Unraveling the protective mechanisms of Chuanfangyihao against acute lung injury: Insights from experimental validation

Fu,Hongfang; Liang,Xiao; Tan,Wanying; Hu,Xiaoyu

doi:10.3892/etm.2023.12234

Unraveling the protective mechanisms of Chuanfangyihao against acute lung injury: Insights from experimental validation

Authors:
- Hongfang Fu
- Xiao Liang
- Wanying Tan
- Xiaoyu Hu
View Affiliations

Affiliations: Infectious Disease Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China, School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 610072, P.R. China
Published online on: September 28, 2023 https://doi.org/10.3892/etm.2023.12234
Article Number: 535
Copyright: © Fu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Chuanfangyihao (CFYH) is an effective treatment for acute lung injury (ALI) in clinical practice; however, its underlying mechanism of action remains unclear. Therefore, the aim of the present study was to elucidate the pharmacological mechanism of action of CFYH in ALI through experimental validation. First, a rat model of ALI was established using lipopolysaccharide (LPS). Next, the pathological changes in the lungs of the rats and the pathological damage were scored. The wet/dry weight ratios were measured, and ROS content was detected using flow cytometry. ELISA was used to examine IL‑6, TNF‑α, IL‑1β, IL‑18, and LDH levels. Immunohistochemistry was used to detect Beclin‑1 and NLRP3 expression. Western blotting was performed to analyze the expression of HMGB1, RAGE, TLR4, NF‑κB p65, AMPK, p‑AMPK, mTOR, p‑mTOR, Beclin‑1, LC3‑II/I, p62, Bcl‑2, Bax, Caspase‑3, Caspase‑1, and GSDMD‑NT. The mRNA levels of HMGB1, RAGE, AMPK, mTOR, and HIF‑1α were determined using reverse transcription quantitative PCR. CFYH alleviated pulmonary edema and decreased the expression of IL‑6, TNF‑α, TLR4, NF‑κB p65, HMGB1/RAGE, ROS, and HIF‑1α. In addition, pretreatment with CFYH reversed ALI‑induced programmed cell death. In conclusion, CFYH alleviates LPS‑induced ALI, and these findings provide a preliminary clarification of the predominant mechanism of action of CFYH in ALI.

View Figures

View References

1	Monsel A, Zhu YG, Gudapati V, Lim H and Lee JW: Mesenchymal stem cell derived secretome and extracellular vesicles for acute lung injury and other inflammatory lung diseases. Expert Opin Biol Ther. 16:859–871. 2016.PubMed/NCBI View Article : Google Scholar
2	Wang LP and Tang XQ: Study on early warning signals of acute lung injury. Life Sci Res. 25:532–539. 2021.
3	Zambon M and Vincent JL: Mortality rates for patients with acute lung injury/ARDS have decreased over time. Chest. 133:1120–1127. 2008.PubMed/NCBI View Article : Google Scholar
4	Matthay MA, Zemans RL, Zimmerman GA, Arabi YM, Beitler JR, Mercat A, Herridge M, Randolph AG and Calfee CS: Acute respiratory distress syndrome. Nat Rev Dis Primers. 5(18)2019.PubMed/NCBI View Article : Google Scholar
5	Al Masry A, Boules ML, Boules NS and Ebied RS: Optimal method for selecting PEEP level in ALI/ARDS patients under mechanical ventilation. J Egypt Soc Parasitol. 42:359–372. 2012.PubMed/NCBI View Article : Google Scholar
6	Fan E, Del Sorbo L, Goligher EC, Hodgson CL, Munshi L, Walkey AJ, Adhikari NKJ, Amato MBP, Branson R, Brower RG, et al: An official American thoracic society/European society of intensive care medicine/society of critical care medicine clinical practice guideline: Mechanical ventilation in adult patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 195:1253–1263. 2017.PubMed/NCBI View Article : Google Scholar
7	Duggal A, Rezoagli E, Pham T, McNicholas BA, Fan E, Bellani G, Rubenfeld G, Pesenti AM and Laffey JG: LUNG SAFE Investigators and the ESICM Trials Group. Patterns of use of adjunctive therapies in patients with early moderate to severe ARDS: Insights from the LUNG SAFE study. Chest. 157:1497–1505. 2020.PubMed/NCBI View Article : Google Scholar
8	Rosenberg OA: Pulmonary surfactant preparations and surfactant therapy for ARDS in surgical intensive care (a literature review). Creat Surg Oncol. 9:50–65. 2019.
9	Badet M, Bayle F, Richard JC and Guérin C: Comparison of optimal positive end-expiratory pressure and recruitment maneuvers during lung-protective mechanical ventilation in patients with acute lung injury/acute respiratory distress syndrome. Respir Care. 54:847–854. 2009.PubMed/NCBI View Article : Google Scholar
10	Fukuda Y: Acute lung injury/acute respiratory distress syndrome: progress in diagnosis and treatment. Topics: I. Pathogenesis and pathophysiology: 4. Pathophysiology and histopathology of ALI/ARDS. Nihon Naika Gakkai Zasshi. 100:1536–1540. 2011.PubMed/NCBI View Article : Google Scholar : (In Japanese).
11	Zhang X, Zheng J, Yan Y, Ruan Z, Su Y, Wang J, Huang H, Zhang Y, Wang W, Gao J, et al: Angiotensin-converting enzyme 2 regulates autophagy in acute lung injury through AMPK/mTOR signaling. Arch Biochem Biophys. 672(108061)2019.PubMed/NCBI View Article : Google Scholar
12	Su JS, Liu ES and Zhao XM: Advances in the treatment of acute lung injury/acute respiratory distress syndrome with traditional chinese medicine. Jilin J Tradit Chin Med. (37)2019.(In Chinese).
13	Wang SB: Clinical characteristics and risk factors of severe pneumonia in 165 cases of novel coronavirus pneumonia. Chengdu University of TCM, 2021 (In Chinese).
14	Liu M: Effect of chuanfang no: L exposure on COVID-19 a retrospective cohort study based on propensity score matching. Chengdu University of TCM, 2021 (In Chinese).
15	Huang JH, Huang XH, Chen ZY, Zheng QS and Sun RY: Dose conversion among different animals and healthy volunteers in pharmacological study. Chin J Clin Pharmacol Ther. 9:1069–1072. 2004.
16	Arck PC: When 3 Rs meet a forth R: Replacement, reduction and refinement of animals in research on reproduction. J Reprod Immunol. 132:54–59. 2019.PubMed/NCBI View Article : Google Scholar
17	Kilkenny C, Browne W, Cuthill IC, Emerson M and Altman DG: NC3Rs Reporting Guidelines Working Group. Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol. 160:1577–1579. 2010.PubMed/NCBI View Article : Google Scholar
18	Wang GQ: The effect and mechanism of Lianggesan on fluid transportion in endotoxin acute lung injury tissue. So Med Univ, 2014 (In Chinese).
19	Wang XH, Yan SG, Hui Y, Shi J and Li JT: Mechanism of ephedrae Herba-rhei Radix et Rhizoma drug pair on treating acute lung injury based on alveolar macrophage M2 polarization. Chin Tradit Herbal Drugs. 53:2715–2722. 2022.(In Chinese).
20	Pei CX, Wang XM, Wu YC, Wang ZX, Huang DM, Yang Q, et al: Studies on mechanism of platycodin D inhibiting apoptosis and protecting acute lung injury via Bax/bcl-2/caspase-3 signaling pathway. Modernization Tradit Chin Med Materia Medica-World Sci and Tech. 23:3551–3558. 2021.(In Chinese).
21	Mikawa K, Nishina K, Takao Y and Obara H: ONO-1714, a nitric oxide synthase inhibitor, attenuates endotoxin-induced acute lung injury in rabbits. Anesth Analg. 97:1751–1755. 2003.PubMed/NCBI View Article : Google Scholar
22	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
23	Cumming G, Fidler F and Vaux DL: Error bars in experimental biology. J Cell Biol. 177:7–11. 2007.PubMed/NCBI View Article : Google Scholar
24	Huang X, Xiu H, Zhang S and Zhang G: The role of macrophages in the pathogenesis of ALI/ARDS. Mediators Inflamm. 2018(1264913)2018.PubMed/NCBI View Article : Google Scholar
25	Janz DR and Ware LB: Biomarkers of ALI/ARDS: Pathogenesis, discovery, and relevance to clinical trials. Semin Respir Crit Care Med. 34:537–548. 2013.PubMed/NCBI View Article : Google Scholar
26	Bos LD, Martin-Loeches I and Schultz MJ: ARDS: Challenges in patient care and frontiers in research. Eur Respir Rev. 27(170107)2018.PubMed/NCBI View Article : Google Scholar
27	Spieth PM and Zhang H: Pharmacological therapies for acute respiratory distress syndrome. Curr Opin Crit Care. 20:113–121. 2014.PubMed/NCBI View Article : Google Scholar
28	Zhao R, Wang B, Wang D, Wu B, Ji P and Tan D: Oxyberberine prevented lipopolysaccharide-induced acute lung injury through inhibition of mitophagy. Oxid Med Cell Longev. 2021(6675264)2021.PubMed/NCBI View Article : Google Scholar
29	Yu WY, Gao CX, Zhang HH, Wu YG and Yu CH: Herbal active ingredients: potential for the prevention and treatment of acute lung injury. Biomed Res Int. 2021(5543185)2021.PubMed/NCBI View Article : Google Scholar
30	Hao X, Liu Y, Zhou P, Jiang Q, Yang Z, Xu M, Liu S, Zhang S and Wang Y: Integrating network pharmacology and experimental validation to investigate the mechanisms of huazhuojiedu decoction to treat chronic atrophic gastritis. Evid Based Complement Alternat Med. 2020(2638362)2020.PubMed/NCBI View Article : Google Scholar
31	Li C: Multi-compound pharmacokinetic research on Chinese herbal medicines: Approach and methodology. Zhongguo Zhong Yao Za Zhi. 42:607–617. 2017.PubMed/NCBI View Article : Google Scholar : (In Chinese).
32	Li Z, Li WJ, Shang XY and Yu KY: Effect of Zhenwu Decoction on myocardial mitochondrial damage and cardiomyocyte apoptosis in heart failure rats by SIRT1 signaling pathway. Chin Arch Tradit Chin Med. 36:1062–1067. 2018.(In Chinese).
33	Wang YH, Li WJ and Li Z: Effect of serum containing Zhenwu Decoction on cardiomyocyte apoptosis and Bcl-2 and Bax protein expression induced by isoproterenol in Rats. Liaoning J Trad Chin Med. 45:1305–1308+1346. 2018.(In Chinese).
34	Yang PQ, Li QY and Fang S: Effect of Zhenwu Decoction combined with Benazepril on the curative effect and cardiopulmonary function of chronic pulmonary heart disease in acute stage. J Emerg Trad Chin Med. 31:854–856. 2022.(In Chinese).
35	Zhang Z, Zhao S, Han YP, Jin F, Shang JR, Wang JP and Fang CY: Effect of Buyang Huanwu Decoction on Keap1/Nrf2/HO-1 antioxidant signaling pathway in rats with idiopathic pulmonary fibrosis. Chin J Exp Trad Med formula. 1–10, (In Chinese).
36	National Pharmacopoeia Commission, Pharmacopoeia of the People's Republic of China (2020 Edition), China Medical Sciences Press, 2020.
37	Gao XM: Traditional Chinese pharmacy. China Traditional Chinese Medicine Press, 2002-1.
38	Li H, Li Y, Song C, Hu Y, Dai M, Liu B and Pan P: Neutrophil extracellular traps augmented alveolar macrophage pyroptosis via AIM2 inflammasome activation in LPS-induced ALI/ARDS. J Inflamm Res. 14:4839–4858. 2021.PubMed/NCBI View Article : Google Scholar
39	Song C, Li H, Li Y, Dai M, Zhang L, Liu S, Tan H, Deng P, Liu J, Mao Z, et al: NETs promote ALI/ARDS inflammation by regulating alveolar macrophage polarization. Exp Cell Res. 382(111486)2019.PubMed/NCBI View Article : Google Scholar
40	Chen H, Bai C and Wang X: The value of the lipopolysaccharide-induced acute lung injury model in respiratory medicine. Expert Rev Respir Med. 4:773–783. 2010.PubMed/NCBI View Article : Google Scholar
41	Fujita M, Kuwano K, Kunitake R, Hagimoto N, Miyazaki H, Kaneko Y, Kawasaki M, Maeyama T and Hara N: Endothelial cell apoptosis in lipopolysaccharide-induced lung injury in mice. Int Arch Allergy Immunol. 117:202–208. 1998.PubMed/NCBI View Article : Google Scholar
42	Fukatsu M, Ohkawara H, Wang X, Alkebsi L, Furukawa M, Mori H, Fukami M, Fukami SI, Sano T, Takahashi H, et al: The suppressive effects of Mer inhibition on inflammatory responses in the pathogenesis of LPS-induced ALI/ARDS. Sci Signal. 15(eabd2533)2022.PubMed/NCBI View Article : Google Scholar
43	Li N, Geng C, Hou S, Fan H and Gong Y: Damage-associated molecular patterns and their signaling pathways in primary blast lung injury: New research progress and future directions. Int J Mol Sci. 21(6303)2020.PubMed/NCBI View Article : Google Scholar
44	Wang G, Han D, Zhang Y, Xie X, Wu Y, Li S and Li M: A novel hypothesis: Up-regulation of HO-1 by activation of PPARγ inhibits HMGB1-RAGE signaling pathway and ameliorates the development of ALI/ARDS. J Thorac Dis. 5:706–710. 2013.PubMed/NCBI View Article : Google Scholar
45	Xu Y, Li J, Lin Z, Liang W, Qin L, Ding J, Chen S and Zhou L: Isorhamnetin alleviates airway inflammation by regulating the Nrf2/Keap1 pathway in a mouse model of COPD. Front Pharmacol. 13(860362)2022.PubMed/NCBI View Article : Google Scholar
46	Meyer A, Zoll J, Charles AL, Charloux A, de Blay F, Diemunsch P, Sibilia J, Piquard F and Geny B: Skeletal muscle mitochondrial dysfunction during chronic obstructive pulmonary disease: Central actor and therapeutic target. Exp Physiol. 98:1063–1078. 2013.PubMed/NCBI View Article : Google Scholar
47	Bouitbir J, Charles AL, Echaniz-Laguna A, Kindo M, Daussin F, Auwerx J, Piquard F, Geny B and Zoll J: Opposite effects of statins on mitochondria of cardiac and skeletal muscles: A ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1. Eur Heart J. 33:1397–1407. 2012.PubMed/NCBI View Article : Google Scholar
48	Yu J, Wang Y, Li Z, Dong S, Wang D, Gong L, Shi J, Zhang Y, Liu D and Mu R: Effect of heme oxygenase-1 on mitofusin-1 protein in LPS-induced ALI/ARDS in rats. Sci Rep. 6(36530)2016.PubMed/NCBI View Article : Google Scholar
49	Lee SY, Li MH, Shi LS, Chu H, Ho CW and Chang TC: Rhodiola crenulata extract alleviates hypoxic pulmonary edema in rats. Evid Based Complement Alternat Med. 2013(718739)2013.PubMed/NCBI View Article : Google Scholar
50	Balamurugan K: HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 138:1058–1066. 2016.PubMed/NCBI View Article : Google Scholar
51	Eltzschig HK and Carmeliet P: Hypoxia and inflammation. N Engl J Med. 364:656–665. 2011.PubMed/NCBI View Article : Google Scholar
52	Devraj G, Beerlage C, Brüne B and Kempf VA: Hypoxia and HIF-1 activation in bacterial infections. Microbes Infect. 19:144–156. 2017.PubMed/NCBI View Article : Google Scholar
53	Cummins EP, Keogh CE, Crean D and Taylor CT: The role of HIF in immunity and inflammation. Mol Aspects Med. 47-48:24–34. 2016.PubMed/NCBI View Article : Google Scholar
54	Zhao J, Jiang P, Guo S, Schrodi SJ and He D: Apoptosis, autophagy, NETosis, necroptosis, and pyroptosis mediated programmed cell death as targets for innovative therapy in rheumatoid arthritis. Front Immunol. 12(809806)2021.PubMed/NCBI View Article : Google Scholar
55	Van Opdenbosch N and Lamkanfi M: Caspases in cell death, inflammation, and disease. Immunity. 50:1352–1364. 2019.PubMed/NCBI View Article : Google Scholar
56	Kesavardhana S, Malireddi RKS and Kanneganti TD: Caspases in cell death, inflammation, and pyroptosis. Annu Rev Immunol. 38:567–595. 2020.PubMed/NCBI View Article : Google Scholar
57	Liu X, Gao C, Wang Y, Niu L, Jiang S and Pan S: BMSC-derived exosomes ameliorate LPS-induced acute lung injury by miR-384-5p-controlled alveolar macrophage autophagy. Oxid Med Cell Longev. 2021(9973457)2021.PubMed/NCBI View Article : Google Scholar
58	Wu D, Zhang H, Wu Q, Li F, Wang Y, Liu S and Wang J: Sestrin 2 protects against LPS-induced acute lung injury by inducing mitophagy in alveolar macrophages. Life Sci. 267(118941)2021.PubMed/NCBI View Article : Google Scholar
59	Zhao X, Yu Z, Lv Z, Meng L, Xu J, Yuan S and Fu Z: Activation of alpha-7 nicotinic acetylcholine receptors (α7nAchR) promotes the protective autophagy in LPS-induced acute lung injury (ALI) in vitro and in vivo. Inflammation. 42:2236–2245. 2019.PubMed/NCBI View Article : Google Scholar
60	Ning L, Wei W, Wenyang J, Rui X and Qing G: Cytosolic DNA-STING-NLRP3 axis is involved in murine acute lung injury induced by lipopolysaccharide. Clin Transl Med. 10(e228)2020.PubMed/NCBI View Article : Google Scholar
61	Klionsky DJ, Codogno P, Cuervo AM, Deretic V, Elazar Z, Fueyo-Margareto J, Gewirtz DA, Kroemer G, Levine B, Mizushima N, et al: A comprehensive glossary of autophagy-related molecules and processes. Autophagy. 6:438–448. 2010.PubMed/NCBI View Article : Google Scholar
62	Kim J, Kundu M, Viollet B and Guan KL: AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 13:132–141. 2011.PubMed/NCBI View Article : Google Scholar
63	Alers S, Löffler AS, Wesselborg S and Stork B: Role of AMPK-mTOR-Ulk1/2 in the regulation of autophagy: Cross talk, shortcuts, and feedbacks. Mol Cell Biol. 32:2–11. 2012.PubMed/NCBI View Article : Google Scholar
64	Tanida I, Ueno T and Kominami E: LC3 and autophagy. Methods Mol Biol. 445:77–88. 2008.PubMed/NCBI View Article : Google Scholar
65	Mizushima N and Levine B: Autophagy in human diseases. N Engl J Med. 383:1564–1576. 2020.PubMed/NCBI View Article : Google Scholar
66	Qu L, Chen C, He W, Chen Y, Li Y, Wen Y, Zhou S, Jiang Y, Yang X, Zhang R and Shen L: Glycyrrhizic acid ameliorates LPS-induced acute lung injury by regulating autophagy through the PI3K/AKT/mTOR pathway. Am J Transl Res. 11:2042–2055. 2019.PubMed/NCBI
67	Wei F, Jiang X, Gao HY and Gao SH: Liquiritin induces apoptosis and autophagy in cisplatin (DDP)-resistant gastric cancer cells in vitro and xenograft nude mice in vivo. Int J Oncol. 51:1383–1394. 2017.PubMed/NCBI View Article : Google Scholar
68	Dikic I and Elazar Z: Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 19:349–364. 2018.PubMed/NCBI View Article : Google Scholar
69	Masuda GO, Yashiro M, Kitayama K, Miki Y, Kasashima H, Kinoshita H, Morisaki T, Fukuoka T, Hasegawa T, Sakurai K, et al: Clinicopathological correlations of autophagy-related proteins LC3, beclin 1 and p62 in gastric cancer. Anticancer Res. 36:129–136. 2016.PubMed/NCBI
70	Fan TJ, Han LH, Cong RS and Liang J: Caspase family proteases and apoptosis. Acta Biochim Biophys Sin (Shanghai). 37:719–727. 2005.PubMed/NCBI View Article : Google Scholar
71	Zhang Y, Yang X, Ge X and Zhang F: Puerarin attenuates neurological deficits via Bcl-2/Bax/cleaved caspase-3 and Sirt3/SOD2 apoptotic pathways in subarachnoid hemorrhage mice. Biomed Pharmacother. 109:726–733. 2019.PubMed/NCBI View Article : Google Scholar
72	Choudhary GS, Al-Harbi S and Almasan A: Caspase-3 activation is a critical determinant of genotoxic stress-induced apoptosis. Methods Mol Biol. 1219:1–9. 2015.PubMed/NCBI View Article : Google Scholar
73	Schroder K and Tschopp J: The inflammasomes. Cell. 140:821–832. 2010.PubMed/NCBI View Article : Google Scholar
74	Zhang ZQ and Sun LL: Clinical significance of IL-1β and IL-18 in acute lung injury. Hainan Med J. 28:1954–1956. 2017.(In Chinese).
75	McVey MJ, Steinberg BE and Goldenberg NM: Inflammasome activation in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 320:L165–L178. 2021.PubMed/NCBI View Article : Google Scholar
76	Karmakar M, Minns M, Greenberg EN, Diaz-Aponte J, Pestonjamasp K, Johnson JL, Rathkey JK, Abbott DW, Wang K, Shao F, et al: N-GSDMD trafficking to neutrophil organelles facilitates IL-1β release independently of plasma membrane pores and pyroptosis. Nat Commun. 11(2212)2020.PubMed/NCBI View Article : Google Scholar
77	Shi J, Gao W and Shao F: Pyroptosis: Gasdermin-mediated programmed necrotic cell death. Trends Biochem Sci. 42:245–254. 2017.PubMed/NCBI View Article : Google Scholar
78	Liu Y, Zhou J, Luo Y, Li J, Shang L, Zhou F and Yang S: Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo. Chin Med. 16(127)2021.PubMed/NCBI View Article : Google Scholar
79	D'Arcy MS: Cell death: A review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 43:582–592. 2019.PubMed/NCBI View Article : Google Scholar
80	Tan S and Chen S: The mechanism and effect of autophagy, apoptosis, and pyroptosis on the progression of silicosis. Int J Mol Sci. 22(8110)2021.PubMed/NCBI View Article : Google Scholar
81	Ge Y, Xu X, Liang Q, Xu Y and Huang M: α-Mangostin suppresses NLRP3 inflammasome activation via promoting autophagy in LPS-stimulated murine macrophages and protects against CLP-induced sepsis in mice. Inflamm Res. 68:471–479. 2019.PubMed/NCBI View Article : Google Scholar
82	Wong WT, Li LH, Rao YK, Yang SP, Cheng SM, Lin WY, Cheng CC, Chen A and Hua KF: Repositioning of the β-blocker carvedilol as a novel autophagy inducer that inhibits the NLRP3 inflammasome. Front Immunol. 9(1920)2018.PubMed/NCBI View Article : Google Scholar
83	Guo R, Wang H and Cui N: Autophagy regulation on pyroptosis: Mechanism and medical implication in sepsis. Mediators Inflamm. 2021(9925059)2021.PubMed/NCBI View Article : Google Scholar
84	Fernández A, Ordóñez R, Reiter RJ, González-Gallego J and Mauriz JL: Melatonin and endoplasmic reticulum stress: Relation to autophagy and apoptosis. J Pineal Res. 59:292–307. 2015.PubMed/NCBI View Article : Google Scholar
85	Ma C, Zhang D, Ma Q, Liu Y and Yang Y: Arbutin inhibits inflammation and apoptosis by enhancing autophagy via SIRT1. Adv Clin Exp Med. 30:535–544. 2021.PubMed/NCBI View Article : Google Scholar
86	Nakahira K, Cloonan SM, Mizumura K, Choi AMK and Ryter SW: Autophagy: A crucial moderator of redox balance, inflammation, and apoptosis in lung disease. Antioxid Redox Signal. 20:474–494. 2014.PubMed/NCBI View Article : Google Scholar
87	Changle Z, Cuiling F, Feng F, Xiaoqin Y, Guishu W, Liangtian S and Jiakun Z: Baicalin inhibits inflammation of lipopolysaccharide-induced acute lung injury toll like receptor-4/myeloid differentiation primary response 88/nuclear factor-kappa B signaling pathway. J Tradit Chin Med. 42:200–212. 2022.PubMed/NCBI View Article : Google Scholar
88	Liu Z, Wang P, Lu S, Guo R, Gao W, Tong H, Yin Y, Han X, Liu T, Chen X, et al: Liquiritin, a novel inhibitor of TRPV1 and TRPA1, protects against LPS-induced acute lung injury. Cell Calcium. 88(102198)2020.PubMed/NCBI View Article : Google Scholar : (Epub ahead of print).