Pentacyclic Triterpene Acid Research Articles

Advances in Research on Semi-Synthesis, Biotransformation and Biological Activities of Novel Derivatives from Maslinic Acid

Since ancient times, humans have turned to medicinal plants for treating various ailments and curing specific diseases, as these natural plants serve as the primary source of a range of phytochemicals, including triterpenes. Maslinic acid (MA), also known as (2α,3β)-2,3-dihydroxyolean-12-en-28-oic acid, is a pentacyclic triterpene acid present in numerous plants including olive, known for its high safety profile in humans. Recent experimental data increasingly suggests that MA exhibits diverse biological properties and therapeutic effects on various organ diseases, highlighting its significant potential for clinical applications due to its diverse potential pharmacological activities that promote health and resist various diseases, such as hypoglycemic, neuroprotective, anti-tumor, anti-inflammatory, antioxidant and multiple other biological activities. However, the undesirable pharmacokinetic properties of MA, such as high lipophilicity, pose a limitation to its application and development, impacting its bioavailability. Consequently, extensive research spanning decades has focused on structurally modifying MA to overcome these limitations and enhance its pharmacokinetic and therapeutic characteristics, leading to the identification of several potential lead compounds. In this review, we focus on the progress of research in recent years on MA with interest to its chemical and enzymatic modifications as well as the relationships between the modified structures or derivatives and their biological activities.

Neuroprotective Effect of Boswellia serrata against 3-NP Induced Experimental Huntington’s Disease

Objectives:: The study aimed to assess the neuroprotective effect of Boswellia serrata against 3-NP-induced experimental Huntington’s disease. Background:: Previous studies have shown Boswellia to have sedative, analgesic, and anti-tumour effects. Boswellia serrata yields four pentacyclic triterpene acids and boswellic acid, a bioactive substance that prevents leukotriene biogenesis. Methods:: The potential neuroprotective effect of Boswellia serrata against 3-nitro propionic acid (3-NP)-induced Huntington's disease (HD) was examined at oral doses of 45 mg/kg, 90 mg/kg, and 180 mg/kg. In this study, HD was induced by 3-NP at a dose of 10 mg/kg in Wistar rats. The study used 56 Wistar rats (8 per group) for biochemical (inflammatory markers, acetylcholinesterase activity) and behavioural (elevated plus maze, Y-maze, open-field, tail suspension tests, etc.) assessments. Additionally, a histological examination of the brain was carried out. In addition, the analysis of Boswellia serrata extract was performed by different analytical techniques, like UV spectrophotometer, FTIR, and HPLC methods. Results:: In the brain, succinate dehydrogenase is a mitochondrial enzyme irreversibly inhibited by 3-NP. Administration of 3-NP resulted in HD with altered behavioural and motor changes in rats. Treatment with Boswellia serrata resulted in remarkable protection of rats against 3-NP-induced behaviour and motor deficits in a dose-dependent manner. Moreover, in rats administered with 3-NP, Boswellia serrata improved memory performance and lowered levels of inflammatory biomarkers. These results have also been supported by histopathological analysis. Acetyl-11-keto-p-boswellic acid was found to be the main active component of Boswellia serrata extract. Conclusion:: Boswellia serrata at a dose of 180 mg/kg exhibited better protection compared to the other doses against HD induced by 3-NP. More detailed studies based on molecular targets are needed for the Boswellia serrata to transition from the bench to the bedside for use as an adjuvant in HD patients.

Maslinic acid alleviates alcoholic liver injury in mice and regulates intestinal microbiota via the gut-liver axis.

Maslinic acid (MA), a pentacyclic triterpene acid, is widely distributed in natural plants and mainly found in the fruit and leaves of olives and hawthorn. MA has been reported as having many health-promoting functions, such as anticancer, anti-inflammation and neuroprotective activities. According to previous study, hawthorn extract has certain hepatoprotective effects. However, the detailed mechanism is still unclear, especially the effect of MA on gut microbiota. Our study reveals that MA effectively counteracts alcohol-induced liver injury and oxidative stress. It mitigates alcohol-induced intestinal barrier damage, reverses increased permeability and reduces translocation of lipopolysaccharide (LPS). This prevents LPS/Toll-like receptor 4 activation, leading to decreased TNF-α and IL-1β production. Furthermore, MA rebalances gut microbiota by reversing harmful bacterial abundance and enhancing beneficial bacteria post-alcohol consumption. MA, through modulation of gut microbiota, alleviates alcohol-induced liver injury via the gut-liver axis. These findings support the potential use of MA as a functional food ingredient for preventing or treating alcoholic liver disease. © 2024 Society of Chemical Industry.

Triterpene acids from Rosa roxburghii Tratt fruits exert anti-hepatocellular carcinoma activity via ROS/JNK signaling pathway-mediated cell cycle arrest and mitochondrial apoptosis

BackgroundRosa roxburghii Tratt (RRT) is a famous healthy and medicinal edible fruit in southwest China and has been shown to have some hepatoprotective properties. However, whether the active components, such as the triterpene acids from Rosa roxburghii Tratt fruits (TAR), have anti-hepatocellular carcinoma (HCC) effects and the potential molecular mechanisms are still unclear. PurposeThis study aimed to investigate the anti-HCC effects and potential action mechanisms of triterpene components in RRT fruits. MethodsThe triterpene acids in TAR were analyzed by using UPLC-Q-Exactive Orbitrap/MS, and the main components were virtual screening for targets based on pharmacophore and then performed enrichment analysis. HepG2 cells were used for in vitro experiments, including MTT assay, wound healing assay, and flow cytometry to detect cell cycle, reactive oxygen species (ROS) level, caspase-3 activity, and mitochondrial membrane potential (MMP) changes. Moreover, the western blot was used to detect mitochondrial apoptosis and ROS/ c-Jun N-terminal kinase (JNK) signaling pathway-related proteins. ResultsThe main components in TAR are pentacyclic triterpene acids (mainly euscaphic acid and roxburic acid). TAR could inhibit cell viability, cell migration ability and suppress the proliferation of HepG2 cells through G2/M cell cycle arrest. On the other hand, TAR could induce HepG2 cells apoptosis, which was achieved by causing the accumulation of ROS and activation of the JNK signaling pathway, and our research showed that this apoptosis was mediated through the mitochondrial pathway. In addition, the free radical scavenger N-acetyl cysteine (NAC) could attenuate TAR-induced ROS accumulation and JNK signaling pathway activation, which ultimately reversed mitochondrial apoptosis. ConclusionTAR could activate the ROS/JNK signaling pathway, which could inhibit the proliferation through G2/M cell cycle arrest and promote apoptosis through the mitochondrial pathway in HCC cells. This supports the anti-tumor potential in RRT fruits.

Low and high doses of oral maslinic acid protect against Parkinson’s disease via distinct gut microbiota-related mechanisms

The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson’s disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum. However, the effects of MA in PD mice were not dose-responsive, since similar beneficial effects for low and high doses of MA were observed. Further mechanism studies indicated that low dose MA administration favored probiotic bacterial growth in PD mice, which helped to increase striatal serotonin, 5-hydroxyindole acetic acid, and γ-aminobutyric acid levels. High dose MA treatment did not influence GM composition in PD mice but significantly inhibited neuroinflammation as indicated by reduced levels of tumor necrosis factor alpha and interleukin 1β in the SNpc; moreover, these effects were mainly mediated by microbially-derived acetic acid in the colon. In conclusion, oral MA at different doses protected against PD via distinct mechanisms related to GM. Nevertheless, our study lacked in-depth investigations of the underlying mechanisms involved; future studies will be designed to further delineate the signaling pathways involved in the interactive actions between different doses of MA and GM.

Discovery of Novel Pentacyclic Triterpene Acid Amide Derivatives as Excellent Antimicrobial Agents Dependent on Generation of Reactive Oxygen Species.

Developing new agricultural bactericides is a feasible strategy for stopping the increase in the resistance of plant pathogenic bacteria. Some pentacyclic triterpene acid derivatives were elaborately designed and synthesized. In particular, compound A22 exhibited the best antimicrobial activity against Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac) with EC50 values of 3.34 and 3.30 mg L-1, respectively. The antimicrobial mechanism showed that the compound A22 induced excessive production and accumulation of reactive oxygen species (ROS) in Xoo cells, leading to a decrease in superoxide dismutase and catalase enzyme activities and an increase in malondialdehyde content. A22 also produced increases in Xoo cell membrane permeability and eventual cell death. In addition, in vivo experiments showed that A22 at 200 mg L-1 exhibited protective activity against rice bacterial blight (50.44%) and citrus canker disease (84.37%). Therefore, this study provides a paradigm for the agricultural application of pentacyclic triterpene acid.

Identification, quantitative determination and isolation of pomolic acid from lavender (Lavandula angustifolia Mill.) wastes

Lavender essential oil production wastes have been investigated as a highly available source of pentacyclic triterpenic acids. Ultrasound assisted extraction was addressed as a simple and scalable procedure for efficient production of enriched extracts from dry plant material with good yields. Flowers and stalks have been processed separately. Analytical studies have been performed basing on both HPLC and qNMR methods. The qNMR analysis proved to be a much more convenient alternative to HPLC and its application resulted in identification, isolation and quantitative determination of substantial amounts of pomolic acid in the obtained extracts, along with widely explored ursolic and oleanolic acids. The ultrasound assisted extraction of lavender flowers with 96% ethanol resulted in a 3.3% yield of triterpenic acids, with a substantial share of pomolic acid that constitutes 1% of the plant material dry weight. Selective extraction of flowers with ethylacetate resulted in an enriched product containing 67.8% of triterpenic acids, including 16.2% of pomolic acid. Quantification of pomolic acid is reported for the first time in this vegetal source. These results demonstrate the relevant potential of lavender wastes as a sustainable raw material for the production of pomolic acid - a highly valued compound of increased nutraceutical and pharmaceutical interest.

Network pharmacological analysis of corosolic acid reveals P4HA2 inhibits hepatocellular carcinoma progression

BackgroundCorosolic acid is a pentacyclic triterpene acid with hypoglycemic, anti-inflammatory, and anti-cancer effects. However, its potential targets in hepatocellular carcinoma (HCC) are unknown, hindering clinical utilization.MethodsDifferentially expressed proteins of the Bel-7404 cell line were identified with tandem mass tag analysis and differentially expressed genes (DEGs) of an HCC TCGA dataset using bioinformatics. Gene functions and pathways were inferred using the DAVID database. Online databases were used to establish P4HA2 expression in HCC (GEPIA2) and its relationship with patient survival (UALCAN and The Human Protein Atlas), the association between P4HA2 expression and immune cell infiltration (TIMER2), and DNA methylation of the P4HA2 gene (MethSurv). Cell proliferation, cell cycle, and cell death were assessed with PI and SYTOX-Green staining, CCK-8, and colony formation assays. Protein expression levels were detected by Western blotting.ResultsA total of 44 differentially expressed proteins and 4498 DEGs were identified. Four genes whose proteins were also found in the differential protein profile but with opposing expressions were selected as candidate targets. The candidate gene prolyl 4-hydroxylase subunit alpha 2 (P4HA2) was recognized as the only potential target due to its high expression in public datasets, association with poor patient survival, and relation to immune cell infiltration in HCC tissues. Moreover, the DNA methylation status in 4 CpG islands of the P4HA2 gene correlated with a poor prognosis. Furthermore, corosolic acid treatment inhibited the proliferation of HCC cell lines Bel-7404 and HepG2 in a dose-dependent manner, caused G2/M phase cell cycle arrest, and promoted cell death. In addition, the treatment reduced P4HA2 protein levels.ConclusionOur results indicate that P4HA2 is a potential target of corosolic acid. Thus, they contribute to understanding molecular changes in HCC after corosolic acid treatment and facilitate finding new treatment regimens.

Comprehensive Characterization of Secondary Metabolites in Fruits and Leaves of Cloudberry (Rubus chamaemorus L.)

Cloudberry (Rubus chamaemorus L.) is a circumpolar boreal plant rich in bioactive compounds and is widely used in food and in folk medicine. In this study, a combination of two-dimensional NMR spectroscopy and liquid chromatography–high-resolution mass spectrometry was used for the comprehensive characterization of secondary metabolites in cloudberry lipophilic and hydrophilic extracts. Special attention was paid to the leaf extractives, which are highly enriched in polyphenolic compounds, the content of which reaches 19% in the extract (in gallic acid equivalent). The chemical composition of the polyphenolic fraction is represented mainly by the glycosylated derivatives of flavonoids, hydroxycinnamic (primarily caffeic), gallic (including the structure of galloyl ascorbate) and ellagic acids, catechin, and procyanidins. The contents of aglycones in the polyphenolic fraction were 64 and 100 mg g−1 for flavonoids and hydroxycinnamic acids, respectively, while the content of free caffeic acid was 1.2 mg g−1. This determines the exceptionally high antioxidant activity of this fraction (750 mg g−1 in gallic acid equivalent) and the ability to scavenge superoxide anion radicals, which is 60% higher than that of Trolox. The lower polar fractions consist mainly of glycolipids, which include polyunsaturated linolenic acid (18:3), pentacyclic triterpenic acids, carotenoid lutein, and chlorophyll derivatives, among which pheophytin a dominates. Along with the availability, the high antioxidant and biological activities of cloudberry leaf extracts make them a promising source of food additives, cosmetics, and pharmaceuticals.

Maslinic acid attenuates UVB-induced oxidative damage in HFF-1 cells.

Oxidative damage is one of the major mechanisms of ultraviolet B (UVB)-induced damage to the skin. Maslinic acid (MA) is a natural compound of pentacyclic triterpene acids. It has been proved to have anti-inflammatory and antioxidant properties. This study aimed to explore the effects of MA on oxidative damage in human foreskin fibroblast cells (HFF-1) and the potential molecular mechanisms. A specific dose of UVB radiation was used to induce oxidative damage in HFF-1. Based on this, we performed measurements of cell proliferation, reactive oxygen species (ROS) levels, antioxidant enzyme activity, inflammation-related mediators, and NF-κB nuclear localization with or without the addition of MA. MA significantly promoted cell proliferation viability at 10 and 20 μM. The addition of MA 24 h before UVB irradiation was more effective at enhancing cell proliferation and also produced lower ROS levels compared to co-cultured fibroblasts and MA for 24 h after irradiation. However, there was no statistically significant difference between groups at concentrations of 10 and 20 μM. The pretreatment group with MA had elevated superoxide dismutase and catalase activities, decreased IL-6 generation, and lowered mRNA levels of IL-6, TNF-α and MMP3 in comparison with the UVB-irradiated group without additional MA. Meanwhile, the nuclear translocation of NF-κB and the degradation of IκB were inhibited by MA pretreatment. Taken together, these findings suggest that MA may alleviate UVB-induced oxidative damage in HFF-1 by inhibiting the nuclear translocation of NF-κB.

Asiatic acid as a leading structure for derivatives combining sub-nanomolar cytotoxicity, high selectivity, and the ability to overcome drug resistance in human preclinical tumor models

Amides and rhodamine B conjugates of different pentacyclic triterpene acids have been shown outstanding cytotoxicity for human tumor cells. Starting from asiatic acid, a new rhodamine B hybrid has been synthesized, and its cytotoxic activity was investigated employing several human tumor cell lines (A375 (melanoma), HT29 (colorectal carcinoma), MCF7 (breast adenocarcinoma), A2780 (ovarian carcinoma), HeLa (cervical carcinoma), (NIH 3T3 (non-malignant murine fibroblasts). For these conjugates of this kind it has been established that the spacer attached to the carboxyl group at ring E governs the magnitude of the cytotoxicity. These asiatic acid - rhodamine B conjugates were highly cytotoxic for human tumor cell lines but also selective. For example, 7, an acetylated homopiperazinyl spacered rhodamine B conjugate, held an EC50 = 0.8 nM for A2780 ovarian carcinoma cells. Additional staining experiments showed the rhodamine B conjugates to act as mitocans and to effect apoptosis. In further tests using 3D spheroid models of colorectal- and mamma carcinoma, 7 demonstrated activity in the lower nanomolar range and the ability to overcome resistance to clinically used standard chemotherapeutic drugs. Therefore 7 induces cytotoxic effects leading to an equal response in the chemotherapy of both sensitive and resistant tumor models. Analyses of mitochondrial function and glycolysis and respiration derived ATP production confirmed compound 7 to act as mitocan but also revealed a rapid perturbation of the cellular energy metabolism as the primary mechanism of action, which is completely different to conventional chemotherapeutic drugs and thereby explains the ability of compound 7 to overcome chemotherapeutic drug resistance.

Lonp1 and Sig-1R contribute to the counteraction of ursolic acid against ochratoxin A-induced mitochondrial apoptosis.

Ochratoxin A (OTA), a secondary fungal metabolite with nephrotoxicity, is widespread in numerous kinds of feeds and foodstuffs. Ursolic acid (UA), a water-insoluble pentacyclic triterpene acid, exists in a wide range of food materials and medicinal plants. Our earlier researches provided preliminary evidence that mitochondria- and mitochondria-associated endoplasmic reticulum membranes (MAMs)-located stress-responsive Lon protease 1 (Lonp1) had a protective function in OTA-induced nephrotoxicity, and the renoprotective function of UA against OTA partially due to Lonp1. However, whether other MAMs-located protiens, such as endoplasmic reticulum stress (ERS)-responsive Sigma 1-type opioid receptor (Sig-1R), contribute to the protection of UA against OTA-induced nephrotoxicity together with Lonp1 needs further investigation. In this study, the cell viability, reactive oxygen species, and protein expressions of human proximal tubule epithelial-originated kidney-2 (HK-2) cells varied with OTA and/or UA/CDDO-me/AVex-73/Sig-1R siRNA treatments were determined. Results indicated that a 24 h-treatment of 5μM OTA could significantly induce mitochondrial-mediated apoptosis via repressing Lonp1 and Sig-1R, thereby enhancing the protein expressions of GRP78, p-PERK, p-eIF2α, CHOP, IRE1α, and Bax, and inhibiting the protein expression of Bcl-2 in HK-2cells, which could be remarkably relieved by a 2 h-pre-treatment of 4μM UA (P<0.05). In conclusion, through mutual promotion between Lonp1 and Sig-1R, UA could effectively relieve OTA-induced apoptosis in vitro and break the vicious cycle between oxidative stress and ERS, which activated the mitochondrial apoptosis pathway.

Design, semi-synthesis and molecular docking of new antibacterial and antibiofilm triazole conjugates from hydroxy-triterpene acids and fluoroquinolones

Maslinic acid- and oleanolic acid-based hyrids with potent antibacterial and antibiofilm activities were designed and semi-synthesized from pentacyclic triterpene acids isolated from olive oil manufacturing solid waste.

The inhibitory mechanism of pentacyclic triterpenoid acids on pancreatic lipase and cholesterol esterase

Inhibiting pancreatic Lipase (PL) and cholesterol esterase (CEase) can effectively control blood triglycerides and cholesterol levels. The interaction characteristics of pentacyclic triterpenoid acids (oleanolic acid [OA], ursolic acid [UA], and corosolic acid [CA]) with PL and CEase were studied by inhibition kinetics, multispectroscopy, and molecular docking methods. Enzyme inhibition and inhibition kinetics showed that pentacyclic triterpenoid acids effectively inhibited PL and CEase in a competitive manner with IC50 values ranging from 0.077 mg/mL to 0.446 mg/mL. UV–Vis, fourier transform infrared, fluorescence quenching, and circular dichroism analysis demonstrated that OA, UA, and CA disrupted the conformation of PL and CEase through hydrogen bonding and hydrophobic forces, resulting in loose protein structures. Molecular docking analysis revealed that pentacyclic triterpenoid acids could stably bind at key residues in the active site of PL and CEase. Molecular dynamics (MD) simulation further confirmed the stable binding of pentacyclic triterpene acids to PL and CEase. This study suggested that OA, UA, and CA could have an essential value as digestive enzyme inhibitors.

Maslinic Acid: A New Compound for the Treatment of Multiple Organ Diseases.

Maslinic acid (MA) is a pentacyclic triterpene acid, which exists in many plants, including olive, and is highly safe for human beings. In recent years, it has been reported that MA has anti-inflammatory, antioxidant, anti-tumor, hypoglycemic, neuroprotective and other biological activities. More and more experimental data has shown that MA has a good therapeutic effect on multiple organ diseases, indicating that it has great clinical application potential. In this paper, the extraction, purification, identification and analysis, biological activity, pharmacokinetics in vivo and molecular mechanism of MA in treating various organ diseases are reviewed. It is hoped to provide a new idea for MA to treat various organ diseases.

A novel pentacyclic triterpene acid from the stem barks of Combretum fragrans F. Hoffm (Combretaceae)

A phytochemical study was carried out on stem bark of Combretum fragrans F. Hoffm., a medicinal plant belonging to the Combretaceae family and used traditionally in the treatment of various ailments. Column chromatography separation on silica gel of the crude methanol extract from stem barks of C. fragrans led to the isolation of a new pentacyclic triterpene acid, with a 3,6-epoxide bridge and trivially named as fragransinic acid (1), along with four known compounds: betulin (2), betulinic acid (3), bellericagenin B (4) and a mixture of β-sitosterol (5) and stigmasterol (6). Structures were elucidated by extensive spectroscopic analyses including 1D and 2D NMR, mass spectrometry as well as by comparison with literature data. The above compounds were isolated for the first time from C. adenogonium. Implications for chemosystematics and traditional medicine were briefly discussed.

Synthesis of an ursolic acid organic salt based low-molecular-weight supramolecular hydrogel with unique thermo-responsiveness behavior

Low-molecular-weight supramolecular hydrogels (LMWSHs) are widely used in biomedical area and soft materials with desirable stimuli-responsiveness and self-healing abilities. Natural product hydrogelators (NPHGs) based LMWSHs can be synergistically used as drug matrix due to the low toxicity, good biocompatibility, biodegradability and biological activity from hydrogelator. Usually NPHGs based LMWSHs are obtained in organic reagents or following complex modifications. This work introduces a pentacyclic triterpene acid, ursolic acid, derivatives based LMWSH that formed in aqueous solution following simple preparation of 1-ethyl-3-methylimidazolium ursolic salt ([EMIM][UA]). Surprisingly, the gelator [EMIM][UA] based LMWSH showed unusual heating-induced irreversible transparent-turbid transitions in sol state at the gelator concentration lower than the minimum gelation concentration (MGC), but self-assembled to form LMWSH upon cooling like a conventional low-molecular-weight gelator (LMWG) at the gelator concentration higher than MGC. Rarely observed in the LMWSH system, a large number of crystallites were formed in both sol and gel state by increasing temperature, which was analogous to lower critical solution temperature (LCST) phase behavior in polymer systems. Moreover, the formed LMWSH displayed enormous viscoelasticity as chewing gum at room temperature with a porous honeycomb structure based supramolecular network. The good stability and injectability of the formed LMWSH, together with the in vitro drug releasing ability, demonstrated the potential of the formed LMWSH to be the drug delivery system for sustained drug releasing.

Maslinic Acid Attenuates Ischemia/Reperfusion-Induced Acute Kidney Injury by Suppressing Inflammation and Apoptosis Through Inhibiting NF-κB and MAPK Signaling Pathway.

Inflammation and apoptosis are the major contributors to the mechanisms of acute kidney injury (AKI) due to renal ischemia-reperfusion injury (IRI). Maslinic acid (MA), a pentacyclic triterpene acid mostly found in dietary plants, the current study was to demonstrate the renoprotective effect of MA on IRI-induced AKI, and to investigate the role of inflammation and apoptosis-related signaling pathways as a molecular mechanism. C57BL/6J mice were subjected to IRI for 72 h, and MA was daily administered by intraperitoneal injection during this period. In parallel, rat renal proximal tubule cells (NRK52E) were prophylactically treated with MA and then exposed to hydrogen peroxide (H2O2). MA treatment significantly inhibited the mRNA expression of interleukin (IL-1β), tumor necrosis factor-α (TGF-α), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1(ICAM-1). Also, MA reduced the expression of Bax/Bcl2 ratio and cleaved caspase-3. In NRK52 cells, MA inhibited the IκBα degradation, blocked NF-κB/p65 phosphorylation, and nuclear translocation. The phosphorylation of ERK, JNK, and p38 was attenuated by MA in IRI-induced kidney injury and H2O2-stimulated NRK52 cells. The expression levels of IL-1β, MCP-1, and ICAM-1 were upregulated in H2O2-stimulated NRK52E cells, which was attenuated by NF-κB inhibitor. H2O2 treatment increased the Bax/Bcl2 ratio and cleaved caspase-3 in NRK52E cells, which was counteracted by MAPK inhibitors. Together, our data demonstrate that MA suppresses IR-induced AKI injury through NF-κB and MAPK signaling pathways and that MA is a promising agent in the treatment of kidney diseases.

Molecular Mechanisms Underlying the Effects of Olive Oil Triterpenic Acids in Obesity and Related Diseases.

Dietary components exert protective effects against obesity and related metabolic and cardiovascular disturbances by interfering with the molecular pathways leading to these pathologies. Dietary biomolecules are currently promising strategies to help in the management of obesity and metabolic syndrome, which are still unmet medical issues. Olive oil, a key component of the Mediterranean diet, provides an exceptional lipid matrix highly rich in bioactive molecules. Among them, the pentacyclic triterpenic acids (i.e., oleanolic acid) have gained clinical relevance in the last decade due to their wide range of biological actions, particularly in terms of vascular function, obesity and insulin resistance. Considering the promising effects of these triterpenic compounds as nutraceuticals and components of functional foods against obesity and associated complications, the aim of our review is to decipher and discuss the main molecular mechanisms underlying these effects driven by olive oil triterpenes, in particular by oleanolic acid. Special attention is paid to their signaling and targets related to glucose and insulin homeostasis, lipid metabolism, adiposity and cardiovascular dysfunction in obesity. Our study is aimed at providing a better understanding of the impact of dietary components of olive oil in the long-term management of obesity and metabolic syndrome in humans.

Maslinic acid activates renal AMPK/SIRT1 signaling pathway and protects against diabetic nephropathy in mice

BackgroundDiabetic nephropathy has been a devastating complication. Clinically, there is an urgent need for nephroprotective agents to delay the onset of diabetic nephropathy and ameliorate its symptoms. Maslinic acid is a pentacyclic triterpene acid with protective effect on multiple organs against oxidative stress and inflammation. In this research, we hypothesized that maslinic acid protects renal function against diabetic nephropathy.MethodsC57BL/6 J male mice administrated with 50 mg/kg of Streptozocin (STZ) daily were used to establish diabetic mouse model (blood glucose levels > 300 mg/dL). Urinary levels of albumin, total proteins, and creatinine were analyzed by an automatic analyzer. H&E staining was used to evaluate renal damage. qRT-PCR and ELISA were performed to investigate the inflammation and oxidative stress in renal tissues. Western blot was used to assess the activation of AMPK signaling.ResultsMaslinic acid treatment alleviated the loss of body weight and blood glucose in diabetic mice. Renal structure and function were protected by maslinic acid in diabetic mice. 20 mg/kg maslinic acid treatment for 8 weeks significantly alleviated the oxidative stress and inflammation in the kidney of diabetic rats. Maslinic acid treatment activated the renal AMPK/SIRT1 signaling pathway.ConclusionMaslinic acid ameliorates diabetic nephropathy and activates the renal AMPK/SIRT1 signaling pathway.