What’s next? In the loop we have the following species to start our I + D phases:

Lupulus humulus (Hops)

The plant of Humulus lupulus L. is well-known throughout the world as the raw material in the brewing industry. The female inflorescences (hop cones or “hops”), rich in polyphenolic compounds and acylphloroglucides are widely used to preserve beer and to give it a characteristic aroma and flavour. In addition hop cones have long been used for medicinal purposes. In particular, hop preparations were mainly recommended for the treatment of sleeping disorders, stress and anxiety as a mild sedative, and for the activation of gastric function as bitter stomachic (Lin et al., 2019; Kyrou et al., 2017; Franco et al., 2012; Kurasawa et al., 2005).

In line with a growing interest in the health benefits of plants used in traditional medicine, Humulus lupulus has received particular attention by the researchers and, as a result, a significant number of articles have been published.

Starting from the second half of the 20th century, several phytochemical studies were performed to investigate the composition of hop cones and other parts of the plant, leading to the isolation and identification of pharmacologically relevant compounds such as flavanones, chalcones, phloroglucinol derivatives. During the past decade, many pharmacological investigations in vitro and in vivo tried to produce scientific evidence of the reported traditional uses. The effect of hop plant at the central nervous system level and in particular its efficacy in sleeping disturbances has been repeatedly studied in laboratory animals, but the results are sometimes contradictory and still require a deep investigation. Moreover the number of clinical studies supporting the use of hops as a sedative is rather limited: therefore the effectiveness of hops in the treatment of sleeplessness is still questionable.

In recent years the estrogenic properties as well as the potential cancer chemopreventive activities of hops have been investigated and some active compounds from hop have received much attention (Lin et al., 2019; di Sotto et al., 2018; Jiang et al., 2018; Nuutinen, 2018; Kyrou et al., 2017). Among these, 8-prenylnaringenin is considered as one of the most potent phytoestrogens currently known, while xanthohumol proved to possess a broad spectrum of cancer inhibiting mechanisms (Liu et al., 2015; Zanoli et al., 2008; Chadwick et al., 2006). 

Artemisia afra

Artemisia afra is one of the most popular and commonly used medicinal herbs in “Traditional African Medicine” (TAM). Artemisia afra grows in the mountainous regions of Kenya, Tanzania, Uganda and even northern Ethiopia; it is also widely distributed in southern Africa, such as South Africa, Namibia and Zimbabwe. Its different uses indicate that Artemisia afra has antiviral, antibacterial and anti-inflammatory activities (Liu et al, 2008). In TAM, it has generally been used to treat a variety of conditions including coughs, colds, headaches, gastric disorders, colic, asthma, malaria, diabetes, bladder disorders, influenza, seizures, fever, inflammation of the heart, and rheumatism (Thring & Weitz, 2006).

  Even with its wide use, however, only limited research has been conducted on this species (Van Wyk et al., 2008).

It has been confirmed that among all species of the genus Artemisia, even in comparison with Artemisia annua, Artemisia afra has the highest antioxidant properties (Ferreira, 2009). So far, 131 compounds have been identified in the species Artemisia afra. Most of these can be classified as monoterpenes and sesquiterpenes; and among the most characteristic substances are artemisyl acetate, 1,8-cineole, artemisia ketone, thujone α-copaeno/alcamphor, santolin alcohol (Asfaw et al., 2005). In addition, A. afra is rich in pentacyclic triterpenes with strong immunomodulatory and antimalarial activity. (Kriel, 2010). 

Artemisia thuscula

Artemisia thuscula, an endemic plant of the Canary Islands, is renowned for its traditional medicinal use for its antifungal, antibacterial and anti-cancer activity. In fact, ethanolic extracts of this plant showed interesting cytotoxic activity against Fusarium fungi and antibiotic activity against Gram-positive bacteria (Cosoveanu et al., 2018). In addition, diuretic properties have been attributed to Artemisia thuscula (Benjumea et al., 2005). Studies show that it has a high content of sesquiterpene lactones such as vulgarin and tabarin (Gonzalez et al., 1998), which have been shown to have a high anti-cancer potential (Kweon et al., 2015). 

Artemisia capillaris

Artemisia capillaris (Yin-Chen) is a famous plant used, like Artemisia annua, in the traditional Chinese medicine (TCM). In this case, Artemisia capillaris has been used for centuries to treat acute and chronic hepatitis in China. Enins are a characteristic constituent of this medicinal plant, which may be responsible for the anti-hepatitis B virus properties (Geng et al., 2018).  In addition, Artemisia capillaris has other scientifically proven antiviral properties, as it has been used empirically to control hand, foot and mouth disease (HFMD), which is commonly caused by enterovirus 71 (Yen et al., 2017). Other components present in this plant such as hydroxyacetophenone, β-sitosterol, scoparone,

quercetin, arcapillin, capillin, 6,7-dimethylesculetin, capillone, capillarin, cirsilineol, cirsimaritin, and capilarisin have been shown to have anti-inflammatory, choleretic, hepatoprotective, anti-fibrotic, and anti-tumor activities (Jang et al, 2015). 

Urtica dioica (Stinging nettle)

Urtica dioica L. belongs to the family Urticaceae, is a perennial herb commonly known as ′stinging nettle′. Originally native to Europe, much of temperate Asia and western North Africa  Urtica dioica has been known in the world as a medicinal herb for a long time. The leaves and stems bear many stinging hairs or trichomes, which act like hypodermic needles, injecting histamine (an organic nitrogenous compound involved in local immune and inflammatory responses) and other chemicals that cause a painful sting or paresthesia (Andersen et al., 2015). Indeed, urticaria, a form of contact dermatitis, derives from this plant species.

Urtica dioica is widely used by the traditional medicinal practitioners for curing various diseases such as nephritis, haematuria, jaundice, menorrhagia, arthritis and wound healing (Dhouibi et al., 2020; Haouari et al.,, 2019; Kargozar et al., 2019; Bouassida et al., 2017; Joshi et al., 2014). Phytochemical studies revealed the presence of many valuable chemical compounds like phytosterols, saponins, flavonoids, tannins, proteins and amino acids. The plant has been reported to have other various pharmacological activities like antibacterial, antioxidant, analgesic, anti-inflammatory, antiviral, immunomodulatory, hepatoprotective, anti-colitis and anticancer effects (Dhouibi et al., 2020; Esposito et al., 2019; de Vico et al., 2018). Moreover,  Urtica dioica is also used as food, fiber, paint and cosmetics. 

Thymus spp (Thyme)

The genus Thymus L. (thyme) of the Lamiaceae family comprises over 200 different species. The Thymus species have wide application in medicine as well as in food seasoning and flavoring, but only a few species are economically important, particularly those used as spices such as the leaves of Thymus vulgaris, native to southern Europe, and Thymus zygis. Other important thyme species are also those with known pharmacological activity, such as Thymi herba and Serpylli herba are used for the treatment of catarrhs of the upper respiratory tract, bronchitis, and pertussis (Schött et al., 2017).

Furthermore, thyme also has antioxidative properties and antimicrobial activities against a wide range of gram-positive and gram-negative bacteria, yeast, and fungi (Vinciguerra  et al., 2019; Manconi et al., 2018). 

These versatile pharmacological effects can be attributed to the secondary plant metabolites, especially to essential oil and polyphenols (Schött et al., 2017). The composition of the essential oil in the genus Thymus L. varies widely. In the pharmacological relevant Thymus species, monoterpenes and sesquiterpenes dominate with a content of about 80% while non-terpenoid aliphates, benzene derivatives, and phenylpropanoids have been found only sporadically (Perez  et al., 2019; Feriotto et al., 2018). Despite the numerous compounds known for essential thyme oil, there are only a few substances with a content higher than 10%. In particular, these are for the pharmacologically relevant Thymus species monoterpenes such as thymol, carvacrol, p-cymene, γ-terpinene, and β-linalool, whereas sesquiterpenes like β-caryophyllene and β-bisabolene are characteristic for Serpylli herba (Dehghani et al., 2019). 

Mentha spp (Mint)

The genus Mentha L., included in the family Lamiaceae, are herbaceous-looking, aromatic, fast-growing perennials linked to watercourses. Of Mediterranean origin, they are distributed mainly in Europe, Asia and Africa (Morales et al., 2009). The most widely used species, Mentha piperita (mint) and Mentha spicata (peppermint), are grown in a major way to obtain their essential oils, which contain highly valuable terpenes and have various uses in cosmetics, nutraceutics, pharmaceuticals, food and perfumery industries (Anwar et al., 2019; Shasany et al., 2005). 

Among the main applications are those that are eminently culinary, as a flavouring and condiment for many dishes and infusions; but on the other hand, they are also widely used for their essential oils to flavour liqueurs, sweets, chewing gums, toothpastes and cigarettes among others.

The leaves contain flavonoids (apigenol, luteol, eryiodictyol-7-O-rutoside), monoterpene (menthol, chin), diterpenoids (β-betulenol), phenolic acids, triterpenes and tannins; while the essential oil contains menthol, carvone, cineol, thymol, pinene, limonene, acetic and isovaleric acid (McKay et al., 2006; Cáceres, 1999). Experimentally, biocidal studies show that ethanolic extract from leaves of the genus mentha has bactericidal, insecticidal, antioxidant and anti-inflammatory activity (Park et al., 2019; Alexa et al., 2018; Rosato et al, 2018); the extract and essential oil has activity against phytopathogenic fungi such as Altenaria tenuis, Botrytis allii, Cladosporium fulvum, Curvularia penniseti, Helminthosporium sp, insects  as Leptinotarsa decemlineata and viruses like herpes (Anwar et al., 2019; Cáceres, 1999). 

Pelargonium graveolens

Pelargonium genus, more than 750 species, probably originates from South Africa and introduced to Europe in the 17th century and have since been hybridized all over the world. Pelargonium graveolens  is a shrubby perennial annual plant growing to a height of 1 meter. The plant has typical small, pink flowers; and the leaves and stalks are the essential parts of this plant. Due to the fact that their essential oils are largely utilized in the perfumery, cosmetic and aromatherapy industries all over the world.

Many chemical constituents such as volatile substances, terpenoids, flavonoids, phenolics, coumarins, cinnamic acids and tannins have been isolated from the plant. Citronellol, trans-geraniol, 10-epi-γ- eudesmol , isomenthone , linalool , geranyl acetate, γ- Cadinene, geranyl butyrate, geranyltiglate and gemacrene D were identified as the major constituents of the Pelargonium graveolens aerial parts essential oil (Fekri  et al., 2019; Asgarpanah  et al., 2015). 

Various studies have revealed the different pharmacological properties of Pelargonium graveolens in a range of in vitro and in vivo test models. The aerial parts of the plant have been demonstrated to possess antibacterial, antifungal, acaricidal and antioxidant activities (Ennaifer et al., 2018; Essid et al., 2017; Asgarpanah  et al., 2015). Additionally, the essential oil has potential immune modulating effects on natural killer cells, improves circulation, treats congestion especially for the breast tissue, promotes healthy immune system, stimulates and cleans the lymphatic system and is helpful for detoxification, hemorrhoids, phlebitis, indigestion and fluid retention (El-Garawani et al., 2019: Careddu  et al., 2018; Timmer et al., 2013).

Nicotiana tabacum (Tobacco)

Nicotiana tabacum is a perennial herbaceous plant native from subtropical America but it is now commercially cultivated and hybridized worldwide. Other varieties are cultivated as ornamental plants or grow as a weed. Nicotiana tabacum is a robust annual herb up to 2.5 meters with characteristic large green leaves (Rawat et al., 2013). All parts are sticky, covered with short viscid-glandular hairs, or trichomes, which exude a yellow secretion containing nicotine.

The pharmacological activities of Nicotiana tabacum is mostly due to its content of nicotine which stimulates

the nicotine receptors leading to release of substances such as acetylcholine, norepinephrine, dopamine, serotonin, vasopressin and growth hormone (Bono et al., 2019; Wilar et al., 2019; Valentine et al., 2018). Nicotine which is the major component of tobacco has been demonstrated to accelerate angiogenesis and wound healing in genetically diabetic mice (Rawat et al., 2013).The ethno medical uses include the use of the leaves (decoction) as antispasmodics, diuretics, emetics, expectorants, sedatives, and in rheumatic swellings, anesthetics, antibacterial, anticonvulsants and for anti-fungal activities (Capdesuñer  et al., 2019; Schorderet  et al., 2019; Gomes  et al., 2018; Shang  et al., 2018).