However， excessive or chronic persistent ERS can induce apoptosis， inflammation， oxidative stress and other pathways to eventually cause cell damage. In recent years， a large number of studies have confirmed that ERS is closely associated with the occurrence and development of DN. In the case of DN， ERS is involved in the damage or protection of podocytes， glomerular mesangial cells， renal tubular epithelial cells， and glomerular endothelial cells. The regulation of ERS has become one of the hotspots in the prevention and treatment of DN and has received extensive attention in the field of traditional Chinese medicine. This paper systematically expounds the role of ERS in the occurrence and development of DN and summarizes the ERS-targeted regulation of DN by traditional Chinese medicine， with a view to providing certain research ideas for the prevention and control of DN with traditional Chinese medicine.

Endothelial cells in the inner wall of blood vessels respond to physical and chemical signals of the body by regulating vascular homeostasis， vascular tension， cell adhesion， cell proliferation， coagulation resistance and inflammatory factors， to maintain the stability of blood vessels. Angiogenesis is the key condition for tumor evolution， and the pathological mode of tumor angiogenesis provides nutrients and oxygen for tumor growth and promotes its proliferation. In recent years， endothelial cells have participated in tumor vascular infiltration and driven angiogenesis， which is considered to be the point link in tumor metastasis. By regulating metabolic remodeling， vascular endothelial cells provide the materials and energy needed in the process of tumor angiogenesis， and their abnormal metabolic characteristics facilitate their adaption to the changes of tumor microenvironment， which is often regarded as an important basis for tumor angiogenesis. The ''Yin fire'' theory in traditional Chinese medicine， originating from Huangdi's Internal Classic （Huang Di Nei Jing）， originally meant Yin deficiency generates internal heat， and belonged to the category of fire of internal injury. After the deduction and changes by physicians over the ages， the pathogenesis of ''spleen and stomach Qi deficiency-Yin fire rising-Qi and fire disharmony'' was gradually formed. The pathogenesis of metabolic remodeling of endothelial cells manifests the pathological characterization of Yin fire in an objective way， which is consistent with the disease state of uncontrolled and hyperactive tumor neovascularization. Changes in spleen and stomach Qi deficiency as well as imbalance of Qi movement lead to the failure of water and food in distribution， and thus metabolic disorders occur. Long term retention turns in phlegm and blood stasis， which combat with blood vessels， and result in abnormal local environment （formation of tumor microenvironment）， adverse pulse channel （imbalance of endothelial cell metabolism）， and tumor neovascularization. Under the guidance of ''Yin fire'' syndrome elements and by focusing on the correlation between Qi and fire， prescriptions are made based on the treatment method of ''strengthening the body and regulating Qi'' to regulate the metabolic function of endothelial cells， thus achieving a relatively balanced state of the body and inhibiting tumor angiogenesis. As a result， this study， centering on the metabolic remodeling of endothelial cells and ''Yin fire'' theory， elucidated the academic ideas， with the purpose of providing some theoretical support for the intervention of tumor vascularization by Chinese medicine.

Diabetic cardiomyopathy （DCM） is one of the complications of diabetes. It refers to a specific type of idiopathic cardiomyopathy that occurs in individuals with diabetes， distinct from other cardiovascular diseases such as coronary heart disease， valvular heart disease， or congenital heart disease. It has also been identified as one of the leading causes of death in diabetic patients for many years. Research has shown that the pathogenesis of DCM is closely associated with insulin resistance， activation of various inflammatory responses， increased oxidative stress， impaired coronary microcirculation， and accumulation of advanced glycation end products （AGEs）. Among various inflammatory responses， the activation of the NOD-like receptor protein 3 （NLRP3） inflammasome can induce the secretion of a large amount of pro-inflammatory cytokines through the cascade reaction of inflammation， subsequently mediating cellular pyroptosis and promoting myocardial damage. Currently， extensive experimental studies on traditional Chinese medicine （TCM） have been conducted in China and abroad based on the significant role of the NLRP3 inflammasome in the prevention and treatment of DCM. These studies have demonstrated that Chinese medicinal extracts， such as Astragalus polysaccharide and ginsenoside Rb₁， single drugs like Coriolus and Cordyceps， and Chinese medicinal formulas like Didangtang and modified Taohe Chengqitang， as well as acupuncture and TCM exercise therapy， can regulate the relevant pathways of the NLRP3 inflammasome to inhibit its assembly or activation， reduce inflammatory responses， inhibit myocardial remodeling in DCM， and improve cardiac function. This article reviewed the relationship between the NLRP3 inflammasome and DCM， as well as the research progress on TCM in exerting anti-inflammatory effects in this field， aiming to provide new insights for the development of therapeutic approaches for DCM.