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Plant-Derived Antimycotics: Potential of Asteraceous Plants

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Rai, M.K., Deepak Acharya and P. Wadegaonkar (2003). Plant derived-antimycotics: Potential of Asteraceous plants, In: Plant-derived antimycotics:Current Trends and Future prospects, Haworth press, N-York, Londin, Oxford, pp 165-185.

Plant-Derived Antimycotics: Potential of Asteraceous Plants 

 1Mahendra Rai, Deepak Acharya2 and P. A. Wadegaonkar1

 1Department of Biotechnology

             Amaravati University, Amaravati- 444602, Maharastra state, India

E-mail: mkrai123@rediffmail.com   and  mkrai@123india.com

2Microbiology Research Lab, Danielson College

Chhindwara- 480 001,   M.P.  state,  India

deep_acharya@ rediffmail.com

 

Abstract

 

   New spectrum of opportunistic human mycotic infection are increasing day-to-day due to increase in number of AIDS and cancer patients. Such fungal pathogens form new combination with immunocompromised or immunosuppressed hosts. Sometimes,  azoles do not respond well in mycotic infections.  Due to this reason, there has been a search for newer generation of drugs to combat such complex mycotic pathogens. This has attracted the researchers towards drugs from plants, microbes and also from other synthetic sources. The fact that the Asteraceous plants posses antimycotic potential has been realized in the recent past in India and abroad, and is being practiced  from time immemorial  in India. A large number of plants of this family have been evaluated and proved to be antimycotic. Essential oils obtained from these plants are also antimycotic in  nature.

 

   The present review is aimed to discuss different aspects of antimycotic efficacy of Asteraceous plants, particularly antifungal nature of plant extracts and essential oils, role of sesquiterpene lactones, mechanism of action,  and future prospects of promising plants in order to combat mycosis.

 

Key words:  Plant-derived,  antimycotics,  Asteraceae,  opportunistic,  human pathogenic fungi

 

Introduction

           

   The treatment of human mycosis has been a  great challenge before the clinicians and dermatologists. In one hand, the opportunistic fungal infections are increasing with alarming rate, while on the other, allergic reactions of the skin are increasing day to day. The later is due to a higher rate of sensitization power of the present generation of antimycotic agents. Potential human pathogenic fungi in general and opportunistic fungal infections in particular are usually treated by  the use of drugs belonging to the imidazole family. But these potent antimycotics are in the hands of rich and not responding to the new spectrum of opportunistic fungal infections which are common in immunocompromised hosts. Therefore, to combat newly borne spectrum of fungal infections, step should be taken to make the benefits of successful pharmaceutical research available to all and especially to those who are in the greatest need. In fact,  it is the need of hour to search for new antifungal agents of herbal origin which are relatively economically affordable, safer and easily available to common men. Moreover,  sometimes imidazole derivatives are not effective owing to which alternative drugs are required (Lowey et al., 1985). A perusal of literature indicates that many investigators have reported fungistatic and bacteriostatic properties of extracts of higher plants (Bhakuni et al.,1969, 1971;  Dhar et al., 1974;  Ray and Majumdar, 1975, 76; Tansey and Appleton, 1975; Jain and Agarwal,1976; Dhawan et al., 1977; Misra and Dixit,1979; Jain et al.,1980 a, b;  Wahab et al., 1981; Barde and Singh,1983; Ikram and Haq, 1984; Singh and Deshmukh, 1984; Rai, 1987; Rai and Upadhyay, 1988, 89; Mares, 1989; Mares and Fasulo, 1990; Yadav and Saini, 1990; Lima et al., 1992, 1993;  Perrucci et al., 1994; Rahalison et al., 1994; Villarreal, 1994; Grosvenor et al.,1995;  Rai, 1995; Adams et al., 1996; Jain,1996;  Narayanarao et al., 1996;  Gopallakrishnan et al., 1997; Rai et al.,1997, 99;  Rai and Acharya, 1999;  Singh, 2000). Many antimycotic agents were introduced for the treatment of mycosis during recent past. Most of these active agents are only useful for topical application because of their toxic nature. They are broad spectrum antimycotics which are effective agaist fungi that infect human beings. In the treatment of mycosis, such kind of active agent is preferred because here a broad spectrum therapy is required (Gellin et al.,1972; Emmett and Marrs, 1973 and Tronnier and Kosen, 1985).

 

   The antifungal activity of nonvolatile constituents of higher plants has earlier been reviewed by some workers (Dekker,1969; Thapliyal and Nene, 1969; Calpouzos, 1969; Fawcett and  Spencer, 1970; Dixit and Tripathi, 1982; Mahadevan, 1982). Many plants produce essential oils as secondary metabolites. But,  their exact role in the life processes of the plant is unknown.  A review of literature reveals that a large number of essential oils were reported to possess fungitoxic activity (Barnes, 1963; Korta and Starzyk, 1963;  Maruzzella, 1963; Hiller, 1964; Birch,1966; Korbely and Florian, 1971; Garg, 1974;  Zutschi et al., 1975; Overeem, 1976; Gautam et al.,1980; Jain et al.,1980 a, b; Ikram and  Haq 1980,1984; Deshmukh et al.,1986; Singh et al., 1986; Kishore and Dwivedi, 1991;  Jain and Agarwal, 1992; Perrucci et al., 1994;  Mwosu and Okafor, 1995; Goren et al., 1996; Gopallakrishnan et al., 1997; Rai et al., 1999). The most members of family Asteraceae are known to contain essential oils which usually have antifungal / cytotoxic sesquiterpene lactons.

 

International status

 

   A survey of literature indicates that many investigators have studied herbal antifungal agents in the recent past in abroad (Maruzzella and Logeuri, 1959; Maruzzella and Balter, 1959; Maruzzella et al., 1959; Tokin,1960;  Fawcett and Spencer, 1970; Birner and Nicolis, 1973; Burden and Bailey, 1975; Kobayashi and Madoff, 1977;  Fromting and Bulmer, 1978; Daphne et al.,1982; Rahalison et al., 1993; McCutchen et al.,1994; Villarreal et al.,1994; Mwosu and Okafor, 1995; Demchenko et al., 1995;  Alkofahi et al. 1996; Goren et al., 1996; Khan and Evans, 1996; Navarro et al.,1996;  Achola et al.,1997; Al Magboul et al., 1997).  Maruzzella et al. during 1956-1963 did a major work in this direction and tested about 119 essential oils, out of which, 59 were reported as very effective antimicrobial agent. Tokin (1960) studied the antibiotic substance produced by higher plants in detail. He proposed the name Phytoncide to biologically active substance produced by higher plants and studied phytoncide of Onion, Garlic and some other plants which contain the strongest antibiotic properties. Aizeman (1978) studied antibiotic properties of about 1500 varieties of higher plants selected from USSR, Tarkmann, and SSR. Ikram and Haq (1984) screened about 100 medicinal plants of Pakistan for their antimicrobial activity. But only a few exhibited remarkable activity.  Mares (1987) found lactones to be antidermatophytic. Extracts of Rhuburb was reported to be effective against Trichophyton, Microsporum and Epidermophyton (Itsuo, 1985).  McCutchen et al. (1994) screened more than one hundred methanolic plant extracts for antifungal activity against 9 fungal species. Eighty-one were found to have some antifungal activity and 30 extracts showed activity against 4 or more of the fungi assayed. They reported Artemisia ludoviciana and A. tridenta to be active against 9 fungi.

 

National Status

 

   Although, several investigators have contributed much on antimycotic activity of medicinal plants, yet the work is very fragmentory and meagre (Jain and Agarwal, 1976; Rao, 1976; Thind and Dahiya, 1976; Sharma et al., 1978; Misra and Dixit, 1979; Mishra et al., 1979; Tripathi and Dixit, 1981; Alankara  et al., 1981; Asthana et al., 1982; Chandra et al., 1982b;  Singh and Deshmukh, 1984;  Chauhan and Saxena, 1985; Deshmukh et al.,1986; Rai, 1987, 1988, 1993;  Tripathi et al., 1988; Radhika, 1992; Rai and Vasanth, 1995;  Pattnaik et al.,1996, Rai et al., 1997; Rai and Acharya 1999,  2000;  Singh, 2000).  Screening of Indian plants for a wide range of activity (antimalarial, antiprotozoic, antiviral, antihelminthic, anticancer, antifungal, etc.) have been carried out by various investigators. A perusal of literature indicates that many investigators have reported fungistatic and bacteriostatic properties of extracts of higher plants (Dhar et al., 1968; Bhakuni et al.,1969, 1971;  Dhar et al., 1973, 74;  Ray and Majumdar, 1975, 76; Jain and Agarwal,1976; Dhawan et al., 1977; Misra and Dixit,1979;  Dhawan et al., 1980; Jain et al.,1980;  Wahab et al., 1981; Barde and Singh,1983;  Aswal et al., 1984; Singh and Deshmukh, 1984; Abraham et al.,1986; Rai, 1987; Rai and Upadhyay, 1988; Yadav and Saini, 1990; Rai, 1995;  Jain,1996;  Narayanarao et al., 1996;  Gopallakrishnan et al., 1997; Rai et al.,1997, 1999;  Rai and Acharya, 1999). However, Bhakuni et al., (1971) reported that antifungal activity could be observed only in 3-extracts out of 300 plants which indicates that more thorough investigation is required for the search of antifungal activity. 

 

   The investigators of Central Institute of Medicinal and Aromatic Plants, Lucknow, have screened about 3,231 material from 3,051 plants for their biological activity (Dhar et al., 1968; Bhakuni et al. 1969, 1971; Dhar et al.; 1973, 74; Dhawan et al., 1977, 80). Only 10-plants exhibited activity against ogens of superficial mycosis. Out of these plants only Artemisia dranunculus (member of Asteraceae) showed fungitoxic activity against pathogenic fungi.

 

Noteworthy contribution in the field 

 

   A  review of  literature reveals that  a significant contribution has been made on antimycotic potential of  family Asteraceae (Rao, 1976;  Mathela and Sinha, 1978; Geda and Bokadia, 1979; Chandra and Dikshit, 1981; Wahab et al.,1981; Chandra et al., 1982b; Daphne et al.,1982;  Devi and Nandkumar 1983;  Singh et  al.,1986; Rai and Upadhyay, 1990; Yadav and Saini, 1990; Kishore and Dwivedi, 1991; Rai, 1993; Villarreal et al.,1994; Alkofahi et al., 1996; Khan and Evans, 1996; Miguel et al., 1996; Romanelli et al.,1996;  Al Magboul et al.,1997; Rai et al., 1997; Singh, 1999; Rai and Acharya,1999). Rao (1976) studied the antimicrobial effect of the essential oil of Ageratum conyzoides. Mathela and Sinha (1978) tested some indigenous essential oils for their antibacterial and antifungal activity.  Aster beduncularis, A. thomsonii were found to be antifungal. Geda and Bokadia (1979) reported antifungal activity of Blumea membranacea. Pandey et al. (1982a) recorded fungitoxic and phytotoxic properties of the essential oil of Caesulia axillaris. Chauhan and Saxena (1985) studied the antifungal activity of the leaves of Inula cuspidata. Bader et al. (1990) found fungicidal activity in  Solidago virgaurea against Candida albicans.  Antimycotic potential of Parthenium hysterophorus against human pathogenic fungi  was  investigated  by Rai and Upadhyay (1990) and (Rai, 1993, 1994, 1995).  Rai and Vasanth (1995) evaluated sensitivity of three keratinophilic fungi  to some vicolides isolated from Pentanema indica. Goren et al. (1996) reported cytotoxic and antibacterial activities of sesquiterpene lactones isolated from Tanacetum praeteritum. Romanelli et al. (1996) observed pharmacological activities of methanolic extracts of Centaurea deusta and Crepis lacera. A notable  contribution has been made by Alkofahi et al. (1996),  who reported antimicrobial activity of 52 medicinal plants of Jordan. Achillea aleppica extract showed highly antifungal activity. Miguel et al. (1996) isolated chemical constituents from Lychnophora salicifolia  which later exhibited antifungal activity by the disc diffusion methods. Zheng et al. (1996) isolated two new flavones from Artemisia giraldi and observed antifungal activity against Aspergillus flavus and Trichoderma viride. Artemisia mexicana posessed strong in vitro antifungal activity against Candida albicans, Navarro et al. (1996). Al Magboul et al.(1997) isolated vernolepin and vernodalin from Vernonia amydalina and studied fungicidal activity against Aspergillus niger and Candida albicans. Vasanth (1996) studied the chemistry and biology of Pentanema indicum and observed very good antifungal activity of the plant against Candida albicans and C. krusei. Hamsaveni et al. (1992) also studied the antimicrobial efficacy of Pentanema indica. Achola et al. (1997) observed pharmacological activities of Gutenbergia cordifolia. Rai and Acharya (1999) evaluated in vitro activity of 31 plant extracts of family Asteraceae against Fusarium oxysporum and Trichophyton mentagrophytes. The maximum antimycotic activity against both the fungi was exhibited by flower extract of Tagetes erecta. 

 

Antifungal potential of  some  important Asteraceous plants

 

Achillea spp.

 

   Antifungal activity in the leaf oil of  A. fragrantissima was reported against C. albicans, a causal organism of common tinea pedis (Barel et al., 1991). Similarly,  Kedzia et al., (1990) found strong activity of leaf oil  extracted  from A. millefolii against Candida albicans. Abbasoglu and Kusmenoglu (1994) recorded slight antifungal activity in the aerial parts of its four species.

 

Ageratum conyzoides 

 

   Rao (1976a) and Sharma et al.  (1978)  reported antimycotic activity in leaf oil  of A. conyzoides against various plant pathogens, viz., Alternaria helianthi, Colletotrichum capsici, Fusarium moniliforme, F.  solani, Helminthosporium oryzae, H. turcicum, Pennicilium chrysogenum, P. javanicum,  Pyricularia setariae,  P.  oryzae, Pythium vexans, Rhizoctonia bataticola and R. solani. Fungistatic nature of the oil at 0.2 % (2.0 x 103 Ál/ l) concentration against various fungi was reported  by Chandra  and Dikshit (1981).  Later, Chandra (1984) found that the oil controlled the blue mould rot during storage of oranges, caused by Penicillium italicum at 0.1 % (1.0 x 103  Ál/ l) concentration. Mycelial growth of  dermatophytes, viz., Epidermophyton floccosum, Microsporum canis and Trichophyton mentagrophytes was completely checked when dipped in 4000 ppm (4.0 x 103  Ál/ l) dose of the oil  (Singh et al., 1986).

 

A. houstonianum

 

   Pandey et al.  (1983a)  found  the  antifungal activity in essential oil of leaf  at 100 ppm (0.1 x 103  Ál/ l) concentration, possessing fungistatic nature against Blastomyces dermatidis, Epidermophyton floccosum, Histoplama capsulatum, Trichophyton mentagrophytes, T. simii, T. terrestre, T. tonsurans, T. verrucosum and T. vialaceum.  However, it killed Microsporum gypseum within 1 second at 300 ppm (0.3 x 103  Ál/ l) dose by contact.  The  chemical  of the oil which is responsible for antifungal activity  was  found to be thermostable and fungistatic against Fusarium lateritium at 0.05 percent (0.5 x 103  Ál/ l) concentration.

 

Anaphalis contorta   

 

            Saxena et al.  (1984)  reported that the leaf oil of the plant showed antifungal activity against  Aspergillus niger, Microsporum gypseum, and  Penicillium notatum

 

Arnica latifolia

 

   A  significant antimycotic activity of oil was reported against Candida albicans, Cephalosporium sacchari, Ceratocystis paradoxa, Curvularia lunata, Epidermophyton floccosum, Fusarium moniliforme, Helminthosporium sacchari, Physalosporo tocumenensis, Trichophyton rubrum and Sclerotium rolfsii  (Singh, 1976).

 

Artemisia absinthium

 

            Kaul et al. (1976) noted the toxicity of oil at 1: 1000 (1.0 x 103  Ál/ l) dilution against Candida species and Aspergillus niger.

 

A. afra

 

The essential oil present in leaf possess high degree of fungitoxicity  (Graven et al., 1992).

 

A. capillaris

 

             The antimycotic activity in essential oil of   A. capillaris is due to Capillin  (Imai, 1956).  Ikenaka et al. (1956) reported that the oil showed toxicity to Alternaria kikuchiana, Aspergillus awamori, A. niger, A. oryzae, Gibberella fujikuroi, G. bataticola, G. sanbinetti, Colletotrichum miyabeanus, Penicillium chrysogenum, Pyricularia oryzae and Rhizopus javanicus.  

 

A. cina

 

            The oil of A. cina was found to be active against Candida albicans and  Microsporum  species  (Vichkanova et al., 1972).

 

A. giraldi 

   

            Zheng et al. (1996) reported toxicity in oil of Artemesia giraldi  against Aspergillus flavus and Trichoderma viride.  This must be due to the flavones present in oil.

 

A. martima   

  

The antimycotic  activity of  A. martima against  Microsporum gypseum, Trichophyton equimum and  T. rubrum  was reported by Dikshit and  Hussain (1984).

 

A. mexicana

 

 Artemesia mexicana posessed strong in vitro antifungal activity against Candida albicans (Navarro et al.,1996).

 

A. pallens and A. vulgaris 

 

               Fungitoxicity in essential oil  of A. pallens and A. vulgaris was reported against Fusarium moniliforme, Helminthosporum longisporum, Trichoderma viride and Colletotrichum species. (Laxmi and Rao,  1991).

 

A. parviflora

 

                Mehrotra et al.  (1993)  found fungitoxicity  in essential oil  against Candida albicans and Sporotrichum species.  

 

A.  vestita

 

The antifungal activity of the oil at 1: 1000 (1.0 x 103  Ál/ l) dilution was reported against  Nannizzia fulva,  N. gypsia and N. incurvata  (Kaul et al., 1976; Gautam et al., 1980).

 

A. herba-alba and A. judaica

 

               Charchari  et al.  (1996) reported  remarkable antifungal activity in essential oil of A. herba-alba and A. judaica  against Candida albicans, C. stellatoidea, C. tropicalis, Microsporum canis, M. gypseum, Trichophyton interdigitale and Aspergillus terreus.

 

Blumea membranacea 

 

            The antimycotic activity of the oil was reported against Alternaria helianthi, Fusarium moniliforme, Helminthosporum oryzae, H. turcicum, Pyricularia setariae and Rhizoctonia solani (Zutschi and Mehta, 1977;  Sharma et al.,  1978). Later,  its toxicity was reported against Aspergillus luchuensis, A. sydowi and  Cladosporium cladosporioides (Geda and Bokadia, 1979).

 

Caesulia axillaris 

 

            Zutschi et al. (1975)  found  antifungal activity in essential oil of Caesulia axillaris. Pandey et al. (1982a) also reported antimycotic potential of the plants against Helminthosporium oryzae    The oil showed a broad fungitoxic spectrum besides superiority over eight synthetic fungicides. 

 

   The antifungal factor of the oil was thermostable, durable upto 180 days of storage and could bear increased inoculam density (Pandey et al., 1982a).

 

Cirsium dipsacolepsis

 

               Cyperenal isolated from the plant possessed strong antibiotic activity agaist bacteria and fungi. The antifungal activity was measured against  Rhizoctonia solani (Achenbach and Benirschke, 1994).

 

Eupatorium ayapana

 

Antimycotic activity in oil was recorded against species of Aspergillus, Curvularia and Penicillium (Chourasia and Kher, 1978).  Further, antifungal activity of the oil  was also noted against Alternaria spp., Aspergillus spp., Cladosporium herbarum, Cunninghamella echinulata, Fusarium spp., Helminthosporium sacchari, Microsporum spp., Mucor mucedo, Penicillium digitatum, Rhizopus spp. and Trichophyton spp (Sharma and Singh, 1979).

 

E. cappilifolium

 

            The leaves yielded 1 per  cent oil which was fungistatic to various fungi at 1000 ppm (1.0 x 103  Ál/ l) doze (Chandra et al., 1982b). They further reported that the fungitoxicity of the oil was enhanced at pH 7 and pH 9. Rao et al. (1992) observed antifungal activity in the leaf oil against Colletotrichum falcatum, Curvularia pallescens, and Periconia atro-purpurea.

 

E. triplinerve

 

               Antifungal activity in oil  extracted from the leaves of the plant was recorded against Aspergillus, Curvularia, Fusarium, Paecilomyces, Trichurus, and Helminthosporium (Garg, 1974;  Yadav and Saini, 1990). 

 

Glossocordia bosvallia

 

               Antimycotic activity of the essential oil against plant pathogenic as well as human pathogenic fungi, viz., Aspergillus niger, Botryodiplodia theobromae, Botryothichum keratinophilum, Chrysosporium tropicum, Microsporum gypseum, Malbranchea pulchella, Phytopthora parasitica var. piperina and Rhizopus nodosus was reported  by Pathak and Dixit (1984).

 

Helianthella quiquenervis

 

   Castaneda et al. (1996) evaluated the  antifungal  efficacy of plant against three fungi, viz., Candida albicans, Aspergillus niger, Trichophyton mentagrophytes.

 

Helichrysum italicum

 

               Chirkina and Osipova (1974) isolated eugenol, furfurol, geraniol, neurol and a- pinene in oil extracted from flowers and found to be antifungal against  Candida albicans.

 

Inula cuspidata 

 

            The oil  is  highly antifungal against Aspergillus species  (Chauhan and  Saxena, 1985).

 

I.  helenium

 

            Bourrel et al. (1993)  reported  antimycotic activity in essential oil against 7 test fungi.

 

I.  racemosa

 

             The toxicity in oil  of  I.  racemosa  was reported against Alternaria helianthi, Colletotrichum capsici,  F. moniliforme, Fusarium solani, Helminthosporium turcicum, H. oryzae, Pyricularia setariae, Phythium vexans, Rhizoctonia bataticola and R. solani  (Misra and Dixit, 1978; Mishra et al., 1979).

 

Jasonia spp.

 

               Hammerschmidt et al. (1993) found  antifungal activity in essential oil extracted from J. candicans and J. montana  against Trichophyton mentagrophytes, Cryptococcus neoformans and Candida albicans.

 

Parthenium hysterophorus

 

            Sharma and Singh (1979) reported a remarkable  antimycotic activity in oil.  The oil completely inhibited the growth of Alternaria spp., Aspergillus spp., Cladosporium herbarum, Cunninghamella echinulata, Fusarium spp., Helminthosporium sachhari, Microsporum spp., Mucur mucedo, Penicillium digitatum, Rhizopus  spp., Trichophyton spp. and Trichothecium roseum. Antimycotic potential of different extracts of  Parthenium hysterophorous against human pathogenic fungi  was  also investigated  by Rai and Upadhyay (1990) and (Rai, 1993, 1994, 1995).

 

P. argentatum  and P. tomentosa

 

               Fungistatic sesquiterpenoides isolated from the plants demonstrated significant antifungal activity against A. niger ( Maatooq  and Hoffmann, 1996).

 

Pectis elongata

 

            Prudent et al. (1995) found the leaf oil toxic against six fungi.

 

Pentanema indica

 

            Rai and Vasanth (1995) reported the sensitivity of vicolides isolated from  Pentanema indica to Microsporum gypseum,  Chrysosporium tropicum and Trichophyton mentagrophytes.

 

Sphaeranthus indicus  

 

            The oil showed antimycotic activity against Cephalosporium sacchari, Ceratocystis paradoxa, Curvularia lunata, Fusarium moniliforme, Helminthosporium sacchari, Physalospora tucumanensis and Sclerotium rolfsii  (Rao and  Joseph, 1971).

 

Tagetes erecta   

 

            Kishore and Dwivedi (1991) reported that the essential oil of leaf completely inhibited the mycelial growth of Pythium aphanidermatatum at 200 ppm (2.0 x 103 Ál/ l) dilution. Rai and  Acharya (1999) recorded maximum antimycotic activity of the aquous extract and essential oil of the plant against Fusarium oxysporum and Trichophyton mentagrophytes

 

Sesquiterpenes as antimycotics 

 

   The dermatophytes and other fungal pathogens have been found to be sensitive to sesquiterpene lactones  which are present as active agent in Asteraceous plants  (Magboul et al., 1977; Lima et al., 1993;  Mares et al., 1993; Maatooq  and Hoffmann, 1996).    

 

   Magboul et al. (1977)  reported antimycotic activity of Vernolepin and Vernodalin isolated from Vernonia amygdalina  Del.  They found that  Aspergillus niger and Candida albicans were sensitive to both the pigments.  Villarreal et al. (1994)  stated that only one sesquiterpene lactone, viz., taraxasterol  showed  antimycotic activity against Candida albicans.  Maatooq  et al. (1996) reported fungistatic activity of partheniol and  guayulone (a new dinorsesquiterpenoid diketone), two pigments isolated from Parthenium argentatum x P. tomentosa  (guayule hybrid). Artemisinin, a sesquiterpene isolated from  Artemisia annua (sweet wormwood) was found to be strongly antifungal. Two new flavones, 4',6,7-trihydroxy-3',5'-dimethoxy-flavone and 5',5-dihydroxy-3',4',8-trimethoxyflavone were isolated from Artemisia giraldii and their structures were identified by spectroscopic methods. These two new  flavones also showed antimycotic activity against  Aspergillus flavus, and Trichoderma viride (Zheng et al., 1996). Sesquiterpene lactones isolated from various plants have shown their potential against the infections caused by various fungi in general, and dermatophytes in particular.

Mechanism of action

 

   The actual mechanism of action of  unsaturated sesquiterpene lactones is not yet clearly known. But, there are reports which indirectly suggest its action as an auxin inhibitor.  Cavallito and Haskel  (1945) suggested that the action of lactones is due to their specific reactivity with sulphydryl (-SH) group.  Later, the study was supported by many workers  (Thimann and Bonner,  1949;  Hall et al.,  1980).  It is assumed that the inhibitory action of  unsaturated lactones should be prevented by BAL (2, 3-dimercaptaol-propanol) or cysteine, a compound known to protect -SH group from inactivating  the substances.

  

   Mares (1987) also worked on mode of action of protoanemonin,  a sesquiterpene lactone of family Ranunculaceae. She reported that Rhodotorula was the most sensitive yeast and Epidermophyton floccosum was the most sensitive dermatophyte. The variation in sensitivity may be due to varying pemeability of  the mycelial and spore walls of different fungi tested. However,  it is known that the ability of unsaturated g-lactones to act as inhibitory substances against several microorganisms is owing to the ability of the molecule to penetrate the microbial cell.

   According to Hall et al.  (1980),  the mechanism of action of anticancerous sesquiterpene lactones like protoanemonin  is  based  on  the  capacity  of  substances  to react with -SH groups by a Michael type of addition. Mares (1987) stated that the moiety of the molecules containing  Protoanemonin, Coumarin and its derivatives may react with sulphydryl groups.

 

   There are many key regulators, e.g., D.N.A. polymerase, phosphofructokinase, and microtubular proteins of mitotic apparatus contains exposed -SH groups which could be susceptible to interaction with the type of substance. Mares  (1987)  assumed that  inhibitory activity of protoanemonin on growth is due to inactivation of sulphydryl containing enzymes necessary for cellular replications. The lack of inhibition of yeast's growth if L-cysteine was added to the culture medium is evidence for this hypothesis. In fact, L-cysteine could remain bound to the antibiotic,  thus,  preventing the binding, and the inhibition of several metabolic enzymes.

 

   Protoanemonin induced the ultrastructural modifications in Microsporum cookei which may be attributed to an interaction of molecule with thiolic groups. Further, it was assumed that the alterations in shape and polarity of the hyphae must be due to effect of protoanemonin on the SH  group.

 

 Conclusions  and Future perspectives

 

   Emergence of dreaded diseases like AIDS and cancer are responsible for increase in number of secondary infections generally caused by opportunistic fungi due to their immunocompromising capacity. The azoles and other antifungal drugs often fails to respond well to these infections.  Therefore, there has been greater need to search for alternative antifungal agents from microbes or plants.  Asteraceae being the largest family of the plant kingdom, and also owing to  presence of essential oils in them, may prove to be  the best natural alternative  antifungal drugs.   Traditional utilization of some of these  plants  against  skin-infections provide evidence  that  they contain antifungal  properties.  Most members of the family are the great reservoirs of  precious volatile oils containing sesquiterpenes as active chemicals.  The antimycotic nature of  most  volatile oils  have been  established by investigators all over the world. 

 

  The existing costly therapy of fungal infections does not bode well for the millions of individuals particularly in the developing world.   The plant extracts or essential oils are easily available secondary metabolites  and  are within the reach of needed  down trodden and poor people.

 

   There are some basic advantages of utilization of  asteraceous plant-derived  products /essential oils by  immunocompromising  patients suffering from cancer or  severe burn .  These oils  will provide soothing  fragrance, tone up infected  skin and also ameliorate the areas  of the body  colonized by  secondary pathogens in general and mycotic infections in particular.  These natural products  are extremely useful for cancer patients not only for fighting against secondary mycotic infections but also for alleviating the severity of the disease as most antifungal sesquiterpenes are  anticancerous,  too !

 

Further, it is necessary to unzip the mystery  of  proper mechanism of action of sesquiterpene  on  fungal pathogen as well as on  hosts. 

 

Tremendous therapeutical  and commercial potential  exists  in  the antimycotic agents (essential oils) of  asteraceous plants.  But the need of the hour is to tap  these  valuable natural resources.  Revitalization of   natural curative power of plants, like Tagetes erecta, T. patula, Eupatorium triplinerve and Tridax procumbens  will generate awareness  among the people  for  utility of these plants.  Eventually,  there is a pressing need to search for more  plants  containing volatile substances which can be useful in combating  mycotic infections. In new antifungal drug targeting strategies, asteraceous essential oils should be given prime importance because majority of the promising antifungal essential oils may generate new drug candidate. In 21st century, discovery of plant-based antifungal drugs might be a biotechnologically-driven process  with increasing importance attached to discovery of   drugs from  asteraceous plants.

 

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