Cocos nucifera (L.) (Arecaceae): A phytochemical and pharmacologicalreview

Traditional uses

All parts of the fruit of the coconut tree can be used. Both the green coconut waterand solid albumen ripe fruits are used industrially and in home cooking in many ways(5). Additionally, several parts of thefruit and plant have been used by people in different countries for the treatment ofvarious pathological conditions (Table2).

Currently, appreciation of natural coconut water is growing. Industry is using thehusk fiber from the pith as raw material for carpets, car seat stuffing, and inagricultural as fertilizers. The hard core is used to make handcrafts. The stalk andleaves of the coconut tree are useful in construction, and sugar, vinegar, andalcohol can be extracted from the inflorescence (6).

In Brazil, extract from the husk fiber of C. nucifera is used totreat diarrhea (7). In Papua New Guinea, theleaves and roots of young plants are chewed as treatment for diarrhea andstomachaches (8,9). In Fiji, coconut oil is used to prevent hair loss and coconutwater is used to treat renal disease (10). InGhana, people use coconut milk to treat diarrhea (11). In Guatemala, the husk fiber extract is used as an antipyretic, toreduce renal inflammation, and as a topic ointment for dermatitis, abscesses, andinjuries (12). In Haiti, a decoction of thedry pericarp is used for oral treatment of amenorrhea, and the oil is applied as anointment to burns (13); an aqueous extractfrom the husk fiber is also used for oral asthma treatment (14). In India, infusions made with the coconut inflorescence areused for the oral treatment of menstrual cycle disorders (15). In Indonesia, the oil is used as a wound ointment, thecoconut milk is used as an oral contraceptive, and fever and diarrhea are treatedwith the root extract (16–18). In Jamaica, the husk fiber extract is usedto treat diabetes (19,20). In Mozambique, the fruit is consumed by men as anaphrodisiac (21). Peruvians use the aqueousextract of the fresh coconut fiber orally for asthma, as a diuretic, and forgonorrhea (22). In Trinidad, bark extract isused orally for amenorrhea and dysmenorrhea, and bark tea is used to treat venerealdiseases (23). In Mexico, coconut is used totreat various disorders associated with urogenital tract infection byTrichomonas vaginalis (24). A decoction of the white flesh of the fruit is used in rural Malaysia totreat fever and malaria (25). In Kenya, thefruit is used to relieve skin rash caused by HIV infection (26).

Phytochemistry

Phytochemical studies of the coconut fiber (mesocarp) ethanolic extract revealed thatthe presence of phenols, tannins, leucoanthocyanidins, flavonoids, triterpenes,steroids, and alkaloids (27), while a butanolextract recovered triterpenes, saponins, and condensed tannins (28). Notably, compounds like flavonoids having antioxidant actionare widely distributed in edible vegetables, fruits, and many herbs (29–31).Condensed tannins are reported to possess antihelminthic activity by binding toproteins present in the cuticle, oral cavity, esophagus, and cloaca of nematodes,thus intensifying the physical and chemical damage in helminth (32).

The lyophilized extract and fractions, as well as ethyl acetate extracts, from theC. nucifera fiber are rich in polyphenols, compounds such ascatechins, epicatechins, tannins, and flavonoids (7,33–35).

The constituents of the liquid albumen were identified as vitamin B, nicotinic acid(B3, 0.64 µg/mL), pantothenic acid (B5, 0.52 µg/mL), biotin (0.02 µg/mL), riboflavin(B2, <0.01 ng/mL), folic acid (0.003 µg/mL), with trace quantities of vitamins B1,B6, and C, pyridoxine, thiamine, folic acid, amino acids, L-arginine, plant hormones(auxin, 1,3-diphenylurea, cytokinin), enzymes (acid phosphatase, catalase,dehydrogenase, diastase, peroxidase, RNA polymerases), and growth-promoting factors(36–38). Furthermore, oil extracted from the solid albumen is primarily lauricacid and alpha tocopherol (39,40). Root phenolic compounds were identified asflavonoids and saponins (41). Other compoundsidentified in leaf epicuticular wax were lupeol methylether, skimmiwallin,[3b-methoxy-25-ethyl-9,19-cyclolanost-24(241)-ene], and isoskimmiwallin[3b-methoxy-24-ethyl-9,19-cyclolanost-25(251)-ene] (42) (Figure 2).

Figure 2

Structures of the main phytoconstituents isolated from Cocosnucifera (L.).

Pharmacological activities of extracts, fractions, and isolatedconstituents

Several studies have been conducted to identify the active molecules in coconut andtheir possible pharmacological and biological activities. Various extracts,fractions, and isolated compounds from different parts of the coconut fruit weretested, showing different activities, including antihypertensive; analgesia;vasodilation; protection of kidney, heart, and liver functions; protection againstulcers; and anti-inflammatory, anti-oxidant, anti-osteoporosis, antidiabetes,antineoplastic, bactericidal, antihelminthic, antimalarial, leishmanicidal,antifungal, and antiviral activities (43–47). These effects are described below and alsolisted in Supplementary Table S1.

Analgesic activity

Crude husk-fiber extract and two aqueous extract fractions of molecular weights lessthan (F1) and greater than (F2) 1 kDa were studied for their analgesic activity byacetic acid-induced abdominal writhing, tail-flick, and hot plate tests in mice(44). All three extracts induced peripheraland central antinociceptive activity. Oral administration of the crude extract (50,100, or 150 mg/kg) significantly inhibited writhing by 24%, 34%, and 52.4%,respectively, when compared with a control group. Fractions F1 and F2 reduced totalwrithing at 10 and 50 mg/kg. In the tail-flick test, oral pre-treatment with crudeextract (100 and 150 mg/kg), F1 (10 and 50 mg/kg), or F2 (10 and 50 mg/kg) producedeffects better or similar to morphine (5 mg/kg) until 80 min. However, with theexception of F1 (50 mg/kg, 60 min after administration), neither crude extract (150mg/kg) nor F2 (50 mg/kg) significantly increased the latency of mice response tothermal stimulation in the hot-plate test. The mechanism of action of the extractswere also evaluated using the opioid antagonist naloxone (5 mg/kg), which inhibitedthe antinociceptive effect of the crude extract, F1, and F2, indicating a probableaction on opioid receptors.

In another study, an ethanol extract of the husk fiber (40, 60, or 80 mg/kg) showedsignificant analgesic properties, as indicated by a reduction in the number ofwrithes and stretches induced in mice by 1.2% acetic acid (41). The results were similar to those in animals that receivedaspirin (68 mg/kg), paracetamol (68 mg/kg), or morphine sulfate (1.15 mg/kg).Furthermore, administration of the ethanol extract along with morphine or pethidinenot only produced analgesia in mice but also potentiated the analgesic effect ofthese two drugs.

These studies were performed using coconut husk fiber extracts, suggesting that thispart of the plant is a highly potent analgesic. Cocos nucifera mayenable the production of new low-cost medicines for several ailments and may providea very inexpensive source of new analgesic drugs. Further investigations arewarranted. Further bioassay-guided fractionation and isolation of specific moleculesare highly recommended so that the chemical moiety responsible for the activity canbe identified and its mechanism of action established.

Anti-inflammatory activity

Aqueous crude extracts of husk fiber of C. nucifera are used totreat arthritis and other inflammatory ills in Northeastern Brazil's traditionalmedicine (7).

A study using animal models of inflammation (formalin test and subcutaneous air pouchmodel) showed that aqueous crude extracts of C. nuciferavar.typica (50, or 100 mg/kg) significantly inhibited (P<0.05) thetime that animals spent licking their formalin-injected paws and reduced inflammationinduced by subcutaneous carrageenan injection by reducing cell migration,extravasation of protein, and TNF-α production (45)

Husk fiber extracts were also tested on rat paw edema induced by carrageenan,histamine, and serotonin (44). Animals werepre-treated by oral administration of crude extract (50, 100 or 150 mg/kg), F1 or F2(1, 10, or 50 mg/kg), promethazine (30 mg/kg), or methysergide (5 mg/kg). The crudeextract significantly (P<0.05) reduced histamine (at 150 mg/kg) andserotonin-induced rat paw edema (at 100 and 150 mg/kg). Even when mice were treatedwith 1 mg/kg of F1, a significant inhibitory effect was observed in histamine andserotonin-induced edema. However, F2 did not inhibit the edema induced by anypro-inflammatory agent.

Animal tests revealed significant activity supporting the use of these husk fiberextracts in traditional medicine (35). The chemical constituents responsible fortheir activity should be isolated, identified, and researched to establish safetydoses.

Anti-bacterial, antifungal, and anti-viral activities

Brushing the teeth with fibrous coconut husks is a common oral hygiene practice amongrural people of South India (46). In thiscontext, the antimicrobial properties of alcoholic extracts of the husk againstcommon oral pathogens were analyzed by the agar well diffusion method (47). There was significantconcentration-dependent antimicrobial activity, expressed as a zone of inhibitionwith respect to all tested organisms except Actinomyces species.However, the effect of the C. nucifera extract was less than that ofchlorhexidine.

Ethanolic (cold and hot percolation), dry-distilled, and aqueous extracts of coconutendocarp were compared with gentamicin and ciprofloxacin for their antibacterialactivities against methicillin-resistant Staphylococcus aureus(MRSA), methicillin-sensitive S. aureus, Pseudomonasaeruginosa, Escherichia coli, Klebsiellapneumonia, Acinetobacter baumannii, Citrobacterfreundii, Enterococcus, Streptococcuspyrogens, Bacillus subtilis, and Micrococcusluteususing the Kirby-Bauer disc diffusion method. The endocarp extractsshowed strong antimicrobial activity against B. subtilis, P.aeruginosa, S. aureus, and M. luteusbut had no effect on E. coli (26). The dry-distilled extract (1 mg/mL and 200 μg/mL) could inhibit thegrowth of B. subtilis and Aspergillus spp. but wasinactive against R. oligosporus at all concentrations (48). The crude aqueous extract of husk fiber andfive fractions obtained by thin layer chromatography (TLC) were also tested (10, 50,and 100 mg/kg) against E. coli, S. aureus, and MRSAvia agar diffusion; they were active only against S. aureus andMRSA, with a minimum inhibitory concentration (MIC) of 1024 mg/mL for both (45).

In another study, the antimicrobial activity of mesocarp powder extracted with sixcommon organic solvents was evaluated by the disk diffusion method (49). The pathogens E. coliandS. typhi were used. The antimicrobial activity against E.coli was higher with the benzene solvent, while bioactivity towardS. typhi was more effective with the diethyl ether extract.Potential bio-components responsible for the antimicrobial activity were identifiedas tocopherol, alcohol palmitoleyl, cycloartenol, and β-sitosterol.

The in vitro antilisterial activities and time kill regimes of crudeaqueous and n-hexane extracts of the husk fiber of C.nucifera were tested (50). Theaqueous extracts were active against 29 of 37 Listeria isolatesexamined, while the n-hexane extracts were active against 30 (bothat 25 mg/mL). The diameters of the zones of inhibition were 12–17 mm and 12–24 mm,respectively, while those of the control antibiotics were 20–50 mm for ampicillin and22–46 mm for tetracycline. The MICs of the susceptible bacteria were 0.6–2.5 mg/mLfor the aqueous fraction and 0.6–5.0 mg/mL for the n-hexane extract.The mean reduction in viable cell count in the time kill assay with the aqueousextract ranged from 0.32 to 3.2 log₁₀ CFU/mL after 4 h of interaction andfrom 2.6 to 4.8 log₁₀ CFU/mL after 8 h at 1× and 2× MIC. With then-hexane extract, the values were 2.8–4.8 log₁₀CFU/mLafter 4 h of interaction and 3.5–6.2 log₁₀ CFU/mL after 8 h in 1× and 2×MIC. For the aqueous extract, bactericidal activity was observed against three of thetested Listeria strains at a concentration of 2× MIC after 8 hexposure, while the n-hexane fraction was bactericidal against allfive test bacteria at both MICs after 8 h.

In studies with crude extract and five TLC fractions (I-V) of fiber mesocarp ofC. nucifera fruit, in vitro antimicrobialactivity was seen in all trial strains of S. aureus tested withfractions II-V (7). Antifungal activity wasdemonstrated as growth inhibition of Candida albicans,Cryptococcus neoformans or Fonsecaea pedrosoi.Antiviral action was only seen with the crude extract and fraction II. Theantifungal, antimicrobial, and antiviral effects were attributed to condensed tanninsand catechins present in the crude extract and fractions II-V, especially fractionII, which had a higher concentration of these compounds.

Studies with alcohol extract of ripe dried coconut shell have demonstrated actionagainst Microsporum canis, M. gypseum, M.audouinii, Trichophyton mentagrophytes, T.rubrum, T. tonsurans, and T. violaceum(51). This activity was attributed mainlyto the high content of phenolic compounds. In another study, virgin oil from coconutpulp prevented growth of C. albicans (52).

Coconut oil is very effective against a variety of viruses with lipid capsules, suchas visna virus, cytomegalovirus, and Epstein-Barr virus (53). The medium chain saturated fatty acids from coconut oildestroy and break the membranes and interfere with viral maturation.

These reports indicate that various parts of C. nucifera should befurther tested for antibacterial, antifungal, and antiviral activities in differentanimal models. Future studies should consider formulations and exact dose levelssuitable for use in humans to treat various strains of bacteria, viruses, andfungi.

Antioxidant activity

There is considerable interest in the consumption of certain foods to prevent theonset of diseases. Evidence suggests that diets rich in phenolic compounds cansignificantly enhance human health because of the effects of phenolic antioxidants(54). Studies with virgin coconut oil (VCO)indicated that the total phenolic content was almost seven times that of commercialcoconut oil, because the process of obtaining refined oil destroys some of thebiologically active components (55). In the1,1-diphenyl-2-picrylhydrazyl (DPPH) test, VCO had higher antioxidant activitycompared to refined coconut oil (56).

The antioxidant activity of C. nucifera endocarp extracts wasevaluated by DPPH radical scavenging, nitric oxide radical scavenging, and alkalinedimethyl sulfoxide (DMSO) methods. The DPPH analysis demonstrated that ethanolic(cold and hot percolation), dry-distilled, and aqueous extracts of endocarp hadsignificant antioxidant activity (4.1828, 3.31, 20.83, 1.0179 μg/mL, respectively)comparable with that of standard ascorbic acid (48).

In another study, the antioxidant potential of four varieties of coconut (greendwarf, yellow dwarf, red dwarf, and Malaysian yellow) were evaluated and comparedwith industrialized and lyophilized water of the green dwarf variety (57). All varieties were effective at eliminatingDPPH (50% inhibition concentration (IC₅₀) 73 mL) and nitric oxide (0.1 mL;inhibition percent (IP) 29.9%) as well as the in vitro production ofthiobarbituric acid (1 mL; IP 34.4%). The green dwarf variety, which is commonlyused, was especially potent compared with another variety of coconut. In cellculture, green dwarf water protected against oxidative damage induced by hydrogenperoxide.

Micronutrients, such as inorganic ions and vitamins present in coconut water, playvital roles in helping the antioxidant defense system of the human body (58). Some evidence points toward an antioxidantaction of coconut water. Thus, administering coconut water (6 mL/100 g of bodyweight) to female rats intoxicated with carbon tetrachloride recovered the action ofantioxidant enzymes (superoxide dismutase and catalase levels) and decreased lipidperoxidation (59). Coconut water is also richin L-arginine (30 mg/dL), which significantly reduces the generation of free radicals(60) and has antioxidant activity (61), as well as ascorbic acid (15 mg/100 mL),which decreases lipid peroxidation in rats (62).

In summary, many parts of C. nucifera plants have proven to containphenolic compounds and flavonoids that support antioxidant activity.

Antineoplastic activity

Different molecular weight fractions of husk fiber aqueous extracts of C.nucifera (typical A variety, commonly known as “olho-de-cravo”, and thecommon variety) were tested on human erythroleukemia cell line K562 and Lucena 1, amultidrug-resistant (MDR) and vincristine-resistant derivative of K562. Bothvarieties showed cytotoxicity against K562 cells and decreased by 50% the viabilityand anti-MDR activity of Lucena 1 cells. In both varieties, the antitumoral activitywas concentrated in fractions with molecular weights between 1 and 10 kDa (63).

There is great potential for future research on antineoplastic activity, as only onestudy has been reported. Because coconut is extensively cultivated in Brazil and itsfiber is often discarded, it may offer an inexpensive source for new antineoplasticdrugs.

Antiparasitic activity

The antihelminthic activity of liquid extract of the bark of the green coconut(LBGC), as well as butanol extract obtained from LBGC, was tested on mouse intestinalnematodes (28). Thirty-six naturally infectedmice were distributed into 6 treatment groups as follows: group I, 1000 mg/kg ofLBGC; group II, 2000 mg/kg of LBGC; group III, 500 mg/kg of butanol extract; groupIV, 1000 mg/kg of butanol extract; group V, 0.56 mg/kg febendazole; and group VI, 3%dimethylsulfoxide. The LBGC did not show antihelminthic activity against the mousenematodes compared with the negative control group (P>0.05). However, the butanolextract at 500 and 1000 mg/kg had mean efficacy of 62.72% and 98.36%, respectively(P<0.05).

The ovicidal and larvicidal activity of the liquid from the coconut husk (LCCV) andbutanolic LCCV extract were also tested against Haemonchus contortus(28). In egg hatching and larvaldevelopment tests, 2.5 mg/mL LCCV and 10 mg/mL butanolic extract showed 100% ovicidalactivity. Their larvicidal effects were 81.30% and 99.80% at 65 and 80 mg/mL,respectively.

These results suggest that coconut extracts can be used to control gastrointestinalnematodes and that more studies are needed to evaluate their use in humans.

Anti-Leishmania activity

The in vitro leishmanicidal effects of C. nuciferaon Leishmania amazonensis were evaluated (33). The polyphenolic-rich extract obtained from coconut huskfiber completely inhibited the cellular growth of L. amazonensispromastigote forms (MIC 10 μg/mL) and killed 100% of both developmental stages of theparasite after 60 min (at 10 and 20 μg/mL). In addition, pretreatment of mouseperitoneal macrophages with 10 μg/mL of C. nuciferapolyphenolic-rich extract reduced by approximately 44% their rate of association withL. amazonensispromastigotes with a simultaneous increase of 182%in nitric oxide production by macrophages compared with untreated macrophages.

Ethyl acetate extract (EAE) from husk fiber water was tested against L.braziliensis infected hamsters (35). Administering EAE (0.2 mL, 300 mg/kg) for 21 consecutive days did notreduce edema of infected footpad nor the weight of lymph node drainage but reducedskin lesions after 14 days.

These results offer new promise for the development of drugs against leishmaniasisfrom coconut extracts because of their potent effects and the absence of invivo allergic reactions or in vitro cytotoxic effects inmammalian systems. Further studies with these and other species of the parasite arenecessary to elucidate the role of C. nucifera in eliminating thisetiological agent and its healing activity.

Depressant and anticonvulsant activity

Ethanol extract of root of C. nucifera (EECN) at 40, 60, and 80mg/kg, ip, significantly enhanced the duration of sleep induced bypentobarbital (40 mg/kg, ip), diazepam (3 mg/kg,ip), and meprobamate (100 mg/kg, ip) in mice,suggesting a probable depressive action on the central nervous system (41). The anticonvulsant action of EECN was alsoobserved in pentylenetetrazole-induced seizure models. In the animals treated with 25mg/kg, ip, EECN, 60.7% had seizures and died 30 min later. In thegroup that received EECN at 80 mg/kg, ip, no animals had seizures ordied, even after 24 h. The components responsible for this depressant activity needto be identified, as well as the mechanism involved in this action. Research on thetoxicity of these extracts is also warranted to guarantee the safety of possiblefuture treatments.

Renal protective activity

Coconut water had prophylactic action against nephrolithiasis in an experiment with aWistar rat model (64). Rats were divided intothree groups. Group I (control) was fed standard rat diet. Group II was administered0.75% ethylene glycol in drinking water to induce nephrolithiasis. Group III wasgiven coconut water in addition to ethylene glycol. All treatments lasted 7 weeks.Analysis of urine samples revealed a drastic decrease in the number of calciumoxalate crystals in group III compared with group II. Coconut water alsosignificantly lowered the levels of creatinine and urea in group III animals,significantly reduced lipid peroxidation (group II: 38.99±3.36 mol MDA/mg protein/15min; group III: 27.68±2.45 mol MDA/mg protein/15 min) and decreased the enzymeactivities of superoxide dismutase and catalase. These results demonstrate thatcoconut water has important properties against urolithiasis and therefore must beinvestigated as a potential treatment for this condition.

Antimalarial activity

Antimalarial activity of different crude methanol extracts (50, 100, 200, and 400mg/kg, treated orally) was investigated in vivo againstPlasmodium berghei (NK65) in mice during early, established, andresidual infections. Chloroquine (20 mg/kg) and pyrimethamine (1.2 mg/kg) were usedas reference drugs. The methanol white flesh extract of C. nuciferaproduced a dose-dependent chemotherapeutic activity in all three invivo-assessment models. In the established malaria infection, there was asignificant (P<0.05) decrease after treatment with the extract (200 and 400 mg/kg)compared to the reference drug for the treatment of the disease (25). These results suggest that the Malaysianfolkloric medicinal application of C. nucifera has a pharmacologicalbasis; however, chloroquine was much more effective at suppression and curing, andthe extract did not increase the survival time of infected mice, indicating the needfor additional studies to elucidate how C. nucifera can be used totreat malaria.

In another study, the antimalarial and toxicity potentials of husk fiber extracts offive Nigerian varieties of C. nucifera were evaluated invitro. The results showed that only the West African Tall ethyl acetateextract fraction (WATEAEF) was active against P. falciparum W2strain with a selectivity index of 30.3. The phytochemicals present in the WATEAEFwere alkaloids, tannins, and flavonoids. The same extract fraction was activein vivo against P. berghei NK65, causing morethan 50% reduction in parasitemia on days 4 and 6 after inoculation at various doses.However, parasitemia varied on days 8 and 10, and results with WATEAEF were no betterthan with chloroquine. Additionally, treatment with 250 and 500 mg/kg body weightWATEAEF significantly increased (P<0.05) plasma creatinine concentration comparedwith controls (65). Despite the reduction inparasitemia, the extract cannot yet be considered an appropriate treatment formalaria. More studies are needed to clarify the adverse effects and effectiveness ofthe coconut extracts, especially in infections caused by P.falciparum (the main agent in humans).

Antitrichomonal activity

The crude methanol extracts of 22 plants used in Mexican folk medicine were testedin vitro against Trichomonas vaginalis. Thesusceptibility tests were performed using a previously described subculture method(66). Trophozoites (4×10⁴) wereincubated for 48 h at 37°C in the presence of different concentrations (2.5–200mg/mL) of the crude extracts in DMSO. Each test included metronidazole as a positivecontrol, a negative control (culture medium plus trophozoites and DMSO), and a blank(culture medium). The experiments were performed in duplicate and repeated at leastthree times. The crude methanol extract of C. nucifera husk fiberdemonstrated excellent antitrichomonal activity (IC₅₀ value of 5.8 μg/mL),standing out among the other tested plants, although the activity was less than thatof metronidazole. Further research is needed to isolate the substances responsiblefor this activity and to test appropriate doses so that they can be used in thetreatment of trichomoniasis (24).

Cardioprotective activity

An important biological action of coconut was demonstrated using an experimentalmodel of myocardial infarction induced by isoproterenol in rats (67). Feeding these animals with tender coconutwater (West Coast Tall variety) protected against the induction of myocardialinfarction and decreased mitochondrial lipid peroxidation.

In another study, dietary coconut sprout (West Coast Tall variety) was tested onisoproterenol-induced myocardial infarction in rats (68). There was a decrease in the levels of cardiac markers (CK-MB andtroponin-T) in serum of the group pretreated with coconut sprout (50, 100, or 200mg/100 g body weight) orally for 45 days. Rats fed with 100 mg/100 g body weightshowed better results than other treatment groups. In addition, pretreatment withcoconut sprout decreased oxidative stress in the heart and increased antioxidantstatus. Biochemical analyses showed that sprouts contains bioactive components, suchas vitamins, alkaloids, and polyphenols.

Tender coconut water could also reduce total cholesterol, very-low densitylipoprotein, low density lipoprotein, and triglyceride levels in serum (69). Administering coconut water (4 mL/100 g bodyweight) in male rats counteracted the increases in these substances promoted bycholesterol feeding.

The results presented here support the cardioprotective effects of coconut water. Itsadministration could reduce oxidative stress and cell damage in animals with inducedmyocardial infarction and reverse increases in cholesterol levels in animals fedhigh-fat diets. Therefore, further research is warranted on its potential use toprevent a second ischemic event or in the treatment of dyslipidemic states.

Hepatoprotective activity

The hepatoprotective effect of tender coconut water was investigated in carbontetrachloride (CCl₄)-intoxicated female rats. The animals were dividedinto three groups: normal control rats, CCl₄-treated control rats, andtender coconut water pretreated rats intoxicated with CCl₄. Carbontetrachloride caused elevated serum glutamate oxaloacetate transaminase and glutamatepyruvate transaminase levels and also lead to liver necrosis and fatty liver, whilerats pretreated with coconut water showed decreased activities of these enzymes(59). With only one report describing theseeffects, there remains room to develop studies to define the real role of C.nucifera in this action.

Antidiabetic activity

The antidiabetic activity of purified coconut kernel protein (CPK) was evaluated inalloxan-induced diabetes (150 mg/kg body weight, ip) (70). CPK was isolated from dried coconut kerneland administered to Sprague-Dawley rats with a semi-synthetic diet for 45 days. Itattenuated the increase in glucose and insulin levels in these diabetic rats.Glycogen levels in the liver and the activities of carbohydrate-metabolizing enzymesin the serum of treated diabetic rats reverted to normal levels compared with healthycontrol animals. Histopathology revealed that CPK feeding also reduced thediabetes-related pancreatic damage in treated rats compared with the diabeticcontrol. These results are probably due to the effects of CPK on pancreatic β cellregeneration through arginine, an important amino acid found at high concentrationsin CPK by HPLC.

The effects of mature coconut water were also evaluated and compared withglibenclamide in alloxan-induced diabetic rats (71). Treatment of diabetic rats with lyophilized mature coconut water(1000 mg/kg body weight) or glibenclamide (0.6 mg/kg body weight) reduced bloodglucose levels (129.23±1.95 and 120±2.3 mg/dL, respectively) when compared with theuntreated control (275.32±4.25 mg/dL). Coconut water also increased insulin levelsand liver glycogen concentrations and reduced glycated hemoglobin levels in diabeticrats. In addition, elevated levels of liver function enzymes markers like alkalinephosphatase, serum glutamate oxaloacetate transaminase, and serum glutamate pyruvatetransaminase in diabetic rats were significantly reduced upon treatment with maturecoconut water. It was also observed that diabetic rats showed altered levels of bloodurea, serum creatinine, and albumin, and the albumin/globulin ratio was significantlyreversed by treatment with mature coconut water and glibenclamide.

Administering immature coconut inflorescence methanol extract (West Coast Tallvariety) to diabetic rats significantly reduced fasting glucose levels and increasedinsulin levels compared with a diabetic control (72). The 200 mg/kg body weight dose showed better antihyperglycemiceffects than other doses.

These studies demonstrated that different parts of C. nuciferacanbenefit diabetic rats, similar to oral hypoglycemic agents currently used clinicallyto control diabetes. Therefore, clinical trials and biochemical analyzes arerecommended to isolate the compounds responsible for these actions and to establishthem as drugs.

Effects on bone structure

VCO was investigated in postmenopausal osteoporosis rats to determine its effects onbone microarchitecture (73). Rats weresupplemented with VCO (8% mixed with the standard rat chow diet) for 6 weeks. VCOadministration significantly increased bone volume, prevented a reduction intrabecular number, and lowered the trabecular separation compared with theovariectomized control. Bone histology revealed that the trabecular bones of theovariectomized group appeared to be sparser and less dense than in the group treatedwith VCO. Treatment of ovariectomized rats with VCO seemed to reverse the effects ofestrogen deficiency on bone structure. With only one report on the anti-osteoporosisactivity of C. nucifera available, there is a need for furtherstudies.

Antihypertensive activity

The anti-hypertensive activity of an ethanolic extract of C.nucifera endocarp (EEC) using the deoxycorticosterone acetate (DOCA)salt-induced model of hypertension was observed. Administering EEC significantlyreduced the mean systolic blood pressure in DOCA salt-induced hypertensive rats (from185.3±4.7 to 145.6±6.1 mm Hg). This effect was attributed to the direct activation ofthe nitric oxide/guanylate cyclase pathway as well as stimulation of muscarinicreceptors and/or the cyclooxygenase pathway. These activities can be explained by thepresence of phenolic compounds and flavonoids in the extract used (74). Based on these results, C.nucifera should be studied further for its potential use againstcardiovascular diseases.