GRAVIOLA (Annona muricata)

Common names: Soursop, Paw-Paw, Graviola, Guanabana

Traditional, Ethnobotanical Uses: for diarrhea (fruit), cough, hypertension, rheumatism, tumors, cancer, asthma, childbirth, lactagogue (fruit), malaria, tranquilizer, skin rashes, parasites (seeds), worms (seeds), liver problems, arthritis (used externally).

Graviola is a fruit tree native to North and South America and the Caribbean, where it is known by such names as Paw-Paw, Soursop, and Guanabana. The species native to South America is the Guanabana tree, and it is prized for its fruit, which is used in drinks, ice cream, and marmalades. The leaves and seeds of the tree have long been used by native peoples for an astounding variety of ailments, ranging from parasites (the seeds), to high blood pressure and cancer.

Although research on the Graviola tree began in the 1940s, it was greatly intensified in the 1970’s with screening of thousands of plants by the National Cancer Institute. Initial screening demonstrated cytoxicity against cancer cells by several Annona species. In the 1990’s an upsurge in interest in the use of herbs to improve health and in new drug discovery from natural products spread throughout the world.

Scientific research has validated through animal studies the use of various parts of the graviola (guanabana) tree for hypertension, as a vasodilator, as an antispasmodic (smooth muscle relaxer), and as cardiodepressant (slowing of heart rate). Mikolajczak, McLaughlin, and Rupprecht (1989) discovered effective pesticidal activity in Annonaceous Acetogenins.

Sundarrao et. al. confirmed antibacterial and antitumor activities of an Annona species native to New Guinea. Gbeassor et. al. (1990) and Antoun (1993) have found antimalarial bioactives in Annona muricata. Padma et. al. (1998) confirmed anti-viral activity of Annona muricata against the Herpes simplex virus.*

Recent Advances in Annonae Research

Summary of Mechanism of Action Research Findings:

An article in The Journal of Natural Products (1999) stated: : “The Annonaceous acetogenins are promising new antitumor and pesticidal agents that are found only in the plant family Annonaceae. Chemically, they are derivatives of long-chain fatty acids. Biologically, they exhibit their potent bioactivities through depletion of ATP levels via inhibiting complex I of mitochondria and inhibiting the NADH oxidase of plasma membranes of tumor cells. Thus, they thwart ATP-driven resistance mechanisms.”

Three different research groups have conducted mechanism of action studies on annonaceous acetogenins and have each has confirmed that these chemical compounds are highly effective inhibitors of Complex I in mitochondrial electron transport systems in tumors. Many of the acetogenins have a cytotoxicity with ED50 values as low as 10-9 ug/ml. In the studies conducted by separate research groups all have confirmed significant anti-tumor, anti-cancer and selective toxicity against several different types of cancer cells which they studied. One of the eight published clinical studies demonstrated that one of the acetogenins in Graviola was selectively cytotoxic to colon adenocarcinoma cells. In this study the Annonaceous acetogenins were shown to possess 10,000 times the potency of adriamycin.

Following are excerpts from different publications summarizing various findings of research related to members of the genus Annonae, of which Annona muricata (Graviola) is a member.

Recent Advances in Annonaceous Acetogenins (National Cancer Institute, 1997)

“Annonaceous acetogenins are waxy substances consisting of C32 or C34 long chain fatty acids which have been combined with a 2-propanol unit at C-2 to form a lactone. They are only found in several genera of the plant family, Annonaceae. Their diverse bioactivities as antitumor, immunosuppressive, pesticidal, antiprotozoal, antifeedant, anthelmitic, and antimicrobial agents, have attracted more and more interest worldwide. Recently, we reported that the Annonaceous acetogenins can selectively inhibit the growth of cancerous cells and also inhibit the growth of adriamycin resistant tumor cells. As more acetogenins have been isolated and additional cytotoxicity assays have been conducted, we have noticed that, although most of acetogenins have high potencies among several solid human tumor cell lines, some of the derivatives within the different structural types and some positional isomers showed remarkable selectivities among certain cell lines, e.g., against prostate cancer (PC-3). We now understand the primary modes of action for the acetogenins. They are potent inhibitors of NADH: uniquinone oxidoreductase, which is I an essential enzyme in complex I leading to oxidative phosphorylation in mitochondria. A recent report shoed that they act directly at the uniquinone-catalytic site(s) within complex I and in microbial glucose dehydrogenase. They also inhibit the uniquinone-linked NADH oxidase that is peculiar to the plasma membranes of cancerous cells.”

Selective Bibliography of Research

Alali, F.Q., et. al., Annonaceous acetogenins: recent progress. J. Nat Prod. 1999 March; 62(3): 504-40. Review.

Bories, C. et. Al., Antiparasitic Activity of Annona Muricata and Annona Cherimolia Seeds Planta Med 57 5: 434-436 (1991)

Carbajal, D., et. al., Pharmacological Screening of Plant Decoctions Commonly Used in Cuban Folk Medicine. J Ethnopharmacol 33 1/2: 21-24 (1991)

De Feo, V. 1992. Medicinal and magical plants in the northern Peruvian Andes. Fitoterapia 63, 417-440

Gbeassor. M. et. al. In Vitro Antimalaria Activity of Six Medicinal Plants. Phytother Res 4 3: 115-117 (1990)

Hasrat, J.A., et. al. Isoquinoline derivatives isolated from the fruit of Annona muricata a 5-Htergic 5HT1A receptor agonists in rats: unexploited antidepressive (lead) products. J Pharm Pharmacol. 1997 Nov; 49(11): 1145-1149.

Heinrich, M. et. Al., Parasitological and Microbiological Evaluation of Mixe Indian Medicinal Planta (Mexico) J Ethnopharmacol 36: 1: 81-85 (1992)

Hopp, D.C and J.L. McLaughlin, Use of Selectively Cytotoxic Annonaceous Acetogenins, filed Feb. 4, 1997, P-97006.00 U.S.