Polysaccharide-Rich Fractions from Ganoderma resinaceum (Ganodermataceae) as Chemopreventive Agents in N-Diethylnitrosamine-Induced Hepatocellular Carcinoma in Wistar Rats

Abstract

Hepatocellular carcinoma (HCC) is one of the most common and lethal diseases worldwide. Its treatment remains ineffective and the prognosis remains severe, thus favoring the emergence of a preventive approach. Mushroom-derived polysaccharides offer great opportunities because of their less toxicity and bioactivities. The present study aimed to investigate the chemopreventive effects of water-soluble polysaccharides from Ganoderma resinaceum on HCC. Two G. resinaceum polysaccharide-rich fractions (GRP I and GRP II) were obtained following hot water and alcohol precipitation. Their proteins, phenol compounds, and total neutral sugar content were assayed. The in vitro antiproliferative effect was assessed in MDA-MB 231, Hela, and HepG2 using the MTT assay. Further, for the in vivo study, seven groups of nine rats each received N-diethylnitrosamine (100 mg/kg BW), vehicle (NaCl 0.9%), doxorubicin (10 mg/kg BW), or G. resinaceum polysaccharides (125 and 250 mg/kg BW). Liver cancer initiation and progression was assessed by evaluating histomorphology of liver section, hepatic injury markers, hematology, cytokines/chemokines levels, and stress oxidative markers. GRP II presented higher protein and sugar and lower phenol compound content than GRP I. GRP exhibited CC50 of 340 and 261.7 in HepG2 cells after 48 h. Moreover, GRP I and GRP II (125 and 250 mg/kg) prevented the alteration of the histoarchitecture of the liver induced by the DEN. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetoprotein (AFP), proinflammatory cytokines (G-CSF, IFNγ, and TNFα), and chemokines (eotaxin and fractalkine) levels were significantly decreased in the GRP I- and GRP II-treated groups, while anti-inflammatory cytokines (IL-10 and IL-12p70) levels were increased. The antioxidant defense was also stimulated by reducing malondialdehyde (MDA) and nitric oxide (NO2) levels, increasing catalase (CAT) and superoxide dismutase (SOD) activities, and reducing glutathione (GSH) levels. Our results indicate that GRP I exhibits chemopreventive effects by inhibiting cell proliferation and restoring liver architecture, antioxidant enzymes, and cytokines/chemokines balance.

Perspectivas do potencial imunomodulador e antineoplásico de polissacarídeos e outras biomoléculas de Ganoderma spp.

“…Nas últimas três décadas, uma variedade de compostos bioativos tem sido identificada no gênero Ganoderma, incluindo triterpenóides, esteróides, xantonas, alcaloides, polissacarídeos e compostos fenólicos. Exemplo desses compostos incluem as ganodermatropinas, ácidos ganodéricos, como GA-A, GA-B, GA-C1, GA-C2, GA-β, GA-T, GA-Q, GA-H, além de ganoderol A e B, ganodermanodiol e ganodermanontriol (Ahmad et al, 2013;Ahmad et al, 2021;Ma et al, 2013;Silva et al, 2013;Wu et al, 2013). Alguns desses compostos bioativos e seus mecanismos de ação são destacados na Tabela 1.…”

The roles and potential mechanisms of plant polysaccharides in liver diseases: a review

“…A polysaccharide known as PFP-1, obtained from the fruiting body of Pleurotus geesteranus, has exhibited the ability to mitigate oxidative stress and inflammatory responses. This effect is achieved through the activation of Nrf2-mediated signaling pathways and regulation of the TLR4-mediated NF-κB signaling pathways, presenting a potential therapeutic strategy against ALD (Song et al, 2021). Additionally, research has indicated that the lipidlowering impact of ASP may stem from its dual inhibition of lipid synthesis and CD36-mediated lipid uptake.…”