Inhibition of Intestinal Adenoma Formation in APCMin/+ Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta

Abstract

BackgroundMutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APCMin/+ mice.Methods APCMin/+ mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D.ResultsRiccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2–3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps.ConclusionsOur results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity.

Neuroprotective effect of paeoniflorin on H2O2-induced apoptosis in PC12 cells by modulation of reactive oxygen species and the inflammatory response

“…NF-κB, a proinflammatory transcription factor, functions as the 'first responder' to various generators of cellular stress, including free radicals and pro-inflammatory cytokines (e.g. TNF-α) and bacterial biomolecules) (27). In the present study, H 2 O 2 was observed to induce an inflammatory response involving NF-κB and its associated signals.…”

Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute

“…Colorectal cancer (CRC) is one of the leading causes of cancer mortalities worldwide, and is the third most common cancer type and the fifth leading cause of mortality in China ( 1 – 3 ). The majority of CRCs develop sporadically (70–80%), and the somatic loss of tumor suppressor gene, adenomatous polyposis coli ( APC ), was revealed to be present in 85% of patients with CRC and familial adenomatous polyposis ( 4 – 6 ). It has previously been demonstrated to have significant pro-apoptosis and anti-proliferative effects in several different types of cancers in vivo and in vitro ( 1 – 3 ).…”

Bryophytes in Cibodas Botanical Garden: Diversity and Potential Uses

“…This liverwort has a thin with the dark green color thallus, flat margin, and papilla on the rhizoid. D. hirsuta produces secondary metabolites called Riccardin D which can inhibit the growth of tumor cells (Liu et al, 2012). (Lee et al, 1977) Anthoceros punctatus Anthocerotaceae Agriculture (mychorrhiza) (Schüßler, 2000) Barbula javanica Pottiaceae Decorative plant, medicinal plant (antimicrobial) (Schenk, 1997); (Singh et al, 2007); (Vats & Alam, 2013) Bazzania sp.…”

“…(Lee et al, 1977) Anthoceros punctatus Anthocerotaceae Agriculture (mychorrhiza) (Schüßler, 2000) Barbula javanica Pottiaceae Decorative plant, medicinal plant (antimicrobial) (Schenk, 1997); (Singh et al, 2007); (Vats & Alam, 2013) Bazzania sp. Lepidoziaceae Medicinal plant (antimicrobial) (Alam et al, 2015) Brachymenium nepalense Bryaceae Antimicrobial; medicinal plant ; (Wankhede & Manik, 2015) Bryum billardieri Bryaceae Decorative plant (Schenk, 1997) Campylopus crispifolius Dicranaceae Decorative plant (Schenk, 1997) Campylopus micholitzii Dicranaceae Decorative plant (Schenk, 1997) Campylopus umbellatus Dicranaceae Decorative plant (Schenk, 1997) Cyathodium foetidissimum Targioniaceae Fragrance; fixative plant (Allen et al, 2017) Dicranoloma reflexum Dicranaceae Decorative plant, medicinal plant (Junairiah et al, 2016) Dumortiera hirsuta Marchantiaceae Medicinal plant (antitumor) (Liu et al, 2012) Ectropothecium ichnotocladum Hypnaceae Decorative plant (Schenk, 1997); (Glime, 2013) Fissidens crassinervis Fissidentaceae Medicinal plant (antibacterial) (Glime, 2013) Fissidens javanicus Fissidentaceae Medicinal plant (antibacterial) (Glime, 2013) Frullania sp. Jubulaceae Medicinal plant (antibacterial, anti-cancer) (Glime, 2013); (Asakawa, 2007) Heteroscyphus argutus Geocalycaceae Medicinal plant (anticancer) (Lin et al, 2012) Hyophila involuta Pottiaceae Medicinal plant (antibacterial); ecocity (Glime, 2013); (Singh et al, 2016) Hypnodendron sp.…”