[Screening and expression analysis of transcription factors involved in genuineness of Codonopsis pilosula in Shanxi].

This study aims to mine the transcription factors that affect the genuineness of Codonopsis pilosula in Shanxi based on the transcriptome data of C. pilosula samples collected from Shanxi and Gansu, and then analyze the gene expression patterns, which will provide a theoretical basis for the molecular assisted breeding of C. pilosula. Gene ontology(GO) functional annotation, conserved motif prediction, and gene expression pattern analysis were performed for the differential transcription factors predicted based on the transcriptome data of C. pilosula from different habitats. A total of 61 differentially expressed genes(DEGs) were screened out from the transcriptome data. Most of the DEGs belonged to AP2/ERF-ERF family, with the conserved motif of [2X]-[LG]-[3X]-T-[3X]-[AARAYDRAA]-[3X]-[RG]-[2X]-A-[2X]-[NFP]. Forty-three of the DEGs showed significantly higher gene expression in C. pilosula samples from Shanxi than in the samples from Gansu, including 11 genes in the AP2/ERF-ERF family, 5 genes in the NAC fa-mily, 1 gene in the bHLH family, and 2 genes in the RWP-RK family, while 18 transcription factors showed higher expression levels in the samples from Gansu. GO annotation predicted that most of the DEGs were enriched in GO terms related to transcriptional binding activity(103), metabolic process(26), and stress response(23). The expression of transcription factor genes, CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 was higher in the samples from Shanxi and in the roots of C. pilosula. CpNAC92, CpbHLH128, and CpRAP2-7 responded to the low temperature, temperature difference, and iron stresses, while CpNAC100 only responded to low temperature and iron stresses. The screening and expression analysis of the specific transcription factors CpNAC92, CpNAC100, CpbHLH128, and CpRAP2-7 in C. pilosula in Shanxi laid a theoretical foundation for further research on the mechanism of genuineness formation of C. pilosula.

Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhi-zi-chi decoction (ZZCD), from "Treatise on Febrile Diseases", is a typical traditional Chinese medicine herb pair, which consists of Gardeniae Fructus (GF) and Semen Sojae Praeparatu (SSP). In clinical research, ZZCD was widely used to fight depression, remove annoyance. Many studies have reported that gut microbiota is critical target for the influence of depress through gut-brain axis, and our previously studies have found that ZZCD exhibiting antidepressant effect was through the gut-brain axis. However, the specific mechanism by which gut microbiota mediates the pharmacokinetics parameters of active compounds from ZZCD during the process of depression treatment has not yet been studied. AIM OF THE STUDY: To explore the differences in pharmacokinetics characters of bioactive iridoids from ZZCD and study the changes of gut microbiota at different stages of depression with the personalized medicine of ZZCD. MATERIALS AND METHODS: A new strategy exploring the relationship among disease phenotypes (D), intestinal microbiota (I), enzymes (E) and traits of metabolism (T) named as "DIET" was established. Firstly, a fast, selective and sensitive ultra-performance liquid chromatography coupled with tandem mass spectrometer (UPLC-MS/MS) was established and validated to quality the main bioactive compounds from ZZCD and compare the pharmacokinetics and bioavailability of different iridoids prototypes and metabolites from ZZCD between normal and chronic unpredictable mild stress rats. Subsequently, the activity of corresponding metabolic enzymes of anti-depressive compounds, ß-glucosidases and sulfotransferases, were analyzed by ρ-nitrophenyl-ß -D-glucopyranoside and sulfotransferases ELISA kits, respectively. Finally, 16S rRNA gene sequencing was adopt to analyze intestinal bacteria composition for the treatment of depression by ZZCD. RESULTS: The antidepressant effect of ZZCD was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide and genipin 1-gentiobioside, under the depression state. With the ZZCD treatment, the depression was improved, but the exposures of anti-depressive compounds from ZZCD gradually decreased. Meanwhile, there were the corresponding decreased trends on the activity of ß-glucosidases and sulfotransferases. With the consumption of ZZDC and the improvement of depression, the exposures of anti-depressive iridoid glycosides decreased and the activity of metabolism enzymes restored. Meanwhile, the dysbiosis of pathogenic bacteria (Bacteroidota) induced by depression was ameliorated and the probiotics (Firmicutes) at the phylum and genus level raised, the two phyla are closely related to the production of ß-glucosidase and sulfotransferases. CONCLUSIONS: It is the first proposed that ZZCD could personalized to treat depression at different stages targeting gut microbiota and gut microbiome could emerged as a potential diagnostic and therapeutic biomarker in depression.

Antimicrobial Activity of Tannic Acid In Vitro and Its Protective Effect on Mice against Clostridioides difficile.

Clostridioides difficile infection (CDI), recurrently reported as an urgent threat owing to its increased prevalence and mortality, has attracted significant attention. As the use of antibiotics to treat CDI has many limitations, such as high recurrence rate, the need to actively seek and develop other drugs that can effectively treat CDI with fewer side effects has become a key issue in CDI prevention and treatment. This study aimed to evaluate the inhibitory effect of Galla chinensis (GC) and its main component, tannic acid (TA), against C. difficile in vitro and its therapeutic effect on CDI in vivo. When GC and TA concentrations were 250 and 64 mg/L, respectively, the cumulative antibacterial rate against C. difficile reached 100%. The sub-MIC of TA significantly inhibited C. difficile sporulation, toxin production, and biofilm formation in vitro. Compared with the CDI control group, TA-treated mice lost less weight and presented a significantly improved survival rate. TA significantly reduced the number of spores in feces, decreased serum TcdA level, and increased serum interleukin 10 (IL-10). Based on the inhibitory effect of TA on C. difficile in vitro and its therapeutic effect on the CDI mouse model, we consider TA as a potentially effective drug for treating CDI. IMPORTANCE Clostridioides difficile is one of the major pathogens to cause antibiotic-associated diarrhea. Although antibiotic treatment is still the most commonly used and effective treatment for CDI, the destruction of indigenous intestinal microbiota by antibiotics is the main reason for the high CDI recurrence rate of about 20%, which is increasing every year. Moreover, the growing problem of drug resistance has also become a major hidden danger in antibiotic treatment. GC has been used to treat diarrhea in traditional Chinese medicine. In the present study, we evaluated the inhibitory effect of TA, the main component of GC, on dissemination and pathogenic physiological functions of C. difficile in vitro, as well as its therapeutic efficacy in a CDI model. Overall, TA is considered to be a potentially effective drug for CDI treatment.

[Correlation between drug-induced liver injury in rats caused by Xianling Gubao oral preparation and extraction process].

In light of the liver injury risk associated with the oral administration of Xianlin Gubao oral preparation, this study compared the differences in liver injury induced by two different extraction processes in rats and explored the correlation between hepatotoxicity and extraction process from the perspective of the differences in the content of the relevant components. Thirty male Sprague-Dawley(SD) rats were randomly divided into a normal group, tablet extract groups of different doses, and capsule extract groups of different doses, with 6 rats in each group. Each group received continuous oral administration for 4 weeks. The assessment of liver injury caused by different extracts was conducted by examining rat body weight, liver function blood biochemical indicators, liver coefficient, and liver pathological changes. In addition, a high-performance liquid chromatography(HPLC) method was established to simultaneously determine the content of icariin, baohuoside I, and bakuchiol in the extracts to compare the differences in the content of these three components under the two extraction processes. The results showed that both extracts caused liver injury in rats. Compared with the normal group, the tablet extract groups, at the studied dose, led to slow growth in body weight, a significant increase in triglyceride levels(P<0.05), a significant decrease in liver-to-brain ratio(P<0.05), and the appearance of hepatic steatosis. The capsule extract groups, at the studied dose, resulted in slow growth in body weight, a significant increase in aspartate aminotransferase levels(P<0.05), a significant decrease in body weight, liver weight, and liver-to-brain ratio(P<0.05), and the presence of hepatic steatosis and inflammatory cell infiltration. In comparison, the capsule extraction process had a higher risk of liver injury. Furthermore, based on the completion of the liquid chromatography method, the content of icariin and baohuoside Ⅰ in the capsule extract groups was 0.83 and 0.81 times that in the tablet extract groups, respectively, while the bakuchiol content in the capsule extract group was 29.80 times that in the tablet extract groups, suggesting that the higher risk of liver injury associated with the capsule extraction process may be due to its higher bakuchiol content. In summary, the differences in rat liver injury caused by the two extracts are closely related to the extraction process. This should be taken into consideration in the formulation production and clinical application.

Theacrine, a Potent Antidepressant Purine Alkaloid from a Special Chinese Tea, Promotes Adult Hippocampal Neurogenesis in Stressed Mice.

Daily intake of tea has been known to relate to a low risk of depression. In this study, we report that a special variety of tea in China, Camellia assamica var. kucha (kucha), possesses antidepressant effects but with less adverse effects as compared to traditional tea Camellia sinensis. This action of kucha is related to its high amount of theacrine, a purine alkaloid structurally similar to caffeine. We investigated the antidepressant-like effects and mechanisms of theacrine in chronic water immersion restraint stress and chronic unpredictable mild stress mice models. PC12 cells and primary hippocampal neural stem cells were treated with stress hormone corticosterone (CORT) to reveal the potential antidepression mechanism of theacrine from the perspective of adult hippocampus neurogenesis. Results of behavioral and neurotransmitter analysis showed that intragastric administration of theacrine significantly counteracted chronic stress-induced depression-like disorders and abnormal 5-hydroxytryptamine (5-HT) metabolism with less central excitability. Further investigation from both in vivo and in vitro experiments indicated that the antidepressant mechanism of theacrine was associated with promoting adult hippocampal neurogenesis, via the modulation of the phosphodiesterase-4 (PDE4)/cyclic adenosine monophosphate (cAMP)/cAMP response-element binding (CREB)/brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway. Collectively, our findings could promote the prevalence of kucha as a common beverage with uses for health care and contribute to the development of theacrine as a potential novel antidepressant medicine.

Neoisoliquiritin exerts tumor suppressive effects on prostate cancer by repressing androgen receptor activity.

BACKGROUND: Prostate cancer (PCa) is a major cause of morbidity and mortality in men in both developed and developing countries. Androgens and the androgen receptor (AR) play predominant roles in the progression of PCa. Neoisoliquiritin (NEO) belongs to the class of licorice (Glycyrrhiza) flavonoids, which have a variety of biological activities including anti-depressant, anti-tumor-promoting, and anti-inflammation properties. Licorice root has cancer chemopreventive effects and has been given to PCa patients as an ingredient of PC-SPES, a commercially available combination of eight herbs. Therefore, we determined if NEO can suppress the proliferation of PCa cells. PURPOSE: We investigated whether and how NEO exerts its anti-neoplastic activity against PCa. METHODS: The Cell Counting Kit 8 and flow cytometry were used to evaluate the effects of NEO on the proliferation and cell cycle progression of AR-dependent (LNCaP) and AR-independent (PC3) PCa cells. RNA sequencing was employed to examine the genome-wide changes in responsiveness to NEO in LNCaP cells. Quantitative PCR, Western blotting, docking, chromatin immunoprecipitation, and dual-luciferase reporter assays were conducted to determine the mechanism of action of NEO and its potential cross-talk with AR. A LNCaP xenograft nude mouse model was used to determine the inhibitory effects of NEO on AR-dependent PCa tumors in vivo. RESULTS: NEO inhibited LNCaP cell proliferation in vitro by inducing G0/G1 phase cell cycle arrest. Conversely, NEO treatment had no effect on PC3 cells. Transcriptomic analysis indicated that AR signaling might be the key target of NEO in preventing PCa. NEO regulated AR-mediated cell growth suppression and AR-sensitized cell cycle arrest in LNCaP cells. NEO also blocked several key steps in the AR signaling pathway, including proposed targeting to the ligand binding pocket of AR by computer modeling, modulating AR-androgen response element DNA-binding activity, inhibiting the expression and transcriptional activity of AR, and suppressing downstream AR signaling. CONCLUSIONS: NEO negatively regulates AR expression and activity, thus supporting the tumor suppressive role for NEO in AR-dependent PCa.

Adaptation in the Dorsal Belt and Core Regions of the Auditory Cortex in the Awake Rat.

The rat auditory cortex is divided anatomically into several areas, but little is known about the functional differences in information processing among these areas. Three tonotopically organized core fields, namely, the primary (A1), anterior (AAF), and ventral (VAF) auditory fields, as well as one non-tonotopically organized belt field, the dorsal belt (DB), were identified based on their response properties. Compared to neurons in A1, AAF and VAF, units in the DB exhibited little or no response to pure tones but strong responses to white noise. The few DB neurons responded to pure tones with thresholds greater than 60 dB SPL, which was significantly higher than the thresholds of neurons in the core regions. In response to white noise, units in DB showed significantly longer latency and lower peak response, as well as longer response duration, than those in the core regions. Responses to repeated white noise were also examined. In contrast to neurons in A1, AAF and VAF, DB neurons could not follow repeated stimulation at a 300 ms inter-stimulus interval (ISI) and showed a significant steeper ISI tuning curve slope when the ISI was increased from 300 ms to 4.8 s. These results indicate that the DB processes auditory information on broader spectral and longer temporal scales than the core regions, reflecting a distinct role in the hierarchical cortical pathway.

Increased ski expression levels are associated with a higher risk and poor prognosis in patients with gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most commonly diagnosed primary mesenchymal tumors of the gastrointestinal tract and 30% of GISTs are associated with a high recurrence risk or metastasis. The current risk classification criteria of the National Comprehensive Cancer Network are based on tumor size, mitotic activity and localization. Investigating additional biomarkers associated with clinical risk may aid in the diagnosis of GIST and improves prediction of patient prognosis. In the present study, the value of using the expression levels of the oncoprotein ski as a prognostic predictor for GISTs was investigated. The results demonstrated that high ski expression levels were correlated with high risk and recurrence rates and indicated poor prognosis regarding median disease-free survival. Overall, the present study suggests that ski expression levels may serve as a predictor for clinical risk and prognosis of patients with GISTs.

Association between vitamin D and prediabetes: A PRISMA-compliant meta-analysis.

BACKGROUND: Previous studies showed conflicting results for associations between vitamin D and prediabetes. The study aimed to make a systematic review and meta-analysis for the association between vitamin D and prediabetes. METHODS: We searched for articles identifying associations between vitamin D and prediabetes published in English until July 2019 in following databases (PubMed, Web of Science, EMBASE, Medline, Google Scholar, and Cochrane databases). Finally, we conducted these analyses (heterogeneities examination, meta-regression analyses, sensitivity analysis, and publication bias examination) using STATA 12.0 software (Stata Corporation, College Station, TX, USA). Q test and I were applied to examine heterogeneities between studies. RESULTS: Twelve studies were finally included in the present study. The study included 4 studies to explore the association between serum levels of 25-hydroxy (OH) vitamin D and risks of prediabetes (including 3094 participants). Additionally, the present study included 8 studies (including 865 individuals with prediabetes treated with vitamin D supplementation and 715 patients treated with placebo) to assess differences in therapeutic effects between individuals with prediabetes treated with vitamin D supplementation and those treated with placebo. The present study showed no significant associations between low serum levels of 25(OH) vitamin D and high risk of prediabetes. Additionally, the study showed no significant differences in changes of hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and homeostatic model assessment of insulin resistance (HOMA-IR) between individuals with prediabetes treated with vitamin D and those patients given placebo, whereas meta-analysis showed significantly greater changes in 2-hour oral glucose tolerance test (2HPG) in individuals with prediabetes treated with vitamin D, compared with individuals with prediabetes treated with placebo. CONCLUSION: The study supported that low serum levels of 25(OH) vitamin D increased the risk of prediabetes. In addition, vitamin D supplementation improves impaired glucose tolerance in prediabetes. However, more large-scale clinical trials are essential to explore the association between vitamin D and prediabetes.

Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.

OBJECTIVE: Acylcarnitine metabolism disorder contributes significantly to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). There are, however, few ideal medications for NAFLD, which work by targeting acylcarnitine metabolism. The aim of this study was to investigate the protective effects of theacrine, a rare purine alkaloid isolated from Camellia assamica var. kucha, against acylcarnitine metabolism disorder in NAFLD. METHODS: The pharmacological activities of theacrine were studied using high-fat diet (HFD)-fed ApoE-/- and C57BL/6J mice models. Oleate-treated HepG2 and L-02 cells were used to investigate the molecular mechanism of theacrine on acylcarnitine metabolism. The target of theacrine was confirmed in vitro as the blockade of sirtuin 3 (SIRT3) and protein kinase A. RESULTS: Theacrine inhibits hepatic steatosis and liver inflammation and improves energy expenditure in HFD-fed mice. Theacrine ameliorates acylcarnitine metabolism disorder in HFD-fed mice and oleate-treated hepatocytes by improving fatty acid oxidation. The underlying mechanism involves theacrine's activation of the mitochondrial deacetylase SIRT3 and consequently, the increased activity of long-chain acyl coenzyme A dehydrogenase (LCAD) through deacetylation. CONCLUSION: Theacrine promotes acylcarnitine metabolism in NAFLD through the SIRT3/LCAD signaling pathway. The target of theacrine's activities on NAFLD is identified as SIRT3.

Tanshinone Suppresses Arecoline-Induced Epithelial-Mesenchymal Transition in Oral Submucous Fibrosis by Epigenetically Reactivating the p53 Pathway.

Oral submucous fibrosis (OSF) induced by chewing of the areca nut has been considered to be a precancerous lesion with a high probability of developing oral squamous cell carcinoma. Tanshinone (TSN) is the main component extracted from Salvia miltiorrhiza, a traditional Chinese medicine, which was found to have diverse pharmacological effects, such as anti-inflammatory and antitumor. In the current study, we aimed to identify the inhibitory effects and the underlying mechanism of TSN on OSF progress. We found that treatment with TSN inhibited the arecoline-mediated proliferation of primary human oral mucosal fibroblasts and reversed the promotive effects of arecoline on the EMT process. By RNA deep sequencing, we screened two possible targets for TSN: LSD1 and p53. We confirmed that p53 is much lower in OSF than in normal mucous tissues. In addition, p53 and its downstream molecules were decreased by arecoline treatment in oral mucosal fibroblasts, which was reversed by treatment with TSN in a dose-dependent manner. Our results also revealed that arecoline stimulation resulted in hypermethylation of the promoter of TP53 and subsequent downregulation of p53 levels, which was reversed by TSN. Furthermore, we identified that LSD1 could epigenetically activate TP53 by recruiting H3K27me1 and H3K4m2 to its promoter. Our findings provide new insights into the mechanism by which TSN influences arecoline-induced OSF and rationale for the development of clinical intervention strategies for OSF and even oral squamous cell carcinoma.

[HPLC-MS/MS determination of residual amount of 4 plant growth retardants in 6 dried root and Rhizome Herbs].

HPLC-MS/MS was applied to the determination of residual amount of plant growth retardant such as paclobutrazol, daminozide, chlormequat and mepiquat chloride in dried root and rhizome herbs. The sample was extracted twice with acetonitrile containing 0.1% formic acid. The separation was performed on a Waters Atlantis HILIC column with an elution system consisting of acetonitrile-5 mmol•L⁻¹ ammonium acetate solution with 0.1% formic acid, methanol and acetonitrile. The MS spectrum was acquired in positive mode with multiple reactions monitoring (MRM). The linear range was 6-1 500 µg•kg⁻¹, and the optimized method offered a good linear correlation (r>0.997 8), excellent precision (RSD<11%) and acceptable recovery (from 79.3% to 103.3%). Four kinds of plant growth retardant have detected in some ofhenise herbs like Ophiopogonis Radix, Angelicae Sinensis Radix, Achyranthis Bidentatae Radix, Alismatis Rhizoma, Chuanxiong Rhizama and Notoginseng Radix et Rhizama, is among the more severe cases, dwarf lilyturf, multi-effect azole detection quantity is 63.4~1 351.66 µg•kg⁻¹, and Daminozide was detected in Ophiopogonis Radix, Angelicae Sinensis Radix, Chuanxiong Rhizama, Alismatis Rhizoma.

Icariin Attenuates OGD/R-Induced Autophagy via Bcl-2-Dependent Cross Talk between Apoptosis and Autophagy in PC12 Cells.

Icariin (ICA), an active component of Epimedium brevicornum Maxim, exerts a variety of neuroprotective effects such as antiapoptosis. However, the mechanisms underlying antiapoptosis of ICA in neurons exposed to oxygen-glucose deprivation and reperfusion (OGD/R) are unclear. The B-cell lymphoma-2 (Bcl-2) protein family plays an important role in the regulation of apoptosis and autophagy through Bcl-2-dependent cross talk. Bcl-2 suppresses apoptosis by binding to Bax and inhibits autophagy by binding to Beclin-1 which is an autophagy related protein. In the present study, MTT result showed that ICA increased cell viability significantly in OGD/R treated PC12 cells (P < 0.01). Results of western blotting analysis showed that ICA increased Bcl-2 expression significantly and decreased expressions of Bax, cleaved Caspase-3, Beclin-1, and LC3-II significantly in OGD/R treated PC12 cells (P < 0.01). These results suggest that ICA protects PC12 cells from OGD/R induced autophagy via Bcl-2-dependent cross talk between apoptosis and autophagy.

Tea consumption is inversely associated with depressive symptoms in the elderly: A cross-sectional study in eastern China.

BACKGROUND: Epidemiological studies suggest that higher tea consumption was associated with lower risk of depressive symptoms, but this has not been found consistently. Moreover, the effect of different types of tea on depressive symptoms needs to be further explored. This study aimed to examine the association between tea consumption and depressive symptoms in Chinese elderly. METHODS: We analyzed the baseline data from Zhejiang Major Public Health Surveillance Program including 9371 participants. Depressive symptoms was assessed through the application of Patient Health Questionnaire-9 scale (PHQ-9). Logistic regression models, controlled for an extensive range of potential confounders, were generated to evaluate the association between tea consumption and risk of depressive symptoms. RESULTS: The black tea drinkers had a significantly decreased risk of depressive symptoms (p<0.01), whereas no association was found in green tea drinkers. Compared with non-drinkers, the adjusted ORs (95% CIs) were 0.48 (0.23, 0.99) and 0.35 (0.17, 0.72) for participants consuming <3 cups and ≥3 cups of black tea per day, respectively (P for trend: <0.01). A linear association between concentration of black tea and depressive symptoms was also confirmed in our study. LIMITATIONS: Cross-sectional data could not make a causation conclusion, and the observed association in our study could not be ascribed to any specific component in tea. CONCLUSIONS: Our results indicated that higher black tea consumption was associated with a lower prevalence of depressive symptoms in the elderly.

[Detection of agent "zhuanggenling" and investigation of utilization of plant growth retardants in traditional Chinese medicine cultivation].

Plant growth retardant as one of plant growth regulator can inhibit the cell division, elongation and growth rate in shoot apical meristem (SAM), which can be reversed by gibberellin regulate the product of photosynthesis transfer to the root and rhizome part. As commonly used plant growth retardant, paclobutrazol, uniconazole, chlorocholine chloride, mepiquat chloride, choline chloride and daminozide are used to promote the growth of root and rhizome, call as "zhuanggenling", "pengdasu", "pengdaji" etc. Single or recombination of plant growth regulator is registered as pesticide, and called as pesticide "zhuanggenling" in this paper. Growth regulator which registered as a foliar fertilizer or fertilization was called agricultural fertilizer "zhuanggenling" in this paper. The author investigate the usage of "zhuanggenling" in the root and rhizome of medicinal plants cultivation from 2012 to 2014 in Sichuan province, Huangyuan town, Mianyang (Ophiopogonis Radix); Pengzhou Aoping town (Chuanxiong Rhizoma); Pengshan Xiejia town (Alismatis Rhizoma); Jiangyou Taiping town and Zhangming town (Aconiti Lateralis Radix Praeparata); Yunnan Wenshan (Notoginseng Radix et Rhizoma); Henan province, Wuzhidafeng Town (Rehmanniae Radix, Achyranthis Bidentatae Radix, Dioscoreae Rhizoma); Gansu Min county (Codonopsis Radix, Angelicae Sinensis Radix); Gansu Li county (Rhei Radix et Rhizoma). The result showed that "zhuanggenling" were applied in the most medicinal plant cultivation except Rhei Radix et Rhizoma. It has been applied widespreadly in Ophiopogonis Radix, Alismatis Rhizoma, Achyranthis Bidentatae Radix, Codonopsis Radix; Rehmanniae Radix, commonly in Angelicae Sinensis Radix application, and occasionally in Chuanxiong Rhizoma, Aconiti Lateralis Radix Praeparata, Notoginseng Radix et Rhizoma and Dioscoreae Rhizoma. In 53 collected sample from plantation areas, fifteen (28%) were pesticide "zhuanggenling", thirty-eight (72%) were pesticide "zhuanggenling". UPLC analysis results showed that 38 farmers fertilizer "zhuanggenling" content of 6 kinds of plant growth retardant. It is regarded that fertilizer "zhuanggenling" was dominant in medicinal plant cultivation, and that the plant growth retardant is added widespreadly in farm fertilizer "zhuanggenling". All evidence proves conclusively that "zhuanggenling" have been used in the proper way, whereas some others have been misused or even abused in the use regarding to type, number, use frequency. The root or rhizoma are increased to 20%-200%. But there is lack of evaluation to appraise the quality of medicinal materials from the aspects of research or industry. "zhuanggenling" has become a important Chemical control material besides fertilizer, insecticidal sterilization of pesticide

Effects of carnosine on cyclophosphamide-induced hematopoietic suppression in mice.

Cyclophosphamide is one of the most widely used chemotherapeutic agents in treating cancers. Chemotherapy drug-induced oxidative stress produces side effects. The severity of myelosuppression increases with a high dose of cyclophosphamide. Chicken soup or chicken essence, a traditional Chinese aliment, is a popular health supplement for patients with cancers or other diseases in Asia. As a major functional component of chicken meat extract, carnosine (beta-alanyl-L-histidine), a dipeptide of the amino acids beta-alanine and histidine, has been shown to have strong antioxidant activities. In the present study, we investigated the effects of carnosine on hematopoietic suppression in mice treated with cyclophosphamide. As expected, we found that cyclophosphamide administration (with a single dose of 150 mg/kg) induced a rapid (within 24 hours) and severe hematopoietic suppression in mice. We further showed that carnosine administration (100 mg/kg/day or 200 mg/kg/day for continuous seven days) could substantially improve suppressed hematopoietic functions and accelerate the recovery of leukocyte counts, bone marrow spontaneous proliferation, colony stimulating activity (CSA) in serum, and production of endogenous cytokines such as interleukin-3 (IL-3) and stem cell factor (SCF). These results indicate that carnosine has the potential to promote the recovery from hematopoietic suppression induced by cyclophosphamide. Our data suggest that carnosine holds a potential in clinical application to minimize the side effects induced by chemotherapeutic agents such as cyclophosphamide and thus will substantially improve the overall anti-tumor effects of the standard chemotherapies.

[Comparative study on mathematical set-based drug release kinetics method and Kalman filter method applied in evaluating drug release of multi-component traditional Chinese medicine preparations].

OBJECTIVE: To provide a mathematical set-based method for evaluating drug release kinetics of multi-component traditional Chinese medicine preparations. METHOD: With Fuzheng Huayu prescription as the study model, a mathematical set-based method for evaluating drug release kinetics was established to guide the preparation of drug release system of Fuzheng Huayu prescription, and a quantitative evaluation was made for its multi-component drug release characteristics. Its accuracy was verified by Kalman filtering method. RESULT: The comparison between the two showed that the sample No. 4 of Fuzheng Huayu drug release system showed synchronized drug release with its reference preparation Fuzheng Huayu capsules. CONCLUSION: The results verified the accuracy and rationality of the evaluation method based on mathematics set. Meanwhile, it displayed the release of target preparations according to asynchronous coefficient (k) and other parameters, and found the orientation of regulating and improving the unit drug release dosage from relevant error parameters of various characteristic peak information, in order to purposefully regulate relevant components, and enable target preparations to meet the synchronized drug release requirements of the reference preparation. Meanwhile, it provided an effective measure for evaluating the quantitative characterization and synchronized release behavior of multi-component traditional Chinese medicines.

Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.

Theacrine (1,3,7,9-tetramethyluric acid), a purine alkaloid, has proven to be beneficial in maintaining several brain functions and is being studied for potential medicinal uses in recent years. In this study, we isolated theacrine from Camellia assamica var. kucha and investigated its protective effects on liver damage induced by restraint stress in mice. Results showed that 18 h of restraint stress could induce liver damage, with an obvious increase in levels of plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST). This finding was further confirmed by hepatic pathological examination, which showed inflammatory cell infiltration and focal necrosis of hepatocytes. However, oral administration of theacrine (10, 20, 30 mg/kg for 7 consecutive days) was found to decrease plasma ALT and AST levels, reduce hepatic mRNA levels of inflammatory mediators (IL-1ß, TNF-α, IL-6, and IFN-γ), and reverse the histologic damages in stressed mice. Simultaneously, theacrine also significantly decreased the content of malondialdehyde and increased oxygen radical absorbance capacity (ORAC) level in the plasma and liver of stressed mice. These results suggested that the protective effects of theacrine on stress-induced liver damage might be correlated with its antioxidative activity. The antioxidative capacity of theacrine was further evaluated by in vitro ORAC and cellular antioxidant activity assay. The results suggested that the antioxidative capacity of theacrine was not due to the direct action on free radical clearance. Moreover, the elevated activities and gene expressions of superoxide dismutase, catalase, and glutathione peroxidase, as well as the reduced activity of xanthine oxidase by theacrine treatment in stressed mice suggested that the antioxidative activity might be due to the strengthening of the antioxidant system in vivo. On the basis of the above results, theacrine is possibly a good candidate for protecting against or treating lifestyle diseases and might contribute to the study of natural products.

[Review on application of plant growth retardants in medicinal plants cultivation].

Plant growth retardants are widely used in cultivation of medicinal plant, but there is still lack of scientific guidance. In order to guide the use of plant growth retardants in medicinal plant cultivation efficiently and reasonably, this paper reviewed the mechanism, function characteristic, plant and soil residue of plant growth retardants, such as chlorocholine chloride, mepiquat chloride, paclobutrazol, unicnazle and succinic acid, and summarized the application of plant growth retardants in medicinal plants cultivation in recent years, with focus on the effect of growth and yield of the officinal organs and secondary metabolites.

Anti-inflammatory effects of a polyphenols-rich extract from tea (Camellia sinensis) flowers in acute and chronic mice models.

While beneficial health properties of tea leaves have been extensively studied, less attention is paid to the flowers of tea. In this study, the anti-inflammatory effects of hot water extract of tea (Camellia sinensis) flowers were investigated. Pharmacological studies found that administration of tea flowers extract (TFE) could effectively inhibit croton oil-induced ear edema and carrageenin-induced paw edema. Furthermore, administration of TFE also protected against Propionibacterium acnes (P. ances) plus lipopolysaccharide-(LPS-) induced liver inflammation by reversing the histologic damage and plasma alanine aminotransferase (ALT) increase. Moreover, the levels of nitric oxide (NO), tumor necrosis factor-(TNF)-α and interleukin-(IL-) 1ß mRNA in mouse liver were markedly suppressed after treatment with TFE in mice with immunological liver inflammation. These results indicated that tea flowers had potent anti-inflammatory effects on acute and immunological inflammation in vivo, and may be used as a functional natural food.