Ganoderic acid I

Shedding light on the mechanisms underlying the environmental regulation of secondary metabolite ganoderic acid in Ganoderma lucidum using physiological and genetic methods.[Pubmed:30951869]

Fungal Genet Biol. 2019 Apr 2;128:43-48.

The secondary metabolites of fungi are often produced at very low concentrations, and until recently the regulatory mechanisms of secondary metabolite biosynthesis have been unclear. Ganoderma lucidum is a macrofungus that is widely used as a traditional Chinese medicine or medicinal mushroom: ganoderic acid (GA) is one of the main active ingredients. Here, we review research from the last decade on which and how environmental factors regulate GA biosynthesis. These environmental factors are mainly three components: a single chemical/biological or biochemical signal, physical triggers, and nutritional conditions. Because G. lucidum is a non-model Basidiomycete, a combination of physiological and genetic research is needed to determine how those environmental factors regulate GA biosynthesis. The regulation of GA biosynthesis includes ROS, Ca(2+), cAMP and phospholipid signaling, and cross-talk between different signaling pathways. The regulatory mechanisms for the synthesis of this secondary metabolite, from the perspective of physiology and genetics, in G. lucidum will provide ideas for studying the regulation of fungal secondary metabolism in other non-model species, especially those fungi with limitations in genetic manipulation.

Antioxidant potential of ganoderic acid in Notch-1 protein in neuroblastoma.[Pubmed:30511344]

Mol Cell Biochem. 2018 Dec 3. pii: 10.1007/s11010-018-3485-7.

Neuroblastoma is a childhood tumor arising from developing a sympathetic nervous system and causes around 10% of pediatric tumors. Despite advancement in the use of sophisticated techniques in molecular biology, neuroblastoma patient's survivability rate is very less. Notch pathway is significant in upholding cell maintenance and developmental process of organs. Notch-1 proteins are a ligand-activated transmembrane receptor which decides the fate of the cell. Notch signaling leads to transcription of genes which indulged in numerous diseases including tumor progression. Ganoderic acid, a lanosterol triterpene, isolated from fungus Ganoderma lucidum with a wide range of medicinal values. In the present study, various isoforms of the ganoderic acid and natural inhibitors were docked by molecular docking using Maestro 9 in the Notch-1 signaling pathway. The receptor-based molecular docking exposed the best binding interaction of Notch-1 with ganoderic acid A with GScore (- 8.088), kcal/mol, Lipophilic EvdW (- 1.74), Electro (- 1.18), Glide emodel (- 89.944) with the active participation of Arg 189, Arg 199, Glu 232 residues. On the other hand natural inhibitor, curcumin has GScore (- 7.644), kcal/mol, Lipophilic EvdW (- 2.19), Electro (- 0.73), Glide emodel (- 70.957) with Arg 75 residues involved in docking. The ligand binding affinity of ganoderic acid A in Notch-1 is calculated using MM-GBSA (- 76.782), whereas curcumin has (- 72.815) kcal/mol. The QikProp analyzed the various drug-likeness parameters such as absorption, distribution, metabolism, excretion, and toxicity (ADME/T) and isoforms of ganoderic acid require some modification to fall under Lipinski rule. The ganoderic acid A and curcumin were the best-docked among different compounds and exhibits downregulation in Notch-1 mRNA expression and inhibits proliferation, viability, and ROS activity in IMR-32 cells.