Contents
What is a cucumber
Cucumber (Cucumis sativus L.) is a widely cultivated fruit and it’s a member of the Cucurbitaceae family, which includes species with therapeutic potential such as melon, squash, and pumpkin 1). Cucumber is a creeping vine that bears cucumiform fruits but are eaten as vegetables. Cucumber is widely consumed fresh in salads or fermented (pickles) or as a cooked vegetable. The cucumber is originally from South Asia, but now grows on most continents. Many different types of cucumber are traded on the global market. Cucumber is susceptible to fruit rot caused by the oomycete pathogen, Phytophthora capsici 2). Though Phytophthora capsici infects vegetative tissues in most crops, in cucumber, the fruits are the primary target of infection 3). Cucumber is primarily eaten immature, and they’re typically harvested at 8–12 days post-pollination, while fruit ripening and seed maturity is at ~30–35 days post-pollination 4).
Cucumber varieties
Cucumbers are classified into three main cultivar groups: “slicing”, “pickling”, and “burpless”.
Slicing cucumber
Cucumbers grown to eat fresh are called slicing cucumbers. The main varieties of slicers mature on vines with large leaves that provide shading. They are mainly eaten in the unripe green form, since the ripe yellow form normally becomes bitter and sour. Slicers grown commercially for the North American market are generally longer, smoother, more uniform in color, and have a much tougher skin. Slicers in other countries are smaller and have a thinner, more delicate skin, often having fewer seeds and being sold in a plastic skin for protection. Sometimes these are known as English cucumbers. This variety may also be called a “telegraph cucumber”, particularly in Australasia. Smaller slicing cucumbers can also be pickled.
Pickling cucumber
Pickling with brine, sugar, vinegar, and spices creates various, flavored products from cucumbers and other foods. Although any cucumber can be pickled, commercial pickles are made from cucumbers specially bred for uniformity of length-to-diameter ratio and lack of voids in the flesh. Those cucumbers intended for pickling, called picklers, grow to about 7 to 10 cm (3 to 4 in) long and 2.5 cm (1 in) wide. Compared to slicers, picklers tend to be shorter, thicker, less regularly shaped, and have bumpy skin with tiny white or black-dotted spines. Color can vary from creamy yellow to pale or dark green. The process of pickling led to the use of paraffin wax as a seal for jars used to preserve pickled and other preserved foods, and to the Mason jar made from thick glass able to tolerate high temperatures used in processing pickles and other foods for long-term shelf-life. The liquid made from pickling is called “pickle juice.”
Gherkin
Gherkins, also called cornichons, baby dills, or baby pickles, are small, whole, unsliced cucumbers, typically those 1 inch (2.5 cm) to 5 inches (13 cm) in length, often with bumpy skin, and pickled in variable combinations of brine, vinegar, spices, and sugar. In the United Kingdom, gherkins may be prepared predominantly in vinegar, imparting an acidic flavor “punch” as a side-dish for meals.
Although gherkins may be grown in greenhouses, they are commonly grown as a field crop, processed locally, and packaged in jars in Canada, the United States, and India. India, Turkey, Ukraine and Mexico compete as producers for the global gherkin market, with the European Union, United States, Canada, and Israel as major importers.
The word gherkin derived in the mid-17th century from early modern Dutch, gurken or augurken for “small pickled cucumber”. The term, West Indian gherkin, has been applied to Cucumis anguria L., a related species of Cucumis sativus, the most common cucumber plant.
Burpless cucumber
Burpless cucumbers are sweeter and have a thinner skin than other varieties of cucumber, and are reputed to be easy to digest and to have a pleasant taste. They can grow as long as 2 feet (0.61 m). They are nearly seedless, and have a delicate skin. Most commonly grown in greenhouses, these parthenocarpic cucumbers are often found in grocery markets, shrink-wrapped in plastic. They are sometimes marketed as seedless or burpless, because the seeds and skin of other varieties of cucumbers are said to give some people gas.
Other cultivars
- Lebanese cucumbers are small, smooth-skinned and mild, yet with a distinct flavor and aroma. Like the English cucumber, Lebanese cucumbers are nearly seedless.
- East Asian cucumbers are mild, slender, deep green, and have a bumpy, ridged skin. They can be used for slicing, salads, pickling, etc., and are available year-round. They are usually burpless as well.
- Persian cucumber, which are mini, seedless, and slightly sweet, are available from Canada during the summer, and all year-round in the US. Easy to cut and peel, it is on average 4–7 in (10–18 cm) long. They are commonly eaten chopped up in plain yogurt with mint or sliced thin and long with salt and lemon juice. Vines are parthenocarpic, requiring no pollinators for fruit set.
- Beit Alpha cucumbers are small, sweet parthenocarpic cucumbers adapted to the dry climate of the Middle East.
- Apple cucumbers are short, round cucumbers grown in New Zealand and parts of Europe, known for their light yellow-green color and mildly sweet flavor. When mature, the fruit may grow tiny spines, and contains numerous edible green seeds. The fruit is usually eaten raw, with skin.
- Schälgurken cucumbers are eaten in Germany. Their thick skins are peeled and then they braised or fried, often with minced meat or dill. They are often known by the term ‘Schmorgurken’.
- Dosakai is a yellow cucumber available in parts of India. These fruits are generally spherical in shape. It is commonly cooked as curry, added in sambar or soup, daal and also in making dosa-aavakaaya (Indian pickle) and chutney; it is also grown and available through farms in Central California.
- Kekiri is a smooth skinned cucumber, relatively hard, and not used for salads. It is cooked as spicy curry. It is found in dry zone of Sri Lanka. It becomes orange colored when the fruit is matured.
- Armenian cucumbers (also known as yard long cucumbers) are fruits produced by the plant Cucumis melo var. flexuosus. This is not the same species as the common cucumber (Cucumis sativus) although it is closely related. Armenian cucumbers have very long, ribbed fruit with a thin skin that does not require peeling, but are actually an immature melon. This is the variety sold in Middle Eastern markets as “pickled wild cucumber”.
Cucumber nutrition
In a 100-gram serving, raw cucumber (with peel) is 95% water, provides 67 kilojoules (16 Calories) and supplies low content of essential nutrients, as it is notable only for vitamin K at 16% of the Daily Value.
Table 1. Cucumber (raw) nutrition facts
Nutrient | Unit | Value per 100 g | |||||
Approximates | |||||||
Water | g | 95.23 | |||||
Energy | kcal | 15 | |||||
Energy | kJ | 65 | |||||
Protein | g | 0.65 | |||||
Total lipid (fat) | g | 0.11 | |||||
Ash | g | 0.38 | |||||
Carbohydrate, by difference | g | 3.63 | |||||
Fiber, total dietary | g | 0.5 | |||||
Sugars, total | g | 1.67 | |||||
Sucrose | g | 0.03 | |||||
Glucose (dextrose) | g | 0.76 | |||||
Fructose | g | 0.87 | |||||
Lactose | g | 0 | |||||
Maltose | g | 0.01 | |||||
Galactose | g | 0 | |||||
Starch | g | 0.83 | |||||
Minerals | |||||||
Calcium, Ca | mg | 16 | |||||
Iron, Fe | mg | 0.28 | |||||
Magnesium, Mg | mg | 13 | |||||
Phosphorus, P | mg | 24 | |||||
Potassium, K | mg | 147 | |||||
Sodium, Na | mg | 2 | |||||
Zinc, Zn | mg | 0.2 | |||||
Copper, Cu | mg | 0.041 | |||||
Manganese, Mn | mg | 0.079 | |||||
Selenium, Se | µg | 0.3 | |||||
Fluoride, F | µg | 1.3 | |||||
Vitamins | |||||||
Vitamin C, total ascorbic acid | mg | 2.8 | |||||
Thiamin | mg | 0.027 | |||||
Riboflavin | mg | 0.033 | |||||
Niacin | mg | 0.098 | |||||
Pantothenic acid | mg | 0.259 | |||||
Vitamin B-6 | mg | 0.04 | |||||
Folate, total | µg | 7 | |||||
Folic acid | µg | 0 | |||||
Folate, food | µg | 7 | |||||
Folate, DFE | µg | 7 | |||||
Choline, total | mg | 6 | |||||
Betaine | mg | 0.1 | |||||
Vitamin B-12 | µg | 0 | |||||
Vitamin B-12, added | µg | 0 | |||||
Vitamin A, RAE | µg | 5 | |||||
Retinol | µg | 0 | |||||
Carotene, beta | µg | 45 | |||||
Carotene, alpha | µg | 11 | |||||
Cryptoxanthin, beta | µg | 26 | |||||
Vitamin A, IU | IU | 105 | |||||
Lycopene | µg | 0 | |||||
Lutein + zeaxanthin | µg | 23 | |||||
Vitamin E (alpha-tocopherol) | mg | 0.03 | |||||
Vitamin E, added | mg | 0 | |||||
Tocopherol, beta | mg | 0.01 | |||||
Tocopherol, gamma | mg | 0.03 | |||||
Tocopherol, delta | mg | 0 | |||||
Vitamin D (D2 + D3) | µg | 0 | |||||
Vitamin D | IU | 0 | |||||
Vitamin K (phylloquinone) | µg | 16.4 | |||||
Lipids | |||||||
Fatty acids, total saturated | g | 0.037 | |||||
04:00:00 | g | 0 | |||||
06:00:00 | g | 0 | |||||
8:0 | g | 0 | |||||
10:0 | g | 0 | |||||
12:0 | g | 0 | |||||
14:0 | g | 0.005 | |||||
15:0 | g | 0 | |||||
16:0 | g | 0.028 | |||||
17:0 | g | 0 | |||||
18:0 | g | 0.005 | |||||
20:0 | g | 0 | |||||
22:0 | g | 0 | |||||
24:0 | g | 0 | |||||
Fatty acids, total monounsaturated | g | 0.005 | |||||
14:1 | g | 0 | |||||
15:1 | g | 0 | |||||
16:1 undifferentiated | g | 0 | |||||
17:1 | g | 0 | |||||
18:1 undifferentiated | g | 0.005 | |||||
20:1 | g | 0 | |||||
22:1 undifferentiated | g | 0 | |||||
Fatty acids, total polyunsaturated | g | 0.032 | |||||
18:2 undifferentiated | g | 0.028 | |||||
18:3 undifferentiated | g | 0.005 | |||||
18:4 | g | 0 | |||||
20:2 n-6 c,c | g | 0 | |||||
20:3 undifferentiated | g | 0 | |||||
20:4 undifferentiated | g | 0 | |||||
20:5 n-3 (EPA) | g | 0 | |||||
22:5 n-3 (DPA) | g | 0 | |||||
22:6 n-3 (DHA) | g | 0 | |||||
Fatty acids, total trans | g | 0 | |||||
Cholesterol | mg | 0 | |||||
Phytosterols | mg | 14 | |||||
Amino Acids | |||||||
Tryptophan | g | 0.005 | |||||
Threonine | g | 0.019 | |||||
Isoleucine | g | 0.021 | |||||
Leucine | g | 0.029 | |||||
Lysine | g | 0.029 | |||||
Methionine | g | 0.006 | |||||
Cystine | g | 0.004 | |||||
Phenylalanine | g | 0.019 | |||||
Tyrosine | g | 0.011 | |||||
Valine | g | 0.022 | |||||
Arginine | g | 0.044 | |||||
Histidine | g | 0.01 | |||||
Alanine | g | 0.024 | |||||
Aspartic acid | g | 0.041 | |||||
Glutamic acid | g | 0.196 | |||||
Glycine | g | 0.024 | |||||
Proline | g | 0.015 | |||||
Serine | g | 0.02 | |||||
Other | |||||||
Alcohol, ethyl | g | 0 | |||||
Caffeine | mg | 0 | |||||
Theobromine | mg | 0 | |||||
Flavan-3-ols | |||||||
(+)-Catechin | mg | 0 | |||||
(-)-Epigallocatechin | mg | 0 | |||||
(-)-Epicatechin | mg | 0 | |||||
(-)-Epicatechin 3-gallate | mg | 0 | |||||
(-)-Epigallocatechin 3-gallate | mg | 0 | |||||
(+)-Gallocatechin | mg | 0 | |||||
Flavones | |||||||
Apigenin | mg | 0 | |||||
Luteolin | mg | 0 | |||||
Flavonols | |||||||
Isorhamnetin | mg | 0 | |||||
Kaempferol | mg | 0.1 | |||||
Myricetin | mg | 0 | |||||
Quercetin | mg | 0 | |||||
Isoflavones | |||||||
Daidzein | mg | 0 | |||||
Genistein | mg | 0 | |||||
Total isoflavones | mg | 0 | |||||
Proanthocyanidin | |||||||
Proanthocyanidin dimers | mg | 0 | |||||
Proanthocyanidin trimers | mg | 0 | |||||
Proanthocyanidin 4-6mers | mg | 0 | |||||
Proanthocyanidin 7-10mers | mg | 0 | |||||
Proanthocyanidin polymers (>10mers) | mg | 0 |
Table 2. Cucumber (raw and peeled) nutrition facts
Nutrient | Unit | Value per 100 g | |||||
Approximates | |||||||
Water | g | 96.73 | |||||
Energy | kcal | 10 | |||||
Energy | kJ | 44 | |||||
Protein | g | 0.59 | |||||
Total lipid (fat) | g | 0.16 | |||||
Ash | g | 0.36 | |||||
Carbohydrate, by difference | g | 2.16 | |||||
Fiber, total dietary | g | 0.7 | |||||
Sugars, total | g | 1.38 | |||||
Sucrose | g | 0 | |||||
Glucose (dextrose) | g | 0.63 | |||||
Fructose | g | 0.75 | |||||
Lactose | g | 0 | |||||
Maltose | g | 0 | |||||
Galactose | g | 0 | |||||
Starch | g | 0.08 | |||||
Minerals | |||||||
Calcium, Ca | mg | 14 | |||||
Iron, Fe | mg | 0.22 | |||||
Magnesium, Mg | mg | 12 | |||||
Phosphorus, P | mg | 21 | |||||
Potassium, K | mg | 136 | |||||
Sodium, Na | mg | 2 | |||||
Zinc, Zn | mg | 0.17 | |||||
Copper, Cu | mg | 0.071 | |||||
Manganese, Mn | mg | 0.073 | |||||
Selenium, Se | µg | 0.1 | |||||
Fluoride, F | µg | 1.3 | |||||
Vitamins | |||||||
Vitamin C, total ascorbic acid | mg | 3.2 | |||||
Thiamin | mg | 0.031 | |||||
Riboflavin | mg | 0.025 | |||||
Niacin | mg | 0.037 | |||||
Pantothenic acid | mg | 0.24 | |||||
Vitamin B-6 | mg | 0.051 | |||||
Folate, total | µg | 14 | |||||
Folic acid | µg | 0 | |||||
Folate, food | µg | 14 | |||||
Folate, DFE | µg | 14 | |||||
Choline, total | mg | 5.7 | |||||
Betaine | mg | 0.1 | |||||
Vitamin B-12 | µg | 0 | |||||
Vitamin B-12, added | µg | 0 | |||||
Vitamin A, RAE | µg | 4 | |||||
Retinol | µg | 0 | |||||
Carotene, beta | µg | 31 | |||||
Carotene, alpha | µg | 8 | |||||
Cryptoxanthin, beta | µg | 18 | |||||
Vitamin A, IU | IU | 72 | |||||
Lycopene | µg | 0 | |||||
Lutein + zeaxanthin | µg | 16 | |||||
Vitamin E (alpha-tocopherol) | mg | 0.03 | |||||
Vitamin E, added | mg | 0 | |||||
Tocopherol, beta | mg | 0 | |||||
Tocopherol, gamma | mg | 0.02 | |||||
Tocopherol, delta | mg | 0 | |||||
Vitamin D (D2 + D3) | µg | 0 | |||||
Vitamin D | IU | 0 | |||||
Vitamin K (phylloquinone) | µg | 7.2 | |||||
Lipids | |||||||
Fatty acids, total saturated | g | 0.078 | |||||
04:00:00 | g | 0 | |||||
06:00:00 | g | 0 | |||||
8:0 | g | 0 | |||||
10:0 | g | 0 | |||||
12:0 | g | 0 | |||||
14:0 | g | 0.01 | |||||
15:0 | g | 0 | |||||
16:0 | g | 0.058 | |||||
17:0 | g | 0 | |||||
18:0 | g | 0.01 | |||||
20:0 | g | 0 | |||||
22:0 | g | 0 | |||||
24:0 | g | 0 | |||||
Fatty acids, total monounsaturated | g | 0.01 | |||||
14:1 | g | 0 | |||||
15:1 | g | 0 | |||||
16:1 undifferentiated | g | 0 | |||||
17:1 | g | 0 | |||||
18:1 undifferentiated | g | 0.01 | |||||
20:1 | g | 0 | |||||
22:1 undifferentiated | g | 0 | |||||
Fatty acids, total polyunsaturated | g | 0.019 | |||||
18:2 undifferentiated | g | 0.01 | |||||
18:3 undifferentiated | g | 0.01 | |||||
18:4 | g | 0 | |||||
20:2 n-6 c,c | g | 0 | |||||
20:3 undifferentiated | g | 0 | |||||
20:4 undifferentiated | g | 0 | |||||
20:5 n-3 (EPA) | g | 0 | |||||
22:5 n-3 (DPA) | g | 0 | |||||
22:6 n-3 (DHA) | g | 0 | |||||
Fatty acids, total trans | g | 0 | |||||
Cholesterol | mg | 0 | |||||
Amino Acids | |||||||
Tryptophan | g | 0.007 | |||||
Threonine | g | 0.012 | |||||
Isoleucine | g | 0.012 | |||||
Leucine | g | 0.025 | |||||
Lysine | g | 0.025 | |||||
Methionine | g | 0.012 | |||||
Cystine | g | 0.007 | |||||
Phenylalanine | g | 0.031 | |||||
Tyrosine | g | 0.002 | |||||
Valine | g | 0.012 | |||||
Arginine | g | 0.031 | |||||
Histidine | g | 0.002 | |||||
Alanine | g | 0.031 | |||||
Aspartic acid | g | 0.037 | |||||
Glutamic acid | g | 0.204 | |||||
Glycine | g | 0.025 | |||||
Proline | g | 0.012 | |||||
Serine | g | 0.025 | |||||
Other | |||||||
Alcohol, ethyl | g | 0 | |||||
Caffeine | mg | 0 | |||||
Theobromine | mg | 0 | |||||
Isoflavones | |||||||
Daidzein | mg | 0 | |||||
Genistein | mg | 0 | |||||
Total isoflavones | mg | 0 | |||||
Proanthocyanidin | |||||||
Proanthocyanidin dimers | mg | 0 | |||||
Proanthocyanidin trimers | mg | 0 | |||||
Proanthocyanidin 4-6mers | mg | 0 | |||||
Proanthocyanidin 7-10mers | mg | 0 | |||||
Proanthocyanidin polymers (>10mers) | mg | 0 |
Health benefits of cucumber
Cucumber is a popular crop used in Indian traditional medicine since ancient times. Traditionally, cucumber plant has been used to treat headaches and hyperlipidemia, and to prevent constipation 7). Cucumber seeds and cucumber fruit have refreshing properties, soothing irritated skin and reducing swelling 8). Cucumber is very high in water content and very low in calories. Cucumber has potential anti-diabetic, anti-hyperglycemic, lipid lowering and antioxidant activity in animal studies 9), 10). Cucumber has a cleansing action within the body by removing accumulated pockets of old waste materials and chemical toxins 11). Fresh cucumber fruit juice is used for nourishing the skin 12). It gives a soothing effect against skin irritations and reduces swelling. Cucumber also has the power to relax and alleviate the sunburn’s pain 13). The cucumber fruit is refrigerant (cooling), hemostatic (an agent that causes bleeding to stop), tonic and useful in hyperdipsia (intense thirst), sunstroke (heat stroke) 14). The cucumber seeds also have a cooling effect on the body and they are used to prevent constipation 15). Several bioactive compounds have been isolated from cucumber including cucurbitacins, cucumegastigmanes I and II, cucumerin A and B, vitexin, orientin, isoscoparin 2″-O-(6‴-(E)-p-coumaroyl) glucoside, apigenin 7-O-(6″-O-p-coumaroylglucoside) 16). Despite huge exploration of cucumber in agricultural field, comparatively very few studies have been published about its chemical profile and its therapeutic potential.
Moreover, cucumber has been reported to have antiinflammatory and antioxidant properties 17).
Cucumber is known to be rich in cucurbitacins 18). Cucurbitacins are mostly found in the members of the family Cucurbitaceae and are responsible for the bitter taste of cucumber. Pharmacological activities such as anti-bacterial and anti-tumor effects have been attributed to these structurally diverse triterpens 19). Cucurbitacins have become interesting subjects in science due to their medicinal and toxic properties 20). Cucurbitacins are usually concentrated in fruits and roots at maturity and are responsible for bitter taste of cucumber. Cucumber seeds exhibit very low concentration of cucurbitacins 21). The diversity of cucurbitacins lies in side chain derivatives that contribute to pharmacological actions 22). They are known according to their structural composition and designated by the letters: A, B, C, D, E, F, G, H, I, J, K, L, O, P, Q, R and S. Cucurbitacins have also been identified outside the cucurbitaceae family including members of Scrophulariaceae, Begoniaceae, Primulaceae, Liliaceae, Tropaeolaceae and Rosaceae families 23). Various cucurbitacins are made from chemical modification of cucurbitane (19(10–9ß)-abeo-5α-lanostane) with numerous activities such as anti-inflammatory, antitumor promotion, chemopreventive, hepatoprotective, anti-microbial, anthelmintic, antifeedant and antioxidant 24). CuE is one of the cucurbitacins and is an active secondary methabolite with inhibition of cell adhesion actions 25) and modulatory activity effect on the peripheral human lymphocytes 26). The compound has also been found to be a strong antifeedant for the flea beetle, bilirubin–albumin binding in human plasma and with inhibitory activity on cancer cell proliferation, actin polymerization and permeability 27). The compound also acts as agent to protect against certain diseases in plants due to its toxicity property 28). Cu E displays superior cytotoxicity due to more hydrophobicity than the other cucurbitacins 29).
Various biological activities attributed to Cucurbitacins with probable mechanish of action (s) have been summarized in Table 3 below.
Figure 1. Cucurbitacin analogs chemical structures
[Source 30)]Table 3. Reported biological activities of cucurbitacins with probable mechanism of action
[Source 31)]Anti-inflammatory activity
Cucurcitacin analogues viz. Cucurbitacin R and DHCB have been reported to possess anti-inflammatory potential and their action is reported to be mediated by inhibition of tumor necrosis factors (TNF)-α and other mediators of inflammation such as nitric-oxide synthase-2 and cyclo-oxygenase-2 32). Cucurbitacins B, D, E and I have been reported to inhibit cyclooxygenase (COX)-2 enzymes with no effect on COX-1 enzymes 33). The anti-inflammatory response of 23, 24-dihydrocucurbitacin D (DHCD) have been hypothesized to get mediated through blocking of NF-κ B activation thereby obstructing the release of nitrous oxide. DHCD can be taken up as probable lead and appraised for providing a promising anti-inflammatory agent 34).
Antitumor activity
Very less information is available on the role of Cucurbitacins at molecular level which has lead to slow advancement in the development of Cucurbitacins as anti-cancer agents. Cucurbitacin B (CuB) is a naturally occurring compound that is found abundantly in cucumbers and other vegetables, and it is known to exert anti-cancer activities (primarily via apoptosis-induction) in several human cancers 35). Cucurbitacin B, a bioactive compound from cucumber, inhibits prostate cancer growth 36). In relation to cancer, targets of Cucurbitacin actions involve growth inhibition, arrest of cell cycle at G2/M phase and induction of apoptosis in cancer cell. The mechanisms underlying anti-tumorigenic potentials of Cucurbitacins involve inhibition of Janus kinase/Signal Transducer Activator of Transcription 3 (JAK/STAT3) signaling pathway whose activation is required for the proliferation and sustainment of cells. The role of Cucurbitacin I in suppressing phosphotyrosine STAT3 in cancer cell lines and cancerous lung cells of humans has been reported 37). Although Cucurbitacin B, E, and I act by inhibiting the activation of both JAK2 and STAT3, Cucurbitacin A and I acts by inhibition of only JAK2 and STAT3 respectively 38). It has been reported that Cucurbitacin E inhibited tumor angiogenesis by inhibiting JAK-STAT3 and mitogen activated protein kinases (MAPK)- signaling pathways 39). The role of interference with actin cytoskeleton has been attributed to anti-proliferative effects of Cucurbitacin B and E. The anti-proliferative activities have been correlated directly with the disruption of the F-actin cytoskeleton 40). It has been proposed that the combination of Cucurbitacin B with docetaxel may augment the chemotherapeutic effects by suppression STAT3 in patients with laryngeal cancer 41). It is expected that cucumber fruits have anti-tumor effects since they have been reported to contain Cucurbitacin C 42). It has been reported that cucurbitacin B exerts an anticancer effect by inhibiting telomerase via down-regulating both the human telomerase reverse transcriptase and c-Myc expression in breast cancer cells 43).
Anti-artherosclerotic activity
There have been reports on Cucurbitacin B and E in glycosidic form to exhibit inhibitory effect on lipid oxidation products like- malonaldehyde and 4-hydroxynonenal 44). These reports bolster the therapeutic role of Cucurbitacins in artherosclerosis, which involves modification of lipoproteins by involvement of- malonaldehyde and 4-4-hydroxynonenal 45).
Antidiabetic activity
There have been a plethora of reports on the role of Cucurbitacins for their cytotoxic, hepatoprotective, cardiovascular, and antidiabetic effects 46). Cucurbitane triterpenoids present in momordica fruits (bitter melon) are noted for antidiabetic and anticancer activities, this may provide leads as a class of therapeutics for diabetes and obesity 47). The 5’-adenosine monophosphate-activated protein kinase (AMPK) pathway is suggested as a probable mechanism for the stimulation of GLUT4 translocation by triterpenoids from M. charantia. It is particularly interesting in relation to diabetes and obesity because activation of AMPK increases fatty acid oxidation, inhibits lipid synthesis, and can improve insulin action 48). An analogue of 23,24-dihydrocucurbitacin F from Hintonia latiflora has been reported to possess significant hypoglycemic and antihyperglycemic effects. The probable mechanism underlying– antihyperglycemic effect could be stimulation of insulin release and regulation of hepatic glycogen metabolism 49).
Free Radical Scavenging and Analgesic Activities
The aqueous fruit extract of cucumber (Cucumis sativus L.) was screened for free radical scavenging and analgesic activities. The cucumber extract was subjected to in vitro antioxidant studies at 250 and 500 μg/ml and analgesic study at the doses 250 and 500 mg/kg, respectively 50). The free radical scavenging was compared with ascorbic acid, BHA (Butylated hydroxyl anisole), whereas, the analgesic effect was compared with Diclofenac sodium (50 mg/kg). The cucumber fruit extract showed maximum antioxidant and analgesic effect at 500 μg/ml and 500 mg/kg, respectively 51). The presence of flavonoids and tannins in the extract as evidenced by preliminary phytochemical screening suggests that these compounds might be responsible for free radical scavenging and analgesic effects 52).
Anti-encephalitogenic effects
Cucumber leaf extract was characterized by the predominance of triterpenoids cucurbitacins and significant levels of phenolics. Effects of cucumber leaf extract on CD4+ T helper cells and macrophages, as the major encephalitogenic (tending to cause encephalitis) cells in the autoimmunity of the central nervous system were investigated in this study 53). Cucumber leaf extract potently inhibited production of major pathogenic CD4+ T helper cells cytokines: interferon-gamma and interleukin-17, as well as of nitric oxide and reactive oxygen species in macrophages 54). Antigen-presenting activity of macrophages and dendritic cells was also affected by cucumber leaf extract 55). The effects of cucumber leaf extract were co-incident with modulation of NFκB and p38 mitogen associated protein kinase signaling. Concentrations of cucumber leaf extract used in vitro did not show toxic effects on zebrafish embryos. Moreover, cucumber leaf extract inhibited generation of encephalitogenic cells in animal study. These results demonstrate that cucumber leaf extract deserve further investigation on its anti-encephalitogenic therapeutic properties 56).
Ulcerative colitis in laboratory animals
In acetic acid induced ulcerative colitis in wistar rats study 57) showed pretreatment with cucumber aqueous extract for 7 days exhibited significant effect in lowering of ulcer area, ulcer index as well as neutrophil infiltration at a dose of 250 and 500 mg/kg in acetic acid induced colitis 58). That animal study demonstrated cucumber aqueous extract is of potent therapeutic value in the amelioration of experimental colitis in laboratory animals by inhibiting the inflammatory mediator. However more test tube and animal studies are needed to identify the bioactive compounds.
Miscellaneous activity
It has been reported that the concentration of Cucurbitacin C in the leaves is an important parameter in spider mite resistance in cucumber, perhaps by acting as an antagonist of a spider mite ecdysteroid receptor 59). The steroid like resemblance of Cucurbitacin D may possess therapeutic effects via inhibition of Na+/K+-ATPase 60). The role of Cucurbitacins as preventive and radical scavenging antioxidant has also been reported 61). Cucurbitacins have also been reported to possess adaptogenic activity. Cucurbitacins have been reported to increase the rat capillary permeability and to demonstrate antifertility effects in female mice 62). Cucurbitacin D has been reported to inhibit ovulation in mice. There has been protective role of Cucurbitacins acting as allomones in many plant species. Role of Cucurbitacins as anti-feedants for few insects, birds and as kairomones (Cucurbitacin B, E, D, I and L) for diabroticite beetles have been reported 63). It is reported that Cucurbitacins act via Cuc receptors located on the maxillary palpi. They arrest the searching behavior of diabroticite beetles and produce a compulsive feeding behavior 64). Role of Cucurbitacin B and D in controlling diabrotic beetles can be an interesting approach 65).
Cucurbitacins Toxicity Reports
Cucurbitacins have been reported as highly toxic compounds and instances of severe poisoning and death in sheep and cattle that consumed bitter fruits of Cucumis and Cucurbita are well documented 66). The range of toxicity of Cucurbitacins based on few in-vivo toxicity reports, has been found to be between 2 -12.5 mg/kg. Although a report on toxicity of Cucurbitacin R at level as high as 375 mg/Kg p.o and 67 mg/kg i.p is available.[65] The presence of a double bond at C-23 and acetyl group at C-25 have been found to augment the toxicity of Cucurbitacins.[66] Cucurbitacin’s strong biological activity was found to be very close to their toxic dose, which renders them unlikely to be biological agents.[48] The extreme bitterness of Cucurbitacins should deter humans from being exposed to substantial quantities of the compounds. Nevertheless, some poisonings have been reported after consumption of Cucurbitaceous food plants.[8] Cucurbitacins are found to be fatal when fruits of Luffa cylindrical (L.) were consumed.[67] Gastrointestinal symptoms have also been reported in a Japanese population consuming the bottle gourd, which contained Cucurbitacin D.[68] The toxicity of Cucurbitacins C, D, E, and I have been assessed and these compounds ascertained to be lethal. Plants with Cucurbitacins C, D, E and I must be avoided as their consumption can lead to illness or even death.[17] The appearance of toxic symptoms varies with the animal species used in the experiment, the route of administration of the compound, and the quantity that has been administered.[42]
Summary of Cucurbitacins
Although Cucurbitacins are highly toxic compounds and often their biological activities are close to their toxic dose level, these compounds possess immense pharmacological potential 67). Apart from their toxic nature cucurbitacins have been proved to possess pharmacological effectiveness against inflammation, cancer, artherosclerosis and diabetes 68). The reports on their toxicity must not overshadow the potential use of these compounds as potent medicinal agents. The chemical modification of various functional groups of these compounds to reduce toxic effects may provide important lead compounds for future research. Various Cucurbitacin analogues have been explored and are well established for toxic nature and their effectiveness against tumor cell lines. In modern drug discovery from medicinal plants, the importance of Cucurbitaceae species has been markedly recognized in empirical control of diabetes 69). The information on absorption, distribution, metabolism and excretion of these compounds is scarce and can be an area of exploration keeping in concern their toxic effects in mammals 70).
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