Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice

Main Article Content

David Feder
Túlio de Almeida Hermes
Lucas Prezotto Giordani
Bruno Machado Bertassoli
Giuliana Petri
Fabio Perazzo
Fernando Luiz Affonso Fonseca
Alzira Alves de Siqueira Carvalho


Introduction: Uncaria tomentosa (Willd. ex Roem. & Schult.) DC. (Rubiaceae) or UT is a medicinal plant with antiviral, antimutagenic, anti-inflammatory and antioxidant properties. Duchenne muscular dystrophy (DMD) is a severe muscle wasting disease caused by mutations in the dystrophin gene; this deficiency leads to sarcolemma instability, inflammation, muscle degeneration and fibrosis. Objective: Considering the importance of inflammation to dystrophy progression and the anti-inflammatory activity of UT, in the present study we evaluated whether oral administration of UT extract would ameliorate dystrophy in the mdx mice, a DMD model. Methods: Eight-week-old male mdx mice were submitted to 200 mg/kg body weight daily UT oral administration for 6 weeks. General histopathology was analysed, and muscle tumor necrosis factor α, transforming growth factor-β, myostatin and osteopontin transcript levels were assessed. The ability of mice to sustain limb tension to oppose their gravitational force was measured. Data were analysed with the unpaired Student’s t-test. Results: Morphologically, both untreated and UT-treated animals exhibited internalised nuclei, increased endomysial connective tissue and variations in muscle fibre diameters. Body weight and muscle strength were significantly reduced in the UT-treated animals. Blood creatine kinase was higher in UT-treated compared to untreated animals. In tibialis anterior, myostatin, transcript was more highly expressed in the UT-treated while in the diaphragm muscle, transforming growth factor-β transcripts were less expressed in the UT-treated. Conclusion: While previous studies identified anti-inflammatory, antiproliferative and anticarcinogenic UT effects, the extract indicates worsening of dystrophic muscles phenotype after short-term treatment in mdx mice.


Download data is not yet available.

Article Details

How to Cite
Feder, D., Hermes, T. de A., Giordani, L. P., Bertassoli, B. M., Petri, G., Perazzo, F., Fonseca, F. L. A., & Carvalho, A. A. de S. (2024). Short-term treatment with Uncaria tomentosa aggravates the injury phenotype in mdx mice. ABCS Health Sciences, 49, e024204.
Original Articles


Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, et al. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012;71(3):304-13.

Bogdanovich S, Perkins KJ, Krag TO, Khurana TS. Therapeutics for Duchenne muscular dystrophy: current approaches and future directions. J Mol Med (Berl). 2004;82(2):102-15.

Liew WK, Kang PB. Recent developments in the treatment of Duchenne muscular dystrophy and spinal muscular atrophy. Ther Adv Neurol Disord. 2013;6(3):147-60.

Zhou L, Lu H. Targeting fibrosis in Duchenne muscular dystrophy. J Neuropathol Exp Neurol. 2010;69(8):771-6.

Farini A, Sitzia C, Erratico S, Meregalli M, Torrente Y. Influence of immune responses in gene/stem cell therapies for muscular dystrophies. Biomed Res Int. 2014;2014:818107.

Bulfield G, Siller WG, Wight PA, Moore KJ. X chromosome-linked muscular dystrophy (mdx) in the mouse. Proc Natl Acad Sci U S A. 1984;81(4):1189-92.

Stedman HH, Sweeney HL, Shrager JB, Maguire HC, Panettieri RA, Petrof B, et al. The mdx mouse diaphragm reproduces the degenerative changes of Duchenne muscular dystrophy. Nature. 1991;352(6335):536-9.

Tidball JG, Wehling-Henricks M. Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis. Curr Opin Rheumatol. 2005;17(6):707-13.

Kramerova I, Kumagai-Cresse C, Ermolova N, Mokhonova E, Marinov M, Capote J, et al. Spp1 (osteopontin) promotes TGFbeta processing in fibroblasts of dystrophin-deficient muscles through matrix metalloproteinases. Hum Mol Genet. 2019;28(20):3431-42.

Mariot V, Le Guiner C, Barthelemy I, Montus M, Blot S, Torelli S, et al. Myostatin Is a Quantifiable Biomarker for Monitoring Pharmaco-gene Therapy in Duchenne Muscular Dystrophy. Mol Ther Methods Clin Dev. 2020;18:415-21.

Sandoval M, Okuhama NN, Zhang XJ, Condezo LA, Lao J, Angeles FM, et al. Anti-inflammatory and antioxidant activities of cat's claw (Uncaria tomentosa and Uncaria guianensis) are independent of their alkaloid content. Phytomedicine. 2002;9(4):325-37.

Rojas-Duran R, Gonzalez-Aspajo G, Ruiz-Martel C, Bourdy G, Doroteo-Ortega VH, Alban-Castillo J, et al. Anti-inflammatory activity of Mitraphylline isolated from Uncaria tomentosa bark. J Ethnopharmacol. 2012;143(3):801-4.

Sandoval-Chacon M, Thompson JH, Zhang XJ, Liu X, Mannick EE, Sadowska-Krowicka H, et al. Antiinflammatory actions of cat's claw: the role of NF-kappaB. Aliment Pharmacol Ther. 1998;12(12):1279-89.

Miranda RR, Freitas JJS. The anti-proliferative effects of the ethanolic extract of Uncaria tomentosa in Ehrlich ascitic carcinoma. Rev Paraense Med. 2008;22(2).

Carlson G. The use of four limb hanging tests to monitor muscle strength and condition over time. Glendae, USA: Midwestern University Glendale, 2011.

Maglara AA, Vasilaki A, Jackson MJ, McArdle A. Damage to developing mouse skeletal muscle myotubes in culture: protective effect of heat shock proteins. J Physiol. 2003;548(Pt 3):837-46.

Aguinaga JY, Claudiano GS, Marcusso PF, Ikefuti C, Ortega GG, Eto SF, et al. Acute Toxicity and Determination of the Active Constituents of Aqueous Extract of Uncaria tomentosa Bark in Hyphessobrycon eques. J Toxicol. 2014;2014:412437.

Altamirano F, Perez CF, Liu M, Widrick J, Barton ER, Allen PD, et al. Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. PloS One. 2014;9(9):e106590.

Vetrone SA, Montecino-Rodriguez E, Kudryashova E, Kramerova I, Hoffman EP, Liu SD, et al. Osteopontin promotes fibrosis in dystrophic mouse muscle by modulating immune cell subsets and intramuscular TGF-beta. J Clin Invest. 2009;119(6):1583-94.

Micheletto MLJ, Hermes TA, Bertassoli BM, Petri G, Perez MM, Fonseca FLA, et al. Ixazomib, an oral proteasome inhibitor, exhibits potential effect in dystrophin-deficient mdx mice. International journal of experimental pathology. 2021;102(1):11-21.

Kornegay JN, Childers MK, Bogan DJ, Bogan JR, Nghiem P, Wang J, et al. The paradox of muscle hypertrophy in muscular dystrophy. Phys Med Rehabil Clin N Am. 2012;23(1):149-72.

Hartel JV, Granchelli JA, Hudecki MS, Pollina CM, Gosselin LE. Impact of prednisone on TGF-beta1 and collagen in diaphragm muscle from mdx mice. Muscle Nerve. 2001;24(3):428-32.;2-e

Andreetta F, Bernasconi P, Baggi F, Ferro P, Oliva L, Arnoldi E, et al. Immunomodulation of TGF-beta 1 in mdx mouse inhibits connective tissue proliferation in diaphragm but increases inflammatory response: implications for antifibrotic therapy. J Neuroimmunol. 2006;175(1-2):77-86.

Zhang P, He J, Wang F, Gong J, Wang L, Wu Q, et al. Hemojuvelin is a novel suppressor for Duchenne muscular dystrophy and age-related muscle wasting. J Cachexia Sarcopenia Muscle. 2019;10(3):557-73.

Dubach-Powell J. Quantitative determination of muscle fiber diameter (minimal Feret’s diameter) and percentage of centralized nuclei. Switzerland: Santhera Pharmaceuticals, 2008.

Quattrocelli M, Barefield DY, Warner JL, Vo AH, Hadhazy M, Earley JU, et al. Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy. J Clin Invest. 2017;127(6):2418-32.

Lee SJ. Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol. 2004;20:61-86.

Wagner KR. Muscle regeneration through myostatin inhibition. Curr Opin Rheumatol. 2005;17(6):720-4.

Pasteuning-Vuhman S, Meulen JWB, van Putten M, Overzier M, Ten Dijke P, Kielbasa SM, et al. New function of the myostatin/activin type I receptor (ALK4) as a mediator of muscle atrophy and muscle regeneration. FASEB J. 2017;31(1):238-55.

Muhammad I, Dunbar DC, Khan RA, Ganzera M, Khan IA. Investigation of Una De Gato I. 7-Deoxyloganic acid and 15N NMR spectroscopic studies on pentacyclic oxindole alkaloids from Uncaria tomentosa. Phytochemistry. 2001;57(5):781-5.

Sheng Y, Akesson C, Holmgren K, Bryngelsson C, Giamapa V, Pero RW. An active ingredient of Cat's Claw water extracts identification and efficacy of quinic acid. J Ethnopharmacol. 2005;96(3):577-84.

Kosmider A, Czepielewska E, Kuras M, Gulewicz K, Pietrzak W, Nowak R, et al. Uncaria tomentosa Leaves Decoction Modulates Differently ROS Production in Cancer and Normal Cells, and Effects Cisplatin Cytotoxicity. Molecules. 2017;22(4).

Reid MB, Li YP. Tumor necrosis factor-alpha and muscle wasting: a cellular perspective. Respir Res. 2001;2(5):269-72.

Ermolova NV, Martinez L, Vetrone SA, Jordan MC, Roos KP, Sweeney HL, et al. Long-term administration of the TNF blocking drug Remicade (cV1q) to mdx mice reduces skeletal and cardiac muscle fibrosis, but negatively impacts cardiac function. Neuromuscul Disord. 2014;24(7):583-95.

Whitehead NP, Yeung EW, Allen DG. Muscle damage in mdx (dystrophic) mice: role of calcium and reactive oxygen species. Clin Exp Pharmacol Physiol. 2006;33(7):657-62.

Pilarski R, Zielinski H, Ciesiolka D, Gulewicz K. Antioxidant activity of ethanolic and aqueous extracts of Uncaria tomentosa (Willd.) DC. J Ethnopharmacol. 2006;104(1-2):18-23.

Bors M, Bukowska B, Pilarski R, Gulewicz K, Oszmianski J, Michalowicz J, et al. Protective activity of the Uncaria tomentosa extracts on human erythrocytes in oxidative stress induced by 2,4-dichlorophenol (2,4-DCP) and catechol. Food Chem Toxicol. 2011;49(9):2202-11.

Bors M, Sicinska P, Michalowicz J, Wieteska P, Gulewicz K, Bukowska B. Evaluation of the effect of Uncaria tomentosa extracts on the size and shape of human erythrocytes (in vitro). Environ Toxicol Pharmacol. 2012;33(2):127-34.

Dreifuss AA, Bastos-Pereira AL, Avila TV, Soley Bda S, Rivero AJ, Aguilar JL, et al. Antitumoral and antioxidant effects of a hydroalcoholic extract of cat's claw (Uncaria tomentosa) (Willd. Ex Roem. & Schult) in an in vivo carcinosarcoma model. J Ethnopharmacol. 2010;130(1):127-33.

Navarro-Hoyos M, Alvarado-Corella D, Moreira-Gonzalez I, Arnaez-Serrano E, Monagas-Juan M. Polyphenolic Composition and Antioxidant Activity of Aqueous and Ethanolic Extracts from Uncaria tomentosa Bark and Leaves. Antioxidants. 2018;7(5).