Triterpenoid compound betulin attenuates allergic airway inflammation by modulating antioxidants, inflammatory cytokines and tissue transglutaminase in ovalbumin-induced asthma mice model

Abstract

Objectives This study hypothesized that to analyse the anti-inflammatory effect of triterpenoid compound betulin in ovalbumin (OVA)-induced asthmatic mice. Methods In this study, betulin was intraperitoneally administered in OVA-challenged and sensitized mice. The effect of betulin on inflammatory cells, lung function, reactive oxygen species (ROS) production, antioxidants status, oxidative stress markers, serum IgE level and inflammatory cytokines status in BALF was examined by enzyme-linked immunosorbent assay. The expression of tTG, TGF-β1, MMP-9 and TIMP-1 in lung tissue was scrutinized by RT-qPCR analysis, and the expression of TREM-1, p-IκB-α and NF-κBp65 proteins in lung tissue was examined by western blot analysis. Key findings We found that the betulin treatment has effectively attenuated the proliferation of inflammatory cells, reduced the ROS generation, elevated the antioxidant enzymes and attenuated the level of oxidative markers in asthma induced mice. Moreover, reduced the level of serum IgE and pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IFN-γ. Betulin treatment down-regulated the expression of MMP-9, tTG and TGF-β1 genes; moreover, betulin treatment effectively down-regulated the TREM-1, p-IκB-α and NF-κBp65 proteins level in lung. Conclusion Betulin exhibited effective anti-asthmatic activity by attenuating the accumulation of inflammatory cells, expression of tTG, TGF-β1 and MMP-9 genes in lung tissue.

Triterpenoids as Reactive Oxygen Species Modulators of Cell Fate

“… 28 Another natural product with promising antioxidant properties is betulin (compound 16 , Figure 1 ). 29 Betulin has displayed potent effects against inflammatory cells by reducing ROS generation, increasing antioxidant enzyme expression, and attenuating the level of oxidative markers in an ovalbumin-induced mouse model of asthma. The study showed treatment with compound 16 downregulated the expression of genes involved in remodeling during inflammation such as MMP-9 (matrix metallopeptidase 9), t TG (tissue transglutaminase), and TGF-β1(transforming growth factor beta 1).…”

“…The combined studies indicate the betulin compounds might be complementary to current anti-inflammatory treatments. 29 …”

“…These cytokines regulate the inflammatory response in order to clear foreign entities by changing the abundance of various cell populations through binding to their corresponding cellular receptors. The combined studies indicate the betulin compounds might be complementary to current anti-inflammatory treatments …”

Atractylodin induces oxidative stress‐mediated apoptosis and autophagy in human breast cancer MCF‐7 cells through inhibition of the P13K/Akt/mTOR pathway

“…In cancer and asthmatic cases, the SOD activity was reduced compared to healthy adults. [ 30,31 ] In the current investigation, we noticed the diminished antioxidant activities and increased ROS activities in atractylodin administrated MCF‐7 cells. The oxidative stress generated by ROS can cause cancer cells to express the apoptotic protein p53, which can induce DNA, protein, and lipid damage.…”

Ursolic Acid and Related Analogues: Triterpenoids with Broad Health Benefits

“…Betulin shows a wide range of pharmaceutical effects such as anti-HIV, anti-inflammatory, and anti-cancer properties [ 146 , 158 ]. Kamaraj et al reported that ovalbumin (OVA)-induced lung inflammation and hypersensitivity were attenuated by reducing the production of ROS and pro-inflammatory cytokines through the down-regulation of MMP-9 expression, tissue transglutaminase (tTG), TGF-β1 gene expression and by reducing TREM-1, p-IκB, and NF-κB p65 protein levels in the lung [ 159 ]. In an experimental mammary cancer model, orally supplemented betulin restored antioxidant activity and modulated the expression of both MAPKs and AhR/Nrf2-associated proteins [ 160 ], indicating that betulin has strong anti-inflammatory and anti-cancerogenic properties.…”