Chemical characterization, computational analysis and biological views on Daphne gnidioides Jaub. & Spach extracts: Can a new raw material be provided for biopharmaceutical applications?

https://doi.org/10.1016/j.compbiolchem.2020.107273Get rights and content

Highlights

  • Plants are precious sources of bioactive compounds.

  • Vicenin-2 and 3-O-p-coumaroyl-5-O-caffeoylquinic acid were the main identified compounds in leaf and both root and stem extracts, respectively.

  • D. gnidioides had promising antibacterial and anticancer activities.

  • D. gnidioides may have exhibited its anticancer effect against the HeLa cell line by increasing autophagic gene expression.

  • The extracts of D. gnidioides exhibited significant tyrosinase inhibitory effects.

Abstract

The scientific world tends to turn to natural products such as medicinal and aromatic plants because of the inadequacy of commercially available synthetic drugs as antibiotics or anticancer, and their adverse effects on healthy tissues. One of these plants is Daphne gnidioides Jaub. & Spach, which belongs to the Thymelaeaceae family, and there is no data in the literature on its biological activity. This study is aimed to elucidate the chemical profiles and in vitro anticancer, antibacterial and DNA protection and enzyme inhibitory properties of methanol extracts of root, stem, and leaf of D. gnidioides Jaub. & Spach. Polyphenolic components of the extracts were characterized by HPLC-MS/MS. The highest phenolic content was detected in the leaf extract (TIPC = 43.5 ± 0.5 mg/g DE), followed by stem (TIPC = 27.3 ± 0.7 mg/g DE) and root (TIPC = 18.3 ± 0.2 mg/g DE) extracts. Vicenin-2 and 3-O-p-coumaroyl-5-O-caffeoylquinic acid were the main identified compounds in leaf and both root and stem extracts, respectively. The extracts did not show any protective effect on DNA against experimental Fenton’s reagent. The minimum inhibitory concentration and the minimum bactericidal concentration values for the root and leaf extracts against tested bacterial strains ranged from 31.25 to 500 μg/mL. After 48 h interaction of the cancer cell lines with the extracts, only the stem extract had significant cytotoxicity on HeLa cells (IC50 = 86.16 μg/mL). No remarkable activity of the extracts, which was tested against MDA-MB-231, was detected (IC50 > 1000 μg/mL). These data showed that D. gnidioides Jaub. & Spach stem extract inhibited the survival of HeLa cells in a time-dependent manner. After the treatment of IC50 concentration of stem extract with HeLa cells, an increase in LC3-II autophagic gene expression was detected. Also, the extracts exhibited significant tyrosinase inhibitory effects which were confirmed by molecular docking. To sum up, the tested extracts could be used as a starting point for the development of new multifunctional drugs.

Introduction

Medicinal and aromatic plants are valuable sources of bioactive compounds with a panel of potential biological activity aimed to cure various diseases and to maintain a healthy life (Nile et al., 2017). They have been used for various purposes such as food, pharmaceuticals, and cosmetics from the beginning of humankind. Nowadays, the most prominent and researched properties of medicinal and aromatic plants are their use for therapeutic purposes. Many drugs used in modern medicine have already obtained from plants (Yuan et al., 2016).

The genus Daphne is included in the Thymelaeaceae family and seven species (Daphne gnidioides Jaub. & Spach, Daphne glomerata Lam., Daphne sericea Vahl., Daphne mezereum L., Daphne pontica L., Daphne mucronata Royle, Daphne oleoides Schreber) grow naturally in Turkey (Tan, 1982). Daphne species are mainly used in Turkish traditional folk medicine against various diseases such as ulcers, gout, rheumatism, abscess, wound and diarrhea (Grieve and Leyel, 1967; Yeşilada et al. 1999; Sezik et al., 2001). D. gnidioides is grown naturally in the northeastern Mediterranean (Ari et al., 2014). Flavonoids, coumarins, diterpenes, triterpenes, and steroids are major components in the plant(Stout et al., 1970; Ulubelen et al., 1986; Taninaka et al., 1999).

Due to synthetic drugs are not always adequate in the treatment of diseases and many have the adverse effects on the living organism, the scientists have focused on developing more effective and safer agents. Besides, the discovery of such agents and their integration into modern medicine will contribute to the elimination of the mentioned problems. Biological activity studies of Daphne species showed that abortive, anticancer, anti-inflammatory, antimicrobial, antiparasitic, antioxidant, immunostimulant, hemostatic, and hypotensive properties (Kogiso et al., 1976; Katti and Tandon, 1979; Ulubelen et al., 1986; Craker and Simon 1987; Dagang et al., 1991; Cerrati et al., 1992; Yeşilada et al., 1997). To the best of our knowledge, there is no previous report about the biological activities of D. gnidioides in the literature. The current study presents pieces of information about chemical analysis and biological properties of D. gnidioides. In this context, methanol extracts of root, stem, and leaf of D. gnidioides were prepared. The chemical analysis of the extracts was performed using HPLC-MS/MSn. Biological properties of the extracts were investigated in terms of anticancer, antibacterial, DNA protection activity and enzyme inhibition activities.

Section snippets

Plant materials and extract preparation

Daphne gnidioides Jaub. & Spach samples were gathered in the Mediterranean region of Turkey (Antalya (Akseki): 673 m, 36S 395817E; 4082048 N, Voucher no: Zengin and Sanda 1001). The plants were identified by botanist Dr. M. Aydin Sanda (Mus Alpaslan University, Turkey). The plant materials (stems, roots, and leaves) were dried at 22 °C for 10 days. The dehydrated parts of the plant were crushed with a laboratory mill (particle size about 1 mm), and then the grounded plant materials were kept in

HPLC-ESI-MSn

The characterization of the chemical compounds by HPLC-ESI-MSn using the negative ion mode, which provides higher sensitivity and information than the positive mode for phenolic compounds was performed. The base peak chromatograms of the different parts of D. gnidioides are indicated in Fig. 6, keeping the same numbering for compounds based on their retention time. Apigenin, gallic acid, esculetin, kaempferol, luteolin, quercetin, and vicenin-2 were used for the characterization of the detected

Conclusion

This work was report a preliminary investigation based on in vitro biological activity and chemical profiles of D. gnidioides extracts. DNA preservation, antibacterial, anticancer and enzyme inhibitory activities of extracts were analyzed. These biological activities could be associated with high vicenin-2 (16) and 3-O-p-coumaroyl-5-O-caffeoylquinic acid (38) content in the extracts. The antibacterial activity of the leaf extract was determined against S. haemolyticus at low concentrations

Credit Author Statement

Tevfik Hasan Can: Data curation; Methodology; Software; Writing - original draft

Enis Fuat Tufekci: Data curation; Methodology; Software; Writing - original draft

Yasemin Celik Altunoglu: Data curation; Methodology; Software; Writing - original draft

Mehmet Cengiz Baloglu: Data curation; Methodology; Software; Writing - original draft

Eulogio J. Llorent-Martínez: Methodology; Software; Writing - original draft

Azzurra Stefanucci: Methodology; Software; Writing - original draft

Adriano Mollica:

Funding information

This work was supported by the Scientific Research Project Unit of Kastamonu University [grant numbers KUBAP-01/2018-6].

Declaration of Competing Interest

The authors declare no conflicts of interest.

Acknowledgments

Technical and human support provided by CICT of Universidad de Jaén (UJA, MINECO, Junta de Andalucía, FEDER) is gratefully acknowledged.

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