Research Article Stachys pilifera Benth. Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats through the Antioxidant Pathways Nazanin Danaei , 1 Esmaeel Panahi kokhdan , 1 Hossein Sadeghi , 1 Heibatollah Sadeghi , 1 Sajad Hassanzadeh , 1 Davuod Rostamzadeh , 1 Nahid Azarmehr , 1 and Salar Hafez Ghoran 1,2 1 Medicinal Plants Research Center, Yasuj University of Medical Sciences, Yasuj, Iran 2 Department of Chemistry, Faculty of Science, Golestan University, Gorgan, Iran Correspondence should be addressed to Esmaeel Panahi kokhdan; esmaeel_panahi@yahoo.com and Hossein Sadeghi; h_sadeghi_m@yahoo.com Received 23 November 2021; Revised 21 August 2022; Accepted 12 September 2022; Published 30 September 2022 Academic Editor: Antonio Vassallo Copyright © 2022 Nazanin Danaei et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background and Aim. Fibrosis of the lungs is an interstitial lung disease whose diagnosis and treatment are not well-established. Stachys pilifera Benth. (Lamiaceae) has been proven to have antioxidant and anti-inflammatory properties. is study was performed to determine the effect of S. pilifera extract on bleomycin-induced pulmonary fibrosis in rats. Methods. In this experimental study, 35 male Wistar rats (120–180 g) were divided into five groups (n  7) as follows: intratracheal instillation of bleomycin (BLM, 7.5 IU/kg) was administered to group II. e third and fourth groups received BLM plus Stachys pilifera hydroalcoholic extract (SPHE) (300 mg/kg/day, gavage). Vitamin E (500 mg/kg/day, gavage) was given to group V in addition to BLM. After 14 days, the animals were euthanized to assess biochemical parameters and lung histopathology. Malondialdehyde (MDA), nitric oxide (NO), total thiol (TSH), and glutathione (GSH) levels were measured. In addition, hydroxyproline (HYP) levels along with histological changes in lung tissue were also assessed. Results. MDA, NO, and HYP elevations induced by BLM toxicity were significantly inhibited by SPHE (300 and 600 mg/kg), and Vit E. SPHE also significantly increased GSH and TSH levels in comparison to the BLM group.HPLC analyses showed the presence of thymol (55.47 ng/mL) and carvacrol (109.91 ng/mL) in SPHE as potential bioactive phenolic compounds. Conclusion. e results suggest that SPHE alleviates the development of BLM-induced pulmonary fibrosis by inhibiting the proliferation of fibroblasts mediated by antioxidant pathways. Other mechanisms underlying this Effect of SPHE need to be clarified through further research. 1. Introduction Idiopathic pulmonary fibrosis (IPF) is a chronic and pro- gressive lung disease characterized by proliferation and differentiation of fibroblasts and accumulation of extracel- lular matrix, primarily collagen, leading to irreversible damage to lung architecture [1, 2]. In some acute lung injury survivors, excessive alveolar injury stimulated the pro- liferation and repair system. As a result, many pulmonary interstitial cells and fibroblasts filled the damaged alveolar interstitium with neovascularization, causing excessive al- veolar repair and pulmonary fibrosis [3]. Due to the limited possibility of initial diagnosis and intervention, the average life of patients with IPF is 3 to 5 years after diagnosis. e incidence of IPF is estimated to range from 6.8 to 16.3 per 100,000 [4]. Although the cause of IPF is unknown, envi- ronmental pollution, viral infections, genetic factors, in- flammation, and oxidative stress are involved [5]. In addition, some drugs, such as bleomycin (BLM), metho- trexate, and nitrofurantoin, induce pulmonary fibrosis [6]. Lungs are more exposed to exogenous oxidants than other organs due to their unique position and function. Antiox- idants in epithelial lining fluid counteract these oxidants. However, this defense system can be disrupted by the overproduction of reactive oxygen species (ROS) and re- active nitrogen species (RNS) in disease states. In order to Hindawi Evidence-Based Complementary and Alternative Medicine Volume 2022, Article ID 6208102, 9 pages https://doi.org/10.1155/2022/6208102