EXCLI Journal 2013;12:291-312 – ISSN 1611-2156 Received: November 29, 2012, accepted: March 24, 2013, published: April 04, 2013 Review article: HIGH THERAPEUTIC POTENTIAL OF SPILANTHES ACMELLA: A REVIEW Veda Prachayasittikul1, Supaluk Prachayasittikul2*,Somsak Ruchirawat3, Virapong Prachayasittikul1* 1 Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand 2 Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok 10700, Thailand 3 Laboratory of Medicinal Chemistry, Chulabhorn Research Institute and Chulabhorn Graduate Institute, Bangkok 10210, Thailand * corresponding authors: 1 E-mail: [email protected]; Telephone: 662-441-4376, Fax: 662-441-4380 2 E-mail: [email protected]; Telephone: 662-441-4376, Fax: 662-441-4380 ABSTRACT Spilanthes acmella, a well known antitoothache plant with high medicinal usages, has been recognized as an important medicinal plant and has an increasingly high demand worldwide. From its traditional uses in health care and food, extensive phytochemical studies have been reported. This review provides an overview and general description of the plant species, bio- active metabolites and important pharmacological activities including the preparation, purifi- cation and in vitro large-scale production. Structure-activity relationships of the bioactive compounds have been discussed. Considering data from the literature, it could be demonstrat- ed that S. acmella possesses diverse bioactive properties and immense utilization in medicine, health care, cosmetics and as health supplements. As a health food, it is enriched with high therapeutic value with high potential for further development. Keywords: Spilanthes acmella, bioactive metabolites, bioactivities, structure-activity rela- tionships, in vitro production INTRODUCTION The World Health Organization has esti- mated that about 80 % of the population in Plants contain a diverse group of highly developing countries are unable to afford valuable and readily available resource of drugs and rely on traditional medicines es- bioactive metabolites, e.g. alkaloids, tan- pecially those that are plant-based (Eluma- nins, essential oils and flavonoids (Jagan lai et al., 2012) such as India (Jain et al., Rao et al., 2012; Prachayasittikul et al., 2006; Little, 2004), Sri Lanka (Ediriweera 2008, 2009b 2010a), which have been used 2007), Bangladesh (Rahmatullah et al., in medicinal practices for a long time 2010), China and Japan (Little, 2004) in- (Tiwari et al., 2011). Thus far, medicinal cluding Thailand (Phongpaichit et al., plant is an alternative medicine (Consult, 2005; Sawangjaroen et al., 2006). 2003) that is still in use and is a popular The practice of botanical healing slowly choice for primary health care(Vanamala disappeared from western countries with et al., 2012). However, if improperly used the introduction and advent of science and plants can also be toxic (Perry et al., 2000). technology (Tyagi and Delanty, 2003). 291 EXCLI Journal 2013;12:291-312 – ISSN 1611-2156 Received: November 29, 2012, accepted: March 24, 2013, published: April 04, 2013 However, the uses of traditional medicine employed as therapeutics and health care dramatically increased in Europe and (Abascal and Yarnell, 2010). Therefore, North America in the last 50 years (Tyagi Spilanthes acmella Murr. is a plant of great and Delanty, 2003). interest owing to its known reputation as Herbal medicines have been utilized for an antitoothache plant and hold tremen- many purposes, particularly in medical dous medicinal usages. This review focus- care as antiasthmatics (86.79 %), anti- es on the general background, therapeutic rheumatics (62 %) (Jain et al., 2006), diu- uses, bioactive compounds and large-scale retics (60.22 %) (Kumar et al., 2010; production. Vanamala et al., 2012), antiinflammation (29.62 %), anticancer (9.75 %), antidiabe- General tics (8.33 %), antimicrobials, antifungals, Spilanthes (Compositae or Asteraceae) antioxidants, antiallergy, analgesics, anti- is a genus comprising of over 60 species obesity and antihypertention. In dental care that are widely distributed in tropical and it has been employed as anticariogenic subtropical regions of the world, such as (Ferrazzano et al., 2011), analgesic Africa, America, Borneo, India, Sri Lanka (Abascal and Yarnell, 2010; Kroll, 1995), and Asia (Sahu et al., 2011; Tiwari et al., local anesthetic (Abascal and Yarnell, 2011). S. acmella is native to Brazil and is 2010), wound healing agents (Abascal and cultivated throughout the year as ornamen- Yarnell, 2001, 2010; Jagan Rao et al., tal or medicinal plant. It is an annual or 2012), antiinflammation (Abascal and short-lived herb that is 40-60 centimeters Yarnell 2001, 2010) and recurrent aph- tall. It is grown in damp area (Tiwari et al., thous stomatitis treatment (Abascal and 2011; Wongsawatkul et al., 2008) and has Yarnell 2010). It has also been used for low rate of germination or poor vegetative beauty care (Artaria et al., 2011; Demarne propagation (Tiwari et al., 2011). Its flow- and Passaro, 2009) and as health food e.g. ers and leaves have pungent taste and curcumin (Curcuma longa Linn.) (Kohli et when touched it is accompanied by tin- al., 2005), ginger (Zingiber officinale) gling sensation and numbness (Wong- (Kubra and Rao, 2011), lemon grass sawatkul et al., 2008). The plant species (Cymbopogon citrates Stapf) (Nanasombat has been used commonly as a folk remedy, and Teckchuen, 2009), green shallot (Alli- e.g. for toothache, rheumatic and fever um cepa var. aggregatum) (Rabinowitch (Wongsawatkul et al., 2008), as fresh and Kamenetsky, 2002), garlic (Allium sa- vegetable (Tiwari et al., 2011) as well as tivum L.) (Borek, 2010), holy basil (Oci- spice for Japanese appetizer (Leng et al., mum sanctum Linn.) (Singh et al., 1996), 2011). sweet basil (Ocimum basilicum L.) (Lee et al., 2005), hairy basil (Ocimum basilicum Traditional uses L.f. var. citratum Back.) (Chanwitheesuk The whole plants (e.g. flowers, leaves, et al., 2005) and kitchen mint (Mentha roots, stems and aerial parts) of Spilanthes cordifolia Opiz.) (Özbek and Dadali, have been used in health care (Leng et al., 2007). 2004; Ospina De Nigrinis et al., 1986; Recently, health foods, herbs as well as Purabi and Kalita, 2005; Research, 1976; dietary supplements enriched with medici- Rios-Chavez et al., 2003; Senthilkumar et nal ingredients such as antioxidants and al., 2007; Tiwari and Kakkar, 1990) and bioactive metabolites have drawn consid- food (Barman et al., 2009; Boonen et al., erable attention worldwide, especially 2010; Wu et al., 2008).Particularly, S. ac- herbs that are used as food and traditional mella or S. oleracea (paracress or eyeball medicine (Tyagi and Delanty, 2003). Our plant), is a well-known antitoothache plant concern centers around medicinal plants (Sahu et al., 2011) and has been used as bearing bioactive compounds, which are traditional medicine for many purposes 292 EXCLI Journal 2013;12:291-312 – ISSN 1611-2156 Received: November 29, 2012, accepted: March 24, 2013, published: April 04, 2013 (Table 1). So far, various Thai medicinal ticularly, anandamide (N-arachidonoyl- plants have been used for the remedy of ethanolamine, 9) is an endogenous canna- toothache as well as used in dental applica- binoid cerebral neurotransmitter (Fig- tions (Table 2). ure 1). Spilanthol was first isolated in 1945 Bioactive metabolites from the flower head ethanol (EtOH) ex- Extensive phytochemical investigations tract of S. acmella. In early 1903, it was of S. acmella had previously been reported. first obtained from the different plant spe- It constitutes a diverse group of com- cies, S. acmella L.var. oleracea Clarke pounds. Major isolates were lipophilic al- (Gokhale and Bhide, 1945). Aside from kylamides or alkamides bearing different being found in S. acmella, spilanthol was number of unsaturated hydrocarbons (al- also found in other plant species as shown kenes and alkynes), such as spilanthol (1) in Table 3 (Rios, 2012). or affinin (2E,6Z,8E)-N-isobutyl-2,6,8- The synthesis of spilanthol was reported decatrienamide (Gokhale and Bhide, 1945; in multistep and afforded low overall Ramsewak et al., 1999) and amide deriva- yields. However, an efficient synthetic tives 2–8 (Figure 1). In general, when al- method had been developed (Wang et al., kamides are chewed, a pungent taste is re- 1998). Thus far, the spilanthol is commer- leased and causes itch and salivation (Rios, cially available in form of alcoholic (65 % 2012). Alkamides are structurally related EtOH) extract or A. Vogel Spilanthes. to animal endocannabinoids and is highly active in the central nervous system. Par- Table 1: Traditional uses and applications of S. acmella Health care Treatment Plant References extract Medical Rheumatism, fever leaves, Bunyapraphatsara and Chokechareunporn, Diuretics flowers 1999; Farnsworth and Bunyapraphatsara, 1992 Flu, cough, rabies diseases, Yadav and Singh, 2010 Tuberculosis, antimalarials, Haw and Keng, 2003 Antibacterials Antifungals, skin diseases leaves Tiwari et al., 2011 Immunomodulatory Sahu et al., 2011 Antiscorbutic Leng et al., 2011; Sahu et al., 2011 Local anesthetics Tiwari et al., 2011 Digestive Leng et al., 2011; Sahu et al., 2011 Obesity control flowers Yuliana et al., 2011 (lipase inhibitor) Snake bite whole plant Tiwari et al., 2011 Dental Toothache leaves, Haw and Keng, 2003; Tiwari et al., 2011 flower Toothpaste leaves Savadi et al.,