Idiopathic pulmonary fibrosis (IPF) is a multi-stage progressive fibrosing interstitial lung disease which has a poor prognosis with median survival time of 2–4 years after diagnosis (Samarelli et al., 2021). A pathological characteristic of IPF is excessive accumulation of extracellular matrix (ECM) components, causing diffuse pulmonary fibrosis, parenchyma remodeling, limited gas exchange, and respiratory failure. Although the pathogenesis of IPF is not completely elucidated, current evidence suggests that this chronic disorder is initiated by alveolar epithelial damage in combination with an abnormal wound-healing response (Wilson and Wynn, 2009). In particular, injuries to alveolar epithelial cells trigger an inflammatory cascade during which alveolar epithelial cell-generated chemoattractants attract immune cells to damaged lung tissues. In the absence of disease, this acute inflammatory phase is followed by provisional matrix deposition which facilitates the repair and regeneration of functional alveolar epithelium. However, unresolved or repetitive injuries in IPF cause the wound-healing process to become dysregulated, leading to an aberrant epithelial-to-mesenchymal transition (EMT); failed epithelial repair; and the proliferation, migration, and activation of collagen-producing fibroblasts/myofibroblasts (Chanda et al., 2019; Wilson and Wynn, 2009).

Although IPF is primarily caused by multiple sequential pathological events including inflammation, an EMT, and the proliferation and differentiation of lung fibroblasts, patients with established IPF usually benefit from anti-fibrotic drugs but not classical anti-inflammatory agents (e.g., corticosteroids) (Raghu et al., 2018). Consequently, there are few treatment options for IPF; nintedanib and pirfenidone constitute the only approved anti-fibrotic agents. Moreover, although these agents demonstrated benefits in clinical trials, they have been ineffective in reversion of lung fibrogenesis; clinically significant improvement is often absent in patients with the established IPF (Sgalla et al., 2018). Therefore, recent discoveries of new anti-fibrotic agents have attracted considerable attention. Notably, many agents of plant origin possess potent anti-fibrotic activities. For example, polyphenols and flavonoids (e.g., resveratrol, quercetin, luteolin, and apelin) can suppress bleomycin-induced lung fibrosis by exerting anti-inflammatory and antioxidant activities (Hosseini et al., 2018). Additionally, certain alkaloids, including isoliensinine and matrine, effectively ameliorated experimental lung fibrosis (Dudala et al., 2021). These findings suggest that plant extracts and their bioactive compounds can serve as alternative treatment options for IPF.

Mimosa pudica L. is native to Vietnam and many other tropical countries. This plant has traditionally been used to treat headache, insomnia, bronchitis, diarrhea, dysentery, fever, and hypertension (Ahmad et al., 2012; Varnika et al., 2012). Previous studies have revealed various biological actions of M. pudica (MP) including, but not limited to, anti-depressant, anti-convulsant, diuretic, anti-microbial, and anti-inflammatory properties (Ahmad et al., 2012). Notably, we and other research groups have also demonstrated the promising potential of M. pudica in the treatment of lung-associated pathological conditions. MaliPrabha and colleagues observed that aqueous extract from roots of M. pudica exhibited anti-asthmatic activities (MaliPrabha et al., 2011). Likewise, Yang et al. reported the suppressive effect of M. pudica ethanol extract on ovalbumin-induced airway inflammation (Yang et al., 2011). In consistent to these observations, we found that aqueous extract from above-ground parts of M. pudica alleviated Sephacryl S-200 induced pulmonary inflammatory response in rats (Nguyen et al., 2012). In another study from our group, this preparation also showed antispasmodic effects on histamine-stimulated hamster trachea (Nguyen et al., 2011). Phytochemically, leaves and roots of M. pudica contain a wide range of chemical derivatives including phenols, flavonoids, alkaloids, saponins, terpenoids, tannins, carbohydrates, and proteins (Adurosakin et al., 2023). It is worth noting that many of the compounds reported to be present in M. pudica such as rutin, luteolin, apigenin, quercetin, gallic acid, and L-mimosine have been found to inhibit the development of pulmonary fibrosis in animal models (Boots et al., 2020; Chen and Zhao, 2016; Karunarathne et al., 2023; Li et al., 2015; Nikbakht et al., 2015).

MP exerts pharmacological effects against lung disorders and contains many components with anti-fibrotic activities. Surprisingly, there is no direct evidence that MP provides any therapeutic benefit with respect to lung fibrosis. In this study, we investigated the abilities of an MP extract to counteract various pathological events during lung fibrosis, such as alveolar epithelial cell inflammation, the EMT, and the proliferation and differentiation of lung fibroblasts. We found that a crude extract from MP at least partially prevented these pathological processes. The inhibitory effects of the MP extract on lung fibrosis progression were confirmed using an animal model of bleomycin-induced pulmonary fibrosis. Furthermore, we demonstrated that the anti-lung fibrotic effects of MP arose from FOXO3 stabilization mediated by the suppression of ERK1/2 phosphorylation.