- Winter melon
- Winter melon nutrition facts
- Winter melon bioactive compounds
- Winter melon uses
- Antioxidant effects
- Antibacterial, antihelmintic, and larvicidal effects
- Anti-inflammatory effect
- Anticancer effects
- Gastrointestinal protective effects
- Antidiarrheal effect
- Antidiabetic effects
- Antiobesity and lipid-lowering effect
- Effects on Alzheimer’s disease
- Effects on memory and cognitive behavior
- Anticonvulsant effects
- Antidepressant and anxiolytic effects
- Analgesic and antifever effects
- Bronchodilatator effect
- Antihypertensive effect
- Kidney protective effects
- Antiageing of skin
- Winter melon safety and side effects
Winter melon also known as Benincasa hispida, wax gourd, ash gourd, white gourd, winter gourd, tallow gourd, ash pumpkin, winter melon, Chinese preserving melon, kundur fruit, chalkumra, and (alu) puhul, is a fruit the family Cucurbitaceae that is eaten as a vegetable when mature 1. The taste is rather bland but sweet 2. Winter melon fruit is covered in a fuzzy coating of fine hairs when young. The immature melon has thick white flesh that tastes sweet. The mature fruit sheds its hairs and forms a waxy white coating, giving the name of “wax gourd.” The gourd wax coating increases the long shelf life of it. Winter melon can grow of a length up to 80 cm and also have broad leaves and yellow flowers 3.
Winter melon fruit contains 93–96% water and is rich in nutrients such as vitamin C, vitamin B2 (riboflavin), sodium (Na), and calcium (Ca) 6, 7, 8. Phenolic compounds such as astilbin, catechin, and naringenin have been isolated from winter melon fruit 9. Other bioactive compound constituents include triterpenes (alnusenol, multiflorenol, isomultiflorenol), sterols (lupeol, lupeol acetate, β-sitosterol), glycosides, saccharides, carotenes, β-sitosterin, tannins, and uronic acid 10, 11. However more studies are needed to be done to isolate and identify the bioactive chemical components contained in winter melon 12.
Several lab animal and test tube studies on the functionality of winter melon fruit extracts have reported their antioxidant, anti-inflammatory, anti-ulcerogenic, antidiabetic, and anti-Alzheimer’s efficacy (see Figure 2 below) 13, 14, 15, 16, 17, 18, 19, 20, 2. However, there have been no randomized studies on the effect of ash gourd (winter melon) on the prevention of diseases in human 21. In Chinese medicine, winter melon crust is used to treat urinary dysfunction, and the fruits are used to treat fever 21. In Ayurveda, winter melon fruits are also used to treat epilepsy, lung diseases, asthma, cough, and urinary retention 21.
Figure 1. Winter melon
Figure 2. Winter melon uses
Footnotes: Diagram with different parts (aerial parts, flower, fruit pulp unripe, fruits, fruit pulp mature, and seeds) of Benincasa hispida (Thunb.) Cogn, traditional uses, and its most important pharmacological properties.
Abbreviations: PPARγ = peroxisome proliferator-activated receptor gamma; C/EBPα = CCAAT enhancer-binding protein alpha; CAT = catalase; SOD = superoxidase dismutase; GSH = reduced glutathione; LPO = lipid peroxidations.[Source 21 ]
Winter melon nutrition facts
Winter melon fruit contains 93–96% water, proteins (0.30-0.70/100 g), carbohydrates (1.10-4.00/100 g), fat (0.02-0.20/100 g), fiber (0.50-2.10/100 g), and ash (0.27-0.70/100 g).
Vitamins present in the edible portion (per 100 g) of winter melon are vitamin C (13 mg), thiamin (vitamin B1) (0.04 mg), riboflavin (vitamin B2) (0.11 mg), niacin (vitamin B3) (0.4 mg), and vitamin E. Major minerals in the edible portion (per 100 g) include sodium (Na) (111 mg), potassium (K) (6 mg), calcium (Ca) (19 mg), iron (Fe) (0.4 mg), and phosphorus (P) (19 mg) 22, 23, 24, 25. The fruit contains water-soluble polysaccharides 26, such as arabinogalactans 27.
The fruit pulp contains homogalacturonan, β-(1 → 4)-D-galactan, acidic arabinan 28 and natural sugars (e.g., glucose and fructose) 29. The mature fruit also contains organic acids such as malic and citric acid. The fruit also contain many volatile compounds, including (E,E)-2,4-nonadienal, (E)-2-hexenal, n-hexanal, n-hexyl formate, (E,E)-2,4-heptadienal, (Z)-3-hexenal, (E)-2-heptenal, 1-octen-3-ol, 2,5-dimethylpyrazine, 2-methyl pyrazine, 2-ethyl-5-methyl pyrazine, and 2,6-dimethylpyrazine, 2,3,5-trimethylpyrazine 30.
Winter melon seeds contain proteins 31, carbohydrates, phenolic compounds, amino acids, flavonoids, sterols 32, glycosides, alkaloids, fixed oils and fats, phenolic compounds, steroids 33 and unsaturated fatty acids 34. The peel contains alkaloids, saponins, steroids, carbohydrates, flavonoids 35, tannins, carotenoids, oxalates, and phytate 25.
The root contains proteins 31.
Table 1. Winter melon, ash gourd, wax gourd, chinese preserving melon (raw per 100 gram)
|Total lipid (fat)||0.2||g|
|Carbohydrate, by difference||3||g|
|Fiber, total dietary||2.9||g|
|Vitamin C (ascorbic acid)||13||mg|
|Thiamin (vitamin B1)||0.04||mg|
|Riboflavin (vitamin B2)||0.11||mg|
|Niacin (vitamin B3)||0.4||mg|
|Pantothenic acid (vitamin B5)||0.133||mg|
|Vitamin A, RAE||0||µg|
|Vitamin A, IU||0||IU|
|Vitamin D (D2 + D3), International Units||0||IU|
|Vitamin D (D2 + D3)||0||µg|
|Fatty acids, total saturated||0.016||g|
|Fatty acids, total monounsaturated||0.037||g|
|Fatty acids, total polyunsaturated||0.087||g|
|Fatty acids, total trans||0||g|
Abbreviations: SFA = saturated fatty acid; MUFA = monounsaturated fatty acid; PUFA = polyunsaturated fatty acid; SFA 16:0 = palmitic (hexadecanoic acid); SFA 18:0 = stearic (octadecanoic acid); MUFA 18:1 = oleic acid; PUFA 18:2 = linoleic acid[Source 22 ]
Winter melon bioactive compounds
Winter melon is rich in phenolic compounds. Several other bioactive compounds present in it are isomultiflorenyl acetate, isovitexin, 1-sinapoylglucose, multiflorenol, 5-gluten-3-β-ylacetate, alnusenol, and benzylalcolcohol-O-α-l-arabinopyranosyl-(1-6)-β-d-glucopyranoside 36. The most representative phytochemicals present in winter melon is shown Table 2.
Table 2. Winter melon chemical phytoconstituents
|E-2-hexenal, n-hexanal and n-hexyl formate; however, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, 2,3,5-trimethylprazine, 2-methylpyrazine, 2-ethyl-5-methylpyrazine||Fruit||Taipei, Taiwan/China||30|
|Triterpenes, sterols, flavonoid C-glycoside, benzyl glycoside, alnusenol, multiflorenol||Fruit||Kyoto/Japan||38|
|Osmotin-like protein||Seeds||New York/USA||39|
|Astilbin, catechin, naringenin||Fruit||Hainan/China||36|
|W-sitosterol, V-amyrin, quercetin||Stem||Visakhapatnam/India||42|
|Linoleic, palmitic, oleic, and stearic acids||Fruit||Temerloh, Pahang/Malaysia||44|
|Acetoin, octanal, nonanal||—||Mumbai/India||45|
|α-Tocopherol, δ-tocopherol, linoleic acid, β-sitosterol, campesterol, stigmasterol, Δ5-avenasterol||Fruit||Serdang, Selangor/Malaysia||46|
|Galactose, glucose, xylose, sorbose||Peel||Karnataka/India||47|
|Linoleic acid, linolenic acid||Seeds||Serdang, Selangor/Malaysia||48|
|Myristic acid, palmitoleic acid, oleic acid, linoleic acid, stearic acid, α-linolenic acid, palmitic acid, other saturated and unsaturated fatty acids||Seed oil||Serdang, Selangor/Malaysia||49|
|3α,29-O-di-trans-cinnamoyl-D:C-friedooleana-7,9(11)-diene, oleanolic acid 28-O-β-D-xylopyranosyl-[β-D-xylopyranosyl-(1 → 4)]-(1 → 3)-α-L-rhamnopyranosyl (1 → 2)-α-L-arabinopyranoside, oleanolic acid 28-O-β-D-glucopyranosyl-(1 → 3)-β-D-xylopyranosyl-[β-D-xylopyranosyl-(1 → 4)]-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranoside, multiflorenol, isomultiflorenyl acetate, stigmasterol, stigmasterol 3-O-β-D-glucopyranoside, α-spinasterol, α-spinasterol 3-O-β-D-glucopyranoside, β-sitosterol, daucosterol, arbutin, nicotinic acid, (+)-pinonesinol, ethyl β-D-glucopyranoside||Fruit||Jinghong/China||50|
|Phloem lectin-like protein||Exudate||Fukuoka/Japan||51|
|Linoleic acid, palmitic acid, oleic acid, stearic acid||Seeds||Rambagh, Allahabad/India||52|
|Gallic acid||Fruit||Kota Bharu/Malaysia||53|
|Gallic acid, linoleic acid||Seeds||Serdang, Selangor/Malaysia||34|
|Ascorbic acid||Fruit||Kubang Kerian, Kelantan/Malysia||55|
|β-Carotein, ascorbic acid||Peel||Mysore/India||25|
|Gallic acid, catechin, epicatechin, rutin, quercetin, quercetin-3-D-galactoside, trans-ferrulic acid, oleanolic acid, ursolic acid||Fruit||Buzau/Romania||19|
Winter melon uses
Scientific reports suggest that winter melon possesses many important nutritious substances, including vitamins, natural sugars, amino acids, organic acids, and mineral elements 57, 23, 58. Winter melon fruit contains 93–96% water and is rich in nutrients such as vitamin C (ascorbic acid), vitamin B2 (riboflavin), sodium (Na), and calcium (Ca) 6, 7, 8. Phenolic compounds such as astilbin, catechin, and naringenin have been isolated from winter melon fruit 9. Other bioactive compound constituents include triterpenes (alnusenol, multiflorenol, isomultiflorenol), sterols (lupeol, lupeol acetate, β-sitosterol), glycosides, saccharides, carotenes, β-sitosterin, tannins, and uronic acid 10, 11.
In India, winter melon is used as a winter season vegetable for a wide variety of diseases. Its medicinal properties have been also recognized in the Ayurvedic system of medicine, spiritual traditions of India and Yoga 21. In Vietnam, its soup (cooked with pork short ribs) is traditionally used by breastfeeding mothers 21. In north India and almost all regions in Bangladesh, it is added with pulses like as moong which usually crushed, along with wax gourd, makes a dish locally called bori, which after sun drying is used in curry dishes and eaten with rice or chapati 59. To make wax gourd soup in China, it is used in stir-fries or added into pork or pork/beef bones, which often served in the scooped-out gourd, carved by scraping off the waxy coating. It is also cut into pieces, candied and normally eaten during the time of New Year festivals, or used as filling in Sweetheart cake. For the Moon Festival, the Chinese and Taiwanese also used it in moon cakes as a base filling. It is candied by the people of the Philippines and is used as a pastry filling for bakpia. In some savoury soups and stir-fries, it also acts as an ingredient. In Nepal, India, and Bangladesh, the tendrils, shoots, and leaves of the plant are consumed as green vegetables 23.
Winter melon is widely used in Chinese medicine, in the treatment of fever, cough accompanied by thick mucus and urinary disorders, it is used especially in bark with a very good diuretic effect 21. The fruit is recommended for overweight people who want to follow diets 21. In Ayurvedic medicine, it is used in the treatment of epilepsy, cough, lung disease, hiccups, asthma, internal bleeding, and urinary retention. In India, a fruit compote called Petha Cubes is made from the pulp of the fruit, which is recommended for vegetarians 60.
Winter melon fruit is also used in peptic ulcer, and it is also used in diabetes mellitus, urinary infection, hemorrhages from internal organs, insanity, epilepsy, and other nervous disorders in Ayurveda 61. The fruit is sweet and traditionally used as a cooling, styptic, antiperiodic, laxative, diuretic, tonic, aphrodisiac, and cardiotonic, and also in jaundice, dyspepsia, urinary calculi, blood disease (e.g., hemorrhages from internal organs), insanity, epilepsy, asthma, diabetes, vitiated conditions of pitta, fever, menstrual disorders, and balancing the body heat 53.
Antioxidants are man-made or natural substances that may prevent or delay some types of cell damage 62. Antioxidants are found in many foods, including fruits and vegetables 62. Antioxidants are also available as dietary supplements. Table 3 shows the antioxidant effects of various parts of winter melon.
The body’s trillions of cells face constant threat from chemicals called free radicals. In very high levels, free radicals are capable of damaging cells and genetic material. The body generates free radicals as the inevitable byproducts of turning food into energy. Free radicals are also formed after exercising or exposure to cigarette smoke, air pollution, and sunlight 62. Oxidative stress is a term used for free radical diseases 63, 64. It is defined as the imbalance between free radicals and antioxidants, given that oxidants (free radicals) are more and have a destructive potential on the human body 65, 66.
The methanolic ash gourd seed extract showed a concentration-dependent (25-200 μg/mL) 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide radical scavenging effects 67. Another study revealed that the ethanolic winter melon seed extract shows better DPPH and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging along with total phenolic content (TPC) than its ethyl acetate and n-hexane extracts 48. The seed oil (0.1 mg/mL) also showed significant 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radical scavenging capacity 68. This study also determined the total phenolic content in seed oil. The aqueous extract of ash gourd plant reduced reactive oxygen species (ROS) in human umbilical vein endothelial cells (HUVECs) 69.
Polysaccharides of fruit extract showed 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals scavenging activity with an EC50 (half-maximal effective concentration) value of 0.98 mg/mL 56. The seed oil also showed DPPH and ABTS radical scavenging capacity. However, the antioxidant activity was lower than the catechin and BHT at the same concentration (0.1 mg/mL) 49. Petroleum ether and methanol fruit extracts increased in catalase (CAT) levels in gastric ulcer rats 70. Hispidalin isolated from this herb also showed DPPH radical scavenging and inhibition of lipid peroxidation capacity 71. The aqueous fruit extract significantly increased the antioxidant status as well as levels of vitamin C concentration in gastric juice of rats 72.
Table 3. Antioxidant properties of winter melon parts
|Extract/isolated compounds||Test system||Results||References|
|Crude oil from seeds||DPPH|
|DPPH: EC50 = 0.1 mg/mL|
ABTS: EC50 = 0.1 mg/mL
Significant antioxidant effect
Standards: methyl ether, fatty acids
|Seeds extract||DPPH, ABTS, total phenolic content||EC50 = 10 − 100 μg/mL|
Significant antioxidant effect
Standards: methyl ether, fatty acids
|Methanolic and aqueous peel extracts||DPPH||EC50 = 10 − 100 μg/mL|
Concentration-dependent radical scavenging activity
The methanolic extract exhibited a better antioxidant effect
|Aqueous seeds extract||TPC, TFC|
DPPH, ABTS, H2O2, linoleic acid oxidation nitrite scavenging assay
|TPC: EC50 = 81.3 ± 1.4 μg gallic acid/g|
TFC: EC50 = 486.8 ± 4.1 μg catechin/g dry mass
DPPH: EC50 = 0.6 − 3 mg/mL
Concentration-dependent antioxidant activity
Standards: catechin 0.05-0.5 mg/mL, BHT, ascorbic acid 10 mg/mL
ABTS radical scavenging assay
|DPPH: EC50 = 0.1 mg/mL|
The antioxidant activity of the seed oil was lower than the catechin and BHT at the same concentration.
Lipid peroxidation assay
|DPPH: EC50 = 2 − 40 μg/mL|
EC50 = 40 μg/mL
Significant DPPH radical scavenging and inhibition of lipid peroxidation capacity
Standard: methyl ether
|Methanol, ethanol, aqueous peel extracts||DPPH|
Reducing power assay
|Significant antioxidant effect|
Standard: acarbose 20, 40, 60, 80, 100 μg/mL
|Significant antioxidant effect|
|Polysaccharides of fruit extract||DPPH||EC50 = 0.98 mg/mL|
Significant antioxidant effect
Abbreviations: TPC = total phenolic contents; TFC = total flavonoid contents (TFC); ABTS = 2, 2′-azinobis (3-ethylbenzothiazoline-6-sulfonic acid); DPPH = 2,2-diphenyl-1-picrylhydrazyl free radical-scavenging ability; BHT = antioxidant butylated hydroxytoluene; FAME = fatty acid methyl ester; EC50 = the half-maximal effective concentration.[Source 21 ]
Antibacterial, antihelmintic, and larvicidal effects
Due to the excessive use of antibiotics that can lead to the development of antibiotic resistance of various strains of bacteria 75, 76, attempts have been made to use natural antibiotic alternatives 77. Most of these options include plants with antiviral and antibacterial properties that can be effective against gram-negative and gram-negative germs, which are often difficult to eradicate 78. The methanolic ash gourd whole plant extract (500 μg/disc) was found to act against Pseudomonas aeruginosa and Vibrio parahaemolyticus 79. In the latter case, the zone of inhibition was 6 mm only. Hispidalin, an isolated compound from winter melon seeds, was found to act against several bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Salmonella enterica) and fungi (e.g., Aspergillus flavus, Penicillium chrysogenum, Fusarium Solani, and Colletotrichum gloeosporioides) 71. In this case, the minimum inhibitory concentrations (MIC = the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation) were 30-120 and 100-200 μg/mL for bacterial and fungal strains, respectively. Moreover, the aqueous, methanol, and petroleum extracts of winter melon seeds showed significant therapeutic efficacy with methanol extract being the best comparable to the antibiotic ciprofloxacin. In other study, the aqueous peel extract showed strong antibacterial activity against S. aureus (MIC = 14.5 μg/mL), Micrococcus luteus (MIC = 8.6 μg/mL), E. coli (MIC = 6.1 μg/mL), and Klebsiella pneumoniae (MIC = 13.4 μg/mL) 20. The herb shows prebiotic activity 80. Table 4 shows the antibacterial, antihelminthic and larvacidal effects of various parts of winter melon.
Ethanolic ash gourd seeds extract (20, 40 and 60 mg) showed a dose-dependent anthelmintic activity on Pheretima posthuma 81. The phloem lectin-like protein from the exudate of ash gourd exerted an inhibitory effect on the Samia ricini larvae 51.
Table 4. Antimicrobial, anthelmintic, and larvicidal effects of winter melon parts
|Extract/isolated compounds||Dose/concentration model (in vitro/in vivo)||Results/mechanisms||References|
|Methanolic whole plant extract||Pseudomonas aeruginosa|
|IC50 = 500 μg/disc|
Zone of inhibition = 6 mm
|Hispidalin||Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Salmonella enterica;|
Fungi: Penicillium chrysogenum, Fusarium solani, Aspergillus flavus, Colletotrichum gloeosporioides
Standard: acetoin (0.01–20 μg/μl)
|Antibacterial: MIC = 30 − 120 μg/mL,|
Antifungal: MIC = 100 − 200 μg/mL
|Aqueous peel extract||Staphylococcus aureus, Micrococcus luteus, Escherichia coli, Klebsiella pneumoniae|
Standard: DMSO 150 μL
|Antibacterial: MIC = 6.1 − 14.5 μg/mL||20|
|Anthelmintic effect (antiparasitic to treat infections with parasitic worms)|
|Ethanolic seed extract||Pheretima posthuman/in vitro|
Standard: phenytoin sodium
|IC50 = 20, 40, and 60 mg|
Dose-dependent anthelmintic effect
|Larvicidal effect (insecticide that is specifically targeted against the larval life stage of an insect)|
|Phloem lectin-like protein from the exudate||Samia ricini larvae/in vitro|
Standards: Precision Plus Protein™, serum albumin
|↑ inhibitory activity against the larvae|
Dose: 70 μg/g
Abbreviations: IC50 = value concentration that inhibits cell growth by 50%; MIC = minimum inhibitory concentration.[Source 21 ]
The methanolic ash gourd seeds extract (100-300 mg/kg, orally) showed dose-dependent anti-inflammatory effects on carrageenan-induced paw oedema rat (n = 6) model 67. The winter melon fruit peel methanolic extract showed an anti-inflammatory effect on egg albumin-induced inflammation in rats 83. The petroleum ether and methanolic fruit extract of winter melon (300 mg/kg, oral) showed a dose-dependent anti-inflammatory effect on cotton pellet-induced granuloma models in rats, carrageenan-induced paw oedema, and histamine-induced paw edema 74.
The winter melon fruit, seed, and root proteins (10-1000 μg/mL) exerted a concentration-dependent cytotoxic effect on Artemia salina (a species of brine shrimp) 21. The median lethal concentration (LC50) values of ash gourd fruit, seed, and root extract were 44, 41, and 50 μg/mL, respectively 31. In this study, the ash gourd root proteins inhibited the proliferation of HeLa and K-562 cells by 28.50 and 36.60%, respectively 31. Another study reveals that the whole winter melon plant methanolic extract (5-50 μg/mL) exerted a cytotoxic effect on Artemia salina (a species of brine shrimp) (LC50: 45.187 μg/mL) 79. Moreover, the aqueous winter melon seed extract (20-800 μg/mL) did not exert cytotoxic effects on HUVECs and normal fibroblast (NIH/3T3) cells. On male C57BL/6 mice, the extract showed a potent inhibitory effect on basic fibroblast growth factor- (bFGF-) induced angiogenesis 84. The aqueous extract (1–20 μg/mL) also reduced cell adhesion molecules activation by inhibiting monocyte adhesion, ROS, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) on high glucose (25 mM) induced HUVECs cells 85.
Table 5 shows the cytotoxic (toxic to cells) and anti-cancer effects of various parts of winter melon.
Table 5. Anticancer effects of various parts of winter melon
|Extract/isolated compounds||Model dose/concentration||Results/mechanisms||References|
|Aqueous seed extract||HUVECs, NIH/3T3 cells/in vitro|
Male C57BL/6 mice/in vivo
IC50 = 20 − 800 μg/mL
|No cytotoxicity on HUVECs, NIH/3T3 cells|
decrease bFGF-induced angiogenesis in mice
|Fruit, seed, root proteins||HeLa, K-562 cells/in vitro|
IC50 of fruit, seeds root extract = 44, 40-50 μg/mL
IC50 = 10 − 1000 μg/mL in Artemia salina
IC50 = 10–50 μg/mL on HeLa, K-562 cells
Standards: lysozime, tyrosine, carbonic anhydrase, ovalbumin, albumin
|Decrease cell proliferation by 28.50-36.80%||31|
|Aqueous extract||HUVECs cells/in vitro|
IC50 = 1–20 μg/mL on high glucose (25 mM)
Standards: glucose 25 mM, glucose and ABH 5 μg/ml, 20 μg/ml
|Decrease cell adhesion molecules activation,|
Decrease ROS, NF-κB
Decrease inhibiting monocyte adhesion
|Methanolic/whole plant extract||Artemia salina/in vitro|
IC50 = 45.186 μg/mL
Standard: DMSO, vincristine sulphate 0.91 μg/mL
|Increase cytotoxic effect concentration-dependent||79|
Abbreviations: IC50 = value concentration that inhibits cell growth by 50%; bFGF = basic fibroblast growth factor; ROS = reactive oxygen species; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; NNGH = N-isobutyl-N-(4-methoxyphenylsulfonyl)-glycylhydroxamic acid.[Source 21 ]
Gastrointestinal protective effects
Fresh ash gourd juice (1-4 mL/animal, orally), ethanol (12, 24 and 48 mg/kg, orally), and petroleum ether extract (0.75, 1.5 and 3 mg/kg, orally) in swimming stress, aspirin plus restraint, serotonin-induced ulcers, and indomethacin plus histamine displayed a dose-dependent anti experimental ulcers effect in rats and mice 60.
The petroleum ether and methanol winter melon fruit extracts (300 mg/kg, orally) significantly reduced ulcer index, vascular permeability, and malondialdehyde (MDA) content, while an increase in CAT levels in comparison to the control group in pylorus ligated gastric ulcers, ethanol-induced gastric mucosal damage, and cold restraint stress- (CRS-) induced gastric ulcer rat models 70. The winter melon fruit extract (1 mL/kg, orally) also decreased ulcer index as well as malondialdehyde (MDA), superoxide dismutase (SOD), and vitamin C levels in indomethacin-induced gastric ulcer in rats 86.
The hydromethanol, ethyl acetate, and aqueous ripe winter melon fruit extracts (20 mg/kg, orally/alternative days) were treated for 14 days in ranitidine (5 mg/kg, orally) induced hypochlorhydria in rats 72. The aqueous extract showed better effects on the test animals. It increased the antioxidant status as well as levels of pepsin, vitamin C, and gastric juice chloride concentration than the other extracts 72. On the other hand, the extract of winter melon fruits with the whole plant of Fumaria vaillantii Loisel (earthsmoke) (1 : 1) (20 mg/kg, orally) was administrated in ranitidine (5 mg/kg) induced hypochlorhydria in rats as pre-and cotreatment manners. The extract significantly enhanced the concentration of pepsin, iron levels in serum, chloride level in gastric juice, and liver along with blood hemoglobin level in experimental animals 87.
A prospective pilot study on dyspeptic patients (n = 20) (baseline between 30 days and 45 days) aged between 18 and 45 years with only single dose of 200 mL winter melon fruit juice every morning in empty stomach for thirty days suggests that a significant improvement of pain, nausea, belching, retrosternal burning, and bowel habits among the patients 88. Table 6 shows the gastrointestinal -protective effects of various parts of winter melon.
Table 6. Gastrointestinal protective effects of various parts of winter melon
|Fresh juice, petroleum ether, alcoholic/fruits extract||Aspirin plus restraint, serotonin-induced ulcers, indomethacin plus histamine|
Dose: 1 ml/mouse
|↓ulcer index formed by several ulcerogenic||60|
|Fresh juice, ethanol, petroleum ether extracts (5% v/v)||Aspirin plus restraint, swimming stress, indomethacin plus histamine, and serotonin-induced ulcers|
Rats and mice/in vivo
Fresh juice (1-4 mL/animal, p.o.),
Dose: ethanol extract 12, 24, and 48 mg/kg, p.o.
Dose: petroleum ether extract 0.75, 1.5, 3 mg/kg, p.o.
|Dose-dependent anti-ulcerogenic effect|
The fresh juice treatment for 3 months did not change the indices (i.e., WBC, RBC counts HCT, HB, MCV, MCH urea, and sugar)
No behavioural changes in experimental animals.
|Petroleum ether, methanol/fruits extract||Pylorus ligated (PL) gastric ulcers, ethanol-induced gastric mucosal damage, cold restraint-stress- (CRS-) induced gastric ulcer|
Dose: 300 mg/kg, p.o.
|Fruit extract||Indomethacin-induced gastric ulcer|
Dose: 1 mL/kg, p.o.
|↓ulcer index, ↓MDA|
↓SOD, ↓vitamin C
|Hydromethanol, aqueous ripe fruit, ethyl acetate extracts||Ranitidine (5 mg/kg) induced hypochlorhydria|
Dose: 20 mg/kg, p.o./alternative days for 14 days
|The aqueous extract showed better effects: ↑antioxidant status, ↑pepsin, ↑vitamin C, ↑chloride in gastric juice||72|
|Fruit extract with the whole plant of Fumaria vaillantii Loisel (1 : 1)||Ranitidine (5 mg/kg) induced hypochlorhydria|
Dose: 20 mg/kg, p.o.
|↑iron levels in serum, ↑pepsin, ↑gastric juice chloride level and liver ↑blood haemoglobin level||87|
|Fruit juice||Prospective pilot study|
Dyspeptic patients (n = 20) (baseline between 30-45 days); age 18-45 years; 200 mL single-dose every morning in empty stomach for thirty days
↓belching retrosternal burning
|Methanolic fruit extract||Castor oil-induced diarrheal, PGE2-induced, enter pooling and charcoal meal models|
Dose: 200, 400, and 600 mg/kg, orally by gavage
|Dose-dependent antidiarrheal effect|
↓PGE2- induced, enter pooling ↓gastrointestinal motility
|Methanolic fruit extract||Castor oil, charcoal meal, and antienter pooling models in rats/in vivo|
Dose: 200, 400, 600 mg/kg, p.o.
|↓ activity against castor oil-induced diarrhoea; ↓PGE2 induced enter pooling ↓gastrointestinal motility||90|
Abbreviations: ↑(increased); ↓(decreased); WBC = white blood cells; RBC = red blood cells; HCT = hematocrit; HB = hemoglobin; MCV = mean corpuscular volume; MCH = mean corpuscular haemoglobin concentration; MDA = malondialdehyde; CAT = catalase; SOD = superoxide dismutase; PGE2 = prostaglandin E2.[Source 21 ]
The winter melon fruit methanolic extract displayed potential antidiarrheal activity on the castor oil-induced diarrheal rat model 90. It was also seen to inhibit induced PGE2, enter pooling, and reduce in the motility of gastro-intestine in charcoal meal rats 90. The same extract also possessed a significant inhibitory activity against castor oil-induced diarrhoea and induced PGE2, enter pooling and gastrointestinal motility at 200, 400, and 600 mg/kg (orally) in castor oil, charcoal meal, and antienter pooling models in rats 90.
The methanolic winter melon
stem extract (50,100, 200 mg/kg, orally) dose-dependently lowered the blood glucose level in alloxan-induced diabetic rats 42. The chloroform fruit extract (250 and 500 mg/kg, orally) dose-dependently ameliorated the derangements in lipid metabolism in alloxan-induced diabetic albino rats after 14 days of treatment 91. The study reveals that the methanol, ethanol, and aqueous winter melon peel extracts showed significant α-amylase inhibition activity 25. The ethanol and ethyl ethanoate winter melon leaf extracts lowered the blood glucose level of the diabetic mice in a dose-dependent manner 92. Antidiabetic effects of various parts of winter melon have been shown in Table 7.
Table 7. Winter melon antidiabetic, antiobesity, lipid-lowering and neuroprotective effects
|Extract/isolated compounds||Model dose/concentration||Results/potential mechanisms||References|
|Hexane, chloroform, ethyl acetate/aqueous fruit extract||3T3-L1 cells/in vitro||Hexane extract: ↓adipocyte differentiation, ↓PPARγ, ↓C/EBPα, ↓leptin gene expression, ↓lipids accumulation, ↑releasing of glycerol, ↑ triglycerides||93|
|Methanolic/stem extract||Alloxan-induced diabetes|
Dose: 50,100, 200 mg/kg p.o.
|↓blood glucose level dose-dependent||42|
|Chloroform/fruits extract||Alloxan-induced diabetes|
Dose: 250, 500 mg/kg p.o.
|Dose-dependently ameliorated the disorders in the metabolism of lipids in diabetic mice||91|
|Ethanol, hexane, ethyl ethanoate/leaf extract||STZ-induced diabetes|
Dose: 0.2-1 g/kg, i.p
|Ethanol, ethyl ethanoate extracts: ↓blood glucose level||92|
|Methanolic fruit extract||Mice/in vivo|
Dose: 0.2-1 g/kg, i.p.
|Antiageing of skin|
|Petroleum ether, chloroform, ethyl acetate, methanol/dried fruit pulp extract||Stratum corneum of human skin and dansyl chloride fluorescence models|
|Cream prepared from the fruit extract showed the significant antiageing effect||95|
|Effects on other diseases|
|Fruit methanol extract||Antigen-antibody induced reaction in rats exudate cells/in vitro||↓histamine release, anti-inflammatory effect|
Triterpenes, sterols, multiflorenol, alnusenol exerted better inhibitory effects
|Methanolic fruits extract||Histamine and acetylcholine-induced bronchospasm|
Guinea pigs/in vivo
Dose: 50, 200, 400 mg/kg, p.o.
|Bronchodilator effect: dose-dependent protection against histamine and acetylcholine-induced bronchospasm||96|
|Petroleum ether, methanolic/fruits extract||Histamine stimulated paw oedema carrageenan- stimulated paw oedema cotton pellet stimulated granuloma|
Dose: 300 mg/kg, p.o.
|Juice||Isolated rat aortic ring/in vitro|
Cultured porcine endothelial cells/in vitro
Dose: 0.4–1.6 mL/kg, i.v.
|Antihypertensive effect dose-dependent|
↑relaxation, ↓contraction of isolated rat aortic ring
↑NO in cultured porcine aortic endothelial cells
|Methanolic fruit extract||Renal ischemia/reperfusion injury model|
Dose: 500 mg/kg/day, p.o. for 5 days
↓MDA, ↑SOD, CAT, ↑GSH
|Ethanolic seeds extract||Ethylene glycol induced chronic|
Dose:250, 500 mg/kg, p.o. for 35 days
↓ urinary oxalate, ↓endogenous oxalate synthesis; ↓urinary protein excretion, ↓kidney oxalate and calcium; ↓elevated serum levels of sodium, creatinine, calcium, phosphorus
|Fruit juice||Morphine addiction model|
Dose: 1 mL/mouse, p.o.
|The development of morphine addiction prevented along with the suppression of opioid withdrawal symptoms||100|
|Methanolic fruit extract||Spontaneous motor, muscle relaxant, antihistaminic effect and barbiturate induced hypnosis models|
Mice, rats, and guinea pigs/in vivo
Dose: 200-3000 mg/kg, p.o.
|↑ barbiturate induced hypnosis|
↑ antihistaminic activity
|Fruit methanol extract||Pentylenetetrazole, strychnine, picrotoxin, and maximal electro seizures model|
Dose: 0.2-1 g/kg, p.o.
|Dose-dependent anticonvulsant activity||102|
|Methanolic fruit extract||Acetic acid-induced writhing and hot plate|
Dose: 200, 400, 600 mg/kg, p.o.
|Dose-dependent analgesic effect||103|
|Aqueous pulp extract||Colchicine-induced Alzheimer’s model|
Dose: 100-450 mg/kg, p.o.
|↑SOD, ↑CAT, ↑GSH, ↓LPO dose-dependent||24|
|Ethanolic seed extract||Rats/in vivo|
Dose: 250, 500 mg/kg, p.o.
|Dose-dependent analgesic and antipyretic effects||104|
|Methanolic fruit extract||Marble-burying and motor coordination tests|
Dose: 200, 400, 600 mg/kg, p.o.
|Significant dose-dependent anticompulsive effect||105|
|Methanolic leaf extract||Acetic acid-induced writhing|
Dose: 50, 100, 200, 400 mg/kg, p.o.
|Dose-dependent analgesic effect||106|
|Fruit peel methanolic extract||Egg albumin-induced inflammation in rats; acetic acid-induced writhing, formalin-induced pain, hot plate-induced, and pentylenetetrazol-induced convulsions|
Dose: 50, 100, 200, 400 mg/kg, p.o.
|Dose-dependently (0.25-1.5 g/kg) inhibited acetic acid-induced writhing, formalin-induced pain licking, and hot plate-induced pain in mice.|
Significantly inhibition of egg albumin-induced inflammation in rats and pentylenetetrazol-induced convulsion in mice
|Ethanolic seed extract||Anticonvulsant activity|
Dose: 250, 500 mg/kg, p.o.
|Dose-dependent anticonvulsant effects||81|
|Methanolic fruit extract||TST and FST model|
Dose: 50, 100, 200 mg/kg, p.o.
|Dose-dependent antidepressant effect possibly through GABAergic involvement.||107|
|Petroleum ether, methanolic, aqueous/fruit extracts||Motor coordination, locomotor, cognitive behaviour, anxiolytic, haloperidol-induced catalepsy, and anticonvulsant models|
Dose: 100, 200, 400 mg/kg, p.o.
|Dose-dependent anxiolytic, analgesic, and nootropic activity||108|
Antiobesity and lipid-lowering effect
Lipids are fatty organic substances that are the largest source of energy for the body. The vast majority of fats are stored in solid form in various organs or skin, and a small part circulates in the blood in liquid form 109. Imbalances in lipid metabolism lead to pathophysiological changes and the appearance of chronic diseases such as cardiovascular disease, fatty liver, endocrine disorders, and diabetes 110. Methanolic fruit extract (0.2-1 g/kg) reduced food intake, suggesting anorectic activity in mice 94. Hexane fraction from the aqueous winter melon fruit extract inhibited adipocyte differentiation by blocking leptin gene expression, peroxisome proliferator-activated receptor gamma (PPARγ), and CCAAT enhancer-binding protein alpha (C/EBPα), resulting in the reduction of lipid accumulation, increased releasing of glycerol and intracellular triglycerides in 3T3-L1 cells 93.
Effects on Alzheimer’s disease
The winter melon fruit extract at a dose of 400 mg/kg (orally) showed a protective effect on colchicine-induced Alzheimer’s disease in rats, possibly through the presence of both vitamin E and β-carotene protecting rat neurons against oxidative stress 24. On the other hand, the aqueous fruit pulp extract (100-450 mg/kg, p.o.) dose-dependently increased SOD, CAT, and GSH, while reduced in LPO levels in the colchicine-induced Alzheimer’s rat model 24.
Effects on memory and cognitive behavior
The methanolic winter melon fruit extract (200, 400, or 600 mg/kg, orally) showed a significant dose-dependent anticompulsive effect in marble-burying and motor coordination test models in mice 105. The petroleum ether, methanolic, and aqueous winter melon fruit extracts (100, 200, and 400 mg/kg, p.o.) showed a dose-dependent nootropic activity in the cognitive behaviour mouse model 108. Kumar and Nirmala 111 also studied the possible nootropic (enhance memory or other cognitive functions) effects of the winter melon fruit on experimental animals.
The winter melon fruit methanol extract (0.2-1 g/kg, orally) showed a dose-dependent anticonvulsant activity in pentylenetetrazole, strychnine and picrotoxin, and maximal electro seizures model 102. On the other hand, winter melon fruit peel methanolic extract exerted a dose-dependent (0.25-1.5 g/kg) anticonvulsant effect on pentylenetetrazol-induced convulsion in mouse models 83. Ethanolic winter melon seed extract (250 and 500 mg/kg, p.o.) showed a dose-dependent anticonvulsant effect in anticonvulsant activity in Swiss albino mice 81.
Antidepressant and anxiolytic effects
Methanolic winter melon fruit extract (50, 100, and 200 mg/kg, p.o.) showed a dose-dependent antidepressant-like effect in TST and FST models possibly through GABAergic involvement in Swiss mice 107.
Petroleum ether, methanolic, and aqueous winter melon fruit extracts (100, 200, and 400 mg/kg, p.o.) confirmed a dose-dependent anxiolytic activity in mice 108. Effects of various parts of winter melon on the nervous system are shown in Table 7 above.
Analgesic and antifever effects
The methanolic winter melon fruit extract (200, 400, and 600 mg/kg, orally) showed a dose-dependent analgesic effect in acetic acid-induced writhing and hot plate model in mice 103. The ethanolic winter melon seed extract (250 and 500 mg/kg, p.o.) exerted a dose-dependent analgesic and antipyretic effect in Wistar albino rats 104. Winter melon fruit peel methanolic extract also dose-dependently (0.25-1.5 g/kg) inhibited acetic acid-induced writhing, formalin-induced pain licking, and hot plate-induced pain in mice 83.
In another study, the methanolic winter melon seed extract (100-300 mg/kg, p.o.) also showed a dose-dependent analgesic effect on the rats (n = 6) model 67. The methanolic leaf extract (50-400 mg/kg, p.o.) exerted a dose-dependent analgesic effect in an acetic acid-induced writhing mouse model 106. Petroleum ether, methanolic, and aqueous winter melon fruit extracts (100, 200 and 400 mg/kg, p.o.) showed a dose-dependent analgesic effect in the mouse model 108. The ash gourd juice juice (1 mL, p.o.) prevents morphine addiction development along with the suppression of opioid withdrawal symptoms in mice 100. In experimental animals such as rats, mice, and guinea pigs, the methanolic winter melon fruit extract (200-3000 mg/kg, p.o.) significantly potentiated the barbiturate stimulated hypnosis 101.
Winter melon fruit methanol extract inhibited histamine release 38. The methanolic extract (50, 200, and 400 mg/kg, orally) of winter melon exhibited significant protection in guinea pigs against the histamine and acetylcholine-induced bronchospasm 96. The methanolic winter melon fruit extract (200-3000 mg/kg, p.o.) showed significant antihistaminic activity on experimental animals (e.g., rats, mice, and guinea pigs) 101.
The ACE inhibitory effect of the winter melon plant may show the pharmacological basis in the treatment of high blood pressure for its long time uses in traditional Chinese medicine. The winter melon fruit juice (0.4 – 1.6 mL/kg, i.v.) dose-dependently lowered blood pressure, concentration-dependently showed relaxation of isolated rat aortic rings and produced nitric oxide (NO) from the cultured porcine aortic endothelial cells 97. Polysaccharides of winter melon fruit extract showed an antiglycation effect 56.
Kidney protective effects
Methanolic winter melon fruit extract (500 mg/kg/day, orally) for five days reduced the MDA content, while the increase in SOD, CAT, and GSH levels in renal ischemia/reperfusion injury in female Wistar albino rats 98. Winter melon seed ethanolic extract (250 and 500 mg/kg, orally) for 35 days significantly lowered the increased urinary oxalate, presenting a regulatory action on endogenous oxalate synthesis; decreased in the urinary excretion and kidney retention levels of protein, oxalate, and calcium; and reduced the increased serum levels of sodium, calcium, phosphorus, and creatinine levels in ethylene glycol induced chronic hyperoxaluria in Wistar albino rat 99.
Effects of various parts of winter melon on the kidney are shown in Table 7 above.
Antiageing of skin
A cream prepared from the dried ash gourd fruit pulp extract (petroleum ether, chloroform, ethyl acetate, and methanol) showed a significant antiageing effect on the stratum corneum of human skin and dansyl chloride fluorescence models 95.
Winter melon safety and side effects
The fresh ash gourd juice (5% v/v) treatment for 3 months did not change the total white blood cells (WBC), red blood cells (RBC), hemoglobin (HB), mean corpuscular haemoglobin (MCH), hematocrit (HCT), mean corpuscular volume (MCV), sugar, and urea levels in rats and mice 60. The treatment also caused no behavioural changes in experimental animals 60. The methanolic extract of winter melon fruit was nontoxic and did not cause the death of mice, rats, and guinea pigs in doses up to 3.0 g/kg 101. Other studies, performed in female and male rats, concluded that the standardized hydroalcoholic (70% ethanol) extract of the fruit pulp of winter melon administered orally was relatively safe when to female and male rats 112. Up to oral dose (1000 mg/kg body weight/day) level, no-observe-adverse-effect-level (NOAEL) was obtained for the extract in the 90-days toxicity study. The ethanolic seed extract up to 5000 mg/kg (orally) did not exert toxicity in rats 104. There is a report of Di-2-ethylhexyl phthalate (DEHP), a popularly used plasticizer, contaminated winter melon fruit collected from southern and northern provinces in China and is harmful to human health 41.References
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