Evaluation of Dimer of Epicatechin from an Endophytic Fungus Curvularia australiensis FC2AP on Acute Toxicity Levels, Anti-Inflammatory and Anti-Cervical Cancer Activity in Animal Models

Abstract

Cervical cancer, as the most frequent cancer in women globally and accounts almost 14% in India. It can be prevented or treated with vaccines, radiation, chemotherapy, and brachytherapy. The chemotherapeutic agents cause adverse post effects by the destruction of the neighboring normal cells or altering the properties of the cells. In order to reduce the severity of the side effects caused by the chemically synthesized therapeutic agents, the current research developed an anti-cancer agent dimer of epicatechin (DoE), a natural bioactive secondary metabolite (BSM) mediated from an endophytic fungus Curvularia australiensis FC2AP. The investigation has initiated with the evaluation of inhibiting the angiogenesis which is a main activity in metastasis, and it was assessed through Hen’s Egg Test on Chorio Allantoic Membrane (HET-CAM) test; the BSM inhibited the growth of blood vessels in the developing chick embryo. Further the DoE was evaluated for its acute toxicity levels in albino mice, whereas the survival dose was found to be 1250 mg/kg and the lethal dose was 1500 mg/kg body weight of albino mice; hematological, biochemical, and histopathological analyses were assessed. The anti-inflammatory responses of the DoE were evaluated in carrageenan induced Wistar rats and the reduction of inflammation occurred in a dose-dependent manner. By fixing the effective dose for anti-inflammation analysis, the DoE was taken for the anti-cervical cancer analysis in benzo (a) pyrene induced female Sprague-Dawley rats for 60 days trial. After the stipulated days, the rats were taken for hematological antioxidants, lipid peroxidation (LPO), member bound enzymes, cervical histopathological and carcinogenic markers analyses. The results specified that the DoE has the capability of reducing the tumor in an efficient way. This is the first report of flavonoid-DoE production from an endophytic fungus C. australiensis has the anticancer potentiality and it can be stated as anti-cancer drug.

Endophytic fungal isolation from Blumea axillaris: Identification and biological activity of secondary metabolites

“…Moreover, the previous researches in our laboratory on endophytic fungi exhibited antimicrobial, antioxidant, anti-angiogenic and anti-cancer activities from different crude and purified extracts of C. australiensis, Alternaria citrimacularis, Al. alternata and Cladosporium cladosporides (Mani et al, 2015a, b;Mani et al, 2021). Our first report will significantly contribute a vital role in pharma industries in the development of antioxidant and anti-cancer therapeutics.…”

Determination of Chemical Composition and Investigation of Biological Activities of Ocimum basilicum L.

“…The same anti-inflammatory action was observed in vitro with O. basilicum leaf ethanolic extract on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells by inhibiting NO production [ 106 ]. Moreover, specific pro-inflammatory cytokines (IL-2, IL-β, and TNF-α) and inflammatory mediators (iNOS and NO) were inhibited by the action of O. basilicum methanolic extract [ 107 ]. The observed effects of basil could be attributed to its compounds and those that are in the minority or to the synergy between them.…”

Mediterranean Diet as a Shield against Male Infertility and Cancer Risk Induced by Environmental Pollutants: A Focus on Flavonoids

“…Matzkin et al [213], reported how anti-inflammatory and antioxidant compounds could exert a beneficial role in the improvement of physio-pathological state of the aged male gonad [214]. Similarly, a dimer of epicatechin from the endophytic fungus Curvularia australiensis reverted the tumorigenic effect of B[a]P exposure in female rats on induced cervical cancer by reducing oxidative stress markers and pro-inflammatory ones, thus ameliorating lesion histopathology [215]. Other authors [216] investigated the molecular mechanisms associated with the cytoprotective effect of quercetin and its metabolites against benzo[a]pyrene (B[a]P), suggesting the involvement of other mechanisms beyond the an-tioxidant activity.…”