The genus Hymenocrater: a comprehensive review

Abstract

Context: The genus Hymenocrater Fisch. et Mey. (Lamiaceae) contains over 21 species in the world. Some species have been used in folk medicine around the world. The present review comprises the ethnopharmacological, phytochemical and therapeutic potential of various species of Hymenocrater.

Objective: This review brings together most of the available scientific research regarding the genus Hymenocrater. Through this review, the authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Hymenocrater species.

Methods: This review has been compiled using references from major databases such as Chemical Abstracts, Medicinal and Aromatic Plants Abstracts, ScienceDirect, SciFinder, Google Scholar, Scopus, PubMed, Springer Link and books, without limiting the dates of publication. General web searches were also carried out using Google and Yahoo search engines by applying some related search terms (e.g., Hymenocrater spp., phytochemical, pharmacological, extract, essential oil and traditional uses). The articles related to agriculture, ecology, and synthetic works and those using languages other than English or Persian have been excluded.

Results: The genus Hymenocrater contains essential oil. Flavonoids, phenolic acids and terpenoids are important constituents of this genus. The pharmacological studies confirmed that the species of the genus Hymenocrater showed antimicrobial, antiparasitic, antioxidant, anticancer and antidiabetic activities.

Conclusion: This review discusses the current knowledge of Hymenocrater species that review therapeutic potential, especially their effects on the cancer cells and gaps offering opportunities for future research.

Keywords:

• Anticancer
• antidiabetic
• antimicrobial
• antioxidant
• antiparasitic
• flavonoids
• Lamiaceae
• phenolic acids
• terpenoids

Introduction

Since ancient times, plants have been one of the first and most available resources used for treating illnesses, and throughout history, there has always been a close relationship between man and plants, and the medicinal effects of plants and their uses are well known. Currently, according to the World Health Organization (WHO), as much as 80% of the world's people depend on traditional medicine for their primary health care needs. There are considerable economic benefits in the development of indigenous medicines and in the use of medicinal plants for the treatment of various diseases. Traditional medicine involves the use of plant parts in crude form, either fresh or dried for preventing or healing various forms of ailments (Joharchi & Amiri 2012). The potential of plants as a source of new drugs is still largely unexplored (Morteza-Semnani 2015). Some species of the Hymenocrater Fisch. et Mey. (Lamiaceae) genus have been investigated from different points of view: identification of essential oils composition, antimicrobial, antifungal, and antioxidant activities, anatomical and pollen morphology, ornamentation and palynological studies (El-Gazzar & Watson 1968; Fazly Bazzaz & Haririzadeh 2003; Firouznia et al. 2005; Zaidi & Crow 2005; Barazandeh 2006; Ryding 2007; Akramian et al. 2008; Moon et al. 2008a,b; Jafari & Jafarzadeh 2008; Ahmadi et al. 2010; Miguel 2010; Ryding 2010a,b; Prakash et al. 2015). In our continuing research on the plants of the genus Hymenocrater (Morteza-Semnani et al. 2010, 2012), some of the main reports on the botanical, ethnopharmacological, phytochemical and biological activities of the species of Hymenocrater were reviewed. This is the first comprehensive review of the genus Hymenocrater. The authors hope to attract the attention of natural product researchers throughout the world to focus on the unexplored potential of Hymenocrater species. This genus needs to be investigated systematically so that potential species can be exploited as therapeutic agents.

Distribution of the genus Hymenocrater

Hymenocrater, Stachyioideae subfamily, has 21 species in the world (Taherpour et al. 2011; Shahriari et al. 2013); it is found in Iran, Iraq, Pakistan, Afghanistan, Turkey and Turkmenistan (Mozaffarian 1996; Satil et al. 2007; Jafari & Jafarzadeh 2008; Zaidi & Crow 2012; Serpooshan et al. 2014). There are 12 species distributed in the southern part of central Asia, the Caucasus, Asia Minor and Iran (Hassanzadeh et al. 2011; Drew & Sytsma 2012). It is represented by 11 species in Flora Iranica, nine of them, H. bituminosus Fisch. & C.A. Mey., H. calycinus (Boiss.) Benth., H. elegans Bunge, H. incanus Bunge, H. longiflorus Benth., H. oxyodontus Rech. f., H. platystegius Rech. f., H. sessilifolius Benth. and H. yazdianus Rech. f., have been widely distributed in Iran, four species including H. yazdianus, and H. incanus, H. platystegius and H. oxyodontus are endemic to Iran, two species in Flora of the USSR and one species in east Turkey (Rechinger 1982; Mozaffarian 1996; Kashipazha et al. 2004; Firouznia et al. 2005; Satil et al. 2007; Zarezadeh et al. 2007; Jamzad 2009; Baghestani Maybodi et al. 2010; Azimova & Glushenkova 2012; Esmaili et al. 2012; Serpooshan et al. 2014; Soodmand et al. 2015). The genus Hymenocrater is named Gol-e-Arvaneh in Persian (Mozaffarian 1996; Razzaghi-Abyaneh & Rai 2013). Hymenocrater spp. has been found in Razavi, North and South Khorasan, Azerbaijan, Fars, Golestan, Isfahan, Kermanshah, Kurdistan, Mazandaran, Qazvin, Tehran and Yazd Provinces (Rechinger 1982; Mirza et al. 2001; Ghelichnia 2002; Ghahreman et al. 2006; Ghollassi 2008; Jankju et al. 2011; Nadaf & Mortazavi 2011; Esmaili et al. 2012; Ekrami 2013; Sadeghian et al. 2015).

General morphology

There are low shrubs and perennial herbs (Mirza et al. 2001), subshrubs, glabrous or pubescent with gray or yellowish-gray bark, numerous erect branches and ovate or broad ovate, dentate, acute leaves. Flowers are usually numerous, sessile or short-pediceled, cylindrical or infundibular, corolla long and indistinctly 2-lipped, in 2–7 flowered cymes or semiverticles forming a pyramidal or subspicate inflorescens. Nutless ovoid, smooth of finely tuberculate (Hassanzadeh et al. 2011).

Ethnopharmacology

Prior to the development of modern medicine, traditional medicine systems that have evolved over the centuries among various communities were still maintained as a great traditional knowledge basis in herbal medicines (Amiri et al. 2012). Plants belonging to this genus are pharmacologically active and have been used in folk medicine all around the world (Al-Anee et al. 2014). Hymenocrater genus surprisingly possess antioxidant properties as well as antidiabetic, anticlotting, anti-inflammatory and anticancer activities, because of the presence of important metabolites including rosmarinic acid and rutin in the aerial branches (Safamansouri et al. 2014). Hymenocrater bituminosus is an ornamental plant (Azimova & Glushenkova 2012). It is reported in the Flora of the USSR that H. bituminosus has commercial value due to a lemon aroma (Satil et al. 2007). Traditional uses of the species of the genus Hymenocrater from different origins are summarized in Table 1.

Table 1. Traditional uses of Hymenocrater spp. from different origins.

Scientific name	Origin	Local name	Part used	Uses	Ref.
H. elegans	Northeast of Iran,Khorasan Province,Zangelanlo district	Shonook	Flower and leaves	Respiratory ailments, carminative,hypnotic and nerve tonic	Amiri et al. (2012)
H. longiflorus	Iran, Kurdistan & KermanshahProvinces	Soor-Halale, SoorSanduo,Gole Arvaneh-Avarmani.	Aerial parts	Anti-inflammatory, sedative,anti-skin allergic reaction(for skin diseases and insect bite)	Taherpour et al. (2011)and Shahriari et al. (2013)
H. longiflorus	Iran, Kermanshah Province,Oramanat region	Oraman’s tulip	–	House freshener, an anti-mosquitoagent and for some medical practices	Taran et al. (2013)
H. longiflorus	Iran	Arvaneh	Stem and leaves	Air freshener and purifier	Abedini et al. (2014)
H. sessilifolius	Pakistan, Balochistan Province	–	Leaves and shoots	Cure of fever, headache, giddiness,cardiac diseases and wounds	Zaidi & Crow Jr (2005, 2012)
H. sessilifolius	Pakistan, North region of BalochistanProvince, Ziarat District	Soursanda	Plant extract	As a cooling medicine,Also used Perfume	Sarangzai et al. (2013)

Phytochemistry

Flavonoids and essential oils are important constituents of the genus Hymenocrater (Zaidi & Crow 2012). Fazly Bazzaz et al. (1997) reported the presence of alkaloids (+, +, 2+), flavonoids (+, +, +), saponins (+, 3+, 3+) and tannins (3+, 2+, 2+) in the aerial parts of H. bituminosus, H. calycinus and H. platystegius, respectively, collected from the various parts of Khorasan Province in Iran by the qualitative chemical analysis. The total phenolic and flavonoid contents of methanol extract of the aerial parts of H. calycinus collected from Bojnurd, North Khorasan Province in Iran, were found to be more than those of ethyl acetate and dichloromethane extracts (Soodmand et al. 2015). Some compounds have been isolated from the extracts of Hymenocrater spp. so far (Figure 1). Rosmarinic acid has been reported from the genus Hymenocrater (Pedersen 2000). Rosmarinic acid, β-sitosterol, ursolic acid, quercetin-3-O-rutinoside (rutin) and 3-(3,4-dihydroxyphenyl) lactic acid 2-O-quinic acid were identified in the extracts of H. calycinus grown in Iran (Gohari et al. 2009, 2011). β-Sitosterol was also found in H. bituminosus (Azimova & Glushenkova 2012). Ten compounds including cirsimaritin, rosmarinic acid, apigenin-7-O-glucoside, genistein, apigenin, acacetin, carnosic acid, caffeic acid, ferulic acid and isorhamnetin were identified as flavonoids and phenolic acids in the methanol extract of H. longiflorus grown in Iraq (Al-Anee et al. 2015).

Figure 1. The structures of isolated compounds from the extracts of Hymenocrater species.

There are several studies on the chemical composition of the essential oil of Hymenocrater spp. (Mirza et al. 2001; Firouznia et al. 2005; Barazandeh 2006; Akramian et al. 2008; Akhlaghi et al. 2009; Masoudi et al. 2009; Firouznia et al. 2009; Ahmadi et al. 2010; Morteza-Semnani et al. 2010; Taherpour et al. 2011; Azimova & Glushenkova 2012; Masoudi et al. 2012; Morteza-Semnani et al. 2012; Sabet Teimouri et al. 2012; Shahriari et al. 2013). Chemically, essential oils are very complex natural mixtures which may contain components at quite different concentrations. They are characterized by major components at fairly high concentrations, compared with other components present in trace amounts. Generally, these major components determine the biological properties of the essential oil. The components include two groups with different biosynthetical origins: the main group is composed of terpenes, and the other of aromatic and aliphatic constituents, all characterized by their low molecular weight (Abad et al. 2012). Phytol, spathulenol, β-caryophyllene, hexacosane and heneicosane were found as main components of the essential oil from the aerial parts of H. platystegius collected from six different locations of Khorasan-e-razavi in Iran (Sabet Teimouri et al. 2012). Citral was identified in H. bituminosus oil (Azimova & Glushenkova 2012). Table 2 summarizes reported major components (>5%) of Hymenocrater species and Figure 2 illustrates the chemical structures of the most commonly occurring major volatile compounds.

Figure 2. Chemical structures of the most commonly occurring major volatile components of Hymenocrater species.

Table 2. Major essential oil components (>5%) of Hymenocrater species.

Compound	Hymenocrater species^a	Origin	Amount (%)	Ref.
Abietal	H. calycinus (AP)	Iran, Khorasan Province, Village of Nodeh in west of Bojnourd	6.1	Firouznia et al. (2005)
Abietatriene	H. calycinus (AP)	Iran, Khorasan Province, Village of Nodeh in west of Bojnourd	13.4	Firouznia et al. (2005)
Bicyclogermacrene	H. calycinus (AP)	Iran, Golestan Province, Golestan forest	6.9	Firouznia et al. (2005)
(–)-Bornyl acetate	H. longiflorus (AP)	Iran, Kurdistan Province	5.61	Taherpour et al. (2011)
β-Bourbonene	H. elegans (L)	Iran, Tehran Province, Firoozkooh	7.1	Barazandeh, 2006
δ-Cadinene	H. longiflorus (AP)	Iran, Kurdistan Province	6.13	Taherpour et al. (2011)
α-Cadinol	H. longiflorus (AP)	Iran, Kermanshah Province, Paveh	20.43	Shahriari et al. (2013)
δ-Cadinol	H. longiflorus (AP)	Iran, Kermanshah Province, Oramanat mountains	18.49	Ahmadi et al. (2010)
cis-Calamenene	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	11.2	Masoudi et al. (2009)
trans-Calamenene	H. elegans (AP)	Iran, Khorasan Province, Baba-amane in East of Bojnourd	5.2	Firouznia et al. (2009)
β-Caryophyllene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	6.6	Firouznia et al. (2005)
	H. calycinus (AP)	Iran, Golestan Province, Golestan forest	32.8	Firouznia et al. (2005)
	H. elegans (L)	Iran, Tehran Province, Firoozkooh	9.7	Barazandeh (2006)
	H. incanus (AP)	Iran, Fars Province, near Abadeh	17.7	Mirza et al. (2001)
	H. longiflorus (AP)	Iran, Kurdistan Province	18.05	Taherpour et al. (2011)
	H. yazdianus (L)	Iran, Yazd Province, Yazd	13.9	Masoudi et al. (2012)
Caryophyllene oxide	H. calycinus (AP)	Iran, Khorasan Province, Village of Nodeh in west of Bojnourd	5.0	Firouznia et al. (2005)
	H. calycinus (AP)	Iran, Golestan Province, Golestan forest	16.1	Firouznia et al. (2005)
	H. elegans (AP)	Iran, Khorasan Province, Baba-amane in East of Bojnourd	12.9	Firouznia et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	7.7	Masoudi et al. (2009)
	H. yazdianus (L)	Iran, Yazd Province, Yazd	10.4	Masoudi et al. (2012)
1,8-Cineole	H. calycinus (AP)	Iran, Mazandaran Province, the suburb of Noor	12.2	Morteza-Semnani et al. (2012)
	H. elegans (AP)	Iran, Mazandaran Province, the suburb of Noor	8.3	Morteza-Semnani et al. (2010)
	H. incanus (AP)	Iran, Fars Province, near Abadeh	16.9	Mirza et al. (2001)
	H. platystegius (AP)	Iran, Khorasan Province, Chenaran, Akhlamad	18.6	Akramian et al. (2008)
	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	12.9	Masoudi et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	6.7	Masoudi et al. (2009)
	H. yazdianus (L)	Iran, Yazd Province, Yazd	17.6	Masoudi et al. (2012)
α-Copaene	H. longiflorus (AP)	Iran, Kurdistan Province	9.84	Taherpour et al. (2011)
p-Cymene	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	7.5	Masoudi et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	7.8	Masoudi et al. (2009)
γ-Elemene	H. longiflorus (AP)	Iran, Kurdistan Province	6.79	Taherpour et al. (2011)
β-Eudesmol	H. longiflorus (AP)	Iran, Kurdistan Province	14.92	Taherpour et al. (2011)
Germacrene D	H. elegans (L)	Iran, Tehran Province, Firoozkooh	10.2	Barazandeh (2006)
	H. longiflorus (AP)	Iran, Kermanshah Province, Paveh	5.76	Shahriari et al. (2013)
Hedycaryol	H. longiflorus (AP)	Iran, Kermanshah Province, Paveh	22.2	Shahriari et al. (2013)
	H. longiflorus (AP)	Iran, Kermanshah Province, Oramanat mountains	6.42	Ahmadi et al. (2010)
Hexadecanoic acid	H. calycinus (AP)	Iran, Khorasan Province, Village of Nodeh in west of Bojnourd	10.8	Firouznia et al. (2005)
α-Humulene	H. elegans (L)	Iran, Tehran Province, Firoozkooh	9.6	Barazandeh (2006)
Limonene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	9.0	Firouznia et al. (2005)
	H. platystegius (AP)	Iran, Khorasan Province	23.2	Akhlaghi et al. (2009)
	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	5.8	Masoudi et al. (2009)
Manoyl oxide	H. elegans (AP)	Iran, Mazandaran Province, the suburb of Noor	22.7	Morteza-Semnani et al. (2010)
p-Menth-1-en-8-ol	H. longiflorus (AP)	Iran, Kermanshah Province, Oramanat mountains	9.82	Ahmadi et al. (2010)
α-Muurolol	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	6.1	Firouznia et al. (2005)
(E)-β-Ocimene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	6.1	Firouznia et al. (2005)
	H. incanus (AP)	Iran, Fars Province, near Abadeh	5.3	Mirza et al. (2001)
α-Pinene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	10.5	Firouznia et al. (2005)
	H. calycinus (AP)	Iran, Mazandaran Province, the suburb of Noor	5.7	Morteza-Semnani et al. (2012)
	H. elegans (AP)	Iran, Khorasan Province, Baba-amane in East of Bojnourd	5.6	Firouznia et al. (2009)
	H. incanus (AP)	Iran, Fars Province, near Abadeh	9.2	Mirza et al. (2001)
	H. longiflorus (AP)	Iran, Kurdistan Province	22.47	Taherpour et al. (2011)
	H. longiflorus (AP)	Iran, Kermanshah Province, Oramanat mountains	10.16	Ahmadi et al. (2010)
	H. platystegius (AP)	Iran, Khorasan Province, Chenaran, Akhlamad	20.6	Akramian et al. (2008)
	H. platystegius (AP)	Iran, Khorasan Province	23.4	Akhlaghi et al. (2009)
	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	16.7	Masoudi et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	18.6	Masoudi et al. (2009)
	H. yazdianus (L)	Iran, Yazd Province, Yazd	10.6	Masoudi et al. (2012)
β-Pinene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	6.3	Firouznia et al. (2005)
	H. calycinus (AP)	Iran, Mazandaran Province, the suburb of Noor	6.3	Morteza-Semnani et al. (2012)
	H. incanus (AP)	Iran, Fars Province, near Abadeh	7.0	Mirza et al. (2001)
	H. platystegius (AP)	Iran, Khorasan Province, Chenaran, Akhlamad	9.9	Akramian et al. (2008)
	H. platystegius (AP)	Iran, Khorasan Province	11.7	Akhlaghi et al. (2009)
	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	9.1	Masoudi et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	9.4	Masoudi et al. (2009)
Sabinene	H. calycinus (AP)	Iran, Khorasan Province, Village of Yekeh-Shakh in east of Bojnourd	10.5	Firouznia et al. (2005)
Sclareol	H. elegans (AP)	Iran, Mazandaran Province, the suburb of Noor	12.4	Morteza-Semnani et al. (2010)
Spathulenol	H. calycinus (AP)	Iran, Khorasan Province, Village of Nodeh in west of Bojnourd	35.4	Firouznia et al. (2005)
	H. calycinus (AP)	Iran, Golestan Province, Golestan forest	9.7	Firouznia et al. (2005)
	H. elegans (AP)	Iran, Khorasan Province, Baba-amane in East of Bojnourd	49.5	Firouznia et al. (2009)
	H. platystegius (L)	Iran, Khorasan Province, North of Sabzevar	17.1	Masoudi et al. (2009)
	H. platystegius (S)	Iran, Khorasan Province, North of Sabzevar	17.9	Masoudi et al. (2009)

^a Plant parts: AP: aerial parts; L: leaves; S: stems.

Biological activities

Antimicrobial activity

The methanol extract of the aerial parts of H. calycinus and H. platystegius collected form Khorasan Province in Northeast of Iran were tested for antimicrobial activity using the cylinder plate assay method; H. calycinus extract showed significant activity against Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Pseudomonas aeruginosa and Staphylococcus aureus but H. platystegius extract had no effect on micro-organisms tested (Fazly Bazzaz & Haririzadeh 2003). The extract of H. sessilifolius collected from Balochistan Province of Pakistan showed good activity against Candida albicans and also significant activity against Bacillus subtilis, P. aeruginosa and E. coli (Zaidi & Crow 2005). Rosmarinic acid, as the main component of H. calycinus extract, had an antifungal property against C. albicans (Gohari et al. 2009). Isolated 3-(3,4-dihydroxyphenyl) lactic acid 2-O-quinic acid from H. calycinus extract was not active against S. aureus and E. coli at any concentration below 1 mg/disk but it (500 μg/disc) enhanced antibacterial effect of Ampicillin, Ciprofloxacin, Vancomycin and Cefepime against S. aureus and activated the effects of Ampicillin and Vancomycin against E. coli (Gohari et al. 2010). Ether extract of H. bituminosus showed antifungal activity (Azimova & Glushenkova 2012). The methanol extract of the stem and leaves of H. longiflorus collected from Iran showed antibacterial activity against some tested bacteria (Abedini et al. 2014). Ethanol extract of the flowers of H. longiflorus collected from Kurdistan region in North of Iraq showed antifungal activity against C. albicans and Cryptococcus neoformans at some concentrations (Abu-Mejdad 2014). The polar and essential oil fractions of H. longiflorus collected from Kermanshah Province in Iran showed moderate activity against the S. aureus. The results from the measurements of minimal inhibition concentration (MIC) indicate that the polar sub-fraction was more sensitive with a lower MIC value (40 μg/mL) than the essential oil (an MIC value of 120 μg/mL). Furthermore, the results showed a resistance of all micro-organisms against the non-polar sub-fraction of plant. This weak spectrum of antibacterial activity of essential oil may be due to low or very rare presence of antibacterial constituents, especially 1,8-cineole (eucalyptol) in the oil. The results of antifungal activity assays showed that only the essential oil have significant inhibitory effects on the growth of Aspergillus niger and C. albicans with MIC values of 480 and 240 μg/mL, respectively. This inhibition effect of the essential oil against the two fungal species may be due to the presence of a relatively high proportion of oxygenated monoterpenes in the oil (Ahmadi et al. 2010). The H. elegans oil exhibited concentration-dependent antibacterial activity on B subtilis, S. aureus, E. coli and Salmonella typhi with MIC values of 0.8, 0.8, 1.6 and 1.6 mg/mL, respectively; the essential oil did not show antifungal activity against A. niger and C. albicans (Morteza-Semnani et al. 2010). The H. calycinus oil exhibited concentration-dependent antibacterial activity on B. subtilis, S. aureus, E. coli and S. typhi with MIC values of 1.6, 0.8, 1.6 and 1.6 mg/mL, respectively; the essential oil did not show antifungal activity against A. niger and C. albicans (Morteza-Semnani et al. 2012). Essential oil of H. bituminosus had antibacterial property (Azimova & Glushenkova 2012). The leaf oil of H. yazdianus collected from Yazd Province in Iran showed inhibitory activity against S. epidermidis, E. faecalis, E. coli and S. paratyphi B (MIC values of 31.25 μg/mL) (Masoudi et al. 2012).

Antiparasitic activity

The essential oil and the methanol extract of H. longiflorus exhibited significant toxic activity against the larvae of Echinococcus granulosus with LC₅₀ values of 79.68 and 135.88 μm/mL, respectively (Taran et al. 2013).

Antioxidant activity, anticancer activity and cytotoxicity

The antioxidant activity of essential oil, polar sub-fraction and non-polar sub-fraction H. longiflorus collected from Kermanshah Province in Iran was also determined by 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging, β-carotene linoleic acid assay and reducing power (Ahmadi et al. 2010). The free radical scavenging activity of the methanol extract of H. longiflorus grown in Iraq was evaluated using DPPH assay; the antioxidant activities of the extract may be attributed to its polyphenolic composition (Al-Anee et al. 2015). The aerial parts of H. calycinus collected from Bojnurd in Iran are a potential source of natural antioxidants, phenolic and flavonoids; the total phenolic content and antioxidant ability were depending on the type of solvent (Soodmand et al. 2015).

Hoshyar et al. (2015) reported the correlation of anticancer effects of H. platystegius extract on human breast adenocarcinoma cells with antioxidant properties. The aqueous extract of H. platystegius collected from South Khorasan in Iran possessing high total antioxidant activity, total phenolic content and DPPH radical scavenging activity dramatically decreased the cancer cell viability. The extract inhibited significantly growth of breast cancer cells in a dose- and time-dependent manner.

In the test of induction of lambda-phage formation in lysogenic E. coli K-12(λ), the methanol extract of the aerial parts of H. platystegius collected from Turkman Sahra in Iran showed positive effect. The active extract causes the prophage to be released from the host genome and the phage reverts to the lytic mode and lyses cells. Production of plaque shows this effect. The induction test may provide a useful screen for the detection of potential DNA-reactive agents. Evidence supports a relationship between an agent’s inducing capability and its antitumour activity (Taghvaei et al. 2009). The cytotoxicity of the six fractions of the extract of H. sessilifolius collected from Balochistan Province of Pakistan was determined by flow cytometry on 2 × 10⁶ CFU/mL of C. albicans; the extracts of H. sessilifolius showed non-significant activity against C. albicans and was not toxic for brine shrimps (Zaidi & Crow 2012). The results of in vitro studies of the cytotoxicity and cell cycle arrest of the methanol extract of H. longiflorus collected from north of Iraq on colon cancer (RKO) cell line revealed that this plant had a significant cytotoxicity and showed cell-cycle arrest in the G1 phase at 40 μg/mL 3 h, 40 μg/mL 6 h, 80 μg/mL 3 h and 80 μg/mL 6 h (29.07, 34.54, 38.00 and 56.10%, respectively) as compared with non-treated cells (26.69%). Hymenocrater longiflorus extract decreased the viability of RKO cells and the decrement was in a significant concentration, as well as, time-dependent manner. The cytotoxicity of H. longiflorus extract may belong to its active compounds like phenols, alkaloids, flavonoids, tannins and resins. Some plants secondary metabolites are known as potential anticancer drugs through direct cytotoxicity toward cancer cells or inhibition of tumour development (Al-Anee et al. 2014). Al-Anee et al. (2015) demonstrated that the methanol extract of H. longiflorus grown in Iraq exerts potent antioxidant, cytotoxic and apoptotic effects on the osteosarcoma (U2OS) cells; extract decreased cell viability, and the effect was concentration and time dependent. Exposure to a high concentration (100 μg/mL) of H. longiflorus extract for 24 h induced detachment of a number of cells from the walls of the wells and appeared to cause a form of cell death called anoikis. Anoikis is a cell death program that largely shares its molecular program with apoptosis, but occurs only when the cells are no longer attached to the substrate. Ten compounds detected by HPLC-ESI/MS were also identified as flavonoids and phenolic acids in this extract. High cytotoxic is most likely due to its polyphenolic composition. Flavonoids are considered the most abundant and most effective antioxidant compounds in plants. Apigenin and related flavonoids are potentially useful as antioxidant and may have therapeutic applications in various diseases. Many natural phenols have been reported to scavenge reactive oxygen species, which are implicated in DNA damage, cancer and accelerated cell aging.

It seems likely that the species of Hymenocrater may act at various therapeutic levels, but further studies are required to evaluate the practical values of therapeutic application.

Antidiabetic activity

Natural α-amylase inhibitors of herbal origin are an attractive therapeutic approach to control post-prandial hyperglycaemia via reducing the glucose release from starch and delaying carbohydrate absorption. These compounds are able to inhibit the activity of the carbohydrate hydrolyzing enzymes in the small intestine and potentially useful in control of diabetes. Many species of Lamiaceae (Labiatae) family possess medicinal properties and have been used traditionally for treatment of chronic illnesses including diabetes. The ethyl acetate extract of the aerial parts of H. bituminosus grown in Iran showed significant α-amylase inhibitory activity with IC₅₀ value of 6.6 mg/mL. This study has been carried out on a “model α-amylase” and the results should be checked in future studies on mammalian amylase or in vivo models (Safamansouri et al. 2014).

Discussion and conclusion

Flavonoids, phenolic acids and terpenoids are important constituents of the genus Hymenocrater. The different parts of Hymenocrater spp. of different origins yielded 0.03–2.3% (w/w) essential oil with a pale yellow color and a distinct sharp odour. The quality and yield of essential oils from Hymenocrater spp. is influenced by the harvesting season, fertilizer and pH of soils, the choice and stage of drying conditions, the geographic location, chemotype or subspecies, choice of plant part or genotype, or extraction method (Morteza-Semnani et al. 2004, 2009; Abad et al. 2012). The studies confirm that there is a positive correlation between the chemical content of Hymenocrater spp. and their biological activities.

Rosmarinic acid, β-sitosterol, ursolic acid, quercetin-3-O-rutinoside (rutin), 3-(3,4-dihydroxyphenyl) lactic acid 2-O-quinic acid, cirsimaritin, apigenin, apigenin-7-O-glucoside, genistein, acacetin, carnosic acid, caffeic acid, ferulic acid and isorhamnetin were identified in the extracts of Hymenocrater spp. (Gohari et al. 2009, 2011; Al-Anee et al. 2015). α-Pinene, β-pinene, β-caryophyllene, caryophyllene oxide, spathulenol and 1,8-cineole were found as the most commonly occurring major volatile components in the essential oil of many species of Hymenocrater.

A broad range of biological and physiological activities have been reported for rosmarinic acid, including as an antioxidant, anti-inflammatory, antimutagenic, antibacterial, anticarcinogenic and antiviral, and is used in therapy of herpes simplex and human immunodeficiency virus type 1 (HIV-1) infections (Gohari et al. 2011). α-Pinene, β-pinene, 1,8-cineole, β-caryophyllene, β-sitosterol, apigenin, rutin, caffeic acid, ferulic acid and isorhamnetin have been reported to possess antibacterial effects; α- and β-pinene, 1,8-cineole, β-caryophyllene, caryophyllene oxide, caffeic acid, ferulic acid and genistein possess fungicidal properties; apigenin, rutin, ursolic acid, caffeic acid, ferulic acid, isorhamnetin and genistein have been reported to display antioxidant activity; α-pinene, caffeic acid, ferulic acid, β-sitosterol, apigenin, rutin, isorhamnetin and genistein possess anticancer effects; rutin also shows antidiabetic property (Duke et al. 2003; Rivas da Silva et al. 2012). The appreciable presence of these compounds in the genus Hymenocrater could explain its various activities. In addition, some components that occur in lesser amount may also contribute to the biological activities of Hymenocrater spp., involving probably some type of synergism with the other active compounds.

Pharmacological reports support medicinal potential of genus Hymenocrater for developing new drugs. These plants may have some novel antibiotics, antifungal, antiparasitic, anticancer or antidiabetic compounds that may be effective for treating diseases. Recently, this genus has drawn more attention due to the anticancer effects (Al-Anee et al. 2014, 2015; Hoshyar et al. 2015). Identification of active compounds of Hymenocrater spp. and their mode of action require further investigation for drug development.

Disclosure statement

The authors report that there is no conflict of interest.