Table 1.
No. | Active Compound | Structure | Categories | Source | Experiment Model | Therapeutic Target | Ref. |
---|---|---|---|---|---|---|---|
1. | β-carbolines | Alkaloid | Arenaria kansuensis | In vivo: BLM-induced PF mice; in vitro: A549, RAW264 | Inhibiting NF-κB/p65 and EMT transition | [153] | |
2. | Coelonin | Dihydrophenanthrene | Bletilla striata | In vivo: BLM-induced PF rats | Anti-inflammatory and anti-fibrotic | [154] | |
3. | Celastrol | Triterpenoid | Tripterygium wilfordii and Celastrus regelii. | In vivo: BLM-induced PF rats; in vitro: A549 cells | TGF-β1/Smad2/3-mediated inhibition of EMT | [155] | |
4. | Magnesium isoglycyrrhizinate (MgIG) | Triterpenoid saponin glycoside | Glycyrrhiza glabra | In vivo: radiation-induced PF mice; in vitro: human fetal lung fibroblasts-1 (HFL1) | Inhibiting fibroblast differentiation via p38MAPK/Akt/Nox4 pathway | [156] | |
5. | Alpha-mangostin (α-MG) | Xanthone | Mangosteen (Garcinia mangostana) | In vivo: BLM-induced PF mice; in vitro: mouse primary lung fibroblasts (PLFs) | Inhibiting AMP-activated protein kinase | [157] | |
6. | Gambogic acid | Xanthonoid | Garcinia hanburyi | In vivo: BLM-induced PF rats. In vitro: HLF-1, HPMECs, and A549 cells | Reversing EMT and suppress TGF-β1/Smad3 pathway | [158] | |
7. | Salvianolic acid B (SAB) | Polyphenol | Salviae miltiorrhiza | In vivo: BLM-induced PF mice; in vitro: NIH/3T3 fibroblasts, MRC-5 fibroblasts, A549 cells | Inhibiting TGF-β signaling | [159] | |
8. | Curcumin and curcumol | Curcuminoid | Rhizomes of Curcuma zedoaria | in vitro: human lung fibroblast (HLF) | Inhibiting collagen deposition via autophagy mechanism | [160] | |
9. | Polydatin (PD) | Resveratrol glucoside | Polygonum cuspidatum | In vivo: MP-induced PF mice; in vitro: BEAS-2B cells | NLRP3 inflammasome and NF-κB pathway | [161] | |
10. | Gentiopicroside(GPS) | Secoiridoid glycoside | Gentianascabra, Gentiana lutea | In vivo: BLM-induced PF mice; in vitro: A549 cells | Anti-inflammatory and anti-fibrotic via TGF-β-1 | [162] | |
11. | Dioscin (Dio) | Steroidal saponin | Dioscorea nipponica Makino | In vivo: silica-induced PF mice; in vitro: RAW264.7 cell line, NIH-3T3 cell line | Inhibiting pro-inflammatory cytokines through ASK-1-p38/JNK signaling | [163] | |
12. | β-sitosterol | Phytosterols | stigma and style of maize (Zea mays) | In vitro: human lung adenocarcinoma epithelial cells, A549. | Suppression of EMT via the TGF-β1/Snail pathway | [164] | |
13. | Asiatic Acid | Triterpenoid | Centella Asiatica | In vivo: BLM-induced mice | Anti-inflammatory and anti-fibrotic | [165] | |
14. | Andrographolide | labdane diterpenoid lactone | Andrographis paniculata | In vivo: silica-induced pulmonary fibrosis mice | Anti-inflammatory and EMT transition | [166] | |
15. | zingerone (vanillylacetone) | Ketone | Zingiber officinale | In vivo: BLM-induced PF rats | Inhibiting NF-κB and MAPKs | [167] | |
16. | Tetrandrine (TET-HP-β-CD) | Alkaloid | Stephania tetrandra, S. Moore | In vivo: BLM-induced PF rats | Alleviating inflammation and fibrosis | [168] | |
17. | Juglanin | Flavonoid | Polygonum aviculare | In vivo: BLM-induced PF mice | Inhibition of stimulator of interferon genes (Sting) signaling | [168] | |
18. | Paeonol | Phenols | Paeonia suffruticosa | In vivo: BLM-induced PF mice | Inhibition of MAPKs/Smad3 signaling | [169] | |
19. | Honokiol | Neolignan | Magnolia officinalis | In vivo: BLM-induced PF mice | Inhibiting EMT and TGF-β/Smad signaling both in vitro and in vivo | [170] | |
20. | Phycocyanin | Phycobilins | Cyanobacteria | In vivo: BLM-induced PF mice | Attenuating PF via TLR2-MyD88-NFκB signaling | [171] | |
21. | Schisandrin B | Tanin | Schisandra chinensis | In vitro: A549 cells. BLM-induced PF mice | Attenuating BLM-induced PF via wingless/integrase-1 signaling | [172] | |
22. | Morin | Flavonoid | Maclura pomifera | In vivo: BLM-induced PF mice | Anti-oxidative and anti-inflammatory | [173] | |
23. | Berberine | Alkaloid | Chinese herbs | In vivo: BLM-induced PF mice | Activation of PPAR-γ. Expression of HGF in the colon. | [174] | |
24. | Zingerone | Phenolics, Ketone | Zingiber officinale | In vivo: BLM-induced PF rats | Modulating the expression of TGF-β1 and iNOS | [175] | |
25. | Glaucocalyxin A | Diterpenoid | Rabdosia japonica | In vivo: BLM-induced PF mice | Antagonism of leukocyte infiltration. Proinflammatory cytokine production. | [176] | |
26. | Parthenolide | Sesquiterpene | Tanacetum parthenium | In vivo: BLM-induced PF mice; in vitro: primary lung fibroblast, HFL1 cells, A549 cells | Attenuating BLM-induced PF via NF-κB/Snail signaling | [177] | |
27. | Oridonin | Diterpenoid | Rabdosia rubesecens | In vitro: MRC5 cells, in vivo: BLM-induced PF mice | Regulating TGFβ/Smad pathway | [178] | |
28. | Apigenin | Flavonoid | Vegetables | In vivo: BLM-induced PF mice | Anti-oxidative and PPARγ expression | [179] | |
29. | Salvianolic acid B and sodium tanshinone IIA | Phenolics | Salvia miltiorrhiza | In vitro: MR5 cells | Anti-inflammation and anti-fibrotic | [180] | |
30. | Nimbolide | Terpenoids | Azadirachta indica | In vivo: BLM-induced PF mice; in vitro: TGF-beta induced cell line | Autophagy regulator through attenuation of EMT pathway | [181] | |
31. | Perostilbene | Polyphenol | Blueberries | In vivo: LPS-induced PF mice | Preventing fibrosis by suppressing oxidative stress, inflammation, and apoptosis | [182] | |
32. | Scutellarein | Flavonoid | Scutellaria Lateriflora | In vivo: BLM-induced PF mice; in vitro: human pulmonary fibroblast | Affecting fibroblast differentiation, proliferation, and apoptosis | [183] | |
33. | Sulforaphane | Isothiocyanates | Cruciferous vegetables | In vivo: BLM-induced PF mice; in vitro: A549 cell, MRC-5 cell | Inhibiting EMT transition | [184] | |
34. | Salvianolic acid B | Phenolic acids | Salvia miltiorrhiza | In vivo: BLM-induced PF rats; in vitro: MRC-5 cells | Inhibiting myofibroblast trans-differentiation via upregulation of Nrf2 | [185] | |
35. | GHK peptide | Tripeptide | Plasma protein | In vivo: BLM-induced PF mice | Anti-oxidative and anti-inflammation | [186] | |
36. | Glycyl-L-histidyl-l-lysine (GHK)-Cu | Tripeptide | Plasma protein | In vivo: BLM-induced PF mice | Anti-oxidative and anti-inflammation | [187] | |
37. | Myricetin | Flavonoid | Commercially purchase | In vivo: BLM-induced PF mice; in vitro: human, mouse pulmonary epithelial cell, lung fibroblast cell | Inhibiting TGF-β1 via targeting HSP90β | [188] | |
38. | Wedelolactone | Coumarin | Eclipta prostrata | In vivo: BLM-induced PF mice | Activation of AMPK and regulating Raf-MAPK pathway | [189] | |
39. | Madecacassoside | Pentacyclic triterpenoid | Centella asiatica | In vivo: BLM-induced PF mice | Promoting hepatocyte growth factor in the colon via PPAR-γ | [190] | |
40. | Rutin | Flavonoid | Citrus plant | In vivo: BLM-induced PF mice | Inhibiting TGF-β1-α/SMA/Col I and III pathway | [191] | |
41. | Caffeine | Alkaloid | Tea, coffee, cacao, etc. | ex vivo: precision-cut lung slice model; in vitro: epithelial and lung fibroblast cells | Inhibiting TGF-β activation | [192] | |
42. | Emodin | Anthraquinone | Rhubarb | In vivo: BLM-induced PF rats; in vitro: alveolar epithelial cell | Inhibiting EMT transition, TGF-β1, p-Smad2/3 | [193] | |
43. | Rhapontin | Stilbene glycosides | Rheum genus/ Rhubarb | In vivo: BLM-induced PF mice; in vitro: primary lung fibroblast; LP-stimulated human THP-1 | Reducing collagen deposition, TGF-beta1, α-SMA, HIF-α expression | [194] | |
44. | Hydroxysafflor yellow A (HSYA) | Flavonoid | Carthamus tinctorius | In vivo: BLM-induced PF mice; in vitro: A549 cells | Reducing ECM deposition | [195] | |
45. | Alantolactone and isoalatolactone | Sesquiterpene lactone | Inula helenium L | In vivo: BLM-induced PF mice; in vitro: TGF-β1-induced human lung fibroblasts. | Inhibiting TGF-β1/Smad3 signaling pathway | [196] | |
46. | 4-methoxyphenethylamine | Biological amine | Pericarp of Citrus Reticulata | In vivo: BLM-induced PF rats model; in vitro: human embryonic lung fibroblast | Inhibiting TGF-β1 | [197] | |
47. | Galangin | Flavonoid | Galangal | In vivo: BLM-induced PF mice | Attenuating EMT and inflammatory damage | [198] | |
48. | Quercetin and Gallic acid | Flavonoid | Quercetin and Gallic acid | In vivo: BLM-induced PF rats | Anti-oxidative and anti-inflammatory | [199] | |
49. | Rosavin | Alcohol glycosides | Rhodiola rosea | In vivo: BLM-induced PF mice | Anti-fibrotic and anti-inflammatory | [200] | |
50. | Ascorbic Acid | Vitamin | Fruits | In vivo: PQ-induced PF | Reducing IL-6, IL-17a, TGF-beta | [201] | |
51. | Quercetin | Flavonoid | Diverse plant sources | Amiodarone intra-tracheal instillation | Antioxidant and anti-inflammatory | [202] |
The molecular structures of active compounds were generated from the online repository www.molview.org, accessed on 14 October 2021. Here, each color in molecules denotes each atom. Therefore, gray = carbon, white= hydrogen, red=oxygen, blue=nitrogen, and yellow=sulfur.