OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

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.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; Autophagy ; Cell Cycle Checkpoints ; Diterpenes ; pharmacology ; Epoxy Compounds ; pharmacology ; Humans ; Neoplasms ; drug therapy ; Phenanthrenes ; pharmacology ; Tripterygium ; chemistry

Guanxinshutong capsule (GXSTC) is an effective and safe traditional Chinese medicine used in the treatment of cardiovascular diseases (CVDs) for many years. However, the targets of this herbal formula and the underlying molecular mechanisms of action involved in the treatment of CVDs are still unclear. In the present study, we used a systems pharmacology approach to identify the active ingredients of GXSTC and their corresponding targets in the calcium signaling pathway with respect to the treatment of CVDs. This method integrated chromatographic techniques, prediction of absorption, distribution, metabolism, and excretion, analysis using Kyoto Encyclopedia of Genes and Genomes, network construction, and pharmacological experiments. 12 active compounds and 33 targets were found to have a role in the treatment of CVDs, and four main active ingredients, including protocatechuic acid, cryptotanshinone, eugenol, and borneol were selected to verify the effect of (GXSTC) on calcium signaling system in cardiomyocyte injury induced by hypoxia and reoxygenation. The results from the present study revealed the active components and targets of GXSTC in the treatment of CVDs, providing a new perspective to enhance the understanding of the role of the calcium signaling pathway in the therapeutic effect of GXSTC.
Animals ; Animals, Newborn ; Camphanes ; chemistry ; Cardiotonic Agents ; chemistry ; pharmacology ; Cells, Cultured ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Eugenol ; chemistry ; Gene Expression ; drug effects ; Hydroxybenzoates ; chemistry ; Mass Spectrometry ; Models, Biological ; Myocytes, Cardiac ; drug effects ; Nitric Oxide Synthase Type III ; genetics ; Phenanthrenes ; chemistry ; Rats ; Rats, Sprague-Dawley ; Receptor, PAR-1 ; genetics ; Systems Biology

The present study was designed to explore the influence of water extracts of Atractylodes lancea rhizomes on the toxicity and anti-inflammatory effects of triptolide (TP). A water extract was prepared from A. lancea rhizomes and co-administered with TP in C57BL/6 mice. The toxicity was assayed by determining serum biochemical parameters and visceral indexes and by liver histopathological analysis. The hepatic CYP3A expression levels were detected using Western blotting and RT-PCR methods. The data showed that the water extract of A. lancea rhizomes reduced triptolide-induced toxicity, probably by inducing the hepatic expression of CYP3A. The anti-inflammatory effects of TP were evaluated in mice using a xylene-induced ear edema test. By comparing ear edema inhibition rates, we found that the water extract could also increase the anti-inflammatory effects of TP. In conclusion, our results suggested that the water extract of A. lancea rhizomes, used in combination with TP, has a potential in reducing TP-induced toxicity and enhancing its anti-inflammatory effects.
Animals ; Anti-Inflammatory Agents ; isolation & purification ; pharmacology ; Atractylodes ; chemistry ; Cytochrome P-450 Enzyme System ; genetics ; Diterpenes ; toxicity ; Edema ; chemically induced ; pathology ; Enzyme Induction ; drug effects ; Epoxy Compounds ; toxicity ; Gene Expression Regulation ; drug effects ; Herb-Drug Interactions ; Liver ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Phenanthrenes ; toxicity ; Plant Extracts ; isolation & purification ; pharmacology ; Plants, Medicinal ; chemistry ; Rhizome ; chemistry ; Water ; chemistry

OBJECTIVETo examine whether sodium tanshinone II A sulfonate (STS), the main effective component of Salvia miltiorrhiza is effective in relieving the microcirculatory disturbance of small intestine by suppressing the production of reactive oxygen species (ROS) in rats with sepsis.

METHODSA rat model of sepsis was induced by cecal ligation and puncture (CLP). Rats (n =40) were randomly divided into 4 groups: sham-operated group (sham, n =10), sepsis group (CLP, n =10), STS treatment group (STS, n =10) and ROS scavenger dimethylthiourea (DMTU, n =10) group. Animals in the STS group were injected with STS (1 mg/kg) for 10 min through the right external jugular vein after the CLP operation, and animals in the CLP group were given the same volume of normal saline after the CLP operation. Animals in the DMTU group were intraperitoneally injected with 5 mL/kg of 20% DMTU 1 h before CLP. The histopathologic changes in the intestinal tissues and changes of mesenteric microcirculation were observed. The levels of ROS in intestinal tissues from each group were qualitatively evaluated using a fluorescent microscope. The expressions of apoptosis signal-regulating kinase (ASK1), phosphorylated ASK1 (phospho-ASK1), p38 mitogen-activated protein kinases (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK) and tissue factor (TF) were determined by Western blotting.

RESULTSIt was shown that there were obvious microcirculatory disturbance (P <0.05) and tissue injuries in intestinal tissues after CLP operation. The levels of ROS production, phospho-ASK1, phospho-p38 MAPK and TF were increased. Both STS and DMTU suppressed ROS, phospho-ASK1, phospho-p38 MAPK and TF production, and ameliorated the microcirculatory disturbance and tissues injury (P <0.01).

CONCLUSIONSTS can ameliorate the microcirculatory disturbance of the small intestine by attenuating the production of ROS in rats with sepsis.

Animals ; Intestine, Small ; blood supply ; drug effects ; pathology ; MAP Kinase Kinase Kinase 5 ; metabolism ; Male ; Microcirculation ; drug effects ; Phenanthrenes ; chemistry ; pharmacology ; therapeutic use ; Phosphorylation ; drug effects ; Rats, Wistar ; Reactive Oxygen Species ; metabolism ; Sepsis ; drug therapy ; enzymology ; pathology ; physiopathology ; Thromboplastin ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

The present study was designed to identify bioactive compounds similar to those isolated from Dendrobium genus from its relative specie Eria bambusifolia. Compounds 1-10 were isolated and purified using silica gel, MCI CHP-20 gel, Sephadex LH-20, and Lichroprep RP-18 chromatography methods. Their structures were elucidated by means of extensive spectroscopic analyses. The cytotoxicity of these compounds against five human cancer cell lines was tested. Erathrins A and B (1 and 2) were new compounds, and compound 1 represented a novel carbon framework having a phenanthrene-phenylpropane unit with a dioxane moiety. Moreover, compound 1 showed selective cytotoxic activity against HL-60 cells (IC50 = 14.50 μmol·L(-1)). These results provided a basis for future development of these agents as anticancer lead compounds.
Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; Cell Survival ; drug effects ; Dendrobium ; chemistry ; HL-60 Cells ; Humans ; Molecular Structure ; Phenanthrenes ; chemistry ; pharmacology ; Plant Extracts ; chemistry ; pharmacology

The study is aimed to investigate the effect of plant growth regulators on yield and quality of the Salvia miltiorrhiza. The plant growth regulators was spraying on Salvia plants in July or August in field experiment, then the yield, ingredient content and the antioxidant activity were determined. The results showed that plant growth regulator 'Zhuanggenling' could increase the yield of Salvia with root-planting by 38.45%. Plant growth regulator 'Duoxiaozuo' could increase the yield of Salvia with seedling planting by 14.19%. Both plant growth regulator significantly reduced the antioxidant activity of Salvia in vitro, but they had no significant effect on active ingredient contents.
Diterpenes, Abietane ; analysis ; Phenanthrenes ; analysis ; Plant Extracts ; analysis ; Plant Growth Regulators ; pharmacology ; Salvia miltiorrhiza ; chemistry ; drug effects ; growth & development

OBJECTIVETo observe the analgesic effect of triptolide (TP) of high, middle and low doses on rats with adjuvant arthritis (AA), and the expressions of inducible nitric oxide synthase (iNOS) and substance P (SP) in spinal dorsal horn and dorsal root ganglion (DRG) of corresponding sections, in order to discuss the possible mechanism for the analgesic effect of TP on rats with adjuvant arthritis.

METHODFifty SD rats were selected and randomly divided into the normal group (group A), the model group (group B), and TP low (group C), middle (group D), high (group E) dose groups. Except for the group A, all of the remaining groups were injected with 0.1 mL of Freund's complete adjuvant through their right rear toes to establish the model. At 14 d after the model establishment, rats in C, D and E groups were intraperitoneally injected with different doses of TP (0.1 mg x kg(-1) for the group C, 0.2 mg x kg(-1) for the group D, 0.4 mg x kg(-1) for the group E) once a day for 9 days. Then the 50% mechanical withdraw threshold (MWT) was determined. And the expressions of iNOS and SP in lumbar5 (L5) spinal dorsal horn and DRG were detected with the immunohistochemical method.

RESULTThe 50% MWT of rats in the group B was significantly lower than that of the group A (P < 0.01). After being treated with TP, the Thermal withdrawal latencies of groups C, D and E were significantly higher than that of the group B (P < 0.01). TP could notably increase the MWT of AA rats, with a certain dose-effect relationship. The immunohistochemical results indicated that the iNOS and SP expressions significantly increased in the group B (P < 0.01), while the positive expression levels of iNOS and SP in groups C, D and E were significantly lower than that of the group B (P < 0.01), with a certain dose-effect relationship.

CONCLUSIONTP shows a good analgesic effect on AA, and could inhibit the iNOS and SP expressions in spinal dorsal horn and DRG in rats with adjuvant arthritis, which may be one of action mechanisms for the analgesic effect of TP.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Arthritis, Experimental ; drug therapy ; metabolism ; physiopathology ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Epoxy Compounds ; pharmacology ; Female ; Ganglia, Spinal ; drug effects ; metabolism ; Immunohistochemistry ; Male ; Nitric Oxide Synthase Type II ; biosynthesis ; Pain Measurement ; methods ; Phenanthrenes ; pharmacology ; Phytotherapy ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spinal Cord ; drug effects ; metabolism ; Substance P ; biosynthesis ; Time Factors ; Treatment Outcome ; Tripterygium ; chemistry

OBJECTIVETo investigate the anti-angiogenic effect of cryptotanshinone (CPT) on human umbilical vein endothelial cells (HUVECs) and the effect of CPT on Wnt/β-catenin signaling pathway.

METHODSHUVECs were incubated with 0, 2.5, 5, 10, and 20 μ mol/L CPT for detecting cell viability with dimethyl thiazolyl-2,5-diphenyltetrazolium bromide (MTT) assay. Then, HUVECs were incubated with 0, 2.5, 5, and 10 μ mol/L CPT for detecting endothelial cell migration, invasion, and tubular-like structure formation with wound healing, transwell invasion and matrigel tube formation assays, respectively. To gain insight into CPT-mediated signaling, the effects of CPT on T-cell factor/lymphocyte enhancer factor (TCF/LEF) transcription factors were detected by the Dual-luciferase reporter assay. Next, the nuclear expression of β-catenin was evaluated using Western blot and immunochemistry. Finally, vascular endothelial growth factor (VEGF) and cyclin D1, downstream proteins of the Wnt pathway were examined with Western blot.

RESULTSCPT dose-dependently suppressed endothelial cell viability, migration, invasion, and tubular-like structure formation. In particular, CPT blocked β-catenindependent transcription in HUVECs in a dose-dependent manner. In Western bolt, 10 μ mol/L CPT decreased expression of β-catenin in nucleus of HUVECs (P<0.01). In immunohistochemistry, β-catenin was more potent in response to LiCl (an activator of the pathway) treatment. However, the signals were weaker in the nucleus of the CPT (10 μ mol/L) group, compared to the positive control. Also, VEGF and cyclin D1 were both eliminated by CPT in 5 and 10 μ mol/L doses (P<0.05).

CONCLUSIONOur study supported the role of CPT as an angiogenic inhibitor, which may impact on the Wnt/β-catenin signaling pathway.

Blotting, Western ; Cell Movement ; drug effects ; Cell Survival ; drug effects ; Cyclin D1 ; metabolism ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Immunohistochemistry ; Luciferases ; metabolism ; Neovascularization, Physiologic ; drug effects ; Phenanthrenes ; chemistry ; pharmacology ; Vascular Endothelial Growth Factor A ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; metabolism

Anticancer targets of cryptotanshinone were evaluated and rapidly forecasted with PharmMapper, a reverse pharmacophore-based screening platform, as well as drug target databases, including PDTD, DrugBank and TTD. The pathway analyses for the collection of anticancer targets screened were carried out based on the KEGG pathway database, followed by the forecast of potential pharmacological activities and pathways of the effects of cryptotanshinone, and verification of some of the targets screened using whole cell tests. The results showed that a total of eight targets with anticancer potential were screened, including MAP2K1, RARα, RXRα, PDK1, CHK1, AR, Ang-1 R, and Kif11. These targets are mainly related to four aspects of the cancer growth: the cell cycle, angiogenesis, apoptosis, and androgen receptor. The cell tests showed that cryptotanshinone can inhibit the viability of human hepatoma cells SMMC-7721, which is related to the reduction of expression of MAP2K1 mRNA. This method provides a strong clue for the study of the anticancer effects and mechanisms of action of cryptotanshinone in the future.
Antineoplastic Agents, Phytogenic ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; genetics ; metabolism ; Cell Cycle ; Cell Line, Tumor ; Databases, Factual ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Humans ; MAP Kinase Kinase 1 ; metabolism ; Neovascularization, Pathologic ; Phenanthrenes ; pharmacology ; therapeutic use ; Phytotherapy ; RNA, Messenger ; metabolism ; Receptors, Androgen ; metabolism ; Salvia miltiorrhiza ; chemistry