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Monomeric compounds from natural products for the treatment of pulmonary fibrosis: a review

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Abstract

Pulmonary fibrosis (PF) is the end stage of lung injury and chronic lung diseases that results in diminished lung function, respiratory failure, and ultimately mortality. Despite extensive research, the pathogenesis of this disease remains elusive, and effective therapeutic options are currently limited, posing a significant clinical challenge. In addition, research on traditional Chinese medicine and naturopathic medicine is hampered by several complications due to complex composition and lack of reference compounds. Natural product monomers, possessing diverse biological activities and excellent safety profiles, have emerged as potential candidates for preventing and treating PF. The effective anti-PF ingredients identified can be generally divided into flavonoids, saponins, polysaccharides, and alkaloids. Specifically, these monomeric compounds can attenuate inflammatory response, oxidative stress, and other physiopathological processes of the lung through many signaling pathways. They also improve pulmonary factors. Additionally, they ameliorate epithelial–mesenchymal transition (EMT) and fibroblast–myofibroblast transdifferentiation (FMT) by regulating multiple signal amplifiers in the lungs, thereby mitigating PF. This review highlights the significant role of monomer compounds derived from natural products in reducing inflammation, oxidative stress, and inhibiting EMT process. The article provides comprehensive information and serves as a solid foundation for further exploration of new strategies to harness the potential of botanicals in the treatment of PF.

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Data availability

The data collected during the experiment are available from the corresponding authors upon reasonable request to support the plots within this paper and other findings of this study.

References

  • Adamcakova J, Balentova S, Barosova R, Hanusrichterova J, Mikolka P, Prso K, Mokry J, Tatarkova Z, Kalenska D, Mokra D (2023) Effects of green tea polyphenol epigallocatechin-3-gallate on markers of inflammation and fibrosis in a rat model of pulmonary silicosis. Int J Mol Sci 24:1857

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agackiran Y, Gul H, Gunay E, Akyurek N, Memis L, Gunay S, Sirin YS, Ide T (2012) The efficiency of proanthocyanidin in an experimental pulmonary fibrosis model: comparison with taurine. Inflammation 35:1402–1410

    Article  CAS  PubMed  Google Scholar 

  • Alharbi KS, Fuloria NK, Fuloria S, Rahman SB, Al-Malki WH, Javed S, Thangavelu L, Singh SK, Rama RA, Jha NK, Chellappan DK, Dua K, Gupta G (2021) Nuclear factor-kappa B and its role in inflammatory lung disease. Chem Biol Interact 345:109568

    Article  CAS  PubMed  Google Scholar 

  • Ameeramja J, Perumal E (2018) Possible modulatory effect of tamarind seed coat extract on fluoride-induced pulmonary inflammation and fibrosis in rats. Inflammation 41:886–895

    Article  CAS  PubMed  Google Scholar 

  • An L, Peng LY, Sun NY, Yang YL, Zhang XW, Li B, Liu BL, Li P, Chen J (2019) Tanshinone IIA activates nuclear factor-erythroid 2-related factor 2 to restrain pulmonary fibrosis via regulation of redox homeostasis and glutaminolysis. Antioxid Redox Signal 30:1831–1848

    Article  CAS  PubMed  Google Scholar 

  • Avila-Carrasco L, Majano P, Sanchez-Tomero JA, Selgas R, Lopez-Cabrera M, Aguilera A, Gonzalez MG (2019) Natural plants compounds as modulators of epithelial-to-mesenchymal transition. Front Pharmacol 10:715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bacchetti T, Morresi C, Bellachioma L, Ferretti G (2020) Antioxidant and pro-oxidant properties of carthamus tinctorius, hydroxy safflor yellow A, and safflor yellow A. Antioxidants 9:119

    Article  PubMed  PubMed Central  Google Scholar 

  • Behr J (2013) Evidence-based treatment strategies in idiopathic pulmonary fibrosis. Eur Respir Rev 22:163–168

    Article  PubMed  PubMed Central  Google Scholar 

  • Behr J, Prasse A, Kreuter M, Johow J, Rabe KF, Bonella F, Bonnet R, Grohe C, Held M, Wilkens H, Hammerl P, Koschel D, Blaas S, Wirtz H, Ficker JH, Neumeister W, Schonfeld N, Claussen M, Kneidinger N, Frankenberger M, Hummler S, Kahn N, Tello S, Freise J, Welte T, Neuser P, Gunther A, Investigators R (2021) Pirfenidone in patients with progressive fibrotic interstitial lung diseases other than idiopathic pulmonary fibrosis (RELIEF): a double-blind, randomised, placebo-controlled, phase 2b trial. Lancet Respir Med 9:476–486

    Article  CAS  PubMed  Google Scholar 

  • Bergman ME, Davis B, Phillips MA (2019) Medically useful plant terpenoids: biosynthesis, occurrence, and mechanism of action. Molecules 24:3961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bi Z, Wang Y, Zhang W (2021) A comprehensive review of tanshinone IIA and its derivatives in fibrosis treatment. Biomed Pharmacother 137:111404

    Article  CAS  PubMed  Google Scholar 

  • Burman A, Tanjore H, Blackwell TS (2018) Endoplasmic reticulum stress in pulmonary fibrosis. Matrix Biol 68–69:355–365

    Article  PubMed  PubMed Central  Google Scholar 

  • Chauhan PS, Dash D, Singh R (2017) Intranasal curcumin inhibits pulmonary fibrosis by modulating matrix metalloproteinase-9 (MMP-9) in ovalbumin-induced chronic asthma. Inflammation 40:248–258

    Article  CAS  PubMed  Google Scholar 

  • Chen H, Chen Q, Jiang CM, Shi GY, Sui BW, Zhang W, Yang LZ, Li ZY, Liu L, Su YM, Zhao WC, Sun HQ, Li ZZ, Fu Z (2018) Triptolide suppresses paraquat induced idiopathic pulmonary fibrosis by inhibiting TGFB1-dependent epithelial mesenchymal transition. Toxicol Lett 284:1–9

    Article  CAS  PubMed  Google Scholar 

  • Chitra P, Saiprasad G, Manikandan R, Sudhandiran G (2013) Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-kappaB dependant TGF-beta activation: a biphasic experimental study. Toxicol Lett 219:178–193

    Article  CAS  PubMed  Google Scholar 

  • Chitra P, Saiprasad G, Manikandan R, Sudhandiran G (2015) Berberine inhibits Smad and non-Smad signaling cascades and enhances autophagy against pulmonary fibrosis. J Mol Med (berl) 93:1015–1031

    Article  CAS  PubMed  Google Scholar 

  • Cho IH, Choi YJ, Gong JH, Shin D, Kang MK, Kang YH (2015) Astragalin inhibits autophagy-associated airway epithelial fibrosis. Respir Res 16:51

    Article  PubMed  PubMed Central  Google Scholar 

  • Cui X, Sun X, Lu F, Jiang X (2018) Baicalein represses TGF-beta1-induced fibroblast differentiation through the inhibition of miR-21. Toxicol Appl Pharmacol 358:35–42

    Article  CAS  PubMed  Google Scholar 

  • Divya T, Velavan B, Sudhandiran G (2018) Regulation of transforming growth factor-β/smad-mediated epithelial-mesenchymal transition by celastrol provides protection against bleomycin-induced pulmonary fibrosis. Basic Clin Pharmacol Toxicol 123:122–129

    Article  CAS  PubMed  Google Scholar 

  • El-Baba C, Baassiri A, Kiriako G, Dia B, Fadlallah S, Moodad S, Darwiche N (2021) Terpenoids’ anti-cancer effects: focus on autophagy. Apoptosis 26:491–511

    Article  CAS  PubMed  Google Scholar 

  • Feng F, Cheng P, Xu S, Li N, Wang H, Zhang Y, Wang W (2020) Tanshinone IIA attenuates silica-induced pulmonary fibrosis via Nrf2-mediated inhibition of EMT and TGF-beta1/Smad signaling. Chem Biol Interact 319:109024

    Article  CAS  PubMed  Google Scholar 

  • Gao Y, Lu J, Zhang Y, Chen Y, Gu Z, Jiang X (2013) Baicalein attenuates bleomycin-induced pulmonary fibrosis in rats through inhibition of miR-21. Pulm Pharmacol Ther 26:649–654

    Article  CAS  PubMed  Google Scholar 

  • Guan R, Wang X, Zhao X, Song N, Zhu J, Wang J, Wang J, Xia C, Chen Y, Zhu D, Shen L (2016) Emodin ameliorates bleomycin-induced pulmonary fibrosis in rats by suppressing epithelial-mesenchymal transition and fibroblast activation. Sci Rep 6:35696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guan S, Liu Q, Han F, Gu W, Song L, Zhang Y, Guo X, Xu W (2017) Ginsenoside Rg1 ameliorates cigarette smoke-induced airway fibrosis by suppressing the TGF-β1/smad pathway in vivo and in vitro. Biomed Res Int 2017:1–12

    Google Scholar 

  • Guo K, Chen J, Chen Z, Luo G, Yang S, Zhang M, Hong J, Zhang L, Chen C (2020) Triptolide alleviates radiation-induced pulmonary fibrosis via inhibiting IKKbeta stimulated LOX production. Biochem Biophys Res Commun 527:283–288

    Article  CAS  PubMed  Google Scholar 

  • Haak AJ, Tan Q, Tschumperlin DJ (2018) Matrix biomechanics and dynamics in pulmonary fibrosis. Matrix Biol 73:64–76

    Article  CAS  PubMed  Google Scholar 

  • Hasan M, Paul NC, Paul SK, Saikat ASM, Akter H, Mandal M, Lee S-S (2022) Natural product-based potential therapeutic interventions of pulmonary fibrosis. Molecules 27:1481

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He H, Tang H, Gao L, Wu Y, Feng Z, Lin H, Wu T (2015) Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis in rats. Mol Med Rep 11:4190–4196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hewlett JC, Kropski JA, Blackwell TS (2018) Idiopathic pulmonary fibrosis: epithelial-mesenchymal interactions and emerging therapeutic targets. Matrix Biol 71–72:112–127

    Article  PubMed  PubMed Central  Google Scholar 

  • Hosseini S, Imenshahidi M, Hosseinzadeh H, Karimi G (2018) Effects of plant extracts and bioactive compounds on attenuation of bleomycin-induced pulmonary fibrosis. Biomed Pharmacother 107:1454–1465

    Article  CAS  PubMed  Google Scholar 

  • Huang X, He Y, Chen Y, Wu P, Gui D, Cai H, Chen A, Chen M, Dai C, Yao D, Wang L (2016) Baicalin attenuates bleomycin-induced pulmonary fibrosis via adenosine A2a receptor related TGF-beta1-induced ERK1/2 signaling pathway. BMC Pulm Med 16:132

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang XT, Liu W, Zhou Y, Hao CX, Zhou Y, Zhang CY, Sun CC, Luo ZQ, Tang SY (2019) Dihydroartemisinin attenuates lipopolysaccharide-induced acute lung injury in mice by suppressing NF-κB signaling in an Nrf2-dependent manner. Int J Mol Med 44:2213–2222

    CAS  PubMed  PubMed Central  Google Scholar 

  • Impellizzeri D, Talero E, Siracusa R, Alcaide A, Cordaro M, Maria ZJ, Bruschetta G, Crupi R, Esposito E, Cuzzocrea S, Motilva V (2015) Protective effect of polyphenols in an inflammatory process associated with experimental pulmonary fibrosis in mice. Br J Nutr 114:853–865

    Article  CAS  PubMed  Google Scholar 

  • Javad-Mousavi SA, Hemmati AA, Mehrzadi S, Hosseinzadeh A, Houshmand G, Rashidi NMR, Mehrabani M, Goudarzi M (2016) Protective effect of Berberis vulgaris fruit extract against Paraquat-induced pulmonary fibrosis in rats. Biomed Pharmacother 81:329–336

    Article  CAS  PubMed  Google Scholar 

  • Ji Y, Dou Y-N, Zhao Q-W, Zhang J-Z, Yang Y, Wang T, Xia Y-F, Dai Y, Wei Z-F (2016) Paeoniflorin suppresses TGF-β mediated epithelial-mesenchymal transition in pulmonary fibrosis through a Smad-dependent pathway. Acta Pharmacol Sin 37:794–804

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jin M, Sun C-Y, Pei C-Q, Wang L, Zhang P-C (2013) Effect of safflor yellow injection on inhibiting lipopolysaccharide-induced pulmonary inflammatory injury in mice. Chin J Integr Med 19:836–843

    Article  CAS  PubMed  Google Scholar 

  • Kim KK, Sheppard D, Chapman HA (2018) TGF-β1 signaling and tissue fibrosis. Cold Spring Harb Perspect Biol 10:a022293

    Article  PubMed  PubMed Central  Google Scholar 

  • Kinnula VL, Fattman CL, Tan RJ, Oury TD (2005) Oxidative stress in pulmonary fibrosis: a possible role for redox modulatory therapy. Am J Respir Crit Care Med 172:417–422

    Article  PubMed  PubMed Central  Google Scholar 

  • Kolosova I, Nethery D, Kern JA (2011) Role of Smad2/3 and p38 MAP kinase in TGF-β1-induced epithelial-mesenchymal transition of pulmonary epithelial cells. J Cell Physiol 226:1248–1254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lan X, Zhao J, Zhang Y, Chen Y, Liu Y, Xu F (2020) Oxymatrine exerts organ- and tissue-protective effects by regulating inflammation, oxidative stress, apoptosis, and fibrosis: from bench to bedside. Pharmacol Res 151:104541

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Kinniry PA, Arguiri E, Serota M, Kanterakis S, Chatterjee S, Solomides CC, Javvadi P, Koumenis C, Cengel KA, Christofidou-Solomidou M (2010) Dietary curcumin increases antioxidant defenses in lung, ameliorates radiation-induced pulmonary fibrosis, and improves survival in mice. Radiat Res 173:590–601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li L, Hou X, Xu R, Liu C, Tu M (2017) Research review on the pharmacological effects of astragaloside IV. Fundam Clin Pharmacol 31:17–36

    Article  CAS  PubMed  Google Scholar 

  • Li XH, Xiao T, Yang JH, Qin Y, Gao JJ, Liu HJ, Zhou HG (2018) Parthenolide attenuated bleomycin-induced pulmonary fibrosis via the NF-kappaB/Snail signaling pathway. Respir Res 19:111

    Article  PubMed  PubMed Central  Google Scholar 

  • Li J, Liu J, Yue W, Xu K, Cai W, Cui F, Li Z, Wang W, He J (2020a) Andrographolide attenuates epithelial-mesenchymal transition induced by TGF-β1 in alveolar epithelial cells. J Cell Mol Med 24:10501–10511

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li X, Mo N, Li Z (2020b) Ginsenosides: potential therapeutic source for fibrosis-associated human diseases. J Ginseng Res 44:386–398

    Article  PubMed  Google Scholar 

  • Liu M-W, Liu R, Wu H-Y, Li Y-Y, Su M-X, Dong M-N, Zhang W, Qian C-Y (2015) Radix puerariae extracts ameliorate paraquat-induced pulmonary fibrosis by attenuating follistatin-like 1 and nuclear factor erythroid 2p45-related factor-2 signalling pathways through downregulation of miRNA-21 expression. BMC Complement Altern Med 16:1–5

    Article  Google Scholar 

  • Liu B, Cao B, Zhang D, Xiao N, Chen H, Li GQ, Peng SC, Wei LQ (2016a) Salvianolic acid B protects against paraquat-induced pulmonary injury by mediating Nrf2/Nox4 redox balance and TGF-beta1/Smad3 signaling. Toxicol Appl Pharmacol 309:111–120

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Chu H, Ma Y, Wu T, Qian F, Ren X, Tu W, Zhou X, Jin L, Wu W, Wang J (2016b) Salvianolic acid B attenuates experimental pulmonary fibrosis through inhibition of the TGF-β signaling pathway. Sci Rep 6:27610

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Q, Shi X, Tang L, Xu W, Jiang S, Ding W, Feng Q, Chu H, Ma Y, Li Y, Lu J, Pu W, Zhou X, Jin L, Wang J, Wu W (2018) Salvianolic acid B attenuates experimental pulmonary inflammation by protecting endothelial cells against oxidative stress injury. Eur J Pharmacol 840:9–19

    Article  CAS  PubMed  Google Scholar 

  • Liu H, Yu H, Cao Z, Gu J, Pei L, Jia M, Su M (2019a) Kaempferol modulates autophagy and alleviates silica-induced pulmonary fibrosis. DNA Cell Biol 38:1418–1426

    Article  CAS  PubMed  Google Scholar 

  • Liu MW, Su MX, Tang DY, Hao L, Xun XH, Huang YQ (2019b) Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression. BMC Pulm Med 19:35

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu T, Xu L, Wang C, Chen K, Xia Y, Li J, Li S, Wu L, Feng J, Xu S, Wang W, Lu X, Fan X, Mo W, Zhou Y, Zhao Y, Guo C (2019c) Alleviation of hepatic fibrosis and autophagy via inhibition of transforming growth factor-β 1/Smads pathway through shikonin. J Gastroenterol Hepatol 34:263–276

    Article  CAS  PubMed  Google Scholar 

  • Lu P, Li J, Liu C, Yang J, Peng H, Xue Z, Liu Z (2022) Salvianolic acid B dry powder inhaler for the treatment of idiopathic pulmonary fibrosis. Asian J Pharm Sci 17:447–461

    Article  PubMed  PubMed Central  Google Scholar 

  • Luppi F, Kalluri M, Faverio P, Kreuter M, Ferrara G (2021) Idiopathic pulmonary fibrosis beyond the lung: understanding disease mechanisms to improve diagnosis and management. Respir Res 22:109

    Article  PubMed  PubMed Central  Google Scholar 

  • Ma X, Chen R, Liu X, Xie J, Si K, Duan L (2013) Effects of matrine on JAK-STAT signaling transduction pathways in bleomycin-induced pulmonary fibrosis. Afr J Tradit Complement Altern Med 10:442–448

    CAS  PubMed  PubMed Central  Google Scholar 

  • Millar MW, Fazal F, Rahman A (2022) Therapeutic targeting of NF-κB in acute lung injury: a double-edged sword. Cells 11:3317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moss BJ, Ryter SW, Rosas IO (2022) Pathogenic mechanisms underlying idiopathic pulmonary fibrosis. Annu Rev Pathol 17:515–546

    Article  CAS  PubMed  Google Scholar 

  • Ng-Blichfeldt J-P, de Jong T, Kortekaas RK, Wu X, Lindner M, Guryev V, Hiemstra PS, Stolk J, Königshoff M, Gosens R (2019) TGF-β activation impairs fibroblast ability to support adult lung epithelial progenitor cell organoid formation. Am J Physiol-Lung Cell Mol Physiol 317:L14–L28

    Article  CAS  PubMed  Google Scholar 

  • Nie Y, Yang Y, Zhang J, Cai G, Chang Y, Chai G, Guo C (2017) Shikonin suppresses pulmonary fibroblasts proliferation and activation by regulating Akt and p38 MAPK signaling pathways. Biomed Pharmacother 95:1119–1128

    Article  CAS  PubMed  Google Scholar 

  • Nie Y, Zhang D, Qian F, Wu Y (2019) Baccatin III ameliorates bleomycin-induced pulmonary fibrosis via suppression of TGF-beta1 production and TGF-beta1-induced fibroblast differentiation. Int Immunopharmacol 74:105696

    Article  CAS  PubMed  Google Scholar 

  • Nikbakht J, Hemmati AA, Arzi A, Mansouri MT, Rezaie A, Ghafourian M (2015) Protective effect of gallic acid against bleomycin-induced pulmonary fibrosis in rats. Pharmacol Rep 67:1061–1067

    Article  CAS  PubMed  Google Scholar 

  • Otoupalova E, Smith S, Cheng G, Thannickal VJ (2020) Oxidative stress in pulmonary fibrosis. Compr Physiol 10:509–547

    Article  PubMed  Google Scholar 

  • Pang X, Shao L, Nie X, Yan H, Li C, Yeo AJ, Lavin MF, Xia Q, Shao H, Yu G, Jia Q, Peng C (2021) Emodin attenuates silica-induced lung injury by inhibition of inflammation, apoptosis and epithelial-mesenchymal transition. Int Immunopharmacol 91:107277

    Article  CAS  PubMed  Google Scholar 

  • Parimon T, Yao C, Stripp BR, Noble PW, Chen P (2020) Alveolar epithelial type II Cells as drivers of lung fibrosis in idiopathic pulmonary fibrosis. Int J Mol Sci 21:2269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pekovic-Vaughan V, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GTJ, Fukada Y, Meng Q-J (2014) The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis. Genes Dev 28:548–560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng L, Wen L, Shi Q-F, Gao F, Huang B, Meng J, Hu C-P, Wang C-M (2020) Scutellarin ameliorates pulmonary fibrosis through inhibiting NF-κB/NLRP3-mediated epithelial–mesenchymal transition and inflammation. Cell Death Dis 11:978

    Article  PubMed  PubMed Central  Google Scholar 

  • Peng D, Fu M, Wang M, Wei Y, Wei X (2022) Targeting TGF-β signal transduction for fibrosis and cancer therapy. Mol Cancer 21:104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Phan THG, Paliogiannis P, Nasrallah GK, Giordo R, Eid AH, Fois AG, Zinellu A, Mangoni AA, Pintus G (2021) Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis. Cell Mol Life Sci 78:2031–2057

    Article  CAS  PubMed  Google Scholar 

  • Piao XM, Huo Y, Kang JP, Mathiyalagan R, Zhang H, Yang DU, Kim M, Yang DC, Kang SC, Wang YP (2020) Diversity of ginsenoside profiles produced by various processing technologies. Molecules 25:4390

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qian W, Cai X, Qian Q, Zhang W, Wang D (2018) Astragaloside<scp>IV</scp>modulates<scp>TGF</scp>-β1-dependent epithelial-mesenchymal transition in bleomycin-induced pulmonary fibrosis. J Cell Mol Med 22:4354–4365

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Resende VQ, Reis-Goes KH, Finato AC, de Fátima Almeida-Donanzam D, dos Santos AR, Perico J, Amorim BC, Venturini J (2022) Combined silymarin and cotrimoxazole therapy attenuates pulmonary fibrosis in experimental paracoccidioidomycosis. J Fungi 8:1010

    Article  CAS  Google Scholar 

  • Rodriguez LR, Bui SN, Beuschel RT, Ellis E, Liberti EM, Chhina MK, Cannon B, Lemma M, Nathan SD, Grant GM (2019) Curcumin induced oxidative stress attenuation by N-acetylcysteine co-treatment: a fibroblast and epithelial cell in-vitro study in idiopathic pulmonary fibrosis. Mol Med 25:1–12

    Article  CAS  Google Scholar 

  • Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola M (2016) Pirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: a systematic review and meta-analysis. Pulm Pharmacol Ther 40:95–103

    Article  CAS  PubMed  Google Scholar 

  • Ruby H, Rebecca J, Jean T (2016) EMT: 2016. Cell 166:21–45

    Article  Google Scholar 

  • Ryu C, Sun H, Gulati M, Herazo-Maya JD, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G (2017) Extracellular mitochondrial DNA is generated by fibroblasts and predicts death in idiopathic pulmonary fibrosis. Am J Respirat Crit Care Med 196:1571–1581

    Article  CAS  Google Scholar 

  • Savin IA, Zenkova MA, Sen’kova AV (2022) Pulmonary fibrosis as a result of acute lung inflammation: molecular mechanisms, relevant in vivo models, prognostic and therapeutic approaches. Int J Mol Sci 23:14959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scott KA, Cox PB, Njardarson JT (2022) Phenols in pharmaceuticals: analysis of a recurring motif. J Med Chem 65:7044–7072

    Article  CAS  PubMed  Google Scholar 

  • Shaikh SB, Prabhakar Bhandary Y (2020) Effect of curcumin on IL-17A mediated pulmonary AMPK kinase/cyclooxygenase-2 expressions via activation of NFκB in bleomycin-induced acute lung injury in vivo. Int Immunopharmacol 85:106676

    Article  CAS  PubMed  Google Scholar 

  • Slika H, Mansour H, Wehbe N, Nasser SA, Iratni R, Nasrallah G, Shaito A, Ghaddar T, Kobeissy F, Eid AH (2022) Therapeutic potential of flavonoids in cancer: ROS-mediated mechanisms. Biomed Pharmacother 146:112442

    Article  CAS  PubMed  Google Scholar 

  • Sriram N, Kalayarasan S, Sudhandiran G (2009) Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm Pharmacol Ther 22:221–236

    Article  CAS  PubMed  Google Scholar 

  • Stewart AG, Thomas B, Koff J (2018) TGF-beta: master regulator of inflammation and fibrosis. Respirology 23:1096–1097

    Article  PubMed  Google Scholar 

  • Sun Q, Liu Q, Zhou X, Wang X, Li H, Zhang W, Yuan H, Sun C (2022) Flavonoids regulate tumor-associated macrophages—from structure-activity relationship to clinical potential (Review). Pharmacol Res 184:106419

    Article  CAS  PubMed  Google Scholar 

  • Turgut NH, Kara H, Elagoz S, Deveci K, Gungor H, Arslanbas E (2016) The protective effect of naringin against bleomycin-induced pulmonary fibrosis in wistar rats. Pulm Med 2016:1–12

    Article  Google Scholar 

  • Veith C, Drent M, Bast A, van Schooten FJ, Boots AW (2017) The disturbed redox-balance in pulmonary fibrosis is modulated by the plant flavonoid quercetin. Toxicol Appl Pharmacol 336:40–48

    Article  CAS  PubMed  Google Scholar 

  • Wang L, Jin M, Zang B-X, Wu Y (2011) Inhibitory effect of safflor yellow on pulmonary fibrosis. Biol Pharm Bull 34:511–516

    Article  CAS  PubMed  Google Scholar 

  • Wang C, Song X, Li Y, Han F, Gao S, Wang X, Xie S, Lv C (2013) Low-dose paclitaxel ameliorates pulmonary fibrosis by suppressing TGF-β1/Smad3 pathway via miR-140 upregulation. PLoS ONE 8:e70725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, He F, Chen L, Li Q, Jin S, Zheng H, Lin J, Zhang H, Ma S, Mei J, Yu J (2018a) Resveratrol inhibits pulmonary fibrosis by regulating miR-21 through MAPK/AP-1 pathways. Biomed Pharmacother 105:37–44

    Article  CAS  PubMed  Google Scholar 

  • Wang Z-L, Wang S, Kuang Y, Hu Z-M, Qiao X, Ye M (2018b) A comprehensive review on phytochemistry, pharmacology, and flavonoid biosynthesis of Scutellaria baicalensis. Pharm Biol 56:465–484

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Wu Q, Ding L, Song S, Li Y, Shi L, Wang T, Zhao D, Wang Z, Li X (2021a) Therapeutic effects and molecular mechanisms of bioactive compounds against respiratory diseases: traditional chinese medicine theory and high-frequency use. Front Pharmacol 12:734450

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Li X, Chen H, Han L, Ji X, Wang Q, Wei L, Miu Y, Wang J, Mao J, Zhang Z (2021b) Resveratrol alleviates bleomycin-induced pulmonary fibrosis via suppressing HIF-1α and NF-κB expression. Aging 13:4605–4616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Hu K, Cai X, Yang B, He Q, Wang J, Weng Q (2022a) Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis. Acta Pharm Sin B 12:18–32

    Article  PubMed  Google Scholar 

  • Wang L, Zhu T, Feng D, Li R, Zhang C (2022b) Polyphenols from chinese herbal medicine: molecular mechanisms and therapeutic targets in pulmonary fibrosis. Am J Chin Med 50:1063–1094

    Article  PubMed  Google Scholar 

  • Wei X, Chen Y, Huang W (2018) Ginsenoside Rg1 ameliorates liver fibrosis via suppressing epithelial to mesenchymal transition and reactive oxygen species production in vitro and in vivo. BioFactors 44:327–335

    Article  CAS  Google Scholar 

  • Wei Y, Sun L, Liu C, Li L (2023) Naringin regulates endoplasmic reticulum stress and mitophagy through the ATF3/PINK1 signaling axis to alleviate pulmonary fibrosis. Naunyn-Schmiedeberg’s Arch Pharmacol 396:1155–1169

    Article  CAS  Google Scholar 

  • Wollin L, Wex E, Pautsch A, Schnapp G, Hostettler KE, Stowasser S, Kolb M (2015) Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis. Eur Respir J 45:1434–1445

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Li Y, Wang Y, Xu D, Li C, Liu M, Sun X, Li Z (2014) Tanshinone IIA attenuates bleomycin-induced pulmonary fibrosis via modulating angiotensin-converting enzyme 2/ angiotensin-(1–7) axis in rats. Int J Med Sci 11:578–586

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiao Y, Zhou L, Zhang T, Qin C, Wei P, Luo L, Luo L, Huang G, Chen A, Liu G (2020) Anti-fibrosis activity of quercetin attenuates rabbit tracheal stenosis via the TGF-beta/AKT/mTOR signaling pathway. Life Sci 250:117552

    Article  CAS  PubMed  Google Scholar 

  • Xue Z, Zhao F, Sang X, Qiao Y, Shao R, Wang Y, Gao S, Fan G, Zhu Y, Yang J (2021) Combination therapy of tanshinone <scp>IIA</scp> and puerarin for pulmonary fibrosis via targeting <scp>IL6-JAK2-STAT3</scp> / <scp>STAT1</scp> signaling pathways. Phytother Res 35:5883–5898

    Article  CAS  PubMed  Google Scholar 

  • Yang T, Wang J, Pang Y, Dang X, Ren H, Liu Y, Chen M, Shang D (2016) Emodin suppresses silica-induced lung fibrosis by promoting Sirt1 signaling via direct contact. Mol Med Rep 14:4643–4649

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang DX, Qiu J, Zhou HH, Yu Y, Zhou DL, Xu Y, Zhu MZ, Ge XP, Li JM, Lv CJ, Zhang HQ, Yuan WD (2018) Dihydroartemisinin alleviates oxidative stress in bleomycin-induced pulmonary fibrosis. Life Sci 205:176–183

    Article  CAS  PubMed  Google Scholar 

  • Yao J, Fang X, Zhang C, Yang Y, Wang D, Chen Q, Zhong G (2020) Astragaloside IV attenuates hypoxia-induced pulmonary vascular remodeling via the Notch signaling pathway. Mol Med Rep 23:1

    Article  Google Scholar 

  • You H, Wei L, Sun W-L, Wang L, Yang Z-L, Liu Y, Zheng K, Wang Y, Zhang W-J (2014) The green tea extract epigallocatechin-3-gallate inhibits irradiation-induced pulmonary fibrosis in adult rats. Int J Mol Med 34:92–102

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You X, Jiang X, Zhang C, Jiang K, Zhao X, Guo T, Zhu X, Bao J, Dou H (2022) Dihydroartemisinin attenuates pulmonary inflammation and fibrosis in rats by suppressing JAK2/STAT3 signaling. Aging 14:1110–1127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu H, Lin L, Zhang Z, Zhang H, Hu H (2020) Targeting NF-κB pathway for the therapy of diseases: mechanism and clinical study. Signal Transduct Target Ther 5:209

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yuan L, Zou C, Ge W, Liu Y, Hu B, Wang J, Lin B, Li Y, Ma E (2020) A novel cathepsin L inhibitor prevents the progression of idiopathic pulmonary fibrosis. Bioorg Chem 94:103417

    Article  CAS  PubMed  Google Scholar 

  • Zhan H, Huang F, Ma W, Zhao Z, Zhang H, Zhang C (2016) Protective effect of ginsenoside Rg1 on bleomycin-induced pulmonary fibrosis in rats: involvement of caveolin-1 and TGF-beta1 signal pathway. Biol Pharm Bull 39:1284–1292

    Article  CAS  PubMed  Google Scholar 

  • Zhang YE (2017) Non-smad signaling pathways of the TGF-β family. Cold Spring Harbor Perspect Biol 9:022129

    Article  Google Scholar 

  • Zhang YQ, Liu YJ, Mao YF, Dong WW, Zhu XY, Jiang L (2015) Resveratrol ameliorates lipopolysaccharide-induced epithelial mesenchymal transition and pulmonary fibrosis through suppression of oxidative stress and transforming growth factor-beta1 signaling. Clin Nutr 34:752–760

    Article  CAS  PubMed  Google Scholar 

  • Zhang Z, Qu J, Zheng C, Zhang P, Zhou W, Cui W, Mo X, Li L, Xu L, Gao J (2018) Nrf2 antioxidant pathway suppresses Numb-mediated epithelial-mesenchymal transition during pulmonary fibrosis. Cell Death Dis 9:83

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Lu P, Qin H, Zhang Y, Sun X, Song X, Liu J, Peng H, Liu Y, Nwafor EO, Li J, Liu Z (2021) Traditional Chinese medicine combined with pulmonary drug delivery system and idiopathic pulmonary fibrosis: Rationale and therapeutic potential. Biomed Pharmacother 133:111072

    Article  CAS  PubMed  Google Scholar 

  • Zhao H, Li C, Li L, Liu J, Gao Y, Mu K, Chen D, Lu A, Ren Y, Li Z (2020) Baicalin alleviates bleomycin-induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway. Mol Med Rep 21:2321–2334

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Huang X, Hecker L, Kurundkar D, Kurundkar A, Liu H, Jin TH, Desai L, Bernard K, Thannickal VJ (2013) Inhibition of mechanosensitive signaling in myofibroblasts ameliorates experimental pulmonary fibrosis. J Clin Invest 123:1096–1108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou YX, Zhang H, Peng C (2014) Puerarin: a review of pharmacological effects. Phytother Res 28:961–975

    Article  CAS  PubMed  Google Scholar 

  • Zhou Y, Li M, Shen T, Yang T, Shi G, Wei Y, Chen C, Wang D, Wang Y, Zhang T (2022) Celastrol targets cullin-associated and neddylation-dissociated 1 to prevent fibroblast-myofibroblast transformation against pulmonary fibrosis. ACS Chem Biol 17:2734–2743

    Article  CAS  PubMed  Google Scholar 

  • Zhu T, Zhang W, Xiao M, Chen H, Jin H (2013) Protective role of andrographolide in bleomycin-induced pulmonary fibrosis in mice. Int J Mol Sci 14:23581–23596

    Article  PubMed  PubMed Central  Google Scholar 

  • Zou J, Gao P, Hao X, Xu H, Zhan P, Liu X (2018) Recent progress in the structural modification and pharmacological activities of ligustrazine derivatives. Eur J Med Chem 147:150–162

    Article  CAS  PubMed  Google Scholar 

  • Zou M, Zhang G, Zou J, Liu Y, Liu B, Hu X, Cheng Z (2020) Inhibition of the ERK1/2-ubiquitous calpains pathway attenuates experimental pulmonary fibrosis in vivo and in vitro. Exp Cell Res 391:111886

    Article  CAS  PubMed  Google Scholar 

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Funding

Innovative Research Group Project of the National Natural Science Foundation of China, 82173462, Fu Gao, 81972968, yanyong yang.

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Authors and Affiliations

  1. University of Shanghai for Science and Technology, 516, Jungong Road, Shanghai, 200093, China

    Zhuqing Li & Fu Gao

  2. Basic Medical Center for Pulmonary Disease, Naval Medical University, 800, Xiangyin Road, Shanghai, 200433, China

    Yanyong Yang & Fu Gao

  3. Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, 800, Xiangyin Road, Shanghai, 200433, People’s Republic of China

    Yanyong Yang & Fu Gao

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  1. Zhuqing Li
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  2. Yanyong Yang
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  3. Fu Gao
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Li, Z., Yang, Y. & Gao, F. Monomeric compounds from natural products for the treatment of pulmonary fibrosis: a review. Inflammopharmacol (2024). https://doi.org/10.1007/s10787-024-01485-0

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