Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease. Recently approved molecular/ gene treatments do not solve the downstream inflammation-linked pathophysiological issues such that supportive therapies are required to improve therapeutic efficacy and patients' quality of life. Over the years, a plethora of bioactive natural compounds have been used for human healthcare. Among them, plumbagin, a plant-derived analog of vitamin K3, has shown interesting potential to counteract chronic inflammation with potential therapeutic significance. In this work we evaluated the effects of plumbagin on DMD by delivering it as an oral supplement within food to dystrophic mutant of the fruit fly Drosophila melanogaster and mdx mice. In both DMD models, plumbagin show no relevant adverse effect. In terms of efficacy plumbagin improved the climbing ability of the dystrophic flies and their muscle morphology also reducing oxidative stress in muscles. In mdx mice, plumbagin enhanced the running performance on the treadmill and the muscle strength along with muscle morphology. The molecular mechanism underpinning these actions was found to be the activation of nuclear factor erythroid 2-related factor 2 pathway, the re-establishment of redox homeostasis and the reduction of inflammation thus generating a more favorable environment for skeletal muscles regeneration after damage. Our data provide evidence that food supplementation with plumbagin modulates the main, evolutionary conserved, mechanistic pathophysiological hallmarks of dystrophy, thus improving muscle function in vivo; the use of plumbagin as a therapeutic in humans should thus be explored further.

Cervia D, Z.S. (2024). Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling. FREE RADICAL BIOLOGY & MEDICINE, 225, 193-207 [10.1016/j.freeradbiomed.2024.09.037].

Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling

Pincigher L
Secondo
Investigation
;
Zalambani C
Investigation
;
Barbalace MC
Formal Analysis
;
Prata C
Formal Analysis
;
Malaguti M
Methodology
;
Hrelia S
Writing – Original Draft Preparation
;
2024

Abstract

Duchenne muscular dystrophy (DMD) is a progressive muscle-wasting disease. Recently approved molecular/ gene treatments do not solve the downstream inflammation-linked pathophysiological issues such that supportive therapies are required to improve therapeutic efficacy and patients' quality of life. Over the years, a plethora of bioactive natural compounds have been used for human healthcare. Among them, plumbagin, a plant-derived analog of vitamin K3, has shown interesting potential to counteract chronic inflammation with potential therapeutic significance. In this work we evaluated the effects of plumbagin on DMD by delivering it as an oral supplement within food to dystrophic mutant of the fruit fly Drosophila melanogaster and mdx mice. In both DMD models, plumbagin show no relevant adverse effect. In terms of efficacy plumbagin improved the climbing ability of the dystrophic flies and their muscle morphology also reducing oxidative stress in muscles. In mdx mice, plumbagin enhanced the running performance on the treadmill and the muscle strength along with muscle morphology. The molecular mechanism underpinning these actions was found to be the activation of nuclear factor erythroid 2-related factor 2 pathway, the re-establishment of redox homeostasis and the reduction of inflammation thus generating a more favorable environment for skeletal muscles regeneration after damage. Our data provide evidence that food supplementation with plumbagin modulates the main, evolutionary conserved, mechanistic pathophysiological hallmarks of dystrophy, thus improving muscle function in vivo; the use of plumbagin as a therapeutic in humans should thus be explored further.
2024
Cervia D, Z.S. (2024). Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling. FREE RADICAL BIOLOGY & MEDICINE, 225, 193-207 [10.1016/j.freeradbiomed.2024.09.037].
Cervia D, Zecchini S, Pincigher L, Roux-Biejat P, Zalambani C, Catalani E, Arcari A, Del Quondam S, Brunetti K, Ottria R, Casati S, Vanetti C, Barbala...espandi
File in questo prodotto:
File Dimensione Formato  
Cervia+et+al+accepted+manuscript.pdf

embargo fino al 24/09/2025

Tipo: Postprint
Licenza: Licenza per Accesso Aperto. Creative Commons Attribuzione - Non commerciale - Non opere derivate (CCBYNCND)
Dimensione 2 MB
Formato Adobe PDF
2 MB Adobe PDF   Visualizza/Apri   Contatta l'autore

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/994814
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 1
social impact