NF-κB inhibitory sesquiterpene lactones from Lebanese Laurus nobilis

doi:10.1016/j.phytol.2019.02.003

Phytochemistry Letters

Volume 30, April 2019, Pages 120-123

https://doi.org/10.1016/j.phytol.2019.02.003 Get rights and content

Highlights

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Twenty one sesquiterpenes were isolated from the leaves of Laurus nobilis.
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Two sesquiterpene lactones, laurenoperoxylides A (1) and B (2) were first reported in nature.
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Sesquiterpene lactones from L. nobilis inhibited LPS-induced NF-κB transcriptional activity in RAW 264.7 cells.
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Potent inhibition on NF-κB transcriptional activity was exerted by 11-exo-methylensantonin (9) (IC₅₀ value of 4.0 μM).

Abstract

The leaves of Laurus nobilis, commonly called as bay leaves, have been traditionally used for the treatment of inflammatory symptoms. As a part of the research on the characterization of bioactive constituents from natural products, twenty one sesquiterpene lactones were isolated from the leaves of L. nobilis. Among them, laurenoperoxylides A (1) and B (2) were first reported in nature and sivosinolide (11), altissin (12), maroniolid (13) and 4α-hydroxy-guaia-10(14), 11(13)-diene-12,6α-olide (20) were first isolated from this plant. The anti-inflammatory activity of isolated compounds was evaluated by measuring their effects on the NF-κB transcriptional activity induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages cells. Among twenty one sesquiterpenes, 11-exo-methylenesantonin (9) exerted the most potent inhibition with an IC₅₀ value of 4.0 μM. Santamarine (4), magnolialide (5) and zaluzanin D (18) also significantly inhibited NF-κB activity with IC₅₀ values of <10 μM. Conclusively, sesquiterpene lactones from L. nobilis inhibited LPS-induced NF-κB transcriptional activity in RAW 264.7 cells, which support the use of L. nobilis against inflammation.

Graphical abstract

Introduction

Laurus nobilis L. (Lauraceae) which is commonly known as bay, sweet bay, true laurel, or Roman laurel, is an evergreen tree with aromatic properties. It is widely cultivated in the Mediterranean area and Europe. Dried leaves of L. nobilis are used as spices in foods. They are also used in perfumes and soaps of the cosmetics industry. Traditionally, they have been used for the treatment of rheumatism, earaches, and gastrointestinal inflammation (Heinerman, 1983; Hafizoǧlu and Reunanen, 1993). Previous studies have demonstrated that the leaves of L. nobilis possess antimicrobial and antioxidant activities (Jakupovic et al., 1986; Julianti et al., 2012). Essential oils and various monoterpenes and sesquiterpenes are reported as the major constituents of the leaves of L. nobilis (Cisero et al., 1992; Caputo et al., 2017).

Inflammation is a protective response to variety of aggressors (Serhan, 2017). Although it is a defense mechanism, the complex events in the uncontrolled inflammation reaction can cause extensive tissue damages that can further progress to painful and/or chronic states (Chen et al., 2017). Inflammation is also involved in different diseases e.g. arthritis, atherosclerosis, allergy, the metabolic syndrome, sepsis and auto-immune diseases as well as cancer (Libby et al., 2002). Nuclear factor-κB (NF-κB) is a key regulator of the cellular inflammatory and immune responses (Albert and Baldwin, 1996). NF-κB activates the expression of a wide range of target genes, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) (Albert and Baldwin, 1996; Kim et al., 2017). The constitutive activation of NF-κB has been associated with a number of human diseases, including inflammatory diseases and cancers (Makarov, 2000). Therefore, identification of NF-κB inhibitors is expected to provide a direction for the development of novel anti-inflammatory and anticancer agents (Makarov, 2000; Jin et al., 2006).

As a part of our ongoing search for anti-inflammatory compounds from traditional medicinal plants, L. nobilis was chosen in this study. To the best of our knowledge, there is lack of scientific reports revealing the anti-inflammatory activity of L. nobilis leaves. Therefore, the aim of our investigation was to characterize the anti-inflammatory constituents from L. nobilis by measuring the inhibitory effect on NF-κB activation. Inhibitory activity of L. nobilis on NF-κB activation was evaluated using an NF-κB reporter gene assay system in LPS-stimulated RAW 264.7 cells.

Section snippets

Plant material

The dried leaves of L. nobilis were collected from South of Lebanon on August 2014. Identification was conducted by the herbarium of College of Pharmacy, Chungbuk National University of Korea (Osong, Cheongju, Korea), where voucher specimen (CBNU-2014-LN) is deposited (Fig. 1).

General experimental

NMR spectra were determined with a Bruker DRX 400, 500 MHz spectrometer using CDCl₃ and CD₃OD as solvents. ESI-MS and HRESIMS data were recorded on VG Auto-spec Ultima mass spectrometers and a Bruker maXis 4 G

Results and discussion

Leaves of L. nobilis have been traditionally used for the treatment of inflammatory symptoms, therefore, we tried to find out the active compounds to support traditional uses. The methanolic extract was fractionated into n-hexane, CH₂Cl₂, EtOAc and n-BuOH fractions. Further fractionation of CH₂Cl₂ and EtOAc soluble fractions by several chromatographic methods resulted in the isolation of twenty one compounds.

Acknowledgements

This work was supported by Medical Research Center program (2017R1A5A20155541) through the National Research Foundation of Korea.

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View full text

NF-κB inhibitory sesquiterpene lactones from Lebanese Laurus nobilis

Highlights

Abstract

Graphical abstract

Introduction

Section snippets

Plant material

General experimental

Results and discussion

Acknowledgements

Eur. J. Med. Chem.

Food Chem.

Phytochemistry

Food Chem.

Phytochemistry

Phytochemistry

Mol. Med. Today

Phytomedicine

Bioorg. Med. Chem.

Phytochemistry

The NF-κB and IκB proteins: new discoveries and insights

Ann. Rev. Immunol.

Studies on the syntheses of sesquiterpene lactones. 11. The syntheses of 3-epizaluzanin C, zaluzanin C, zaluzanin D, and related compounds 3. α-hydroxyguaia-1 (10), 4 (15), 11 (13)-trieno-12, 6. α-lactone and 3.α.-hydroxyguaia-4 (15), 9, 11 (13)-trieno-12, 6. α-lactone

J. Org. Chem.

Laurus nobilis: composition of essential oil and its biological activities

Molecules

Inflammatory responses and inflammation-associated diseases in organs

Oncotarget

Synthesis of sesquiterpene derivatives as potential antitumor agents; elemane derivatives

Arch. Pharm. Res.

Sesquiterpene lactones of Laurus nobilis leaves

J. Nat. Prod.

Sesquiterpenoids and other chemical components from the roots of Dolomiaea souliei

Chem. Nat. Comp.