The role and mechanism of estrogen receptor in the treatment of postmenopausal osteoporosis by Gushukang / 中国组织工程研究

BACKGROUND:The specific mechanism of Gushukang,as a Chinese traditional patent medicine for the treatment of postmenopausal osteoporosis of kidney deficiency and blood stasis,needs further studies. OBJECTIVE:To investigate the effect of Gushukang on serum sex hormones,bone microstructure and estrogen receptor in postmenopausal osteoporosis. METHODS:Firstly,network pharmacological analysis was performed.The active ingredients and action targets of Gushukang and the targets of postmenopausal osteoporosis were obtained respectively.Cytoscape was used to construct the active ingredient-target network.STRING database and Cytoscape were used for protein-protein interaction analysis and screening of core targets.DAVID database was used for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses of intersection targets.Then the ovariectomized Sprague-Dawley rats were used in the animal experiment.Gushukang was administered by gavage for 3 months.The serum estrogen level was detected by ELISA,the bone microstructure was detected by microCT,and the protein expression of estrogen receptor α and estrogen receptor β in bone tiusse was detected by western blot. RESULTS AND CONCLUSION:The network pharmacological research results identified 132 active ingredients and 150 targets of Gushukang and 1155 targets of postmenopausal osteoporosis.After intersections with 1155 postmenopausal osteoporosis targets,87 targets of active ingredients of Gushukang against postmenopausal osteoporosis were obtained.By constructing the active ingredient-target network,it was found that the active ingredients at the core were quercetin,kaempferol,luteolin,naringin and isorhamnetin,and the targets at the core were NCOA2,ESR2,AR,F2,ESR1 and PTGS1.The final targets obtained after the protein-protein interaction analysis and screening included MAPK8,ESR1,JUN,R3C1,RELA and FOS,of which ESR1 was the common core target obtained from the two analyses.KEGG enrichment analysis showed estrogen,tumor necrosis factor,apoptosis and other signaling pathways.Therefore,animal experiments focused on the effect of Gushukang on different subtypes of estrogen receptors in the estrogen signaling pathway.The results showed that in the Gushukang group,bone microstructure was significantly improved,serum estrogen level had no significant change,but the protein expression of estrogen receptor α and β in bone tissue was significantly increased.All the findings indicate that the mechanism of Gushukang in the treatment of postmenopausal osteoporosis may be related to its hormone-like effect and the enhancement of estrogen receptor expression.

The Osteoprotective Effect of Gusong Yigu Decoction on Ovariectomized Rats Based on PI3K/Akt Signal Pathway / 中药新药与临床药理

Objective To explore the mechanism of Gusong Yigu Decoction(inchuding Astragali Radix,Codonpsis Radix,Angelicae Sinensis Radix,etc.)in the treatment of postmenopausal osteoporosis(PMOP)based on network pharmacology and animal experiment.Methods The effective ingredients and corresponding targets of Gusong Yigu Decoction were collected by using TCMSP database.GeneCards,TTD,and other databases were used to collect PMOP target proteins.R language was used to obtain the intersection targets and draw Wayne diagram.STRING database was used for the establishment of protein-protein interaction network.At last,GO function enrichment and KEGG pathway enrichment were performed on all common targets.The ovariectomized SD rats were used in the animal experiment.Gusong Yigu Decoction was administered by gavage for 12 weeks.The changes of bone histomorphology were detected by HE staining,the mRNA and protein levels of phosphatidylinositol 3-kinase(PI3K)and protein kinase B(Akt)in bone tissue of proximal tibial were tested by qRT-PCR and Western Blot,respectively.Results A total of 91 effective ingredients of Gusong Yigu Decoction in the treatment of PMOP,70 common targets of drugs-diseases were obtained.GO enrichment analysis mainly included DNA-binding transcription activator activity,RNA polymerase II-specific,ubiquitin protein ligase binding.KEGG pathway enrichment analysis included PI3K/Akt signaling pathway,TNF signaling pathway,and apoptosis.The animal experiment showed that bone histomorphology was significantly improved,meanwhile the mRNA and protein expressions of PI3K and Akt were significantly increased in Gusong Yigu Decoction group(P＜0.01).Conclusion Gusong Yigu Decoction may improve bone microstructure through multiple channels and targets.Gusong Yigu Decoction can increase the number and thickness of bone trabeculae and reduce the separation of bone trabeculae by activating PI3K/Akt signaling pathway,and thus play an anti-osteoporosis role in postmenopausal osteoporosis.

Infrastructure of radiation oncology in China: a national survey for development and allocation of radiotherapy equipment during the 14 th Five-Year Plan period / 中华放射肿瘤学杂志

Objective:To investigate the current status of radiotherapy personnel and equipment in China, and to provide data basis for scientific allocation and effective use of radiotherapy equipment during the 14 th Five-year Plan period. Methods:From October to December 2020, a group of experts from China Association of Medical Equipment carried out an online questionnaire investigating the basic situation of radiotherapy in China, and the contents of the survey include radiotherapy centers, professional personnel, equipment, technology, equipment utilization rate, forecast of personnel and equipment in the next five years, etc. The data were reviewed by provincial medical societies/associations.Results:There were 1538 radiotherapy centers and 32978 radiotherapy professionals in Mainland China, including 18966 radiotherapy physicians, 4475 physicists and 9537 technicians. There were 2139 linear accelerators, 57 cobalt 60 accelerators, 457 afterloaders, 6 proton/heavy ion machines, 1034 conventional 2D simulators, 1208 CT simulators, and 89 MR simulators. 1459 centers can provide 3D conformal radiotherapy, 1256 centers can deliver intensity-modulated radiotherapy, 514 centers can offer volumetric modulated arc therapy, 422 centers can provide brachytherapy. According to the estimated data reported by the participating centers, in the next five years, the demand of professionals and machines will be increased by 4868 radiotherapy physicians, 2078 physicists and 3796 technicians, and 994 linacs, 896 CT simulators, 313 MR simulators and 54 proton heavy ions.Conclusions:The radiotherapy industry in China grows fast. During the 14 th Five-Year Plan period, the radiotherapy industry still has strong market demand as well as increase demand of personnel and equipment. Strengthening the market competitiveness of domestic radiotherapy enterprises, improving the equipment utilization rate in primary hospitals, providing comprehensive and systematic training and promoting standardized clinical application can resolve the issues of the lack and unbalanced distribution of radiotherapy resources, and maintain the fast and sustainable development of radiotherapy in China.

Effect of Balance Training with Balance Assessment Training System on Balance after Stroke / 中国康复理论与实践

Objective:To investigate the effects of Huber 360 neuromuscular control training and evaluation system (Huber 360) on balance dysfunction for patients with stroke. Methods:From January to November, 2020, 16 patients with stroke were randomly assigned to control group (n = 8) and observation group (n = 8). Both groups received routine motor function training, while the observation group accepted Huber 360 training in addition, for three weeks. They were assessed with Berg Balance Scale, Huber 360, 10-meter Walking Test and Timed 'Up & Go' Test before and after training. Results:All the indexes improved after training in both groups (t > 1.368, P < 0.05), and improved more in the observation group than in the control group (t > 2.230, P < 0.05). Conclusion:Huber 360 can promote the recovery of balance for stroke patients.

Current situation and prospect of surgical treatment for spontaneous brainstem hemorrhage / 中国综合临床

The incidence of spontaneous brainstem hemorrhage is about 10% of primary intracerebral hemorrhage, but its mortality and disability rate are much higher than other diseases.The anatomical characteristics and dense functional nuclei of the brain stem are closely related to the high difficulty of operation for brain stem hemorrhage.The surgical treatment of primary brain stem hemorrhage is divided into two types: craniotomy hematoma removal and hematoma aspiration.At present, there is no unified consensus on the surgical indications for brainstem surgery, and the support of large-scale multicenter clinical observation results and evidence-based medicine evidence is lacking.None of the existing treatment methods has made a breakthrough in the treatment of brainstem hemorrhage, and doctors are often confused because of the lack of evidence in clinical work.It is of positive significance to seek an effective treatment for brainstem hemorrhage.

Main Functions of Traditional Chinese Medicine Classical Prescription Wandaitang / 中国实验方剂学杂志

Wandaitang, which is one of classical traditional Chinese medicine(TCM) prescriptions, is derived from Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology. It is commonly used in modern clinical practice, and included in the Catalogue of Ancient Classical Prescriptions (The First Batch). Collected Exegesis of Recipes of Fu Qingzhu' s Obstetrics and Gynecology and Chen Shi-duo' s Bianzhenglu have a complicated relationship. Both of them have another biography, named Nvke Xianfang and Bianzheng Qiwen. The composition of Wandaitang in the four books is slightly different, while the prescription's explanations and other records are almost the same. The research and development of Wandaitang should be based on the records of Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology. Compared with other classical literatures, Collected Exegesis of Recipes of Fu Qingzhu's Obstetrics and Gynecology was published in a late period and less reproduced in other ancient books. To study the function of Wandaitang, we need to analyze the records in the original book. In addition, we need to make a multi-angle analysis by reference to the theory of TCM, the composition of drugs, the significance of compatibility, as well as the understanding of modern famous doctors, clinical reports and experimental studies in all aspects. The study found that the functions of Wandaitang were relatively concentrated, but with wide major functions involving internal medicine, surgery, gynecological, pediatric, andrological and other departments. According to the study, the authors believe that the functions of the classical TCM prescription of Wandaitang are invigorating spleen to eliminate dampness, dispersing the liver and rectifying Qi, and invigorating Yang. It can be used to treat leucorrhea, diarrhea, edema and stranguria with the syndromes of pale, languid, little food, loose stool and depression. Wandaitang can also be used to treat vaginitis, cervicitis, pelvic inflammatory disease, irritable bowel syndrome, chronic colitis, chronic nephritis, nephrotic syndrome and chronic prostatitis.

UPLC characteristic fingerprint and chemical pattern recognition of Angong Niuhuang Pills / 中国中药杂志

To establish the UPLC fingerprint of Zhongyi Angong Niuhuang Pills, in order to evaluate its quality by chemical pattern recognition. The method was developed on a column of Poroshell 120 EC-C_(18), with methanol-0.1% formic acid solution as the mobile phase for gradient elution at a flow rate of 0.4 mL·min~(-1). The column temperature was 30 ℃,and the detective wavelength was 254 nm. The similarity of 24 batches of Angong Niuhuang Pills was compared by using Traditional Chinese Medicine Chromatographic Fingerprint Similarity Evaluation System(2004 A). Hydrophobic cluster analysis,principal components analysis and partial least squares discriminant analysis were conducted by using SIMCA 13.0 software to investigate different components among these products. The UPLC characteristic fingerprint was established in this study. And 17 common peaks were identified by standard reference and UPLC-MS. The similarity of 24 batches samples were above 0.980,which can be classified into three categories for pattern recognition. Baicalin,berberine,jatrorrhizine,wogonin and wogonoside were identified as the main markers that cause differences of various batches. The method is simple,rapid,accurate and reproducible,and can provide scientific basis for improving the quality standard of Zhongyi Angong Niuhuang Pills.

Effect of ERRα in silencing DKK1 and SOST recombinant adenovirus vector-transfected MG63 Cells and bone-related proteins / 医学研究生学报

Objective WNT signaling pathway plays an important role in the formation, differentiation and maturation of bone cells, it is a classical intracellular signaling pathway involved in bone metabolism. DKK1 and Sost play a negative regulatory role in regulating bone mass and osteoblast differentiation, and are negative regulators of WNT signaling pathway. Estrogen-related receptor alpha (ERRα) regulates the functional activity of osteoblasts. The aim of study was to investigate the effect of ERRα on the transfection of MG63 cells and related proteins by the WNT signaling pathway inhibitor Dickkopf (DKK)1 and sclerostin (SOST) adenovirus vectors.Methods The cultured MG63 cells were divided into blank control group, silencing DKK1 group, silencing SOST group, silencing (DKK1+SOST) group, ERRα intervention empty adenovirus group, ERRα intervention silencing DKK1 group, ERRα intervention silencing SOST group, ERRα intervention silencing (DKK1+SOST) group. MG63 cells were transfected with packaged silencing DKK1 and SOST adenovirus vectors according to different groups. The activity of MG63 cells was detected by MTT assay, the activity of ALP was detected by alkaline phosphatase kit, and the concentration of calcium ion was analyzed by flow cytometry. Western blot was used to detect the expressions of low density lipoprotein associated protein 5 (LRP5), bone morphogenetic protein 2 (BMP2), osteopontin (OPN), osteoprotegerin(OPG).Results (1) Compared with blank control group, silencing DKK1, SOST, DKK1+SOST group and ERRα overexpression in the empty adenovirus group could increase cell activity, ALP activity, and decrease calcium ion concentration and increase the expressions of LRP5, BMP2, OPN, and OPG. Differences between groups were statistically significant(P0.05).Conclusion ERRα Overexpression can increase the activity of MG63 cells, ALP activity, LRP5, BMP2, OPN, and OPG proteins, and decrease the calcium ion concentration in silencing DKK1 and SOST adenovirus-transfected cells.

Research progress of PERK signaling pathway under endoplasmic reticulum stress in tumor / 实用肿瘤学杂志

During growth,invasion and metastasis,tumor cells undergo endoplasmic reticulum stress(ERS)under hypoxia,hy-poglycemia and other environmental stresses.In response to ERS,tumor cells induce unfolded protein response(UPR).PERK signa-ling pathway as a key pathway to activate UPR can promote survival,proliferation,invasion and protection of tumor cells by increasing tumor tolerance to adverse microenvironment,inducting angiogenesis,inducing autophagosome formation and activating apoptotic signal molecules.Tumor cells are induced apoptotic and autophagic death when UPR reaches a certain extent.

Bushen Jianpi Huoxue decoction increases the proliferation of Sost-overexpressed adenovirus transfected osteoblasts and alkaline phosphatase activity / 中国组织工程研究

BACKGROUND: Chinese herbs have been shown to affect osteoblasts through Wnt/β-catenin signaling pathway. Sclerostin (Sost) is an inhibitor of Wnt signaling pathway and an inhibitor of osteogenesis, and it is also an antagonistic factor that regulates the differentiation and proliferation of osteoblasts. Bushen Jianpi Huoxue decoction (BJHD) is the empirical formula in the prevention and treatment of osteoporosis at the Affiliated Orthopedics Hospital, Guangzhou University of Chinese Medicine. BJHD can promote osteogenesis and effectively treat osteoporosis. OBJECTIVE: To observe the effect of BJHD on the cell proliferation, alkaline phosphatase activity and expression levels of related proteins in Sost-overexpressed adenovirus transfected osteoblasts. METHODS: The osteoblasts were divided into two groups: blank control group (empty adenovirus transfection) and Sost overexpressed group (Sost overexpression and adenovirus transfection). Two groups were cultured with blank serum and medicine serum. The cell proliferation was tested by cell counting kit-8 assay, and alkaline phosphatase activity was tested by alkaline phosphatase kit. Expression levels of bone regulation-related proteins were tested by western blot assay. RESULTS AND CONCLUSION: Compared with the blank serum, medicine serum could increase the cell viability at 24, 48 and 72 hours in both groups (P ＜ 0.01). Compared with the blank serum, medicine serum increased the alkaline phosphatase activity (P ＜ 0.01). Compared with the blank serum, medicine serum in the blank control group decreased the expression of low-density lipoprotein receptor-related protein 5 and osteoprotegerin (P ＜ 0.01), but showed no effect on the expression of osteopontin and tumor necrosis factor α. Medicine serum in the Sost-overexpressed group decreased the expression of low-density lipoprotein receptor-related protein 5, osteoprotegerin and osteopontin, increased the expression of tumor necrosis factor α (P ＜ 0.01). These results indicate that BJHD can increase the proliferation of recombinant adenovirus transfected Sost-overexpressed osteoblasts and alkaline phosphatase activity, and regulate the expression of low-density lipoprotein receptor-related protein 5, osteoprotegerin, osteopontin, and tumor necrosis factor α.

Metabolic Profiling Analysis of Rice Leaf Based on Hydrophilic Interaction Chromatography Combined with Reversed Phase Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry / 分析化学

A metabolic profiling analysis method for metabolomic studies of rice leaf was established based on HSS T3 combined with XBridge Amide Q-TOF LC/MS by comparing the influences of different extraction methods in rice leaves of metabolites. The extraction and separation of rice leaf metabolites using three different methods including methanol-chloroform-water,methanol-chloroform-ammonia,methanol-methyl tert-butyl ether -water and different chromatographic systems were compared by the numbers of peaks, identified metabolites and the metabolic pathways. The results showed that the method of methanol-chloroform-water reached the highest coverage rate of metabolites in rice leaves,and the maximum number of unique metabolites including prephenic acid, luteolin, α-linolenic acid, aconitic acid, gibberellin A12 aldehyde, isovitexin, L-Glutamate were detected. Metabolites with different polarity in rice leaf could be detected by HSS T3 and XBridge Amide. A total of 16 kinds of organic acids, 17 kinds of nucleotides, 21 kinds of amino acids, 66 kinds of fatty acids,11 kinds of phospholipids and 7 kinds of sphingolipids were identified. XBridge Amide had an absolute advantage in detecting phospholipids and sphingolipids. The metabolic pathways involved purine metabolism, pyrimidine metabolism, tricarboxylic acid cycle, arginine metabolism, fatty acid metabolism, phospholipid metabolism, sphingolipid metabolism, phenylalanine metabolism and vitamin B2 synthesis. It showed certain complementarity between the two columns in identifying metabolites and involved the metabolic pathways. The established method is expected to be useful for the metabolomic studies of rice.

Development of Two-Dimensional Liquid Chromatography Coupled with Tandem Mass Spectrometry for Identification of Extracted Proteins of Rice Leaves: Hydrophilic Interaction-Reversed-phase Approach / 分析化学

A two-dimensional liquid chromatography method was developed for the analysis of rice leaves proteomics based on the coupling of hydrophilic interaction liquid chromatography-reversed-phase liquid chromatography with online tandem mass spectrometry. The influence of pH value of chromatographic mobile phase on the orthogonality of the hydrophilic interaction-reversed-phase two-dimensional liquid chromatography was evaluated by the changes of standard peptide retention. The results indicated that the better orthogonality (R2=0.34113) was achieved from the system with hydrophilic interaction columns(pH 9.3) in the first and C18columns(pH 3.3) in the second LC dimension. Coupled with multiple fraction concatenation strategy,the orthogonality of two-dimensional liquid chromatography was further evaluated in the analysis of complex rice leaf proteins. The results showed that more than 50% of the total peptides were identified less than two times, and the peptides obtained from first-dimension were well distributed across the elution window,indicating that the method showed significant orthogonality in the identification of complex rice leaf proteins. Based on the proteome discoverer software,207345 peptides belonged to 2930 protein clusters were identified.

Effects of Bcl-2 and BaK gene silencing on cell apoptosis and osteogenesis activity of MG-63 cell lines / 实用医学杂志

Objective To explore the effects of Bcl-2 and BaK gene silencing on cell apoptosis ,osteogen-esis activity and free Ca2+concentration of MG-63 cell lines. Methods The siRNA sequences targeted Bcl-2 and BaK respectively were designed;Bcl-2 and BaK silencing adenovirus vector scramble RNA vector and empty vec-tor were constructed to transfect MG-63 cell lines. MTT method was used to examine cell viability;ALP and flow cytometry were conducted to observe osteogenesis activity and free Ca2+concentration. Results Bcl-2 gene silenc-ing decreased cell viability,reduced osteogenesis activity and increased free Ca2+ concentration when compared with controls but BaK gene silencing had the opposite effects. The effect of Bcl-2+BaK gene silencing on cell was similar to the empty control. Conclusions Cell apoptosis,osteogenesis activity and free Ca2+concentration of MG-63 change following Bcl-2 and BaK gene silencing,implicating their roles in osteoporosis.

Effects of Bcl-2 and BaK gene silencing on cell apoptosis and osteogenesis activity of MG-63 cell lines / 实用医学杂志

Objective To explore the effects of Bcl-2 and BaK gene silencing on cell apoptosis ,osteogen-esis activity and free Ca2+concentration of MG-63 cell lines. Methods The siRNA sequences targeted Bcl-2 and BaK respectively were designed;Bcl-2 and BaK silencing adenovirus vector scramble RNA vector and empty vec-tor were constructed to transfect MG-63 cell lines. MTT method was used to examine cell viability;ALP and flow cytometry were conducted to observe osteogenesis activity and free Ca2+concentration. Results Bcl-2 gene silenc-ing decreased cell viability,reduced osteogenesis activity and increased free Ca2+ concentration when compared with controls but BaK gene silencing had the opposite effects. The effect of Bcl-2+BaK gene silencing on cell was similar to the empty control. Conclusions Cell apoptosis,osteogenesis activity and free Ca2+concentration of MG-63 change following Bcl-2 and BaK gene silencing,implicating their roles in osteoporosis.

Berberine action targets and its absorption behavior：how to use old drug for new mechanisms / 中国中药杂志

A variety of pharmacological effects of berberine (BBR) are constantly being discovered with the deepening of BBR research. What followed is how to rationally use the drug according to these new pharmacological effects. Because of some cardiac toxicity and poor oral absorption, conflicts may arise between improving the bioavailability and controlling the toxicity of BBR. Meanwhile some new therapeutic uses of BBR, such as hypolipidemia, hypoglycemia as well as prevention and treatment of neurodegenerative diseases, need long-termoral administration, thereby may lead to alteration of intestinal flora and potentially affect body's other physiological functions. Based on the stated targets of BBR and related pharmaceutical properties, comprehensive analysis of these issues was conducted in this study. Some suggestions were presented below：the effect of long-term oral administration on body function, especially the intestinal flora, needs to be further investigated; risks shall be considered in changing the composition of the formulation to improve the absorption rate of oral administration; for the medication with higher concentration demand (such as anti-cancer), targeted drug-delivery is worthy to be considered.

Effects of XBP1 on glioma cell viability and glycolysis under hypoxia / 中国肿瘤临床

Objective:To determine the effect of hypoxic stress on glioma cell XBP1 expression, the relationship between XBP1 expres-sion and sugar metabolism, the influence of XBP1 repression on the survival rate of glioma cells under normoxia and hypoxia, and the influence of XBP1 on glioma cell glycolysis. Methods:We tested XBP1 activation in human glioma cell lines cultured under normoxia and hypoxia. XBP1 expression was repressed with siRNA technology. Cells were treated with oxidative phosphorylation inhibitor. We then detected the variation in cell apoptosis, sugar metabolism mode, and cell apoptosis and glycolysis products under normoxia and hypoxia. Results:XBP1 activation increased under hypoxia. Silencing XBP1 expression reduced glioma cell survival level, ATP and lactic acid production, and glucose consumption under hypoxia. After inhibiting cell oxidative phosphorylation, XBP1 repression significantly reduced the survival level of glioma cells. Conclusion:Hypoxia can activate XBP1 in glioma cells. Under hypoxia, XBP1 silencing de-presses cell activity and glycolysis. Glycolysis of glioma cells under hypoxia depends on XBP1 activation.

Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression / 中国天然药物

Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.

Reproductive toxicity of brazilein in ICR mice / 中国天然药物

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.

Transmembrane transport behavior of in vitro HepG2 cells of ananas and its effect on lipids and glucose distribution / 中国中药杂志

Pineapple (Ananas comosus) leaves contain mainly phenolic components with antioxidant and hypolipidemic effects. One of the principle components is p-coumaric acid. In this study, the transport behavior of p-coumaric acid, was observed after the administration of pineapple leaf phenols in vitro. Simultaneously, the effect of the phenols on glucose, total cholesterol and triglycerides transportation and metabolism in HepG2 cells was also observed. The results showed that the phenols had good transport characteristics. 5 min after the administration, p-coumaric acid of the phenols could be detected, and the content of p-coumaric acid reached the peak concentration after 60 min of the administration. p-coumaric acid of phenols have time-and dose-dependent manner. While promoting glucose transporter (GLUT4) and low density lipoprotein receptor (LDLR) expression, the phenols decreased intracellular lipid content. This reduction of intracellular lipid content was highly correlated with the promotion of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) expression, while the reduction of intracellular glucose levels was correlated with glycogen synthesis in the cells.

Effect of baicalin on pattern recognition receptor TLR2/4-NOD2 and its significance of druggability / 中国中药杂志

Activation pattern recognition receptors can cause the startup of downstream signaling pathways, the expression of inflammatory factors, and finally immunological inflammatory reaction. Either exogenous pathogenic microorganisms or endogenous tissue components can activate these pattern recognition receptors as ligands at varying degrees, and then cause the immunological inflammatory reaction. Therefore, it is of great significance to inhibit relevant receptors, as well as the immunological inflammatory reaction, in order to avoid tissue injury during the course of disease. Baicalin is able to specifically inhibit the expression of TLR2/4-NOD2, inhibit the expression of inflammatory factors IL-1beta, IL-6 and TNF-alpha, and thereby reducing the injury of the tissue cells during the course of disease. This effect is non-specific with tissues, which is of great theoretical and practical significance in druggability. In addition, the drug metabolism and toxicity of baicalin are also discussed for its druggability in this article.