Table 1.

Summary of Iridoid-Containing Plant Species Investigated for Anti-Inflammatory Properties

Species Name	Plant Part(s) Used	Isolated Iridoid Glycoside	Common Uses / Biological Activity	In vitro Studies	In vivo Studies	Proposed Mechanism of Action	References
Ajuga bracteosa Wall. ex Benth. (Lamiaceae)	Whole plant	6-deoxyharpagide (1); raptoside (2)	Hepatitis; pneumonia; bone disease	Yes	Yes	COX-2 inhibition.	[46-48]
Boschniakia rossica (Cham. & Schltdl.) Standl. (Orobanchaceae)	Whole plant	Boschnaloside (3); 8-epideoxyloganic acid (4)	Antisenile agent	Yes	Yes	TNF-α, iNOS, COX-2 inhibtion.	[49-53]
Bouchea fluminensis (Vell.) Moldence (Verbenaceae)	Aerial parts	Lamiide (5)	Bowel stimulator; anti-inflammatory agent	Yes	Yes	Inhibition of phospholipid peroxidation and free radical scavenging activity.	[56-58]
Catalpa ovata G. Don. (Bignoniaceae)	Stem	Catalposide (6)	Anti-inflammatory agent	Yes	Yes	Inhibition of the production of TNF-α and NO with significant decreases in mRNA levels of TNF-α and inducible NO synthase.	[64-67]
						Attenuates the induction of intestinal epithelial pro-inflammatory gene expression and reduces the severity of trinitrobenzene sulfonic acid-induced colitis in mice.
						Inhibits the production of tumour necrosis factor-α (TNF-α), interleukin-1 (IL-1), and interleukin-6 (IL-6), and the activation of nuclear factor-B.
Cornus officinalis Siebold et Zucc (Cornaceae)	Fruit	Cornel iridoid glycoside (CIG); morroniside (7); loganin (8); cornuside (10); 7-O-cinnamoyl-morroniside (11)	Anti-inflammatory and haemostasis-promoting agent	Yes	Yes	Ihibition of IL-1, IL-6, TNF-α, PGE2, iNOS and E-selectin expression, NO production, NFκB and COX-2.	[68-76]
						Suppression of ICAM-1, VCAM-1 and MCP-1.
Enicostema axillare (Lam.) A.Raynal (Gentianaceae)	Whole plant	Swertiamarin (12)	Diabetes mellitus; rheumatism; ulcers; hernia; swelling; itching and anti-inflammatory agent	Yes	Yes	Anti-oxidant and hepatoprotective.	[45; 77-79]
						Inhibits TBX2.
Eucommia ulmoides Oliv. (Eucommiaceae)	Bark and leaves	Aucubin (14); Genipin (16);	Diabetes mellitus; hypertension; anti-oxidant and anti-inflammatory agent	Yes	Yes	Concentration-dependent inhibition on lipid peroxidation induced by Fe2+/ascorbate.	[80-83]
						Concentration-dependent inhibition of NO production and iNOS expression upon stimulation by lipopolysaccharide / interferon-g.
						Blockage of lipopolysaccharide indicating that it exhibits inhibitory effect on NO production through the inhibition of NFK-B activation.
						Promotes wound healing.
Gardenia jasminoides J.Ellis (Rubiaceae)	Fruit	Geniposide (13); Genipin (16)	Sedative; diuretic; cholagogue; antiphlogistic; anti-inflammatory; anti-oxidant and anti-thrombotic agent	Yes	Yes	Inhibition of lipopolysaccharide-stimulated iNOS expression or COX-2 promoter activity.	[84-92]
Gentiana lutea L. (Gentianaceae)	Roots	Gentiopicroside (18)	Gastric stimulation and anti-inflammatory agent	No	Yes	Reversal of NR2B over-expression during the chronic phases of persistent inflammation caused by hind paw administration of complete Freund’s adjuvant.	[45; 93-95]
Harpagophytum procumbens (Burch.) DC. ex Meisn. subsp. procumbens (Pedaliaceae)	Secondary tubers	Harpagoside (19); harpagide (20); 8-coumaroyl-harpagide (21); pagoside (22)	Rheumatism; arthritis; sores; ulcers and boils	Yes	No	Inhibition of the biosynthesis of cysteinyl-leukotrienes and TBX2.	[44; 96-108]
						Suppression PGE2 synthesis and NO production by inhibiting LPS-stimulated enhancement of the COXe-2 and iNOS mRNAs expressions.
Himatanthus sucuuba (Spruce ex Müll. Arg.) Woodson (Apocynaceae)	Bark; latex; leaves	Plumericin (23); isoplumericin (24)	Wound healing; laxative; hallocinogen; tumours; boils; oedema; arthritis; gastritis; verminosis	No	Yes	-	[109-111]
Kigelia africana (Lam.) Benth. (Bignoniaceae)	Bark; Fruit; Flower	Verminoside (25)	Psoriasis; eczema; venereal disease	Yes	Yes	Verminoside inhibits iNOS expression and NO release in the LPS induced J774.A1 macrophage cell line.	[112-116]
Lamiophlomis rotate (Benth. ex Hook. f) (Lamiaceae)	Aerial parts; roots	Loganin (8) (and others)	Detumescence; haemostasis; pain alleviation; blood circulation promotion	Yes	Yes	Lamiophlomis rotata injection increased phagocytosis by mouse peritoneal macrophages, and decreased the LPS-induced production of IL-1.	[117-118]
Mentzelia scabra subsp. chilensis (Gay) Weigend (Loasaceae)	Aerial parts	Mentzeloside (syn. deutzioside) (26)	Gastric ulcers; helminth infections	No	Yes	Dose-dependent inhibitory activity on carrageenan induced rat-paw oedema.	[119-120]
Phillyrea latifolia L.(Oleaceae)	Aerial parts	Oleuropeoside (27); ligustroside (28)	Oropharyngeal inflammation; burns; headaches	Yes	No	Inhibition of PGE2 release.	[121-123]
Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae)	Root	Picroside II (29); picroside III (30); picroside V (31); 6-feruloyl catalpol (32); picroside I (34); kutkoside (35)	Jaundice; indigestion; common fever; acute viral hepatitis and bronchial asthma	Yes	Yes	Stimulation of the cell-mediated and humoral components of the immune system.	[43; 124-129]
Plantago asiatica L. (Plantaginaceae)	Seeds	Aucubin (14)	Bronchitis; diarrhoea; constipation, wounds	No	Yes	Oral wound healing.	[83; 130-131]
Rehmannia glutinosa Steud.(Scrophulariaceae)	Root	Catalpol (15)	Contact dermatis and rhinitis; promotes blood circulation; improves kidney function	Yes	Yes	Inhibition of the secretion of both TNF-α and IL-1.	[132-133]
						Neuroprotective by attenuating LPS-induced the expression of iNOS.
Russelia equisetiformis (Schltdl. & Cham.)	Whole plant	10-O-cinnamoyl sinuatol (36)	Diabetes; leukemia; pain and inflammation	Yes	Yes	Inhibition of pro-inflammatory mediators.	[134-136]
Scrophularia auriculata ssp. pseudoauriculata, (Scrophulariaceae)	Aerial parts	Scropolioside A (38); scrovalentinoside (39)	Inflammatory skin diseases	Yes	Yes	In vivo scropolioside A reduces both oedema formation and cell infiltration whereas in vitro it reduces the proliferation of activated T-lymphocytes.	[39-40]
						Inhibition of the production of PGE2, leukotriene B4, NO, IL-1β, IL-2, IL-4, TNF-α and interferon-γ.
Scrophularia deserti Delile (Scrophulariaceae),	Aerial parts	Harpagoside (19); scropolioside-D2 (40); koelzioside (41)	Fever; kidney diseases; diabetes mellitus; inflammation of the mouth, lungs, large intestines, bladder and heart	No	Yes	-	[137-139]
Scrophularia frutescens L. (Scrophulariaceae)	Aerial parts	Harpagoside (19)	Joint and lower back pain and inflammation	Yes	Yes	Hydrolysed products of harpagoside with glucosidase treatment showed a significant inhibitory effect on COX-2 activity.	[44; 140-141]
Scrophularia scorodonia L. (Scrophulariaceae)	Aerial parts	Aucubin (14);harpagoside (19); harpagide (20); 8-acetylharpagide (42); scorodioside (43); scropolioside B (44); bartsioside (45)	Inflammatory diseases	Yes	No	Inhibition of TXB2, PGE2 and LTC4 release.	[142-143]
Sideritis perfoliata L. subsp. perfoliata (Lamiaceae)	-	Ajugoside (46)	Rheumatism; ulcers; digestive disorders	Yes	No	Lipoxygenase inhibition.	[144]
Stachytarpheta cayennensis (L.C. Rich) Vahl (Verbenaceae)	Flower; leaves; roots	Ipolamiide (47)	Pain; inflammation; fever; liver and gastric disturbances	Yes	Yes	Inhibition of leukocyte accumulation and influx.	[56; 145-148]
						Inhibitory effect on histamine and bradykinin.
Syringa species(Oleaceae)	Leaves	Iridoid glycoside-rich fraction; Syringopicroside (48)	Acute enteritis; icteric hepatitis; acute mastitis; bacillary dysentery; upper respiratory tract infections	Yes	Yes	Reduction of the activity of myeloperoxidase, depression of malondialdehyde and NO levels and inhibition of the protein and mRNA expressions of NFK-B and TNF-α and IL-6.	[149-151]
Verbascum lasianthum Boiss. (Scrophulariaceae)	Aerial parts	Aucubin (14); catalpol (15); geniposidic acid (17); ajugol (49)	Respiratory disorders; urinary tract infections; earache; inflammatory skin disorders	No	Yes	-	[155]
Verbascum mucronatum Lam (Scrophulariaceae)	-	Catalpol (15); ajugol (49); lasianthoside (50); picroside IV (51)	Respiratory disorders; urinary tract infections; earache and inflammatory skin disorders	-	Yes	-	[152; 156]
Verbascum pterocalycinum var. mutense Hub.-Mor. (Scrophulariaceae)	Flowers	Ajugol (49); picroside IV (51)	Respiratory disorders; urinary tract infections; earache, inflammatory skin disorders	No	Yes	-	[157-158]
Verbena officinalis L. (Verbenaceae)	Whole plant	Verbenalin (52)	Detoxing agent; diuretic; expectorant and anti-rheumatic	No	Yes	Topically and orally administered extracts showed anti-inflammatory activity in the TPA-induced ear inflammation model and in carrageenan-induced rat-paw oedema.	[159-163]
Veronica anagallis-aquatic L. (Plantaginaceae)	Aerial parts	Catalposide (6);veronicoside (53); verproside (54)	Influenza; pain; haemoptysis; laryngopharyngitis and hernia	-	Yes	Catalposide significantly inhibited the production of NO in LPS-stimulated RAW 264.7 macrophages in a dose-dependent manner. RT-PCR and Western blot analyses demonstrates that catalposide also suppressed the expression of the iNOS gene and protein and inhibited the activation of LPS-induced NF-κB.	[43; 66; 163]
Vitex peduncularis Wall. ex Schauer (Verbenaceae)	Root bark or young stem bark	Pedunculariside (55); agnuside (56)	Malaria type fever, especially black water fever	Yes	No	Selective inhibition of COX-2.	[164-165]