Skeletal muscle (SkM) is a highly dynamic tissue that responds to physiological adaptations or pathological conditions, and SkM mitochondria play a major role in bioenergetics, regulation of intracellular calcium homeostasis, pro-oxidant/antioxidant balance, and apoptosis. Flavonoids are polyphenolic compounds with the ability to modulate molecular pathways implicated in the development of mitochondrial myopathy. Therefore, it is pertinent to explore its potential application in conditions such as aging, disuse, denervation, diabetes, obesity, and cancer. To evaluate preclinical and clinical effects of flavonoids on SkM structure and function. We performed a systematic review of published studies, with no date restrictions applied, using PubMed and Scopus. The following search terms were used: “flavonoids” OR “flavanols” OR “flavones” OR “anthocyanidins” OR “flavanones” OR “flavan-3-ols” OR “catechins” OR “epicatechin” OR “(−)-epicatechin” AND “skeletal muscle.” The studies included in this review were preclinical studies, clinical trials, controlled clinical trials, and randomized-controlled trials that investigated the influence of flavonoids on SkM health. Three authors, independently, assessed trials for the review. Any disagreement was resolved by consensus. The use of flavonoids could be a potential tool for the prevention of muscle loss. Their effects on metabolism and on mitochondria function suggest their use as muscle regulators.

Neurological damage from traumatic spinal cord injury (SCI) results in a grade of disability ranging from mild to severe motor and sensory dysfunction. It occurs more frequently in men of productive age. Treatment essentially consists of anti-inflammatories and rehabilitation. Other treatments are only partially effective, and inadequate treatment and secondary conditions often cause premature mortality. The search for pharmacological approaches is a continuous effort. This study aimed to assess the effects of a natural compound on spinal cord injury (SCI) as an alternative damage prevention maneuver. We evaluated the protective effects of the flavanol (+)-epicatechin (EC) in a rat model of moderate trauma-induced SCI on protein markers of damage events. The results showed that EC induced significant protection against SCI. No changes were found in angiopoietin-1, beclin-1, myelin basic protein, glial fibrillary acidic protein, neurofilament heavy polypeptide, and neuronal nuclear antigen after the injury, suggesting that damage progression was impeded. The reduction in damage translates into better movement. The results suggest that (+)-epicatechin may be a suitable alternative for treating SCI.

Prostate cancer is the most common malignancy and the second leading cause of cancer associated deaths among US men. As an androgen‐driven disease, prostate cancer is critically dependent upon androgen receptor (AR) signaling. Accordingly, most prostate cancer patients respond very well to androgen deprivation therapy. The current problem lies with the fact that nearly all patients progress to a lethal form of the disease after androgen deprivation therapy known as castration resistant prostate cancer (CRPC). Once patients reach the stage of CRPC, treatment options are frustratingly limited and average survival times range from two to three years only. Thus, there is a compelling need to develop effective treatments for patients suffering from CRPC. Sonic hedgehog (SHH) signaling is a stromal‐epithelial interacting pathway that is critical for prostate development and cell growth. SHH signaling is induced by androgen deprivation thereby leading to re‐activation of AR target genes to promote prostate cancer cell growth in the absence of androgens. Furthermore, AR interacts with GLI proteins, downstream effectors in the SHH pathway. Therefore, GLI3‐dependent SHH signaling in androgen deprived cells could promote re‐activation of AR target genes and consequently lead to CRPC. It is currently unknown how GLI3‐dependent SHH signaling is induced in CRPC. Several studies have found that MED12, a subunit of Mediator, is commonly mutated in prostate cancer and, interestingly, MED12 has been shown to play a critical role in restricting GLI3‐dependent SHH signaling. We therefore hypothesize that MED12 mutations promote GLI3‐dependent SHH signaling in prostate cancer to drive progression towards CRPC. We generated stable MED12 knockdown cells, which likely recapitulates a MED12 mutant setting, followed by proliferation and qPCR assays in androgen replete and androgen deprived conditions to test our hypothesis. Our results show that MED12 knockdown promotes prostate cancer growth specifically in an androgen deprived setting and that this hyper‐active growth is dependent upon GLI3. Furthermore, we also show that GLI3 target genes are sharply upregulated when MED12 expression is low and androgens are absent. The collective results of our study therefore indicate that prostate cancer patients with MED12 mutations could relapse to CRPC after androgen deprivation therapy by hyperactivating the GLI3 dependent SHH signaling pathway. Importantly, our results thus suggest that therapeutic agents that target the SHH signaling pathway could prove to be beneficial for MED12 mutant prostate cancer patients.