OBJECTIVES: To explore the therapeutic mechanism of Guizhi Fuling (GZFL) Pellets against cervical cancer. METHODS: Publicly available databases were used to identify the targets of GZFL Pellets and cervical cancer to construct the protein-protein interaction (PPI) network, followed by GO biological process and KEGG pathway enrichment analysis of the hub genes. The "Traditional Chinese Medicine-Active Ingredients-Targets-Pathways" network for GZFL Pellets in cervical cancer treatment was generated using Cytoscape v10.0.0, and molecular docking of the drug and potential targets was performed to predict the specific targets of active components in Guizhi Fuling Pellets. The inhibitory effects of hederagenin, an active ingredient in GZFL Pellets, was tested in cultured cervical cancer cells and in nude mice bearing cervical cancer xenografts. RESULTS: GZFL Pellets contain 338 active components targeting 247 action sites. A total of 10127 cervical cancer-related targets were obtained, and among them 195 were identified as potential therapeutic targets of GZFL Pellets for cervical cancer treatment, including the key targets of GABRA1, PTK2, JAK2, HTR3A, GSR, and IL-17. Molecular docking study showed low binding energies of the active components such as hederagenin, campesterol, and stigmasterol for protein-molecule interaction. GO enrichment analysis suggested that GZFL Pellets inhibited cervical cancer primarily by regulating responses to steroid hormones, oxidative stress, and lipopolysaccharides. Among the active components of GZFL Pellets, hederagenin was found to inhibit cervical cancer cells in vitro and significantly reduced STAT3 phosphorylation level in the cancer cells. In nude mice bearing cervical cancer xenografts, hederagenin effectively inhibited tumor growth rate without causing obvious adverse effects. CONCLUSIONS GZFL Pellets inhibit cervical cancer cell growth through its multiple active components that target different pathways. Among these components, hederagenin inhibits tumor cell growth possibly by directly binding to JAK2 protein to inhibit STAT3 phosphorylation.
Female ; Animals ; Uterine Cervical Neoplasms/pathology* ; Mice, Nude ; Humans ; Mice ; Oleanolic Acid/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Molecular Docking Simulation ; Xenograft Model Antitumor Assays ; Cell Line, Tumor ; STAT3 Transcription Factor/metabolism* ; Protein Interaction Maps ; Janus Kinase 2/metabolism*

Oleanolic acid (OA) is a pentacyclic triterpenoid compound extracted from olea europaeal, a traditional Chinese medicine herb. OA has been used in the clinic as a hepatoprotective medicine in China since 1970s. In our previous study, we observed that OA could ameliorate hyperlipidemia in animal models. In the present study, we conducted a small-scale clinical trial to evaluate the hypolipidemia effect of OA in hyperlipidemic patients. Hyperlipidemic patients were administrated with OA for four weeks (4 tablets once, three times a day). The blood samples of the patients were collected before and after OA treatment. The biological parameters were measured. Furthermore, three patients' blood samples were studied with DNA microarray. After OA administration, the TC, TG, and HDLC levels in serum decreased significantly. DNA microarray analysis results showed that the expressions of 21 mRNAs were significantly changed after OA treatment. Bioinformatics analysis showed 17 mRNAs were up-regulated and 4 mRNAs were down-regulated significantly after OA treatment. Five mRNAs (CACNA1B, FCN, STEAP3, AMPH, and NR6A1) were selected to validate the expression levels by qRT-PCR. Therefore, OA administration differentially regulated the expression of genes involved in lipid metabolism. The data showed a clinical evidence that OA could improve hyperlipidemia and also unveiled a new insight into the molecular mechanisms underlying the pharmacological effect of OA on hyperlipidemia.
China ; Computational Biology ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; drug effects ; Humans ; Hyperlipidemias ; blood ; drug therapy ; genetics ; metabolism ; Lipid Metabolism ; drug effects ; Male ; Middle Aged ; Oleanolic Acid ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; Treatment Outcome

OBJECTIVEOleanolic acid (OA) has been reported to have anticancer effects, but the extent of its cytotoxicity, its ability to interact with nuclear DNA, its action against skin melanoma, as well as the molecular mechanism of its action against cell proliferation and in support of cell death are still unexplored. This led us to examine the efficacy of OA, a bioactive compound isolated from Phytolacca decandra, on these issues in the present investigation.

METHODSStudies related to analyses of cell viability, drug-DNA interaction, cell proliferation, cell cycle and epidermal growth factor receptor (EGFR) activity were performed. To investigate whether cells undergo apoptosis, studies like fluorescence microscopy, poly (ADP-ribose) polymerase (PARP) degradation, annexin V-fluorescein isothiocyanate/propidium iodide assay, alteration in mitochondrial membrane potential and activity of some relevant signaling proteins were performed.

RESULTSOA displayed a minimal and negligible cytotoxic effect on normal HaCaT cells (skin keratinocytes) and peripheral blood mononuclear cells but by contrast it reduced A375 cell viability significantly. OA interacted with nuclear DNA quickly after exposure. It acted as an anti-proliferative agent. It suppressed EGFR activity. OA administration led the cells to mitochondria-dependent caspase 3-mediated apoptosis.

CONCLUSIONOA interacts with cellular DNA, inhibits proliferation possibly through modulating EGFR activity and induces mitochondria-dependent caspase 3-mediated apoptosis in A375 cells which would qualify it as a potent anticancer agent.

Antineoplastic Agents ; isolation & purification ; therapeutic use ; Apoptosis ; drug effects ; Cell Line, Tumor ; DNA, Neoplasm ; drug effects ; Humans ; Melanoma ; drug therapy ; Microscopy, Fluorescence ; Oleanolic Acid ; isolation & purification ; therapeutic use ; Phytolacca ; chemistry ; Phytotherapy ; methods ; Plant Extracts ; isolation & purification ; therapeutic use ; Receptor, Epidermal Growth Factor ; drug effects ; physiology ; Signal Transduction ; drug effects ; Skin Neoplasms ; drug therapy

Humans ; Liver Diseases ; drug therapy ; prevention & control ; Oleanolic Acid ; analogs & derivatives ; therapeutic use ; Phytotherapy ; Saponins ; therapeutic use

Total aralosides of Aralia elata (Miq) Seem (TASAES) from Chinese traditional herb Longya Aralia chinensis L was found to improve cardiac function. The present study was to determine the protective effects of TASAES on diabetic cardiomyopathy, and the possible mechanisms. Therefore, a single dose of streptozotocin was used to induce diabetes in Wister rats. Diabetic rats were immediately treated with low, medium and high doses of TASAES at 4.9, 9.8 mg/kg and 19.6 mg/kg body weight by gavage, respectively, for eight weeks. Cardiac function was evaluated by in situ hemodynamic measurements, and patch clamp for the L-type Ca2+ channel current (ICa2+-L) and transient outward K+ channel current (Ito). Histopathological changes were observed under light and electron microscope. The expression of pro-fibrotic factor, connective tissue growth factor (CTGF) was monitored using immunohistochemistry staining. Compared with diabetic group, medium and high doses, but not low dose, of TASAES showed a significant protection against diabetes-induced cardiac dysfunction, shown by increased absolute value of left ventricular systolic pressure (LVSP) and maximum rates of pressure development (+/-dp/dt(max)), and enhanced amplitude of ICa2+-L (P < 0.05). Histological staining indicated a significant inhibition of diabetes-caused pathological changes and up-regulation of CTGF expression (P < 0.05). The results suggest that TASAES prevents diabetes-induced cardiac dysfunction and pathological damage through up-regulating ICa2+-L in cardiac cells and decreasing CTGF expression.
Animals ; Aralia/*chemistry ; Calcium Channels, L-Type/physiology ; Cardiomyopathies/*drug therapy/etiology/physiopathology ; Connective Tissue Growth Factor/metabolism ; Diabetes Mellitus, Experimental/*complications ; Drugs, Chinese Herbal/*chemistry ; Heart/drug effects/physiopathology ; Hemodynamics ; Male ; Myocardium/pathology ; *Oleanolic Acid/analogs & derivatives/therapeutic use ; Patch-Clamp Techniques ; Potassium Channels/physiology ; Rats ; Rats, Wistar ; Saponins/*therapeutic use ; Treatment Outcome

OBJECTIVETo study the effect of SSd on lipid peroxidation during experimental hepatic fibrosis progression.

METHODThe experimental models of hepatic fibrosis were induced by intraperitoneal injection of dimethylnitrosamine (DMN) on rats. SSd was administered by intraperitoneal injection for 4 weeks. Serum was analyzed for alanine and aspartate aminotransferase (ALT and AST), hyaluronic acid (HA), laminin (LN), collagen IV (IV-C), malonaldehyde (MDA) and superoxide dismutase (SOD) activities. Liver samples were measured for MDA contents and SOD activities in normal group, model group and SSd group.

RESULTSSd significantly decreased ALT and AST activities and lowered HA, LN and IV-C contents. It enhanced SOD activities in liver, while reduced MDA contents both in serum and liver.

CONCLUSIONSSd has obvious effects of protecting hepatocytes and resisting hepatic fibrosis, and the mechanism may be associated with its anti-lipid peroxidation effect.

Animals ; Aspartate Aminotransferases ; blood ; Collagen Type IV ; blood ; Dimethylnitrosamine ; adverse effects ; Hyaluronic Acid ; blood ; Laminin ; blood ; Lipid Peroxidation ; drug effects ; Liver Cirrhosis ; blood ; chemically induced ; drug therapy ; metabolism ; Malondialdehyde ; blood ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Rats ; Saponins ; pharmacology ; therapeutic use ; Superoxide Dismutase ; blood

OBJECTIVETo study the anti-inflammatory and analgesic actions of Aike Mixture (AKM).

METHODSA total of 100 male mice were randomly assigned into 5 groups: a normal control group, a drug control group (a hydrocortisone subgroup and an atropine subgroup), a high-dose AKM group, a mid-dose AKM group and a low-dose AKM group. Xylene was spread on the left ear of the experimental mice to induce inflammation, and 1% acetic acid solution injected into the abdominal cavity to produce pain so as to cause the body bend. Different doses of AKM were given and their actions observed.

RESULTSAKM had obvious anti-inflammatory effect on the xylene-induced ear tumefaction and inhibited the pain-caused body bend in the AKM groups, with significant difference from the normal control (P < 0.01).

CONCLUSIONAKM has good anti-inflammatory and analgesic effects, which is of clinical significance in the treatment of chronic prostatitis.

Animals ; Chronic Disease ; Disease Models, Animal ; Drug Combinations ; Male ; Mice ; Mice, Inbred ICR ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; therapeutic use ; Phytotherapy ; Prostatitis ; drug therapy ; Saponins ; pharmacology ; therapeutic use

OBJECTIVETo provide fundamental information for its exploiting. Aralia echinocaulis by the resource and identification study on.

METHODResource survey and various identification were carried out.

RESULTThe county level distribution and ecological environment of A. echinocaulis were initially observed. It mainly distributed in the mountainous areas of the Yangtze River basin and the south, and was usually used as folk drug. This study also displayed its morphological, microscopic and chemophysical identification features.

CONCLUSIONThe morphological features of original plant and crude drug, and the anatomical and chemophysical characteristics of A. echinocaulis are of identification value, and the species are also of greater development and utilization potentiality, but the resource does not support the sustainable utilization. Therefore, artificial propagation is apparently crucial to its exploitation.

Aralia ; anatomy & histology ; chemistry ; Arthritis, Rheumatoid ; drug therapy ; China ; Conservation of Natural Resources ; Drugs, Chinese Herbal ; analysis ; therapeutic use ; Ecosystem ; Humans ; Oleanolic Acid ; analysis ; Pharmacognosy ; Phytotherapy ; Plant Leaves ; cytology ; Plant Roots ; chemistry ; cytology ; Plants, Edible ; anatomy & histology ; Plants, Medicinal ; anatomy & histology ; chemistry ; Stomach Ulcer ; drug therapy ; Triterpenes ; analysis