Hepatoprotective effect of Matricaria chamomilla aqueous extract against 1,2-Dimethylhydrazine-induced carcinogenic hepatic damage in mice

Abstract

Dimethylhydrazine (DMH) is a potent colonic and hepatic carcinogen that is metabolized into oxyradicals causing liver injury and DNA mutations. Matricaria chamomilla is a well-documented medicinal herb that possesses anti-inflammatory, antioxidant and antitumor activities and is commonly used to treat diverse ailments. The present study aimed to reveal the hepatoprotective effects of Matricaria chamomilla aqueous extract during an intermediate stage of colorectal cancer (CRC) in mice. Male Balb/c mice were divided into six groups: group A served as control, group B received chamomile extract (150 mg/Kg b.w.) orally for 12 weeks, and groups C-F received weekly intraperitoneal injections of DMH (20 mg/Kg b.w.) once a week for 12 weeks. In addition to DMH, groups D and F received chamomile during the initiation and post-initiation stages, respectively. Blood and liver samples were collected for biochemical and molecular analyses. The results showed that DMH induced hepatic injury in mice as shown by significant increase in serum aspartate aminotransferase and alanine aminotransferase. The changes in biochemical parameters were accompanied by activation of the Wnt signaling pathway leading to increased hepatocytes proliferation as well as inflammation evidenced by high levels of pro-inflammatory enzymes cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS). The results also showed potential hepatoprotective effects of chamomile extract against DMH-induced liver injury, proliferation and inflammation. Chamomile restored the biochemical and molecular parameters and this improvement was more pronounced in mice pretreated with the extract. In conclusion, chamomile extract may exert its hepatoprotective activities against DMH probably due to the antioxidant, antiproliferative and anti-inflammatory properties of its flavonoids.

Keywords: Biochemistry; Biological sciences; COX-2; Cancer research; Chamomile; Dimethylhydrazine; Hepatobiliary system; Liver injury; Microbiology; Molecular biology; Oncology; Pharmaceutical chemistry; Pharmaceutical science; Toxicology; Wnt signaling; iNOS.

Figure 1

Schematic representation of treatment schedule.

Figure 2

Effect of chamomile on the levels of AST (A) and ALT (B) in liver tissues of treated mice. Data represented are the mean of three determinations ±SD. (∗), (∗∗), (∗∗∗), and (∗∗∗∗) correspond to P < 0.05, 0.01, 0.001, and 0.0001 respectively.

Figure 3

Effect of chamomile on the expression levels of Wnt5a (A), β-catenin (B), GSK3β (C), APC (D), Tcf4 (E), and Lef1 (F) genes in liver tissues of treated mice. Expression levels of treated and control groups were normalized to their respective GAPDH. Fold expression was determined relative to the control. All bars represent mean of three determinations ±SD. (∗), (∗∗), (∗∗∗), and (∗∗∗∗) on bars and on lines drawn upwards, that represent inter-categorical statistical significance, correspond to P < 0.05, <0.01, <0.001, and <0.0001 respectively.

Figure 4

Effect of chamomile on the expression levels of c-Myc (A) and Cyclin D1 (B) genes in liver tissues of treated mice. Expression levels of treated and control groups were normalized to their respective GAPDH. Fold expression was determined relative to the control. All bars represent mean of three determinations ±SD. (∗), (∗∗), (∗∗∗), and (∗∗∗∗) on bars and on lines drawn upwards, that represent inter-categorical statistical significance, correspond to P < 0.05, <0.01, <0.001, and <0.0001 respectively.

Figure 5

Effect of chamomile on the level of COX-2 (A) and activity of iNOS (B) in liver tissues of treated mice. Data are represented as mean ± SD. (∗), (∗∗), (∗∗∗), and (∗∗∗∗) correspond to P < 0.05, 0.01, 0.001, and 0.0001 respectively.