Fungal natural alkaloid schizocommunin activates the aryl hydrocarbon receptor pathway

Abstract

Activation of AhR by schizocommunin is linked to increased expression of xenobiotic metabolizing enzymes associated with immune and allergic responses.

Curcumin Suppresses the Lipid Accumulation and Oxidative Stress Induced by Benzo[a]pyrene Toxicity in HepG2 Cells

“…Upon interaction with its ligand, AhR is translocated into the nucleus and acts as a transcription factor inducing the expression of Cyp1a1 and Cyp1b1 , which are involved in the phase-I reactions of drug metabolism and also known as inducers of ROS production [ 35 , 38 ]. The expression of Cyp1a1 is further induced by cellular ROS, and the increased expression contributes to the cellular lipid accumulation [ 40 ].…”

“…To determine whether the modulatory effects of curcumin on the B[a]P toxicity in HepG2 cells are regulated via the AhR pathways, the fluorescence intensities in the cells upon B[a]P and curcumin treatments were measured via immunostaining methods (Figure 3). The HepG2 cells treated with B[a]P showed an increased fluorescence intensity compared with that of the control, and curcumin cotreatment with B[a]P attenuated the increased expression of AhR in HepG2 cells (Figure 3A,B Upon interaction with its ligand, AhR is translocated into the nucleus and acts as a transcription factor inducing the expression of Cyp1a1 and Cyp1b1, which are involved in the phase-I reactions of drug metabolism and also known as inducers of ROS production [35,38]. The expression of Cyp1a1 is further induced by cellular ROS, and the increased Upon interaction with its ligand, AhR is translocated into the nucleus and acts as a transcription factor inducing the expression of Cyp1a1 and Cyp1b1, which are involved in the phase-I reactions of drug metabolism and also known as inducers of ROS production [35,38].…”

“…The activation of AhR turns on the expression of cytochrome P450 family 1 subfamily A polypeptide 1 ( Cyp1a1 ) and subfamily B polypeptide 1 ( Cyp1b1 ). These genes are known for their activities in the metabolism of xenobiotics and function in the generation of ROS [ 34 , 35 , 36 , 37 , 38 ]. Recent studies have shown that especially CYP1A1 acts as a primary regulator in AhR-mediated lipid production, thereby causing lipid accumulation, and CYP1A1 expression, stimulated by ROS, also contributes to the accumulation of lipid droplets in hepatocytes [ 39 , 40 ].…”

Advances in deep eutectic solvents and water: applications in metal- and biocatalyzed processes, in the synthesis of APIs, and other biologically active compounds

“…96 Nagarajan and Ghosh have recently reported on a DES-mediated synthesis of two important natural alkaloids like bouchardatine and schizocommunin, 97 the former known to have biological properties as anti-cancer, anti-inflammatory and anti-tubercolar activities, 98 the latter showing a cytotoxic activity against murine linphoma cells and human hepatoma cells, and also knowing to be a potent activator of the aryl hydrocarbon receptor. 99 The quinazolinone skeleton of bouchardatine ( 48) was obtained by preliminarily reacting anthranilamide (45) with indole-2-carboxaldehyde ( 46) in a L-(+)-tartaric acid-DMU (3 : 7) melt at 90 °C for 8 h to give the quinazolinone intermediate 47 in 81% yield, which was finally formylated at indole C3 position to provide 48, according to a procedure previously reported by the same research group (Scheme 20a). 100 Schizocommunin (52), in turn, was prepared by first treating 45 with acetaldehyde (49) in the above green melt at 90 °C for 2 h to give dihydroquinazolinone 50 in 79% yield.…”

Compounds detection and inhibition activity of chloroform and ethyl acetate extracts of Schizophyllum commune on some cancer cell types

“…The results obtained are in line with the research of Teoh et al (2017) that the S. commune mushroom extract was positive for alkaloids. Filip et al (2019) reported that S. commune produces an alkaloid compound, namely schizocommunin, which can inhibit cervical cancer cells, it was characterized as a cytotoxic pigment with potential anticancer activity against murine lymphoma.…”