. 2021 Jun 30;13(7):991. doi: 10.3390/pharmaceutics13070991

Table 1.

Anti-inflammatory effects of SL-containing natural extracts in different in vitro and in vivo experimental models. The affected inflammatory pathways are described, as well as the experimental outcomes observed in each study, and the extract concentration range tested. ↓—decrease; ↑—increase.

Source	Main SLs	Model		Extract Concentration Range	Inflammatory Pathways	Consequences	References
Cichorium intybus L.	Dihydrolactucin, lactucin, deoxylactucin, jacquinelin and dihydrolactucopicrin	In vitro	RAW 264.7 murine macrophages + LPS	IC₅₀ (μg/mL): 117 for COX-2; 39 for iNOS; 48 for TNF-α; 22 for IL-1β; 21 for NO	-	↓ COX-2, iNOS, TNF-α, IL-1β, NO	[17]
		In vivo	Paw edema model: Wistar rats + carrageenan (subcutaneous)	50–100 mg/kg (oral administration)	-	↓ paw volume (edema)
		In vivo	Arthritis model: Wistar rats + collagen (intravenous)	200 mg/kg (oral administration)	-	↓ paw volume (edema)
Artemisia leucodes L.	Leukomisin and austricin	In vitro	RAW264.7 murine macrophages + LPS	2–100 μg/mL	-	↓ COX-2, iNOS, IL-1β, NO	[18]
		In vitro	COX-1 and -2 enzymatic assay	45–225 μg/mL		↓ COX-2
		In vivo	Paw edema model: Wistar rats + carrageenan (subcutaneous)	50–200 mg/kg (oral administration)		↓ paw edema
		In vivo	Chronic inflammation model: Wistar rats + cotton implant granuloma test	50 mg/kg (oral administration)		↓ granuloma and inflammatory cell infiltrate
Artemisia khorassanica L.	Unspecified	In vitro	J774A.1 murine macrophages + LPS	10–100 μg/mL	↓ NF-κB	↓ COX-2, PGE₂, iNOS, NO, TNF-α and IL-1β	[19]
Artemisia sps (A. kopetdaghensis, A. santolina, A. Sieberi, A. Fragrans, A. Absinthium, A. ciniformis)	Saturated, unsaturated and unusual SLs	In vitro	J774A.1 murine macrophages + LPS	10–100 μg/mL	-	↓ COX-2, PGE₂, iNOS and NO	[20]
Eupatorium perfoliatum L.	Diguaiaperfolin (dimeric guaianolide) and Eupafolin (flavonoid)	In vitro	RAW264.7 murine macrophages + LPS	1–100 μg/mL	-	↓ NO, CSF-3, IL-6, IL-1α, IL-1β, TNF, Chemokine (C-C motif) ligand (CCL)-2, CCL22 and CXCL10	[21]
Xanthium spinosum L.	Ziniolide	In vitro	Rat polymorphonuclear leukocytes (PMNLs) + ionophore A23187 and Ca²⁺	0–100 μg/mL	↓ NF-κB and arachidonic acid	↓ 5-LOX	[22]
			Human platelets + ionophore A23187	25–200 μg/mL		↓ COX-1 and 12-LOX; ↑ 15(S)-HETE
			HeLa cells + Phorbol 12-myristate 13-acetate (PMA)	12.5–100 μg/mL		↓ NF-κB activation
Arnica montana L.	Helenalin and dihydrohelenalin ester derivatives	In vitro	Jurkat T cells + TNF-α or PMA	0.5–10 μL/mL	↓ NF-κB and NFAT	↓ NF-κB and NFAT DNA-binding	[23]
Arnica montana L.	Helenalin and dihydrohelenalin ester derivatives	In vitro	Human PBMCs from healthy donors + LPS	0.001–10 μL/mL	↓ NF-κB and NFAT	↓ TNF-α and IL-1β	[23]
Centaurea L. species (C. aphrodisea, C. athoa, C. hyalolepis, C. iberica, C. polyclada)	SL fraction (athoin, 14-O-acetylathoin and methyl-14-O-acetylathoin-12-oate in C. athoa)	In vitro	SW1353 human chondrosarcoma cells + PMA	0–100 μg/mL	↓ NF-κB	↓ NF-κB activity	[24,25]
		In vitro	RAW264.7 murine macrophages + LPS	0–100 μg/mL		↓ NO
		In vivo	Paw edema model: Wistar rats + carrageenan (subcutaneous)	6.75–50 mg/kg (oral administration)		↓ edema
Inula helenium L	Alantolactone and isoalantolactone	In vitro	bEnd.3 mouse endothelial cells + TNF-α	0.6–2.4 μg/mL	↓ NF-κB and MAPKs	↓NF-κB inhibitor (IκB)-α, NF-κB p65, p38 and c-Jun N-terminal kinase (JNK) phosphorylation	[26]
			RAW264.7 murine macrophages + LPS			↓ IL-1, IL-6 and iNOS
			Primary synovial fibroblasts from rheumatoid arthritis patients + TNF-α			↓ IL-1, MCP-1 and MMP-3
		In vivo	Adjuvant-induced mice arthritis model	12.5–50 mg/kg (oral administration)		↓ paw swelling
		In vivo	Collagen-induced mice arthritis model	12.5–50 mg/kg (oral administration)		↓ paw swelling
Arctium lappa L.	Onopordopicrin	In vivo	Colitis model: Wistar rats + Trinitrobenzene Sulfonic Acid (TNBS) (enteral instillation)	25–50 mg/kg (oral administration)	-	↓ TNF-α and COX-2; ↓ histological damage; ↓ mucin layer loss; ↓ neutrophil infiltration	[27]
Vernonia scorpioides L.	Diacethylpiptocarphol and related hirsutinolides	In vivo	Acute ear edema model: Swiss mice + 12-O-tetradecanoylphorbol acetate (TPA) (topical)	0.003–1 mg (topical)	↓ NF-κB	↓ neutrophil infiltration, edema and epidermal proliferation	[29]
Vernonia scorpioides L.	Diacethylpiptocarphol and related hirsutinolides	In vivo	Chronic ear edema model: Swiss mice + arachidonic acid (topical) or croton oil (topical)	1 mg (topical)	↓ NF-κB		[29]