•  Published: 29 July 2020

by Michele Zaccai ¹,Ludmila Yarmolinsky ²,Boris Khalfin ^2,3,Arie Budovsky ⁴,Jonathan Gorelick ²,Arik Dahan ³ andShimon Ben-Shabat ^3,*

¹ Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel

² Eastern R&D Center, Kiryat Arba 9010000, Israel

³ Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel

⁴ Research & Development Authority, Barzilai University Medical Center, Ashkelon 7830604, Israel

Abstract

Lilium candidum L., known as Madonna, meadow, or white lily, is a bulbous plant from the Liliaceae family, originating in the Middle East. L. candidum has been abundantly used in folk medicine since ancient times to relieve a variety of ailments, including age-related diseases, burns, ulcers, and coughs. The aim of this article is to investigate the anti-inflammatory and anti-diabetic activities of L. candidum extracts and its active phytochemicals. Some active volatile phytochemicals were identified using gas chromatography–mass spectrometry (GC-MS) analysis. Significant (p < 0.001) anti-diabetic properties of the extracts kaempferol, linalool, citronellal, and humulene were demonstrated by an elevation in glucose uptake by adipocytes. The significant (p < 0.01) effect of the plant extracts kaempferol, citronellal, and humulene on the secretion of pro-inflammatory cytokines interleukin 6 (IL-6) and interleukin 8 (IL-8) was demonstrated using enzyme-linked immunosorbent assay. Altogether, L. candidum and its rich collection of phytochemicals hold promising medicinal potential, and further investigations of its therapeutic prospects are encouraged.

Keywords: Lilium candidum; phytochemicals; medicinal activities

1. Introduction

The prevalence of age-related diseases (ARDs) including cardiovascular diseases, cancer, type 2 diabetes, neurodegenerative diseases, and obesity is rapidly increasing worldwide [1]. Recent studies provide strong evidence suggesting an essential role of chronic inflammation in the pathogenesis of the above-mentioned ARDs [2,3,4]. In addition, genotoxic stress, which is a component of a wide variety of pathological conditions, not only causes extensive DNA damage but also activates pathways leading to chronic inflammation (the ERK, JNK, and p38 MAPK pathways) and transcription of pro-inflammatory cytokines (TNF-α, IL-1β, interleukin 6 (IL-6)), chemokines (interleukin 8 (IL-8)), adhesion molecules (VCAM-1, ICAM-1, P-, E-selectin), and other pro-inflammatory enzymes including iNOS and COX-2 [5]. This in turn leads to an elevated pro-inflammatory status that is likely to set the stage for increased vulnerability to many ARDs [6].

Unfortunately, current therapeutic agents have inadequate efficacy and many serious adverse effects in treating all kinds of ARDs [7]. All possible options should be considered in order to develop new drugs that are more effective. In fact, many medicinal plants are able to cope with inducers and/or consequences of stress such as thermal or oxidative insults, ionizing radiation, DNA damage, exposure to carcinogens, and inflammatory burden, which is one of the important determinants of survival and longevity [8,9].

Lilium candidum L. has been well known in folk medicine for a long time, not only in the plant’s native regions (Balkans, Middle East) but also in other parts of the world in which it was naturalized, such as various European countries, North Africa, and Mexico. In folk medicine worldwide, L. candidum is prominently associated with dermal conditions, cosmetics, and anti-inflammatory remedies [10,11,12]. A vast ethnopharmacological research study performed in the Campidano Valley and Urzulei district in Italy revealed many medicinal benefits of L. candidum. Among them were application of lily petals and a decoction of bulbs soaked in milk as pectoral poultices, application of petals soaked in spirit as a wound-healing remedy, and the use of oil prepared from flowers as a treatment for mastitis [13]. In addition, ethnopharmacological research in Lucca province in Italy demonstrated the use of L. candidum bulbs as an anti-viral agent to treat shingles (Herpes zoster), and its bulbs and flowers for treatment of skin and articular diseases [14]. L. candidum was also successfully used in anti-inflammatory and dermatological remedies in the Catalan district of the Eastern Pyrenees [14].

L. candidum L., commonly known as Madonna, meadow, or white lily, is a geophyte from the Liliaceae family growing in the wild in several countries of the Middle East. The origin of L. candidum is believed to be in Lebanon and Israel, as well as several parts of Greece [15,16,17], thus Israel represents the Southern border of L. candidum distribution and only few populations are found in the Carmel and the Galilee regions. It is considered an endangered species and as such the plants are protected [15,18]. A collection of wild L. candidum ecotypes from different locations exhibited genetic variation in morphologic and phenologic traits, as well as in phytotoxicity of their leaf extracts [18,19].

Effective delivery of herbal compounds and plant extracts is a very important issue, since drawbacks such as hydrophobicity, insolubility in water, high volatility, and instability pose a challenge [20,21]. The application of innovative drug delivery systems including phytosomes, nanoparticles, hydrogels, microspheres, transferosomes and ethosomes, self-nanoemulsifying drug delivery systems (SNEDDS), self-microemulsifying drug delivery systems (SMEDDS) and so on may improve the biopharmaceutical features of the delivered compounds [22,23].

Owing to its rare beauty, its fragrance, and its glorious symbolism, L. candidum appears to be a fascinating plant. It is therefore not surprising that Madonna lily has also been sought for therapeutic reasons. However, most L. candidum therapeutic properties known from folk tradition have not yet been investigated by scientific methods except anti-fungal [24], anti-cancer [25,26], and anti-viral [27] properties. Thus, the present study is aimed at identifying the presence of selected volatile compounds of the plant, assessing the medicinal potential of all known compounds using bioinformatics, and investigating anti-inflammatory and anti-diabetic activities of L. candidum extract and its active phytochemicals.

Keywords: Herb, Alternative medicine, Insomnia, Sleep, Meta-analysis, Systematic review

Reference:

https://www.mdpi.com/2223-7747/9/8/959/htm