IngredientsMaslinic acid [MA, (2α,3β)-2,3-dihydroxyolean-12-en-28-oic acid] is a pentacyclic triterpene acid with a molecular formula of C30H48O4, a molecular weight of 472.7, and melting and boiling points of 267–269°C and 570.0 ± 50.0°C, respectively. More formally, it is a pentacyclic triterpenoid that is olean-12-ene substituted by hydroxy groups at positions 2 and 3 and a carboxy group at position 28 (the 2α,3β stereoisomer).
Maslinic acid is also known as crategolic acid or (2α,3β)-2,3-dihydroxyolean-12-en-28-oic acid. Historically, maslinic acid was named "crategolic acid," since it was first isolated from Crataegus oxyacantha L.
Maslinic acid is a compound of 30 carbon atoms grouped in five cycles that have several substituents. It presents two hydroxyl groups bound to carbons 2 and 3, one carboxyl group bound to carbon 17, and a double bond between carbons 12 and 13. It is a highly hydrophobic compound of low water solubility. Its aqueous solubility is approximately 3.6 μg·L−1, which drastically reduces its bioavailability.
Maslinic acid belongs to the oleanane series of pentacyclic triterpenes. The triterpenes of the oleane family include erythrodiol, oleanolic acid, and maslinic acid. Together with oleanolic acid, maslinic acid represents the total triterpenic fraction found in virgin olive oil (VOO). This molecule differs from oleanolic acid by only two vicinal hydroxyl groups at the C-2 and C-3 positions, in addition to the carboxyl radical.
Maslinic acid is synthesized in plants via the cytoplasmic acetate/mevalonate pathway that leads to oxidosqualene. Oxidosqualene is cyclized by various oxidosqualene cyclases, among them β-amyrin synthase, which catalyzes the transformation of oxidosqualene into β-amyrin. Afterwards, β-amyrin is converted by successive reactions into erythrodiol, oleanolic acid, and finally maslinic acid.
Maslinic acid is a natural triterpene present in high concentrations in the waxy skin of olives. It is a pentacyclic triterpene compound first isolated from Crataegus oxyacantha L. and is primarily sourced from Olea europaea L., found in the non-glyceride fraction of olive pomace. Maslinic acid was first detected in Crataegus oxyacantha L., but the growing interest in this triterpene because of its wide range of health-enhancing activities has led to its identification in other natural sources, with it being present in more than 30 plants worldwide.
The concentration of maslinic acid increases as the olive oil quality decreases, from values of 38 mg/kg for extra virgin to 227 mg/kg for 9.3%-acidity virgin olive, and to 721 mg/kg for crude pomace olive oils. Maslinic acid is also found in a high concentration (0.8% by weight) in the solid residues (called orujo) from olive oil production.
The level of triterpenic acids in several types of commercial black and green olives ranged from 460 to 1470 mg/kg fruit, which represents a much higher value than reported for virgin olive oils. Both oleanolic and maslinic acids are concentrated on the surface of olive leaves to form a physical barrier that prevents microbes from penetrating into the leaf. They are also present in high concentrations in the epicarp of the fruit, forming part of the waxes that cover them.
Consumption of 33 g of virgin olive oil per day would provide 6 mg maslinic acid. However, consumption of the same amount of crude pomace olive oil (approximately 721 mg/kg maslinic acid) would provide 24 mg maslinic acid.
Maslinic acid has been quantified in edible vegetables such as table olives (295–1318 mg/kg dry weight), spinach (1260 mg/kg), and eggplant (840 mg/kg); in aromatic herbs like mustard (330–1740 mg/kg) and basil (320–350 mg/kg); and in legumes such as chickpeas (61.9 mg/kg) and lentils (26.3–39.5 mg/kg).
Maslinic acid has recently been quantified in edible vegetables such as table olives, spinach and eggplant, aromatic herbs like mustard and basil, legumes such as chickpeas and lentils, and to a lesser extent in some fruits like mandarin and pomegranate.
The triterpene has been found in plants used in traditional Asian medicine for the treatment of diverse conditions. These include the leaves of loquat (Eriobotrya japonica), which have been used as antitussive and anti-inflammatory for chronic bronchitis, and also as diuretic, digestive, and antipyretic; the flowers of Campsis grandiflora, employed for female disorders like uterine hemorrhage; the whole plant of Geum japonicum, used as a diuretic; and Agastache rugosa, for the treatment of anorexia and other intestinal disorders.
Maslinic acid is also isolated from Salvia canariensis. It is also primarily derived from shanzha (Crataegus pinnatifida Bunge).
Maslinic acid is a pentacyclic triterpene found in a variety of natural sources, ranging from herbal remedies used in traditional Asian medicine to edible vegetables and fruits present in the Mediterranean diet. It is important to note that maslinic acid was only chemically identified and isolated in the modern scientific era; traditional use refers specifically to the plants in which it is found, rather than to the isolated compound itself.
Plants containing pentacyclic triterpenes are widely distributed throughout the world. China and other Asian countries have a long history of using plants containing pentacyclic triterpenes as herbal remedies to cure diseases and treat symptoms. The specific plants that contain maslinic acid—such as loquat leaves, Crataegus species, and Agastache rugosa—were integral components of traditional Asian medical systems.
Within the Mediterranean tradition, olive is a plant widely cultivated for a long time and has typically been grown on a large scale in districts along the shore of the Mediterranean. It has been used not only as an oil-stuff, but also as salt-preserved foods, as a material for cosmetics, and even as a herb (a medicinal plant).
The triterpene has been found in plants used in traditional Asian medicine for the treatment of diverse conditions. For example, the leaves of loquat (Eriobotrya japonica) have been used as antitussive and anti-inflammatory for chronic bronchitis, and also as diuretic, digestive, and antipyretic.
Other maslinic acid-containing plants with traditional applications include the flowers of Campsis grandiflora, employed for female disorders like uterine hemorrhage; the whole plant of Geum japonicum, used as a diuretic; and Agastache rugosa, for the treatment of anorexia, vomiting, and other intestinal disorders.
Maslinic acid is a member of the oleanane-type pentacyclic triterpene family. Lupeol, α- and β-amyrin are examples of pentacyclic triterpene alcohols, which not only constitute secondary metabolites themselves, but also might undergo oxidation reactions to yield other derivatives, such as betulinic, ursolic, and maslinic acids.
Within olive-derived products, maslinic acid co-occurs with closely related structural analogue oleanolic acid. Pomace olive oil, an olive oil sub-product, is a promising source of bioactive triterpenoids such as oleanolic acid and maslinic acid. The two compounds are often studied together, as they share biosynthetic pathways but differ in their additional 2α-hydroxyl substitution in maslinic acid, which confers distinct biological properties.
Research has focused on the mechanistic action of maslinic acid in regulating the inflammation pathways through modulation of arachidonic acid metabolism, including the nuclear factor-kappa B (NF-κB)/COX-2 expression, and upstream protein kinase signaling. Protein kinase C (PKC) plays a central role in the activation of NF-κB (p50/p65). Once activated, the IκB protein is degraded which allows NF-κB to translocate from the cytoplasm to the nucleus, where it transcribes downstream proinflammatory genes such as TNF-α, COX-2, iNOS, and IL-6. It was shown that maslinic acid inhibited PKC activation, IκBα degradation, and NF-κB nuclear translocation, which may correlate with its anti-inflammatory properties.
Maslinic acid can be considered an anti-inflammatory agent because it suppresses the production of prostaglandin E2 (PGE2), which is involved in triggering skin inflammation. PGE2 levels increase during inflammation and attract immune system cells, resulting in swelling, redness, and itching. Apart from inhibiting PGE2 production, maslinic acid also reduces the expression of COX-2.
The antioxidant potential of maslinic acid has been attributed to its ability to scavenge reactive oxygen species (ROS), upregulate enzymatic and nonenzymatic antioxidants, suppress ROS-generating enzymes (such as NADPH oxidase and iNOS), and stimulate the nuclear accumulation and DNA binding activity of the nuclear factor erythrocyte 2-related factor 2 (Nrf2) and subsequently upregulate heme-oxygenase-1 (HO-1).
Maslinic acid has been found to attenuate intracellular oxidative stress via inhibition of nitric oxide (NO) and hydrogen peroxide (H2O2) production and reduction of pro-inflammatory cytokine generation in murine macrophages.
Maslinic acid significantly enhanced TNFα-induced inhibition of pancreatic cancer cell proliferation and invasion, and potentiated TNFα-induced cell apoptosis by suppressing TNFα-induced NF-κB activation in a dose- and time-dependent manner. It inhibited TNFα-induced IκBα degradation, p65 phosphorylation, and nuclear translocation, and decreased the expression levels of NF-κB-regulated genes involved in tumor cell proliferation (Cyclin D1, COX-2 and c-Myc), apoptosis (Survivin, Bcl-2, Bcl-xl, XIAP, IAP-1), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF).
The different expression phenotype induced by maslinic acid suggested that it exerts its chemopreventive action mainly by inhibiting cell-survival signaling and inflammation. These changes eventually induce G1-phase cell cycle arrest and apoptosis.
Maslinic acid is able to stimulate NADPH production through regulation of the two oxidative phase dehydrogenases of the pentose phosphate pathway. A key objective of research has been to study the effects of maslinic acid on the kinetic behaviour and on the molecular expression of two NADPH-generating systems, NADP-dependent isocitrate dehydrogenase (NADP-IDH) and malic enzyme (ME), in the liver and white muscle of fish.
Maslinic acid treatment can reduce cellular inflammatory responses and apoptotic progression by modulating NF-κB and MAPK signaling pathways following ischemia-reperfusion stress.
A foundational observation is that maslinic acid has been isolated not only from various plants used in traditional herbal medicine, but also from edible vegetables and fruits. The biological activities of maslinic acid have been assessed in different experimental models, from tumor cell lines to animal models of several diseases, supported by the lack of adverse effects in vivo after oral administration of the triterpene. It is critical to note that the overwhelming majority of evidence comes from in vitro (cell culture) and animal studies. Controlled human clinical trials of isolated maslinic acid are, as of the available literature, absent or very limited.
In vitro evidence: Maslinic acid is known to inhibit proliferation and induce apoptosis in colon cancer cell lines without affecting normal intestinal cells. The in vitro cytotoxic activity of maslinic acid has been systematically explored in several types of cancer, including human colorectal adenocarcinoma (HT-29 and Caco-2 cell lines), pancreatic cancer (Panc-28 cells), human salivary gland adenoid cystic carcinoma, soft tissue sarcoma, human hepatocellular carcinoma (HepG2 cells), and human breast adenocarcinoma (MCF-7 cell line).
Animal model evidence — transgenic mice: The chemopreventive efficacy and associated mechanisms of maslinic acid were evaluated on spontaneous intestinal tumorigenesis in ApcMin/+ mice. Twenty-two mice were randomized into 2 groups: a control group and a maslinic acid group fed a maslinic acid–supplemented diet for six weeks. Maslinic acid treatment reduced total intestinal polyp formation by 45% (P<0.01).
Animal model evidence — carcinogen-induced model: The chemopreventive activity of maslinic acid was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH), a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either maslinic acid at 5, 10, or 25 mg/kg dissolved in (2-hydroxypropyl)-β-cyclodextrin 20% or the solvent for 49 days. Maslinic acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg by 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of maslinic acid found in the colon and the reduction of ACF (r = 0.999, p = 0.019) and MDF (r = 0.997, p = 0.049).
Evidence strength: Evidence is preclinical only. The animal model data are internally consistent and mechanistically supported, but no human clinical trials of isolated maslinic acid in cancer prevention or treatment have been reported in the available literature. Available data is limited and the exact way maslinic acid therapeutically targets oncogenic cell signal transduction cascades in different cancers has yet to be fully unraveled.
Research has reviewed the inhibitory effect of maslinic acid and its derivatives on lung cancer, colon cancer, ovarian cancer, gastric cancer, lymphatic cancer, leukemia, breast cancer, pancreatic cancer, melanoma, prostate cancer, renal cell carcinoma, gallbladder cancer, and bladder cancer, among others.
Evidence revealed that maslinic acid, a widely distributed pentacyclic triterpene in common foodstuffs, exhibited pronounced inhibitory effects against various cancer cell lines. All such evidence is in vitro or from animal models. No human interventional trials in oncology for isolated maslinic acid have been identified in the reviewed literature.
The anti-inflammatory properties of maslinic acid have been demonstrated predominantly in preclinical models. It was shown that maslinic acid inhibited PKC activation, IκBα degradation, and NF-κB nuclear translocation, which may correlate with its anti-inflammatory properties.
Pro-inflammatory cytokines and cell adhesion molecules were decreased in vitro and in vivo following maslinic acid administration in ischemia-reperfusion injury models, indicating that maslinic acid may ameliorate ischemia-reperfusion injury (IRI) by inhibiting the inflammatory response.
Evidence strength: Preclinical (in vitro and animal). No human anti-inflammatory clinical trials for isolated maslinic acid are documented in the reviewed sources.
Experiments from several animal models, as well as from in vitro studies, have confirmed protective effects and showed that maslinic acid can address cardiac, neural, renal, bone, and hepatic damage by attenuating oxidative stress and inflammation.
In a streptozotocin-induced diabetic retinopathy rat model, maslinic acid significantly lowered levels of reactive oxygen species (ROS) and malondialdehyde (MDA) but significantly increased nuclear levels of Nrf2, protein levels of Bcl-2, and total levels of superoxide dismutase (SOD) and reduced glutathione (GSH) in the retinas of control and type 1 diabetic mellitus rats. Maslinic acid was found to prevent diabetic retinopathy by antioxidant potential mediated by the activation of Nrf2.
Evidence strength: Predominantly preclinical. Antioxidant mechanisms are well-characterized in vitro and in animal models.
Maslinic acid (from dry olive-pomace oil) showed glycogen phosphorylase (GP) inhibition and blood glucose-lowering effects in adrenaline-induced diabetic mice.
A study investigated for the first time the dietary intervention with a pomace olive oil with high concentrations of the triterpenic acids (oleanolic and maslinic acid) during diet-induced obesity in mice. The results demonstrated that obese mice, when switched to a triterpenic acid-enriched pomace olive oil diet for 10 weeks, showed a substantial reduction of body weight, insulin resistance, adipose tissue inflammation, and particularly, improvement of vascular function despite high caloric intake. This study examined the oil fraction containing both oleanolic and maslinic acids in combination, not isolated maslinic acid, limiting conclusions about maslinic acid alone.
Evidence strength: Animal model data only; no isolated human clinical trials of maslinic acid for diabetes or metabolic syndrome are available in the reviewed sources.
The cardioprotective and metabolic actions of olive oil intake have been partly attributed to its minor components. Among them, the pentacyclic triterpenic acids, oleanolic and maslinic acids, have gained importance in terms of vasoprotection, metabolism, and cancer.
In an ischemia-reperfusion model, maslinic acid treatment could reduce cellular inflammatory responses and apoptotic progression by modulating NF-κB and MAPK signaling pathways following ischemia-reperfusion stress.
Evidence strength: Primarily preclinical in vitro and animal data. Direct human cardiovascular clinical trials for isolated maslinic acid have not been identified in the reviewed literature.
Research found that maslinic acid administration prevented axonal damage by increasing Akt and p-GSK-3β expression in a cerebral ischemia model. Maslinic acid's neuroprotective effects have been demonstrated in experimental ischemia models, suggesting potential for brain injury protection.
Evidence strength: Preclinical only. Human neuroprotection trials have not been identified in the reviewed sources.
Maslinic acid has been studied as an antiparasitic agent, particularly against Plasmodium species and other parasites. The in vivo anti-malarial activity of maslinic acid was analysed using a four-day blood-suppressive test. Mice were inoculated intraperitoneally with red blood cells from Plasmodium yoelii-infected mice. Chemotherapy treatment started with a single dose of maslinic acid by intraperitoneal injection at 40 mg/kg/day for 4 days. Maslinic acid increased the survival rate of mice from 20% to 80% and led to immune protection after lethal Plasmodium yoelii infection.
Maslinic acid induced the rupture of the plasma and nuclear membranes in Toxoplasma gondii by a mechanism involving inhibition of proteases thought to be involved in protein processing and/or degradation.
The use of maslinic acid as an antiparasitic agent is protected by a patent owned by the University of Granada (patent filed March 29, 2007; Patent Number: WO/2007/034009).
Evidence strength: Animal model data only. No human anti-malarial or antiprotozoal clinical trials for isolated maslinic acid are reported in the reviewed sources.
Research found significant antimicrobial activity of maslinic acid derivatives against Streptococcus pyogenes and a mild effect against Staphylococcus aureus, whereas no activity was observed for E. faecalis, E. coli, and P. aeruginosa.
Evidence strength: Preclinical in vitro data only.
Some of the most rigorously designed dose-response studies of maslinic acid have been conducted in aquaculture contexts. Five groups of 180 trout of a mean body mass of 20 g were fed for 225 days with diets containing 0, 1, 5, 25, and 250 mg of maslinic acid per kg of diet. Maslinic acid, when added to the diet at a concentration of 25 and 250 mg/kg, stimulated hepatic protein-synthesis rates, the hyperplasia level, and the cellular glycogen store in the liver.
Higher body weights and muscle growth rates were found in both groups of fish fed 100 mg maslinic acid per kg of diet. Feed-efficiency rate, protein-efficiency ratio, and protein productive value were higher in the maslinic acid-treated groups than in controls. Fractional and absolute protein-synthesis and degradation rates in white muscle were higher than in the control, resulting in a higher protein-accumulation rate and tissue growth.
These animal studies have informed hypotheses about maslinic acid as a potential growth-promoting or anabolic supplement in humans, but direct extrapolation is not supported by clinical data.
No established human clinical dosage has been determined for maslinic acid as an isolated supplement. The following dosages have been employed in referenced experimental studies:
The amount of maslinic acid in natural edible sources is low, and data about its pharmacokinetics show that the triterpene has a poor oral bioavailability. Researchers have formulated maslinic acid in the form of solid lipid nanoparticles (SLNs) with different shell compositions. These SLNs improved the solubility of maslinic acid up to 7.5 mg/mL, are stable in a wide range of pH, and increase the bioaccessibility of maslinic acid after in vitro gastrointestinal digestion.
Consumption of 33 g of virgin olive oil per day would provide 6 mg maslinic acid. Approximately 70% of this is estimated to be absorbed.
Plasma concentrations versus time were best characterized by a two-open compartment model with first-order absorption and linear elimination. Maslinic acid had a relatively rapid oral absorption with a peak concentration after administration at 0.51 h and a bioavailability of 5.13%. Once in the bloodstream, it distributed extensively into tissues, since the central and peripheral distribution volumes were 8.41 L/70 kg and 63.6 L/70 kg.
Despite its intriguing properties, the bioavailability of maslinic acid is significantly compromised due to its lipophilic core. This low oral bioavailability (5.13% in rats) represents a major limitation for its development as a nutraceutical or pharmaceutical agent, prompting active research into formulation strategies such as nanoparticulate delivery systems.
The available preclinical safety data for maslinic acid is encouraging, though it is limited to animal models. No human safety trials have been identified in the reviewed sources.
The single oral administration of maslinic acid at 1000 mg/kg to mice did not produce any signs of morbidity or mortality. The repeated daily oral administration of 50 mg/kg of maslinic acid for 28 days did not induce any sign of toxicity during the experimental period. Body weight did not differ between mice that received the triterpene and the control group. Hematological and biochemical variables were not affected by the treatment. Histopathologic examination of the organs revealed that there were no differences between the control and the treated mice.
Taken together, the results obtained from the acute and repeated intake of maslinic acid indicate that the compound does not exert any adverse effects on the variables tested in mice, thus suggesting a sufficient margin of safety for its putative use as a nutraceutical.
The absence of adverse effects in hematological, clinical biochemical, and histopathological evaluations implies a high safety margin for orally administered maslinic acid.
Maslinic acid displays low toxicity towards non-tumoral cells and can be regarded as safe in therapeutic applications.
No known drug interactions for isolated maslinic acid in humans have been identified in the reviewed literature. The inhibition of NF-κB signaling—a documented mechanism of maslinic acid—is shared by several pharmaceutical agents, and the potential for pharmacodynamic interactions with immunosuppressants, anti-inflammatory drugs, or anticoagulants has not been assessed in human studies. Researchers have noted that maslinic acid's inhibition of NF-κB and downstream pathways overlaps with the pharmacology of certain chemotherapeutic agents, which may be relevant for combination contexts, but this has not been studied in human clinical settings.
Maslinic acid is a natural pentacyclic triterpene present in a variety of plant species, many of them being common ingredients of plant-based dietary patterns, such as the Mediterranean diet. A number of studies assessing its biological effects have raised interest in this compound. These include not only health-enhancing properties such as cardioprotective or neuroprotective, but also a therapeutic potential that may help in the treatment of several disorders, such as cancer, diabetes, or parasitoses.
However, the amount of maslinic acid in natural edible sources is low, and data about its pharmacokinetics show that the triterpene has a poor oral bioavailability. The biological activities of maslinic acid have been assessed in different experimental models, from tumor cell lines to animal models of several diseases. In summary, maslinic acid is arising as a novel natural and safe molecule with different biological targets, which might lead to considering it as a nutraceutical in the future.
The field faces several significant translational challenges: the compound's low water solubility and poor oral bioavailability limit therapeutic concentrations achievable through dietary or oral supplement routes; the near-complete absence of human clinical trials means that no therapeutic dosage, indication, or efficacy claim can be substantiated for humans; and most mechanistic studies have been conducted in cell lines or rodent models. There are visible knowledge gaps about the ability of maslinic acid to modulate oncogenic and tumor suppressor microRNAs in various cancers. Active research into novel delivery systems, including solid lipid nanoparticles, is ongoing to address bioavailability constraints.
Health conditions that Maslinic acid may help support.
Body systems that Maslinic acid may help support.
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