Table 3.

This table shows the plants/herbal combination products included in this review, in alphabetic order, and possible herb–drug interaction mechanisms and risks that could cumulate. The right column lists drugs applied in RA/osteoarthritis/IBD treatment that are, or could, be affected.

Plant	Drug Interactions/Risks	Drugs Affected
Aloe vera gel	Depends on product quality; see 3.2.1.
Artichoke	-	-
Ash leaf	-	-
Bilberry	Anthocyanins have been discussed as platelet aggregation inhibitors [53]; decreased platelet activation in metabolic syndrome patients [54]	(NSAIDs)
Blackcurrant leaf	-	-
Bogbean leaf	No interactions known (contraindication: gastric or duodenal ulcer) [55]	-
Boswellia	Unspecific CYP450 inhibition [56] and transport protein modulation (OATP1B3, MRP2, pGP) in vitro [57,58]; two case reports of elevated INR in warfarin patients [59] (possibly by CYP interaction)	Caution with cyclosporine and tacrolimus
Cannabis sativa	Increases central nervous system (CNS) depression [60]	Opioids, SSNRI (e.g., duloxetine)
	Inhibition of UGT1A9 and UGT2B7 [60]; CYP3A4 and 2C9 substrate, possible influence on CYP1A2 [61] (induction by THC, induction or inhibition by CBD)	Duloxetine (several drugs in other fields; propofol, anticoagulants!)
	in vitro: inhibition of several CYP enzymes by cannabinoids and main metabolites, including CYP 2B6, 2C9, 2D6; minor inhibition: 1A2, 2C19, 3A4 [60,62]	Several drugs, including opioids, NSAIDs and possibly cyclosporine and tacrolimus (CBD) [63]
	anticholinergic agents (risk of tachycardia)	(several drugs in other fields)
Chamomile	Minor CYP3A4 inhibition in vitro [64]; case reports of elevated cyclosporine serum level [65,66]	Cyclosporine
Cranberry	Case reports of potentiated warfarin effect; clinical studies: no difference [67]
	One case report of lowered tacrolimus serum concentration [68]	Tacrolimus
Devil’s claw	Possible CYP3A4 inhibition (in vitro data only)	Cyclosporine
Echinacea	May diminish therapeutic effect of immunosuppressants	Methotrexate, leflunomide, azathioprine, biologicals, JAK- inhibitors, cyclosporine, tacrolimus, systemic glucocorticoids
	Possible influence on CYP3A4	cyclosporine
English plantain	-	-
Evening primrose oil	Possible inhibition of platelet aggregation	NSAIDs
Fennel	-	-
Flaxseed	Can delay or reduce drug absorption; 1 h time-lag between application [69]	Minerals, vitamins, drugs
	obstruction risk with drugs that inhibit peristaltic movements	Opioids
Garlic	Inhibition of CYP2E1 [70], but not 2D6 and 3A4 [70,71]; induces pGP [72]	Cyclosporine, tacrolimus
	Elevated bleeding risk due to platelet inhibition suspected [53,73]; contradicting clinical data [73,74]	Monitor patients on anticoagulants when starting/ending garlic preparations; caution with antiplatelet drugs (NSAIDs, especially ASA)
Ginger	Contradicting data regarding CYP2C9, 3A4, and pGP inhibition in vitro [75,76,77]; cases of interactions with dabigatran (pGP) [78], phenprocoumon (CYP2C9) [79], and crizotinib (CYP3A4, 2C9; pGP) [80]; no effect in a clinical study with warfarin (CYP2C9) [81]; elevated tacrolimus AUC in rats [82]	CYP2C9, 3A4 and pGP substrates with narrow therapeutic window, such as cyclosporine, tacrolimus
	Inhibits platelet aggregation in vitro [83]	Caution with anticoagulant and platelet-aggregation inhibiting drugs (NSAIDs)
Ginkgo	Possible inhibition of platelet aggregation	NSAIDs, especially ASA
Ginseng	Possible inhibition of platelet aggregation (conflicting data)	(NSAIDs, especially ASA)
	Possible CYP3A4 inhibition	cyclosporine, tacrolimus
	Possible blood glucose lowering effect	chloroquine, hydroxychloroquine
Grape seeds	[84,85]	-
Green tea	Inhibition of OATP1A2, 1B3, 2B1, pGB; risk of liver injury; possible CYP3A4 inhibition	Methotrexate, leflunomide, azathioprine, cyclosporine, tacrolimus
Lemon balm	-	-
Lime/linden flowers	-	-
Meadowsweet	Contains salicylates (possibly elevated bleeding risk and GI injury with NSAIDs; may reduce renal elimination)	NSAIDs, glucocorticoids; 5- aminosalicylates; may reduce clearance of methotrexate
Milk thistle	Inhibits UDP1A6 in vitro [86]; CYP3A4 and 2C9 inhibition suspected, but no relevant influence in small clinical studies [87,88,89,90,91]; case report of warfarin interaction, probably due to CYP2C9 inhibition [92]	Caution with CYP3A4 and 2C9 substrates with small therapeutic windows (such as cyclosporine)
Myrrh, chamomile, coffee charcoal	Can impair absorption of simultaneously applied drugs [93]	Caution with cyclosporine
	minor CYP3A4 inhibition in vitro [64]; case reports of elevates cyclosporine serum level [65,66] (chamomile) Myrrh: CYP3A4 induction in vitro [94]
Nettle herb	-	-
Peppermint	Peppermint tea inhibits CYP3A4 induction by rifampicin in vitro [95]; oil: contradicting results on CYP inhibition in vitro [96,97]; enhanced cyclosporine bioavailability in rats [98]	Cyclosporine, tacrolimus?
Psyllium	Can delay or reduce drug absorption; 1 h time-lag between application [99]	Vitamins, minerals, drugs prednisolone/ fludrocortisone [100]
Rose hip	-	-
Saw palmetto	Case report bleeding [101]; most literature argues against interaction [102,103,104]	(Warfarin?)
Soybean	in vitro: no relevant effect on CYP2D6 and 3A4 [64,77,105]	-
St. John’s wort	Induces CYP2C9, 2C19, 3A4; pGP [106] Serotonin syndrome [107]	Cyclosporine, tacrolimus, tofacitinib, glucocorticoids, omeprazole, opioids (and many more in other fields), SSNRI
Turmeric	Possible inhibition of CYP2D6, 2C9, 3A4 Elevated AUC of tacrolimus in rats [82]	Caution with cyclosporine, tacrolimus, coumarins
	Inhibition of sulfotransferase and glutathione transferase	Acetaminophen
Valerian	Increases CNS depression	Opioids, SSNRI (e.g., duloxetine)
	No CYP1A2, 2D6, 2E1, 3A4 interactions found [108,109,110]
Willow bark	Contains salicylates (possibly elevated bleeding risk and GI injury with NSAIDs; may reduce renal elimination)	NSAIDs, glucocorticoids; 5- aminosalicylats; may reduce clearance of methotrexate; (warfarin)
Wormwood	-	-