Ginsenoside Rb3 alleviates smoke‐induced lung injury via the H19/miR‐29b‐3p/HGMB1/TLR4 signalling pathway

Abstract

The over‐activation of inflammation is involved in the pathogenesis of smoke‐induced lung injury (SILI), while Rb3 treatment may alleviate smoke‐induced lung injury by down‐regulating the expression of H19, a regulator of miR‐29b expression. Moreover, HMGB1 is an important mediator of inflammation. Therefore, in this study, we set up an animal model of SILI and treated it with Rb3 to study the effect of Rb3 on the treatment of SILI and the involvement of H19/miR‐29b/HMGB1/TLR4 signalling. SILI mice treated with Rb3 before H&E staining and TUNEL assay were conducted to observe the pathological damages and status of apoptosis in each group. Real‐time PCR, Western blot, computational analysis and luciferase assays were utilized to establish the signalling pathway involved in the pathogenesis of SILI and the action of Rb3 treatment. Rb3 treatment alleviated pathological changes in the lungs while decreasing the levels of W/D ratio and cell apoptotic index. H19 was validated to sponge miR‐29b‐3p, while HMGB1 mRNA was validated to be a target gene of miR‐29b‐3. As a result, a signalling pathway of H19/miR‐29b‐3p/HMGB1 was established. Cell viability was evidently reduced after 72 hours of treatment with CSE, but the treatment of Rb3 elevated the expression of H19 and HMBG1 in the presence of CSE. Also, CSE‐induced inhibition of miR‐29b‐3p expression was restored by Rb3. The findings of this study collectively demonstrated that Rb3 exhibited its therapeutic effect during the treatment of SILI via modulating the H19/miR‐29b‐3p/HMBG1 signalling pathway.

Targeting non-coding RNA H19: A potential therapeutic approach in pulmonary diseases

“…It is not difficult to see from the table that there are currently three drugs targeting H19 to treat lung diseases, namely melatonin, Curcumenol and Ginsenoside Rb3. Both Curcumenol and Ginsenoside Rb3 inhibit H19 expression through the H19/miR-19b-3p/ FTH1 axis and the H19/miR-29b-3p/HGMB1/TLR4 axis to promote ferroptosis in lung cancer cells and reduce inflammation (Tan et al, 2021;Zhang et al, 2022). But Wang showed that melatonin upregulated H19 expression to suppress PAH, in contrast to other reports that H19 promoted this disease (Wang et al, 2018a).…”

“…H19 acts as a sponge for miR-29b-3p to regulate its expression negatively. In addition, miR-29b-3p inhibited the expression of toll-like receptor 4 (TLR4) and alleviated lung injury by inhibiting the expression of HMGB1 mRNA (Tan et al, 2021). TLR4 promoted the production of inflammatory mediators (Yang et al, 2020).…”

“…Infection of the lungs and damage to the immune barrier by pathogens are the leading cause of pneumonia (Torres et al, 2021). Sun showed that H19 was significantly increased in LPS-induced pneumonia models and sponging of miR-22-3p positively regulated NLRP3 to promote cell pyroptosis (Sun et al, 2021). The NLRP3 inflammasome promoted the activation and release of protease caspase-1 to induce gasdermin D-mediated pyroptosis (Huang et al, 2021).…”

The Renshen Chishao Decoction Could Ameliorate the Acute Lung Injury but Could Not Reduce the Neutrophil Extracellular Traps Formation

“…Our result showed that the lncRNAs, participating in the pulmonary inflammation and apoptosis [ 39 , 40 ], were also the RC decoction target genes. The Renshen was reported to regulate the lncRNA levels: the ginsenoside Rb3 increased the lncRNA H19 level and alleviated the smoke-induced lung injury [ 41 ].…”

Ginsenoside Rd inhibits migration and invasion of tongue cancer cells through H19/miR-675-5p/CDH1 axis

“…A recent study showed that ginsenoside Rb3 can regulate H19, 16 indicating that ginsenoside Rd can inhibit tongue cancer by regulating H19. Noncoding RNA H19 is highly expressed in various cancers.…”