Neurotrophic and anti-neuroinflammatory constituents from the aerial parts of Coriandrum sativum

doi:10.1016/j.bioorg.2020.104443

Bioorganic Chemistry

Volume 105, December 2020, 104443

https://doi.org/10.1016/j.bioorg.2020.104443 Get rights and content

Highlights

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Three new compounds were isolated from aerial parts of Coriandrum sativum.
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The structures were elucidated by chemical and spectroscopic methods.
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Compounds 1–3 and 7 exhibited potent NGF secretion in C6 glial cells.

Abstract

In the course of our continuing search for biologically active compounds from medicinal sources, we investigated the MeOH extract of the aerial parts of Coriandrum sativum Linn. An extended phytochemical investigation of the aerial parts of C. sativum led to the isolation and identification of seven compounds (1–7) including two new isocoumarin glycosides (1–2) and a new phenolic glycoside (5). The chemical structures of the new compounds (1, 2, and 5) were elucidated by analysis of 1D and 2D NMR (¹H and ¹³C NMR, COSY, HSQC, and HMBC) and HRESIMS data as well as by using chemical methods. All the isolates were evaluated not only for their potential neurotrophic activity by means of induction of nerve growth factor (NGF) in C6 glioma cells but also for production of nitric oxide (NO) levels in lipopolysaccharide (LPS)-activated murine microglia BV-2 cells to assess their anti-neuroinflammatory activity. Compounds 1–3 and 7 were stimulants of NGF release, with levels of NGF stimulated at 127.23 ± 1.89%, 128.22 ± 5.45%, 121.23 ± 6.66%, and 120.94 ± 3.97%, respectively. Furthermore, the aglycones of 1 and 2 (1a and 2a) showed more potent NGF secretion activity and anti-neuroinflammatory effect than did their glycosides (1a : 130.81 ± 5.45% and 2a : 134.44 ± 5.45%).

Graphical abstract

Introduction

Neurodegenerative diseases, including Alzheimer s disease (AD), Parkinson s disease (PD), Huntington s disease, and multiple sclerosis (MS), deteriorate the human body s activity for multiplex reasons with aging and led to cognitive/memory disorders [1]. These diseases can result from the structural breakdown and dysfunction of neurons including neuroinflammation and depletion of neurotrophic factors. Therefore, much studies have been focused on finding neuroprotective and neurotrophic substances for neurodegenerative diseases. BV-2 cells, mouse-derived microglial cells, are important cells involved in the central nervous system (CNS), and the increase in nitric oxide (NO) and cytokines is a major biomarker of neuroinflammation [2], [3]. Activation of microglia by lipopolysaccharide (LPS) results in cytotoxicity and neuroinflammation through an increase in inflammatory mediators such NO, cytokines and reactive oxygen species (ROS). In addition, increase of cytokines such as interleukin6 (IL6), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-_KB), tumor necrosis factor-α (TNF-α) by LPS lead to neuronal cell death [4]. Thus, we did screening of anti-neuroinflammatory effect of the compound in BV-2 cells. Additionally, we screened the nerve growth factor (NGF) production in astrocyte C6 cells. C6 cells are rat-derived glial cells and are the most abundant cells in the brain. These cells play a very important function in repairing brain tissue when being damaged [5]. NGF is one of main neurotrophic factor which is related with nerve growth, maintenance, proliferation and neuronal survive. It is also responsible for the extension and maintenance of axons in neurons. Thus, the efficacy of NGF for neuronal repair may be a better alternative for the treatment of various neuronal disorders [6].

Coriandrum sativum Linn. (Apiaceae) generally known as “coriander” or “cilantro” is an annual plant native to regions spanning from Southern Europe and Northern Africa to Southwestern Asia [7]. In addition to the wide usage of C. sativum as a spice around the world, the aerial parts of this plant have been used in a traditional medicine for treating hypertension, gastrointestinal disorders, and anti-inflammation [8], [9]. Previous phytochemical investigations have isolated isocoumarins, aliphatic lactones, and monoterpene derivatives [10], [11], [12] with a variety of biological effects such as cytotoxic, antioxidant, antibacterial, gastric mucosal protective, and anti-inflammatory activities [13], [14], [15]. In this study, an extended phytochemical investigation of the aerial parts of C. sativum afforded three new compounds, two isocoumarin glycosides (1 and 2), and a phenolic glycoside (5), along with four known glycosides (3, 4, 5, and 7) (Fig. 1). The chemical structures of the isolated compounds were deduced by means of their physico-chemical properties, spectroscopic data, such as UV, IR, MS and NMR spectra (¹H and ¹³C NMR, COSY, HMQC, HMBC, and NOESY), ECD spectrum, GC–MS, and chemical reactions. We evaluated all the isolated compounds for their potential anti-neuroinflammatory and neurotrophic activities.

Section snippets

General experimental procedures

Optical rotations were obtained on a JASCO P-1020 polarimeter. Ultraviolet (UV) spectra were recorded on a Shimadzu UV-1601 UV visible spectrophotometer. Infrared (IR) spectra were measured on a Bruker IFS-66/S FT-IR spectrometer. NMR spectra were recorded on a Bruker AVANCE III 700 MNR spectrometer. HRESIMS data were acquired on a Waters SYNAPT G2 Q-TOF mass spectrometer. An Agilent GC system 7820A Series equipped with a 5977B Mass Selective Detector (MSD) system was controlled by the Enhanced

Structural elucidation of isolated compounds

Compound 1 was isolated as a yellowish gum. The molecular formula was established to be C₁₆H₂₀O₉ from the [M+Na]⁺ positive ion peak m/z 379.1002 (calcd for C₁₆H₂₀O₉Na, 379.1005) in its HRESIMS spectrum. The IR spectrum of 1 indicated the presence of a hydroxy group (3474 cm⁻¹) and an α,β-unsaturated lactone group (1719 cm⁻¹) [23]. The ¹H NMR spectrum of 1 displayed the presence of an 1,3,4,5-tetrasubstituted aromatic ring [δ_H 6.79 (1H, d, J = 2.2 Hz, H-7), and 6.45 (1H, d, J = 2.2 Hz, H-5)], an

Conclusion

In this study, we isolated two new isocoumarins (1 and 2) and one new phenolic glycoside (5), together with four known compounds (3, 4, 6, and 7) from the aerial parts of C. Sativum, and all the purified compounds were evaluated for their anti-neuroinflammatory, and neurotrophic activities. Compounds 1a and 2a showed moderate anti-neuroinflammatory activity through inhibition of NO production from BV-2 cells, and compounds 1–4, 1a, and 2a exhibited potent NGF secretion in C6 glial cells.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science and Technology (2016R1A2B2008380). We are thankful to the Korea Basic Institute (KBSI) for the measurements of NMR spectra.

References (36)

M. Sawada et al.
Production of tumor necrosis factor-alpha by microglia and astrocytes in culture
Brain Res.
(1989)
Y. Ding et al.
Chapter Fourteen - The role of PPARδ signaling in the cardiovascular system
Prog. Mol. Biol. Transl.
(2014)
V. Prachayasittikul et al.
Coriander (Coriandrum sativum): a promising functional food toward the well-being
Food Res. Int.
(2018)
M. Taniguchi et al.
Three isocoumarins from Coriandrum sativum
Phytochemistry
(1996)
O. Ceska et al.
Coriandrin, a novel highly photoactive compound isolated from Coriandrum sativum
Phytochemistry
(1988)
J.-N. Wei et al.
Phytochemical and bioactive profile of Coriandrum sativum L.
Food Chem.
(2019)
J.C. Matasyoh et al.
Chemical composition and antimicrobial activity of the essential oil of Coriandrum sativum
Food Chem.
(2009)
C.-R. Zhang et al.
Evaluation of coriander spice as a functional food by using in vitro bioassays
Food Chem.
(2015)
T. Warashina et al.
Constituents from the bark of Tabebuia impetiginosa
Phytochemistry
(2004)
J.A. Marco et al.
Flavonoids and other phenolics from Artemisia hispanica
Phytochemistry
(1988)

K.J. Park et al.

Phenolic constituents from the twigs of Betula schmidtii collected in Goesan, Korea

Phytochemistry

(2019)

K. Krohn et al.

Dihydroisocoumarins from fungi: isolation, structure elucidation, circular dichroism and biological activity

Phytochemistry

(1997)

C.S. Kim et al.

Salicin derivatives from Salix glandulosa and their biological activities

Fitoterapia

(2015)

G. Bringmann et al.

Cis- and trans-isoshinanolone from Dioncophyllum thollonii: absolute configuration of two ‘known', wide-spread natural products

Phytochemistry

(1999)

T. Kanchanapoom et al.

Iridoid and phenolic diglycosides from Canthium berberidifolium

Phytochemistry

(2002)

A. Pabst et al.

Phenylbutan-2-one β-D-glucosides from raspberry fruit

Phytochemistry

(1990)

C. Spuch et al.

Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer's disease and Parkinson's disease)

J. Drug Deliv.

(2011)

J.E. Yuste et al.

Implications of glial nitric oxide in neurodegenerative diseases

Front. Cell. Neurosci.

(2015)

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Neurotrophic and anti-neuroinflammatory constituents from the aerial parts of Coriandrum sativum

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

General experimental procedures

Structural elucidation of isolated compounds

Conclusion

Declaration of Competing Interest

Acknowledgments

Brain Res.

Prog. Mol. Biol. Transl.

Food Res. Int.

Phytochemistry

Phytochemistry

Food Chem.

Food Chem.

Food Chem.

Phytochemistry

Phytochemistry

Phytochemistry

Phytochemistry

Fitoterapia

Phytochemistry

Phytochemistry

Phytochemistry

Liposomes for targeted delivery of active agents against neurodegenerative diseases (Alzheimer's disease and Parkinson's disease)

J. Drug Deliv.

Implications of glial nitric oxide in neurodegenerative diseases

Front. Cell. Neurosci.