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Table 3 Plants and their bioactive component for pulmonary fibrosis

From: A review on importance of bioactive compounds of medicinal plants in treating idiopathic pulmonary fibrosis (special emphasis on isoquinoline alkaloids)

S no. Plant name Active ingredient type Name of compound Extracted from Model organism used Insertion through (plant/compound) Compound used to induce IPF for study Levels in effected group Application of plant extract/bioactive compound Effective dose Reference
1 Nelumbo mucifera Bisbenzylisoquinline Neferine Seed embryo Kunming mice Intratracheal Bleomycin (20 mg/kg) Hydroxyproline content: − 255.77 ± 97.17 μg/lung;
269.74 ± 40.92 μg/lung
Endothelin-1: 187.97 ± 49.90 pg/
100 mg protein
SOD: − 75.18 ± 13.89 and 85.28 ± 20.80 U/mg protein); MPO,MDA,TGFβ1,NF-κB, TNF-α are increased
Hydroxyproline content: − 193.07 ± 39.55 μg/lung and 201.08 ± 71.74 μg/lung
Endothelin-1: 123.98 ± 18.91 pg/100 mg protein
SOD: 102.62 ± 27.44 U/mg protein; MPO, MDA, TGFβ1, NF-κB, TNF-α are decreased
98% pure 20 mg/kg [71]
2 Arenaria kansuensis β-Carboline alkaloids Monoacetylarenarine B, 3-hydroxymethyl-β-carboline, glusodichotomine, arenarine A, cordysinin C, 7-methoxy-1-oxo-1,2,3,4-tetrahydro-β-carboline, 3-hydroxy-β-carboline, arenarine D, β-carboline-1-carboxylic acid, 1,2,3,4-tetrahydro-1,3,4-trioxo-β-carbo1ine, arenarine B, cordysinin E Crude extract Adult male and female Kunming mice Gastric gavage Bleomycin (2.5 U/kg) Increase in macrophages, TNF-α, TGF-β1and IL-1β TNF-α, TGF-β1 and IL-1β decreased; survival rate increased; macrophages decreased 100–150 mg/kg dose [72, 73]
3 Mahonia aquifolium Isoquinoline alkaloids Berberine, berbamine, palmatine, magnoflorine and jatrorrhizine Stem bark Male Wistar rats Intraperitoneal Bleomycin MPO, MDA, TGFβ1, NF-κB, TNF α are increased; SOD, CAT, GPx, GSH, vitamins A, C, E are decreased MPO, MDA, TGFβ1, NF-κB, TNFα are decreased; SOD, CAT, GPx, GSH, vitamins A, C, E are increased 200 mg/kg/day [74,75,76]
4 Camellia sinensis Tea catechin Epigallocatechin-3-gallate (EGCG) Black tea extract Swiss albino mice Oral gavage Bleomycin (50 μL of 5 mg/kg body weight) IL-10, TNF-α increases
INF-γ decreases
IL-10, TNF-α decreases
INF-γ increases
25 mg /kg body weight/day and 50 mg/kg body weight/day [77]
5 Punica granatum Dilactone Ellagic acid Seed extract Male Spraque-Dawley rats Gastric Gavage Bleomycin 7.5 IU/kg Assessed by lung histology that showed increased inflammatory cell infiltration Reduced inflammatory cell infiltration and reduced collagen deposition 400 mg/kg dose of pomegranate extract; [78]
Wistar rats Bleomycin and cyclophosphamide 10 U/kg/body weight
150 mg/kg body weight respectively
Hydroxy proline MPO,GSH, NO production increased Hydroxy proline MPO,GSH, NO production are attenuated 15 mg/kg body weight of ellagic acid [79]
6 Acnistus arborescens, Withania obtusifolia Steroidal lactone Withaferin A Leaves Mice Intraperitoneally Bleomycin (0.025 U) Invasiveness of fibroblasts with increased vimentin expression Decreased vimentin expression, collagen increased beclin 1 and LC3B expression 2 mg per kg body weight [80,81,82]
7 Pistacia chinensis Phenolic, flavonoid compound Gallic acid, rutin Bark Male Sprague-Dawley Orally CCl4 (30%) Rise in hydrogen peroxide, NO, eosinophils, lymphocytes, monocytes; Decrease in CAT, POD, GSH, GPx, GST, leukocytes, neutrophils, Haemoglobin Showed protective effect by bringing all these levels to normal by ameliorating toxicity. 400 mg/kg body weight [83]
8 Rosmarinus officinalis Phenolic diterpene Rosmarinic acid and carnosic acid Leaves Male Wistar rats Intraperitoneal injection Bleomycin (4 mg/kg) Lower CAT, GST and increased MDA Normalized levels and showed lower fibrotic score 75 mg/kg [84]
9 Nigella sativa Enzymes, vitamins, aromatic oils Thymoquinone Seeds Male Wistar rats Oral gavage Bleomycin (2 mg/kg) Inflammatory score 3.8 + 0.89; fibrosis 4.88 + 0.21 TGF-β reduction; inflammatory score 1.2 + 0.45; fibrosis 1.83 + 0.68 1 mL/kg/day [85, 117]
10 Pistacia lentiscus Essential fatty acids Linoleic and palmitic acid Seeds Male Wistar Rat Orally Bleomycin (50μL of 4 mg/kg body weight) Decreased CAT, POD, SOD and increase in MDA, hydrogen peroxide, TGF-β1; Fibrosis score (mg g−1) 7.91 + 0.23 Normalize the levels of CAT, POD, SOD, MDA, TGF-β1; Fibrosis score (mg g−1) 4.62 + 0.09 3g/kg, body weight [86]
11 Linum usitatissimum Fatty acids Omega 3 and omega 6 Seeds Male Wistar rats Gavage Bleomycin 4.8 mg/kg body weight Fibrosis score 3.7 + 0.94; inflammatory score 3.3 + 0.48; and decrease in CAT, SOD Fibrosis 3.0 + 1.05; Inflammatory score 1.9 + 0.87; SOD, CAT levels are raised. Here the fatty acid content is increased in cells 2 mL/kg body weight [87]
12 Passiflora edulis Flavonoids Cyanidin-3-O-glucoside, quercetin-3-O-glucoside and edulilic acid Peel C57BL/6J mice Oral Bleomycin (50 μL of 0.05 U) SOD is decreased and MPO, hydroxyproline is increased Hydroxyproline deposition is supressed, MPO levels are reduced and SOD levels are increased 100 mg/kg body weight [88]
13 Tanacetum parthenium Sesquiterpene lactone Parthenolide Crude extract Mice; A549 cell lines Intragastric Bleomycin (5 mg/kg body weight) Increases TGF-β1, NF-κB, Snail, IL-4, TNF-α, collagen deposition, α SMA, vimentin Inhibit TGF-β1, NF-κB, Snail, IL-4, TNF-α, collagen deposition, vimentin, α SMA and rise in MMP, E-cadherin 50 mg/kg [89]
14 Curcuma longa Polyphenol Curcumin Crude extract Male Wistar rats Oral Bleomycin (0.75 U/100 g) increases TNF-α release, and superoxide and NO production Reduced hydroxyproline 300 mg/kg [90]
15 Cordyceps sinensis Purine nucleoside antimetabolite and antibiotic Cordycepin Crude extract Male Sprague-Dawley rats Intragastric Bleomycin (2.5 mg/kg) Rise in TIMP-1, TGF-β1, collagen and ROS TIMP-1, TGF-β1, collagen and ROS are reduced 1.35 g/kg [91]
16 Salvia officinalis Phenolic compounds Vanillic, gallic, ellagic, rosmarinic and carnosic acids Leaves Male Wistar rats Intraperitoneal Bleomycin (4 mg/kg) Rise in MDA, collagen with decrease in SOD, CAT The levels were normalized by reduction of MDA and increase in SOD, CAT 150 mg/kg [92]
17 Silybum marianum Flavonolignan Silymarin Fruits BALB/c mice Intraperitoneally Bleomycin (1.5 U/kg) Rise in MPO, TNF-α, IL-6, MDA and reduction of GST, GSH. Induced GST, GSH and reduced MPO, TNF-α, IL-6, MDA 100 mg/kg [93, 94]
18 Oxalis corniculata C-glycosyl flavonoids Isoorientin, isovitexin and swertisin Crude extract Female Sprague-Dawley rats Intragastrically CCl4 (20%) Reduction of CAT, POD, GSH, GPx, GST. Visibility of pulmonary edema and fibrosis Rise in CAT, POD, GSH, GPx, GST levels. No occurrence of edema and fibrosis 200 mg/kg body weight [95, 117]
19 Tinospora cordifolia Isoquinoline alkaloids Berberine, palmatine, magnoflorine and jatrorrhizine Leaf, stem root Male Wistar albino rat Intraperitoneally Bleomycin (2.5 U/kg) Rise in NF-κB, iNOS, TNF-α, TGF-β1 Inhibited NF-κB, iNOS and reduced TNF-α, TGF-β1 200 mg/kg [76, 96]
20 Phyllanthus emblica Polyphenolics, Flavanoids Gallic acid, rutin, caffeic acid, kaempferol, pyrogallol Leaf Sprague-Dawley male rats Orally CCl4 (30 %) Reduction of CAT, POD, GSH, GPx, GST Rise in CAT, POD, GSH, GPx, GST levels; disrupted alveoli, macrophages infiltration was reversed to normal 200, 400 mg/kg [97, 98]
21 Angelica sinensis Polysaccharides Heteropolysaccharides Root Sprague-Dawley rats Intragastrically Bleomycin (5 mg/kg) TGF-β1 increased
DANCR mediates Angelica Sinensis-induced suppression by rise in FOXO3 protein levels
Angelica Sinensis reduce the DANCR expression which in turn suppresses AUF1-intervened FOXO3 translation to overwhelm the EMT and pulmonary fibrosis 20 mg/kg with adenovirus-associated packaging DANCR sequence [99]
22 Citrus reticulate Flavonoids Hesperidin, narirutin, rutin Pericarp Sprague-Dawley rats Orally Bleomycin (5 mg/kg) Low MMP-9 and rise in TIMP-1 and TNF-α Rise in MMP-9 and reduced TIMP-1 and TNF-α 32 mg/kg/day [100, 101]
23 Houttuynia cordata Amino acids, flavonoids, polysaccharides, volatile acids Quercetin, quercitrin, hyperoside and rutin Whole plant Male Wistar rats Orally Bleomycin (15 mg/kg) IFN-γ, TNF-α, hydroxyproline, MDA, lung weight are increased whereas CAT, body weight is decreased IFN-γ, TNF-α, hydroxyproline, MDA, lung weight is reduced with rise in CAT, body weight 1 g/kg [102]
24 Carthamus tinctorius L Flavonoid Hydroxysafflor yellow A Whole plant Male C57BL/6 mice Intraperitoneally Bleomycin (4.5 mg/kg) Increased collagen deposition, TGF-β1, α-SMA, hydroxyproline, CTGF, inhibited TGF-β induced collagen production Hydroxysafflor yellow A 60 mg/kg/day [103]
25 Eriobotrya japonica Triterpene acids Oleanolic acid, a-hydroxyoleanolic acid, arjunic acid, euscaphic acid, ursolic acid Leaves Male Sprague-Dawley rats Intragastrically Bleomycin (5 mg/kg) Rise in TNF-α and TGF-β1 Reduction of TNF-α and TGF-β1 Triterpene acids (450 mg/kg) [104]
26 Centella asiatica Triterpenoid saponin Madecassoside Leaves Mice Orally Bleomycin (5 mg/kg) Rise in TGF-β1, oxidative damage, MPO. Increased SOD and glutathione and reduced leucocyte in BALF, MPO and oxidative damage Madecassoside (40 mg/kg) [105]