Pharmacological potential of Manilkara zapota (L.) P. Royen (Sapodilla): a narrative review

Abstract

Herbal medicine is safe and effective in treating various diseases. Traditional herbal medicine plays a tremendous role in treatment of various diseases and accompanying complications, hence herbal medicine requires remarkable attention in further research for the development of numerous active formulations for treatment of health troubles. The plant needs special consideration for development and research of unidentified compound and characterization of novel active molecules that overcome multiple pathological abnormalities. The genus Manilkara contains 135 plants around the world. This overview discusses all the virtues of most important and commonly used plant Manilkara zapota (L.) P. Royen (M. zapota), also known as Sapodilla. M. zapota has various traditional beneficial effects in treatment of various diseases and disorders dating back to prehistoric times and used in ancient traditional system of herbal medicine.

1. INTRODUCTION

Plants are the original part of environment and also help make our life on Earth incredible by providing food, oxygen, medicine, as well as multiple economic benefits. Plants have various active components that play a crucial role in treating various diseases. A plant's botanical importance is responsible for introducing a complete array of biological activities into a plant.¹ The use of herbal medicines, which can be used alone or in combination with prescription medicines to treat diseases.² The majority of pharmacological molecules are derived from natural resources. For example, Food and Drug Administration approved artesunate for malaria treatment in 2020.³ For human safety, World Health Organization (WHO) supports use of traditional medicine. Traditional medicine, as defined by WHO, is body of knowledge, skills, practices based on theories, and experiences native to different cultures, whether explainable or not, that are also used to maintain health, prevention, diagnosis, improvement or treatment of diseases. Around 80% of world's population uses traditional medicine for basic health care and finds relief from their ailments.⁴ Traditional Chinese Medicine (TCM), a medical philosophy that is at least 23 centuries old, aims to prevent or treat disease by maintaining or restoring Yin-Yang balance.⁵ Unani medicine is a conventional healing and health maintenance method practiced in South Asia.⁶ One of the oldest health systems still in use today, Ayurveda is based on theoretical practices and fundamental principles. The scope of Ayurveda was actually more limited to botany, chemistry and pharmacology of medicinal plants.⁷

Recent research studies have focused on use of whole plants and other parts of plants to treat human ailments. There are many historical examples from present day, especially from India. Humans have revered and respected plants, retained them as inherited resources and used reserve resources for food.⁸ Ancient medicines are an elementary and fundamental part of alternative health care used worldwide. In ancient times, herbs were used based on practitioner's skill, knowledge and experience, while modern drug therapy has worked on basis of efficacy and safety.⁹ This review includes taxonomy, traditional knowledge, phytochemicals, pharmacological activity and therapeutic information by Manilkara zapota (L.) P. Royen.

Manilkara zapota (L.) P. Royen (M. zapota) belonging to Sapotaceae family.¹⁰ M. zapota is native to Central America, southern Mexico, and Caribbean.¹¹ It is cultivated throughout India.¹²

2. SYNONYMS/VERNACULAR NAMES

M. zapota is also known as Chikoo, Naseberry, Sopota, Sapodilla, Achras-zapotilla, Mimusopusmanilkara, and Achrassapota. The species name is Sapota-zapotilla, Sapota and Sapote.¹⁰ Achras is a controversial name.¹³ Manilkara zapotilla Gillys is earliest known name of Sapodilla.¹⁴ M. zapota is known by native names of different.^10,12,15

3. BOTANICAL DESCRIPTION

M. zapota is evergreen tree, about 20 m in height and round canopy shape due to the profuse branching system. Plant parts seep out milky latex known as “Chicle”.

3.1. Root

Roots are shallow.¹⁶

3.2. Leaves

Leaves are evergreen, pinkish in colour then turns to dark green at maturity stage. Secondary veins are made angle with midrib.

3.3. Flowers

Flowers are bisexual, small in size and bell shaped.

3.4. Fruits

Sapodilla is brown colour berry circular and oval in shape, fruit size is about 5 to 10 cm in size. Unripe fruit is hard, pulpy, and juicy fruit convert when ripe.¹⁷

3.5. Seeds

Seeds are hard brown or black colour with white margin.

3.6. Reproductive biology

It shows self-incompatibility. Flowers are bisexual and cross pollination can occur easily. Stigma grows beyond corolla which cause pollination easily.¹⁸

4. PHYTOCONSTITUENTS

M. zapota showed presence of phenols, steroids, saponins and glycosides in low polar chloroform and high polar methanol extract.¹⁹ Maximum number of phytoconstituents were present in medium polar acetone extract.²⁰ Various active constituents and chemical structures are presented in Table 1. Beside flavonoids and polyphenols M. zapota contains quercitol, myricetin-3-O-α-rhamnoside, sapotin, sapotinine, saccharose, (+)catechin, (+)-gallocatechin, myricitrin, polyphenyl oxidase, β-carotene, dihydromyricetin, 4-O-galloylchlorogenic acid, oleanolic acid, n-octacosane and two sterols-β-sitosterol, n-triacontane, and potassium, malic acid, adipic acid, salicylic acid, syringic acid, chlorogenic acid, threonic acid, proline, serine, threonine, valine, vanillin, guaiacol.^11,14,21

Table 1.

Various active constituents of M. Zapota (Sapodilla)

Sr. No.	Part of plant	Active constituents
1.	Root	Arginine, Lysine22
2.	Seed	Methyl chlorogenate, 4-O-galloychlorogenic acid, Lupeol acetate, oleanolic acid, Apigenin-7-O-a-L-rhamnoside, Methyl 4-O-galloylchlorogenate, Caffeic acid, n-triacontane, n-octacosane, stigmasterol and 2 sterols-β-sitosterol22
3.	Leaves	Rhamnose, Glucose, Sucrose, Succinic acid, Malic acid, Adipic acid, 3-Oxoadipic acid, Salicylic acid, 3,4-dihydrobenzoic acid, Vanillic acid, Gallic acid, Caffeic acid, Ferulic acid, Syringic acid, Chlorogenic acid, Afzeleehic, Epicatechin, Epigallocatechin Myricetin-3-O-Rhamnoside, Laricitrin-3-O-rhamnoside, Prodelphinidin B, 2-Hydroxybenzaldehyde, Guaiacol, Pyroglutamic acid, Thronic acid, Vanillin, 3-Hydrxy coumarin, Shikimic acid, Aesculetin, Quinic acid, Norathyriol, Hydroquinone glucuronide, Leucodelphinidin, Apigenin-7-O-α-L-rhamnoside 3-glucogallic acid, 3-p-Coumaroyl-Quinic acid, Oleanolic acid, 3-O- Galloyl quinic acid, Lupeol acetate, Erythrodiol22,23
4.	Fruit	Catechin, Quercetin, Kaempferol, Chlorogenic acid, p-hydrobenzoic, Ellagic Acid, ferulic Acid, Trans cinnamic acid, Lucopine,30 Epicatechin, Leucocyanidin, Leucodelphinidin, Leucopelargonidin and Gallic acid15

5. NUTRITIONAL VALUE OF M. ZAPOTA (SAPODILLA) FRUIT

Because of good source of sugar from M. zapota (12%-14%), sapodilla fruit is very healthy.²⁴

6. TRADITIONAL USES OF M. ZAPOTA

(a) M. zapota strengths intestine, boosts immunity and prevents bacterial infections, anaemia. (b) It is highly useful in pregnancy. It reduces nausea, dizziness, weakness.¹² (c) M. zapota contains tannins providing astringent, antioxidant, antiviral, antibacterial, property of plant, helps in treating dysentery, haemorrhage, ingestion, and diarrhoea.²⁵ (d) M. zapota is used in treatment of diarrhoea, cold, and cough.²⁶ (e) M. zapota have potential for analgesic, anti-hyperglycaemic, and hypo-cholestrolemic activity.^27,28 (f) Crushed seeds are used for treat stones of bladder, kidney, and rheumatis. (g) Leaf decoction is used to cure fever, haemorrhage, wounds, and ulcers. (h) Bark of plant is preferred for treatment of gastrointestinal disorders, pain, fever, and inflammation.^29,30 (i) Flowers and fruits decoction is used as expectorant which taken for treatment of pulmonary disorder, boost nervous system functions for anxiety, depression, stress, and insomnia.³¹ (j) Vitamin A and fibre present in sapota which prevents from lung cancer, oral cavity cancer, colon cancer, seeds for prevent odema, useful for dysentery, constipation and piles. (k) Seed paste is effective against sting and venomous bites.³²

7. PHARMACOLOGICAL POTENTIAL

M. zapota was recognised as potential source of drug discovery shown in Figure 1.

Figure 1. Pharmacological activity of Manilkara zapota (L.) P. Royen.

7.1. Anti-microbial activity

Salunkhe et al ³³ reported that methanolic extract of leaves of M. zapota and Psidium gaujava was antimicrobial. Antimicrobial activity was measured by well method. M. zapota and Psidium gaujava leaf methanolic extract, active against gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis) and gram-negative bacteria (Escherichia coli, Salmonella typhi). Two gram positive and negative bacteria were tested at five different concentrations with ratio of 2∶0, 1.6∶0.4, 0.6∶1.4, 1∶1, and 0∶2. The zone of inhibition was measured in Staphylococcus aureus (18 mm), Bacillus subtilis (20 mm), Salmonella typhi (13.8 mm) and Escherichia coli (13.8 mm).³³

According to Kiriyanthan et al,³⁴ M. zapota copper nanoparticles (Mz-Cu-NPs) from aqueous leaf extract showed antimicrobial properties and also anticancer properties. The synthesized nanoparticles were assessed by well-plate method against plant fungal pathogens, bacterial species. Using optical density to detect bacterial growth of 883.69 µg/µL. Mz-Cu-NPs showed significant antibacterial property compared to control sample. With increasing concentration, inhibition also increased. Up to 50% of inhibition was minimal in B.subtilis. Alternaria alternata and Botrytis cinerea, two plant fungal pathogens, were growth-inhibited when exposed to Mz-Cu-NPs at concentration of 10 µg/µL. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay was used for in vitro anticancer activity of breast cancer cell lines (MCF7) and healthy Vero cells lines. Anticancer activity was assessed at concentrations of 53.89 and 883.69 µg/µL, Mz-Cu-NPs showed cytotoxicity for MCF-7 cells but not for Vero cells.³⁴

7.2. Anti-diabetic activity

According to Paul et al,³⁵ M. zapota seeds and leaves extracted with petroleum ether and methanol both exhibited hypoglycemic activity by using an alloxan monohydrate-induced diabetes model and an oral glucose tolerance test. Swiss albino mice were used. The oral glucose test was performed for 120 min with doses of polysaccharides from mountain Z. latifolia swollen culm (PMZL) 150 mg/kg and methanol extract of M. Zapota seeds (MMZS) 150 and 300 mg/kg. Results from diabetes caused by alloxan monohydrate at day 7 were normal (5.6 ± 0.1), diabetes control (3.8 ± 0.1), PMZL (18.9 ± 0.3) (150 mg/kg), MMZS (7.3 ± 0.1) (150 mg/kg) PMZL (6.8 ± 0.1) (300 mg/kg), MMZS (6.5 ± 0.1) (300 mg/kg), Metformin (6.0 ± 0.1) (100 mg/kg). M. zapota leaves extracted in petroleum ether and seeds extracted in methanol had lower blood glucose levels.³⁵

7.3. Anti-oxidant activity

Islam et al ²³ reported that an ethanolic extract of M. zapota leaves exhibited antioxidant activity. At 100 g/mL, it was discovered that 2,2-diphenyl-1-picrylhydrazyl was inhibited by 86.28%. Assays for cupric and ferric-reducing antioxidants were performed. Strong reducing power was demonstrated by the ethanol extract of M. zapota leaves at concentration of 100 µg/mL with values of (53.30 ± 2.85) μM Ferric reducing ability of plasma and (40.09 ± 3.61) μM ascorbic acid equivalent Cupric reducing antioxidant capacity. Ethanol extract of M. zapota leaves had potent antioxidant capacity.²³

Leelarungrayub et al ³⁶ reported that M. zapota fruit extract exhibited antioxidant activity. The anti-oxidant activity was assessed using superoxide scavenging assay, hydroxyl scavenging assay, hydrogen peroxide scavenging assay, and nitric oxide scavenging assay. Superoxide radicals (33.78 ± 2.21) mg, hydroxyl radicals (8.22 ± 1.32) mg, hydrogen peroxide (54.49 ± 2.41) mg, and nitric oxide (22.95 ± 3.78) mg were results of scavenging assays with IC50 values. Active substances like polyphenol are in charge of anti-oxidant activity. Anti-inflammatory activity was also reported for M. zapota fruit extract. Peripheral blood mononuclear cells induced by lipopolysaccharide for in vitro anti-inflammatory activity. Sandwich Enzyme linked immunosorbent assay technique was used. TNF-, IL-23, and IL-2 produced results with effect sizes of 0.47, 0.23, and 0.47.³⁶

7.4. Anti-cancer activity

Silver nanoparticles from M. zapota leaf aqueous extract exhibited cytotoxicity against colorectal carcinoma cells by successfully inhibiting cell migratory potential. Trypan blue dye exclusion assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay, and cell migration assay are used to measure cytotoxicity. A549, human colorectal carcinoma (HCT 116), and cervical cancer cells (HeLa) cells were 3 in vitro (human) cancer cell lines carcinoma effect. IC50 for values for HCT 116, HeLa, and A549 were (8 ± 3), (16 ± 2), and (29 ± 3) µg/mL at 72 h, respectively. Compared to HeLa and A549 in human colorectal carcinoma cells, leaf aqueous extract silver nanoparticles showed high cytotoxicity.³⁷

7.5. Hepato-protective

According to Alrashood et al,³⁸ aqueous extract of M. zapota fruit demonstrated CCl₄-induced hepatic toxicity through analysis of biomarkers for liver function, serum lipid levels, malondialdehyde, nonprotein sulfhydryls, and histopathology. Hepatocyte population changes at 500 mg/kg lyophilized sapodilla extract were negligible. Proanthocyanins have a number of positive health effects, including hepatoprotection, which may be attributed to their ability to inhibit apoptosis in hepatic cells.³⁸

7.6. Gastro intestinal disorders

According to Ansari et al,³⁹ antidiarrheal, antispasmodic, antisecretory, antiulcer, and gastrointestinal motility effects of M. zapota fruit aqueous extract (Mz. Aq) and chloroform extract were estimated. Aqueous extract from M. zapota fruit demonstrated pharmacological activity against ethanol-induced ulcer method, hematoxylin and eosin staining, enzyme linked immunosorbent assay, castor oil-induced diarrhoea. At 300 mg/kg, complete protection was demonstrated. Rats were exposed to ethanol (1 mL/100 g), and M. zapota chloroform (300 mg/kg) and Mz. Aq (300 mg/kg) showed 76% protection³⁹ .

According to Manirjjaman et al,⁴⁰ M. zapota leaves in methanolic and petroleum ether demonstrated anti-diarrheal activity. Castor oil caused albino mice to become diarrheic, and magnesium sulphate showed anti-diarrheal properties. Castor oil-induced diarrhoea showed the greatest protection at 72.53% at petroleum ether leaves extract (200 mg/kg), and magnesium sulphate-induced diarrhoea showed the greatest protection at 77.94% at petroleum ether leaves extract of M. zapota (400 mg/kg). M. zapota leaves methanolic and petroleum ether demonstrated moderate anti-diarrheal activity. Flavonoids and saponins, which are phyto-constituents, are in charge of the anti-diarrheal activity.⁴⁰

7.7. Anti-inflammatory activity

Konuku et al,⁴¹ reported that M. zapota leaf extracts in methanolic and ethyl acetate showed anti-inflammatory activity. This activity was performed using both in vitro (phospholipase A₂ assay and lipoxygenase assay) and in vivo (carrageenan-induced hind paw edema in rats) methods. The ethyl acetate extract had the more inhibitory effect on PLA₂ activity when used at a concentration of 100 µg/mL. Ethyl acetate extract (400 mg/kg body weight) was found to inhibit swelling of hind paws caused by carrageenan by 70%. Results over methanolic extract demonstrated significant anti-inflammatory activity, which can be attributed to presence of substances like flavonoids, steroids, and terpenoids.⁴¹

7.8. Analgesic activity

Manirujjaman et al ⁴² found that analgesic activity was assessed using acetic acid-induced writhing technique. At dosages of 200 mg/kg body weight, M. zapota leaf methanolic and petroleum ether extract indicated 96.42% and 94% pain inhibition. Because of presence of polyphenols and alkaloids, methanolic and petroleum ether extracts of M. zapota leaves showed high analgesic efficacy.

7.9. Anti-arthritic activity

According to Singh et al,⁴³ an ethanolic extract of M. zapota leaves displayed anti-arthritic action. Using a denaturation inhibition technique, anti-arthritic efficacy is in vitro assessed. The ethanolic extract of M. zapota leaves 75.84% ± 2.31% suppression of protein denaturation at 250 g/mL suggests that M. zapota may be used as an anti-arthritic agent.⁴³

8. CONCLUSION

The more beautiful and amazing flora that nature has endowed us with improves and beautifies our way of life. Plants with a comprehensive pharmacological profile, therapeutic benefits of polyphenols, triterpenoids, carbohydrates, steroids, flavonoids have effect on a number of diseases, including diabetes, cancer, inflammation, gastrointestinal disorders and arthritis, and bacterial infections. M. zapota is one of them that is particularly amazing. This review highlights useful knowledge about M. zapota, including its phytocomponents, traditional uses, and pharmacological activities. In order to find new treatments for diseases such as malaria, mosquito repellent, pancreatic cancer, anxiety, etc., studies need to investigate various optimized conditions for extracting different parts of plants. The abundance of antioxidants, phenolic compounds, triterpenoids, steroids and flavonoids will fascinate researchers and inspire them for treatment of diseases, herbal preparations are more reliable and safer. As a result, it could be a better alternative for treating various diseases.