The effect of ursolic and oleanolic acids on human skin fibroblast cells

Wójciak–Kosior, Magdalena; Paduch, Roman; Matysik-Woźniak, Anna; Niedziela, Piotr; Donica, Helena

doi:10.5603/fhc.2011.0050

Cited by 26 publications

(18 citation statements)

References 16 publications

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“…In accordance with this conclusion. Martin et al observed disrupted stress fibers in a human astrocytoma cell line after oleanolic acid treatment [87], whereas the same compound showed no alteration of cytoskeletal structures in primary human dermal fibroblasts [88], supporting our findings in primary keratinocytes.…”

Section: Discussionsupporting

confidence: 89%

From a Traditional Medicinal Plant to a Rational Drug: Understanding the Clinically Proven Wound Healing Efficacy of Birch Bark Extract

et al. 2014

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BackgroundBirch bark has a long lasting history as a traditional medicinal remedy to accelerate wound healing. Recently, the efficacy of birch bark preparations has also been proven clinically. As active principle pentacyclic triterpenes are generally accepted. Here, we report a comprehensive study on the underlying molecular mechanisms of the wound healing properties of a well-defined birch bark preparation named as TE (triterpene extract) as well as the isolated single triterpenes in human primary keratinocytes and porcine ex-vivo wound healing models.Methodology/Principal FindingsWe show positive wound healing effects of TE and betulin in scratch assay experiments with primary human keratinocytes and in a porcine ex-vivo wound healing model (WHM). Mechanistical studies elucidate that TE and betulin transiently upregulate pro-inflammatory cytokines, chemokines and cyclooxygenase-2 on gene and protein level. For COX-2 and IL-6 this increase of mRNA is due to an mRNA stabilizing effect of TE and betulin, a process in which p38 MAPK and HuR are involved. TE promotes keratinocyte migration, putatively by increasing the formation of actin filopodia, lamellipodia and stress fibers. Detailed analyses show that the TE components betulin, lupeol and erythrodiol exert this effect even in nanomolar concentrations. Targeting the actin cytoskeleton is dependent on the activation of Rho GTPases.Conclusion/SignificanceOur results provide insights to understand the molecular mechanism of the clinically proven wound healing effect of birch bark. TE and betulin address the inflammatory phase of wound healing by transient up-regulation of several pro-inflammatory mediators. Further, they enhance migration of keratinocytes, which is essential in the second phase of wound healing. Our results, together with the clinically proven efficacy, identify birch bark as the first medical plant with a high potential to improve wound healing, a field which urgently needs effective remedies.

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Section: Discussionsupporting

confidence: 89%

From a Traditional Medicinal Plant to a Rational Drug: Understanding the Clinically Proven Wound Healing Efficacy of Birch Bark Extract

et al. 2014

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“…Intriguingly, OA and its derivatives has no cytotoxicity to normal human cells [15], [16]. These inhibitory effects of OA are involved with its suppression of some specific intracellular signaling pathways, such as STAT3, JNK, Akt and NF-kappaB signaling pathways [10], [12], [14].…”

Section: Introductionmentioning

confidence: 99%

Oleanolic Acid Suppresses Migration and Invasion of Malignant Glioma Cells by Inactivating MAPK/ERK Signaling Pathway

et al. 2013

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Mitogen-activated protein kinases/Extracellular signal-regulated kinase (MAPK/ERK) pathway is essential for migration and invasion of malignant glioma. It is efficient to inhibit migration and invasion of glioma cells by targeting this pathway. Oleanolic acid (OA) has been well demonstrated to suppress survival, growth and angiogenesis of glioma cells. However, it is still unknown if OA affects the migration and invasion of glioma cells. We utilized U-87 MG glioma cell lines and primary glioma cells from patients to study the effect of OA on migration and invasion of glioma cells with multidisciplinary approaches. In this study, we found that OA significantly decreased the ability of glioma cells to migrate and invade. Epithelial-mesenchymal transition (EMT) of glioma cells was also suppressed by OA treatment. Furthermore, MAPK/ERK pathway was greatly inhibited in glioma cells under OA treatment. MAPK/ERK reactivation induced by a recombinant lentiviral vector, Lv-MEK, was able to rescue the inhibitory effect of OA on migration and invasion of glioma cells. Taken together, we provided evidences that OA was a MAPK/ERK pathway-targeting anti-tumor agent. Although the concentrations we used exceeded its physiological level, OA may be used to prevent migration and invasion of glioma cells by developing its derivatives with enhanced bioactivity.

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“…Interestingly, Factin has also been implicated to play a key role in cell migration and wound healing [23]. In line with these studies, a recent evaluation of compound toxicity on HDF has demonstrated the correlation between actin polymerization and cytotoxic and anti-proliferative activity [24]. Additionally, the level of polymerized actin has been demonstrated to follow the ageing process with higher expression of F-actin in HDF from aged donors compared to younger ones [25].…”

Section: Introductionmentioning

confidence: 88%

Structural activity relationship analysis (SAR) and in vitro testing reveal the anti‐ageing potential activity of acetyl aspartic acid

Gillbro

Lundahl

Westman

et al. 2015

Intern J of Cosmetic Sci

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Synopsis Background Acetyl aspartic acid (A‐A‐A) was discovered through gene array analysis with corresponding connectivity mapping (Cmap), aiming for identification of new compounds with anti‐ageing properties. Objective The aim of this study was to use structural activity relationship (SAR) analysis to identify a predictive mechanism of action of A‐A‐A. The findings from SAR will be further characterized by in vitro activity testing. Furthermore, we aimed to investigate the role of polymerized filamentous F‐actin in ageing fibroblasts and to evaluate the effect of A‐A‐A on this model. Methods To predict the mode of action of A‐A‐A, we used the PASS computer program as a SAR model. In vitro, scratch motility tests with immortalized keratinocytes were used as a model for wound healing potential. Matrix metalloproteinase 1‐3 (MMP 1‐3) was analysed using multiplex protein assays (Luminex), and polymerized actin was detected by phalloidin staining in dermal fibroblasts (HDF). Results SAR analysis predicted that A‐A‐A would possess both epidermal and dermal activities with identification of wound healing and MMP inhibition potential. Further in vitro studies confirmed the wound healing potential using keratinocyte scratch motility assays. We were also able to confirm the dermal activities predicted by inhibition of MMP (MMP 1–3) in HDF by A‐A‐A. In addition, we found a positive relationship between age and F‐actin expression. We also discovered that stimulation of HDF with A‐A‐A for 72 h significantly reduced the polymerized cytoskeletal network as visualized by inhibition of F‐actin expression. In fact, A‐A‐A leveraged the expression of F‐actin in middle‐aged female fibroblasts (50 years of age) to the level of young female fibroblasts (30 years of age), corresponding to a 40% reduction in F‐actin expression. Conclusion Using an in silico and in vitro approach, we were able to demonstrate that A‐A‐A has the capacity to target different compartments of the skin through keratinocyte regeneration, MMP inhibition and relief in fibroblasts stiffness by reduction of F‐actin cytoskeletal network in HDF.

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The effect of ursolic and oleanolic acids on human skin fibroblast cells

Cited by 26 publications

References 16 publications

From a Traditional Medicinal Plant to a Rational Drug: Understanding the Clinically Proven Wound Healing Efficacy of Birch Bark Extract

From a Traditional Medicinal Plant to a Rational Drug: Understanding the Clinically Proven Wound Healing Efficacy of Birch Bark Extract

Oleanolic Acid Suppresses Migration and Invasion of Malignant Glioma Cells by Inactivating MAPK/ERK Signaling Pathway

Structural activity relationship analysis (SAR) and in vitro testing reveal the anti‐ageing potential activity of acetyl aspartic acid

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