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Journal of Ethnopharmacology 115 (2008) 361–380

Review

Dragon’s blood: Botany, chemistry and therapeutic uses

Deepika Gupta a, Bruce Bleakley b, Rajinder K. Gupta a,∗a University School of Biotechnology, GGS Indraprastha University, K. Gate, Delhi 110006, India

b Department of Biology & Microbiology, South Dakota State University, Brookings, South Dakota 57007, USA

Received 25 May 2007; received in revised form 10 October 2007; accepted 11 October 2007Available online 22 October 2007

Abstract

Dragon’s blood is one of the renowned traditional medicines used in different cultures of world. It has got several therapeutic uses: haemostatic,antidiarrhetic, antiulcer, antimicrobial, antiviral, wound healing, antitumor, anti-inflammatory, antioxidant, etc. Besides these medicinal applica-tions, it is used as a coloring material, varnish and also has got applications in folk magic. These red saps and resins are derived from a number ofdisparate taxa. Despite its wide uses, little research has been done to know about its true source, quality control and clinical applications. In this
review, we have tried to overview different sources of Dragon’s blood, its source wise chemical constituents and therapeutic uses. As well as, alittle attempt has been done to review the techniques used for its quality control and safety. © 2007 Elsevier Ireland Ltd. All rights reserved.
Keywords: Dragon’s blood; Croton; Dracaena; Daemonorops; Pterocarpus; Therapeutic uses

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3621.1. Mythology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3621.2. Historical uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3621.3. Ethnomedicinal uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

2. Sources of Dragon’s blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3632.1. Croton spp. (Euphorbiaceae) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

2.1.1. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3632.1.2. Bioactivities and therapeutic uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363

2.2. Daemonorops spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3712.2.1. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3712.2.2. Bioactivities and therapeutic uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

2.3. Dracaena spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3712.3.1. Chemical constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3712.3.2. Bioactivities and therapeutic uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371

2.4. Pterocarpus spp. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3753. Quality control and safety . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3754. Conservation needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
5. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376

∗ Corresponding author. Mobile: +91 9871263252; fax: +91 11 23865941/2.E-mail address: [email protected] (R.K. Gupta).

0378-8741/$ – see front matter © 2007 Elsevier Ireland Ltd. All rights reserved.doi:10.1016/j.jep.2007.10.018

mailto:[email protected]

dx.doi.org/10.1016/j.jep.2007.10.018

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. Introduction

Plants are used worldwide for the treatment of diseases andovel drugs continue to be developed through research fromhese plants. There are more than 20,000 species of higher plant,sed in traditional medicines and are reservoirs of potential newrugs. As the modern medicine and drug research advanced,hemically synthesized drugs replaced plants as the source ofost medicinal agents in industrialized countries. Nevertheless

lants are an important source of lead compounds. However, ineveloping countries, the majority of the world’s population can-ot afford pharmaceutical drugs and use their own plant basedndigenous medicines.

Dragon’s blood is a deep red resin, which has been useds a famous traditional medicine since ancient times by manyultures. The term “Dragon’s blood” refers to reddish resinousroducts, usually encountered as granules, powder, lumps orticks used in folk medicine. Dragon’s blood has been used foriverse medical and artistic applications. It has astringent effectnd has been used as a hemostatic and antidiarrhetic drug.he origin of Dragon’s blood is believed to be from Indiancean island of Socotra, now part of Yemen (Angiospermhylogeny Group, 1974). However, there exists a great degreef confusion regarding the source and identity of Dragon’slood. Several alternative sources of Dragon’s blood fromanary Islands, Madeira, and South East Asia and also fromast and West Africa have been identified (Alexander andiller, 1995). Dragon’s blood was a name applied to many

ed resins described in the medical literature, e.g. East Indianragon’s blood (from the fruit of Daemonorops draco (Willd.)lume), Socotran or Zanzibar Dragon’s blood (exudates ofracaena cinnabari Balf. f.), Canary Dragon’s blood (exudates

ormed from incisions of the trunk of Dracaena draco (L.) L.),est Indian Dragon’s blood (exudates of Pterocarpus draco

.), Mexican Dragon’s blood (resin of Croton lechleri Mull.rg.) and the Venezuelan Dragon’s blood (resin of Crotonossypifolium Vahl) (Sollman, 1920).

Mabberley (1998) suggests that Dragon’s blood was pro-uced originally from Dracaena cinnabari, later from Dracaenaraco and more recently from Daemonorops spp. Zheng etl. (2004a,b,c) confirms this view and suggests Pterocar-us spp., Daemonorops draco and Croton spp. as substitutesor Dracaena spp. Thus, the term “Dragon’s blood” in gen-ral is used for all kinds of resins and saps obtained fromour distinct plant genera; Croton (Euphorbiaceae), DracaenaDracaenaceae), Daemonorops (Palmaceae), and PterocarpusFabaceae).

.1. Mythology

According to a Greek myth, Landon, the hundred-headedragon, guardian of the Garden of the Hesperides (the nymphaughters of Atlas, the titan who holds up earth and heaven)
as killed by either Hercules (in his quest) or Atlas (as punish-ent) while bringing back three golden apples from the garden,
epending upon the version of the myth. Landon’s red bloodowed out upon the land and from it sprung up the trees known

deis

rmacology 115 (2008) 361–380

s “Dragon Trees” (The Eleventh Labor of Hercules: The Applesf The Hesperides).

Dragon’s blood was also called “Indian cinnabar” by Greeksriters. The name “Dragon’s blood” dates back to the 1st cen-

ury AD when a Greek sailor wrote, about an island calledioscorida where the trees yielded drops of cinnabar, in a ship-ing manual “Periplus of the Erythrean Sea”. Plinius (1601) alsoescribed that the resin got its name from an Indian legend basedn Brahma and Shiva. Emboden (1974) and Lyons (1974) hadlso summarized the history and mythology of Dragon’s blood.ccording to Lyons, the struggle between a dragon and an ele-hant that, at its climax, led to the mixing of the blood of thewo creatures resulted in a magical substance, “Dragon’s blood”mbued with medicinal properties.

.2. Historical uses

The crimson red resin was highly prized in the ancient world.ragon’s blood (Dracaena cinnabari) was used as a dye andedicine in the Mediterranean basin. Miller and Morris (1988)ention use of Dracaena resin as a coloring matter for varnishes,

inctures, toothpastes, plaster, and for dying horn to make it lookike tortoiseshell. Mabberley (1998) also notes that resinous saproduced via incisions in the bark or stem of the Dracaenainnabari was used by the Ancients to stain horn to resem-le tortoiseshell. People in Socotra used resin from Dracaenainnabari for dying wool, glue pottery, breath freshener, to dec-rate pottery and houses and even as lipstick (Alexander andiller, 1996). Due to the belief that it is the blood of the mythi-

al animal, the dragon, it is also used in alchemy and for ritualagic.Dragon’s blood from both Dracaena and Daemonorops were

lso used for ceremonies in India. Sometimes Dracaena resin,ut more often Daemonorops resin, was used in China as redarnish for wooden furniture. These resins were used to colorhe surface of writing paper for banners and posters, used espe-ially for weddings and for Chinese New Year. These red resinsere also used as pigment in paint, enhancing the color ofrecious stones and staining glass, marble and the wood fortalian violins. Fulling (1953) reported that Daemonorops resinas used in the preparation of drawings. Powdered forms ofaemonorops resin were used extensively as an acid resist byhotoengravers during the 1930s (Pankow, 1988). In modernimes Daemonorops resin is still used as a varnish for violins,n photoengraving, as an incense resin, and as body oil. Dae-onorops resin is also added to red ink to make “Dragon’slood Ink,” which is used to inscribe magical seals and

alismans.Spanish naturalist and explorer P. Bernabe Cobo (1956)

ecorded for the first time that Croton’s sap was used widelyhroughout the indigenous tribes of Mexico, Peru, and Ecuadorn 1600s. In African-American folk magic or voodoo thisesin is used in mojo hands for money-drawing or love-
rawing, and is used as incense to cleanse a space of negativentities or influences. In neopagan witchcraft, it is used toncrease the potency of spells for protection, love, banishing andexuality.

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.3. Ethnomedicinal uses

Dragon’s blood was used by early Greeks, Romans, andrabs for its medicinal properties. Locals of Moomy city onocotra island used the Dragon’s blood (Dracaena) as a sortf cure-all, using it for things such as general wound healing,coagulant, curing diarrhoea, lowering fevers, dysentery dis-

ases, internal ulcers of mouth, throat, intestines and stomach,s an antiviral for respiratory and stomach viruses and for skinisorders such as eczema. Dioscorides and other early Greekriters described its medicinal uses. Dragon’s blood (Dracaena)

s used for treating dysentery, diarrhoea, hemorrhage and exter-al ulcers in Yemeni folk medicine (Milburn, 1984). Dracaenaesin has strong astringent properties and is used as a muscleelaxant (Milner, 1992). Gerarde and Johnson (1633) stated thatragon’s blood (Dracaena) was used for over flow of courses

menses), in fluxes, dysenteries, spitting of blood and fasteningf loose teeth. It was also used to treat gonorrhea, stoppage ofrine, watery eyes and minor burns (Parkinson, 1640). In China,he red resin of Dracaena cochinchinensis was used by localeople for treatment of wounds, leucorrhea, fractures, diarrhoeand piles as well as for intestinal and stomach ulcers (Cai andu, 1979).Daemonorops resin is also used in traditional Chinese

edicine to stimulate circulation, promote tissue regenerationy aiding the healing of fractures, sprains and ulcers and to con-rol bleeding and pain (Bensky and Gamble, 1993). The medicalpplications of Dragon’s blood resins, mainly the Daemonoropsesin have been attributed to the presence of benzoic acid, whichhow antiseptic properties (Piozzi et al., 1974; Badib, 1991).roton’s sap is a common household remedy used in Peru, otheratin American countries, and among the Latin American pop-lation of the United States. Croton’s sap is taken orally to cureifferent types of diarrhoea and cholera by the indigenous peoplef Amazon basin (Carlson and King, 2000). Other ethnomedi-al uses of the sap of Croton lechleri in Peru are found in thereatment of bone fractures, leucorrhea, piles and hemorrhoidsSoukup, 1970). Sap of Croton lechleri was also used to speedp internal healing after an abortion (Castner et al., 1998) and inaginal baths taken before childbirth (Duke and Vasquez, 1994).

Croton’s sap has been reviewed by many researchers for itsherapeutic uses (Jones, 2003; Gonzales and Valerio, 2006).arious therapeutic properties of Dragon’s blood (Crotonpp.) have been described such as wound and ulcer healing,ntidiarrhoeic, anticancer, anti-inflammatory and antirheumaticroperties (Bettolo and Scarpati, 1979; Perdue et al., 1979; Chent al., 1994; Pieters et al., 1995; Phillipson, 1995; Gabriel et al.,999; Holodniy et al., 1999; Miller et al., 2000).

. Sources of Dragon’s blood

Dragon’s blood is a bright red resin that is obtained from dif-erent species of four distinct plant genera; Croton, Dracaena,
aemonorops, and Pterocarpus. Table 1 summarizes the differ-
nt botanical sources and common names of Dragon’s blood.earson and Prendergast (2001) have reviewed Dragon’s bloodamples from different sources kept at Royal Botanic Gardens

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macology 115 (2008) 361–380 363

ew. The Economic Botany Collections at the Royal Botanicardens Kew (curated by the Centre for Economic Botany)

ontains perhaps the largest (80 accessions comprising of 34racaena accessions, 40 Daemonorops and 6 Croton) and most

eliably identified assembly of Dragon’s blood resins.In this review, we discuss chemistry and therapeutic uses of

arieties of Dragon’s blood differentiated according to the plantaxa from which they are obtained. Structures of some of theompounds reported from these sources are given in Fig. 1.

.1. Croton spp. (Euphorbiaceae)

Croton lechleri Mull. Arg., the tree growing in Mexico,enezuela, Ecuador, Peru and Brazil, is possibly the best-knownource for Dragon’s blood. Other species are Croton draconoides

ull. Arg., Croton draco Schlect & Cham., Croton urucuranaaill., C. xalapensis Kunth, Croton gossypifolium Vahl, Cro-

on erythrochilus Mull. Arg. and Croton palanostigma Klotzsch.hen the trunk of the tree is cut or wounded, dark red, sappy

esin oozes out, known as Sangre de Drago (Dragon’s blood).

.1.1. Chemical constituentsTable 2 summarizes the compounds reported from Dragon’s

lood of Croton spp.

.1.2. Bioactivities and therapeutic uses

.1.2.1. Antimicrobial and antiviral activity. Sangre de DragoCroton) has been evaluated as a source of potential chemother-peutic agents based on its ethnomedicinal uses. Chen et al.1994) had studied the antibacterial properties of blood-red sapf Croton lechleri from Ecuador and reported compounds 2, 4, 6-rimethoxyphenol, 1, 3, 5-trimethoxybenzene, crolechinic acidnd korberins A and B present in the sap to exhibit antibacterialctivity individually.

The aqueous ethanol extract, some fractions of the methanolxtract, catechin and acetyl aleuritolic acid of Sangre de Dragobtained from Croton urucurana are reported to show inhibitionf Staphylococcus aureus and Salmonella typhimurium (Perest al., 1997). Later, Gurgel et al. (2005) reported in vitro antifun-al activity of Sangre de Drago from Croton urucurana, whichould be due to the presence of catechins like gallocatechin andpigallocatechin. Antiviral properties of Croton’s sap have alsoeen evaluated. Extracts of Sangre de Drago have been reportedo have antiviral activity against influenza, parainfluenza, Her-es simplex viruses I and II, and Hepatitis A and B (Chen etl., 1994; Ubillas et al., 1994; Sidwell et al., 1994; Meza, 1999).P-303 from Croton’s sap is the most studied constituent for itsntiviral activity (Wyde et al., 1991, 1993; Barnard et al., 1992;oike et al., 1992; Gilbert et al., 1993). SP-303 has shown initro activity against Herpes simplex viruses (HSV-1 and HSV-), inhibition of thymidine kinase mutants of the viruses, andronounced activity against acyclovir-resistant strains (Barnardt al., 1993; Safrin et al., 1993; Ubillas et al., 1994). Clini-
al studies of SP-303 have also been done on AIDS patientsOrozco-Topete et al., 1997). Sethi (1977) reported taspine tonhibit reverse transcriptase enzyme in cultures of several tumoriruses.

364 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361–380

Table 1Botanical sources and common names of Dragon’s blood

Species Plant family Geographical origin Vernacular names

Croton spp. Euphorbiaceae Tropics and subtropicsworldwide

Sangre de draco (Venezuela), Dragon’s bloodCroton, Arleiia, Ian huiqui (Ecuador), Yawargradwascca (Peru), Sangre de Drago/Grado

Croton draco Schltdl. & Cham.Croton lechleri Mull. Arg.Croton draconoides Mull. Arg.Croton urucurana Baill.C. xalapensis KunthCroton gossypifolium VahlCroton erythrochilus Mull. Arg.Croton palanostigma Klotzsch

Daemonorops spp. Palmaceae South East Asia Jerang or Djerang (Indonesia), Longxuejie(China), Draconis Resina and Sanguisdraconis (Sumatra), Kirin-kakketsu (Japan)

Daemonorops draco (Willd) BlumeD. didymophylla Becc.D. micracantha (Griff.) Becc.D. motleyi Becc.D. rubra (Reinw. ex Blume) BlumeD. propinqua Becc.

Dracaena spp. Dracaenaceae Socotra, Canary Islands,Madeira, East Africa

Zanzibar drop

D. cinnabari Balf. f.D. cochinchinensis (Lour.) S.C. ChenDracaena draco (L.) L.

Pterocarpus spp. Fabaceae West Indies and SouthAmerica

East India kino, Malabar kino, Kino gum,Guadaloupe Dragon’s blood, Padauk

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.1.2.2. Antitumor and cytotoxic activity. There are variouseports showing Sangre de Drago (Croton) to exhibit cytotox-city. Guerrero and Guzman (2004) carried out brine shrimpethality test (BSLT) to check the cytotoxicity of Croton lechleri.roton lechleri sap has been reported to be used for treatment ofancer by many researchers (Hartwell, 1969; Pieters et al., 1992;ai et al., 1993a,b). Recently, Gonzales and Valerio (2006) have

eviewed Croton lechleri for its anticancer activity.A number of compounds isolated from Sangre de Drago

Croton) are found to show cytotoxicity. Taspine from Crotonechleri sap has shown potent activity against KB and V-79 cells,hile flavan-3-ols and proanthocyanidins, which are the major

omponents of the sap, are not cytotoxic (Itokawa et al., 1991;hen et al., 1994). Compound 3′, 4-O-dirnethylcedrusin fromroton spp. was found not to stimulate cell proliferation, but

ather protected cells against degradation in a starvation mediumPieters et al., 1993). Chen et al. (1994) proposed that antitu-or activity of Croton’s sap might be because of mechanisms

ther than cytotoxicity such as immunostimulation. Antiprolif-rative effect of latex of Croton lechleri was also determinedn vitro on the human myelogenous leukemia K562 cells lineRossi et al., 2003). Peres et al. (1997) have reported use of
roton urucurana against cancer. Croton draco is also used to
reat cancer (Gupta et al., 1996). Latex of Croton draconoidesnd Croton erythrochilus are also reported to be used againstancer (Piacente et al., 1998). Sandoval et al. (2002) evalu-

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ted the effects of Sangre de Drago (Croton palanostigma) onuman cancer cells, AGS (stomach), HT29 and T84 (colon) andeported induction of apoptosis, and microtubular damages inhese cell lines.

.1.2.3. Antihemorrhagic activity. Castro et al. (1999) investi-ated the activity of organic extracts of Croton draco againstemorrhagic activity induced by the venom of the snake Both-ops asper. Total inhibition of hemorrhage was observed,robably owing to the chelation of zinc required for the catalyticctivity of venom’s hemorrhagic metalloproteinases. Aqueousxtracts of Croton urucurana antagonized the hemorrhagicctivity of the venom of Bothrops jararaca and proantho-yanidins were involved in this activity (Esmeraldino et al.,005).

.1.2.4. Immunomodulatory activity. The human immuneesponse is a highly complex system involving both innate anddaptive mechanisms. A biological or pharmacological effectf compounds on humoral or cellular aspects of the immuneesponse is referred as immunomodulating activity. Risco etl. (2003) determined immunomodulatory activity of Sangre de
rago from Croton lechleri in vitro and found that it exhibited aotent inhibitory activity on classical (CP) and alternative (AP)athways of complement system and inhibited the proliferationf activated T-cells.

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Tsacheva et al. (2004) evaluated latex of Croton draco, itsxtracts and several latex components (flavonoid myricitrin, thelkaloid taspine and the cyclopeptides P1 and P2) for their influ-nce on both CP and AP activation pathways of the complementystem using a hemolytic assay and the best inhibition was foundor the classical pathway.

.1.2.5. Antiulcer and antidiarrhoeal activity. There areeports showing potent antiulcer and antidiarrhoeal activity ofangre de Drago (Croton). The extracts from Croton speciesave been shown to impair the capsaicin-stimulated ion trans-

tsre

Fig. 1. Structure of some of the compounds reporte

macology 115 (2008) 361–380 365

ort across guinea pig ileum when added to the serosal bathn Ussing chambers and thus may prove to be a cost-effectivereatment for gastrointestinal ulcers (Miller et al., 2000). Use ofatex of Croton lechleri has also been reported in the treatmentf different types of diarrhoea (Ubillas et al., 1994; Carlsonnd King, 2000). SP-303, a heterogeneous proanthocyanidinligomer of Croton lechleri was found to inhibit in vivo cholera
oxin-induced fluid secretion and in vitro cAMP-mediated Cl−ecretion and thus may provide a useful broad-spectrum antidiar-hoeal agent (Gabriel et al., 1999). Evaluation of safety andfficacy of orally administered SP-303 was done for the symp-
d from different sources of Dragon’s bloods.


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omatic treatment of diarrhoea in travelers (DiCesare et al.,002) and in AIDS patients (Holodniy et al., 1999; Koch et al.,999; Koch, 2000). Fischer et al. (2004) derived a novel extractB-300 from Croton lechleri that inhibited cAMP-regulatedhloride secretion, mediated by the cystic fibrosis transmem-rane conductance regulator Cl− channel (CFTR) in humanolonic T84 cells and may prove to be a potent antidiarrhoealgent. Rozhon et al. (1998) have a patent on the use of proan-hocyanidin polymer from Croton species as an antidiarrhoeal,hich was issued to Shaman Pharmaceuticals, Inc. USA. The

ompany has products based on extract from Croton lech-eri sap in the market, named as NSF and NSF-1B, claimingclinically demonstrated relief from diarrhoea that won’t causeonstipation.”

Gurgel et al. (2001) evaluated antidiarrhoeal activity ofed sap obtained from Croton urucurana on castor oil-nduced diarrhoea in rats, cholera toxin-induced intestinal
ecretion in mice and on small intestinal transit in micend suggested potential utility of the red sap from Cro-on urucurana in controlling secretory diarrhoea associatediseases.
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inued )

.1.2.6. Analgesic activity. Peres et al. (1998a) isolated severalompounds showing analgesic activity, namely campesterol,itosterol, stigmasterol, acetyl aleuritolic acid, catechin, gallo-atechin and sitosterol glucoside from Croton urucurana anduggested existence of more potent analgesic compounds orxistence of a synergistic effect.

.1.2.7. Antioxidative activity. Desmarchelier et al. (1997) sug-ested that Sangre de Drago (Croton lechleri) is highly effectiven scavenging peroxyl and hydroxyl radicals at high concen-rations. However, prooxidant activity was observed at loweroncentrations. When administered to mice subcutaneously,atex of Peruvian Croton lechleri inhibited hepatic lipid peroxi-ation but only at concentration of 200 mg/kg in the livers of thenimals; higher concentrations showed toxicity (Desmarcheliernd de Moraes Barros, 2003).

Later, Risco et al. (2003) reported that depending upon
he concentration, latex of Croton lechleri showed antioxi-ant or prooxidant properties, and stimulated or inhibited thehagocytosis. Lopes et al. (2004) also evaluated antioxidantctivity of Croton lechleri sap against the yeast Saccha-

D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361–380 367

(Cont

rtfap

2

Fig. 1.

omyces cerevisiae and against maize plantlets treated with
he oxidative agents, apomorphine and hydrogen peroxide andound that sap inhibited the cytotoxic effect of the alkaloidpomorphine in haploid yeast cultures as well as in maizelantlets.
PaMC

inued )

.1.2.8. Anti-inflammatory activity. In a study on edema in rats,
erdue et al. (1979) reported, for the first time, anti-inflammatoryctivity of alkaloid taspine isolated from Croton latex. Later,iller et al. (2001) concluded from a series of studies that theroton sap inhibits neurogenic inflammation by directly block-


Fig. 1. (Continued )


Conti

iase

2ai2s

(smaff

Fig. 1. (

ng sensory afferent nerve activation at both the prejunctionalnd postjunctional level. The latex from Croton lechleri hastrong anti-inflammatory activity when administered i.p. (Riscot al., 2003).

.1.2.9. Mutagenic and antimutagenic activity. The mutagenic
nd antimutagenic activity of Croton lechieri sap was exam-ned through the Ames/Salmonella test and no mutagenicity of-aminoanthracene was found in the Salmonella typhimuriumtrains T98 and T100 (Rossi et al., 2003). Later, Lopes et al.
2c2

nued ).

2004) reported mutagenic activity of Croton lechieri sap fortrain TA1535 of Salmonella typhimurium in the presence ofetabolic activation, a weak mutagenic activity for strain TA98

nd in a haploid Saccharomyces cerevisiae strain XV185-14cor the lys1-1, his1-7 locus-specific reversion and hom3-10rameshift mutations.

.1.2.10. Wound healing activity. Sangre de Drago (Croton) isommonly used as liquid bandage in the Amazon (Jones, 1995,003). Vaisberg et al. (1989) reported a significant increase


Table 2Chemical constituents reported from Croton spp.

Compound name Bioactivity References

Croton draco Schltdl. & Cham.1-Hydroxyjunenol; 2,3-dihydrovomifoliol; 3,4,5-tri

methoxycinnamyl alcohol; 9(11)-dehydrokaurenicacid; 9-dehydrovomifoliol; hardwikiic acid;p-hydroxybenzal-dehyde; p-methoxybenzoic acid;scopoletin; taspine (1)

Murillo et al. (2001)

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

1998b)Acetyl aleuritolic acid Antibacterial activity, Analgesic

activityPeres 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 lechleri Mull. Arg.Taspine (1) Anti-inflammatory activity, wound

healing activity, cytotoxic activityPerdue 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 ofcell 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 acidmethyl ester; benzofuran-5-yl,2-3-dihydro:2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-3-methoxy-carbonyl-propen-1-oic acid methylester

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, antibacterialactivity

2,4,6-Trimethoxyphenol Antibacterial activity3,4-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-methybutylacetate; eucalyptol; 1-butyl acetate;3-methyl-2-pentanol

Bellesia et al. (1996)

oeal a

ittiiw

v4

Isoboldine (13); norisoboldine (12); magnoflorine (14)SB-300 (MW = 3000 Da) Antidiarrh

n the rate of wound repair on topical application of the Cro-on lechleri sap to skin wounds of mice and found taspine as
he cicatrizant (wound healing) principle. A significant increasen numbers of migrating cells in an in vitro test for wound-ng of human fibroblasts also suggested role of taspine foround healing (Vaisberg et al., 1989). From the sap of Peru-
lat1

Milanowski et al. (2002)ctivity Fischer et al. (2004)

ian Sangre de Drago (Croton sp.), a lignan known as 3′,-O-dimethylcedrusin was isolated which protected endothe-
ial cells from undergoing degradation in a starvation mediumnd stimulated endothelial cells, however at high concentra-ions it inhibited the cell proliferation (Pieters et al., 1992,993). Porras-Reyes et al. (1993) performed a number of tests

ophar

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o determine how taspine accelerated wound healing and foundhat taspine enhanced wound healing via increased fibroblast

igration.Chen et al. (1994) studied the wound healing activity of Cro-

on lechieri sap and concluded that several factors—the ability toorm a film that protects against microbial invasion of wounds;ree radical scavenging activity of procyanidins; the high contentf polyphenolics capable of binding proteins and enzymes; andhe anti-inflammatory and strong antibacterial action of polyphe-ols, together facilitating improved healing of damaged tissue,ay contribute to the wound repairing properties of sap. They

ested individual constituents of the sap and found endothelialell proliferation was increased by Procyanidin B-4 and mostotently by (−)-epigallocatechin and (+)-gallocatechin. Lewist al. (1992) has patented for taspine in DMSO (solvent), whichealed wounds faster than DMSO alone.

.2. Daemonorops spp.

Dragon’s blood resin is also obtained as deep red teardrop-haped lumps, separated physically from the immature fruit ofhe South-East Asian rattan- or cane-palm, Daemonorops ofhe Indonesian islands. The botanical source was previouslydentified as Calamus draco Willd. (Daemonorops draco Willd.lume) by Barry et al. (1926), who also described the resinous

ayer as being isolated by placing the fruits in sacks and poundinghem and the pulp being treated with boiling water. Subsequentlyhe resin was kneaded into balls or long sticks. Various gradesave been identified by Howes (1949). Other species as source ofesin are D. didymophylla Becc., D. micracantha (Griff.) Becc.,. motleyi Becc., D. rubra (Reinw. ex Blume) Blume and D.ropinqua Becc.

.2.1. Chemical constituentsTable 3 summarizes the compounds reported from resin of

aemonorops draco (Willd.) Blume.


.2.2.1. Antimicrobial and antiviral activity. Previously,itscher et al. (1972) reported in vitro activity of commercial

esin obtained from Daemonorops draco against Staphylococ-us aureus and Mycobacterium smegmatis. This led to furthervaluation of resin’s components exhibiting antimicrobialctivity. Rao et al. (1982) reported that the antimicrobialctivity of the resin from Daemonorops draco was due to theresence of compounds Dracorhodin and Dracorubin. Theseompounds were found to be active against Staphylococcusureus (ATCC 13709), Klebsiella pneumoniae (ATCC 10031),ycobacterium smegmafis (ATCC 607) and Candida albicans

ATCC 10231).

.2.2.2. Antitumor and cytotoxic activity. Dracorhodin per-hlorate, a synthetic analogue of Dracorhodin, red pigment
solated from exudates of the fruit of Daemonorops draco,as been reported to induce human melanoma A375-S2 cellnd human premyelocytic leukemia HL-60 cell death throughhe apoptotic pathway (Xia et al., 2005, 2006). M. Xia et al.
1aol

macology 115 (2008) 361–380 371

2004), M.Y. Xia et al. (2004), also studied the mechanismf Dracorhodin perchlorate induced apoptosis and concludedhat Dracorhodin perchlorate induced cell death via alterationf Bax/Bcl-XL ratio and activation of caspases.

.2.2.3. Hemostatic and antithrombotic activity. Daemonoropsraco has been studied for its ‘hemostatic’ and ‘vasoactive–ntithrombotic’ activity in Chinese medicinal system (Kiangsunstitute of Modern Medicine, 1977). Studies have providedvidences that (2S)-5-methoxy-6-methyl-flavan-7-ol (MMF)ossess antiplatelet activity (Tsai et al., 1995). Later, under-ying mechanism for antiplatelet activity of MMF was relatedo inhibition of thromboxane formation via the inhibition ofyclooxygenase and suppression of [Ca2+]i (intraplatelet Ca2+)ncrease (Tsai et al., 1998).

.3. Dracaena spp.

The name Dracaena is derived from the Greek worddrakainia’ meaning a female dragon (Stern, 1992). The mosttriking source is the Dracaena cinnabari Balf. f. which isndemic to the island of Socotra (Yemen) west of Somalia. Pal-nurus, a survey ship of Leut. J.R. Wellsted of the East Indiaompany gave first description of the Dragon’s blood tree, Dra-aena cinnabari, calling it Pterocarpus draco (http://www.rbg-eb2.rbge.org.uk/soqotra/history/page07.html) while under-

aking a survey of Socotra for the Indian Government in 1835.owever, the species was first named and described by the Scot-

ish botanist Sir lsaac Bailey Balfour when he visited the islandn 1880 (Balfour, 1888). Three grades of Dracaena resin weredentified by Balfour (1883), the most valuable being tear-liken appearance, followed by one made of small chips and frag-

ents, and the cheapest being a molten mixture of fragmentsnd refuse.

Voyagers to the Canary Islands in the 15th century obtainedragon’s blood as dried garnet colored drops from another

pecies Dracaena draco (L.) L., a native to the Canary Islandsnd Morocco. The canarian dragon tree Dracaena draco wasrst described in 1402 (Boutier and Le Verrier, 1872). The resin

s exuded from the wounded trunk or branches of the tree. Dra-aena cochinchinensis (Lour.) S.C. Chen is another species usedn China as source of Dragon’s blood.

.3.1. Chemical constituentsTable 4 summarizes the compounds reported from Dracaena

pp., used as source of Dragon’s blood.


.3.2.1. Antimicrobial and antiviral activity. Mothana andindequist (2005) reported antimicrobial activity of chloro-

orm and methanol extract of Dracaena cinnabari resin fromsland Soqotra against Staphylococcus aureus (ATCC 6538),acillus subtilis (ATCC 6059), Micrococcus flavus (SBUG
6) and Escherichia coli (ATCC 11229). Kumar et al. (2006)lso reported antimicrobial activity of exudes of red resinf Dracaena cinnabari collected from India against Bacil-us cereus var mycoides (ATCC 11778), Bacillus pumilus
http://www.rbg-web2.rbge.org.uk/soqotra/history/page07.html


Table 3Chemical constituents reported from Daemonorops draco (Willd.) Blume


Dracorhodin (17) Apoptic activity Brockmann and Junge (1943), Robertson andWhalley (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-methylflavanCardillo et al. (1971), Arnone et al. (1997)

Abietic acid; dehydroabietic acid; isopimaric acid; pimaricacid; 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 activityPoehland 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; D2Anti-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;

Ford et al. (2001)

4

(cSmP(Mev

ari1octra

2(fADccfa

3a1ltc10GDHttcDbft

2DsdLi

�-elemene; �-cadinene,6-Dihydroxy-2-methoxy-3-methyldihydrochalcone

ATCC 14884), Bacillus subtilis (ATCC 6633), Bordetella bron-hiseptica (ATCC 4617), Micrococcus luteus (ATCC 9341),taphylococcus aureus (ATCC 29737), Staphylococcus epider-idis (ATCC 12228), Klebsiella pneumoniae (ATCC 10031),seudomonas aeruginosa (ATCC 9027), Streptococcus faecalis

MTCC 8043), and Aspergillus niger (MTCC 1344). Recently,othana et al. (2006) also reported antiviral activity of methanol

xtract of resin of Dracaena cinnabari against Herpes simplexirus and Human influenza virus.

Thus, Dracaena resin could be a rich source of antimicrobialgents with possibly novel mechanisms of action. Interestingly,esin from Dracaena cochinchinensis has been produced bynfection with Fusarium and Cladosporium spp. (Wang et al.,999). In another study done by Jiang et al. (2003), inoculationf fungi Fusarium 9568D in abiotic branch and wood of Dra-aena cochinchinensis resulted in emergence of red resin fromhe inoculation points after 4–5 months incubation. The emergedesin was found to resemble the natural resin by UV-IR spectranalysis.

.3.2.2. Antitumor and cytotoxic activity. Vachalkova et al.1995) studied carcinogenicity of three homoisoflavanoids andour flavanoids isolated from the resin of Dracaena cinnabari.l-Fatimi et al. (2005) reported cytotoxic activity of resin ofracaena cinnabari from Yemen against human ECV-304

ells. Dracaena draco has been found to be a rich source ofytotoxic steroidal saponins. Darias et al. (1989) reported,or the first time, the use of sap of Dracaena draco as annticarcinogen. Steroidal saponins, (25R)-spirost-5-en-3�-ol

aitB

Shen et al. (2007)

-O-{O-�-l-rhamnopyranosyl-(1 → 2)-�-d-glucopyranoside}nd (23S,24S)-spirosta-5,25(27)-diene-1�,3�,23,24-tetrol-O-{O-2,3,4-tri-O-acetyl-�-l-rhamnopyranosyl-(1 → 2)-�--arabinopyranosyl}24-O-�-d-fucopyranoside, isolated fromhe aerial parts of Dracaena draco are reported to show potentytostatic activity against HL-60 cells with IC50 value being.3 and 2.6 �g/ml, respectively compared with etoposide (IC50.3 �g/ml) used as a positive control (Mimaki et al., 1999).onzalez et al. (2003) also reported new steroidal saponins,raconin A and Draconin B with cytotoxic activities againstL-60 cells from bark of Dracaena draco. The mechanism of

hese compounds’ cytotoxicity was also evaluated and foundo be via activation of apoptotic process. Recently a newytotoxic steroidal saponin, Icogenin, has been isolated fromracaena draco. Icogenin also inhibited growth of HL-60 cellsy induction of apoptosis (Hernandez et al., 2004). Dioscin,rom Dracaena draco also displayed cytotoxic activity similaro Icogenin.

.3.2.3. Analgesic activity. Liu et al. (2004) observed that bothragon’s blood resin (D. cochichinensis) and loureirin B could

uppress TTX-S voltage-gated sodium currents depending uponose, which could be reason for its analgesic effect. Later,iu et al. (2005) studied the effects of Dragon’s blood and

ts component loureirin B on tetrodotoxin-sensitive (TTX-S)
nd tetrodotoxin-resistant (TTX-R) sodium currents in trigem-nal ganglion (TG) neurons using the whole-cell patch-clampechnique and found that both Dragon’s blood and loureirin
suppressed two types of peak sodium currents depending


Table 4Chemical constituents reported from Dracaena spp.


Dracaena cinnabari Balf. 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

effectsGonzalez et al. (2000), Forejtnıkova 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. ChenLoureirin 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 etal. (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)


Table 4 (Continued )


25(R,S)-Dracaenosides E–H; M; O–Q; dracaenosidesI–L; R; 25(S)-dracaenoside N;25(R,S)-spirost-5-en-3-ol3-O-�-l-rhamnopyranosyl-(1,2)-[�-l-rhamnopyranosyl-(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-glucopyranosyl25(R,S)-furost-5-en-3,22�,26-triol3-O-�-l-rhamnopyranosyl-(1,2)-[�-d-glucopyranosyl(1,3)]-�-d-glucopyranoside; 26-O-�-d-glucopyranosyl25(R,S)-spirost-5-en-3,22�,26-triol3-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-dihydroxydracaenoneC; 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-(1 → 6)-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-methylflavanCamarda 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-(1 → 2)-�-l-arabinopyranoside}(45);(23S)-spirost-5,25(27)-diene-1�,3�,23-triol1-O-{O-�-l-rhamnopyranosyl-(1 → 2)-�-l-arabinopyranoside}(46);(23S,24S)-spirosta-5,25(27)-diene-1�,3�,23,24-tetrol1-O-{O-(4-O-acetyl-�-l-rhamnopyranosyl)-(1 → 2)-�-l-arabinopyranoside} (47);(23S,24S)-spirosta-5,25(27)-diene-1�,3�,23,24-tetrol1-O-{O-2,3,4-tri-O-acetyl-�-l-rhamnopyranosyl-(1 → 2)-�-l-arabinopyranosyl}24-O-�-d-fucopyranoside (48); (25R)-spirost-5-en-3�-ol3-O-{O-�-l-rhamnopyranosyl-(1 → 2)-�-d-glucopyranoside} (33);spirost-5,25(27)-diene-1�,3�-diol1-O-{O-�-l-rhamnopyranosyl-(1 → 2)-�-l-arabinopyranoside}(34);(23S)-spirost-5,25(27)-diene-1�,3�,23-triol1-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-tetrol1-O-{O-�-l-rhamnopyranosyl-(l → 2)-O-�-l-arabinopyranoside}(36)

Cytostatic activity Mimaki et al. (1999)

(23S,24S)-Spirosta-5,25(27)-diene-1�,3�,23,24-tetrol1-O-{O-�-l-rhamnopyranosyl}-(1 → 2)-�-l-arabinopyranoside}(43)

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


Table 4 (Continued )


(2S)-4′,7-Dihydroxy-8-methylflavan; 3-(4-hydroxybenzyl)-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-methylendioxychromanGonzalez 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), Forejtnıkova 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)

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umber given in parentheses corresponds to the structure of that compound giv

pon dose. Further, Liu et al. (2006) explored the materialasis for efficacy of modulation of Dragon’s blood on theetrodotoxin-resistant (TTX-R) sodium currents in dorsal rootanglion (DRG) neurons. They suggested that analgesic effectf Dragon’s blood may be explained on the basis of interfer-nce with pain messages caused by the modulation of Dragon’slood on TTX-R sodium currents in DRG neurons and could beue to the synergistic effect of three components cochinchinenin, cochinchinenin B, and loureirin B. Recently, Chen and Liu

2006) carried out a computer simulation research for the effectsf Dragon’s blood and its component loureirin B on sodiumhannel in dorsal root ganglion cells.

.3.2.4. Antioxidative activity. Juranek et al. (1993) haveeported antioxidant activity of three homoisoflavans isolatedrom resin of Dracaena cinnabari. Machala et al. (2001) studiedomoisoflavonoids and chalcones, isolated from the Dracaenainnabari, for their potential to inhibit cytochrome P4501ACYP1A) enzymes and Fe (II)/NADPH dependent in vitroeroxidation of microsomal lipids isolated from C57B1/10ouse liver and found chalcones were poor antioxidantshile 7,8-methylenedioxy-3 (4-hydroxybenzyl) chromane, aomoisoflavonoid, exhibited a strong antioxidant activity.

.4. Pterocarpus spp.

Pterocarpus officinalis Jacq., previously known as Pterocar-
us draco L., is the only species known as a source of Dragon’slood. According to a description in the Bulletin of the Botani-al Department, Jamaica, No. 45, July, 1893, when an incisions made in the bark, drops of red sap ooze out, flow slowly down
br

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Melo et al. (2006)Hernandez et al. (2006)

Fig. 1.

he bark and gradually harden. No major studies have been donen this source of Dragon’s blood. Trimble (1895), studied resinrom Pterocarpus draco L. and obtained 34.85% tannins fromhis resin.

. Quality control and safety

Since Dragon’s blood, as a name, has been applied to resinsbtained from different species from different continents; theres a great need to identify them apart. There are other substi-utes as well, which are available in the market for Dragon’slood such as Eucalyptus resinifera Sm. (Edwards et al., 2001).powdered dark red coral from the Indian Ocean is also sold in

emeni markets as “Dragon’s blood”. Glasgow’s Professor ofhemistry, J. Dobbie and G. Henderson first tackled the issuef chemical identification of the various resins under the namef Dragon’s blood in 1883, on request of Prof. Bayley BalfourPearson, 2002). They reported, “the resins known as Dragon’slood differ widely from one another, not only in their degree ofurity, but also in their appearance” and that “specimens labeleds having come from the same locality must, in reality, in someases, have been derived from very different sources” (Dobbiend Henderson, 1883). Dobbie and Henderson (1884) arrangeded resins in four distinct groups: 1. Those soluble in chloroform,arbon disulphide, and benzene completely; 2. Those soluble inhloroform, but insoluble in carbon disulphide and benzene;. Those soluble in chloroform and benzene and partly in car-
on disulphide; and 4. Those, which are insoluble in all threeeagents.
Edwards et al. (1997) described Dragon’s blood resin (Dra-aena spp.) found on Socotra Island as the probable genuine

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ource in antiquity, on the basis of Fourier transform Ramanpectroscopic studies of several resins generically known asragon’s blood from different botanical and geographical

ources. They have since described a Raman spectroscopicethod to identify fake and unknown Dragon’s blood resins

rom different botanical origins (Edwards et al., 2001, 2004).ll Dracaena spectra show the strong bands in the wave num-er region 1605–1500 cm−1 and can be generally identified byhe strongest band at 1605 cm−1, the shoulder at ca. 1560 cm−1.owever, specimen degradation can be recognized by the lossf this shoulder at 1560 cm−1. Also, vibrational bands near170 cm−1 seen in the Dracaena draco spectra could be used asiomarkers for Dracaena species. The main feature distinguish-ng Daemonorops Dragon’s blood resins from those of Dracaenas the presence of the narrow and intense band at 1600 cm−1, theoublets at 1510–1540 cm−1 and 1420–1450 cm−1 region andlso the medium intensity band at 1001 cm−1. Croton speci-en is distinguished by a broad band at 1612 cm−1, and also by

he medium intensity band at 784 cm−1. Later, Edwards et al.2004) identified the key molecular biomarker bands of Dragon’slood in the region 1400–1700 cm−1, which could be adopteds a protocol for the identification of the botanical and possibleeographical sources of modern Dragon’s blood resins.

No major toxicity has been reported from Dragon’s blood.he American Herbal Products Association (1997) lists San-re de Drago (Croton) as Class I, meaning it can be consumedafely when used appropriately. There are some instances whenragon’s blood has been misrepresented as ‘opium’ and dis-

ributed for use as a ‘drug’. Ford et al. (2001) had identified aed substance as Dragon’s blood incense from Daemonoropsraco that was being mixed with marijuana and smoked asn alternative to opium in Virginia. They also screened theubstance for toxicity in various in vitro tests and suggestedhat that the abuse potential for Dragon’s blood incenses is

inimal.

. Conservation needs

Dragon’s blood is used in traditional medicine for diversepplications. Overexploitation of sources of Dragon’s bloods a matter of concern as is the case of Croton lechleri, ineru and Ecuador. Because of the overexploitation and trade,

t was identified as potentially threatened amongst the 22pecies in the Workshop of Specialists in Ethnobotany andconomic Botany held in 1997 (http://www.traffic.org/ecuador/xecutivesummary.html). Dracaena cinnabari was also listeds vulnerable in the IUCN red list of threatened species (Miller,004). Dracaena draco was reported as vulnerable species on theanary Islands due to overexploitation of the trees for Dragon’slood in the middle ages (Lucas and Synge, 1978). It was alsoited in IUCN Red List of Threatened Species (2006). Predom-
nantly, resin of Daemonorops draco is the principal source ofommercially harvested Dragon’s blood. Plant cell, tissue andrgan culture could be an alternative approach for economic pro-uction of Dragon’s blood plants and the secondary metaboliteshey produce.
A

B

rmacology 115 (2008) 361–380

. Conclusion

Although Dragon’s blood has proved to be popular alter-ative or complementary medicine used in the treatmentf many diseases, clinical trial evaluation of these claimssing currently accepted protocols is needed. One suchotential new drug for AIDS-related diarrhoea is, “Cro-elemer” developed originally by Shaman Pharmaceuticalsrom Croton lechleri. Since 2001, “Crofelemer” has beenurchased by the American pharmaceutical company, Napoharmaceuticals and is currently undergoing clinical trialshttp://www.aumag.org/lifeguide/WWSeptember05.html,ttp://www.botanical.com/botanical/mgmh/d/dragon20.html,ttp://www.drugs.com/npp/dragon-s-blood.html#ref3).

This resin offers huge potential and we need to investi-ate whether purified compounds isolated from Dragon’s blooday have better therapeutic potential as compared to crude

xtract. Since there is considerable variation in the chemicalomposition among various samples of Dragon’s Blood, qualityontrol/assurance needs to be established for the traditional med-cal trade. This review is an effort to highlight the potential androblems related to the sources and possibilities of isolating newharmaceutically active molecules, using traditional knowledgen our search, for new and effective dugs molecules.

cknowledgements

We are grateful to Prof. Ulrike Lindequist, Institute ofharmacy, Ernst-Moritz-Arndt-University, Germany for her

horough revision of this review and providing us with her invalu-ble suggestions. We acknowledge the financial support fromICTE (8023/RID/NPROJ/RPS-38/2004-05).

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