5. UTILITY  
Parts Used : Virtually, the whole plant: leaves, fruits, seeds, bark, roots, and flowers.  

·Fruits : Fruits are much appreciated in several Latin American countries, principally as fresh fruit, sweetened juice, and ice cream and in yogurt. In Brazil, this fruit’s juice is known as champola; in Puerto Rico, as carato . Today, ice cream prepared from Annona muricata L. can be found in several gourmet supermarkets in the United States. This fruit can also be preserved in canned sugar syrup. Canned fruits can easily be mashed or blended in order to obtain a delicious dessert, although the fresh fruit is more estimated for this purpose. Since several years ago, the pulp of Annona muricata L. has been canned and sold in Mexican restaurants of New York and other cities in the North of the United States. In the Virgin Island, the fruits are employed as bait in fish traps.   The less acid and less fibrous fruits can be sliced or crushed and chopped and then added to fruit salads or vegetable salads, or refrigerated and served as dessert with sugar and a few of milk or cream.

Among the more than 60 species in the genus Annona, the fruit of Annona muricata L. is the biggest and the only one suitable for processing and canning. In order to prepare juice, the pulp and seeds have to be pressed and strained or mashed with clothes in order to extract the creamy and delicious juice that then will be shake together with milk or water and sweetened. Other way to prepare juice consists in mixing the pulp with a similar quantity of boiling water and then straining and sweetening it. If an electric mixer is to be used, such as an electric blender, be sure to remove all the seeds before, because they are fairly toxic and no one seed should be accidentally crushed within the juice.  

In Puerto Rico, a juice of Annona muricata L. containing 12% to 15% of pulp is produced. When canned, this juice can endure for one year or more. In Guatemala, a carbonated juice is prepared as a soda pop. In the Western Indies, sometimes a fermented beverage, similar to cider is also prepared. In the Philippines, a vacuum-concentrated juice is produced, the same way condensed milk is prepared. Frequently, the juices prepared with Annona muricata L. are added with natural colorants, green or pink colored, in order to make them more attractive. Strained pulp mixed with wine or brandy and seasoned with nutmeg is a delicatessen. Likewise, the juice of Annona muricata L. thickened with a few of gelatin is served as a delicious dessert.   The juice obtained from the fruit is used as diuretic and as a remedy for hematuria (presence of blood in urine) and urethritis. Drunk on an empty stomach, this juice is believed to alleviate liver diseases and leprosy. Fresh flesh of an acid fruit put as cataplasm is used in order to expulse ticks and accelerate cicatrization; for this, the flesh has to stay without change for 3 days. Eaten as a fruit or drunk as juice, the fruits are used in order to combat worms and parasites, reduce fever, increase milk produced by women after childbirth (lactagogue), and as astringent against diarrhea and dysentery. Ripe fruits are rich in vitamin B1, B2, and C, and in phosphorus.  

In the Dominican Republic, a cream is prepared with this fruit. They also prepare a dessert by cooking the pulp in sugar syrup with cinnamon and lemon peel. The pulp can also be used in order to prepare tarts, jellies, sugar syrup conserves, and nectar. Unripe fruits are customarily cooked and eaten as vegetable in Puerto Rico. In Indonesia, these fruits are served in soups. In Northeast Brazil, unripe fruits are roasted or fried. When boiled in water for an hour, partially ripe fruits (including peel) become tender, with their pulp white colored, creamy and flour-like, and an aroma very similar to tender maize. Unripe fruits are very astringent, and pulverized and cooked are used as medicine against dysentery. Food value for 100 g of edible portion:   Calories 61.3-53.1 Humidity 82.8g Protein 1.00g Fat 0.97g Carbohydrates 14.63g Fiber 0.79g Ash 60g Calcium 10.3 mg Phosphorus 27.7 mg Iron 0.64 mg Vitamin A (B-carotene) 0 Thiamin 0.11 mg Riboflavin 0.05 mg Niacin 1.28mg Ascorbic Acid 29.6 mg

Amino acids :   tryptophan 11 mg methionine 7 mg lysine 60 mg   Analysis performed in the FIM laboratory of Nutrition, La Havana, Cuba.   In the Brazilian Amazonia, oil extracted from unripe fruits is mixed with olive oil and used externally against neuralgias, rheumatism, and arthritic pains. In Jamaica, Haiti and Western Indies, the whole fruit or a juice obtained from fruit are used in order to reduce fever, combat parasites and against diarrhea, as well as to increase milk secretion in breast-feeding mothers (lactagogue).  

·Seeds : Seeds contain approximately 45% of yellow-colored, non-secant oil, which is irritant venom that can cause a severe ocular inflammation. Ground seeds are used as vermifuge and anti-helminthic, against internal and external parasites, such as head louses and worms and in order to combat pea louses; besides, seeds have been used in order to kill moths and cockroaches. Petroleum ether seed extracts and chloroform seed extracts are toxic for black scarab larvae that live in carpets. The oil extracted from seeds kill head louses. The oil has also been traditionally used as venom in order to capture fishes. In the Caribbean, a tincture prepared with pulverized seeds and golden rum is used as a strong emetic.  

·Leaves : A leaf decoction is used in order to combat head louses and bed bugs. This decoction is also used as a sedative, antispasmodic, hypotensor, and nervine (it is, to tone up nerves and stimulate its action). In the Peruvian Andes, for example, leaves of Annona muricata L. are used for preparing a tea against inflammation of mucous membranes, such as that produced during catarrh. In the Peruvian Amazonia, the leaves are used against diabetes, as well as sedative and antispasmodic. In Guyana, native tribes prepare a leaf tea and use it as sedative and heart tonic. In the Brazilian Amazonia, a leaf tea is also prepared and is used against liver diseases, whereas an oil extracted from leaves and unripe fruits is mixed with olive oil and used externally against neuralgias, rheumatism, and arthritic pains. This oil has also been used for childbirth difficulties, asthma, and asthenia. In all the Western Indies, leaves of Annona muricata L. are pretty regarded for having sedative or soporific properties. In British Guyana, the leaves in water are even said to be useful in order to sober a drunk.

In Hollander Antilles, the leaves are put into the cover of pillows or spread over the bed in order to produce a profound overnight sleeping. A leaf tea or leaf infusion is also customarily drunk for the same purpose. In the Ecuadorian province of Esmeraldas, a leaf decoction of Annona muricata L. is drunk as analgesic and antispasmodic. In Africa, this decoction is also administered to children in case of fever; they are also gently bathed with it. In some parts of Western Indies, a decoction of tender shoots or leaves is commonly used as remedy for gallbladder diseases, as well as for colds, catarrh, diarrhea, dysentery and indigestion. This decoction is used to be said to ‘cool the blood’ and be able to stop vomits and help during childbirth. A decoction of Annona muricata L. is also used as wet compresses on inflammations and swelled feet. Chewed leaves mixed with saliva are applied on incisions after surgery in order to disappear the swelling around the cut without producing a scar. Mashed leaves are used as cataplasm in order to alleviate eczemas and other skin disorders, and rheumatism, and the syrup from tender leaves is poured on skin eruptions.  

·Roots : Roots are used as sedative, antispasmodic, hypotensive and nervine (to tone up nerves and stimulate its action). Roots are drunk as tea. Traditionally, the root has been used as venom for fishing. In the Peruvian Amazonia, the roots are also used against diabetes. They are also used as vermifuge and its bark as an antidote against venom.  

·Bark : Stem bark has been used in tannery. The bark has also been used, as well as roots and seeds, as venom for fishing. In the Peruvian Amazonia, the bark is used against diabetes, as well as sedative and antispasmodic. In Guyana, native tribes prepare a bark tea and use it as sedative and heart tonic. The bark is also used as sedative and nervine (it is, to tone up and stimulate nerves), for heart diseases, cold, flu, childbirth difficulties, asthma, asthenia, hypertension, and against parasites. Bark fibers have been used in textiles.  

·Wood : The wood is pale, aromatic, soft, light in weight, and nondurable. Traditionally, the wood has been used in order to make yokes for ox, because this wood is said not to provoke hair losing on their necks. In Colombia, the wood is regarded as good for making wooden water pipes and barrel staves. The wood of Annona muricata L. is also employed in order to manufacture wooden tools: farming implements (yokes), tool handles, etc. Analyses in Brazil have shown that its cellulose content is among 65% and 76%, highly enough in order to have potential as a source of pulp for paper industry. Finally, this wood can be used as a good source of heat (lumber).  

·Flowers : The flowers of Annona muricata L. are said to alleviate catarrh. They have a profound odor.  

Properties : Annona muricata L. is used as/for/against:
against dermatosis/dermatitis against eczema anti depressive anti diarrheic anti helminthic antibacterial anticancer anticonvulsive antifungal antimicrobial antineoplasic antiparasitic antispasmodic antitumor antiviral astringent blood depurative cardiodepressor cytostatic cytotoxic detoxifier diaphoretic (induces an increase of respiration) digestive disorders dysentery dyspepsia febrifuge hypotensive insecticide nervine pectoral piscicide sedative stomachic vasodilator vermifuge  
   Studies performed on animals by several researchers have shown that both the bark and leaves have hypotensive, antispasmodic, anticonvulsive, and vasodilator activities. The activity of Annona muricata L. as smooth muscle relaxant and cardiodepressor has also been demonstrated in animals . The hypotensive activity of Annona muricata L. was demonstrated again in 1991, in a study carried out in rats. The activity of Annona muricata L. against microorganisms and parasites has also been shown. There exist a series of studies accumulated in several years showing that leaf, bark, root, stem, and seed extracts have antibacterial properties in vitro which act against a series of pathogens; moreover, the bark of Annona muricata L. has antifungal properties.

In 1990 and 1993 two studies that shown that Annona muricata L. is active against malaria were conducted. Insecticide properties have also been shown for the leaves, roots, and seeds; the seeds resulted to be, according to a research in 1940, the most active as insecticide. A 1997 study, on the other hand, discovered some new alkaloids in the fruit with antidepressive effects in animals. In 1976, an investigative program in medicinal plants carried out by the National Cancer Institute of the United States, discovered that the leaves and stems of Annona muricata L. are cytotoxic against cancer cells, so that researchers have been insisting in this topic since then. The major part of anticancer searching in Annona muricata L. has been concentrated in a series of novel phytochemicals called annonaceous acetogenins. Annona muricata L. produces these natural products in its leaves, stems, bark, and seeds. Three independent research groups have succeeded separately in isolating these acetogenic compounds in Annona muricata L. These acetogenic compounds have shown significant antitumor and anticancer activities, as well as a selective toxicity against several types of cancer cells, without any damage to healthy cells. These discoveries have been published in 8 different clinical studies.  

Several acetogenins have shown selective toxicity against tumor cells in very low doses, as low as 1 ppm (parts per million). In 1998, four studies were published; these studies also mentioned the phytochemicals and acetogenins that are showing the strongest anticancer, antitumor, and antiviral activities. Hence, specific acetogenins have been reported to be selectively toxic for these types of cancer cells: lung carcinoma, solid human-breast cancer tumor, prostatic adenocarcinoma, pancreatic carcinoma, colonic adenocarcinoma, liver cancer, human lymphoma, and multiple-drug resistant human-breast adenocarcinoma. Annonaceous acetogenins are only found in the botanical family Annonaceae , which encompasses plants such Annona muricata L. “soursop”, Annona cherimolia, “cherimoya”, etc. In general, a series of annonaceous acetogenins obtained from several species of this family with antitumoral, antiparasitic, pesticide, antiprotozoaria, antihelminthic, and antimicrobial activities, have been reported.

In three different laboratories, several studies related to the way of action of these acetogenins have recently been conducted. These studies have shown that acetogenins are excellent inhibitors of certain enzymatic processes that only occur in cell membranes of cancer tumor cells. The Purdue University, in West Lafayette, Indiana, United States, has conducted the major amount of research in acetogenins. Most of these studies have been funded by the National Cancer Institute of the United States or the National Institute of Health, also from the United States. As a result, the team of the University of Purdue has obtained at least 9 patents in the United States and the rest of the world related to the uses and antitumoral and insecticide properties of these acetogenins. Recently, the annonaceous acetogenins have been reported to selectively inhibit the growing of cancer cells, as well as inhibit the growing of tumor cells resistant to adriamycin. As more acetogenins are being isolated and more cytotoxicity assays are performed, it has became evident that, although most acetogenins have a high strength against several solid human tumor cell lines, some of the derivatives among the different structural types as well as some positional isomers show a notable selectivity against certain cell lines; i. e., against prostate cancer (PC-3). The primary ways of action for acetogenins are now understood. Acetogenins are powerful inhibitors of NADH:ubiquinone oxidoreductase, which is an essential enzyme in complex I that conduces to oxidative phosphorilation in mitochondria. A recent report has shown that acetogenins act directly on the catalytic site(s) of ubiquinone in complex I and in microbial glucose dehydrogenase. Acetogenins also inhibit ubiquinone-linked NADH oxidase which is characteristic of cancer cell plasmatic membranes.  

In 1997, the University of Purdue published information indicating that several annonaceous acetogenins not only are effective in order to kill tumors that are acceptedly resistant to anticancerous agents, but also seem to have certain special affinity for such resistant cells. The explanation for this is already known. The cancer cells that survive chemotherapy can develop resistance against the agent originally used, as well as against other drugs, even if those drugs are not related to the agent originally used. This phenomenon is called ‘multidrug resistance’.   One of the mechanisms by which cancer cells develop resistance to chemotherapy drugs is through creation of an effluent pump called ‘P-glycoprotein-mediated pump’. These kinds of pumps are able to push anticancer agents out of the cell before these anticancer agents can kill the cell. In average, only near 2% of cancer cells of any given person could develop this pump, but this 2% eventually could grow and expand in order to create multiple-drug resistant tumors.   Some of the most recent researches in acetogenins have reported that acetogenins were able to deactivate these intercellular pumps, killing this way the multiple-drug resistant tumors. Investigators in Purdue reported that acetogenins kill cancer cells resistant to multiple drugs preferably through the blocking of ATP transference –the major source of cell energy—inside the cells. A tumor cell needs energy in order to grow and reproduce and a great additional quantity of energy in order to let its pump to function and expel the agents that attack the cell. Inhibiting the flux of energy toward the cell, this cell no more can put its pump to work. When acetogenins block the ATP transference inside the tumor cells for a while, these cells remain without enough energy in order to operate their maintenance processes and thus die. Normal cells rarely develop such a pump; hence, they do not require big amounts of energy in order to put the pump to work and, generally, they are not affected by ATP inhibitors.  

Researchers in Purdue reported that 14 different acetogenins proved largely showed strong properties for blocking ATP (including several found only in Annona muricata L.). They also reported that 13 of these 14 acetogenins proved were stronger against multiple-drug resistant breast-cancer cells than the other 3 standard drugs (adriamycin, vincristin, and vinblastin) they used as control. In March 2002, Japanese researchers published an interesting in vivo study. They were studying several acetogenins found in several plant species. In their study, they inoculated mice with Lewis lung carcinoma cancer cells. One third received nothing; other third received chemotherapy drug adriamycin, and the final third received the principal acetogenin of Annona muricata L., called ‘annonacin’ (in dose of 10 mg/kg). After 2 weeks, 5 of the 6 of the untreated control group were still alive, so that the size of their lung tumor was measured. The group treated with adriamycin showed a 54.6% reduction of the tumor mass relative to the control group, but 50% (3 of 6) of the animals had died due to toxicity. Those mice who received annonacin where all alive, and the tumor had been inhibited in 57.9% --slightly better than with adriamycin—and without toxicity. This led the researchers to conclude that annonacin resulted less toxic in mice.

Considering antitumoral activity and toxicity, annonacin could be used in order to develop a potential anticancerous agent. It is important to note, however, that annonacin only inhibited the normal growing of lung tumors during this period of 2 weeks; but it did not eradicate tumors nor stopped its growing at all. Research in cancer is continuing with these important plants and their chemical products as several pharmaceuticals and universities continue researching, testing, patenting, and trying to synthesize these chemicals in new drugs for chemotherapy. Additionally, researchers have reported that NADH dehydrogenase inhibitors can suppress HIV infection. Because this is a familiar propriety to annonaceous acetogenins, the University of Purdue has sent several acetogenins found in Annona muricata L. and other plans of the genus Annona to the Anti-AIDS Monitoring Program of the National Institute of Health. The investigative efforts still continue in this field. More than 350 annonaceous acetogenins have been isolated from 37 plant species. Near 50% of more than 80 Annonaceae species tested are significantly bioactive and are worthy for fractioning; hence, these kind of compounds can be expected to continue growing exponentially in the future, provided that monetary support can be achieved for such studies.  

Other uses : Reforestation / Restoration . Annona muricata L. is a species with potential for productive reforestation in degraded zones in the forest. Recovery of degraded lands. This plant species has been employed in order to rehabilitate abandoned mining sites. Dune fixation. Green fences in agro habitats. Shadow / Refuge. Against winds. Ornamental. Melliferous (flowers). Apiculture.  

Chemical Compounds : Scientific studies about bioactive compounds in Annona muricata L. begun in 1940 decade. Since then, a series of active principles and phytochemicals have been found and characterized, and their natural medical action has been validated through scientific research.  
annocatalin annohexocin annomonicin annomontacin annomuricatin A & B annomuricin A through E annomutacin annonaceous acetogenins annonacin (multiple iso, cis, one, etc.) annonacinone annopentocin A through C cis-annonacin cis-corossolone cohibin A through D corepoxylone coronin corossolin corossolone donhexocin epomuricenin A & B gigantetrocin A & B gigantetrocin gigantetrocinone gigantetronenin goniothalamicin iso-annonacin javoricin montanacin montecristin muracin A through G muricapentocin muricatalicin muricatalin muri-catenol muricatetrocin A & B muricatin D muricatocin A through C muricin H muricin I muricoreacin murihexocin 3 murihexocin A through C murihexol murisolin robustocin rolliniastatin 1 & 2 saba-delin solamin uvariamicin I & IV xylomaticin
  Alkaloids: annonain and annoniin. In the bark: muricin (possibly des-N-methylisocoridin or des-N-methylcoridin) and muricinin (C₁₈H ₁₉O₄, possibly des-N-methylcorituberin). Muricin is believed to be identical to reticulin. The bark is rich in hydrocyanic acid, whereas only short amounts are found in leaves and roots and traces in fruits. Muricin and muricinin have insecticide properties.   


6. DOSE AND CONTRAINDICATIONS

Dose :
-           Taylor (2002) reported, for therapeutic use, a dose of 5 to 7 grams per day as capsules or tablets, divided in 3 or 4 doses. -           Instead of the previously mentioned, Taylor also reports the use of a standard infusion (one cup, two or three times per day) or a standard tincture (2 mL to 4 mL, 3 times per day).  

Contraindications :
-           Individuals with arterial hypotension (low arterial tension) should avoid its use. The hypotensive, vasodilator, and cardiodepressor effects of Annona muricata L., already known in animals, make it contraindicated for individuals taking antihypertensive medicines. Ask your physician before taking any product of Annona muricata L. in order to control your blood pressure and fix the dose according to your requirements.
-           Medicines derived from Annona muricata L. could be contraindicated in combination with substances inhibitory of MAO and with some prescription antidepressive medicines. A study in which a bark-stem extract was administered intragastrically to rats (100 mg/kg) reported an increase in the dopamine, norepinefrin and monomin oxidase activity, as well as an inhibition in serotonin secretion in rats with induced stress. Although it needs to be proved in humans, if you are taking any prescription antidepressive or any drug inhibitory of MAO, consult your physician before taking Annona muricata L.
-           Derivatives from extracts of Annona muricata L. could cause certain sedation or somnolence. If it is true that, in a study performed in mice it has not been showed toxicity of Annona muricata L. leaves alcohol extracts at a low concentration (100 mg/kg) nor side effects, at a higher concentration (300 mg/kg), mice were observed to reduce their exploratory activities and experiment certain slight abdominal contractions. If you feel certain sedation or somnolence, you will reduce dose.
-           Avoid the use in pregnant women. Research performed in rats have shown that some of the active principles found in the leaves and bark of Annona muricata L. have a stimulant activity of uterus, so that it could be self-defeating for pregnancy. -           Prolonged used of natural medicines derived from Annona muricata L., especially when used in order to treat chronic diseases, could lead the elimination of beneficial bacteria present in the digestive tract. Effectively, antibacterial properties of Annona muricata L. have been proved in vitro. If you decide to use this plant for more than 30 days, it is recommended to supplement your diet with probiotics and digestive enzymes.
-           Administered in very high doses, Annona muricata L.-based medicines could cause nausea or vomit. Effectively, in a study performed in pigs, some active principles in Annona muricata L. were shown to have certain emetic (vomitive) properties. If this occurs, you will reduce dose up to a level in which these problems cease.  


Drug Interactions:
-           No drug interactions have been reported. However, hypotensive (diminishing of blood pressure) and cardiodepressor effects of Annona muricata L. could interact (potentiate) hypotensive and cardiodepressor medicines. More research is needed related to this; meanwhile, ask your physician if you are taking these kind of medicines. -           On the other hand, Annona muricata L. could also potentiate the effects of sedatives and antidepressives and interfere with drugs inhibitory of MAO. Ask always your physician.  

7. AGRONOMIC PRACTICES  

Cultivation : Annona muricata L. is cultivated in several tropical countries. In the United States, this plant species only grows in Florida, but just a little. In Brazil, there exist near 2 000 hectares. The small trees require much heat, humidity, and water and do not survive with temperatures under 0º C. Annona muricata L. can grow under direct sunlight or slight shadow. In tropical countries, this plant species proliferates from sea level to a little more than 1 000 m asl, particularly in humid regions. It does not tolerate floodable soils and its roots are superficial, so that this plant species does not require deep soils.  

Propagation : Generally, Annona muricata L. propagates by seeds. It also propagates by graft and shoots. Seeds can be stored for several months before seeding. Seed germination generally takes 3 weeks, although under none optimal conditions germination can delay for 2 or 3 months. Six-to-nine-month-old seedlings are large enough in order to be planted in soil or used as stump for grafting. For grafting, Annona reticulata , Annona montana or Annona glabra have been satisfactorily tested as stump. Annona glabra has a dwarfing effect. Grafts on Annona squamosa and Annona cherimolia live for a short time, in spite of the fact that Annona muricata L. is a good stump for Annona squamosa in Ceylon and India.  

Yield : Pretty low. Roughly reaches 7 metric tons per hectare when planted from seeds. Individual trees yield is very variable, which suggest the necessity of a clone selection of the best specimens in order to improve fruit yield. Fructification tends to be continuous along a year, although in any particular region there exists a main harvest season. Trees start fructification between 3 and 5 years old.  

Problems : Sometimes a low fruit formation is present as a result of poor pollination, adverse climatic conditions, and attack of a series of plagues and diseases (FAO 1986).   

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