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Review Article
Journal of Chinese Integrative Medicine: Volume 9   November, 2011   Number 11

DOI: 10.3736/jcim20111103
An updated review on medicinal herb genus Spilanthes
1. Kishan Lal Tiwari (School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh 492010, India )
2. Shailesh Kumar Jadhav (School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh 492010, India E-mail: shailesh_07@sify.com)
3. Veenu Joshi (School of Studies in Biotechnology, Pt. Ravishankar Shukla University, Raipur, Chhattisgarh 492010, India )
Abstract: Herbal medicine has been used in medical practice for thousands of years and recognized especially as a valuable and readily available resource for healthcare in Asian nations. India is a vast repository of medicinal plants that can be developed as a safe and economical system of medicine for the treatment of various ailments. Unfortunately, most of the traditionally used medicinal plants are yet unexplored or have not been fully examined by modern medical science. Therefore, exploring traditionally reported medicinal plants to leverage their potential for the betterment of human health is of great importance. The present review examines a promising medicinal plant genus Spilanthes. In recent years, many new compounds and activities of this plant genus have been established. The present review therefore, aims to compile up-to-date and comprehensive information of genus Spilanthes with special emphasis on phytochemical and ethnomedical uses, scientifically documented pharmacological activities and tissue culture methods for conservation.
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Received June 26, 2011; accepted September 16, 2011; published online November 15, 2011.
Full-text LinkOut at PubMed. Journal title in PubMed: Zhong Xi Yi Jie He Xue Bao.

Correspondence: Shailesh Kumar Jadhav, PhD, Professor; Tel: +91-77-12263022; E-mail: shailesh_07@sify.com

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-  Top
-  Article and Author Info
-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


     The World Health Organization has estimated that 80% of the population of developing countries relies on plant-based traditional medicines to maintain their primary health care needs. High treatment costs and side effects along with drug resistance are major problems associated with synthetic drugs. Since traditional medicine is not only easily accessible but also affordable, there is an increased emphasis on the use of plants to treat human diseases. Therefore, the global markets are turning to plants as a potential and realistic source of ingredients for healthcare products.
     Secondary metabolites are found to be the source of various phytochemicals that could be used directly or as intermediates for the production of pharmaceuticals, as additives in cosmetic, food or drink supplements. In recent years, the aim of searching for novel treatments against a variety of illnesses has lead to the discovery of many new compounds from plants. Nowadays, researchers and academicians focus on the active principle responsible for the pharmacological activity of traditionally used medicinal plants. One such medicinal plant genus is Spilanthes, which has great market potential due to its numerous medicinal uses[1]. The present review highlights the up-to-date phytochemistry and medicinal uses and in vitro conservation method of this medicinally useful plant.

 
  

1  General introduction
    
Genus Spilanthes belongs to the Asteraceae family and is widely distributed in tropical and sub-tropical regions of the world[1]. In India, plants of this genus are reported from some of the regions of South India, Chhattisgarh and Jharkhand[2]. There are recent reports of their presence in Jhalarapatan in Jhalawar district of state Rajasthan[3, 4]. The plant genus grows naturally in damp areas, near lakes or ponds and near sewage discharge areas. It is commonly known as the toothache plant, paracress, eyeball plant and spot plant.
     Around 60 species of genus Spilanthes have been reported from different regions of the world[5]. Out of these, five species occur in India namely S. acmella Murr., S. acmella L. var. oleracea Clarke, S. calva L., S. paniculata L., and S. mauritiana L.[2]. S. calva, S. paniculata, and S. mauritiana grow wildly. S. oleracea is rare in occurrence whereas S. acmella is an acutely threatened species[6]. The genus Spilanthes is also mentioned as Acmella in some of the literature. S. americana, S. ocymifolia, S. alba, S. uliginosa, S. nervosa, S. urens, S. paraguyensis, S. oppositifolia, S. macraei, S. ciliate, S. costata, S. repens and S. beccabunga are examples of the known important species of genus Spilanthes which grow in different parts of the world.
     Plants of genus Spilanthes are generally around 40 to 60 cm tall. The stems are prostrate in some of the species and erect in others, with opposite, triangular or lanceolate leaves and dentate or almost entire margins. The flower heads are yellow, cone-like or ovoid, long-peduncled and solitary. The roots are long and tapering and also emerge from the nodal regions in prostrate plants. In some of the species, the heads have a dark red spot in the center. The seeds are small and grey, black in color. This plant genus grows throughout the year in tropical regions with rich soil and organic compost. Regular watering and shady conditions are essential for the proper growth of the plant genus. Genus Spilanthes has no serious disease problems although it may occasionally suffer from spider mite damage. It has poor vegetative propagation and a low rate of germination[7]. However, stem cuttings are often used for its propagation.

Jump to Section
-  Top
-  Article and Author Info
-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


2  Phytochemistry of Spilanthes
    
Phytochemicals are the chemical compounds that occur naturally in plants and have protective or disease-preventive properties, but are not essential nutrients. However, an analysis of phytochemicals is vital to make proper use of any medicinal plant.
     Different phytochemicals like alkaloids, glycosides, flavanoids, tannins, anthraquinones, saponins and cardiac glycosides have been reported in Acmella calva[8]. Alkamides are the most abundant phytochemicals present in genus Spilanthes which account for most of its biological activity. Alkamides have been identified in several species of Spilanthes including S.acmella, S. americana, S. oppositifolia, S. ocymifolia, S. ciliata, S. calva and S. mauritiana. Alkamides are bitter in taste and could stimulate salivation.
     Several secondary volatile metabolites like sesquiterpenes, alkamides and oxygenated compounds have been isolated and identified in S. americana[9]. However, the most abundant alkamide found was spilanthol. The molecular formula of spilanthol was determined as (2E,6Z,8E)-N-isobutylamide-2,6,8-decatrienamide[10]. It is present in the roots, flower heads and whole aerial parts of genus Spilanthes[11], and the flower heads and root part of the plant genus have been reported to be especially rich in this active principle content[12]. Spilanthol has a strong pungent taste; it may produce local astringency and anaesthetic effects[13].
     The structure of spilanthol and three other alkamides isolated from the flower head of S. acmella var. oleraceae has been determined by spectroscopic methods[14]. In another study, structures of the pungent alkamides of S. acmella L. were determined by using nuclear magnetic resonance spectroscopy and high-performance liquid chromatography-mass spectrometry (HPLC-MS) with atmospheric-pressure chemical ionization and electron-impact ionization[15]. The structure of some alkamides are given in Figure 1.
Recently, the LC-electrospray ionisation-MS method has been developed for the identification and quantification of spilanthol in S. acmella (L.) Murr.[16].
     Different compounds reported in genus Spilanthes along with their nature are shown in Table 1.

Figure 1  Structure of some alkamides present in Spilanthes

Table 1  Secondary metabolites in Spilanthes

Spilanthes species

Reported secondary metabolites and their chemical nature

S. acmella





 

N-isobutylamide: spilanthol[17], undeca-2E,7Z,9E-trienoic acid isobutylamide[17], undeca-2E-en-8,10-diyonic acid isobutylamide[17], 2E-N-(2-methylbutyl)-2-undecene-8,10-diynamide[14], 2E,7Z-N-isobutyl-2,7-tridecadiene-10,12-diynamide[14], 7Z-N-isobutyl-7-tridecene-10,12-diynamide[14]
Phytosterol: β-sitosterol[18], stigmasterol[18, 19], α- and β-amyrins[18]
Essential oil: limonene[20], β-caryophyllene[20], (Z)-β-ocimene[20], germacrene D[20], myrcene[20]
Hydrocarbon: mixture of C22 to C35 normal hydrocarbons[21]
Alcohol: myricyl alcohol[18, 19]

S. alba

N-isobutylamide: spilanthol[22], undeca-2E,7Z,9E-trienoic acid isobutylamide[22], acetylenic amides, acetylenes[22]

S. oleracea
 

N-isobutylamide: spilanthol[23], 2-methyl-butylamide[23], (Z)-non-2-en-6,8-diynoic acid isobutylamide[23], (Z)-dec-2-en-6,8-diynoic acid isobutylamide[23]

S. ocymifolia

Phenylethylamide: N-2-phenylethylcinnamamide[24]

S. calva

Flavonoid glucoside: tetrahydroxdihydrochalcone 3′-0-glucoside[25]

S. leiocarpa

Eudesmanolide[26]

S. americana

 

Sesquiterpene: α- and β-bisabolenes[9], caryophyllene[9], cadinenes[9]
N-isobutylamide: N-(isobutyl)-2E,6Z,8E-decatrienamide[9], N-(isobutyl)-6Z,83-decadienamide[9]
Phenylethylamide: N-(2-phenelethyl)2E,6Z,8E-decatrienamide[9]

Jump to Section
-  Top
-  Article and Author Info
-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


3  Ethnomedical uses
    
Various medical beliefs and practices of indigenous cultures are associated with the genus Spilanthes. Traditionally, the whole Spilanthes plant is used in the treatment of dysentery. In Cameroon, the plant is used as a snakebite remedy and in the treatment of articular rheumatism[27]. It is supposed to be useful in cases of tuberculosis[28]. In Germany, the plant extract is used for the treatment of soreness or bruising[29]. In India, S. acmella flower heads are used to treat stammering in children. Other traditional uses of Spilanthes according to the parts of the plant used are presented in Table 2.

Table 2  Traditional uses of different parts of Spilanthes

Part used

Traditional uses

Flowers
 

Relieve toothache[30], in stomatitis and throat complaints[30], cure paralysis of tongue[31], remedy for stammering[31], as spice[32]

Leaves
 

Stimulant[33], sialagogue[7], local anaesthetic[33], in bacterial and fungal skin diseases[34], as diuretic and lithotriptic[4], as salad[35]

Roots

Purgative and laxative[27], in cold and flu[27], in headache, asthma and rheumatism[19]

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-  Article and Author Info
-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  

4  Pharmacological activities
    
The genus Spilanthes includes many plant species that are being used for the treatment of various disorders including life-threatening diseases. Researchers have done different in vivo and in vitro pharmacological screenings to authenticate the traditional uses. These studies have revealed the potential of the plant to be developed as a curative agent from natural resources. Table 3 shows a detailed description of reported pharmacological activities on different Spilanthes species.

Table 3  Different pharmacological activities reported on various Spilanthes species

Pharmacological activity

Species

Part used

Type of extract

Models used

Reference
number

Diuretic

S. acmella

Flowers

CWE

Hydrated rats

36

S. acmella

Leaves
 

Petroleum ether,
chloroform and ethanol

Hydrated Wistar albino rats
 

37
 

Antimalarial, larvicidal

S. acmella
Murr.

Flowers
 

Ethanol
 

Anopheles, Aedes, Culex larvae
 

38
 

S. acmella, S.
calva,S.
paniculata

Flowers

 

Hexane

 

A. stephensi, A. culicifacies, C.
quinquefasciatus
larvae
 

39

 

S. mauritiana

Aerial parts

Methanol extract

Aedes aegypti larvae

40

S. mauritiana

Leaves

Crude powder

A. gambiae, Culex larvae

41

Insecticidal

S. calva

Leaves
and flowers

Petroleum ether, ethyl
acetate and methanol

Helopeltis theivora

42

S. acmella
Murr.

Leaves
and flowers

Aqueous

Chilo partellus

43

S. acmella

NA

NA

Periplaneta Americana

44

Vasorelaxant

S. acmella
Murr.

Aerial parts

Chloroform, hexane,
ethyl acetate, methanol

Phnenylephrine-induced rat

45

Antioxidant

S. acmella
Murr.

Aerial parts

Chloroform, hexane,
ethyl actate, methanol

2,2-Diphenyl-1-picrylhydrazyl (DPPH)
and superoxide dismutase (SOD) assay

45

S. acmella

Leaves, stems

Methanol

DPPH, SOD assay

46

Antinociception,
antihyperalgesic

S. acmella

Flowers

CWE

Formalin test of nociception and
carrageenan-induced thermal hyperalgesia
in rats

47

Acmella uliginosa
(Sw.) Cass

Flowers

Methanol

Chemicals (acetic acid-induced abdominal
constriction and formalin-, capsaicin-,
glutamate-induced paw-licking test) and
thermal models (hot-plate test) of
nociception in mice

48

Anti-inflammatory

S. acmella

Aerial parts

Aqueous

Carragenan-induced paw edema in rats

49

S. acmella

Aerial parts

Ethanol

Lipopolysaccharide-activated murine
macrophage model

50

Antimicrobial

S. paniculata

Leaves

NA

Bacillus subtilis, Staphylococcus aureus,
Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa,Candida
albicans
and Microsporum gypseum

51

S. americana

Whole plant

Aqueous, ethanol and
hexane

Staphylococcus aureus, Streptococcus
hemolytic
, Bacillus cereus, Pseudomonas
aeruginosa
and Escherichia coli

52

S. mauritiana

Roots and
flowers

NA

Staphylococcus, Enterococcus,
Pseudomonas
, Escherichia and
Klebsiella, Salmonella

53

S. acmella
Linn.

Flower heads

Petroleum ether

Fusarium oxysporium, F. moniliformis,
Aspergillus niger
and A. paraciticus

54

S. mauritiana

Roots and
flowers

NA

Candida species and Aspergillus species

55

S. calva

Roots

Methanol

Oral microflora: Streptococcus mutans, Lactobacillus acidophilus and Candida albicans

56

Immunomodulatory

S. acmella
Murr.

Leaves

Ethanol

Macrophage function in mice

57

S. acmella

Leaves

Ethanol

Neutrophil adhesion test in rat

58

HIV-1 protease inhibitor

S. acmella L.

Whole
plant

Chloroform, methanol
and water

In vitro HIV-1 protease solution assay
method

59

Convulsant

S. acmella

Whole
plant

Hexane

Electroencephalo-graph behaviour of rats

60

Antiviral

S. americana

Flowers

NA

NA

32

Antimutagenic

S. calva

NA

Chloroform

Ames Salmonella/microsome assay

61

Pancreatic lipase-inhibitory

S. acmella

Flowers

Ethanol

In vitro test

62

Antihepatoxic

S. ciliata

Whole
plant

Ethanol

Paracetamol-induced hepatic damage in rats

63

Antipyretic

S. acmella
Murr.

NA

Aqueous

Aspirin-treated rats

64

Local anaesthetic

S. acmella
Murr.

NA

Aqueous

Xylocaine-induced guinea pig and frog

64

Aphrodisiac

S. acmella L.
Murr.

Flowers

Ethanol

Nitric oxide release in human corpus
cavernosum cell line and penile erection in rats

65

Analgesic

S. acmella

Aerial parts

Aqueous

Acetic acid-induced writhing response in albino mice

49

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-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  

CWE: cold water extract; NA: data not available.

5  Marketed preparations
    
Genus Spilanthes is well known for its "folklore remedy". It is a potential medicinal plant which is also used for culinary purposes by tribes in various parts of the world. However, apart from its use by tribes, it is commercially cultivated and marketed in different parts of the world that indicates the increasing economic potential of this herb. Application of genus Spilanthes contributing to its economic potential includes its use in pharmaceuticals, as a nutritional supplement[66] and beauty care cosmetics[66-68], etc. A recent cosmetic product "Gatuline" claims that topical application of the extract of genus Spilanthes (Acmella oleracea) could reduce muscle tension and decrease facial wrinkles. Gatuline is being used as a non-injectable, cheap and easy-to-apply herbal Botox replacement (a popular cosmetic injectable preparation used to prevent the development of wrinkles)[69].

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-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


6  Tissue culture studies
    
With the increasing worldwide demand for plant-derived medicines, there has been a simultaneous increase in the demand for raw materials. However, the increasing human and livestock populations have affected the status of wild plants, particularly those used for making herbal medicines. Due to the multifold uses, genus Spilanthes is being overexploited by local populations as well as pharmaceutical companies. In addition, until now, little information is available on the biosynthetic pathway of alkamides. It has therefore become imperative to develop methods for large-scale propagation, conservation, and optimizing production of secondary metabolites. In this context, plant tissue culture is a useful tool for the conservation and rapid propagation of medicinally important and endangered plants.
     An efficient micropropagation protocol has been developed for S. acmella L. using seedling leaf explants through callus organogenesis. The best green and compact callus was obtained on 1 μmol/L naphthyl acetic acid and 10 μmol/L benzyladenine (BA) on the 15th day. The callus differentiated an average of 12.90±0.32 shoot buds in 50% cultures[70].
     S. acmella has been micropropagated using leaf explants which gave 20.00±0.47 shoots per explant with 3.0 mg/L BA and 1.0 mg/L indoleacetic acid[71].
     S. mauritiana DC. was successfully grown in vitro through axillary bud culture; 1.0 μmol/L BA and 0.1 μmol/L naphthaleneacetic acid resulted in maximum shooting response with minimal callusing[72].
     The aseptic axillary buds of S. acmella L. formed multiple shoots within five weeks when cultured on Murashige and Skoog medium supplemented with 2.0 mg/L N6-BA[73].
The nodal explants of S. acmella when placed vertically in a Erlenmeyer flask (250, 500, or 1 000 mL) produced more multiple shoots than those cultured in 350 mL jam bottles and 500 mL tex-Z flask. It has been also observed that temperatures above 28 ℃ caused abnormalities of in vitro plantlets[34].
     An efficient plant regeneration protocol was developed for S. calva using nodal segments grown on Murashige and Skoog medium containing 4.54 μmol/L thidiazuron which showed a better growth response and produced 22.3±0.3 shoots per explant after 35 d.
     S. acmella (L.) Murr. can be conserved at low temperature (4 ℃) up to 60 d by encapsulating shoot tips using 3% sodium alginate and 100 mmol/L calcium chloride and maximum percent response for the conversion of encapsulated shoot tips into plantlets was obtained on growth regulator-free full-strength liquid MS medium[74].
     In a gas chromatography-MS analysis, spilanthol was detected in the mother plant, flower heads and in vitro plantlets with similar retention time. Thus in vitro culture technique can become an alternative way to extract this valuable compound rather than from plants in the field[75].

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-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


7  Conclusion
 
   Genus Spilanthes is a plant of choice for many health-related disorders. Its traditional uses have been proved pharmacologically. The active ingredient spilanthol is proposed to be responsible for most of its biological activities. There are many other alkamides and secondary compounds reported from the plant, which can be investigated for the similar effects. Despite the fact that similar alkamides are reported from many other species of Spilanthes, S. acmella has been more extensively explored and found more potent pharmacologically. However, there is a paradox as some of the workers reported the convulsant activity of hexane extract of S. acmella. Thus there is a need for optimisation and demarcation of dose, responsible for its convulsant activity and other pharmacological activities which will be a step towards a safe and effective use of the plant.

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-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


8  Acknowledgements
    
The authors are thankful to Council of Scientific and Industrial Research (CISR), New Delhi, India for providing financial assistance.

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-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  


9  Competing interests
    
The authors declare that they have no competing interests.

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-  Article and Author Info
-  Introduction
-  General introduction
-  Phytochemistry of Spilanthes
-  Ethnomedical uses
-  Pharmacological activities
-  Marketed preparations
-  Tissue culture studies
-  Conclusion
-  Acknowledgements
-  Competing interests
-  References
  
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