Fcγ and Complement Receptors and Complement Proteins in Neutrophil Activation in Rheumatoid Arthritis: Contribution to Pathogenesis and Progression and Modulation by Natural Products

Table 4

Plant extracts and isolated natural products that modulate the complement system activity and/or activation.

Therapy	Source	Model	Effect	Reference
Bridelia ferruginea; (stem bark extract)		In vitro	↓ classical and alternative pathways of the CS.	[167]
Magnolia fargesii; (flower buds extract)		In vitro	↓ classical pathway of the CS more effectively than rosmarinic acid.	[168]
Rosmarinic acid	Melissa officinalis; Rosmarinus officinalis	In vitro	↓ activity of the C3 convertase of the classical pathway of the CS.	[165]
		In vivo	↓ endotoxin-induced CS activation in a rabbit model of circulatory shock.	[166]
	Commercial	In vivo	↓ cobra venom factor-induced paw edema and passive cutaneous anaphylaxis in rats.	[165]
		In vivo	Selective inhibition of complement-dependent inflammation.	[165]
		In vivo	↓ cobra venom factor-induced systemic neutropenia.; ↓ neutrophil migration to the lungs, ↓ bronchoalveolar vascular leakage, ↓ blood pressure alterations, ↓ TNF-α levels in serum and bronchoalveolar lavage fluid in an animal model of acute respiratory distress syndrome.	[169]
		In vivo	↓ complement factor B and MAC expression, ↓ infiltration of inflammatory cells, ↓ fibrosis in renal tissues, ↑ kidney function without impairing liver function and lipid metabolism in animal models of human autosomal dominant polycystic kidney disease.	[170]
Campneoside II^a; Isocampneoside II^b; Isoilicifolioside A^c; Ilicifolioside A^d	Paulownia tomentosa (wood)	In vitro	↓ hemolytic activity of the classical pathway of the CS more effectively than tiliroside and rosmarinic acid.	[171]
3,5-Dicaffeoylquinic acid; 1,3,4,5-Tetracaffeoylquinic acid	Bridelia ferruginea (stem bark)	In vitro	↓ hemolytic activity of the classical and alternative pathways of the CS more strongly than rosmarinic acid.; ↓ activation of the C1 component and the terminal route of the CS.	[167]
Entadamide A; Homogentisic acid	Entada phaseoloides (seed)	In vitro	↓ hemolytic activity of the CS more strongly than their glycosylated analogues entadamide A--D-glucopyranoside and homogentisic acid 2---D-glucopyranoside (phaseoloidin), respectively.	[172]
Kaempferol 3-O-rhamnoside; Kaempferol 3-O-rutinoside; Morindaoside^e	Morinda morindoides (stem bark)	In vitro	↓ hemolytic activity of the classical and alternative pathways of the CS.	[173]
Myricetin; Myricetin 3,3′,4′,5′-tetramethyl ether; Quercetin 3,7,3′,4′-tetramethyl ether	Bridelia ferruginea (stem bark)	In vitro	↓ hemolytic activity of the alternative pathway of the CS more effectively than rosmarinic acid.	[167]
Podocarpaside I	Actaea podocarpa (roots)	In vitro	Moderate inhibition of the hemolytic activity of the CS.	[174]
Tiliroside^f	Magnolia fargesii (flower buds)	In vitro	↓ hemolytic activity of the classical pathway of the CS more strongly than rosmarinic acid.; Its hydrolysis products kaempferol, astragalin, and -coumaric acid do not exert significant anticomplement activity.	[168]

CS: complement system; MAC: membrane attack complex; TNF-α: tumor necrosis factor-α.
^a2-(3,4-Dihydroxyphenyl)-2-hydroxyethyl-3-O-α-L-rhamnopyranosyl-4-O-(3,4-dihydroxycinnamoyl)--D-glucopyranoside.
^b(R,S)-7-(3,4-Dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl(1→3)-β-D-(6-O-caffeoyl)-glucopyranoside.
^c(R,S)-β-Ethoxy-β-(3,4-dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl(1→3)--D-(6-O-E-caffeoyl)-glucopyranoside.
^dβ-Ethoxy-β-(3′,4′-dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl-(1→3)-4-O-caffeoyl--D-glucopyranoside.
^eKaempferol 7-O-[-L-rhamnopyranosyl-(1→6)]-[-D-glucopyranosyl-(1→2)]--D-glucopyranoside.
^fKaempferol 3-O-β-D-(6′′-O-coumaroyl)glucopyranoside.