Elsevier

Phytochemistry

Volume 170, February 2020, 112212
Phytochemistry

The asarone-derived phenylpropanoids from the rhizome of Acorus calamus var. angustatus Besser

https://doi.org/10.1016/j.phytochem.2019.112212Get rights and content

Highlights

  • Three previously undescribed phenylpropanoids were isolated from Acorus calamus var. angustatus Besser.

  • Chiral γ-asaronol were further identified by Mosher's method and ECD spectra.

  • Structures were elucidated by NMR, HRMS and ECD.

  • Four compounds exerted noticeable neuroprotective activity against H2O2-induced SH-SY5Y cell injury.

Abstract

Phenylpropanoids comprise a broad spectrum of biologically active natural products. As part of our ongoing research on antiepileptic active compounds from traditional Chinese herb, Acorus calamus var. angustatus Besser, three undescribed phenylpropanoids and twenty-two known ones were isolated. All the undescribed structures were determined by a combination of 1D and 2D NMR, HRMS. In addition, γ-asaronol was identified as racemates and its absolute configuration were determined by the modified Mosher's method and ECD spectral data. Furthermore, some selected isolated compounds were evaluated for their cell viability and neuroprotective activities in H2O2-induced SH-SY5Y cells. α-Asaronol, β-asaronol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol and 1,2,4-trimethoxy-5-(3-methoxypropyl)benzene exerted potential protective activity from neuronal oxidative stress in all test concentrations ranging from 0.01 to 100 μM, in which the neuroprotective activity of β-asaronol was the best.

Introduction

Plants of the genus Acorus (family Acoraceae) (e.g., Acorus calamus var. angustatus Besser (synonym Acorus tatarinowii Schott), Acorus calamus L. and Acorus gramineus Aiton) and Asarum (family Aristolochiaceae) (e.g., Asarum europaeum L.) have generated considerable interest due to their important biological and pharmacological properties, especially their sedative (Zanoli et al., 1998), hypolipidemic (Parab and Mengi, 2002), digestive (Shoba and Thomas, 2001), immunosuppressive (Mehrotra et al., 2003), anti-inflammatory (Muthuraman et al., 2011), anti-oxidative (Muthuraman et al., 2011), diuretic (Ghelani et al., 2016), insecticidal (Park et al., 2003), antifungal (Lee et al., 2004), anticancer (Kim et al., 2011), antispasmodic (Gilani et al., 2006) as well as anticonvulsive (Cho et al., 2001) effects. Over the past half century, many phytochemists, pharmacologists and medicinal chemists have involved in this field and tried their best to seek some really active chemical components or potential drug candidates therefrom. These endeavors resulted in the isolation of various organic molecules including alkaloids (Kim et al., 2015; Li et al., 2017; Tong et al., 2010a, 2010c), amides (Wang et al., 1997a), diterpenes (Wang et al., 1997b), flavonoids (Chang et al., 2010; Singh, 2012), lignans (Lu et al., 2015; Luo et al., 2016; Ni et al., 2016; Zhang et al., 2018), phenylpropanes (Della Greca et al., 1989; Gao et al., 2017; Hu and Feng, 2000; Tong et al., 2010b), and sesquinlignans (Ni et al., 2011) as well as a variety of sesquiterpenoids (Hao et al., 2012; Ni et al., 2016; Tong et al., 2010b, 2010c). Among these natural products, 2,4,5-trimethoxyl phenylpropanoids such as α-asarone (1a) and β-asarone (1b) were reported to be major constituents and played an important role in treating respiratory diseases and central nervous system disorders (Rajput et al., 2014). However, the content of other 2,4,5-trimethoxyl analogues was quite low and few paper referred to this kind of rare phenylpropanoids isolated from genus Acorus (Gao et al., 2017; Hu and Feng, 2000). Recently, we found that α-asaronol (2a) (one of rat metabolites of α-asarone (Cartus and Schrenk, 2016)) could easily penetrate blood-brain barrier (rats) (Sun et al., 2019) and exhibited excellent antiepileptic activity with low acute toxicity (He et al., 2018; Jin et al., 2019). Considering the potential bioactivities of 2,4,5-trimethoxyl phenylpropanoids and their importance of being basic monomer unit to form some complex bioactive compounds such as lignin (Lu et al., 2015) and sesquiterpene (Xiao et al., 2013), we are once again committed to discovering some previously undescribed phenylpropanoid monomer compounds from Acorus calamus var. angustatus Besser.

The rhizomes of Acorus calamus var. angustatus Besser were collected in the lower reaches of the Yangtze River area and extracted with 95% aqueous EtOH and EtOAc to give an EtOH and EtOAc extract respectively. Both of them showed antiepileptic and sedative effects in whole animal experiments. Herein, purification of the EtOH extract mainly led to the isolation three pairs of cis-trans-isomers (1a/1b, 2a/2b and 4a/4b) (supporting information, Fig. S29) and one pair of enantiomer of phenylpropanoids (8a/8b) (Fig. 2A), while the EtOAc section led to 120 (Fig. 1). Among them, three phenylpropanoids 5–7 were undescribed, chiral isomers (8a and 8b) (Cartus et al., 2015) were subjected to chiral separation and identification, others including α-asarone (1a), β-asarone (1b), α-asaronol (2a) (Zheng et al., 2015), β-asaronol (acoramol, 2b) (Kim et al., 2012), (E)-3-(2,4,5-trimethoxyphenyl)acrylaldehyde (3a) (Kikuzaki et al., 2001), (Z)-3-(2,4,5-trimethoxyphenyl)acrylaldehyde (3b) (Saxena, 1986), (E)-3-(2,4,5-trimethoxyphenyl)acrylic acid (4a) (Koul et al., 1988), (Z)-3-(2,4,5-trimethoxyphenyl)acrylic acid (4b) (Koul et al., 1988), 1′-oxoasarone (9) (Cartus et al., 2015), γ-asarone (10), 3-(3,4-dimethoxyphenyl)propan-1-ol (11) (Bode et al., 1996), tatarinoids A (12) (Tong et al., 2010b), tatarinoids B (13) (Tong et al., 2010b), 7,8-dihydroxydihydroasarone (14) (Hu and Feng, 2000), acorusin C (15) (Ni et al., 2016), acorusin D (16) (Ni et al., 2016), tatarinowin A (17) (Tong et al., 2010b), (±)-pinoresinol (18) (Cowan et al., 2001), acortatarin B (19) (Geng et al., 2012), and (+)-acortatarinowin E (20) (Lu et al., 2015), were known compounds. All molecular structures of isolated compounds were established on the basis of comprehensive spectroscopic analysis or spectral data comparison to literature values. Among them, compounds 2–9 were isolated from Acorus calamus var. angustatus Besser for the first time. Details of the isolation, structure elucidation, and a plausible biogenetic pathway of some phenylpropanoids were reported in this paper. Furthermore, their cell viability and neuroprotective activities were also evaluated in vitro.

Section snippets

Structure elucidations

Compound 5 was isolated as a white, amorphous solid. The sodium adduct ion at m/z 261.1097 [M + Na]+ by HR-ESIMS displayed that the molecular formula of 5 was C13H18O4. The UV spectrum of 5 exhibited absorption maxima at 261 and 314 nm. The 1H and 13C NMR data (Table 1) were similar to those of 2a (Zheng et al., 2015), except for the presence of resonances of an additional methoxy group. This newly added methoxy group was confirmed by the HMBC at C-9 position of 5 (supporting information, Fig.

Conclusions

In conclusion, this work presented the isolation and structure elucidation of three undescribed rare phenylpropanoids (57). The common characteristic was that the benzene ring contained 2,4,5-trimethoxy group. Three pairs of cis-trans isomers (2a/2b, 3a/3b and 4a/4b) and a pair of enantiomers (8a/8b) were firstly found in Acorus calamus var. angustatus Besser. Moreover, the chiral characteristics of 8a/8b were further elucidated. Biosynthetic analysis suggested that compound 5–7 were derived

General experimental procedures

Melting points were determined in open capillary tubes using a WRS-1B melting point apparatus (Shanghai Yice Apparatus & Equipment Co., Ltd, Shanghai, China) and were uncorrected. UV spectra were recorded on an Agilent 8453 UV−VIS spectrophotometer (Agilent Technologies Co., Ltd., USA). Optical rotations were measured with a RUDOLPH AUTOPOL IV Laboratory Polarimeter (Rudolph Research Analytical, Hackettstown, USA). ECD spectra were recorded on a Chirascan spectrophotometer (Applied Photophysics

Author contributions

Yajun Bai and Ying Sun contributed equally to this work.

Declaration of competing interest

The authors have declared that there is no competing financial interest.

Acknowledgements

This work was supported by The Development and Application of Supercritical Fluid Chromatography (2013YQ170525; subproject: Application Research of Supercritical Fluid Chromatography in Chinese Traditional Medicine and Its Metabolites, 2013YQ17052509), Program for Changjiang Scholars and Innovative Research Team in University of Ministry of Education of China (IRT_15R55), The project for Innovative Research Team of Research and Technology of Shaanxi Province (2013KCT-24), The Technology Support

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