Soursop

Generic name: Annona Muricata L.
Brand names: Araticum-grande, Araticum-manso, Cachiman épineux, Coração-de-rainha, Corossol épineux, Graviola, Guanábana, Guanábano, Jaca-de-pobre, Jaca-do-Pará, Sauersack, Sirsak, Stachelannone

Usage of Soursop

Clinical trials are lacking(Cercato 2015) and unlikely to be forthcoming due to the toxicity of annonacin.

Anti-inflammatory effects

Animal data

In obese mice fed A. muricata leaf extract for 24 weeks, no significant changes were observed in tumor necrosis factor alpha (TNF-alpha) or interleukin 6 (IL-6); however, the low and medium doses (50 and 100 mg/kg, respectively) significantly increased IL-10 compared with untreated obese controls.(Sasso 2019) In contrast, significant decreases in interferon-gamma and TNF levels were observed with A. muricata leaf extract fractions in mice infected with Toxoplasma gondii.(Miranda 2021) Topical application of an aqueous extract of A. muricata leaves in an acute cutaneous inflammation model significantly improved ear weight, edema, and myeloperoxidase activity compared with controls (P<0.001 for each). Both the extract and the positive control (dexamethasone) reduced leukocyte infiltration as well as dermal thickness (P<0.001 for each) compared with the vehicle group.(Cercato 2021)

Antimicrobial/Antiviral/Molluscicidal activity

Animal and in vitro data

The oleoresin from A. muricata leaf demonstrated greater inhibitory and bactericidal activity than streptomycin and ampicillin against several pathogenic species, including Bacillus cereus, Enterobacter cloacae, Pseudomonas aeruginosa, Salmonella enterica, and Staphylococcus aureus. The oleoresin minimum inhibitory concentrations (MICs) ranged from 0.0025 to 0.01 mg/mL, whereas those for the 2 positive controls ranged from 0.05 to 0.5 mg/mL. Similarly, the minimum bactericidal concentrations for the A. muricata leaf oleoresin were 0.005 to 0.04 mg/mL and for the 2 positive controls were 0.1 to 0.5 mg/mL.(Cagnini 2022) Antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) was demonstrated by A. muricata, with the highest activity exhibited by stem extracts (aqueous and ethanolic) and the lowest by the seed (aqueous) and peel (ethanolic). The lowest MIC (0.25 mg/mL) was observed with the ethanolic root extract, with MICs of other root, stem, seed, and leaf extracts ranging from 1 to 16 mg/mL. In comparison, ampicillin, streptomycin, and tetracycline MICs were 32, 64, and 32 mg/mL, respectively. Four of 10 A. muricata extracts investigated demonstrated antagonistic effects on ampicillin activity against MRSA, while many of the extracts potentiated the effects of streptomycin and tetracycline by a range of 1- to 32-fold, with the aqueous root extract having the highest synergistic effect.(Neglo 2021)

In a study to determine A. muricata antibacterial and antifungal activities against foodborne disease microorganisms, fungicidal and fungistatic activity, although present, was lower for A. muricata leaf oleoresin than bifonazole and ketoconazole. Minimum fungicidal concentration for the leaf oleoresin ranged from 5 to 40 mg/mL compared with 0.2 to 3.5 mg/mL for the controls.(Cagnini 2022)

In another study, activity against both a standard strain and a clinical isolate of herpes simplex virus was demonstrated by an ethanolic extract of A. muricata stem bark.(Padma 1998)

Antiparasitic activity of A. muricata has been demonstrated for several pathogens. Acetogenins extracted from the fruit pericarp were responsible for antileishmanial activity demonstrated in an in vitro experiment.(Jaramillo 2000) Another study demonstrated in vitro activity of the leaf extract against some Leishmania species and Trypanosoma cruzi.(Osorio 2007) Both therapeutic and prophylactic effects were observed with A. muricata leaf extract for trichinellosis both in vitro as well as in mice infected with Trichonella spiralis,(El-Wakil 2021) while the ethanolic extract and some of its fractions demonstrated activity against T. gondii in vitro. These results were confirmed in vivo, with increased survival rates and decreased parasite loads that appeared to be independent of phenolic content.(Miranda 2021) Antimalarial effects of A. muricata leaf extract have also been demonstrated using a Plasmodium berghei severe malaria model in mice.(Onohuean 2021)

Ethanolic leaf extracts of A. muricata have shown molluscicidal activity thought to be, at least in part, due to the annonacin acetogenins.(Luna 2006, Moghadamtousi 2015)

Antioxidant effects

Animal data

The oxidative stress biomarker malondialdehyde was significantly reduced with an acetogenin-rich fraction of A. muricata in a rat benign prostatic hyperplasia (BPH) model, and other antioxidant activities were increased.(Ogbu 2020) Similarly, potent antioxidant power was detected with an aqueous A. muricata leaf extract in an acute cutaneous inflammation mouse model in which radical formation, scavenging activity, lipoperoxidation, and cellular release of reactive oxygen species were significantly improved with the extract compared with controls (P<0.001).(Cercato 2021)

Benign prostatic hyperplasia

Animal data

In a BPH rat model, 7-day administration of an acetogenin-rich fraction of A. muricata leaves significantly reduced prostate-specific antigen levels, prostate weight, relative prostate weight, and prostate protein compared with untreated controls (P<0.05). The extract produced similar results to the positive control (dutasteride). Antioxidant effects appeared to be a primary mechanism.(Ogbu 2020)

Cancer

In vitro data

Studies identifying the specific acetogenin compounds in the seeds, leaves, root, and stem bark have explored the potent cytotoxicity of these compounds. Activity against certain human cancer cell lines has been demonstrated in vitro.(Chang 2001, Kim 1998a, Kim 1998b, Liaw 2002, Rieser 1996, Tundis 2017, Zeng 1996)

Diabetes and metabolic disorders

Animal and experimental data

The ethanolic bark extract has been shown to possess antidiabetic and hypolipidemic effects in rats.(Cercato 2015) A systematic review that explored the effects of A. muricata on hyperglycemia failed to identify any clinical studies that met inclusion criteria; therefore, the review included only rodent (n=8 studies), in vitro (n=6), and in silico studies (n=1). Results from different doses and from different plant parts demonstrated a significant reduction in blood glucose with soursop administered (predominantly orally) for 28 to 48 days compared with controls. Its effect was reported to be similar to that of insulin. Intestinal glucose absorption was decreased (P<0.05) while muscle tissue glucose absorption was increased. Significant improvements in basal insulin levels (P<0.001) and overall insulin levels (P<0.05) in a diabetic model was also demonstrated with the extract compared with controls. In vitro studies found that pulp- and leaf-based extracts of soursop exhibited greater enzymatic inhibition than acarbose and greater alpha-glucosidase inhibition than alpha-amylase. Meanwhile, the in silico study reported that the enzymatic inhibition of soursop is not competitive and pointed to acetogenins as a main active component.(Martín del Campos-Rayas 2022)

An aqueous A. muricata leaf extract given for 24 weeks to obese mice led to significant weight loss compared with both the normal control (P=0.003) and obese untreated controls (P=0.034), particularly with a 100 mg/kg extract dose. A lower conversion of feed into body mass was noted in this group. No significant changes were noted in fasting glucose, total cholesterol, or HDL; however, the 150 mg/kg dose significantly decreased LDL in a dose-dependent manner (P=0.038) and lowered the atherogenic index (P=0.025) compared with untreated obese controls.(Sasso 2019)

Mosquito larvicidal activity

In vitro data

Potent larvicidal activity by the saline extract of A. muricata seed kernels was demonstrated against mosquito vectors of pathogenic diseases, including Aedes aegypti (dengue, yellow fever, Zika virus), Anopheles stephensi (malaria), Culex quinquefasciatus (filariasis), and Culex tritaeniorhynchus (Japanese encephalitis). It showed lower activity against the nontarget species Chironomus costatus.(Parthiban 2020)

Spinal cord injury

Animal data

In a study investigating therapeutic effects and antioxidant properties of A. muricata on secondary cell damage after experimental spinal cord injury, pretreatment with A. muricata leaf extracts 7 days prior to induced spinal cord trauma in rats significantly improved biochemical and histopathological structure compared with untreated controls; however, paraplegia remained evident in all untreated and treated groups.(Keskin 2022)

Soursop side effects

Information is lacking. A single study evaluated the hemagglutination effect of lectin isolated from the seeds.(Damico 2003) The clinical importance of this finding is unclear.

Before taking Soursop

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking. Toxic neurological effects have been demonstrated in rats(Lannuzel 2006) and cytotoxicity has been demonstrated in vitro.(Chang 2001, Kim 1998a, Kim 1998b, Liaw 2002, Rieser 1996, Zeng 1996) Annonacin crosses the blood-brain barrier.(Lannuzel 2006)

How to use Soursop

Clinical trial data are lacking to support specific dosing recommendations.

Warnings

As an indication of potential toxicity, one report estimated that the amount of annonacin ingested by an adult eating one fruit daily for a year is comparable with the intravenous dose used to induce brain lesions in rats. One fruit contains approximately 15 mg of annonacin, and a can of commercial nectar contains 36 mg.(Champy 2005)

Based on an epidemiological observation of higher parkinsonism rates among populations regularly consuming the fruits and traditional medicines of the Annonaceae family, especially graviola, a group of researchers has investigated the plausibility of a causal relationship. Among individuals presenting with atypical parkinsonism on the Caribbean island of Guadeloupe, the majority were unresponsive to levodopa, with 1 in 2 patients reporting a high consumption of fruit and decoctions of A. muricata leaves.(Lannuzel 2006, Lannuzel 2007) Patients younger than 65 years of age had some resolution of symptoms (eg, gait disorders, bradykinesia, rigidity) when consumption was stopped.(Lannuzel 2002, Lannuzel 2003, Lannuzel 2007)

Annonacin and the alkaloids reticuline and coreximine have been evaluated for toxic effects on rat dopaminergic neurons in vitro. The mechanisms of action remain unclear but are suspected to involve the inhibition of dopamine uptake, as well as effects on neuronal energy production and mitochondrial respiration.(Kotake 2004, Lannuzel 2006, Lannuzel 2007) Nigral and striatal degeneration in rats has been demonstrated(Champy 2004, Champy 2005) and alkaloid-induced cell death was also observed.(Lannuzel 2002, Lannuzel 2007)

Ethanolic extracts from A. muricata seeds were highly active in brine shrimp lethality testing. The fruit seeds are considered toxic and unsuitable for use as animal fodder.(Rieser 1996)

What other drugs will affect Soursop

None well documented.

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