Acredinone C and the Effect of Acredinones on Osteoclastogenic and Osteoblastogenic Activity

Abstract

A new inhibitor, acredinone C (1), of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation was isolated from the culture broth of the fungus Acremonium sp. (F9A015) along with acredinones A (2) and B (3). The structure of acredinone C (1), which incorporates benzophenone and xanthone moieties, was established by the analyses of combined spectroscopic data including 1D and 2D NMR and MS. All of the acredinones studied efficiently inhibited the RANKL-induced formation of TRAP(+)-MNCs in a dose-dependent manner without any cytotoxicity up to 10 μM. Acredinone A showed dual activity in both osteoclast and osteoblast differentiation in vitro and good efficacy in an animal disease model of bone formation.

Austalide K from the Fungus Penicillium rudallense Prevents LPS-Induced Bone Loss in Mice by Inhibiting Osteoclast Differentiation and Promoting Osteoblast Differentiation

“…In particular, few anti-osteoporotic compounds with dual action except acredinone have been derived from microorganisms [ 18 ]. In the present study, we identified the novel activity on bone metabolism of austalide K, isolated from cultures of the marine fungus Penicillium rudallense , by demonstrating the simultaneous regulation of the genes related to osteoclast and osteoblast differentiation, as in the acredinone study [ 14 ].…”

“…These are essential genes for the generation of mature multinucleated osteoclasts [ 22 , 23 , 24 ]. In addition, the average percentage reduction of gene expression of the osteoclatogenic major factors by austalide K was more than 80%, compared to around 50% by acredinone [ 14 ]. This means that austalide K strongly inhibited the expression of osteoclast-related genes and might be used as a scaffold for much more effective osteoporotic treatment medicines.…”

“…Strontium ranelate is first drug to be approved in Europe that has been promoted as a dual-action agent (increase of new bone formation and reduction of bone resorption). Even though it has significant efficacy against osteoporosis, the European Pharmacovigilance Risk Assessment Committee has recommended its limited use due to associated heart problems [ 14 ]. For this reason, the US FDA has not approved the drug for use in the United States [ 15 , 16 ].…”

Benzophenones-natural metabolites with great Hopes in drug discovery: structures, occurrence, bioactivities, and biosynthesis

“…Additionally, 140 had marked bone-formation potential in the in vivo mouse model, thence, 140 could be a potential lead as an anabolic agent and/or anti-resorptive agent to prohibit and heal bone disorders. 87…”

Marine Pharmacology in 2016–2017: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action

“…Table 3 presents not only the pharmacological activity (an IC 50 ), but also the molecular mechanism of action of the following marine natural compounds: Fungus Acremonium sp. (F9A015) polyketide acredinone C (235) [256]; algal terpenoid astaxanthin (207) [257]; sponge Axinyssa sp. bisabolene sesquiterpene (236) [258]; sponge Carteriospongia sp.…”