Dioscin exhibits protective effects on in vivo and in vitro asthma models via suppressing TGF‐β1/Smad2/3 and AKT pathways

Abstract

Dioscin is a natural product that possesses protective effects on multiple chronic injuries, but its effects on asthma are not fully understood. Herein, we evaluated its effects on asthmatic mice established by ovalbumin (OVA) sensitization and challenges and further explored the mechanism. Inflammatory cells in bronchoalveolar lavage fluids (BALFs) were analyzed using Diff‐Quik staining. OVA‐specific immunoglobulin E (IgE)/IgG1 in serum and inflammatory cytokines (interleukin 4[IL‐4], IL‐5, IL‐13, and tumor necrosis factor‐α) in BALFs and lung tissues were measured using Enzyme‐Linked Immunosorbent Assay Kits. Hematoxylin and eosin, periodic acid–Schiff, and immunohistochemistry staining showed histopathological changes in lung tissues. Epithelial–mesenchymal transition (EMT) in human bronchial epithelial (16HBE) cells was assessed by immunofluorescence staining. Hydroxyproline content was used to evaluate collagen deposition. Polymerase chain reaction and Western blot were performed to measure messenger RNA and protein expression. We found that dioscin treatment (particularly at the dose of 80 mg/kg) significantly inhibited pulmonary inflammation in asthmatic mice, as evidenced by the decreased serum OVA‐specific IgE/IgG1 and the reduced inflammatory cells and cytokines in BALFs and lung tissues. Moreover, dioscin effectively ameliorated the goblet cell hyperplasia, mucus hypersecretion, collagen deposition, and smooth muscle hyperplasia in the airways of asthmatic mice. Mechanistically, dioscin restrained the activated TGF‐β1/Smad2/3 and protein kinase B (AKT) signal pathways in lung tissues and potently reversed the TGF‐β1‐induced EMT and phosphorylation of Smad2/3 and AKT in 16HBE cells. Collectively, dioscin displayed protective effects on OVA‐induced asthmatic mice via adjusting TGF‐β1/Smad2/3 and AKT signal pathways, supporting the fact that dioscin could be a candidate for chronic asthma prevention in the future.

Retracted: Connexin 43 upregulation by dioscin‐inhibited gastric cancer metastasis by suppressing PI3K/Akt pathway

“…Dioscin is a kind of steroidal saponins of Chinese herbal medicine, which has a protective effect on many kinds of chronic injury and antitumor effects (Liu et al, 2022;Shang et al, 2022). Previous evidence had demonstrated that Dioscin upregulates the expression of Cx43 and improves gap junction communication in B16 cells (Kou et al, 2017;Zhang et al, 2022).…”

Medicine Targeting Epithelial-Mesenchymal Transition to Treat Airway Remodeling and Pulmonary Fibrosis Progression

“…Dioscin, a kind of steroidal saponins extracted from some medicinal plants, has multiple medicinal efects including anti-infammatory and anticancer efects. It was reported that dioscin restrained chronic asthmatic mice by altering TGF-β1/Smad2/3 and Akt signalling pathways and reversed TGF-β1-induced EMT in 16HBE cells [63].…”

“…Icariin [61] OVA-induced asthma in mice MAPK/Erk Nodakenin [62] OVA-induced asthma in mice IL-4, IL-5, IL-13, MMP2/9, and NF-κB Dioscin [63] OVA-induced asthma in mice TGF-induced HBE16 TGF-β/Smad…”

Dioscin inhibiting EGFR-mediated Survivin expression promotes apoptosis in oral squamous cell carcinoma cells

“…Numerous research has suggested that dioscin has broad-spectrum pharmacological activities, such as anti-oxidative, anti-fibrosis, anti-proliferation, anti-allergic, anti-viral, anti-inflammation, anti-fungal, immunoregulation, anti-hyperuricemia, anti-aging, pro-autophagic, anti-thrombotic, and cholesterol-lowering effects and possesses fewer side effects compared with the drugs with the same effect in current clinical application relatively speaking 12 - 14 . Dioscin also provided obvious protective effects on various metabolic disorders, such as fatty acid metabolism and the damage of organs, including the kidney, liver, lung, and heart 15 - 17 . Furthermore, dioscin reduced chemoresistance 18 and regulated M1 macrophage polarization and differentiation of myeloid-derived suppressor cells 19 .…”