Effects of non‐euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice

Iannotti, Fabio Arturo; Pagano, Ester; Moriello, Aniello Schiano; Alvino, Filomena Grazia; Sorrentino, Nicolina Cristina; D’Orsi, Luca; Gazzerro, Elisabetta; Capasso, Raffaele; Leonibus, Elvira De; Petrocellis, Luciano De; Marzo, Vincenzo Di

doi:10.1111/bph.14460

Cited by 62 publications

(63 citation statements)

References 67 publications

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“…In addition to histological and functional protection in the dystrophin‐deficient soleus, PGC‐1α overexpression also altered gene expression suggestive of increased autophagy in the same animals used herein (Hollinger et al, ). In studies using limb muscle of approximately the same age, dystrophin deficiency has been shown to increase LC3I protein abundance while effects on LC3II are equivocal (Fiacco et al, ; Iannotti et al, ). In the present investigation evaluating the gastrocnemius, our data suggest increased autophagosome formation following PGC‐1α overexpression (increased LC3II) and increased degradation (similar p62).…”

Section: Discussionmentioning

confidence: 99%

PGC‐1α overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin‐deficient skeletal muscle

et al. 2020

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Duchenne muscular dystrophy (DMD) is caused by the absence of functional dystrophin protein and results in progressive muscle wasting. Dystrophin deficiency leads to a host of dysfunctional cellular processes including impaired autophagy. Autophagic dysfunction appears to be due, at least in part, to decreased lysosomal abundance mediated by decreased nuclear localization of transcription factor EB (TFEB), a transcription factor responsible for lysosomal biogenesis. PGC‐1α overexpression decreased disease severity in dystrophin‐deficient skeletal muscle and increased PGC‐1α has been linked to TFEB activation in healthy muscle. The purpose of this study was to determine the extent to which PGC‐1α overexpression increased nuclear TFEB localization, increased lysosome abundance, and increased autophagosome degradation. We hypothesized that overexpression of PGC‐1α would drive TFEB nuclear translocation, increase lysosome biogenesis, and improve autophagosome degradation. To address this hypothesis, we delivered PGC‐1α via adeno‐associated virus (AAV) vector injected into the right limb of 3‐week‐old mdx mice and the contralateral limbs received a sham injection. At 6 weeks of age, this approach increased PGC‐1α transcript by 60‐fold and increased TFEB nuclear localization in gastrocnemii from PGC‐1α treated limbs by twofold compared to contralateral controls. Furthermore, lamp2, a marker of lysosome abundance, was significantly elevated in muscles from limbs overexpressing PGC‐1α. Lastly, increased LC3II and similar p62 in PGC‐1α overexpressing‐limbs compared to contralateral limbs are supportive of increased degradation of autophagosomes. These data provide mechanistic insight into PGC‐1α‐mediated benefits to dystrophin‐deficient muscle, such that increased TFEB nuclear localization in dystrophin‐deficient muscle leads to increased lysosome biogenesis and autophagy.

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Section: Discussionmentioning

confidence: 99%

PGC‐1α overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin‐deficient skeletal muscle

et al. 2020

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“…on transcription and synthesis of pro-inflammatory markers (i.e. IL-6 receptors, TNF-α, TNF-β1, and inducible nitric oxide synthase) in the gastrocnemius and diaphragm of dystrophic MDX mice (a mouse model of Duchenne muscular dystrophy) [91]. In this investigation, CBD attenuated mRNA expression of each marker and reduced plasma concentrations of IL-6 and TNFα.…”

Section: Exercise-induced Muscle Damage-muscle Function Soreness Anmentioning

confidence: 66%

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

et al. 2020

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Cannabidiol (CBD) is a non-intoxicating cannabinoid derived from Cannabis sativa. CBD initially drew scientific interest due to its anticonvulsant properties but increasing evidence of other therapeutic effects has attracted the attention of additional clinical and non-clinical populations, including athletes. Unlike the intoxicating cannabinoid, Δ 9-tetrahydrocannabinol (Δ 9-THC), CBD is no longer prohibited by the World Anti-Doping Agency and appears to be safe and well-tolerated in humans. It has also become readily available in many countries with the introduction of over-the-counter "nutraceutical" products. The aim of this narrative review was to explore various physiological and psychological effects of CBD that may be relevant to the sport and/ or exercise context and to identify key areas for future research. As direct studies of CBD and sports performance are is currently lacking, evidence for this narrative review was sourced from preclinical studies and a limited number of clinical trials in non-athlete populations. Preclinical studies have observed robust anti-inflammatory, neuroprotective and analgesic effects of CBD in animal models. Preliminary preclinical evidence also suggests that CBD may protect against gastrointestinal damage associated with inflammation and promote healing of traumatic skeletal injuries. However, further research is required to confirm these observations. Early stage clinical studies suggest that CBD may be anxiolytic in "stress-inducing" situations and in individuals with anxiety disorders. While some case reports indicate that CBD improves sleep, robust evidence is currently lacking. Cognitive function and thermoregulation appear to be unaffected by CBD while effects on food intake, metabolic function, cardiovascular function, and infection require further study. CBD may exert a number of physiological, biochemical, and psychological effects with the potential to benefit athletes. However, well controlled, studies in athlete populations are required before definitive conclusions can be reached regarding the utility of CBD in supporting athletic performance.

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“…CBD may be useful for treating bladder dysfunction [112]. It is also reported that CBD), cannabidivarin (CBDV) and tetrahydrocannabidivarin (THCV), can reduce inflammation and restore functional autophagy and positively enhance muscle function in vivo [113].…”

Section: Medicalmentioning

confidence: 99%

Cannabis, the Plant of the Unlimited Possibilities

Dölle

Kurzmann

2019

AIR

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This review paper gives an overview of Cannabis Sativa, also known as hemp, which has been cultivated and used century's B.C. due to its medical, hallucinogenic and agricultural properties. Cannabis has been described in 1938 as the billion-dollar plant but has lost its value in the U.S. due to regulatory and legislative issues. Hemp has seen as new push In the U.S. with the introduction of the 2018 Farm Bill which allows on a federal level to grow hemp, pending on individual state regulations. Currently, industrial hemp production is allowed in at least 38 U.S. States under strict regulations. Today hemp is used in counties that do not have as strict regulations as the U.S. in a variety of applications such as beauty products, carpets, cooking oil, personal care products and textiles. Hemp can be considered as an alternative feedstock due to its low lignin and high cellulose level for biofuel application as an alternative to replace petroleum-based fuels and gases. In the U.S. hemp research in these areas has stalled due to the complexity of the law. Beside industrial application such as ropes, textiles, shoes, etc., hemp today is used in pharmaceutical and medical applications, by extracting Δ9-tetrahydrocannabinol and cannabinoids from the leaves and fluorescence of the hemp plant that contain no more than of up to 0.3% of these compounds. The use of hemp plants with higher levels are strictly forbidden in most countries. Several extraction processes of cannabinoids from hemp are used They all use a solvent for extraction but differ in terms of efficiency, usage range and other factors influencing the extraction. Nonetheless, overconsumption of cannabis products can be associated with several side effects, that can cause serious physiological and psychological damage in the human body may cause serious damage.

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Effects of non‐euphoric plant cannabinoids on muscle quality and performance of dystrophic mdx mice

Abstract: We provide new insights into plant cannabinoid interactions with TRP channels in skeletal muscle, highlighting a potential opportunity for novel co-adjuvant therapies to prevent muscle degeneration in DMD patients.

Cited by 62 publications

References 67 publications

PGC‐1α overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin‐deficient skeletal muscle

PGC‐1α overexpression increases transcription factor EB nuclear localization and lysosome abundance in dystrophin‐deficient skeletal muscle

Cannabidiol and Sports Performance: a Narrative Review of Relevant Evidence and Recommendations for Future Research

Cannabis, the Plant of the Unlimited Possibilities

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