Gen info
- Synsepalum is a genus of trees and shrubs in the chicle family, Sapotaceae, described as a genus in 1852. The genus is native to the tropical lowlands of Africa.
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Synsepalum dulcificum is a plant in the Sapotaceae family, native to tropical Africa.
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The name "miracle fruit" originated from the major component "miraculin", which is responsible for taste alternation. It was first discovered by European explorers, and later described by Daniell in 1852. Kurihara and Beidler identified the miraculin compound in 1968, and Brouwer et al termed it. (60)
- The common name "Miracle fruit" is shared by Synsepalum dulcificum, Gymnema sylvestre, and Thaumatococcus daniellii, species that alter the perceived sweetness of foods.
(63)
 Botany
Synsepalum dulcificum is a shrub that grows up to 10 feet in cultivation. Leaves are 5 to 10 centimeters long, 2 to 3.7 centimeters wide, glabrous below, and clustered at the end of branchlets. Fruit is orange- colored containing one seed. Seeds are the size of coffee beans.
Miracle plant grows up to a height of around 3 m in cultivation. Leaves measure 5 to 10 cm in length and 2 to 3.7 cm in width and are grown in shady areas with plenty of water and nutrients. Changes in the color of the fruit in S. dulcificum can be seen starting at the yellowish stage and become more noticeable as the fruit ripens (red color). Seed maturation was also indicated by reddish brown to black coloration. At 70 to 74 days following the flower blossom, the color of S. dulcificum fruit changes to entirely bright red.[7] The optimum temperature needed for miracle fruit plant survival is >7°C. Flowers are cream in hue while budding, but mature to a dark red or brown tint. Ripe fruits are small ellipsoid berries that are brilliant red in color, typically packed at the branches’ terminals, about 2 to 2.5 cm long, 1 cm wide, and with a coffee bean form. Seed is huge and elliptical, dark brown in color, encased in a translucent pulp with a thin red skin. Pulp contains the sweetening action. Flowers blossom in the summer, and the fruits can be harvested in the winter. Only the fruit accumulates miraculin, and production begins 6 weeks after pollination. (60)
Distribution
- Introduced to the Philippines.
- Native to Benin, Cameroon, Central African Republic, Congo, Gabon, Ghana, Ivory Coast, Nigeria, Zaire.
 Constituents
- Proximate and nutrient analysis of pulp yielded 7.75% protein, 59.55% moisture, 4.36% ash, 6.24% crude fiber, 3.26% fat and 18.84% carbohydrate. Mineral analysis yielded 100 ppm calcium, 24.20 ppm iron, 9.49 ppm zinc, 6.22 ppm copper, 0.01 ppm chromium, and 0.01 ppm cobalt. Vitamin analysis yielded 0.04% vitamin A, 22.69% vitamin C, 0.01% vitamin D and 0.02% vitamin K.
(see study below) (4)
- Fruit contains a glycoprotein molecule called miraculin. (see study below / Miraculin)
- The main compound of the fruit, miraculin, the taste-altering component, is a 44-kDa active glycoprotein, consisting of sugars (glucosamine, mannone, fucose, xylose, and galactose), nitrogen, carbohydrates, and nearly 191 amino acid residues.
The fruit pulp is the part that contains miraculin, accounting for only 4.44% of the fresh fruit's weight. Miraculin does not have a sweet flavor, but when activated at an acidic pH, it changes the taste from sour to sweet. It is 400,000 times sweeter than sucrose in molar terms. (60)
- In a study on amino acid profile of the berry, the highest essential amino acid was leucine (2.35 g/00g), the lowest was methionine (o,31 g/100g protein). Non essential amino acid was highest with glutamic acid (3.43 g/100g protein) and lowest was glycine (0.38 g.100g protein). (7)
- Leaves yielded lupeol, lupenone, and lupeol acetate. (9)
- Study showed the leaves to be rich in protein, fiber, and polysaccharide. Total amino acid 8.65 g/100g, with 41.5% essential amino acid. Leaf essential oil showed major compounds of spathulenol, limonene, diisooctyl phthalate, dibutyl phthalate, palmitic acid and linalool. (see study below)
(11)
- Stems yielded a new amide, dihydro-feruloyl-5-methoxytyramine (1),
together with 13 known compounds, including (+)-syringaresinol (2), (+)-epi-syringaresinol (3), 4-acetonyl-3,5-dimethoxy-p-quinol (4), cis-p-coumaric acid (5), trans-p-coumaric acid (6), p-hydroxybenzoic acid (7), syringic acid (8), vanillic acid (9), veratric acid (10), N-cis-feruloyltyramine (11), N-trans-feruloyltyramine (12) and N-cis-caffeoyltyramine (13). (see study below) (14)
- Study evaluated the amino acid profile and oxidizable vitamin content of the berry. Among the essential amino acids, leucine (2.35g/100g protein) was highest and among non-essential fatty acids, glutamic acid (3.43 g/100g protein) was highest. Among oxidizable vitamins, vitamin C (1.33 mg/100g) was more abundant than vitamin A (2.54 µg) and vitamin E (0.78 mg/100g). (see study below) (16)
- Study of leaf essential oil yielded 44 components with major chemical compounds, viz. spathulenol (24.194%), limonene (15.805%), diisooctyl phthalate (12.402%), dibutyl phthalate (10.326%), palmitic acid (4.865%) and linalool (2.139%). (see study below) (18)
- Quantitative phytochemical analysis of the pulp yielded flavonoids 57.01%, tannins 7.12%, saponins 3.45%, alkaloids 0.0001%, glycosides 0.0001%, resins 0.0003%, terpenoids 0.0002%, steroids 0.0001%, and cyanogenic glygosides 0.0003%. (22)
- Antinutrient analysis of the pulp yielded 5.6% oxalate, 0.03% phytates and 0.02% hemagglutinin.
(22)
- Amino acid composition of the pulp yielded
8.055% tryptophan, 1.35% phenylalanine, 0.7% isoleucine, 0.5% tyrosine, 1.05% methionine, 0.4% proline, 0.69% valine, 1.1% threonine, 0.4% histidine, 0.5% alanine, 1.02% glutamine, 1.6% glutamic acid, 0.7% glycine, 0.3% serine, 1% arginine, 0.1% aspartic acid, 1.23% asparagine, 0.6% lysine and 0.6% leucine. (22)
- Study of miracle berry flesh identified and quantified 12 phenolics at levels from 0.3 kaempferol to 17.8 mg/100 g fresh weight for epicatechin. Total phenolics and total flavonoid contents were 1448.3 GA and 9.9 QR equiv/100 g FW for the flesh, respectively, and 306.7 GA and 3.8 mg QR Equiv/100 g FW for the seeds. (see study below) (27)
- Phytochemical screening of fruit showed tannins, flavonoids, steroids, and cardiac glycosides, with an absence of alkaloids and saponins. Total phenolic and flavonoid content were 0.262 mg/g tannic acid equivalent and 0.672 mg/g quercetin equivalent, respectively. (see study below) (30)
- Study isolated ficumone, a 2-oxetanone, from the fruits of S. dulcificum, characterized as (R*)-4-hydroxy-2-oxetanone. (32)
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Study of stems isolated a new amide, dihydro-feruloyl-5-methoxytyramine (1), along with 13 known compounds, including (+)-syringaresinol (2), (+)-epi-syringaresinol (3), 4-acetonyl-3,5-dimethoxy-p-qionol (4), cis-p-coumaric acid (5), trans-p-coumaric acid (6)m p-hydroxybenzoic acid (7), syringic acid (8), vanillic acid (9), veratric acid (10), N-cis-feruloyltyramine (11), N-trans-feruloyltyramine (12), and N-cis-caffeoyltyramine (13). (see study below) (35)
- Study of proximate composition of leaves and whole fruits yielded carbohydrates (40.38 and 17.44%), crude fiber 17.58 and 3.63%), crude protein 8.42 and 10.26%), ash content (2.87 and 3.95%) crude fat (1.97 and 2.32%) and moisture 27.78 and 62.40%). Mineral micronutrients yielded calcium (3100 and 1395 mg/kg), magnesium (300.8 and2678.8 mg/kg), potassium (2500 and 2900 mg/kg), sodium (1986 and 1531 mg/kg). Micronutrient yield: zinc (52 and 17 mg/kg),
iron (243 and102mg/kg), copper (48 and 89 mg/kg), manganese (44 and 34 mg/kg). Anti-nutrients: oxalate 31.5 and 28.5 mg/100g), phytate (59.5 and 34.7 mg/100g), nitrate (180 and 95 mg/100g). Phytochemical yields were alkaloid (0.90 and 1.37%), flavonoids (0.12 and 0.58 %), cardiac glycosides (0.06 and 0.14%), tannins (0.65 and 0.34%), phenol (0.147 and 0.231%), and anthraquinones (0.006 and non-detectable %) for leaves and whole fruit respectively. (39)
- Study isolated ficumone (1), a 2-oxetanone from the fruits of S. dulcificum and characterized as (R*)-4-hydroxy-2-oxetanone by spectroscopic methods. (46)
- Study evaluated seeds for nutritional and antinutritional composition.
Proximate composition of seeds showed 44.30% moisture content, 1.44% ash, 1.33% crude fat, 1.30% crude fiber, 12.32% protein, and 39.31% carbohydrate. Mineral analysis yielded potassium, sodium, manganese, calcium, phosphorus, and iron. Vitamin analysis (mg/g) yielded 4.84 vitamin, 3.02 vitamin A, and 0.47 vitamin. Antinutritional analysis yielded oxalate 8.42%, phytate 4.57%, and hemagglutinin 3.74%. (56)
- Ethanol, methanol and ethyl acetate extracts of leaves yielded alkaloids, saponins, flavonoids, tannin, anthraquinones, terpenoids, cardiac glycosides, and phlobatannin. Total phenolic content of extracts ranged from 0.02 µg/ml TAE - 0.09 µg/ml TAE at 1000 µg/extract concentration. Total flavonoid content ranged from 0.32 mg/g QE in EA extract to 14.38 mg/g QE in the ME. (see study below)
(59)
 Properties
- It has the unique effect on taste receptors, making acidic and bitter fruits taste sweet. When held in the tongue, strong sweetness is sensed for over 1 hour each time a sour solution is tasted. This property is attributed to a glycoprotein called "miraculin." (see study below) (14)
- Studies have suggested sour-taste modifying, tyrosinase inhibiting, antidiabetic, antioxidant, antiproliferative, hepatoprotective, anticancer , antibacterial, antihyperuricemic, anticonvulsant, anticoagulant, thrombolytic, catalytic, antihyperuricemic properties.
Parts used
Fruit, leaves.
 Uses
Edibility / Culinary
- In tropical West Africa, fruit pulp is used to sweeten palm wine.
- In India, used as vegetable. In Rajasthan, leaves used in preparing bread by mixing with Bajra. In Tamil Nadu, leaves and tender shoots cooked and eaten as vegetable. (19)|-
- Study showed potential for use in making red wine. (see study below) (54)
Folkloric
- The Visayans in Ipil and Siay, Zamboanga Sibugay, use the miracle fruit for treatment of diabetes, hypertension, and UTI. (48).
- Leaves have been used for heartburn, indigestion, poor appetite, diabetes, and high blood pressure.
- In Japan, popular among patients with diabetes and dieters.
- In India, poultice of plant applied to stomach in abdominal complaints, erysipelas.
Others
- "Psychedelic" berry: A non-narcotic ingredient in social soirées referred to as "flavor tripping" parties.
- Taste Improvement: Study shows improvement of taste in chemotherapy patients. While miracle fruit doesn't work for everyone, study shows it improved the metallic taste from chemotherapy in about 70% of participants. (see study below) (8) (12)
Studies
• Improvement of Insulin Resistance / Anti-Diabetic: Study employed miracle fruit (Synsepalum dulcificum) to investigate the effect of insulin resistance induced by fructose-rich chow in rats. A single oral dose of miracle fruit powder decreased the plasma glucose in a dose dependent manner. Results suggest miracle fruit can be a adjuvant for treating diabetes mellitus with insulin resistance because of its ability to improve insulin sensitivity. (3)
• Antioxidant Vitamin Composition: Study for antioxidant vitamins composition of S. dulcificum pulp yielded vitamin A 0.04%, vitamin C 22.69%, vitamin D 0.01%, vitamin K 0.02%. (see proximate and micronutrient study above). (4)
• Miraculin: Miraculin (MCL) is a homodimeric protein isolated from the red berries of Richadella dulcifica. A cell-based assay quantitatively evaluated the acid-induced sweetness of MCL and found that MCL activated hT1R2-hT1R3 pH-dependently as pH decreased and receptor activation occurred every time an acid solution was applied. Study suggests MCL binds hT1R2-hT1R3 an an antagonist at neutral pH and functional changes into an agonist at acidic pH, the mechanism for its taste modifying activity. (5)
• Molecular Mechanisms of Sweet Taste Enhancers: Positive allostric modulators of human sweet taste have been developed as a new way of reducing dietary sugar intake. Study showed the sweet taste enhancers work at the molecular level, with a similar mechanism as the natural umami taste enhancer molecules. Whereas sweeteners bind to the hinge region and induce closure of the Venus flytrap domain of T1R2, the enhancers bind close to the opening and further stabilize the close and active conformation of the receptor. (6)
• Improvement of Food Palatability in Chemotherapy Patients: A pilot study of the S. dulcificum fruit in 8 patients with cancer evaluated if consumption of the miracle fruit could improve chemotherapy-associated taste changes. All participants reported positive taste changes with the supplement. (8)
• Essential Oil / Leaves / Flavonoids / Antibacterial / Anti-Tumor: Study of essential oil of leaf displayed varying degrees of antibacterial activity against tested bacteria except for Pseudomonas aeruginosa. It showed dose dependent antitumor activity against human K562 cancer cell line. Leaf total flavonoids can reduce BUN, LD, and MDA, enhance mice liver glycogen and activity of CAT, SOD, and antitumoral activity. (10)
• Effect of Pulp on Biochemical Parameters: Study of methanol extract of pulp showed no negative effect on some biochemical parameters in albino rats. No toxicity was seen up to 5,000 mg/kg. There was reduction in total serum cholesterol and LDL, with an increase in HDL concentration. A glucose lowering effect was attributed to modifications in glucose uptake in the intestine. (11)
• Treatment of Taste Alteration in Chemotherapy: A pilot study reported on a single institution trial that assessed whether MF improved dysgeusia in cancer patients receiving chemotherapy. Patients were randomized in a crossover fashion. At baseline, 20 (87%) complained of metallic taste and 78% of no taste. Of 24 patients who completed the study, 30% reported improvement in taste, 35% thought MF was helpful, with a 52% response when considering stabilization of taste. Furthermore, study concludes MF is safe for use in patients undergoing chemotherapy. (12)
• Antioxidant / Phenolics and Flavonoids in Skin, Pulp, and Seeds: Study showed the free phenolic content in the skin was 3 times that of the pulp and 4 times that in seeds. Antioxidant activities in skin and pulp were comparable, and significantly higher in seeds. (13)
• Antioxidant / Inhibition of Human Melanoma Proliferation / Stems: Study evaluated the properties of 13 pure constituents isolated from the stems. Compounds 2 ad 3 showed significant inhibition effects on human melanoma cells. Results also showed moderate DPPH, ABT radical scavenging, metal chelating and reducing power. (14)
• Amino Acid and Oxidizable Vitamin Profile: Study evaluated the amino acid profile of Synsepalum dulcificum berry. Among the essential amino acids, leucine (2.35g/100g protein) was highest while methionine (0.31 g/100g protein) was lowest. Among non-essential fatty acids, glutamic acid (3.43 g/100g protein) was highest while glycine (0.38 g/100g protein) was lowest. Among oxidizable vitamins, vitamin C (1.33 mg/100g) was more abundant than vitamin A (2.54 µg) and vitamin E (0.78 mg/100g). (16)
• Antitumor / Antibacterial / Leaf Essential Oil: Antibacterial assay of leaf essential oil showed varying degrees of activity against all tested bacteria except for Pseudomonas aeruginosa. Antitumoral activity using MTT assay exhibited dose dependent activity against human K562 cancer cell line. (see constituents above) (18)
• α-Glucosidase Inhibitory Activity / Antioxidant /
Seeds and Leaves: Study evaluated the monosaccharide composition, molecular weight, and in vitro bioactivities (antioxidant, α-glucosidase inhibition) of polysaccharides from seeds and leaves. The antioxidant and α-glucosidase inhibition of leaf polysaccharide were significantly greater than seed polysaccharides. MFL-P showed remarkably better α-glucosidase inhibition than acarbose. Results suggest miracle fruit leaf polysaccharide has potential as a functional factor with both antioxidant and antidiabetic activities in food applications. (19)
• Herb-Drug Interactions: Compounds isolated from Synsepalum dulcificum have antioxidant activity which may, theoretically, interfere with the actions of chemotherapeutic drugs, such as doxorubicin and platinum compounds. (20)
• Antidiabetic Potential / Methanolic and Flavonoid-Rich Leaf Extracts: Study investigated the antidiabetic potentials of both methanolic and flavonoid-rich leaf extracts of S. dulcificum in type 2 diabetic Wistar albino rats. Biochemical parameters such as liver and kidney functions, lipid profile, lipid peroxidation and antioxidant enzymes and histopathology were assessed. Administration of the extracts for 21 days significantly (p<0.05) improved observed pathologic changes associated with type 2 diabetes. (21) Study evaluated the antidiabetic mechanisms of a methanol and flavonoid-rich leaf extracts of Synsepalum dulcificum (MSD and FSD, respectively). Leaf extracts stimulated insulin secretion in type 2 diabetic rats. The extracts reduced levels of inflammatory markers, TBF-α and IL-6, and inhibited α-amylase and α-glucosidase, and reduced the level of HbA1c and insulin. (37)
• Anti-Hyperuricemic / Inhibition of Xanthine Oxidase: Extracts isolated from miracle fruit exhibited potential for reduction of uric acid and inhibited xanthine oxidase activity in vitro and in monosodium urate (MSU)-treated RAW264.7 macrophages. Butanol extracts attenuated oxonic acid potassium salt-induced hyperuricemia in mice by lowering serum uric acid and activating hepatic xanthine oxidase. Effects were comparable to allopurinol and suggests a potential for the butanol extract as a novel anti-hyperuricemic agent. (23)
• Acute Toxicity Study
/ Benefit on Biochemical Parameters: Study evaluated the beneficial effects of methanol extract of S. dulcificum on some biochemical parameters in a rat model. Acute toxicity study showed the methanol extract was not toxic up to 5000 mg/kbw per day for 28 days. 100 mg/kbw doses of ME significantly reduced (p<0.05) serum levels of bilirubin, LDL, ALT, and glucose after 14 days. HDL was significantly increase (p<0.05). (24)
• Antioxidant / Leaves: Study evaluated the total phenols, total flavonoids, and total antioxidant content of a methanol leaf extract of S. dulcificum. HPLC confirmed the presence of polyphenols and carotenoids. Extract yielded flavonoids, saponins, terpenoids, and cardiac glycosides. IC50 of the extract for DPPH, NO, OH-, and ABTS radical scavenging assays were 139.45 µg/ml, 119.17 µg/ml, 147.65 µg/ml, and 135.83 µg/ml, respectively. Results showed potential in preventing and ameliorating diseases associated with free radicals. (25)
• Effect of Seed Oil In Women with Damaged Hair / Clinical Trial: Hair breakage is a common unrecognized form of hair loss in women, most often the result of hair weathering and traumatic grooming practices. A randomized, double-blind, placebo-controlled trial evaluated the safety and efficacy of a hair oil containing MSFO (miracle fruit seed oil) and its effects in long-haired women with excessive hair breakage. Results showed increased levels of unbroken hairs by reducing hair breakage. The MDSO showed to be a safe and effective option for treatment of women suffering from hair breakage and damaged hair. (26)
• Free Radical Scavenging / Phenolic and Flavonoid Content / Flesh and Seed: Free radical scavenging and reducing percentage of the flesh extract was 96.3% and 32.5% in DPPH and ABTS assays, respectively, along with a high FRAP of 22.9 mmol/100g for the flesh extract. Results suggest the miracle berry as an antioxidant-rich food. (see constituents above) (27)
• Methods for Early Fruiting: Study reports on the beneficial effect of water supply and fertilization on both vegetative and reproductive growth in S. dulcificum. Water supply is the most important factor unlocking flowering, while a combination of N, P, and K at dose of 1.5 g for all consistently resulted in highest performance for growth and yield traits. Study results will intensity breeding and horticultural development. (28)
• Cytotoxicity
on Human Colorectal Cancer Cells / Stem and Berry: Study showed cytotoxicity of S. dulcificum stem methanolic extract, stem EtOH, berry EtOH extracts on human colon cancer (HCT-116 and HT-29) cell lines via induced apoptosis caused by up-regulation of expression of early apoptotic genes, c-fos and c-jun. (29)
• Hepatoprotective
/ Antioxidant and Prooxidative / Fruit: Study evaluated the effect of S. dulcificum on oxidative stress and hepatotoxicity markers in rats. Results showed the berry fruit extract at lower dose range of <100 mg/kg may boost antioxidant defense and exert hepatoprotective properties while higher doses may be pro-oxidative. (see constituents above) (30)
• Antioxidant / Leaves: Study isolated 17 compounds from an ethyl acetate extract of leaves. Compounds 6, 7. 13, and 14 exhibited significant antioxidant activity in DPPH and ABTS assays. (33)
• Antidiabetic / Inclusion in Yogurt / Pulp: Study evaluated the in vitro evidence of potential inhibition of α-amylase and α-glucosidase enzymes, followed by inclusion of extracts of S. dulciificum to enhance the therapeutic properties of yogurt. Screening of seed, leaf, and pulp of S. dulcificum showed the pulp extracts contained significantly (p<0.05) higher antidiabetic activities than the other plant parts. The pulp also showed stronger anti-diabetic properties than standard drug, acarbose. The incorporation into yogurt showed higher (p<0.05) anti-diabetic activities than plain yogurt. Highest α-glucosidase and α-amylase inhibitory activities were shown on day 7 of storage. Results suggest potential for the pulp as functional factor with antidiabetic activities in food application. (34)
• Inhibition of Melanoma Proliferation / Antioxidant / Stems: Study of stems isolated a new amide, dihydro-feruloyl-5-methoxytyramine, along with 13 known compounds. Compounds 2 and 3 showed significant inhibition of human melanoma cells proliferation, Compounds showed moderate DPPH, ABTX radical scavenging, metal chelating and reducing power compared to positive controls. (see constituents above) (35)
• Miraculin Yield of Nine Morphotypes: Miracle fruit is an understudied tropical fruit species with potential as a source of natural, non-caloric sweetener. The fruit contains miraculin, a natural sweetener, that changes the perception of sour foods and beverages to sweet. It has a role in reducing sugar content in some food and beverages applications. Study evaluated the fruit yield and miraculin content of nine plant morphotypes. The plants followed synchronized flowering periods with six harvest peaks within a single year. Total average yielded ranged from 0.06 to 3.44 kg/tree/year for individual plants. Study identified variation in both yield and miraculin content. Results may be useful in the selection of superior plant types and provide information for a potential industry growing natural, non-caloric sweetener miraculin. (36)
• Biochemical and Antioxidant Potential of Dried Fruits: Study evaluated the biochemical content and antioxidant activity of methanol extracts of S. dulcificum dried fruits. Phytochemical screening yielded alkaloids, flavonoids, phenolic compounds and tannins. Quantitative analysis the seeds had greater amounts of phenols (157.88 ± 2.09 mg GAE / g dry matter) than dried fruit pulp (54.09 ± 2.24 mg GAE / g dry matter). Flavonoid content was lower in seed (0.013 ± 0.02 mg EQ /g) and high in the fruit pulp (0.13 ± 0.05 mg EQ /g). The seed extracts showed good antioxidant activity by both DPPH and FRAP assays, correlating with phenol content and other phytoconstituents. (38)
• Protective Effect on Lead-Acetate Induced Toxicity / Leaves: Study evaluated the protective effect of methanolic leaf extract and flavonoid-rich leaf extract of S. dulcificum on lead-acetate induced toxicity in Wistar albino rats. Results showed the extracts, especially at high doses, significantly (p<0.05) ameliorated the harmful effects of lead administration in the liver and kidney and hematological indices. (40)
• Antihyperglycemic / Hepatoprotective / Fruit: Study evaluated the antihyperglycemic and hepatic safety of miracle fruit compared to aspartame in alloxan-induced diabetic mice. Miracle fruit (MF) ethanol extract contained more flavonoids and tannins and higher DPPH radical scavenging activity (76.61%) compared to MF aqueous extract (o<0.05), The MF ethanol extract revealed 10 antioxidants with quercetin as the major polyphenol. Sensory analysis showed masking of undesirable sourness. Subchronic administration showed amelioration of hyperglycemia in mice compared to aspartame. Aspartame significantly elevated alanine aminotransferase, along with destructive liver effects on histopathology. Hepatic architecture was restored by the MF extract. Results suggest effective antihyperglycemic with hepatoprotective properties and a healthier alternative sweetening agent in place of aspartame. (41)
• Cholesterol Lowering Activity / Seeds: Study evaluated the effect of various extracts of S. dulcificum on the compositional changes of plasma lipids in hamsters fed a high-cholesterol control diet. The 2% ethanol extract decreased the plasma total cholesterol, Two triterpenoids (lupeol acetate and ß-amyrin acetate) were isolated from the ethanol extract of seed. (42)
• Effect on Hand and Finger Motor Skills / Seed Oil / Randomized Study: A randomized, double-blind, placebo controlled study evaluated the safety and efficacy of a compression wrist band containing MFSO and its ability to improved hand and finger motor skills. The MFSO group showed clinically meaningful average improvement, Results suggest the MSFO wristband may improved manual dexterity skills and the ability to maintain this performance. (43)
• Anticonvulsant / Seeds: Study evaluated the anticonvulsant potential of an aqueous fraction of S. dulcificum seed extract in mice. The AF exhibited 33.33% protection against mortality in PTYZ- and strychnine-induced convulsion tests and caused a dose-dependent reduction in time of recovery of the animals from MES-induced seizure. (44)
• Miraculin / Seeds: Miraculin has the power of modifying a disagreeable taste into a pleasant one. It causes citric acid, ascorbic acid, acetic acid, and hydrochloric acid, which are normally sour to be perceived as sweet when held in the mouth. Study evaluated the methanol fruit extract and chloroform pulp extract for tyrosinase inhibition by calculation of hydroxylation of L-tyrosine to L-dopa using in vitro mushroom tyrosinase assay and free radical scavenging antioxidant potential using DPPH assay. (45)
• Antibacterial against Listeria monocytogenes / Leaves: Study evaluated the potential of leaf extracts of S. dulcificum, S. crispus and M. alba for antibacterial activity against L. monocytogenes. Results suggest that an antibacterial compound against L. monocytogenes can be found from S. dulcificum and M. alba from both mature and young leaves. (47)
• Antioxidant / S. dulcificum and C. papaya / Seed Oil: Study evaluated the chemical composition and antioxidant properties of C. papaya and S. dulcificum seed oil. GC-MS analysis of S. dulcificum seed oil revealed the presence of saturated and polyunsaturated fatty acids palmitic acid (34.22%) and linoleic acid (33.74%). Papaya seed oil yielded three free fatty acids with monounsaturated fatty acids, oleic (43.43%) and cis-vaccenic (27.84%) acids as major components. The miracle berry showed higher antioxidant capacity at 60.05% at 1 mg/mL. Activities of the two oils were dose dependent. Total antioxidant capacity of S. dulcificum and C. papaya were 3.259 and 2.925 mg GAE/mL of dry oil, respectively. Results suggest potential rich sources of dietary, nutraceutical, and industrial raw material. (49)
• Antibacterial against Oral Pathogens / Leaves: Study evaluated the antibacterial activity of leaves of S. dulcificum against cariogenic bacteria. Results showed MIC of S. dulcificum leaves aqueous extract against Streptococcus mutans and S. sobrinus were 16 mg/mL and 8 mg/mL, respectively. There was no inhibitory effect against Lactobacillus salivarius. GC-MS study identified 42 compounds and major bioactive compounds were heterocyclic and phenolic compounds. Results suggest potential for oral care products application. (50)
• Nano-Robots from Seeds of S. dulcificum / Antidiabetic: Diabetes mellitus presents as Type 1, Type 2, and gestational diabetes. The body needs insulin to use the glucose for energy. However, with diabetes there can be a lack of insulin or adequate but non-functioning insulin or insulin resistance. Study reports on the latest in nanotechnology that can cure diabetes through the use of nano-robots from sprouted seeds or germinated seed of S. dulcificum that can induce and control the production rate on insulin in the pancreas. Creation of nano-robots with onivyde is designed with nano-electric biosensor. (51)
• Anti-Hyperuricemic / Leaves: Xanthine oxidase is a hepatic enzyme that catalyzes a two-step oxidation of hypoxanthine to xanthine to uric acid. Study evaluated the potential of miracle fruit leaf ethanol and water extract to prevent and treat hyperuricemia. The leaf extracts could reduce serum uric acid levels in rats with hyperuricemia induced by potassium oxonate. The ethanol leaf extract was more effective than the water extract. The leaf extract yielded three compounds in decreasing sequence: quercetin-3-O-α-L-rhamnopyranoside (1.74 g/100g), hyperoside (0.77 g/100g), and quercetin (0.17 g/100g). The leaf extract, together with quercetin derivatives could be useful for the prevention and treatment of hyperuricemia. (52)
• Silver Nanoparticles / Antimicrobial / Anticoagulant / Thrombolytic / Leaves and Seeds: Study reports on the eco-friendly synthesis of AgNPs mediated by leaf and seed extracts of S. dulcificum. Phenolic compounds and proteins were involved in the phytosynthesis. The AgNPs inhibited the growth of drug-resistant strains of Pseudomonas aeruginosa and Klebsiella granulomatis and inhibited the growth of Aspergillus flavus and A. niger. The NPs also also exhibited blood anticoagulant activities and thrombolysis. Results suggest potential for biomedical and catalytic applications. (53)
• Miracle Berry Red Wine: Study evaluated the effects of varying pH and inocula levels during fermentation on the wine parameters (soluble solids, pH, titratable acidity, acid taste index, total phenols and antioxidant activity). Results suggest it is possible to produce red wine from miracle berry rich in antioxidant with possible health promoting benefits. Varying pH and inoculum levels can affect the quality of the wine produced. (54)
• Anticancer / Antimicrobial / Fruits: Study evaluated petroleum ether and ethanol extracts of dried fruit of S. dulcificum against six bacterial strains (Bacillus subtilis, Staphylococcus aureus, Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumonia and Proteus vulgaris) and two colorectal cancer lines HCT-116 and PCE (primary colon epithelial) cell lines by MTT assay. The petroleum ether extract exhibited stronger antimicrobial activity than the ethanol extract. The ethanol extract showed significant anticancer activity (p<0.05) with IC50s ranging from 14.00 to 8.54 µg/mL at 24, 48 and 72 h, and IC50s on PCE ranging from 236.25 to 196.72 µg/ml. (55)
• Nutritional and Antinutritional Composition of Seeds: Study evaluated the nutritional (proximate, mineral, vitamin) and antinutritional compositions of S. dulcificum seeds. Results showed the seeds have appreciable nutritional contents (proteins, minerals and vitamins) and low antinutrient content. (see constituents above) (56)
• Antitumor Against Hepatocellular Carcinoma / Triterpenoids / Leaves: Study of leaves isolated two pairs of enantiomeric coumarinolignans, synsepalumins A and B (1 and 2), three new pentacyclic triterpenoids, 3-O-cis-p-coumaroyl-2α,3β,29-trihydroxy-olean-12-en-28-oic acid (3), 3-O-trans-p-coumaroyl-2α,3β,29-trihydroxy-olean-12-en-28-oic acid (4), and 3-O-cis-p-coumaroyl-3β,19α-hydroxy-urs-12-en-28-oic acid (6), along with twenty-five known compounds (5, 7−30). Compound 4 (SMG-1) significantly inhibited proliferation of HepG2 (IC50 13.9 µM) and HCCLM3 (IC50 11.8 µM) cells. SMG-1 induced reactive oxygen to increase level of BNIP3 through JNK/p53 pathway and decreased mitochondrial membrane potential, resulting in activation of mitophagy. SMG-1 upregulated Bax and cytoplasm level of Cyt-c to promote Caspase-9/Caspase-3-mediated apoptosis in HCC cells. Results suggest ability to treat HCC. (57)
• Inhibition of Lung Adenocarcinoma / Fruit: Study evaluated the mechanism of action of SD on lung adenocarcinoma using network pharmacology. Study identified 335 chemical components of which 107 were related to tumor immunity. ADME screening found 11 compounds that might be inhaled into the human body and affect the growth of lung adenocarcinoma. In vitro experiments showed SD could inhibit growth of lung adenocarcinoma A549 cells, reduce expression of PCNA (p<0.05), significantly increase expression of Caspase-3 (p<0.05), reduce phosphorylation of EGFR (p<0.05), inhibit expression of P13K and AKT phosphorylation (p<0.001). Results suggest SD can inhibit the growth of lung adenocarcinoma A549 cells, possibly via inhibition of EGFR/JAK/STAT3 and EGFR/P13K/AKT signaling pathway. Substances affecting antitumor effect may be catechin, taxifolin, betaine, epigallocatechin gallate, erucamide, guanosine, kaempferol, lanosterol, morin, oleanolic acid, and quercetin. (58)
• Radical Scavenging / Leaves: Study evaluated the antioxidant and phytochemical properties of ethanol and ethyl acetate extracts of leaves of S. dulcificum using DPPH, total antioxidant activity, FRAP, total flavonoid and total phenolic content. The methanol extract showed highest yield (17.4%). At 250 µg/ml concentration, the ME showed highest IC50 (89.94 µg/mL). Total antioxidant activity (ascorbic acid equivalent) at 250 µg/ml ranged from 41.7 AAE in EA extract to 58.98 AAE in the methanol extract, Results suggest great potential for antioxidant activity against oxidative stress. (see constituents above) (59)
• Taste-Modifying Mechanism of Miraculin: The taste-modifying mechanism differs from the fundamental sweet chemical pathway. The proposed mechanism is an interaction between miraculin (MCL) and the taste receptors T1R2 and T1R3. Flavor is first detected by taste buds in the taste papillae on the tongue and upper and lower palates and throat, with cell membranes that generate microvilli housing nerve receptors. Miraculin binds to the epithelial plasma membrane of the taste receptor, which is a heterodimer made up of T1R2 and T1R3 which undergo conformational change in an acidic environment. Glycans associated with miraculin bind and activate them. The carbohydrate part of the miraculin molecule attach to the sweet receptor site, resulting in a pH dependent activation (between pH 4.8 and 6.5) of human sweet taste receptor cells. However, unlike sugary foods, miracle fruit does not provide a sweet taste when consumed alone, but does so when combined with H+ ions. At the subcortical level, the sour taste disappears, while the neuronal signal of sweet taste reaches the brain cortex. When a ligand binds to a sweet taste receptor, the G-protein coupled receptor is directly activated, resulting in a sense of sweetness. (60)
• Effect on Renal, Hepatic, and Reproductive Indices with Prolonged Use / Leaves: Study evaluated the in vivo toxicological endpoints of ethanol leaf extract of S. dulcificum in male and female rats. The extract was orally administered for 45 days. The LD50 was estimated at 4750 mg/kg in mice. Results showed significant increases in liver enzymes and creatinine, with decrease in HDL cholesterol and albumin. There was a significant increase in enzymatic and nonenzymatic antioxidants and a significant reduction in malondialdehyde (MDA). There were significant increase in reproductive markers of sperm count, motility and abnormality. Results suggest prolonged use of ethanol leaf extract could result in hepatic and renal dysfunctions and may increase the risk for male infertility and cardiovascular disease. . (61)
• Dried Fruits as Novel Food: Study evaluated the potential of dried fruits of S. dulcificum as a novel food (NF). The NF is pitted and dried (by lyophilisation) fruits of S. dulcificum The NF contains glycoprotein miraculin (≤2.5%). The NF was proposed as food supplement for the adult population (except for pregnant and lactating women) at a maximum dose of 0.9 g daily. The Panel suggests the NF is not nutritionally disadvantageous. Study did not raise concerns on genotoxicity. A 2,000 mg/kbw per day was not associated with adverse effects. The Panel concludes the NF is safe at intake level of 10 mg/kbw per day, corresponding to maximum daily intake of 0.7 g, rather than the 0.9 g/d proposed. (62)
Availability
- Cultivated.
- Fruit available commercially as actual berries (frozen because of high moisture and perishability), freeze-dried fruit granules and fruit tablets.
- Berries, fruit extracts and fruit seed oil in the cybermarket.
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