[Research status and prospect of primary processing of traditional Chinese medicinal materials].

The primary processing is important links and closely related to the quality of traditional Chinese medicinal materials, and is not only cleaning of remove the non-officinal parts, drying for termination the physiological status of organisms, but also retaining the most active substances, decreasing the toxic components, and promoting the transformation among chemical ingredients through primary processing. So the traditional primary processing endows with characters, quality, specifications and properties of traditional Chinese medicine, and embodies some important science truth. The traditional primary processing method and technology systems are derived from the long-term practices and experiences, which are distinctive, colorful, diverse, and scientific, which are helpful to development and utilization of traditional Chinese medicine resources. This paper systemically expounds the research status of the Chinese medicine processing method, summarizes the problems in the primary processing of traditional Chinese medicinal materials research, and prospects its bright future.

Development of ß-amino-carbonyl compounds as androgen receptor antagonists.

AIM: Androgen receptor (AR) antagonists have proven to be useful in the early control of prostate cancer. The aim of this study was to identify and characterize a novel ß-amino-carbonyl-based androgen receptor antagonist. METHODS: Different isomers of the ß-amino-carbonyl compounds were obtained by chiral separation. The bioactivities of the isomers were evaluated by AR nuclear translocation, mammalian two-hybrid, competitive receptor binding and cell proliferation assays. The expression of genes downstream of AR was analyzed with real-time PCR. The therapeutic effects on tumor growth in vivo were observed in male SCID mice bearing LNCaP xenografts. RESULTS: Compound 21 was previously identified as an AR modulator by the high-throughput screening of a diverse compound library. In the present study, the two isomers of compound 21, termed compounds 21-1 and 21-2, were characterized as partial AR agonists in terms of androgen-induced AR nuclear translocation, prostate-specific antigen expression and cell proliferation. Further structural modifications led to the discovery of a androgen receptor antagonist (compound 6012), which blocked androgen receptor nuclear translocation, androgen-responsive gene expression and androgen-dependent LNCaP cell proliferation. Four stereoisomers of compound 6012 were isolated, and their bioactivities were assessed. The pharmacological effects of 6012, including AR binding, androgen-induced AR translocation, NH2- and COOH-terminal interaction, growth inhibition of LNCaP cells in vitro and LNCaP xenograft growth in nude mice, were mainly restricted to isomer 6012-4 (1R, 3S). CONCLUSION: Compound 6012-4 was determined to be a novel androgen receptor antagonist with prostate cancer inhibitory activities comparable to bicalutamide both in vitro and in vivo.

Involvement of estrogen receptor-ß in farrerol inhibition of rat thoracic aorta vascular smooth muscle cell proliferation.

AIM: To investigate the effect of farrerol, a major active component isolated from a traditional Chinese herb "man-shan-hong" (the dried leaves of Rhododendron dauricum L) on fetal bovine serum (FBS)-induced proliferation of cultured vascular smooth muscle cells (VSMCs) of rat thoracic aorta. METHODS: VSMCs proliferation, DNA synthesis and cell cycle progression were studied using the MTT assay, bromodeoxyuridine (BrdU) incorporation and flow cytometry, respectively. The mRNA levels of cell cycle proteins were quantified using real-time RT-PCR, and the phosphorylation of ERK1/2 was determined using Western blotting. Reporter gene and receptor binding assays were employed to study the interaction between farrerol and estrogen receptors (ERs). RESULTS: Farrerol (0.3-10 µmol/L) inhibited VSMC proliferation and DNA synthesis induced by 5% FBS in a concentration-dependent manner. The effects were associated with G(1) cell cycle arrest, down-regulation of cell cycle proteins and reduction in FBS-induced ERK1/2 phosphorylation. Using a reporter gene, it was found that farrerol (3 µmol/L) induced 2.1-fold transcription of ER. In receptor binding assays, farrerol inhibited the binding of [(3)H]estradiol for ERα and ERß with IC(50) values of 57 µmol/L and 2.7 µmol/L, respectively, implying that farrerol had a higher affinity for ERß. Finally, the inhibition of VSMC proliferation by farrerol (3 µmol/L) was abolished by the specific ERß antagonist PHTPP (5 µmol/L). CONCLUSION: Farrerol acts as a functional phytoestrogen to inhibit FBS-induced VSMC proliferation, mainly via interaction with ERß, which may be helpful in the treatment of cardiovascular diseases related to abnormal VSMCs proliferation.

Anthropometry did not approach adequate predictive accuracies for detecting elevated fasting plasma glucose or hemoglobin A1c levels among Chinese children aged 7-9 years.

AIMS/INTRODUCTION: Elevated concentrations of fasting plasma glucose (FPG) or hemoglobin A1c (HbA1c) are well-established independent risk factors for progression to diabetes, cardiovascular comorbidities and mortality. Most previous studies on the relationships of anthropometric measures with hyperglycemia were carried out among adults and adolescents, but few data are available for the performance predication of the predictors for diagnosing elevated FPG or HbA1c among young children. MATERIALS AND METHODS: Involving 5,556 students of aged 7-9 years, a school-based cross-sectional survey was carried out between March and June 2019 in Shenzhen, China. Receiver operating characteristic curve analysis was utilized. RESULTS: The median was 4.6 (interquartile range [IQR] 4.3-4.8) mmol/L for FPG and 5.3% (IQR 5.1-5.5%) for HbA1c levels for all participants. For detecting elevated FPG, weight (0.651, IQR 0.583-0.719) and waist circumference (0.650, IQR 0.584-0.717) showed the highest area under the curve and 95% confidence interval, followed by body mass index and the z-score of body mass index (both 0.635, IQR 0.567-0.703); other anthropometric measures showed poorer diagnostic efficiencies or no ability. For detecting elevated HbA1c, lower efficiencies for the Conicity Index (0.651, IQR 0.583-0.719), waist-to-height ratio, waist-to-hip ratio and waist-to-chest ratio were shown. The correlations of FPG and HbA1c levels with anthropometric indices were weak (Spearman's r ≤ 0.179). CONCLUSIONS: None of the evaluated anthropometric indicators approached an adequate predictive accuracy for the detection of elevated FPG or HbA1c levels in Shenzhen children aged 7-9 years. The current study did not recommend anthropometry screening for prediabetes in young children.

Hydroxylation of the triterpenoid nigranoic acid by the fungus Gliocladium roseum YMF1.00133.

The ability of the fungus Gliocladium roseum YMF1.00133 to transform the bioactive nigranoic acid (=(24Z)-9,19-cyclo-3,4-secolanosta-4(28),24-diene-3,26-dioic acid) was investigated. Three new products from the co-cultures of nigranoic acid and G. roseum YMF1.00133 were obtained by employing a combination of Sephadex LH-20 and silica-gel column chromatography. The major metabolite was identified as 15beta-hydroxynigranoic acid, and the minor metabolites as 6alpha,15beta-dihydroxynigranoic acid and 7beta,15beta-dihydroxynigranoic acid by mass spectrometry and NMR spectroscopy. This is the first report of the biotransformation of the A-ring-secocycloartene triterpenoid, nigranoic acid.

Tetramethylpyrazine protects palmitate-induced oxidative damage and mitochondrial dysfunction in C2C12 myotubes.

AIMS: Tetramethylpyrazine (TMP), one of the active ingredients isolated from a Chinese herbal prescription, possesses protective effects against oxidative stress caused by high glucose in endothelial cells. In this study, the role of TMP in preventing muscle cells from palmitate-induced oxidative damage was investigated and the possible mechanisms of action elucidated. MAIN METHODS: Mitochondrial reactive oxygen species (ROS) were measured in C2C12 myotubes, a palmitate-induced oxidative stress cell model, with or without TMP. Both mitochondrial membrane potential (MMP) and oxygen consumption were assessed in conjunction with quantification of mitochondrial DNA and mitochondrial biogenesis-related factors, such as peroxisome proliferator-activated receptor-γ coactivator 1 α (PGC1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam), by real-time polymerase chain reaction. Expression of mitochondrial respiratory chain complex III as an index of mitochondrial function was evaluated by immunoblotting, and glucose transport into the C2C12 myotube examined by analyzing 2-deoxy-[(3)H]glucose uptake. KEY FINDINGS: TMP significantly alleviated palmitate-induced mitochondrial ROS production, mitigated mitochondrial dysfunction and increased D-loop mRNA expression as compared with the control. This was accompanied by a marked reversal of palmitate-induced down-regulation in the expression of mitochondrial biogenesis-related factors (PGC1α, NRF1 and Tfam) and decreased glucose uptake in C2C12 myotubes. As a result, cell respiration, as reflected by the elevated expression of mitochondrial respiratory chain complex III and oxygen consumption, was enhanced. SIGNIFICANCE: TMP is capable of protecting C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction, and improving glucose uptake in muscle cells partially through the up-regulation of mitochondrial biogenesis.

A new lignan glycoside from Peperomia duclouxii.

A new lignan glycoside was isolated from the n-BuOH extract of Peperomia duclouxii C. DC., and its structure was elucidated to be 2-(4''-hydroxy-3'', 5''-dimethoxybenzyl)-3-(5'-methoxy-3', 4'-methylenedioxybenzyl)butyrolactone-4''-O-beta-D-glucopyranoside (1) by spectral methods.

Overexpression of heat-shock protein 20 in rat heart myogenic cells confers protection against simulated ischemia/reperfusion injury.

AIM: To explore whether overexpression of the small heat shock protein HSP20 in rat cardiomyocytes protects against simulated ischemia/reperfusion (SI/R) injury. METHODS: Recombinant adenovirus expressing HSP20 was used to infect rat H9c2 cardiomyocytes at high efficiency, as assessed by green fluorescent protein. H9c2 cells were subjected to SI/R stress; survival was estimated through assessment of lactate dehydrogenase and cell apoptosis through caspase-3 activity. RESULTS: Overexpression of HSP20 decreased lactate dehydrogenase release by 21.5% and caspase-3 activity by 58.8%. Pretreatment with the protein kinase C inhibitor Ro-31-8220 (0.1 micromol/L) for 30 min before SI/R canceled the protective effect of HSP20. The selective mitochondrial K+ATP channel inhibitor 5-hydroxydecanoate (100 micromol/L) had a similar effect. However, the non-selective K+ATP channel inhibitor glibenclamide (100 micromol/L) had no significant effect. CONCLUSION: These data indicate that the protective effect of HSP20 in vitro is primarily due to reduced necrotic and apoptotic death of cardiomyocytes, possibly via the protein kinase C/mitochondrial K+ATP pathway.

Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts.

AIM: To explore whether overexpression of HSP20 in the myocardium could protect against ischemia/reperfusion injury in rats. METHODS: Rat hearts were injected with vector, recombinant adenovirus encoding green fluorescent protein (Ad.GFP) or recombinant adenovirus encoding wild-type HSP20 (Ad.HSP20) in the left ventricle. Four days later, hearts were removed and expression of HSP20 was measured in the left ventricle. Subsets of animals in the vector-, Ad.GFP- , and Ad.HSP20-treated groups were subjected to 20-min ischemia and 120-min reperfusion. Myocardial injury was evaluated by infarct size and level of serum cardiac troponin T and creatine phosphokinase. Apoptosis of cardiomyocytes was determined by TUNEL staining. Cardiac function was evaluated by hemodynamic indexes. RESULTS: Infarct size and serum cardiac troponin T and creatine phosphokinase levels were significantly reduced in Ad.HSP20-treated hearts compared with vector- and Ad.GFP-treated hearts. The ratio of TUNEL-positive cardiomyocytes to total number of cardiomyocytes in the Ad.HSP20 group was significantly reduced as compared with the vector and Ad.GFP groups. Left ventricular end systolic pressure, and maximal rate of pressure increase (+dp/dt(max)) and decrease (-dp/dt(min)) values were increased significantly, while left ventricular end diastolic pressure was decreased significantly in Ad.HSP20-treated hearts compared with vector- and Ad.GFP-treated hearts. CONCLUSION: These data indicate that the cardioprotective effects of HSP20 may contribute to the reduction of myocardial necrosis and apoptosis in ischemia/reperfusion injury in rats.