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1.  Searching the Cytochrome P450 Enzymes for the Metabolism of Meranzin Hydrate: A Prospective Antidepressant Originating from Chaihu-Shugan-San 
PLoS ONE  2014;9(11):e113819.
Meranzin hydrate (MH), an absorbed bioactive compound from the Traditional Chinese Medicine (TCM) Chaihu-Shugan-San (CSS), was first isolated in our laboratory and was found to possess anti-depression activity. However, the role of cytochrome P450s (CYPs) in the metabolism of MH was unclear. In this study, we screened the CYPs for the metabolism of MH in vitro by human liver microsomes (HLMs) or human recombinant CYPs. MH inhibited the enzyme activities of CYP1A2 and CYP2C19 in a concentration-dependent manner in the HLMs. The Km and Vmax values of MH were 10.3±1.3 µM and 99.1±3.3 nmol/mg protein/min, respectively, for the HLMs; 8.0±1.6 µM and 112.4±5.7 nmol/nmol P450/min, respectively, for CYP1A2; and 25.9±6.6 µM and 134.3±12.4 nmol/nmol P450/min, respectively, for CYP2C19. Other human CYP isoforms including CYP2A6, CYP2C9, CYP2D6, CYP2E1 and CYP3A4 showed minimal or no effect on MH metabolism. The results suggested that MH was simultaneously a substrate and an inhibitor of CYP1A2 and CYP2C9, and MH had the potential to perpetrate drug-drug interactions with other CYP1A2 and CYP2C19 substrates.
PMCID: PMC4245237  PMID: 25427198
2.  Identification of potential anticancer compounds from Oplopanax horridus 
Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two triterpenoids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents.
PMCID: PMC3729876  PMID: 23746754
Oplopanax horridus; Phytochemistry; Polyynes; Oplopantriol A; Falcarindiol; Anticancer; Cell cycle; Apoptosis; Structure-activity relationship
3.  Chemopreventive Effects of Oplopantriol A, a Novel Compound Isolated from Oplopanax horridus, on Colorectal Cancer 
Nutrients  2014;6(7):2668-2680.
Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the compound’s growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.
PMCID: PMC4113763  PMID: 25045937
Oplopanax horridus; oplopantriol A; OPT A; chemoprevention; colorectal cancer; HCT-116; SW-480; apoptosis; cell cycle; tumor necrosis factors; death receptor signaling pathway
4.  Quercetin Significantly Inhibits the Metabolism of Caffeine, a Substrate of Cytochrome P450 1A2 Unrelated to CYP1A2*1C  (−2964G>A) and *1F (734C>A) Gene Polymorphisms 
BioMed Research International  2014;2014:405071.
Background. Quercetin is abundant in plants and human diets. Previous studies indicated that quercetin inhibited the activity of CYP1A2, and the combination of quercetin with the substrates of CYP1A2 might produce herb-drug interactions. This research aims to determine the effects of quercetin and the CYP1A2 gene polymorphisms, namely, CYP1A2*1C  (−2964G>A) and *1F (734C>A), on the metabolism of caffeine. Method. The experiment was designed into two treatment phases separated by a 2-week washout period. Six homozygous individuals for the CYP1A2*1C/*1F (GG/AA) genotype and 6 heterozygous individuals for the CYP1A2*1C/*1F (GA/CA) genotype were enrolled in the study. Quercetin capsules (500 mg) were given to each volunteer once daily for 13 consecutive days, and after that, each subject was coadministrated 100 mg caffeine capsules with 500 mg quercetin on the 14th day. Then a series of venous blood samples were collected for HPLC analysis. Correlation was determined between pharmacokinetics of caffeine and paraxanthine with caffeine metabolite ratio. Results. Quercetin significantly affected the pharmacokinetics of caffeine and its main metabolite paraxanthine, while no differences were found in the pharmacokinetics of caffeine and paraxanthine between GG/AA and GA/CA genotype groups. Conclusion. Quercetin significantly inhibits the caffeine metabolism, which is unrelated to CYP1A2*1C (−2964G>A) and *1F (734C>A) gene polymorphisms.
PMCID: PMC4082882  PMID: 25025048
5.  Lignans from the bark of Eucommia ulmoides inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells 
Chinese Medicine  2014;9:8.
Tree bark of Eucommia ulmoides Oliv., (commonly well-known as “Du-zhong” in China), has been used to treat hypertension, hypercholesterolemia, hyperglycemia, hepatic fibrosis and renal injury. This study aims to investigate the effects of lignans extracted from the bark of Eucommia ulmoides Oliv. on Ang II-induced proliferation and extracellular matrix biosynthesis in rat mesangial cells.
Rat mesangial cells (RMCs) were cultured in vitro and divided into six groups (control, Ang II, losartan, and low, middle and high concentration lignans groups). RMC proliferation was measured by MTT assay. RT-qPCR and western blotting were used to detect mRNA and protein expression of collagen type I (Col I), collagen type III (Col III), collagen type IV (Col IV), fibronectin and aldose reductase (AR).
Cellular proliferation induced by Ang II was significantly suppressed by Eucommia lignans of different concentrations (P = 0.034, P < 0.001, and P < 0.001). Treatment of cells with Ang II increased Col I, Col III, Col IV, and fibronectin mRNA expression, which was observed at the protein level (P < 0.001, P < 0.001, P = 0.004, and P = 0.004, respectively). The increased mRNA expression and protein levels of Col I, Col III, Col IV, and fibronectin were diminished remarkably with by treatment Eucommia lignans, and elevated AR expression stimulated by Ang II was significantly inhibited by Eucommia lignans.
Eucommia lignans (Du-zhong) inhibited Ang II-stimulated extracellular matrix biosynthesis in mesangial cells.
PMCID: PMC3937011  PMID: 24524265
6.  Simple Patterned Nanofiber Scaffolds and Its Enhanced Performance in Immunoassay 
PLoS ONE  2013;8(12):e82888.
Cancer has become the leading cause of death worldwide; early diagnosis and treatment of cancers is critical for the survival of the patients. The concentration of cancer markers in easy-to-access biological fluids can provide great assistance in screening for occult primary cancers, distinguishing malignant from benign findings, determining prognosis and prediction for cancer patients. The multiplex detection technology of a panel of cancer markers can greatly increase the accuracy of disease diagnosis. Herein, we briefly fabricate a high-throughput micro-immunoassay based on the electrospun polystyrene (PS) substrates to improve detection sensitivity. The immunoassay was evaluated by analyzing three different cancer biomarkers (AFP, CEA, VEGF). For AFP, CEA, VEGF immunofluorescence assay, the LOD of assay conducted on electrospun PS substrates before or after plasma and the conventional PS substrates were 0.42, 0.10, 1.12 ng/mL, 0.57, 0.09, 1.24 ng/mL, and 159.75, 26.19, 385.59 pg/mL, respectively (P < 0.05). Due to the high porosity and large surface area-to-volume ratio which is the foremost merit of nanostructures, and the plasma treatment which make the hydrophobic PS nanofibers hydropholic, the nanofibers substrates showed sufficient retention of immunoassay functionality and high potential for capture molecules immobilization. Consequently, the immunofluorescence assay conducted on electrospun PS substrates could significantly enhance the sensitivity and limits of detection.
PMCID: PMC3858307  PMID: 24340065
7.  Single-layer continuous suture contributes to the reduction of surgical complications in digestive tract anastomosis involving special anatomical locations 
Molecular and Clinical Oncology  2013;2(1):159-165.
The key point of digestive cancer surgery is reconstruction and anastomosis of the digestive tract. Traditional anastomoses involve double-layer interrupted suturing, manually or using a surgical stapler. In special anatomical locations, however, suturing may become increasingly difficult and the complication rate increases accordingly. In this study, we aimed to investigate the feasibility and safety of a new manual suturing method, the single-layer continuous suture in the posterior wall of the anastomosis. Between January, 2007 and August, 2012, 101 patients with digestive cancer underwent surgery in Xi’an Gaoxin Hospital. Of those patients, 27 underwent surgery with the new manual method and the remaining 74 underwent surgery using traditional methods of anastomosis of the digestive tract. Surgical time, intraoperative blood loss, drainage duration, complications, blood tests, postoperative quality of life (QOL) and overall expenditure were recorded and analyzed. No significant differences were observed in surgical time, intraoperative blood loss, temperature, blood tests and postoperative QOL between the two groups. However, compared with the control group, the new manual suture group exhibited a lower surgical complication rate (7.40 vs. 31.08%; P=0.018), lower blood transfusion volume (274.07±419.33 vs. 646.67±1,146.06 ml; P=0.053), shorter postoperative hospital stay (14.60±4.19 vs. 17.60±6.29 days; P=0.038) and lower overall expenditure (3,509.85±768.68 vs. 6,141.83±308.90 renminbi; P=0.001). Our results suggested that single-layer continuous suturing for the anastomosis of the digestive tract is feasible and safe and may contribute to the reduction of surgical complications and overall expenditure.
PMCID: PMC3916195  PMID: 24649327
anastomosis; gastric cancer; rectal cancer; single-layer; continuous suture
8.  Benefits of hypoxic culture on bone marrow multipotent stromal cells 
Cultivation of cells is usually performed under atmospheric oxygen tension; however, such a condition does not replicate the hypoxic conditions of normal physiological or pathological status in the body. Recently, the effects of hypoxia on bone marrow multipotent stromal cells (MSCs) have been investigated. In a long-term culture, hypoxia can inhibit senescence, increase the proliferation rate and enhance differentiation potential along the different mesenchymal lineages. Hypoxia also modulates the paracrine effects of MSCs, causing upregulation of various secretable factors, including the vascular endothelial growth factor and interleukin-6, and thereby promoting wound healing and diabetic fracture healing. Finally, hypoxia plays an important role in mobilization and homing of MSCs, primarily by its ability to induce stromal cell-derived factor-1 expression along with its receptor, CXCR4. After transplantation, an ischemic environment, that is the combination of hypoxia and lack of nutrition, can lead to apoptosis or cell death, which can be overcome by the hypoxic preconditioning of MSCs and overexpression of prosurvival genes like Akt, HO-1 and Hsp70. This review emphasizes that hypoxia is an important factor in all major aspects of stem cell biology, and the mechanism involved in the hypoxic inducible factor-1signaling pathway behind these responses is also discussed.
PMCID: PMC3484415  PMID: 23119226
Mesenchymal stem cells; hypoxia; hypoxic preconditioning; proliferation; differentiation potential; apoptosis; migration; engraftment; HIF-1
9.  Chemical and pharmacological studies of Oplopanax horridus, a North American botanical 
Journal of Natural Medicines  2011;66(2):249-256.
Oplopanax horridus (OH) or Devil's club is an ethnobotanical used by the indigenous people native to the Pacific Northwest. There are three species in the genus Oplopanax, and OH is the only species that is distributed in North America. Compared with the extensive research on OH's “cousin,” American ginseng, there is comparatively little about the chemical makeup and pharmacological effects of OH. Nevertheless, there has been some research over the past few years that shows promise for future usage perspectives of OH. To date, seventeen compounds were isolated and elucidated including polyynes, glycosides, lignans, and polyenes, with most of the attention being paid to the polyynes. GC and HPLC were used to determine the contents of volatile compounds and polyynes in the essential oil and extracts of OH. For the pharmacological studies, antibacterial and anti-diabetes effects of polyynes were reported. Our recent study has focused more on the anticancer effects of OH and the involved mechanisms of action. In this review, we will summarize the research status in the botany, phytochemistry and pharmacology of OH.
PMCID: PMC3345165  PMID: 22101399
Oplopanax horridus; Devil's club; Polyynes; Phytochemistry; Pharmacology; Anticancer

Results 1-9 (9)