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    362 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    1. Introduction

    Plants are used worldwide for the treatment of diseases and

    novel drugs continue to be developed through research from

    these plants. There are more than 20,000 species of higher plant,

    used in traditional medicines and are reservoirs of potential new

    drugs. As the modern medicine and drug research advanced,

    chemically synthesized drugs replaced plants as the source of

    most medicinal agents in industrialized countries. Nevertheless

    plants are an important source of lead compounds. However, in

    developing countries, the majority of the worldspopulation can-

    not afford pharmaceutical drugs and use their own plant based

    indigenous medicines.

    Dragons blood is a deep red resin, which has been used

    as a famous traditional medicine since ancient times by many

    cultures. The term Dragons blood refers to reddish resinous

    products, usually encountered as granules, powder, lumps or

    sticks used in folk medicine. Dragons blood has been used for

    diverse medical and artistic applications. It has astringent effect

    and has been used as a hemostatic and antidiarrhetic drug.The origin of Dragons blood is believed to be from Indian

    Ocean island of Socotra, now part of Yemen (Angiosperm

    Phylogeny Group, 1974).However, there exists a great degree

    of confusion regarding the source and identity of Dragons

    blood. Several alternative sources of Dragons blood from

    Canary Islands, Madeira, and South East Asia and also from

    East and West Africa have been identified (Alexander and

    Miller, 1995). Dragons blood was a name applied to many

    red resins described in the medical literature, e.g. East Indian

    Dragons blood (from the fruit ofDaemonorops draco(Willd.)

    Blume), Socotran or Zanzibar Dragons blood (exudates of

    Dracaena cinnabariBalf. f.), Canary Dragons blood (exudatesformed from incisions of the trunk ofDracaena draco(L.) L.),

    West Indian Dragons blood (exudates of Pterocarpus draco

    L.), Mexican Dragons blood (resin of Croton lechleri Mull.

    Arg.) and the Venezuelan Dragons blood (resin of Croton

    gossypifoliumVahl) (Sollman, 1920).

    Mabberley (1998) suggests that Dragons blood was pro-

    ducedoriginally fromDracaena cinnabari, later fromDracaena

    draco and more recently from Daemonorops spp. Zheng et

    al. (2004a,b,c) confirms this view and suggests Pterocar-

    pus spp., Daemonorops draco and Croton spp. as substitutes

    for Dracaena spp. Thus, the term Dragons blood in gen-

    eral is used for all kinds of resins and saps obtained from

    four distinct plant genera; Croton (Euphorbiaceae), Dracaena(Dracaenaceae), Daemonorops (Palmaceae), and Pterocarpus

    (Fabaceae).

    1.1. Mythology

    According to a Greek myth, Landon, the hundred-headed

    dragon, guardian of the Garden of the Hesperides (the nymph

    daughters of Atlas, the titan who holds up earth and heaven)

    was killed by either Hercules (in his quest) or Atlas (as punish-

    ment) while bringing back three golden apples from the garden,

    depending upon the version of the myth. Landons red blood

    flowed out upon the land and from it sprung up the trees known

    as Dragon Trees (TheEleventh Labor of Hercules: TheApples

    of The Hesperides).

    Dragons blood was also called Indian cinnabar by Greeks

    writers. The name Dragons blood dates back to the 1st cen-

    tury AD when a Greek sailor wrote, about an island called

    Dioscorida where the trees yielded drops of cinnabar, in a ship-

    ping manual Periplus of the ErythreanSea. Plinius (1601) also

    described that the resin got its name from an Indian legend based

    on Brahma and Shiva.Emboden (1974)andLyons (1974)had

    also summarized the history and mythology of Dragons blood.

    According to Lyons, the struggle between a dragon and an ele-

    phant that, at its climax, led to the mixing of the blood of the

    two creatures resulted in a magical substance, Dragons blood

    imbued with medicinal properties.

    1.2. Historical uses

    The crimson red resin was highly prized in the ancient world.

    Dragons blood (Dracaena cinnabari) was used as a dye and

    medicine in the Mediterranean basin.Miller and Morris (1988)mention useofDracaena resin as a coloring matterfor varnishes,

    tinctures, toothpastes, plaster, and for dying horn to make it look

    like tortoiseshell.Mabberley (1998)also notes that resinous sap

    produced via incisions in the bark or stem of the Dracaena

    cinnabari was used by the Ancients to stain horn to resem-

    ble tortoiseshell. People in Socotra used resin from Dracaena

    cinnabarifor dying wool, glue pottery, breath freshener, to dec-

    orate pottery and houses and even as lipstick (Alexander and

    Miller, 1996).Due to the belief that it is the blood of the mythi-

    cal animal, the dragon, it is also used in alchemy and for ritual

    magic.

    Dragons blood from bothDracaena andDaemonorops werealso used for ceremonies in India. Sometimes Dracaenaresin,

    but more often Daemonorops resin, was used in China as red

    varnish for wooden furniture. These resins were used to color

    the surface of writing paper for banners and posters, used espe-

    cially for weddings and for Chinese New Year. These red resins

    were also used as pigment in paint, enhancing the color of

    precious stones and staining glass, marble and the wood for

    Italian violins.Fulling (1953)reported thatDaemonoropsresin

    was used in the preparation of drawings. Powdered forms of

    Daemonoropsresin were used extensively as an acid resist by

    photoengravers during the 1930s (Pankow, 1988). In modern

    times Daemonorops resin is still used as a varnish for violins,

    in photoengraving, as an incense resin, and as body oil. Dae-monorops resin is also added to red ink to make Dragons

    Blood Ink, which is used to inscribe magical seals and

    talismans.

    Spanish naturalist and explorer P. Bernabe Cobo (1956)

    recorded for the first time that Crotons sap was used widely

    throughout the indigenous tribes of Mexico, Peru, and Ecuador

    in 1600s. In African-American folk magic or voodoo this

    resin is used in mojo hands for money-drawing or love-

    drawing, and is used as incense to cleanse a space of negative

    entities or influences. In neopagan witchcraft, it is used to

    increase the potency of spells for protection, love, banishing and

    sexuality.

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    D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 363

    1.3. Ethnomedicinal uses

    Dragons blood was used by early Greeks, Romans, and

    Arabs for its medicinal properties. Locals of Moomy city on

    Socotra island used the Dragons blood (Dracaena) as a sort

    of cure-all, using it for things such as general wound healing,

    a coagulant, curing diarrhoea, lowering fevers, dysentery dis-

    eases, internal ulcers of mouth, throat, intestines and stomach,

    as an antiviral for respiratory and stomach viruses and for skin

    disorders such as eczema. Dioscorides and other early Greek

    writers describedits medicinal uses. Dragons blood (Dracaena)

    is used for treating dysentery, diarrhoea, hemorrhage and exter-

    nal ulcers in Yemeni folk medicine (Milburn, 1984).Dracaena

    resin has strong astringent properties and is used as a muscle

    relaxant (Milner, 1992).Gerarde and Johnson (1633)stated that

    Dragons blood (Dracaena) was used for over flow of courses

    (menses), in fluxes, dysenteries, spitting of blood and fastening

    of loose teeth. It was also used to treat gonorrhea, stoppage of

    urine, watery eyes and minor burns (Parkinson, 1640). In China,

    the red resin ofDracaena cochinchinensis was used by localpeople for treatment of wounds, leucorrhea, fractures, diarrhoea

    and piles as well as for intestinal and stomach ulcers (Cai and

    Xu, 1979).

    Daemonorops resin is also used in traditional Chinese

    medicine to stimulate circulation, promote tissue regeneration

    by aiding the healing of fractures, sprains and ulcers and to con-

    trol bleeding and pain (Bensky and Gamble, 1993). The medical

    applications of Dragons blood resins, mainly theDaemonorops

    resin have been attributed to the presence of benzoic acid, which

    show antiseptic properties (Piozzi et al., 1974; Badib, 1991).

    Crotons sap is a common household remedy used in Peru, other

    Latin American countries, and among the Latin American pop-ulation of the United States.Crotons sap is taken orally to cure

    different types of diarrhoeaand cholera by theindigenous people

    of Amazon basin (Carlson and King, 2000).Other ethnomedi-

    cal uses of the sap ofCroton lechleri in Peru are found in the

    treatment of bone fractures, leucorrhea, piles and hemorrhoids

    (Soukup, 1970).Sap ofCroton lechleriwas also used to speed

    up internal healing after an abortion (Castner et al., 1998)and in

    vaginal baths taken before childbirth (Duke and Vasquez, 1994).

    Crotons sap has been reviewed by many researchers for its

    therapeutic uses (Jones, 2003; Gonzales and Valerio, 2006).

    Various therapeutic properties of Dragons blood (Croton

    spp.) have been described such as wound and ulcer healing,

    antidiarrhoeic, anticancer, anti-inflammatory and antirheumaticproperties (Bettolo and Scarpati, 1979; Perdue et al., 1979; Chen

    et al., 1994; Pieters et al., 1995; Phillipson, 1995; Gabriel et al.,

    1999; Holodniy et al., 1999; Miller et al., 2000).

    2. Sources of Dragons blood

    Dragons blood is a bright red resin that is obtained from dif-

    ferent species of four distinct plant genera; Croton, Dracaena,

    Daemonorops, andPterocarpus.Table 1summarizes the differ-

    ent botanical sources and common names of Dragons blood.

    Pearson and Prendergast (2001)have reviewed Dragons blood

    samples from different sources kept at Royal Botanic Gardens

    Kew. The Economic Botany Collections at the Royal Botanic

    Gardens Kew (curated by the Centre for Economic Botany)

    contains perhaps the largest (80 accessions comprising of 34

    Dracaenaaccessions, 40Daemonoropsand 6Croton) and most

    reliably identified assembly of Dragons blood resins.

    In this review, we discuss chemistry and therapeutic uses of

    varieties of Dragons blood differentiated according to the plant

    taxa from which they are obtained. Structures of some of the

    compounds reported from these sources are given in Fig. 1.

    2.1. Croton spp. (Euphorbiaceae)

    Croton lechleri Mull. Arg., the tree growing in Mexico,

    Venezuela, Ecuador, Peru and Brazil, is possibly the best-known

    source for Dragons blood. Otherspeciesare Crotondraconoides

    Mull. Arg.,Croton dracoSchlect & Cham.,Croton urucurana

    Baill., C. xalapensis Kunth, Croton gossypifolium Vahl, Cro-

    ton erythrochilus Mull. Arg. and Croton palanostigma Klotzsch.

    When the trunk of the tree is cut or wounded, dark red, sappy

    resin oozes out, known as Sangre de Drago (Dragons blood).

    2.1.1. Chemical constituents

    Table 2summarizes the compounds reported from Dragons

    blood ofCrotonspp.

    2.1.2. Bioactivities and therapeutic uses

    2.1.2.1. Antimicrobial and antiviral activity. Sangre de Drago

    (Croton) has been evaluated as a source of potential chemother-

    apeutic agents based on its ethnomedicinal uses. Chen et al.

    (1994)had studied the antibacterial properties of blood-red sap

    ofCrotonlechleri from Ecuador andreportedcompounds 2, 4, 6-

    trimethoxyphenol, 1, 3, 5-trimethoxybenzene, crolechinic acidand korberins A and B present in the sap to exhibit antibacterial

    activity individually.

    The aqueous ethanol extract, some fractions of the methanol

    extract, catechin and acetyl aleuritolic acid of Sangre de Drago

    obtained from Croton urucurana are reported to show inhibition

    ofStaphylococcus aureus and Salmonella typhimurium (Peres

    et al., 1997). Later, Gurgel et al. (2005) reported in vitro antifun-

    gal activity of Sangre de Drago fromCroton urucurana, which

    could be due to the presence of catechins like gallocatechin and

    epigallocatechin. Antiviral properties ofCrotons sap have also

    been evaluated. Extracts of Sangre de Drago have been reported

    to have antiviral activity against influenza, parainfluenza, Her-

    pes simplex viruses I and II, and Hepatitis A and B (Chen etal., 1994; Ubillas et al., 1994; Sidwell et al., 1994; Meza, 1999).

    SP-303 fromCrotons sap is the most studied constituent for its

    antiviral activity (Wyde et al., 1991, 1993; Barnard et al., 1992;

    Soike et al., 1992; Gilbert et al., 1993). SP-303 has shown in

    vitroactivity against Herpes simplex viruses (HSV-1 and HSV-

    2), inhibition of thymidine kinase mutants of the viruses, and

    pronounced activity against acyclovir-resistant strains (Barnard

    et al., 1993; Safrin et al., 1993; Ubillas et al., 1994). Clini-

    cal studies of SP-303 have also been done on AIDS patients

    (Orozco-Topete et al., 1997). Sethi (1977)reported taspine to

    inhibit reverse transcriptase enzyme in cultures of several tumor

    viruses.

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    364 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    Table 1

    Botanical sources and common names of Dragons blood

    Species Plant family Geographical origin Vernacular names

    Crotonspp. Euphorbiaceae Tropics and subtropics

    worldwide

    Sangre de draco (Venezuela), Dragons blood

    Croton,Arleiia,Ian huiqui(Ecuador),Yawar

    gradwascca (Peru), Sangre de Drago/Grado

    Croton dracoSchltdl. & Cham.

    Croton lechleriMull. Arg.Croton draconoidesMull. Arg.

    Croton urucuranaBaill.

    C. xalapensisKunth

    Croton gossypifoliumVahl

    Croton erythrochilusMull. Arg.

    Croton palanostigmaKlotzsch

    Daemonoropsspp. Palmaceae South East Asia Jerang or Djerang (Indonesia), Longxuejie

    (China), Draconis Resina and Sanguis

    draconis (Sumatra), Kirin-kakketsu (Japan)

    Daemonorops draco(Willd) Blume

    D. didymophyllaBecc.

    D. micracantha(Griff.) Becc.

    D. motleyiBecc.

    D. rubra(Reinw. ex Blume) BlumeD. propinquaBecc.

    Dracaenaspp. Dracaenaceae Socotra, Canary Islands,

    Madeira, East Africa

    Zanzibar drop

    D. cinnabariBalf. f.

    D. cochinchinensis(Lour.) S.C. Chen

    Dracaena draco(L.) L.

    Pterocarpusspp. Fabaceae West Indies and South

    America

    East India kino, Malabar kino, Kino gum,

    Guadaloupe Dragons blood, Padauk

    P. officinalisJacq.

    2.1.2.2. Antitumor and cytotoxic activity. There are variousreports showing Sangre de Drago (Croton) to exhibit cytotox-

    icity. Guerrero and Guzman (2004) carried out brine shrimp

    lethality test (BSLT) to check the cytotoxicity ofCroton lechleri.

    Croton lechleri sap has been reported to be used for treatment of

    cancer by many researchers (Hartwell, 1969; Pieters et al., 1992;

    Cai et al., 1993a,b). Recently, Gonzales and Valerio (2006) have

    reviewedCroton lechlerifor its anticancer activity.

    A number of compounds isolated from Sangre de Drago

    (Croton) are found to show cytotoxicity. Taspine from Croton

    lechleri sap hasshown potent activity against KB and V-79 cells,

    while flavan-3-ols and proanthocyanidins, which are the major

    components of the sap, are not cytotoxic (Itokawa et al., 1991;

    Chen et al., 1994). Compound 3, 4-O-dirnethylcedrusin fromCroton spp. was found not to stimulate cell proliferation, but

    rather protected cells against degradation in a starvation medium

    (Pieters et al., 1993). Chen et al. (1994) proposed that antitu-

    mor activity ofCrotons sap might be because of mechanisms

    other than cytotoxicity such as immunostimulation. Antiprolif-

    erative effect of latex ofCroton lechleri was also determined

    in vitro on the human myelogenous leukemia K562 cells line

    (Rossi et al., 2003). Peres et al. (1997) have reported use of

    Croton urucuranaagainst cancer. Croton dracois also used to

    treat cancer (Gupta et al., 1996).Latex ofCroton draconoides

    and Croton erythrochilus are also reported to be used against

    cancer (Piacente et al., 1998). Sandoval et al. (2002) evalu-

    ated the effects of Sangre de Drago (Croton palanostigma

    ) onhuman cancer cells, AGS (stomach), HT29 and T84 (colon) and

    reported induction of apoptosis, and microtubular damages in

    these cell lines.

    2.1.2.3. Antihemorrhagic activity. Castro et al. (1999)investi-

    gated the activity of organic extracts ofCroton draco against

    hemorrhagic activity induced by the venom of the snake Both-

    rops asper. Total inhibition of hemorrhage was observed,

    probably owing to the chelation of zinc required for the catalytic

    activity of venoms hemorrhagic metalloproteinases. Aqueous

    extracts of Croton urucurana antagonized the hemorrhagic

    activity of the venom of Bothrops jararaca and proantho-

    cyanidins were involved in this activity (Esmeraldino et al.,2005).

    2.1.2.4. Immunomodulatory activity. The human immune

    response is a highly complex system involving both innate and

    adaptive mechanisms. A biological or pharmacological effect

    of compounds on humoral or cellular aspects of the immune

    response is referred as immunomodulating activity. Risco et

    al. (2003)determined immunomodulatory activity of Sangre de

    Drago fromCroton lechleri in vitroand found that it exhibited a

    potent inhibitory activity on classical (CP) and alternative (AP)

    pathways of complement system and inhibited the proliferation

    of activated T-cells.

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    D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 365

    Tsacheva et al. (2004) evaluated latex ofCroton draco, its

    extracts and several latex components (flavonoid myricitrin, the

    alkaloid taspine and the cyclopeptides P1 and P2) for their influ-

    ence on both CP and AP activation pathways of the complement

    system using a hemolytic assay andthe best inhibition was found

    for the classical pathway.

    2.1.2.5. Antiulcer and antidiarrhoeal activity. There are

    reports showing potent antiulcer and antidiarrhoeal activity of

    Sangre de Drago (Croton). The extracts from Croton species

    have been shown to impair the capsaicin-stimulated ion trans-

    port across guinea pig ileum when added to the serosal bath

    in Ussing chambers and thus may prove to be a cost-effective

    treatment for gastrointestinal ulcers (Miller et al., 2000).Use of

    latex ofCroton lechlerihas also been reported in the treatment

    of different types of diarrhoea (Ubillas et al., 1994; Carlson

    and King, 2000). SP-303, a heterogeneous proanthocyanidin

    oligomer ofCroton lechleriwas found to inhibit in vivocholera

    toxin-induced fluid secretion and in vitrocAMP-mediated Cl

    secretionand thus may provide a useful broad-spectrum antidiar-

    rhoeal agent (Gabriel et al., 1999). Evaluation of safety and

    efficacy of orally administered SP-303 was done for the symp-

    Fig. 1. Structure of some of the compounds reported from different sources of Dragons bloods.

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    366 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    Fig. 1. (Continued)

    tomatic treatment of diarrhoea in travelers (DiCesare et al.,

    2002)and in AIDS patients (Holodniy et al., 1999; Koch et al.,

    1999; Koch, 2000).Fischer et al. (2004)derived a novel extract

    SB-300 from Croton lechleri that inhibited cAMP-regulated

    chloride secretion, mediated by the cystic fibrosis transmem-

    brane conductance regulator Cl channel (CFTR) in human

    colonic T84 cells and may prove to be a potent antidiarrhoeal

    agent.Rozhon et al. (1998)have a patent on the use of proan-

    thocyanidin polymer fromCrotonspecies as an antidiarrhoeal,which was issued to Shaman Pharmaceuticals, Inc. USA. The

    company has products based on extract from Croton lech-

    leri sap in the market, named as NSF and NSF-1B, claiming

    clinically demonstrated relief from diarrhoea that wont cause

    constipation.

    Gurgel et al. (2001) evaluated antidiarrhoeal activity of

    red sap obtained from Croton urucurana on castor oil-

    induced diarrhoea in rats, cholera toxin-induced intestinal

    secretion in mice and on small intestinal transit in mice

    and suggested potential utility of the red sap from Cro-

    ton urucurana in controlling secretory diarrhoea associated

    diseases.

    2.1.2.6. Analgesic activity. Peres et al. (1998a)isolated several

    compounds showing analgesic activity, namely campesterol,

    sitosterol, stigmasterol, acetyl aleuritolic acid, catechin, gallo-

    catechin and sitosterol glucoside from Croton urucurana and

    suggested existence of more potent analgesic compounds or

    existence of a synergistic effect.

    2.1.2.7. Antioxidative activity. Desmarchelier et al. (1997)sug-

    gested that Sangre de Drago (Croton lechleri) is highly effectivein scavenging peroxyl and hydroxyl radicals at high concen-

    trations. However, prooxidant activity was observed at lower

    concentrations. When administered to mice subcutaneously,

    latex of PeruvianCroton lechleriinhibited hepatic lipid peroxi-

    dation but only at concentration of 200 mg/kg in the livers of the

    animals; higher concentrations showed toxicity (Desmarchelier

    and de Moraes Barros, 2003).

    Later, Risco et al. (2003) reported that depending upon

    the concentration, latex of Croton lechleri showed antioxi-

    dant or prooxidant properties, and stimulated or inhibited the

    phagocytosis.Lopes et al. (2004) also evaluated antioxidant

    activity of Croton lechleri sap against the yeast Saccha-

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    D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 367

    Fig. 1. (Continued)

    romyces cerevisiae and against maize plantlets treated with

    the oxidative agents, apomorphine and hydrogen peroxide and

    found that sap inhibited the cytotoxic effect of the alkaloid

    apomorphine in haploid yeast cultures as well as in maize

    plantlets.

    2.1.2.8. Anti-inflammatory activity. In a study on edema in rats,

    Perdueet al.(1979) reported, for the firsttime,anti-inflammatory

    activity of alkaloid taspine isolated from Croton latex. Later,

    Miller et al. (2001)concluded from a series of studies that the

    Crotonsap inhibits neurogenic inflammation by directly block-

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    368 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    Fig. 1. (Continued)

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    D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 369

    Fig. 1. (Continued).

    ing sensory afferent nerve activation at both the prejunctional

    and postjunctional level. The latex from Croton lechleri has

    strong anti-inflammatory activity when administered i.p. (Risco

    et al., 2003).

    2.1.2.9. Mutagenic and antimutagenic activity. The mutagenic

    and antimutagenic activity of Croton lechieri sap was exam-

    ined through the Ames/Salmonella test and no mutagenicity of

    2-aminoanthracene was found in the Salmonella typhimurium

    strains T98 and T100 (Rossi et al., 2003). Later, Lopes et al.

    (2004)reported mutagenic activity ofCroton lechieri sap for

    strain TA1535 of Salmonella typhimurium in the presence of

    metabolic activation, a weak mutagenic activity for strain TA98

    and in a haploid Saccharomyces cerevisiae strain XV185-14c

    for the lys1-1, his1-7 locus-specific reversion and hom3-10

    frameshift mutations.

    2.1.2.10. Wound healing activity. Sangre de Drago (Croton) is

    commonly used as liquid bandage in the Amazon (Jones, 1995,

    2003). Vaisberg et al. (1989) reported a significant increase

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    370 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    Table 2

    Chemical constituents reported fromCrotonspp.

    Compound name Bioactivity References

    Croton dracoSchltdl. & Cham.

    1-Hydroxyjunenol; 2,3-dihydrovomifoliol; 3,4,5-tri

    methoxycinnamyl alcohol; 9(11)-dehydrokaurenic

    acid; 9-dehydrovomifoliol; hardwikiic acid;

    p-hydroxybenzal-dehyde; p-methoxybenzoic acid;scopoletin; taspine (1)

    Murillo et al. (2001)

    Croton urucuranaBaill.

    Sonderianin (2) Antibacterial activity Craveiro and Silveira (1982),Peres et al. (1997,

    1998b)

    Acetyl aleuritolic acid Antibacterial activity, Analgesic

    activity

    Peres et al. (1997, 1998a)

    -Sitosterol;-sitosterol-O-glucoside; campesterol;

    catechin; gallocatechin; stigmasterol

    Analgesic activity

    12-Epi-methyl-barabascoate (3);

    15,16-epoxy-3,13(16)-clerodatriene-2-one (4)

    Peres et al. (1998b)

    Fucoarabinogalactan (CU-1) Milo et al. (2002)

    Croton lechleriMull. Arg.

    Taspine (1) Anti-inflammatory activity, wound

    healing activity, cytotoxic activity

    Perdue et al. (1979),Vaisberg et al. (1989),

    Itokawa et al. (1991),Pieters et al. (1993),Porras-Reyes et al. (1993),Chen et al. (1994),

    Milanowski et al. (2002)

    3,4-O-Dimethylcedrusin (7) Wound healing activity, inhibition of

    cell proliferation

    Pieters et al. (1990, 1992, 1993, 1995)

    Procyanidin B-1 and B-4 (27) Cai et al. (1991)

    Catechin; epigallocatechin; epicatechin; gallocatechin Cai et al. (1991),Chen et al. (1994)

    Catechin (4--8)-gallocatechin (4--6) gallocatechin;

    catechin (4--8)-gallocatechin (4--8)-gallocatechin;

    gallocatechin (4--6)-epigallocatechin; gallocatechin

    (4--8)-epi-catechin; gallocatechin

    (4--8)-gallocatechin (4--8)-epi-gallocatechin

    Cai et al. (1991),Phillipson (1995)

    Benzofuran-5-yl,2-3-dihydro:2-(3-dimethoxy-phenyl)

    7-methoxy-3-methoxy-carbonyl-propan-1-oic acid

    methyl ester; benzofuran-5-yl,2-3-dihydro:2-(4-

    hydroxy-3-methoxyphenyl)-7-methoxy-3-methoxy-carbonyl-propen-1-oic acid methyl

    ester

    Pieters et al. (1992)

    -Sitosterol; bincatriol; crolechinol (10); crolechinic acid

    (11); daucosterol; hardwickiic acid

    Cai et al. (1993a),Chen et al. (1994)

    1,3,5-Trimethoxybenzene Cytotoxic activity, antibacterial

    activity

    2,4,6-Trimethoxyphenol Antibacterial activity

    3,4-Dimethoxybenzyl alcohol; 3,4-dimethoxy phenol;

    4-hydroxyphenethyl alcohol and its acetate;

    -sitostenone; sitosterol--d-glucopyranoside

    Cai et al. (1993a)

    Korberin A (5); korberin B (6) Antibacterial activity Cai et al. (1993b),Chen et al. (1994)

    4-O-Methylcedrusin (8) Pieters et al. (1993)

    SP-303 (MW = 2200 Da) Antiviral activity Ubillas et al. (1994),Sidwell et al. (1994)

    Catechin-(4--8)-epigallocatechin Phillipson (1995)

    Ethyl acetate; ethyl propionate; 2-methyl butanol;2-methylbutyl acetate; propyl acetate; 3-methybutyl

    acetate; eucalyptol; 1-butyl acetate;

    3-methyl-2-pentanol

    Bellesia et al. (1996)

    Isoboldine (13); norisoboldine (12); magnoflorine (14) Milanowski et al. (2002)

    SB-300 (MW =3000 Da) Antidiarrhoeal activity Fischer et al. (2004)

    in the rate of wound repair on topical application of the Cro-

    ton lechleri sap to skin wounds of mice and found taspine as

    the cicatrizant (wound healing) principle. A significant increase

    in numbers of migrating cells in an in vitro test for wound-

    ing of human fibroblasts also suggested role of taspine for

    wound healing (Vaisberg et al., 1989). From the sap of Peru-

    vian Sangre de Drago (Croton sp.), a lignan known as 3,

    4-O-dimethylcedrusin was isolated which protected endothe-

    lial cells from undergoing degradation in a starvation medium

    and stimulated endothelial cells, however at high concentra-

    tions it inhibited the cell proliferation (Pieters et al., 1992,

    1993).Porras-Reyes et al. (1993)performed a number of tests

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    to determine how taspine accelerated wound healing and found

    that taspine enhanced wound healing via increased fibroblast

    migration.

    Chen et al. (1994)studied the wound healing activity ofCro-

    ton lechieri sapand concludedthat several factorsthe ability to

    form a film that protects against microbial invasion of wounds;

    free radical scavenging activity of procyanidins; the high content

    of polyphenolics capable of binding proteins and enzymes; and

    the anti-inflammatoryand strong antibacterial action of polyphe-

    nols, together facilitating improved healing of damaged tissue,

    may contribute to the wound repairing properties of sap. They

    tested individual constituents of the sap and found endothelial

    cell proliferation was increased by Procyanidin B-4 and most

    potently by ()-epigallocatechin and (+)-gallocatechin.Lewis

    et al. (1992)has patented for taspine in DMSO (solvent), which

    healed wounds faster than DMSO alone.

    2.2. Daemonorops spp.

    Dragons blood resin is also obtained as deep red teardrop-shaped lumps, separated physically from the immature fruit of

    the South-East Asian rattan- or cane-palm, Daemonorops of

    the Indonesian islands. The botanical source was previously

    identified asCalamus dracoWilld. (Daemonorops dracoWilld.

    Blume) byBarry et al. (1926),who also described the resinous

    layer asbeingisolatedby placing thefruits in sacks andpounding

    them andthe pulp being treated with boiling water. Subsequently

    the resin was kneaded into balls or long sticks. Various grades

    have been identifiedby Howes (1949). Other species as sourceof

    resin areD. didymophyllaBecc.,D. micracantha(Griff.) Becc.,

    D. motleyiBecc., D. rubra (Reinw. ex Blume) Blume and D.

    propinquaBecc.

    2.2.1. Chemical constituents

    Table 3summarizes the compounds reported from resin of

    Daemonorops draco(Willd.) Blume.

    2.2.2. Bioactivities and therapeutic uses

    2.2.2.1. Antimicrobial and antiviral activity. Previously,

    Mitscher et al. (1972)reportedin vitro activity of commercial

    resin obtained from Daemonorops dracoagainst Staphylococ-

    cus aureus and Mycobacterium smegmatis. This led to further

    evaluation of resins components exhibiting antimicrobial

    activity. Rao et al. (1982) reported that the antimicrobial

    activity of the resin from Daemonorops draco was due to thepresence of compounds Dracorhodin and Dracorubin. These

    compounds were found to be active against Staphylococcus

    aureus(ATCC 13709), Klebsiella pneumoniae(ATCC 10031),

    Mycobacterium smegmafis(ATCC 607) and Candida albicans

    (ATCC 10231).

    2.2.2.2. Antitumor and cytotoxic activity. Dracorhodin per-

    chlorate, a synthetic analogue of Dracorhodin, red pigment

    isolated from exudates of the fruit of Daemonorops draco,

    has been reported to induce human melanoma A375-S2 cell

    and human premyelocytic leukemia HL-60 cell death through

    the apoptotic pathway (Xia et al., 2005, 2006). M. Xia et al.

    (2004), M.Y. Xia et al. (2004), also studied the mechanism

    of Dracorhodin perchlorate induced apoptosis and concluded

    that Dracorhodin perchlorate induced cell death via alteration

    of Bax/Bcl-XL ratio and activation of caspases.

    2.2.2.3. Hemostatic and antithromboticactivity. Daemonorops

    draco has been studied for its hemostatic and vasoactive

    antithrombotic activity in Chinese medicinal system (Kiangsu

    Institute of Modern Medicine, 1977). Studies have provided

    evidences that (2S)-5-methoxy-6-methyl-flavan-7-ol (MMF)

    possess antiplatelet activity (Tsai et al., 1995). Later, under-

    lying mechanism for antiplatelet activity of MMF was related

    to inhibition of thromboxane formation via the inhibition of

    cyclooxygenase and suppression of [Ca2+]i(intraplatelet Ca2+)

    increase (Tsai et al., 1998).

    2.3. Dracaena spp.

    The name Dracaena is derived from the Greek word

    drakainia meaning a female dragon (Stern, 1992). The moststriking source is the Dracaena cinnabari Balf. f. which is

    endemic to the island of Socotra (Yemen) west of Somalia. Pal-

    inurus, a survey ship of Leut. J.R. Wellsted of the East India

    Company gave first description of the Dragons blood tree, Dra-

    caena cinnabari, calling itPterocarpus draco(http://www.rbg-

    web2.rbge.org.uk/soqotra/history/page07.html) while under-

    taking a survey of Socotra for the Indian Government in 1835.

    However, the species was first named and described by the Scot-

    tish botanist Sir lsaac Bailey Balfour when he visited the island

    in 1880 (Balfour, 1888).Three grades of Dracaenaresin were

    identified byBalfour (1883),the most valuable being tear-like

    in appearance, followed by one made of small chips and frag-ments, and the cheapest being a molten mixture of fragments

    and refuse.

    Voyagers to the Canary Islands in the 15th century obtained

    Dragons blood as dried garnet colored drops from another

    speciesDracaena draco(L.) L., a native to the Canary Islands

    and Morocco. The canarian dragon tree Dracaena draco was

    first described in 1402 (Boutier and Le Verrier, 1872).The resin

    is exuded from the wounded trunk or branches of the tree. Dra-

    caena cochinchinensis (Lour.) S.C. Chen is another species used

    in China as source of Dragons blood.

    2.3.1. Chemical constituents

    Table 4summarizes the compounds reported fromDracaenaspp., used as source of Dragons blood.

    2.3.2. Bioactivities and therapeutic uses

    2.3.2.1. Antimicrobial and antiviral activity. Mothana and

    Lindequist (2005) reported antimicrobial activity of chloro-

    form and methanol extract ofDracaena cinnabari resin from

    island Soqotra against Staphylococcus aureus (ATCC 6538),

    Bacillus subtilis (ATCC 6059), Micrococcus flavus (SBUG

    16) and Escherichia coli (ATCC 11229). Kumar et al. (2006)

    also reported antimicrobial activity of exudes of red resin

    of Dracaena cinnabari collected from India against Bacil-

    lus cereus var mycoides (ATCC 11778), Bacillus pumilus

    http://www.rbg-web2.rbge.org.uk/soqotra/history/page07.htmlhttp://www.rbg-web2.rbge.org.uk/soqotra/history/page07.html
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    Table 3

    Chemical constituents reported fromDaemonorops draco(Willd.) Blume

    Compound name Bioactivity References

    Dracorhodin (17) Apoptic activity Brockmann and Junge (1943),Robertson and

    Whalley (1950),Rao et al. (1982),Gao et al. (1989),

    Xia et al. (2005)

    2,4-Dihydroxy-5-methyl-6-methoxychalcone;

    2,4-dihydroxy-6-methoxychalcone;5-methoxy-7-hydroxyflavan (15)

    Cardillo et al. (1971)

    Nordracorhodin (16); nordracorubin (18) Cardillo et al. (1971),Rao et al. (1982)

    (2S) 5-Methoxy-6-methylflavan-7-ol (21) Antiplatelet effects Cardillo et al. (1971),Tsai et al. (1995, 1998)

    (2S)-5-Methoxyflavan-7-ol (22);

    5,7-dimethoxy-6-methylflavan

    Cardillo et al. (1971),Arnone et al. (1997)

    Abietic acid; dehydroabietic acid; isopimaric acid; pimaric

    acid; sandaracopimaric acid

    Piozzi et al. (1974),Trease and Evans (1978)

    Secobiflavanoid Merlini and Nasini (1976)

    Dracorubin (19) Rao et al. (1982)

    Polysaccharide (MW = 25,000) Anticoagulant activity Gibbs et al. (1983)

    Dracoalban; dracoresene; dracoresinotannol Hsu (1986)

    Dammaradienol Antiviral activity, Anti-inflammatory

    activity, cytotoxic activity

    Poehland et al. (1987),Bianchini et al. (1988),

    Akihisa et al. (1996),Shen et al. (2007)

    Dracooxepine Arnone and Nasini (1989)

    Dracoflavan A Arnone and Nasini (1990)

    2,4-Dimethoxy-3-methylphenol; dracoflavan B1; B2; C1;

    C2; D1; D2

    Anti-inflammatory activity Arnone et al. (1997)

    1,6-Germacradien-5-ol; benzoic acid; bicyclogermacrene;

    cis-9,10-dihydrocapsenone; germacrene-d;-copaene;

    -cubebene;-humulene; -caryophyllene;-cubebene;

    -elemene;-cadinene

    Ford et al. (2001)

    4,6-Dihydroxy-2-methoxy-3-methyldihydrochalcone Shen et al. (2007)

    (ATCC 14884),Bacillus subtilis (ATCC 6633),Bordetella bron-

    chiseptica (ATCC 4617), Micrococcus luteus (ATCC 9341),

    Staphylococcus aureus(ATCC 29737),Staphylococcus epider-

    midis (ATCC 12228), Klebsiella pneumoniae (ATCC 10031),

    Pseudomonas aeruginosa (ATCC 9027), Streptococcus faecalis(MTCC 8043), andAspergillus niger(MTCC 1344). Recently,

    Mothana et al. (2006) also reported antiviral activity of methanol

    extract of resin ofDracaena cinnabariagainst Herpes simplex

    virus and Human influenza virus.

    Thus,Dracaenaresin could be a rich source of antimicrobial

    agents with possibly novel mechanisms of action. Interestingly,

    resin from Dracaena cochinchinensis has been produced by

    infection with Fusarium and Cladosporium spp. (Wang et al.,

    1999).In another study done byJiang et al. (2003),inoculation

    of fungi Fusarium9568D in abiotic branch and wood ofDra-

    caena cochinchinensisresulted in emergence of red resin from

    the inoculation points after 45months incubation. Theemergedresin was found to resemble the natural resin by UV-IR spectra

    analysis.

    2.3.2.2. Antitumor and cytotoxic activity. Vachalkova et al.

    (1995)studied carcinogenicity of three homoisoflavanoids and

    four flavanoids isolated from the resin ofDracaena cinnabari.

    Al-Fatimi et al. (2005)reported cytotoxic activity of resin of

    Dracaena cinnabari from Yemen against human ECV-304

    cells. Dracaena draco has been found to be a rich source of

    cytotoxic steroidal saponins. Darias et al. (1989) reported,

    for the first time, the use of sap of Dracaena draco as an

    anticarcinogen. Steroidal saponins, (25R)-spirost-5-en-3-ol

    3-O-{O--l-rhamnopyranosyl-(12)--d-glucopyranoside}and (23S,24S)-spirosta-5,25(27)-diene-1,3,23,24-tetrol

    1-O-{O-2,3,4-tri-O-acetyl--l-rhamnopyranosyl-(1 2)--l-arabinopyranosyl}24-O--d-fucopyranoside, isolated fromthe aerial parts ofDracaena dracoare reported to show potent

    cytostatic activity against HL-60 cells with IC50 value being

    1.3 and 2.6g/ml, respectively compared with etoposide (IC500.3g/ml) used as a positive control (Mimaki et al., 1999).

    Gonzalez et al. (2003) also reported new steroidal saponins,

    Draconin A and Draconin B with cytotoxic activities against

    HL-60 cells from bark ofDracaena draco. The mechanism of

    these compounds cytotoxicity was also evaluated and found

    to be via activation of apoptotic process. Recently a new

    cytotoxic steroidal saponin, Icogenin, has been isolated from

    Dracaena draco. Icogenin also inhibited growth of HL-60 cells

    by induction of apoptosis (Hernandez et al., 2004). Dioscin,

    fromDracaena draco also displayed cytotoxic activity similarto Icogenin.

    2.3.2.3. Analgesic activity. Liu et al. (2004)observed that both

    Dragons blood resin (D. cochichinensis) and loureirin B could

    suppress TTX-S voltage-gated sodium currents depending upon

    dose, which could be reason for its analgesic effect. Later,

    Liu et al. (2005) studied the effects of Dragons blood and

    its component loureirin B on tetrodotoxin-sensitive (TTX-S)

    and tetrodotoxin-resistant (TTX-R) sodium currents in trigem-

    inal ganglion (TG) neurons using the whole-cell patch-clamp

    technique and found that both Dragons blood and loureirin

    B suppressed two types of peak sodium currents depending

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    Table 4

    Chemical constituents reported fromDracaenaspp.

    Compound name Bioactivity References

    Dracaena cinnabariBalf. f.

    ()-7,4-Dihydroxy-3-methoxyflavan Braz et al. (1980),Achenbach et al. (1988),

    Masaoud et al. (1995c)

    4,4-Dihydroxy-2 -methoxychalcone (9) Meksuriyen and Cordell (1988),Masaoud et al.

    (1995c)7,4-Dihydroxyflavone (23) Meksuriyen and Cordell (1988),Maxwel1 et al.

    (1989),Masaoud et al. (1995c)

    (2S)-7-Hydroxyflavan; (2S)-7-hydroxyflavan-4-one (20);

    7-hydroxy-3-(4-hydroxybenzyl)-8-methoxychroman;

    7-hydroxy-3-(4-hydroxy benzyl) chroman; loureirin C

    (24)

    Suchy et al. (1991),Masaoud et al. (1995c)

    3-(4-Hydroxybenzyl)-7,8-methylendioxychroman Antioxidant activity Suchy et al. (1991),Masaoud et al. (1995c),

    Machala et al. (2001),Deepika and Gupta (2007)

    2-Methoxysocotrin-5-ol, socotrin-4-ol;

    homoisosocotrin-4-ol

    Masaoud et al. (1995a)

    Cinnabarone (29) Masaoud et al. (1995b),Deepika and Gupta (2007)

    (2S)-7,3-Dihydroxy-4-methoxyflavan;

    4-hydroxy-2-methoxydihydrochalcone;

    7-hydroxy-3-(3-hydroxy-4-methoxybenzyl)chroman

    Masaoud et al. (1995c)

    24-Methylenecycloartanol; 31-norcycloartanol; 4,

    14-dimethylcholest-8-en-3-ol;

    4-methylcholest-7-en-3-ol; betulin; campesterol;

    cholest-4-en-3-one; cholesterol; cycloartanol;

    lanost-7-en-3-ol; lupeol; sitosterol;

    stigmast-22-en-3-ol; stigmastanol; stigmasterol

    Masaoud et al. (1995d)

    Damalachawin (30) Himmelreich et al. (1995)

    2,4,4-Trihydroxydihydrochalcone Antitumor activity, chemoprotective

    effects

    Gonzalez et al. (2000),Forejtnkova et al. (2005)

    Dracophane (27) Vesela et al. (2002)

    2,4-Dihydroxy-4,6-dimethoxydihydrochalcone; 3-(4-

    hydroxy-2-methoxyphenyl)-1-phenyl-1-propanone;

    3,7-dihydroxy-4 -methoxyflavan;

    3,7-dihydroxy-4 -methoxy homoisoflavan;

    4,6-dihydroxy-7-methoxyhomoisoflavan;

    4,6-dihydroxy-7-methoxyhomoisoflavan;

    4,7-dihydroxy-5-methoxyhomoisoflavan;

    4,7-dihydroxy-3 -methoxy flavan;

    4,7-dihydroxyhomoisoflavan;

    4,7-dihydroxy-8-methylflavan;

    4,7,8-trihydroxyhomoisoflavan;

    7-hydroxy-5-methoxy-6-methylflavan;

    7-hydroxy-3-(4-hydroxy benzyl)-4-chromanone;

    7,10-dihydroxy-11-methoxydracae none;

    10-hydroxy-11-methoxydracaenone; loureirin A

    Deepika and Gupta (2007)(unpublished report)

    Dracaena cochinchinensis(Lour.) S.C. Chen

    Loureirin A; loureirin c (24); loureirin B Analgesic activity Meksuriyen and Cordell (1988),Lu et al. (1998),

    Zhou et al. (2001a,b),Liu et al. (2004, 2005, 2006),

    Chen and Liu (2006),Zheng et al. (2006a,b)

    7,4-Dihydroxyflavane Antifungal activity Wang et al. (1995),Zhou et al. (2001a,b),Zheng et

    al. (2006a,b)

    7-Hydroxy-4-methoxyflavan;

    6-hydroxy-7-methoxy-3-(4-hydroxybenzyl)chromane;

    2,3,5,6-tetrachloro-1,4-dimethoxybenzene;

    4-hydroxy-3,5-dimethoxystilbene

    Lu et al. (1998)

    2, 4, 4-Trihydroxydihydrochalcone; 2, 4,

    4-trihydroxy-6-methoxydihydrochalcone

    Lu et al. (1998),Zhou et al. (2001a,b)

    2-Methoxysocotrin-5-ol; socotrin-4-ol; 2, 4,

    4-trihydroxychalcone; 2-methoxy-4,

    4-dihydroxychalcone; cochinchinenins

    Analgesic activity Zhou et al. (2001a,b),Liu et al. (2006)

    2-Methoxy-4,4-dihydroxychalcone (9) Zhou et al. (2001a,b),Zheng et al. (2006a,b)

    Dracaenoside A; B; C; D Zheng and Yang (2003a,b)

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    Table 4 (Continued)

    Compound name Bioactivity References

    25(R,S)-Dracaenosides EH; M; OQ; dracaenosides

    IL; R; 25(S)-dracaenoside N;

    25(R,S)-spirost-5-en-3-ol

    3-O--l-rhamnopyranosyl-(1,2)-[-l-rhamno

    pyranosyl-(1,4)]--d-glucopyranoside;

    25(R,S)-spirost-5-en-3-ol 3-O--l-rhamnopyranosyl-(1,2)--l-glucopyranosyl-(1,3)]--d-glucopyranoside;

    26-O--d-glucopyranosyl

    25(R,S)-furost-5-en-3,22,26-triol

    3-O--l-rhamnopyranosyl-(1,2)-[-d-glucopyranosyl

    (1,3)]--d-glucopyranoside; 26-O--d-glucopyranosyl

    25(R,S)-spirost-5-en-3,22,26-triol

    3-O--l-rhamnopyranosyl-(1,2)-[-l-

    rhamnopyranosyl-(1,4)]--d-glucopyranoside

    Zheng et al. (2004a,b,c)

    7,4-Dihydroxyflavone (23);

    7,4-dihydrohomoisoflavanone (26);

    7,4-homoisoflavane (25); 10,11-dihydroxydracaenone

    C; dracaenogenin A and B

    Zheng et al. (2006a,b)

    1-(4-O--d-Glucopyranosyl)benzyl-ethan-2-ol;

    3,4-dihydoxy-1-allylbenezene-4-O--l-

    rhamnopyranosyl-(16)-O--d-glucopyranoside;

    1-hydroxy-3,4,5-trimethoxy benzene-1-O--l-

    apiopyranosyl-(1 6)-O--d-glucopyranoside;

    lophenol;-sitosterol; stigma-5, 22-diene-3-ol;

    tachioside

    Zheng et al. (2006a,b)

    Dracaena draco(L.) L.

    7,4-Dihydrohomoisoflavanone (26);

    7,4-homoisoflavane (25)

    Camarda et al. (1983)

    7-Hydroxy-3-(4-hydroxybenzyl)chroman-4-one Camarda et al. (1983),Gonzalez et al. (2000)

    7-Hydroxy-3-(4-hydroxybenzyl)chroman Camarda et al. (1983),Gonzalez et al. (2000, 2003)

    (2S)-4,7-Dihydroxy-3-methoxy-8-methylflavan;

    (2S)-4,5-dihydroxy-7-methoxy-8-methylflavan

    Camarda et al. (1983),Gonzalez et al. (2000, 2004)

    10-Hydroxy-11-methoxydracaenone Meksuriyen et al. (1987),Gonzalez et al. (2000)

    3,4,5-Trimethoxycinnamyl alcohol Ponpipom et al. (1987),Gonzalez et al. (2000)

    4,4-Dihydroxy-2-methoxychalcone (9) Achenbach et al. (1988),Gonzalez et al. (2000)

    (23S)-Spirost-5,25(27)-diene-1,3,23-triol

    1-O-{4-O-acetyl--l-rhamnopyranosyl-(12)--l-arabinopyranoside}(45);(23S)-spirost-5,25(27)-diene-1,3,23-triol

    1-O-{O--l-rhamnopyranosyl-(1 2)--l-arabinopyranoside}(46);(23S,24S)-spirosta-5,25(27)-diene-1,3,23,24-

    tetrol

    1-O-{O-(4-O-acetyl--l-rhamnopyranosyl)-(12)--l-arabinopyranoside}(47);(23S,24S)-spirosta-5,25(27)-diene-1,3,23,24-tetrol

    1-O-{O-2,3,4-tri-O-acetyl--l-rhamnopyranosyl-(1 2)--l-arabinopyranosyl}24-O--d-fucopyranoside (48); (25R)-spirost-5-en-3-ol

    3-O-{O--l-rhamnopyranosyl-(1 2)--d-glucopyranoside}(33);spirost-5,25(27)-diene-1,3-diol

    1-O-{O--l-rhamnopyranosyl-(1 2)--l-arabinopyranoside}(34);(23S)-spirost-5,25(27)-diene-1,3,23-triol

    1-O-{O--l-rhamnopyranosyl-(1 2)-O-[-d-xylopyranosyl-(l 3)]--l-arabinopyranoside}(35);26-O--d-glucopyranosyl-22-O-methylfurosta-

    5,25(27)-diene-l,3,22,26-tetrol

    1-O-{O--l-rhamnopyranosyl-(l2)-O--l-arabinopyranoside}(36)

    Cytostatic activity Mimaki et al. (1999)

    (23S,24S)-Spirosta-5,25(27)-diene-1,3,23,24-tetrol

    1-O-{O--l-rhamnopyranosyl}-(1 2)--l-arabinopyranoside}

    (43)

    Mimaki et al. (1999),Hernandez et al. (2004)

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    Table 4 (Continued)

    Compound name Bioactivity References

    (2S)-4,7-Dihydroxy-8-methylflavan; 3-(4-hydroxy

    benzyl)-5,7-dimethoxychroman;

    5,7-dihydroxy-3-(4-hydroxybenzyl)-chromone;

    5,7-dihydroxy-3-(4-hydroxy benzyl)-chroman-4-one;

    7-hydroxy-3-(4-hydroxybenzyl) chromone;

    isoliquiritigenin; liquiritigenin; xenognosin

    Gonzalez et al. (2000)

    Loureirin C (24) Gonzalez et al. (2000, 2003)

    (2S)-3,7-Dihydroxy-4-methoxy-8-methylflavan Gonzalez et al. (2000, 2004)

    7-Hydroxy-3-(4-hydroxybenzyl)-8-methoxychroman;

    3-(4-hydroxybenzyl)-7,8-methylendioxychroman

    Gonzalez et al. (2000),Hernandez et al. (2004)

    ()-7,4-Dihydroxy-3-methoxyflavan Gonzalez et al. (2000, 2003, 2004)

    2,4,4-Trihydroxydihydrochalcone Chemoprotective effects Gonzalez et al. (2000),Forejtnkova et al. (2005)

    Methyl protodioscin (39); draconin C (42); draconin A

    (40); draconin B (41)

    Apoptic activity Gonzalez et al. (2003)

    ()-3-Hydroxy-4-methoxy-7-hydroxy-8-methylflavan;

    3-O-[-l-rhamnopyranosyl(1 4)--

    dglucopyranosyl] diosgenin (38); 4-allylcatecol;

    -sitosterol; diosgenin (31); isoliquiritigenin;

    sitoindoside i;trans--apo-8-carotenal; dioscin (37)

    Cytotoxic activity Gonzalez et al. (2003),Hernandez et al. (2004)

    (2S)-4,7-Dihydroxy-3-methoxyflavan;

    (2S)-4,7-dihydroxy-3-methoxyflavan; diosgenone

    (32); shonanin; syringaresinol; icogenin (44)

    Cytotoxic activity Hernandez et al. (2004)

    Dracoflavylium Melo et al. (2006)

    Dracol; icodeside Cytotoxic activity Hernandez et al. (2006)

    Number given in parentheses corresponds to the structure of that compound given inFig. 1.

    upon dose. Further, Liu et al. (2006) explored the material

    basis for efficacy of modulation of Dragons blood on the

    tetrodotoxin-resistant (TTX-R) sodium currents in dorsal root

    ganglion (DRG) neurons. They suggested that analgesic effect

    of Dragons blood may be explained on the basis of interfer-

    ence with pain messages caused by the modulation of Dragons

    blood on TTX-R sodium currents in DRG neurons and could bedue to the synergistic effect of three components cochinchinenin

    A, cochinchinenin B, and loureirin B. Recently,Chen and Liu

    (2006) carried out a computer simulation research for the effects

    of Dragons blood and its component loureirin B on sodium

    channel in dorsal root ganglion cells.

    2.3.2.4. Antioxidative activity. Juranek et al. (1993) have

    reported antioxidant activity of three homoisoflavans isolated

    from resin ofDracaena cinnabari. Machala et al. (2001) studied

    homoisoflavonoids and chalcones, isolated from the Dracaena

    cinnabari, for their potential to inhibit cytochrome P4501A

    (CYP1A) enzymes and Fe (II)/NADPH dependent in vitroperoxidation of microsomal lipids isolated from C57B1/10

    mouse liver and found chalcones were poor antioxidants

    while 7,8-methylenedioxy-3 (4-hydroxybenzyl) chromane, a

    homoisoflavonoid, exhibited a strong antioxidant activity.

    2.4. Pterocarpus spp.

    Pterocarpus officinalisJacq., previously known asPterocar-

    pus dracoL., is the only species known as a source of Dragons

    blood. According to a description in the Bulletin of the Botani-

    cal Department, Jamaica, No. 45, July, 1893, when an incision

    is made in the bark, drops of red sap ooze out, flow slowly down

    the bark and gradually harden. No major studies have been done

    on this source of Dragons blood.Trimble (1895),studied resin

    fromPterocarpus dracoL. and obtained 34.85% tannins from

    this resin.

    3. Quality control and safety

    Since Dragons blood, as a name, has been applied to resins

    obtained from different species from different continents; there

    is a great need to identify them apart. There are other substi-

    tutes as well, which are available in the market for Dragons

    blood such asEucalyptus resiniferaSm. (Edwards et al., 2001).

    A powdered dark red coral from the Indian Ocean is also sold in

    Yemeni markets as Dragons blood. Glasgows Professor of

    Chemistry, J. Dobbie and G. Henderson first tackled the issue

    of chemical identification of the various resins under the name

    of Dragons blood in 1883, on request of Prof. Bayley Balfour

    (Pearson, 2002).They reported, the resins known as Dragons

    blood differ widely from one another, not only in their degree ofpurity, but also in their appearance and that specimens labeled

    as having come from the same locality must, in reality, in some

    cases, have been derived from very different sources (Dobbie

    and Henderson, 1883).Dobbie and Henderson (1884)arranged

    redresins in four distinct groups: 1. Those soluble in chloroform,

    carbon disulphide, and benzene completely; 2. Those soluble in

    chloroform, but insoluble in carbon disulphide and benzene;

    3. Those soluble in chloroform and benzene and partly in car-

    bon disulphide; and 4. Those, which are insoluble in all three

    reagents.

    Edwards et al. (1997)described Dragons blood resin (Dra-

    caena spp.) found on Socotra Island as the probable genuine

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    376 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380

    source in antiquity, on the basis of Fourier transform Raman

    spectroscopic studies of several resins generically known as

    Dragons blood from different botanical and geographical

    sources. They have since described a Raman spectroscopic

    method to identify fake and unknown Dragons blood resins

    from different botanical origins (Edwards et al., 2001, 2004).

    AllDracaenaspectra show the strong bands in the wave num-

    ber region 16051500 cm1 and can be generally identified by

    the strongest band at 1605cm1, the shoulder at ca. 1560 cm1.

    However, specimen degradation can be recognized by the loss

    of this shoulder at 1560 cm1. Also, vibrational bands near

    1170 cm1 seen in theDracaena dracospectra could be used as

    biomarkers forDracaena species. The main feature distinguish-

    ingDaemonorops Dragons bloodresins fromthoseofDracaena

    is the presence of the narrow and intense band at 1600 cm1, the

    doublets at 15101540 cm1 and 14201450 cm1 region and

    also the medium intensity band at 1001 cm1. Croton speci-

    men is distinguished by a broad band at 1612 cm1, and also by

    the medium intensity band at 784 cm1. Later,Edwards et al.

    (2004) identified the keymolecularbiomarkerbands of Dragonsblood in the region 14001700 cm1, which could be adopted

    as a protocol for the identification of the botanical and possible

    geographical sources of modern Dragons blood resins.

    No major toxicity has been reported from Dragons blood.

    The American Herbal Products Association (1997) lists San-

    gre de Drago (Croton) as Class I, meaning it can be consumed

    safely when used appropriately. There are some instances when

    Dragons blood has been misrepresented as opium and dis-

    tributed for use as a drug. Ford et al. (2001)had identified a

    red substance as Dragons blood incense from Daemonorops

    draco that was being mixed with marijuana and smoked as

    an alternative to opium in Virginia. They also screened thesubstance for toxicity in various in vitro tests and suggested

    that that the abuse potential for Dragons blood incenses is

    minimal.

    4. Conservation needs

    Dragons blood is used in traditional medicine for diverse

    applications. Overexploitation of sources of Dragons blood

    is a matter of concern as is the case of Croton lechleri, in

    Peru and Ecuador. Because of the overexploitation and trade,

    it was identified as potentially threatened amongst the 22

    species in the Workshop of Specialists in Ethnobotany andEconomic Botany held in 1997 (http://www.traffic.org/ecuador/

    executivesummary.html). Dracaena cinnabari was also listed

    as vulnerable in the IUCN red list of threatened species ( Miller,

    2004).Dracaena draco wasreported as vulnerable species on the

    Canary Islands due to overexploitation of the trees for Dragons

    Blood in the middle ages (Lucas and Synge, 1978).It was also

    cited in IUCN Red List of Threatened Species (2006). Predom-

    inantly, resin ofDaemonorops draco is the principal source of

    commercially harvested Dragons blood. Plant cell, tissue and

    organ culture could be an alternative approach for economic pro-

    duction of Dragons blood plants and the secondary metabolites

    they produce.

    5. Conclusion

    Although Dragons blood has proved to be popular alter-

    native or complementary medicine used in the treatment

    of many diseases, clinical trial evaluation of these claims

    using currently accepted protocols is needed. One such

    potential new drug for AIDS-related diarrhoea is, Cro-

    felemer developed originally by Shaman Pharmaceuticals

    from Croton lechleri. Since 2001, Crofelemer has been

    purchased by the American pharmaceutical company, Napo

    Pharmaceuticals and is currently undergoing clinical trials

    (http://www.aumag.org/lifeguide/WWSeptember05.html,

    http://www.botanical.com/botanical/mgmh/d/dragon20.html,

    http://www.drugs.com/npp/dragon-s-blood.html#ref3).

    This resin offers huge potential and we need to investi-

    gate whether purified compounds isolated from Dragons blood

    may have better therapeutic potential as compared to crude

    extract. Since there is considerable variation in the chemical

    composition among various samples of Dragons Blood, quality

    control/assurance needsto be established for the traditionalmed-ical trade. This review is an effort to highlight the potential and

    problems related to the sources and possibilities of isolating new

    pharmaceutically active molecules, using traditional knowledge

    in our search, for new and effective dugs molecules.

    Acknowledgements

    We are grateful to Prof. Ulrike Lindequist, Institute of

    Pharmacy, Ernst-Moritz-Arndt-University, Germany for her

    thorough revisionof this review andproviding us with herinvalu-

    able suggestions. We acknowledge the financial support from

    AICTE (8023/RID/NPROJ/RPS-38/2004-05).

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