|
1
|
Bispo IMC, Granger HP, Almeida PP, Nishiyama PB, de Freitas LM. Systems biology and OMIC data integration to understand gastrointestinal cancers. World J Clin Oncol 2022; 13:762-778. [PMID: 36337313 PMCID: PMC9630993 DOI: 10.5306/wjco.v13.i10.762] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/22/2021] [Accepted: 10/02/2022] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal (GI) cancers are a set of diverse diseases affecting many parts/ organs. The five most frequent GI cancer types are esophageal, gastric cancer (GC), liver cancer, pancreatic cancer, and colorectal cancer (CRC); together, they give rise to 5 million new cases and cause the death of 3.5 million people annually. We provide information about molecular changes crucial to tumorigenesis and the behavior and prognosis. During the formation of cancer cells, the genomic changes are microsatellite instability with multiple chromosomal arrangements in GC and CRC. The genomically stable subtype is observed in GC and pancreatic cancer. Besides these genomic subtypes, CRC has epigenetic modification (hypermethylation) associated with a poor prognosis. The pathway information highlights the functions shared by GI cancers such as apoptosis; focal adhesion; and the p21-activated kinase, phosphoinositide 3-kinase/Akt, transforming growth factor beta, and Toll-like receptor signaling pathways. These pathways show survival, cell proliferation, and cell motility. In addition, the immune response and inflammation are also essential elements in the shared functions. We also retrieved information on protein-protein interaction from the STRING database, and found that proteins Akt1, catenin beta 1 (CTNNB1), E1A binding protein P300, tumor protein p53 (TP53), and TP53 binding protein 1 (TP53BP1) are central nodes in the network. The protein expression of these genes is associated with overall survival in some GI cancers. The low TP53BP1 expression in CRC, high EP300 expression in esophageal cancer, and increased expression of Akt1/TP53 or low CTNNB1 expression in GC are associated with a poor prognosis. The Kaplan Meier plotter database also confirmed the association between expression of the five central genes and GC survival rates. In conclusion, GI cancers are very diverse at the molecular level. However, the shared mutations and protein pathways might be used to understand better and reveal diagnostic/prognostic or drug targets.
Collapse
Affiliation(s)
- Iasmin Moreira Costa Bispo
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Henry Paul Granger
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Palloma Porto Almeida
- Division of Experimental and Translational Research, Brazilian National Cancer Institute, Rio de Janeiro 20231-050, Brazil
| | - Patricia Belini Nishiyama
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Leandro Martins de Freitas
- Núcleo de Biointegração, Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45.029-094, Bahia, Brazil
| |
Collapse
|
|
2
|
Xu T, Liu X. Oleuropein inhibits invasion of squamous cell carcinoma of the head and neck through TGF-β1 signaling pathway. BMC Cancer 2022; 22:942. [PMID: 36050634 PMCID: PMC9434901 DOI: 10.1186/s12885-022-09979-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 08/05/2022] [Indexed: 11/17/2022] Open
Abstract
Background Squamous cell carcinoma of the head and neck (SCCHN) is globally the sixth most common cancer. TGF-β1 is a key regulator of cell proliferation and differentiation, and it induces the epithelial-mesenchymal transition (EMT) by activating Smad2 signaling in SCCHN cells. Previous studies have revealed that oleuropein (OL) can inhibit the EMT alterations and migration of cancer cells. The aim of this study was to examine the involvement of TGF-β1 signaling pathway in SCCHN and the effect of OL on it. Methods Through in vitro experiments at cellular level and in vivo evaluation in mouse xenograft tumor model, with morphological and Western blotting assays, we examined the effects of OL on TGF-β1-mediated signaling pathway in Tu686, CAL-27 and 686LN-M2 tumor cell lines. Results We found that OL reversed the TGF-β1-induced EMT, and changed the morphology of cells and the expression levels of epithelial and interstitial markers. Wound-healing and transwell invasion assays indicated that OL reversed the TGF-β1-promoted cell migration and invasion dramatically. The effects of OL were also verified in xenograft tumor model of mice, and the findings were identical to the in vitro assays. Conclusion This study demonstrated that OL inhibits the growth and metastasis of SCCHN by interfering with the TGF-β1 signaling pathway, and the findings are beneficial for the development of prevention and treatment strategy of SCCHN. Due to the low toxicity and less side effects, OL may be of potential value in the inhibition of metastasis of SCCHN and improve survival. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-022-09979-2.
Collapse
Affiliation(s)
- Ting Xu
- Department of Otolaryngology, Wuxi Second Clinical Medical College of Nantong University, No. 68, Zhongshan Road, Liangxi District, Wuxi, Jiangsu, 214002, People's Republic of China.
| | - Xuan Liu
- Department of Otolaryngology, Wuxi Second Clinical Medical College of Nantong University, No. 68, Zhongshan Road, Liangxi District, Wuxi, Jiangsu, 214002, People's Republic of China
| |
Collapse
|
|
3
|
Pan J, Zang Y. LINC00667 Promotes Progression of Esophageal Cancer Cells by Regulating miR-200b-3p/SLC2A3 Axis. Dig Dis Sci 2022; 67:2936-2947. [PMID: 34313922 DOI: 10.1007/s10620-021-07145-5] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Accepted: 06/30/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Recently, more and more evidence indicated that the long non-coding RNA was strictly related to the occurrence and progression of human cancers, including esophageal cancer (EC). We observed that LINC00667 was increased in EC, but the function of LINC00667 was unclear. Therefore, the function and potential molecular mechanism of LINC00667 in the progression of EC need to be further studied. METHODS Quantitative real-time PCR was used to investigate the levels of LINC00667, miR-200b-3p, and SLC2A3. The levels of protein involved in cell cycle, cell apoptosis, epithelial-mesenchymal transition, as well as SLC2A3 were quantitatived by western blot. The role of LINC00667 in the proliferative, migratory and invasive capabilities of EC cells were measured by cell counting kit-8 assay, EdU assay, flow cytometry assay, wound healing assay and transwell assay, respectively. Interaction between LINC00667 and miR-200b-3p or miR-200b-3p and SLC2A3 were confirmed using a luciferase reporter assay. RESULTS In this work, we found that LINC00667 expression was up-regulated in EC cell lines, and LINC00667 knockdown inhibited cell proliferation, migration, and invasion in EC cells. In addition, it showed that LINC00667 functioned as competitive endogenous RNA for miR-200b-3p by the DIANA-LncBase database. Moreover, we used targetscan online software to predict SLC2A3 as a target gene of miR-200b-3p. Subsequently, rescue experiments confirmed that knocking out SLC2A3 could reverse the inhibitory effect of miR-200b-3p on EC cells transfected with sh-LINC00667. CONCLUSION Herein, we revealed the novel mechanism of LINC00667 on regulating metastasis-related gene by sponge regulatory axis during EC metastasis. Our results demonstrated that LINC00667 plays a critical role in metastatic EC by mediating sponge regulatory axis miR-200b-3p/SLC2A3. To explore function of LINC00667/miR-200b-3p/SLC2A3 axis may provide an informative biomarker of malignancy and a highly selective anti-EC therapeutic target.
Collapse
Affiliation(s)
- Jindun Pan
- Department of Gastroenterology, Taishan Hospital, Taian, Shandong Province, China.
| | - Yunhong Zang
- Department of Gastroenterology, Taishan Hospital, Taian, Shandong Province, China
| |
Collapse
|
|
4
|
Zheng Y, Liu Z, Yang X, Liu L, Ahn KS. An updated review on the potential antineoplastic actions of oleuropein. Phytother Res 2021; 36:365-379. [PMID: 34808696 DOI: 10.1002/ptr.7325] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2021] [Revised: 10/20/2021] [Accepted: 10/26/2021] [Indexed: 12/11/2022]
Abstract
Oleuropein is an ester of elenolic acid and hydroxytyrosol (3, 4-dihydroxyphenylethanol). It is a phenolic compound and the most luxuriant in olives. The detailed information related to the anticancer effects of oleuropein was collected from the internet database PubMed/Medline, ResearchGate, Web of Science, Wiley Online Library, and Cnki using appropriate keywords until the end of October 2021. Oleuropein has been shown to have antioxidant, anticancer, antiinflammatory, cardioprotective, neuroprotective, and hepatoprotective effects. Previous studies also revealed that oleuropein could effectively inhibit the malignant progression of esophageal cancer, gastric cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, ovarian cancer, prostate cancer, and cervical cancer. Recently, the role of oleuropein in inhibiting tumor cell proliferation, invasion, and migration and inducing tumor cell apoptosis has gained extensive attention. In this review, we have summarized the latest research progress related to the antioncogenic mechanisms and the potential role of oleuropein in targeting different human malignancies. Based on these findings, it can be concluded that oleuropein can function as a promising chemopreventive and chemotherapeutic agent against cancer, but its more detailed anticancer effects and underlying mechanisms need to be further validated in future preclinical as well as clinical studies.
Collapse
Affiliation(s)
- Yudong Zheng
- Department of Pharmacology, Basic Medical School of Yangtze University, Jingzhou, China
| | - Zhenzhen Liu
- Department of Pharmacology, Basic Medical School of Yangtze University, Jingzhou, China
| | - Xiulan Yang
- Department of Pharmacology, Basic Medical School of Yangtze University, Jingzhou, China
| | - Lian Liu
- Department of Pharmacology, Basic Medical School of Yangtze University, Jingzhou, China
| | - Kwang Seok Ahn
- Kyung Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| |
Collapse
|
|
5
|
Emma MR, Augello G, Di Stefano V, Azzolina A, Giannitrapani L, Montalto G, Cervello M, Cusimano A. Potential Uses of Olive Oil Secoiridoids for the Prevention and Treatment of Cancer: A Narrative Review of Preclinical Studies. Int J Mol Sci 2021; 22:ijms22031234. [PMID: 33513799 PMCID: PMC7865905 DOI: 10.3390/ijms22031234] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/22/2021] [Accepted: 01/23/2021] [Indexed: 02/07/2023] Open
Abstract
The Mediterranean diet (MD) is a combination of foods mainly rich in antioxidants and anti-inflammatory nutrients that have been shown to have many health-enhancing effects. Extra-virgin olive oil (EVOO) is an important component of the MD. The importance of EVOO can be attributed to phenolic compounds, represented by phenolic alcohols, hydroxytyrosol, and tyrosol, and to secoiridoids, which include oleocanthal, oleacein, oleuropein, and ligstroside (along with the aglycone and glycosidic derivatives of the latter two). Each secoiridoid has been studied and characterized, and their effects on human health have been documented by several studies. Secoiridoids have antioxidant, anti-inflammatory, and anti-proliferative properties and, therefore, exhibit anti-cancer activity. This review summarizes the most recent findings regarding the pharmacological properties, molecular targets, and action mechanisms of secoiridoids, focusing attention on their preventive and anti-cancer activities. It provides a critical analysis of preclinical, in vitro and in vivo, studies of these natural bioactive compounds used as agents against various human cancers. The prospects for their possible use in human cancer prevention and treatment is also discussed.
Collapse
Affiliation(s)
- Maria Rita Emma
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
| | - Giuseppa Augello
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
| | - Vita Di Stefano
- Department of Biological, Chemical, and Pharmaceutical Science and Technology (STEBICEF), University of Palermo, 90133 Palermo, Italy;
| | - Antonina Azzolina
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
| | - Lydia Giannitrapani
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy
| | - Giuseppe Montalto
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
- Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties, University of Palermo, 90133 Palermo, Italy
| | - Melchiorre Cervello
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
- Correspondence: (M.C.); (A.C.); Tel.: +39-091-680-9534/511/555 (M.C.); +39-091-680-9589 (A.C.)
| | - Antonella Cusimano
- Institute for Biomedical Research and Innovation, National Research Council (CNR), 90146 Palermo, Italy; (M.R.E.); (G.A.); (A.A.); (L.G.); (G.M.)
- Correspondence: (M.C.); (A.C.); Tel.: +39-091-680-9534/511/555 (M.C.); +39-091-680-9589 (A.C.)
| |
Collapse
|
|
6
|
Assessment of the Nutraceutical Effects of Oleuropein and the Cytotoxic Effects of Adriamycin, When Administered Alone and in Combination, in MG-63 Human Osteosarcoma Cells. Nutrients 2021; 13:nu13020354. [PMID: 33503913 PMCID: PMC7911555 DOI: 10.3390/nu13020354] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 01/14/2021] [Accepted: 01/19/2021] [Indexed: 12/14/2022] Open
Abstract
Oleuropein (OLEU) is the most distinguished phenolic compound found in olive fruit and the leaves of Olea europaea L., with several pharmacological properties, including anti-cancer actions. Adriamycin (ADR) is an anthracycline widely used as a chemotherapeutic agent, although it presents significant side effects. The aim of the present study was to investigate the effect of oleuropein alone (20 μg/mL) and in co-treatment with ADR (50 nM), in MG-63 human osteosarcoma cells. Therefore, cellular and molecular techniques, such as MTT assay, flow cytometry, real-time Polymerase Chain Reaction (PCR), western blot and Elisa method, as well as Nuclear Magnetic Resonance (NMR) spectroscopy, were applied to unveil changes in the signal transduction pathways involved in osteosarcoma cells survival. The observed alterations in gene, protein and metabolite levels denote that OLEU not only inhibits MG-63 cells proliferation and potentiates ADR’s cytotoxicity, but also exerts its action, at least in part, through the induction of autophagy.
Collapse
|
|
7
|
Atwa SM, Handoussa H, Hosny KM, Odenthal M, El Tayebi HM. Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma. World J Hepatol 2020; 12:1211-1227. [PMID: 33442449 PMCID: PMC7772730 DOI: 10.4254/wjh.v12.i12.1211] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2020] [Revised: 09/30/2020] [Accepted: 10/29/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight. However, such therapy has a modest response in hepatocellular carcinoma (HCC). Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade. Non-coding ribonucleic acid (ncRNA) driven regulation is a major mechanism of epigenetic modulation. Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) regulation, and based on the literature, we hypothesized that miR-155-5p, miR-194-5p and long non-coding RNAs (lncRNAs) X-inactive specific transcript (XIST) and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1. Recently, nutraceutical therapeutics in cancers have received increasing attention. Thus, it is interesting to study the impact of oleuropein on the respective study key players. AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1. METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p, miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA, respectively. In addition, Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1. HCC and normal tissue samples were collected for scanning of PD-L1, XIST and MALAT-1 expression. To study the interaction among miR-155-5p, miR-194-5p, lncRNAs XIST and MALAT-1, as well as PD-L1 mRNA, a series of transfections of the Huh-7 cell line was carried out. RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PD-L1, MALAT-1 and XIST. MALAT-1 and XIST were predicted to target PD-L1 mRNA. PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls; however, MALAT-1 was barely detected. MiR-194 induced expression elevated the expression of PD-L1, XIST and MALAT-1. However, overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST, while it had a negative impact on MALAT-1 expression. Knockdown of XIST did have an impact on PD-L1 expression; however, following knockdown of the negative regulator of X-inactive specific transcript (TSIX), PD-L1 expression was elevated, and abolished MALAT-1 activity. Upon co-transfection of miR-194-5p with siMALAT-1, PD-L1 expression was elevated. Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression. Upon co-transfection of miR-194 with siTSIX, PD-L1 expression was upregulated. Interestingly, the same PD-L1 expression pattern was observed following miR-155-5p co-transfections. Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1, XIST, and miR-155-5p, upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile. CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC, have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway.
Collapse
Affiliation(s)
- Sara M Atwa
- Pharmaceutical Biology Department, German University in Cairo, Cairo 11865, Egypt
| | - Heba Handoussa
- Pharmaceutical Biology Department, German University in Cairo, Cairo 11865, Egypt
| | - Karim M Hosny
- Department of General Surgery, Faculty of Medicine, Cairo University, Cairo 11562, Egypt
| | - Margarete Odenthal
- Institute for Pathology, University Hospital Cologne, Cologne 50924, Germany
| | - Hend M El Tayebi
- Molecular Pharmacology Research Group, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt.
| |
Collapse
|
|
8
|
Potential Protective Role Exerted by Secoiridoids from Olea europaea L. in Cancer, Cardiovascular, Neurodegenerative, Aging-Related, and Immunoinflammatory Diseases. Antioxidants (Basel) 2020; 9:antiox9020149. [PMID: 32050687 PMCID: PMC7070598 DOI: 10.3390/antiox9020149] [Citation(s) in RCA: 64] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 02/06/2020] [Accepted: 02/07/2020] [Indexed: 12/12/2022] Open
Abstract
Iridoids, which have beneficial health properties, include a wide group of cyclopentane [c] pyran monoterpenoids present in plants and insects. The cleavage of the cyclopentane ring leads to secoiridoids. Mainly, secoiridoids have shown a variety of pharmacological effects including anti-diabetic, antioxidant, anti-inflammatory, immunosuppressive, neuroprotective, anti-cancer, and anti-obesity, which increase the interest of studying these types of bioactive compounds in depth. Secoiridoids are thoroughly distributed in several families of plants such as Oleaceae, Valerianaceae, Gentianaceae and Pedialaceae, among others. Specifically, Olea europaea L. (Oleaceae) is rich in oleuropein (OL), dimethyl-OL, and ligstroside secoiridoids, and their hydrolysis derivatives are mostly OL-aglycone, oleocanthal (OLE), oleacein (OLA), elenolate, oleoside-11-methyl ester, elenoic acid, hydroxytyrosol (HTy), and tyrosol (Ty). These compounds have proved their efficacy in the management of diabetes, cardiovascular and neurodegenerative disorders, cancer, and viral and microbial infections. Particularly, the antioxidant, anti-inflammatory, and immunomodulatory properties of secoiridoids from the olive tree (Olea europaea L. (Oleaceae)) have been suggested as a potential application in a large number of inflammatory and reactive oxygen species (ROS)-mediated diseases. Thus, the purpose of this review is to summarize recent advances in the protective role of secoiridoids derived from the olive tree (preclinical studies and clinical trials) in diseases with an important pathogenic contribution of oxidative and peroxidative stress and damage, focusing on their plausible mechanisms of the action involved.
Collapse
|
|
9
|
Castejon ML, Sánchez-Hidalgo M, Aparicio-Soto M, Montoya T, Martín-LaCave I, Fernández-Bolaños JG, Alarcón-de-la-Lastra C. Dietary oleuropein and its new acyl-derivate attenuate murine lupus nephritis through HO-1/Nrf2 activation and suppressing JAK/STAT, NF-κB, MAPK and NLRP3 inflammasome signaling pathways. J Nutr Biochem 2019; 74:108229. [PMID: 31698204 DOI: 10.1016/j.jnutbio.2019.108229] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 07/17/2019] [Accepted: 08/14/2019] [Indexed: 12/16/2022]
Abstract
Systemic lupus erythemathosus (SLE) is a chronic inflammatory and autoimmune disease which can affect multiple organ systems, without an effective and safe treatment. Olive leaf extracts are of special interest for their therapeutic effects. Oleuropein (OL) is the most abundant constituents of olive leaf extract and possesses many beneficial properties. In this study, we evaluated the effects of dietary OL and its new derivate, peracetylated oleuropein (Per-OL), in a pristane-induced SLE model. Mice received an injection of pristane or saline solution and were fed with experimental diets: enriched with OL and Per-OL. The levels of proinflammatory cytokines and markers were evaluated by enzyme-linked immunosorbent assay. The protein expressions of inducible nitric oxide synthase, microsomal prostaglandin E synthase 1, heme oxygenase (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear transcription factor-kappa B (NF-κB) and inflammasome nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) pathways activation were determined in kidneys by Western blot. OL and Per-OL significantly reduced renal damage and decreased serum matrix metalloproteinase 3 and prostaglandine E2 kidneys levels. Our findings indicate that Nrf2 and HO-1 antioxidant protein expressions were up-regulated in mice fed with OL and Per-OL diets, whereas the activation of JAK/STAT, MAPK, NF-κB and NLRP3 inflammasome pathways was significantly ameliorated. These results suggest that OL and Per-OL supplementation might provide a new alternative approach as a preventive/palliative treatment of nephritis in SLE management.
Collapse
Affiliation(s)
- M L Castejon
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | - M Sánchez-Hidalgo
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | - M Aparicio-Soto
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | - T Montoya
- Department of Pharmacology, Faculty of Pharmacy, University of Seville, Seville, Spain
| | - I Martín-LaCave
- Department of Normal and Pathological Cytology and Histology, Faculty of Medicine, University of Seville, Seville, Spain
| | - J G Fernández-Bolaños
- Department of Organic Chemistry, Faculty of Chemistry, University of Seville, Seville, Spain
| | | |
Collapse
|