Intervention of Traditional Chinese Medicine in NLRP3 Signaling Pathway for Prevention and Treatment of Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease （AD） is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein （Aβ） excessive deposition， neuroinflammatory response， Tau protein hyperphosphorylation， and other factors， and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single， so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow， as well as the loss of vital energy， is the internal mechanisms underlying the occurrence and development of AD， which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）. Activating the NLRP3 signaling pathway increases neuroinflammatory response， intervenes in microglial polarization， and regulates Aβ sedimentation， cellular autophagy， brain homeostasis， etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years， as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds， such as Danggui Shaoyaosan， modified Shuyu Wan， Qingxin Kaiqiao prescription， Kaixin San， Jiedu Yizhi prescription， and modified Buwang San， traditional Chinese medicine monomer extracts， such as silibinin， Lycium barbarum polysaccharides， liquiritigenin， salidroside， baicalin， cinnamaldehyde， betaine， acacetin， and Hericium erinaceus， and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.

Gypenoside granules improved lipid metabolism in C57BL/6J mice with hyperlipidemia / 中国药科大学学报

@#To investigate the hypolipidemic effects of gypenosides granules and its combination with lipitor, a model of hyperlipidaemia C57BL/6J mice was established by high-fat diet feeding for 4 weeks. The mice were randomly divided into blank group, model group, lipitor group(10 mg/kg of lipitor), low dose group(90 mg/kg of gypenosides granules), medium dose group(120 mg/kg of gypenosides granules), high dose group(180 mg/kg of gypenosides granules)and the combination group(180 mg/kg of gypenosides granules and 10 mg/kg of lipitor). After 4 weeks of continuous administration, the contents of serum lipid indexes, serum ALT, AST and apolipoprotein B(ApoB)were measured. The liver tissues of mice were observed by H&E staining. The expression levels of key factors involved in hepatic cholesterol metabolism were observed by RT-PCR and Western blot methods, such as adenosine triphosphate combined box transporter A1(ABCA1), liver X receptor(LXRα), cholesterol 7 alpha hydroxylase(CYP7A1)and type BΙ scavenger receptor(SR-BΙ). The results revealed that gypenosides granules significantly decreased the mice body weight, total abdominal fat area and the level of serum total cholesterol(TC). The combination group showed a more significant reduction in TC level than the other administration groups. Moreover, gypenosides granules treatment remarkably increased the protein expression of ABCA1 and up-regulated the mRNA expression of ABCA1, CYP7A1 and SR-BI. The above results suggest that gypenosides granules can significantly reduce blood lipid contents, and the combination therapy with lipitor show better the lipid-lowering effect. Meanwhile, gypenosides granules can decrease the level of serum transaminase. Preliminary exploration suggests the lipid-lowering mechanism of gypenosides granules may be involved in cholesterol reversal to regulate the level of TC.

Detection of Metabolism Function of Microbial Community of Corpses by Biolog-Eco Method / 法医学杂志

Objective To detect the changes of microbial community functional diversity of corpses with different postmortem interval(PMI)and to evaluate forensic application value for estimating PMI. Methods The cultivation of microbial community from the anal swabs of aSusscrofaand a human corpse placed in field environment from 0 to 240 h after death was performed using the Biolog-Eco Mi-croplate and the variations of the absorbance values were also monitored. Combined with the technology of forensic pathology and flies succession, the metabolic characteristics and changes of microbial commu-nity on the decomposed corpse under natural environment were also observed.Results The diversity of microbial metabolism function was found to be negatively correlated with the number of maggots in the corpses. The freezing processing had the greatest impact on average well color development value at 0 h and the impact almost disappeared after 48 h. The diversity of microbial metabolism of the samples be-came relatively unstable after 192 h. The principal component analysis showed that 31 carbon sources could be consolidated for 5 principal components(accumulative contribution ratio >90%). The carbon source tsquare-analysis showed thatN-acetyl-D-glucosamine andL-serine were the dominant carbon sources for estimating the PMI(0=240 h)of theSusscrofaand human corpse.Conclusion The Biolog-Eco method can be used to reveal the metabolic differences of the carbon resources utilization of the microbial community on the corpses during 0-240 h after death, which could provide a new basis for estimating the PMI.

Trimethoxystilbene and its effects on the proliferation and apoptosis of PASMCs / 中南大学学报(医学版)

OBJECTIVE@#To synthesize 3, 5, 4' -trimethoxystilbene (TMS) by methylation of resveratrol (Res), a natural compound extracted from polygonum cuspidatum, to identify the chemical structure of TMS, to test its pharmacokinetics, and to determine the effects of TMS on the growth inhibition and apoptosis in pulmonary artery smooth muscle cells (PASMCs).@*METHODS@#The chemical structure of TMS was analyzed by UV- and IR- absorption spectrometry, (1)H-NMR and (13)C-NMR spectroscopy and mass spectrometry. We measured the bioavailability, the characteristics of intestinal absorption, and the distribution of TMS in body and excretions of SD rats after oral administration of TMS. The acute toxicity of TMS in mice was tested. PASMCs were prepared from pulmonary artery of SD rats. The PASMCs were divided into 8 groups. Group of A (control) was cultured without TNF-α, TMS, or Res. Group of B (TNF-α) was cultured with 100 pg/mL TNF-α. Groups of C-E (low-high concentrations of TMS) were cultured with 100 pg/mL TNF-α and 5, 10, 20 μmol/L TMS, respectively. Groups of F-H (low-high concentrations of Res) were cultured with 100 pg/mL TNF-α and 50, 100, 200 μmol/L Res, respectively. The proliferation of PASMCs after treatment was determined by MTT assay. The apoptosis of PASMCs after treatment was determined by flow cytometry.@*RESULTS@#The UV absorption map of TMS showed λmax(MeOH) at 318, 306.2, and 217.8 nm. Analysis of infrared spectrum of TMS showed IRvKBr max /cm at 2999, 2935, 2836, 1591, 1511 and 1456/cm. The (1)H-NMR map showed that the synthetic product contained three hydroxy groups, while (13)C-NMR map showed 17 carbon signals and some symmetrical structural fragments. Electospray ionization mass spectrometry of the productshowed m/z peaks corresponded to 271[M+H](+), 256[M+H-CH(3)](+) and 241[256-CH(3)](+); the implied relative molecular weight is 270 and the implied molecular formula is C17H18O3. These data confirm the product is 3,5,4' - trimethoxystilbene. The absolute bioavailability of TMS was 45.4%. TMS was well absorped in the upper small intestine; it was excreted in stool and bile and distributed into several tissues. The maximal tolerance dose (MTD) of TMS was 5.85 g/kg. MTT assay showed TMS inhibited the proliferation of PASMCs in a dose-dependent manner. The extent of growth inhibition in A-H groups were (4.07±2.12)%, (6.54±4.78)%, (9.35±4.26)%, (16.75±5.34)%, (23.74±7.07)%, (6.78±5.58) %, (8.81±5.16) %, and (17.81±6.03) %, respectively. Flow cytometry showed the extent of apoptosis in PASMCs (after being treated with TMS for 24 h) was significantly higher than that in PASMCs treated only with TNF-α. The apoptosis rates of A-H groups were (2.63±0.74)%, (3.54±0.81)%, (5.77±4.62)%, (11.68±5.35)%, (18.79±4.15)%, (4.11±3.59)%, (6.33±4.8) %, and (12.47±5.06)%, respectively.@*CONCLUSION@#We have confirmed our synthetic product as 3,5,4'-trimethoxystilbene (TMS), with the molecular formula of C17H18O3 and appropriate molecular weight and absorbption and NMR spectra. The bioavailability of TMS was to 45%. It strongly inhibits the proliferation of PASMCs in a dose-dependent manner and induces apoptosis of PASMCs.

RP-HPLC study of resveratrol derivative (BTM-0512) in rat plasma and tissue distribution / 药学学报

This paper described a rapid and se nsitive HPLC method to analyze (E)-3, 5,4'-trimethoxystilbene (BTM-0512) in rat plasma and tissues. The analysis used a BDS Hypersil C18 analytical column (250 mm×4.6 mm ID, 5 μm) and acetonitrile / water as the mobile phase. The UV detection wavelength was 319 nm. Proteins were precipitated with acetonitrile and diethylstilbestrol as internal standard. The method was validated according to State Food and Drug Administration of China and ICH of Technical Requirements for Registration of Pharmaceuticals for Human Use Guidelines. The limit of interday precision values (%RSD) were in the range of 2.6% -5.1% and 2.4% -4.8%, respectively.Mean accuracy and absolute recoveries of BTM-0512 ranged from 95.3% - 100. 1% and 95.9% -100.9% for plasma and tissues, respectively. This method can be quite useful for BTM-0512 pharmacokinetic and tissue distribution studies, for purpose which multiple plasma and tissue samples can be analyzed quickly with high reproducibility.

Killing effect of 17-allylamino-17-demethoxygeldanamycin on a breast cancer cell line / 医学研究生学报

Objective:To study the anti-proliferation effects of a heat shock protein 90(Hsp90) inhibitor,17-allylamino-17-demethoxygeldanamycin(17-AAG),on a human breast cancer cell line,SKBr3,and related mechanism.Methods:MTT assay was used to detect the growth inhibition of SKBr3 cells.Cell cycle and apoptosis were analyzed by flow cytometry.Alteration of human epidermal growth factor receptor 2(HER2) in SKBr3 cells being treated with 17-AAG were measured by immunohistochemistry.Results:17-AAG significantly inhibited growth of SKBr3 cells in vitro in a dose-dependent manner with an IC_(50) value at 3.09 ?g/ml.Under concentrations of 0,0.625,1.250,2.500,5.000 and 10.000(?g/ml,)the percentages of cell apoptosis were(1.03?0.08)%,(3.68?0.67)%,(7.06?1.12)%,(11.23?1.36)%,(20.32?1.98)%,and(31.65?2.96)%;the percentages of cells at G_(0)/G_(l) phase were 58.61%,54.34%,49.55%,43.73%,35.52%,and 27.46%;the percentages of cells at S phase were 29.57%,25.21%,19.65%,22.98%,19.71%,and 15.46%;the percentages of cells at G_(2) /M phase were 11.82%,20.45%,30.18%,33.29%,44.77%,and 57.08%,respectively.The level of HER2 expression in SKBr3 cells being treated with 17-AAG,compared to that in control cells,was reduced significantly.Conclusion:17-AAG can inhibit the growth of human breast cancer cell and enhance its apoptosis.It may be a promising anti-tumor drug.

The separation of baicalin by aqueous two-phase extraction system / 中成药

AIM:To explore the extraction mechanism of the separation-purification of baicalin in aqueous two-phase systems. METHODS:By experiment,nonionic surfactant PEG-K_2PHO_4-H_2O two aqueous phase system was selected to phase-forming conditions,and the effect of temperature,pH,salt composition on partition of baicalin PEG/salt system. RESULTS:The extraction rate of baicalin in aqueous two-phase system was up to 98.6%. CONCLUSION:The two aqueous phase system for baicalin extraction is easy to operate has good reproductivity,and can be applied in mass production.