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

Triptolide (TP) is a major active component in Tripterygium root, but its therapeutic window was very narrow due to its severe multi-organ toxicity. In this work, the effect of TP combined with glycyrrhetic acid (GA) on mRNA expression and activity of four cytochrome P450 (CYP) enzymes in rat liver was studied after intragastric administration of TP (0.05, 0.3 and 0.6 mg x kg(-1) x day(-1)) and TP (0.6 mg x kg(-1) x day(-1)) combined with GA (30 mg x kg(-1) x day(-1)) for 7 consecutive days. Compared with the control, the high dose of TP significantly up-regulated the mRNA expression levels of CYP2E1, 1A2, 3A1 and 2C11, the co-administration of TP and GA further up-regulated the mRNA expression levels of CYP3A1, 2C11 and 2E1 as compared with the high dose of TP. Meanwhile, TP at high dose and combined with GA significantly increased CYP3A-associated testosterone 6beta-hydroxylation activity (2.2-fold and 4.1-fold, respectively) as compared with the control. Because TP is mainly metabolized by CYP3A2 in male rats, the present work indicated that TP-induced increase of CYP3A activity might be an important reason for the rapidly metabolic clearance of TP in rat liver, and GA can reduce the hepatotoxicity of TP by promoting its hepatic metabolic clearance. Furthermore, the results also suggest that the drug interactions might be occurred when TP and GA were co-administered with other CYP3A substrate drug.
Animals ; Aryl Hydrocarbon Hydroxylases ; genetics ; metabolism ; Cytochrome P-450 CYP1A2 ; genetics ; metabolism ; Cytochrome P-450 CYP2E1 ; genetics ; metabolism ; Cytochrome P-450 CYP3A ; genetics ; metabolism ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Cytochrome P450 Family 2 ; Diterpenes ; administration & dosage ; isolation & purification ; pharmacology ; Dose-Response Relationship, Drug ; Drug Combinations ; Drug Interactions ; Enzyme Activation ; Epoxy Compounds ; administration & dosage ; isolation & purification ; pharmacology ; Glycyrrhetinic Acid ; isolation & purification ; pharmacology ; Liver ; enzymology ; Male ; Phenanthrenes ; administration & dosage ; isolation & purification ; pharmacology ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; RNA, Messenger ; metabolism ; Rats ; Rats, Wistar ; Steroid 16-alpha-Hydroxylase ; genetics ; metabolism ; Tripterygium ; chemistry

The investigation on Salvia przewalskii Maxim was carried out to find the relationship of the constituents and their pharmacological activities. The isolation and purification were performed by various chromatographies such as silica gel, Sephadex LH-20, RP-C18 column chromatography, etc. Further investigation on the fraction of the 95% ethanol extract of Salvia przewalskii Maxim yielded przewalskin Y-1 (1), anhydride of tanshinone-II A (2), sugiol (3), epicryptoacetalide (4), cryptoacetalide (5), arucadiol (6), 1-dehydromiltirone (7), miltirone (8), cryptotanshinone (9), tanshinone II A (10) and isotanshinone-I (11). Their structures were elucidated by the spectral analysis such as NMR (Nuclear Magnetic Resonance) and MS (Mass Spectrometry). Compound 1 is a new compound. Compounds 4 and 5 are mirror isomers (1 : 3). Compounds 4, 5, 6, 8, 11 were isolated from Salvia przewalskii Maxim for the first time.
Diterpenes ; chemistry ; isolation & purification ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; Molecular Structure ; Phenanthrenes ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Salvia ; chemistry

Apoptosis ; drug effects ; Arsenicals ; isolation & purification ; pharmacology ; Diterpenes ; isolation & purification ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Epoxy Compounds ; isolation & purification ; pharmacology ; Hematologic Neoplasms ; pathology ; Humans ; Oxides ; isolation & purification ; pharmacology ; Phenanthrenes ; isolation & purification ; pharmacology ; Quercetin ; isolation & purification ; pharmacology ; Tumor Cells, Cultured

After oral administration of Salvia miltiorrhiza (Danshen in Chinese), Panax notoginseng (Sanqi in Chinese) and Danshen Sanqi combination suspensions to Beagle dogs, the plasma concentration-time profiles of danshensu, tanshinone II(A), cryptotanshinone, notoginsenoside R1, ginsenoside Rg1 and Rb1 were analyzed by LC-MS/MS. Pharmacokinetic parameters were calculated and analyzed with BAPP 2.0 software. The results showed that the Cmax and AUC of danshensu, notoginsenoside R1, ginsenoside Rg1 and Rb1 in Danshen Sanqi combination group all decreased in comparison with those of Danshen or Sanqi given alone, while the CLz/F and Vz/F increased to some extent. No significant differences of the pharmacokinetics of tanshinone II(A) and cryptotanshinone were observed between groups.
Administration, Oral ; Animals ; Area Under Curve ; Diterpenes, Abietane ; blood ; pharmacokinetics ; Dogs ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; isolation & purification ; pharmacokinetics ; Female ; Ginsenosides ; blood ; pharmacokinetics ; Lactates ; blood ; pharmacokinetics ; Male ; Panax notoginseng ; chemistry ; Phenanthrenes ; blood ; pharmacokinetics ; Plants, Medicinal ; chemistry ; Salvia miltiorrhiza ; chemistry

This study is to explore whether the Wnt/beta-catenin signaling pathway is involved in the process of tripchlorolide (T4) protecting against oligomeric Abeta(1-42)-induced neuronal apoptosis. Primary cultured cortical neurons were used for the experiments on day 6 or 7. The oligomeric Abeta(1-42) (5 micromol x L(-1) for 24 h) was applied to induce neuronal apoptosis. Prior to treatment with Abeta(1-42) for 24 h, the cultured neurons were pre-incubated with T4 (2.5, 10, and 40 nmol x L(-1)), Wnt3a (Wnt signaling agonists) and Dkk1 (inhibitors) for indicated time. Then the cell viability, neuronal apoptosis, and protein levels of Wnt, glycogen synthase kinase 3beta (GSK3beta), beta-catenin and phospho-beta-catenin were measured by MTT assay, TUNEL staining and Western blotting, respectively. The result demonstrated that oligomeric Abeta(1-42) induced apoptotic neuronal cell death in a time- and dose-dependent manner. Pretreatment with T4 significantly increased the neuronal cell survival and attenuated neuronal apoptosis. Moreover, oligomeric Abeta(1-42)-induced phosphorylation of beta-catenin and GSK3beta was markedly inhibited by T4. Additionally, T4 stabilized cytoplasmic beta-catenin. These results indicate that tripchlorolide protects against the neurotoxicity of Abeta by regulating Wnt/beta-catenin signaling pathway. This may provide insight into the clinical application of tripchlorolide to Alzheimer's disease.
Amyloid beta-Peptides ; antagonists & inhibitors ; toxicity ; Animals ; Apoptosis ; drug effects ; Cell Survival ; drug effects ; Cells, Cultured ; Cerebral Cortex ; cytology ; Diterpenes ; isolation & purification ; pharmacology ; Female ; Fetus ; Glycogen Synthase Kinase 3 ; metabolism ; Glycogen Synthase Kinase 3 beta ; Neurons ; cytology ; drug effects ; Neuroprotective Agents ; isolation & purification ; pharmacology ; Peptide Fragments ; antagonists & inhibitors ; toxicity ; Phenanthrenes ; isolation & purification ; pharmacology ; Phosphorylation ; Plants, Medicinal ; chemistry ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Tripterygium ; chemistry ; Wnt Proteins ; metabolism ; beta Catenin ; metabolism

OBJECTIVETo investigate the effects of polysaccharide fraction of Cordyceps sinensis (PSCS) on triptolide (TPL)-induced apoptosis in the HL-60 cells and the involved molecular mechanism.

METHODSThe cultured leukemia HL-60 cells were divided into three groups: control group, TPL group (cells were treated with 5 ng/ml TPL only), and PSCS+TPL cells group (cells treated with 5 ng/ml TPL and 100 microg/ml or 200 microg/ml PSCS for 18 h). Cell viability was tested by MTT assay and apoptotic cells were quantitatively measured by flow cytometry with Annexin V/PI double stain.The expressions of Caspase-3, 6, 7, 9 and NF-kappa B proteins were tested by Western blot.

RESULTMTT assay showed that different concentrations of PSCS inhibited the cell viability. Flow cytometry indicated that TPL markedly increased the apoptosis rate of the HL-60 cells, and PSCS enhanced the apoptosis in a dose-dependent manner. Western blot showed that TPL did not inhibit the expression of the Caspase-3, 6, 7, 9 and NF-kappa B proteins, and when cells were treated with PSCS, the expression of proteins decreased with the PSCS concentration rising.

CONCLUSIONPSCS can enhance TPL-induced apoptosis in HL-60 cells and inhibit the expression of NF-kappa B and Caspase 3,6,7,9,which might be the possible signaling pathway of inducing apoptosis.

Apoptosis ; drug effects ; Caspases ; metabolism ; Cordyceps ; chemistry ; Diterpenes ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Epoxy Compounds ; pharmacology ; HL-60 Cells ; Humans ; NF-kappa B ; metabolism ; Phenanthrenes ; pharmacology ; Polysaccharides ; isolation & purification ; pharmacology

OBJECTIVETo investigate the feasibility of extracting the fat-soluble and the water-solubility substances from Salviae Miltiorrhizae with O/W Microemulsion.

METHODWith the yield of Tanshinone IIA and Salvianolic acid B as index, compere with efficiency of extracting Salviae Miltiorrhizae by suing the different media (water, alcohol and microemulsion), using different extraction methods (heat, microwave, ultrasonic), using different formulations of O/W microemulsion.

RESULTThe extracting yield of Tanshinone IIA and Salvianolic acid B are more than 70% by using microemulsion at mean time. It is good of the abilities of extraction of liposolubility compounds such as the Tanshinone IIA by the microemulsion. The formulations of microemulsion have remarkable effect for extracting Salviae Miltiorrhizae.

CONCLUSIONIt is feasibiale that extracted Salviae Miltiorrhizae by using O/W microemulsion as a solvents.

Benzofurans ; chemistry ; isolation & purification ; Diterpenes, Abietane ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Oils ; chemistry ; Phenanthrenes ; chemistry ; isolation & purification ; Reproducibility of Results ; Salvia miltiorrhiza ; chemistry ; Water ; chemistry

Extracts of Chinese herb Tripterygium wilfordii Hook. f. (TWHF) have been found to have potent anti-inflammatory and immunosuppressive functions and widely used in China for treatment of rheumatoid arthritis. Also they have been considered to be the potential drugs in the treatment of tumor and acute graft rejections. With the progress of neuroimmunological research on neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson disease (PD) and multiple sclerosis (MS), the neuroprotective strategies to rescue neurons from immunological injury are currently being explored. Recently, studies have indicated that extracts of TWHF such as triptolide, tripchlorolide and (5R)-5-hydroxytriptolide are able to attenuate progression of these neuroimmunologic disorders in vitro and in vivo. Accumulating evidence has shown that they can promote neuronal survival and neurite growth and facilitate functional recovery of brain injury by invoking distinct mechanisms that are related to their neuroprotective roles as inhibitor of neuroinflammatory toxicity of activated-microglia, antioxidants, calcium channel blockers, neurotrophic actions, modulating T cell functions, inhibitor of transcriptional activation of NF-kappaB on genes and signaling. Significant pharmaceutical strategies against neuroimmunologic disorders will hopefully be discovered by understanding the valuable components of TWHF.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Antioxidants ; pharmacology ; Diterpenes ; isolation & purification ; pharmacology ; therapeutic use ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; therapeutic use ; Epoxy Compounds ; isolation & purification ; pharmacology ; therapeutic use ; Humans ; NF-kappa B ; metabolism ; Neurodegenerative Diseases ; drug therapy ; prevention & control ; Phenanthrenes ; isolation & purification ; pharmacology ; therapeutic use ; Structure-Activity Relationship ; Tripterygium ; chemistry

OBJECTIVETo optimize formulation of tanshinone II(A)-loaded PLGA nanoparticles and compare the difference of two methods in preparation and quality of nanoparticles.

METHODThe two methods were nanoprecipitation method and emulsion-evaporation method. Single factor experiments and central composite design and response surface method were used to optimize the formulation of nanoparticles. The nanoparticles were characterized at size, morphology, entrapment efficiency, drug loading, drug recovery rate, crystallinity and drug release in vitro.

RESULTThe mean diameters were 225 nm and 183 nm, the entrapment efficiency were 95.49% and 87.99%, the drug loading were 2.03% and 0.16%, and the drug recovery rates were 38.42% and 17.59% respectively for nanoprecipitation method and emulsion-evaporation method.

CONCLUSIONNanoprecipitation method was better than emulsion-evaporation method for preparation of tanshinone II(A)-loaded PLGA nanoparticles.

Chemical Precipitation ; Crystallization ; Diterpenes, Abietane ; Emulsions ; Lactic Acid ; chemistry ; Nanoparticles ; chemistry ; Particle Size ; Phenanthrenes ; chemistry ; isolation & purification ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Polyglycolic Acid ; chemistry ; Polymers ; chemistry ; Quality Control ; Salvia miltiorrhiza ; chemistry ; Technology, Pharmaceutical ; methods ; Volatilization