Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema / 中国中药杂志

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

Anti-tumor Application and Pharmacological Mechanism of Xihuangwan： A Review / 中国实验方剂学杂志

Malignant tumors are currently seriously endangering human health and life， which has become one of the main causes of death in China. In modern Western medicine， they are mainly tackled by surgery， chemotherapy， and radiotherapy， but the death toll continues to rise year by year. At present， most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects， affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance， making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine （TCM）， it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore， the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors， and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan， a classic heat-clearing prescription， is composed of Calculus Bovis， Moschus， Olibanum， and Myrrh and has the effects of clearing away heat， removing toxin， eliminating edema， and dissipating mass， which is mainly used to treat carbuncle， pustule， scrofula， multiple abscess， and cancer caused by heat-toxin obstruction. In modern clinical practice， it has been employed in patients with lung cancer， breast cancer， gastric cancer， liver cancer， colorectal cancer， and other malignant tumors， especially during the advanced stage， as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids （such as masticinic acids）， volatile oils， steroids （like porcine deoxycholic acid）， and bilirubin， which have been proved effective in anti-tumor. This paper reviewed the prescription source， pharmaceutical research， clinical anti-tumor research， and pharmacological mechanisms of Xihuangwan， which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.

Historical Evolution and Clinical Application of Classical Prescription Xiao Xumingtang / 中国实验方剂学杂志

Xiao Xumingtang in The Catalogue of Famous Ancient Classics （The First Batch） issued by the National Administration of Traditional Chinese Medicine is derived from the Important Prescriptions Worth a Thousand Gold for Emergency （Bei Ji Qian Jin Yao Fang） written by SUN Si-miao in the Tang dynasty. The present study systematically explored the origin， development， historical evolution， and clinical application of Xiao Xumingtang. As revealed by the results， Xiao Xumingtang as well as its analogues are primary prescriptions indicated for apoplexy before the Tang and Song dynasties and serve as the benchmark for the treatment of apoplexy. After the Song dynasty， due to the changes in the understanding of the pathogenesis of apoplexy and the limitations of the understanding of Xiao Xumingtang， its clinical application to apoplexy gradually decreased. In modern times， it has been re-recognized and applied， during which its clinical applications have undergone great changes. Its clinical applications are extensive， involving a variety of diseases related to the brain and nervous systems， such as stroke and its sequelae， peripheral facial paralysis， rheumatoid arthritis， hypertension， and other diseases related to the motor nervous system. Its primary indications are stroke and its sequelae， followed by peripheral facial paralysis. Other new indications are gradually found. This study is expected to provide references for the clinical application of Xiao Xumingtang and the transformation of new drugs.

Thoughts on path of R&D and registration of innovative traditional Chinese medicine with synchronous transformation of "series prescriptions" / 中国中药杂志

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.

In vitro and in vivo anti-HMPV activity of JH001 isolated from Chinese medicinal herbs / 中国药理学与毒理学杂志

OBJECTIVE Human metapneumovirus (hMPV) is semblable to respiratory syncytial virus (RSV) which causes respiratory infections typically characterized by cough, runny nose, fever, and nasal congestion but sometimes progressing to bronchiolitis and pneumonia. Whereas, there is no corresponding drug to inhabit the virus. Studies of new compounds with potential anti-HMPV activity could produce clinical value. Chinese herbal medicine played a great role during COVID-19, therefore we choose some small molecular (JH001) extracted from botany to investigate therapeutic effect on hMPV and the underlying mechanisms. METHODS In this study, 16HBE cells were used as a model to explore in vitro antiviral effect. Cytotoxicity assays were performed before the antiviral tests, cell viability of 16HBE cells handled by different concentration of JH001 was estimated by Cell Counting Kit-8 (CCK-8). Then RT-qPCR, immunofluores?cence, and flow cytometer were used to test the viral titer after cells infected with hMPV. Eventually, 6-8 weeks mice were infected intranasally with 60 μL of hMPV, the control group was treated with 0.9％ saline water, other groups were administered with JH001 and ribavirin, then the lung virus titer and protective effect in lung were judged. RESULTS The obtained JH001 exhibited no cytotoxicity to 16HBE cells during 6.25 - 200 μmol · L-1. RT-QPCR demonstrated that JH001 showed obvious inhabitation to the viral replication and showed great significance compared with saline. And fluo?rescence exhibited distinct decrease of hMPV-N protein, flow cytometer results showed that MFI decrease evidently. Sig?nificant reduction of N-gene expression was observed in those mice treated with JH001 compared with saline group, which indicated that JH001 probably had protective and therapeutic effect on viral replication. CONCLUSION This study illustrated that JH001 might be a promising option for small molecular against hMPV and JH001 might be worthy of fur?ther development and used as a potential therapeutic strategy for other respiratory viruses in the future.

Comparative study on anti-inflammatory effect of Lonicerae Japonicae Flos and Lonicerae Flos / 中国中药杂志

The aim of this paper was to observe the anti-inflammatory action and mechanism of Lonicerae Japonicae Flos extract and Lonicerae Flos extract in xylene-induced ear swelling experiment and lipopolysaccharide(LPS)-induced RAW264.7 cell inflammatory model. In vivo, xylene-induced mouse auricle swelling model was used to detect the auricle swelling degree and swelling inhibition rate of Lonicerae Japonicae Flos extract and Lonicerae Flos extract; the pathological changes of mice auricle were observed by hematoxylin eosin(HE) staining. In vitro, RAW264.7 inflammatory cell model was induced by LPS, where the cytotoxic effects of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on RAW264.7 cells were detected by CCK-8 method; Griess method was used to detect the effect of Lonicerae Japonicae Flos extract and Lonicerae Flos extract on nitric oxide(NO) production, and ELISA method was used to detect the content of inflammatory factors interleukin-6(IL-6), IL-1β, and tumor necrosis factor-α(TNF-α). At last, Western blot was used to detect the protein changes of cyclooxygenase 1(COX1), COX2 and inducible nitric oxide synthetase(iNOS) for RAW264.7 cells. The results showed that both Lonicerae Japonicae Flos extract and Lonicerae Flos extract could significantly inhibit the degree of auricle swelling caused by xylene in mice and the inhibition rate was positively correlated with the drug dose. Furthermore, both of them could reduce the infiltration of lymphocytes and neutrophils in mouse ear tissues. For in vitro experiments, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract inhibited NO secretion in RAW264.7 cells, down-regulated the release of IL-1β, IL-6 and TNF-α, and down-regulated iNOS protein and COX2, NF-κB p65 protein content. In conclusion, both Lonicerae Japonicae Flos extract and Lonicerae Flos extract have good anti-inflammatory effect, and the mechanism may be related with the inhibition of NF-κB signaling pathway.

Hepatotoxicity Effect of Xanthii Fructus on Immune-sensitive Rat Model Induced by Endotoxin / 中国实验方剂学杂志

Objective:To investigate the pharmaceutical idiosyncratic hepatotoxicity effect of Xanthii Fructus on the immune-sensitive rat model induced by endotoxin lipopolysaccharide （LPS）. Method:The SD rats were randomly divided into five groups： control group， model group， and three Xanthii Fructucs groups. The immune-sensitive rat model was established by LPS （iv. 0.7 mg·kg-1， twice every 7 days）. Then， the rats in control and model groups received the equal volume of distilled water， while the rats in Xanthii Fructus groups were administrated with water extract of Xanthii Fructus intragastrically （1.67， 5.01， 16.7 g·kg-1， respectively） for 14 days. The serum and liver of the rats were collected on the 7th and 14th day to examine the levels of hepatotoxic biomarkers， including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bilirubin （TBil）， alkaline phosphatase （ALP）， and total bile acids （TBA）， and liver histopathology. In addition， inflammatory factors， including interleukin-1β（IL-1β）， interleukin-2（IL-2）， interleukin-6（IL-6）， interleukin-10（IL-10）and tumor necrosis factor-α（TNF-α）of the idiosyncratic hepatotoxicity rats， were determined by enzyme-linked immunosorbent assay（ELISA）. Result:The immune-sensitive model rats showed elevated levels of IL-1β， IL-6（P<0.05，P<0.01）， and mild inflammatory cells infiltrated in portal area of liver significantly （P<0.05）， with no significant changes in hepatotoxic biomarkers. Meanwhile， there was no significant change between Xanthii Fructus groups and model rats in the levels of hepatotoxic biomarkers， inflammatory factors and hepatic lesions. Conclusion:Water extract of Xanthii Fructus intragastrically does not affect the levels of hepatotoxic biomarkers， inflammatory factors and hepatic lesions in rats induced by LPS intravenously. That is to say， Xanthii Fructus does not induce pharmaceutical idiosyncratic hepatotoxicity.

Application of an effect-constituents index for the quality evaluation of the traditional Chinese medicine rhubarb / 药学学报

To explore the application of an effect-constituents index (ECI) for the quality evaluation of rhubarb, we carried out the simultaneous determination of 12 chemical components by ultra-performance liquid chromatography and used the ICR mouse constipation model to determine the diarrhea biopotency of these 12 components. With the diarrhea biopotency of sennoside A as a reference, the diarrhea biopotency weight coefficient of each chemical component was obtained. A multi-component chemical quantitative analysis combined with the biopotency weight coefficients for rhubarb was developed, named the diarrhea ECI. Animal experiment ethics requirements were approved by the Animal Experimental Ethics Committee of the 302 Hospital of the People's Liberation Army (Grant Number: IACUC-2015-012). The results showed that there were significant differences in the content of the 12 chemical components in different batches of processed products of rhubarb. Especially worthy of attention was the content of aloe-emodin-8-O-β-D-glucoside in sample Rh03, nearly 40-fold higher than that in Rh07 (4.79 vs 0.12 mg·g-1), and the content of rhein-8-O-β-D-glucoside in sample Rh03, nearly 45 times higher than that in Rh07 (3.56 vs 0.08 mg·g-1). The actual measured diarrhea biopotencies of the 12 chemical components ranged from 61.65 ± 4.28 to 233.84 ± 5.58 U·mg-1. The calculated diarrhea effect-constituents indices of 16 rhubarb samples ranged from 1.07 (Rh15) to 19.38 (Rh03), and the actual measured diarrhea biopotencies of 16 rhubarb samples based the ICR mouse constipation model ranged from 23.84 U·g-1 (Rh16) to 310.94 U·g-1 (Rh05). The correlation between the diarrhea ECIs and the actual measured diarrhea biopotencies of 16 rhubarb samples was good (r = 0.969 5), suggesting that the diarrhea effect-constituents indices may be the most suitable for evaluating the quality of different rhubarbs with regard to diarrhea.

Quality evaluation and toxicity assay for injectable traditional Chinese medicine using Microtox technology / 药学学报

Injectable traditional Chinese medicine often contains multiple components including undefined toxic substances, can have high variability between batches, with undefined mechanisms of action. It is urgent to improve the quality and consistency and reduce the toxicity risk of traditional Chinese medicine. The Microtox technology is a simple, rapid method for the detection of toxic substances in the environment that uses non-pathogenic luminescent bacteria as an indicator, and the change in luminosity as an index. Using this bioassay we have systematically applied Microtox technology for the detection of microtoxicity in injectable traditional Chinese medicine. As a new method of bioactivity characterization, Microtox technology is expected to be used in the detection of quality fluctuations and toxicity risks at an early stage in the preparation of injectable traditional Chinese medicines and to improve the quality of injectable traditional Chinese medicine.

Traditional Chinese medicine (tumor) prevention and evaluation model based on ultra-early immune response information amplification index naCTL and multidimensional immunoinformatic index TCR/BCR/HLA effective diversity / 中国中药杂志

The best time of tumor intervention is before the formation of tumor. However,due to the limited number of tumor cells,it is difficult to quantify tumor cells and immunity by the current methods available( such as CTC,ct DNA). This affects the tumor prevention in this period,and the in-depth detection,intervention and evaluation of traditional Chinese medicine( TCM)( tumor) prevention. Due to the limitations of the current detection,the evaluation system turns to detect tumor neoantigen-specific CTL( naCTL) that are directly relating to tumor cells and proliferate to high order of magnitudes after activation,and immune repertoire( TCR/BCR/HLA) effective diversity,introduces immune checkpoints,uses information of " disease" in Western medicine and " syndrome" in TCM( prevention),and sets up a multi-dimensional statistical immunity model using a variety of data analysis and related algorithms. This model can amplify the ultra-early information of tumor,indirectly evaluate the quantity and status of tumor cells,and provide quantitative measurement and new evaluation methods for the normalization of immunity and TCM( tumor) prevention. This model is not only one of important evaluation methods for resisting tumor immunity and treating TCM( tumor) prevention,but also will reveal the scientific connotation of TCM syndrome from the perspective of immunology.

Generalized science of Chinese material medica-from preventive treatment of disease to Chinese medicine health industry / 中国中药杂志

Based on the systematic summary of the results of the fourth general survey of traditional Chinese medicine resources, the cultivation of large varieties of Chinese material medica and the latest research on health industrial development, the novel concepts and scientific connotations of generalized science of Chinese material medica are put forward, and the basic ideas and methods of a new Chinese medicine academic system, the cultivation system of large varieties of Chinese medicinal materials and the application system of the large health industry are constructed. This kind of generalized science of Chinese material medica, rooted in the traditional Chinese culture and the theory of "preventive treatment of disease", can avoid the narrow prospect induced by the increasing specialization and refinement of knowledge of science of Chinese material medica. It will play an important role in the modernization, industrialization, internationalization of traditional Chinese medicine.

New method for evaluating pharmacodynamics of traditional Chinese medicine compounds based on its moderate regulation and principle of balanced adjustment of immunity under pan-immunomic / 中国中药杂志

For the basic research on the traditional Chinese medicine(TCM), objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds are hardly to break though. While, the modern immunology points out that the body is a counterbalance state and immune imbalance is the root of sickness. The thinking mode of treating diseases in traditional Chinese medicine is also "balance", considering disease is the result of bias which present the imbalance of "Yin counters Yang", "exterior counters interior", "cold counters heat" and "weak counters strong". The Chinese herbal compound formula preparation was applied on disease therapy based on theory of Chinese medicine, which was confirmed by long period clinical application. It is composed of multi-compounds and has the characteristic of multi-targeting. Integrative medicine has spawned pan-immunomics, and the evaluation of immune function (immune balance) has become an important basis for diagnosis and treatment models of integrative medicine. In addition, balance is the core idea of whole-systemic conception of traditional Chinese medicine. Therefore, we speculate that immune balance under pan-immunomic can bridge the traditional Chinese medicine and modern integrative medicine and is the important basis for objective syndrome of traditional Chinese medicine and evaluation criteria of traditional Chinese medicine compounds. According to the bridging theory, we attempt to utilize informatics and statistical methods to construct an evaluation system for pharmacodynamics of traditional Chinese medicine based on its moderate regulation and the balanced adjustment of immunity under pan-immunomic, which further reveal the scientific essence of the whole-systemic view of traditional Chinese medicine. This research brings out a new valuable strategy and provides a theoretical basis for accelerating the transformation of traditional Chinese medicine, especially the exploitation of Chinese herbal compound formula, and constructing the new drug innovation and review system for traditional Chinese medicine. Besides as a reference for traditional Chinese medicine objective syndrome and pharmacodynamics of traditional Chinese medicine compounds, the evaluation system can screen the immunity of sub-health population also. With the continuous accumulation of clinical sample and data, the evaluation system will be more accurate and intelligent.

Moderation-integrated-balance presupposition of Chinese medicine compound and pharmacological problems in traditional Chinese drug research / 中国中药杂志

The moderation-integrated-balance presupposition (MIBP) of Chinese medicine compound was first proposed in this paper based on the review of function characteristics and action principles of Chinese medicine compound. Furthermore, the pharmacological problems of traditional Chinese drug research were discussed in details. The results were of important value in accelerating the transformation of traditional Chinese medicine compound, and constructing the new drug innovation and review system for traditional Chinese medicine.

Optimization of reaction conditions and methodological investigation on microtox-based fast testing system for traditional Chinese medicine injection / 中国中药杂志

Vibrio fischeri CS234 was used to establish and optimize microtox assay system, laying a foundation for the application of this method in comprehensive acute toxicity test of traditional Chinese medicine (TCM) injections. Firstly, the Plackett-Burman method was carried out to optimize the factors which would affect Vibrio fischeri CS234 luminescence. Secondly, ZnSO4•7H2O was chosen as reference substance to establish its reaction system with quality control samples. The optimal luminescence conditions were achieved as follows: ①At a temperature of (15±1) ℃, Vibrio fischeri CS234 lyophilized powders were balanced for 15 min, then, 1 mL resuscitation fluid was added and blended for 10 min. 100 μL bacteria suspension was taken to measure the initial luminescence intensity, and then 1 mL resuscitation fluid or test sample was immediately added; after reaction for 10 min, corresponding luminescence intensity was measured again. Resuscitation diluent, osmotic pressure regulator and ZnSO4•7H2O stock solution showed no interference to the determination of Vibrio fischeri CS234 luminescence intensity, so this method was of good specificity. The within-and between-batch precisions of quality controls and the lower limit of quantification (LLOQ) samples were <5% and <10% respectively, while the accuracy ranged between 85.8% and 103.2%. The standard curve equation of ZnSO4•7H2O ranged from 3.86 mg•L⁻¹ to 77.22 mg•L⁻¹ (final concentrations) was y=21.78lnx-15.14, R2=0.998; meanwhile, IC₅₀ of ZnSO4•7H2O to Vibrio fischeri CS234 was 19.90 mg•L⁻¹. ZnSO4•7H2O stock solution and its quality controls were continuously investigated for 120 h and 8 h respectively, and their RSD was lower than 2%, indicating stability at room temperature and 4 ℃ storage conditions. Between pH 4.5-8.0, luminescence intensity of Vibrio fischeri CS234 was controlled within ±10%, and such pH value range could meet the testing needs of the vast majority of traditional Chinese medicine injections. The Vibrio fischeri strain CS234 assay system was specific, stable, sensitive, accurate and adaptable after optimization, so it was suitable for the comprehensive acute toxicity assessment of TCM injections.

Study on molecular mechanism of Euodiae Fructus on liver toxicity in MICE / 中国中药杂志

<p><b>OBJECTIVE</b>To study the molecular mechanism of extracts from Euodia rutaecarpa on hepatotoxicity in mice.</p><p><b>METHOD</b>Totally 30 KM mice were divided into 3 groups and orally administrated extracts from E. rutaecarpa for consecutively 15 days. The expressions of Erkl/2, CDK8, CK1e, Stat3 and Src were detected by Western blotting method.</p><p><b>RESULT</b>The extracts from E. rutaecarpa could up-regulated Erkl/2, CDK8 and CK1e expressions (P <0.01) and down-regulate Stat3 and Src (P <0.01).</p><p><b>CONCLUSION</b>The molecular mechanism of E. rutaecarpa on hepatotoxicity may be correlated with Erkl/2, CDK8, CKle, Stat3 and Src signal molecules.</p>

Dynamic accumulation regulation of curcumin, demethoxycurcumin and bisdemethoxyeurcumin in three strains of curcuma longae rhizome / 中国中药杂志

The paper is aimed to study the dynamic accumulation regulation of curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxyeurcumin (BDMC) in three strains of Curcuma longa, and provide scientific references for formalized cultivation, timely harvesting, quality control and breeding cultivation of C. longa. The accumulation regulation of the three curcumin derivatives was basically the same in rhizome of three strains. The relative contents decreased along with plant development growing, while the accumulation per hectare increased with plant development growing. The accumulation of curcuminoids per hectare could be taken as the assessment standard for the best harvest time of C. longa. A3 was the best strain in terms of Cur and BDMC content.

Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose / 中国中药杂志

To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD < 15%). The precision, accuracy, recovery and applicability were found to be adequate for pharmacokinetic studies. Pharmacokinetic parameters of THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

Effects of rhein on the function of human mesangial cells in high glucose environment / 药学学报

<p><b>AIM</b>To study the mechanisms of anti-diabetic nephropathy of rhein on cultured human mesangial cells (HMCs).</p><p><b>METHODS</b>To mimic the hyperglycemic (HG) environment of diabetic nephropathy, 30 mmol x L(-1) glucose were added to 10% FBS RPMI 1640. The HMCs were treated with rhein for 8, 24, 48 or 72 h, at these time, the bioactivity, total activity of transforming growth factor-beta1 (TGFbeta1), activity of p38MAPK (p38 mitogen-activated protein kinases, by using immunoprecipitate and Western blot), MMP-2 (matrix metalloproteinase-2), and MMP-9 (matrix metalloproteinase-9, by using gelatinase zymography) and the proliferation of HMCs in high glucose media were measured. Meanwhile the levels of secretion of FN in cultured HMCs were measured.</p><p><b>RESULTS</b>The results showed that rhein markedly inhibit the proliferation of HMCs, significantly reduce the bioactivity of TGFbeta1 and FN secretion in HMCs, and decrease the increased activity of p38MAPK, but showed no action on the activities of MMP-2 and MMP-9.</p><p><b>CONCLUSION</b>Rhein reduced the secretion of FN and inhibited the proliferation of HMCs may through inhibiting the bioactivities of TGFbeta1 and p38MAPK.</p>