The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis

Ashraf, Sadaf; Radhi, Masar; Gowler, Peter R W; Burston, James J.; Gandhi, Raj D.; Thorn, Graeme J.; Piccinini, Anna M.; Walsh, David A.; Chapman, Victoria; Moor, Cornelia H. de

doi:10.1038/s41598-019-41140-1

Cited by 30 publications

(44 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As cordycepine is similar to adenosine in structure, it can inhibit processes in which adenosine is involved (Xia et al 2017). Cordycepin reduces osteoarthritis symptoms, i.e., synovial inflammation, joint pathology, and pain behavior (Ashraf et al 2019). It has been proved that cordycepin inhibits senescence of cells in rodents through the NRF2 (nuclear factor erythroid 2-related factor 2) and AMPK (AMP-activated protein kinase) pathways in the inflammatory process.…”

Section: Secondary Metabolites: Role In Infection and Possible Applicmentioning

confidence: 99%

Entomopathogenic fungi: unconventional applications

Litwin

Nowak

Różalska

2020

Rev Environ Sci Biotechnol

158

View full text Add to dashboard Cite

Entomopathogenic fungi (EPF) are microorganisms that cause fatal diseases of arthropods. The infection process involves several stages that consist of direct contact of the fungus with the surface of the cuticle of the attacked insect. The factors that determine the effectiveness of the infection process include lytic enzymes, secondary metabolites, and adhesins produced by EPF. Because of their high insecticidal effectiveness, these fungi are commonly used as biopesticides in organic farming. As the environment and farmlands are contaminated with many compounds of anthropogenic origin (e.g., pesticides), the effects of these toxic compounds on EPF and the mechanisms that affect their survival in such a toxic environment have been studied in recent years. This review presents information on the capacity of EPF to remove toxic contaminants, including alkylphenols, organotin compounds, synthetic estrogens, pesticides and hydrocarbons. Moreover, these fungi produce numerous secondary metabolites that can be potentially used in medicine or as antimicrobial agents. Despite their huge potential in biocontrol processes, the use of EPF has been underestimated due to a lack of knowledge on their abilities. In our work, we have presented the available data on the possibilities of the additional and unconventional use of these microorganisms.

show abstract

Section: Secondary Metabolites: Role In Infection and Possible Applicmentioning

confidence: 99%

Entomopathogenic fungi: unconventional applications

Litwin

Nowak

Różalska

2020

Rev Environ Sci Biotechnol

158

View full text Add to dashboard Cite

show abstract

“…Reports include claims of efficacy in animal models of bone loss 23 , vascular disorder 24 , cognitive dysfunction 25 , sleep disorders 26 , cancer 21,27 , neuronal degeneration 28 , hyperlipidaemia 29 , oxidative stress 30 , hyperglycaemia 31 , asthma and lung inflammation 32 and viral infection 33 . Indeed, we have recently shown that oral cordycepin is effective in rodent models of osteoarthritis and demonstrated that it acts as an anti-inflammatory pain killer 34 . However, there seems to be lack of data on absorption and disposition of cordycepin as only extremely limited information can be found in the literature 35,36 .…”

Section: Introductionmentioning

confidence: 99%

“…As is the case for adenosine and its analogues, oral absorption and bioavailability of cordycepin is not well understood, despite multiple in vivo pharmacology studies performed with oral administration and the oral route being the intended route of administration for cordycepin 23–25,27,29,34,37,38 . The information on the oral absorption processes and the biotransformation of cordycepin is critical in elucidating the exposure-effect relationship, especially given that there is strong evidence that cordycepin needs to be converted to cordycepin 5′-triphosphate (CordyTP) in order to exert at least some of its pharmacological effects 19,39–41 .…”

Section: Introductionmentioning

confidence: 99%

A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin

Lee

Radhi

Cipolla

et al. 2019

Sci Rep

Self Cite

View full text Add to dashboard Cite

Although adenosine and its analogues have been assessed in the past as potential drug candidates due to the important role of adenosine in physiology, only little is known about their absorption following oral administration. In this work, we have studied the oral absorption and disposition pathways of cordycepin, an adenosine analogue. In vitro biopharmaceutical properties and in vivo oral absorption and disposition of cordycepin were assessed in rats. Despite the fact that numerous studies showed efficacy following oral dosing of cordycepin, we found that intact cordycepin was not absorbed following oral administration to rats. However, 3′-deoxyinosine, a metabolite of cordycepin previously considered to be inactive, was absorbed into the systemic blood circulation. Further investigation was performed to study the conversion of 3′-deoxyinosine to cordycepin 5′-triphosphate in vitro using macrophage-like RAW264.7 cells. It demonstrated that cordycepin 5′-triphosphate, the active metabolite of cordycepin, can be formed not only from cordycepin, but also from 3′-deoxyinosine. The novel nucleoside rescue metabolic pathway proposed in this study could be responsible for therapeutic effects of adenosine and other analogues of adenosine following oral administration. These findings may have importance in understanding the physiology and pathophysiology associated with adenosine, as well as drug discovery and development utilising adenosine analogues.

show abstract

“…Cordycepin suppresses proliferation and activates apoptosis in human epithelial endometriotic cells in vitro [406]. Osteoarthritis patients exhibit elevated CPSF4 expression, resulting in high levels of inflammatory genes [407]. Cordycepin has also been shown to reduce inflammatory gene induction in cell culture [408], and symptoms in rodent models of osteoarthritis [407].…”

Section: Targeting Mrna 3 End Formation As a Novel Therapymentioning

confidence: 99%

Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders

2020

View full text Add to dashboard Cite

A crucial feature of gene expression involves RNA processing to produce 3′ ends through a process termed 3′ end cleavage and polyadenylation (CPA). This ensures the nascent RNA molecule can exit the nucleus and be translated to ultimately give rise to a protein which can execute a function. Further, alternative polyadenylation (APA) can produce distinct transcript isoforms, profoundly expanding the complexity of the transcriptome. CPA is carried out by multi-component protein complexes interacting with multiple RNA motifs and is tightly coupled to transcription, other steps of RNA processing, and even epigenetic modifications. CPA and APA contribute to the maintenance of a multitude of diverse physiological processes. It is therefore not surprising that disruptions of CPA and APA can lead to devastating disorders. Here, we review potential CPA and APA mechanisms involving both loss and gain of function that can have tremendous impacts on health and disease. Ultimately we highlight the emerging diagnostic and therapeutic potential CPA and APA offer.

show abstract

The polyadenylation inhibitor cordycepin reduces pain, inflammation and joint pathology in rodent models of osteoarthritis

Cited by 30 publications

References 61 publications

Entomopathogenic fungi: unconventional applications

Entomopathogenic fungi: unconventional applications

A novel nucleoside rescue metabolic pathway may be responsible for therapeutic effect of orally administered cordycepin

Emerging Roles of RNA 3′-end Cleavage and Polyadenylation in Pathogenesis, Diagnosis and Therapy of Human Disorders

Contact Info

Product

Resources

About