Nexrutine® preserves muscle mass similar to exercise in prostate cancer mouse model.

Darpan I Patel,Amber Gallegos,Derek Wallace,Nicolas Musi,Addanki Pratap Kumar,Kira Abuchowski,Paul Rivas

doi:10.14814/phy2.14217

Abstract

Muscle loss is a debilitating side effect to prostate cancer (PCa) experienced by nearly 60% of men. The purpose of this study was to test the hypothesis that Nexrutine®, a bark extract from the Phellodendrum amurense, can protect against prostate cancer induced muscle loss in a similar manner as exercise, using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Forty‐five, 8‐ to 10‐week old TRAMP mice were randomized to either control, Nexrutine® (600 mg/kg pelleted in chow) or exercise (voluntary wheel running). Mice were serially sacrificed at weeks 4, 8, 12, and 20, at which time either the left or right gastrocnemius muscle was harvested, weighted, and frozen. Proteolysis inducing factor (PIF), ubiquitin, and NF‐κB concentrations were quantified using ELISA kits. Nexrutine® and exercise were equally able to protect TRAMP mice against PCa‐induced muscle loss (P = 0.04). Both interventions decreased intramuscular PIF concentrations at 20 weeks compared to control (P < 0.05). A treatment effect was also observed when all time points were combined with exercise significantly lowering PIF concentrations (P < 0.01). Exercise significantly lowered intramuscular ubiquitin concentrations in weeks 4, 8, and 20 compared to control mice (P < 0.001). A treatment effect was also observed with exercise significantly lowering ubiquitin compared to control mice (P < 0.001). No significant changes were observed for NF‐κB. The results of this investigation demonstrate that PCa‐induced muscle loss can be attenuated with the herbal supplement Nexrutine®. This investigation provides preliminary evidence to support continued research into Nexrutine® as a potential exercise analog in protecting against muscle loss.

Highlights

In men with prostate cancer (PCa), a large percentage of men will suffer from muscle loss, a debilitating adverse effect, induced both by chronic illnesses or treatment paradigms (Cheung et al, 2018)
The primary findings of this study suggest that the natural product Nexrutineâ protects skeletal muscle against tumor-associated decline in muscle mass
This is clinically important as these results show that intervening with Nexrutineâ can have similar effects as exercise in protecting skeletal muscle against tumor-derived factors that lead to atrophy and muscle loss

Summary

Introduction

In men with prostate cancer (PCa), a large percentage of men will suffer from muscle loss, a debilitating adverse effect, induced both by chronic illnesses or treatment paradigms (Cheung et al, 2018). Either tumor-derived or host-derived, initiate the inflammatory response stimulating proteolysis and muscle loss (Tracey et al, 1988; Todorov et al, 1996; Li et al, 1998; Li and Reid, 2000; Schaap et al, 2006; Senf et al, 2013). Proteolysis-inducing factor (PIF) is a tumorsecreted protein that has been hypothesized to be a catalyst for stimulating protein degradation in muscle (Lorite et al, 1998; Cabal-Manzano et al, 2001; Tisdale, 2002). Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

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