A New Betulin Derivative Stimulates the Synthesis of Collagen in Human Fibroblasts Stronger than its Precursor

Drąg-Zalesińska, Małgorzata; Rembiałkowska, Nina; Borska, Sylwia; Saczko, Jolanta; Drąg, Marcin; Poręba, Marcin; Kulbacka, Julita

doi:10.21873/invivo.11577

Cited by 14 publications

(22 citation statements)

References 15 publications

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“…BE and its derivatives proved their efficacy in the induction of cytotoxicity in cancer cells [3]. Moreover, the compounds were potent in regenerative medicine studies [27]. However, no other study considered the application of the analyzed natural compound as an anti-inflammatory agent.…”

Section: Discussionmentioning

confidence: 99%

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

et al. 2022

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Betulin is a heavily studied natural compound for its use as an anticancer or pro-regenerative agent. The structural similarity between betulin to steroids gives rise to the idea that the substance may as well act as an anti-inflammatory drug. This study is the first to describe the anti-inflammatory properties of betulinic acid, betulin, and its derivatives with amino acids 1,4-diaminebutane (Dab), 1,3-diaminepropane (Dap), Ornithine (Orn), and lysine (Lys) on murine macrophages from lymphoma site. The compounds were compared to dexamethasone. To establish the response of the macrophages to the natural compounds, we tested the viability as well as sensitivity to the inflammatory signaling (IFNγR). IL-6 secretory properties and HSP-70 content in the cells were examined. Furthermore, we characterized the effects of compounds on the inhibition of cyclooxygenase-2 (COX-2) activity both in the enzymatic assays and molecular docking studies. Then, the changes in COX-2 expression after betulin treatment were assessed. Betulin and betulinic acid are the low-cytotoxicity compounds with the highest potential to decrease inflammation via reduced IL-6 secretion. To some extent, they induce the reorganization of IFNγR with nearly no effect on COX-2 activity. Conversely, Bet-Orn and Bet-Lys are highly cytotoxic and induce the aggregation of IFNγR. Besides, Bet-Lys reduces the activity of COX-2 to a higher degree than dexamethasone. Bet-Orn is the only one to increase the HSP-70 content in the macrophages. In case of IL-6 reduction, all compounds were more potent than dexamethasone.

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Section: Discussionmentioning

confidence: 99%

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

et al. 2022

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“…Collagen produced by the body is synthesized mainly by fibroblasts, i.e., the main structural protein found in skin, tendon and bone. Additionally, collagen has been found to have many pharmaceutical, medicinal, nutritional and cosmetic applications [ 16 , 17 ]. Pinoresinol, which is present in Mc fruit, has several functions.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Morinda citrifolia Activities through Pinoresinol and α-EG Related Gene Expression

Sudmoon

Kaewdaungdee

Ameamsri

et al. 2022

Plants

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α-EG is a unique substance that was first found in the leaves and fruits of Morinda citrifolia (Mc) growing in Thailand using GC-MS at 52.33% and 54.12%. It was then concentrated and its abundance quantified, along with that of pinoresinol, via GC, compared to the standards in leaves, ufp, rfp, rawfs, and seeds. α-EG and pinoresinol, which have collagen stimulating, skin whitening, and an inhibitory effect on wrinkle formation, were found in different concentrations and amounts. Three different concentrations of the five Mc part extracts were tested on NHDF for gene expression related to the aforementioned activities, COL1A1, COL1A2, and COL3A1, FGF1 and FGF7 by qRT-PCR. The results showed various expression levels, both stimulatory and inhibitory, with different concentrations of plant parts and genes. Similar results were revealed when the experiments were performed with Morus alba (Ma), which was found to contain 20.48 g protein p/100 g leaves at concentrations of 3.11 mg/mL. The studied Mc parts seem to have advantages based on the stated objectives, gene type and level of activity of each plant part. Rawfs and leaves supplemented with Ma samples were selected for toxicity tests with PBMCs. The lack of both cell and DNA toxicity from the rawfs indicated that they can be used safely.

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“…The antibody was diluted with PBS buffer in the proportion 1:200. The detailed protocol was performed according to our previous study [12]. The quantification of the level of stained reaction in treated cells that revealed immunocytochemical reaction was estimated as a percentage values.…”

Section: Methodsmentioning

confidence: 99%

The effect of dental gel formulation on human primary fibroblasts — an in vitro study

Sterczała

Kulbacka

Saczko

et al. 2020

Folia Histochem Cytobiol.

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Introduction. In ordinary dental practice, the dentist often meets with patients suffering from ulcers, aphtha with edema, bleeding gums, bothersome burning, and dry mouth. These are prosthetic, orthodontic patients, after surgery, in various age ranges. Protefix ® gel is a soothing and regenerating preparation aimed at patients with mucosal problems. The aim of our study was to evaluate the protective properties and the safety of Protefix ® gel application after dental procedures in vitro. Material and methods. Human gingival fibroblasts (HGFs) were isolated from normal gingival tissues, cultured to full monolayer and exposed to Protefix ® gel in the concentration from 1 to 100%. The viability of cells was examined by MTT assays. Cell migration as a response of treated cells was assessed. The expression of collagen III was estimated by immunocytochemistry after 20 minutes or 24 hours incubation with Protefix ® gel. Results. The obtained results indicated that the verified gel significantly stimulated fibroblasts' proliferation, and mitochondrial activity determined by MTT assay increased almost twofold for lower gel concentrations. The immunohistochemical detection of collagen III revealed an increased expression after incubation with 5% gel. Conclusions. The results proved that the gel is safe for cells derived from human gingiva and moreover has regenerative properties, which can be of great importance in the treatment of gingivitis after retraction and surgical procedures, or even ordinary daily injuries of oral cavity.

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A New Betulin Derivative Stimulates the Synthesis of Collagen in Human Fibroblasts Stronger than its Precursor

Cited by 14 publications

References 15 publications

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

Betulin and Its Derivatives Reduce Inflammation and COX-2 Activity in Macrophages

Investigation of Morinda citrifolia Activities through Pinoresinol and α-EG Related Gene Expression

The effect of dental gel formulation on human primary fibroblasts — an in vitro study

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