Paeoniflorin Coordinates Macrophage Polarization and Mitigates Liver Inflammation and Fibrogenesis by Targeting the NF-[Formula: see text]B/HIF-1α Pathway in CCl4-Induced Liver Fibrosis.

Liver fibrosis is a disease largely driven by resident and recruited macrophages. The phenotypic switch of hepatic macrophages can be achieved by chemo-attractants and cytokines. During a screening of plants traditionally used to treat liver diseases in China, paeoniflorin was identified as a potential drug that affects the polarization of macrophages. The aim of this study was to evaluate the therapeutic effects of paeoniflorin in an animal model of liver fibrosis and explore its underlying mechanisms. Liver fibrosis was induced in Wistar rats via an intraperitoneal injection of CCl4. In addition, the RAW264.7 macrophages were cultured in the presence of CoCl2 to simulate a hypoxic microenvironment of fibrotic livers in vitro. The modeled rats were treated daily with either paeoniflorin (100, 150, and 200[Formula: see text]mg/kg) or YC-1 (2[Formula: see text]mg/kg) for 8 weeks. Hepatic function, inflammation and fibrosis, activation of hepatic stellate cells (HSC), and extracellular matrix (ECM) deposition were assessed in the in vivo and in vitro models. The expression levels of M1 and M2 macrophage markers and the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway factors were measured using standard assays. Paeoniflorin significantly alleviated hepatic inflammation and fibrosis, as well as hepatocyte necrosis in the CCl4-induced fibrosis model. Furthermore, paeoniflorin also inhibited HSC activation and reduced ECM deposition both in vivo and in vitro. Mechanistically, paeoniflorin restrained M1 macrophage polarization and induced M2 polarization in the fibrotic liver tissues as well as in the RAW264.7 cells grown under hypoxic conditions by inactivating the NF-[Formula: see text]B/HIF-1[Formula: see text] signaling pathway. In conclusion, paeoniflorin exerts its anti-inflammatory and anti-fibrotic effects in the liver by coordinating macrophage polarization through the NF-[Formula: see text]B/HIF-1[Formula: see text] pathway.

SNS alleviates depression-like behaviors in CUMS mice by regluating dendritic spines via NCOA4-mediated ferritinophagy.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression is one of the most common mood disturbances worldwide. The Si-ni-san formula (SNS) is a famous classic Traditional Chinese Medicine (TCM) widely used to treat depression for thousands of years in clinics. However, the mechanism underlying the therapeutic effect of SNS in improving depression-like behaviors following chronic unpredictable mild stress (CUMS) remains unknown. AIM OF THE STUDY: This study aimed to investigate whether SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy in vitro and in vivo. STUDY DESIGN AND METHODS: In vivo, mice were exposed to CUMS for 42 days, and SNS (4.9, 9.8, 19.6 g/kg/d), fluoxetine (10 mg/kg/d), 3-methyladenine (3-MA) (30 mg/kg/d), rapamycin(1 mg/kg/d), and deferoxamine (DFO) (200 mg/kg/d) were conducted once daily during the last 3 weeks of the CUMS procedure. In vitro, a depressive model was established by culture of SH-SY5Y cells with corticosterone, followed by treatment with different concentrations of freeze-dried SNS (0.001, 0.01, 0.1 mg/mL) and rapamycin (10 nM), NCOA4-overexpression, Si-NCOA4. After the behavioral test (open-field test (OFT), sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST), dendritic spines, GluR2 protein expression, iron concentration, and ferritinophagy-related protein levels (P62, FTH, NCOA4, LC3-II/LC3-I) were tested in vitro and in vivo using immunohistochemistry, golgi staining, immunofluorescence, and Western blot assays. Finally, HEK-293T cells were transfected by si-NCOA4 or GluR2-and NCOA4-overexpression plasmid and treated with corticosterone(100 µM), freeze-dried SNS(0.01 mg/mL), rapamycin(25 nM), and 3-MA(5 mM). The binding amount of GluR2, NCOA4, and LC3 was assessed by the co-immunoprecipitation (CO-IP) assay. RESULTS: 3-MA, SNS, and DFO promoted depressive-like behaviors in CUMS mice during OFT, SPT, FST and TST, improved the amount of the total, thin, mushroom spine density and enhanced GluR2 protein expression in the hippocampus. Meanwhile, treatment with SNS decreased iron concentrations and inhibited NCOA4-mediated ferritinophagy activation in vitro and in vivo. Importantly, 3-MA and SNS could prevent the binding of GluR2, NCOA4 and LC3 in corticosterone-treated HEK-293T, and rapamycin reversed this phenomenon after treatment with SNS. CONCLUSION: SNS alleviates depression-like behaviors in CUMS mice by regulating dendritic spines via NCOA4-mediated ferritinophagy.

[Bioinformatics and expression analysis on MYB-related family in Angelica dahurica var. formosana].

In recent years, the MYB-related gene family has been found pivotal in plant growth and development. MYB-related gene family in Angelica dahurica var. formosana was systematically investigated based on "Chuanzhi No. 2" through transcriptome database search and bioinformatics and the temporal and spatial expression patterns were analyzed through real-time fluorescence-based quantitative polymerase chain reaction(PCR). The results showed that 122 MYB-related proteins family were identified, mainly including the unstable hydrophilic proteins with good thermal stability. Most of the proteins were located in nuclei. The majority of the proteins had the structures of random coil and α-helix. Five MYB-related proteins family of A. dahurica var. formosana had membrane-binding domains. The conserved domain analysis of MYB-related proteins family of A. dahurica var. formosana showed that the MYB domains of genes in five subgroups, similar to 2 R-, 3 R-, and 4 R-MYB proteins, contained three evenly distributed Trp(W) residues in the MYB repeat sequence. The phylogenetic analysis of MYB-related proteins family in A. dahurica var. formosana and Arabidopsis thaliana showed that the MYB-related members were unevenly distributed in five subgroups, and A. thaliana and A. dahurica var. formosana had almost the same number of genes in the CCA1-like subgroup. There were differences in the number, type, and distribution of motifs contained in 122 encoded proteins. Transcription factors with similar branches had similar domains and motifs. The expression pattern analysis showed that the transcription factors AdMYB53, AdMYB83, and AdMYB89 responded to hormones to varying degrees, and they were highly expressed in leaves and responded quickly in roots. This study lays a foundation for further investigating the function of MYB-related transcription factors of A. dahurica var. formosana and solving the corresponding biological problems such as bolting early.

The Role of TGF-ß Signaling Pathways in Cancer and Its Potential as a Therapeutic Target.

The transforming growth factor-ß (TGF-ß) signaling pathway mediates various biological functions, and its dysregulation is closely related to the occurrence of malignant tumors. However, the role of TGF-ß signaling in tumorigenesis and development is complex and contradictory. On the one hand, TGF-ß signaling can exert antitumor effects by inhibiting proliferation or inducing apoptosis of cancer cells. On the other hand, TGF-ß signaling may mediate oncogene effects by promoting metastasis, angiogenesis, and immune escape. This review summarizes the recent findings on molecular mechanisms of TGF-ß signaling. Specifically, this review evaluates TGF-ß's therapeutic potential as a target by the following perspectives: ligands, receptors, and downstream signaling. We hope this review can trigger new ideas to improve the current clinical strategies to treat tumors related to the TGF-ß signaling pathway.

New C21-steroidal aglycones from the roots of Cynanchum otophyllum and their anticancer activity.

Naturally occurring C21-steroidal aglycones from Cynanchum exhibit significant antitumor effects. To expand the chemical diversity and get large scale C21-steroidal aglycones, the extracts of the roots of Cynanchum otophyllum were treated with 5% HCl in aqueous and the resulting hydrolysate was investigated. Nine new C21-steroidal aglycones (1-9) namely cynotogenins A-I, along with seventeen known analogous (10-26), were isolated from the hydrolysate. The structures of compounds 1-9 were elucidated by spectroscopic analysis (IR, HR-ESI-MS, 1D and 2D NMR) and comparison of observed spectroscopic data with those of reported in the literature. Aglycones 2-5 with rare cis-cinnamoyl group as well as 8 and 9 with 5ß,6ß-epoxy group were found from the genus of Cynanchum for the first time. The cytotoxicities of compounds 1-26 toward human cancer HeLa, H1299, HepG2, and MCF-7 cells were evaluated and preliminary structure-activity relationship (SAR) was discussed. Moreover, compound 20 inhibits HepG2 cell apoptosis and induces of G0/G1 phase arrest in a dose dependent manner.

[Chemical constituents from lipophilic parts of stems of Celastrus monospermus].

The chemical constituents from lipophilic parts of the stems of Celastrus monospermus were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods including silica gel, ODS and Sephadex LH-20, and the structures of compounds were determined by spectral data analyses. Twenty six compounds were obtained and identified as 3-oxofriedelane(1), 3-oxofriedelan-28-al(2), 3,12-dioxofriedelane(3), 3ß-hydroxyolean-12-en(4), 3-oxo-28-hydroxyfriedelane(5), 3-oxo-29-hydroxyfriedelane(6), 3-oxo-11ß-hydroxyfriedel-ane(7), 3-oxo-16α-hydroxyfriedelane(8), 3,12-dioxo-28-hydroxyfriedelane(9), 1,3-dioxo-15α-hydroxyfriedelane(10), 3ß,6α-dihydroxyolean-12-en(11), 3-oxo-7α,26-dihydroxyfriedel-ane(12), oleanolic acid(13), 3,15-dioxofriedelane(14), 3α-friedelinol(15), 3,12-dioxofriedelan-28-al(16), 3-oxo-12α-hydroxyfriedelane(17), 3,15-dioxo-12α-hydroxyfriedelane(18), 3ß,11ß-dihydroxyolean-12-en(19), 1ß,3ß-dihydroxylupan-20(29)-en(20), 3-oxo-12α,28-dihydroxyfriedelane(21), 3ß,23-epoxyfriedelan-28-oic acid(22), salaquinone A(23), 2α,3ß-dihydroxyfriedelan-28-oic acid(24), 23-nor-6-oxodemethylpristimerol(25) and 3-oxo-friedelan-27,28-dioic acid(26). Among them, compounds 8, 10-15, 18-20, 22-26 were obtained from this plant for the first time, and compounds 8, 10, 12, 14-15, 18, 22-24, 26 were separated from the genus Celastrus for the first time.

[Effect of paeoniflorin on oxidative stress and energy metabolism in mice with lipopolysaccharide (LPS)-induced brain injury].

Paeoniflorin is the main active ingredient of Chinese herbaceous peony. This study is to investigate the protective effect of paeoniflorin (Pae) on acute brain damage induced by lipopolysaccharide (LPS) in mice. The mice were randomly assigned to the normal control, model control (LPS), as well as groups of paeoniflorin and lipopolysaccharide (Pae + LPS). Then the mice were administered intraperitioneally with normal saline or Pae (10, 30 mg · kg(-1)) once daily for 6 d. One hour after intrapertioneally treatment on the seventh day, each group were injected LPS (5 mg · kg(-1)) to establish the endotoxin lipopolysaccharide inflammation model except the normal group. The mice were sacrificed after 6 h and the brain homogenates were prepared and measured. The malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2), succinatedehydrogenase (SDH), Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase were dectected by the colorimetric method. The levels of HO-1 and Nrf2 protein in subcellular fractions of brain tissue were detected by Western blot. The results demonstrated that the administration with paeoniflorin reduced the levels of the MDA production; significantly increase the activities of antioxidant enzyme (SOD and GSH-PX). In addition, paeoniflorin could enhance the total antioxidant capacity, decrease the level of H2O2, and increase the activities of SDH, Na(+)-K(+)-ATPase and Ca(2+)-Mg(2+)-ATPase. Furthermore, paeoniflorin can increase the expression of HO-1 and activate the nuclear transfer of Nrf2. Taking together, these findings suggest that paeoniflorin alleviate the acute inflammation in mice brain damage induced by LPS, which is related with its antioxidant effect and improvement of energy metabolism.

[Four properties law of nature data of Chinese materia medica in "Chinese herbal medicine (CHM)"].

OBJECTIVE: In order to provide theoretical clues and data support for the use of Chinese medicine clinical drug, experimental study of Chinese materia medica and development of new resources of Chinese materia medica, the four properties as the core, the relationships of property, flavor, channel tropism and toxicity in nature data of Chinese materia medica were analyzed. METHOD: The spearman rank correlation method was employed to analyze 8 356 Chinese drugs with characteristic of four properties from " Chinese Herbal Medicine" based on data level coding. RESULT: It was discovered that four properties showed significant positive correlations with tastes of "pungent and sweet" , channels of "spleen" , "stomach" , "kidney" and "toxicity" , but also showed significant negative correlations with tastes of "bitter" and "light" and six channels such as "large intestine" , "heart", "bladder" , "gallbladder" , "small intestine" and "lung" (in descending order of correlation ) (P <0. 01). CONCLUSION: It was indicated that the more hot the Chinese medicine nature, the more possible it contained "toxicity" , tastes of "pungent" and "sweet" , and the more possible it was belong to channels of "spleen" , "stomach" and "kidney". As well, the more cold the Chinese medicine nature, the more possible it contained tastes of "bitter" and "light", and the more possible it was belong to six channels such as "large intestine", etc.

[Mining rules on determination of four properties based on traditional Chinese medicine functional combination].

OBJECTIVE: It laid the foundation of the large sample data mining for a comprehensive summary concerning four properties theory of traditional Chinese medicine (TCM), and also provided theory clues on determination of four properties for the new resource development of TCM and the clinical use of Chinese medicine. METHOD: Four properties data of 8 980 Chinese medicines from "Chinese herbal medicine (CHM)" and associated function index data were chose as data sets. Then, the IBM SPSS Clementine 14.1 data mining platform and Apriori model were adopted to mining classification-association rules, setting the minimum support threshold of rule antecedent and the minimum confidence threshold as 0.5% and 60%. RESULT: 11 classification-association rules involved in warm, cold and mild natures were found. CONCLUSION: It was discovered that the TCM with functions of "dispelling wind-cold, warming the middle, stopping pain and expelling wind-removing dampness, tonifying kidney yang, unblocking meridians and expelling wind-removing dampness, dispelling cold to stop pain, strengthening sinews-bones and expelling wind-removing dampness" was likely warm-natured, with functions of "tonifying the lung" was likely mild-natured, and with functions of " clearing heat and drying dampness, clearing heat and purging fire, eliminating restlessness" was likely cold-natured.

The extracts of Fructus Akebiae, a preparation containing 90% of the active ingredient hederagenin: serotonin, norepinephrine and dopamine reuptake inhibitor.

Fructus Akebiae is a traditional Chinese herbal extract that has been used for the treatment of depressive disorders in China. Previous studies demonstrated that Fructus Akebiae extracts (FAE) displayed a potent antidepressant-like activity in animal behavior tests and found that the specific active ingredient from the extracts of Fructus Akebiae is hederagenin. However, the underlying mechanism is unknown. Here we provide evidences that FAE enhances the signaling of central monoamines via inhibition of the reuptake of the extracellular monoamines including serotonin (5-HT), norepinephrine (NE) and dopamine (DA). In rat brain membrane preparations and HEK293 cells transfected with human serotonin transporter (SERT), NE transporter (NET) and DA transporter (DAT), we found that FAE displayed marked affinity to rat and cloned human monoamine transporters in ex vivo and in vitro experiments, using competitive radio ligand binding assay. In uptake assays using rat synaptosomes and transfected cells, FAE was found to significantly inhibit all three monoamine transporters in a dose- and time-dependent manner, with a comparable or better potency to their corresponding specific inhibitors. In contrast, FAE (10 µM), showed no significant affinity to a variety array of receptors tested from CNS. In support of our uptake data, in vivo microdialysis studies showed that administration of FAE (12.6, 25, 50 mg/kg) significantly increased extracellular concentrations of 5-HT, NE and DA in frontal cortex of freely moving rats. Taken together, our current study showed for the first time that FAE is a novel triple inhibitor of monoamine transporters, which may be one the mechanisms of its antidepressant activity.

Analysis of the essential oils of Coriandrum sativum Using GC-MS coupled with chemometric resolution methods.

The essential oils extracted from Coriandrum sativum L. were analyzed by GC-MS coupled with chemometric resolution methods. Through the chemometric resolution methods, peak clusters were uniquely resolved into the pure chromatographic profiles and mass spectra of each component. Qualitative analysis was performed by comparing the pure mass spectra with those in the NIST 05 mass spectral library. Quantitative analysis was performed using the total volume integration method. A total of 118 constituents were detected, of which 104 were identified, accounting for 97.27% of the total content. The results indicate that GC-MS combined with chemometric resolution methods can greatly enhance the capability of separation and the reliability of qualitative and quantitative results. The combined method is an economical and accurate approach for the rapid analysis of the complex essential oil samples in Coriandrum sativum L.

Antidepressant effect of the extracts from Fructus Akebiae.

Fructus Akebiae is a common ingredient in many traditional Chinese medicine complex prescriptions for the treatment of mental disorders. Previous studies indicate that the main chemical compositions of Fructus Akebiae are triterpenoid saponins with hederagenin as their sapogenin. In the present study, we enriched hederagenin from the extracts of Fructus Akebiae with a purity of approximately 70%. Using behavioral tests sensitive to antidepressant drugs, we demonstrated that acute and sub-chronic administration of the extracts of Fructus Akebiae produced antidepressant-like effects, as evidenced by decreases in the duration of immobility in forced swim and tail suspension tests in mice and reversal of chronic unpredicted mild stress-induced inhibition of sucrose consumption in rats. In addition, the extracts decreased the levels of plasma adrenocorticotrophic hormone and serum corticosterone in rats exposed to chronic unpredicted mild stress. Both behavioral and biochemical effects of the extracts were mimicked by the proven antidepressant escitalopram. These results suggest that the extracts of Fructus Akebiae exert antidepressant activity. Administration of the extracts may be beneficial for patients with depressive disorders.

[The origin and development of special methods of "expiration and inspiration" (Tuna) in pre-Qin and Han dynasties].

Tuna (special methods of expiration and inspiration) was generated in the working life and health activities of the early stage of the human race in ancient times. It developed in the period of the Qin, Han and three kingdoms, developing the theory of bionic expiration and inspiration as well as the breath of the upper pubic region (Dantian); the skill of the Qi conduction school emerged so that the skills of embryonic breath and the upper pubic region breath came into being. The skill of meditation of the Chan sect of the Western Regions was also introduced into the central plains at this time. The skill of counting breath had a profound impact on the skill of embryonic breath of the Taoism elixir school.

[Research on developmental characteristic of the theory of ZANG-fu differentiation of syndromes in the period of Jin-Tang Dynasties.].

In the period from Jin to Tang dynasties, the Theory of Zang-fu differentiation of syndromes had been set up and prosperous. During this period, the first summary of the theory appeared, and the eight principles of Zang-fu differentiation, pulse diagnosis combining with Zang-fu theory upgraded to a new higher level, the application of medicines and prescriptions perfected. This theory was completely diffused into clinical practice. Since Taoism specifically stressed the theory of Zang-fu differentiation of syndromes, this theory expanded its influence and promoted its development.

[Determination of organochlorine pesticide residue in nine Chinese herbs by gas chromatography].

OBJECTIVE: To determine organochlorine pesticide residue in 9 Chinese herbs. METHODS: The organochlorine pesticides were extracted from the herbs with mixed solvents of n-hexane and acetone by a solid-phase extraction cartridge Florisil. Capillary gas chromatography was used to separate the samples. RESULTS: Good linearities were obtained for 11 organochlorine pesticides. The average recoveries at two concentration levels ranged from 79.9% to 89.0%,and from 86.3% to 104.8%, with relative standard deviations of 1.8% to 7.1%, respectively and detection limit of 2 g/kg. The residues of the organic pesticides exceeded national standard in Pogostemon cablin and Panax notoginseng. CONCLUSION: Capillary gas chromatography combined with electron capture detection provides a practical means for detecting organic pesticide residue in Chinese herbal medicines, and the limits of pesticide residues should be formulated in Chinese pharmacopoeia.

[Studies on developmental features of theories of syndrome differentiation of zang-fu viscera in Qin and Han Dynasties].

The formation of the theories of visceral manifestations as well as channels and collaterals in the books Huangdi Neijing (Inner Canon of Huangdi) and Nan Jing (Classic of Questioning) laid down the theoretical foundation for the theories of syndrome differentiation of zang--fu viscera. From the early occurrence of syndrome classification to that of the disease manifestations of zang and fu viscera, the theories of syndrome differentiation of zang--fu viscera were basically not put into practice until Shanghan Zabing Lun (Treatise on Cold Pathogenic and Miscellaneous Diseases) appeared. The theories of syndrome differentiation of zang--fu viscera in the Qin and Han Dynasties were not systematic and were scattered, indicating that it was a period of gestation for the theories.

[Fingerprinting of Panax notoginseng by high-performance liquid chromatography].

Fingerprinting of Panax notoginseng was performed by high-performance liquid chromatography using Agilent Hypersil C18 (250.0 mm x 4.0 mm, 5 microm) column with the mobile phase of acetonitrile and water and gradient elution. The detection wavelength was set at 203 nm. The method is simple and reliable to identify and evaluate the quality of Panax notoginseng.