Table 1.

Effects of ginseng and ginsenosides on rheumatic diseases

Disease	Compound	Effects	Experimental models	Ref.
RA	CK	Decreases MMP-1 and MMP-9 production	Human RA fibroblast-like synoviocytes	[36]
	G-Rb1	Decreases TNF-α expression Ameliorates clinical arthritic scores Reduces immune cell infiltration and cartilage destruction	Human RA fibroblast-like synoviocytes Human PBMCs Human chondrocytes Collagen-induced arthritic mice	[37]
	Pn-BE	Inhibits TNF-α, IL-1β, iNOS, and MMP-13 expression Suppresses NF-κB and MAPK signaling pathways Attenuates onset and progression of CIA	Human THP-1 cells Mouse RAW264.7 cells Human SW1353 cells Collagen-induced arthritic mice	[38]
	PNS	Improves clinical symptoms Reduces arthritic indexes	Human RA patients	[39]
OA	CK	Reduces RANKL expression Inhibits RANKL-induced osteoclastogenesis/osteoclast activity Increases ALP and COLI levels Reduces ROS and NO levels	Human RA fibroblast-like synoviocytes Mouse RAW264.7 cells Human CD14+ monocytes Mouse MC3T3-E1 cells	[36]
				[51]
	G-Rg3	Decreases MMP-1 and MMP-13 expression Increases COLII and ACAN expression Suppresses SA-β-GAL level and telomerase activity	Human chondrocytes	[52]
	G-Rb1	Decreases Notch1, JAG1, and MMP-13 expression Increases COLII expression	Human SW1353 cells ACLT OA rats	[53]
	G-Rg5	Prevents cartilage destruction, synovial membrane disintegration, and apoptotic cell death in knee joints Increases proteoglycan, collagen, and BMP-2 expression Decreases MMP-13, IL-1β, TNF-α, NO, and iNOS expression	LTMMR OA rat chondrocytes LTMMR OA rats	[55]
	G-Rg1	Decreases MMP-13, COX-2, and PGE2 expression Increases COLII and ACAN expression Attenuates cartilage destruction	Human OA chondrocytes ACLT OA rats	[56]
SLE	SPGF	Decreases disease activity scores Ameliorates SLE symptoms Improves clinical SLE indexes	Human SLE patients	[62]
	Ginsenosides + prednisone	Improves SLEDAI, ESR, C3, and anti-dsDNA levels Decreases disease syndrome scores Improves disease symptoms	Human SLE patients Human SLE patients	[63]
				[64]

ACAN, aggrecan; ACLT, anterior cruciate ligament transection; ALP, alkaline phosphatase; BMP-2, bone morphogenetic protein 2; C3, complement 3; CIA, collagen-induced arthritic; CK, compound K; COLI, type I collagen; COLII, type 2 collagen; COX-2, cyclooxygenase-2; dsDNA, double-stranded DNA; ESR, erythrocyte sedimentation rate; IL-1β, interleukin-1β; iNOS, inducible nitric oxide synthase; JAG1, jagged 1; LTMMR, ligament transection and medial meniscus resection; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; NF-κB, nuclear factor-kappa B; NO, nitric oxide; OA, osteoarthritis; PBMCs, peripheral blood mononuclear cells; PGE₂, prostaglandin E₂; RA, rheumatoid arthritis; RANKL, receptor activator of NF-κB ligand; ROS, reactive oxygen species; SA-β-GAL, senescence-associated β-GAL; SLE, systemic lupus erythematosus; SLEDAI, SLE disease activity index; SPGF, saponins of ginseng fruit; TNF-α, tumor necrosis factor-α.