Here is a three-part list of herbs that may potentially help you. Do keep in mind that this is not the final version and there will be future updates. The first part is composed of herbs that are very safe to use and are some of the best antifibrotics you could find. The second part includes herbs that are toxic in nature or have some serious side effects or contraindications. Please do your own research before using them, these should be avoided as there are far better alternatives. If you are so desperate and can’t get anything else, only use them in low doses. I have tested most of the herbs in the first two parts, so I have some experience with them. The last part includes herbs that I have no experience with, but studies have shown their potential benefits against fibrosis. This last part might include a lot of toxic herbs, so once again, be wary.

Many of the herbs listed here are also active against lung and renal fibrosis, so there are some very universal antifibrotics. Since most of the herbs on this list are Chinese herbs, there are a lot of Chinese references that I haven’t cited yet as it’s a bit challenging to not only translate the articles, but also input all the data for references.

Personal favorites that are non-toxic or only come with minor side effects depending on your situation

Salvia miltiorrhiza (root)

  • One of the best herbs for fibrosis in general
  • Reduces levels TGF-ß1, procollagen I and III; inhibits α-SMA, CTGF, TIMP-1 1,2
  • Increases GSH in liver and decreases lipid peroxidation 3
  • Inhibits hepatic stellate cell activation 4

Ligusticum chuanxiong (root)

  • Two phtalides, namely Z,Z′-6,8′,7,3′-diligustilide and levistolide A inhibit proliferation of HSCs 5
  • Tetramethylpyrazine inhibits activation of HSCs, reduces inflammation associated with liver fibrosis, alleviates histopathological changes, decreases levels of liver enzymes and reduces collagen deposition 6

Prunella vulgaris/asiatica (flower spikes)

  • Inhibits activation of HSCs; reduces formation of fibrous septa and liver lesions; promotes ECM degradation 7
  • Reduces elevated ALT, AST, type III collagen and hyaluronic acid 7
  • Regulates expression of α-SMA, TGF-ß1, Smad2, TIMP-1, MMP-2, MMP-13 7
  • Decreases serum IL-4, IL-8, TNF-α and PDGF 7

Phoenix dactylifera (fruit/seed)

  • This is the flesh of the date fruit or its seed, so enjoy one of the best dried fruits for fibrosis even though it’s full of carbohydrates
  • Reduces TGF-ß1, collagen deposition, inactivates hepatic stellate cells 8
  • Decreases serum levels of ALT, FasL; improves histopathology of liver and alleviates cirrhosis 9
  • Hepatoprotective; restores SOD, GST; reduces incidence of liver lesions 10

Astragalus membranaceus (root)

  • Astragalosides decrease TGF-ß1, TNF-α, levels of hepatic enzymes, hyaluronic acid, procollagen type III, hydroxyproline and MDA; they also restore SOD and GSH-px levels 11

Zingiber officinale (root)

  • Decreases levels of hepatic enzymes, MDA, total bilirubin 12
  • Increases levels of GSH, SOD, SDH, LDH, G-6-Pase, AP and 5’NT 12
  • Protects against fibrosis through modulation of TGF-β1/Smad3 and NF-ĸB/IĸB pathways 13

Gynostemma pentaphyllum (leaf)

  • Saponins (gypenosides) and triterpenes isolated from this plant inhibit HSC activation 14,15
  • Gypenosides reduce levels of TGF-ß1, TGF-ßR1, ALT, AST, α-SMA, collagen type I, hydroxyproline and thus reduce deposition of collagen 16

Rabdosia rubescens/japonica (leaf)

  • Oridonin, one of the main constituents, inhibits HSC proliferation and fibrogenesis through decrease in α-SMA, ECM type I collagen and fibronectin 17

Curcuma zedoaria (root)

  • Contains curcumol and ß-elemenes which possess antifibrotic properties 18
  • Inhibits growth of hepatic myofibroblast cells and HSCs 19

Curcuma wenyujin (root)

  • Contains ß-elemenes with antifibrotic properties
  • Inhibits proliferation and activation of HSCs via blocking TGF-ß/Smad pathways, and regulation of MMP-2 and TIMP-1 20

Lonicera japonica (flower)

  • Sweroside inhibits COL1 and TIMP1 and upregulates miR-29a 21

Schisandra chinensis (fruit/seed)

  • Not as effective as other herbs on this list since seeds are hard to get and fruits have antinutrient compounds, but at least it’s not toxic
  • Downregulates TGF-ß1, α-SMA, COL1A1, AST, ALT; alleviates collagen deposition in liver parenchyma 22

Nigella sativa (seed)

  • Thymoquinone downregulates several fibrosis-related genes, α-SMA, type I collagen, TIMP-1, expression of TLR4 23–25

Panax ginseng (root)

  • Ginsenoside Rb1 inhibits TGF-ß1, MMP-2, TIMP1, type I/III collagen, α-SMA 26
  • 20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol (intestinal metabolite of ginsenosides Rb1 and Rb2) induces apoptosis of HSCs 27

Panax notoginseng (root)

  • Saponins attenuate collagen deposition, downregulate ALT, AST, TGF-ß1, TNF-α, IL-6 28

Lycium barbarum (fruit/leaf)

  • Polysaccharides downregulate AST, ALT, ALP, α-SMA, TNF-α, MCP-1, IL-1ß, TLR4, TLR2, NF-κB 29

Epimedium saggitatum (leaf)

  • Icaritin reduces the number of activated HSCs, normalizes levels of AST, ALT, hydroxyproline and type I collagen 30

Alpinia officinarum (root)

  • Galangin decreases lipid peroxidation and inhibits HSC activation and proliferation through reduction of MDA, hydroxyproline, α-SMA and TGF-ß1 31

Patrinia scabiosaefolia/villosa (leaf)

  • Alleviates liver fibrosis and promotes hepatocyte regeneration

Drynaria fortunei (root)

  • Naringenin reduces accumulation of ECM, fibronectin, PAI-1, collagen Iα1 and inhibits Smad3 through TGF-ß signalling 32
  • Naringin inhibits HSC activation, modulates PI3K/Akt pathway, and decreases deposition of collagen and fibronectin 33,34

Herbs that may come with some side effects, but might offer some relief depending on the dosage

  1. Angelica sinensis (root) {estrogenic, irritating} 35
  2. Coptis chinensis (root) {may interfere with bilirubin metabolism and increase its serum levels} 36
  3. Phellodendron amurense/chinensis (bark) {may interfere with bilirubin metabolism and increase its serum levels} 36
  4. Moringa oleifera (seed) {potential hepatotoxicity} 37
  5. Platycodon grandiflorum (root) {potential nephrotoxicity} 38–40
  6. Paeonia lactiflora/rubra (root) {contains compounds that bind to testosterone receptors} 41,42
  7. Artemisia annua (leaf) {potential hepatotoxicity, neurotoxicity} 43,44
  8. Artemisia iwayomogi (leaf) {potential hepatotoxicity, neurotoxicity} 45–47
  9. Rheum palmatum (root) {potential hepatotoxicity, nephrotoxicity} 48–50
  10. Aloe vera {potential hepatotoxicity, nephrotoxicity} 51
  11. Scutellaria baicalensis (root) {potential hepatotoxicity} 52–55
  12. Paris polyphylla (root) {potential hepatotoxicity} 56–58
  13. Stephania tetrandra (root) {potential nephrotoxicity} 59–63
  14. Curcuma longa (root) {potential reproductive toxicity} 64–66
  15. Ganoderma lucidum (mushroom) {potential hepatotoxicity} 67–69
  16. Cordyceps sinensis (mushroom) {potential nephrotoxicity} 70,71
  17. Pueraria lobata (root) {estrogenic} 72–75
  18. Evodia rutaecarpa {potential neuro-/hepato-/nephrotoxicity) 76
  19. Artemisia capillaris {potential hepatotoxicity} 46,77–79
  20. Sophora flavescens {potential hepatotoxicity, nephrotoxicity} 80,81
  21. Glycyrrhiza glabra {potential neuro-/hepato-/nephrotoxicity) 82–84
  22. Leonurus cardiaca/ heterophylla {potential nephrotoxicity} 85
  23. Gardenia jasmoides {potential hepatotoxicity} 18,86
  24. Sparganium stoloniferum {estrogenic} 87
  25. Amygdalin containing herbs 88
  26. Andrographis paniculata {potential hepato-/nephrotoxicity} 89
  27. Cnidium monnieri {irritating} 90
  28. Cuscuta chinensis {potential nephrotoxicity} 91
  29. Lindera obtusiloba 92
  30. Magnolia officinalis (bark) {potential nephrotoxicity} 93

Herbs that I have no experience with and may or may not be toxic + they might be hard to get

  1. Anoectochilus formosanus 94,95
  2. Toona sinensis (leaf) 96
  3. Cyclea peltata (root) 97
  4. Micromeria croatica 98
  5. Cichorium glandulosum 99
  6. Graptopetalum paraguayense 100,101
  7. Allium senescens 102
  8. Sedum sarmentosum 103,104
  9. Siraitia grosvenori (fruit) 105
  10. Helicteres angustifolia 106
  11. Pronephrium penangianum 107
  12. Momordica charantia (fruit) 108
  13. Prosopis juliflora (leaf) 109
  14. Polygonum plebeium 110
  15. Acanthus ilicifolius 111
  16. Mesona procumbens 112
  17. Angelica gigas 113
  18. Boesenbergia rotunda 114,115
  19. Pinnigorgia sp. 116
  20. Penthorum chinense 117
  21. Forsythia suspensa (fruit) 118
  22. Brassica alba (seed) 119
  23. Scabiosa comosa (flower) 120
  24. Gypsophila elegans 121,122
  25. Sanguis Draxonis 123
  26. Garcinia mangostana 124,125
  27. Fraxinus rhynchophylla 126
  28. Swertia mussotii 127
  29. Dictamnus dasycarpus (bark) {potential hepatotoxicity} 128
  30. Terminalia bellirica (fruit) {potential hepatotoxicity} 129,130
  31. Sedum mexicanum 131
  32. Orostachys japonicas 132,133
  33. Ampelopsis brevipedunculata 134,135
  34. Saururus chinensis 136,137
  35. Plantago asiatica (seed) 138
  36. Spatholobus suberectus {estrogenic}
  37. Mallotus pugen/apelta
  38. Hovenia dulcis (fruit) {potential hepatotoxicity} 139,140

References

1. Wasser, S., Ho, J. M. S., Ang, H. K. & Tan, C. E. L. Salvia miltiorrhiza reduces experimentally-induced hepatic fibrosis in rats. J. Hepatol. 29, 760–771 (1998).

2. Hsu, Y.-C. et al. Antifibrotic effects of Salvia miltiorrhiza on dimethylnitrosamine-intoxicated rats. J. Biomed. Sci. 12, 185–195 (2005).

3. Lee, T.-Y., Chiu, J.-H., Wang, G.-J. & Lin, H.-C. Long-term administration of Salvia miltiorrhiza ameliorates carbon tetrachloride-induced hepatic fibrosis in rats. JPP 55 (2003). doi:10.1211/0022357022098

4. Nan, J.-X. et al. Anti-fibrotic effects of a hot-water extract from Salvia miltiorrhiza roots on liver fibrosis induced by biliary obstruction in rats. J. Pharm. Pharmacol. JPP 53, 197–204 (2001).

5. Lee, T.-F., Lin, Y.-L. & Huang, Y.-T. Studies on Antiproliferative Effects of Phthalides from Ligusticum chuanxiong in Hepatic Stellate Cells. Planta Med. 73, 527–534 (2007).

6. Wu, X. et al. Tetramethylpyrazine reduces inflammation in liver fibrosis and inhibits inflammatory cytokine expression in hepatic stellate cells by modulating NLRP3 inflammasome pathway. IUBMB Life 67, 312–321 (2015).

7. Hu, Y.-X. et al. Antihepatofibrotic Effects of Aqueous Extract of Prunella vulgaris on Carbon Tetrachloride-Induced Hepatic Fibrosis in Rats. Planta Med. 82, 97–105 (2015).

8. Al-Rasheed, N. M. et al. Aqueous Date Flesh or Pits Extract Attenuates Liver Fibrosis via Suppression of Hepatic Stellate Cell Activation and Reduction of Inflammatory Cytokines, Transforming Growth Factor- β 1 and Angiogenic Markers in Carbon Tetrachloride-Intoxicated Rats. Evid. Based. Complement. Alternat. Med. 2015, 247357 (2015).

9. A. Assirey, E., M. Wagih, H. & N. Mahran, H. Phoenix dactylifera L. Extract Diminished Apoptotic Effect in Cirrhotic Liver of a Rat Model. Int. J. Pharmacol. 15, 92–101 (2019).

10. Abdelaziz, D. H. A. & Ali, S. A. The protective effect of Phoenix dactylifera L. seeds against CCl4-induced hepatotoxicity in rats. J. Ethnopharmacol. 155, 736–743 (2014).

11. Gui, S.-Y. et al. Effects and mechanisms of crude astragalosides fraction on liver fibrosis in rats. J. Ethnopharmacol. 103, 154–159 (2006).

12. Motawi, T. K., Hamed, M. A., Shabana, M. H., Hashem, R. M. & Aboul Naser, A. F. Zingiber officinale acts as a nutraceutical agent against liver fibrosis. Nutr. Metab. (Lond). 8, 40 (2011).

13. Hasan, I. H., El-Desouky, M. A., Hozayen, W. G. & Abd El Aziz, G. M. Protective Effect of Zingiber Officinale against CCl 4 -Induced Liver Fibrosis Is Mediated through Downregulating the TGF-β1/Smad3 and NF-κB/IκB Pathways. Pharmacology 97, 1–9 (2016).

14. Zhang, X., Shi, G., Sun, Y., Wu, X. & Zhao, Y. Triterpenes derived from hydrolyzate of total Gynostemma pentaphyllum saponins with anti-hepatic fibrosis and protective activity against H2O2-induced injury. Phytochemistry 144, 226–232 (2017).

15. Shi, G., Wang, X., Zhang, H., Zhang, X. & Zhao, Y. New dammarane-type triterpene saponins from Gynostemma pentaphyllum and their anti-hepatic fibrosis activities in vitro. J. Funct. Foods 45, 10–14 (2018).

16. Chen, J. et al. Gypenosides Ameliorate Carbon Tetrachloride-Induced Liver Fibrosis by Inhibiting the Differentiation of Hepatic Progenitor Cells into Myofibroblasts. Am. J. Chin. Med. 45, 1061–1074 (2017).

17. Bohanon, F. J. et al. Oridonin inhibits hepatic stellate cell proliferation and fibrogenesis. J. Surg. Res. 190, 55–63 (2014).

18. Jia, Y. et al. Curcumol induces RIPK1/RIPK3 complex-dependent necroptosis via JNK1/2-ROS signaling in hepatic stellate cells. Redox Biol. 19, 375–387 (2018).

19. Kim, D.-I., Lee, T.-K., Jang, T.-H. & Kim, C.-H. The inhibitory effect of a Korean herbal medicine, Zedoariae rhizoma, on growth of cultured human hepatic myofibroblast cells. Life Sci. 77, 890–906 (2005).

20. Xie, H. et al. Raw and vinegar processed Curcuma wenyujin regulates hepatic fibrosis via bloking TGF-β/Smad signaling pathways and up-regulation of MMP-2/TIMP-1 ratio. J. Ethnopharmacol. 246, 111768 (2020).

21. Gong, J. et al. Sweroside ameliorated carbon tetrachloride (CCl4)-induced liver fibrosis through FXR-miR-29a signaling pathway. J. Nat. Med. 1–9 (2019). doi:10.1007/s11418-019-01334-3

22. Shin, S. Y. et al. Schisandra chinensis inhibiting TGFβ-induced activation of hepatic stellate cells. Appl. Biol. Chem. 61, 607–616 (2018).

23. Bai, T., Lian, L.-H., Wu, Y.-L., Wan, Y. & Nan, J.-X. Thymoquinone attenuates liver fibrosis via PI3K and TLR4 signaling pathways in activated hepatic stellate cells. Int. Immunopharmacol. 15, 275–281 (2013).

24. Bai, T. et al. Thymoquinone alleviates thioacetamide-induced hepatic fibrosis and inflammation by activating LKB1–AMPK signaling pathway in mice. Int. Immunopharmacol. 19, 351–357 (2014).

25. Ghazwani, M. et al. Anti-fibrotic effect of thymoquinone on hepatic stellate cells. Phytomedicine 21, 254–260 (2014).

26. Lo, Y.-T., Tsai, Y.-H., Wu, S.-J., Chen, J.-R. & Chao, J. C.-J. Ginsenoside Rb1 Inhibits Cell Activation and Liver Fibrosis in Rat Hepatic Stellate Cells. J. Med. Food 14, 1135–1143 (2011).

27. Park, E.-J., Zhao, Y.-Z., Kim, J. & Sohn, D. A Ginsenoside Metabolite, 20- O – β – D -Glucopyranosyl-20( S )-protopanaxadiol, Triggers Apoptosis in Activated Rat Hepatic Stellate Cells via Caspase-3 Activation. Planta Med. 72, 1250–1253 (2006).

28. Peng, X. et al. Relationship between anti-fibrotic effect of Panax notoginseng saponins and serum cytokines in rat hepatic fibrosis. Biochem. Biophys. Res. Commun. 388, 31–34 (2009).

29. Gan, F. et al. Lycium barbarum polysaccharides improve CCl4-induced liver fibrosis, inflammatory response and TLRs/NF-kB signaling pathway expression in wistar rats. Life Sci. 192, 205–212 (2018).

30. Li, J. et al. Icaritin induces cell death in activated hepatic stellate cells through mitochondrial activated apoptosis and ameliorates the development of liver fibrosis in rats. J. Ethnopharmacol. 137, 714–723 (2011).

31. Wang, X. et al. Antifibrotic activity of galangin, a novel function evaluated in animal liver fibrosis model. Environ. Toxicol. Pharmacol. 36, 288–295 (2013).

32. Liu, X. et al. Smad3 Specific Inhibitor, Naringenin, Decreases the Expression of Extracellular Matrix Induced by TGF-β1 in Cultured Rat Hepatic Stellate Cells. Pharm. Res. 23, 82–89 (2006).

33. Shi, H. et al. Naringin in Ganshuang Granule suppresses activation of hepatic stellate cells for anti-fibrosis effect by inhibition of mammalian target of rapamycin. J. Cell. Mol. Med. 21, 500–509 (2017).

34. El-Mihi, K. A., Kenawy, H. I., El-Karef, A., Elsherbiny, N. M. & Eissa, L. A. Naringin attenuates thioacetamide-induced liver fibrosis in rats through modulation of the PI3K/Akt pathway. Life Sci. 187, 50–57 (2017).

35. Xu, T., Pan, Z., Dong, M., Yu, C. & Niu, Y. Ferulic acid suppresses activation of hepatic stellate cells through ERK1/2 and Smad signaling pathways in vitro. Biochem. Pharmacol. 93, 49–58 (2015).

36. Wang, N. et al. Berberine Inhibition of Fibrogenesis in a Rat Model of Liver Fibrosis and in Hepatic Stellate Cells. Evidence-Based Complement. Altern. Med. 2016, 1–11 (2016).

37. Hamza, A. A. Ameliorative effects of Moringa oleifera Lam seed extract on liver fibrosis in rats. Food Chem. Toxicol. 48, 345–355 (2010).

38. Lim, J.-H. et al. Protective effect of the roots extract of Platycodon grandiflorum on bile duct ligation-induced hepatic fibrosis in rats. Hum. Exp. Toxicol. 32, 1197–1205 (2013).

39. Lee, K.-J. D.-W. Y.-C. Y.-S. S.-Y. S.-H. Y.-S. H.-G. Saponin isolated from Platycodon grandiflorum induces cell cycle arrest in hepatic stellate cells. Proc. PSK Conf. 103.3-104 (2003).

40. Lee, K.-J. D.-W. Y.-C. Y.-S. S.-Y. S.-H. H.-G. An aqueous extract isolated from Platycodon grandiflorum reduced acetaldehyde-induced collagen and alpha-SMA expression in hepatic stellate cells. Proc. PSK Conf. 113.3-113 (2003).

41. Kong, D. et al. Paeonol inhibits hepatic fibrogenesis via disrupting nuclear factor-κB pathway in activated stellate cells: In vivo and in vitro studies. J. Gastroenterol. Hepatol. 28, 1223–1233 (2013).

42. Kuo, J.-J., Wang, C.-Y., Lee, T.-F., Huang, Y.-T. & Lin, Y.-L. Paeoniae Radix Reduces PDGF-Stimulated Hepatic Stellate Cell Migration. Planta Med. 78, 341–348 (2012).

43. Chen, Q. et al. Dihydroartemisinin alleviates bile duct ligation-induced liver fibrosis and hepatic stellate cell activation by interfering with the PDGF-βR/ERK signaling pathway. Int. Immunopharmacol. 34, 250–258 (2016).

44. Xu, Y., Liu, W., Fang, B., Gao, S. & Yan, J. Artesunate ameliorates hepatic fibrosis induced by bovine serum albumin in rats through regulating matrix metalloproteinases. Eur. J. Pharmacol. 744, 1–9 (2014).

45. Han, J.-M. et al. Aqueous extract of Artemisia iwayomogi Kitamura attenuates cholestatic liver fibrosis in a rat model of bile duct ligation. Food Chem. Toxicol. 50, 3505–3513 (2012).

46. Wang, J.-H., Choi, M.-K., Shin, J.-W., Hwang, S.-Y. & Son, C.-G. Antifibrotic effects of Artemisia capillaris and Artemisia iwayomogi in a carbon tetrachloride-induced chronic hepatic fibrosis animal model. J. Ethnopharmacol. 140, 179–185 (2012).

47. PARK, E.-J. et al. The Ethanol-soluble Part of a Hot-water Extract from Artemisia iwayomogi Inhibits Liver Fibrosis Induced by Carbon Tetrachloride in Rats. J. Pharm. Pharmacol. 52, 875–881 (2000).

48. Lin, Y.-L., Wu, C.-F. & Huang, Y.-T. Phenols from the Roots of Rheum palmatum Attenuate Chemotaxis in Rat Hepatic Stellate Cells. Planta Med. 74, 1246–1252 (2008).

49. Lin, Y.-L., Wu, C.-F. & Huang, Y.-T. Effects of rhubarb on migration of rat hepatic stellate cells. J. Gastroenterol. Hepatol. 24, 453–461 (2009).

50. Tsang, S. W. & Bian, Z.-X. Anti-fibrotic and Anti-tumorigenic Effects of Rhein, a Natural Anthraquinone Derivative, in Mammalian Stellate and Carcinoma Cells. Phyther. Res. 29, 407–414 (2015).

51. Woo, S. W. et al. Aloe Emodin Suppresses Myofibroblastic Differentiation of Rat Hepatic Stellate Cells in Primary Culture. Pharmacol. Toxicol. 90, 193–198 (2002).

52. Pan, T.-L., Wang, P.-W., Leu, Y.-L., Wu, T.-H. & Wu, T.-S. Inhibitory effects of Scutellaria baicalensis extract on hepatic stellate cells through inducing G2/M cell cycle arrest and activating ERK-dependent apoptosis via Bax and caspase pathway. J. Ethnopharmacol. 139, 829–837 (2012).

53. Chen, H., Liang, T., Lee, I., Huang, Y. & Lin, Y. Effect of Scutellaria baicalensis on hepatic stellate cells. Planta Med. 80, PG12 (2014).

54. Nan, J.-X., Park, E.-J., Kim, Y.-C., Ko, G. & Sohn, D. H. Scutellaria baicalensis inhibits liver fibrosis induced by bile duct ligation or carbon tetrachloride in rats. J. Pharm. Pharmacol. 54, 555–563 (2002).

55. Park, E.-J., Zhao, Y.-Z., Lian, L., Kim, Y.-C. & Sohn, D. H. Skullcapflavone I from Scutellaria baicalensis Induces Apoptosis in Activated Rat Hepatic Stellate Cells. Planta Med. 71, 885–887 (2005).

56. Han, Y. et al. Rhizoma Paridis saponins ameliorates hepatic fibrosis in rats by downregulating expression of angiogenesis‑associated growth factors. Mol. Med. Rep. 49, 3548–3554 (2019).

57. Hong, Y. et al. Paridis Rhizoma Sapoinins attenuates liver fibrosis in rats by regulating the expression of RASAL1/ERK1/2 signal pathway. J. Ethnopharmacol. 192, 114–122 (2016).

58. Man, S. et al. Anti-fibrosis and anti-cirrhosis effects of Rhizoma paridis saponins on diethylnitrosamine induced rats. J. Ethnopharmacol. 151, 407–412 (2014).

59. Chen, Y.-W., Wu, J.-X., Chen, Y.-W., Li, D.-G. & Lu, H.-M. Tetrandrine inhibits activation of rat hepatic stellate cells in vitro via transforming growth factor-beta signaling. World J. Gastroenterol. 11, 2922–6 (2005).

60. Yin, M.-F., Lian, L.-H., Piao, D.-M. & Nan, J.-X. Tetrandrine stimulates the apoptosis of hepatic stellate cells and ameliorates development of fibrosis in a thioacetamide rat model. World J. Gastroenterol. 13, 1214–20 (2007).

61. Chen, Y., Li, D., Wu, J., Chen, Y. & Lu, H. Tetrandrine inhibits activation of rat hepatic stellate cells stimulated by transforming growth factor-β in vitro via up-regulation of Smad 7. J. Ethnopharmacol. 100, 299–305 (2005).

62. Hsu, Y.-C. et al. Antifibrotic effects of tetrandrine on hepatic stellate cells and rats with liver fibrosis. J. Gastroenterol. Hepatol. 22, 99–111 (2007).

63. Zhao, Y.-Z. et al. Tetrandrine induces apoptosis in hepatic stellate cells. Phyther. Res. 18, 306–309 (2004).

64. Lin, Y.-L., Lin, C.-Y., Chi, C.-W. & Huang, Y.-T. Study on antifibrotic effects of curcumin in rat hepatic stellate cells. Phyther. Res. 23, 927–932 (2009).

65. Kang, H.-C. et al. Curcumin inhibits collagen synthesis and hepatic stellate cell activation in-vivo and in-vitro. J. Pharm. Pharmacol. 54, 119–126 (2002).

66. El-Mansy, A., Mazroa, S., Hamed, W., Yaseen, A. & El-Mohandes, E. Histological and immunohistochemical effects of Curcuma longa on activation of rat hepatic stellate cells after cadmium induced hepatotoxicity. Biotech. Histochem. 91, 170–181 (2016).

67. Wu, Y.-W., Fang, H.-L. & Lin, W.-C. Post-treatment of Ganoderma lucidum reduced liver fibrosis induced by thioacetamide in mice. Phyther. Res. 24, n/a-n/a (2009).

68. Lin, W.-C. & Lin, W.-L. Ameliorative effect of Ganoderma lucidum on carbon tetrachloride-induced liver fibrosis in rats. World J. Gastroenterol. 12, 265–70 (2006).

69. Wang, G.-J., Huang, Y.-J., Chen, D.-H. & Lin, Y.-L. Ganoderma lucidum extract attenuates the proliferation of hepatic stellate cells by blocking the PDGF receptor. Phyther. Res. 23, 833–839 (2009).

70. Liu, Y.-K. & Shen, W. Inhibitive effect of cordyceps sinensis on experimental hepatic fibrosis and its possible mechanism. World J. Gastroenterol. 9, 529–33 (2003).

71. Peng, J. et al. Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs. Exp. Biol. Med. 238, 668–677 (2013).

72. Wang, S. et al. Puerarin protects against CCl4-induced liver fibrosis in mice: possible role of PARP-1 inhibition. Int. Immunopharmacol. 38, 238–245 (2016).

73. Guo, C. et al. Anti-fibrotic effects of puerarin on CCl4-induced hepatic fibrosis in rats possibly through the regulation of PPAR-γ expression and inhibition of PI3K/Akt pathway. Food Chem. Toxicol. 56, 436–442 (2013).

74. Zhang, S., Ji, G. & Liu, J. Reversal of chemical-induced liver fibrosis in Wistar rats by puerarin. J. Nutr. Biochem. 17, 485–491 (2006).

75. Xu, L. et al. Puerarin, isolated from Pueraria lobata (Willd.), protects against hepatotoxicity via specific inhibition of the TGF-β1/Smad signaling pathway, thereby leading to anti-fibrotic effect. Phytomedicine 20, 1172–1179 (2013).

76. Yang, D., Li, L., Qian, S. & Liu, L. Evodiamine ameliorates liver fibrosis in rats via TGF-β1/Smad signaling pathway. J. Nat. Med. 72, 145–154 (2018).

77. Liu, X. & Zhao, X. Scoparone attenuates hepatic stellate cell activation through inhibiting TGF-β/Smad signaling pathway. Biomed. Pharmacother. 93, 57–61 (2017).

78. Kim, Y.-I. J.-H. S.-W. I.-H. S. L. ;Woo. H.-J. Y.-C. Artemisia capillaris Thunb. inhibits cell growth and induces apoptosis in human hepatic stellate cell line LX2. Orient. Pharm. Exp. Med. 10, 254–262 (2010).

79. Han, J.-M. et al. Artemisia capillaris extract protects against bile duct ligation-induced liver fibrosis in rats. Exp. Toxicol. Pathol. 65, 837–844 (2013).

80. Wu, X.-L., Zeng, W.-Z., Jiang, M.-D., Qin, J.-P. & Xu, H. Effect of Oxymatrine on the TGFbeta-Smad signaling pathway in rats with CCl4-induced hepatic fibrosis. World J. Gastroenterol. 14, 2100–5 (2008).

81. Shi, G.-F. & Li, Q. Effects of oxymatrine on experimental hepatic fibrosis and its mechanism in vivo. World J. Gastroenterol. 11, 268–71 (2005).

82. Qu, Y., Zong, L., Xu, M., Dong, Y. & Lu, L. Effects of 18α-glycyrrhizin on TGF-β1/Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis. Int. J. Clin. Exp. Pathol. 8, 1292–301 (2015).

83. Wang, J. Y., Zhang, Q. S., Guo, J. S. & Hu, M. Y. Effects of glycyrrhetinic acid on collagen metabolism of hepatic stellate cells at different stages of liver fibrosis in rats. World J. Gastroenterol. 7, 115–9 (2001).

84. Moro, T. et al. Glycyrrhizin and its metabolite inhibit Smad3-mediated type I collagen gene transcription and suppress experimental murine liver fibrosis. Life Sci. 83, 531–539 (2008).

85. Zhang, J. et al. Stachydrine ameliorates carbon tetrachloride-induced hepatic fibrosis by inhibiting inflammation, oxidative stress and regulating MMPs/TIMPs system in rats. Biomed. Pharmacother. 97, 1586–1594 (2018).

86. Chen, Y.-H. et al. Gardenia jasminoides attenuates hepatocellular injury and fibrosis in bile duct-ligated rats and human hepatic stellate cells. World J. Gastroenterol. 18, 7158 (2012).

87. Dattaroy, D. et al. Sparstolonin B (SsnB) attenuates liver fibrosis via a parallel conjugate pathway involving P53-P21 axis, TGF-beta signaling and focal adhesion that is TLR4 dependent. Eur. J. Pharmacol. 841, 33–48 (2018).

88. Luo, H. et al. Amygdalin inhibits HSC-T6 cell proliferation and fibrosis through the regulation of TGF-β/CTGF. Mol. Cell. Toxicol. 12, 265–271 (2016).

89. Lin, L. et al. Andrographolide Ameliorates Liver Fibrosis in Mice: Involvement of TLR4/NF- κ B and TGF- β 1/Smad2 Signaling Pathways. Oxid. Med. Cell. Longev. 2018, 1–11 (2018).

90. Liu, Y.-W., Chiu, Y.-T., Fu, S.-L. & Huang, Y.-T. Osthole ameliorates hepatic fibrosis and inhibits hepatic stellate cell activation. J. Biomed. Sci. 22, 63 (2015).

91. Kim, J. S. et al. Anti-fibrotic effects of Cuscuta chinensis with in vitro hepatic stellate cells and a thioacetamide-induced experimental rat model. Pharm. Biol. 55, 1909–1919 (2017).

92. Ruehl, M. et al. Extracts of Lindera obtusiloba induce antifibrotic effects in hepatic stellate cells via suppression of a TGF-β-mediated profibrotic gene expression pattern. J. Nutr. Biochem. 20, 597–606 (2009).

93. Park, E.-J., Zhao, Y.-Z., Kim, Y. H., Lee, B.-H. & Sohn, D. H. Honokiol Induces Apoptosis via Cytochrome c Release and Caspase Activation in Activated Rat Hepatic Stellate Cells in vitro. Planta Med. 71, 82–84 (2005).

94. Wu, J. Bin, Chuang, H. R., Yang, L. C. & Lin, W. C. A standardized aqueous extract of anoectochilus formosanus ameliorated thioacetamide-induced liver fibrosis in mice: The role of Kupffer cells. Biosci. Biotechnol. Biochem. 74, 781–787 (2010).

95. Shih, C. C., Wu, Y. W. & Lin, W. C. Aqueous extract of Anoectochilus formosanus attenuate hepatic fibrosis induced by carbon tetrachloride in rats. Phytomedicine 12, 453–460 (2005).

96. Fan, S. et al. Toona sinensis Roem (Meliaceae) leaf extract alleviates liver fibrosis via reducing TGFβ1 and collagen. Food Chem. Toxicol. 45, 2228–2236 (2007).

97. Rakesh N Pillai, Beny Baby, AJM Christina, A. A. Anti fibrotic effect of ethanolic extract of Cyclea peltata (H.F and T) roots, on carbon tetrachloride induced liver fibrosis. Res. J. Pharm. Technol. 2, 201–205 (2009).

98. Vladimir-Knežević, S. et al. Micromeria croatica ethanolic extract reduces inflammation, oxidative stress and fibrosis in CCl4-induced mouse liver injury. Abstr. B. 188 (2014).

99. Qin, D., Wen, Z., Nie, Y. & Yao, G. Effect of Cichorium Glandulosum Extracts on CCl4-Induced Hepatic Fibrosis. Iran. Red Crescent Med. J. 15, e10908 (2013).

100. Su, L.-J. et al. Graptopetalum Paraguayense Ameliorates Chemical-Induced Rat Hepatic Fibrosis In Vivo and Inactivates Stellate Cells and Kupffer Cells In Vitro. PLoS One 8, e53988 (2013).

101. Hsu, W.-H. et al. Graptopetalum paraguayense Inhibits Liver Fibrosis by Blocking TGF-β Signaling In Vivo and In Vitro. Int. J. Mol. Sci. 20, 2592 (2019).

102. Shin, G.-M. et al. Anti-hepatofibrosis effect of Allium senescens in activated hepatic stellate cells and thioacetamide-induced fibrosis rat model. Pharm. Biol. 56, 632–642 (2018).

103. Lin, Y., Luo, H. & Jin, Q. [Study on effect of total flavanones of Sedum sarmentosum on apoptosis of hepatic stellate cells and its mechanism]. Zhongguo Zhong Yao Za Zhi 40, 3273–7 (2015).

104. Lin, Y. et al. Flavanones from Sedum sarmentosum Bunge Alleviate CCl 4 -Induced Liver Fibrosis in Rats by Targeting TGF- β 1/T β R/Smad Pathway In Turn Inhibiting Epithelial Mesenchymal Transition. Evidence-Based Complement. Altern. Med. 2018, 1–10 (2018).

105. Cao, F. et al. Mogroside IVE attenuates experimental liver fibrosis in mice and inhibits HSC activation through downregulating TLR4-mediated pathways. Int. Immunopharmacol. 55, 183–192 (2018).

106. Huang, Q. et al. Effect and mechanism of methyl helicterate isolated from Helicteres angustifolia (Sterculiaceae) on hepatic fibrosis induced by carbon tetrachloride in rats. J. Ethnopharmacol. 143, 889–895 (2012).

107. Tsang, S. W., Zhang, H.-J., Chen, Y.-G., Auyeung, K. K.-W. & Bian, Z.-X. Eruberin A, a Natural Flavanol Glycoside, Exerts Anti-Fibrotic Action on Pancreatic Stellate Cells. Cell. Physiol. Biochem. 36, 2433–2446 (2015).

108. Yue, J. et al. Cucurbitane triterpenoids from the fruit of Momordica charantia L. and their anti-hepatic fibrosis and anti-hepatoma activities. Phytochemistry 157, 21–27 (2019).

109. Hassan, S. M., Taha, A. M., Eldahshan, O. A., Sayed, A. A. & Salem, A. M. Modulatory effect of Prosopis juliflora leaves on hepatic fibrogenic and fibrolytic alterations induced in rats by thioacetamide. Biomed. Pharmacother. 115, 108788 (2019).

110. Rehman, A. U. et al. Anti-fibrotic effects of polygonum plebeium r.br. in CCl4-induced hepatic damage and fibrosis in rats. Biomed. Res. Ther. 5, 2223–2234 (2018).

111. Chen, S.-R., Chen, X.-P., Lu, J.-J., Wang, Y. & Wang, Y.-T. Potent natural products and herbal medicines for treating liver fibrosis. Chin. Med. 10, 7 (2015).

112. Shyu, M.-H., Kao, T.-C. & Yen, G.-C. Hsian-tsao (Mesona procumbens Heml.) prevents against rat liver fibrosis induced by CCl4 via inhibition of hepatic stellate cells activation. Food Chem. Toxicol. 46, 3707–3713 (2008).

113. Choi, Y. J. et al. Decursin attenuates hepatic fibrogenesis through interrupting TGF-beta-mediated NAD(P)H oxidase activation and Smad signaling in vivo and in vitro. Life Sci. 108, 94–103 (2014).

114. Salama, S. M., Abdulla, M. A., Alrashdi, A. S. & Hadi, A. H. A. Mechanism of Hepatoprotective Effect of Boesenbergia rotunda in Thioacetamide-Induced Liver Damage in Rats. Evid. Based. Complement. Alternat. Med. 2013, 157456 (2013).

115. Salama, S. M., Bilgen, M., Al Rashdi, A. S. & Abdulla, M. A. Efficacy of Boesenbergia rotunda Treatment against Thioacetamide-Induced Liver Cirrhosis in a Rat Model. Evidence-Based Complement. Altern. Med. 2012, 1–12 (2012).

116. Kuo, L.-M. et al. The Bioactive Extract of Pinnigorgia sp. Induces Apoptosis of Hepatic Stellate Cells via ROS-ERK/JNK-Caspase-3 Signaling. Mar. Drugs 16, 19 (2018).

117. Zhou, F., Wang, A., Li, D., Wang, Y. & Lin, L. Pinocembrin from Penthorum chinense Pursh suppresses hepatic stellate cells activation through a unified SIRT3-TGF-β-Smad signaling pathway. Toxicol. Appl. Pharmacol. 341, 38–50 (2018).

118. Zhang, Y., Miao, H., Yan, H., Sheng, Y. & Ji, L. Hepatoprotective effect of Forsythiae Fructus water extract against carbon tetrachloride-induced liver fibrosis in mice. J. Ethnopharmacol. 218, 27–34 (2018).

119. Cao, S. et al. Semen Brassicae ameliorates hepatic fibrosis by regulating transforming growth factor-β1/Smad, nuclear factor-κB, and AKT signaling pathways in rats. Drug Des. Devel. Ther. 12, 1205 (2018).

120. Ma, Y. et al. Flavonoid-rich Scabiosa comosa inflorescence extract attenuates CCl4-induced hepatic fibrosis by modulating TGF-β-induced Smad3 phosphorylation. Biomed. Pharmacother. 106, 426–433 (2018).

121. Huang, Q. F. et al. Protective effect of isoorientin-2″-O-α-l-arabinopyranosyl isolated from Gypsophila elegans on alcohol induced hepatic fibrosis in rats. Food Chem. Toxicol. 50, 1992–2001 (2012).

122. Lin, X. et al. Gypsophila elegans isoorientin attenuates CCl4-induced hepatic fibrosis in rats via modulation of NF-κB and TGF-β1/Smad signaling pathways. Int. Immunopharmacol. 28, 305–312 (2015).

123. Hu, J.-P. et al. Loureirin B inhibits the proliferation of hepatic stellate cells and the Wnt/β-catenin signaling pathway by regulating miR-148-3p. Cell. Mol. Biol. Lett. 23, 35 (2018).

124. Chin, Y.-W., Shin, E., Hwang, B. Y. & Lee, M. K. Antifibrotic Constituents from Garcinia mangostana. Nat. Prod. Commun. 6, 1934578X1100600 (2011).

125. Rahmaniah, R. et al. Alpha mangostin Inhibits Hepatic Stellate Cells Activation Through TGF-β/Smad and Akt Signaling Pathways: An in vitro Study in LX2. Drug Res. (Stuttg). 68, 153–158 (2018).

126. Peng, W.-H. et al. Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1. J. Ethnopharmacol. 127, 606–613 (2010).

127. Chen, K., Wu, T., Zhang, R. & Song, H. Effects of swertiamarin on TGF-β 1 / Smad signaling pathway in rats with carbon tetrachloride-induced liver fibrosis. (2017).

128. Wu, X.-X. et al. Cortex Dictamni extract induces apoptosis of activated hepatic stellate cells via STAT1 and attenuates liver fibrosis in mice. J. Ethnopharmacol. 135, 173–178 (2011).

129. Chuang, H.-Y. et al. Hydrolysable tannins of tropical almond show antifibrotic effects in TGF-β1-induced hepatic stellate cells. J. Sci. Food Agric. 91, 2777–2784 (2011).

130. Chen, Y.-X. et al. Ethyl acetate fraction of Terminalia bellirica fruit inhibits rat hepatic stellate cell proliferation and induces apoptosis. Ind. Crops Prod. 76, 364–373 (2015).

131. Lee, S.-L., Chin, T.-Y., Lai, C.-L. & Wang, W.-H. Sedum mexicanum Britt. Induces Apoptosis of Primary Rat Activated Hepatic Stellate Cells. Evid. Based. Complement. Alternat. Med. 2015, 194373 (2015).

132. Koppula, S. et al. Anti-fibrotic effects of Orostachys japonicus A. Berger (Crassulaceae) on hepatic stellate cells and thioacetamide-induced fibrosis in rats. Nutr. Res. Pract. 11, 470 (2017).

133. Kim, Y. Il et al. Effect of Orostachys japonicus on Cell Growth and Apoptosis in Human Hepatic Stellate Cell Line LX2. Am. J. Chin. Med. 39, 601–613 (2011).

134. Yum, M. J. et al. Protective effects of Ampelopsis brevipedunculata against in vitro hepatic stellate cells system and thioacetamide-induced liver fibrosis rat model. Pharm. Biol. 55, 1577–1585 (2017).

135. Yabe, N. & Matsui, H. Ampelopsis brevipedunculata (Vitaceae) extract inhibits a progression of carbon tetrachloride-induced hepatic injury in the mice. Phytomedicine 7, 493–498 (2000).

136. Lee, J.-H. et al. Sauchinone attenuates liver fibrosis and hepatic stellate cell activation through TGF-β/Smad signaling pathway. Chem. Biol. Interact. 224, 58–67 (2014).

137. Wang, L. et al. The hepatoprotective and antifibrotic effects of Saururus chinensis against carbon tetrachloride induced hepatic fibrosis in rats. J. Ethnopharmacol. 126, 487–491 (2009).

138. Wang, Y. & Yan, D. Plantamajoside exerts antifibrosis effects in the liver by inhibiting hepatic stellate cell activation. Exp. Ther. Med. 18, 2421–2428 (2019).

139. Fang, H.-L., Lin, H.-Y., Chan, M.-C., Lin, W.-L. & Lin, W.-C. Treatment of Chronic Liver Injuries in Mice by Oral Administration of Ethanolic Extract of the Fruit of Hovenia dulcis. Am. J. Chin. Med. 35, 693–703 (2007).

140. Liu, X., Zhnag, H. & Wang, F. [Effect of Hovenia dulcis extract on expression of MMP-13 and TIMP-1 in hepatic tissue]. Zhongguo Zhong Yao Za Zhi 31, 1097–100 (2006).