Irigenin, a novel lead from Iris confusa for management of Helicobacter pylori infection with selective COX-2 and HpIMPDH inhibitory potential

Abstract

The development of new natural drugs for Helicobacter pylori (H. pylori) management has recently received significant attention. Iris confusa (I. confusa) was long used for the treatment of bacterial infections and gastritis. This study aimed at evaluating its effect on management of H. pylori infection and exploring its bioactive metabolites. The inhibitory potential of the polar (PF), non-polar (NPF) fractions and the isolated compounds against H. pylori using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in addition to their cyclooxygenases (COX-1 and COX-2), and nitric oxide (NO) inhibitory activities were assessed. The most biologically active compound was tested for its selective H. pylori inosine-5′-monophosphate dehydrogenase (HpIMPDH) inhibitory potential. Chromatographic purification of PF and NPF allowed isolation of tectoridin, orientin, irigenin, tectorigenin, isoarborinol and stigmasterol. The PF exhibited significant anti-H. pylori (MIC 62.50 µg/mL), COX-1, COX-2 (IC50 of 112.08 ± 0.60 and 47.90 ± 1.50 µg/mL respectively, selectivity index SI of 2.34), and NO (IC50 47.80 ± 0.89 µg/mL) inhibitory activities, while irigenin was the most potent isolated compound. Irigenin was found to have a promising activity against HpIMPDH enzyme (IC50 of 2.07 ± 1.90 μM) with low activity against human hIMPDH2 (IC50 > 10 μM) than clarithromycin, assuring its selectivity. Overall, I. confusa and its isolated compounds may serve as a potential source of plant-based drugs for H. pylori control. This study scientifically validated the claimed anti-bacterial activity of I. confusa and revealed irigenin potential as a novel lead exhibiting anti H. pylori activity in a first record.

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

“…[31,32] Selective inhibition of COX-2, another molecular target, has been shown to alter the development and progression of cancer in clinical trials. [33,34]…”

“…[29] The COX‐2 gene regulates through transcriptional and posttranscriptional mechanisms [30] COX‐2 expression mainly controls by different transcription factors like CRE binding protein (CREB), C/EBP activator protein 1 (AP‐1), and NF‐κB [31,32] . Selective inhibition of COX‐2, another molecular target, has been shown to alter the development and progression of cancer in clinical trials [33,34] …”

Genome assembly of the bearded irisIris pallidaLam

“…Researchers have isolated PTP1B inhibitors from Iris sanguinea Hornem. ex Donn 1 , antioxidant isoflavonoids 2 and the cytotoxic triterpenoid Belamchinenin A 3 from Iris domestica , the anti- Helicobacter pylori isoflavonoid irigenin from Iris confusa Sealy 4 , and anti-biofilm extracts from several iris species 5 . These compounds were extracted from their producer organisms, requiring several kilograms of plant material to yield compounds in milligram quantities 1,3 .…”

“…Natural products are often extracted from producer species without knowledge of their biosynthesis, so industrial-scale production of natural products is hampered by plant availability. Iris species produce natural products in many compound classes [1][2][3][4][5] but until now, no iris genome has been sequenced using PacBio long-read sequencing. The long-read genome assembly and mapped transcriptome of Iris pallida Lam.…”