Triterpenes from Poria cocos are revealed as potential retinoid X receptor selective agonists based on cell and in silico evidence

Abstract

Poria cocos is an edible and medicinal fungus that is widely used in Traditional Chinese Medicines as well as in modern applications. Retinoid X receptor (RXR) occupies a central place in nuclear receptor signaling, and a pharmacological RXRdependent pathway is involved in myeloid cell function. Here, structural information for 82 triterpenes from P. cocos and 17 known RXR agonists was collected in a compound library and retrieved for a molecular docking study. Three triterpenes, 16α-hydroxytrametenolic acid (HTA), pachymic acid (PA), and polyporenic acid C (PPAC), were identified as novel RXR-specific agonists based on luciferase reporter assays and in silico evidence. Treatment with HTA, PA, and PPAC significantly induced differentiation of the human promyelocytic leukemia cell line HL-60 with EC50 values of 21.0 ± 0.52, 6.7 ± 0.37, and 9.4 ± 0.65 μM, respectively. These effects were partly blocked by the RXR antagonist UVI3003, suggesting that an RXRdependent pathway may play an important role in their anti-acute promyelocytic leukemia (APL) effects. Taken together, triterpenes from P. cocos are revealed as naturally occurring RXR selective agonists with the potential for anti-cancer activity.These results suggest a novel approach to the treatment or prevention of APL. K E Y W O R D Sacute promyelocytic leukemia, naturally occurring agonist, Poria cocos, retinoid X receptor, Traditional Chinese Medicines, triterpenes 494 | XU et al.

16α-Hydroxytrametenolic Acid from Poria cocos Improves Intestinal Barrier Function Through the Glucocorticoid Receptor-Mediated PI3K/Akt/NF-κB Pathway

“…Prior to molecular docking, the crystal structure of the ligand-binding domain of GR (Protein Data Bank (PDB) code: 1NHZ) was downloaded as previously described. 29 The initial setup of the GR structure for docking was performed using the Protein Preparation Wizard module in Maestro (Schrodinger, LLC). 30 The grid was sized to 20 Å in each direction at the center of the binding pocket.…”

“…Cells were maintained in basic Dulbecco's modified Eagle's medium as described. 29 Cell Viability. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was employed to detect the cytotoxicity of triterpenoids from P. cocos on Caco-2, 293T, and RAW 264.7 cells, respectively.…”

“…The transfection procedure was performed according to an established method. 29 A glucocorticoidresponsive element (GRE) was employed, with the sequence 5′-AGCTAGAACATCCTGTACAGCAGAGCTAGAACATCCTGTA-CAGCAG-3′ cloned into pLuc-MCS.…”

“…Caco-2, 293T, and RAW 264.7 cells were purchased from the Shanghai Institute of Cell Biology (Shanghai, China). Cells were maintained in basic Dulbecco’s modified Eagle’s medium as described …”

Poria cum Radix Pini Rescues Barium Chloride-Induced Arrhythmia by Regulating the cGMP-PKG Signalling Pathway Involving ADORA1 in Zebrafish

“…In addition, it can also inhibit tumour growth and exert antitumour effects by enhancing the body's immune function. Triterpenes and polysaccharide compounds are the main active components of PRP (Xu et al, 2020;Yi et al, 2020). Studies have shown that triterpenes (poria cocoic acid) can inhibit the secretion of IL-2 and IFN-γ and affect the killing of target cells by cytotoxic T cells and the apoptosis of cardiomyocytes (Wu et al, 2014).…”