Mechanism action of herbal medicines

Herbal therapies effective in IBD act through several mechanisms which are discussed below. The propriety of the cells mediating innate immunity including natural killer cells, dendritic cells, neutrophils, and macrophages are altered in IBD. The responses of mucosal T helper cells as well as overexpression of some cytokines including interferon gamma (IFN-γ), TNF-α, interleukin (IL)-1b, IL-6 and IL-12 are determined in IBD patients.[21] TNF-α secretion induces alterations in ion transport and epithelial permeability that may lead to lesions and mucosal inflammation.[22] Therefore, factors the regulating T-cells and pro-inflammatory cytokines have the potential to decrease inflammation scores and then improve the patient's IBD.

Some trials have revealed that Curcuma longa has potential to decrease the pro-inflammatory cytokines such as TNF-α, IFN-γ, IL-1β, and IL-12 [Table 1].[23,24]

Studies inspecting herbal medicines effects in animal models of colitis

TNF=Tumor necrosis factor; NO=Nitric oxide; IL=Interleukin; NOS=Nitric oxide synthase; COX=Cyclooxygenase; NF=Nuclear factor; WBC=White blood cell; DSS=Dextran sulfate Sodium; TNBS=Trinitrobenzene sulfonic acid; NF-κB= Nuclear factor kappa-light-chain-enhancer of activated B cells; ↓=Decrease

Leukotriene B4 (LTB4) is a potent proinflammatory mediator playing an important role in IBD,[32] overexpression of LTB4 has been reported in IBD.[33] Nicotine derived from Nicotiana tabacum has been revealed to moderate LTB4 level in dinitrobenzene–sulfonic acid-induced colitis, therefore, it may help to improve IBD.[34]

The microbial content of the GI tract has essential role in the pathogenesis of IBD. It appears that in areas of GI tract that the level of luminal bacteria is more than normal, the possibility of disease progress.[35] Garlic (Allium sativum)withthe antibacterial properties can help to decrease microbial content then improve IBD.[36]

Overexpression of nuclear factor-kappa B (NF-κB) has been observed in IBD. The NF-κB proteins are eukaryotic transcription factors which usually play crucial roles in regulation of inflammation as well as in inflammatory responses in IBD.[37,38] In response to proinflammatory stimuli, the NF-κB Kinase (IKK) induces transcriptional factor NF-κB.[39] Therefore, the suppressors of IKK and NF-κB can be employed for IBD treatment. Curcumin derived from C. longa,[24] a medicinal plant from Commiphora,[40] and theaflavin-3,3´-digallate derived from Camellia sinensis[28] can recede IKK and NF-κB. Boswellic acid, derived from Boswellia spp. can cause suppression of NF-κB activation and reduction of the proinflammatory cytokines such as IFN-γ, ILs 1, 2, 4, and 6 as well as an enhancement in macrophages phagocytosis.[41,42]

Nitric oxide (NO) as well as inducible isoform of NO synthase (iNOS in IBD is increased.[43,44,45] Some herbal remedies, including a glycoside derived from Polygonum multiflorum,[46] a glycoprotein derived from Gardenia jasminoides,[27] theaflavin-3,3′-digallate derived from Clonorchis sinensis,[28] and curcumin,[23] are effective against IBD by decreasing the levels of NO and iNOS [Table 1].

Two isoforms of cyclooxygenase, i.e., Cox-1 and Cox-2 catalyze the synthesis of prostaglandins. Prostaglandins produced through Cox-1 play an important role in GI homeostasis maintenance such as blood flow and gastric cytoprotection. Prostaglandins synthesized through Cox-2 moderate inflammatory responses.[47,48] Some trials have revealed that curcumin and G. jasminoides are able to reduce Cox-2 level.[6,23,24,27]

Patients with IBD exacerbations have shown an enhancement in platelet numbers.[49] Platelets have several important roles such as modulatory role for the activity of other inflammatory cells, release of inflammatory mediators, recruitment, and chemotaxis.[50] Therefore, herbal antiplatelet drugs such as Angelica sinensis can suppress platelet activation, moderate the injury of endothelial cells, and improve microtransmission in IBD patients.[51,52]