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ABSTRACT: We aimed to explore the anti-inflammatory effects of total alkaloids in Rubus aleaefolius Poir. (TARAP) on non-alcoholic fatty liver disease, and to investigate the possible molecular mechanisms. A rodent non-alcoholic fatty liver disease (NAFLD) model was established by administration of a modified high-fat diet ad libitum for 8 weeks. Rats were treated with polyene phosphatidylcholine (PP), TARAP low‑dose (0.72 g/kg body weight/day) and TARAP high-dose (1.44 g/kg body weight/day). The model group and the control group received distilled water. After treatment for 4 weeks, the blood samples were obtained from the abdominal aorta, and the levels of serum ALT, AST, GGT, ALP, TG, TC, HDL-C and LDL-C were measured. Changes in liver tissue morphology were evaluated by H&E staining. The expression levels of nuclear factor (NF)-κB, cyclooxygenase-2 (COX‑2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α in rat livers were assayed by reverse transcription‑polymerase chain reaction (RT-PCR) and immunohistochemistry. Both TARAP and PP attenuated hepatic steatosis induced by the high-fat diet. The modified high-fat diet caused a significant increase in ALT, AST, GGT, ALP, TG, TC, LDL-C levels and a decrease in HDL-C levels. TARAP and PP treatment abrogated the increase in the levels of liver enzymes and the levels of TG, TC, LDL-C, as well as suppressed the increase in HDL-C levels. The results of RT-PCR and immunohistochemical assay showed that PP and TARAP treatment decreased the expression of NF-κB, COX-2, IL-6 and TNF-α. In conclusion, these results suggest that TARAP may protect against NAFLD through regulation of the NF-κB pathway.
International Journal of Molecular Medicine 04/2013; 31(4):931-7. · 1.98 Impact Factor
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ABSTRACT: Cancer cells are characterized by an uncontrolled increase in cell proliferation. G1 to S transition is one of the two main checkpoints used by cells to control the cell cycle progress and cell proliferation. G1/S progression is highly regulated by multiple intracellular signaling transduction cascades including Akt and p53 pathways, which therefore becomes a promising target for the development of novel anticancer therapy. Scutellaria barbata D. Don (SB) is a major component in many Chinese medicine formulas that have long been used in China to clinically treat various cancers including colorectal cancer (CRC). Recently, we reported that the ethanol extract of SB (EESB) is able to induce cancer cell apoptosis via activation of the mitochondrion-dependent pathway and inhibit tumor angiogenesis through suppression of Hedgehog signaling. To further elucidate the precise mechanisms of its antitumor activity, in the present study we evaluated the effect of EESB on the proliferation of human colon carcinoma HT-29 cells and investigated the underlying molecular mechanism. We found that EESB could inhibit the proliferation of HT-29 cells through blocking the G1/S cell cycle progression. In addition, EESB treatment profoundly promoted antiproliferative p21 expression, but inhibited the expression of pro-proliferative PCNA, cyclin D1 and CDK4 in HT-29 cells. Moreover, the phosphorylation/activation of Akt was significantly suppressed by EESB treatment, whereas that of p53 was enhanced. These results suggest that EESB could effectively induce G1/S arrest in human colon carcinoma cells via modulation of multiple cell cycle-related signaling pathways.
Oncology Reports 01/2013; · 1.84 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the therapeutic efficacy of Qianliening capsule (QC) against benign prostatic hyperplasia (BPH) in vivo in a BPH rat model, as well as to investigate the effects of QC on prostatic cell apoptosis and the possible molecular mechanisms mediating its anti-BPH activity. Fifty male Sprague‑Dawley (SD) rats were randomly classified into five groups. The rats of the four groups were castrated and subcutaneously injected with testosterone propionate to generate BPH. One week after model establishment, BPH rats were orally administrated with various doses of QC daily for 28 days. The prostatic tissues from BPH rats were collected to evaluate prostatic index (PI). The histological changes of prostate were observed by hematoxylin and eosin staining. TUNEL analysis was performed to examine cell apoptosis. The mRNA expression of Bcl-2 and Bax in prostatic tissues was determined by reverse transcription‑polymerase chain reaction (RT-PCR). The protein expression of Bcl-2, Bax and cleaved caspase 3 were examined by immunohistochemistry. Administration with QC significantly decreased PI in a dose-dependent manner (P<0.05 or P<0.01) and improved prostatic hyperplasia in BPH rats. Additionally, QC treatment induced prostatic cell apoptosis in a dose-dependent manner. Moreover, QC promoted the cleavage of caspase 3, an indicator of apoptosis, in a dose-dependent manner. Furthermore, following QC treatment, the expression ratio of pro‑apoptotic Bax to anti‑apoptotic Bcl-2 in prostatic tissues was increased in a dose-dependent manner. As a result, QC was effective in the treatment of BPH in rats. Promoting apoptosis of prostatic cells may therefore be one of the mechanisms by which QC treats BPH.
Molecular Medicine Reports 01/2013; · 0.42 Impact Factor
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ABSTRACT: Sonic hedgehog (SHH) signaling pathway promotes the process of angiogenesis, contributing to the growth and progression of many human malignancies including colorectal cancer (CRC), which therefore has become a promising target for cancer chemotherapy. Hedyotis diffusa Willd (HDW), as a well-known traditional Chinese herbal medicine, has long been used in China for the clinic treatment of various cancers. Recently, we reported that HDW can inhibit colorectal cancer growth in vivo and in vitro via suppression of the STAT3 pathway. In addition, we demonstrated the anti-angiogenic activity of HDW in vitro. To further elucidate the mechanism of the tumoricidal activity of HDW, by using a CRC mouse xenograft model we evaluated the in vivo effect of the ethanol extract of HDW (EEHDW) on tumor angiogenesis, and investigated the underlying molecular mechanisms. We found that EEHDW could significantly reduce intratumoral microvessel density (MVD), indicating its activity of antitumor angiogenesis in vivo. EEHDW suppressed the activation of SHH signaling in CRC xenograft tumors since it significantly decreased the expression of key mediators of SHH pathway. EEHDW treatment inhibited the expression of the critical SHH signaling target gene VEGF-A as well as its specific receptor VEGFR2. Taken together, we propose for the first time that Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of SHH-mediated tumor angiogenesis.
International Journal of Oncology 12/2012; · 2.40 Impact Factor
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ABSTRACT: Hedyotis diffusa Willd (HDW) has long been used as an important component in several Chinese medicine formulae to clinically treat various types of cancer, including colorectal cancer (CRC). Previously, we reported that HDW inhibits CRC growth via the induction of cancer cell apoptosis and the inhibition of tumor angiogenesis. In the present study, to further elucidate the mechanism of HDW-mediated antitumor activity, we investigated the effect of HDW ethanol extract (EEHDW) on the proliferation of HT-29 human colon carcinoma cells. We found that EEHDW reduced HT-29 cell viability and survival in a dose- and time-dependent manner. We also observed that EEHDW treatment blocked the cell cycle, preventing G1 to S progression, and reduced mRNA expression of pro-proliferative PCNA, Cyclin D1 and CDK4, but increased that of anti-proliferative p21. Our findings suggest that Hedyotis diffusa Willd may be an effective treatment for CRC via the suppression of cancer cell proliferation.
Experimental and therapeutic medicine 08/2012; 4(2):307-310.
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Qiaoyan Cai,
Jiumao Lin,
Lihui Wei,
Ling Zhang,
Lili Wang,
Youzhi Zhan,
Jianwei Zeng, Wei Xu,
Aling Shen,
Zhenfeng Hong,
Jun Peng
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ABSTRACT: Signal Transducer and Activator of Transcription 3 (STAT3), a common oncogenic mediator, is constitutively activated in many types of human cancers; therefore it is a major focus in the development of novel anti-cancer agents. Hedyotis diffusa Willd has been used as a major component in several Chinese medicine formulas for the clinical treatment of colorectal cancer (CRC). However, the precise mechanism of its anti-tumor activity remains largely unclear. Using a CRC mouse xenograft model, in the present study we evaluated the effect of the ethanol extract of Hedyotis diffusa Willd (EEHDW) on tumor growth in vivo and investigated the underlying molecular mechanisms. We found that EEHDW reduced tumor volume and tumor weight, but had no effect on body weight gain in CRC mice, demonstrating that EEHDW can inhibit CRC growth in vivo without apparent adverse effect. In addition, EEHDW treatment suppressed STAT3 phosphorylation in tumor tissues, which in turn resulted in the promotion of cancer cell apoptosis and inhibition of proliferation. Moreover, EEHDW treatment altered the expression pattern of several important target genes of the STAT3 signaling pathway, i.e., decreased expression of Cyclin D1, CDK4 and Bcl-2 as well as up-regulated p21 and Bax. These results suggest that suppression of the STAT3 pathway might be one of the mechanisms by which EEHDW treats colorectal cancer.
International Journal of Molecular Sciences 01/2012; 13(5):6117-28. · 2.60 Impact Factor
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ABSTRACT: Signal transducer and activator of transcription 3 (STAT3) plays an important role in tumor cell survival and proliferation and thus has become a major focus in the development of anti-cancer therapies. Patrinia scabiosaefolia has been used for the treatment of various types of cancer. However, the precise mechanism of the anti-cancer activity of Patrinia scabiosaefolia remains unclear. In this study, we evaluated the effect of the ethanol extract of Patrinia scabiosaefolia (EEPS) on proliferation and apoptosis in human multiple myeloma U266 cells that persistently express phosphorylated STAT3, and investigated the possible molecular mechanisms mediating its biological effects. We found that EEPS inhibited the phosphorylation of STAT3 in U266 cells. Consequently, the inhibitory effect of EEPS on STAT3 activation resulted in the suppression of cell proliferation and the induction of cell apoptosis. Moreover, EEPS treatment inhibited the expression of cyclin D1 (a promoter of cell proliferation) and Bcl-2 (an inhibitor of apoptosis), two important target genes of the STAT3 signaling pathway. Our findings for the first time demonstrate that Patrinia scabiosaefolia inhibits proliferation and promotes the apoptosis of cancer cells via inhibition of the STAT3 pathway, which may in part explain its anti-cancer activity.
Molecular Medicine Reports 03/2011; 4(2):313-8. · 0.42 Impact Factor
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ABSTRACT: Hedyotis Diffusa Willd has been used as a major component in several Chinese medicine formulations for the clinical treatment of colorectal cancer. However, the molecular mechanism of the anti-cancer activity of Hedyotis Diffusa Willd remains unclear. In the present study, we investigated the cellular effects of the ethanol extract of Hedyotis Diffusa Willd (EEHDW) in the HT-29 human colon carcinoma cell line. We found that EEHDW inhibited the growth of HT-29 cells demonstrating EEHDW-induced cell morphological changes and reduced cell viability in a dose- and time-dependent manner. Furthermore, we observed that EEHDW treatment resulted in DNA fragmentation, loss of plasma membrane asymmetry, collapse of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and increase of the ratio of pro-apoptotic Bax to anti-apoptotic Bcl-2, suggesting that the HT-29 cell growth inhibitory activity of EEHDW was due to mitochondrion-mediated apoptosis, which may partly explain the anti-cancer activity of Hedyotis Diffusa Willd.
International Journal of Oncology 11/2010; 37(5):1331-8. · 2.40 Impact Factor
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ABSTRACT: Inhibition of tumor angiogenesis has become an attractive target of anticancer chemotherapy. However, drug resistance and cytotoxicity against non-tumor associated endothelial cells limit the long-term use and the therapeutic effectiveness of angiogenesis inhibitors, thus increasing the necessity for the development of multi-target agents with minimal side effects. Traditional Chinese medicine (TCM) formulas, which have relatively fewer side effects and have been used clinically to treat various types of diseases, including cancer, for thousands of years, are considered to be multi-component and multi-target agents exerting their therapeutic function in a more holistic way. Hedyotis Diffusa Willd (EEHDW) has long been used as an important component in several TCM formulas to treat various types of cancer. Although recently we reported that EEHDW promotes cancer cell apoptosis via activation of the mitochondrial-dependent pathway, the precise mechanism of its tumoricidalactivity still remains to be clarified. In the present study, we investigated the angiogenic effects of the ethanol extract of EEHDW. Cell cycle analysis was perfomed using flow cytometry. Cell viability was analyzed using MTT assay. We found that EEHDW inhibited angiogenesis in vivo in chick embryo chorioallantoic membrane (CAM). In addition, we observed that EEHDW dose- and time-dependently inhibited the prolife-ration of human umbilical vein endothelial cells (HUVEC) by blocking the cell cycle G1 to S progression. Moreover, EEHDW inhibited the migration and tube formation of HUVECs. Furthermore, EEHDW treatment down-regulated the mRNA and protein expression levels of VEGF-A in HT-29 human colon carcinoma cells and HUVECs. Our findings suggest that inhibiting tumor angiogenesis is one of the mechanisms by which EEHDW is involved in cancer therapy.
Molecular Medicine Reports 4(6):1283-8. · 0.42 Impact Factor
