Received: 1 August 2017 Revised: 9 September 2017 Accepted: 14 September 2017 DOI: 10.1002/ptr.5946 REVIEW Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent Ipek Süntar1 | Seyed Mohammad Nabavi2 | Davide Barreca3 | Nicolas Fischer4 | Thomas Efferth4 1 Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, 06330 Medicinal plants have always had great value for the human population due to their valuable Ankara, Turkey constituents and potential bioactivities. The objective of this review is to present an updated 2 Applied Biotechnology Research Center, overview of an important medicinal plant genus Nepeta L., from the family Lamiaceae, revealing Baqiyatallah University of Medical Sciences, its traditional utilization, biological activity, phytoconstituents, and mechanisms of action. For this 1435916471 Tehran, Iran purpose, a literature survey was carried out by using SciFinder, ScienceDirect, Scopus, PubMed, 3 Department of Chemical, Biological, Pharmaceutical, and Environmental Sciences, and Web of Science followed by a revision of the bibliographies of the related articles. We have University of Messina, Italy described and analyzed the role of plants in drug discovery and the importance of Nepeta species. 4 Institute of Pharmacy and Biochemistry, Information on the utilization purposes of Nepeta species in folk medicine has been emphasized, Johannes Gutenberg University of Mainz, and scientific studies on the biological effects and secondary metabolites are addressed. Nepeta Staudinger Weg 5, 55128 Mainz, Germany species are characterized by terpenoid‐type compounds and phenolic constituents, which exert Correspondence several activities such as an antimicrobial, repellent against major pathogen vector mosquitoes, Ipek Süntar, Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Etiler, insecticide, larvicide against Anopheles stephensi, cytotoxic anticarcinogen, antioxidant, 06330 Ankara, Turkey. anticonvulsant, analgesic, anti‐inflammatory agent, and antidepressant, revealing its importance Email: [email protected] in medicinal and agricultural fields. On the basis of numerous studies, the Nepeta genus Davide Barreca, Department of Chemical, Biological, Pharmaceutical, and Environmental demonstrates remarkable therapeutic effects against various diseases. However, clinical studies Sciences, University of Messina, Italy. are warranted to confirm preclinical findings. Email: [email protected] KEYWORDS biological activity, folk medicine, Lamiaceae, Nepeta, phytochemistry 1 | INTRODUCTION and commonly distributed in temperate regions (Hedge, 1992; Kumar, Mathela, Tewari, & Bisht, 2014; Lawrence, 1992). Since time immemorial, natural products have been widely used for the The genus Nepeta L. (catmint), a large genus of the family treatment of human diseases (Suppakul, Miltz, Sonneveld, & Bigger, Lamiaceae, is named after the ancient Italian City of Nephi (J. Hussain, 2003). In particular, plants possess economically and therapeutically Rehman, & Hussain, 2010; J. Hussain, Ullah, Hussain, Hussain, & Shah, valuable metabolites; therefore, plant products gained extensive 2008). It is also known as Glechoma and Cataria and it contains about importance to be used for medicinal purposes (Balandrin, Klocke, 280 annual and perennial species, the majority of which are aromatic Wurtele, & Bollinger, 1985; Yildirim, Karakas, & Turker, 2013). One plants native to temperate Europe, Asia, North Africa, and North of the most important plant families that have great economic value America (Jamila et al., 2011; Naghibi, Mosaddegh, Mohammadi as medicinal, cosmetic, and food products is the family Lamiaceae, Motamed, & Ghorbani, 2005; Shakeri et al., 2014). Nevertheless, the which is composed of about 252 genera and more than 6,700 species greatest diversity of Nepeta species has been reported for two areas, Iran and the Western Himalayas (Jamzad et al., 2003; Pojarkova, 1954). In Iran, the Nepeta genus is represented by 75 species, of which, Abbreviations: CNS, central nervous system; DPPH, 2,2‐diphenyl‐1‐ 54% are endemic. The species used as medicinal herbs in Iran are picrylhydrazyl; GC, gas chromatography; IC50, half‐maximal inhibitory concentration; ILK, integrin‐linked kinase; LC50, lethal concentration, 50%; Nepeta ispahanica Boiss., Nepeta binaloudensis Jamzad, Nepeta LD50, lethal dose, 50%; MIC, minimum inhibitory concentration; MITF, bracteata Benth., Nepeta pogonosperma Jamzad et Assadi, and Nepeta microphthalmia‐associated transcription factor; PKB/AKT, protein kinase B/AKT; pungens (Bunge) Benth. Approximately 30 species have been PMS, premenstrual syndrome; RD50, median repellent dose value; WHO, World Health Organization recorded in India, mostly in the temperate Himalaya (J. Hussain, Phytotherapy Research. 2017;1–14. wileyonlinelibrary.com/journal/ptr Copyright © 2017 John Wiley & Sons, Ltd. 1 2 SÜNTAR ET AL. Rehman, Hussain, Al‐Harrasi, et al., 2012), and 58 species have been cough, rheumatism, and wound healing (Mükemre, Behçet, & found in Pakistan (J. Hussain et al., 2010). On the other hand, the Çakılcıoğlu, 2015). In Serbia, infusion prepared from the herb of Nepeta genus is represented by 33 species in Turkey, 17 of which N. cataria L. was utilized to relieve menstrual difficulties and treat have been reported to be endemic (Kaya, Demirci, & Baser, 2007). ovarian cysts (Zlatkovic, Bogosavljevic, Radivojevic, & Pavlovic, The wide variety and high content of terpenoid, flavonoid, and phe- 2014). The extract and smoke of the whole plant of Nepeta lagopsis nolic compounds of Nepeta species provide diverse pharmacological Benth. was reported to be used to heal wounds (Rehman, Mashwani, effects, justifying its traditional utilization for medicinal purposes. Khan, Ullah, & Chaudhary, 2015), and a decoction prepared from aerial Several species are known for their medicinal properties and are parts of Nepeta praetervisa Rech. f. was used against helminth infections used in folk medicine for their diuretic, diaphoretic, antitussive, in Pakistan (Bibi et al., 2016). On the other hand, in China, N. cataria was antispasmodic, antiasthmatic, febrifuge, emmenagogue, and sedative used with several other plants in medicinal plant formulations for the activities (Formisano, Rigano, & Senatore, 2011; Nestorović et al., treatment of mastitis, measles, dermatitis, dysentery, chronic rhinitis, 2010; Shakeri et al., 2014). Nepeta species have been assessed chronic tonsillitis, and swollen sore throat (Zhang et al., 2015). mainly for their potential antitumor, anti‐inflammatory, and antimicrobial effects (Afshar, Nematpour, Meshkani, & Khafi, 2017; J. Hussain, Rehman, Hussain, Ali, & Al‐Harrasi, 2012; Kumar, 3 | BIOLOGICAL ACTIVITY STUDIES ON Mathela, Tewari, & Singh, 2014; Nestorović et al., 2010; Nostro, Nepeta L. GENUS Cannatelli, Crisafi, & Alonzo, 2001). The leaves of Nepeta species are also prepared and consumed as herbal tea, and the essential oils 3.1 | In vitro and in vivo studies are used as perfumes or fragrances and for food flavoring (Khajeh, Yamini, & Shariati, 2010). The feline and canine attractant, insect 3.1.1 | Antimicrobial activity repellant, arthropod defense, antibacterial, antifungal, and antiviral In the study conducted by Nostro et al. (2001), the effect of N. cataria effects and other biological activity features are generally attributed extract on 44 Staphylococcus aureus strains was studied. In doing so, to the terpenoid constituents found in Nepeta species (Kumar, the effect of subminimum inhibitory concentrations on coagulase, Mathela, Tewari, & Singh, 2014; Nestorović et al., 2010; Tucker & deoxyribonuclease, thermonuclease, and lipase production and on Tucker, 1988; Wagner & Wolf, 1977). Besides the terpenoid‐type in vitro adherence was assessed. The enzymes, deoxyribonuclease, compounds including monoterpenes, sesquiterpenes, cyclopentanoid thermonuclease, and lipase were found to be inhibited by one‐half iridoid derivatives, and nepetalactones, the presence of other and one‐fourth minimum inhibitory concentrations (MICs), and a secondary metabolites including phenolics and flavonoids was shown reduction of adherence was demonstrated (Nostro et al., 2001). A for Nepeta species according to phytochemical analyses (Bicchi, varying degree of growth inhibitory activity against some Sclerotium, Mashaly, & Sandra, 1984; Formisano et al., 2011; Kaya et al., Macrophomina, and Fusarium species was indicated by former reports 2007; Khalil, Gedara, Lahloub, Halim, & Voehler, 1997; Rapisarda, on the antifungal characteristics of the essential oils of some Nepeta Galati, Tzakou, Flores, & Miceli, 2001; Shakeri et al., 2014). Essential species (Saxena & Mathela, 1996). The objective of the study by oils containing an iridoid or lactone skeleton were found to be more Kumar, Mathela, Tewari, and Singh (2014) was not only to identify effective than those having regular terpene constituents with regard the antifungal constituents of Nepeta elliptica Royle ex Benth. but also to their antimicrobial potential, which might be attributed to their to evaluate the growth of mycelium and spore germination inhibition higher hydrogen bonding capacity (Bisht et al., 2010; Kumar, potential of the oil and its almost exclusive constituent (7R)‐trans, Mathela, Tewari, & Singh, 2014). Among the Nepeta species, Nepeta trans‐nepetalactone (>85% in the oil) against five plant pathogenic cataria L. is the most intensively studied species. On the other hand, fungi.