Kushwaha, Asha D., and Deepika Saraswat. A nanocurcumin and
pyrroloquinoline quinone formulation prevents hypobaric
hypoxia-induced skeletal muscle
atrophy by modulating NF-κB signaling pathway. High Alt Med Biol. 23:249-263, 2022. Background: Hypobaric
hypoxia (HH)-induced deleterious skeletal muscle damage depends on exposure time and availability of
oxygen at cellular level, which eventually can limit human work performance at high altitude (HA). Despite the advancements made in pharmacological (performance enhancer,
antioxidants) and nonpharmacological
therapeutics (acclimatization strategies), only partial success has been achieved in improving physical performance at HA. A distinctive combination of nanocurcumin (NC) and
pyrroloquinoline quinone (PQQ) has been formulated (named NCF [nanocurcumin formulation], Indian patent No. 302877) in our laboratory, and has proven very promising in improving cardiomyocyte adaptation to chronic HH. We hypothesized that NCF might improve skeletal muscle adaptation and could be a performance enhancer at HA. Material and Methods: Adult Sprague-Dawley rats (220 ± 10 g) were divided into five groups (n = 6/group): normoxia vehicle control,
hypoxia vehicle control,
hypoxia NCF,
hypoxia NC, and
hypoxia PQQ. All the animals (except those in normoxia) were exposed to simulated HH in a chamber at temperature 22°C ± 2°C, humidity 50% ± 5%, altitude 25,000 ft for 1, 3, or 7 days. After completion of the stipulated exposure time, gastrocnemius and soleus muscles were excised from animals for further analysis. Results: Greater lengths of hypoxic exposure caused progressively increased muscle ring finger-1 (MuRF-1; p < 0.01) expression and
calpain activation (0.56 ± 0.05 vs. 0.13 ± 0.02 and 0.44 ± 0.03 vs. 0.12 ± 0.021) by day 7, respectively in the gastrocnemius and soleus muscles.
Myosin heavy chain type I (slow oxidative) fibers significantly (p > 0.01) decreased in gastrocnemius (>50%) and soleus (>46%) muscles by the seventh day of exposure. NCF supplementation showed (p ≤ 0.05) tremendous improvement in skeletal muscle acclimatization through effective alleviation of oxidative damage, and changes in
calpain activity and atrophic markers at HA compared with
hypoxia control or treatment alone with NC/PQQ. Conclusion: Thus, NCF-mediated anti-oxidative, anti-inflammatory effects lead to decreased proteolysis resulting in mitigated skeletal muscle
atrophy under HH.