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

Table 2.

Antioxidant activity of lignans ex vivo and in vivo.

Lignan	Source	Model		Target	Dose, Road	Ref.
Dibenzocyclooctadiene structure group
Gomisin A	Schisandra chinensis Baill.	CCl₄-induced hepatotoxicity		↓MDA content, ↑SOD	50–100 mg/kg of rat, i.p.	[127]
Gomisin N	Synthetic	ethanol-injured model		↓iROS, ↑GSH/GSSG, ↑CAT, ↑SOD, ↑GPx, ↑SIRT1/AMPK, ↓CYP2E1	5–20 mg/kg of mice, p.o.	[38]
Schisandrin A	Synthetic	ovariectomy-induced osteoporosis		↓iROS level, ↑Nrf2	100 mg/kg of mice, i.p.	[43]
Schisandrin B	Schisandra chinensis (Turcz.) Baill.	I/R injury model		↑GSH/GSSG level	1.2 mmol/kg of rat, e.v.p.	[128]
	Synthetic	CCl₄-induced hepatotoxicity		↑mtGSH/GSSG level, ↓mtMDA content, ↑GR, ↑GST, ↑GPx	2 mmol/kg of mice, p.o.	[129,130]
		ethanol-injured model		↓iROS, ↑GSH/GSSG level, ↑α-TOC, ↓MDA content, ↑GR, ↑GST, ↑MnSOD, ↑GPx	10 mg/kg of rat, i.g.	[131]
		Aβ-infused model		inhibition of ROO^•-induced oxidation, ↑ORAC, ↑GSH/GSSG level, ↓MDA content, ↑SOD	25–50 mg/kg of rat, p.o.	[132]
		TSCI model		↑SOD	50 mg/kg of rat, p.o.	[133]
		I/R injury model		↓MDA content, ↑SOD	80 mg/kg of rat, p.o.	[134]
		STZ-induced diabetic model		↓iROS level, ↑Nrf2 ↑Bcl-2/Bax	20 mg/kg of mice, p.o.	[135]
		acute stress-induced anxiety		↓iROS level, ↓Keap1, ↑Nrf2, ↑SOD, ↑GSH/GSSG level	30–60 mg/kg of mice, p.o.	[136]
		pirarubicin-induced cardiotoxicity		↑SOD2, ↑CAT ↑Bcl-2/Bax	50 mg/kg of rat, diet	[137]
Schisandrin C	Synthetic	Ang II-induced endothelial deficit model		↓iROS level ↑Nrf2, ↑NQO-1, ↑HO-1, ↓Keap1	10 mg/kg of mice, i.g.	[138]
Schisantherin A	Schisandra chinensis (Turcz.) Baill.	Aβ-infused model		↓MDA content, ↑GSH/GSSG level, ↑SOD, ↑GPx	0.1 mg/kg of mice, i.c.v.	[139]
	Schisandra chinensis (Turcz.) Baill.	chronic fatigue/D-galactose-induced LMI model		↑GSH/GSSG level, ↓MDA content, ↓Keap1, ↑Nrf2, ↑HO-1, ↑SOD, ↑CAT, ↑Bcl-2/Bax	2.5–5 mg/kg of mice, i.g.	[140,141]
	Synthetic	MCAO/R-induced brain injury		↓MDA level, ↑SOD, ↑Trx, ↑PRDx, ↓NOX4	5–10 mg/kg of rat, i.g.	[142]
Dibenzylbutane structure group
Nordihydroguaiaretic acid	Synthetic	ozone-induced lung injury	↓tyrosine nitration level		20 mg/kg of rat, Alzet osmotic pumps	[61]
	Synthetic	K₂Cr₂O₇-induced renal injury	↓NAG, ↑GPx		17 mg/kg of rat, mini-osmotic pumps	[143]
	Larrea tridentata	ALIOS-fed model	↑GPx4, ↑PRDx3, ↑PPARα		2.5 g/kg of mice, diet	[144]
Secoisolariciresinol diglucoside	Linum usitatissimum Linn.	metabolic syndrome model	↓TBARS, ↓iROS, ↑GSH/GSSG level, ↑SOD, ↑CAT, ↑GPx		20 mg/kg of rat, p.o.	[145]
	Synthetic	CCl₄-induced hepato- and nephrotoxicity	↓MDA content, ↑CAT, ↑SOD, ↑POX, ↓LPO		12.5–25 mg/kg of rat, p.o.	[72]
	Synthetic	MCT-induced heart failure	↓iROS level, ↑SOD, ↑CAT, ↑GPx		25 mg/kg of rat, p.o.	[146]
	Synthetic (LGM2605)	CLP-induced sepsis	↓iROS level		100 mg/kg of mice, i.p.	[76]
	Synthetic (LGM2605)	NRC painful model	↓8-OHG		200 mg/kg of rat, s.c.	[147]
	Linum usitatissimum Linn.	CdCl₂-injured model	↑SOD, ↑CAT, ↑GPx, ↑GR		10 mg/kg of rat, s.c.	[148]
	Synthetic	BaP-injured model	↑GSH/GSSG, ↓MDA, ↑SOD, ↑CAT ↓p-p38, ↓p-ERK, ↑MKP-1, ↓miR-101A		100 mg/kg of mice, i.g.	[149]
	Synthetic	aging ovaries	↓iROS level		7–70 mg/kg of mice, i.g.	[150]
Dibenzylbutyrolactone structure group
Arctigenin	Arctium lappa Linn.	WFST model		↑Nrf2, ↑SOD, ↑GR, ↑GPx, ↑Trx1, ↑UCP2, ↑p-AMPK, ↑p-p53, ↑p21, ↑PGC-1α, ↑PPARα	15 mg/kg of rat, i.p.	[80]
	Arctium lappa Linn.	ethanol-induced gastric ulcer		↓MDA content, ↑SOD	0.05–0.45 mg/kg of rat, p.o.	[151]
	Synthetic	JEV-infected model		↓ ROS level, ↑ SOD1	10 mg/kg of mice, i.p.	[152]
		LPS-injured model		↑GSH/GSSG level, ↓MDA content, ↑SOD, ↑CAT, ↑HO-1	50 mg/kg of mice, i.p.	[153]
		I/R injury model		↓MDA content, ↑SOD, ↑GPx ↑Nox1, ↑Trx1, ↑Nrf2	50–200 mg/kg of rat, i.g.	[154]
		AMI model		↓MDA content, ↑SOD, ↑GPx, ↑CAT, ↑HO-1	100–200 μmol/kg of rat	[155]
		Hep G2 xenograft model		↑p-p38, ↑p-JNK,↑Bax,↑TNF-α	20 mg/kg of mice, s.c.	[86]
		BLM-induced skin fibrosis		↑GSH/GSSG level, ↓MDA content, ↑SOD, ↑Nrf2, ↑HO-1	3 mg/kg of mice, i.p.	[156]
		I/R injury model		↓iROS level, ↓MDA content, ↑SOD ↑AMPK/SIRT1	100 μmol/kg of rat, i.p.	[87]
		cadmium-intoxicated model		↑GSH/GSSG, ↓8-oxo-dG level, ↓MDA, ↑GSR, ↑GCL, ↑GPx, ↑CAT ↑Nrf2, ↑HO-1, ↑NQO1	80 mg/kg of rat, i.g.	[157]
Hinokinin	Synthetic	HFD/STZ-induced type 2 diabetes		↓MDA, ↑SOD, ↑CAT, ↑GPx, ↑GST, ↑HO-1, ↑Nrf2, ↓Keap-1	20–40 mg/kg of mice, p.o.	[158]
Matairesinol	Synthetic	CLP-induced sepsis		↓MDA content, ↑SOD, ↑CAT, ↑GPx, ↑Nrf2, ↑HO-1, ↑AMPK	5–20 mg/kg of rat, p.o.	[93]
Furofuranoid structure group
Fargesin	Synthetic	I/R injury model		↓MDA content, ↓ROS level, ↑SOD, ↑GPx, ↑CAT	15 μmol/kg of rat, i.v.	[159]
Isoeucommin A	Eucommia ulmoides Oliv.	H₂O₂-injured RTECs		↑SOD, ↑HO-1, ↑Nrf2	31.25–125 μM	[104]
				↑GSH/GSSG level	62.5–125 μM
				↓MDA content	125 μM
		STZ-induced diabetic nephropathy		↓MDA content, ↑GSH/GSSG level	2.5–10 mg/kg of rat, i.v.
		STZ-induced diabetic nephropathy		↑SOD	5–10 mg/kg of rat, i.v.
Pinoresinol diglucoside	Synthetic	Aβ-infused model		↓iROS level, ↓MDA content, ↑SOD, ↑CAT, ↑Nrf2, ↑HO-1 ↑Bcl-2/Bax	5–10 mg/kg of mice, i.g.	[160]
Pinoresinol diglucoside	Synthetic	MCAO model		↓iROS level, ↓MDA content, ↑GSH/GSSG level, ↑SOD, ↑GPx, ↑Nrf2, ↑NQO-1, ↑HO-1	5–10 mg/kg of mice, i.v.	[161]
Sesamin	Synthetic	STZ-induced diabetes		↓MDA content, ↑SOD	20 mg/kg of rat, p.o.	[162]
		nickel-induced hepatotoxicity		↓iROS, ↓TBARS, ↑GSH/GSSG level, ↓8-OHdG, ↑SOD, ↑CAT, ↑GPx ↑PI3K/AKT, ↑Bcl-2/Bax	60–120 mg/kg of mice, p.o.	[163]
		CCl₄-induced hepatotoxicity		↓iROS, ↓TBARS level ↓p-JNK, ↓p-c-Jun, ↓cCYC, ↓Bax, ↓Bak, ↓Bcl-2	60–120 mg/kg of mice, p.o.	[164]
		fluoride-exposed model		↓iROS, ↓TBARS, ↑GSH/GSSG level, ↑SOD, ↑CAT, ↑GPx, ↑GST ↓p-JNK, ↓p-c-Jun, ↑Bcl-2/Bax	0.5–1 g/kg of carp, diet	[165]
	Sesamum indicum Linn.	DOX-treated model		↓iROS level, ↓MDA content ↑SOD, ↑CAT, ↑GPx	20–40 mg/kg of rat, i.g.	[166]
		6-OHDA model		↓iROS level, ↓MDA content, ↑SOD	20 mg/kg of rat, p.o.	[167]
		LPS-treated model		↑SOD, ↓MDA content	10 mg/kg of rat, p.o.	[168]
		LPS-treated model		↑GSH/GSSG level, ↓MDA content ↑SOD, ↑CAT, ↑Nrf2	100 mg/kg of mice, p.o.	[169]
		DSS-induced colitis		↓iROS level, ↑GSH/GSSG level, ↓MDA content, ↑SOD, ↑Nrf2, ↓Keap1, ↑HO-1, ↑NQO1, ↑GCLC, ↑GCLM, ↑GR, ↑p-AKT, ↑p-ERK1/2	50–100 mg/kg of mice, i.g.	[113]
		cisplatin-injured model		↓MDA content, ↑SOD, ↑Nrf2 ↓nitrate/nitrite ratio	5 mg/kg of rat, p.o.	[170]
		adult Drosophila		↑Nrf2/Cnc	2 mg/mL, diet	[171]
Syringaresinol	Panax ginseng C.A. Meyer	Sod1^–/– double-mutant model		↓iROS level, ↓8-isoprostane level ↓FoxO3a, ↓MMP-2	50 mg/kg of mice, p.o.	[172]
Syringaresinol	Sargentodoxa cuneata	STZ-induced diabetes		↑Nrf2, ↑NQO-1, ↑HO-1, ↓Keap1, ↑SOD, ↑Bcl-2/Bax	25 mg/kg of mice, p.o.	[116]

6-OHDA, 6-hydroxydopamine; 8-OHG, 8-hydroxy-2-deoxyguanosine; α-TOC, α-tocopherol; Aβ, amyloid β; ALIOS model, American lifestyle-induced obesity syndrome model; AMI, acute myocardial infarction; Ang, angiotensin; BaP, benzo[a]pyrene; BLM, bleomycin; CLP, cecal ligation and puncture; Cnc, Drosophila Nrf2 orthologue; DOX, doxorubicin; DSS, dextran sulfate sodium; e.v.p., ex vivo pretreatment; HFD, high fat diet; i.c.v., intracerebroventricular administration; i.g., intragastric administration; i.p., intraperitoneal injection; i.v., intravenous injection; JEV, Japanese encephalitis virus; LMI, learning and memory impairment; LPO, lipid peroxidation; MCAO, middle cerebral artery occlusion model; MCT, monocrotaline; miR-101, microRNA 101a; MKP-1, protein-mitogen-activated protein kinase phosphatase 1; NAG, N-acetyl-β-D-glucosaminidase; NRC, nerve root compression; p.o., oral administration; RTECs, renal tubular epithelial cells; s.c., subcutaneous injection; STZ, streptozotocin; WFST, weight-loaded forced swimming test. Downward-pointing red arrows reflect the downregulatory action, upward-pointing green arrows reflect the upregulatory action.