05/05/2022

Focus on the research by Mutakin, M. et al. "Pharmacological Activities of Soursoup

With its scientific name Annona muricata, graviola is a plant widely used in traditional medicines to support and prevent many diseases. Known in particular for its acetogenins, graviola seems to have pharmacological activities that have been extensively tested, in vitro and in vivo, by modern science. Focus on the review by Mutakin, M. et al. of 49 studies published between 1981 and 2021 [1].

What is graviola?

Commonly known as Guanabana or soursop, due to the sweet and sour taste of its fruit, graviola is a fruit plant belonging to the Annonaceae family. It is widely cultivated in tropical and subtropical regions, such as Southeast Asia, South America and the rainforests of Africa.

The different parts of this plant are known and traditionally used for different benefits: the seeds for parasitic infections; the fruit for arthritis, nervous disorders and diarrhoea; and the leaves for cystitis and insomnia [2,3].

Annona Muricata contains various substances. These include acetogenins (annomuricins and annonacin), alkaloids (corex- imine and reticuline), flavonoids (quercetin) and vitamins. Each of these substances has an effect on our body [1].

Key points of the review "Pharmacological Activities of Soursop

The review published in January 2022 by Mutakin, M. et al. looks at Graviola's chemical compounds, traditional uses and pharmacological activities based on the analysis of 49 studies published between 1981 and 2021.

According to studies, Graviola is traditionally used for skin diseases, respiratory diseases, fever, diarrhoea, bacterial infections, diabetes, hypertension, headaches and insomnia. 

The main pharmacological activities demonstrated in the studies are: anti-cancer (25%), anti-ulcer (17%), anti-diabetic (14%), anti-protozoal (10%), anti-diarrhoea (8%), antibacterial (8%), antiviral (8%), anti-hypertensive (6%) and wound healing (4%).

Explanations.

Traditional medical uses of graviola

The review by Mutakin, M. et al[1] includes a number of studies that have looked at the traditional uses of the different parts of Graviola. These studies highlighted the following uses and characteristics:

• respiratory and skin diseases [4].
• stomach ache [5,6].
• cystitis [2]
• diabetes [4,5,6]
• diarrhoea [2,7] and dysentery [3]
• fever [2,4]
• bacterial, fungal [2] and parasitic infections [4,5,6]
• analgesic [4] and sedative [2,4] activities
• anthelmintic, antispasmodic, anti-hypertensive and anti-inflammatory activities [2,4].

 

Pharmacological activities of graviola

Graviola is widely used as a traditional medicine because of its pharmacological properties. These properties were studied in 49 research papers, reviewed by Mutakin, M. et al [1] and included anti-cancer (25%), anti-ulcer (17%), anti-diabetic (14%), anti-protozoal (10%), anti-diarrhoeal (8%), anti-bacterial (8%), anti-viral (8%), anti-hypertensive (6%) and wound healing (4%) properties.

According to studies, the anticancer activity of Graviola is related to several mechanisms depending on the parts of Annona muricata used. Fruit, stem, seed and twig extracts help inhibit matrix metalloproteinases (MMPs) [8]. Leaf, twig and root extracts help to inhibit the growth of cancer cells [9, 13]. In the case of lung [10], colorectal [11] and breast cancer [12], it seems that the use of Graviola leaf extract induces apoptosis. In addition, several compounds of Annonca muricata show antiproliferative effects: acetogenins in the case of prostate [14] and colorectal cancer [13], annomuricin E [13], annonacin [15].

Studies have also been carried out on the anti-ulcer effect of Graviola. This effect would be due to the high concentration of flavonoids, tannins and phenolic acids, which have effects due to their antioxidant, anti-inflammatory and gastroprotective properties [1]. Several studies demonstrate gastric protective activities by reducing the ulceration process through activation of prostaglandin synthesis and suppression of aggressive factors in the gastric mucosa [16]. Other studies have demonstrated anti-ulcer activity through the regulation of Bax and Hsp70 [17].  

The anti-diabetic activity of Annona Muricata is thought to be due to the antioxidant properties contained in the fruits and leaves of Graviola [18] [4] as well as to the flavonoids that inhibit the activity of α-glucosidase suppressing carbohydrate hydrolysis and glucose uptake and inhibiting the metabolism of carbohydrates to glucose [19].

Similarly, the anti-diarrhoea activity of Annona Muricata is thought to be due to the flavonoids, triterpenoids and saponins that play a role in inhibiting intestinal motility and secretions that cause diarrhoea [20].

As for the action on hypertension, research has shown that extracts of Annona muricata fruit and leaves have anti-hypertensive properties [18], particularly by lowering blood pressure [21].

Finally, studies on Graviola have demonstrated antibacterial and antiviral activities. One study reported that bioactive compounds of Annona muricata, such as alkaloids, attack the bacterial membrane (plasma and outer membrane), resulting in broad spectrum antibacterial activity [22]. Several studies have demonstrated antiviral activity of Annona muricata through the presence of rutin [23]. Also, acetogenins can be considered as antiviral agents, especially against SARS-CoV-2, and should be studied in vitro and in vivo [24].

Toxicity and danger of graviola

Several studies have been conducted to determine the toxicity of Annona muricata. In general, the level of toxicity depends on the part of the plant as well as the solvent. Indeed, one study showed that the aqueous extract of A. muricata had an LD50 of > 5 g/kg, while that of the ethanolic extract was > 2 g/kg. Another study reported an LD50 of >211 mg/kg for the aqueous leaf extract, which is above the recommended daily consumption limit for humans. Another study reported that acetogenin is a neurotoxin which at high doses can be neurotoxic and cause neurodegenerative disorders. Some alkaloids in A. muricata are also thought to affect nerve cells.

However, the doses studied that produced negative effects are equivalent to eating one fruit every day for one year. Thus, research on annonacin neurotoxicity indicates that neurodegenerative disorders caused by these compounds occur as a result of continuous exposure or consumption.

Therefore, in order to avoid the development of neurodegenerative disorders that could be caused by Annona muricata compounds, excessive and continuous consumption is not recommended. Furthermore, further research and clinical trials on pure compounds are needed to ensure the safety of Annona muricata as a potential medicine for various diseases.

 

N.B.: The scientific research presented is for information purposes only. This information should not be read to recommend or endorse specific products. Food supplements are not intended to diagnose, treat, cure or prevent any disease.

 

 

Sources

[1] Mutakin, M., Fauziati, R., Fadhilah, F. N., Zuhrotun, A., Amalia, R., & Hadisaputri, Y. E. (2022). Pharmacological Activities of Soursop (Annona muricata Lin.). Molecules, 27(4), 1201.

[2] Moghadamtousi, S.Z.; Fadaeinasab, M.; Nikzad, S.; Mohan, G.; Ali, H.M.; Kadir, H.A. Annona muricata (Annonaceae): A Review of Its Traditional Uses, Isolated Acetogenins and Biological Activities. Int. J. Mol. Sci. 2015, 16, 15625-15658.

[3] De Souza, E.B.R.; Da Silva, R.R.; Afonso, S.; Scarminio, I.S. Enhanced Extraction Yields and Mobile Phase Separations by Solvent Mixtures for the Analysis of Metabolites in Annona muricata L. Leaves. J. Sep. Sci. 2009, 32, 4176-4185.

[4] Adewole, S.O.; Ojewole, J.A.O. Protective Effects of Annona muricata Linn. (Annonaceae) Leaf Aqueous Extract on Serum Lipid Profiles and Oxidative Stress in Hepatocytes of Streptozotocin-Treated Diabetic Rats. Afr. J. Tradit. Complement. Altern. Med. 2009, 6.

[5] Gavamukulya, Y.; Wamunyokoli, F.; El-Shemy, H.A. Annona muricata: Is the Natural Therapy to Most Disease Conditions Including Cancer Growing in Our Backyard? A Systematic Review of Its Research History and Future Prospects. Asian Pac. J. Trop. Med. 2017, 10, 835-848.

[6] Ssenyange, C.W.; Namulindwa, A.; Oyik, B.; Ssebuliba, J. Plants Used to Manage Type Ii Diabetes Mellitus in Selected Districts of Central Uganda. Afr. Health Sci. 2015, 15, 496-502.

[7] Shaw, D.; Graeme, L.; Pierre, D.; Elizabeth, W.; Kelvin, C. Pharmacovigilance of Herbal Medicine. J. Ethnopharmacol. 2012, 140, 513-518.

[8] Drishya, G.; Nambiar, J.; Shaji, S.K.; Vanuopadath, M.; Achuthan, A.; Kumar, A.; Alias, A.; Sherif, A.; Joseph, C.; Divya, P.; et al. RECK and TIMP-2 mediate inhibition of MMP-2 and MMP-9 by Annona muricata. J. Biosci. 2020, 45, 1

[9] Pieme, A.A.; Kumar, G.G.; Dongmo, S.S.; Moukette, M.M.; Boyoum, F.F.; Ngogang, Y.Y.; Saxena, K.K. Antiproliferative Activity and Induction of Apoptosis by Annona muricata (Annonaceae) Extract on Human Cancer Cells. BMC Complement. Altern. Med. 2014, 14, 1-10.

[10] Moghadamtousi, S.Z.; Kadir, H.A.; Paydar, M.; Rouhollahi, E.; Karimian, H. Annona muricata Leaves Induced Apoptosis in A549 Cells through Mitochondrial-Mediated Pathway and Involvement of NF-κB. BMC Complement. Altern. Med. 2014, 14, 1-13

[11] Abdullah, M.; Syam, A.F.; Meilany, S.; Laksono, B.; Prabu, O.G.; Bekti, H.S.; Indrawati, L.; Makmun, D. The Value of Caspase-3 after the Application of Annona muricata Leaf Extract in COLO-205 Colorectal Cancer Cell Line. Gastroenterol. Res. Pract. 2017, 2017, 165

[12] Kim, J.Y.; Dao, T.T.P.; Song, K.; Park, S.B.; Jang, H.; Park, M.K.; Gan, S.U.; Kim, Y.S. Annona muricata Leaf Extract Triggered Intrinsic Apoptotic Pathway to Attenuate Cancerous Features of Triple Negative Breast Cancer MDA-MB-231 Cells. Evid.-Based Complement. Altern. Med. 2018, 2018, 916

[13] Indrawati, L.; Ascobat, P.; Bela, B.; Abdullah, M.; Surono, I.S. The Effect of an Annona muricata Leaf Extract on Nutritional Status and Cytotoxicity in Colorectal Cancer: A Randomized Controlled Trial. Asia Pac. J. Clin. Nutr. 2017, 26, 606-612.

[14] Yang, C.; Gundala, S.R.; Mukkavilli, R.; Vangala, S.; Reid, M.D.; Aneja, R. Synergistic Interactions among Flavonoids and Acetogenins in Graviola (Annona muricata) Leaves Confer Protection against Prostate Cancer. Carcinogenesis 2015, 36, 656-665.

[15] Yap, C.; Subramaniam, K.; Khor, S.; Chung, I. Annonacin Exerts Antitumor Activity through Induction of Apoptosis and Extracellular Signal-Regulated Kinase Inhibition. Pharmacogn. Res. 2017, 9, 378.

[16] Bento, E.B.; de Brito Júnior, F.E.; de Oliveira, D.R.; Fernandes, C.N.; de Araújo Delmondes, G.; Cesário, F.R.A.S.; de Sousa Rodrigues, C.K.; dos Santos Sales, V.Antiulcerogenic Activity of the Hydroalcoholic Extract of Leaves of Annona muricata Linnaeus in Mice. Saudi J. Biol. Sci. 2016, 25, 609-621.

[17] Harsha, C.; Banik, K.; Bordoloi, D.; Kunnumakkara, A.B. Antiulcer Properties of Fruits and Vegetables: A Mechanism Based Perspective. Food Chem. Toxicol. 2017, 108, 104-119.

[18] Adefegha, S.A.; Oyeleye, S.I.; Oboh, G. Distribution of Phenolic Contents, Antidiabetic Potentials, Antihypertensive Properties, and Antioxidative Effects of Soursop (Annona muricata L.) Fruit Parts in Vitro. Biochem. Res. Int. 2015, 2015, 347673.

[19] Hardoko, Y.H.; Halim, Y.; Wijoyo, S.V. In Vitro Antidiabetic Activity of "Green Tea" Soursop Leaves Brew through α-Glucosidase Inhibition. Int. J. PharmTech Res. 2015, 8, 30-37.

[20] Afroz, N.; Ahsanul Hoq, M.; Jahan, S.; Mainul Islam, M.; Ahmed, F.; Shahid-Ud-Daula, A.F.M.; Hasanuzzaman, M. Methanol Soluble Fraction of Fruits of Annona muricata Possesses Significant Antidiarrheal Activities. Heliyon 2020, 6, e03112.

[21] Nwokocha, C.R.; Owu, D.U.; Gordon, A.; Thaxter, K.; Mccalla, G.; Ozolua, R.I.; Young, L. Possible Mechanisms of Action of the Hypotensive Effect of Annona muricata (Soursop) in Normotensive SpragueDawley Rats. Pharm. Biol. 2012, 50, 1436-1441.

[22] De Pinto, N.C.C.; Campos, L.M.; Evangelista, A.C.S.; Lemos, A.S.O.; Silva, T.P.; Melo, R.C.N.; de Lourenço, C.C.; Salvador, M.J.; Apolônio, A.C.M.; Scio, E.; et al. (Soursop) Extract Targets the Cell Membranes of Gram-Positive and Gram-Negative Bacteria. Ind. Crops Prod. 2017, 107, 332-340.

[23] Balderrama-Carmona, A.P.; Silva-Beltrán, N.P.; Gálvez-Ruiz, J.C.; Ruíz-Cruz, S.; Chaidez-Quiroz, C.; Morán-Palacio, E.F. Antiviral, Antioxidant, and Antihemolytic Effect of Annona muricata L. Leaves Extracts. Plants 2020, 9, 1650.

[24] Prasad, S.K.; Pradeep, S.; Shimavallu, C.; Kollur, S.P.; Syed, A.; Marraiki, N.; Egbuna, C.; Gaman, M.A.; Kosakowska, O.; Cho, W.C.; et al. Evaluation of Annona muricata Acetogenins as Potential Anti-SARS-CoV-2 Agents Through Computational Approaches. Front. Chem. 2021, 8, 1-7.