Dragons Blood Research

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

369 Fig. 1. (Continued) sensory afferent nerve activation at both the prejunctionaland postjunctional level. The latex from Croton lechleri has strong anti-inflammatory activity when administered i.p. (Riscoet al., 2003). 2.1.2.9. Mutagenic and antimutagenic activity. The mutagenic and antimutagenic activity ofCroton lechieri sap was examined 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 of Croton 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 370 D. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361–380 Chemical constituents reported from Croton spp. Compound name Bioactivity References Murillo et al. (2001) Croton urucurana Baill. Sonderianin (2) Antibacterial activity Craveiro and Silveira (1982), Peres et al. (1997, 1998b) Acetyl aleuritolic acid Antibacterial activity, Analgesic activity Peres et al. (1997, 1998a) Peres et al. (1998b) Fucoarabinogalactan (CU-1) Milo et al. (2002) Croton lechleri Mull. 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), Cai et al. (1991)Catechin; epigallocatechin; epicatechin; gallocatechin Cai et al. (1991), Chen et al. (1994) in the rate of wound repair on topical application of the Croton 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 wounding of human fibroblasts also suggested role of taspine for wound healing (Vaisberg et al., 1989). From the sap of Peruvian Sangre de Drago (Crotonsp.), a lignan known as 3-dimethylcedrusin was isolated which protected endothelial cells from undergoing degradation in a starvation medium and stimulated endothelial cells, however at high concentrations it inhibited the cell proliferation (Pieters et al., 1992,1993). Porras-Reyes et al. (1993) performed a number of tests. Gupta et al. / Journal of Ethnopharmacology 115 (2008) 361–380 371 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 of Croton lechieri sap and concluded that several factors—the ability to form a film that protects against microbial invasion of wounds; free radical scavenging activity of procyanidins; the high contentof polyphenolics capable of binding proteins and enzymes; andthe anti-inflammatory and strong antibacterial action of polyphenols, 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. Lewiset al. (1992) has patented for taspine in DMSO (solvent), which healed wounds faster than DMSO alone.

2.2. Daemonorops spp.

Dragon’s blood resin is also obtained as deep red teardropshaped 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 as Calamus draco Willd. (Daemonorops draco Willd. Blume) by Barry et al. (1926), who also described the resinous layer as being isolated by placing the fruits in sacks and pounding them and the pulp being treated with boiling water. Subsequently the resin was kneaded into balls or long sticks. Various grades have been identified byHowes (1949) . Other species as source of resin are D. didymophylla Becc., D. micracantha (Griff.) Becc., D. motley Becc., D. rubra (Reinw. ex Blume) Blume and D. propinqua Becc.

2.2.1. Chemical constituents

summarizes 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) reported in vitro activity of commercial resin obtained from Daemonorops draco against Staphylococcus aureus and Mycobacterium smegmatis. This led to further evaluation of resin’s components exhibiting antimicrobial activity. Rao et al. (1982) reported that the antimicrobial activity of the resin from Daemonorops draco was due to the presence 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 perchlorate, 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 antithrombotic activity. Daemonorops draco has been studied for its ‘hemostatic’ and ‘vasoactiveantithrombotic’ activity in Chinese medicinal system ( Kiangsu Institute of Modern Medicine, 1977

5. Conclusion Although Dragon’s blood has proved to be popular alternative 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 investigate whether purified compounds isolated from Dragon’s blood may have better therapeutic potential as compared to crude extract. Since there is considerable variation in the chemical composition among various samples of Dragon’s Blood, quality

control/assurance needs to be established for the traditional medical 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 drugs molecules. Acknowledgements

We are grateful to Prof. Ulrike Lindequist, Institute of Pharmacy, Ernst-Moritz-Arndt-University, Germany for her thorough revision of this review and providing us with her invaluable suggestions. We acknowledge the financial support from AICTE (8023/RID/NPROJ/RPS-38/2004-05)