Elsevier

Phytochemistry

Volume 177, September 2020, 112432
Phytochemistry

Isolation, structure elucidation and neuroprotective effects of caffeoylquinic acid derivatives from the roots of Arctium lappa L.

https://doi.org/10.1016/j.phytochem.2020.112432Get rights and content

Highlights

  • Five undescribed caffeoylquinic acid derivatives were isolated from the roots of Arctium lappa L.

  • Structures were elucidated by spectroscopic data.

  • The more caffeoyl groups on the quinic ring, the better the antioxidant activity.

  • The maloyl-containing compounds had better anti-N-methyl-D-aspartate activity.

Abstract

Five undescribed caffeoylquinic acid derivatives (CQAs), along with fifteen known CQAs, were isolated from the roots of Arctium lappa L.(burdock). The chemical structures of compounds were determined using extensive spectroscopic analyses, including UV, IR, NMR and MS. Further in vitro bioactive investigation demonstrated the neuroprotective effects of these compounds against the neurotoxicity of hydrogen peroxide (H2O2) and N-methyl-D-aspartate (NMDA). 1,3,5-tri-O-caffeoylquinic acid and 1,4,5-tri-O-caffeoylquinic acid significantly reduced H2O2-induced human neuroblastoma SH-SY5Y cell death with concentration for 50% of maximal effect (EC50) values of 17.3 and 19.3 μM. Meanwhile, 3,5-di-O-caffeoyl-1-O-maloylquinic acid displayed protective effect against NMDA-induced cell injury with EC50 values of 18.4 μM. Overall, the more caffeoyl, the better the antioxidant activity, while the maloyl-containing compounds had better anti-NMDA activity.

Introduction

Arctium lappa L.(burdock), a two-year-old herbaceous plant of the genus Arctium belonging to the family Asteraceae, is widely grown as edible vegetables in many countries and used in traditional Chinese medicine in China. The roots of burdock are usually used as ingredients. With the in-depth study of the burdock, it was found that the roots of burdock can also be used as a drug with multiple pharmacological effects, such as anti-inflammatory effects of water-soluble polysaccharides and L-arginine to prevent early atherosclerosis (Lee et al., 2020; Zhang et al., 2019), antioxidation (Sohn et al., 2011; Lee et al., 2012), and so on. Burdock is rich in protein, oligosaccharides and other nutrients, and also contains polyphenols, burdock aldehydes (Machado et al., 2012). A lot of chlorogenic acid compounds and water-soluble polysaccharides were isolated from burdock roots (Yoshihiko et al., 1995; Jiang et al., 2016b; Wang et al., 2019).

Oxidative stress plays a pivotal role in neurodegeneration (Wadhwa et al., 2019). It is well known that polyphenolic components has antioxidant activities, which are rich in the roots of burdock, such as caffeoylquinic acid derivatives (Wang et al., 2016; Yuan et al., 2012). Polyphenols, which are common natural products in many fruits and vegetables, can be used as excellent antioxidant additive agent. NMDA receptors (NMDARs) form glutamate-gated ion channels, which widely expressed in the central nervous system, played important physiological roles in the development of the nervous system, such as regulating neuronal survival (Paoletti, 2011). NMDA receptor subunits play different roles in neurotoxicity. Excitotoxicity is triggered by the selective activation of NR2B-containing NMDARs (Liu et al., 2007, 2012). Up to now, there is no more choice of drugs for ischemic stroke except for thrombolytic drugs. Selective GluN2B-NMDA receptor antagonists are considered as the breakthrough to solve this problem. The discovery of a new type of active lead compound is an important way to solve the clinical application limitations of GluN2B-NMDA receptor antagonists.

In our previous study, CQAs in the roots of burdock were chosen as the research object based on the optimal molecular docking results of MQA and GluN2B subunits. The activity was evaluated by the antagonistic ability of GluN2B-NMDA receptor and neuroprotective effect (Tian et al.,2015a, 2015b, 2016; Jiang et al., 2016a). In order to continue our research, it is needed to isolated more compounds to investigate their neuroprotective effects. In this study, five undescribed CQAs (15) and fifteen known CQAs (620) were isolated from the roots of burdock. All the data for chlorogenic acids presented in this paper uses the recommended IUPAC (International Union of Pure and Applied Chemistry) numbering system (IUPAC, 1976). Furthermore, neuroprotective effects against H2O2 and NMDA-induced SH-SY5Y cell injury were evaluated by MTT assay. The structure-activity relationships between neuroprotective effects of CQAs were also explained in detail (see Fig. 1).

Section snippets

Structure elucidation of undescribed compounds

Compound 1 was obtained as a yellowish amorphous powder. Its UV spectrum (in MeOH) showed the absorption peaks at 330, 295 (sh), 245 nm, which reflected the features of caffeic acid substituted compounds (Lee et al., 2010). Its IR (KBr disc) spectrum indicated the presence of hydroxy (3398.1 cm−1, br), carbonyl (1695.7, 1630.0 cm−1), aromatic ring (1601.8, 1516.7 cm−1), trans double bond (1279.6, 977.3 cm−1) (Zou et al., 2014). The sodium adduct ion peak was at m/z 817.1597 ([M+Na]+) by

Conclusions

In conclusion, 14 compounds were isolated from the roots of Burdock in this study, including five undescribed compounds (1–5)and nine known compounds (6–14). Among these compounds, compounds 7, 8, 10, 11 were obtained from the Arctium for the first time in the present investigation. To evaluate the antioxidant activity of the compounds, the bioactivities against H2O2 were determined by MTT assay. The results showed that compounds 6, 7 had a good performance of antioxidant effects, which could

General experimental procedures

Open column chromatography was performed with macroporous absorption resin D101 (0.3–1.25 mm, Zhengzhou Qinshi Technology Co., Ltd., Henan, China), ODS (50–75 μm, YMC Co., Ltd. in Japan) and sephadex LH-20 (Amersham Biosciences, USA). For thin layer chromatography (TLC), a pre-coated silica-gel 60 F254 (0.25 mm, Merck) was used. Semi-preparative HPLC was conducted on PU-2087 Pump equipped with UV–vis detector (JASCO model 2075) and a YMC-Pack Pro ODS-A C18 (Ф 250 × 10 mm ID, S-5 μm, 12 nm)

Declaration of competing interest

The authors declare no conflict of interest.

Acknowledgments

This work was financially supported by National Natural Science Foundation of China (Grant Number: 81673328).

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