Comprehensive evaluation of chemical constituents and antioxidant activity between crude and processed Polygalae radix based on UPLC-Q-TOF-MS/MS combined with multivariate statistical analysis.

Polygalae radix (PR) is a famous herbal medicine obtained by drying the root of Polygala tenuifolia Willd., one of the traditional Chinese medicines (TCM) that can be used for healthy food. There are three main processed methods of PR, including removing the xylem of roots (Polygalae Cortex, PC), frying PC with licorice (LP), and frying PC with honey (HP). While processing is believed to enhance efficacy and reduce toxicity, it is crucial to understand the differences in chemical composition and biological activities between crude and processed PR. This study used ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) combined with multivariate statistical analysis to analyze the chemical profiles and differences between the crude and processed products. Total polyphenol contents (TPC), total flavonoid contents (TFC), total saponin contents (TSC) and antioxidant activity of the processed and crude PR were also investigated. A total of 131 chemical compounds, including 42 saponins, 44 oligosaccharide esters, 25 xanthones, 2 organic acids, 3 Carbohydrates, and 15 components detected in auxiliary materials, were detected in all samples. Notably, PC exhibited significant changes among the three processed products, with the content of 62 compounds being higher. Processing of licorice (LP) and honey (HP) decreased the content of several compounds due to temperature and moisture influences. Comprehensive comparison of the antioxidant capacity of crude and processed PR showed that the antioxidant capacity of PC was higher than that of PR, HP, and LP. Our results can provide a scientific basis for further developing and applying P. tenuifolia resources.

Dermal repeated dose toxicity study of the anti-breast cancer drug Formestane cream in Bama minipig.

Formestane (4-OHA) has been proven to be highly effective with high systemic tolerability in treating ER+ breast cancer. However, its intramuscular administration and associated side effects make it unsuitable for adjuvant treatment, leading to its withdrawal from the market. In contrast, Formestane cream may offer a solution by providing a more convenient route of administration and retaining its tumor-shrinking effects. This suggests that 4-OHA cream could have promising clinical applications. However, before clinical application, it is necessary to evaluate the potential toxicity of the cream in animals. This study evaluated the toxicity of 4-OHA cream on female Bama minipigs in vivo by analyzing hematology, biochemistry, and histopathology. The results showed that there was no significant difference between the cream-treated group and the control normal group for each parameter analyzed, indicating that 4-OHA cream was non-dermal toxic to minipigs. This finding provides a basis for the safe clinical use of the cream.

Enterolactone and trabectedin suppress epithelial ovarian cancer synergistically via upregulating THBS1.

Epithelial ovarian cancer (EOC) is the most common and fatal subtype of ovarian malignancies, with no effective therapeutics available. Our previous studies have demonstrated extraordinary suppressive efficacy of enterolactone (ENL) on EOC. A chemotherapeutic agent, trabectedin (Trabe), is shown to be effective on ovarian cancer, especially when combined with other therapeutics, such as pegylated liposomal doxorubicin or oxaliplatin. Thrombospondin 1 (THBS1), a kind of matrix glycoprotein, plays important roles against cancer development through inhibiting angiogenesis but whether it is involved in the suppression of EOC by ENL or Trabe remains unknown. To test combined suppressive effects of ENL and Trabe on EOC and possible involvement of THBS1 in the anticancer activities of ENL and Trabe. The EOC cell line ES-2 was transfected with overexpressed THBS1 by lentivirus vector. We employed tube formation assay to evaluate the anti-angiogenesis activity of ENL and of its combined use with Trabe after THBS1 overexpression and established drug intervention and xenograft nude mouse cancer models to assess the in vivo effects of the hypothesized synergistic suppression between the agents and the involvement of THBS1. Mouse fecal samples were collected for 16S rDNA sequencing and microbiota analysis. We detected strong inhibitory activities of ENL and Trabe against the proliferation and migration of cancer cells and observed synergistic effects between ENL and Trabe in suppressing EOC. ENL and Trabe, given either separately or in combination, could suppress the tube formation capability of human microvascular endothelial cells, and this inhibitory effect became even stronger with THBS1 overexpression. In the ENL plus Trabe combination group, the expression of tissue inhibitor of metalloproteinases 3 and cluster of differentiation 36 was both upregulated, whereas matrix metalloproteinase 9, vascular endothelial growth factor, and cluster of differentiation 47 were all decreased. With the overexpression of THBS1, the results became even more pronounced. In animal experiments, combined use of ENL and Trabe showed superior inhibitory effects to either single agent and significantly suppressed tumor growth, and the overexpression of THBS1 further enhanced the anti-cancer activities of the drug combination group. ENL and Trabe synergistically suppress EOC and THBS1 could remarkably facilitate the synergistic anticancer effects of ENL and Trabe.

Naringenin suppresses epithelial ovarian cancer by inhibiting proliferation and modulating gut microbiota.

BACKGROUND: Ovarian cancer has the highest mortality among all gynecological malignancies; currently, no effective therapeutics are available for its treatment. Naringenin has been shown to inhibit the progression of various cancers, but its inhibitory effect on ovarian cancer remains unknown. PURPOSE: This study aimed to evaluate the inhibitory effects of naringenin on ovarian cancer and elucidate the underlying mechanisms. METHODS: Cancer cell proliferation was detected by cell counting kit-8 and crystal violet assays, and the migration capability was determined by wound healing and transwell assays. Western blotting and immunohistochemistry assays were employed to determine the expression levels of the epidermal growth factor receptor, phosphatidylinositol 3-kinase (PI3K) and cyclin D1 in vitro and in vivo, respectively. An ES-2 xenograft nude mouse model was established for the in vivo experiments, and fecal samples were collected for intestinal microbiota analysis by 16S rDNA sequencing. RESULTS: Naringenin suppressed the proliferation and migration of A2780 and ES-2 cancer cell lines and downregulated PI3K in vitro. In animal experiments, naringenin treatment significantly decreased the tumor weight and volume, and oral administration exhibited greater effects than intraperitoneal injection. Additionally, naringenin treatment ameliorated the population composition of the microbiota in animals with ovarian cancer and significantly increased the abundances of Alistipes and Lactobacillus. CONCLUSION: Naringenin suppresses epithelial ovarian cancer by inhibiting PI3K pathway expression and ameliorating the gut microbiota, and the oral route is more effective than parenteral administration.

Deep Tumor Penetrating Gold Nano-Adjuvant for NIR-II-Triggered In Situ Tumor Vaccination.

Local tumor photothermal treatment with the near-infrared light at the second window (NIR-II) is a promising strategy in triggering the in situ tumor vaccination (ISTV) for cancer therapy. However, limited penetration of photothermal agents within tumors seriously limits their spatial effect in generating sufficient tumor-associated antigens, a key factor to the success of ISTV. In this study, a nano-adjuvant system is fabricated based on the NIR-II-absorbable gold nanostars decorated with hyaluronidases and immunostimulatory oligodeoxynucleotides CpG for ISTV. The nano-adjuvant displays a deep tumor penetration capacity via loosening the dense extracellular matrix of tumors. Upon NIR-II light irradiation, the nano-adjuvant significantly inhibits the tumor growth, induces a cascade of immune responses, generates an obvious adaptive immunity against the re-challenged cancers, boosts the abscopal effect, and completely inhibits the pulmonary metastases. The study highlights an advanced nano-adjuvant formulation featuring deep tumor penetration for NIR-II-triggered ISTV.

Sensitive silica-alumina modified capacitive non-Faradaic glucose sensor for gestational diabetes.

A highly sensitive silica-alumina (Si-Al)-modified capacitive non-Faradaic glucose biosensor was introduced to monitor gestational diabetes. Glucose oxidase (GOx) was attached to the Si-Al electrode surface as the probe through amine-modification followed by glutaraldehyde premixed GOx as aldehyde-amine chemistry. This Si-Al (∼50 nm) modified electrode surface has increased the current flow upon binding of GOx with glucose. Capacitance values were increased by increasing the glucose concentrations. A mean capacitance value was plotted and the detection limit was found as 0.03 mg/mL with the regression coefficient value, R² = 0.9782 [y = 0.8391x + 1.338] on the linear range between 0.03 and 1 mg/mL. Further, a biofouling experiment with fructose and galactose did not increase the capacitance, indicating the specific glucose detection. This Si-Al-modified capacitance sensor detects a lower level of glucose presence and helps in monitoring gestational diabetes.

Congener-Induced Sulfur-Related Metabolism Interference Therapy Promoted by Photothermal Sensitization for Combating Bacteria.

Metabolic homeostasis is vital for individual cells to keep alive. Stronger metabolic homeostasis allows bacteria to survive in vivo and do persistent harm to hosts, which is especially typical in implant-associated infection (IAI) with biofilm intervention. Herein, based on the competitive role of selenium (Se) and sulfur (S) in bacteria metabolism as congeners, a congener-induced sulfur-related metabolism interference therapy (SMIT) eradicating IAI is proposed by specific destruction of bacteria metabolic homeostasis. The original nanodrug manganese diselenide (MnSe2 ) is devised to generate permeable H2 Se in bacteria, triggered by the acidic microenvironment. H2 Se, the congener substitution of H2 S, as a bacteria-specific intermediate metabolite, can embed itself into the H2 S-utilization pathway and further alternatively disrupt the downstream sulfur-related metabolism state inside bacteria. A proteomic study indicates ribosome-related proteins are heavily downregulated and the basic metabolic pathways are mainly disordered after SMIT, revealing the destruction of bacteria metabolic homeostasis. The efficiency of SMIT is significantly promoted with the mild temperature sensitization provided by the photothermal treatment (PTT) of MnSe2 nanoparticles, verified by the proteomic study and the anti-IAI effect in vitro and in vivo. With the intelligent nanodrug, a PTT-promoted SMIT strategy against IAI is provided and a new insight into the interference design toward metabolic homeostasis with biochemical similarity is demonstrated.

Antitumor Effects of Baicalein and Its Mechanism via TGFß Pathway in Cervical Cancer HeLa Cells.

BACKGROUND: Due to dual-regulating carcinogenesis, the TGFß pathway is an ideal and alternative tumor target. Natural flavonoids possess the similar structures to estrogen and could exert an important benefit to cervical cancer. The present study aimed to screen the inhibitor of TGFß pathway from natural flavonoids and evaluate the function and mechanism of the TGFß pathway inhibitor on cervical cancer. MATERIALS AND METHODS: The cervical cancer HeLa cells were firstly treated with different flavonoids and probed by western blot for screening the inhibitor of TGFß pathway. And then, the effect of the identified inhibitor on cell proliferation was studied by CCK-8 and clone formation assay. Then, RT-PCR and western blot assay were performed to evaluate the effect of identified inhibitor on mTOR/p70S6K pathway, and the cell migration and EMT pathway were also examined using scratching analysis and western blot assay. Finally, the role of TGFß was assessed via the classic inhibitor of TGFß/SMAD pathway. RESULTS: Screening data by western blot assay showed that baicalein displayed the best inhibitor effect on TGFß expression. CCK-8 and clone formation assay showed that baicalein inhibited the cell proliferation and clone cell number. RT-PCR and western bolt for probing mTOR, p70S6K, and 4EBP1 revealed that baicalein could suppress their expression and phosphorylation. The scratching analysis and western blot assay displayed that baicalein inhibited the cell migration and EMT progression in HeLa. The use of SB431542, a TGFß inhibitor, revealed that TGFß was crucial to baicalein-regulating cell proliferation and migration in HeLa cells. CONCLUSION: Baicalein, a medicine agent screened from natural flavonoids targeting TGFß pathway, could suppress mTOR/p70S6K pathway-mediated cell proliferation and EMT pathway-related migration via TGFß pathway in cervical cancer HeLa cells.

Niobium Carbide MXene Augmented Medical Implant Elicits Bacterial Infection Elimination and Tissue Regeneration.

Incurable bacterial infections, impenetrable microbial biofilm, and irreversible antibiotic resistance are among the most dangerous threats for humans. With few effective strategies available in antimicrobial and antibiofilm development, innovative methodologies inspired by the advances in other fields such as nanomedicine are becoming more and more attractive to realize innovative antibacterial agents. Herein, a 2D niobium carbide (Nb2C) MXene titanium plate (Nb2C@TP)-based clinical implant with practical multimodal anti-infection functions was developed. Such emerging modes are capable of destroying biofilms for direct bacteria elimination through down-regulating bacterial energy metabolism pathways, suppressing biofilm formation, and enhancing as-formed biofilm detachment via an activating accessory gene regulator. Another intriguing feature of this nanomedicine is the sensitization ability toward bacteria via photothermal transduction, which reduces the temperature necessary for bacteria eradication and mitigates possible normal tissue damage. Moreover, the Nb2C@TP medical implant is able to alleviate proinflammatory responses by scavenging excessive reactive oxygen species in infectious microenvironments, benefiting angiogenesis and tissue remodeling.

The effect of comprehensive assessment and multi-disciplinary management for the geriatric and frail patient: A multi-center, randomized, parallel controlled trial.

BACKGROUND: A comprehensive geriatric assessment (CGA) of elderly patients is useful for detecting the patients vulnerabilities. Exercise and early rehabilitation, nutritional intervention, traditional Chinese medicine (TCM), standardized medication guidance, and patient education can, separately, improve and even reverse the physical frailty status. However, the effect of combining a CGA and multi-disciplinary management on frailty in elderly patients remains unclear. The present study assessed the effects of a CGA and multi-disciplinary management on elderly patients with frailty in China. METHODS: In this study, 320 in patients with frailty ≥70 years old will be randomly divided into an intervention group and a control group. The intervention group will be given routine management, a CGA and multi-disciplinary management involving rehabilitation exercise, diet adjustment, multi-drug evaluation, acupoint massage in TCM and patient education for 12 months, and the control group will be followed up with routine management for basic diseases. The primary outcomes are the Fried phenotype and short physical performance battery (SPPB). The secondary outcomes are the clinical frailty scale (CFS), non-elective hospital readmission, basic activities of daily living (BADL), 5-level European quality of life 5 dimensions index (EQ-5D), nutrition risk screening-2002 (NRS-2002), medical insurance expenses, fall events, and all-cause mortality. In addition, a cost-effectiveness study will be carried out. DISCUSSION: This paper outlines the protocol for a randomized, single-blind, parallel multi-center clinical study. This protocol, if beneficial, will demonstrate the interaction of various intervention strategies, will help improve elderly frailty patients, and will be useful for clinicians, nurses, policymakers, public health authorities, and the general population. TRIAL REGISTRATION: Chinese Clinical Trials Register, ChiCTR1900022623. Registered on April 19, 2019, http://www.chictr.org.cn/showproj.aspx?proj=38141.

[Prescription compatibility connotation and action mechanism of Siwu Decoction in treating primary dysmenorrhea].

The aim of this paper was to study the prescription compatibility connotation in the treatment of primary dysmenorrhea(PD) and verify the mechanism as predicted by network pharmacology of Siwu Decoction(SWD). Mice PD model was constructed by using estradiol benzoate-oxytocin. PD mice were randomly divided into 8 groups, namely normal group, model group, positive group, complete formula group, Rehmanniae Radix Praeparata-free group, Paeoniae Radix Alba-free group, volatile oil-free group, Chuan-xiong Rhizoma and Angelicae Sinensis Radix-free group. Latent time, writhing times, inhibition rate, prostaglandin F_2_α(PGF_2_α) and prostaglandin E_2(PGE_2) levels in serum, endothelin-1, Ca~(2+), expression levels of prostaglandin synthase 2 G/H(PTGS2), estrogen receptor(ESR1), glucocorticoid receptor gene(NR3 C1) mRNA and protein expression levels in the uterus homogenate and pathological changes of uterine tissue were index to explore the prescription compatibility connotation and verify the mechanism of SWD in the treatment of PD. Compared with the extraction liquid of the whole recipe, the effect of Rehmanniae Radix Praeparata-free group and Paeoniae Radix Alba-free group with volatile oil were slightly lower, the effect of essential oil-free group was significantly lower, and the effect of Chuanxiong Rhizoma and Angelicae Sinensis Radix-free group was worse than that of the whole recipe. The relative expression levels of PTGS2 protein and mRNA were significantly reduced by the SWD. The relative expressions of protein and mRNA of ESR1, NR3 C1 were significantly increased. SWD treats PD by regulating the expression of key proteins PTGS2, ESR1 and NR3 C1.Its main medicinal herbs were Angelicae Sinensis Radix and Chuanxiong Rhizoma. Active components were mainly in volatile oil, but Paeo-niae Radix Alba and Rehmanniae Radix Praeparata also had some contributions.

Suppressive activities of mangiferin on human epithelial ovarian cancer.

BACKGROUND: Epithelial carcinoma is a subtype of ovarian cancers, with the highest lethality among all ovarian cancer subtypes. Hitherto surgical excision combined with chemotherapy has been the most extensively employed method in clinical treatment. However, the disease relapses very frequently, calling for more effective therapies. Mangiferin, a natural xanthone glucoside, has displayed promising anti-cancer activities by in vitro studies, but its therapeutic value in epithelial ovarian cancer treatment, either by in vivo or in vitro studies, remained to be known. PURPOSE: This study aimed to determine the suppressive activities of mangiferin on human epithelial ovarian cancer and elucidate the underlying molecular mechanisms. STUDY DESIGN AND METHODS: We employed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and the crystal violet assay to determine the half maximal inhibitory concentration (IC50) values of mangiferin with paclitaxel as a positive control and the inhibitory effects of mangiferin on the proliferation of two human epithelial ovarian cancer cell lines. Wound healing and Transwell assays were used to determine anti-metastastic activities of mangiferin. ES-2 xenograft nude mouse model was used for the in vivo experiments. Western blotting, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assays were carried out for evaluating the expression level of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9). RESULTS: In the present study, we demonstrated by both in vitro and in vivo assays that mangiferin suppressed the progress of epithelial ovarian cancer in a dose-dependent manner. In the animals treated with mangiferin, the tumor volume and weight were reduced significantly. Analyses of involved molecular events demonstrated that mangiferin down-regulated the expression of metastasis-associated proteins MMP2 and MMP9. CONCLUSION: Mangiferin strongly inhibited the progression of human epithelial ovarian cancer by down-regulating MMP2 and MMP9.

[Research progress on triptolide functionalized nanoparticulate drug delivery systems for tumor treatment].

Nowadays,the advantages of traditional Chinese medicine(TCM) for treatment of tumors are increasingly prominent.Triptolide shows wide-spectrum and highly effective anti-tumor activity. Moreover,nano-carrier-based triptolide drug delivery system is more powerful in improving water solubility and pharmacokinetic behavior of the drug,but it is easy to cause toxic and side effects that should not be neglected on human body. Because of tumor vascular heterogeneity and PEGylation dilemma,nanoparticulate drug delivery systems need to overcome multiple physiological and pathological barriers from drug administration to functioning. It is difficult for traditional triptolide nanoparticulate drug delivery systems to achieve active accumulation of nano-drug in tumor tissues and specific drug release in tumor target site solely relying on enhanced permeability and retention effect of solid tumor,limiting their application and clinical transformation in treatment of tumors. Based on the traditional nano-preparation system,the new functionalized nano-drug delivery system further enhances the nano-drug enrichment,penetration and controlled release at the tumor sites,which is of great significance in improving bioavailability,anti-tumor efficacy and reducing the side effects of drugs. In this paper,we summarized and analyzed the researches on new triptolide functionalized nano-drug delivery system from four perspectives,including tumor active targeting,tumor microenvironment response,polymer-drug conjugates,and multidrug co-delivery for tumor treatment,expecting to provide ideas for in-depth research and clinical application of triptolide and some other active anti-tumor TCM ingredients.

[Research progress on anti-tumor effects and mechanisms of triptolide and its combined application].

Tumors are major chronic diseases and seriously threaten human health all over the world. How to effectively control and cure tumors is one of the most pivotal problems in the medical field. At present,surgery,radiotherapy and chemotherapy are still the main treatment methods. However,the side effects of radiotherapy and chemotherapy cannot be underestimated. Therefore,it is of great practical significance to find new anti-cancer drugs with low toxicity,high efficiency and targeting to cancer cells. With the increasing incidence of tumor,the anti-tumor effect of traditional Chinese medicine has increasingly become a research hotspot. Triptolide,which is a natural diterpenoid active ingredient derived from of Tripterygium wilfordii,as one of the highly active components,has anti-inflammatory,immunosuppressive,anti-tumor and other multiple effects. A large number of studies have confirmed that it has good anti-tumor activity against various tumors in vivo and in vitro. It can play an anti-tumor role by inhibiting the proliferation of cancer cells,inducing apoptosis of cancer cells,inducing autophagy of cancer cells,blocking the cell cycle,inhibiting the migration,invasion and metastasis of cancer cells,reversing multidrug resistance,mediating tumor immunity and inhibiting angiogenesis. On the basis of literatures,this paper reviews the anti-tumor effect and mechanism of triptolide,and analyzes the current situation of triptolide combined with other chemotherapy drugs,in order to promote deep research and better clinical application about triptolide.

[Effect of neoflavonoid latifolin isolated from Dalbergia odorifera on acute myocardial ischemia in rats and its mechanism of Nrf2 signaling pathway].

The present study was designed to evaluate the cardioprotective effect of latifolin on pituitrin(Pit) or isoproterenol(ISO)-induced myocardial injury in rats, and further investigate its underlying mechanisms. Rats were administrated sublingually with pituitrin or subcutaneously with isoproterenol to induce acute myocardial ischemia in rats, and lead II electrocardiograph was recorded. In rats with isoproterenol, ELISA assay or colorimetric method was used to detect the content or activity of myocardial injury markers in serum, and the SOD activity and MDA content in myocardium were detected by colorimetric assay; histopathological examination was conducted by HE staining; the frozen section of myocardial tissues was used for DCFH-DA fluorescent staining to detect the content of ROS in myocardium; Western blot was used to detect the protein expression levels of Nrf2, Keap1, HO-1 and NQO1 in myocardium. Results showed that latifolin significantly inhibited ST-segment changes induced by pituitrin or isoproterenol, and increased heart rate. Further mechanism study showed that latifolin reduced cardiac troponin I(cTnI) level, aspartate transaminase(AST) and lactate dehydrogenase(LDH) activities in serum, increased myocardial superoxide dismutase(SOD) activity and reduced myocardial malondialdehyde(MDA) level, and protected myocardium with less necrosis, infiltration of inflammatory cells and fracture of myocardial fibers. Furthermore, latifolin obviously reduced ROS level in myocardium, inhibited the expression of Kelch-like ECH-associated protein-1(Keap1), increased the nuclear translocation of nuclear factor erythroid 2 related factor 2(Nrf2), and promoted the expression of Heme oxygenase-1(HO-1) and NAD(P)H quinone oxidoreductase-1 (NQO1) in myocardial tissues. Our data suggest that latifolin has a potent protective effect against pituitrin or isoproterenol-induced myocardial injury, which may be related to inhibition of oxidative stress by activating Nrf2 signaling pathway.

Study on pharmacokinetics and tissue distribution of single dose oral tryptanthrin in Kunming mice by validated reversed-phase high-performance liquid chromatography with ultraviolet detection.

BACKGROUND: Tryptanthrin is a major active constituent of several Chinese herbal plants, such as Isatidis radix. Tryptanthrin had been demonstrated to have several beneficial pharmacological effects in vitro for human diseases, including antitumor, anti-inflammatory and antibacteria activities. In contrast to the extensive in vitro investigations, the in vivo disposition process of tryptanthrin was explored limitedly. METHODS: In this study, the pharmacokinetics (PK) and tissue distribution of tryptanthrin in Kunming mice following a single oral dose of 80 mg/kg tryptanthrin were investigated for the first time. Mouse plasma, liver, heart, spleen, lung, kidney and brain were collected and analyzed using a validated reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-HPLC-UV) method after biological sample preparation by a simple liquid-liquid extraction. RESULTS: The chromatographic analysis was performed on a Diamonsil C18 column (5 µm, 250 mm × 4.6 mm) and ultraviolet detection was set at a wavelength of 251 nm. The analysis was achieved with a mobile phase of methanol (A) and water (B) (60:40, v/v) at a flow rate of 1.0 mL/min. The method was linear over the concentration range of 4.0-400.0 µg/mL with a lower limit of quantification of 0.10-0.30 µg/mL. Inter- and intraday precisions (relative standard deviations %) were all within 2.93%. Recoveries of tryptanthrin were more than 86.44%. Maximal tryptanthrin concentrations in plasma and tissues of mice were reached within 2.5 hours. The actual highest concentration (Cmax) in mouse plasma was 3.13 µg/mL, the area under the curve (AUC0-t ) was 9.38 h µg/mL, and the terminal half-life was 2.27 hours. The volume of distribution was 343.89 mL, the clearance rate was 204.58 mL/h, and the PK of tryptanthrin in mice after oral administration was fit to 2 compartment 1 st Order. After oral dosing of tryptanthrin to Kunming mice, the analyte was well distributed to the plasma and main tissues. Cmax was found in the liver with a mean value of 3.54 µg/g, followed by that in the kidney, lung, spleen, heart, and brain. CONCLUSION: In this study, a validated RP-HPLC-UV method was developed and successfully applied to PK and tissue distribution of oral tryptanthrin in mice. We confirmed that tryptanthrin was closely related and targeted to plasma, liver, kidney, and lung. These results indicate that tryptanthrin will have a good clinical application in the liver, kidney, or lung. The clinical use of tryptanthrin should focus on its pharmacodynamics and safety study in these tissues.

[Research on suitable distribution of Paris yunnanensis based on remote sensing and GIS].

Paris yunnanensis is a kind of rare medicinal herb, having a very high medicinal value. Studying its suitable ecological condition can provide a basis for its rational exploitation, artificial cultivation, and sustainable utilization. A practicable method in this paper has been proposed to research the suitable regional distribution of P. yunnanensis in Sichuan province. By the case study of P. yunnanensis in Sichuan province, and according to related literatures, the suitable ecological condition of P. yunnanensis such as altitude, mean annual temperature (MAT), annual precipitation, regional slope, slope ranges, vegetative cover, and soil types was analyzed following remote sensing (RS) and GIS.The appropriate distribution regionof P. yunnanensis and its area were extracted based on RS and GIS technology,combing with the information of the field validation data. The results showed that the concentrated distribution regions in counties of Sichuan province were, Liangshan prefecture, Aba prefecture, Sertar county of Ganzi prefecture, Panzhihua city, Ya'an city, Chengdu city, Meishan city, Leshan city, Yibin city, Neijiang city, Luzhou city, Bazhong city, Nanchong city, Guangyuan city and other cities and counties area.The suitable distribution area in Sichuan is about 7 338 km², accounting for 3.02% of the total study regional area. The analysis result has high consistency with the filed validation data, and the research method for P. yunnanensis distribution region based onspatial overlay analysis and the extracted the information of land usage and ecological factors following the RS and GIS is reliable.

[Application of remote sensing and GIS in study of suitability distribution of Swertia mussotii, a Tibetan medicine in Sichuan province].

Swertia mussotii is a kind of rare medicinal materials, the relevant researches are mainly concentrated on its medicinal efficacy and medicinal value till now, researches of adaptive distribution by applying remote sensing and GIS are relatively less. This study is to analyze the adaptive distribution of S.mussotii in Sichuan province by applying remote sensing and GIS technology, and provide scientific basis for the protection and development of wild resources, artificial cultivation and adjustment of Chinese medicine industrial distribution in Sichuan province. Based on literature review and ecological factors such as altitude, annual precipitation and annual average temperature, this study extracted ecological factors, overlay analysis in GIS, as well as combining GPS field validation data by means of remote sensing and GIS, discusses the adaptive distribution of SMF sin Sichuan province. ①The area of adaptive distribution of S. mussotii in Sichuan province is 1 543.749 km², mainly in Dege county, Ganzi county, Daofu county, Kangding county, Barkam, Jinchuan county, Xiaojin county, Danba county, Daocheng county, Xiangcheng county, Xinlong county, Aba county, Muli county and other counties and cities, accounts for about 7.25% in total area. ② Combining statistical information and field validation, this study found that S. mussotii adaptive distribution gained by remote sensing and GIS is in conformity with its actual distribution. The study shows that remote sensing and GIS technology are feasible to obtain the S. mussotii adaptive distribution, they can further be applied to studies on adaptive distributions of other rare Chinese medicinal herb.

[Protective Effects of Different Extracts of Imperatae Rhizoma in Rats with Adriamycin Nephrosis and Influence on Expression of TGF-ß1, and NF-κB p65].

OBJECTIVE: To study the protective effect of Imperatae Rhizoma extract on renal tissues in rats with Adriamycin nephrosis, and to explore the possible mechanism. METHODS: The nephrosis model was induced by adriamycin 6.5 mg/kg intravenously in rats. The rats were randomly divided into seven groups, including normal group, model group, predisone group, petroleum ether groups, ethyl acetate group ,alcohol group, and water parts group, and treated for eight weeks. The protein content of 24 hours urine excretion was tested respectively by automatic biochemistry analyzer each week. After eight weeks, BUN, CRE, TCHO, TG, TP and ALB in serum were examined by automatic biochemistry analyzer. The TNF-α in serum was measured by ELISA. The expression of TGF-ß1, and NF-κB p65 in renal tissues were detected by immunohistochemistry respectively. The pathological changes in the renal were observed by light microscope. RESULTS: Compared with the model group ,the proteinuria of the rats in ethyl acetate group obviously reduced at the 6th, 7th, 8th week, the content of TNF-α in serum and the expression of TGF-ß1, and NF-κB p65 in renal tissues significantly reduced, but the content of TP and ALB in serum were increased obviously. In the alcohol and water parts groups ,the level of TG in serum and the protein content of 24 hours urine excretion of the 6th and 7th week were significantly decreased. The ethyl acetate, alcohol and water parts groups ameliorated the changes of pathology in renal. CONCLUSION: The different extracts of Imperatae Rhizoma had different protective effect in rats with adriamycin nephrosis, and the effect of ethyl acetate group was more stronger than that of other groups. The mechanism may be related to reducing the expression of NF-κB p65 and TGF-ß1, and the content of TNF-α inrenal tissues of rats.

Identification of miRNAs and their targets in tea (Camellia sinensis).

MicroRNAs (miRNAs) are endogenous small RNAs playing a crucial role in plant growth and development, as well as stress responses. Among them, some are highly evolutionally conserved in the plant kingdom, this provide a powerful strategy for identifying miRNAs in a new species. Tea (Camellia sinensis) is one of the most important commercial beverage crops in the world, but only a limited number of miRNAs have been identified. In the present study, a total of 14 new C. sinensis miRNAs were identified by expressed sequence tag (EST) analysis from 47452 available C. sinensis ESTs. These miRNAs potentially target 51 mRNAs, which can act as transcription factors, and participate in stress response, transmembrane transport, and signal transduction. Analysis of gene ontology (GO), based on these targets, suggested that 37 biological processes were involved, such as oxidation-reduction process, stress response, and transport. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis inferred that the identified miRNAs took part in 13 metabolic networks. Our study will help further understanding of the essential roles of miRNAs in C. sinensis growth and development, and stress response.