Distinctive quality control method for solid-state fermented Isaria cicadae from strain Ic-17-7 and application in a rat model of type 2 diabetes / 中国天然药物

This work was aimed to establish a quality control method for evaluating the effects on glucose and lipids of the fruiting body of Isaria cicadae Miquel from strain Ic-17-7 (Ic-17-7fb) using a rat model of type 2 diabetes (T2DM). Random amplified polymorphic DNA, sequence-characterized amplified region, and high-performance liquid chromatography (HPLC) were used for the quality control of Ic-17-7fb. The pharmacological effects on streptozocin (STZ)-induced high fat diet (HFD)-fed Albino Wistar rats were evaluated. The rats underwent the following treatments: control, metformin, Ic-17-7fb (0.166 and 0.5 g·kg

Panax notoginseng saponins prevent colitis-associated colorectal cancer development: the role of gut microbiota / 中国天然药物

Gut microbiota dysbiosis is a risk factor for colorectal cancer (CRC) in inflammatory bowel disease (IBD). In this study, the effects of Panax notoginseng saponins (PNS) on colitis-associated CRC progression were evaluated on an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model. In vivo, PNS significantly relieved AOM/DSS-induced colon tumorigenesis and development by reducing the disease activity index (DAI) scores and colon tumor load. The 16S rRNA data of fecal samples showed that the microbiome community was obviously destructed, while PNS could recover the richness and diversity of gut microbiota. Especially, PNS could increase the abundance of Akkermansia spp. which was significantly decreased in model group and negatively correlated with the progression of CRC. Moreover, ginsenoside compound K (GC-K) was evaluated on the effects of human CRC cells, which was the main bio-transformed metabolite of PNS by gut microbiota. Our data showed that PNS played important role in the prevention of the progression of CRC, due to their regulation on the microbiome balance and microbial bio-converted product with anti-CRC activity.

Quantification of Panax notoginseng saponins metabolites in rat plasma with in vivo gut microbiota-mediated biotransformation by HPLC-MS/MS / 中国天然药物

Panax notoginseng saponins (PNS) are the major components of Panax notoginseng, with multiple pharmacological activities but poor oral bioavailability. PNS could be metabolized by gut microbiota in vitro, while the exact role of gut microbiota of PNS metabolism in vivo remains poorly understood. In this study, pseudo germ-free rat models were constructed by using broad-spectrum antibiotics to validate the gut microbiota-mediated transformation of PNS in vivo. Moreover, a high performance liquid chromatography-electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS) was developed for quantitative analysis of four metabolites of PNS, including ginsenoside F1 (GF1), ginsenoside Rh2 (GRh2), ginsenoside compound K (GCK) and protopanaxatriol (PPT). The results showed that the four metabolites could be detected in the control rat plasma, while they could not be determined in pseudo germ-free rat plasma. The results implied that PNS could not be biotransformed effectively when gut microbiota was disrupted. In conclusion, gut microbiota plays an important role in biotransformation of PNS into metabolites in vivo.

Application of expression quantitative trait loci analysis in pharmacogenomics / 药学学报

In the era of genome-wide association study (GWAS), a large number of drug response-related loci have been identified in the non-coding sequences. The interpretation of these loci in mechanism is concerned with the effects on the mRNA expression level of these genes. Expression quantitative trait loci (eQTL) studies indicate the relationship of genome variants and the level of mRNA. Its elucidation of the relationship between genetic variation and gene expression, gene interaction and gene regulatory network provides an efficacious mean for pharmacogenomics. The effects of gene polymorphism on drug responses have been unraveled thoroughly in studies which combined pharmacogenomics with eQTL and GWAS.

Phenolic constituents from Oplopanax horridus / 中国中药杂志

The chemical constituents were isolated and purified by various chromatographic techniques indluding silica gel, reverse phase silica gel, sephadex LH-20 and pre-HPLC and identified by their physicochemical properties and spectral data. Sixteen phenolic compounds had been isolated and n-butanol extracts which were fractionated from the ethanol extract of Oplopanax horridus roots bark. Their structures were identified as below, including 7 phenylpropanoid compounds, ferulic acid (1), 3-acetylcaffeic acid (2), caffeic acid (3), homovanillyl alcohol 4-O-beta-D-glucopyranoside (4), 3-hydroxyphenethyl alcohol 4-O-beta-D-glucopyranoside (5), 3, 5-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (6), and 3-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (7). Three coumarins, scopoletin (8), esculetin (9) and 3'-angeloyl-4'-acetyl-cis-knellactone (10). And 6 lignan compounds, (+)-isolaricires-inol-9'-O-beta-D-glucopyranoside (11), 3, 3'-dimethoxy-4, 9, 9'-trihydroxy-4', 7-epoxy-5', 8-lignan-4, 9-bis-O-beta-D-glucopyranoside (12), (+)-5, 5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (13), (-)-5,5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (14), (-)-pinoresinol 4'-O-beta-D-glucopyranoside (15), and (+)-5, 5'-dimethoxylariciresinol 9'-O-beta-D-glucopyranoside (16). All compounds were isolated and identified for the first time from this plant All the constituents except compounds 4, 6, 12 and 13 were obtained for the first time from the genus Oplopanax.

A strategy for detecting absorbed bioactive compounds for quality control in the water extract of rhubarb by ultra performance liquid chromatography with photodiode array detector / 中国结合医学杂志

<p><b>OBJECTIVE</b>To detect absorbed bioactive compounds of the water extract whose pharmacodynamic effect was craniocerebral protection for quality control assessment.</p><p><b>METHODS</b>Anthraquinones in water extract of rhubarb (WER), in cerebrospinal fluid (CSF) of patients with traumatic brain injury (TBI) and in ipsilateral cortex of TBI rats following oral WER were respectively explored by ultra performance liquid chromatography with photodiode array detector (UPLC-PDA) method developed in the present study. The effects of anthraquinones absorbed into injured cortex on superoxidase dismutase (SOD) activity in TBI rats were detected. The antioxidative anthraquinones absorbed into target organ were evaluated for quality control of WER.</p><p><b>RESULTS</b>Anthraquinones in WER were aloe-emodin, rhein, emodin, chrysophanol, and physcion. Only the last anthraquinone was found in CSF and in ipsilateral cortex under this chromatographic condition. Physcion increased SOD activity in TBI rats significantly.</p><p><b>CONCLUSIONS</b>Physcion was the main active compound of rhubarb against craniocerebral injury via antioxidant pathway. According to our strategy, the exploration of physcion suggested the possibility of a novel quality control of WER in treating TBI injury.</p>

Translational approach for pharmacogenomics and personalized medicine / 药学学报

Pharmacogenetics and pharmacogenomics are promising fields that will enable personalized therapy. However, one of the most important issues to be conquered in the practice of personalized medicine is the translation of scientific discoveries into better therapeutic outcomes. The international pharmacogenetic and pharmacogenomic approaches made in the field of personalized medicine and drug discovery are summarized in this review.

Theoretical and experimental studies on solubility parameters of multiple components for traditional Chinese materia medica with HPLC / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the theories and methods to determine solubility parameters of multiple components for the traditional Chinese material medica (TCMM) with HPLC.</p><p><b>METHOD</b>The mathematical expresses to determin the solubility parameters were established according to chromatographic and Hildebrand-Scatchard theories, The HPLC experiments were carried out at 40 degrees C on an Alltech Apollo C18 column (4.6 mm x 250 mm, 5 microm) eluted with acetone and water in gradient mode. The flow rate was 1.0 mL min(-1), and the detection wavelength was 254 nm. The injection volume was 1 0 microL.</p><p><b>RESULT</b>The mathematical expresses between the retention time and the solubility parameters were established and used to determin caffeine solubility parameter as 28.31 J(1/2) cm(-3/2) in accordance with 28.84 J(1/2) cm(-3/2) reported by literature, and those of aloe-emodin, rhein, emodin, physcione as 39.70 J(1/2) cm(-3/2), 39.08 J(1/2) cm(-3/2), 38.37 J(1/2) cm(-3/2), 36.42 J(1/2) cm(-3/2) respectively.</p><p><b>CONCLUSION</b>The retention time of HPLC can be used to determine the solubility parameters of multiple componets. The established method is useful for the compatibility rule study of traditional Chinese medicine.</p>

Polymorphism of vitamin D receptor Fok I and colorectal cancer risk in Chinese / 中南大学学报(医学版)

OBJECTIVE@#To explore the frequency of vitamin D receptor (VDR) Fok I polymorphism in healthy Chinese and colorectal tumor patients,and to study the correlation between VDR Fok I polymorphism and the pathogenesis of colorectal tumor.@*METHODS@#After the preparation of gDNA by common method,VDR genotypes were determined by Fok I restriction endonuclease digestion of PCR-amplified DNA in 69 colorectal cancer patients and 218 healthy persons.@*RESULTS@#The F allele frequencies of VDR in healthy persons and in colorectal tumors patients were 61.5% and 49.3%, respectively, with statistical difference (P< 0.05). The genotype frequencies of FF, Ff and ff in healthy persons and in colorectal tumors patient were (39.5%,44%,16.5%) and (29.1%,40.5%,30.4%), respectively,with statistical differences (P< 0.05). The odds ratio of ff and Ff genotypes were 2.51 (95% confidence interval,1.21 approximately 5.18) and 2.00 (95% confidence intervals,1.01approximately 3.96), respectively (P< 0.01).@*CONCLUSION@#Fok I polymorphism is a common single nucleotide polymorphism (SNP) of VDR in Chinese population,and the VDR Fok I polymorphism may lower the risk of colorectal tumor.

Advance in cytochrome P450 1A2 / 中南大学学报(医学版)

CYP1A2 is an important cytochrome P450 enzymes, which is involved in metabolism of many clinical drugs and activation of some precarcinogens. CYP1A2 activity can be influenced by various factors including genetic polymorphism, drugs, food and so on, in which the CYP1A2 genetic polymorphism is the basis of difference on the activity and induction of CYP1A2. Therefore,the genotyping of CYP1A2 plays an important part in individualization of therapy.

A new qualitative and quantitative analytical method of chromatographic fingerprints: total quantum statistical moment / 药学学报

A new qualitative and quantitative analytical method of the chromatographic fingerprints: the Total Quantum Statistical Moment (TQSM) has been eluciated and established according to statistical moment principle. The study was carried out with model drugs as the alcohol extracted liquid for Radix et Rhizoma Rhei (AELRR) by HPLC under the chromatographic conditions that the column was C18, 4.6 mm x 250 mm, 5 microm; the detection of wavelengths was set at 254 nm; a solution of acetonitrile: 1% acetic acid water (from 0:100 to 100:0) was carried with gradient elution as the mobile phase; the ratio of flow was 1 mL min(-1); the temperature was 40 degrees C. The coefficients were dealt with Excel document. It has been established the expressions that consists of four main parameters: 1) total quantum zero moment as AUC(T), area under curve; 2) total quantum respondent ratio as AUCPW(T), area under curve per weight; 3) total quantum center moment as MCRT(T), mean chromatographic retention time of total quantum, expressed by lambda(T); 4) total quantum variance as VCRT(T), variance of mean chromatographic retention time of total quantum, expressed by sigma2(T), by which we have obtained. The TQSM's parameters of the AELRR, such as AUC(T) as 3.273 x 10(8) microV s, AUCPW(T) as 2.286 x 10(6) microV s mg (-1), MCRT(T) as 33.50 min, VCRT(T) as 484.4 min2, and total quantum concentration as 143.2 mg mL(-1). The total quantum statistic moment can be characterized the curve of chromatographic fingerprints with expressive parameters above, also used to quantitative analyses by AUC(T), to qualitative analyses by AUCPW(T), MCR(T), and VCRT(T).

Effects of the flavonoids on cytochrome P-450 CYP1, 2E1, 3A4 and 19 / 药学学报

Flavonoids are present in fruits, vegetables and beverages derived from plants, and in many dietary supplements or herbal remedies. A number of naturally occurring flavonoids have been shown to modulate the CYP450 system, including the induction or inhibition of these enzymes. This review focuses on the flavonoid effects on cytochrome P450 (CYP) enzyme CYP1, 2E1, 3A4 and 19. Flavonoids alter CYPs by various mechanisms, including the stimulation of gene expression via specific receptors and/or CYP protein, or mRNA stabilization and so on. But in vivo and in vitro, the effects of flavonoids are not always coincident as a result of concentrations of flavonoids, genetic and environmental factors. As well, flavonoids may interact with drugs through the induction or inhibition of their metabolism. Much attention should be paid to the metabolism interaction of the flavonoids when coadministered with other drugs.

Mechanism of mono-hydroxylation of daidzein in human liver microsomes / 药学学报

<p><b>AIM</b>To identify the cytochrome P450 (CYP) isoform (s) involved in daidzein mono-hydroxylated metabolites using human liver microsomes.</p><p><b>METHODS</b>Kinetic analysis of the rates of formation of mono-hydroxylated metabolites of daidzein, including 7,8,4'-trihydroxyisoflavone (7,8,4'-THI), 7,3',4'-trihydroxyisoflavone (7,3',4'-THI) and 6,7,4'-trihydroxyisoflavone (6,7,4'-THI), was performed using human liver microsomes (HLM) and recombinant enzymes at substrate concentrations ranging from 0.5 to 400 micromol x L(-1). Nine selective inhibitors or substrate probes specific for different CYP isoforms were applied for screening the isoform(s) responsible for mono-hydroxylated metabolism of daidzein.</p><p><b>RESULTS</b>Michaelis-Menten kinetic parameters were best fitted to one-component enzyme kinetic model. The mean Km (micromol x L(-1) ) and V(max) (micromol x g(-1) x min(-1)) values were 27 +/- 10 and 4. 8 +/- 2.1, 54 +/- 22 and 2.3 +/- 1.0, 51 +/- 29 and 2.2 +/- 0.8, for the formation rates of 7,8,4'-THI, 7,3',4'-THI, and 6,7,4'-THI, respectively. Furafylline, the CYP1A2 specific inhibitor, estrogen, and monoclonal antibody raised against human CYP1A2 (MAB-1A2) apparently inhibited the formation of mono-hydroxylated metabolites, The IC50 of Fur for the formation of 7,3',4'-THI, 6,7,4'-THI and 7,8,4'-THI was 1.0, 0.9 and 0. 8 mol x L(-1), respectively. The IC50 of estrogen for the formation of 7,3',4'-THI, 6,7,4'-THI and 7,8,4'-THI were 51, 60 and 64 mol x L(-1) respectively. The IC50 of MAB-1A2 for the formation of the mono-hydroxylated products was 1 mol x L(-1), but neither other selective inhibitor nor substrate probes, including coumarin (CYP2D6), sulphaphenzole ( CYP2C9/10), omeprazole ( CYP2C19), quinidine (CYP2D6), diethyldithiocarbamate (CYP2E1), troleandomycin (CYP3A4) and keteconazole (CYP3A4), did so with human liver microsomes.</p><p><b>CONCLUSION</b>The in vitro studies indicated that daidzein mono-hydroxylated products were principally metabolized by CYP1A2 in human.</p>