Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model

Zhao, Benqi; Kang, Qian; Peng, Yu; Xie, Yuanping; Chen, Cheng; Li, Bingshao; Wu, Qing

doi:10.3390/ijms18081750

Cited by 18 publications

(6 citation statements)

References 24 publications

(25 reference statements)

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“…15) Moreover, ELE has been reported to have radical scavenging action in vitro, 16) and to elevate superoxide dismutase activity and catalase activity in erythrocytes in diabetes model mice. 17) From these findings and the present results, the underlying mechanism of the anti-colitis effect of ELE may involve regulation of cytokines and ROS.…”

Section: Discussionsupporting

confidence: 70%

Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Murakami

Tasaka

Takatori

et al. 2018

Biological & Pharmaceutical Bulletin

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Ulcerative colitis (UC) is a refractory disease that causes chronic inflammation or ulceration in the mucosa of the large intestine with multiple relapses. Although several drugs, including 5-aminosalicylic acid, steroids, immunosuppressants, and infliximab, are used for UC therapy, patients suffer from side effects of these drugs, and a new safer therapeutic agent is desired. Eucommia ulmoides OLIV. leaf extract (ELE) has an anti-inflammatory effect. Therefore, we examined the effect of ELE on UC using a chronic dextran sulfate sodium (DSS)-induced colitis model in mice. Chronic DSS-induced colitis was triggered by alternately repeating 5 days' DSS and 7 days' water administration in mice for 29 d. The severity of DSS-induced colitis was evaluated by daily body weight and bloody stool score, and colon length and myeloperoxidase (MPO) activity in colon tissue on day 29. ELE (3 or 9%) was administered in combination by feeding for 29 d, and the effect on colitis was evaluated. The mice given DSS exhibited chronic colitis symptoms with body weight loss, increased bloody stool score and MPO activity, and shortened colon length. Administration of 3 or 9% ELE suppressed the body weight loss, bloody stool score, colon shortening, and MPO activity in a dose-dependent manner. Histological analysis showed that the ELE-treated mice had less damages and leukocyte infiltration in the mucosal layer of the large intestine compared to DSS alone group. These results suggested that ELE has the potential to prevent the development of DSS-induced colitis and a therapeutic effect on UC in a safe manner.

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Section: Discussionsupporting

confidence: 70%

Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Murakami

Tasaka

Takatori

et al. 2018

Biological & Pharmaceutical Bulletin

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“…After 1 week of acclimatization, mice (n = 8/group) were randomly allocated into three experimental groups, namely control, AOM/DSS, and TB treatment groups. The AOM/DSS model was established as described previously [ 34 ]. The AOM/DSS and TB groups were intraperitoneally injected with AOM (10 mg/kg bw);the control group was injected with PBS only.…”

Section: Methodsmentioning

confidence: 99%

Theabrownin Alleviates Colorectal Tumorigenesis in Murine AOM/DSS Model via PI3K/Akt/mTOR Pathway Suppression and Gut Microbiota Modulation

Leung

El-Nezami

2022

Antioxidants

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Colorectal cancer (CRC) is one of the most common and fatal cancers worldwide, yet therapeutic options for CRC often exhibit strong side effects which cause patients’ well-being to deteriorate. Theabrownin (TB), an antioxidant from Pu-erh tea, has previously been reported to have antitumor effects on non-small-cell lung cancer, osteosarcoma, hepatocellular carcinoma, gliomas, and melanoma. However, the potential antitumor effect of TB on CRC has not previously been investigated in vivo. The present study therefore aimed to investigate the antitumor effect of TB on CRC and the underlying mechanisms. Azoxymethane (AOM)/dextran sodium sulphate (DSS) was used to establish CRC tumorigenesis in a wild type mice model. TB was found to significantly reduce the total tumor count and improve crypt length and fibrosis of the colon when compared to the AOM/DSS group. Immunohistochemistry staining shows that the expression of the proliferation marker, Ki67 was reduced, while cleaved caspase 3 was increased in the TB group. Furthermore, TB significantly reduced phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and the downstream mechanistic target of rapamycin (mTOR)and cyclin D1 protein expression, which might contribute to cell proliferation suppression and apoptosis enhancement. The 16s rRNA sequencing revealed that TB significantly modulated the gut microbiota composition in AOM/DSS mice. TB increased the abundance of short chain fatty acid as well as SCFA-producing Prevotellaceae and Alloprevotella, and it decreased CRC-related Bacteroidceae and Bacteroides. Taken together, our results suggest that TB could inhibit tumor formation and potentially be a promising candidate for CRC treatment.

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“…28 In AOM/DSS model, DSS-induced colitis is known to increase production of ROS and RONS that could cause DNA oxidation. 29 Mechanically, ROS and RONS are able, in turn, to damage either directly or indirectly mitochondria, creating a positive feedback loop, thus resulting in mitochondrial dysfunction. 30 It has long thought that mitochondria are less functional in inflamed intestinal epithelium and in tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibited colitis and colitis-associated cancer (CAC) through protecting mitochondrial structures of colorectal epithelial cells in mice

Wang

Cui

2018

Cancer Biology & Therapy

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Although a mountain of papers have showed that metformin plays a role in inhibiting cancers, but the mechanism underpinning this has not yet fully elucidated. Herein, we used AOM/DSS model, the clinicopathological features are similar to those found in humans, to investigate the effects of metformin as well as combination with 5-FU in the prevention of colitis and colitis associated cancer (CAC). Oral metformin significantly inhibited DSS-induced ulcerative colitis and AOM/DSS-induced CAC. Metformin also ameliorated 5-FU-induced colorectal gastrointestinal symptoms in mice. Metformin combination with 5-FU strongly inhibited colorectal cancer. Metformin reduced levels of the NFκB signaling components p-IKKα/β, p-NFκB, p-IκBα in colorectal mucosal cells. Transmission electron microscopy analysis suggested that the inhibition of metformin on colitis and CAC might associate with its biological activity of protecting mitochondrial structures of colorectal epithelial cells. Further analysis by Mito Tracker Red staining assay indicated that metformin prevented H 2 O 2-induced mitochondrial fission correlated with a decrease of mitochondrial perimeter. In addition, metformin increased the level of NDUFA9, a Q-module subunit required for complex I assembly, in colorectal epithelial cells. These observations of metformin in the inhibition of colitis and CAC might associate with its activity of activating the LKB1/AMPK pathway in colorectal epithelial cells. In conclusion, metformin inhibited colitis and CAC through protecting the mitochondrial structures of colorectal epithelial cells.

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Effect of Angelica sinensis Root Extract on Cancer Prevention in Different Stages of an AOM/DSS Mouse Model

Cited by 18 publications

References 24 publications

Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Effect of <i>Eucommia ulmoides</i> Leaf Extract on Chronic Dextran Sodium Sulfate-Induced Colitis in Mice

Theabrownin Alleviates Colorectal Tumorigenesis in Murine AOM/DSS Model via PI3K/Akt/mTOR Pathway Suppression and Gut Microbiota Modulation

Metformin inhibited colitis and colitis-associated cancer (CAC) through protecting mitochondrial structures of colorectal epithelial cells in mice

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