. 2022 May 27;23(11):6031. doi: 10.3390/ijms23116031

Table 3.

Anti-inflammatory activity of lignans in vitro.

Lignan	Source	In Vitro Model	Target	Concentration	Ref.
Arylnaphthalene structure group
Sevanol	Thymus armeniacus	HEO of X. laevis	↓hASIC3	IC₅₀ 353 ± 23 μM	[119]
	Thymus armeniacus	HEO of X. laevis	↓rASIC1a	IC₅₀ 2.2 ± 0.6 mM	[119]
	Synthetic	HEO of X. laevis	↓rASIC3	IC₅₀ 175 ± 18 μM	[120,121]
		HEO of X. laevis	↓rASIC1a	IC₅₀ 227.5 ± 37.4 μM	[120,121]
		RA-treated SH-SY5Y cells	↓hASIC1a	300 μM	[118]
Aryltetralin structure group
(+)-Isolariciresinol 3a-O-β-D-glucopyranoside	Carissa spinarum Linn.	COX-2 assay	↓COX-2	IC₅₀ 0.3 μM	[30]
Sauchinone	Saururus chinensis	LPS-stimulated RAW264.7	↓NO production	IC₅₀ 4.08 μM	[124]
	Saururus chinensis	LPS-stimulated RAW264.7	↓iNOS, ↓TNF-α, ↓COX-2	1–30 μM	[125]
	Synthetic	AngII-induced mesangial cells	↓TGF-β,	0.1–1 μM	[35]
	Synthetic	AngII-induced mesangial cells	↓NLRP3, ↓ICAM-1, ↓MCP-1, ↓IL-1β, ↓NF-κB p65	1 μM	[35]
Dibenzocyclooctadiene structure group
Schisandrin A	Schisandra chinensis (Turcz.) Baill.	LPS-stimulated RAW 264.7 macrophages	↓NO level, ↓iNOS, ↓PGE₂, ↓COX-2, ↓NF-κB, ↑IκBα, ↓p-JNK, ↓p-p38 MAPK	25–100 μM	[173]
	Synthetic	LPS-stimulated RAW 264.7 macrophages	↓ iNOS, ↓ COX-2, ↓ TNF-α, ↓ IL-1β, ↑ IκB-α, ↓ p-JNK, ↓ p-p38 MAPK, ↓ p-ERK, ↓ p-PI3K, ↓ p-Akt	200 μM	[40]
		DON-induced cytotoxicity in HT-29 cells	↓ PGE₂, ↓ COX-2, ↓ NF-κB, ↓ IL8, ↓ p-p38, ↓ p-ERK	2.5–10 μM	[42]
		RANKL-induced osteoclast differentiation	↓ PGE₂, ↓ COX-2, ↓ NF-κB, ↓ IL8, ↓ p-p38, ↓ p-ERK	50–200 μM	[43]
Schisandrin B	Synthetic	Con A-induced lymphocytes	↓ NF-κB, ↓ p-MEK, ↓ p-p38, ↓ p-ERK, ↓ p-JNK, ↑ IκBα, ↓ IL-2, ↓ IL-4, ↓ IL-6, ↓ IFN-γ	25–50 μM	[46]
		Ang II/TNF-α/ROS-induced HUVECs	↓NF-κB, TNF-α, ↓p-Smad2/3, ↓vimentin, ↓α-SMA, ↓Snail/slug, ↓TGF-β, ↓Twist, ↑VE-cadherin	10 μM	[176]
		TH17 cell differentiation	↓p-STAT3	1 μM	[178]
		H/R-induced H9c2 cell injury	↓ IL-1β, ↓ TNF-α, ↓ IL-6, ↓ IL-8, ↓ TGF-β, ↑ IL-10	20 μM	[50,51]
		LPS+ATP-treated intestinal epithelial cells	↓TNF-α, ↓IL-6, ↓IL-18, ↓IL-1β, ↓NLRP3, ↑p-AMPK	40 μM	[177]
Schisandrin C	Synthetic	LPS-stimulated HDPCs	↓ NO level, ↓ p-ERK1/2, ↓ p-SAPK/JNK, ↓ p-p38, ↓ NF-κB	10–20 μM	[52]
Schisantherin A	Schisandra chinensis (Turcz.) Baill.	H/R-induced HK-2 cells	↓ TNF-α, ↓ IL-1β, ↓ IL-6	5–20 μM	[53]
	Schisandra chinensis (Turcz.) Baill.	LPS-stimulated BV-2 microglial cells	↓ NF-κB, ↓ IKK, ↑ IκB, ↓ TNF-α, ↓ IL-6, ↓ IL-1β, ↑ IL-10 ↓ iNOS, ↓ COX-2 ↓ p-p38, ↑ p-ERK, ↓ p-JNK, ↓ p-Akt	50 μM	[54]
	Synthetic	LPS-stimulated NRK-52E cells	↓NF-κB, ↓TNF-α, ↓Rantes	25–50 μM	[55]
Dibenzylbutane structure group
Nordihydroguaiaretic acid	Synthetic	IL-1β-induced PC12 cells	↓APP secretion and processing	10 μM	[183]
		IFN-γ- induced rat brain astrocytes/C6 cells	↓IRF-1, ↓IP-10 ↓p-STAT1, ↓p-STAT3,↓p-↓JAK2	5–20 μM	[184]
		RANKL-induced bone marrow-derived macrophage/RAW-D cells	↓ osteoclast differentiation, ↓ RANKL-induced signal cascade ↓ NFATc1, ↓ p-ERK	1–10 μM	[185]
Secoisolariciresinol diglucoside	Linum usitatissimum Linn.	iron treated H9c2 cells	↓ TNF-α, ↑ IL-10	500 μM	[73]
	Linum usitatissimum Linn.	CdCl₂-injured model	↓MPO, ↓NO level	10 mg/kg of rat	[148]
	Synthetic (LGM2605)	asbestos-exposed MFs	↓iNOS, ↓IL-1β, ↓IL-6, ↓IL-18, ↓TNFα	50–100 μM	[74,75]
Dibenzylbutyrolactone structure group
Arctigenin	Forsythia fructus	pro-inflammatory enzyme assays	↓ PLA2, ↓ COX-1, ↓ COX-2, ↓ 5-LOX	100 μM	[186]
	Arctium lappa Linn.	bone marrow-derived MDSCs	↑Arg-1, ↑iNOS	10–20 μM	[187]
	Synthetic	LPS-treated Raw264.7 cells	↓ iNOS, ↓ p-STAT, ↓ IL-1β, ↓ IL-6, ↓ MCP-1, ↓ p-JAK2	5–50 μM	[78]
		TGF-β1-induced HK-2 cells	↓ NF-κB p65, ↓ MCP-1	0.5–1 μM	[83]
		OA-treated WRL68 hepatocytes	↓ ICAM-1, ↓ IL-1β, ↓ IL-6, ↓ IL-7, ↓ IL-8, ↓ TNFα	50 μM	[85]
		LPS-treated RAW264.7 cells	↓TNF-α, ↓IFN-γ, ↓IL-17, ↓IL-1β, ↓CXCL10, ↑TGF-β1, ↑IL-4	10–100 μM	[188]
		LPS-treated RAW264.7 cells	↓TNF-α, ↓IFN-γ, ↓IL-17, ↓IL-1β, ↓CXCL10, ↑TGF-β1, ↑IL-4	10–100 μM	[188]
		IL-1β–stimulated human chondrocytes	↓ TNF-α, ↓ COX-2, ↓ iNOS, ↓ IL-6, ↓ PGE₂, ↓ NO, ↑ IκBα, ↓ p65, ↓ PI3K, ↓ Akt	10–50 μM	[189]
		scintillation proximity assay	↓PDE4	IC₅₀ 3.76 ± 0.28 μM	[190]
		LPS-stimulated human PBMCs	↓ TNF-α	IC₅₀ 35.18 ± 6.01 μM
		LPS-treated RAW264.7 cells	↓TNF-α, ↑p-CREB, ↓PDE4	100 μM
		OGD-injured H9c2 cardiomyocytes	↓NF-κB, ↑IKBα, ↓TNF-α, ↓IL-1β, ↓IL-6	50–200 μM	[87]
		silica-injured RAW 264.7 macrophages	↓iNOS, ↓Arg-1, ↓TLR-4, ↓NLRP3, ↓TGF-β	1 μM	[88]
Hinokinin	Aristolochia indica L.	LPS-stimulated THP-1 cells	↓ IL-6	20.5 ± 0.5 μM	[191]
Hinokinin	Aristolochia indica L.	LPS-stimulated THP-1 cells	↓ TNF-α	77.5 ± 27.5 μM	[191]
Matairesinol	Synthetic	naive CD4⁺ T cells	↓p-p38, ↓p-ERK, ↓ROR-γt	20 μM	[192]
Matairesinol	Synthetic	LPS-stimulatedNSC-34neurons andBV2microglia	↓TNF-α, ↓IL-1β, ↓IL-6, ↓IFN-γ, ↓IL-8, ↓MCP1, ↓MAPK, ↓JNK, ↓NF-κB	5–20 μM	[93]
Matairesinol-7′-hydroxyl	Piceaabies	TNF-α-induced HAEC	↓ICAM-1, ↓VCAM-1, ↓monocyte adhesion	0.1–100 μM	[193]
			↓p-NF-κB	10–100 μM
			↓p-ERK	100 μM
Nortrachelogenin	Synthetic	LPS-stimulated J774 macrophages	↓PGE₂, ↓NO, ↓iNOS	1–30 μM	[194]
			↓MCP-1, ↓IL-6	3–30 μM
			↓mPGES-1	30 μM
Furanoid structure group
(−)-Olivil	Osmanthus fragrans var. aurantiacus	LPS-activated RAW264.7 cells	↓NO level	IC₅₀ 85.6 ± 1.49 μM	[195]
Taxiresinol	Osmanthus fragrans var. aurantiacus	LPS-activated RAW264.7 cells	↓NO level	IC₅₀ 58.1 ± 1.42 μM	[195]
Taxiresinol	Perovskiaatriplicifolia Benth	RBL-1 leukemia cells	↓leukotriene C4 release	IC₅₀ 3.4 ± 0.09 μM	[196]
Furofuranoid structure group
Dendranlignan A	Dendranthema morifolium (Ramat.)	LPS-induced H9c2 cells	↓TNF-α, ↓IL-6, ↓IFN-γ ↓p-cJUN, ↓p-P65, ↓p-IRF3	10 μM	[103]
(+)-Diayangambin	Piper fimbriulatum	human mononuclear cells	↓proliferation	1.5 μM	[197]
(+)-Diayangambin	Piper fimbriulatum	LPS-stimulated RAW264.7 macrophages	↓ PGE₂	10 μM	[197]
Fargesin	Magnolia fargesii	PMA-stimulated THP-1	↓iNOS, ↓COX-2, ↓IL-1β, ↓TNF-α, ↓AP-1, ↓NF-κB, ↓JNK	5–20 μM	[198]
Fargesin	Magnolia sp.	LPS-stimulated RAW264.7	↓iNOS, ↓COX-2, ↓NF-κB	25 μM	[199]
Koreanaside A	Forsythia koreana	LPS-stimulated RAW 264.7 macrophages	↓iNOS, ↓COX-2, ↓IL-6, ↓TNF-α, ↓p-IκBα, ↓p-TAK1	20–80 μM	[200]
Koreanaside A	Forsythia koreana	LPS-stimulated RAW 264.7 macrophages	↓AP-1, ↓p-c-Fos, ↓p-p65, ↓NF-κB, ↓p-IKKα/β, ↓p-STAT1, ↓p-STAT3, ↓p-JAK1, ↓p-JAK2	40–80 μM	[200]
Phillygenin	Forsythia koreana	RAW 264.7 cells	↓PGE₂, ↓NO, ↓iNOS, ↓NF-κB	1–100 μM	[201]
Pinoresinol	Synthetic	IL-1β-stimulated Caco-2 cells	↓ PGE₂, ↓ MCP-1, ↓ NF-κB	50–100 μM	[202]
Pinoresinol	Synthetic	IL-1β-stimulated Caco-2 cells	↓IL-6	10–100 μM	[202]
Pinoresinol diglucoside	Eucommia ulmoides	oxLDL-induced HUVEC cytotoxicity	↓ eNOS, ↓ p-p38MAPK, ↓ p-NF-κB p65	1 μM	[109]
Sesamin	Sesamum indicum Linn.	oxLDL-induced HUVECs cytotoxicity	↓NF-κB, ↓IL-8	12.5–100 μM	[110]
		FPR-transfected ETFR cells, THP1 cells	↓cell migration, ↓NF-κB activation, ↓ERK1/2 phosphorylation	6.25–50 μM	[203]
		KA-induced PC12 and BV-2 cells	↓ERK1/2, ↓p38 MAPK, ↓COX-2	10–50 μM	[111]
		RPMC	↓histamine release	25–100 μM	[204]
		HMC-1	↓TNF-α, ↓IL-6, ↓p38 MAPK, ↓NF-κB	25–100 μM	[204]
	Synthetic	RLE-6TN and L2 cells	↑A20, ↑TAX1BP1	10 μM	[205]
epi-Sesamin	Asarum siebodlii	HUVEC	↓EPCR shedding	1–10 μM	[206]
Syringaresinol	Perovskiaatriplicifolia Benth	RBL-1 leukemia cells	↓leukotriene C4 release	IC₅₀ 7.9 ± 0.04 μM	[196]
	Rubia philippinensis	LPS-stimulated RAW 264.7 cells	↓iNOS, ↓COX-2, ↓TNF-α, ↓IL-1β, ↓IL-6, ↓PGE₂, ↓ERK1/2, ↓JNK, ↓p38 MAPK	25, 50, 100 μM	[207]
		High glucose-treated NRVM	↓TNF-α, ↓IL-6, ↓IL-1β, ↓TGF-β, ↓p-Smad2/3	50, 100 μM	[116]
		LPS⁺ ATP-treated H9c2 cells	↓IL-1β, ↓IL-18, ↑SIRT1 expression, ↓NLRP3 inflammasome activation	100 μM	[208]
	Albiziae cortex	BV2 microglia cells	↓TNF-α, ↓IL-6, ↓IL-1β, ↓COX-2, ↓NO, ↑M2 phenotype, ↓NF-κB	25, 50, 100 μM	[209]

AKT, protein kinase B; APP, amyloid precursor protein; ASIC 1/3 h/r, acid-sensing ion channel isoform 1/3 type human/rat; BV-2 cells, murine microglial cell line; COX-2, cyclooxygenase-2; CREB, cAMP-response element binding protein; DON, trichothecene toxin deoxynivalenol; EPCR, endothelial protein C receptor; ERK, extracellular signal-regulated kinase; ETFR, epitope-tagged human FPR cell; FPR, formyl peptide receptor; H9c2 cells, embryonic rat heart derived cell line; HAEC, human aortic endothelial cells; HDPCs, human dental pulp cells; HEO of X. laevis, heterologously expressing oocytes of Xenopus laevis frog; HK-2, human renal tubular epithelial cells; HMC-1, human mast cell line 1; H/R, hypoxia/reoxygenation; HUVECs, human umbilical vein endothelial cells; IκBα, inhibitor of κB; IKKα/β, IκB kinase; IL, interleukin; iNOS, inducible nitric oxide synthase; IP-10, inducible protein-10; IRF-1, interferon regulatory factor-1; JAK2, Janus kinase 2/signal transducer; JNK, c-Jun N-terminal kinase; KA, kainic acid; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; mPGES-1, microsomal prostaglandin E synthase-1; MPO, myeloperoxidase; NF-κB, nuclear factor-κB; NLRP3, nod-like receptor family pyrin domain containing 3; NRK-52E cells, normal rat kidney cell line; NRVM, neonatal rat ventricular myocytes; OA, oleic acid; OGD, oxygen glucose deprivation; oxLDL, oxidized low-density lipoprotein; PBMCs, human peripheral blood mononuclear cells; PC12 cells, rat pheochromacytoma cell line; PDE, phosphodiesterase; PGE2, prostaglandin E2; PMA, phorbol-12-myristate-13-acetate; PPAR, peroxisome proliferator-activated receptor; RA, retinoic acid; RANKL, receptor activator of NF-κB ligand; RLE-6TN, rat lung epithelial-6-T-antigen negative cell line; ROR-γt, retinoid-related orphan receptor-γt; RPMC, rat peritoneal mast cell; SH-SY5Y, human neuroblastoma cell line; SIRT1, NAD-dependent deacetylase sirtuin-1; STAT3, signal transducer and activator of transcription 3; TAK1, TGF-β-activated kinase 1; TGF-𝛽, transforming growth factor-𝛽; TNF-α, tumor necrosis factor α. Downward-pointing red arrows reflect the downregulatory action, upward-pointing green arrows reflect the upregulatory action.