Table 1 Details about some traditional Chinese medicines improving pulmonary fibrosis by inhibiting epithelial cell-mesenchymal transformation
No | Source | Genus information | Traditional efficacy | Active compound | Experiment model | Administration dose | Therapeutic target | Cytokine | Refs. |
|---|---|---|---|---|---|---|---|---|---|
1 | Scutellariae radix | Scutellaria | Clearing away heat and dampness, purging fire and detoxifying | Astragalus polysaccharides | BLM-induced PF mice and A549 cells | Mice (200 mg/kg) | Inhibit NF-κB signaling | TGF-β1, NF-κB, α-SMA, Collagen I, CHOP | [140] |
2 | Baicalin | BLM-induced PF rats and RPF | Rats (50 mg/kg) | Regulation of CaMKII and PI3K/AKT signaling | PI3K, AKT, Bax, Bcl-2 | [141] | |||
Cell (20, 40, 60, 80 μg/mL) | |||||||||
3 | Radiation-induced EMT model | Cell (2, 10, 50 μmol/L) | Suppress EMT | Smad2/3, ERK, GSK3β | [142] | ||||
4 | Baicalein | MRC-5 cells | Cell (1–80 μmol/L) | Inhibit miR-21 | STAT3, TGF-β1, COL1 A1, α-SMA, | [143] | |||
5 | Calycosin, CA | BLM-induced PF mice and MLE-12 cells | Mice (7, 14 mg/kg) | Inhibit AKT/GSK3β/β-catenin signaling | AKT, GSK3β, β-catenin, E-cadherin | [144] | |||
Cell (0–80 μmol/L) | |||||||||
6 | Curcumae longae rhizoma | Zingiberaceae | Promoting blood circulation and removing blood stasis, Regulating menstruation and relieving pain | Curcumin | HUVEC cells | Cell (5, 10 μmol/L) | Regulation of NRF2-DDAH-ADMA-NO signaling | TGF-β1, Nrf2, DDAH, PRMT, ERK1/2 | [145] |
7 | BLM-induced PF mice and A549 cells | Mice (75 mg/kg) | Suppress EMT | EGFR, Ki67 | [146] | ||||
Cell (20 μmol/L) | |||||||||
8 | A549 cells | Cell (20 μmol/L) | Inhibit TGF-β1/Smad/non Smad signaling | TGF-β1, Smad | [147] | ||||
9 | A549 cells | Cell (0–1000 μmol/L) | Suppress EMT | ROS, α-SMA, TGF-β1 | [148] | ||||
10 | NHLF cells | Cell (10 μmol/L) | Down-regulation of hsa-miR-6724-5p expression | KLF10 | [149] | ||||
11 | CCD-19Lu cells | Cell (0–50 μmol/L) | activate PPARγ | TGF-β1, α-SMA, PPARγ | [150] | ||||
12 | BLM-induced PF mice | Mice (75, 150 mg/kg) | Activates PPARγ and CREB signaling | PPARγ, CREB | [151] | ||||
13 | Andrographis herba | Acanthaceae | Clearing heat and detoxification, cooling blood | Andrographolide | NIH 3T3, PLF cells | Rats (10 mg/kg) | Inhibits TGF-β1/Smad2/3 and Erk1/2 signaling | TGF-β1, Smad2/3 | [132] |
Cell (2, 5, 10 μmol/L) | |||||||||
14 | BLM-induced PF rats and A549 cells | Rats (10 mg/kg) | Regulation of AKT/mTOR signaling | AKT, mTOR | [134] | ||||
15 | Silica-induced PF mice | Mice (3, 10 mg/kg) | Inhibition of ECM precipitate formation | GSH, NF-κB, CTGF | [131] | ||||
16 | A549 cells | Cell (0–20 μmol/L) | Inhibits A and B signaling | TGF-β1, Smad2/3, MMP-9 | [133] | ||||
17 | Salviae miltiorrhizae | Lamiaceae | Promoting blood circulation and removing blood stasis, reducing swelling and relieving pain | Tanshinone IIA | BLM-induced PF mice and PLFs, NIH-3T3 cells | Mice (5, 10, 20 mg/kg) | Inhibition of TGF-β1-Smad3 signaling | Nrf2, TGF-β1 | [152] |
Cell (0.01–500 μmol/L) | |||||||||
18 | Salvianolic acid B | BLM-induced PF rats and MRC-5 cells | Rats (20 mg/kg) | Regulates Nrf2 signaling | Nrf2, α-SMA, TGF-β1 | [138] | |||
Cell (40 μmol/L) | |||||||||
19 | Salvianolic acid B/sodium tanshinone IIA sulfonate | THP-1 cells | Cell (0–600 μg/mL) | Inhibit TGF-β1 signaling | TGF-β1, α-SMA | [153] | |||
20 | Cryptotanshinone | BLM-induced PF mice and A549, NIH/3T3, HPF cells | Mice (30, 60 mg/kg) | Suppress EMT | [139] | ||||
Cell (0–20 μmol/L) | |||||||||
21 | Rhei radix et rhizoma | Polygonaceae | Purging and defecating, clearing heat and detoxification | Emodin | Silica-induced PF mice and A549 cells | Mice (25, 50, 100 mg/kg) | Regulation of NF-κB and TGF-β1/Smad3 signaling | NF-κB, TGF-β1 | [136] |
22 | RLE-6TN, A549 cells | Cell (50, 100, 200 nmol/L) | Suppress EMT | Notch1, C-MYC | [135] | ||||
23 | rhapontin | BLM-induced PF rats and THP-1 cells | Rats (25, 50, 100 mg/kg) | Regulation of TGF-β/Smad signaling | TGF-β, Smad | [137] | |||
Cell (50 μmol/L) | |||||||||
24 | Various plant sources | quercetin | RLE/Abca3 cells | Cell (20 μmol/L) | Regulation of Smad and b-catenin signaling | Smad, b-catenin | [154] | ||
25 | BLM-induced PF mice and HELF cells | Mice (25, 50, 100 mg/kg) | Inhibits SphK1/S1P signaling | TGF-β, SphK1, S1P | [155] | ||||
Cell (10, 20, 40 μmol/L) | |||||||||
26 | Polygoni cuspidati rhizoma et radix | Polygonaceae | Clearing heat and detoxification, promoting blood circulation and removing blood stasis | Polydatin | BLM-induced PF rats and A549 cells | Rats (10, 40, 160 mg/kg) | Inhibit TGF-β1/Smad signaling | TGF-β1, Smad2/3, Erk1/2 | [156] |
Cell (0–120 μmol/L) | |||||||||
27 | BLM-induced PF rats and HFL-1 cells | Rats (100 mg/kg) | Regulation of TGF-β/Smad signaling | TGF-β, Smad2/3, TNF-α, IL-1β | [157] | ||||
Cell (50, 150 mmol/L) | |||||||||
28 | Astragali radix | Fabaceae | Replenishing qi and solidifying the surface, strengthening the upright and dispelling evil | astragaloside IV | A549 cells | Cell (20 mg/mL) | Inhibit the expression of NLRP3 | NLRP3, TGF-β1, Smad2/3, α-SMA | [158] |
29 | BLM-induced PF rats and A549 cells | Rats (20 mg/kg) | Inhibit TGF-β1/PI3K/Akt signaling | TGF-β1, PI3K, Akt | [159] | ||||
Cell (100 μg/mL) | |||||||||
30 | Tripterygium wilfordii Hook. f | Ranunculaceae | Clearing heat and detoxification, promoting blood circulation and removing blood stasis | Triptolide | HFL-1 cells | Cell (5, 10, 15, 20 nmol/L) | Regulation of FAK/calin signaling | FAK, calain | [160] |
31 | paraquat-induced PF mice and BEAS-2B cells | Mice (0.25 mg/kg) | Suppress EMT | TGF-β1, α-SMA, Smad3, E-cadherin | [161] | ||||
32 | Schisandrae chinensis fructus | Magnoliaceae | Astringent and astringent, replenishing qi and invigorating fluid | schisantherin A | BLM-induced PF mice and A549 cells | Mice (1, 2, 4 mg/kg) | Inhibition of ERK signaling | ERK, α-SMA, IL-1β, IL-6, TNF-α | [162] |
Cell (0.625, 10 μmol/L) | |||||||||
33 | schisandrin B | BLM-induced PF mice | Mice (5, 10, 20 mg/kg) | Inhibits Wnt signaling | MMP7, SOD, TGF-β1 | [163] | |||
34 | Inulae flos | Asteraceae | Clearing heat and detoxification, eliminating phlegm and relieving cough | Inula japonica Thunb.extract | Mlg, CAGA-NIH3T3 cells | Cell (0–80 μmol/L) | Inhibit TGF-β1/Smad3 signaling | TGF-β1, Smad3 | [164] |
35 | BLM-induced PF mice | Mice (100, 200, 400 mg/kg) | Regulates GSK3β signaling | GSK3β, COX-2, GSK3β, p65 | [165] | ||||
36 | Ferulae resina | Apiaceae | Activating qi to relieve pain, warming menstruation and dispelling cold | ferulic acid | Silica-induced PF mice | Mice (100, 300 mg/kg) | Inhibit TGF-β1 signaling | TGF-β1, Smad2/3, CTGF, Slug | [166] |
37 | Psoraleae fructus | Fabaceae | Warm the kidney and consolidate the essence, strengthen the muscles and bones | Psoralen | BLM-induced PF mice and NIH3T3 cells | Mice (5 mg/kg) | Inhibition of ECM precipitate formation | TNF-α, IL‐1β | [167] |
Cell (5, 10, 20, 40 μmol/L) | |||||||||
38 | Atractylodis rhizoma | Asteraceae | Invigorating spleen and stomach, tonifying qi and blood | atractylon | OVA-induced asthma mice and TC-1 cells | Mice (25 mg/kg) | Regulate the mmu_circ_0000981/miR-211-5p/ TGFBR2 axis | TFGBR2, Vimentin, α-SMA, collagen | [168] |
39 | Angelicae sinensis radix | Apiaceae | Tonifying blood and activating blood, regulating menstruation and relieving pain | Angelica Sinensis Polysaccharide | BLM-induced PF rats and RLE-6TN cells | Rats (20 mg/kg) | Suppress EMT | DANCR, AUF1 | [169] |
Cell (μmol/L) | |||||||||
40 | Pyrethrum parthenium (L.) Sm | Asteraceae | Dispelling wind and relieving pain and headache | Parthenolide | BLM-induced PF mice and A549 cells | Mice (12.5, 25, 50 mg/kg) | Inhibits NF-κB/Snail signaling | NF-κB, Snail | [170] |
Cell (5, 10 μmol/L) | |||||||||
41 | Erigeron breviscapus | Asteraceae | Promoting blood circulation and removing blood stasis, clearing heat and detoxification | Scutellarin | BLM-induced PF mice and A549 cells | Mice (30, 60, 90 mg/kg) | Regulation of NF-κB/NLRP3 signaling | NF-κB, NLRP3 | [171] |
Cell (0.1, 0.2, 0.4 mmol/L) | |||||||||
42 | Scutellarein | BLM-induced PF mice | Mice (10 mg/kg) | Inhibits PI3K/Akt signaling | PI3K, Akt, Smad2/3, α-SMA | [172] | |||
43 | Spirulina platensis | phycocyanin | BLM-induced PF mice | Mice (50 mg/kg) | Regulation of TLR2-MyD88-NF-κB signaling | TLR2, NF-κB | [173] | ||
44 | Curcuma aromatica Salisb | Zingiberaceae | Promoting blood circulation and removing blood stasis, reducing swelling and relieving pain | Curdione | BLM-induced PF mice and HPFS cells | Mice (100 mg/kg) | Inhibition of TGF-β/Smad3 signaling | TGF-β1, α-SMA, Collagen 1, Erk1/2 | [174] |
Cell (100–500 μmol/L) | |||||||||
45 | Citrus aurantium L | Rutaceae | Soothing the liver and regulating qi, resolving phlegm and relieving cough | Hesperidin | A549 cells | Cell (40–200 μmol/L) | Inhibit TGF-β/Smad2/3 signaling | TGF-β1, Smad2/3, Smad4, Smad7 | [175] |
46 | Alpiniae officinarum rhizoma | Zingiberaceae | Regulating qi and relieving pain, removing dampness and resolving phlegm | Galangin | BLM-induced PF mice and A549 cells | Mice (25, 50 mg/kg) | Suppress EMT | TGF-β1, E-cadherin | [176] |
Cell (0–100 μmol/L) | |||||||||
47 | Aronia melanocarpa | Rosaceae | Cyanidin-3-galactoside | Silica-induced PF mice | Mice (100, 200, 400 mg/kg) | Inhibition of TGF-β/mTOR signaling through the NRF2/HO-1 pathway | TGF-β1, p-mTOR, NRF2 | [177] | |
48 | Carthami flos | Asteraceae | Promoting blood circulation and removing blood stasis, regulating menstruation and relieving pain | safflower yellow | paraquat-induced PF rats | Rats (50 mg/kg) | Regulate Hippo signaling | Hippo, Smad2/3, TGF-β1 | [178] |
49 | Juglans mandshurica | Juglandaceae | Moistening the intestines and relieving defecation, tonifying the kidney and strengthening yang | Juglanin | BLM-induced PF mice and MRC-5, MLE-12 cells | mice (80 mg/kg) | Suppress Sting | Sting, MMP-9, α-SMA, TGF-β1 | [179] |
Cell (0–160 μmol/L) | |||||||||
50 | Trigonellae semen | Fabaceae | Warming the middle and dispelling cold, regulating qi and relieving pain | Diosgenin | BLM-induced PF rats | Rats (100 mg/kg) | Regulation of TGF-β/Smad signaling | TGF-β1, snail, NF-κB, COX-2, IL-1β | [180] |
Cell (10–30 μmol/L) | |||||||||
51 | Gynostemma pentaphyllum (Thunb.) Makino | Cucurbitaceae | Clearing heat and detoxification, lowering blood pressure | Gypenoside, Gyps | BLM-induced PF mice | Mice (200 mg/kg) | Inhibits AKT/mTOR/c-Myc signaling | AKT, mTOR | [181] |
52 | Sophorae fla vescentis radix | Fabaceae | Clearing heat and detoxification, diuresis and purging gonorrhea | Matrine | MRC-5 cells | Cell (10 μmol/L) | Inhibit TGF-β/Smad2/3 signaling | TGF-β, Smad2/3 | [182] |
53 | Vaccinium spp. | Ericaceae | Pterostilbene | A549 cells | Cell (0–100 μmol/L) | Inhibit TGF-β1 signaling | TGF-β1, Bcl-2, BAX, P62, P-21 | [183] | |
54 | Cyanobacteria | C-Phycocyanin | Oleic acid-induced PF mice and A549, HFL-1 cells | Mice (1, 3, 9 mg/kg) | Regulation of TGF-β/Smad and MAPK signaling | TGF-β1, MAPK | [184] | ||
Cell (10, 30 μmol/L) | |||||||||
55 | Eclipta prostrata (L.) L | Saururaceae | Clearing heat and detoxification, stopping bleeding and generating hair | wedelolactone | BLM-induced PF mice and PLFs cells | Mice (2, 10 mg/kg) | Inhibition of RAF1-MAPKs signaling | Col I, α-SAM, AMPK | [185] |
Cell (10 μmol/L) | |||||||||
56 | Nelumbinis semen | Nelumbonaceae | Clear the heart and calm the mind, moisturize the lungs and relieve cough | Lotus Plumule Extract | BLM-induced PF mice | Mice (80, 160, 240 mg/kg) | Inhibit TGF-β1/Smad3 signaling | TGF-β, α-SMA | [186] |
57 | Gentianae radix et rhizoma | Gentianaceae | Clearing heat, dryness and dampness, purging liver and gallbladder fire | Gentiopicroside | BLM-induced PF mice | Mice (2.5, 10 mg/kg) | Anti-inflammatory | TNF-α, IL‐1β, TGF-β1, CTGF | [187] |
58 | Siratia grosvenorii | Cucurbitaceae | Clear heat and moisturize the lungs and open pharynx | Mogrol | BLM-induced PF mice and NIH3T3 cells | Mice (1, 5, 10 mg/kg) | Regulation of TGF-β1 and AMPK signaling | TGF-β1, AMPK | [188] |
Cell (1, 5, 10 μmol/L) | |||||||||
59 | Mangifera indica L. | Anacardiaceae | Clearing heat and detoxification, invigorating the stomach and eliminating food | Mangiferin | BLM-induced PF rats and A549 cells | Rats (40 mg/kg) | Inhibit TGF-β1/Smad2/3 signaling | TLR4, TGF-β1 | [189] |
Cell (10 μg/mL) | |||||||||
60 | Atractylodis rhizoma | Asteraceae | Invigorate the spleen and appetizer, remove dampness and dissipate phlegm | Atractylodin | BLM-induced PF mice and A549 cells | Mice (50, 100 mg/kg) | Inhibit TGF-β1/Smad signaling | TGF-β1, Snail | [190] |
Cell (0–100 μmol/L) | |||||||||
61 | Indigo naturalis | Brassicaceae | Clearing heat and detoxification, reducing swelling and relieving pain | Indirubin | BLM-induced PF mice and PMLFs HPFs cells | Mice (12.5, 25 mg/kg) | Inhibit TGF-β1/Smad signaling | TGF-β1, Collagen I, α-SMA, Smad2/3 | [191] |
Cell (2.5–60 μmol/L) | |||||||||
62 | Ginseng radix et rhizoma | Araliaceae | Replenish qi and nourish blood, invigorate body and quench thirst | ginsenoside Rg3 | BLM-induced PF mice and LL 29 cells | Mice (5 mg/kg) | Inhibits nuclear localization of HIF-1α | HIF-1α, TGF-β1 | [192] |
63 | Inonotus sanghuang | Clearing heat and detoxification, promoting blood circulation and removing blood stasis | Inonotus sanghuang extract (ISE) | BLM-induced PF mice and A549 cells | Mice (0.6% w/w) | Inhibit TGF-β1/Smad signaling | TGF-β1, Smad2/3 | [193] | |
Cell (2, 4 μg/mL) | |||||||||
64 | Hippophae fructus | Elaeagnaceae | Invigorate the stomach and eliminate food, relieve cough and expectoration | Isorhamnetin | BLM-induced PF mice | Mice (10, 30 mg/kg) | Suppress EMT | PERK, α-SMA, Collagen I , TGF-β1 | [194] |
Cell (25, 50, 100 μmol/L) | |||||||||
65 | Zingiberis rhizoma recens | Zingiberaceae | Warm the middle to dissipate the cold, solve the surface and dissipate the cold | 6 gingerol | BLM-induced PF mice and | Mice (100, 250 mg/kg) | Activates SIRT1 signaling signaling | SIRT1, α-SMA, TNF-α, IL-6, IL-1β | [195] |
human embryonic lung fibroblasts MRC-5 | Cell (10, 20 μmol/L) | ||||||||
66 | Silybi fructus | Asteraceae | Clearing heat and detoxification, soothing the liver and promoting gallbladder | Silibinin | Silica-induced PF mice | Mice (100, 300 mg/kg) | Anti-inflammatory Inhibits EMT | IL-1β, smad 2/3, α-SMA, TGF-β1 | [196] |
67 | Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang (Vitaceae) | Lamiaceae | Promoting blood circulation and regulating menstruation, diuresis and detumescence | Dihydromyricetin | BLM-induced PF mice and MLG cells | Mice (50, 100, 200 mg/kg) | Inhibit TGF-β1/Smad signaling | TGF-β1, α-SMA | [197] |
68 | PMLFs, PHLFs cells | Cell (100, 200, 300 μmol/L) | Regulation of STAT3/p-STAT3/GLUT1 signaling | STAT3,p-STAT3,GLUT1 | [198] | ||||
69 | Dendrobii officinalis caulis | Orchidaceae | Lung heat coughing, deficiency heat dispelling thirst | Polysaccharides from Dendrobium officinale | BLM-induced PF rats | Rats (200 mg/kg) | Inhibition of TGF-β1-Smad2/3 signaling | TGF-β, Smad2/3, α-SMA, Collagen I I | [199] |
70 | Galla chinensis | Anacardiaceae | Restrain the lungs and reduce the fire, astringent intestines and stop diarrhea | Tannic acid | BLM-induced PF mice | Mice (10 mg/kg) | Inhibit TGF-β receptor signaling | TGF-β, Smad2/3 | [200] |
Cell (1, 3 μmol/L) | |||||||||
71 | Camptotheca acuminata Decne | Nyssaceae | Relieve cough and resolve phlegm | Hyperoside | BLM-induced PF mice | Mice (50 mg/kg) | Regulation of AKT/GSK3b signaling | AKT, GSK3b | [201] |
72 | armeniacae semen amarum | Rosaceae | Moistening the bowels, relieving cough and resolving phlegm | amygdalin | smoking combined with LPS-induced COPD mice and BEAS-2B cells | mice (5, 10, 20 mg/kg) | Inhibit TGF-β/Smad2/3 signaling | TGF-β, Smad2/3 | [202] |
Cell (0–2000 μg/mL) | |||||||||
73 | Arenaria kansuensis Maxim | Caryophyllaceae | Clearing heat and detoxification, diuresis and purging gonorrhea | A. kansuensis ethanol extract | paraquat-induced PF rats | Rats (170, 350, 700 mg/kg) | Inhibit NF-κB/TGF-β1/Smad2/3 signal transduction | TGF-β1, Smad2/3 | [203] |
74 | Myrica rubra Sieb | Myricaceae | Moistening the lung and relieving cough, invigorating body and relieving thirst | Myricetin | BLM-induced PF mice and A549, HFL1 cells | Mice (25, 50, 100 mg/kg) | Regulation of TGF-β/Smad and non-Smad signaling | TGF-β, Smad | [204] |
cell (μmol/L) | |||||||||
75 | Epimedii folium | Berberidaceae | Kidney deficiency and impotence, sore waist and knees | Icariin | BLM-induced PF mice and NIH3T3, HLF-1 cells | Mice (0.04, 0.02, 1 mg/kg) | Inhibit TGF-β1 signaling | TGF-β1, α-SMA | [205] |
Cell (3 μmol/L) | |||||||||
76 | Houttuyniae herba | Saururaceae | Heat-clearing and detoxification, sore waist and knees | Sodium Houttuyfonate | BLM-induced PF mice | Mice (45, 90 mg/kg) | Anti-inflammatory | IL-1β, TNF-α | [206] |
77 | Hypericum longistylum | Hypericaceae | Promoting blood circulation and removing blood stasis, reducing swelling and relieving pain | Hypericum longistylum | MLFC cells | Cell (0–80 μmol/L) | Inhibition of TGF-β/Smad3 signaling | TGF-β | [207] |
78 | Aurantii fructus immaturus | Rutaceae | Regulating qi stagnation, resolving phlegm and relieving cough | Neohesperidin | BLM-induced PF mice and NIH3T3, MLg, A549 cells | Mice (20 mg/kg) | Inhibition of TGF-β/Smad3 signaling | TGF-β1, Smad2/3, Erk, p-38, JNK | [208] |
cell (0–200 μmol/L) | |||||||||
79 | Multiple plant sources | Hederagenin | BLM-induced PF rats | Rats (10, 20, 50 mg/kg) | Adjust Ras/JNK/NFAT4 axis | JNK, NFAT4 | [209] | ||
80 | Polyporus | Polyporaceae | Diuresis, detumescence and phlegm | Polyporus Polysaccharide | BLM-induced PF mice and HLF cells | Mice (50, 100 mg/kg) | Inhibit TGF-β1/Smad2/3 signaling | TGF-β1, Smad2/3 | [210] |
Cell (1 mg/mL) | |||||||||
81 | Podocarpus nagi | Podocarpaceae | Clearing heat and detoxification, dispelling wind and promoting dampness | Nagilactone D | BLM-induced PF mice and WI-38, VA-13, HFL-1 cells | Mice (1, 3 mg/kg) | Inhibition of TGF-β/Smad3 signaling | TGF-β1, Collagen I, α-SMA | [211] |
Cell (1, 2 μmol/L) |