Zerumbone Inhibits Helicobacter pylori Urease Activity

Abstract

Helicobacter pylori (H. pylori) produces urease in order to improve its settlement and growth in the human gastric epithelium. Urease inhibitors likely represent potentially powerful therapeutics for treating H. pylori; however, their instability and toxicity have proven problematic in human clinical trials. In this study, we investigate the ability of a natural compound extracted from Zingiber zerumbet Smith, zerumbone, to inhibit the urease activity of H. pylori by formation of urease dimers, trimers, or tetramers. As an oxygen atom possesses stronger electronegativity than the first carbon atom bonded to it, in the zerumbone structure, the neighboring second carbon atom shows a relatively negative charge (δ−) and the next carbon atom shows a positive charge (δ+), sequentially. Due to this electrical gradient, it is possible that H. pylori urease with its negative charges (such as thiol radicals) might bind to the β-position carbon of zerumbone. Our results show that zerumbone dimerized, trimerized, or tetramerized with both H. pylori urease A and urease B molecules, and that this formation of complex inhibited H. pylori urease activity. Although zerumbone did not affect either gene transcription or the protein expression of urease A and urease B, our study demonstrated that zerumbone could effectively dimerize with both urease molecules and caused significant functional inhibition of urease activity. In short, our findings suggest that zerumbone may be an effective H. pylori urease inhibitor that may be suitable for therapeutic use in humans.

Anthocyanins of Hierbamora (Solanum nigrescens): Revealing their Nutraceutical Potential for Controlling Hypertriglyceridemia and Helicobacter pylori Viability

“…[33] Recent studies sustain that zerumbone from Zingiber zerumbet, inhibits the urease activity of H. pylori by formation of urease dimers, trimers, or tetramers. [34] This kind of interaction seems to be a new form to change protein function by natural products from plants.…”

“…The turbidimetric method of triolein hydrolysis was used to determine V max and K m of PL. [34] The enzyme was adjusted to a final concentration of 150 μg mL À 1 (1 units mL À 1 ) in 100 mM Tris buffer pH 9.0, containing triolein (0.3 mM) sodium deoxycholate (20 mM), colipase (3 mg L À 1 ) and calcium chloride (0.02 mM). Enzymatic reactions had a final volume of 0.3 mL and were initiated by its incubation at 37 °C for 30 min with two concentrations (100 and 150 μg mL À 1 ) of SNAF, pure cyanidin-3-O-rutinoside-5-glucoside and pure petunidin-3-(cis-p-coumaroyl)-rutinoside-5-glucoside and different substrate concentrations (0.2-2.2 mM).…”

Healthy Zerumbone: From Natural Sources to Strategies to Improve Its Bioavailability and Oral Administration

“…It has an anti-virulence effect by inhibiting the biofilm formation and hyphal growth of Candida albicans in a concentration-dependent manner. In addition, it exhibits significant cytotoxic activity against lung, colon, leukemia, ovarian, skin, liver and breast cancers, with selective cytotoxic activity on human tumor cell lines, not found with the structural analogue, α-humulene, that lacks the carbonyl group ( Figure 1 ) [ 4 , 5 , 6 , 13 , 14 ]. Several studies have reported the antitumor activity of zerumbone in vitro, as well as in vivo models such as breast, colorectal, cervical, lung, renal cell carcinoma and skin cancers [ 4 ].…”

Asclepain cI, a proteolytic enzyme from Asclepias curassavica L., a south American plant, against Helicobacter pylori

“…These factors allow H. pylori to move within the viscous gastric mucosa, facilitate its attachment to epithelial cells and counteract the acidic environment of the human stomach. Also, the production of carbon dioxide (CO 2 ) and ammonia (NH 3 ) by urea hydrolysis, provides a nitrogen source for the bacterium (Cheok et al, 2021 ; Woo et al, 2021 ).…”