Chong-Zhi Wang

University of Chicago, Chicago, Illinois, United States

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Publications (139)405.41 Total impact

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    ABSTRACT: American ginseng is a commonly consumed herbal medicine in the United States and other countries. Ginseng saponins are considered to be its active constituents. We have previously demonstrated in an in vitro experiment that human enteric microbiota metabolize ginseng parent compounds into their metabolites. In this study, we analyzed American ginseng saponins and their metabolites in human plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). Six healthy male volunteers ingested 1 g of American ginseng twice a day for 7 days. On day 7, biological samples were obtained and pretreated with solid phase extraction. The ginseng constituents and their metabolites were characterized, including 5 ginseng metabolites in plasma, 10 in urine, and 16 in feces. For the plasma, urine and feces samples, the levels of ginsenoside Rb1 (a major parent compound) were 8.6, 56.8 and 57.7 ng/mL, respectively, and the levels of compound K (a major metabolite) were 58.4 ng/mL, 109.8 ng/mL and 10.06 μg/mL, respectively. It suggested that compound K had a remarkably high level in all three samples. Moreover, in human feces, ginsenoside Rk1 and Rg5, Rk3 and Rh4, Rg6 and F4 were detected as the products of dehydration. Further studies are needed to evaluate the pharmacological activities of the identified ginseng metabolites.
    No preview · Article · Feb 2016
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    ABSTRACT: Daphne genkwa Sieb.et Zucc. is a well-known medicinal plant. This study was designed to investigate the anticancer effects of total flavonoids in D. genkwa (TFDG) in vitro and in vivo. HT-29 and SW-480 human colorectal cancer cells were cultured to investigate the anticancer activity of TFDG. In addition, the Apc(Min/+) mouse model was applied in the in vivo experiment. Results of the cell experiment revealed that TFDG possessed significant inhibitory effects on HT-29 and SW-480 human colorectal cancer cells (both p < 0.01). Furthermore, our in vivo data showed that after treatment with TFDG, there was a significant increase in life span (both p < 0.01) and tumor numbers were reduced in the colon (both p < 0.01), which was supported by the data of tumor distribution, body weight changes and organ index. Our results also indicated that expressions of interleukin (IL)-1α, IL-1β, IL-6, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in gut tissue were downregulated by treatments of TFDG, and immunity cytokine secretions in the serum were regulated after oral administration of TFDG. Taken together, these findings suggested that TFDG has a potential clinical utility in colorectal cancer therapeutics, and TFDG's action is likely linked to its ability to regulate immune function and inhibit the production of inflammatory cytokines. Copyright © 2015 John Wiley & Sons, Ltd.
    No preview · Article · Dec 2015 · Phytotherapy Research
  • Chong-Zhi Wang · Lian-Wen Qi · Chun-Su Yuan
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    ABSTRACT: Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.
    No preview · Article · Oct 2015 · The American Journal of Chinese Medicine
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    ABSTRACT: Baicalin is a major constituent of Scutellaria baicalensis, which is a commonly used herbal medicine in many Asian countries. After oral ingestion, intestinal microbiota metabolism may change parent compound's structure and its biological activities. However, whether baicalin can be metabolized by enteric microbiota and the related anticancer activity is not clear. In this study, using human enteric microbiome incubation and HPLC analysis, we observed that baicalin can be quickly converted to baicalein. We compared the antiproliferative effects of baicalin and baicalein using a panel of human cancer cell lines, including three human colorectal cancer (CRC) cell lines. In vitro antiproliferative effects on CRC cells were verified using an in vivo xenograft nude mouse model. Baicalin showed limited antiproliferative effects on some of these cancer cell lines. Baicalein, however, showed significant antiproliferative effects in all the tested cancer cell lines, especially on HCT-116 human colorectal cancer cells. In vivo antitumor results supported our in vitro data. We demonstrated that baicalein exerts potent S phase cell cycle arrest and pro-apoptotic effects in HCT-116 cells. Baicalein induced the activation of caspase 3 and 9. The in silico modeling suggested that baicalein forms hydrogen bonds with residues Ser251 and Asp253 at the active site of caspase 3, while interactions with residues Leu227 and Asp228 in caspase 9 through its hydroxyl groups. Data from this study suggested that baicalein is a potent anticancer metabolite derived from S. baicalensis. Enteric microbiota play a key role in the colon cancer chemoprevention of S. baicalensis.
    No preview · Article · Sep 2015 · International Journal of Oncology
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    Chong-Zhi Wang · Yi Cai · Samantha Anderson · Chun-Su Yuan

    Preview · Article · Sep 2015
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    ABSTRACT: To improve the transdermal delivery of ligustrazine, Foeniculum vulgare food origin anisole compounds were employed as promoters. Transdermal fluxes of ligustrazine were determined by Franz-type diffusion cells. Fourier transform-infrared (FT-IR) spectra were used to detect the biophysical changes of the stratum corneum and to explore the mechanism of permeation enhancement. A scanning electron microscope (SEM) was used to monitor the morphological changes of the skin. Among the three anisoles, anisic acid increased the penetration flux of ligustrazine significantly. The ligustrazine flux with anisic acid (11.9 μg/cm2h) was higher than that any other group (p < 0.05). Spectra observations revealed that these anisole enhancers were able to disturb and extract the stratum corneum lipids. In addition, apparent density was used to describe the desquamation extent of the scutella. Multiple mechanisms are involved in the permeation enhancement of ligustrazine, including disturbing and extracting stratum corneum lipid, forming a competitive hydrogen bond. All data suggested that anisole compounds could be a group of safe and active penetration enhancers for transdermal delivery of ligustrazine. © 2015 World Scientific Publishing Company & Institute for Advanced Research in Asian Science and Medicine.
    No preview · Article · Sep 2015 · The American Journal of Chinese Medicine
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    ABSTRACT: Colorectal cancer is the third most common malignant tumor with high morbidity and mortality. To evaluate the antitumor effect of genkwanin on colorectal cancer enhanced by western high-fat diet, we investigated the activity of genkwanin on HT-29 and SW-480 human colorectal cancer lines in vitro and on the APC(Min/+) mice in vivo. In a cell culture system, six different inflammatory cytokines obviously stimulated two cancer cells growth in a concentration-dependent manner, while genkwanin significantly inhibited HT-29 and SW-480 human colorectal cancer cells proliferation and inflammatory cytokine IL-8 secretion. In the APC(Min/+) mice, the body weights, spleen and thymus indexes and immunity cytokine secretions were significantly improved after oral administration 12.5 and 25mg/kg/day of genkwanin. Besides, the tumor multiplicity changes and inflammatory cytokine levels were markedly reduced in two genkwanin-treated groups. The dysplastic adenomatous changes were also obviously ameliorated in gut histopathology. Taken together, our results indicated that genkwanin had a better antitumor activity partly via enhancing host immunity and decreasing the inflammatory cytokine levels. Genkwanin may be an effective chemotherapeutic agent for the treatment of colorectal cancer.
    No preview · Article · Sep 2015 · International immunopharmacology
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    ABSTRACT: Surface molecularly imprinted polymers (MIP@SBA-15) imprinted on the surface of hybrid nanostructured organic/inorganic materials (SBA-15) were prepared for the selective extraction and detection of baicalin (BA) in biological samples. The surface morphologies and characteristics of the imprinted and non-imprinted polymers were characterized by Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), thermogravimetric analysis (TGA) and nitrogen adsorption–desorption isotherms. The results indicated that the polymers were successfully grafted onto the surface of SBA-15 and possessed a highly ordered mesoporous structure. In binding tests, MIP@SBA-15 reached saturated adsorption within 80 min and exhibited significant specific recognition toward BA with a large adsorption capacity. In addition, the prepared MIP@SBA-15 was used as a selective sorbent for solid-phase extraction of BA from biological samples. Recoveries of BA from the liver and spleen ranged from 90.6% to 90.9% with RSD <3.7%. All these results reveal that this method is simple, rapid and sensitive for effectively extracting and detecting trace BA in biological samples.
    No preview · Article · Aug 2015 · RSC Advances
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    Chong-Zhi Wang · Jonathan Moss · Chun-Su Yuan

    Preview · Article · Jul 2015
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    ABSTRACT: American ginseng (Panax quinquefolius L.) is one of the most commonly used herbal medicines in the West. It has been reported to possess significant antitumor effects that inhibit the process of carcinogenesis. However, the mechanisms underlying its anticancer effects remain largely unresolved. In this study, we investigated the cancer chemopreventive effects of American ginseng on the progression of high fat (HF) diet-enhanced colorectal carcinogenesis with a genetically engineered ApcMin/+ mouse model. The metabolic alterations in sera of experimental mice perturbed by HF diet intervention as well as the American ginseng treatment were measured by gas chromatography time-of-flight mass spectrometry (GC-TOFMS) and liquid chromatography time-of-flight mass spectrometry (LC-TOFMS) analysis. American ginseng treatment significantly extended the life span of the ApcMin/+ mouse. Significant alterations of metabolites involving amino acids, organic acids, fatty acids and carbohydrates were observed in ApcMin/+ mouse in sera, which were attenuated by American ginseng treatment and concurrent with the histopathological improvement with significantly reduced tumor initiation, progression and gut inflammation. These metabolic changes suggest that the preventive effect of American ginseng is associated with attenuation of impaired amino acid, carbohydrates and lipid metabolism. It also appears that American ginseng induced significant metabolic alterations independent of the ApcMin/+ induced metabolic changes. The significantly altered metabolites induced by American ginseng intervention include arachidonic acid, linolelaidic acid, glutamate, docosahexaenoate, tryptophan, and fructose, all of which are associated with inflammation and oxidation. This suggests that American ginseng exerts the chemopreventive effects by anti-inflammatory and antioxidant mechanisms.
    Full-text · Article · Jul 2015 · Journal of Proteome Research
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    ABSTRACT: Chemopreventive agents can be identified from botanicals. Recently, there has been strong support for the potential of 6-shogaol, a natural compound from dietary ginger (Zingiber officinale), in cancer chemoprevention. However, whether 6-shogaol inhibits the growth of colorectal tumors in vivo remains unknown, and the underlying anticancer mechanisms have not been well characterized. In this work, we observed that 6-shogaol (15 mg/kg) significantly inhibited colorectal tumor growth in a xenograft mouse model. We show that 6-shogaol inhibited HCT-116 and SW-480 cell proliferation with IC50 of 7.5 and 10 μM, respectively. Growth of HCT-116 cells was arrested at the G2/M phase of the cell cycle, primarily mediated by the up-regulation of p53, the CDK inhibitor p21(waf1/cip1) and GADD45α, and by the down-regulation of cdc2 and cdc25A. Using p53(-/-) and p53(+/+) HCT-116 cells, we confirmed that p53/p21 was the main pathway that contributed to the G2/M cell cycle arrest by 6-shogaol. 6-Shogaol induced apoptosis, mainly through the mitochondrial pathway, and the bcl-2 family might act as a key regulator. Our results demonstrated that 6-shogaol induces cancer cell death by inducing G2/M cell cycle arrest and apoptosis. 6-Shogaol could be an active natural product in colon cancer chemoprevention.
    No preview · Article · Jun 2015 · The American Journal of Chinese Medicine
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    ABSTRACT: Metformin plays an important role in diabetes treatment. Studies have shown that the combined use of oral hypoglycemic medications is more effective than metformin monotherapy. In this double-blind, randomized, placebo-controlled, multicenter trial, we evaluated whether Jinlida, a Chinese herbal medicine, enhances the glycemic control of metformin in type 2 diabetes patients whose HbA1c was ineffectively controlled with metformin alone. A total of 186 diabetes patients were enrolled in this double-Blind, randomized, placebo-controlled, multicenter trial. Subjects were randomly allocated to receive either Jinlida (9 g) or the placebo TID for 12 consecutive weeks. All subjects in both groups also continuously received their metformin without any dose change. During this 12-week period, the HbA1c, FPG, 2h PG, body weight, BMI were assessed. HOMA insulin resistance (HOMA-IR) and β-cell function (HOMA- β) were also evaluated. At week 12, compared to the HbA1c level from week 0, the level of the Jinlida group was reduced by 0.92 ± 1.09% and that of the placebo group was reduced by 0.53 ± 0.94%. The 95% CI was 0.69 - 1.14 for the Jinlida group vs. 0.34 - 0.72 for the placebo group. There was a very significant HbA1c reduction between the two groups after 12 weeks (p < 0.01). Both FG and 2h PG levels of the Jinlida group and placebo group were reduced from week 0. There were a very significant FG and 2h PG level reductions between the two groups after 12 weeks (both p < 0.01). The Jinlida group also showed improved β-cell function with a HOMA-β increase (p < 0.05). No statistical significance was observed in the body weight and BMI changes. No serious adverse events were reported. Jinlida significantly enhanced the hypoglycemic action of metformin when the drug was used alone. This Chinese herbal medicine may have a clinical value as an add-on medication to metformin monotherapy. Chinese Clinical Trial Register ChiCTR-TRC-13003159.
    Preview · Article · Jun 2015 · PLoS ONE
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    ABSTRACT: The present study investigated the flavonoids from Abrus cantoniensis against ethanol-induced gastric ulcers in mice. The flavonoids from A. cantoniensis were extracted with ethanol and purified by macroporous resin and polyamide. The 2,2-diphenyl-1-picrylhydrazyl assay was used to measure the antioxidative activities in vitro. The ethanol-induced ulcer mouse model was used to evaluate the gastroprotective activities of the flavonoids from A. cantoniensis. In addition, a method was established to ensure accuracy for animal ulcer evaluation. The flavonoids from A. cantoniensis showed a strong free radical scavenging capacity with an IC50 of 43.83 µg/mL in the 2,2-diphenyl-1-picrylhydrazyl assay. At doses between 28.16-112.67 mg/kg, the flavonoids conspicuously reduced the ulcer index in ethanol-induced mice (p < 0.001). Significant differences were found in the levels of superoxide dismutase, catalase, glutathione, and myeloperoxidase in the stomach tissues between the flavonoids from the A. cantoniensis groups and the ethanol control group. The gastroprotective effect of the flavonoids from A. cantoniensis could be due to its antioxidative activity of the defensive mechanism. The data revealed that the flavonoids from A. cantoniensis could be a potential therapeutic agent for gastric ulcer prevention and treatment. Georg Thieme Verlag KG Stuttgart · New York.
    No preview · Article · Jun 2015 · Planta Medica

  • No preview · Article · Apr 2015 · Molecules
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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.
    Full-text · Article · Feb 2015 · Nutrients
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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.
    Preview · Article · Jan 2015 · Journal of ginseng research
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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.
    Preview · Article · Jan 2015 · Journal of Pharmacological Sciences
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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.
    No preview · Article · Jan 2015 · Journal of Ethnopharmacology
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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. A genetically engineered Apc (Min/+) mouse model was used in this study. We analyzed the saponin composition of American ginseng used in this project, and evaluated its effects on the progression of high-fat-diet-enhanced CRC carcinogenesis. After oral ginseng administration (10-20 mg/kg/d for up to 32 wk), experimental data showed that, compared with the untreated mice, ginseng very significantly reduced tumor initiation and progression in both the small intestine (including the proximal end, middle end, and distal end) and the colon (all p < 0.01). This tumor number reduction was more obvious in those mice treated with a low dose of ginseng. The tumor multiplicity data were supported by body weight changes and gut tissue histology examinations. In addition, quantitative real-time polymerase chain reaction analysis showed that compared with the untreated group, ginseng very significantly reduced the gene expression of inflammatory cytokines, including interleukin-1α (IL-1α), IL-1β, IL-6, tumor necrosis factor-α, granulocyte-colony stimulating factor, and granulocyte-macrophage colony-stimulating factor in both the small intestine and the colon (all p < 0.01). Further studies are needed to link our observed effects to the actions of the gut microbiome in converting the parent ginsenosides to bioactive ginseng metabolites. Our data suggest that American ginseng may have potential value in CRC chemoprevention.
    Preview · Article · Jan 2015 · Journal of ginseng research
  • Chong-Zhi Wang · Zhiyu Zhang · Samantha Anderson · Chun-Su Yuan
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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.
    No preview · Article · Dec 2014 · The American Journal of Chinese Medicine

Publication Stats

3k Citations
405.41 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
  • 2011
    • University of Macau
      • Institute of Chinese Medical Sciences
      Macao, Macau, Macao
  • 2004-2011
    • University of Illinois at Chicago
      • Department of Emergency Medicine (Chicago)
      Chicago, Illinois, United States