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      Cytoprotective Properties of Citronella Oil ( Cymbopogon nardus (L.) Rendl.) and Lemongrass Oil ( Cymbopogon citratus (DC.) Stapf) through Attenuation of Senescent-Induced Chemotherapeutic Agent Doxorubicin on Vero and NIH-3T3 Cells

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          Abstract

          Objective:

          This study aimed to determine the cytoprotective potentials of citronella ( Cymbopogon nardus (L.) Rendl.) essential oil (CO) and lemongrass ( Cymbopogon citratus (DC.) Stapf) essential oil (LO).

          Methods:

          The essential oils from citronella and lemongrass were obtained by steam-water distillation, then analyzed using Gas Chromatography-Mass Spectrophotometry (GC-MS) to determine the chemical constituents. The antioxidant activity of CO and LO was compared using a total antioxidant capacity kit. The viability of normal kidney epithelial cells Vero and fibroblast NIH-3T3 as the cell models were tested using a trypan blue exclusion assay. The effect of cellular senescence inhibition on both cell models was measured using senescence-associated β-galactosidase (SA-β-gal) staining. The mechanism of action of CO and LO in the protection of cellular damage against doxorubicin was also confirmed through 2’,7’–dichlorofluorescin diacetate (DCFDA) staining to discover the ability to decrease reactive oxygen species (ROS) levels and a gelatin zymography assay to observe the activity of matrix metalloproteinases (MMPs).

          Results:

          The major marker components of CO and LO were citronellal and citral, respectively. Both oils showed low cytotoxic activity against Vero and NIH-3T3 cells, with IC 50 values of over 40 µg/mL. LO exhibited higher antioxidant capacity than CO, but there was no effect on the intracellular ROS level of both oils on Vero and NIH-3T3 cells. However, CO and LO decreased cellular senescence induced by doxorubicin exposure on both cells, as well as suppressed MMP-2 expression.

          Conclusion:

          Both CO and LO decrease the cellular senescence and MMP-2 expression with less cytotoxic effects on normal cells independently from their antioxidant capacities. The results were expected to support the use of CO and LO as tissue protective and anti-aging agents in maintaining the body’s cellular health against chemotherapeutics or cellular damaging agents.

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          Most cited references28

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          Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth

          Curcumin has been reported to exhibit anti-tumorigenic activity; however, since its precise actions remain unclear, its effects are considered to be deceptive. In the present study, we confirmed the anti-tumorigenic effects of curcumin on CML-derived leukemic cells in a xenograft model and in vitro culture system. In vitro pull-down and mass analyses revealed a series of enzymes (carbonyl reductase, glutathione-S-transferase, glyoxalase, etc.) that function in a reactive oxygen species (ROS) metabolic pathway as curcumin-binding targets, the expression of which was up-regulated in human leukemia. Curcumin increased ROS levels over the threshold in leukemic cells, and the antioxidant, glutathione (GSH) and overexpression of curcumin-binding enzymes partially mitigated the up-regulation of ROS and growth inhibition caused by curcumin. These results show that curcumin specifically inhibits tumor growth by increasing ROS levels over the threshold through the miscellaneous inhibition of ROS metabolic enzymes. Curcumin has potential in therapy to regulate ROS levels in tumor cells, thereby controlling tumor growth.
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            Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion

            Background: Previous studies have demonstrated that senescent cancer-associated fibroblasts (CAFs) derived from genetically unstable oral squamous cell carcinomas (GU-OSCC), unlike non-senescent CAFs from genetically stable carcinomas (GS-OSCC), promoted keratinocyte invasion in vitro in a paracrine manner. The mechanism by which this occurs is unclear. Methods: Previous work to characterise the senescent-associated secretory phenotype (SASP) has used antibody arrays, technology that is limited by the availability of suitable antibodies. To extend this work in an unbiased manner, we used 2D gel electrophoresis and mass spectroscopy for protein identification. Matrix metalloproteinases (MMPs) were investigated by gelatin zymography and western blotting. Neutralising antibodies were used to block key molecules in the functional assays of keratinocyte adhesion and invasion. Results: Among a variety of proteins that were differentially expressed between CAFs from GU-OSCC and GS-OSCC, MMP-2 was a major constituent of senescent CAF-CM derived from GU-OSCC. The presence of active MMP-2 was confirmed by gelatine zymography. MMP-2 derived from senescent CAF-CM induced keratinocyte dis-cohesion and epithelial invasion into collagen gels in a TGF-β-dependent manner. Conclusions: Senescent CAFs from GU-OSCC promote a more aggressive oral cancer phenotype by production of active MMP-2, disruption of epithelial adhesion and induction of keratinocyte invasion.
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              MMP-2 and 9 in Chronic Kidney Disease

              Gelatinases are members of the matrix metalloproteinase (MMPs) family; they play an important role in the degradation of the extracellular matrix (ECM). This effect is also crucial in the development and progression of chronic kidney disease (CKD). Its expression, as well as its activity regulation are closely related to the cell signaling pathways, hypoxia and cell membrane structural change. Gelatinases also can affect the development and progression of CKD through the various interactions with tumor necrosis factors (TNFs), monocyte chemoattractant proteins (MCPs), growth factors (GFs), oxidative stress (OS), and so on. Currently, their non-proteolytic function is a hot topic of research, which may also be associated with the progression of CKD. Therefore, with the in-depth understanding about the function of gelatinases, we can have a more specific and accurate understanding of their role in the human body.
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                Author and article information

                Journal
                Asian Pac J Cancer Prev
                Asian Pac J Cancer Prev
                APJCP
                Asian Pacific Journal of Cancer Prevention : APJCP
                West Asia Organization for Cancer Prevention (Iran )
                1513-7368
                2476-762X
                2023
                : 24
                : 5
                : 1667-1675
                Affiliations
                [1 ] Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia.
                [2 ] Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada, Sekip Utara, Yogyakarta 55281, Indonesia.
                Author notes
                [* ]For Correspondence: edy_meiyanto@ugm.ac.id
                Article
                10.31557/APJCP.2023.24.5.1667
                10495914
                37247287
                d8987cc0-a5d0-44cd-941e-ff533f8ae15b

                This work is licensed under a Creative Commons Attribution-Non Commercial 4.0 International License. ( https://creativecommons.org/licenses/by-nc/4.0/)

                History
                : 15 December 2022
                : 22 May 2023
                Categories
                Research Article

                citronella and lemongrass oils,cytoprotective,cellular senescence,mmp-2,fibroblast and kidney cells

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