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Phytoecdysteroids
by Robyn Klein, RH (AHG), MS, Medical Botanist

A western herbalist and medical botanist, Robyn Klein currently teaches courses at Montana State University: Herbal Medicine, Herbal Medicine Laboratory, Medicinal Plants of Montana, Medical Botany, Flowering Plants of the Northern Rocky Mountains, and Plants, People, and Health. Robyns graduate project focused on the phylogenetic analysis of adaptogenic plants and their secondary compounds.

Introduction Plants have survived assaults from organisms and environmental stress for millennia. They have done so by various mechanisms including physical barriers such as thorns and thick cuticles, and by synthesizing an array of defense chemicals as well as other growth and defense mechanisms. Protective mechanisms used by animals and humans are often similar in strategy and complementary in the substances used for protection. Phytoecdysteroids are a class of chemicals that plants synthesize for defense against phytophagous (planteating) insects. These compounds are exact replicas of ecdysteroids, hormones used by the arthropod (insect) and crustacean (crab/lobster) families in the molting process known as ecdysis. Insects that ingest phytoecdysteroids and have not adapted to this defense are subject to serious adverse effects, including reduced weight, molting disruption, and/or mortality (Dinan 2001). Since 1966, when phytoecdysteroids were discovered in plants, they have been shown to stimulate the synthesis of proteins in animals and humans, and to

have adaptogenic, antimutagenic, hypocholesterolemic, immunostimulating, nutritive, and tonic properties (Kholodova 2001; Lafont and Dinan 2003). This paper reviews the importance of phytoecdysteroids as a class of plant compounds responsible for some tonic and adaptogenic effects in medicinal plants.

Figure 1. The most common insect hormones, 20E-hydroxyecdysone (ecdysone) and juvenile hormone.
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Chemistry of phytoecdysteroids The two most common hormones found in insects are the ecdysteroid, 20E-hydroxyecdysone (ecdysone) and the sesquiterpene, juvenile hormone (Figure 1). They are usually accompanied by a number of other minor ecdysteroids. For example, the silkworm, Bombxy mori L., has been found to contain at least 19 ecdysteroids (Kamba et al., 1994). Chemically, phytoecdysteroids are classed as triterpenoids, the group of compounds that includes triterpene saponins, phytosterols, and phytoecdysteroids (Figure 2). Plants synthesize phytoecdysteroids from mevalonic acid in the mevalonate pathway of the plant cell using acetyl-CoA as a precursor (Figure 3). Animals and humans also synthesize some of the same products from the mevalonate pathway, such as ubiquinone and sterols. They cannot, however, synthesize ecdysteroids. Over 250 ecdysteroid analogs have been identified so far in plants, and it has been theorized that there are over 1,000 possible structures which might occur in nature (Dinan 2001). There is evidence that most plants retain the genetic capacity to produce ecdysteroids, but their expression is turned off (Dinan et al. 2001a). The question remains whether the capacity to synthesize ecdysteroids is genetically or environmentally induced. Either way, it may be possible to alter the expression of genes as a way to increase the amount of phytoecdysteroids in plants to increase protection of

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Figure 2. Molecular structure of triterpenoid saponins, phytosterols, and phytoecdysteroids.

Lisa Ganora

crops and to provide raw material to produce dietary supplements (Dinan et al 2001a). Ecdysteroids are polar steroids, almost sugar-like in their solubility properties (Gilbert et al. 2002). While mammalian steroid hormones have more variable structures, they universally lack the polyhydroxylated side chain characteristic of ecdysteroids and are therefore more lipophilic (Gilbert et al. 2002). Most phytoecdysteroids possess a cholest-7-en-6one carbon skeleton (C27), derived biosynthetically from cholesterol and phytosterols, often with a hydroxyl group in the 14-position (Bathori 2002). The carbon number can vary between C19-C29 (sometimes C30) (Lafont 1997). Although variation in the steroid ring structure is not substantial, significant variation lies in the number, position and orientation of the hydroxyl groups and the conjugating moieties linked through these. The commonly hydroxylated sites are the 2-, 3-, 14-, 20R- and 22R- positions, which together give rise to the highly biologically active ponasterone A (25deoxy-20-hydroxyecdysone) (Dinan 2001).

phytoecdysteroids (Dinan 2001). Phytoecdysteroid levels in plants are usually found to be 0.1% or less of their dry weight and have been isolated from all parts of plants in much higher amounts than those present in arthropods (Dinan 2001). Low concentrations of various

Figure 3. Biosynthetic pathway of phytoecdysteroids in the plant cell.

CHLOROPLAST

Mevalonale pathway

acetyl-CoA

deoxyxylulose pathway

CYTOSOL
triterpenes C30 IPP

pyruvate IPP monoterpenes C10

sesquiterpenes C15 phytosterols

diterpenes C20 tetraterpenes C40

phytoecdysterolds

phytols C45

Plant families with known ecdysteroids Approximately 6% of all plant species synthesize
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phytoecdysteroids deter some insects (2-25 ppm), while other insects are resistant to very high concentrations (400-1000 ppm). It appears ecdysteroid concentrations are highest in tissues which are most important for the survival of the plant and that these levels change throughout plant development. The most common phytoecdysteroid found in plants is ecdysone (20Ehydroxyecdysone) (Dinan 2001). While most plant families have at least some species that accumulate ecdysteroids, less than 2% of the worlds flora has been investigated for the presence of ecdysteroids (Dinan et al. 2001a, Dinan et al. 2002) (Table 1). One can search for presence of ecdysteroids in plants at www.ecdybase.org. See also Dinan (2004) for a compilation of ecdysteroids found in vascular plants, algae, fungi and non-arthropod invertebrates. Among plant species highest in phytoecdysteroids is spinach (Spinacia oleracea L., Chenopodiaceae)

containing 50 ug/g fresh weight (Grebenok et al.1994). Other examples are: ajugasterone in Ajuga L., Lamiaceae and Vitex L., Verbenaceae; leuzeasterone in Leuzea carthamoides (syn. Rhaponticum carthamoides (Willd.) Iljin, Asteraceae); 2-deoxy-20-hydroxyecdysone 3glucoside and 3-epi-2-deoxy-20-hydroxyecdysone in Tinospora cordifolia (Willd.) Miers, Menispermaceae (Garcia et al. 1989, Song et al.1991); ecdysterone and inokosterone in Achyranthes bidentata Blume, Amaranthaceae (Gao et al.2000); polypodine B in Leuzea carthamoides (Pis et al., 1994); and ecdysterone, ajugasterone C, ajugasterone C-20, 22- monoacetonide in Rhaponticum uniflorum (L.) DC., Asteraceae (Zhang et al. 2002).

Adaptogenic activity The term adaptogen, coined by Lazarev in 1958, has no correlation in modern pharmacology although scientific

Table 1. Some plant families and species containing phytoecdysteroids. Starred (*) species are recognized as adaptogens.

Phytoecdysteroids
Family
Asteraceae Asteraceae Asteraceae Asteraceae Amaranthaceae Amaranthaceae Amaranthaceae Amaranthaceae Caryophyllaceae Chenopodiaceae Commelinaceae Lamiaceae Lamiaceae Liliaceae Menispermaceae Plumbaginaceae Polypodiaceae Ranunculaceae

Genus/Species
Centaurea L. Leuzea carthamoides* Serratula coronata L.* Rhaponticum uniflorum Achyranthes bidentata*, A. aspera L. Cyathula achyranthoides (Kunth) Moq., C. officinalis K.C. Kuan Gomphrena L. Pfaffia paniculata (Mart.) Kuntze*, P. iresinoides (Kunth) Spreng Silene L. many species Cyanotis somaliensis C.B. Clarke Lamium L. Ajuga turkestanica (Regel) Briq. many species Tinospora cordifolia* Limonium Mill. Polypodium vulgare L., P. aurea L., P. glycyrrhiza D.C. Eaton many species

Citation(s)
Sarker et al 1997 Lafont et al 2004 Dinan 2001 Zhang et al 2002 Gao et al.2000, Lafont et al 2004 Lafont et al. 2004 Savchenko et al. 1998 LeBizec et al. 1997 Zibareva et al. 2002 Dinan et al. 1998 Lafont et al. 2004 Savchenko et al. 2001 Syrov et al. 2001 Dinan et al. 2001b Song et al. 1991 Whiting et al. 1998 Lafont et al. 2004 Dinan et al., 2002

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Table 2. Comparison between bioactivity of phytoecdysteroids and adaptogenic plant species. Starred citations (*) represent human clinical studies. The remaining citations are in vitro or in vivo using animal test subjects or animal cells.
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research on the anabolic and adaptogenic properties of plants has been published in the Russian literature since the mid-1960s. Lazarev (1946, 1962) showed that ingestion of certain plant extracts could improve stress markers in laboratory animals. Brekhman suggested three criteria that described their remedial action (Brekhman & Dardymov 1969). An adaptogen should: 1) be innocuous and cause minimal disturbance to the

normal physiological function, 2) have a nonspecific action; and, 3) have a normalizing action irrespective of the direction of the preceding pathological changes. While the definition of an adaptogen refers specifically to these three criteria, other bioactive properties are nonetheless characteristic of adaptogens. These include anabolic, antioxidant, hepatoprotective, and hypoglycemic activity. Phytoecdysteroids have also been

Comparison between bioactivity of phytoecdysteroids & adaptogenic plant species.

Phytoecdysteroids
Anabolic (increase in protein synthesis) ecdysterone (Chermnykh et al 1988) ecdysterone (Kosovskii et al 1989)
-ecdysone, 2-deoxyecdysterone, ecdysterone, sileneoside A, turkesterone (Syrov et al 1997)

Adaptogenic Plant Species

Anabolic Achyranthes bidentata (Gao et al. 2000) Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Araliaceae (Asano et al 1986)* Leuzea carthamoides (Koudela et al 1995) Panax ginseng C.A. Mey., Araliaceae (Salam et al 2002) Rhodiola rosea L., Crassulaceae (Spasov et al 2000)* Antioxidant Eleutherococcus senticosus (Yu et al 2003) Gynostemma pentaphylum (Thunb.) Makino, Cucurbitaceae (Lin et al 2000) Ocimum sanctum L., Lamiaceae (Khanna & Bhatia 2003) Panax ginseng (Fu and Ji 2003) Schisandra chinensis (Turcz.) Baill., Magnoliaceae (Chui et al 2002) Tinospora cordifolia (Pahadiya & Sharma 2003) Hepatoprotective Astragalus membranaceus Moench, Fabaceae (Cui et al 2003) Glycyrrhiza glabra L., Fabaceae (Al-Qaraw et al, 2002) Gynostemma pentaphylum (Chen et al 1996) Ocimum sanctum (Sharma et al 2002) Schisandra chinensis (Chui et al 2003) Hypoglycemic Eleutherococcus senticosus (Davydov & Krikorian, 2000)
Ocimum sanctum (Chattopadhyay 1999) Panax quinquefolium L. (Vuksan et al 2001)* Tinospora cordifolia (Stanley & Menon 2003)

Antioxidant ecdysterone (Kuzmenko et al 1997) ecdysterone (Kuzmenko 1999, Kuzmenko et al 1999)

ecdysterone (Kuzmenko et al 2001)

Hepatoprotective ecdysterone, turkesterone (Tashmukhamedova et al 1986)

ecdysterone, cyasterone (Syrov et al 1986) ecdysterone, turkesterone, cyasterone (Syrov et al 1992a) ecdysterone, turkesterone (Syrov & Kushbaktova 2001)

Hypoglycemic ecdysterone, turkesterone (Syrov et al 1992b) cdysterone, inokosterone (Takahashi & Nishimoto 1992*) beta-ecdysterone (Yang et al 2001*) 22-acetylcyasterone, cyasterone, ecdysterone, turkesterone (Kutepova et al 200)

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2001). Many of the species in this tribe have not been tested for adaptogenic activity. Species in the Cardueae genera such as Atractylis L., Carduus L., Carthamus L., Centaurea L., Cnicus L., Cynara L., Saussurea DC., and Silybum Adans, have been used in both indigenous medical practices and in modern herbal medicine. Saussurea is one of the larger genera in Cardueae having at least 300 species widely distributed in Eurasia (Bohm & Stuessy 2001). Saussurea species are currently harvested from the wild for both medicinal and religious purposes in India. Due to habitat specificity and its
Peterson

narrow range of distribution almost all the Saussurea species growing in the high altitude of the Himalayas need conservation (Kala 2003). Some Saussurea species, in particular, Saussurea costus (Falc.) Lipsch. and
Hyles euphorbiae

Saussurea medusa Maxim., may be adaptogenic, as suggested by use in Tibetan and Chinese medicine for wasting of muscles and memory deficit (Tsarong 1994, Fan & Yue 2003). Brekhman and Dardymov (1969) found to have similar bioactivities (Table 2). Some adaptogenic plant species have been tested and found positive for presence of phytoecdysteroids. These are: Achyranthes bidentata (Gao et al 2000), Tinospora cordifolia (Song et al 1991), Pfaffia paniculata (Courtheyn et al 2002), Leuzea carthamoides (Pis et al 1994), Rhaponticum uniflorum (Zhang et al 2002), and Serratula coronata (Bathori et al 1999). The three latter species belong to a larger group of genera encompassing the Cardueae tribe in the Asteraceae. The adaptogenic property of these three Cardueae species has been suggested to be due to phytoecdysteroids (Kholodova mention Carlina biebersteinii Bernh. ex Hornem as a species studied for adaptogenic properties. Carlina biebersteinii is placed in Carlininae, a subtribe of the Cardueae. The history of medicinal use of species in the Cardueae thus suggests that this tribe and closely related species may have adaptogenic activity. Do these species contain phytoecdysteroids as responsible or partly responsible for their bioactivity? Some species related to known adaptogens were found to contain phytoecdysteroids such as Tinospora capillipes Gagnep., Menispermaceae, Achyranthes fauriei H. Lev. & Vaniot, and Achyranthes rubrofusca Wight,

The Nomenclature of Rhaponticum and Leuzea

This current issue of JAHG contains two articles involving species from the Cardueae tribe of the Asteraceae (Compositae). Species from Leuzea, Rhaponticum, and Serratula are being marketed due to their anabolic and adaptogenic properties. There are four traditional subtribes for the family Asteraceae (Compositae): Echinopinae, Carlininae, Centaureinae and Carduinae (syn. Cardueae). The latter tribe contains well-known medicinal genera: Arctium, Atractylis, Carduus, Carlina, Carthamus, Centaurea, Cnicus, Cirsium, Cynara, Leuzea, Rhaponticum, Saussurea, Serratula, and Silybum. The nomenclature for Leuzea and Rhaponticum is particularly confusing because many species of other genera are synonymous. Species of Centaurea, Cnicus, Rhacoma, Rhaponticum, Serratula, and Stemmacantha are commonly listed in plant databases as synonyms for various species of Leuzea. Synonyms for Rhaponticum include not only species in the same genera, but also in Cirsium. Serratula is not secure, either. Various species of Klasea are synonyms for Serratula species. Of particular question is whether to employ the name Leuzea carthamoides or Rhaponticum carthamoides. A recent treatment of the Cardueae tribe has chosen the latter, Rhaponticum carthamoides,

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Amaranthaceae, and Lamium maculatum L., Lamiaceae (Shuya et al 2003). Atragene sibirica L., Ranunculaceae has been described as an adaptogen (Panossian 2003), but this species has not been tested for the presence of phytoecdysteroids. However, many genera of the Ranunculaceae contain phytoecdysteroids (Dinan et al 2002). The presence of phytoecdysteroids in the Ranunculaceae could possibly explain the mechanism of action of the nerve and mood properties of Anemone patens L. It is notable that plant species in the ginseng (Araliaceae) family, many of which have adaptogenic properties, have not been tested for phytoecdysteroids. Since phytoecdysteroid compounds can produce an adaptogenic effect, it is therefore possible that some adaptogenic plant species contain phytoecdysteroids. If so, the mechanism of action for adaptogenic species may involve this class of plant compounds. Phytoecdysteroids may act synergistically with triterpene, phenylpropane and oxylipin compounds.

stabilize both proteins and phospholipids in the cell membrane (Tomaschko 1999, Melzig et al 2001). The enhancement of skeletal muscle growth by ecdysteroids is perhaps best evidenced by their use in inducible gene expression systems to culture skeletal and muscle cells (Xiao et al 2003). The bioactivity of many plant compounds, including phytoecdysteroids, has been linked to nongenomic effects (Ferguson 2001, Dixon & Ferreira 2002, Gohil 2002). These effects arise from hormone ligand binding to a nuclear receptor, resulting in a long series of subcellular processes that include mRNA production and modification, translation into proteins, protein translation and/or insertion into membranes. This process can take hours before a response is seen. Nongenomic effects result in the same response but do not involve direct ligand to receptor binding and the response is almost immediate (Wehling 1995). Ecdysterone is thought to stabilize cell membranes resulting in modifications of membrane proteins, accumulation of ligands, and other membrane associated effects (Tomaschko 1999, Kholodova 2001). Two mediators of the stress response, neurosteroids (Reddy 2003) and aldosterone (Losel et al 2003) are believed to work via nongenomic effects. The binding of phytoecdysteroids in arthropods mimics the dimerization mechanism observed in steroid hormone receptors. In arthropods, ligand binding to the ecdysteroid receptor (EcR) promotes dimerization with the ultraspiracle receptor (USP). This dimerization enhances ecdysteroid binding to EcR (Lafont & Dinan

Mechanism of action of ecdysteroids The design and bioactivity of phytoecdysteroids have likely been shaped by the genetic evolution of organisms interacting over millennia. Bioactive compounds once used by lower organisms as signals for food and danger may have evolved into bioregulating signals in higher organisms such as mammals (Stoka 1999). Mammalian cells recognize phytoecdysteroids. There is evidence that phytoecdysteroids can induce RNA synthesis (Otaka 1969), accelerate translocation (Syrov 1984), and

suggesting that Leuzea carthamoides be an additional synonym. That is, Leuzea carthamoides (Willd.) DC. has been redefined as Rhaponticum carthamoides (Willd.) Iljin. (Greuter 2003). Botanists and herbalists alike must hold firm and not fall into the trap of claiming the latest innovation. It matters only that we recognize that more than one Latin name can be applied to the same species. The genus, Leuzea, has not vanishedjust L. carthamoideswhich is now a synonym of Rhaponticum carthamoides.
References Greuter W 2003, The Euro+Med treatment of Cardueae (Compositae) - generic concepts and required new names Willdenovia. 33:49-

Henriette Kress

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2003). That is, EcR forms a heterodimer with USP. The ultraspiracle receptor belongs to the superfamily of nuclear receptors which are ligand-inducible transcription regulators (Lafont & Dinan 2003). The homologue of USP in animals and humans is the retinoid X receptor (RXR) and when expressed in these systems, EcR has been shown to partner with RXR (Dinan 2001). Experiments indicate that EcR and RXR proteins are capable of forming a hetero-complex, and that both proteins are required for binding to ecdysteroids. Both USP and RXR receptors heterodimerize with other receptors to form active receptor complexes. For RXR, agonistic ligands like the 9-cis retinoic acid are known to bind to RXR and modulate the activity of the RXR dimeric partner

deficient release of stress mediators such as cortisol (McEwen 2002). It is possible that the metabolism of ecdysteroids in animals and humans may produce metabolites that are structurally similar to endogenous steroids (Lafont & Slama 1995). Side effects of synthetic anabolic steroids include acne, increased facial and body hair, impotence, prostate enlargement, gynecomastia, high blood pressure, liver failure, and neurological problems such as aggressive moods, delusions and paranoia. Yet, ecdysteroids have not shown any side effects in humans. Slama and Lafont (1995) summarized toxicity studies, concluding that ecdysteroids have no toxic response in animals. Phytoecdysteroids do not appear to activate mammalian steroid hormone receptors, even at very high concentrations (Dinan 2001). Rats and birds feed on seeds containing amounts as much as 20 grams of 20hydroxyecdysone per kilogram without any apparent problems. The hormonal actions of ecdysteroids seem to be limited to arthropods.

The contribution of phytoecdysteroids may be an important factor in the mechanism of action of many medicinal plants.

(Lafont & Dinan, 2003). The ligand binding cavities of USP and RXR have one part in common, close to helices 3 and 5, but the cavity is wider for USP (Sasorith et al 2002). Baker (1998) showed that the nuclear receptors for ecdysone, thyroid and retinoid X receptor are evolutionarily closely related, having descended from a common ancestor. A phylogeny of nuclear steroid receptors suggests the possibility that ecdysone supplements are recognized in humans via one of more of a broad family of recently identified receptors that can bind a broad variety of ligands (Baker, 1998). The pregnane X receptor (PXR), human nuclear receptor (hPAR), and steroid xenobiotic receptor (SXR), and vitamin D receptor (VDR) because there is research relating antioxidant activity of ecdysteroid administration to vitamin D deficiency are in this family. Glucocorticoid and glucocorticoid metabolites act as agonists for this family of receptors (Carlstedt-Duke 1999). The effect of ecdysteroids on reproductive tissues of animals and humans has shown enhanced sexual activity (Lafont & Dinan 2003). Ecdysteroids have been found to have many pharmacological effects in animals and humans such as increasing acetylcholine esterase activity in the brain, reducing the hyperglycemic response to exogenous glucagon, and decreasing hepatic cholesterol by stimulating excretion of cholesterol in the bile (Slama & LaFont 1995). These effects have important meaning for pathologies related to dysfunctional stress adaptation, which has been hypothesized to be caused by excess or

Commercial preparations containing phytoecdysteroid compounds The history of ecdysteroid supplements began forty years ago when Burdette (1962) discovered that ecdysterone could enhance the rate of protein synthesis in mammalian tissue. Anabolic effects from ecdysterone were found in mice in 1969 by Hikino et al, and separately by Otaka, et al (1969). Syrov attributed the anabolic effects of Pfaffia paniculata extracts to ecdysterone in 1984. Since then, Russian and Chinese Olympic athletes have been suspected of using ecdysteroid supplements (Tsitsimpikou et al 2001). Today, more than 140 dietary supplements containing ecdysone are available on the Internet and elsewhere such as: Syntrabol, Ecdysten, Ecdybol, and MethoxyFactor (Lafont & Dinan 2003). As an example, each 200 mg capsule of Syntrabol contains isinokosterone (20-hydroxyecdysterone). These ergogenic supplements are believed to produce anabolic and growth-promoting effects, and are primarily marketed to weight lifters and sports enthusiasts as pseudo-steroidal muscle enhancers (Slama & LaFont 1995). Plants that contain high amounts of phytoecdysteroids are cultivated in Europe as a source of

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2003 RKD Peterson lady beetle on yellow sweetclover

these compounds for the dietary supplement market. These plant species are primarily represented by Leuzea carthamoides, Rhaponticum uniflorum, and Serratula coronata. Other preparations based on purified ecdysteroids or on ecdysteroid-containing plant powders/extracts are sourced from the following plants: Cyanotis somaliensis (Commelinaceae), Achyranthes aspera, Cyanthula officinalis (Amaranthaceae), Leuzea carthamoides (Asteraceae), Pfaffia paniculata, P. iresinoides (Amaranthaceae), Polypodium vulgare, P. aurea, P. glycyrrhiza (Pteridophyta), and Ajuga turkestanica (Lamiaceae) (Lafont et al 2004). Silkworms (Bombyx mori) contain ecdysteroids and have been shown to enhance the rate of protein synthesis in mammals (Slama & Lafont 1995). The medicinal fungi called dong chong xia cao (Cordyceps sinensis (Berk.) Saccardo Clavicipitaceae) is used to increase stamina and for impotence (e.g., adaptogenic properties) (Koh et al 2003, Buenz et al 2005). Cordyceps is in the same family as ergot that attacks and parasitizes insects. In this case, the host is the larvae of Hepialus armoricanus Oberthur or Holotrichia koraiensis Murayana, Hepialidae. The stalked fruiting bodies of the fungi attached to the larva is the traditional form of dong chong xia cao. Today, Cordyceps sinensis is often mass-produced on grain, not on a larval host. In a recent comparison of bioactive ingredients in various Cordyceps products, ecdysteroids were not even mentioned (Hsu et al 2002). Whether ecdysteroids are a part of the bioactivity of Cordyceps products is not known. Nor is it known whether Cordyceps grown on grain contains phytoecdysteroids, or whether the fungi itself produces ecdysteroids. Phytoecdysteroid compounds may be found in fungi (Lafont et al 2004). Fungi are no longer classed in the plant kingdom; rather, the closest relatives of fungi are animals (Campbell & Reece 2002). Ecdysteroids in mammals can be traced to dietary vegetables and fruits or to human parasites such as worms. In any case, the larvae may be crucial to the bioactivity of the traditional form of Cordyceps. mechanism of action of many medicinal plants, for example, in Cordyceps and adaptogenic plant species. The properties of phytoecdysteroids have not gone unnoticed in the dietary supplement market, yet their potential importance in medicinal plants is not yet fully appreciated by herbalists or ethnobotanists. Only a small percentage of the worlds flora has been tested for the presence of phytoecdysteroids. The similarity between the activity of phytoecdysteroids and adaptogenic plants emphasizes the importance of testing all adaptogenic plant species for presence of ecdysteroids, and alternately, testing all plant species containing ecdysteroids for adaptogenic activity. Phytoecdysteroid research is primarily found in the discipline of entomology (study of insects) and in arthropod endocrinology, which is perhaps why clinical herbalists have missed their importance as a bioactive plant compound. The case of phytoecdysteroids illustrates that bridging the study of plant science and plant-animal co-evolution can provide an integrative perspective on plants and human health. Further, the pharmacological properties of plant remedies can often be supported through an appreciation for similar defense pathways, ligands, and enzymes between insects, plants, and animals (Hippeli et al 1999, Leshem 2000, Clouse 2002, Cock et al 2002, Grassman et al 2002, Nurnberger & Brunner 2002, Rosati et al 2003).

Conclusion The beneficial properties and excellent safety profile of phytoecdysteroid-containing supplements suggest that these plant compounds have an important place in herbal materia medica. The contribution of phytoecdysteroids may be an important factor in the

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Note: References can be found at URL: www.rrreading.com/paragons/phytoecdysteroid.htm

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