Coleus aromaticus Benth.: an update on its bioactive constituents and medicinal properties

Abstract

Coleus aromaticus is a herbal medicine that has been referred for its medicinal properties in traditional, ayurvedic, and folklore medicines. Therefore, various research in the area for biochemical characterization of its biochemical compounds are extensively carried out using various techniques including spectroscopy and chromatography analysis. The list of bioactivities reported for this plant includes antioxidant, antiepileptic, antiurolithic, antidiabetic, anticancer, anthelmintic, antiprotozoal, and antiviral activity. The plant is effectively used against cardiovascular disorders, respiratory disorders, digestive diseases and is used for its larvacidal property, allelopathic property and finds its use even in the food and beverage industry. Along with various healing properties, C. aromaticus possess antimycobacterial property i.e. the plant is effective in inhibiting both bacterial and fungal pathogens. Even though this herb is not cultivated on a larger scale in comparison to other plants of the same genus or family due to their phytochemical dominance but still C. aromaticus finds its use as herbal medicine. With an increasing number of reports on the various bioactivity and medicinal properties of C. aromaticus, this review is an effort to update our current knowledge on C. aromaticus.

KEYWORDS:

• Coleus
• bioactivity
• borage
• herb
• thymol
• carvacrol

Introduction

Herbal medicine is widely used throughout the world due to their safe, cost-effective and their inhibitory nature against various deadly pathogen thus help in maintaining good health. According to the World Health Organization, 80% of the world population is dependent on the traditional use of medicinal plants (Mathur et al. 2011; Sandhya et al. 2011; Swamy and Sinniah 2015). Ayurveda, Unani, Sidda, traditional and folk healthcare management includes the use of herbal medicine. It can be used to benefit the total population thus it is important to explore these plants based on their bioactivity and their bioactive compounds. Pharmaceutical industries involve the use of these bioactive compounds because they are the major source of medicaments and provide a source for the treatment of a wide range of diseases (Arumugam et al. 2016). The modern era of natural medicine has increased the demand for new compounds from medicinal plants (Kumara et al. 2012; Mohanty et al. 2014; Swamy and Sinniah 2015). Several approaches to exploit the herbal wealth of the world are explored to extract these bioactive compounds from a variety of plant species. Even with the limited number of reports on the mechanism of the activity it has become obvious that numerous mechanisms are involved in various activities of a given herbal medicine.

Coleus aromaticus Benth. is used to treat various ailments and is studied for its various bioactivities (Retief 2000). The common names of the plant include Indian borage, Country borage (English), Indian borage, Parna-Yavaani, Peterechur, Panikkurukka, Kapparillaku (India), Da Shou Xiang (China), Indian Mint, Soup Mint (South Africa, US), Indian Borage, Country borage, Spanish thyme, Mexican mint, French thyme, Indian mint (US), Orégano; Orégano de Cartagena (Cuba), Big thyme (St. Vincent, Grenada & other English speaking Caribbean Islands), Broadleaf Thyme (Barbados), Latai, Suganda, Oregan, Toronjil de limón (Philippines), Orielle (France) and Jamaika thymian (Germany). C. aromaticus possess a variety of bioactive compounds. Most of these compounds are volatile in nature and responsible to cure a variety of ailments. These volatile constituents of the plant majorly contribute to the various therapeutic properties. Thymol (Singh et al. 2002) and carvacrol (Castillo and Gonzalez 1999) have discrepancies in being named the active constituent in C. aromaticus. Other bioactive compounds include α-humulene, β-caryophyllene, p-cymene, α-terpineol, β-selinene, and γ-terpinene (Murthy et al. 2009; Senthilkumar and Venkatesalu 2010). These bioactive compounds exhibit many biological properties.

The leaves of C. aromaticus are used to treat conditions like fever, cold, cough, headache, asthma, constipation, and skin diseases (Arumugam et al. 2016). C. aromaticus leaves are highly aromatic thus used to enhance the taste and aroma as a flavouring agent or are consumed raw or included as an ingredient in the preparations of traditional food. C. aromaticus juice was confirmed to reduce leptin levels and have an appetite-enhancing effect (Wadikar and Premavalli 2014). C. aromaticus leaves are used as a substitute for sage or oregano. The leaves are found as pungent in taste by some consumers due to their volatile content (Khare et al. 2011) and are used as meat stuffing or on seafood cuisines such as fish and shellfish (Morton 1992). It was added as a secret ingredient in tomato sauce. In India, the leaves are consumed raw with bread or roti’s and mixed with butter or added to fritters or pakoras. The flesh soft leaves are cooked in batter thus have a crunchy astringent snack. The leaves are sometimes added in beer or wine to add flavour (Morton 1992).

Based on the recent research reports on the various bioactive constituents and their potential of C. aromaticus, a plethora of experimental procedures were used to isolate a suitable drug compound. Many bioactive constituents isolated from C. aromaticus are reported for effective bioactivity, but the mechanism of certain bioactive compounds is to be explored. In this current review, the bioactive constituents, and the potential of these bioactive compounds of C. aromaticus are discussed.

Botanical description

C. aromaticus (synonym: Plectranthus amboinicus) belongs to the family of lamiacaea. It is a perennial, aromatic, large succulent herb, profusely branched and characteristic smelling leaves. The stem is fleshy, about 30–90 cm, densely covered with many short and erect hairs. The roots are thick, tuberous, fasciculate up to 20 cm long, 0.5–2.5 cm thick, conical, fusiform, straight, and strongly aromatic. Leaves are thick, simple, broad, and ovate with a tapering tip studded with hair. The lower surface possesses numerous glandular hairs that give it a frosted appearance. The taste of the leaf is pleasantly aromatic with an agreeable and refreshing odour. Flowers have short pedicel, pale purplish in dense whorls at distant intervals on a long slender raceme. The pale blue corolla is bilabiate, the lower lobes are elongated and concave. The inflorescence grows to a height of 30–60 cm. Racemes are perfect, the calyx is fine-toothed and deflexed in the front. The placentation is axile i.e. the flowers possess four parted ovaries. Fruits are smooth nutlets, pale brown in colour, 0.7 mm long, and 0.5 mm wide. The plant rarely flowers and seeds are difficult to collect (Soni et al. 2012).

Cultivation and propagation

C. aromaticus is a must-have plant of any herb garden. It grows faster and stem cuttings of matured plants are used for propagation because it rarely seeds or sets seed. The plant requires spares watering. It is grown in a semi-shaded and moist location of tropical and subtropical regions of the world. The herb can also adapt to a cooler climate and can be grown as an indoor plant (Dutta 1959). The herb grows well in a well-drained, rich, composite soil of neutral pH and high humidity. In case of the presence of excessive water in the soil, the roots are found to rot. The leaves of C. aromaticus turn yellow with exposure to excessive sunlight or may turn dark when not provided with ample sunlight. The herb grows in a well-drained area. It grows well in tropical and sub-tropical locations (Dutta 1959).

Bioactive constituents

C. aromaticus plant contains many bioactive compounds and therefore has tremendous potential as herbal medicine. The bioactive compounds that contribute to the medicinal potential of this herb involve enzymes, fibre, vitamins, minerals, trace elements, volatile and non-volatile compounds. The bioactive compounds in both essential oil and plant extracts vary in concentration. Table 1 summarizes the bioactive compounds reported in C. aromaticus essential oil and extracts, while Figures 1–4 depict structural details of these compounds.

Figure 1. The structures of amino acids found in Coleus aromaticus.

Figure 2. The structures of non-volatile compounds found in Coleus aromaticus.

Figure 3. The structures of vitamins found in Coleus aromaticus.

Figure 4. The structures of volatile compounds found in Coleus aromaticus.

Table 1. Bioactive constituents of Coleus aromaticus.

Type of compounds	Name of compounds	References
Amino acids	Aspartic acid [C4H7NO4]; thrionine [C4H9NO3]; serine [C3H7NO3]; glutamic acid [C5H9NO4]; proline [C5H9NO2]; glycine [C2H5NO2]; alanine [C3H7NO2]; valine [C5H11NO2]; isoleucine[C6H13NO2]; leucine [C6H13NO2]; tyrosine [C9H11NO3]; phenyl alanine [C9H11NO2]; histidine [C6H9N3O2]; lysine [C6H14N2O2]; arginine [C6H14N4O2]	El-hawary et al. (2012)
Enzymes	Phosphatase; catalase; lipase; oxidase	Khare et al. (2011)
Fibers	Soluble dietary fibers; insoluble dietary fibers	Khare et al. (2011)
Flavonoids	Chrysoeriol [C16H12O6]; cirsimaritin [C17H14O6]; luteolin [C15H10O6]; rutin [C27H30O16]; salvigenin [C18H16O6]; thymoquinone [C10H12O2]; quercetin [C15H10O7]; 5,4`-dihydroxy-6,7-dimethoxy flavone [C17H14O6]; 5,4`-dihydroxy-3,7-dimethoxy flavone [C17H14O6]; 5-O-methyl-luteolin [C16H12O6]; 3,5,7,31 4`-pentahydroxy flavanone [C15H12O7]; 4`,5,7-trihydroxyflavone (apigenin) [C15H10O5]	Hassani et al. (2012), Kweka et al. (2012), Manjamalai and Grace (2012); Verma et al. (2012), Joshi et al. (2011), Uma et al. (2011), Da Costa et al. (2010), Senthilkumar and Venkatesalu (2010), Murthy et al. (2009), Velasco et al. (2009), Kaliappan and Viswanathan (2008), Koba et al., (2011), Ragasa et al. (1999)
Minerals	Calcium; phosphorous; potassium; sodium; magnesium	Khare et al. (2011)
Phenols	Caffeic acid [C9H8O4]; gallic acid [C7H6O5]; p-coumaric acid [C9H8O3]; chlorogenic acid [C16H18O9]; rosmarinic acid [C18H16O8]; salvianolic acid A [C26H22O10]; shimobashiric acid [C36H32O16]	Thilagavathi and Hariram (2016), Joshi et al. (2011), Senthilkumar and Venkatesalu (2010), Murthy et al. (2009), Rasineni et al. (2008), Kumaran and Karunakaran (2007)
Trace elements	Iron; zinc; copper; chromium; manganese	Wadikar and Patki (2016), Khare et al. (2011)
Vitamins	Ascorbic acid [C6H8O6]; α-carotene [C40H56]; β-carotene [C40H56]; tocopherol [C29H50O2]; retinol [C20H30O]; calciferols [C28H44O]; vitamin B complex (thiamin B1 [C12H17N4OS+]; pyridoxin B6 [C8H1111NO3]; riboflavin B2 [C17H20N4O6]; niacin [C6H5NO2]; cyanocobalamine [C63H88CoN14O14P]; folic acid [C19H19N7O6])	El-hawary et al. (2012), Khare et al. (2011)
Volatile compounds	δ-3-carene [C10H16]; p-cymene [C10H14]; limonene [C10H16]; β-myrcene [C10H16]; ocimene [C10H16]; α-phellandrene [C10H16]; β-phellandrene [C10H16]; α-pinene [C10H16]; β-pinene [C10H16]; sabinene [C10H16]; α-terpinene [C10H16]; γ-terpinene [C10H16]; α-terpinolene [C10H16]; α-thujene [C10H16]; α-amorphene [C15H24]; aromadendrene [C15H24]; trans-α-bergamotene [C15H24]; trans-β-bergamotene [C15H24]; γ-cadinene [C15H24]; δ-cadinene [C15H24]; α-calacorene [C15H20]; cis-calamenene [C15H22]; β-caryophyllene [C15H24]; γ-caryophyllene [C15H24]; α-copaene [C15H24]; α-cubebene [C15H24]; (E,Z)-α-farnesene [C15H24]; germacrene D [C15H24]; γ-gurjunene [C15H24]; humulene [C15H24]; α-muurolene [C15H24]; patchoulene [C15H24]; β-selinene [C15H24]; β-sesquiphellandrene [C15H24]; thymol [C10H14O]; camphor [C10H16O]; carvacrol [C10H14O]; carvone [C10H14O]; 1,8-cineole [C10H18O]; eugenol [C10H12O2]; geraniol [C10H18O]; linalool [C10H18O]; methyl carvacrol [C11H16O]; methyl eugenol [C11H14O2]; α-terpineol [C10H18O]; terpinen-4-ol [C10H18O]; thymol methyl ether [C11H16O]; caryophyllene oxide [C15H24O]; β-cedrene epoxide [C15H24O]; β-copaen-4-α-ol [C15H24O]; 1-epi-cubenol [C15H26O]; β-eudesmol [C15H26O]; β-himachalene oxide [C15H24O]; humulene oxide [C15H24O]; spathulenol [C15H24O]; 1,2-benzenediol 4-(1,1-dimethylethyl) [C10H14O2]; chavicol [C9H10O]; methyl chavicol [C10H12O]; α-corocalene [C15H20]; Dihydrocarveol [C10H18O]; durohydroquinone [C10H14O2]; 1,4 eicosadiene [C20H38]; ethyl salicylate [C9H10O3]; (Z)-1,3-hexadiene [C6H10]; (Z)-3-hexen-1-ol [C6H12O]; methyl octanoate [C9H18O2]; 1-octen-3-ol [C8H16O]; oleic acid [C18H34O2]; 2-phenyl ethyl tiglate [C13H16O2]; phytol [C20H40O]; squalene [C30H50]; tetradecanal [C14H28O]; 3,7,11,15–tetramethyl-2-hexadecen-1-ol [C20H40O]; thymol acetate [C12H16O2]; trans-sabinene hydrate [C12H20O2]; 1,2-benzenedicarboxylic acid[C8H6O4]; diethyl ester [(C2H5)2O]; octadecenal [C18H34O]; dibutyl phthalate [C16H22O4]; 9,12,15-octadecatrienoic acid [C18H30O2]; ethyl ester[C6H10O2]; solanesol [C45H74O]	Mamani and Alhaji (2019), Chen et al. (2014), Sabrina et al. (2014), Bhatt et al. (2013), Hassani et al. (2012), Kweka et al. (2012), Manjamalai and Grace (2012); Verma et al. (2012), Rout et al. (2012), Tewari et al. (2012), El-hawary et al. (2012), Khare et al. (2011), Joshi et al. (2011), Uma et al. (2011), Da Costa et al. (2010), Senthilkumar and Venkatesalu (2010), Murthy et al. (2009), Velasco et al. (2009), Koba et al., ((2011), Singh et al. (2002), Mallavarapu et al. (1999), Baslas and Kumar (1981), Dutta (1959)

Phytochemical screening of different parts of C. aromaticus like leaves, stems, and roots revealed the presence of sterols, terpenes, terpenoids, alkaloids, phenol, flavonoids, glycosides, lactones, catechol, and tannins (Dutta 1959; El-hawary et al. 2012) but saponins, steroids were found to be absent (El-hawary et al. 2012). Chemical constituents isolated from C. aromaticus include 76 volatile and 30 non-volatile compounds (Asiimwe et al. 2014). Volatile compounds are majorly contributed by essential oil present in the stunted glandular hair. These glandular hairs are found on the epidermis of various plant parts. Essential oil of C. aromaticus contains major constituents such as thymol, carvacrol, 1,8-cineole, eugenol, α-humulene, p-cymene, α-terpineol, β-selinene, β-caryophyllene, γ-terpinolene, pinene, methyl eugenol, and phellandrene (Dutta 1959; Baslas and Kumar 1981; Murthy et al. 2009; Senthilkumar and Venkatesalu 2010; Girish 2016; Saraswati et al. 2016). Thymol was reported as a major constituent of essential oil extracted from C. aromaticus. Thymol concentration increased in plants propagated via tissue culture than plant propagated using stem cuttings. Carvacrol was reported as a major constituent in leaf extract (Roja et al. 2006; Rout et al. 2012). Volatile compounds such as 1-octen-3-ol, terpine-4-ol, eugenol, trans-caryophyllene, caryophyllene oxide, and α-cadinol were present as minor constituents (Rout et al. 2012). Thymol and cis-caryophyllene were reported to be present in parent ex-plants, tissue culture regenerated plants as well as in the root cultures of C. aromaticus (Rout et al. 2012). The hexane extraction of volatile compounds yields the highest concentration of these compounds when compared to other conventional methods (Khare et al. 2011) followed by GC-MS analysis often used to identify the compound isolated. Non-volatile compounds are majorly contributed by phenols, flavonoids, terpenes, and esters (Ragasa et al. 1999). These non-volatile compounds were extracted by subjecting the chloroform extract using silica gel chromatography (Ragasa et al. 1999) and later identified using UV, HPLC, NMR, and 2-D-NMR (Chiu et al. 2012).

Carvacrol was found as a major constituent of the essential oil extracted from C. aromaticus found in the Western Ghats regions of North West Karnataka, India. Other constituents found were p-cymene, β-caryophyllene and trans-α-bergamotene. methyl chavicol, α-calacorene, and α-corocalene were reported as three new chemotypes of carvacrol found in the essential oil extracted from this C. aromaticus (Chen et al. 2014). The essential oil extracted from C. aromaticus growing in the mid-hill and foothill regions of northern India when investigated yielded a higher concentration of thymol along with γ-terpinene, p-cymene, (e)-caryophyllene, caryophyllene oxide, and 1-octen-3-ol (MeghaRani et al. 2016). This implies that based on the geographic location and climatic conditions, the concentration of the phytoconstituents of C. aromaticus changes. A study conducted by Llarena (Llarena 2016) to identify active principle from C. aromaticus leaf extract using ionic liquids through the spectroscopic determination of rosmarinic acid, caffeic acid, and chlorogenic acid with its Functional groups (Llarena 2016). The functional groups: p-hydroxyl group, double bonds, and keto group (carbonyl group) are mainly found in anti-inflammatory, antioxidant, and anticancer (Mallavarapu et al. 1999; Hassani et al. 2012). C. aromaticus extract when analysed using GC-MS resulted in 1,2-benzene dicarboxylic acid, 2-hexadecane-1-ol, 3,7,11,15-tetramethyl, 9,12,15-octadecatrienoic acid, dibutyl phthalate, diethyl ester, ethyl ester hexadecanoic acid, methyl ester, octadecenal, oleic acid, phytol, and solanesol (Mamani and Alhaji 2019). The essential oil extracted from dried C. aromaticus leaves revealed to have carvacrol, camphor, δ-3-carene, λ-terpinene, o-cymene, and α-terpinene were the major constituents of the oil (Mallavarapu et al. 1999; Hassani et al. 2012). Uma et al. (2011) estimated the presence of 3-methyl-4-isopropyl phenol, squalene, caryophyllene, and phytol and correlated their presence to the use of C. aromaticus as herbal medicine. The essential oil extracted from C. aromaticus in the month of September was found to contain higher concentrations of carvacrol, β-caryophyllene, and oxygenated constituents than the oil produced in May (Joshi et al. 2011). Crystalized aromatic compounds characterized using HPTLC and XRD (X-ray Powder Diffraction) helped identified 35 types of compounds with immunomodulatory properties yielded rosmarinic acid, chlorogenic acid, coumaric acid, and caffeic acid (Thilagavathi and Hariram 2016). Phytochemical analysis of C. aromaticus leaves revealed the presence of flavonoids like apigenin, genkwanin luteolin, quercetin, and salvigenin (Kaliappan and Viswanathan 2008).

Non-volatile compounds such as phenols and flavonoids have been identified from C. aromaticus (Khare et al. 2011), however, existing reports about the isolation of these compounds are minimum. Ethyl acetate extracts of C. aromaticus were exceptionally used to isolate quercetin, luteolin, and eriodyctiol. This extract also contained caffeic acid, chrysoeriol, p-coumaric acid, and rosmarinic acid were identified using UPLC-MS analysis (Ultra Performance Liquid Chromatography-Mass Spectroscopy) (Dutta 1959). Compounds like gallic acid, tannic acid, rutin were isolated from the methanolic stem extract of C. aromaticus. When analysed using HPLC, this extract resulted in the identification of caffeic acid, gallic acid, p-coumaric acid, quercetin, rosmaric acid, and rutin (Joshi et al. 2011). Aqueous extract of C. aromaticus resulted in the identification of major components reported as tannins, flavonoids, saponins, polyuronides, and steroid glycosides such as linalool, carvacrol, geranyl acetate, and nerol acetate (Baslas and Kumar 1981). Four bioactive compounds with transcription factor inhibitor activity isolated from aqueous stem and leaf extracts of C. aromaticus and analysed using HPLC column-based fractionization along with mass spectrometry and NMR identified thymoquinone, shimobashiric acid, salvianolic acid, and rosmarinic acid (Chiu et al.2012).

Bioactivity and medicinal properties

C. aromaticus is widely used as a herbal medicine due to its various bioactivity and medicinal properties. The leaves and leaf juice are used to treat asthma, bilious affections, bladder stones, bronchitis, cholera, colic, common cold, convulsions, cough, diarrhoea, dysentery, dyspepsia, epilepsy, fever, headache, indicated in kidney indigestion, poisonous bites, renal and vesicle calculi, stimulates the functions of the liver, urinary diseases, vaginal discharges, and vitiated conditions of Kapha and Vata (Girish 2016). Whereas, in folk medicine, C. aromaticus is used to expel kidneys and therefore is known as Paashanbhedi (Khare et al. 2011). Pharmacologically the herb is used as antiepileptic, antifungal, antimutagenic, anti-tumorogenic, antiviral, neuropharmacological properties, radioprotective effect, and urolithiasis (Verma et al. 2012). Traditionally in India, it was used to cure diarrhoea (Uma et al. 2011) whereas, a leaf decoction was used to treat asthma, cough, congestive heart failure, dyspepsia, epilepsy, fever, headache, inflammation, kidney troubles, nervous disorders, nasal congestion, spasms, skin ulcerations, stomach-ache, throat infection, and urinary diseases (Morton 1992; Verma et al. 2012; Thilagavathi and Hariram 2016). The various properties exhibited by C. aromaticus are caused by the combinatory action of various bioactive compounds. The explanation of various bioactivity exhibited by C. aromaticus can only be attained by multi-analysis of combinatorial bioactive compounds in animal models. Some of these bioactivity and pharmacological properties are discussed further indetail.

Antioxidant activity

Antioxidants derived from plants are used as dietary supplements in the hope to maintain health and preventing diseases. Antioxidants help in preventing food spoilage. Issues related to the use of artificial antioxidants as food additives causing health risks and toxicity made it unsafe. The replacement of such toxic synthetic antioxidants can prove to be beneficial if antioxidants from natural sources are utilized. The antioxidant activity of C. aromaticus was due to the presence of its bioactive compounds (Gurgel et al. 2009). These bioactive compounds that are mainly responsible for antioxidant activity include carvacrol, flavonoids, rosmarinic acid, caffeic acid, and chlorogenic acid were isolated from leaf extracts (Cheryl 2007). These compounds are reported to possess anticancer and bronchodilator activity which forms the chemical basis of the health benefits of C. aromaticus in folk medicine. Phenolic compounds mainly contribute significantly to the antioxidant potential due to their unique structure of aromatic rings bearing single or multiple hydroxyl groups. The antioxidant property of C. aromaticus leaves strongly inhibits lipid peroxidation, which could reduce the susceptibility of tissues to alloxan-induced oxidative stress (Khattak et al. 2013). Hydroalcoholic extract of C. aromaticus leaves was used to investigate antioxidant, anticlastogenic, and radioprotective effects on Chinese hamster fibroblast cells (V79) exposed to gamma radiations (Rasineni et al. 2008). Effective antioxidant activity of C. aromaticus was reported using the DPPH method (Kumaran and Karunakaran 2007; Thilagavathi and Hariram 2016). In vitro analysis used to evaluate bioactive compounds in the stem of C. aromaticus estimated the presence of major phenols such as rosmarinic acid, caffeic acid, rutin, gallic acid, quercetin, and p-coumaric acid. The extract from the stem of C. aromaticus exhibited properties of antiplatelet aggregation, antibacterial activity, and antiproliferative effect against cancer cell lines: Caco-2, HCT-15, and MCF-7. These appreciable biological activities along with the presence of biomolecules in the methanolic extract of stem thus indicate C. aromaticus posse the potential application as functional food ingredients and nutraceuticals (Candrappa et al. 2009).

The presence of carvacrol and thymol was reported to be responsible for antioxidant properties tested in vivo and in vitro in cells that induced lung cancer and gastric adenocarcinoma (Günes-Bayir et al. 2018; Günes-Bayir et al. 2020). C. aromaticus essential oil is cheaper than possesses no side effects in most of the tested animal models. The presence of these antioxidant components in C. aromaticus makes it an essential component in pharmaceutical drug formulations (Rao et al. 2006). Boiling water extracts of C. aromaticus act as an effective antioxidant that could prevent peroxide-mediated oxidative DNA damage (Krithiga and Jayachitra 2012). Ethanolic leaf extract of C. aromaticus revealed lowered content of total flavonoids and total phenolics and antioxidant activity (Bhatt et al. 2013). C. aromaticus is a rich source of various biological active products. The leaves growing in UV-B radiation were analysed and were reported to have an increased level of thymol (Manjamalai and Grace 2012; Ramadas et al. 2014). Due to anti-inflammatory properties, crushed leaves are used to heal burns and the leaves are reported to have bronchodilator activity and used to treat tuberculosis (Khare et al. 2011).

Antiepileptic activity

C. aromaticus leaves were reported to be used as an antiepileptic and anticonvulsive drug (Castillo and Gonzalez 1999). This was predicted based on the presence of enormous bioactive components such as alkaloids, flavonoids, and saponins in alcoholic extract favoured anticonvulsive activity. C. aromaticus was reported to treat nervous disorders including convulsions and epilepsy (Khanum et al. 2011). Different extracts of C. aromaticus plant parts such as leaf, stem, and root alcoholic extract were studied for their anticonvulsive activity on swiss mouse models that were already subjected to pentylenetetrazole-induced seizures and maximum electric shock-induced seizures (Kumari and Prasad 2014).

Antiurolithic effects

During the past few decades, C. aromaticus extract was tested for a positive effect against the increasing amount of calcium oxalate crystals getting deposited in the kidney. The extracts of C. aromaticus leaves are used to treat urinary diseases and relieve kidney troubles (Morton 1992). This suggested that different bioactive compounds present in the leaf extract are responsible for the antiurolithic effect. C. aromaticus extract attenuates the urinary excretion of calcium oxalate without affecting the phosphate as tested in rat models (Wadikar and Patki 2016). A study of the antiurolithiatic activity of C. aromaticus in ethylene glycol induced urolithic rats revealed that hydroalcoholic extract of C. aromaticus leaves significantly reduced cholesterol levels and triglyceride levels in urolithic rats. The hydroalcoholic extract of C. aromaticus leaves revealed potential antioxidant in vitro activity (Jaya et al. 2014). Leaf extract of the plant efficiently enhances the amount of urine secreted as well as helps in electrolyte excretion (sodium, potassium, calcium) (Bhattacharjee and Majumder 2013). Bioactive compounds present in the plant extract efficiently help the liver to function normally by neutralizing the toxic effects of naphthalene. Therefore, proving the hepatoprotective effect of C. aromaticus (Ghosh et al. 2000). Jose and Janardhanan (2005) reported fresh juice extracted from C. aromaticus leaves to have antiurolithic activity. Histopathological studies helped to report antiurolithic activity of C. aromaticus on ethylene glycol induced nephrolithiasis in rats thereby proving that the bioactive compounds in C. aromaticus extract contain one or more bioactive compound responsible for antiurolithic activity (Sur et al. 2003; Venkatesh et al. 2010). C. aromaticus leaf juice was reported to be used as a natural remedy to cure Urolithiasis (Vijayavel et al. 2013), a condition where stony concretions form in the bladder or the urinary tract. C. aromaticus leaf juice caused a significant reduction of calcium oxalates and total protein content in urine while histopathological studies revealed the absence of crystal in renal tubules of tested animal models.

Antidiabetic effects

C. aromaticus exhibited antihyperglycemic effects and therefore possesses the ability to heal diabetes. C. aromaticus has a hypoglycemic effect on blood glucose profile and liver antioxidant enzyme activities tested on alloxan-induced diabetic rats (Yoganarasimhan 2000). Suryowati et al. (2013) analysed the effect of the extract of C. aromaticus and proved that the treatment of STZ-treated rats with C. aromaticus restored the balance of lipid and carbohydrate metabolism. The extract exhibited significant antihyperglycemic as well as antihyperlipidemic effects. Antihyperlipidemic activity of C. aromaticus extract on diabetic rats induced by streptozotocin. C. aromaticus has the property to act against diabetes and acts towards α-amylase enzyme inhibition (Warrier et al.1996). The essential oil extracted from C. aromaticus leaves and the bioactive constituent Carvacrol positively inhibited diabetes-linked α-amylase and α-glucosidase (Bole and Jayashree 2014).

Activity against cardiovascular disorders

C. aromaticus was reported to be used as a treatment of congestive heart failure (Morton 1992). Aqueous extracts of the fresh leaves of C. aromaticus were used as an exhibited dose-dependent positive inotropic activity on the isolated frog heart without affecting the heart rate. Aqueous extract of C. aromaticus leaf was reported to increase sodium reflux and caused increased levels of intracellular availability of calcium (Bole and Jayashree 2014). The extracts from tissue cultured C. aromaticus, when compared with extracts prepared from C. aromaticus leaves, revealed a significant effect in maintaining good heart health due to the presence of biochemical production (Bole and Jayashree 2014). Fresh leaf aqueous extract of C. aromaticus and tissue cultured plants revealed a positive inotropic effect on isolated frog heart possibly by increasing sodium influx, that led to higher intracellular availability of calcium (Hole et al. 2009).

Anticancer activity

Koba et al. (2011) reported that the hydroalcoholic extracts of C. aromaticus had both anti-inflammatory and antitumor activities. Govindaraju and Arulselvi (Govindaraju and Arulselvi 2018) reported that essential oil from C. aromaticus leaves and its purified constituent, carvacrol, were studied for antiproliferative activity and cytotoxicity on human melanoma cancer (A375) cells. The effect on cell cycle arrest; DNA fragmentation and apoptosis by the cleavage of poly-(ADP ribose)-polymerase (PARP) and Bcl-2 gene expression were examined (Govindaraju and Arulselvi 2018). Carvacrol was reported to induce apoptosis by direct activation of the mitochondrial pathway, which plays a vital role in the anti-cancer effect (Günes-Bayir et al. 2017). Gurgel et al. (2009) reported significant inhibition of the growth of Sarcoma-180 tumour in mice treated with C. aromaticus hexane extracts. The hexane extract of C. aromaticus was compared with methotrexate, a cancer-treating drug that may cause profoundly serious, life-threatening side effects but completely reduced the tumour growth, revealed that tumour size was reduced and did not reveal any mortality in tested mice. Thymoquinone suppressed the expression of lipopolysaccharide-induced TNF-α (tumour necrosis factor-alpha). Synthesized 2-alkylidenyl-4-cyclopentene-1,3-diones designed based on the structure of thymoquinone had the potential to act as TNF-α inhibitors (Tewari et al. 2012). Ramalakshmi et al. (2014) reported that ethanolic extract of C. aromaticus revealed significant anticancer activity through inducing apoptosis in the A549 (human lung cancer) cell line. The severity of the side effects was greatly reduced with the tumour growth destroyed with the use of hexane extracts of C. aromaticus (Ramalakshmi et al. 2014). Copper oxide nanoparticles (CuO NPs) are produced using C. aromaticus leaf extract was developed to deliver miRNA-29b to A549 cells. This delivery system was an effective delivery method for miRNAs to cancer cells, with superior performance compared to traditionally available transfection agents, therefore has proved to be an efficient platform for intracellular miRNA delivery and improving therapeutic outcomes for lung cancer (Wu et al. 2019). It was reported to have cytotoxic activity, antitumor properties, and was used for the treatment of cancer (Dash and Sachidananda 2006).

Anthelmintic effects

Glycosides, tannins, and flavonoids extracted from C. aromaticus are reported to exhibit anthelmintic property by several investigators. C. aromaticus was proved to have these compounds by various investigators through phytochemical tests. Chloroform and methanolic extracts of C. aromaticus revealed significant anthelmintic activity (Prameela and Oommen 2011). Methanolic extract of C. aromaticus roots has maximum anthelmintic activity when compared to other herbal and synthetic drugs (Hussain et al. 2012). C. aromaticus extract exhibits maximum anthelmintic activity due to the presence of secondary metabolites like glycoside and flavonoids that interfere with the energy generation in helminth parasites by either uncoupling oxidative phosphorylation or, binding to the glycoprotein on the cuticle of the parasite, therefore causes its death (Choudhary 2013). Whereas Chaluvaraju et al. (2015) reported that various leaf extracts revealed significant anthelmintic activity. The overall bioactive compounds including tannins present in the leaves are considered responsible for anthelmintic activity. Herbal preparations containing C. aromaticus can be used as an alternative to synthetic drugs. C. aromaticus extracts has no side effects while synthetic anthelmintics such as benzimidazoles, piperazine, diethylcarbamazine citrate, ivermectin, levamisole, etc., exhibited adverse effects like anorexia, nausea, vomiting, dizziness, diarrhoea, occasional fever, rashes (Gilman et al. 2001).

Activity against respiratory disorders

Arumugam et al. (2016) compiled all the reports on the use of C. aromaticus in the treatment of respiratory disorder. C. aromaticus was reported to treat used for the treatment of chronic coughs, asthma, bronchitis, and sore throat (Morton 1992; Jain and Lata 1996; Ruiz et al. 1996). Similarly, C. aromaticus leaves were reported to have a positive bronchodilator activity (Ruiz et al. 1996). The essential oil extracted from C. aromaticus was reported to be used to treat asthma (Carbajal et al. 1991). C. aromaticus leaf juice or decoction or juice was administered orally to treat asthma. catarrhal infections are treated using C. aromaticus leaf extract as it helps to clear the build-up of thick phlegm in an airway (Castillo and Gonzalez 1999). Carvacrol and thymol are the main reason for the use of C. aromaticus to treat respiratory diseases. Carvacrol and thymol are excellent expectorants and therefore a drink or a bath of C. aromaticus juice/decoction was recommended to treat bronchitis, cough, influenza, and throat problems (Cano and Volpato 2004).

Activity against digestive diseases

The leaves of C. aromaticus are used as carminative and to treat indigestion and diarrhoea (Morton 1992; Gurib-Fakim et al. 1995; Jain and Lata 1996; Ong and Nordiana 1999; Cartaxoa et al. 2010). C. aromaticus was reported to have a prebiotic effect and stimulated the growth of probiotic bacteria Lactobacillus plantarum that utilizes bioactive compounds to produce necessary metabolic enzymes (Ong and Nordiana 1999). Lactobacillus plantarum incubated in C. aromaticus hot water extract was reported to utilize sugars present in the extract and reported β-galactosidase activity. Therefore when C. aromaticus leaves are used in cases of diarrhoea, the microbial gut balance was reported to be balanced (Arumugam et al. 2016). Fresh C. aromaticus leaf juice was used to treat constipation (Shubha and Bhatt 2015).

Antiprotozoal activity

C. aromaticus tested in vivo against Plasmodium berghei infections in mice models revealed significant antimalarial activity by reduction of parasitemia, therefore C. aromaticus extract was effective against P. berghei infection (Ramli et al. 2014). Similarly, an aqueous extract of C. aromaticus leaves was found to be effective against P. berghei (Periyanayagam et al. 2008). The essential oil of C. aromaticus reduced the viability of Leishmania braziliensis promastigotes (De Lima et al. 2014) while methanolic extract of C. aromaticus revealed significant activity against L. chagasi and L. amazonensis (Tempone et al. 2008).

Inhibitory activity against microorganisms

C. aromaticus possess both antibacterial as well as antifungal action, therefore one can rightly say it to have an ‘Antimycobacterial activity’. Essential oil, as well as different solvent extracts from leaves of C. aromaticus, possess great anti-microbial activity on both bacteria and fungi. It was tested against some drug-resistant and phytopathogenic microbes by disc diffusion, agar diffusion method using aqueous, chloroform, ethanol, petroleum ether, acetone extracts of C. aromaticus. C. aromaticus leaves are used as an active ingredient in natural antibiotic formulations (Lukhoba et al. 2006). Prudent et al. (1995) studied the bacteriostatic and fungistatic of C. aromaticus extract. Girish (2016) compiled that C. aromaticus had antibacterial property against 28 genera of bacteria, while antifungal activity against 14 genera of fungi. C. aromaticus exhibited inhibitory effects against both gram-negative and gram-positive human pathogenic bacterial strains (Chandrappa et al. 2010). Velasco et al. (2009) characterized carvacrol as found to be the major constituent and revealed antibacterial activity against important enteric pathogens such as Salmonella sp., Shigella sp., diarrheagenic Escherichia coli, and Vibrio sp. Whereas Da Costa et al. (2010) revealed that phytochemical analysis revealed thymol, p-cymene, γ-terpinene, and β-caryophyllene as major constituents, and the essential oil extracted from leaves demonstrated antibacterial activity against Staphylococcus aureus, Proteus vulgaris, and Aeromonas caviae as well as moderate fungicidal activity against Aspergillus niger.

Leaf extract of C. aromaticus was proved to be more efficient than standard Gentamycin and Bavistin against Bacillus firmus and Aspergillus niger (Roja et al. 2006). The flavonoids extracted from the C. aromaticus leaf extracts salvigenin and cirsimaritin were revealed to have antimicrobial properties and inhibited the growth of Pseudomonas aeruginosa, B. subtills, E. coli, Staphylococcus aureus, Candida albicans, Tricophyton mentagrophytes, and Aspergillus niger (Ragasa et al. 1999). Inhibitory activity of ethanolic extract of C. aromaticus via both well and disc diffusion methods (Kumaran and Karunakaran 2007). The acetone extract was reported with the presence of high polyphenol content and exhibited high appreciable antibacterial activity with the least MIC values against the pathogens S. aureus, B. cereus, E. coli, and Yersinia enterocolitica (Thilagavathi and Hariram2016).

Leaf discs from the leaves of C. aromaticus were tested against reproductive tract infecting microorganisms and exhibited an inhibitory effect in the order Candida krusei, C. albicans, Proteus mirablis, E. coli, S. aureus, Enterococcus faecalis, Klebsiella pneumoniae, and Neisseria gonohorreae (Pritima and Pandian 2007). The leaf extracts of C. aromaticus helped improve seed germination percentage, seedling vigour, and yield of okra and helped to deal with the fungal pathogens infecting the plant (Begum et al. 2009). C. aromaticus revealed inhibitory effect against S. epidermis, S. aureus, Serratia marcencens, P. aeruginosa, Proteus Vulgaris, methicillin-resistant S. aureus (MRSA), E. coli, Bacillus subtilis, C. albicans, and C. tropicalis. All these bacteria were inhibited by essential oil extracted from C. aromaticus except P. aeruginosa. Essential oil effectively inhibited with a bigger zone of inhibition against E. coli, S. aureus, and C. tropicalis tested and compared against commercial antibiotics: streptomycin and nystatin (Sabrina et al. 2014).

Essential oil and hydroalcoholic extract of C. aromaticus revealed significant antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) strains and decreased the ocharatoxin production of Aspergillus ochraceus (Murthy et al. 2009). Antimicrobial activity of ethanolic and aqueous extracts of C. aromaticus was tested against wastewater pathogens such as E. coli, Pseudomonas sp., Klebsiella sp., Bacillus sp., Staphylococcus sp. and the inhibitory effect was found highest against E. coli and Bacillus sp. (Malini et al. 2013). C. aromaticus leaf extract prepared in petroleum ether, alcohol, and water was tested against four respiratory pathogens: Sporothrix fragilis, Nocardia asteroides, Bacteroides vulgatis, and Bacteroides fragilis (Uma et al. 2012). The extract revealed as a positive inhibiter to all the above pathogens except B. fragilis.

The essential oil extracted from C. aromaticus leaves effectively inhibited the growth of C. albicans and A. niger (Revathi et al. 2011). Similarly, C. aromaticus leaf extracts prepared using water, crude alcohol, Soxhlet water, and Soxhlet alcoholic revealed significant antibacterial activity against five human pathogens found in sputum (Themozhi et al. 2011). The hydroalcoholic extract of C. aromaticus revealed mild to moderate inhibition for both bacteria and fungi using the cup plate method. The inhibitory action of C. aromaticus against bacteria and fungi can prove to be an additional advantage in the therapeutic role that the plant plays in the current pharmaceutic industry (Majee et al. 2013). Paul et al. (2014) revealed that multi-drug resistant bacteria such as Bacillus sp., S. aureus, Serratia sp., E. coli, Serratia sp., Streptococcus sp., Klebsiella sp., Vibrio sp., S. typhi, S. paratyphi A, Enterobacter sp., and Pseudomonas were found to be inhibited by crude extracts of fresh and oven-dried leaves of C. aromaticus. This indicated C. aromaticus extracts could be used as an antimicrobial agent against various multi-drug-resistant pathogenic microorganisms. The essential oil extracted from C. aromaticus had small interference on the anti-yeast effect of some clinically used antifungals agents (Oliveira et al. 2007). This revealed that the combined effect of certain medicinal plants and/or derivatives with industrial drugs particularly antimicrobials may interfere with the expected therapeutic effects of these industrial drugs.

A comparative study of Ocimum tenuiflorum and C. aromaticus leaves against selected human gram-positive and gram-negative bacteria suggested that C. aromaticus possessed higher antibacterial activity towards all selected common clinical pathogen and had a higher inhibitory effect towards gram-positive bacteria compared to gram-negative bacteria (Jiyauddin et al. 2015). In vitro antimicrobial activity of the essential oils of C. aromaticus against seven bacteria: B. megaterium, B. subtilis, E. coli, S. aureus, Proteus vulgaris, P. aeruginosa, and X. campestris, and eight fungi viz., A. niger, A. parasiticus, Rhizoctonia oryzae, Colletotrichum musae, Fusarium solani, Candida albicans and Alternaria brassicicola (Deena et al. 2002). Jayachitra and Chitra (2015) reported an aqueous ethanolic extract of C. aromaticus leaves was screened for their antibacterial potential against Klebsiella, Pseudomonas, and Staphylococcus. The essential oil extracted from dried leaves of C. aromaticus revealed higher inhibition against positive Gram S. aureus than negative Gram E. coli (Joshi et al. 2011). This was reported by Ramalakshmi et al. (2014) for E. coli, Salmonella typhi, and Proteus spp. Antimycobacterial bioactive compounds identified in C. aromaticus are β-caryophyllene, α-terpinolene, p-cymene, and carvacrol. All the above reports prove that C. aromaticus has effective antimycobacterial properties.

Antiviral activity

C. aromaticus leaf extracts prepared in different solvents: hexane, ethanol, and chloroform have revealed significant antiviral activity against Bombyx mori Nuclear Polyhedrosis Virus (Manimegalai et al. 2010) (BmNPV: affects a wide range of silkworm breeds); Herpes Simplex Virus-1 (HSV1); Vesicular Stomatitis viruses (VSV) (Ali et al. 1996) and Herpes Simplex Virus-2 (HSV2) (Rasmi 1998). Similarly, leaf juice from C. aromaticus exhibited anti-HIV inhibition activity (Rasmi 1998). Ethanolic extract of C. aromaticus revealed to have antiviral activity on Vero cell lines when tested against Herpes Simplex Virus-1 (HSV1) and Vesicular Stomatitis (VSV) viruses (Kusumoto et al. 1995). C. aromaticus leaf extracts thus are reported to exhibit antiviral activity.

Other beneficial properties

C. aromaticus possess anti-influenza properties, whereas the leaf juice help in wound healing (Vera et al. 1992). Studies conducted on animal models revealed therapeutic efficacy in treating rheumatoid arthritis (Chang et al. 2010) along with antiepileptic effect (Buznego and Perez Saad 1999). C. aromaticus leaves and leaf extract are consumed as breast milk stimulants (Santosa 2002; Koba et al. 2011; Bhatt and Negi 2012). The leaves are consumed to treat reproductive issues such as childbirth and to treat male and female infertility (Koba et al. 2011; Bhatt and Negi 2012). The polysaccharides extracted from dried plant parts of C. aromaticus revealed anticoagulant activity (Yoon et al. 2002). The leaf extracts of C. aromaticus, Aegle marmelos, and Vitex negundo can be used as an alternative to chemical pesticides and revealed significant larvicidal activity against instars and pupa of Culex quinquefasciatus (Dass and Mariappan 2014).

The essential oil of C. aromaticus and the isolated constituents are used as natural larvicides to control larvae of Culex tritaeniorhynchus, Aedes albopictus, and Anopheles subpictus (Govindarajan et al. 2013). The essential oil extracted from C. aromaticus revealed significant larvicidal property against An. gambiae and thus can be used against the African malaria vector mosquito (Kweka et al. 2012). Similarly, Jaya et al. (2014) demonstrated that the essential oils of C. aromaticus along with Ageratum conyzoides and Hyptis suaveolens had significant in vivo and in vitro insecticidal efficacy and was recommended as a non-phytotoxic herbal insecticide against Tribolium castaneum contamination. Similarly, a study conducted using essential oil of C. aromaticus against white termites (Odontotermes obesus Rhamb.), resulting in 100% mortality. Essential oil of C. aromaticus was reported to be more effective than commonly used synthetic insecticides Primoban-20 and Thiodan (Singh et al. 2002).

The C. aromaticus hydroalcoholic extract (CAE) revealed radioprotective potential that was essential for chemoprevention and in combating various free-radical mediated human pathological conditions (Rasineni et al. 2008). Boomi et al. (2019) demonstrated that AuNPs synthesized using C. aromaticus leaf extracts could be an alternative and effective source of UV protection, antibacterial and anticancer agents.

The allelopathic property of C. aromaticus was studied by testing water suspension of dried powder of C. aromaticus leaves against a troublesome aquatic weed, water hyacinth (Eichhornia crassipes Mart.). This experiment resulted in 100% mortality of the tested water hyacinth (Kathiresan 2000). The effect of manuring, drying method, and soaking time on the allelopathic property of C. aromaticus on water hyacinth was carried out by Gnanavel and Kathiresan (2007). This proved that both drying and soaking treatments of C. aromaticus were significantly effective in reducing fresh weight and chlorophyll content of E. crassipes. The allelopathic property of C. aromaticus indicates its ability in effective weedkilling.

Kumar et al. (2007) reported that C. aromaticus leaf extract exhibited mast cell stabilization property in rat peritoneal mast cells. Aqueous extract of leaves and roots of C. aromaticus possessed wound healing activity tested on excisional wound model in albino rats. This was confirmed using histopathological examinations of healing tissues (Jain et al. 2012). Poultice prepared using C. aromaticus leaves are used against centipede and scorpion bites (Hussain et al. 2012). C. aromaticus was reported to be an excellent treatment for dental cavities and to avoid oral bacterial growth. But when used along with mouthwash, Carvacrol present in C. aromaticus revealed antagonistic effects (Santos et al. 2015).

Along with the use of C. aromaticus for its above-described properties, C. aromaticus also finds its application in the food and beverage industry. Other than the use of C. aromaticus leaves as a flavouring agent, stuffing, or fritters, it is also used as an appetiser, in soup mix or to prepare chutney. Wadikar and Premavalli (2011) reported the appetising potential of C. aromaticus. A ready-to-drink C. aromaticus beverage (or karpurvalli beverage) had a significant appetising effect when compared to ginger or ajowan beverages and increased food intake and weight gain. A similar appetising effect was reported for a ready-to-eat C. aromaticus munch (or karpurvalli munch) with a shelf life of 8 months. Furia and Bellanca (1975) reported that Carvacrol, isolated from C. aromaticus may be added to baked goods (120 ppm) and in non-alcoholic beverages (26 ppm), whereas thymol can be added in chewing gums (100 ppm) and non-alcoholic beverages (2.5–11 ppm) (Pawan et al. 2014). Pawan et al. (2014) reported that C. aromaticus leaves can be used to prepare chutney that can be served with hot rice and fritters. C. aromaticus was reported to prepare a ready to reconstitute soup mix with a shelf life of 6 months (Wadikar and Premavalli 2013).

Conclusion

Coleus aromaticus is packed with many bioactive compounds and nutrients. These bioactive compounds are responsible for their bioactivities and medicinal properties. C. aromaticus has proved to be effective in curing multiple diseases. Thus, it can be stated that this herb is a suitable drug candidate that can be further explored and exploited to meet the global demand for natural, cost-effective, and safer bioactive compounds. The abundant availability of C. aromaticus in India as a must-have plant at home and in herbal gardens helps understand the use as a medicinal drug over its other relatives. This abundant availability of C. aromaticus and the presence of various bioactive compounds further opens new research vistas to strengthen its claim as an effective medicinal drug candidate. Additional research is highly recommended to authenticate the effectiveness of each bioactive compound extracted from C. aromaticus.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

Data sharing does not apply to this article as no new data were created or analysed in this study.