Gac

Gac (Momordica cochinchinensis Spreng.): A Comprehensive Reference

1. Identity, Taxonomy, and Botanical Description

Scientific and Common Names

Gac, from the Vietnamese gấc (pronounced [ɣək˦˥]), bears the scientific name Momordica cochinchinensis and is a species of plant in the melon and cucumber family Cucurbitaceae, native to countries throughout Southeast Asia and to Queensland, Australia. In English it is variously called "sweet gourd," "baby jackfruit," "spiny bitter gourd," and "red melon." It is sometimes called the "fruit from heaven" due to its health reputation and auspicious color. In China its seeds are designated as a traditional medicine under the name mù biē zǐ (木鳖子), meaning "wooden turtle seed." The species epithet "cochinchinensis" derives from the Cochinchina region of Vietnam, although it is grown in many Asian countries including Bangladesh, China, and India.

Taxonomic History

This species was first described in 1790 by the Portuguese botanist João de Loureiro, who published it in his book Flora cochinchinensis, giving it the combination Muricia cochinchinensis and noting that it was found in "Cochinchinâ, & Chinâ." In 1826 the German botanist Kurt Polycarp Joachim Sprengel transferred the species to the genus Momordica. The genus name Momordica is derived from the Latin word mordeo meaning "to bite," a reference to the seeds' appearance as though chewed.

Plant Morphology

Momordica cochinchinensis is a perennial tendril climber that may reach up to 15 metres (50 feet) long and a stem diameter up to four centimetres. The Gac plant is a type of vigorously perennial vine where males and females flower on separate plants (dioecious). The palmate leaves have 3 to 5 lobes and are carried on a petiole measuring 6–10 cm long. The ripe fruit, typically round or ovoid, features an exterior skin covered in short spines and is harvested from August to February in outdoor growing systems. Gac fruit colour changes gradually from green to yellow, dark orange, and finally red as an indicator of ripeness in around 9–10 weeks after pollination.

Geographic Range and Cultivation

Indigenous to South and Southeast Asia, including Vietnam, China, Thailand, and India, it is known as Gac in Vietnam, "Cochinchin gourd" in English, and has various other names such as baby jackfruit and sweet gourd. Despite its rich cultural heritage and nutritional value, Gac fruit is currently cultivated on a limited commercial scale primarily in Vietnam and Thailand. Gac grows on dioecious vines and is usually collected from fence climbers or from wild plants. The vines can commonly be seen growing on lattices at the entrances to rural homes or in gardens. It only fruits once a year, and is found seasonally in local markets.

Anatomical Parts Used

The fruit is composed of several distinct anatomical layers, each with different phytochemical profiles and uses: an outer spiny peel, a yellow mesocarp (pulp), a bright red seed aril, and hard seeds. Only the bright red seed pulp (aril) of the ripe fruit is used in Vietnam, primarily in the preparation of "xoi gac" (red rice). Many parts of Gac, such as roots, seeds, and oil, are utilized in traditional medicine.

Dosage Forms and Preparations

Gac is commercially available in multiple forms. The aril is consumed fresh, cooked into traditional dishes, pressed into oil, or processed into freeze-dried powder. Supplement products include:

• Aril oil: Cold-pressed from the seed membrane. The total carotene concentration in gac fruit oil has been measured at 5,700 micrograms per ml, of which beta-carotene constituted 2,710 micrograms per ml. Sixty-nine percent of total fat was unsaturated, and 35% of that was polyunsaturated.
• Freeze-dried aril powder: Used in clinical research and commercial supplements.
• Juice/beverage blends: More recently, the fruit has begun to be marketed outside of Asia in the form of juice dietary supplements because of its allegedly high phytonutrient content.
• Seed extracts (Momordicae Semen): Used in Traditional Chinese Medicine (TCM) formulations, topical ointments, and pharmaceutical research.

2. Traditional and Historical Use

Vietnam

For more than 1,200 years, native countries like China and Vietnam have widely used Gac fruit as food and traditional medicine. Because it has a relatively short harvest season (which peaks in December and January), making it less abundant than other foods, Gac is typically served at ceremonial or festive occasions in Vietnam, such as Tết (the Vietnamese New Year) and weddings. Gac fruit is incorporated into xôi gấc, a glutinous rice dish molded into shapes and served with a specialty Vietnamese ham. Xôi gấc is comprised of Gac fruit arils cooked into a paste with cinnamon, sugar, and salt and then stirred into rice to give the dish a red hue. The color red is believed to bring promises of longevity, luck, and wealth in the coming year.

In Vietnam, the seed membranes are used to aid in the relief of dry eyes, as well as to promote healthy vision. The fruit, especially the aril, is rich in carotenoids, β-carotene, and lycopene, which can be used for the treatment of infantile rickets, xeroma, and night blindness, according to traditional Vietnamese documents.

China (Traditional Chinese Medicine)

Seeds of Momordica cochinchinensis, known in traditional Chinese medicine (TCM) as "Mubiezi," have been utilized in China for more than 1,200 years. They are traditionally used for a variety of internal and external purposes that include the treatment of inflammatory swelling, scrofula, tinea, diarrhea, as well as suppurative skin infections such as sores, carbuncles, furuncles, and boils. Its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1,000 years.

Thailand and Other Southeast Asian Cultures

In Thailand, immature gac fruits and shoots are taken as vegetables. In Guangxi province, southwest China, people also have the custom of eating Momordica cochinchinensis seedlings, which are rich in vitamin C, vitamin B₂, lycopene, beta-carotene, and total carotenoids. Young leaves are consumed as vegetables by the Karen communities in Thailand, in Bali, Indonesia, and in the Philippines. Young fruits, leafy shoot, and flowers are used in curries in Thailand.

3. Key Constituents and Active Compounds

More than 60 chemical constituents have been isolated from M. cochinchinensis. These are distributed across the different anatomical parts of the fruit: aril, seeds, peel, and pulp.

Carotenoids (Aril and Pulp)

Carotenoids are the most extensively studied and quantitatively dominant bioactive constituents of Gac, particularly concentrated in the aril.

• Lycopene: On average in three fruits, total carotenoid concentrations were 497 (±154) μg/g fresh material with lycopene dominating and exceeding beta-carotene concentrations by a factor of approximately five (408 μg/g versus 83 μg/g). Comparative analyses have revealed lycopene concentrations in Gac fruit to be at least five times higher than those found in other well-known fruits such as grapefruit, tomato, papaya, guava, and watermelon.
• Beta-carotene (β-carotene): A precursor to vitamin A. The lycopene and β-carotene concentrations of the edible portion of Gac fruit have been reported to be 802 and 175 μg/g, respectively. Gac aril contains approximately 380 μg/g of lycopene and 101 μg/g of β-carotene.
• Other carotenoids: Including alpha-carotene, zeaxanthin, and lutein. Both the yellow pulp and peel of the Gac fruit also serve as rich reservoirs of carotenoids, with the total carotenoid content in the pulp recorded at 283 μg/g, a concentration notably higher than that of other carotenoid-rich fruits.

Tocopherols (Vitamin E)

The alpha-tocopherol concentration in the aril pulp has been measured at 76 μg/g fresh weight. The oil is a rich source of beta-carotene, vitamin E, and essential fatty acids.

Fatty Acids

Both aril and seeds are rich in monounsaturated and polyunsaturated fatty acids, with oil containing 69% unsaturated fats, including 35% as polyunsaturated fats. Gac has a high concentration of linoleic acid (omega-6) and omega-3 fatty acids. The presence of substantial fat in the aril plays an important mechanistic role: the enhanced bioavailability of β-carotene in Gac-infused rice is believed to be influenced by various components within the Gac fruit, including the presence of a significant amount of fat, known to promote the intestinal absorption of β-carotene.

Saponins (Seeds)

Several constituents have been identified in Gac seeds, including trypsin inhibitors (e.g., MCoTI-I, MCoTI-II, and MCoTI-III), saponins (e.g., Momordica Saponin I and Momordica Saponin II), and phenolic compounds (e.g., gallic acid and p-hydroxybenzoic acid). Momordica saponin I has been identified as a potent inhibitor of nitric oxide (NO) production and transcriptional activation of inflammatory genes. Furthermore, this compound demonstrates suppression against the activation of inflammatory signaling proteins. Another noteworthy saponin found in Gac seeds is a quillaic acid glycoside, exhibiting inhibitory effects on the induction of IL-6 and iNOS expression, as well as NO synthesis in RAW 264.7 cells.

Cyclotide Peptides (MCoTI-I, MCoTI-II, MCoTI-III)

The discovery of two macrocyclic peptides from Momordica cochinchinensis suggests that these cyclic peptides are more prevalent than originally thought. The two peptides, MCoTI-I and MCoTI-II, are trypsin inhibitors. They are both 34-amino-acids long, and consist of a cyclic peptide backbone and three disulfide bonds. MCoTI-II, a cyclic knottin peptide natural product of gấc fruit, has been the centre of various molecular engineering efforts. To target medicinally relevant proteins, surface-exposed loops of the mini-protein have been purposefully modified or entirely selected de novo to install bioactive epitopes. MCoTI-cyclotides show very little toxicity to human cells (IC₅₀ >100 μM) and therefore represent a desirable molecular scaffold for engineering new compounds with unique biological properties.

Phenolics and Flavonoids

The major active components of Gac, which are extracted with 70% ethanol, are lycopene, carotenoids, phenolics, and flavonoids. Total phenolic, flavonoid, and saponin contents have been quantified, with leaf extracts showing higher values and stronger antioxidant activity compared to fruit.

Ribosome-Inactivating Proteins

Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor, and anti-AIDS activities have been identified from Cucurbitaceae plants including M. cochinchinensis. These compounds have been isolated primarily from the seeds and have been the subject of laboratory investigation but have not been studied in clinical human trials.

4. Mechanisms of Action

Provitamin A Activity

Beta-carotene present in the Gac aril acts as a precursor to retinol (vitamin A) following enzymatic cleavage in the intestinal wall. In this strategy, provitamin A carotenoids, particularly β-carotene, which provide vitamin A after enzymatic cleavage, play a key role. The co-presence of dietary fat in the aril matrix significantly enhances this bioavailability: fat promotes micellization of carotenoids in the intestinal lumen, which is a rate-limiting step in their absorption.

Antioxidant Mechanisms

Both lycopene and beta-carotene are potent scavengers of reactive oxygen species (ROS), particularly singlet oxygen. These carotenoids possess antioxidant, anti-inflammatory, cardioprotective, and anticancer effects. Gac fruit is a rich source of antioxidant compounds. The aril, which was extracted with 70% ethanol, had the highest DPPH scavenging activity (IC₅₀ = 865 μg/mL).

Anti-Inflammatory Mechanisms

Research indicates that Gac seed extract exhibits anti-gastritis effects, particularly evident in ethanol and diclofenac-induced gastritis in rat models. Notably, Gac seeds harbor various triterpenoids and saponins, with Momordica saponin I identified as a potent inhibitor of nitric oxide (NO) production and transcriptional activation of inflammatory genes. Furthermore, this compound demonstrates suppression against the activation of inflammatory signaling proteins.

Anticancer Mechanisms (Preclinical)

Water extracts of the aril were effective against colon cancer in vivo and in vitro by inducing necrosis, attributed to an unknown 35 kDa protein. At the cellular level, in colorectal cancer cell lines, treated cells became rounded up and there was a loss of contact with neighboring cells, leading to a reduction of cell viability. The MCoTI-II cyclotide scaffold has also been exploited for cancer drug design: the grafted MCoTI-II peptides were cytotoxic to a cancer cell line and showed high stability in human serum. The most potent grafted MCoTI-II peptide inhibited lipopolysaccharide (LPS)-mediated activation of NF-κB in murine macrophages.

5. Scientific Evidence by Area of Use

5.1 Vitamin A Status and Visual Health

This is the area supported by the strongest and most direct clinical evidence for Gac.

Key Clinical Trial (Vuong et al., 2002 — American Journal of Clinical Nutrition): Preschoolers (n = 185) participated in a 30-day controlled supplementation trial in rural Vietnam, where vitamin A deficiency is a concern, and where Gac fruit has been identified as having the highest β-carotene concentration among indigenous fruits and vegetables. Children with low hemoglobin concentrations were assigned to one of three groups: a fruit group who received xoi gac containing 3.5 mg β-carotene per serving; a powder group who received rice mixed with 5.0 mg synthetic β-carotene powder; and a control group who received rice without fortification. The mean increase in plasma β-carotene concentrations in the fruit and powder groups was significantly greater than that in the control group (P < 0.0001). In this supplementation trial among Vietnamese children, gac increased serum vitamin A levels more than synthetic beta-carotene.

In-vitro bioaccessibility study: Using a simulated digestion procedure, the bioaccessibility of β-carotene (29.5±1.7%) and lycopene (51.3±2.6%) from Gac fruit aril were found to be significantly higher than from carrot root and tomato fruit. Irrespective of the ultimate reason, Gac fruit aril provided a highly bioaccessible form of both lycopene and provitamin A (β-carotene), thus offering a most valuable dietary source of both carotenoids.

Evidence assessment: The clinical evidence for Gac's ability to raise plasma retinol and β-carotene in deficient children is reasonably robust for a food-based intervention — supported by a controlled trial (n = 185, 30 days) and mechanistically consistent with established carotenoid absorption science. The superiority of Gac over synthetic β-carotene powder in one trial may reflect the role of its native fat matrix in enhancing absorption. Extrapolation to a general well-nourished population, or to specific ophthalmic endpoints such as macular degeneration, is not supported by current clinical evidence.

5.2 Antioxidant Activity

The bioavailability of carotenes and lycopenes in xoi gac was assessed by an in-vitro digestion technique, simulating the gastric and small intestinal phases of digestion, and by incubation of cultures of Caco-2 human intestinal cells with diluted aqueous (micellar) fraction of digesta. Results suggested that Gac seed membrane and oil are an excellent source of bioaccessible carotenes and lycopene.

Evidence assessment: Antioxidant activity is well-documented in cell culture and in-vitro assays. There is no published randomized controlled trial in humans specifically measuring systemic antioxidant endpoints (e.g., oxidative stress biomarkers) after Gac supplementation alone. The mechanistic basis (high lycopene and beta-carotene content with demonstrated bioaccessibility) is scientifically plausible, but direct clinical translation remains to be established.

5.3 Anticancer Activity

Momordicae Semen summarized constituents including saponins, fatty acids, volatile constituents, proteins, peptides, and other components. Effects and mechanisms on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were investigated.

Colorectal cancer (in vitro): Colorectal cancer cell lines HCT116 and HT29 were treated with Gac aril extract; cytotoxicity and anti-proliferation were analyzed using MTT/MTS and colony formation assays. Cells became rounded and lost contact with neighboring cells, leading to a reduction in cell viability. The cytotoxic effects evaluated showed IC₅₀ for HCT116 and HT29 cells at 2.16 mg/mL and 1.29 mg/mL, respectively, but it was not toxic to normal HEK293 cells at the same dose.

Melanoma (in vitro): Water was best for extracting trypsin inhibitors (581.4 ± 18.5 mg trypsin/mg) and reducing the viability of MM418C1 and D24 melanoma cells (75.5 ± 1.3 and 66.9 ± 2.2%, respectively); the anticancer potential against the MM418C1 cells was highly correlated with trypsin inhibitors (r = 0.92, p < 0.05), but there was no correlation between anticancer potential and antioxidant activity. Water yielded a Gac seed extract, rich in trypsin inhibitors, which had high anticancer potential against two melanoma cell lines.

Breast cancer (in vitro): M. cochinchinensis aril from 44 different samples in Australia, Thailand, and Vietnam were extracted using different solvents and tested for anticancer potential. Anticancer activity on breast cancer (MCF7 and BT474) and melanoma (MM418C1 and D24) cells were compared to control fibroblasts. The cytotoxicity of the cells following treatment with the aril extract was determined using CCK-8 assay.

Glioblastoma (in vitro / in silico): Cytotoxicity assays on LN229 glioblastoma cells revealed significant viability reduction (IC₅₀: 0.48–0.92 mg/mL) after extract treatment. Leaf extract showed 80% inhibition of cell migration in a wound healing assay. LC-Q-Orbitrap-MS–based metabolomics identified diverse phytochemicals. Molecular docking highlighted Piperitol, 7-Hydroxy-5-Methoxy-6-Methylflavan, and Nogiragenin with strong affinities toward glioblastoma targets EGFR, PTEN, and TTN.

Cyclotide-based cancer scaffolds: MCoCC-1, a 3.3 kDa cyclotide unique to Gac seeds which does not have trypsin inhibitor activity, has been shown to exhibit high cytotoxicity against the human melanoma MM96L cell line; cell survival was decreased 43% in the presence of 2 µM MCoCC-1.

Evidence assessment: All anticancer data for Gac to date are from in vitro cell lines and animal models; no human clinical trials have examined Gac or its extracts as a cancer treatment or prevention agent. Evidence is preliminary and should not be interpreted as clinical efficacy.

5.4 Anti-Inflammatory Activity

Modern pharmacological studies and clinical practice demonstrate that some chemical constituents of M. cochinchinensis possess wide pharmacological activities, such as anti-tumor, anti-oxidation, anti-inflammatory, etc. Anti-inflammatory effects have been documented in cell-based and animal models via inhibition of nitric oxide production (Momordica Saponin I), suppression of IL-6 and iNOS expression, and inhibition of 5-lipoxygenase (5-LOX).

Evidence assessment: Evidence is restricted to in vitro and animal models. No controlled human clinical trials of Gac's anti-inflammatory activity have been published in the peer-reviewed literature.

5.5 Cyclotide Scaffolds for Drug Development

Naturally occurring cyclic peptides have emerged as intriguing and relevant scaffolds for next-generation drug design. Peptides from the highly constrained cyclotide family provide an exceptional opportunity for drug discovery, given their characteristic head-to-tail cyclic structure and cystine-knotted core that confer favourable pharmaceutical properties. As a result, MCoTI-II has been the centre of various molecular engineering efforts.

A strategy using mRNA display enabled the selection of potent cyclotide-based FXIIa (blood coagulation factor XIIa) inhibitors from a library comprising more than 10¹² members based on the MCoTI-II cyclotide scaffold. The most potent and selective inhibitor, cMCoFx1, has a pM inhibitory constant toward FXIIa with greater than three orders of magnitude selectivity over related serine proteases, realizing specific inhibition of the intrinsic coagulation pathway.

Overall, research demonstrates the application of the MCoTI-II scaffold for the development of stable peptide drugs for cancer therapy, though all such applications remain at preclinical and early-research stages.

5.6 Nutritional Deficiency (Oil Preservation and Community Use)

A study developed a method to collect and preserve Gac fruit oil, to evaluate the nutritional composition of the oil, and to assess the acceptability of the oil by typical Vietnamese homemakers. One hundred women participated in training to learn how to prepare the fruits and operate the oil press. The average daily consumption of Gac fruit oil was estimated at 2 ml per person. The daily beta-carotene intake (from Gac fruit oil) averaged approximately 5 mg per person. Although the beta-carotene concentration declines with time without a preservative or proper storage, it was still high after three months.

6. Body Systems and Health Areas

• Visual system: Via provitamin A (β-carotene) conversion to retinol; traditionally used for night blindness, dry eyes, and xerophthalmia. Gac fruit might thus contribute to alleviating most severe health implications of vitamin A deficiency, such as anaemia and xerophthalmia, the prevailing cause of preventable childhood blindness, as well as mortality from infectious diseases.
• Immune system: MC has numerous pharmacological effects reported to treat many disease conditions such as infections, immune-stimulating, antioxidant, anti-inflammatory, and anticancer actions.
• Digestive and gastrointestinal system: Traditional use for diarrhea, gastritis, sores, and swelling; Gac seed extract has shown anti-gastritis activity in rat models.
• Oncology (preclinical): In vitro studies across colorectal, breast, melanoma, and glioblastoma cell lines. Clinical evidence is absent.
• Inflammatory conditions: Via saponin-mediated suppression of NO, IL-6, and iNOS pathways, documented in cell and animal models.
• Skin and wounds: The oil isolated from M. cochinchinensis has been reported to cure purulent finger inflammation in 3 to 7 days in TCM clinical practice reports, though rigorous trial evidence is lacking.
• Haematological system: As provitamin A source, Gac supplementation in deficient populations has been associated with improvements in haemoglobin and reduction in microcytic anaemia in supplementation trials.

7. Dosages Reported in Studies

Only dosages explicitly documented in identified scientific sources are listed here.

• Children in the clinical supplementation trial received xoi gac containing 3.5 mg β-carotene per serving (fruit group) or rice mixed with 5.0 mg synthetic β-carotene powder (powder group), daily over 30 days.
• In a community oil use study in Vietnam, average daily consumption of Gac fruit oil was estimated at 2 ml per person, yielding approximately 5 mg of beta-carotene per day.
• In an in vitro antioxidant assay, the aril extracted with 70% ethanol had a DPPH IC₅₀ of 865 μg/mL.
• In colorectal cancer cell line studies, IC₅₀ values for Gac aril extract were 2.16 mg/mL (HCT116 cells) and 1.29 mg/mL (HT29 cells).
• MCoCC-1 cyclotide from Gac seeds decreased human melanoma MM96L cell survival by 43% in the presence of 2 µM.

No standardized or consensus clinical dosage for Gac supplements has been established in the peer-reviewed literature. The dosing data above are from specific research contexts and should not be interpreted as recommended intake levels.

8. Safety, Toxicity, and Notable Considerations

Fruit Aril: General Safety

The aril of Gac, as used traditionally in foods such as xoi gac, has an extensive history of dietary use without reports of adverse effects in the published scientific literature. All parts of the Gac fruit including its peel, pulp, and aril have been identified as exceptionally rich sources of bioavailable carotenoids. Excessive intake of β-carotene and lycopene from any dietary source may result in carotenodermia (a reversible yellowing of the skin), a phenomenon documented with high-dose carotenoid supplementation generally.

Seed Toxicity

The seeds are not eaten; they are removed from the aril and are mostly considered as waste. However, in traditional medicine, Gac seeds are purported to have an array of therapeutic effects on a variety of conditions, such as fluxes, liver and spleen disorders, haemorrhoids, wounds, bruises, swelling, and pus. The seeds contain saponins and ribosome-inactivating proteins that may be toxic in isolation at high doses. Research on saponin acute toxicity from M. cochinchinensis seeds has been conducted in animal models; human safety data are limited.

Cyclotide Safety Profile

MCoTI-cyclotides show very little toxicity to human cells (IC₅₀ >100 μM) and therefore represent a desirable molecular scaffold for engineering new compounds with unique biological properties. However, this assessment is based on laboratory cell studies, not on clinical human safety data.

Pregnancy

Proteins with abortifacient, ribosome inactivating, immunomodulatory, antitumor, and anti-AIDS activities have been identified from Cucurbitaceae plants including M. cochinchinensis. Traditional Chinese medicine has historically classified the seeds as potentially abortifacient. There are no controlled human safety studies in pregnant women; seed-based preparations in particular have historically been contraindicated in pregnancy in TCM practice.

Carotenoid Bioavailability and Storage

Although the beta-carotene concentration in Gac oil declines with time without a preservative or proper storage, it was still high after three months. Processing conditions (heat, oxygen, light) are documented to degrade carotenoid concentrations. Processing can compromise benefits due to the degradation of active compounds under harsh conditions.

Evidence Limitations

The literature on its biological activity against disease-causing cell damage such as diabetes, obesity, and cancer was found to be limited. It is unknown whether the aril extract is cytotoxic to other cancer cell types beyond those studied. The overall body of human clinical evidence for Gac is small; the large majority of pharmacological and safety data derives from in vitro experiments and animal models, which may not translate directly to human outcomes.

References

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