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Rendiconti Lincei. Scienze Fisiche e Naturali
https://doi.org/10.1007/s12210-022-01122-4
REVIEW
Dragon’s Blood: antioxidant properties fornutraceuticals
andpharmaceuticals
IsabellaS.A.Peres1· KiaraA.O.Conceição1· LarissaA.F.Silva1· NadiaG.Khouri2· CristianaM.P.Yoshida1·
ViktorO.C.Concha1· MassimoLucarini3· AlessandraDurazzo3· AntonelloSantini4 · ElianaB.Souto5,6·
PatriciaSeverino7
Received: 19 March 2022 / Accepted: 25 November 2022
© The Author(s) 2023
Abstract
Plants are the source of a large spectrum of phytochemicals, and the combined and concerted action of biologically active
compounds lead to the potential beneficial properties of each plant matrix. A great attention is being addressed over the
years toward herbs and medicinal plants. Dragon’s Blood is a reddish resin oil extracted from Croton lechleri tree. It has
been extensively used by indigenous cultures of the Amazon River since ancient times due to the beneficial nutraceutical
and pharmaceutical properties. This perspective aims at providing a current framework on Dragon’s Blood with focus on
antioxidant properties for nutraceuticals and pharmaceuticals in a novelty integrated and multidisciplinary manner, high-
lighting the current knowledge, the main research lines, and emerging strategies. A literature quantitative research analysis
approach was applied as starting point. The literature search was carried out by means of the Scopus database; 365 documents
have been retrieved in the year range from 1854 to 2021, and a total of 269 terms were identified. Among the top-recurring
keywords appear: unclassified drug, nonhuman, plant extract/s, Dragon’s Blood, dracaena, Dragon Blood, chemistry, human,
animal/s, plant resin. Source, chemical composition, potential nutraceutical, and therapeutical applications of Dragon’s
Blood are discussed here. The anti-inflammatory, wound healing, antidiarrheals, anticancer, antirheumatic, antiseptic, and
antioxidant activities identified in the Dragon’s Blood extracts can open novel perspectives for its use in food and pharma-
ceutical industries. While different bioactive compounds have already been identified in Dragon’s Blood extract, only a few
studies can be found in literature.
Keywords Medicinal plants· Natural products· Dragon’s Blood· Croton lechleri· Antioxidant· Antibacterial· Antiviral·
Anti-inflammatory
1 Introduction
Plants are the source of a large spectrum of phytochemicals,
and the combined and concerted action of biologically active
compounds lead to the potential beneficial properties of each
plant matrix (Santini and Novellino 2017; Durazzo etal.
2018, 2020). A great attention is being addressed along the
years toward the traditional medicine (Fitzgerald etal. 2020;
Yeung etal. 2020) by exploiting the features, properties, and
applications of herbs and medicinal plants (Naz etal. 2015;
Begum etal. 2020; Durazzo etal. 2021a, b; Sharifi-Rad etal.
2021, Durazzo etal. 2022], taking into account biodiversity
and sustainability (Guarino and Pignatti 2010; Pignatti and
Cipriani 2010; Pignatti 2013; Attorre etal. 2018; Durazzo
and Lucarini 2021; Chung etal. 2021).
In this context, Dragon’s Blood tree (Croton lechleri) is
particularly interesting for its beneficial properties associ-
ated since centuries to the red exudate produced, which is
popularly known as grade blood or blood of water (Guerra
etal. 2022). This species belongs to the Euphorbiaceae fam-
ily and is found in the Amazon region in Brazil. It usually
has a length of 5–6m but can reach up to 20m. What dif-
ferentiates it from other trees is that a reddish sap is exuded
when its bark is cut. Such sap is called blood of the dragon
and is vastly used since centuries as a popular holistic medi-
cine (Sun etal. 2019; Salazar-Gomez etal. 2022).
* Nadia G. Khouri
khouri.g.nadia@gmail.com
* Antonello Santini
asantini@unina.it
Extended author information available on the last page of the article
Rendiconti Lincei. Scienze Fisiche e Naturali
1 3
This perspective aims at providing a current framework
on Dragon’s Blood with focus on antioxidant properties for
nutraceuticals and pharmaceuticals in a novelty integrated
and multidisciplinary manner, highlighting the current
knowledge, the main research lines, and emerging strategies.
A literature quantitative research analysis approach was
applied as starting point, to give a current snapshot of the
current trend raised in the international research context
by this topic. A search throughout the Scopus online data-
base has been carried out by means of the string TITLE-
ABS-KEY (“dragon’s blood*”), and the “full records and
cited references” were exported and processed using the
VOSviewer software (version 1.6.16, 2020; www. vosvi ewer.
com, accessed on 8 December 2021) (Waltman etal. 2010).
The search returned 365 publications covering the time
range from 1854 to 2021, and a total of 269 terms were iden-
tified and visualized as a term map in Fig.1. Figure1 allows
for the identification of the main terms correlated to Drag-
on’s Blood, and also identifies the main existing research
lines focused on this topic. It is interesting to observe that
among the top-recurring keywords, appear: unclassified
drug, nonhuman, plant extract/s, dragon’s blood, dracaena,
dragon blood, chemistry, human, animal/s, plant resin.
The most recent review is focused on the advanced
research progress on anti-tumor effect of Chinese Dragon’s
Blood (Tian etal. 2021), whereas the most cited review is
published by Gupta etal. in the Journal of Ethnopharmacol-
ogy and it is addressed on botany, chemistry, and therapeutic
uses of Dragon's Blood (Gupta etal. 2008) and in 2017,
Bayerl published an interesting “Editorial” document on
Dragon’s Blood (Bayerl 2017).
The main subject areas explored are as follows: Phar-
macology, Toxicology and Pharmaceutics, Biochemistry,
Genetics and Molecular Biology, Chemistry, Medicine,
Agricultural and Biological Sciences, Environmental Sci-
ence, and others.
In the context of the environmental impact and sustain-
ability perspective, it is worth mentioning the works on
Fig. 1 Term map for the Dragon’s Blood research. Bubble size rep-
resents the number of publications. Bubble color represents the cita-
tions per publication (CPP). Two bubbles are closer to each other
if the terms co-appeared more frequently (bibliometric data were
extracted from the Scopus online database and elaborated by the
VOSviewer software)
Rendiconti Lincei. Scienze Fisiche e Naturali
1 3
sustainable land use management needed to conserve the
Dragon's Blood tree of Socotra Island representing a vul-
nerable endemic umbrella species (Maděra etal. 2019);
the socio economic roles of Dragon’s Blood in participa-
tive rehabilitation of degraded forest and land (Letari etal.
2019); the Dragon’s Blood secretion and its ecological sig-
nificance (Jura-Morawiec etal. 2016, 2022).
Dragon’s Blood can be used in the treatment of gastric
diseases and infections, and it is also capable of healing
wounds. Native people use the sap of the plant on burns and
wounds to stop bleeding, speed up healing, and protect from
infections (Jiang etal. 2017; Sun etal. 2019).
Dragon's Blood is one of the strongest healing agents
known, it dries quickly when applied, and forms a sec-
ond skin that promotes collagen formation and fibroblasts
chemotaxis (Namjoyan etal. 2015). Croton lechleri etha-
nolic extract also exhibited antibacterial activity against
superinfected skin ulcers in Colombian hospitalized patients
(Corrales-Ramirez etal. 2013), and it had a highly signifi-
cant bacterial inhibition when compared with the standard
treatment in the clinic.
Different bioactive compounds were reported from
Dragon’s Blood resin (Jaronski etal. 2017). It is an astrin-
gent latex with cellulose and Dragon’s Blood resin as active
ingredients. It is composed of alcohol esters resinous, tan-
nins (dimethylcedrusine, etc.), polyphenols (gallic acid,
etc.), alkaloids (Namjoyan etal. 2015), proanthocyanidins,
steroids (sitosterols, catechins), saponins, and lignans (Fan
etal. 2014; Luo etal. 2015). Among the identified com-
pounds, there are some that are linked directly with the prop-
erties of the Dragon’s Blood. According to the literature,
the alkaloid taspine proved to be the main active compound
responsible for wound healing. It is associated with the for-
mation of collagen, promoting healing by migrating fibro-
blasts to the injury site on the skin (Vaisberg etal. 1989;
Namjoyna etal. 2015; Canedo-Téxon etal. 2019). Besides
taspine, flavonoid compounds with antioxidant properties
act as reducing agents, eliminating free radicals, since they
donate hydrogen to free radicals. Flavans, flavanones, poly-
meric flavonoids, chromogen ketones, and flavanols can also
be acknowledged, since they are secondary plant metabo-
lites involved in the defense against ultraviolet radiation or
aggression by pathogens, contributing to plant pigmenta-
tions and antioxidant. Additionally, these compounds also
demonstrated benefits in the prevention of various diseases
associated with oxidative stress, such as cancer, cardiovas-
cular, and neurodegenerative diseases (Escobar etal. 2018).
About proanthocyanidins, Rossi etal. (2011) showed that it
is responsible for 90% of the dry weight of Dragon’s Blood,
characterized by its antioxidant and antibacterial properties.
Regarding compounds in lower concentration, the lignan
3´,4-O-dimethylcedrusin is highlighted due to its participa-
tion in wound healing and there are korbein-A and korbein-B
(De Martino etal. 2008). The main chemical compounds of
Dragon’s Blood are listed in Table1.
2 Extraction andproperties
Trees known as “dragon” or “dragon’s blood” have shared
healing properties, although they belong to distinct botani-
cal families. Croton lechleri (Euphorbiaceous) is found in
Peru, Ecuador, Colombia, and northern Brazil (Rossi etal.
2011). Also, Croton urucurana are usually sighted in the
southeast, mid-west, and southern regions of Brazil, as well
as in Argentina and Uruguay. Both species are relatives and
their respective sap has a similar pharmacological activ-
ity. In the state of Minas Gerais (Brazil), Dragon’s Blood
is often called “water bleeds”, as it grows near rivers and
ponds (Martins etal. 2016). A large volume of latex was
extracted indiscriminately in Colombia, Ecuador, and Peru,
with the falling of the trees (Aguirre etal. 2001). As an
example, in 1998, 50.607 L of Croton lechleri latex were
exported mainly to Europe, United States, and Japan (Galy
etal. 2000). Currently, the latex collection for commercial
purposes occurs on a smaller scale that supplies regional
communities. The Dragon’s Blood latex extraction is simi-
lar to seringals, by cutting the trunk at breast height in a
V-shape, then a reddish-colored sap exudes. Also, indige-
nous-influenced extraction is highlighted, where the inci-
sions are made in tree trunks and the drops of latex are col-
lected. This process begins when the tree aged 6–7years or
when its DAP (diameter to breast height) reaches approxi-
mately 25–27cm. An incision is made at 1.30m of the soil
and the recommended extraction is at morning during the
full moon for 5–9h. This method produces regularly an
average of 2.0–3.5 L of latex (Aguirre etal. 2001; Osakada
2009). Latex conservation can be done by adding sugarcane
liquor to prevent the product from crystallizing. The final
product should be packed in an airtight container and stored
in refrigerated places. This latex has from 3 to 6months
of storage life (Vásquez and Bach 2015). Dragon’s Blood
has interesting properties for medicinal applications (Sun
2019). It can treat scarring by stimulating skin rejuvenation,
which explains its antioxidant property. Other characteris-
tics of Dragon’s Blood are its antibacterial, antiviral, and
anti-inflammatory activity, and can be exploited for several
medicinal uses (Fig.2).
2.1 Wound healing
The Dragon’s Blood healing properties are associated to
the two most active components present in the sap, taspine
and dimethylcedrusin. Both are efficient in healing, but
also in the treatment of gastric and duodenal ulcers (Sun
etal. 2019). A process of taspine isolation and its use in
Rendiconti Lincei. Scienze Fisiche e Naturali
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Table 1 Main chemical compounds of Dragon’s Blood
Groups Compounds
Alkaloids Taspine, pyridine, aportineindole, quinoline, tropanes, anthraquinones, unsaturated fatty acids, anthraquinones and
triterpenes
Phenolic compounds Gallic acid, coumaric p-acid, sirinic acid, ferulic acid, vanillic acid, salicylic acid and others with less concentrations
Polyphenol compounds Stylbens, flavonoids, dihydroflavonoids, catechins, sirinic acid, and proanthocyanidins
Flavonoids 7,4'-Dihydroxyflavone, 7,4'-dihydroxy-dihydroflavone,
4'-methoxy-3′7-dihydroxyflavone, 4',7-dihydroxy-flavan,
7-hydroxy-4'-methoxyflavane, 4',7-dihydroxy-3'-meth-
oxyflavan,
2'-methoxyisocotrin-5'-ol, socotrin-4'-ol, and cochin-
chinenin C
Chalcones 4,4'-Trihydroxychalcone, 2'-methoxy-4,4'-dihydroxychal-
cone, 2'-methoxysocotrin-5'-ol and 2-methoxy-4,4'-
dihydroxychalcone
Dihydro-chalcones Loureirin A, loureirin B, loureirin C, loureirinD,2,4,4'-
trihydroxydihydrochalcone, cochinchinenin A,
4,4'-dihydroxy,4-hydroxy-2-methoxydihydrochalcone,
2,6-methoxydihydrochalcon,
4'-dihydroxy-4,6-dimethoxy-dihydrochalcone
Flavanols Catechin and epicatechin, gallocatechin, epigallocatechin
Tannins Hydrolyzed This compound has a central polyol group (mostly β-d-
glucose, and also quinic acid, other phenols, and glyco-
sides); and hydroxyls esterified by gallic acid (phenolic
part)
Condensed The condensed one have a "polymeric" structure of flavan-
3-ol, such as catechin, or flavan-3,4-diol, of leucocya-
nidin
Quinones p-Benzoquinone and anthraquinone
Fig. 2 Medicinal applications of
Dragon’s Blood
Rendiconti Lincei. Scienze Fisiche e Naturali
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wound healing, acting on various mechanisms that lead
to skin regeneration, in varicose ulcers and bedsores has
been described (Vaisberg etal. 1989; Namjoyan etal. 2016;
Guerra etal. 2022). Dragon’s Blood polyphenols and proan-
thocyanidins are potent antioxidants that could act against
free radicals that cause skin aging (Escobar etal. 2018). In
cosmetics, these compounds increase the collagen synthesis
reducing the wrinkles formation and promote skin rejuve-
nation, and also protect the skin against UV rays. It is very
effective in the treatment of acne and can be combined with
the essential oil of Cypress (Cupressus Sempervirens) or
Pitanga (Eugenia Uniflora). Polyphenols also play an impor-
tant role in healing and eliminating free radicals, mainly
proanthocyanidins, which stimulate wound contraction and
healing. In this way, the gel produced from the latex of Cro-
ton lechleri called also “Sangre de Drago”, has a therapeutic
effect (Namjoyan etal. 2015; Apaza Ticona 2021). A sum-
mary of the healing properties is shown in Fig.3.
2.2 Antiviral andantibacterial activities
The latex of Croton lechleri Dragon’s Blood plant has
antibacterial and antiviral properties through its second-
ary metabolites belonging to phenol, terpenoids, alkaloids,
leptins, polypeptides (Gupta and Gupta 2011; Bayerl 2017)
groups, among others. The pure extract of the plant Croton
lechleri Mull Arg. has secondary metabolites with antibacte-
rial and antiviral properties as displayed in Fig.4, including
2,4,6-trimethoxyphenol, 1,3,5-trimethoxybenzene, korberin
A and B, crolechinicacid, proanthocyanidins, catechins, epi-
catechins, gallocatechins, galloepicatechins, flavonols phe-
nol, terpenoids, alkaloids, leptins and polypeptides (Gupta
and Gupta 2011; Lopes at al. 2013; Bayerl 2017) groups.
Experiments have shown that sap inhibits the action of
various types of viruses, such as herpes simplex, hepatitis
virus (Olson 2015), influenza and parainfluenza (due to the
influenza virus), cytomegalovirus, and respiratory syncyt-
ial viruses (Vilchez and Braulio 2018). The Shaman Phar-
maceuticals Company developed a drug, named Virend®,
containing antiviral compounds extracted and isolated from
the Dragon’s Blood bark and resin for the treatment of her-
pes. They also developed an oral drug called Provir® for the
treatment of respiratory viral infections (King and Tempesta
1994; Snell 2001). Croton lechleri has a large community of
endophytic fungi with great antibacterial potential against
bacteria pathogenic to humans, especially against Gram-
positive bacteria (Ferreira etal. 2021; Sebastiao 2018). It
showed antibacterial effect on Staphylococcus aureus ATCC
43300 in concentrations above 77%. The antimicrobial activ-
ity of Dragon’s Blood resin obtained from Dracaena cin-
nabari Balf f. dichloromethane extract was attributed to the
high concentration of phenolics, flavonoids, and flavonols,
being proposed as a natural food preservative (Gupta and
Gupta 2011).
2.3 Anti‑inflammatory activity
The intragastric administration of Dragon’s Blood in carra-
geenan-inflamed or sciatic nerve-injured rats demonstrated
its potent anti-inflammatory and analgesic effects by inhib-
iting hyperalgesia and paw edema, and by reducing the
expression of cyclooxygenase-2 protein or preprotachykinin-
A mRNA (Li etal. 2012) blocks the activation of nerve fib-
ers that release pain signals to the brain, and functions as an
Fig. 3 Healing properties of
Dragon’s Blood
Rendiconti Lincei. Scienze Fisiche e Naturali
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antalgic. The analgesic effect of topical administration of
Dragon’s Blood, which was reported to last up to 6h, has
been exploited in gels containing 1–3% of resin in the treat-
ment of relief of rheumatism arthritis and arthrosis, as well
as against pain caused by herpes zoster, inflammation of the
trigeminal nerve, bursitis, twists, and fibromyalgia (Pieters
etal 1993). Resin can be formulated in creams or gels (in
percentages of 3–5% of the total) with anti-inflammatory
essential oils (e.g., copaiba, oregano, ginger, or wintergreen)
that are also analgesics and can potentiate the bioactivities
of Dragons’ Blood. Immunomodulatory activity of this resin
has also been demonstrated by affecting the activated T cells.
In low doses, it is a phagocytosis inhibitor, and in higher
doses has antioxidant and an activating effect of phago-
cytosis. It shows the ability to inhibit the proliferation of
leukemic cells and cytostatic activity against KB and V-79
tumors. In veterinary, Dragon’s Blood is also very efficient,
treating skin infections, warts, wounds, abscesses, and otitis
(Dietrich 2018).
2.4 Antioxidant andanticancer activities
Antioxidants are substances that block the harmful effect of
free radicals. Natural antioxidants are phenolic compounds
that are formed by benzene groups and hydroxyl substitu-
ents, which have oxy-reducing properties and the ability to
stabilize intermediate compounds (Sandoval etal. 2006).
The evaluation of combined and concerted action of bioac-
tive compounds gives the measurement of antioxidant prop-
erties and indicator of health status (Durazzo 2017; Santini
and Cicero 2020). The Dragon’s Blood is an exceptionally
high and stable antioxidant (Escobar etal. 2018; Pona etal.
2019). The antioxidant capacity of Dragon’s Blood in the
gastric mucosa has been studied in experimental animals. It
was concluded that the bioactive extract presented a posi-
tive effect through the gastric route, confirmed by the lower
lipid peroxidation. It has also been reported that 75% ethanol
extract from Chinese Dragon’s Blood suppressed cell growth
and promoted apoptosis in human hepatoma HepG2 and SK-
HEP-1 cells (Chen etal. 2020). Using RNA interference, the
authors demonstrated the anti-hepatoma activity of the etha-
nolic extract partially through downregulation of Smad3,
one of major members in TGF-β/Smad signaling pathway.
3 Current applications
The most relevant applications of Dragon’s Blood are listed
in Table2. The development of formulations for the topi-
cal administration of Dragon’s Blood using biopolymers
is seldom reported in the literature. The production of a
dressing containing silk fibroin and an aqueous solution
with polyethylene oxide (PEO) of 1000 [KDa] at 3% (w/v)
Dragon’s Blood at 2% (v/v) has been described (Melo etal.
2018). The sample is characterized by continuous fibers
with the presence of porous granules, which is one of the
main requirements of dressings to accelerate cell migration.
Also, tissue healing and antibacterial activity of chitosan and
polyvinyl alcohol were tested with the addition of hydroalco-
holic solution of Croton lechleri formulated in chitosan and
polyvinyl alcohol semi-solid for tissue healing, and tested
its antimicrobial activity against S. aureus, resulting a mini-
mal inhibitory concentration of 0.025g/10mL (León and
Santiago 2007). Chitosan and pullulan have been proposed
to be used as local delivery systems for active ingredients
from plant extracts for the treatment against periodontal
Fig. 4 Antiviral and antibacte-
rial activity of Dragon’s Blood
blocks
Rendiconti Lincei. Scienze Fisiche e Naturali
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pathogenmicroorganisms (Rodriguez-Garcia etal. 2010).
Thickness of chitosan films was on average of 0.03mm and
for pullulan of 0.07mm. Five plant extracts were tested,
and among them was Croton lechleri. The results revealed
that both biopolymers with added plant extracts have
antibacterial activity and can be used as bio-adhesive film
against periodontopathogens tested.
The stability of Dragon’s Blood sap was studied consider-
ing several storage conditions, under different environments
of temperature and relative humidity (Escobar etal. 2018).
In addition, an accelerated aging treatment was performed,
Table 2 Examples of current applications of Dragon’s Blood
Applications Results
Healing Curative effect of the cream made with Croton lechleri Müll atomized latex extract (1.5%)
The administration of Dragon’s Blood increased the rate of wound repair in mice by 31%
It was observed a significant improvement of wound healing from the third day. And on day 14, 95.73% were treated therapeu-
tically and 78.10% with placebo
At days 5 and 7, 80% of those who received phytotherapic treatment with Dragon’s Blood improved the healing in postpartum
cases
Dragon’s Blood was highly effective in the healing process: 92.5% of the cases had abundant tissue granulation and in 100% of
cases avoided infection, inflammation, and dehiscence
Ulcer The administration of Dragon’s Blood to gastric mucous induced a higher cytoprotection, in consequence reduced the lipoper-
oxidation and helped in gastric ulcer treatment
In diabetic patients, the ulcer area decreased substantially. One patient, for example, in the first week had an ulcer with an area
of 237.50 cm2 and in the twelfth week, it decreased to 174.80 cm2
Diarrhea The flow of sodium and water was reduced, which decreased the frequency and consistency of diarrhea. SP-303, a proantho-
cyanidin oligomer isolated from Dragon’s Blood latex plant, was able to shorten the duration of the diarrhea by 21%
Dermatology At concentrations of 125, 250, 500, and 1000µg/mL, inhibitions on the collagen enzyme were observed at 5.67%, 17.33%,
33.41%, and 59.52% respectively, helping the skin rejuvenation
The effectiveness of the Dragon’s Blood-based gel and cream for the treatment of polymorphic acne of grade I and II was
determined by the reduction of acne lesions on the skin of 100% of treated patients
The hydration values, thickness of the dermis and elasticity increased in all groups after 6weeks of application of the cream
containing 3% of Dragon’s Blood extract, thus, being efficiently useful in preventing or improving skin changes associated
with stretch mark
Traumatic
tympanic
membrane
The healing rate and the average cure time of the treated group were better than the control group, so it can be concluded that
Dragon’s Blood powder can improve the cure rate and shorten the treatment time of the traumatic tympanic membrane
In cases of cervicitis, after 5days of Dragon’s Blood application, 10% of the women did not show any improvements, 45%
were cured and the other 45% presented great improvement of the infection
Gynecology After 7days applying Dragon’s Blood moisturizer, the effect on Candida albicans was similar to Clotrimizol effect, implying
that Dragon’s Blood is efficient against candidiasis
Odontology It shows that 97% of the patients in which Croton lechleri was applied had rapid healing. It was possible to demonstrate the
benefits of Dragon’s Blood after simple extraction of teeth, where healing has been achieved quickly
The activity of Croton lechleri latex at concentrations of 75 and 100% showed antibacterial activity, and are acceptable to be
considered as an accessible, natural, and low-cost inhibitory agent for prevention methods in dental caries
The Dragon’s Blood application resulted in a fast analgesic/anti-inflammatory effect, and the removal of tooth decay, disap-
pearance of edema, bleeding and gingival redness was observed. It preserved the membrane of all cells functional functions,
andviability of periodontal ligament cells
Cancer Concentrations of 0.3 and 3.0µg/µL of Dragon’s Blood showed 100% action against the breast cancer cell line
It was observed that 50% of the colorectal cancer cells were inhibited 24h after the Dragon’s Blood application in a concentra-
tion below 50µg/µL
An inhibition of 50% of melanoma cells was achieved by Dragon’s Blood application in a period of 24h in concentration
below 5µg/µL
Maximum inhibition of stomach cancer cells was reached at concentrations > 200µg/mL of Dragon’s Blood after 18h of the
application
Virus The inhibition desired for Parainfluenza I virus was reached at a concentration of 3.0µg/mL of Dragon’s Blood
For herpes type I, 35.6µg/mL of Dragon’s Blood inhibited the activity of the virus, while for herpes type II, 20.5µg/mL was
necessary
RSV (Respiratory Syncytial virus) had its activity inhibited with a concentration of 6.0µg/mL of Dragon’s Blood
The desired inhibition was achieved with a concentration of 50µg/mL of Dragon’s Blood for the type B of hepatitis
Rendiconti Lincei. Scienze Fisiche e Naturali
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subjecting the lyophilized Dragon’s Blood sap to irradia-
tion with UV light, and the effect of these stress conditions
on its antioxidant activity was also evaluated. The results
demonstrated that the concentration of the sap constitu-
ent’s changes at different storage conditions. For example,
the storage conditions were studied in a range of tempera-
ture from 4 to 21ºC, and different conditions of relative
humidity (0, 23, 44, and 56%). The presence of moisture was
evaluated with respect to the Dragon’s Blood degradation.
Regarding the temperature, no significant effect was detected
in the range studied (4ºC and 21ºC at a 0% relative humid-
ity). However, applying UV light irradiation, a reduction of
20% of the sap concentration was observed. The antioxidant
activity remained stable under the studied storage conditions
(under different temperature and relative humidity) (Escobar
etal. 2018). The high stability observed for Dragon’s Blood
sap can confer interesting characteristics in various indus-
trial products, such as food, pharmaceuticals, nutraceuticals
or cosmetics, paints or paper products, being possibly used
as an antioxidant or as an ingredient.
Ingestion of crude extracts or tea formulations of Croton
lechleri may cause mild nausea, bitter taste or diarrhea (Pona
etal. 2019). The use of Dragon’s Blood as a healing agent in
concentrations of 0.1% and concentrations of 0.001% caused
negative effects on the reproductive tract of Wistar Rats,
since it caused a decrease in the values of membrane integ-
rity, acrosome, and cell viability of sperm (Schmuch etal.
2013). To test and evaluate the potential toxic, cytotoxic, and
mutagenic/genotoxic of Croton lechleri, a test with Allium
cepa was performed by diluting 0.5, 1.0, 2.0, and 2.5mL of
the extract in 250mL of water, using root growth, mitotic
index, and the presence of micronuclei as parameters. It was
observed that all the concentrations used of Croton lechleri
inhibited the root growth of the roots of Allium cepa, evi-
dencing its toxic potential. There was also a decrease in the
mitotic index, mainly at the concentration of 2.5mL, indicat-
ing cytotoxicity. In addition to cytotoxicity, the mutagenic
potential was observed through the high micronucleus index,
showing that the “dragon’s sap” should be used with caution
(De Almeida etal. 2019). In another study, to analyze long-
term Dragon’s Blood toxicity, rabbits were administered
Guangxi Dragon’s Blood at rates of 3.0 and 1.5g/kg body
weight, once a day for 90days. It has been observed that the
Dragon’s Blood did not cause changes in the animal’s patho-
logical state, and had no significant effect on blood eryth-
rocytes and leukocytes number, alanine aminotransferase,
urea nitrogen, or weight. There was no functional damage
to the liver or kidney. In the pathological examination under
optical microscope, except for some expansion of the tiny
blood vessel between myocardial cells, there was no damage
to the liver, lungs, kidney, intestine or the adrenal glands,
thus indicating that the use of Dragon’s Blood did not show
toxic reactions (Fan etal. 2014).
Application of nanotechnologies to plants’ extracts of
nutraceutical interest (Daliu etal. 2019; Zielińska etal.
2019; Souto etal. 2020a; Durazzo etal. 2021a, b) repre-
sents a key issue, such as the preparation, characterization,
and dissolution characteristics of Dragon’s Blood extract
nanosuspensions (Wang etal. 2019); the silver nanoparti-
cle’s synthesis by Dragon’s Blood resin ethanol extract and
antiradiation activity (Wang etal. 2019); the assessment of
bioreducing and stabilizing potential of Dragon's Blood resin
extract in synthesis of silver containing nanoparticles (Hasan
etal. 2015); surface-enhanced Raman scattering study of
organic pigments using silver and gold nanoparticles pre-
pared by pulsed laser ablation (Hasan etal. 2013; Fazio etal.
2013). Safety aspects and procedures should be taken into
proper account in view of an optimal use of these techniques
aimed to improve perspective applications of this important
vegetal matrix (Zielińska etal. 2020; Souto etal. 2020b).
4 Conclusion
The latex of Croton lechleri or Dragon’s Blood, which is
known to be used in the Amazonic region, has potential
application in medicine in the treatment of many diseases.
The resin offers huge potential, and studies are needed to
improve the extraction, to purify the compounds isolated
from Dragon’s Blood, and assess completely quality and
control aspects. Also, the correct administration of Croton
lechleri to ensure proper, safe, and responsible uses and
applications should be investigated.
Acknowledgements Not applicable.
Author contributions ISAP, KAOC, LAFS, and NGK have contributed
to the methodology, formal analysis, investigation, resources, software,
data curation, and drafting of the original manuscript, CMPY, VOCC,
ML, AD, AS, EBS, and PS have contributed to the formal analysis,
data curation, writing review and editing of the manuscript, conceptu-
alization, project administration, supervision, and funding acquisition.
All authors have made a substantial contribution to the work and have
approved its publication.
Funding Open access funding provided by Università degli Studi di
Napoli Federico II within the CRUI-CARE Agreement. This research
was funded by Banco do Nordeste (grant FUNDECI/2016.0015),
Coordenação Aperfeiçoamento de Pessoal de Nivel Superior (CAPES)
and Fundação de Ámparo à Pesquisa do Estado de Sergipe (FAPITEC)
(PROCESSO: 88887.159533/2017-00 extração, encapsulação e car-
acterização de bioativos para o interesse biotecnologico). Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq
301964/2019-0 Chamada 06/2019, and Chamada CNPq nº 01/2019).
Data availability Not applicable.
Declarations
Conflict of interest The authors declare no conflict of interest.
Rendiconti Lincei. Scienze Fisiche e Naturali
1 3
Institutional review board Not applicable.
Informed consent Not applicable.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
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otherwise in a credit line to the material. If material is not included in
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Authors and Aliations
IsabellaS.A.Peres1· KiaraA.O.Conceição1· LarissaA.F.Silva1· NadiaG.Khouri2· CristianaM.P.Yoshida1·
ViktorO.C.Concha1· MassimoLucarini3· AlessandraDurazzo3· AntonelloSantini4 · ElianaB.Souto5,6·
PatriciaSeverino7
Isabella S. A. Peres
sgrignoli.isabella@unifesp.br
Kiara A. O. Conceição
andrade.kiara@unifesp.br
Larissa A. F. Silva
laris-sa.aparecida10@unifesp.br
Cristiana M. P. Yoshida
cristiana.yoshida@unifesp.br
Viktor O. C. Concha
viktor.cardenas@unifesp.br
Massimo Lucarini
massi-mo.lucarini@crea.gov.it
Rendiconti Lincei. Scienze Fisiche e Naturali
1 3
Alessandra Durazzo
alessandra.durazzo@crea.gov.it
Eliana B. Souto
ebsouto@ff.up.pt
Patricia Severino
patricia_severino@itp.org.br
1 Institute ofEnvironmental, Chemical andPharmaceutical
Sciences-Biotechnology andNatural Products Laboratory,
Federal University ofSão Paulo, Diadema, SãoPaulo, Brazil
2 Faculty ofChemical Engineering, Laboratory
ofOptimization, Projects andAdvanced Control, State
University ofCampinas, Campinas, SãoPaulo, Brazil
3 CREA-Research Centre forFood andNutrition, Via
Ardeatina 546, 00178Rome, Italy
4 Department ofPharmacy, University ofNapoli Federico II,
Via D. Montesano 49, 80131Naples, Italy
5 Department ofPharmaceutical Technology, Faculty
ofPharmacy, University ofPorto, Rua de Jorge Viterbo
Ferreira, 228, 4050-313Porto, Portugal
6 REQUIMTE/UCIBIO, Faculty ofPharmacy, University
ofPorto, Rua de Jorge Viterbo Ferreira, 228, 4050-313Porto,
Portugal
7 Post-Graduation Programme inIndustrial Biotechnology,
Institute ofTechnology andResearch (ITP), Tiradentes
University, Aracaju, Sergipe, Brazil