Maslinic Acid: A Multifunctional Natural Triterpene with Therapeutic Potential

Maslinic acid (MA), a natural triterpene from Olea europaea L., is a well-known inhibitor of glycogen phosphorylase and elicits multiple biological activities. The purpose of this study was to evaluate the effects of MA on focal cerebral ischemia in hyperglycemic rats. Adult rats were made hyperglycemic by intraperitoneal injection of streptozotocin and were given MA (50 mg/kg or 5 mg/kg) intragastrically for 14 consecutive days.

Maslinic Acid Inhibits the Growth of Malignant Gliomas

Maslinic acid is a triterpenoid which was the natural compound widely distributed in medicinal plants. Recent studies have shown that maslinic acid has strong anticancer activity. It has been identified that it can play anticolon cancer, lung cancer, breast cancer, pancreatic cancer, kidney cancer, and prostate cancer effects by inhibiting cell proliferation and promoting cell apoptosis. Research by Martin et al. showed that maslinic acid can affect the growth and survival of glioma cell lines by regulating the accumulation of reactive oxygen species, but the specific mechanism has not been elucidated. This study found that maslinic acid inhibited the proliferation, migration, and invasion of malignant glioma cells and induced their apoptosis. In vivo, maslinic acid can inhibit the growth of transplanted tumors in nude mice. In order to study the mechanism of action, we first used a high-throughput sequencing method to comprehensively analyze the mechanism of action of maslinic acid. Our research indicates that maslinic acid may be a potential therapeutic drug for malignant glioma.[1]

Following the addition of the maslinic acid, the different performances of U87 and U251 cells were shown by CCK-8, colony formation assay, and Ki67 immunofluorescence and analysis. It was shown that the activity of U87 and U251 cells did decrease with the increase of drug concentration. Meanwhile, the number of U87 and U251 cells with 30 μM and 60 μM maslinic acid was considerably lower than the control group. Therefore, the colony formation experiments also proved that U87 and U251 cells proliferation was significantly inhibited at the concentrations of 30 μM and 60 μM of maslinic acid. At last, it was as expected that the result of the decreased cell proliferation with maslinic acid at 30 μM and 60 μM was captured by Ki67 immunofluorescence and analyses compared with the untreated group. However, maslinic acid of 30 μm did not affect the proliferation of Human Kidney-2 (HK-2) cells, Normal Human Pancreatic Duct Epithelial (HPDE) cells, and Human Umbilical Vein Endothelial Cells (HUVEC). All of the above experiments proved that the growth of these cells could be inhibited with the maslinic acid at the appropriate concentration.

In the past few decades, plant-derived drugs have received more and more attention because they are relatively nontoxic and cheap compared to modern drugs. Medicinal plants and their extracts are widely used because of their antiinflammatory, antioxidant, antidiabetic, anticancer, and other biological properties. A large number of studies have shown that the extracts of many medicinal plants are good for anticancer, such as paclitaxel, camptothecin, and vincristine, and their analogs have been widely used clinically. Maslinic acid is an effective ingredient extracted from olives and belongs to a kind of triterpenoids. Many studies have shown that maslinic acid has anti-inflammatory, antitumor, antidiabetic, antioxidant, and other biological activities. The anticancer activity of maslinic acid has been reported in a variety of cancers, but few studies have explored its efficacy in gliomas. Despite recent advances in imaging diagnosis, surgical treatment, and radiotherapy, the prognosis of malignant glioma is still very poor. It is urgent to find new chemotherapy drugs to improve the quality of life and prognosis of patients. The study of Teng Guan used maslinic acid for the treatment of cerebral ischemic injury in hyperglycemic rats, given intragastrically, and found that maslinic acid had the effect of reducing cerebral ischemic damage in hyperglycemic rats, suggesting that maslinic acid may play a key role through the blood-brain barrier. In recent years, the cross-development of the blood delivery system-brain barrier (BBB) and blood-brain tumor barrier (BBTB) provide a new treatment scheme for glioma and malignant brain metastasis. Peptide carrier drug conjugate (PDC), which recognizes the penetration of BBB/BBTB, has been derived and applied to the treatment of glioma metastasis.

Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy

Maslinic acid (MA) is a pentacyclic triterpene acid and the primary bioactive component extracted from Chinese medicinal herbs (such as hawthorn, olive, and jujube) [5,6]. MA possesses antibacterial, antiviral, antioxidant, and anticancer activities and has attracted significant attention from the medical community. For instance, MA can inhibit cell apoptosis and necrosis, preserve the glomerulus, and thus exhibit a therapeutic effect on cisplatin-triggered nephrotoxicity in rats. Additionally, maslinic acid attenuates inflammatory response, maintains the blood–milk barrier, and modulates intestinal flora, thereby relieving LPS-stimulated mastitis. Furthermore, maslinic acid accelerates mitochondrial apoptosis and reduces HIF-1α expression in lung cancer. Importantly, MA demonstrates gastroprotective activity through various mechanisms, which is beneficial for the mucus barrier. Besides, an MA-enriched diet can affect transcriptomic and metabolomic reprogramming in Apc (Min/+) mice to alleviate intestinal tumorigenesis. However, the detailed functions and associated pathways of MA in FD progression remain unclear.[2]

Mitochondria are organelles that are highly dynamic, and they can produce ATP and participate in the modulation of oxidative stress and cell apoptosis. Moreover, autophagy plays a pivotal role in maintaining mitochondrial homeostasis. Therefore, maintenance of normal autophagy-mediated mitochondrial functions and oxidative stress is vital for cellular functions. Many researchers have investigated autophagy, mitochondrial functions and oxidative stress in FD progression. For instance, quercetin modulates the PI3K/AKT pathway in FD to improve mitochondrial function and reduce inflammation, thereby relieving H2O2-triggered oxidative stress damage. Moreover, Chaihu Shugan San affects mitophagy to enhance gastric motility in FD rats. ZhiShiXiaoPi tang retards the mTOR pathway to restrain autophagy-evoked corticosterone to improve FD. In addition, Shen-Ling-Bai-Zhu-San can stimulate the energy metabolism pathways and weaken oxidative stress in FD. Similar to these previous studies, in this project, it was discovered that the strengthened mitochondrial functions stimulated by CCCP induction were restored after maslinic acid treatment. Furthermore, autophagy was exacerbated after CCCP addition, but this phenomenon was reversed after maslinic acid treatment. The oxidative stress was increased after CCCP treatment, but this effect was alleviated after MA addition.

Maslinic Acid Ameliorates Inflammation via the Downregulation of NF-κB and STAT-1

Maslinic acid (MA), a natural compound of the triterpenoid group derived from olive, prevents the generation of pro-inflammatory cytokines and oxidative stress. In human umbilical vein endothelial cells (HUVECs) treated with lipopolysaccharide (LPS), we characterized the effects of maslinic acid on the regulation of heme oxygenase (HO)-1, cyclooxygenase (COX-)2, and inducible nitric oxide synthase (iNOS). MA was tested in the lung tissues of LPS-treated mice, to determine its effect on levels of iNOS expression and representative inflammatory mediators such as interleukin (IL)-1α and tumor necrosis factor (TNF)-α. We show that MA induced the expression of HO-1, reduced LPS-induced NF-κB-luciferase activity, and inhibited iNOS/NO and COX-2/PGE2, resulting in the downregulation of STAT-1 phosphorylation. Furthermore, our data show that maslinic acid induced the nuclear translocation of Nrf2, increased the binding of Nrf2 to ARE, and decreased IL-1α production in LPS-treated HUVECs. The MA-induced reduction in iNOS/NO expression was reversed by RNAi suppression of HO-1. In mice treated with LPS, MA significantly downregulated levels of iNOS in lung tissue and TNF-α in the bronchoalveolar lavage fluid. Taken together, our findings indicate that maslinic acid exerts a critical anti-inflammatory effect by modulating iNOS via the downregulation of NF-κB and p-STAT-1. Thus, we propose that MA may be an ideal substance to treat inflammatory diseases.[3]

References

[1]Wang Y, Zhang H, Ye Z, Ye Q, Yang X, Mao W, Xu R, Zhang Y. Maslinic Acid Inhibits the Growth of Malignant Gliomas by Inducing Apoptosis via MAPK Signaling. J Oncol. 2022 Jun 28;2022:3347235.

[2]Zheng X, Zhang S, Chen Q. Maslinic acid improves mitochondrial function and inhibits oxidative stress and autophagy in human gastric smooth muscle cells. Open Life Sci. 2025 Jan 27;20(1):20221036.

[3]Lee W, Kim J, Park EK, Bae JS. Maslinic Acid Ameliorates Inflammation via the Downregulation of NF-κB and STAT-1. Antioxidants (Basel). 2020 Jan 25;9(2):106.

You may like