Taichunins E–T, Isopimarane Diterpenes and a 20-<i>nor</i>-Isopimarane, from <i>Aspergillus taichungensis</i> (IBT 19404): Structures and Inhibitory Effects on RANKL-Induced Formation of Multinuclear Osteoclasts

El‐Desoky, Ahmed H.; Inada, Natsumi; Maeyama, Yuka; Kato, Hikaru; Hitora, Yuki; Sebe, Momona; Nagaki, Mika; Kai, Aika; Eguchi, Koichi; Inazumi, Tomoaki; Sugimoto, Yukihiko; Frisvad, Jens Christian; Williams, Robert M.; Tsukamoto, Sachiko

doi:10.1021/acs.jnatprod.1c00486

Cited by 10 publications

(5 citation statements)

References 24 publications

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“…Ophiostomatoids and molds are two major fungal families well known for being highly correlated with the propagation and distribution of the PWN 14 . Although molds do play crucial roles in multiple processes of PWD epidemics 45 , in a way unlike the known contributions of ophiostomatoids to PWN (important food resources) Aspergillus species; most of the plant-associated Aspergillus are mutualists [48][49][50] , one of the PWN-associated Aspergillus fungi, A. arachidicola, has been reported as being harmful to plant and beneficial for insect feeding 48,49 .…”

Section: Discussionmentioning

confidence: 99%

The novel nematicide chiricanine A suppressesBursaphelenchus xylophiluspathogenicity inPinus massonianaby inhibitingAspergillusand its secondary metabolite, sterigmatocystin

Jia¹,

Chen²,

Yu³

et al. 2023

Preprint

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BACKGROUND: Pine wilt disease (PWD) is responsible for extensive economic and ecological damage to Pinus spp. forests and plantations worldwide. PWD is caused by the pine wood nematode (PWN, Bursaphelenchus xylophilus) and transmitted into pine trees by a vector insect, the Japanese pine sawyer (JPS, Monochamus alternatus). Host infection by PWN will attract JPS to spawn, which leads to the co-existence of PWN and JPS within the host tree, an essential precondition for PWD outbreaks. Through the action of their metabolites, microbes can manipulate the co-existence of PWN and JPS, but our understanding on how key microorganisms engage in this process remains limited, which severely hinders the exploration and utilization of promising microbial resources in the prevention and control of PWD. RESULTS: In this study we investigated how the PWN-associated fungus Aspergillus promotes the co-existence of PWN and JPS in the host trees (Pinus massoniana) via its secondary metabolite, sterigmatocystin (ST), by taking a multi-omics approach (phenomics, transcriptomics, microbiome, and metabolomics). We found that Aspergillus was able to promote PWN invasion and pathogenicity by increasing ST biosynthesis in the host plant, mainly by suppressing the accumulation of ROS (reactive oxygen species) in plant tissues that could counter PWN. Further, ST accumulation triggered the biosynthesis of VOC (volatile organic compounds) that attracts JPS and drives the coexistence of PWN and JPS in the host plant, thereby encouraging the local transmission of PWD. Meanwhile, we show that application of an Aspergillus inhibitor (chiricanine A treatment) results in the absence of Aspergillus and decreases the in vivo ST amount, thereby sharply restricting the PWN development in host. This further proved that Aspergillus is vital and sufficient for promoting PWD transmission. CONCLUSIONS: Altogether, these results document, for the first time, how the function of Aspergillus and its metabolite ST is involved in the entire PWD transmission chain, in addition to providing a novel and long-term effective nematicide for better PWD control in the field.

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Section: Discussionmentioning

confidence: 99%

The novel nematicide chiricanine A suppressesBursaphelenchus xylophiluspathogenicity inPinus massonianaby inhibitingAspergillusand its secondary metabolite, sterigmatocystin

Jia¹,

Chen²,

Yu³

et al. 2023

Preprint

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“…Inhibition of RANKL-induced up-regulation of NFATc1, DC-STAMP Eurotiomycetes RAW 264.7 Mouse model of LPS-induced osteolysis 5 mg/kg/day (mouse) Pre-clinical [ 184 ] 6-epi-Notoamide T Inhibition of RANKL-induced osteoclastogenesis. Downregulation of osteoclasts markers ( Nfatc1 , Acp5 , Ctsk , Atp6v0d2 , Dcstamp , Ocstamp ) Eurotiomycetes RAW 264.7 Not tested 5 μM Pre-clinical [ 185 ] Austalide V-X Inhibition of RANKL-induced osteoclastogenesis Eurotiomycetes mDM-BM Not tested 3 μM Pre-clinical [ 186 ] Chlorinated polyketide 2,7 Inhibition of LPS-induced NF-κB activation and RANKL-induced osteoclastogenesis in macrophages Eurotiomycetes RAW 264.7; mDM-BM Not tested 20 μM Pre-clinical [ 187 ] Taichunins G,K,N Inhibition of RANKL-induced osteoclastogenesis Eurotiomycetes RAW 264.7 Not tested 5 μM Pre-clinical [ 188 ] Mactanamide Inhibition of RANKL-induced osteoclastogenesis Eurotiomycetes mDM-BM Not tested 10 μg/mL Pre-clinical [ 189 ] …”

Section: Marine Natural Products As Alternative Players In Mbd Therap...mentioning

confidence: 99%

Metabolic bone disorders and the promise of marine osteoactive compounds

Carletti,

Gavaia,

Cancela

et al. 2023

Cell. Mol. Life Sci.

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Metabolic bone disorders and associated fragility fractures are major causes of disability and mortality worldwide and place an important financial burden on the global health systems. These disorders result from an unbalance between bone anabolic and resorptive processes and are characterized by different pathophysiological mechanisms. Drugs are available to treat bone metabolic pathologies, but they are either poorly effective or associated with undesired side effects that limit their use. The molecular mechanism underlying the most common metabolic bone disorders, and the availability, efficacy, and limitations of therapeutic options currently available are discussed here. A source for the unmet need of novel drugs to treat metabolic bone disorders is marine organisms, which produce natural osteoactive compounds of high pharmaceutical potential. In this review, we have inventoried the marine osteoactive compounds (MOCs) currently identified and spotted the groups of marine organisms with potential for MOC production. Finally, we briefly examine the availability of in vivo screening and validation tools for the study of MOCs.

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“…Taichunins E–T ( 97 – 112 ), along with 1 β , 7 α -dihydroxysandaracopimar-8(14), 15-diene19 ( 113 ) ( Figure 10 ), were obtained. Compound 99 , 103 , and 106 were shown to suppress the receptor activator of nuclear factor-κB ligand-induced formation of multinuclear osteoclasts at 5 μM, and 99 displayed 92% inhibition at a concentration of 0.2 μM in RAW264 cells [ 44 ]. Apsergiloid D ( 114 ) ( Figure 10 ) was isolated from Aspergillus sp.…”

Section: Isopimaranementioning

confidence: 99%

“…The results suggested that Taichunin G ( 99 ), K ( 104 ), and N ( 107 ) obviously reduced TRAP activity and the number of multinucleated osteoclasts, suggesting that these compounds inhibited osteoclast differentiation at 5 μM, and their effects were shown to be dose dependent. Compound 99 exhibited 92% inhibition at a concentration of 0.2 μM [ 44 ].…”

Section: Pharmacologymentioning

confidence: 99%

Pimarane Diterpenes from Fungi

Yao

2022

Pharmaceuticals

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Pimarane diterpenes are a kind of tricyclic diterpene, generally isolated from plant and fungi. In nature, fungi distribute widely and there are nearly two to three million species. They provide many secondary metabolites, including pimarane diterpenes, with novel skeletons and bioactivities. These natural products from fungi have the potential to be developed into clinical medicines. Herein, the structures and bioactivities of 197 pimarane diterpenes are summarized and the biosynthesis and pharmacological researches of pimarane diterpenes are introduced. This review may be useful improving the understanding of pimarane diterpenes from fungi.

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Taichunins E–T, Isopimarane Diterpenes and a 20-nor-Isopimarane, from Aspergillus taichungensis (IBT 19404): Structures and Inhibitory Effects on RANKL-Induced Formation of Multinuclear Osteoclasts

Cited by 10 publications

References 24 publications

The novel nematicide chiricanine A suppressesBursaphelenchus xylophiluspathogenicity inPinus massonianaby inhibitingAspergillusand its secondary metabolite, sterigmatocystin

The novel nematicide chiricanine A suppressesBursaphelenchus xylophiluspathogenicity inPinus massonianaby inhibitingAspergillusand its secondary metabolite, sterigmatocystin

Metabolic bone disorders and the promise of marine osteoactive compounds

Pimarane Diterpenes from Fungi

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