Pharmacological activity of the hydroalcoholic extract from Hovenia dulcis thunberg fruit and the flavonoid dihydromyricetin during hypercholesterolemia induced in rats

Abstract

Cerebrovascular accidents and coronary artery disease are the leading causes of cardiovascular mortalities in Brazil and high levels of LDL cholesterol are one of the main risk factors. In this context, several plant extracts and natural substances have shown promise as cholesterol-lowering. The objective of this study was to evaluate the potential of the hydroalcoholic extract of the fruit of H. dulcis and of dihydromyricetin in cholesterol reduction in hypercholesterolemic rats. Forty-two Wistar male rats were distributed into seven groups of six animals that received diets supplemented with 1% cholesterol and 0.3% cholic acid, with the exception of the control group, which received conventional diets. Animals were treated with oral suspensions containing: atorvastatin 1.0 mg/kg; H. dulcis extract at 50.0 and 100.0 mg/kg and dihydromyricetin at 25.0 and 50.0 mg/kg vehicle (control group). The following biochemical markers were evaluated; total cholesterol, HDL-C, LDL-C, triglycerides, AST, ALT, and alkaline phosphatase. The hypercholesterolemic diet was effective in inducing hypercholesterolemia, increasing total cholesterol by 112.7% relative to the control group. The treatments with two doses of the extract proved to be promising hypocholesterolemic agents, as they were able to substantially reduce total cholesterol and LDL-C, without significantly altering triglycerides, hepatic transaminases, and alkaline phosphatase, thereby encouraging the studies with the plant H. dulcis. The groups treated with the flavonoid dihydromyricetin, although they showed a significant reduction in total cholesterol and LDL-C, and found increases in triglycerides and hepatic transaminases, which is unwanted in the context of hypercholesterolaemia.Uniterms: Hovenia dulcis/pharmacognosy. Hovenia dulcis/hydroalcoholic extract/ cholesterol reduction. Hovenia dulcis/flavonoid dihydromyricetin/cholesterol reduction. Dihydromyricetin/cholesterol reduction. Hypercholesterolemia/experimental study. Medicinal plants.No Brasil, o acidente vascular cerebral e a doença arterial coronariana constituem as principais causas de mortalidade cardiovascular, sendo os altos níveis de colesterol LDL um dos principais fatores de risco. Nesse contexto, diversos extratos vegetais e substâncias naturais isoladas têm se mostrado promissoras como hipocolesterolemiantes. O objetivo do trabalho foi avaliar o potencial do extrato hidroalcoólico dos frutos de Hovenia dulcis e do flavonóide diidromiricetina na redução do colesterol em ratos hipercolesterolêmicos. Quarenta e dois ratos Wistar machos, foram distribuídos em 7 grupos de 6 animais, que receberam dieta suplementada com 1% de colesterol e 0,3% de ácido cólico, à exceção do grupo controle, que recebeu ração convencional. Posteriormente, os animais foram tratados com suspensões orais contendo: atorvastatina 1,0 mg/kg; extrato de H. dulcis de 50,0 e 100,0 mg/kg; diidromiricetina de 25,0 e 50,0 mg/kg e veículo (grupo controle). Avaliaram-se os parâmetros bioquímicos: colesterol total, HDL-C, LDL-C, trigl...

Hovenia dulcis Thunb. pseudofruits as functional foods: Phytochemicals and bioactive properties in different maturity stages

“…The presence of four flavonoids, i.e., myricetin, quercetin, ampelopsin (dihydromyricetin) and taxifolin (dihydroquercetin) was described by Park, Kim, Rehman, Na, and Yoo (2015) in the fruit-stalk of Hovenia dulcis. Myricetin was also isolated from Hovenia dulcis fruits (Guo et al, 2015), as well as dihydromyricetin from fruits (Pinto et al, 2014;Yoo, Mun, & Kim, 2006) and leaves (Chaturvedula & Ruo, 2013). Various flavonol glycosides derived from kaempferol and quercetin have also been identified in the leaves (Cho, Hyun, Moon, & Park, 2013), and up to eigth phenolic compounds, including phenolic acids (vanillic, ferulic and trihydrobenzoic acid), flavan-3-ols (catechin and afzelechin), aromadendrin (a dihydroflavonol), 3,5-dihydroxystilbene, and methyl vanillate have been found in H. dulcis stem bark (Li et al, 2005).…”

The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis—In Vitro Model

“…Based on current results, Esterol10 ® may hold promise as a novel cholesterol-lowering approach with a statin-like but naturally derived mechanism of action [ 5 ] with fewer side effects. These natural extracts, containing antioxidants, or in any case able to counteract oxidative stress, can represent a promising adjuvant therapy in hypercholesterolemia, reducing the risk of cardiovascular diseases by increasing the resistance to oxidation of circulating lipids [ 8 ]. In conclusion, this study demonstrates for the first time that the combination of 10 µM Sage Extract, 10 µM Quercetin, 1 µM Vitamin D3, 1 µM Vitamin K2, 1 µM CoQ10, 1 µM Resveratrol, 9 nM Astaxanthin, 1 µM Sodium Selenite, 1 µM Folic Acid, and 1 µM RYR, called Esterol10 ® , can be a candidate to be an effective treatment to avoid the accumulation of cholesterol, being also capable of modulating the hepatic metabolism.…”

“…Several studies have shown that natural extracts containing antioxidants, or in any case able to counteract oxidative stress, can represent a promising adjuvant therapy in hypercholesterolemia. Indeed, these molecules are able to reduce the risk of cardiovascular diseases by increasing the resistance to oxidation of LDL-C [ 8 ]. Furthermore, AMP-activated protein kinase (AMPK) has recently been evaluated as a key regulator of a naturally extracted active ingredient capable of preventing CVD.…”

Hovenia dulcis Thumberg: Phytochemistry, Pharmacology, Toxicology and Regulatory Framework for Its Use in the European Union

“…In vivo studies also demonstrated the ability of H. dulcis extract to improve lipid metabolism. Pinto et al [ 55 ] evaluated the effect of hydroalcoholic extract of H. dulcis fruit (50.0 and 100.0 mg/kg) and DHM (25.0 and 50.0 mg/kg) in hypercholesterolemic rats. The results demonstrated that both treatments significantly reduced total cholesterol and LDL-C, compared to the control.…”

“…The results demonstrated that both treatments significantly reduced total cholesterol and LDL-C, compared to the control. However, an increase of triglycerides and hepatic transaminases was observed only in rats treated with DHM, suggesting that the crude extract could be more useful than the compound alone [ 55 ]. The effect on lipid metabolism was also demonstrated by administering insoluble dietary fiber obtained from H. dulcis pomace and modified by ball milling and complex enzyme treatment.…”