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Nuclear factor-kappa B (NF-κB) is an important molecule in mediating inflammatory colitis, which can lead to colorectal cancer (CRC). The aim of this study was to evaluate the chemopreventive efficacy of apple polysaccharide extract (AP) in inhibiting NF-κB-mediated inflammation pathways in CRC. We evaluated AP in vitro in HT-29 and SW620 human CRC cells. We also used the azoxymethane and dextran sodium sulphate (AOM/DSS) model to induce colon carcinogenesis in vivo. The chemoprotective effects of AP were assessed using Western blot, immunofluorescence assay, real-time PCR, electrophoretic mobility shift assay, and flow cytometry. AP reduced AOM/DSS-associated toxicities, prevented carcinogenesis, and decreased the expression of TLR4, MD2, MyD88, TRAM, TRIF-related adapter molecule, interferon-β, tumor necrosis factor-α, and interleukin-6. The protective effects of AP may be related to the inhibition of TLR4/MD2-mediated signaling, including MyD88 and TRIF, as well as the inhibition of NF-κB-mediated inflammatory signaling pathways. Therefore, AP could be used in combination therapy for the prevention of colitis-associated colon cancer. [ABSTRACT FROM PUBLISHER]

Du-Zhong has a long history of being used in traditional Chinese formulas to treat bone related diseases. The objective of the present study is to systematically investigate the effects of Du-Zhong cortex extract (DZCE) on disuse-induced osteoporosis. Rats were randomly divided into four groups, and three groups were treated with hind limb suspension (HLS). Control and HLS group received deionized distilled water, while the other two groups received alendronate (2.0 mg/kg/day) and DZCE (300 mg/kg/day) respectively by intragastric gavage for six weeks (two weeks prior to and during the four weeks of HLS). Dual-energy X-ray absorptiometry, assay of biochemical markers, and three-point bending test were employed to determine the effect of various treatments on bone mass, turnover, and strength. The trabecular bone microarchitecture was assessed by microCT analysis. DZCE could effectively prevent the bone loss induced by HLS, which was indicated by decreased levels of bone turnover markers as well as the changes in urinary calcium and phosphorus. The DZCE treatment also enhanced the biomechanical strength of bone and prevented the deterioration of trabecular bone microarchitecture. DZCE administration was able to prevent disuse-induced osteoporosis by regulating the bone metabolism, suggesting that DZCE could be used as an alternative therapy for the prevention of disuse-induced osteoporosis. [ABSTRACT FROM AUTHOR]

Multiple studies have indicated that selective cyclooxygenase-2 (COX-2) inhibitors possess clinically chemopreventive and preclinically anticancer activities. Their long-term use, however, may be limited by the cardiovascular toxicity. This study tried to investigate whether an apple oligogalactan (AOG) could enhance the growth inhibitory effect of celecoxib on colorectal cancer. Caco-2 and HT-29 cell lines were exposed to different concentrations of AOG (0–1 g/L), celecoxib (0–25 μmol/L), and their combination. COX-2 levels were assessed by reverse transcription PCR and Western blot. COX-2 activity was evaluated by measuring prostaglandin E2 concentration. A colitis-associated colorectal cancer (CACC) mouse model was used to determine the effect of the combination in vivo. AOG (0.1–0.5 g/L) could potentiate the inhibitory effect of physiologic doses of celecoxib (5 μmol/L) on cell growth and decrease COX-2 expressions both at RNA and protein levels. In vivo, the combination (2.5% AOG plus 0.04% celecoxib, w/w) prevented against CACC in mice effectively. Our data indicate that AOG could potentiate the growth inhibitory effect of celecoxib on colorectal cancer both in vitro and in vivo through influencing the expression and function of COX-2 and phosphorylation of MAPKs, which suggests a new possible combinatorial strategy in colorectal cancer therapy. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is one of the most common and preventable cancers. Regular consumption of apples is conducive to reduction in CRC risk. Aim of the study: To evaluate effects of modified apple polysaccharide (MAP) on tumorigenesis in a mouse model of colitis-associated colon cancer. Methods: One hundred male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Forty mice were given no further treatment, the rest were fed basal diet blended with three different doses of MAP; 2.5, 5, and 10% (20 mice in each group). Results: MAP significantly protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (18/20) in the mice treated with DMH/DSS, but that was reduced to 25% (5/20), 15% (3/20), and 5% (1/20), respectively, in the mice treated with basal diets plus 2.5, 5, and 10% of MAP. Study of apoptosis of colonic epithelial cells revealed that MAP moderately increased apoptosis, suggesting that the anti-tumor potency of MAP was probably attributed to its ability to induce apoptosis. Western blot analysis demonstrated that carbohydrate-binding protein galectin-3 changed in both the nucleus and the cytoplasm during the process from colitis to colon cancer in the model. And MAP could inhibit the binding of galectin-3 to its ligand: this is, at least in part, the possible mechanism of MAP by enhancing apoptosis and preventing tumorigenesis. Conclusions: These data suggest that MAP has a potential role in clinical prevention and treatment for colon cancer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Saponins of many herbs are known to possess anti-cancer effect. Aim of the study The present study aimed to investigate the growth inhibitory effect of Trillium tschonoskii steroidal saponins in a mouse model of colitis-associated colorectal cancer and a human colorectal cancer cell line HT-29, and isolate some major constituents and evaluate their anti-tumor activity. Materials and methods Forty male ICR mice were administered with 1, 2-dimethyl-hydrazine (DMH) and dextran sodium sulfate (DSS). Ten mice were given no further treatment, the rest were administered with different doses of TTS (5, 10, 20 mg/kg) orally, every three days from the 9th week to the 20th week. Results TTS effectively protected ICR mice against DMH/DSS-induced tumorigenesis. The incidence of tumor development was 90% (9/10) in the mice treated with DMH/DSS, but that was reduced to 50% (5/10), 40% (4/10), and 20% (2/10), respectively, in the mice treated with 5%, 10%, and 20% of TTS. Results of Ki-67 staining, TUNEL assay and caspase-3 activity assay revealed that TTS moderately decreased abnormal proliferation and increased apoptosis of colonic epithelial cells. It inhibited the growth and triggered the apoptosis of HT-29 cells, partly through suppressing mitogen-actived protein kinases (MAPKs) and triggering mitochondrial-mediated apoptotic pathway. Three compounds, namely, Paris saponin VII, polyphylloside III and Paris saponin VI, were important active compounds in TTS. Conclusion These data suggest that TTS has a potential role in clinical prevention and treatment for colorectal cancer. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The fructus Alpinia oxyphylla Miq. (AOM) has been used for treating diarrhea with spleen deficiency and gastralgia for thousands of years. A number of traditional Chinese medicine formulae provide AOM as an alternative herbal treatment for diarrhea, but the scientific basis for this usage has not been well defined. Aim of the study In this study, we tried to investigate the antidiarrheal activity and possible mechanisms of Fructus AOM, aiming to enrich our understanding to the scientific meanings and theoretical significance of Fructus AOM in clinical practice. Materials and methods The fructus of AOM collected from Hainan province in China were macerated in the 95% ethanol to obtain the crude 95% ethanol extract, followed by subjected to chromatographic separation over a Diaion HP20 column to obtain 90% and 50% ethanol eluted fractions. The activities of the crude extract and fractions on castor oil induced acute diarrhea, rhubarb induced chronic diarrhea, gastrointestinal transit (GIT) in mice, and contractions of isolated guinea-pig ileum were evaluated. Additionally, nitric oxide (NO), gastrointestinal peptides gastrin (GAS), motilin (MTL) and somatostatin (SS) levels that related to gastrointestinal motilities were detected to demonstrate the potential mechanisms. Ultimately, LC–MS/MS method was utilized to ensure the chemical consistency. Results The 95% ethanol extract and 90% ethanol eluted fraction significantly delayed the onset time and decreased the wet faeces proportion compared with control group in the castor oil induced acute diarrhea mice. In terms of further evaluation of antidiarrheal activity, the 95% ethanol extract and 90% ethanol elution displayed significant inhibition of the intestinal propulsion at the two highest oral doses of 20 g crude drug/kg and 1 g/kg. Moreover the 95% ethanol extract (10 and 20 g crude drug/kg) and 90% ethanol elution (0.5 and 1 g/kg) could significantly inhibit the GIT, which was partially attributed to the increase in NO and SS levels, and the decreased MTL. In vitro spontaneous contractions of the isolated guinea pig ileum induced by carbachol, neostigmine and histamine were attenuated by both the extract and elution. Phytochemical analysis of 95% ethanol extract and its fractions identified the presence of diphenylheptanes, sesquiterpenes, and flavones as the major components. Conclusions Our in vivo and in vitro data could partly support and justify the traditional usage of Fructus AOM on the treatment of diarrhea in traditional medicine. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Saponins of several herbs are known to induce apoptosis in some cancer cells and are proposed to be promising modulators of drug resistance. In the present study, we extracted Paris saponin VII (PS VII), a kind of saponin, from Trillium tschonoskii Maxim. and observed its effect on adriamycin-resistant breast cancer cells. Materials and methods: An adriamycin-resistant human breast cancer cell line, MCF-7/ADR cells were exposed to different concentrations of PS VII (0–100μmol/L). Then, flow cytometric assays and a human apoptosis array were used to detect apoptotic cells and apoptosis related protein expression. P-glycoprotein levels and intracellular rhodamine 123 (RH-123) accumulations were measured to evaluate the expression and activity of P-glycoprotein. Results: PS VII dose dependently suppressed cell viability as well as triggered apoptosis and modulated drug resistance of MCF-7/ADR cells. Further results showed that PS VII treatment in MCF-7/ADR cells led to increased TNFR1, TRAIL R1/DR4, TRAIL R2/DR5, and FADD expression, and activation of PARP, caspase-8, and 3. In parallel to the alterations, P-glycoprotein expression and activity were also reduced. Conclusion: These findings showed that PS VII might be an effective tumouristatic agent for the treatment of MDR breast cancer. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Poria cocos Wolf (Polyporaceae) is a well-known medicinal fungus, the epidermis (“Fu-Ling-Pi” in Chinese) of the sclerotia is used as a diuretic for treating oedema and promoting the diuretic process. In this paper we report on the diuretic activity in rats of petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract from the epidermis of Poria cocos. Materials and methods: Petroleum ether, ethyl acetate, n-butanol and the remaining fractions of the ethanol extract of Fu-Ling-Pi were orally administered to rats. The urinary excretion rate and the pH and electrolyte excretion were measured in the urine of saline-loaded rats. Results: In this study, all the tested fractions of Fu-Ling-Pi increased the urinary excretion rate. The three doses of the ethyl acetate fraction all produced remarkable urinary output in 6h, and all produced a remarkable increase in Na+ excretion and Cl− excretion. The Na+/K+ value in the experimental group was significantly enhanced compared with that of the control group, but the three doses of the ethyl acetate fraction had no effect on the K+ excretion. The 25-mg/kg and 50-mg/kg doses of the n-butanol fraction showed notable urinary output and produced a remarkable increase of Na+ excretion and Cl− excretion, but the two doses did not produce a remarkable effect on the Na+/K+ value. The petroleum ether and remaining fractions did not show remarkable diuretic activities compared with the control group. Conclusions: This study confirmed that the ethyl acetate and n-butanol fractions present a remarkable diuretic effect, showing that they are the diuretic bioactive fractions of Fu-Ling-Pi. This finding appears to indicate at least two mechanisms for the observed diuretic activity, and the K+-saving diuretic effect may be related to the triterpenoid components of intermediate polarity contained in this fungus, particularly the lanostanes tetracyclic triterpenoids. [Copyright &y& Elsevier]

Saponins of many herbs could inhibit the growth of colorectal cancer cells. In the study, we investigated the effects of Paris saponin Ⅶ (PSⅦ), and elucidated its mechanism in colorectal carcinoma cells and a xenograft mouse model. HT-29 and HCT-116 cells were treated with different concentrations of PSⅦ (0–100 μM). The effects of PSⅦ on HCT-116 cells were assessed using a microarray. Then, apoptotic cells were detected by flow cytometric analysis and apoptosis related protein expression was evaluated by Western blot. A xenograft model of nude mice was used to assess the effect of PSⅦ in vivo. MTT assay showed the IC 50 values of PSⅦ for growth inhibition of HT-29 and HCT-116 cells were 1.02 ± 0.05 μM and 3.50 ± 0.79 μM respectively. Edu assay demonstrated that PSⅦ effectively suppressed the growth of HT-29 and HCT-116 cells. Treatment with 0–3 μM PSⅦ not only triggered apoptosis, but also activated caspase-3 and caspase-9 of HT-29 and HCT-116 cells in a concentration dependent manner. In parallel to the alterations, Bax and Cyto-c expression increased while Bcl-2 decreased. In nude mice, PSⅦ reduced the tumor size and induced the apoptosis of tumor cells. PSVII could suppress IL-6-induced phosphorylation of STAT3 in vitro and blocked STAT3 phosphorylation in vivo. Our results suggest that PSVII suppressed the activation of IL-6/STAT3 pathway, consequently suppressed the growth and proliferation and triggered the apoptosis of CRC cells. These findings indicate that PSⅦ might be an effective tumouristatic agent for the treatment of colorectal cancer. Image 1 [ABSTRACT FROM AUTHOR]