Cuminaldehyde as a Lipoxygenase Inhibitor: In Vitro and In Silico Validation

Abstract

The search for lipoxygenase (LOX) inhibitors has been carried out for decades due to its importance in inflammatory diseases. In the present study, it was observed that the methanolic extract of Cuminum cyminum L. inhibited LOX activity. Activity-guided screening of the C. cyminum crude extracts helped the identification and isolation of cuminaldehyde as a 15-LOX inhibitor. The enzyme kinetics analysis suggested cuminaldehyde to be a competitive inhibitor and the IC 50 value derived from LB plots is 1,370 μM. Binding constants of cuminaldehyde on LOX was deduced by isothermal titration calorimetry. The combined thermodynamics and molecular modeling analyses suggested cuminaldehyde as a competitive LOX inhibitor. It is proposed from the present study that the coordinate bond between the Fe(2+) atom in the active site of the enzyme and the cuminaldehyde may be responsible for the enzyme inhibition. The study suggests that cuminaldehyde may be acting as an anti-inflammatory compound and may be therefore included in the category of leads for developing dual COX-LOX inhibitors as non-steroidal anti-inflammatory drugs (NSAIDs).

Cuminaldehyde: A Potential Drug Candidate

“…In this study by Wei et al [3], it should be pointed out that cuminaldehyde accounted for 48.77 % of the whole content of cumin essential oil, suggesting potential anti-inflammatory effects of cuminaldehyde. Cuminaldehyde itself competitively inhibited the activity of 15-lipoxygenase, an enzyme involved in the production of inflammatory mediators such as leukotrienes, using lipoxygenase inhibition assay [28].…”

The effect of cumin supplementation on metabolic profiles in patients with metabolic syndrome: A randomized, triple blind, placebo‐controlled clinical trial

“…cyminum L. had been demonstrated in cell line studies, which may be explained by CuEO blocking nuclear factor kappa‐light‐chain‐enhancer of activated B cells and inhibition of the phosphorylation of extracellular signal regulated kinase and c‐Jun N‐terminal kinase (Wei et al, ). Cuminaldehyde inhibits 15‐lipoxygenase activity in vitro (Tomy et al, ).…”

“…The antioxidant compounds in cumin oil are γ‐terpinene, β‐pinene, cuminaldehyde, and p‐cymene (Chen et al, ). Cuminaldehyde has presented inhibitory effects on the liver microsomal lipid peroxidation (Reddy & Lokesh, ), scavenging superoxide anions (Krishnakantha & Lokesh, ), which acts as an anti‐inflammatory compound (Tomy et al, ). Taking 50‐ and 100‐mg/d CuEO supplements in diabetic patients for 8 weeks led to a significant reduction in the serum levels of hs‐CRP and TNF‐α (Jafari, Sattari, & Ghavamzadeh, ).…”

Novel cuminaldehyde self-emulsified nanoemulsion for enhanced antihepatotoxicity in carbon tetrachloride-treated mice

“…Natural monoterpenoid, cuminaldehyde, has an aldehyde group and isopropyl moiety at four positions (Figure b) and is a component of cumin oil and oils such as eucalyptus, myrrh and cassia. The health‐promoting effects of cumin oil are attributed to cuminaldehyde, which has other functionalities such as anticancer, antidiabetic, neuroprotection and anti‐inflammation …”

“…The health-promoting effects of cumin oil are attributed to cuminaldehyde, [13] which has other functionalities such as anticancer, [14] antidiabetic, [15] neuroprotection [16] and anti-inflammation. [17] Several conditions and xenobiotics can disrupt the normal functioning of liver. [18] Common xenobiotic used to mimic hepatotoxicity in animal models is carbon tetrachloride (CCl 4 ) which induces oxidative stress, lipid peroxidation and inflammation.…”