Generic placeholder image

Current Molecular Medicine


ISSN (Print): 1566-5240
ISSN (Online): 1875-5666

Research Article

Combined Administration of Andrographolide and Angiotensin- (1-7) Synergically Increases the Muscle Function and Strength in Aged Mice

Author(s): Johanna Abrigo, Felipe Simon, Daniel Cabrera, Cristian Vilos and Claudio Cabello-Verrugio*

Volume 22, Issue 10, 2022

Published on: 14 January, 2022

Page: [908 - 918] Pages: 11

DOI: 10.2174/1566524021666211207112106

Price: $65


Background: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-κB) signaling and attenuates the severity of some muscle diseases.

Objective: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber´s diameter in a murine model of sarcopenia by aging.

Methods: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber´s diameter were measured.

Results: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber´s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber´s diameter.

Conclusion: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber´s diameter are potentiated.

Keywords: Sarcopenia, renin-angiotensin system, weakness, physical performance, Muscle Function, Angiotensin- (1-7).

Fielding RA, Vellas B, Evans WJ, et al. Sarcopenia: An undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on Sarcopenia. J Am Med Dir Assoc 2011; 12(4): 249-56.
[] [PMID: 21527165]
Glass D, Roubenoff R. Recent advances in the biology and therapy of muscle wasting. Ann N Y Acad Sci 2010; 1211: 25-36.
[] [PMID: 21062293]
Sayer AA, Syddall H, Martin H, Patel H, Baylis D, Cooper C. The developmental origins of Sarcopenia. J Nutr Health Aging 2008; 12(7): 427-32.
[] [PMID: 18615224]
Dodds RM, Syddall HE, Cooper R, et al. Grip strength across the life course: normative data from twelve British studies. PLoS One 2014; 9(12): e113637.
[] [PMID: 25474696]
Sayer AA, Syddall HE, Gilbody HJ, Dennison EM, Cooper C. Does Sarcopenia originate in early life? Findings from the Hertfordshire cohort study. J Gerontol A Biol Sci Med Sci 2004; 59(9): M930-4.
[] [PMID: 15472158]
Cruz-Jentoft AJ, Bahat G, Bauer J, et al. Sarcopenia: Revised European consensus on definition and diagnosis. Age Ageing 2019; 48(4): 601.
[] [PMID: 31081853]
Zambelli V, Sigurtà A, Rizzi L, et al. Angiotensin-(1-7) exerts a protective action in a rat model of ventilator-induced diaphragmatic dysfunction. Intensive Care Med Exp 2019; 7(1): 8.
[] [PMID: 30659381]
Cabello-Verrugio C, Morales MG, Rivera JC, Cabrera D, Simon F. Renin-angiotensin system: an old player with novel functions in skeletal muscle. Med Res Rev 2015; 35(3): 437-63.
[] [PMID: 25764065]
Morales MG, Abrigo J, Acuña MJ, et al. Angiotensin-(1-7) attenuates disuse skeletal muscle atrophy in mice via its receptor, Mas. Dis Model Mech 2016; 9(4): 441-9.
[] [PMID: 26851244]
Yoshihara T, Deminice R, Hyatt H, Ozdemir M, Nguyen BL, Powers SK. Angiotensin 1-7 protects against ventilator-induced diaphragm dysfunction. Clin Transl Sci 2021.
[] [PMID: 33742769]
Nozato S, Yamamoto K, Takeshita H, et al. Angiotensin 1-7 alleviates aging-associated muscle weakness and bone loss, but is not associated with accelerated aging in ACE2-knockout mice. Clin Sci (Lond) 2019; 133(18): 2005-18.
[] [PMID: 31519791]
Shen YC, Chen CF, Chiou WF. Andrographolide prevents oxygen radical production by human neutrophils: Possible mechanism(s) involved in its anti-inflammatory effect. Br J Pharmacol 2002; 135(2): 399-406.
[] [PMID: 11815375]
Rajagopal S, Kumar RA, Deevi DS, Satyanarayana C, Rajagopalan R. Andrographolide, a potential cancer therapeutic agent isolated from Andrographis paniculata. J Exp Ther Oncol 2003; 3(3): 147-58.
[] [PMID: 14641821]
Calabrese C, Berman SH, Babish JG, et al. A phase I trial of andrographolide in HIV positive patients and normal volunteers. Phytother Res 2000; 14(5): 333-8.
[<333:AID-PTR584>3.0.CO;2-D] [PMID: 10925397]
Lee TY, Lee KC, Chang HH. Modulation of the cannabinoid receptors by andrographolide attenuates hepatic apoptosis following bile duct ligation in rats with fibrosis. Apoptosis 2010; 15(8): 904-14.
[] [PMID: 20446039]
Lee MJ, Rao YK, Chen K, Lee YC, Chung YS, Tzeng YM. Andrographolide and 14-deoxy-11,12-didehydroandrographolide from Andrographis paniculata attenuate high glucose-induced fibrosis and apoptosis in murine renal mesangeal cell lines. J Ethnopharmacol 2010; 132(2): 497-505.
[] [PMID: 20813180]
Ye JF, Zhu H, Zhou ZF, et al. Protective mechanism of andrographolide against carbon tetrachloride-induced acute liver injury in mice. Biol Pharm Bull 2011; 34(11): 1666-70.
[] [PMID: 22040877]
Xia YF, Ye BQ, Li YD, et al. Andrographolide attenuates inflammation by inhibition of NF-kappa B activation through covalent modification of reduced cysteine 62 of p50. J Immunol 2004; 173(6): 4207-17.
[] [PMID: 15356172]
Acharyya S, Villalta SA, Bakkar N, et al. Interplay of IKK/NF-kappaB signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J Clin Invest 2007; 117(4): 889-901.
[] [PMID: 17380205]
Skeletal muscle diseases, inflammation, and NF-kappaB signaling: insights and opportunities for therapeutic intervention. Int Rev Immunol 2008; 27(5): 375-87.
[] [PMID: 18853344]
Peterson JM, Kline W, Canan BD, et al. Peptide-based inhibition of NF-κB rescues diaphragm muscle contractile dysfunction in a murine model of Duchenne muscular dystrophy. Mol Med 2011; 17(5-6): 508-15.
[] [PMID: 21267511]
Ziaaldini MM, Marzetti E, Picca A, Murlasits Z. Biochemical pathways of sarcopenia and their modulation by physical exercise: A narrative review. Front Med (Lausanne) 2017; 4: 167.
[] [PMID: 29046874]
Oh J, Sinha I, Tan KY, et al. Age-associated NF-κB signaling in myofibers alters the satellite cell niche and re-strains muscle stem cell function. Aging (Albany NY) 2016; 8(11): 2871-96.
[] [PMID: 27852976]
Cabrera D, Gutiérrez J, Cabello-Verrugio C, et al. Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis. Skelet Muscle 2014; 4: 6.
[] [PMID: 24655808]
Abrigo J, Marín T, Aguirre F, et al. N-Acetyl Cysteine attenuates the Sarcopenia and muscle apoptosis induced by chronic liver disease. Curr Mol Med 2019; 20(1): 60-71.
[] [PMID: 31530262]
Aartsma-Rus A, van Putten M. Assessing functional performance in the mdx mouse model. J Vis Exp 2014.
Bonetto A, Andersson DC, Waning DL. Assessment of muscle mass and strength in mice. Bonekey Rep 2015; 4: 732.
[] [PMID: 26331011]
Morales MG, Cabrera D, Céspedes C, et al. Inhibition of the angiotensin-converting enzyme decreases skeletal muscle fibrosis in dystrophic mice by a diminution in the expression and activity of connective tissue growth factor (CTGF/CCN-2). Cell Tissue Res 2013; 353(1): 173-87.
[] [PMID: 23673415]
Cabello-Verrugio C, Acuña MJ, Morales MGG, et al. Fibrotic response induced by angiotensin-II requires NAD(P)H oxidase-induced reactive oxygen species (ROS) in skeletal muscle cells. Biochem Biophys Res Commun 2011; 410(3): 665-70.
[] [PMID: 21693104]
Morales MG, Abrigo J, Meneses C, et al. The Ang-(1-7)/Mas-1 axis attenuates the expression and signalling of TGF-β1 induced by AngII in mouse skeletal muscle. Clin Sci (Lond) 2014; 127(4): 251-64.
[] [PMID: 24588264]
Meneses C, Morales MG, Abrigo J, Simon F, Brandan E, Cabello-Verrugio C. The angiotensin-(1-7)/Mas axis reduces myonuclear apoptosis during recovery from angiotensin II-induced skeletal muscle atrophy in mice. Pflugers Arch 2015; 467(9): 1975-84.
[] [PMID: 25292283]
Takeshita H, Yamamoto K, Nozato S, et al. Angiotensin-converting enzyme 2 deficiency accelerates and angiotensin 1-7 restores age-related muscle weakness in mice. J Cachexia Sarcopenia Muscle 2018; 9(5): 975-86.
[] [PMID: 30207087]
Takeshita H, Yamamoto K, Mogi M, Nozato S, Horiuchi M, Rakugi H. Different effects of the deletion of angiotensin converting enzyme 2 and chronic activation of the renin-angiotensin system on muscle weakness in middle-aged mice. Hypertens Res 2020; 43(4): 296-304.
[] [PMID: 31853045]
Salminen A, Huuskonen J, Ojala J, Kauppinen A, Kaarniranta K, Suuronen T. Activation of innate immunity system during aging: NF-kB signaling is the molecular culprit of inflamm-aging. Ageing Res Rev 2008; 7(2): 83-105.
[] [PMID: 17964225]
Cai D, Frantz JD, Tawa NE Jr, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 2004; 119(2): 285-98.
[] [PMID: 15479644]
Cao PR, Kim HJ, Lecker SH. Ubiquitin-protein ligases in muscle wasting. Int J Biochem Cell Biol 2005; 37(10): 2088-97.
[] [PMID: 16125112]
Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 2005; 37(10): 1974-84.
[] [PMID: 16087388]
Villalobos LA, San Hipólito-Luengo Á, Ramos-González M, et al. The Angiotensin-(1-7)/Mas axis counteracts angiotensin II-dependent and -independent pro-inflammatory signaling in human vascular smooth muscle cells. Front Pharmacol 2016; 7: 482.
[] [PMID: 28018220]
Thoma A, Lightfoot AP. NF-kB and inflammatory cytokine signalling: Role in skeletal muscle atrophy. Adv Exp Med Biol 2018; 1088: 267-79.
[] [PMID: 30390256]
Lightfoot AP, Cooper RG. The role of myokines in muscle health and disease. Curr Opin Rheumatol 2016; 28(6): 661-6.
[] [PMID: 27548653]
Monici MC, Aguennouz M, Mazzeo A, Messina C, Vita G. Activation of nuclear factor-kappaB in inflammatory myopathies and Duchenne muscular dystrophy. Neurology 2003; 60(6): 993-7.
[] [PMID: 12654966]
Schneider C, Gold R, Dalakas MC, et al. MHC class I-mediated cytotoxicity does not induce apoptosis in muscle fibers nor in inflammatory T cells: Studies in patients with polymyositis, dermatomyositis, and inclusion body myositis. J Neuropathol Exp Neurol 1996; 55(12): 1205-9.
[] [PMID: 8957443]
Ruegg UT. Pharmacological prospects in the treatment of Duchenne muscular dystrophy. Curr Opin Neurol 2013; 26(5): 577-84.
[] [PMID: 23995279]
Alvarez K, Fadic R, Brandan E. Augmented synthesis and differential localization of heparan sulfate proteoglycans in Duchenne muscular dystrophy. J Cell Biochem 2002; 85(4): 703-13.
[] [PMID: 11968010]
Acuña MJ, Pessina P, Olguin H, et al. Restoration of muscle strength in dystrophic muscle by angiotensin-1-7 through inhibition of TGF-β signalling. Hum Mol Genet 2014; 23(5): 1237-49.
[] [PMID: 24163134]
Cuthbertson D, Smith K, Babraj J, et al. Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle. FASEB J 2005; 19(3): 422-4.
[] [PMID: 15596483]
Vasilaki A, McArdle F, Iwanejko LM, McArdle A. Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age. Mech Ageing Dev 2006; 127(11): 830-9.
[] [PMID: 16996110]
Kumar A, Davuluri G, Welch N, et al. Oxidative stress mediates ethanol-induced skeletal muscle mitochondrial dysfunction and dysregulated protein synthesis and autophagy. Free Radic Biol Med 2019; 145: 284-99.
[] [PMID: 31574345]
Bak DH, Na J, Im SI, et al. Antioxidant effect of human placenta hydrolysate against oxidative stress on muscle atrophy. J Cell Physiol 2019; 234(2): 1643-58.
[] [PMID: 30132871]
Aravena J, Abrigo J, Gonzalez F, et al. Angiotensin (1-7) decreases myostatin-induced NF-κB +phy. Int J Mol Sci 2020; 21(3): E1167.
[] [PMID: 32050585]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy