Beneficial effects of hydro-alcoholic extract of Zuccagnia punctata against atherosclerosis in normal weight obesity accompanied by hypercholesterolemia rabbit model


Abstract views: 245 / PDF downloads: 163

Authors

  • Agostina Valoy Instituto Superior de Investigaciones Biológicas (INSIBIO), UNT-CONICET, 4000, Tucumán, Argentina https://orcid.org/0000-0001-6204-2677
  • Gabriela Alarcón Instituto Superior de Investigaciones Biológicas (INSIBIO), UNT-CONICET, 4000, Tucumán, Argentina https://orcid.org/0000-0001-8947-498X
  • Julieta Roco Instituto Superior de Investigaciones Biológicas (INSIBIO), UNT-CONICET, 4000, Tucumán, Argentina https://orcid.org/0000-0002-4094-4589
  • Catiana Iris Zampini Universidad Nacional de Tucumán (UNT), Facultad de Ciencias Naturales e Instituto Miguel Lillo, 4000, Tucumán, Argentina https://orcid.org/0000-0001-7941-1678
  • María Ines Isla Instituto de Bioprospección y Fisiología Vegetal (INBIOFIV, UNT-CONICET), 4000, Tucumán,Argentina https://orcid.org/0000-0002-4261-4284
  • Susana Josefina Jerez Instituto Superior de Investigaciones Biológicas (INSIBIO), UNT-CONICET, 4000, Tucumán, Argentina https://orcid.org/0000-0003-2484-6257

DOI:

https://doi.org/10.29228/ijpbp.28

Keywords:

Zuccagnia punctata, Insulin resistance, Hypercholesterolemia, Flavonoids

Abstract

Insulin resistance (IR) increases the synthesis of cholesterol so hypercholesterolemia is one regular feature of obesity. Rich in flavonoids Zuccagnia punctata extract (Zp-E) is a traditional herbal medicine found to be beneficial against hypercholesterolemia-induced oxidative damage. This study aimed to evaluate the effects of Zp-E in a diet-induced rabbit model of IR accompanied by hypercholesterolemia. The major components of the Zp-E were analyzed by using a reversed-phase HPLC method. Male hybrid rabbits (cross between New Zealand and Californian certificated breeds) were separated into six groups: 1: fed on regular chow (SD), 2: fed on SD supplemented with 18% fat and 0.3% cholesterol (HC-HFD), 3, 4, 5: fed on HC-HFD and orally administered 2.5 mg, 5 mg or 10 mg GAE/day of Zp-E, respectively, 6: fed on HC-HFD and orally administered 2.5 mg ezetimibe/kg/day. All diets were administered for 6 weeks. The major compounds of Zp-E identified were chalcones: 2′,4′-dihydroxy-3′-methoxychalcone and 2′,4′-dihydroxychalcone. Zp-E only at 2.5 mg GAE/day reduced total cholesterol and did not modify fasting glucose, visceral abdominal fat, or IR at any of the doses tested. Zp-E normalized TBARS levels, sudanophilic area, and intima/media ratio at all the doses tested while significantly improving acetylcholine relaxation only at 5 mg GAE/day. Despite Zp-E's failure to prevent IR under hypercholesterolemic conditions, the extract showed protective effects on blood vessels by preventing the formation of atherosclerotic plaque through its strong antioxidant properties.

References

Alarcon, G., Roco, J., Medina, M., Medina, A., Peral, M., & Jerez, S. (2018). High fat diet-induced metabolically obese and normal weight rabbit model shows early vascular dysfunction: Mechanisms involved. International Journal of Obesity, 42(9), 1535-1543.

Bonithon-Kopp, C., Touboul, P. J., Berr, C., Leroux, C., Mainard, F., Courbon, D., & Ducimetière, P. (1996). Relation of intima-media thickness to atherosclerotic plaques in carotid arteries: the Vascular Aging (EVA) Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 16(2), 310-316.

Boren, J., Chapman, M. J., Krauss, R. M., Packard, C. J., Bentzon, J. F., Binder, C. J., Daemen, M. J., Demer, L. L., Hegele, R. A., et al. (2020). Low-density lipoproteins cause atherosclerotic cardiovascular disease: pathophysiological, genetic, and therapeutic insights: a consensus statement from the European Atherosclerosis Society Consensus Panel. European Heart Journal, 41(24), 2313-2330.

Chrysant, S. (2011). A new paradigm in the treatment of the cardiovascular disease continuum: focus on prevention. Hippokratia, 15(1), 7-11.

de Lorenzo, A., Del Gobbo, V., Premrov, M. G., Bigioni, M., Galvano, F., & Di Renzo, L. (2007). Normal-weight obese syndrome: early inflammation? The American Journal of Clinical Nutrition, 85(1), 40-45.

de Mutsert, R., Gast, K., Widya, R., de Koning, E., Jazet, I., Lamb, H., le Cessie, S., de Roos, A., Smit, J., et al. (2018). Associations of abdominal subcutaneous and visceral fat with insulin resistance and secretion differ between men and women: the Netherlands epidemiology of obesity study. Metabolic Syndrome and Related Disorders, 16(1), 54-63.

di Renzo, L., Galvano, F., Orlandi, C., Bianchi, A., Di Giacomo, C., La Fauci, L., Acquaviva, R., & De Lorenzo, A. (2010). Oxidative stress in normal‐weight obese syndrome. Obesity, 18(11), 2125-2130.

Georgiev, I. P., Georgieva, Т. M., Ivanov, V., Dimitrova, S., Kanelov, I., Vlaykova, T., Tanev, S., Zaprianova, D., Dichlianova, Е., et al. (2011). Effects of castration-induced visceral obesity and antioxidant treatment on lipid profile and insulin sensitivity in New Zealand white rabbits. Research in Veterinary Science, 90(2), 196-204.

Guerrero-Romero, F., Simental-Mendía, L. E., González-Ortiz, M., Martínez-Abundis, E., Ramos-Zavala, M. G., Hernández-González, S. O., Jacques-Camarena, O., & Rodríguez-Morán, M. (2010). The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp. The Journal of Clinical Endocrinology & Metabolism, 95(7), 3347-3351.

Gylling, H., Hallikainen, M., Pihlajamäki, J., Simonen, P., Kuusisto, J., Laakso, M., & Miettinen, T. A. (2010). Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study 1. Journal of Lipid Research, 51(8), 2422-2427.

Isla, M. I., Moreno, M. A., Nuño, G., Rodriguez, F., Carabajal, A., Alberto, M. R., & Zampini, I. C. (2016). Zuccagnia punctata: a review of its traditional uses, phytochemistry, pharmacology and toxicology. Natural Product Communications, 11(11), 1749-1755.

Isla, M. I., Salas, A., Danert, F. C., Zampini, I. C., & Ordonez, R. M. (2014). Analytical methodology optimization to estimate the content of non-flavonoid phenolic compounds in Argentine propolis extracts. Pharmaceutical Biology, 52(7), 835-840.

Jerez, S., Scacchi, F., Sierra, L., Karbiner, S., & de Bruno, M. P. (2012). Vascular hyporeactivity to angiotensin II and noradrenaline in a rabbit model of obesity. Journal of Cardiovascular Pharmacology, 59(1), 49-57.

Jerez, S., Sierra, L., Coviello, A., & de Bruno, M. P. (2008). Endothelial dysfunction and improvement of the angiotensin II-reactivity in hypercholesterolemic rabbits: role of cyclooxygenase metabolites. European Journal of Pharmacology, 580(1-2), 182-189.

Jerez, S., Sierra, L., Scacchi, F., & de Bruno, M. P. (2010). Hypercholesterolemia modifies angiotensin II desensitisation and cross talk between α1-adrenoceptor and angiotensin AT1 receptor in rabbit aorta. European Journal of Pharmacology, 635(1-3), 149-155.

Karbiner, M. S., Sierra, L., Minahk, C., Fonio, M. C., de Bruno, M. P., & Jerez, S. (2013). The role of oxidative stress in alterations of hematological parameters and inflammatory markers induced by early hypercholesterolemia. Life Sciences, 93(15), 503-508.

Manna, P., & Jain, S. K. (2015). Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. Metabolic Syndrome and Related Disorders, 13(10), 423-444.

Mc Auley, M. T. (2020). Effects of obesity on cholesterol metabolism and its implications for healthy ageing. Nutrition Research Reviews, 33(1), 121-133.

Mercado, M. I., Ruiz, A. I., Zampini, I. C., Nuño, G., Cuello, A. S., Isla, M. I., & Ponessa, G. I. (2013). Arquitectura y morfoanatomía foliar y caulinar de Zuccagnia punctata (Fabaceae). Histolocalización de compuestos bioactivos. Fundación Miguel Lillo; Lilloa, 50(2), 58-68.

Miettinen, T. A., & Gylling, H. (2000). Cholesterol absorption efficiency and sterol metabolism in obesity. Atherosclerosis, 153(1), 241-248.

Moran Vieyra, F. E., Boggetti, H. J., Zampini, I. C., Ordoñez, R. M., Isla, M. I., Alvarez, R. M., De Rosso, V., Mercadante, A. Z., & Borsarelli, C. D. (2009). Singlet oxygen quenching and radical scavenging capacities of structurally-related flavonoids present in Zuccagnia punctata Cav. Free Radical Research, 43(6), 553-564.

Moreno, M. A., Mercado, M. I., Nuño, G., Zampini, I. C., Cuello, A. S., Ponessa, G. I., Sayago, J. E., & Isla, M. I. (2015). Histochemical localization and characterization of chalcones on the foliar surface of Zuccagnia punctata Cav. Insights into their physiological role. Phytochemistry Letters, 13, 134-140.

Nakamura, A., Sato, K., Kanazawa, M., Kondo, M., Endo, H., Takahashi, T., & Nozaki, E. (2019). Impact of decreased insulin resistance by ezetimibe on postprandial lipid profiles and endothelial functions in obese, non-diabetic-metabolic syndrome patients with coronary artery disease. Heart and Vessels, 34, 916-925.

Padilla-Camberos, E., Flores-Fernandez, J. M., Fernandez-Flores, O., Gutierrez-Mercado, Y., Carmona-de la Luz, J., Sandoval-Salas, F., Mendez-Carreto, C., & Allen, K. (2015). Hypocholesterolemic effect and in vitro pancreatic lipase inhibitory activity of an Opuntia ficus-indica extract. BioMed Research International, 2015, 837452.

Payab, M., Hasani‐Ranjbar, S., Shahbal, N., Qorbani, M., Aletaha, A., Haghi‐Aminjan, H., Soltani, A., Khatami, F., Nikfar, S., et al. (2020). Effect of the herbal medicines in obesity and metabolic syndrome: a systematic review and meta‐analysis of clinical trials. Phytotherapy Research, 34(3), 526-545.

Pihlajamäki, J., Gylling, H., Miettinen, T. A., & Laakso, M. (2004). Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men. Journal of Lipid Research, 45(3), 507-512.

Popova, M., Silici, S., Kaftanoglu, O., & Bankova, V. (2005). Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition. Phytomedicine, 12(3), 221-228.

Roco, J., Alarcon, G., Medina, M., Zampini, C., Isla, M. I., & Jerez, S. (2018). Oral administration of Zuccagnia punctata extract improves lipid profile, reduces oxidative stress and prevents vascular dysfunction in hypercholesterolemic rabbits. Phytomedicine, 48, 104-111.

Roco, J., Alarcón, G., Sierra, L., Zampini, I. C., Ines Isla, M., & Jerez, S. (2017). Beneficial effects of hydroalcoholic extract and flavonoids from Zuccagnia punctata in a rabbit model of vascular dysfunction induced by high cholesterol diet. Medicinal Chemistry Research, 26, 2336-2344.

Salas, A. L., Mercado, M. I., Eugenia Orqueda, M., Correa Uriburu, F. M., García, M. E., Pérez, M. J., Alvarez, M. D. l. A., Ponessa, G. I., Maldonado, L. M., et al. (2020). Zuccagnia‐type Propolis from Argentina: A potential functional ingredient in food to pathologies associated to metabolic syndrome and oxidative stress. Journal of Food Science, 85(8), 2578-2588.

Sandoval, V., Sanz-Lamora, H., Arias, G., Marrero, P. F., Haro, D., & Relat, J. (2020). Metabolic impact of flavonoids consumption in obesity: From central to peripheral. Nutrients, 12(8), 2393.

Schmitz, N., Laverty, S., Kraus, V., & Aigner, T. (2010). Basic methods in histopathology of joint tissues. Osteoarthritis and Cartilage, 18, S113-S116.

Sena, C. M., Leandro, A., Azul, L., Seica, R., & Perry, G. (2018). Vascular oxidative stress: impact and therapeutic approaches. Frontiers in Physiology, 9, 1668.

Shahid, U., Butt, S. A., Zareen, N., Shahid, U., Butt, S., & Zareen, N. (2011). Patterns of Sudanophilic Lesions at Ostia of Descending Thoracic and Abdominal Aorta in Cholesterol-Fed Adult Rabbits. International Journal of Morphology, 29(3), 742-746.

Shuster, A., Patlas, M., Pinthus, J., & Mourtzakis, M. (2012). The clinical importance of visceral adiposity: a critical review of methods for visceral adipose tissue analysis. The British Journal of Radiology, 85(1009), 1-10.

Simonen, P. P., Gylling, H. K., & Miettinen, T. A. (2002). Diabetes contributes to cholesterol metabolism regardless of obesity. Diabetes Care, 25(9), 1511-1515.

Solorzano, E. R., Bortolini, C., Bogialli, S., Di Gangi, I. M., Favaro, G., Maldonado, L., & Pastore, P. (2017). Use of a LC-DAD-QTOF system for the characterization of the phenolic profile of the argentinean plant Zuccagnia punctata and of the related propolis: New biomarkers. Journal of Functional Foods, 33, 425-435.

Takeshita, Y., Takamura, T., Honda, M., Kita, Y., Zen, Y., Kato, K. I., Misu, H., Ota, T., Nakamura, M., et al. (2014). The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial. Diabetologia, 57, 878-890.

Valoy, A., Alarcón, G., Roco, J., Zampini, C., Isla, M. I., & Jerez, S. (2023). A Flavonoid-rich Zuccagnia punctata Extract Prevents High Fat Diet-induced Normal Weight Obesity in a Rabbit Model. Planta Medica, 89(3), 245-253.

Velloso, L. A., Folli, F., Perego, L., & Saad, M. J. (2006). The multi‐faceted cross‐talk between the insulin and angiotensin II signaling systems. Diabetes/Metabolism Research and Reviews, 22(2), 98-107.

Wijayatunga, N. N., & Dhurandhar, E. J. (2021). Normal weight obesity and unaddressed cardiometabolic health risk—a narrative review. International Journal of Obesity, 45(10), 2141-2155.

Yang, X., Li, Y., Li, Y., Ren, X., Zhang, X., Hu, D., Gao, Y., Xing, Y., & Shang, H. (2017). Oxidative stress-mediated atherosclerosis: mechanisms and therapies. Frontiers in Physiology, 8, 600.

Downloads

Published

29.07.2023

How to Cite

Valoy, A., Alarcón, G., Roco, J., Zampini, C. I., Isla, M. I., & Jerez, S. J. (2023). Beneficial effects of hydro-alcoholic extract of Zuccagnia punctata against atherosclerosis in normal weight obesity accompanied by hypercholesterolemia rabbit model. International Journal of Plant Based Pharmaceuticals, 3(2), 156–164. https://doi.org/10.29228/ijpbp.28

Issue

Section

Research Articles
Received 2023-03-28
Accepted 2023-07-24
Published 2023-07-29