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

Dudala, Sai Sushma; Venkateswarulu, T. C.; Kancharla, Sushma Chandulee; Kodali, Vidya Prabhakar; Babu, D. John

doi:10.1186/s43094-021-00304-5

Future Journal of Pharmaceutical Sciences

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]
5	Punica granatum	Dilactone	Ellagic acid	Seed extract	Wistar rats	Gastric Gavage	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]

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