Effects Of Maslinic Acid Research Articles

Maslinic Acid Inhibits the Growth of Malignant Gliomas by Inducing Apoptosis via MAPK Signaling.

Background Gliomas are primary malignant brain tumors. Despite recent advances in surgery and clinical neuro-oncology, the prognosis of patients with glioma is still poor. Therefore, there is an urgent need to find new therapeutic drugs. Methods Here, we have studied the anticancer effect of maslinic acid in glioma and explored its potential molecular mechanism. CCK-8, Ki67 immunofluorescence, and colony formation tests are used to detect the proliferation of glioma cells. Transwell and migration experiments are used to detect the function of cell invasion and migration, and RNA-seq was performed to identify differentially expressed genes. Western blot analysis helps us identify important signaling pathways. Finally, the anticancer effect of maslinic acid was confirmed in vivo through tumor xenografting experiments. Results Our experiments obtained high-throughput data on the treatment of maslinic acid in glioma. We found that maslinic acid significantly inhibits the proliferation, invasion, and migration of glioma cells and promotes the apoptosis of glioma cells via suppressing MAPK signaling. Conclusions This is the first time to analyze the mechanism of maslinic acid against glioma based on transcription. Our experiments show that maslinic acid may be a useful natural product for the treatment of glioma.

Biological Effects of Maslinic Acid on Human Epithelial Cells Used in Tissue Engineering.

In the present work, we evaluated the potential of maslinic acid (MA) to improve currently available keratinocyte culture methods for use in skin tissue engineering. Results showed that MA can increase cell proliferation and WST-1 activity of human keratinocytes after 24, 48, and 72 h, especially at the concentration of 5 μg/ml, without affecting cell viability. This effect was associated to a significant increase of KI-67 protein expression and upregulation of several genes associated to cell proliferation (PCNA) and differentiation (cytokeratins, intercellular junctions and basement membrane related genes). When human keratinocytes were isolated from skin biopsies, we found that MA at the concentration of 5 μg/ml significantly increased the efficiency of the explant and the cell dissociation methods. These results revealed the positive effects of MA to optimize human keratinocyte culture protocols for use in skin tissue engineering.

Maslinic Acid Inhibits Cervical Intraepithelial Neoplasia by Suppressing Interleukin- 6 and Enhancing Apoptosis in a Mouse Model.

Cervical Intraepithelial Neoplasia (CIN) directly precedes cervical cancer, and elevated proinflammatory cytokine Interleukins (IL)-6 is implicated in CIN. As maslinic acid exhibits anti-IL-6 property, the present study sought to determine the effect of maslinic acid on CIN in vitro and in vivo using cell cultures and mouse CIN models, respectively. The dose-effect of maslinic acid on HeLa cells, a human cervical cancer cell line, was first evaluated, including cytotoxicity, IL-6 secretion, IL-6 receptor (IL-6R) expression, proliferation potential and apoptosis status. A mouse model of CIN was also established, which was then subjected to increasing doses of maslinic acid treatment, followed by assessment of serum IL-6 level, cervical expression of IL-6R, and the proliferation potential and apoptosis of cervical tissues. Maslinic acid dose-dependently inhibited cell growth and proliferation potential, reduced IL-6 secretion, cervical expression of IL-6R and induced apoptosis of HeLa cells in vitro. In the CIN mouse model, serum IL-6 level and cervical expression of IL-6R were elevated, which could be repressed by maslinic acid administration dosedependently. Additionally, maslinic acid treatment in the CIN mice could also restore the otherwise increased proliferation potential and reduced apoptosis in the cervical tissues. Maslinic acid exhibits potent anti-IL-6 property in the CIN mouse model, and alleviates the diseaserelated abnormality in proliferation potential and apoptosis state of the cervical tissue cells, demonstrating its usefulness as a promising agent in treating CIN.

Effects of maslinic acid on cardiac function in ischemia–reperfusion injury rats

Maslinic acid (MA), a pentacyclic triterpenoid, has been reported to exert broad pharmacological properties. However, it is still unclear whether MA exhibits protective effects against ischemia/reperfusion (I/R) injury. Herein, we...

The effect of maslinic acid on cognitive dysfunction induced by cholinergic blockade in mice.

Alzheimer's disease (AD) is the most prevalent disease associated with cognitive dysfunction. Current AD therapeutic agents have several gastrointestinal or psychological adverse effects and therefore, novel therapeutic agents with fewer adverse effects must be developed. Previously, we demonstrated that oleanolic acid, which is similar in chemical structure to maslinic acid, ameliorates cognitive impairment through the activation of tropomyosin receptor kinase (TrkB)-ERK-cAMP response element-binding protein (CREB) phosphorylation and increased levels of brain-derived neurotrophic factor (BDNF). In the present study, we investigate the effect of maslinic acid on cholinergic blockade-induced memory impairment in mice. Maslinic acid reversed scopolamine-induced memory impairment, as determined by the Y-maze, passive avoidance and Morris water maze tests. In addition, we also observed that ERK-CREB, PI3K and PKB (Akt) phosphorylation levels were increased by maslinic acid administration in the mouse hippocampus. Moreover, we determined that the effects of maslinic acid on scopolamine-induced memory impairment in the passive avoidance test were abolished by a specific TrkB receptor antagonist (ANA-12). Additionally, we observed similar temporal changes in the expression levels between BDNF and tissue plasminogen activator in the hippocampus. These findings suggest that maslinic acid enhances cognitive function through the activation of BDNF and its downstream pathway signalling in the hippocampus and that it might be a potential therapeutic agent for cognitive decline, such as that observed in AD.

Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice

Schizophrenia is a chronic psychotic disorder characterized by positive, negative, and cognitive symptoms. Primary treatments for schizophrenia relieve the positive symptoms but are less effective against the negative and cognitive symptoms. In the present study, we investigated whether maslinic acid, isolated from Syzygium aromaticum (clove), can ameliorate schizophrenia-like behaviors in mice induced by MK-801, an N-methyl-d-aspartate (NMDA) receptor antagonist. After maslinic acid treatment in the MK-801 model, we examined the behavioral alteration and signaling pathways in the prefrontal cortex. Mice were treated with maslinic acid (30 mg/kg), and their behaviors were evaluated through an array of behavioral tests. The effects of maslinic acid were also examined in the signaling pathways in the prefrontal cortex. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion and reversed the MK-801-induced sensorimotor gating deficit in the acoustic startle response test. In the social novelty preference test, maslinic acid ameliorated the social behavior deficits induced by MK-801. The MK-801-induced attention and recognition memory impairments were also alleviated by a single administration of maslinic acid. Furthermore, maslinic acid normalized the phosphorylation levels of Akt-GSK-3β and ERK-CREB in the prefrontal cortex. Overall, maslinic acid ameliorated the schizophrenia-like symptoms induced by MK-801, and these effects may be partly mediated through Akt-GSK-3β and ERK-CREB activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficits, and cognitive impairments.

Anti-inflammatory and anti-arthritic effects of pentacyclic triterpenoids maslinic acid through NF-κB inactivation.

Consumption of olives (Olea europaea L.), including table olives and oil, is associated with low incidence of inflammation-related diseases. In this study, the effects of maslinic acid (MA), the main constituent of olive pomace, on the expression of genes and proteins involved in inflammatory activity in RAW 264.7 cells were investigated. Furthermore, the effect of MA on carrageenan-induced paw edema and collagen antibody induced arthritis in mice was determined. We confirmed the suppressive effects of MA on LPS-induced tumor necrosis factor α production and on the expression of inflammatory response associated genes in RAW 264.7 cells. We also clarified the suppressive effect of MA on LPS-induced nuclear factor-kappa B activation as well as the phosphorylation of IκB-α. Furthermore, MA (200 mg/kg in the edema model or 100 mg/kg in the arthritis model) exerted anti-inflammatory and antiarthritis effects as shown by the suppression of paw edema, arthritis score, inflammatory cells, and destruction of synovium in knee joints. Olive products containing MA are useful as a new preventive and therapeutic food ingredient for inflammatory and arthritic diseases.

Effects of maslinic acid on the proliferation and apoptosis of A549 lung cancer cells.

Maslinic acid (MA) is a pentacyclic triterpene acid that is present in numerous dietary plants. Although certain studies have demonstrated that MA has anti-cancer properties in different cell types, the effect of MA on lung cancer cell proliferation and apoptosis and the potential underlying mechanisms remain to be elucidated. In the present study, A549 lung cancer cells were treated with different doses of MA and it was found that MA significantly inhibited A549 cell growth in a dose-dependent manner. In addition, Annexin V/propidium iodide flow cytometric analysis demonstrated that MA induced apoptosis of A549 cells. The present study also confirmed that MA induced apoptosis by observing morphological alterations. In addition, the effect of MA treatment on the levels of apoptosis-associated proteins was examined. The results demonstrated that MA treatment suppressed the expression of caspase-3, -8 and -9, and increased the expression of cleaved caspase-3, -8 and -9 in a dose-dependent manner. The level of inhibitors of apoptosis (IAPs) and Smac, which are possible upstream factors of caspase proteins, were also examined. It was found that MA treatment increased the protein expression of Smac and decreased the protein levels of c-IAP1, c-IAP2, X-linked inhibitor of apoptosis protein (XIAP) and Survivin in a dose-dependent manner. These results suggested that MA inhibited proliferation and induced apoptosis of A549 cells through regulation of caspase cleavage as well as Smac, c-IAP1, c-IAP2, XIAP and Survivin.

Antiallodynic and Analgesic Effects of Maslinic Acid, a Pentacyclic Triterpenoid from Olea europaea

The effects of maslinic acid (1), a pentacyclic triterpenoid obtained from Olea europaea, were studied in several tests for nociception in mice. Systemic administration of 1 reduced acetic acid-induced writhing, the inflammatory phase of formalin-induced pain, and capsaicin-induced mechanical allodynia. However, it did not induce motor incoordination in the rotarod test. The topical administration of 1 also reduced the inflammatory phase of the formalin test, indicating that at least some of its effects are mediated peripherally. The present results demonstrate for the first time that maslinic acid induces antinociceptive and antiallodynic effects.

The role of maslinic acid in the pentose phosphate pathway during growth of gilthead sea bream(Sparus Aurata)

NADPH produced in the pentose phosphate pathway (PPP) plays a central role in the reductive biosynthesis of membrane lipids, as well as in the maintenance of cell integrity; also, it has a key part in the synthesis of protein, the other member element. For that NADPH is involved in the growth processes. Our main objective is to study the effects of maslinic acid (MA) on kinetics and its molecular nature of NADPH-generating systems in the gilthead sea bream (S. aurata) as well as the possible changes of these enzymes related with several feeding conditions; for this, we have studied the kinetic and expression levels of glucose 6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), both PPP enzymes, in liver and white muscle. MA, a triterpene, stimulates growth, protein turnover rates and hyperplasia in fish. G6PDH and 6PGDH showed hyperbolic kinetics under all experimental conditions. With MA feeding, the specific activity, maximum velocity and catalytic efficiency of both enzymes increased in both tissue. The Michaelis constant changed with MA and fixed diet, and these changes being in relation to the substrate affinity. Moreover, we found that MA increased the protein levels studied, and this behaviour being consistent with the regulation of the number of enzyme molecules. These results show that G6PDH and 6PGDH are two inducible enzymes regulated by MA. Our findings corroborate that MA affect to the activity and expression of G6PDH and 6PGDH, confirming its role as markers of growth.

Maslinic acid induces HO-1 and NOQ1 expression via activation of Nrf2 transcription factor

Maslinic acid, a naturally-occurring pentacyclic triterpene, has been shown to suppress pro-inflammatory enzyme COX-2 expression and inhibit redox sensitive transcription factors NF-κB and AP-1 binding activities. In this study, the effects of maslinic acid at inducing cytoprotective enzymes via the Nrf2-ARE pathway in HepG2 cells were investigated. Results showed that maslinic acid significantly induced HO-1 and NQO1 expression in a concentration-dependent manner and achieves maximal expression at 100μM after six hours of treatment. The up-regulation of HO-1 and NQO1 expression might be resulted from maslinic acid-induced ARE binding activity observed from three to 12h. Maslinic acid also enhanced nuclear Nrf2 protein accumulation up to 172% after three hours of treatment. These results suggest that maslinic acid may induce nuclear Nrf2 accumulation, binding to the ARE and transcriptionally activate HO-1 and NQO1 expression. In addition, maslinic acid significantly induced HO-1 and NQO1 expression in Con-siRNA-transfected cells but this effect was abrogated in cells transfected with Nrf2-siRNA. In conclusion, maslinic acid induces HO-1 and NQO1 enzyme expressions and the transcription factor Nrf2 is essential for the induction of these enzymes.

Effects of Maslinic Acid as a Novel Glycogen Phosphorylase Inhibitor on Blood Glucose and Hepatic Glycogen in Mice

Effects of Maslinic Acid as a Novel Glycogen Phosphorylase Inhibitor on Blood Glucose and Hepatic Glycogen in Mice

Supressive effect of maslinic acid from pomace olive oil on oxidative stress and cytokine production in stimulated murine macrophages

The pentacyclic triterpene maslinic acid (MA) is a natural compound present in the non glyceride fraction of pomace olive oil, also called orujo olive oil. This compound has previously demonstrated antioxidant properties against lipid peroxidation in vitro, but its effects on reactive oxygen and nitrogen-derived species and pro-inflammatory cytokines generated by a cell system have not yet been investigated. In this study, we have tested the effect of MA upon oxidative stress and cytokine production using peritoneal murine macrophages. MA significantly inhibited the enhanced production of nitric oxide (NO) induced by lypopolysaccharide (LPS) when it was measured by the nitrite production with an inhibitory concentration 50% value (IC50) of 25.4 μM. This inhibiting effect seems to be consequence of an action at the level of the LPS-induction of the inducible nitric oxide synthethase (iNOS) gene enzyme expression rather than to a direct inhibitory action on enzyme activity. The secretion of the inflammatory cytokines interleukine-6 and TNF-α from LPS-stimulated murine macrophages was also significantly reduced (p < 0.05 and 0.01) by 50 and 100 μM of MA. In addition, reactive oxygen species were measured after stimulation with phorbol-12-myristate-13-acetate (PMA). Thus, pre-treatment with MA reduced the generation of hydrogen peroxide from stimulated macrophages in a dose-dependent manner (IC50: 43.6 μM) as assayed by the oxidation of the peroxidase enzyme. However, no inhibitory effect on superoxide release, measured by the reduction of ferricytochrome c, was observed after the pretreatment with MA in the culture medium.These results suggest a potential biopharmaceutical use of this hydroxy-pentacyclic triterpene derivative, present in orujo olive oil, on preventing oxidative stress and pro-inflammatory cytokine generation.