Three Selected Edible Crops of the Genus Momordica as Potential Sources of Phytochemicals: Biochemical, Nutritional, and Medicinal Values

Momordica species (Family Cucurbitaceae) are cultivated throughout the world for their edible fruits, leaves, shoots and seeds. Among the species of the genus Momordica, there are three selected species that are used as vegetable, and for medicinal purposes, Momordica charantia L (Bitter melon), Momordica foetida Schumach (Bitter cucumber) and Momordica balsamina L (African pumpkin). The fruits and leaves of these Momordica species are rich in primary and secondary metabolites such as proteins, fibers, minerals (calcium, iron, magnesium, zinc), β-carotene, foliate, ascorbic acid, among others. The extracts from Momordica species are used for the treatment of a variety of diseases and ailments in traditional medicine. Momordica species extracts are reputed to possess anti-diabetic, anti-microbial, anthelmintic bioactivity, abortifacient, anti-bacterial, anti-viral, and play chemo-preventive functions. In this review we summarize the biochemical, nutritional, and medicinal values of three Momordica species (M. charantia, M. foetida and M. balsamina) as promising and innovative sources of natural bioactive compounds for future pharmaceutical usage.

(African pumpkin) are widely cultivated and they belong to the family Cucurbitaceae (Daniel et al., 2014). In some African countries; fruits, leafy shoots and the ripe seeds from these three species are harvested for consumption as vegetable, spices and leaves are mixed with water and consumed as beverages (Cantwell et al., 1996). Momordica species (spp.) are annual crops but can be regarded as perennial crop due to their performance during the season (Krawinkel and Keding, 2006;Tan et al., 2008;Costa et al., 2010;Chen et al., 2011;Abegunde et al., 2018). These crop species are mostly adapted to areas of minimum annual average rainfall such as those that receive an average of 400 mm as well as those with mild and frost-free winters (Tokhtar and Doan, 2014). Momordica spp. require a minimum temperature of 18°C during emergence and germination and during vegetative stage and flowering and an optimal temperature ranging between 24 and 27°C (Tan et al., 2008). Some researchers have stated that the crops adapt and perform well in deep and well-drained sandy loam and slit loam soils which are rich in organic matter and adapt well in soils with optimum soil pH ranging from 4.3 to 8.0 (Tan C. et al., 2015). However, they can adapt to alkaline soils with up to pH of 8.0 (Grover and Yadav, 2004;Harinantenaina et al., 2006;Tan et al., 2008). Momordica spp. are open-pollinated and consist of separate male and female flowers on the same plant (Palada and Chang, 2003). Flowering of Momordica species begins a month after planting until reaching dormancy. The fruits are orange in color and soft when ripe with black seeds (Bakare et al., 2010). The local South African indigenous traditional people have been using Momordica spp. as culinary species or enhance bitterness of the meat and of vegetables (Madala et al., 2014). However, studies on the trend of food consumption for rural residents in developing countries have often focused relatively on the economic factors such as prices, income, and market development Jia et al. (2017), and have rarely covered social and psychological influences.
The use of the plant extracts of Momordica spp. to fully explored their effectiveness, may lead to new drug discovery or advance the use of indigenous herbal medicines for orthodox treatment of certain diseases (Rahmatullah et al., 2012). The aim of this review was to discuss the biochemical, nutritional, and medicinal values of three Momordica spp. (M. charantia, M. foetida and M. balsamina) as promising and innovative sources of natural bioactive compounds for future pharmaceutical usage.

Type of Review
The systematic review method involved six steps: 1) scoping; 2) planning; 3) search process and identification of articles; 4) Screening of articles; 5) assessment of relevancy and 6) Presentation and interpretation of the results. As a rigorous and unbiased method of evaluating and screening the literature attributed to its replicability and exhaustiveness, it is a method of choice suitable for summarizing the current literature on the three Momordica spp (M. charantia, M. foetida and M. balsamina).

Literature Sources and Searching Procedure
The search was conducted from six electronic database (Web of Science, Science.gov, Science Direct, Google Scholar, Scopus and Ebscohost) using the following guidelines: 1) "Momordica charantia" OR "Bitter melon", 2) "Momordica. Foetida" or "Bitter cucumber", and 3) "Momordica. Balsamina" OR "African pumpkin". The common search for peer reviewed article used included the biochemical, nutritional, and medicinal values or composition of Momordica spp. The same search was also conducted using the common names of the species. The search was filtered based on the year of publications (Year 1990(Year -2020 to obtain most recent literature however, it did not exclude the old publications (Year<1990) which form the basic knowledge of the associated literature. Since, the study was limited to qualitative synthesis, the PRISMA 2009 Flow Diagram (Moher et al., 2009) was to modified to exclude the meta-analysis aspects ( Figure 1).
The leaves are an important source of nutrients, in addition they contain 17 amino acids and an adequate mineral composition (Hassan and Umar, 2006;Talukdar and Hossain, 2014;Wardhani et al., 2015;Wang et al., 2016;Nitu and Patidar, 2017). M. balsamina is rich potassium, calcium, magnesium, sodium, phosphorus, manganese, zinc, and iron which contribute to prevent micronutrient deficiencies in human.

NUTRITIONAL VALUE OF THE THREE SELECTED MOMORDICA SPECIES
Momordica charantia L.
M. charantia fruit is commonly eaten unripe as a vegetable and is also used as herbal plant that is useful in metabolic and physiological processes of the human body. It is advisable to add peeled fruits to minimize bitter taste before preparation which involves soaking the fruits and shoots and then boiled, fried or pickled (Kumar and Bhowmik, 2010). M. charantia fruits are known to have high levels of nutritional value (protein, vitamins, thiamine, riboflavin, calcium and iron) compared to other cucurbits it has higher in folate and Vitamin C and the vine tips as an excellent source of Vitamin A. M. charantia leaves can be harvested, cooked and consumed alone or mixed with other indigenous vegetables to limit the bitterness (Hassan and Umar, 2006). The leaves and fruits of M. charantia have been used to make teas and beer or season soups in the Western world (Kumar and Bhowmik, 2010).
M. charantia contains iron, β-carotene, calcium potassium, vitamins, phosphorus and good dietary fiber (Daniel et al., 2014). About 93.2% of the fruit of M. charantia is composed of water, while protein and lipids account for 18.02 and 0.76%, respectively, (Li et al., 2009). Leaves powder from M. charantia contained 38% water, 38.2% dietary fiber, 67% minerals, 45% crude protein and 27% crude fat (Anilakumar et al., 2015). Protein lectin that is found on the seed of M. charantia is responsible for the inhibition of protein synthesis in the intestinal walls of an animal without producing any gastrointestinal symptoms in humans.
M. charantia reduced the accumulation of visceral fat that was fed to rats with high fat diet it and thus help in reducing insulin sensitizing and glucose due to its anti-adiposity effect (Chen et al., 2003;Huang et al., 2008;Dellavalle et al., 2011). Circulating levels of catecholamine and non-esterified fatty acids, lipid oxidation in the liver and muscle are reported to be as a result of M. charantia supplemented rat (Cohen et al., 1998;Waako et al., 2005;Harinantenaina et al., 2006;Bulbul, 2016;Devyani et al., 2016).

Momordica foetida Schumach
The crop is commercially grown for their nutritional value and they are also used for medicinal purposes (Waako et al., 2005).   The leaves of M. foetida are harvested from the wild and consumed when they are prepared as a vegetable in Gabon, Sudan, Uganda, Tanzania, South Africa and Malawi and some other African countries. The leaves of M. foetida are harvested, boiled and consumed with beans or peas together with a staple food. It is utilized in small amounts as a famine food and in emergency situations.
Traditional people prefer to consume M. foetida pulp of ripe fruits even if it has bitter taste (Mada et al., 2013;Mostafa et al., 2018;Ludidi et al., 2019). M. foetida leaves can be mixed with other vegetables to make a stew. It is also sauced with shrimp, meat, pork, and chicken and served with gravy. The leaves are mixed with ground peanuts and honey as a sauce in meat (Thakur et al., 2009;Dellavalle et al., 2011;Oronje et al., 2012;Sen and    M. foetida leaves are used as fodder and protein supplement in some countries and are suitable for increasing rabbits weight (Jabeen and Khanum, 2017). However, reports from Kenya state that cattle avoid M. foetida because of its unusual smell and bitter taste.

Momordica balsamina L.
M. balsamina is important in producing nutrients supplements due its high protein and fat values with low fiber content (Bakare et al., 2010;Costa et al., 2010;Roškar and Lušin, 2012;Ghosh, 2014;Madala et al., 2014;Talukdar and Hossain, 2014;Abegunde et al., 2018). The leaves of M. balsamina are an important source of nutrients, including 17 amino acids (Cohen et al., 1998;Hassan and Umar, 2006;Costa et al., 2010;Semenya and Potgieter, 2015). M. balsamina leaves are mixed with peanuts and honey and used as a meat sauce (Dellavalle et al., 2011;Oronje et al., 2012;Sen and Fongod et al., 2014;Bulbul, 2016;Poyraz and Derdovski, 2016;Mostafa et al., 2018). The fruit of M. balsamina contains the red, soft flesh that surround the edible seed (Tan C. et al., 2015;Birla, 2016;Devyani et al., 2016;Souda et al., 2018). The tender fruits and shoots of M. balsamina are usually boiled with meat and both can be decided to be added to the soup. Young fruits of M. balsamina are cooked and eaten, after peeling it is advisable to put on the salt water to minimize the bitterness before cooking, additionally the South Africans and Nigerians appreciate the fruit for its better taste (Acquaviva et al., 2013;Ghosh, 2014;Souda et al., 2018). The fruits of M. balsamina are frequent ingredients used in Indo Pakistan pickles and they are often used in curries and meat dishes.
Tender shoots of M. balsamina are usually utilized with Okra soup by the Kanuris of Borno State where the plant is locally known as the vegetable (Jabeen and Khanum, 2017). M. balsamina is preferred as an ingredient in aphrodisiac preparations however in Senegal they prefer to use the fruits as purgative agents, poultice and vermifuge (Leung et al., 2009;Souda et al., 2018).

Momordica charantia L.
M. charantia has medicinal value and is also used as a vegetable. The compounds present in M. charantia exert anti-diabetic, anticancerous and anti-tumorous, anti-microbial, anti-viral, antihelmintic, antimalarial, anti-ulcerative and immunomodulatory activities (Gupta et al., 2011;Kulkarni et al., 2021;Lur et al., 2021;Malik et al., 2021). Some of the structures of compounds isolated from M. charantia are listed in Table 1.
The fruit juice and a leaf tea extracted from M. charantia can be used for the treatment of diabetes, malaria, colic, sores and wounds, infections, worms and parasites, as an emmenagogue, and for measles, hepatitis, and fevers (Kumar and Bhowmik, 2010). The anti-oxidants and chemo-protective are mostly available on M. charantia fruit extracts drug that helps with reducing risk of cancer (Dzotam et al., 2016;Khalid et al., 2021). The leaves of M. charantia are used for treatment of wounds as well against worms and parasites. M. charantia has been used as a traditional medicine in China, India, Africa, and the southeastern United States (Grover and Yadav, 2004). In the 1980s, the seeds of M. charantia were investigated in China as a potential contraceptive (Kumar and Bhowmik, 2010). Natural products from M. charantia have been reported to significantly decrease prostaglandin E2, interleukin and tumor necrosis factor and increases transforming growth factor and IL-10 secretion in RAW 264.7 macrophages, Caco-2 cells and THP-1 cells (Tan et al., 2008). The M. charantia fruit effectively enhanced T helper 2 hormonal responses and T helper 1 cellular immunity. A mixture of steroidal saponins contribute to the hypoglycemic and anti-hyperglycemic activity of M. charantia (Nitu and Patidar, 2017). Gentisic acid found as an active metabolite of salicylic acid and relation of the antiinflammatory property of salicylic acid by inhibiting cyclooxygenase-2 (COX-2) mRNA expression and activity as well as prostaglandin E2 (Lii et al., 2009;Semenya and Potgieter, 2015;Wardhani et al., 2015;Madala et al., 2016;Wang et al., 2016).
M. charantia have been reported to exhibit anti-diabetic, anthelmintic, abortifacient, anti-bacterial, anti-viral, hypoglycemic agents and chemo-preventive functions (Grover and Yadav, 2004;Costa et al., 2010;Ghosh, 2014;Bulbul, 2016;Dzotam et al., 2016;Ludidi et al., 2019;Kulkarni ei al. 2021). The fruits and leaves of M. charantia display various biological activities including anti-diabetic, anti-rheumatic, and antiulcer, anti-inflammatory and anti-tumor (Dzotam et al., 2016). M. charantia contains various chemicals that have a hypoglycemic activity which reduces the amount of sugar in the blood, furthermore it stimulates appetite and helps in the entire digestion process. M. charantia is used for the treatment of digestive problems (Ludidi et al., 2019).
The leaves of M. charantia are used to treat diabetes, intestinal gas, promote menstruation, and as anti-viral agent against measles and hepatitis viruses (Tansey et al., 2004;Leung et al., 2009;Costa et al., 2010;Nerurkar et al., 2010;Nitu and Patidar, 2017;Perera et al., 2021;Liu et al., 2021). M. charantia is used by most of the culture for minimizing blood glucose and treating diabetes and as the other admired herbal resource (Leung et al., 2009;Birla, 2016). Hypoglycemic potential of M. charantia has been demonstrated in patients with type 2 diabetes. Emerging evidence also suggest that hypolipidemic action of M. charantia lowers serum cholesterol, hepatic total cholesterol and triglyceride and elevated cholesterol (Chen et al., 2003;Tan et al., 2008). The crop juice is believed significantly to reduce lipid accumulation and increase lipolysis in primary human adipocytes (Tan E. S. et al., 2015;Ingle et al., 2017). Animal studies indicate that M. charantia juice reduces body weight by inducing a reduced adipose hypertrophy, inhibition of lipogenic genes and enlarged plasma catecholamines (Nerurkar et al., 2010).
The ripe fruit of M. charantia fruits had been used as a remedy for tumors, asthma, skin infections and hypertension (Semenya and Potgieter, 2015). The seeds are surrounded by sweet red fleshy pulp that is edible tasting like watermelon (Poyraz and Derdovski, 2016). In some parts of West Africa, the leaves of M. charantia are cooked as part of green vegetable soup for post-natal mothers to prevent loss of blood during labor and purify breast milk. However, M. charantia can be recommended to use for livestock feeding as supplement for protein (Kuete et al., 2010).  (Marquis et al., 1977). Likewise, M. foetida is used for treatment of digestive problems due to its hypoglycemic activity that reduces the amount of sugar in the blood and also stimulate appetite and helps in the entire digestion process (Leung et al., 2009;Kumar and Bhowmik, 2010;Chen et al., 2011;Daniel et al., 2014;Birla, 2016). Additionally, M. foeida has slight anti-spasmodic and anticholinergic effects (Hassan and Umar, 2006;Acquaviva et al., 2013;Ingle et al., 2017;Puškárová et al., 2017). Some of the structures of compounds extracted from M. foetida are listed in Table 2.
Aqueous extract of M. foetida has anti-oxidant activity due to high content in phenolic and flavonoid compounds (Acquaviva et al., 2013). Oxidative stress is closely related with Alzheimer and Parkinson diseases, diabetes, rheumatoid arthritis, and several diseases. The use of anti-oxidants in pharmacology has been instrumental in treatments of stroke and neurodegenerative diseases (Jabeen and Khanum, 2017).
The juice of M. foetida, dried and crushed leaves are used to relieve cough, intestinal disorders, headache, earache, toothache and as an cure for snake bites (Jabeen and Khanum, 2017). Leaves can be dried or boiled and used to treat skin problems, spitting cobra poison and malaria. The roots of M. foetida may be stated to be poisonous, and the crushed seeds are used in East Africa to cure of constipation. M. foetida helps to reduce weight in obese people (Nerurkar et al., 2010;Talukdar and Hossain, 2014).
The fruit pulp of M. foetida is said to be poisonous to common pests such as weevils, moths and ants, making it to be utilized as potential insect repellent in Tanzania. Momordocin isolated from M. foetida has insecticidal ability (Olaniyi and Marquis, 1975;Pinar et al., 1983;Pirillo et al., 1995). In Uganda the M. foetida whole plant is use on their cattle as an ox pecker repellent. In Gabon, M. foetida soaked and dried leaves are used to stuff cushions for commercial purpose. M. foetida is preferred to be grazed by cattle (Kuete et al., 2010;Mada et al., 2013) and is said to be good supplement of protein (Talukdar and Hossain, 2014). The fruits have the essential oils they have been used as insecticides, food additives and aromatherapy (Dandawate et al., 2016).

Momordica balsamina L.
M. balsamina is regarded as the most important medicinal plants popularly used as a source of life saving drugs that is most important to the world's population (Hassan and Umar, 2006;Thakur et al., 2009;Kumar and Bhowmik, 2010;Tan C. et al., 2015;Souda et al., 2018). The crop can be consumed as vegetable in order to supply protein and potassium supplement for diets in poor rural communities, however its high potassium content is known for the executive of hypertension and other cardiovascular conditions (Rahmatullah et al., 2012;Semenya and Potgieter, 2015;Jabeen and Khanum, 2017;Souda et al., 2018). Some of the structures of compounds extracted from M. balsamina are listed in Table 3.
In some parts of Africa and Europe, soaked leaves of M. balsamina are used to treat wounds. Furthermore the fruits and leaves are used for treatment of wounds in Nigeria and Syria as hemostatic anti-septic (Mada et al., 2013;Semenya and Potgieter, 2015;Madala et al., 2016). The fruit of M. balsamina is used as liniment because of its strong smell and mixed with olive oil and almond oil to treat chapped hands, band and hemorrhoids (Mada et al., 2013). In West Africa M. balsamina fruit pulp is mixed with oil as an anti-phlogistic dressing. Mashed fruit of M. balsamina is utilized as poultice and bitter tonic (Semenya and Potgieter, 2015). M. balsamina plant is used as a medicine for treatment of fevers and yaws. However, Tsonga and Zulus have used leaves as tea for blood-liver deficiencies, stomach and intestinal ailments (Kumar and Bhowmik, 2010).
The Portuguese recommended M. balsamina leaves for blood, stomach, and liver deficiencies, furthermore they use leaves for herbal medicine and culinary herb (Thakur et al., 2009;Madala et al., 2014). M. balsamina leaves are used for diabetes, digestion disorder, fevers, ulcers, and mild form of malaria. Additionally, in West Africa M. balsamina is used as medicine in human and animals particular for fever, yaws and purgative (Oloyede and Aluko, 2012;Ingle et al., 2017;Jabeen and Khanum, 2017;Mostafa et al., 2018). M. balsamina roots are used as ingredient in an aphrodisiac preparation and in treatment of urethral discharge on both human and animals. It is advisable to use the whole M. balsamina parts of the plant for used in treating skin disease such as scabies (Waako et al., 2005;Ozusaglam and Karakoca, 2013;Pauliuc and Botau, 2013;Wikaningtyas and Sukandar, 2016). In South Africa, mostly the Pedi people use M. balsamina leaves and tendrils as potherb and anti-emetic, while the Venda people used the leaves infusions as anti-emetic and Congo as colic. M. balsamina leaves and fruit are widely used in Okavango delta for medicinal and spiritual purpose and also as skin aliments in China (Molehin and Adefegha, 2014). In some countries seed can be used as poison in arrow for hunting. The whole plant extract has insecticidal properties (Trakoon-osot et al., 2013;Wardhani et al., 2015;Wang et al., 2016).
The aqueous leaf extract of M. balsamina has also been used to minimize and relieve period pain in young girls and postnatal women used it to stimulate milk production (Tan et al., 2008). In Hausa land of Nigeria and Republic of Niger, the leaves are cooked as part of green vegetables soup for post-natal women, where it is believed to help the mother to restore her lost blood during labor and to cleanse her breast milk (Molehin and Adefegha, 2014).
Anti-oxidants are recognized as ingredient and supplement of good human health because they maintain health and prevent diseases such as cancer, coronary heart disease and even altitude sickness in human and animals (Tan et al., 2008;Ingle et al., 2017;Puškárová et al., 2017). M. balsamina is used for treatment of diabetes, malaria, colic, sores and wounds, infections, worms and parasites, as an emmenagogue, measles, and hepatitis, fevers, diarrheal, cancer, ulcer, HIV, bacterial infection, and constipation (Semenya and Potgieter, 2015;Abegunde et al., 2018;Aryanti and Lamdayani, 2021). In addition, M. balsamina is believed to treat mental illness (Anjamma and Bhavani, 2018). The anti-HIV properties are found at the fruit pulp of M. balsamina (Abidemi, 2013). The leaves and fruit extracts of M. balsamina contain antiplasmodial activity against malaria (Balouiri et al., 2016). The crude extract of protein on African pumpkin seeds contains a hemagglutinating activity attributed by the presence of sugar D-galactose and lactose (Bulbul, 2016). Moreover, several previous studies did test the hemagglutinating activity on human and animals of the different blood type and proved that the hemagglutinating was greater toward O blood type compared to other blood cell type (Scorzoni et al., 2007;Souda et al., 2018).
The fruit juice of M. balsamina exerted hypoglycemic activity, stimulates appetite and helps in the entire digestion process (Kumar and Bhowmik, 2010;Chen et al., 2011). Hypoglycemic potential of M. balsamina has been established in normal and diabetic rats and in patients with type 2 diabetes (Waako et al., 2005;Scorzoni et al., 2007;Leung et al., 2009;Kumar and Bhowmik, 2010;Rahmatullah et al., 2012;Joseph and Jini, 2013;Trakoon-osot et al., 2013;Ludidi et al., 2019). Extract of P-Insulin, polypeptide from the fruits and seeds of M. balsamina rapidly reduces and normalized the blood sugar level in rats.
The leaves have been found to be highly hemolytic and hepatotoxic in rats while the fruits are regarded as toxic to various organs and tissues of rats in very high dose (Semenya and Potgieter, 2015). Thus, it is important to determine the correct dose to optimize its potential use as a medicinal plant.

CONCLUSION AND FUTURE PERSPECTIVE
The biochemical composition of M. charantia, M. foetida and M. balsamina gives them a great and interesting nutritional and medicinal value. Many of its components have singular biological activity and the synergy of them may exert interesting pharmacological properties. Several studies demonstrated that these important plants have the potential to be utilized for medicinal purposes as they exhibit anti-diabetic, anti-microbial, anthelmintic, abortifacient, anti-bacterial, anti-viral, and chemopreventive activities. These species possess a promising and innovative source of natural bioactive agents such as resins, alkaloids, flavonoids, glycosides, steroids, terpenes, cardiac glycoside, saponins, pectin, carbohydrates, amino acids, proteins, fats, fiber, chlorophyll, phosphorus, calcium, potassium, magnesium, sodium, zinc, manganese, and iron. The main biological activities of Momordica spp. has been summarized in Figure 2.
The anti-microbial, anti-parasitic and anti-ulcer activities of Momordica spp. are the mechanisms related with their inhibitory effects against gastrointestinal diseases. In addition, anti-cancer effects of several biochemicals isolated from Momordica spp. has been described. Anti-oxidant activities of Momordica spp. also prevent cancer diseases avoiding oxidative stress and oxidative damage such as lipid peroxidation. Moreover, anti-oxidants exerts anti-aging and neuroprotection effects. Additionally, the hypoglycemic activities of Momordica spp. exert an anti-diabetes effect, the hypocholesterolemic activities exerts a cardioprotective effect, and their low ratio of Na + /K + exerts beneficial effects against hypertension. In addition to being able to be consumed as food or supplement, clinical evidence suggests their effectiveness in managing various ailments such as dysmenorrhea, eczema, emmenagogue, galactagogue, gout, jaundice, kidney (stone), leprosy, leucorrhea, pneumonia, psoriasis, rheumatism, scabies, piles, cancer, coronary heart disease diabetes, digestion disorder, fevers, ulcers, malaria, tumors, asthma, skin infections, and hypertension.
Thus, the review suggests that the three selected crops have medicinal and herbal properties that can be used for various ailments. A better biochemical characterization is needed to better understand of medicinal properties of these plants. This review also assists to understand the commercial properties of the crop since the cultivation as commercial vegetable is currently underway. A better understand of pharmacological activities of Momortica spp. will give added value to these plants and benefit the producers.