Momordica (PROSEA Medicinal plants)

Plant Resources of South-East Asia
Introduction

List of species

Momordica L.

Protologue: Sp. pl. 2: 1009 (1753); Gen. pl. ed. 5: 440 (1754).

Family: Cucurbitaceae

Chromosome number: x= 7, 11, 14; M. charantia: 2n= 22, M. cochinchinensis: 2n= 28

Major species

Momordica charantia L.,
M. cochinchinensis (Lour.) Spreng.

Vernacular names

Momordica (En).

Origin and geographic distribution

Momordica comprises some 45 species and is confined to the Old World tropics, except for the few species introduced into the New World tropics. The majority of species are found in the warmer parts of Africa; Asia harbours only 5-7 species, 3 of which are reported from the Malesian region. M. charantia was probably first domesticated in eastern India and southern China, and then taken to other regions in tropical Asia and Africa from which it occasionally naturalizes. It is thought to have been introduced into Brazil from Africa with the slave trade, and that bird dispersal of the seeds accounts for its spread within South America. M. cochinchinensis occurs wild and cultivated from India to Japan and throughout Malesia.

Uses

A decoction of the root, stem, leaves and fruit of M. charantia may be used as a febrifuge. Most plant parts act as a laxative. Juice from various plant parts is used externally to treat skin disorders, abscesses and burns, and also as a cure for children with diarrhoea and stomach-ache. Leaf juice has been applied as a gargle against sprue, to treat jaundice, and for "female disorders", whereas the flowers are part of a mixture to treat asthma. In Peninsular Malaysia, a decoction of the leaves has been used as an abortifacient. In Indonesia, it is considered to be appetizing, depurative, mildly laxative, useful in treating liver diseases and biliousness; it is also used as a vermifuge to treat pinworms. A little leaf juice is given orally to new-born babies to cleanse the stomach and bowels. Fruits are considered tonic, stomachic, carminative and cooling, and are applied in the treatment of inflammation, rheumatism, gout, pruritus, dermatitis and liver and spleen diseases. The fruits, leaves and roots have long been used in India and Puerto Rico as a folk medicine for diabetes mellitus, though large doses are toxic. In the Philippines, the fruit and young shoots, either in the form of a decoction or as tablets, are used for mild non-insulin dependent diabetes mellitus.

Seeds of M. cochinchinensis are used in local medicine in Burma (Myanmar), Thailand and the Philippines to treat chest complaints, whereas in China and Peninsular Malaysia they are a remedy for abdominal pains, dysentery, mesenteric enlargements, obstructions of liver and spleen and haemorrhoids. They are further used to treat chronic malaria, and after being ground and soaked in alcohol or water they are applied externally to wounds, bruises, burns, skin trouble, ulcers, breast cancer, abscesses, mumps and lumbago. Seeds are indicated as cooling, resolvent, laxative and poisonous. The root is used as an expectorant. Roots and leaves have been reported to be useful in the treatment of oedema of the legs, a kind of rheumatism.

The immature fruits of M. charantia and M. cochinchinensis are a well-known vegetable, whereas leaves and flowers are also eaten as a vegetable or flavouring agent.

Production and international trade

Momordica fruits or any of its derived products for medicinal applications are only traded locally.

Properties

The seeds and the fruit wall of M. charantia are reported to contain a resin, a saponin glycoside of the cucurbitacin type, and alkaloids that may cause vomiting and diarrhoea. Furthermore, several proteins that display a variety of pharmacological effects can be isolated from Momordica.

The proteins α-momorcharin and β-momorcharin, from seeds of M. charantia, have been found to show a hepatotoxic effect on isolated rat hepatocytes. Several immunotoxins were prepared by linking the type 1 ribosome-inactivating protein momordin I to antibodies specific to various cell lines, e.g. bladder carcinoma antibody, CD5-, and CD22-monoclonal antibodies. Treatment with these immunotoxins significantly inhibits tumour development in vitro, e.g. CD5- or CD22-expressing cell lines, with IC₅₀ values generally at pico-molair scale. The treatment alone, or in combination with a general cytostatic significantly inhibits tumour development in vivo, e.g. in mice with transplanted CD22-expressing cells.

The glycoprotein momorcochin-S, purified from the seeds of M. cochinchinensis, shows ribosome-inactivating effects. The protein was linked to a monoclonal antibody (8A) against human plasma cells, and the resulting immunotoxin was found selectively toxic to the target cells. Furthermore, τ-momorcharin, a small ribosome-inactivating protein, can inhibit the protein synthesis in the rabbit reticulocyte cell-free system with an ID₅₀of 55 nM.

Momordin-folate, the conjugate of folic acid with the cytotoxic protein momordin, can selectively kill HeLa and KB cells, two malignant human cell lines, in co-cultures with W138 and Hs67 cells, two normal human cell types. The in vivo antitumour activity of a crude extract from M. charantia was significant for several types of tumour cells in mice at an optimum dose of 8 μg protein administered biweekly and intraperitoneally. It is thought that in vivo enhancement of immune functions may contribute to the antitumour effects of the M. charantia extract.

Expressed juices from M. charantia fruits appreciably reduced the incidence of skin tumours in mice initiated by dimethylbenz[a]anthracene and promoted by croton oil. The extracts of the peel, pulp, seed and whole fruit of M. charantia exhibited marked anti-carcinogenic activity against mouse skin papilloma genesis when applied topically at 100 μm/animal. In vitro and in vivo tests with aqueous and ethanolic extracts of M. cochinchinensis also showed marked antitumour activity.

MAP30, an antiviral protein (30 kDa) from M. charantia , may regulate Herpes simplex virus (HSV) replication in concert with dexamethasone and indomethacin, which are inhibitors of prostaglandin synthesis. EC₅₀ values for MAP30 were 0.1 μM for HSV-2 and 0.3 μM for HSV-1 in human lung WI-38 fibroblasts. MAP30 is also capable of inhibiting infection of HIV-1 in T lymphocytes and monocytes, as well as replication of the virus in infected cells. It was found not toxic to normal uninfected cells; the peptide is probably unable to enter healthy cells. It exhibits a dose-dependent inhibition of integration of viral DNA into the host chromosomes (HIV-1 integrase), which is a vital step in the replicative cycle of the AIDS virus.

M. charantia trypsin inhibitor-II prolonged the prothrombin time of human plasma. Furthermore, a glycoprotein isolated from fresh tuberous roots of M. cochinchinensis was capable of inducing mid-term abortion in mice.

Acylglucosylsterols isolated from the green fruits of M. charantia showed antimutagenic activity and reduced the number of micronucleated polychromatic erythrocytes induced by the well-known mutagen mitomycin C by about 80% in mice, at a dosage range of 12.5-50 μg extract/g. Powder and defatted extract from M. charantia leaves reduced the genotoxic activity of dimethylnitrosamine, methylmethanesulphonate and tetracycline as shown by the reduction of chromosome-breaking effects. M. charantia has also been screened for its genotoxic activity using a plate incorporation assay involving Aspergillus nidulans. The aqueous extract of M. charantia leaves resulted in a significant increase in the frequency of segregant sectors per colony.

Bitter gourd (M. charantia) is often used in folk medicine to treat diabetes. However, its hypoglycaemic activity seems contradictory. The hypoglycaemic activity of bitter gourd in experimental animals is also contradictory. The pulp juice of M. charantia lowered fasting blood glucose levels in normal rats; the effect was more pronounced using saponin-free methanol extract of the pulp juice. The hypoglycaemic effect was also significant in normal rats fed glucose 45 minutes after the extract had been administered. In the insulin-dependent diabetes mellitus model rats, the pulp juice had no significant effect on blood glucose levels in the fasting, and postprandial states. In the non-insulin dependent model rats, however, the saponin-free methanol extract of juice produced a significant hypoglycaemic effect in both these states. Seed and whole plant extracts showed a small but consistent tendency to increase blood glucose levels in the normal rats. In normal mice, an aqueous extract of bitter gourd lowered the glycaemic response to both oral and intraperitoneal glucose, without altering the insulin response. This aqueous extract and the residue after alkaline chloroform extraction had reduced the hyperglycaemia in diabetic mice after 1 hour. The results suggest that bitter gourd extracts administered orally lower glucose concentrations independently of intestinal glucose absorption and involve an extrapancreatic effect. Two glycosides isolated from the tuber of M. cochinchinensis containing oleanolic acid as aglycone showed hypoglycaemic activity in streptozotocin-induced diabetic rats at a dose of 25 mg/kg; intraperitoneal administrations showed higher activity than oral administration. The alcoholic extract of M. charantia administered orally to female Wistar rats at 500 mg/kg reduced glucose levels by 10-16% and 6% after 1 and 2 hours, respectively, in normal rats and by 26% after 3.5 hours in streptozotocin-induced diabetic rats. The extract increased the rate of glycogen synthesis from 14C-glucose in the liver of normally-fed rats by 4-5 times, suggesting that the extract may act at least in part by enhancing glucose utilization in the liver. In normal mice, intraperitoneal administration of a concentrated aqueous extract of bitter gourd improved glucose tolerance after 8 hours, and in streptozotocin-induced diabetic mice the level of hyperglycaemia was reduced by 50% after 5 hours. The bitter gourd extracts did not significantly alter plasma insulin concentrations, suggesting that they may exert an extrapancreatic effect to promote glucose disposal. Oral administration of the aqueous extract (0.5 g/kg) of bitter gourd reduced the fasting glucose levels of hyperglycaemic and normoglycaemic mice; the ethanol extract had no significant effect on glucose levels. The water extract did not improve the tolerance of mice to oral glucose.

In conclusion, a significant number of studies have established the hypoglycaemic activity of bitter gourd; its effect appears to be more acute and transient than cumulative. The fresh aqueous extract of the whole fruit is more effective than dried powder, or dietary consumption. Some studies found that the seed also contained hypoglycaemic principles. In most of the cases where hypoglycaemic activity could not be demonstrated, normoglycaemic animals were experimented upon. The mechanism of hypoglycaemic activity remains unclear. If the hypoglycaemic action of bitter gourd is mediated through its effect on glucose absorption and alterations to the activities of enzymes involved in glucose metabolism, it would be beneficial to both insulin-dependent as well as non-insulin-dependent diabetics. If, however, it has an insulin secretagogue effect, only non-insulin-dependent diabetics would benefit from it.

Nine diabetic patients underwent 3 glucose tolerance tests with 50 g of glucose, 50 ml bitter gourd juice, and a test after 8-11 weeks of consuming fried bitter gourd (250 g) daily. The results indicated that fresh bitter gourd juice brought about a significant reduction in plasma glucose concentration, and an improvement in the response to an oral glucose load. The effect of fried bitter gourd was not so pronounced, although it was significant. A cumulative and gradual hypoglycaemic effect was found in diabetic patients using the aqueous extract at the end of a 3-week trial. When 8 non-insulin dependent diabetes mellitus patients consumed bitter gourd cooked and then fried in oil along with their regular meal, their plasma glucose levels were significantly reduced after 1 hour as compared to those whose meal was not supplemented with bitter gourd. However, improvement in glucose tolerance was not significant. Contradictory to these findings, however, is a study in which bitter gourd in the form of fresh juice, dried powder or the powder given as a tablet did not have any beneficial influence on diabetic patients.

No antimalarial activity could be demonstrated in mice infected with Plasmodium berghei when extracts of M. charantia were administered orally at 1 g/kg for 5 consecutive days. M. charantia fruits and seeds contained components that inhibited hormone-induced lipolysis in isolated rat adipocytes. The haemolytic activity of a fraction obtained from fresh tubers of M. cochinchinensis can be attributed to a sterol-glycoside. The crude saponin (4-6% in dry roots) obtained from M. cochinchinensis also showed haemolytic activity.

Extracts of M. charantia were effective in treating Ascaridia galli worms in birds. Oral administration of M. charantia extract containing 100 mg iron was as effective as a commercial preparation to prevent anaemia in piglets. Chitinase isolated from M. charantia fruits may be strongly bacteriostatic. Pollen from M. charantia completely inhibited spore germination of the pathogenic fungi Cochliobolus lunatus, Cylindrocarpon lichenicola, Fusarium solani and Myrothecium leucotrichum.

Momordicines I and II were isolated from dried leaves of M. charantia. Momordicine I at 0.5 mg/ml and 1 mg/ml showed about 33% and 59% inhibition of Colletotrichum gloeosporioides, respectively, whereas momordicine II at 0.25 mg/ml and 0.5 mg/ml showed about 17% and 23% inhibition, respectively. Against Cladosporium cucumerinum, momordicine I exhibited activity at 0.5 mg/ml, whereas momordicine II did not show any activity up to 1 mg/ml. It was suggested that the difference in activity between the 2 compounds could be due to the higher lipophilicity of the aglycone. The leaf extracts were also effective against Botryodiplodia theobromae, Curvularia lunata, Phytophthora colocasia and Sclerotium rolfsii. The active constituents of the leaves of M. charantia were extracted by cold maceration using 95% ethanol. This extract has antimicrobial activity against Escherichia coli, Salmonella paratyphi and Shigella dysenteriae. Seed extracts of M. charantia resulted in high mortality of the nematodes Meloidogyne incognita and Rotylenchulus reniformis. The petroleum ether extract of M. charantia was active against the bean weevil Callosobruchus chinensis.

Adulterations and substitutes

Extensive studies on immunotoxic and anti-HIV potential of proteins from Momordica may lead to substitution for Trichosanthes and vice versa.

Description

Monoecious or dioecious, annual or perennial herbs, with climbing or trailing stems. Tendrils lateral, one at each node, simple or bifid.
Leaves alternate, blade simple or palmately lobed to 3-7(-15)-foliolate, petiolate, exstipulate.
Inflorescence axillary.
Flowers unisexual, actinomorphic, often subtended by a conspicuous bract. Male flowers solitary, umbellate or in short racemes or fascicles; hypanthium shallow; calyx 5-lobed; petals 5, free, white to yellow, 1-3 of them with a scale at base; stamens 3, inserted towards the base of the hypanthium, 2 bilocular, 1 unilocular, locules curved or flexuose; pistillode absent. Female flowers solitary; perianth usually similar to the male flowers; staminodes 3; ovary inferior, oblong to fusiform, 3-locular with many horizontal ovules, stigmas 3, entire to 2-lobed.
Fruit a berry (pepo), ovoid-ellipsoid to elongate-fusiform, fleshy, ornamented with tubercles, spines, wings or ridges, indehiscent or dehiscent by 3 valves and exposing the seeds enveloped in pulp.
Seeds arillate, usually compressed, with sculptured testa and grooved margins.

Growth and development

Flowering of M. charantia starts within 2 months from sowing, that of M. cochinchinensis after about 2 months. Flowers of M. charantia start opening early in the morning. Anthers dehisce about 2 hours before anthesis. Flowers of Momordica are pollinated by insects, especially bees. Indehiscent Momordica fruits may be shattered and eaten by large birds or mammals. Seeds within dehiscent fruits of M. charantia strongly contrast with the large red aril and are thus easily spotted by birds who eat and disperse them. At higher latitudes, plants of M. cochinchinensis remain dormant in winter and regrow from the tuberous root in spring. They fruit mainly during the rainy season.

Other botanical information

Momordica belongs to the tribe Joliffieae of the subfamily Cucurbitoideae. The tribe contains the least specialized genera of the Cucurbitoideae. Momordica is closely related to Thladiantha, but the latter has 5 stamens or staminodes and straight or only slightly curved anther locules.

Ecology

M. charantia grows well in tropical and subtropical climates. It is adapted to a wide range of environments and can be grown year-round, but is usually cultivated during the warmer season, up to an altitude of 1500 m. It is sensitive to waterlogging. It tolerates a wide range of soils but it thrives in a well-drained sandy loam, rich in organic matter. M. cochinchinensis prefers a warm humid climate with temperatures ranging from 20-35°C and an average rainfall of 1500-2500 mm. It does not tolerate waterlogging and grows well in fertile, well-drained, sandy loams with pH near neutral.

Propagation and planting

M. charantia is most commonly propagated by seed. Pre-germinated seed results in even establishment. Optimum plant density differs per cultivar, but ranges from 6500-11 000 plants per ha. M. cochinchinensis is mainly propagated by its tuberous roots. Since it is dioecious, tubers from male and female plants should be planted together. About 50 000 sprouted tubers per ha are required, but in India a spacing of 1.5 m × 2.5 m is adopted. Mean germination of the seeds of M. cochinchinensis is 50%, and germination may take up to 1 year; cuttings root for about 80%.

In vitro production of active compounds

The antiviral protein MAP30, from M. charantia, has been cloned and expressed. It has similar anti-HIV, anti-viral and anti-tumour activity as the natural MAP30.

Husbandry

Fertilization and furrow irrigation if necessary are important cropping techniques when growing M. charantia on trelises. Wild M. charantia can become a troublesome weed in large-scale plantations of e.g. rubber and oil palm in Indonesia and possibly in other South-East Asian countries too.

Diseases and pests

Serious diseases of bitter gourd are Cercospora leaf spot, downy mildew (caused by Pseudoperonospora cubensis) and bacterial wilt (caused by Pseudomonas solanacearum). Fruit fly (Dacus cucurbitae) is the most destructive insect pest of bitter gourd, whereas root-knot nematodes (Meloidogyne incognita) also attack the crop.

Harvesting

M. charantia usually takes 15-20 days after fruit set to mature, whereas M. cochinchinensis fruits are harvested when they turn yellow or red.

Yield

A fruit yield of 20-30 t/ha is considered satisfactory for M. charantia. Some F₁ hybrids yield up to 40 t/ha. The number of fruits per plant may reach 20-25 during the cropping period. M. cochinchinensis may yield 30-60 fruits per plant, each weighing 1-3 kg. In Japan, the yield of dry roots of 5-year-old plants of M. cochinchinensis was about 10 t/ha.

Handling after harvest

Mature fruits are split and seeds and fruit pulp are separated. Fruit pulp is dried at low temperatures, and an oil can be extracted. This oil, which is rich in β-carotene, is used to treat rachitis, xerophtalmia and night blindness. Seeds are dried in the sun or in ovens. The oil that can be extracted from the kernel is used to treat skin disorders. Roots are washed and dried in the sun or oven, and stored for later use.

Genetic resources and breeding

The world collection of Momordica germplasm is held at NBPGR, New Delhi, India. In South-East Asia, collections are available in the Philippines (NPGRL-IPB, Los Baños) and in Thailand (Department of Horticulture, Kasetsart University, Bangkok). Elsewhere, collections are held in several institutes in India, South Africa, Taiwan and the United States. In many South-East Asian countries, commercial F₁ hybrids often twice as productive as the traditional open-pollinated cultivars, have been released.

Prospects

Since the results with M. charantia in the treatment of diabetes are still somewhat contradictory, more research needs to be done on its hypoglycaemic activity. Furthermore, several compounds from Momordica show interesting pharmacological activities, e.g. immunotoxic and anti-HIV, which merit further research, and may have potential in the development of future medicines.

Literature

Ali, L., Khan, A.K.A., Mamun, M.I.R., Mosihuaman, M., Nahar, N., Alam, M.N. & Rokeya, B., 1993. Studies on hypoglycemic effects of fruit pulp, seed, and whole plant of Momordica charantia on normal and diabetic model rats. Planta Medica 59(5): 408-412.
Bolognesi, A., Barbieri, L., Carnicelli, D., Abbondanza, A., Cenini, P., Falasca, A.I., Dinota, A. & Stirpe, F., 1989. Purification and properties of a new ribosome-inactivating protein with RNA N-glycosidase activity suitable for immunotoxin preparation from the seeds of Momordica cochinchinensis. Biochimica et Biophysica Acta 993(2-3): 287-292.
Bolognesi, A., Tazzari, P.L., Olivieri, F., Polito, L., Lemoli, R., Terenzi, A., Pasqualucci, L., Falini, B. & Stirpe, F., 1998. Evaluation of immunotoxins containing single-chain ribosome-inactivating proteins and an anti-CD22 monoclonal antibody (OM124): in vitro and in vivo studies. British Journal of Haematology 101(1): 179-188.
Bourinbaiar, A.S. & Lee-Huang, S., 1995. The activity of plant-derived antiretroviral proteins MAP30 and GAP31 against Herpes simplex virus infection in vitro. Biochemical and Biophysical Research Communications 219(3): 923-929.
Cakici, I., Hurmoglu, C., Tunctan, B., Abacioglu, N., Kanik, I. & Sener, B., 1994. Hypoglycaemic effect of Momordica charantia extracts in normoglycaemic or cyproheptadine-induced hyperglycaemic mice. Journal of Ethnopharmacology 44(2): 117-121.
Guevara, A.P., Lim-Sylianco, C., Dayrit, F. & Finch, P., 1990. Antimutagens from Momordica charantia. Mutation Research 230(2): 121-126.
Lee-Huang, S., Huang, P.L., Huang, P.L., Bourinbaiar, A.S., Chen, H.C. & Kung, H.F., 1995. Inhibition of the integrase of human immunodeficiency virus (HIV) type 1 by anti-HIV plant proteins MAP30 and GAP31. Proceedings of the National Academy of Sciences 92(19): 8818-8822.
Platel, K. & Srinivasan, K., 1997. Plant foods in the management of diabetes mellitus: vegetables as potential hypoglycaemic agents. Nahrung 41(2): 68-74.
Reyes, M.E.C., Gildemacher, B.H. & Jansen, G.J., 1993. Momordica L. In: Siemonsma, J.S. & Kasem Piluek (Editors): Plant Resources of South-East Asia No 8. Vegetables. Pudoc Scientific Publishers, Wageningen, the Netherlands. pp. 206-210.
Shubhashish Sarkar, Maddali Pranava & Marita, A.R., 1996. Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacological Research 33(1): 1-4.

Selection of species

Authors

Nguyen Huu Hien & Sri Hayati Widodo