Chong-Zhi Wang

University of Chicago, Chicago, Illinois, United States

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Publications (124)361.53 Total impact

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    ABSTRACT: In this study, we evaluated the effects of protopanaxadiol (PPD), a gut microbiome induced ginseng metabolite, in increasing the anticancer effects of a chemotherapeutic agent fluorouracil (5-FU) on colorectal cancer. An in vitro HCT-116 colorectal cancer cell proliferation test was conducted to observe the effects of PPD, 5-FU and their co-administration and the related mechanisms of action. Then, an in vivo xenografted athymic mouse model was used to confirm the in vitro data. Our results showed that the human gut microbiome converted ginsenoside compound K to PPD as a metabolite. PPD and 5-FU significantly inhibited HCT-116 cell proliferation in a concentration-dependent manner (both p < 0.01), and the effects of 5-FU were very significantly enhanced by combined treatment with PPD (p < 0.01). Cell cycle evaluation demonstrated that 5-FU markedly induced the cancer cell S phase arrest, while PPD increased arrest in G1 phase. Compared to the control, 5-FU and PPD increased apoptosis, and their co-administration significantly increased the number of apoptotic cells (p < 0.01). Using bioluminescence imaging, in vivo data revealed that 5-FU significantly reduced the tumor growth up to Day 20 (p < 0.05). PPD and 5-FU co-administration very significantly reduced the tumor size in a dose-related manner (p < 0.01 compared to the 5-FU alone). The quantification of the tumor size and weight changes for 43 days supported the in vivo imaging data. Our results demonstrated that the co-administration of PPD and 5-FU significantly inhibited the tumor growth, indicating that PPD significantly enhanced the anticancer action of 5-FU, a commonly used chemotherapeutic agent. PPD may have a clinical value in 5-FU's cancer therapeutics.
    Nutrients 02/2015; 7(2):799-814. DOI:10.3390/nu7020799 · 3.15 Impact Factor
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    ABSTRACT: The roots and rhizomes of Smilax riparia are called "Niu-Wei-Cai" in traditional Chinese medicine (TCM). This botanical has been used in treating the symptoms of gout and other hyperuricemic-related conditions in TCM. Allopurinol is a commonly used medication to treat hyperuricemia and its complications. In this study, we evaluated whether S. riparia could enhance allopurinol's effects by decreasing the serum uric acid level in a hyperuricemic mouse model induced by potassium oxonate. We examined the effects of allopurinol (5mg/kg) administration alone or in combination with S. riparia saponins (SRS, 500mg/kg) on the serum uric acid (SUA), serum creatinine (SCr) and blood urea nitrogen (BUN) levels in a hyperuricemic mouse model. The effects of allopurinol alone or those of allopurinol plus SRS on the XOD activities were measured. Western blot analysis was used to measure the levels of mURAT1, mGLUT9 and mOTA1 in the mice. Compared with allopurinol alone, the combination of allopurinol and SRS significantly decreased the serum uric acid level and increased the urine uric acid level (both P<0.05), leading to the normalized serum and urine uric acid concentrations. Data on serum and urine creatinine and BUN supported these observations. The attenuation of hyperuricemia-induced renal dysfunction was linked to the inhibition of both serum and hepatic xanthine oxidase (XOD), the down-regulation of renal mURAT1 and mGLUT9, and the up-regulation of mOAT1. The anti-hyperuricemia effects of allopurinol are improved by Smilax riparia co-administration. The results were supported by the measurement of uric acid, creatinine, BUN, XOD, mURAT1, mGLUT9 and mOAT1. Our data may have a potential value in clinical practice in the treatment of gout and other hyperuricemic conditions. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Journal of Ethnopharmacology 01/2015; 162. DOI:10.1016/j.jep.2015.01.012 · 2.94 Impact Factor
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    ABSTRACT: Colorectal cancer (CRC) is a leading cause of death worldwide. Chronic gut inflammation is recognized as a risk factor for tumor development, including CRC. American ginseng is a very commonly used ginseng species in the West.
    Journal of ginseng research 01/2015; DOI:10.1016/j.jgr.2014.12.004 · 2.30 Impact Factor
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    ABSTRACT: Colorectal cancer is a leading cause of cancer-related death, and inflammatory bowel disease is a risk factor for this malignancy. We previously reported colon cancer chemoprevention potential using American ginseng (AG) in a xenograft mice model. However, the nude mouse model is not a gut-specific colon carcinogenesis animal model. In this study, an experimental colitis and colitis-associated colorectal carcinogenesis mouse model, chemically induced by azoxymethane/dextran sodium sulfate (DSS) was established and the effects of oral AG were evaluated. The contents of representative ginseng saponins in the extract were determined. AG significantly reduced experimental colitis measured by the disease activity index scores. This suppression of the experimental colitis was not only evident during DSS treatment, but also very obvious after the cessation of DSS, suggesting that the ginseng significantly promoted recovery from the colitis. Consistent with the anti-inflammation data, we showed that ginseng very significantly attenuated azoxymethane/DSS-induced colon carcinogenesis by reducing the colon tumor number and tumor load. The ginseng also effectively suppressed DSS-induced proinflammatory cytokines activation using an enzyme-linked immunosorbent assay array, in which 12 proinflammatory cytokine levels were assessed, and this effect was supported subsequently by real-time polymerase chain reaction data. AG, as a candidate of botanical-based colon cancer chemoprevention, should be further investigated for its potential clinical utility.
    Journal of ginseng research 01/2015; 39(1):14-21. DOI:10.1016/j.jgr.2014.07.001 · 2.30 Impact Factor
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    ABSTRACT: Among important components of American ginseng, protopanaxadiol (PPD) showed more active anticancer potential than other triterpenoid saponins. In this study, we determined the in vivo effects of PPD in a mouse cancer model first. Then, using human colorectal cancer cell lines, we observed significant cancer cell growth inhibition by promoting G1 cell cycle redistribution and apoptosis. Subsequently, we characterized the downstream genes targeted by PPD in HCT-116 cancer cells. Using Affymetrix high density GeneChips, we obtained the gene expression profile of the cells. Microarray data indicated that the expression levels of 76 genes were changed over two-fold after PPD, of which 52 were upregulated while the remaining 24 were downregulated. Ingenuity pathway analysis of top functions affected was carried out. Data suggested that by regulating the interactions between p53 and DR4/DR5, the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway played a key role in the action of PPD, a promising colon cancer inhibitory compound. Copyright © 2014 Japanese Pharmacological Society. Production and hosting by Elsevier B.V. All rights reserved.
    Journal of Pharmacological Sciences 01/2015; 127(1):83-91. DOI:10.1016/j.jphs.2014.11.003 · 2.11 Impact Factor
  • RSC Advances 01/2015; 5(52):41377-41384. DOI:10.1039/C5RA04424C · 3.71 Impact Factor
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    ABSTRACT: Natural products play an important role in cancer therapeutics, and lately more attentions have been paid to the prevention of major lethal malignancies, such as colorectal cancer (CRC). After oral ingestion, botanicals' parent compounds can be converted to their metabolites by the enteric microbiome, and these metabolites may have different bioactivities and variable bioavailability. In this study, we used an active ginseng metabolite, protopanaxadiol (PPD), as an example to assess its colon cancer preventive effect by comparing its effect with the treatment effect of fluorouracil (5-FU). A xenograft tumor nude mouse model with human colon cancer cell inoculation was used. After preventive PPD or treatment 5-FU administration with the same dose (30 mg/kg), tumor growth inhibition was evaluated by both a Xenogen bioluminescence imaging technique and manual tumor size measurement. Our data showed that preventive PPD very significantly inhibited the tumor growth compared to 5-FU (p < 0.01). Our data suggest that the PPD is a promising cancer prevention agent. More studies are needed to explore the chemopreventive actions of PPD and its potential clinical utility.
    The American Journal of Chinese Medicine 12/2014; DOI:10.1142/S0192415X1420002X · 2.63 Impact Factor
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    ABSTRACT: Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from the roots bark of O. horridus, which was subsequently analyzed by GC/MS. Forty-eight volatile compounds were identified by GC/MS analysis, including (S,E)-nerolidol (52.5%), τ-cadinol (21.6%) and S-falcarinol (3.6%). Accordingly, the volatile oil (100 g) was subjected to chromatographic separation and purification. As a result, the three compounds, (E)-nerolidol (2 g), τ-cadinol (62 mg) and S-falcarinol (21 mg), were isolated and purified from the volatile oil, the structures of which were unambiguously elucidated by detailed spectroscopic analysis including 1D- and 2D-NMR techniques.
    Molecules 12/2014; 19(12):19708-17. DOI:10.3390/molecules191219708 · 2.10 Impact Factor
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    ABSTRACT: To study the chemical constituents from the leaves of Oplopanax horridus.Methods The chemical constituents were isolated and purified by column chromatography on silica gel and Sephadex LH-20 gel columns, 1H-NMR and 13C-NMR were applied for the identification of chemical structure.ResultsTen compounds were isolated and identified as dammara-20,24-dien-3β-ol acetate (1), phytol (2), 16Z,19Z-pentacosadienoic acid (3), β-sitosterol (4), (3S,8S-falcarindiol (5), maltol (6), acankoreagenin (7), daucosterol (8), stigmasterol-3-O-β-D-glucopyranoside (9), and acankoreoside A (10).Conclusion Compounds 1–3, 6, and 10 are isolated from this plant for the first time. Compounds 1–3 and 6 are isolated from the plants in genus Oplopanax Miq. for the first time. Moreover, Compounds 1, 3, and 6 are isolated from the plants in the family of Araliaceae for the first time.
    11/2014; DOI:10.1016/S1674-6384(14)60050-2
  • Chong-Zhi Wang, Chun-Su Yuan
    Cancer Research 10/2014; 74(19 Supplement):2154-2154. DOI:10.1158/1538-7445.AM2014-2154 · 9.28 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the underlying mechanism(s) of the total alkaloids (TA) from Mahonia bealei in treating pyloric ligation-induced gastric ulcers in rats. Animals were sacrificed after 19h of the ligation. Gastric acid, peptic activities, mucin levels, H(+)/K(+)-ATPase activities and the gastrin level were analyzed. To improve the accuracy of the observations, IPP 6.0 software was introduced to measure the area of ulcer. TA (18.56mg/kg/day, i.g.) showed an antiulcer effect by significantly decreasing the gastric ulcer areas (11.28mm(2)) compared with model group (26.36mm(2)). The TA ulcer inhibition ratio was 57.2%, compared with the effect of the positive control, omeprazole (62.96%). The results also showed that TA had a significant effect in inhibiting the release of H(+)/K(+)-ATPase, reducing the content of gastrin and decreasing gastric acidity on experimental animals. However, the TA had no significant effects on gastric mucus secretion and pepsin activity. Data indicated that TA had gastric ulcer protective effects by modulating the H(+)/K(+)-ATPase activity and gastrin level. TA has a potential to be developed as a pharmacological agent for the treatment of gastric ulcers.
    Phytomedicine 09/2014; 21(11):1356–1363. DOI:10.1016/j.phymed.2014.07.007 · 2.88 Impact Factor
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    ABSTRACT: 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.
    Nutrients 07/2014; 6(7):2668-2680. DOI:10.3390/nu6072668 · 3.15 Impact Factor
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    ABSTRACT: American ginseng (Panax quinquefolius) is originally grown in North America. Due to price difference and supply shortage, American ginseng recently has been cultivated in northern China. Further, in the market, some Asian ginsengs are labeled as American ginseng. In this study, forty-three American ginseng samples cultivated in the USA, Canada or China were collected and 14 ginseng saponins were determined using HPLC. HPLC coupled with hierarchical cluster analysis and principal component analysis was developed to identify the species. Subsequently, an HPLC-linear discriminant analysis was established to discriminate cultivation regions of American ginseng. This method was successfully applied to identify the sources of 6 commercial American ginseng samples. Two of them were identified as Asian ginseng, while 4 others were identified as American ginseng, which were cultivated in the USA (3) and China (1). Our newly developed method can be used to identify American ginseng with different cultivation regions.
    Journal of Pharmaceutical and Biomedical Analysis 07/2014; 99C:8-15. DOI:10.1016/j.jpba.2014.06.031 · 2.83 Impact Factor
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    ABSTRACT: Patients suffering from inflammatory bowel disease are at a high risk of developing colorectal cancer. To assess the anticancer potential of botanicals, in this study, we evaluated the effects of Panax notoginseng on azoxymethane/dextran sulfate sodium (DSS)-induced colitis. One week after A/J mice received azoxymethane, the animals received DSS for 8 days or were supplemented with P. notoginseng extract, at 30 or 90 mg/kg. DSS-induced colitis was scored with the disease activity index. The severity of the inflammatory lesions was evaluated by a colon tissue histological assessment. The expression of inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) were also explored. We observed that the effects of P. notoginseng on the reduction of colon inflammation, expressed in disease activity index score, were in a dose-related manner (p < 0.01). P. notoginseng inhibited the reduction of the colon length and the loss of bodyweight in dose-related manner (all p < 0.05). The histological assessment of the colitis and inflammatory-related immunohistochemical data also supported the pharmacological observations. Our data suggest that P. notoginseng is a promising candidate in preventing and treating colitis and inflammation-associated colon carcinogenesis. Copyright © 2013 John Wiley & Sons, Ltd.
    Phytotherapy Research 06/2014; 28(6). DOI:10.1002/ptr.5066 · 2.40 Impact Factor
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    ABSTRACT: The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFα, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-κB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFα that activates epithelial cell NF-κB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFα production. Additionally, TU-100 and ginger alone blocked direct TNFα stimulation of Caco2BBE cells and decreased activation of caspase-3 and polyADP ribose. The present studies demonstrate a new anti-inflammatory action of TU-100 that is microbe-independent and due to its ginger component.
    PLoS ONE 05/2014; 9(5):e97456. DOI:10.1371/journal.pone.0097456 · 3.53 Impact Factor
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    ABSTRACT: The chemical constituents were isolated and purified by various chromatographic techniques indluding silica gel, reverse phase silica gel, sephadex LH-20 and pre-HPLC and identified by their physicochemical properties and spectral data. Sixteen phenolic compounds had been isolated and n-butanol extracts which were fractionated from the ethanol extract of Oplopanax horridus roots bark. Their structures were identified as below, including 7 phenylpropanoid compounds, ferulic acid (1), 3-acetylcaffeic acid (2), caffeic acid (3), homovanillyl alcohol 4-O-beta-D-glucopyranoside (4), 3-hydroxyphenethyl alcohol 4-O-beta-D-glucopyranoside (5), 3, 5-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (6), and 3-dimethoxycinnamyl alcohol 4-O-beta-D-glucopyranoside (7). Three coumarins, scopoletin (8), esculetin (9) and 3'-angeloyl-4'-acetyl-cis-knellactone (10). And 6 lignan compounds, (+)-isolaricires-inol-9'-O-beta-D-glucopyranoside (11), 3, 3'-dimethoxy-4, 9, 9'-trihydroxy-4', 7-epoxy-5', 8-lignan-4, 9-bis-O-beta-D-glucopyranoside (12), (+)-5, 5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (13), (-)-5,5'-dimethoxylariciresinol 4'-O-beta-D-glucopyranoside (14), (-)-pinoresinol 4'-O-beta-D-glucopyranoside (15), and (+)-5, 5'-dimethoxylariciresinol 9'-O-beta-D-glucopyranoside (16). All compounds were isolated and identified for the first time from this plant All the constituents except compounds 4, 6, 12 and 13 were obtained for the first time from the genus Oplopanax.
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    ABSTRACT: Six polyynes OH-1~6, some of which are occur naturally in acetylated form, had been isolated and identified from the root bark of Oplopanax horridus (Devil's Club), a natural dietary supplement and medicinal plant in North America. During the evaluation of the polyynes' potential anticancer activities, sixteen more acetylated derivatives OHR-1~16 have synthesized and their anti-proliferation activity on MCF-7, MDA-MB-231, A549, HepG2 and LO2 cells assayed to elucidate their structure-activity relationships. The results showed that OH-1 ((3S, 8S)-falcarindiol) had the most potent anticancer activity, with IC50 values of 15.3, 23.5, 7.7 and 4.7 μM on MCF-7, A549, HepG2 and MDA-MB-231 cells, respectively. For the primary structure-activity relationship, the anticancer activities of polyynes become weaker if their hydroxyl groups are acetylated, the terminal double bonds transformed into single bonds or they contain one more methylene group in the main skeleton chain.
    Molecules 05/2014; 19(5):6142-62. DOI:10.3390/molecules19056142 · 2.10 Impact Factor
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    ABSTRACT: Genkwa flos (Daphne genkwa Sieb. et Zucc.), a Chinese herbal medicine, has been traditionally used for over two thousand years in China for inflammation related symptoms, including joint pain. To evaluate the antioxidative effects of flavonoid aglycones (FA) isolated from Genkwa flos on adjuvant arthritis in rats and to identify the relationship between antioxidant potential and whole blood viscosity (WBV). FA compounds were identified using LC-MS and the content was assayed by HPLC. Arthritis was induced by an intradermal injection of Freund's complete adjuvant in the footpad. The effects of FA on paw volumes, secondary arthritis scores, histopathology of joints, and body and organ weights were measured. The antioxidant effects of FA and WBV were determined. LC-MS analysis showed that the FA contained four major compounds: luteolin, apigenin, hydroxygenkwanin and genkwanin. FA significantly decreased paw edema, arthritis scores, and weight loss. These observations were consistent with the reduction of oxidative stress and the improvement of the WBV. FA significantly decreased arthritis in a rat model through antioxidant and hemorheological modulatory mechanisms. The Genkwa flos flavonoids may have clinical potential for the treatment of rheumatoid arthritis.
    Journal of ethnopharmacology 03/2014; 153(3). DOI:10.1016/j.jep.2014.03.046 · 2.94 Impact Factor
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    ABSTRACT: The aim of the study was to investigate the anti-rheumatoid arthritic activity of four flavonoids from Daphne genkwa (FFD) in vivo and in vitro. Flavonoids of D. genkwa were extracted by refluxing with ethanol and purified by polyamide resin. An in vivo carrageenan-induced paw edema model, tampon-granuloma model and Freund's complete adjuvant (FCA)-induced arthritis mouse model were used to evaluate the anti-rheumatoid arthritic activities of FFD. Moreover, nitric oxide (NO) release and neutral red uptake (NRU) in lipopolysaccharide (LPS)-induced murine macrophage RAW264.7 cells were used to evaluate the anti-inflammatory effect in vitro. In addition, antioxidant effect of FFD was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. A high dose of FFD significantly reduced the degree of acute inflammatory paw edema in mice as a response to carrageenan administration (p<0.01). FFD displayed a dose-dependent inhibition of granuloma formation in mice (p<0.05). FFD also inhibited chronic inflammation in adjuvant-induced arthritis rats when administered orally at the dose of 50mg/kg/day (p<0.001). In addition, FFD suppressed the production of NO and exhibited immunoregulatory function in LPS-activated RAW264.7 cells in a dose-related manner. Simultaneously, FFD revealed conspicuous antioxidant activity with IC50 values of 18.20μg/ml. FFD possesses significant anti-inflammatory and antioxidant activity, which could be a potential therapeutic agent for chronic inflammatory disorders such as rheumatoid arthritis.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 02/2014; 21(6). DOI:10.1016/j.phymed.2014.01.009 · 2.88 Impact Factor
  • Chemistry & Biodiversity 02/2014; 11(2):181-96. DOI:10.1002/cbdv.201200306 · 1.80 Impact Factor

Publication Stats

2k Citations
361.53 Total Impact Points

Institutions

  • 2004–2015
    • University of Chicago
      • • Department of Anesthesia & Critical Care
      • • Pritzker School of Medicine
      • • Department of Surgery
      Chicago, Illinois, United States
  • 2004–2013
    • University of Illinois at Chicago
      • Department of Emergency Medicine (Chicago)
      Chicago, Illinois, United States
  • 2011
    • University of Macau
      • Institute of Chinese Medical Sciences
      Macao, Macau, Macao
  • 2005
    • China Pharmaceutical University
      • Department of Pharmacognosy
      Nan-ching-hsü, Jiangxi Sheng, China