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: email@example.com and firstname.lastname@example.org
2Microbiology Research Lab, Danielson College
Chhindwara- 480 001, M.P. state, India
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
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.
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.
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
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.
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).
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.
Saxena et al. (1984) reported that the leaf oil of the plant showed antifungal activity against Aspergillus niger, Microsporum gypseum, and Penicillium notatum
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).
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.
The essential oil present in leaf possess high degree of fungitoxicity (Graven et al., 1992).
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.
The oil of A. cina was found to be active against Candida albicans and Microsporum species (Vichkanova et al., 1972).
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.
The antimycotic activity of A. martima against Microsporum gypseum, Trichophyton equimum and T. rubrum was reported by Dikshit and Hussain (1984).
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).
Mehrotra et al. (1993) found fungitoxicity in essential oil against Candida albicans and Sporotrichum species.
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.
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).
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).
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).
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).
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.
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).
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).
Castaneda et al. (1996) evaluated the antifungal efficacy of plant against three fungi, viz., Candida albicans, Aspergillus niger, Trichophyton mentagrophytes.
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.
The oil is highly antifungal against Aspergillus species (Chauhan and Saxena, 1985).
Bourrel et al. (1993) reported antimycotic activity in essential oil against 7 test fungi.
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).
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.
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).
Prudent et al. (1995) found the leaf oil toxic against six fungi.
Rai and Vasanth (1995) reported the sensitivity of vicolides isolated from Pentanema indica to Microsporum gypseum, Chrysosporium tropicum and Trichophyton mentagrophytes.
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).
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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