Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases

Table 1 Anti-Helicobacter pylori effect of curcumin

Year of report	Model of the study	Concentration/doses used	Observations and conclusion	Ref.
1997	In vitro co-culture	20 μmol/L	Demonstrates H. pylori mediated inflammation or IL-8 secretion requires NF-κB activation. Anti-oxidant curcumin can inhibit NF-κB activation and thereby IL-8 secretion. NF-κB activation requires a secreted H. pylori product, which is not secreted by strains mutated in picB/cagE (putative transport protein)	[39]
2002	In vitro	0.78-100 μg/mL	Methanol extract of turmeric rhizome and curcumin, both have the MIC within 6.25-50 μg/mL and more effective against cag (+ve) strains	[38]
2004	In vitro co-culture	Up to 80 μmol/L	H. pylori-induced NF-κB activation and subsequent IL-8 induction and mitogenic response (cell scattering) are inhibited by curcumin. It can inhibit IκBα degradation, activity of IκB kinases (IKKα and β) and NF-κB DNA-binding but cannot suppress mitogen-activated protein kinases (P38MAPK or ERK1/2)	[40]
2006	In vitro	16 μg/mL	Curcumin inhibited H. pylori shikimate dehydrogenase with an IC50 values of 15.4 μmol/L. Curcumin also found to inhibit the growth of H. pylori with MIC at 16 μg/mL	[41]
2007	Pre-clinical trial with 25 H. pylori infected patients	Curcumin 30 mg b.i.d. for 7 d	Found to be not effective in eradicating H. pylori infection. However, despite the presence of bacterium, a significant improvement of dyspeptic symptoms and reduction of serologic signs of gastric inflammation were observed after 2 mo completion of treatment	[42]
2009	In vitro and in vivo mice model	5-50 μg/mL and 25 mg/kg BW (once daily for 7 d) respectively	Potential In vitro anti-H. pylori effect of curcumin re-established, which was irrespective of the genetic makeup of the strains used. Although due to less bioavailability, curcumin’s minimal inhibitory concentration In vitro is high (most strains are within 10-30 μg/mL range), but still showed its efficiency in eradicating H. pylori from infected mice along with restoration of H. pylori induced gastric damage. This study also showed that curcumin-mediated inhibition of H. pylori growth possibly not associated on shikimate pathway	[7]
2009	In vitro co-culture	5 and 10 μmol/L	Non-bactericidal concentration of curcumin failed to inhibit adhesion of H. pylori to epithelial cells but down-regulated H. pylori-induced activation induced cytidine deaminase (AICD, an enzyme which may cause tumorigenesis) expression possibly via inhibition of NF-κB pathway	[43]
2010	Pre-clinical trial with 36 H. pylori infected patients	700 mg orally three times a day for 4 wk	H. pylori eradication rate with curcumin (5.9%) was very poor against conventional triple therapy (78.9%). Triple therapy significantly decreases IL-8 expression but no inhibition was observed in curcumin group	[44]
2010	In vivo rat model	200 or 600 mg/kg BW	Curcumin supplementation exhibits its anti-inflammatory effect by decreasing macromolecular leakage through the suppression of NF-κB p65 expression in gastric epithelium. Curcumin reduces the H. pylori induced gastric inflammation in rat model	[45]
2011	In vitro co-culture and in vivo mice model	60 μmol/L and 25 mg/kg or 50 mg/kg BW (once daily for 7 d) respectively	Elevated levels of MMP-3 and -9 in cultured cells or gastric tissues of mice due to H. pylori infections are inhibited by curcumin. Curcumin is more efficient in re-stabilizing the distorted balance between MMPs and TIMPs than triple therapy, suggests curcumin’s immense therapeutic potential	[8]
2014	Bioinformatics tools/software based analysis	Mucoadhesive microspheres of curcumin	Purpose was to develop and characterize mucoadhesive microspheres of curcumin for treatment of H. pylori mediated gastric aliments. Drug release was found to be slower than free curcumin. Prolonged stomach residence of this molecule is expected to completely eradicate H. pylori infection with other anti-microbials	[46]
2015	In vivo mice model	500 mg/kg three times a week, for 6 and 18 wk	Curcumin treatment exhibited a significant anti-inflammatory role in H. pylori-infected gastric mucosa. Inflammatory mediators (cytokines, chemokines, toll-like receptors and MyD88) which are up regulated with H. pylori infection, has been decreased with curcumin. No sign of inflammation was observed in curcumin treated group	[47]

MMPs: Matrix metalloproteinases; H. pylori: Helicobacter pylori; NF-κB: Nuclear factor-κB; BW: Body weight.