Benzyl salicylate from the stems and stem barks of <i>Cornus walteri</i> as a nephroprotective agent against cisplatin-induced apoptotic cell death in LLC-PK1 cells

Lee, Dahae; Lee, Seoung Rak; Kang, Ki Sung; Kim, Ki Hyun

doi:10.1039/c9ra07009e

Cited by 8 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results on detecting PARP-1 cleavage after treatment with 50 µM CisPt for 24 h are similar to the study of Ju et al 62 who detected the PARP-1 cleavage in HK-2 cells treated with 40 µM CisPt for 24 h. JNKs were reported to be strongly activated via phosphorylation in cells incubated with cisplatin 63 . In our study, expression of phosphorylated JNK isoforms (JNK1 and JNK2) was elevated after cisplatin treatment in all time intervals in dose-dependent manner compared to control cells which is similar to reported finding on increased pJNK expression in HeLa cells after incubation with 50 and 100 µM CisPt for 6 h 64 , and in pig kidney epithelial cells after 25 µM CisPt treatment for 24 h 65 .…”

Section: Discussionsupporting

confidence: 91%

Quantitative spectrofluorometric assay detecting nuclear condensation and fragmentation in intact cells

Majtnerová

Čapek

Petira

et al. 2021

Sci Rep

View full text Add to dashboard Cite

At present, nuclear condensation and fragmentation have been estimated also using Hoechst probes in fluorescence microscopy and flow cytometry. However, none of the methods used the Hoechst probes for quantitative spectrofluorometric assessment. Therefore, the aim of the present study was to develop a spectrofluorometric assay for detection of nuclear condensation and fragmentation in the intact cells. We used human hepatoma HepG2 and renal HK-2 cells cultured in 96-well plates treated with potent apoptotic inducers (i.e. cisplatin, staurosporine, camptothecin) for 6–48 h. Afterwards, the cells were incubated with Hoechst 33258 (2 µg/mL) and the increase of fluorescence after binding of the dye to DNA was measured. The developed spectrofluorometric assay was capable to detect nuclear changes caused by all tested apoptotic inducers. Then, we compared the outcomes of the spectrofluorometric assay with other methods detecting cell impairment and apoptosis (i.e. WST-1 and glutathione tests, TUNEL, DNA ladder, caspase activity, PARP-1 and JNKs expressions). We found that our developed spectrofluorometric assay provided results of the same sensitivity as the TUNEL assay but with the advantages of being fast processing, low-cost and a high throughput. Because nuclear condensation and fragmentation can be typical markers of cell death, especially in apoptosis, we suppose that the spectrofluorometric assay could become a routinely used method for characterizing cell death processes.

show abstract

Section: Discussionsupporting

confidence: 91%

Quantitative spectrofluorometric assay detecting nuclear condensation and fragmentation in intact cells

Majtnerová

Čapek

Petira

et al. 2021

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Interestingly, benzyl salicylate ( 15 ) was more efficient than L-NMMA in inhibiting NO production in LPS-activated RAW 264.7 macrophages. In previous studies, benzyl salicylate was shown to be an active compound with estrogenic activity [ 44 ], and a protective agent against cisplatin-induced damage to cells of the LLC-PK1 kidney proximal tubule cell line [ 21 ]. However, to the best of our knowledge, there are no reports available regarding the inhibition of NO production in LPS-activated RAW 264.7 macrophages by benzyl salicylate.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we identified new tirucallane triterpenoids (cornusalterins N-P) in C. walteri , along with bioactive tirucallane triterpenoids that control adipocyte and osteoblast differentiation [ 20 ]. A nephroprotective agent has also been identified in C. walteri extracts using a model of cisplatin-induced cell death in LLC-PK1 kidney proximal tubule cell line; it was found to decrease the proteins involved in intrinsic apoptosis pathway [ 21 ]. As C. walteri extract has been known to inhibit NO production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) [ 22 ], the present study was carried out for further investigation of the methanol extracts of the stem and stem bark of C. walteri to identify potential anti-inflammatory constituents.…”

Section: Introductionmentioning

confidence: 99%

Identification of Bioactive Natural Product from the Stems and Stem Barks of Cornus walteri: Benzyl Salicylate Shows Potential Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

et al. 2021

Self Cite

View full text Add to dashboard Cite

Cornus walteri (Cornaceae), known as Walter’s dogwood, has been used to treat dermatologic inflammation and diarrheal disease in traditional oriental medicine. As part of an ongoing research project to discover natural products with biological activities, the anti-inflammatory potential of compounds from C. walteri in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages were explored. Phytochemical analysis of the methanol extract of the stem and stem bark of C. walteri led to the isolation of 15 chemical constituents. These compounds were evaluated for their inhibitory effects on the production of the proinflammatory mediator nitric oxide (NO) in LPS-stimulated macrophages, as measured by NO assays. The molecular mechanisms underlying the anti-inflammatory activity were investigated using western blotting. Our results demonstrated that among 15 chemical constituents, lupeol and benzyl salicylate inhibited NO production in LPS-activated RAW 264.7 macrophages. Benzyl salicylate was more efficient than NG-monomethyl-L-arginine mono-acetate salt (L-NMMA) in terms of its inhibitory effect. In addition, the mechanism of action of benzyl salicylate consisted of the inhibition of phosphorylation of IκB kinase alpha (IKKα), IκB kinase beta (IKKβ), inhibitor of kappa B alpha (IκBα), and nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. Furthermore, benzyl salicylate inhibited the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Taken together, these results suggest that benzyl salicylate present in the stem and stem bark of C. walteri has potential anti-inflammatory activity, supporting the potential application of this compound in the treatment of inflammatory diseases.

show abstract

“…Plants 2021, 10, 431 2 of 8 acid on A2780 human ovarian cancer cells and the renoprotective effect of benzyl salicylate on cisplatin-induced damage in LLC-PK1 kidney proximal tubule cells have been explored and evaluated in our previous studies [16,17]. In the present study, we focused on (-)-leucophyllone, a tirucallane triterpenoid isolated from the further phytochemical investigation of the MeOH extract from C. walteri.…”

Section: Isolation and Identification Of (-)-Leucophyllone From C Wamentioning

confidence: 99%

“…Our previous phytochemical analysis on C. walteri led to the isolation of triterpenoids, including betulinic acid methyl ester, lupenone, lupeol, betulinic acid, methyl 3-O-acetyl betulinate, and sterols such as 6β-hydroxysitostenone, 5α-stigmast-3,6-dione, sitostenone, 3β-sitostanol, and 6α-hydroxy-β-sitostenone [16,17]. Among them, the anticancer effect of betulinic acid on A2780 human ovarian cancer cells and the renoprotective effect of benzyl Plants 2021, 10, 431 2 of 7 salicylate on cisplatin-induced damage in LLC-PK1 kidney proximal tubule cells have been explored and evaluated in our previous studies [16,17]. In the present study, we focused on (-)-leucophyllone, a tirucallane triterpenoid isolated from the further phytochemical investigation of the MeOH extract from C. walteri.…”

Section: Introductionmentioning

confidence: 99%

(-)-Leucophyllone, a Tirucallane Triterpenoid from Cornus walteri, Enhances Insulin Secretion in INS-1 Cells

Lee

Kim

Jang

et al. 2021

Plants

Self Cite

View full text Add to dashboard Cite

Phytochemical examination of the MeOH extract from the stems and stem bark of Cornus walteri (Cornaceae) led to the isolation and verification of a tirucallane triterpenoid, (-)-leucophyllone, as a major component. Its structure was elucidated using NMR spectroscopy and liquid chromatography–mass spectrometry. The effect of (-)-leucophyllone on insulin secretion in INS-1 cells was investigated. (-)-Leucophyllone increased glucose-stimulated insulin secretion (GSIS) at concentrations showing no cytotoxic effect in rat INS-1 pancreatic β-cells. Moreover, we attempted to determine the mechanism of action of (-)-leucophyllone in the activation of insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3-kinase (PI3K), Akt, and pancreatic and duodenal homeobox-1 (PDX-1). Treatment of INS-1 cells with (-)-leucophyllone markedly increased the expression of these proteins. Our findings indicate the potential of (-)-leucophyllone as an antidiabetic agent.

show abstract

Benzyl salicylate from the stems and stem barks of Cornus walteri as a nephroprotective agent against cisplatin-induced apoptotic cell death in LLC-PK1 cells

Abstract: Benzyl salicylate from Cornus walteri can be a nephroprotective agent against cisplatin-induced oxidative stress and apoptosis.

Cited by 8 publications

References 41 publications

Quantitative spectrofluorometric assay detecting nuclear condensation and fragmentation in intact cells

Quantitative spectrofluorometric assay detecting nuclear condensation and fragmentation in intact cells

Identification of Bioactive Natural Product from the Stems and Stem Barks of Cornus walteri: Benzyl Salicylate Shows Potential Anti-Inflammatory Activity in Lipopolysaccharide-Stimulated RAW 264.7 Macrophages

(-)-Leucophyllone, a Tirucallane Triterpenoid from Cornus walteri, Enhances Insulin Secretion in INS-1 Cells

Contact Info

Product

Resources

About