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Pistacia lentiscus Hydrosol: Untargeted Metabolomic Analysis and Anti-Inflammatory Activity Mediated by NF-κB and the Citrate Pathway.

ABSTRACT: Pistacia lentiscus shows a long range of biological activities, and it has been used in traditional medicine for treatment of various kinds of diseases. Moreover, related essential oil keeps important health-promoting properties. However, less is known about P. lentiscus hydrosol, a main by-product of essential oil production, usually used for steam distillation itself or discarded. In this work, by using ultra-high-resolution ESI(+)-FT-ICR mass spectrometry, a direct identification of four main classes of metabolites of P. lentiscus hydrosol (i.e., terpenes, amino acids, peptides, and condensed heterocycles) was obtained. Remarkably, P. lentiscus hydrosol exhibited an anti-inflammatory activity by suppressing the secretion of IL-1β, IL-6, and TNF-α proinflammatory cytokines in lipopolysaccharide- (LPS-) activated primary human monocytes. In LPS-triggered U937 cells, it inhibited NF-κB, a key transcription factor in inflammatory cascade, regulating the expression of both the mitochondrial citrate carrier and the ATP citrate lyase genes. These two main components of the citrate pathway were downregulated by P. lentiscus hydrosol. Therefore, the levels of ROS, NO, and PGE₂, the inflammatory mediators downstream the citrate pathway, were reduced. Results shed light on metabolic profile and anti-inflammatory properties of P. lentiscus hydrosol, suggesting its potential as a therapeutic agent.

SUBMITTER: Santarsiero A

PROVIDER: S-EPMC7652607 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Pistacia lentiscus Hydrosol: Untargeted Metabolomic Analysis and Anti-Inflammatory Activity Mediated by NF-κB and the Citrate Pathway.

Santarsiero Anna A Onzo Alberto A Pascale Raffaella R Acquavia Maria Assunta MA Coviello Marianna M Convertini Paolo P Todisco Simona S Marsico Michela M Pifano Corrado C Iannece Patrizia P Gaeta Carmine C D'Angelo Salvatore S Padula Maria Carmela MC Bianco Giuliana G Infantino Vittoria V Martelli Giuseppe G

Oxidative medicine and cellular longevity 20201101

Pistacia lentiscus shows a long range of biological activities, and it has been used in traditional medicine for treatment of various kinds of diseases. Moreover, related essential oil keeps important health-promoting properties. However, less is known about P. lentiscus hydrosol, a main by-product of essential oil production, usually used for steam distillation itself or discarded. In this work, by using ultra-high-resolution ESI(+)-FT-ICR mass spectrometry, a direct identificatio ...[more]

PMID: 33204395

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Project description:Eucalyptus spp. and Pistascia lentiscus are among the Palestinian trees that are traditionally used in folkloric medicine in treating many diseases; leaves of which are thought to have anti-inflammatory, antibacterial and antioxidant effects. The goal of this study is to evaluate the in vitro inhibitory effect of Eucalyptus spp. and Pistascia lentiscus extracts on Lipopolysacaride (LPS)-induced Interlukin-6 (Il-6) and Tumor Necrosis Factor-α (TNF-α) by polymorphonuclear Cells (PMNCs).Polymorphonuclear cells were isolated from the whole blood using Histopaque (Ficol-1077) method and then cultured in an enriched Roswell Park Memorial Institute (RBMI) medium. Supernatants' Interlukin-6 (IL-6) and Tumor Necrosis Factor (TNF-α) levels were determined 24 hour after LPS stimulation. HPLC was employed to determine the concentration of phenolic compounds in the extracts. The concentrations of TNF-α and IL-6 were compared using paired-samples t test.Eucalyptus spp. and Pistascia lentiscus leaves extracts have shown significant reduction in the levels of both Il-6 and TNF-α Gallic acid; a strong anti-inflammatory agent was found to be the major phenolic compound in both leaf extracts. However, other anti-inflammatory phenolic compounds were detected in Pitascia lentiscus extract including syringic acid and p-coumaric acid, while chlorogenic acid was detected in Eucalyptus spp. leaf extract.Reduction in the levels of Il-6 and TNF-α upon the effect of both Eucalyptus spp. and Pistascia lentiscus extract is an indication of their anti-inflammatory effects. Our results may also indicate that the observed anti-inflammatory effect of the above extracts may be due to the presence of gallic acid and other phenolic compounds. List of Abbreviations and Nomenclature: LPS: Lipopolysacaride, Il-6: Interlukin-6, TNF-α: Tumor Necrosis Factor-α, PMNCs: Polymorphonuclear Cells, HPLC: High Performance Liquid Chromatography, ELISA: Enzyme Linked Immune Sorbent Assay, EDTA: Ethylene Diamine Tetra Acetic acid, PBS: phosphate buffered saline, RPMI: Roswell Park Memorial Institute medium FBS: Fetal Bovine Serum.

Project description:Hypertension poses a significant global health burden and is closely associated with cardiovascular morbidity. Pistacia lentiscus var. chia, commonly known as mastic, has emerged as a potential nutraceutical, due to its diverse pharmacological properties, including antioxidant and vasodilatory effects. Yet, its impact on hypertension in translational in vivo models and on hypertension-associated abnormalities in circulation, vasculature and kidneys have not been investigated. Herein we sought to decipher the putative antihypertensive potential of mastic, focusing on vascular and renal endothelium in clinically relevant in vivo models of essential hypertension. Two translational in vivo models of hypertension induced by Angiotensin II and Deoxycorticosterone acetate (DOCA)-High Salt in male rats, were utilized. Mastic administration at a therapeutic dose (220mg/kg, per os) was administered daily for four weeks, after the establishment of hypertension. Non-invasive blood pressure measurements and whole blood RNA sequencing and metabolomics were performed. Real-time PCR and Western blot analysis were conducted in kidney and aorta, to decipher its underlying antihypertensive mechanism. Mastic administration significantly reduced systolic, diastolic, and mean blood pressure in both in vivo hypertensive models. RNA sequencing revealed distinct gene expression profiles, with modulation of immune-related pathways in the Angiotensin II model and metabolic pathways in the DOCA-HS model. Additionally, RNA sequencing analysis revealed that mastic downregulated Rhob, Jun, Txnip and Egr1 mRNA expression in the circulation, paving towards a putative antioxidant and endothelial-targeted mechanism. Metabolomic analysis identified lysophosphatidylinositol upregulation as a consistent effect of mastic in both in vivo models, being implicated with improved endothelial homeostasis. RT-PCR analysis in the kidneys and aorta, showed that mastic increased endothelial markers such as Vegfa and Egr-1 mRNA expression in both experimental models. Concerning the endothelial homeostasis, mastic additionally increased renal nitric oxide synthase phosphorylation in both in vivo models of hypertension. This study highlights the potential of mastic as a natural adjuvant therapy for hypertension. The findings shed new light on its molecular mechanisms of action, providing insights into its protective impact on renal endothelium.

Project description:The rising risks of food microbial contamination and foodborne pathogens resistance have prompted an increasing interest in natural antimicrobials as promising alternatives to synthetic antimicrobials. Essential oils (EOs) obtained from natural sources have shown promising anticancer, antimicrobial, and antioxidant activities. EOs extracted from the resins of Pistacia lentiscus var. Chia are widely utilized for the treatment of skin inflammations, gastrointestinal disorders, respiratory infections, wound healing, and cancers. The therapeutic benefits of P. lentiscusessential oils (PO) are limited by their low solubility, poor bioavailability, and high volatility. Nanoencapsulation of PO can improve their physicochemical properties and consequently their therapeutic efficacy while overcoming their undesirable side effects. Hence, PO was extracted from the resins of P. lentiscusvia hydrodistillation. Then, PO was encapsulated into (2-hydroxypropyl)-beta-cyclodextrin (HPβCD) via freeze-drying. The obtained inclusion complexes (PO-ICs) appeared as round vesicles (22.62 to 63.19 nm) forming several agglomerations (180 to 350 nm), as detected by UHR-TEM, with remarkable entrapment efficiency (89.59 ± 1.47%) and a PDI of 0.1475 ± 0.0005. Furthermore, the encapsulation and stability of PO-ICs were confirmed via FE-SEM, 1H NMR, 2D HNMR (NOESY), FT-IR, UHR-TEM, and DSC. DSC revealed a higher thermal stability of the PO-ICs, reaching 351.0 °C. PO-ICs exerted substantial antibacterial activity against Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli as compared to free PO. PO-ICs showed significant enhancement in the antibacterial activity of the encapsulated PO against S. aureus with an MIC90 of 2.84 mg/mL and against P. aeruginosa with MIC90 of 3.62 mg/mL and MIC50 of 0.56 mg/mL. In addition, PO-ICs showed greater antimicrobial activity against E. coli by 6-fold with an MIC90 of 0.89 mg/mL, compared to free PO, which showed an MIC90 of 5.38 mg/mL. In conclusion, the encapsulation of PO into HPβCD enhanced its aqueous solubility, stability, and penetration ability, resulting in a significantly higher antibacterial activity.

Dataset Information

Pistacia lentiscus Hydrosol: Untargeted Metabolomic Analysis and Anti-Inflammatory Activity Mediated by NF-κB and the Citrate Pathway.

Publications

<i>Pistacia lentiscus</i> Hydrosol: Untargeted Metabolomic Analysis and Anti-Inflammatory Activity Mediated by NF-<i>κ</i>B and the Citrate Pathway.

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