The loss of skeletal muscle mass and strength, defined as muscle atrophy, represents an unresolved enormous medical problem associated with diffuse pathological conditions and aging (sarcopenia) [1,2]. The decrease of bone mass (osteoporosis) is also strictly connected to muscle functionality during aging [3]. The unbalance between myofibrillary protein breakdown (especially myosin heavy chain, MyHC) and synthesis, and the reduction of regenerative potential are the main causes of muscle wasting [1,2]. In the last decades, an increasing interest has been devoted to identify natural active metabolites with proved pharmacological activities, useful in maintenance of healthy longevity and in the prevention/treatment of various diseases [4]. We identified an herbal formulation composed by hydroalcoholic extracts from W. somnifera (W), S. marianum (S) and T. foenum-graecum (T) with remarkable ability to prevent the reduction of myotube size in well characterized in vitro experimental models mimicking muscle atrophy induced by pro-inflammatory cytokines (TNFα/IFNγ) excess of glucocorticoids (dexamethasone, Dex) or nutrient deprivation (starvation, PBS). WST formulation resulted able to sustain muscle trophism per se and extremely efficacious in protecting myotubes against MyHC degradation by activating the anabolic pathway, Akt irrespectively from the atrophic stimulus applied. Moreover, WST was able to i) sustain myoblast differentiation by activating p38 MAPK/myogenin axis in presence of Dex and TNFα/IFNγ; ii) protect muscle cells against TNFα/IFNγ-induced apoptosis; and iii) reduce Dex-dependent activation of the ubiquitin-proteasome system. Phytochemical profiles of the single plant extracts confirmed the presence of multiple metabolites with potential anti-atrophic effects. Furthermore, E. arvense (horsetail), a typical plant of northern Italy recommended as a treatment for osteoporosis [5], emerged from one-hundred medical plant extracts as able to contrast TNFα/IFNγ- or Dex-induced muscle atrophy in vitro. Based on our results, low-cost, non-toxic phytotherapy dietary products containing WST and/or E. arvense could be developed to maintain muscle mass and functionality in aged people and in diffuse atrophying conditions, thus improving the quality of life and reducing health-care costs. [1] Dutt V et al., Pharmacol Res. 2015, 46:86-100; [2] Larsson L et al., Physiol Rev. 2019, 99: 427-511; [3] Curtis E et al., J Cell Physiol. 2015, 230:2618-2625; [4] Rondanelli M et al., Evid Based Complement Alternat Med. 2016, 2016: 5970367; [5] Kotwal SD and Badole SR, Indian J Pharmacol. 2016, 48: 312-315.
Natural products to counteract muscle atrophy
Salvadori L.;Chiappalupi S.;Sorci G.;Riuzzi F
2020
Abstract
The loss of skeletal muscle mass and strength, defined as muscle atrophy, represents an unresolved enormous medical problem associated with diffuse pathological conditions and aging (sarcopenia) [1,2]. The decrease of bone mass (osteoporosis) is also strictly connected to muscle functionality during aging [3]. The unbalance between myofibrillary protein breakdown (especially myosin heavy chain, MyHC) and synthesis, and the reduction of regenerative potential are the main causes of muscle wasting [1,2]. In the last decades, an increasing interest has been devoted to identify natural active metabolites with proved pharmacological activities, useful in maintenance of healthy longevity and in the prevention/treatment of various diseases [4]. We identified an herbal formulation composed by hydroalcoholic extracts from W. somnifera (W), S. marianum (S) and T. foenum-graecum (T) with remarkable ability to prevent the reduction of myotube size in well characterized in vitro experimental models mimicking muscle atrophy induced by pro-inflammatory cytokines (TNFα/IFNγ) excess of glucocorticoids (dexamethasone, Dex) or nutrient deprivation (starvation, PBS). WST formulation resulted able to sustain muscle trophism per se and extremely efficacious in protecting myotubes against MyHC degradation by activating the anabolic pathway, Akt irrespectively from the atrophic stimulus applied. Moreover, WST was able to i) sustain myoblast differentiation by activating p38 MAPK/myogenin axis in presence of Dex and TNFα/IFNγ; ii) protect muscle cells against TNFα/IFNγ-induced apoptosis; and iii) reduce Dex-dependent activation of the ubiquitin-proteasome system. Phytochemical profiles of the single plant extracts confirmed the presence of multiple metabolites with potential anti-atrophic effects. Furthermore, E. arvense (horsetail), a typical plant of northern Italy recommended as a treatment for osteoporosis [5], emerged from one-hundred medical plant extracts as able to contrast TNFα/IFNγ- or Dex-induced muscle atrophy in vitro. Based on our results, low-cost, non-toxic phytotherapy dietary products containing WST and/or E. arvense could be developed to maintain muscle mass and functionality in aged people and in diffuse atrophying conditions, thus improving the quality of life and reducing health-care costs. [1] Dutt V et al., Pharmacol Res. 2015, 46:86-100; [2] Larsson L et al., Physiol Rev. 2019, 99: 427-511; [3] Curtis E et al., J Cell Physiol. 2015, 230:2618-2625; [4] Rondanelli M et al., Evid Based Complement Alternat Med. 2016, 2016: 5970367; [5] Kotwal SD and Badole SR, Indian J Pharmacol. 2016, 48: 312-315.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
