Elsevier

Experimental Gerontology

Volume 62, February 2015, Pages 37-44
Experimental Gerontology

Effect of Eclipta prostrata on lipid metabolism in hyperlipidemic animals

https://doi.org/10.1016/j.exger.2014.12.017Get rights and content

Highlights

  • We used hamsters to evaluate the hypolipidemic effects of Eclipta.

  • The mechanism of the hypolipidemic effects of Eclipta was elucidated for the first time.

  • The content of the active constituents of Eclipta was determined.

  • The anti-oxidant effect of Eclipta was evaluated for the first time in vivo.

Abstract

Eclipta prostrata (Linn.) Linn. is a traditional Chinese medicine and has previously been reported to have hypolipidemic effects. However, its mechanism of action is not well understood. This study was conducted to identify the active fraction of Eclipta, its toxicity, its effect on hyperlipidemia, and its mechanism of action. The ethanol extract (EP) of Eclipta and fractions EPF1–EPF4, obtained by eluting with different concentrations of ethanol from a HPD-450 macroporous resin column chromatography of the EP, were screened in hyperlipidemic mice for lipid-lowering activity, and EPF3 was the most active fraction. The LD50 of EPF3 was undetectable because no mice died with administration of EPF3 at 10.4 g/kg. Then, 48 male hamsters were used and randomly assigned to normal chow diet, high-fat diet, high-fat diet with Xuezhikang (positive control) or EPF3 (75, 150 and 250 mg/kg) groups. We evaluated the effects of EPF3 on body weight gain, liver weight gain, serum lipid concentration, antioxidant enzyme activity, and the expression of genes involved in lipid metabolism in hyperlipidemic hamsters. The results showed that EPF3 significantly decreased body-weight gain and liver-weight gain and reduced the serum lipid levels in hyperlipidemic hamsters. EPF3 also increased the activities of antioxidant enzymes; up-regulated the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), low density lipoprotein receptor (LDLR), lecithin-cholesterol transferase (LCAT) and scavenger receptor class B type Ι receptor (SR-BI); and down-regulated the mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR) in the liver. These results indicate that EPF3 ameliorates hyperlipidemia, in part, by reducing oxidative stress and modulating the transcription of genes involved in lipid metabolism.

Introduction

Aging is a progressive decline in the biochemical and physiological functions of various organs in an individual. The reasons for this decline remain unclear, but it has been proposed that lipid metabolism disorders (Puca et al., 2008) and increased oxidative stress (Ramesh et al., 2012) play a crucial role in aging.

Hyperlipidemia is a metabolic disorder that is specifically characterized by increased concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG), with a concomitant decrease in the concentration of high density lipoprotein cholesterol (HDL-C) in the blood circulation (Gao et al., 2013). High concentrations of serum lipids are also a key risk factor for cardiovascular diseases, including atherosclerosis, myocardial infarction, stroke and cerebrovascular diseases (Watts and Karpe, 2011), which are harmful to the elderly. Therefore, reducing blood lipids is an important strategy for preventing the occurrence and progression of these diseases.

Increased daily intake of a high-fat diet (HFD) is an important contributor to the development of human hyperlipidemia (Sharma et al., 2008). Furthermore, HFD causes oxidative stress in mammals (Ibrahim et al., 1997), which aggravates hyperlipidemia by damaging the structural and functional integrity of a cell (Chan et al., 2006). This is known as the two-hit theory (Huang et al., 2007).

Eclipta prostrata (Linn.) Linn. has traditionally been used as a Chinese food additive and herbal medicine (Jian and Taiyan, 1957) since it was first recorded in 659 (Jing, 1981). It has many pharmacological activities, such as immune system regulation (Jayathirtha and Mishra, 2004) and inflammation promotion (Sawant et al., 2004), and it also prevents liver damage (Ma-Ma et al., 1978), inhibits HIV-1 (Tewtrakul et al., 2007) and has antioxidant activity in vitro (Cai et al., 2004). However, to the best of our knowledge, there are no reports of its antioxidant effects in vivo. E. prostrata can regulate blood lipids in rats (Kim et al, 2008); however, the exact mechanism underlying its hypolipidemic effects is not well understood. Therefore, the objective of this study was to investigate the effect of E. prostrata on the oxidative stress and lipid profile in vivo and to elucidate the underlying mechanism of its hypolipidemic effect.

Additionally, the selection of an ideal hyperlipidemic animal model is the key to studying lipid metabolism. Compared to rats and mice, hamsters are the best animal model for studying lipid metabolism because cholesterol metabolism in hamsters is similar to that in humans (Spady et al., 1986). However, hamsters have not been previously used to study the lipid-reducing mechanism of E. prostrata. To further investigate the hypolipidemic effect of E. prostrata and its possible mechanism of action, we used a hamster model of HFD-induced hyperlipidemia.

Section snippets

Materials

Whole Eclipta plants were procured from Zhangshu Co., Ltd. (Jiangxi Province, China) in March 2012 and were authenticated by Dr. Qiu (Medical College, Xiamen University, Xiamen, China), who specializes in medical plants. A voucher, designated as Co-EP-11, was deposited in the Pharmacology Laboratory at the Medical College, Xiamen University, Xiamen, China.

Fenofibrate was purchased from Sigma-Aldrich (St. Louis, MO, USA), and Xuezhikang was purchased from Beijing Wbl Peking University Biotech

Triterpene, flavonoid and polyphenol contents

Examination of the total triterpene, flavonoid and polyphenol contents of the Eclipta extracts showed that EPF3 contained more triterpenes and polyphenols at 27.06 and 51.58 mg/g of the dry extract mass, respectively, compared to the other extracts (Table 2).

Quantitative determination of wedelolactone in EP and EPF3

Because wedelolactone is the characteristic chemical constituent of E. prostrata, it was evaluated both in EP and EPF3. HPLC analysis of the wedelolactone standard showed a single peak at 350 nm with a retention time of approximately 11 min (

Discussion

Hyperlipidemia is a well-known risk factor for atherosclerosis (Bonetti et al., 2003), which, if there are no other causes, such as infection or malignant tumors arise, is the progressive change of the cardiovascular system (L. Robert, 1999). The development of hyperlipidemia is related to a high-fat diet and oxidative stress (Huang et al., 2007, Ibrahim et al., 1997).

E. prostrata is an herbal medicine that is widely consumed in southern China. E. prostrata regulates blood lipids in rats (Kim

Conflict of interest statement

The authors declare that they have no competing interests.

Acknowledgments

We would like to thank Professor Qiuyan from the Medical College of Xiamen University for his help. This study was supported by the Research Fund of Strait (Xiamen) Technology Platform in Traditional Chinese Medicine (3502Z20100006).

References (36)

Cited by (40)

  • Chinese Torreya grandis cv. Merrillii seed oil affects obesity through accumulation of sciadonic acid and altering the composition of gut microbiota

    2022, Food Science and Human Wellness
    Citation Excerpt :

    Therefore, we have proposed that dietary supplementation of T. grandis seed oil would be a much safer way to alleviate obesity. Hyperlipidemia is characterized by increased TC, TG, and LDL-C levels, and decreased HDL-C level in serum [33,34]. In this study, decreased serum TC (–24.8%), TG (–30.7%), and LDL-C (–26.9%), and increased serum HDL-C (42.2%) were observed in the mice with T. grandis seed oil supplementation.

  • A 26-week toxicological study of Xuezhikang (XZK), red yeast rice extract, in Beagle dogs with a 4-week recovery period

    2020, Regulatory Toxicology and Pharmacology
    Citation Excerpt :

    Furthermore, no XZK-related microscopic observations were made following either the dosing or recovery phases of this study (Supplementary Table 8 and Supplementary Table 9). XZK is a statin-rich compound derived from red yeast rice extracts that is used in traditional Chinese medicine, and which exhibits significant lipid modulating activity (Zhao et al., 2015; Shen et al., 2017). The HMG-CoA reductase inhibitor lovastatin is also present in XZK, as are ergosterol, various flavonoids, unsaturated fatty acids and amino acids (Xie and Zhang, 2017; Zheng et al., 2017).

  • Qualitative distribution of endogenous phosphatidylcholine and sphingomyelin in serum using LC-MS/MS based profiling

    2020, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
View all citing articles on Scopus
1

These authors contributed equally to this work.

View full text