Pycnogenol®-Centellicum® supplementation improves lung fibrosis and post-COVID-19 lung healing.

BACKGROUND: The aim of this study was to evaluate the combination of Pycnogenol® (150 mg/day) (Horphag Research, London, UK) and Centella asiatica (Centellicum® 3×225 mg/day; Horphag Research) (PY-CE) for 8 months in subjects with sequelae of idiopathic interstitial pneumonia (IIP). Recently, post-COVID-19 lung disease is emerging with large numbers of patients left with chronic lung conditions. Considering the antifibrotic activity of the combination PY-CE, we also tested this supplementary management in post-COVID-19 lung patients. METHODS: Nineteen subjects with idiopathic interstitial pneumonia (IIP) were included in the study. High Resolution CT scans at inclusion confirmed the presence of lung fibrosis: 10 patients were treated with the Pycnogenol® Centellicum® combination and 9 subjects with standard management (SM) served as controls. Oxidative stress that was very high in all subjects at inclusion, decreased significantly in the supplement group (P<0.05). The Karnofsky Performance Scale Index significantly improved in the supplement group in comparison with controls (P<0.05). The symptoms (fatigue, muscular pain, dyspnea) were significantly lower after 8 months in supplemented patients (P<0.05) as compared with controls. RESULTS: At the end of the study, the small cystic lesions (honeycombing) and traction bronchiectasis were stable or in partial regression in 4 subjects in the supplemented group (vs. none in the control group) with a significant improvement in tissue edema in the supplemented subjects. On ultrasound lung scans the white (more echogenic) fibrotic component at inclusion was 18.5±2.2% in the images in controls vs. 19.4±2.7% in the supplement group. At the end of the study, there was no improvement in controls (18.9±2.5%) vs. a significant improvement in supplemented subjects (16.2±2.1%; P<0.05). In addition, 18 subjects with post-COVID-19 lung disease were included in the study; 10 patients were treated with the Pycnogenol® Centellicum® combination and evaluated after 4 weeks; 8 patients served as controls. Preliminary results show that symptoms associated with post-COVID-19 lung disease after 4 weeks were significantly improved with the supplement combination (P<0.05). Oxidative stress and the Karnofsky Performance Scale Index were significantly improved in the supplements group as compared with controls (P<0.05). CONCLUSIONS: According to these observations, Pycnogenol® controls and decreases edema and Centellicum® by modulating the apposition of collagen, slows down the development of irregular cicatrization, the keloidal scarring and fibrosis. More time is needed to evaluate this effect in a larger number of post-COVID-19 patients with lung disease. This disease has affected millions of subjects worldwide, leaving severe consequences. Pycnogenol® and Centellicum® may improve the residual clinical picture in post-COVID-19 lung disease (PCL) patients and may reduce the number of subjects evolving into lung fibrosis. The evolution from edema to fibrosis seems to be slower or attenuated with this supplement combination both in Idiopathic pulmonary fibrosis (IPF) and in PCL patients.

Effect and Mechanism of Qingfei Paidu Decoction in the Management of Pulmonary Fibrosis and COVID-19.

Qingfei Paidu decoction (QFPD) has been repeatedly recommended for the clinical treatment of novel coronavirus disease 2019 (COVID-19) in multiple provinces throughout China. A possible complication of COVID-19 lung involvement is pulmonary fibrosis, which causes chronic breathing difficulties and affects the patient's quality of life. Therefore, there is an important question regarding whether QFPD can alleviate the process of pulmonary fibrosis and its potential mechanisms. To explore this issue, this study demonstrated the anti-pulmonary fibrosis activity and mode of action of QFPD in vivo and in vitro pulmonary fibrosis models and network pharmacology. The results showed that QFPD effectively ameliorated the bleomycin-induced inflammation and collagen deposition in mice and significantly improved the epithelial-mesenchymal transition in pulmonary fibrosis in mice. In addition, QFPD inhibited bleomycin-induced M2 polarization of macrophages in pulmonary tissues. An in-depth study of the mechanism of QFPD in the treatment of pulmonary fibrosis based on network pharmacology and molecular simulation revealed that SRC was the main target of QFPD and sitosterol (a key compound in QFPD). QFPD and sitosterol regulate the EMT process and M2 polarization of macrophages by inhibiting the activation of SRC, thereby alleviating pulmonary fibrosis in mice. COVID-19 infection might produce severe fibrosis, and antifibrotic therapy with QFPD may be valuable in preventing severe neocoronavirus disease in patients with IPF, which could be a key factor explaining the role of QFPD in the treatment of COVID-19.

Adrenomedullin Ameliorates Pulmonary Fibrosis by Regulating TGF-ß-Smads Signaling and Myofibroblast Differentiation.

Pulmonary fibrosis is an irreversible, potentially fatal disease. Adrenomedullin (AM) is a multifunctional peptide whose activity is regulated by receptor activity-modifying protein 2 (RAMP2). In the present study, we used the bleomycin (BLM)-induced mouse pulmonary fibrosis model to investigate the pathophysiological significance of the AM-RAMP2 system in the lung. In heterozygous AM knockout mice (AM+/-), hydroxyproline content and Ashcroft scores reflecting the fibrosis severity were significantly higher than in wild-type mice (WT). During the acute phase after BLM administration, FACS analysis showed significant increases in eosinophil, monocyte, and neutrophil infiltration into the lungs of AM+/-. During the chronic phase, fibrosis-related molecules were upregulated in AM+/-. Notably, nearly identical changes were observed in RAMP2+/-. AM administration reduced fibrosis severity. In the lungs of BLM-administered AM+/-, the activation level of Smad3, a receptor-activated Smad, was higher than in WT. In addition, Smad7, an antagonistic Smad, was downregulated and microRNA-21, which targets Smad7, was upregulated compared to WT. Isolated AM+/- lung fibroblasts showed less proliferation and migration capacity than WT fibroblasts. Stimulation with TGF-ß increased the numbers of α-SMA-positive myofibroblasts, which were more prominent among AM+/- cells. TGF-ß-stimulated AM+/- myofibroblasts were larger and exhibited greater contractility and extracellular matrix production than WT cells. These cells were α-SMA (+), F-actin (+), and Ki-67(-) and appeared to be nonproliferating myofibroblasts (non-p-MyoFbs), which contribute to the severity of fibrosis. Our findings suggest that in addition to suppressing inflammation, the AM-RAMP2 system ameliorates pulmonary fibrosis by suppressing TGF-ß-Smad3 signaling, microRNA-21 activity and differentiation into non-p-MyoFbs.

Management of Fibrotic Hypersensitivity Pneumonitis.

Fibrotic hypersensitivity pneumonitis (fHP) is a chronic, often progressive fibrosing form of interstitial lung disease caused by inhaled antigenic exposures. fHP can lead to impaired respiratory function, reduced disease-related quality of life, and early mortality. Management of fHP should start with exposure remediation where possible, with systemic immunosuppression and antifibrotic therapy considered in patients with symptomatic or progressive disease. Nonpharmacologic and supportive management should be offered and, in cases of treatment-resistant, progressive illness, lung transplant should be considered.

Efficacy of the combination of modern medicine and traditional Chinese medicine in pulmonary fibrosis arising as a sequelae in convalescent COVID-19 patients: a randomized multicenter trial.

BACKGROUND: The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a significant number of mortalities worldwide. COVID-19 poses a serious threat to human life. The clinical manifestations of COVID-19 are diverse and severe and 20% of infected patients are reported to be in a critical condition. A loss in lung function and pulmonary fibrosis are the main manifestations of patients with the severe form of the disease. The lung function is affected, even after recovery, thereby greatly affecting the psychology and well-being of patients, and significantly reducing their quality of life. METHODS: Participants must meet the following simultaneous inclusion criteria: over 18 years of age, should have recovered from severe or critical COVID-19 cases, should exhibit pulmonary fibrosis after recovery, and should exhibit Qi-Yin deficiency syndrome as indicated in the system of traditional Chinese medicine (TCM). The eligible candidates will be randomized into treatment or control groups. The treatment group will receive modern medicine (pirfenidone) plus TCM whereas the control group will be administered modern medicine plus TCM placebo. The lung function index will be continuously surveyed and recorded. By comparing the treatment effect between the two groups, the study intend to explore whether TCM can improve the effectiveness of modern medicine in patients with pulmonary fibrosis arising as a sequelae after SARS-CoV-2 infection. DISCUSSION: Pulmonary fibrosis is one of fatal sequelae for some severe or critical COVID-19 cases, some studies reveal that pirfenidone lead to a delay in the decline of forced expiratory vital capacity, thereby reducing the mortality partly. Additionally, although TCM has been proven to be efficacious in treating pulmonary fibrosis, its role in treating pulmonary fibrosis related COVID-19 has not been explored. Hence, a multicenter, parallel-group, randomized controlled, interventional, prospective clinical trial has been designed and will be conducted to determine if a new comprehensive treatment for pulmonary fibrosis related to COVID-19 is feasible and if it can improve the quality of life of patients. TRIAL REGISTRATION: This multicenter, parallel-group, randomized controlled, interventional, prospective trial was registered at the Chinese Clinical Trial Registry (ChiCTR2000033284) on 26th May 2020 (prospective registered).

Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report.

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

Obesity-induced Vitamin D Deficiency Contributes to Lung Fibrosis and Airway Hyperresponsiveness.

Vitamin D (VitD) has pleiotropic effects. VitD deficiency is closely involved with obesity and may contribute to the development of lung fibrosis and aggravation of airway hyperresponsiveness (AHR). We evaluated the causal relationship between VitD deficiency and the lung pathologies associated with obesity. In vivo effects of VitD supplementation were analyzed using high-fat diet (HFD)-induced obese mice and TGF-ß1 (transforming growth factor-ß1) triple transgenic mice. Effects of VitD supplementation were also evaluated in both BEAS-2B and primary lung cells from the transgenic mice. Obese mice had decreased 25-OH VitD and VitD receptor expressions with increases of insulin resistance, renin and angiotensin-2 system (RAS) activity, and leptin. In addition, lung pathologies such as a modest increase in macrophages, enhanced TGF-ß1, IL-1ß, and IL-6 expression, lung fibrosis, and AHR were found. VitD supplementation to HFD-induced obese mice recovered these findings. TGF-ß1-overexpressing transgenic mice enhanced macrophages in BAL fluid, lung expression of RAS, epithelial-mesenchymal transition markers, AHR, and lung fibrosis. VitD supplementation also attenuated these findings in addition to the attenuation of the expressions of TGF-ß1, and phosphorylated Smad-2/3 in lung. Supplementing in vitro-stimulated BEAS-2B and primary lung cells with VitD inhibited TGF-ß1 expression, supporting the suppressive effect of VitD for TGF-ß1 expression. These results suggest that obesity leads to VitD deficiency and worsens insulin resistance while enhancing the expression of leptin, RAS, TGF-ß1, and proinflammatory cytokines. These changes may contribute to the development of lung fibrosis and AHR. VitD supplementation rescues these changes and may have therapeutic potential for asthma with obesity.

Treatment of pulmonary fibrosis in one convalescent patient with corona virus disease 2019 by oral traditional Chinese medicine decoction: A case report / 中西医结合学报

After one-month of oral treatment with traditional Chinese medicine decoction, without using other drugs, the lung inflammatory exudate, pulmonary fibrosis and quality of life of a 61-year-old female patient with corona virus disease 2019 (COVID-19) were significantly improved. No recurrence or deterioration of the patient's condition was found within seven weeks of treatment and follow-up, and no adverse events occurred, indicating that oral Chinese medicine decoction was able to improve the pulmonary inflammation and fibrosis in a patient recovering from COVID-19, but further research is still needed.

A Potential Bioelectromagnetic Method to Slow Down the Progression and Prevent the Development of Ultimate Pulmonary Fibrosis by COVID-19.

Introduction: Right now, we are facing a global pandemic caused by the coronavirus SARS-CoV-2 that causes the highly contagious human disease COVID-19. The number of COVID-19 cases is increasing at an alarming rate, more and more people suffer from it, and the death toll is on the rise since December 2019, when COVID-19 has presumably appeared. We need an urgent solution for the prevention, treatment, and recovery of the involved patients. Methods: Modulated electro-hyperthermia (mEHT) is known as an immuno-supportive therapy in oncology. Our proposal is to apply this method to prevent the progression of the disease after its identification, to provide treatment when necessary, and deliver rehabilitation to diminish the fibrotic-often fatal-consequences of the infection. Hypothesis: The effects of mEHT, which are proven for oncological applications, could be utilized for the inactivation of the virus or for treating the fibrotic consequences. The hypothesized mEHT effects, which could have a role in the antiviral treatment, it could be applied for viral-specific immune-activation and for anti-fibrotic treatments.

A review for natural polysaccharides with anti-pulmonary fibrosis properties, which may benefit to patients infected by 2019-nCoV.

Pulmonary fibrosis (PF) is a lung disease with highly heterogeneous and mortality rate, but its therapeutic options are now still limited. Corona virus disease 2019 (COVID-19) has been characterized by WHO as a pandemic, and the global number of confirmed COVID-19 cases has been more than 8.0 million. It is strongly supported for that PF should be one of the major complications in COVID-19 patients by the evidences of epidemiology, viral immunology and current clinical researches. The anti-PF properties of naturally occurring polysaccharides have attracted increasing attention in last two decades, but is still lack of a comprehensively understanding. In present review, the resources, structural features, anti-PF activities, and underlying mechanisms of these polysaccharides are summarized and analyzed, which was expected to provide a scientific evidence supporting the application of polysaccharides for preventing or treating PF in COVID-19 patients.

Glucosamine protects against radiation-induced lung injury via inhibition of epithelial-mesenchymal transition.

Radiotherapy is one of the most important treatments for chest tumours. Although there are plenty of strategies to prevent damage to normal lung tissues, it cannot be avoided with the emergence of radiation-induced lung injury. The purpose of this study was to investigate the potential radioprotective effects of glucosamine, which exerted anti-inflammatory activity in joint inflammation. In this study, we found glucosamine relieved inflammatory response and structural damages in lung tissues after radiation via HE staining. Then, we detected the level of epithelial-mesenchymal transition marker in vitro and in vivo, which we could clearly observe that glucosamine treatment inhibited epithelial-mesenchymal transition. Besides, we found glucosamine could inhibit apoptosis and promote proliferation of normal lung epithelial cells in vitro caused by radiation. In conclusion, our data showed that glucosamine alleviated radiation-induced lung injury via inhibiting epithelial-mesenchymal transition, which indicated glucosamine could be a novel potential radioprotector for radiation-induced lung injury.

Pharmacodynamic and pharmacokinetic assessment of pulmonary rehabilitation mixture for the treatment of pulmonary fibrosis.

Pulmonary rehabilitation mixture (PRM), a Chinese herbal medicine formula, has been used to treat pulmonary fibrosis for decades. In this study, we systematically evaluated the pharmacodynamic and pharmacokinetic performance of PRM. The pharmacodynamic results showed that PRM could improve the condition of CoCl2-stimulated human type II alveolar epithelial cells, human pulmonary microvascular endothelial cells, human lung fibroblasts and pulmonary fibrosis rats induced by bleomycin, PRM treatment reduced the expression of platelet-derived growth factor, fibroblast growth factor, toll-like receptor 4, high-mobility group box protein 1 and hypoxia-inducible factor 1α. In the pharmacokinetic study, an accurate and sensitive ultra-high performance liquid chromatography tandem mass spectrometry method was developed and validated for the simultaneous determination of calycosin, calycosin-7-O-glucoside, formononetin, ononin and mangiferin of PRM in the rat plasma for the first time. The method was then successfully applied to the comparative pharmacokinetic study of PRM in normal and pulmonary fibrosis rats. The five constituents could be absorbed in the blood after the oral administration of PRM and exhibited different pharmacokinetic behaviors in normal and pulmonary fibrosis rats. In summary, PRM exhibited a satisfactory pharmacodynamic and pharmacokinetic performance, which highlights PRM as a potential multi-target oral drug for the treatment of pulmonary fibrosis.

Treatment effects of the traditional Chinese medicine Shenks in bleomycin-induced lung fibrosis through regulation of TGF-beta/Smad3 signaling and oxidative stress.

Pulmonary fibrosis is a kind of devastating interstitial lung disease due to the limited therapeutic strategies. Traditional Chinese medicine (TCM) practices have put forth Shenks as a promising treatment approach. Here, we performed in vivo study and in vitro study to delineate the anti-fibrotic mechanisms behind Shenks treatment for pulmonary fibrosis. We found that regardless of the prophylactic or therapeutic treatment, Shenks was able to attenuate BLM-induced-fibrosis in mice, down regulate extracellular matrix genes expression, and reduce collagen production. The aberrantly high Smad3 phosphorylation levels and SBE activity in TGF-ß-induced fibroblasts were dramatically decreased as a result of Shenks treatment. At the same time, Shenks was able to increase the expression of antioxidant-related genes, including Gclc and Ec-sod, while reduce the transcription levels of oxidative-related genes, such as Rac1 and Nox4 demonstrated by both in vivo and in vitro studies. Further investigations found that Shenks could decrease the oxidative productions of protein (3-nitrotyrosine) and lipid (malondialdehyde) and increase GSH content both in bleomycin treated mouse lungs and TGF-ß stimulated fibroblasts, as well as inhibit the production of ROS stimulated by TGF-ß to fight against oxidative stress. Overall, Shenks inhibited fibrosis by blocking TGF-ß pathway and modulating the oxidant/antioxidant balance.

Mapping differential cellular protein response of mouse alveolar epithelial cells to multi-walled carbon nanotubes as a function of atomic layer deposition coating.

Carbon nanotubes (CNTs), a prototypical engineered nanomaterial, have been increasingly manufactured for a variety of novel applications over the past two decades. However, since CNTs possess fiber-like shape and cause pulmonary fibrosis in rodents, there is concern that mass production of CNTs will lead to occupational exposure and associated pulmonary diseases. The aim of this study was to use contemporary proteomics to investigate the mechanisms of cellular response in E10 mouse alveolar epithelial cells in vitro after exposure to multi-walled CNTs (MWCNTs) that were functionalized by atomic layer deposition (ALD). ALD is a method used to generate highly uniform and conformal nanoscale thin-film coatings of metals to enhance novel conductive properties of CNTs. We hypothesized that specific types of metal oxide coatings applied to the surface of MWCNTs by ALD would determine distinct proteomic profiles in mouse alveolar epithelial cells in vitro that could be used to predict oxidative stress and pulmonary inflammation. Uncoated (U)-MWCNTs were functionalized by ALD with zinc oxide (ZnO) to yield Z-MWCNTs or aluminum oxide (Al2O3) to yield A-MWCNTs. Significant differential protein expression was found in the following critical pathways: mTOR/eIF4/p70S6K signaling and Nrf-2 mediated oxidative stress response increased following exposure to Z-MWCNTs, interleukin-1 signaling increased following U-MWCNT exposure, and inhibition of angiogenesis by thrombospondin-1, oxidative phosphorylation, and mitochondrial dysfunction increased following A-MWCNT exposure. This study demonstrates that specific types of metal oxide thin film coatings applied by ALD produce distinct cellular and biochemical responses related to lung inflammation and fibrosis compared to uncoated MWCNT exposure in vitro.

Earthworm extract attenuates silica-induced pulmonary fibrosis through Nrf2-dependent mechanisms.

Silicosis is an occupational pulmonary fibrosis caused by inhalation of silica (SiO2) and there are no ideal drugs to treat this disease. Earthworm extract (EE), a natural nutrient, has been reported to have anti-inflammatory, antioxidant, and anti-apoptosis effects. The purpose of the current study was to test the protective effects of EE against SiO2-induced pulmonary fibrosis and to explore the underlying mechanisms using both in vivo and in vitro models. We found that treatment with EE significantly reduced lung inflammation and fibrosis and improved lung structure and function in SiO2-instilled mice. Further mechanistic investigations revealed that EE administration markedly inhibited SiO2-induced oxidative stress, mitochondrial apoptotic pathway, and epithelial-mesenchymal transition in HBE and A549 cells. Furthermore, we demonstrate that Nrf2 activation partly mediates the interventional effects of EE against SiO2-induced pulmonary fibrosis. Our study has identified EE to be a potential anti-oxidative, anti-inflammatory, and anti-fibrotic drug for silicosis.

Efficacy of aerobic physical retraining in a case of combined pulmonary fibrosis and emphysema syndrome: a case report.

INTRODUCTION: Combined pulmonary fibrosis and emphysema has recently been recognized as a syndrome but remains under-diagnosed. Neither clinical management nor therapeutic approaches have been clearly defined. Pulmonary rehabilitation has not been considered within the therapeutic options for combined pulmonary fibrosis and emphysema. In this case we explored the potential benefits of a specific aerobic physical retraining program in the management of combined pulmonary fibrosis and emphysema. CASE PRESENTATION: We describe the case of a 65-year-old Caucasian man with combined pulmonary fibrosis and emphysema and respiratory failure who was receiving long-term oxygen therapy. Our patient underwent physical retraining with moderate intensity aerobic and breathing exercises for four weeks. Clinical and motor tests, as well as questionnaires assessing quality of life and depression levels, were performed prior to and following the retraining. At the end of the retraining program a relevant reduction of long-term oxygen therapy requirement was registered; improvements in terms of physical performance, quality of life, and mood were observed in our patient but no change in respiratory parameters. CONCLUSIONS: A program of aerobic physical retraining appears to be beneficial to patients with combined pulmonary fibrosis and emphysema and may be considered as an additional therapeutic option.

Changes in the pulmonary function test after radioactive iodine treatment in patients with pulmonary metastases of differentiated thyroid cancer.

OBJECTIVE: Pulmonary function test (PFT) is a useful tool for an objective assessment of respiratory function. Impaired pulmonary function is critical for the survival and quality of life in patients with pulmonary metastases of solid cancers including thyroid cancer. This study aimed to evaluate clinical factors associated with severely impaired pulmonary function by serial assessment with PFT in patients with pulmonary metastasis of differentiated thyroid cancer (DTC) who received radioactive iodine treatment (RAIT). PATIENTS: This retrospective study enrolled 31 patients who underwent serial PFTs before and after RAIT for pulmonary metastasis of DTC. We evaluated the risk factors for severe impairment of pulmonary function. RESULTS: The median age of the patients was 44.1 years and 18 of them were female patients. Severe impairment of pulmonary function was observed in five patients (16%) after a median of three RAITs (cumulative I-131 activity = 20.4 GBq). These patients were older and more frequently had mild impairment of baseline pulmonary function, respiratory symptoms, or progressive disease compared with patients with stable pulmonary function. Neither cumulative dose nor number of RAIT was associated with decreased pulmonary function. Coexisting pulmonary diseases, presence of respiratory symptoms, and metastatic disease progression were significantly associated with severe decrease in forced vital capacity during follow-up (p =.047, p =.011, and p =.021, respectively). CONCLUSIONS: Pulmonary function was severely impaired during follow-up in some patients with pulmonary metastasis of DTC after a high-dose RAITs. Neither the number of RAIT nor the cumulative I-131 activity was associated with decreased pulmonary function. Serial PFT might be considered for some high-risk patients during follow-up.

Effects of lettuce glycoside B in ameliorating pulmonary fibrosis induced by irradiation exposure and its anti-oxidative stress mechanism.

The present research assessed the effects of lettuce glycoside B (LGB), a compound separated and purified from Pterocypsela laciniata, on irradiation-induced pulmonary fibrosis and explored the mechanism involved. Animal model of irradiation exposure inducing pulmonary fibrosis was established by Co irradiator. Rats were intraperitoneally treated with LGB (100, 200 and 400 mg/kg) once per day for a month. Lung index data were analyzed. The levels of fibrosis were assessed by hydroxyproline (Hyp) of pulmonary and lung tissue sections after irradiation exposure. Alveolitis and fibrosis levels were calculated from semi-quantitative analysis of hematoxylin and eosin and Masson's trichrome lung section staining. The serum levels of transforming growth factor ß1 (TGF-ß1), interleukin (IL)-6, and tumor necrosis factor-α (TNF-α) were also evaluated. Antioxidant enzymes of superoxide dismutase (SOD) were measured in serum. Moreover, we also measured serum malondialdehyde (MDA) levels, a marker of oxidative stress. Treatment with LGB significantly reduced mortality rates and lung index scores and MDA content, enhanced SOD and other antioxidant enzymes activity, and regulated serum levels of TGF-ß1, IL-6, and TNF-α. These results demonstrated that LGB significantly inhibited irradiation-induced pulmonary fibrosis. Furthermore, the results suggested promising clinical effect of LGB therapies for treating irradiation-induced pulmonary fibrosis.