Quercetin

A total of 20 8-week-old female Wistar rats were obtained from Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and housed under a standard environment (temperature: 22 ± 2 °C, humidity: 55 ± 5%, 12/12-h light/ dark cycle) with free access to water and food. After acclimation for 1 week, all rats were randomly assigned into 4 groups (n = 5): control, BLM, BLM+quercetin (75 mg/kg), and BLM+quercetin (100 mg/kg) groups. The pulmonary fibrosis animal model was constructed by an intratracheal injection of 7.5 IU/kg BLM sulfate (Nippon Kayaku, Tokyo, Japan) dissolved in normal saline on day 7 as previously described (Kalantar et al. 2021) . The rats in the control group received the same volume of normal saline. Rats in the BLM+quercetin (75 mg/kg) and BLM+quercetin (100 mg/kg) groups were orally administrated with 75 mg/ kg and 100 mg/kg of quercetin (Sigma-Aldrich, St. Louis, MO, USA), respectively, from day 1 to day 28. All experimental protocols were approved by the Ethics Committee of Henan Provincial People's Hospital. About 24 h after the last administration, the rats were anesthetized with 50 mg/kg pentobarbital sodium and sacrificed by decapitation. Afterward, the lung tissues were harvested for subsequent analysis. All animal experiments were approved by the Ethics Committee of Henan Provincial People's Hospital.

Human breast carcinoma cell line MCF-7 (HTB-22) was purchased from American Type Culture Collection. Cells were grown in Dulbecco's Modified Eagle's medium (DMEM) (Sigma, Germany) supplemented with 10% fetal bovine serum FBS (Sigma, Germany), 1% L-glutamine (Sigma, Germany) and 1% penicillin/streptomycin (Sigma, Germany), and incubated in a humidified atmosphere containing 5% CO 2 at 37°C. Lonidamine and quercetin (Sigma, Germany) were dissolved in 0.01% dimethylsulfoxide, and cells were treated with 20-100 μM of quercetin, 0.01-10 μM of Lonidamine and according to the results of pure compounds, the cells were then treated with quercetin+Lonidamine combinations at 80/0.1, 80/1 and 80/5 μM concentrations.

Adult female Sprague-Dawley rats weighing 250-300 g were purchased from Beijing Haidian Thriving Experimental Animal Centre (Beijing, China). All procedures for these experiments complied with the guidelines of the Animal Ethics Committee of Hangzhou First People's Hospital (Hangzhou, China). Rats were housed in a standard animal room with a 12-h light/dark cycle.
One hundred rats were randomly assigned to four equal groups via a random number table : (1) sham group, where the rats only underwent laminectomy;
(2) SCI group, where rats underwent SCI; (3) SCI+Vehicle (Veh) group, where rats were intraperitoneally injected with a 1-ml vehicle (1% dimethyl sulfoxide in 1 ml sterile saline) immediately after SCI; and (4) SCI+Quercetin (Que) group, where 100 mg kg -1 Quercetin (Sigma-Aldrich, St Louis, MO, USA) in a 1-ml vehicle was intraperitoneally injected immediately after SCI. All animals in the SCI+Que and SCI+Veh groups were intraperitoneally injected with an equal volume of 100 mg kg -1 Quercetin or vehicle at 12-h intervals for 3 days. The dose and timing of Quercetin were based on previous researches. 15, 17 Different set of animals were used to undertake the analyses.