Sangre de Grado 19 Setie2014
Transcript of Sangre de Grado 19 Setie2014
-
8/10/2019 Sangre de Grado 19 Setie2014
1/20
-
8/10/2019 Sangre de Grado 19 Setie2014
2/20
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.
-
8/10/2019 Sangre de Grado 19 Setie2014
3/20
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.
-
8/10/2019 Sangre de Grado 19 Setie2014
4/20
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.
-
8/10/2019 Sangre de Grado 19 Setie2014
5/20
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.
-
8/10/2019 Sangre de Grado 19 Setie2014
6/20
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-
-
8/10/2019 Sangre de Grado 19 Setie2014
7/20
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-
-
8/10/2019 Sangre de Grado 19 Setie2014
8/20
368 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380
Fig. 1. (Continued)
-
8/10/2019 Sangre de Grado 19 Setie2014
9/20
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
-
8/10/2019 Sangre de Grado 19 Setie2014
10/20
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
-
8/10/2019 Sangre de Grado 19 Setie2014
11/20
D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 371
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 -
8/10/2019 Sangre de Grado 19 Setie2014
12/20
372 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380
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
-
8/10/2019 Sangre de Grado 19 Setie2014
13/20
D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 373
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)
-
8/10/2019 Sangre de Grado 19 Setie2014
14/20
374 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380
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)
-
8/10/2019 Sangre de Grado 19 Setie2014
15/20
D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 375
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
-
8/10/2019 Sangre de Grado 19 Setie2014
16/20
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).
References
Achenbach, H., Stocker, M., Constenla, M.A., 1988. Flavonoid and other con-
stituents ofBauhinia manca. Phytochemistry 27, 18351841.
Akihisa, T., Yasukawa, K., Oinuma, H., Kasahara, Y., Yamanouchi, S., Takido,
M., Kumaki, K., Tamura, T., 1996. Triterpene alcohols from the flow-
ers of compositae and their anti-inflammatory effects. Phytochemistry 43,
12551260.
Alexander, D., Miller, A., 1996. Saving the spectacular flora of Socotra. Plant
Talk 7, 1922.
Alexander, D., Miller, A., 1995. Socotras misty future. New Scientist 147, 32.
Al-Fatimi, M., Friedrich, U., Jenett-Siems, K., 2005. Cytotoxicity of plants usedin traditional medicine in Yemen. Fitoterapia 76, 355358.
American Herbal Products Association, 1997. American Herbal Products Asso-
ciation Botanical Safety Handbook. CRC Press, Boca Raton, FL.
Angiosperm Phylogeny Group, 1974. Annals of the Missouri Botanical Garden
85, 531.
Arnone, A., Nasini, G., 1989. Constituents of Dragons blood: part III. Dracoox-
epine, a novel type of biflavanoid. Heterocycles 29, 11191125.
Arnone, A., Nasini, G., 1990. Constituents of Dragons blood: part IV. Dra-
coflavanA, a novel secotriflavanoid.Journal of the Chemical Society. Perkin
Transactions I, 26372640.
Arnone, A., Nasini, G., Vajnade Pava, O., 1997. Constituents of Dragons blood.
5. Dracoflavans B1, B2, C1, C2, D1, and D2, new A-type deoxyproantho-
cyanidins. Journal of Natural Products 60, 971975.
Badib, A.S., 1991. Medicinal Plants of the Yemen. Maktabah Alirsaid, Sanaa,
p. 15.
http://www.traffic.org/ecuador/executivesummary.htmlhttp://www.traffic.org/ecuador/executivesummary.htmlhttp://www.aumag.org/lifeguide/WWSeptember05.htmlhttp://www.botanical.com/botanical/mgmh/d/dragon20.htmlhttp://www.drugs.com/npp/dragon-s-blood.html%23ref3http://www.drugs.com/npp/dragon-s-blood.html%23ref3http://www.botanical.com/botanical/mgmh/d/dragon20.htmlhttp://www.aumag.org/lifeguide/WWSeptember05.htmlhttp://www.traffic.org/ecuador/executivesummary.htmlhttp://www.traffic.org/ecuador/executivesummary.html -
8/10/2019 Sangre de Grado 19 Setie2014
17/20
D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 377
Balfour, I.B., 1883. The Dragon Blood Tree of Socotra, vol. 30. Translation
Royal Society, Edinburgh, pp. 619623.
Balfour, I.B., 1888. Botany of Socotra, vol. 31. Translation Royal Society,
Edinburgh, pp. 1446.
Barnard, D.L., Huffman, J.H., Nelson, R.M., Morris, J.L.B., Gessaman, A.C.,
Sidwell, R.W., Meyerson, L.R., 1992. Mode of action of SP-303 against
respiratory syncytial virus (RSV). Antiviral Research, 91.
Barnard, D.L., Smeem, D.F., Huffman, J.H., Meyerson, L.R., Sidwell, R.W.,
1993. Antiherpesvirus activity and mode of action of SP-303, a novel plantflavonoid. Chemotherapy 39, 203211.
Barry, Hedley, Drummond, Morrell, 1926. Natural and Synthetic Resins, p.
83-89.
Bellesia, F.F., Pinetti, A.A., Tirillini, B.B., 1996. Headspace analysis ofCroton
lechleriL. sap. Journal of Essential Oil Research 8, 435437.
Bensky, D., Gamble, A., 1993. Chinese Herbal Medicine: Materia Medica,
China.
Bettolo, R.M., Scarpati, M.L., 1979. Alkaloids ofCroton draconoides. Phyto-
chemistry 18, 520.
Bianchini, J.P., Gaydou, E.M., Rafaralahitsimba, G., Waegell, B., Zahra, J.P.,
1988. Dammarane derivatives in the fruit lipids ofOlea madagascariensis.
Phytochemistry 27, 23012304.
Boutier, P., Le Verrier, J., 1872. The Canarian, or Book of the Conquest and
Conversion of the Canarians in the Year 1402, by Jean de Bethencourt, vol.
46. Hakluyt Society Publications, London.Braz, F.R., Diaz, P.P., Gottlieb, O.R., 1980. Tetronic acid and diarylpropanes
fromIryanthera elliptica. Phytochemistry 19, 455459.
Brockmann, H., Junge, H., 1943. Constitution of dracorhodin, a new pigment
from dragons blood. Berichte der Deutschen Chemischen Gesellschaft
76, 751763.
Cai, X.T., Xu,Z.F., 1979. Studies on theplantorigin of Chinese Dragonsblood.
Acta Botanica Yunnanica 1, 19.
Cai, Y., Chen, Z.P., Phillipson, J.D., 1993a. Diterpenes from Croton lechleri.
Phytochemistry 32, 755760.
Cai, Y., Evans, J., Roberts, M.F., Phillipson, J.D., Zenk, M.H., Gleba, Y.Y.,
1991. Polyphenolic compounds from Croton lechleri. Phytochemistry 30,
20332040.
Cai, Y., Chen, Z.P., Phillipson, J.D., 1993b. Clerodane diterpenoids from Croton
lechleri. Phytochemistry 34, 265268.
Camarda, L., Merlini, L., Nasini, G., 1983. Dragons blood from Dracaena
draco, structure of novel homoisoflavonoid. Heterocycles 20, 3943.
Cardillo,G., Merlini,L., Nasini, G.,Salvadori, P., 1971. Constituentsof Dragons
Blood: part I. Structure and absolute configuration of new optically active
flavans. Journal of Chemical Society C, 39673970.
Carlson, T.J.S., King, S.R., 2000. Sangre de Drago (Croton lechleri Muell.-
Arg.)A phytomedicine for the treatment of diarrhoea. Health Notes:
Review of Complementary and Integrative Medicine 7, 315320.
Castner, J.L., Timme, S.L., Duke, J.A., 1998. A Field Guide to Medicinal and
Useful Plants of the Upper Amazon. Feline Press, Gainesville, FL, p. 46.
Castro,O., Gutierrez,J.M.,Barrios,M., Castro, I., Romero,M., Umana, E., 1999.
Neutralization of the hemorrhagic effect induced by Bothrops asper(Ser-
pentes: Viperidae) venom with tropical plant extracts. Revista de Biolog a
Tropical 47, 605616.
Chen, S., Liu, X., 2006. A computer simulation research for the effects of
Dragons blood and its component loureirin B on sodium channel in dor-
sal root ganglion cells. Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 23,
11721176.
Chen, Z.P., Cai, Y., Phillipson, J.D., 1994. Studies on the anti-tumor, anti-
bacterial, and wound-healing properties of Dragons blood. Planta Medica
60, 541545.
Cobo, P.B., 1956. In: Mateos, P.F. (Ed.), Biblioteca de Autores Espanoles
(Series), vols. 91/92. Atlas, Madrid.
Craveiro, A., Silveira, E.R., 1982. 2 Cleistanthane type diterpenes fromCroton
sonderianus. Phytochemistry 21, 25712574.
Darias, V., Bravo, L., Rabanal, R., SanchezMateo, C., GonzalezLuis, R.M.,Her-
nandez Perez, A.M., 1989. New contribution to the ethnopharmacological
study of the Canary Islands. Journal of Ethnopharmacology 25, 7792.
Deepika, G., Gupta, R.K., 2007. Chemical investigation ofDracaena cinnabari
resin in India. Unpublished report.
Desmarchelier, C., Witting Schaus, F., Coussio, I., Cicca, G., 1997. Effects of
Sangre de Drago from Croton lechleri Muell. Arg. on the production of
active oxygen radicals. Journal of Ethnopharmacology 58, 103108.
Desmarchelier, C.J., de Moraes Barros, S.B., 2003. Pharmacological activity of
South American plants: effects on spontaneous in vivolipid peroxidation.
Phytotherapy Research 17, 8082.
DiCesare,D., DuPont,H.L., Mathewson, J.J.,Ashely, D., Martinez-Sandoval, F.,
Pennington, J.E., Porter, S.B., 2002. A double blind, randomized, placebo-
controlled study of SP-303 (Provir) in the symptomatic treatment of acutediarrhoea among travelers to Jamaica and Mexico. American Journal of
Gastroenterology 97, 25852588.
Dobbie, J.J., Henderson, G.G., 1883. The Classification and Properties of red
Resins Known Under the Name of Dragons Blood. W.L. Richardson, Lon-
don.
Dobbie, J.J., Henderson, G.G., 1884. Red resins known as Dragons Blood.
American Journal of Pharmacy 56, 4.
Duke, J., Vasquez, R., 1994. Amazonian Ethnobotanical Dictionary. CRC, Boca
Raton, FL.
Edwards, H.G.M., de Oliveira, L.F., Prendergast, H.D., 2004. Raman spectro-
scopic analysis of Dragons blood resins-basis for distinguishing between
Dracaena (Convallariaceae),Daemonorops(Palmae) and Croton (Euphor-
biaceae). Analyst 129, 134138.
Edwards, H.G.M., de Oliveira, L.F., Quye, A., 2001. Raman spectroscopy of
colored resins used in antiquity: Dragons blood and related substances.Spectrochimia Acta Part A: Molecular and Biomolecular Spectroscopy 57,
28312842.
Edwards, H.G.M., Farwell, D.W., Quye, A., 1997. Dragons blood
Icharacterization of an ancient resinusing Fourier transform Raman spec-
troscopy. Journal of Raman Spectroscopy 28, 243249.
Emboden,W.A., 1974. Bizarre Plants: Magical,Monstrous andMythical. Studio
Vista, London, pp. 98109.
Esmeraldino, L.E., Souza, A.M., Sampaio, S.V., 2005. Evaluation of the effect
of aqueous extract ofCroton urucurana Baillon (Euphorbiaceae) on the
hemorrhagic activity induced by the venom ofBothrops jararaca, using
new techniques to quantify hemorrhagic activity in rat skin. Phytomedicine
12, 570576.
Fischer, H., Machen, T.E., Widdicombe, J.H.,Carlson, T.J.S.,King, S.R., Chow,
J.W.S., Illek, B., 2004. A novel extract SB-300 from the stem bark latex of
Croton lechleri inhibitsCFTR-mediated chloridesecretionin human colonic
epithelial cells. Journal of Ethnopharmacology 93, 351357.
Ford, S.L., Steiner, R.R., Thiericke, R., Young, R., Soine, W.H., 2001. Dragons
Blood incense: misbranded as a drug of abuse? Forensic Science Interna-
tional 115, 18.
Forejtnkova, H., Lunerova, K., Kubnova, R., Jankovska, D., Marek, R., Kares,
R., Suchy, V., Vondracek, J., Machala, M., 2005. Chemoprotective and toxic
potentials of synthetic and natural chalcones and dihydrochalconesin vitro.
Toxicology 208, 8193.
Fulling, E.H., 1953. Dragons blood. Economic Botany 7, 227.
Gabriel, S.E., Davenport, S.E., Steagall, R.J., Vimal, V., Carlson, T., Rozhon,
E.R., 1999. A novel plant-derived inhibitor of cAMP-mediated fluid and
chloride secretion. American Journal of Physiology Gastrointestinal and
Liver Physiology 276, G58G63.
Gao, W.F., Zheng, H., Wang, Y.S., Zhang, Z.H., Lu, J.C., Zhang, S.F., 1989.
Synthesis of dracorhodin. Chinese Journal of Pharmaceuticals (Zhongguo
Yiyao Gongye Zazhi) 20, 247250.
Gerarde, J., Johnson, T. (Eds.), 1633. The Herbal or General History of Plants.
Reprinted by Dover Publications, New York (1975).
Gibbs, A., Green, C., Doctor, V.M., 1983. Isolation and anticoagulant prop-
erties of polysaccharides ofTypha augustata and Daemonorops species.
Thrombosis Research 32, 97108.
Gilbert, B.E., Wyde, P.R., Wilson, P.Z., Meyerson, L., 1993. SP-303 small par-
ticle aerosol treatment of influenza A virus infection in mice and respiratory
syncytial virus infection in cotton rats. Antiviral Research 21, 3745.
Gonzales, G.F., Valerio Jr., L.G., 2006. Medicinal plants from Peru: a review of
plants as potential agents against cancer. Anti-cancer Agents in Medicinal
Chemistry 6, 429444.
Gonzalez, A.G., Hernandez, J.C., Leon, F., Padron, J.I., Estevez, F., Quin-
tana, J., Bermejo, J., 2003. Steroidal saponins from the bark of Dracaena
-
8/10/2019 Sangre de Grado 19 Setie2014
18/20
378 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380
draco and their cytotoxic activities. Journal of Natural Products 66, 793
798.
Gonzalez, A.G., Leon, F., Hernandez, J.C., Padron, J.I., Sanchez-Pinto, L.,
Bermejo, J., 2004. Flavans of dragons blood from Dracaena draco and
Dracaena tamaranae. Biochemical Systematics and Ecology 32, 179184.
Gonzalez, A.G., Leon, F., Sanchez-Pinto, L., Padron, J.I., Bermejo, J., 2000.
Phenolic compounds of Dragons blood from Dracaena draco. Journal of
Natural Products 63, 12971299.
Guerrero, R.O., Guzman, A.L., 2004. Bioactivities of latexes from selectedtropical plants. Revista Cubana de Plantas Medicinales, 9.
Gupta, M.P., Monge, A., Karikas, G.A., Lopez De Cerain, A., Solis, P.N., De
Leon, E., Trujillo, M., Suarez, O., Wilson, F., 1996. Screening of Panama-
nian medicinal plants for brine shrimp toxicity, crown gall tumor inhibition,
cytotoxicityand DNAintercalation. International Journalof Pharmacognosy
34, 1927.
Gurgel, L.A., Sidrimb, J.J.C., Martinsc, D.T., Filhod, V.C., Rao, V.S., 2005.In
vitroantifungal activity of Dragons blood from Croton urucuranaagainst
dermatophytes. Journal of Ethnopharmacology 97, 409412.
Gurgel, L.A., Silva, R.M., Santos, F.A., Martins, D.T., Mattos, P.O., Rao, V.S.,
2001. Studies on the antidiarrhoeal effect of Dragons blood from Croton
urucurana. Phytotherapy Research 15, 319322.
Hartwell, J.L., 1969. Plants used against cancer. Lloydia 32, 158.
Hernandez, J.C., Leon, F., Estevez, F., Quintana, J., Bermejo, J., 2006. A homo-
isoflavonoid and a cytotoxic saponin fromDracaena draco. Chemistry andBiodiversity 3, 6268.
Hernandez, J.C., Leon,F.,Quintana, J., Estevez, F., Bermejo, J., 2004. Icogenin,
a newcytotoxic steroidalsaponinisolatedfromDracaena draco. Bioorganic
and Medicinal Chemistry 12, 44234429.
Himmelreich, U., Masaoud, M., Adam, G., Ripperger, H., 1995. Damalachawin,
a triflavonoid of a new structural type from Dragons blood of Dracaena
cinnabari. Phytochemistry 39, 949951.
Holodniy, M., Koch, J., Mistal, M., Schmidt, J.M., Khandwala, A., Pennington,
J.E., Porter, S.B., 1999. A double blind, randomized, placebo controlled
phase II study to assess the safety and efficacy of orally administered SP-
303for symptomatic treatmentof diarrhoeain patientswith AIDS.American
Journal of Gastroenterology 94, 32673273.
Howes, F.N., 1949. Vegetable Gums and Resins. Chronica Botanica Company,
Waltham, Mass. USA.
Hsu, H.Y., 1986. Oriental Materia Medica: A Concise Guide Pub. Oriental
Healing Arts Instit. of the United States.
Itokawa, H., Ichihara, Y., Mochizuka, M., Enomori, T., Morita, H., Shirota,
O., Inamatsu, M., Takeya, K., 1991. A cytotoxic substance from San-
gre de Grado. Chemical and Pharmaceutical Bulletin (Tokyo) 39, 1041
1042.
Jiang, D.F., Ma, P., Yang, J., Wang, X., Xu, K., Huang, Y., Chen, S., 2003.
Formation of blood resin in abiotic Dracaena cochinchinensis inocu-
lated with Fusarium 9568D. Ying Yong Sheng Tai Xue Bao 14, 477
478.
Jones, K., 1995. Cats Claw: Healing Vine of Peru. Sylvan, Seattle, WA.
Jones, K., 2003. Review of Sangre de Drago (Croton lechleri)A South Amer-
ican tree sap in the treatment of diarrhoea, inflammation, insect bites, viral
infections, and wounds: traditional uses to clinical research. The Journal of
Alternative and Complementary Medicine 9, 877896.
Juranek, I., Suchy, V., Stara,D.,Masterova,I., Grancaiova, Z., 1993. Antioxida-
tive activity of homoisoflavonoids from Muscari racemosumandDracaena
cinnabari. Pharmazie 48, 310311.
Kiangsu Institute of Modern Medicine, 1977. Encyclopedia of Chi-
nese Drugs. Shanghai Scientific and Technical Publications, Shanghai,
pp. 848851.
Koch, J., 2000. A phase III, double-blind,randomized, placebo controlled multi-
center study of SP-303 (ProvirTM) in the symptomatic treatmentof diarrhoea
in patients with acquired immunodeficiency syndrome (AIDS). In: Poster
Presented at 13th International AIDS Conference, Durban, South Africa,
July 14.
Koch, J., Tuveson, J., Carlson, T., Schmidt, J., 1999. A new therapy for HIV-
associated diarrhoeaimproves quality of life.In: Poster Presentedat Seventh
European Conference on Clinical Aspects and Treatment of HIV-Infection,
Lisbon, Portugal, October 2327.
Kumar, V.P., Chauhan, N.S., Padh, H., Rajani, M., 2006. Search for antibacte-
rial and antifungal agents from selected Indian medicinal plants. Journal of
Ethnopharmacology 107, 182188.
Lewis, W.H., Stonard, R.J., Porras-Reyes, B., Mustoe, T.A., 1992. Wound-
healing composition. US Patent 5156847, October 20.
Liu, X., Chen, S., Zhang, Y., Zhang, F., 2006. Modulation of Dragons blood on
tetrodotoxin-resistant sodium currents in dorsal root ganglion neurons and
identification of its material basis for efficacy. Science in China. Series C,
Life Sciences 49, 274285.Liu, X., Su, C., Shijin, Y., Zhinan, M.,2004. Effects of Dragonsblood resin and
its component loureirin B on tetrodotoxin-sensitive voltage-gated sodium
currents in rat dorsal root ganglion neurons. Science in China. Series C, Life
Sciences 47, 340348.
Liu, X., Yin, S., Chen, S., Ma, Q., 2005. Loureirin B: an effective component in
Dragons Blood modulating sodium currents in TG neurons. In: Conference
Proceedings: Annual International Conference of the IEEE Engineering in
Medicine and Biology Society, IEEE Engineering in Medicine and Biology
Society. Conference, vol. 5, pp. 49624965.
Lopes, M.I.L., Saffi, J., Echeverrigaray, S., Henriques, J.A.P., Salvador, M.,
2004. Mutagenic and antioxidant activities ofCroton lechlerisap in biolog-
ical systems. Journal of Ethnopharmacology 95, 437445.
Lu, W.J., Wang, X., Chen, J., Lu, Y., Wu, N., Kang, W., Zheng, Q., 1998.
Studies on the chemical constituents of chloroform extract of Dracaena
cochinchinensis . Yao Xue Xue Bao 33, 755758.Lucas,G.L.I., Synge,H., 1978.The IUCN PlantRed Data Book. IUCN, Morges,
Switzerland.
Lyons, G., 1974. In search of dragons or: the plant that roared. Cactus and
Succulent Journal 44, 267282.
Mabberley, D.J., 1998. The Plant Book. Cambridge University Press (rev. edn
1998).
Machala, M., Kubnova, R., Horavova, P., Suchy, V., 2001. Chemoprotective
potentials of homoisoflavonoids and chalcones of Dracaena cinnabari:
modulations of drug-metabolizing enzymes and antioxidant activity. Phy-
totherapy Research 15, 114118.
Masaoud, M., Himmelreich, H., Ripperger, H., Adam, G., 1995a. New
bioflavonoids fromDracaena cinnabari. Planta Medica 61, 341344.
Masaoud, M., Ripperger, H., Porzel, A., Adam, G., 1995b. Cinnabarone, a
bioflavonoid from Dragons blood ofDracaena cinnabari. Phytochemistry
38, 751753.
Masaoud, M., Ripperger, H., Porzel, A., Adam, G., 1995c. Flavonoids of
Dragons blood fromDracaena cinnabari. Phytochemistry 38, 745749.
Masaoud, M., Schmidt, J., Adam, G., 1995d. Sterols and triterpenoids from
Dracaena cinnabari. Phytochemistry 38, 795796.
Maxwel1, C.A., Hartwig, U.A., Joseph, C.M., Phillips, D.A., 1989. A chalcone
and two related flavonoids from alfalfa roots induce nod gene ofRhizobium
meliloti. Plant Physiology 91, 824847.
Meksuriyen, D., Cordell, G.A., 1988. Traditional medicinal plants of Thailand,
XIII. Flavonoid derivatives fromDracaena loureiri. Journal of the Science
Society of Thailand 14, 324.
Meksuriyen, D., Cordell, G.A., Ruangrungsi, N., Tantivatana, P., 1987.
Traditional medicinal plants of Thailand, IX. 10-Hydroxy-11-
methoxydracaenone and 7,10-Dihydroxy-11-methoxydracaenone
from Dracaena loureiri. Journal of Natural Products 50, 1118
1125.
Melo,M.J.,Sousa, M.,Parola,A.J.,de Melo,J.S.,Catarino, F., Marcalo,J., Pina,
F., 2006. Identificationof 7,4-Dihydroxy-5-methoxyflavylium in Dragons
Blood: to be or not to be an anthocyanin. Chemistry 13, 14171422.
Merlini, L., Nasini, G., 1976. Constituents of Dragons Blood: part II. Struc-
ture and oxidative conversion of novel secobiflavanoid. Journal of Chemical
Society. Perkin Transactions I, 15701576.
Meza, E.N. (Ed.), 1999. Desarrollando Nuestra Diversidad Biocultural: Sangre
de Grado yel Reto de su Produccion Sustentable en el Peru. Universidad
Nacional Mayor de San Marcos, Lima.
Milanowski, D.J., Winter, R.E., Elvin-Lewis, M.P., Lewis, W.H., 2002. Geo-
graphic distributionof three alkaloid chemotypes ofCroton lechleri. Journal
of Natural Products 65, 814819.
Milburn,M., 1984. Dragons Blood in East& WestAfrica, Arabia andthe Canary
Islands. Africa 39, 486493.
-
8/10/2019 Sangre de Grado 19 Setie2014
19/20
D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380 379
Miller, A., 2004. Dracaena cinnabari. In: IUCN 2006. 2006 IUCN Red List of
Threatened Species.
Miller, A.G., Morris, M., 1988. Plants of Dhofar the Southern Region of Oman,
Traditional, Economic and Medicinal Uses. The Office of the Adviser for
Conservationof the Environment, Diwan of Royal Court Sultanateof Oman.
Miller, M.J.S., MacNaughton, W.K., Zhang, X.J., Thompson, J.H., Charbonnet,
R.M., Bobrowski, P., Lao, J., Trentacosti, A.M., Sandoval, M., 2000. Treat-
ment of gastric ulcers and diarrhoea with the Amazonian herbal medicine
sangre de grado. American Journal of Physiology. Gastrointestinal and LiverPhysiology 279, G192G200.
Miller, M.J.S., Vergnolle, N., McKnight, W., Musah, R.A., Davison, C.A.,
Trentacosti, A.M., Thompson, J.H., Sandoval, M., Wallace, J.L., 2001. Inhi-
bition of neurogenic inflammation by the Amazonian herbal medicinesangre
de grado. The Journal of investigative dermatology 117, 725730.
Milner, J.E., 1992. The Tree Book. Colllns & Brown Ltd., London.
Milo, B., Risco, E., Vila, R., Iglesias, J., Canigueral, S., 2002. Characterization
of a Fucoarabinogalactan, the main polysaccharide from the gum exudate of
Croton urucurana. Journal of Natural Products 65, 11431146.
Mimaki, Y., Kuroda, M., Ide Atsushi Kameyama, A., Yokosuka, A., Sashida, Y.,
1999. Steroidal saponins from the aerial parts ofDracaena dracoand their
cytostatic activity on HL-60 cells. Phytochemistry 50, 805813.
Mitscher, L.A., Leu, R.P., Bathala, M.S., Wu, W.N., Beal, J.L., White, R.,
1972. Antimicrobial agents from higher plants. 1. Introduction, rationale
and methodology. Lloydia 35, 157166.Mothana, R.A.A., Lindequist, U., 2005. Antimicrobial activity of some medici-
nal plants of the island Soqotra. Journal of Ethnopharmacoloy 96, 177181.
Mothana, R.A.A., Mentel, R., Reiss, C., Lindequist, U., 2006. Phytochemical
screening and antiviral activity of some medicinal plants from the island
Soqotra. Phytotherapy Research 20, 298302.
Murillo, R.M., Jakupovic, J., Rivera, J., Castro, V.H., 2001. Diterpenes and
other constituents fromCroton draco(Euphorbiaceae). Revista de Biologa
Tropical 49, 259264.
Orozco-Topete, R., Sierra-Madero, J., Cano-Dominguez, C., Kershenovich,
J., Ortiz-Pedroza, G., Vazquez-Valls, E., Garcia-Cosio, C., Soria-Cordoba,
A., Armendariz, A.M., Teran-Toledo, X., Romo-Garcia, J., Fernandez, H.,
Rozhon, E.J., 1997. Safety and efficacy of Virend (R) for topical treatment
of genital and anal herpes simplex lesions in patients with AIDS. Antiviral
Research 35, 91103.
Pankow, D., 1988. Dungeons and Dragons Blood: the development of late 19th
and early 20th century platemaking processes. Journal of the American
Printing History Association 1, 2135.
Parkinson, J., 1640. Theatricum Botanlcum. London.
Pearson, J., 2002. Dragons blood. The Horticulturist 11, 1012.
Pearson, J., Prendergast, D.V., 2001. Collections corner: Daemondrops, Dra-
caenaand other Dragons Blood. Economic Botany 55, 474477.
Perdue, G.P., Blomster, R.N.,Blake, D.A.,Farnsworth, N.R.,1979. South Amer-
ican plants II: taspine isolation and anti-inflammatory activity. Journal of
Pharmaceutical Sciences 68, 124125.
Peres, M.T.L.P., Delle Monache, F., Cruz, A.B., Pizzolatti, M.G., Yunes, R.A.,
1997. Chemical composition and antimicrobialactivityofCrotonurucurana
Baillon (Euphorbiaceae). Journal of Ethnopharmacology 56, 223226.
Peres, M.T.L.P., Delle Monache, F., Pizzolatti, M.G., Santos, A.R.S., Beirith,
A., Calixto, J.B., Yunes, R.A., 1998a. Analgesic compounds of Croton
urucurana Baillon. Pharmacochemical criteria used in their isolation. Phy-
totherapy Research 12, 209211.
Peres, M.T.L.P., Pizzolatti, M.G.,Yunes, R.A.,Delle Monache,F., 1998b.Clero-
dane diterpenes ofCroton urucurana. Phytochemistry 49, 171174.
Phillipson, J.D., 1995. A matter of some sensitivity. Phytochemistry 38,
13191343.
Piacente,S., Belisario,M.A., DelCastillo, H., Pizza, C.,De Feo,V., 1998. Croton
ruizianus: platelet proaggregating activity of two new pregnane glycoides.
Journal of Natural Products 61, 318322.
Pieters, L., De Bruyne, T., Claeys, M., Vlietinck, A., Calomme, M., van den
Berghe, D., 1993. Isolationof a dihydrobenzofuranlignanfrom South Amer-
icanDragons blood (Croton spp.) as an inhibitor of cellproliferation. Journal
of Natural Products 56, 899906.
Pieters, L., De Bruyne, T., Mei, G., Lemiere, G., Vanden Berghe, D., Vlietinck,
A.J., 1992. In vitro and In vivo biological activity of South Ameri-
can Dragons Blood and its constituents. Planta Medica Supplement 58,
A582A583.
Pieters, L., De Bruyne, T., Van Poel, B., Vingerhoets Totte, J., Vanden Berghe,
D., Vlietinck, A., 1995. In vivowound healing activity of Dragons blood
(Crotonspp.), a traditional South American drug, and its constituents. Phy-
tomedicine 2, 1722.
Pieters, L., Vanden Berghe, D., Vlietinck, A.J., 1990. A dihydrobenzofuran
lignan fromCroton erythrochilus. Phytochemistry 29, 348349.
Piozzi, F., Passannanti, S., Paternostro, M.P., Nasini, G., 1974. Diterpenoid resinacids ofDaemonorops draco. Phytochemistry 13, 22312233.
Plinius Secundus, 1601. The Historie of the Worlde. London.
Poehland, B.L., Carte, B.K., Francis, T.A., Hyland, L.J., Allaudeen, H.S.,
Troupe, N., 1987. In vitroantiviral activity of Dammar resin triterpenoids.
Journal of Natural Products 50, 706713.
Ponpipom, M.M., Bugianesi, R.L., Brooker, D.R., Yue, B.Z., Hwang, S.B.,
Shen, T.Y., 1987.Structureactivity relationshipsof Kadsurenoneanalogues.
Journal of Medicinal Chemistry 30, 136142.
Porras-Reyes, B.H., Lewis, W.H., Roman, J., Simchowitz, L., Mustoe, T.A.,
1993. Enhancement of wound healing by the alkaloidtaspine defining mech-
anism of action. In: Proceedings of the Society for Experimental Biology
and Medicine, vol. 203. Society for Experimental Biology and Medicine,
New York, NY, pp. 1825.
Rao, G.S.R., Gehart, M.A., Lee III, R.T., Mitscher, L.A., Drake, S., 1982.
Antimicrobial agents from higher plants: Dragons blood resin. Journal ofNatural Products 45, 646648.
Risco, E., Ghia, F., Vila, R., Iglesias, J., Alvarez, E., Canigueral, S.,
2003. Immunomodulatory activity and chemical characterization of san-
gre de drago (Dragons blood) from Croton lechleri. Planta Medica 69,
785794.
Robertson, A., Whalley, W.B., 1950. The pigments of Dragons blood resin.
PartII. A synthesis of dracorhodin.Journalof ChemicalSociety,18821884.
Rossi, D., Bruni, R., Bianchi, N., Chiarabelli, C., Gambari, R., Medici, A.,
Lista, A., Paganetto, G., 2003. Evaluation of the mutagenic, antimutagenic
and antiproliferative potential ofCroton lechleri (Muell. Arg.) latex. Phy-
tomedicine 10, 139144.
Rozhon, E.J., Khnadwala, A.S., Sabouni, A., 1998. Enteric formulations of
proanthocyanadin polymer antidiarrhoeal compositions. #WO 9816111,
April 23.
Safrin, S.,Phan,L., Elbeik, T., 1993. Evaluationof thein vitro activityof SP-303
against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes
simplex virus. Antiviral Research 20, 117.
Sandoval, M., Okuhama, N.N., Clark, M., Angeles, F.M., Lao, J., Bustamante,
S., Miller,M.J.S.,2002. Sangre de grado Croton palanostigma induces apop-
tosis in human gastrointestinal cancer cells. Journal of Ethnopharmacology
80, 121129.
Sethi, M.L.,1977. Inhibition of RNA-directedDNA polymerase activityof RNA
tumor viruses by taspine. Canadian Journal of Pharmaceutical Sciences 12,
79.
Shen, C.C., Tsai, S.Y., Wei, S.L., Wang, S.T., Shieh, B.J., Chen, C.C., 2007.
Flavonoids isolated from Draconis Resina. Natural product research 4,
377380.
Sidwell,R.W., Huffman, J.H.,Moscon, B.J.,Warren, R.P., 1994. Influenzavirus-
inhibitory effects of intraperitoneally and aerosol-administered SP-303, a
plant flavanoid. Chemotherapy 40, 4250.
Soike, K.F., Zhang, J.Y., Meyerson, L.R., 1992. Reduction of respiratory syn-
cytial virus (RSV) shedding in African green monkeys treated with SP-303.
Antiviral Research, 91.
Sollman, T., 1920. A sketch of the medical history of Dragons Blood. Journal
of the American Pharmaceutical Association 9, 141144.
Soukup, J., 1970. Dictionary of the Common Names of Peruvian Flora and
Catalog of the Genuses, vol. 141. Editorial Salesiana, Lima, Peru.
Stern, W.T., 1992. Dictionary of Plant Names for Gardeners. Cassell Publishers
Ltd., London.
Suchy, V., Bobovnicky, B., Trojanek, J., Budesnsky, M., Ubik, K., 1991.
Homoisoflavans and other constituents of Dragons blood from Dracaena
cinnabari. In:Pezzuto,J.M. (Ed.),Progress on Terrestrialand Marine Natural
Products of Medicinaland Biological Interest. American BotanicalCouncil,
Austin, pp. 110118.
-
8/10/2019 Sangre de Grado 19 Setie2014
20/20
380 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361380
ELHAH,2007. TheEleventh Labor of Hercules:The Applesof TheHesperides.
Trease, G.E., Evans, W.E., 1978. Pharmocognosy, 11th ed. Bailliere Tindall,
London.
Trimble, H., 1895. Re