This proprietary Raintree product has not been the subject of any clinical research. A partial listing of published research on each herbal ingredient in the formula is shown below. Please refer to the plant database files by clicking on the plant names below to see all available documentation and research.

Mullaca (Physalis angulata)
Chiang, H. et al. “Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro.” Anticancer Res. 1992; 12(4): 1155–62.
Kawai, M., et al. “Cytotoxic activity of physalins and related compounds against HeLa cells [leukemia].” Pharmazie 2002; 57(5): 348–50.
Ausseil, F., et al. "High-throughput bioluminescence screening of ubiquitin-proteasome pathway inhibitors from chemical and natural sources." J. Biomol. Screen. 2006 Dec 14;
Kuo, P. C., et al. "Physanolide A, a novel skeleton steroid, and other cytotoxic principles from Physalis angulata." Org. Lett. 2006 Jul; 8(14): 2953-6.
Ichikawa, H., et al. "Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression." Mol. Cancer Ther. 2006; 5(6): 1434-45.
Magalhaes, H. I., et al. "In-vitro and in-vivo antitumour activity of physalins B and D from Physalis angulata." J. Pharm. Pharmacol. 2006; 58(2): 235-41.
Jacobo-Herrera, N. J., et al. "Physalins from Witheringia solanacea as modulators of the NF-kappaB cascade." J. Nat. Prod. 2006; 69(3): 328-31.
Magalhaes, H. I., et al. "In-vitro and in-vivo antitumour activity of physalins B and D from Physalis angulata." J. Pharm. Pharmacol. 2006 Feb; 58(2): 235-41.
Hsieh, W. T., et al. “Physalis angulata induced G2/M phase arrest in human breast cancer cells.” Food Chem Toxicol. 2006; 44(7): 974-83.
Lee, C. C., et al. "Cytotoxicity of plants from Malaysia and Thailand used traditionally to treat cancer." J. Ethnopharmacol. 2005 Sep; 100(3): 237-43.
Wu, S. J., et al. “Antihepatoma activity of Physalis angulata and P. peruviana extracts and their effects on apoptosis in human Hep G2 cells.” Life Sci. 2004 Mar; 74(16): 2061-73.
Leyon, P. V., et al. "Effect of Withania somnifera on B16F-10 melanoma induced metastasis in mice." Phytother. Res. 2004; 18(2): 118-22.
Ismail, N., et al. “A novel cytotoxic flavonoid glycoside from Physalis angulata.” Fitoterapia. 2001 Aug. 72(6):676–79.
Lee, Y. C., et al. “Integrity of intermediate filaments is associated with the development of acquired thermotolerance in 9L rat brain tumor cells.” J. Cell. Biochem. 1995; 57(1): 150–62.
Perng, M. D., et al. “Induction of aggregation and augmentation of protein kinase-mediated phosphorylation of purified vimentin intermediate filaments by withangulatin A.” Mol. Pharmacol. 1994; 46(4): 612–17.
Chiang, H., et al. “Antitumor agent, physalin F from Physalis angulata L.” Anticancer Res. 1992; 12(3): 837–43.
Kusumoto, I., et al. “Inhibitory effect of Indonesian plant extracts on reverse transcriptase of an RNA tumour virus (I).” Phytother. Res. 1992; 6(5): 241–44.
Lee, W. C., et al. “Induction of heat-shock response and alterations of protein phosphorylation by a novel topoisomerase II inhibitor, withangulatin A, in 9L rat brain tumor cells.” Cell Physiol. 1991; 149(1): 66-67.
Chen, C. M., et al. “Withangulatin A, a new withanolide from Physalis angulata.” Heterocycles. 1990; 31(7):1371–75.
Basey, K., et al. “Phygrine, an alkaloid from Physalis species.” Phytochemistry. 1992; 31(12): 4173–76.
Juang, J. K., et al. “A new compound, withangulatin A, promotes type II DNA topoisomerasemediated DNA damage.” Biochem. Biophys. Res. Commun. 1989; 159(3): 1128–34.
Anon. “Biological assay of antitumor agents from natural products.” Abstr.: Seminar on the Development of Drugs from Medicinal Plants Organized by the Department of Medical Science Department at Thai Farmer Bank, Bangkok, Thailand 1982; 129.
Antoun, M. D., et al. “Potential antitumor agents. XVII. physalin B and 25,26-epidihydrophysalin C from Witheringia coccoloboides.” J. Nat. Prod. 1981; 44(5): 579–85.

Anamu (Petiveria alliacea)
Mata-Greenwood, E., et al. “Discovery of novel inducers of cellular differentiation using HL-60 promyelocytic [leukemia] cells.” Anticancer Res. 2001; 21(3B): 1763-70.
An, H., et al. "Synthesis and anti-tumor evaluation of new trisulfide derivatives." Bioorg. Med. Chem. Lett. 2006 Sep; 16(18): 4826-9.
Williams, L. A., et al. "In vitro anti-proliferation/cytotoxic activity of sixty natural products on the human SH-SY5Y neuroblastoma cells with specific reference to dibenzyl trisulphide." West Indian Med. J. 2004 Sep; 53(4): 208-19.
Ruffa, M. J., et al. “Cytotoxic effect of Argentine medicinal plant extracts on human hepatocellular carcinoma cell line.” J. Ethnopharmacol. 2002; 79(3): 335-39.
Rosner, H., et al. “Disassembly of microtubules and inhibition of neurite outgrowth, neuroblastoma cell proliferation, and MAP kinase tyrosine dephosphorylation by dibenzyl trisulphide.” Biochem. Biophys. Acta 2001; 1540(2):166-77.
Jovicevic, L., et al. “In vitro antiproliferative activity of Petiveria alliacea L. on several tumor cell lines.” Pharmacol. Res. 1993; 27(1): 105-06.
Rossi, V., et al. “Antiproliferative effects of Petiveria alliacea on several tumor cell lines.” Pharmacol. Res. Suppl. 1990; 22(2): 434.
Yan, R., et al. “Astilbin selectively facilitates the apoptosis of interleukin-2-dependent phytohemaglutinin-activated Jurkat cells.” Pharmacol. Res. 2001; 44(2): 135-39.
Weber, U. S., et al. “Antitumor activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines”. Res. Commun. Mol. Pathol. Pharmacol. 1998; 99(2): 193-206.
Bassi, A. M., et al. “Comparative evaluation of cytotoxicity and metabolism of four aldehydes in two hepatoma cell lines.” Drug Chem. Toxicol. 1997 Aug; 20(3): 173-87.

Vassourinha (Scoparia dulcis)
Noda, Y., et al. “Enhanced cytotoxicity of some triterpenes toward leukemia L1210 cells cultured in low pH media; possibility of a new mode of cell killing.” Chem. Pharm. Bull. 1997; 45(10): 1665–70.
Kessler, J. H., et al. "Broad in vitro efficacy of plant-derived betulinic acid against cell lines derived from the most prevalent human cancer types." Cancer Lett. 2006 Dec 12;
Mukherjee, R., et al. "Betulinic acid derivatives as anticancer agents: structure activity relationship." Anticancer Agents Med. Chem. 2006 May; 6(3): 271-9.
Phan, M. G., et al. "Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin." Chem. Pharm. Bull. 2006 Apr; 54(4): 546-9.
Hayashi, K., et al. "The role of a HSV thymidine kinase stimulating substance, scopadulciol, in improving the efficacy of cancer gene therapy." J. Gene Med. 2006 Aug; 8(8): 1056-67.
Kasperczyk, H., et al. “Betulinic acid as new activator of NF-kappaB: molecular mechanisms and implications for cancer therapy.” Oncogene. 2005 Oct; 24(46): 6945-56.
Fulda, S., et al. “Sensitization for anticancer drug-induced apoptosis by betulinic acid.” Neoplasia. 2005; 7(2): 162-70.
Garg, A. K., et al. “Chemosensitization and radiosensitization of tumors by plant polyphenols.” Antioxid. Redox. Signal. 2005; 7(11-12): 1630-47.
Wada, S., et al. "Betulinic acid and its derivatives, potent DNA topoisomerase II inhibitors, from the bark of Bischofia javanica." Chem. Biodivers. 2005 May; 2(5): 689-94.
Hayashi, K., et al. “Evaluation of scopadulciol-related molecules for their stimulatory effect on the cytotoxicity of acyclovir and ganciclovir against Herpes simplex virus type 1 thymidine kinase gene-transfected HeLa cells.” Chem. Pharm. Bull. 2004; 52(8):1015-7.
Ahsan, M., et al. “Cytotoxic diterpenes from Scoparia dulcis.” J. Nat. Prod. 2003; 66(7): 958-61.
Fulda, S., et al. “Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroecto-dermal tumors.” Med. Pediatr. Oncol. 2000; 35(6): 616–18.
Fulda, S., et al. “Betulinic acid: A new cytotoxic agent against malignant brain-tumor cells.” Int. J. Cancer 1999; 82(3): 435–41.
Arisawa, M. “Cell growth inhibition of KB cells by plant extracts.” Natural Med. 1994; 48(4): 338–47.
Nishino, H. “Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L." Oncology. 1993; 50(2): 100–3.
Hayashi, T., et al. “Scoparic acid A, a beta-glucuronidase inhibitor from Scoparia dulcis.” J. Nat. Prod. 1992; 55(12): 1748
Hayashi, R. J., et al. “A cytotoxic flavone from Scoparia dulcis L.” Chem. Pharm. Bull. 1988; 36: 4849–51.

Simarouba (Simarouba amara)
Mata-Greenwood, E., et al. “ Novel esters of glaucarubolone as inducers of terminal differentiation of promyelocytic HL-60 [leukemia] cells and inhibitors of 7,12-dimethylbenz[a]anthracene-induced preneoplastic lesion formation in mouse mammary organ culture.” J. Nat. Prod. 2001; 64(12): 1509-13.
Liou, Y. F., et al. "Antitumor agents XLVIII: Structure-activity relationships of quassinoids as in vitro protein synthesis inhibitors of P-388 lymphocytic leukemia tumor cell metabolism." J. Pharm. Sci. 1982 Apr; 71(4): 430-5.
Klocke, J. A., et al. "Growth inhibitory, insecticidal and antifeedant effects of some antileukemic and cytotoxic quassinoids on two species of agricultural pests." Experientia. 1985 Mar 15; 41(3): 379-82.
Rivero-Cruz, J. F., et al. “Cytotoxic constituents of the twigs of Simarouba glauca collected from a plot in Southern Florida.” Phytother. Res. 2005; 19(2): 136-40.
Morre, D. J., et al. “Mode of action of the anticancer quassinoids--inhibition of the plasma membrane NADH oxidase.” Life Sci. 1998; 63(7) :595-604.
Valeriote, F. A., et al. “Anticancer activity of glaucarubinone analogues.” Oncol Res. 1998; 10(4): 201–8.
Ohno, N., et al. “Synthesis of cytotoxic fluorinated quassinoids.” Bioorg. Med. Chem. 1997; 5(8): 1489-95.
Handa, S. S., et al. “Plant anticancer agents XXV. Constituents of Soulamea soulameoides.” J. Nat. Prod. 1983; 46(3): 359–64.
Polonsky, J. “The isolation and structure of 13,18-dehydroglaucarubinone, a new antineoplastic quassinoid from Simarouba amara.” Experientia. 1978; 34(9): 1122–23.
Ghosh, P. C., et al. “Antitumor plants. IV. Constituents of Simarouba versicolor.” Lloydia. 1977; 40(4): 364–69.
Ogura, M. et al. “Potential anticancer agents VI. Constituents of Ailanthus excelsa (Simaroubaceae)." Lloydia. 1977; 40(6): 579–84.

Picão Preto (Bidens pilosa)
Chang, J. S., et al. "Antileukemic activity of Bidens pilosa L. var. minor (Blume) Sherff and Houttuynia cordata Thunb." Am. J. Chin. Med. 2001; 29(2): 303-12.
Wang, J., et al. "Inhibition of 5 compounds from Bidens bipinnata on leukemia cells in vitro." Zhong Yao Cai. 1997; 20(5): 247-9.
Sundararajan, P., et al. "Studies of anticancer and antipyretic activity of Bidens pilosa whole plant." Afr. Health Sci. 2006 Mar; 6(1): 27-30.
Wu, L. W., et al. “Polyacetylenes function as anti-angiogenic agents.” Pharm. Res. 2004; 21(11): 2112-9.
Gupta, M. P., et al. “Screening of Panamanian medicinal plants for brine shrimp toxicity, crown gall tumor inhibition, cytotoxicity and DNA intercalation.” Int. J. Pharmacog. 1996; 34(1): 19–27.
Alvarez, L., et al. “Bioactive polyacetylenes from Bidens pilosa.” Planta Med. 1996; 62(4): 355–57.
Wat, C. K., et al. “Ultraviolet-mediated cytotoxic activity of phenylheptatriyne from Bidens pilosa L.” J. Nat. Prod. 1979; 42(1): 103–11.

Suma (Pfaffia paniculata)
Watanabe, T., et al. “Effects of oral administration of Pfaffia paniculata (Brazilian ginseng) on incidence of spontaneous leukemia in AKR/J mice.” Cancer Detect. Prev. 2000; 24(2): 173–8.
Pinello, K.C., et al. “Effects of Pfaffia paniculata (Brazilian ginseng) extract on macrophage activity.” Life Sci. 2005 Oct 6;
da Silva, T. C., et al. “Inhibitory effects of Pfaffia paniculata (Brazilian ginseng) on preneoplastic and neoplastic lesions in a mouse hepatocarcinogenesis model.” Cancer Lett. 2005 Aug; 226(2): 107-13.
Matsuzaki, P., et al. “Antineoplastic effects of butanolic residue of Pfaffia paniculata.” Cancer Lett. 2005 Jul 25;
Matsuzaki, P., et al. “Effect of Pfaffia paniculata (Brazilian ginseng) on the Ehrlich tumor in its ascitic form.” Life Sci. 2003 Dec; 74(5): 573-9.

Cat’s Claw (Uncaria tomentosa)
Bacher, N., et al. "Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells." Br. J. Haematol. 2006 Mar; 132(5): 615-22.
Stuppner, H., et al. "A differential sensitivity of oxindole alkaloids to normal and leukemic cell lines." Planta Med. (1993 suppl.); 59: A583.
Gonzales, G. F., et al. "Medicinal plants from Peru: a review of plants as potential agents against cancer." Anticancer Agents Med. Chem. 2006 Sep; 6(5): 429-44.
De Martino, L., et al. "Proapoptotic effect of Uncaria tomentosa extracts." J. Ethnopharmacol. 2006 Aug; 107(1): 91-4.
Sheng, Y., et al., "Treatment of chemotherapy-induced leukopenia in a rat model with aqueous extract from Uncaria tomentosa." Phytomedicine. 2000; 7(2): 137–43.
Sheng, Y., et al. "Induction of apoptosis and inhibition of proliferation in human tumor cells treated with extracts of Uncaria tomentosa." Anticancer Res. 1998; 18(5A): 3363–68.
Lemaire, I., et al. "Stimulation of interleukin-1 and -6 production in alveolar macrophages by the neotropical liana, Uncaria tomentosa (una de gato)." J. Ethnopharmacol. 1999; 64(2): 109–15.

Espinheira Santa (Maytenus ilicifolia)
Nakao, H., et al. "Cytotoxic activity of maytanprine isolated from Maytenus diversifolia in human leukemia K562 cells." Biol. Pharm. Bull. 2004; 27(8): 1236-40.
Liu, Z., et al. "Metabolism studies of the anti-tumor agent maytansine and its analog ansamitocin P-3 using liquid chromatography/tandem mass spectrometry." J. Mass. Spectrom. 2005; 40(3): 389-99.
Cassady, J. M., et al. "Recent developments in the maytansinoid antitumor agents." Chem. Pharm. Bull. 2004; 52(1): 1-26.
Ohsaki, A., et al. "Four new triterpenoids from Maytenus ilicifolia." J. Nat. Prod. 2004; 67(3): 469-71.
Horn, R. C., et al. "Antimutagenic activity of extracts of natural substances in the Salmonella/microsome assay." Mutagenesis. 2003 Mar; 18(2): 113-8.
Buffa Filho, W., et al. "Quantitative determination for cytotoxic Friedo-nor-oleanane derivatives from five morphological types of Maytenus ilicifolia (Celastraceae) by reverse-phase high-performance liquid chromatography." Phytochem. Anal. 2002 Mar-Apr; 13(2): 75-8.
Miura, N. et al. "Protective effects of triterpene compounds against the cytotoxicity of cadmium in HepG2 cells." Mol. Pharm. 1999; 56(6); 1324–28. Liu, C., et al. "Eradication of large colon tumor xenografts by targeted delivery of maytansinoids." Proc. Natl. Acad. Sci. 1996 Aug; 93(16): 8618-23.