The Activation of Nrf2/HO-1 by 8-Epi-7-deoxyloganic Acid Attenuates Inflammatory Symptoms through the Suppression of the MAPK/NF-κB Signaling Cascade in In Vitro and In Vivo Models

• Main Authors: Shakina Yesmin Simu (Author), Md Badrul Alam (Author), Sun Yeou Kim (Author)
• Format: Book
• Published: MDPI AG, 2022-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/antiox11091765; 2076-3921
• Keywords: 8-epi-7-deoxyloganic acid; antioxidant; anti-inflammation; MAPKs; NF-κB; Nrf-2; Therapeutics. Pharmacology; RM1-950
• Source: Antioxidants, Vol 11, Iss 9, p 1765 (2022)

In this study, we examined the ameliorative effects of 8-epi-7-deoxyloganic acid (DLA), an iridoid glycoside, on oxidative stress and inflammation in both LPS-stimulated macrophages and mice with carrageenan-induced inflammation. DLA decreased oxidative stress through the up-regulation of heme oxygenase-1 (HO-1) via the activation of nuclear factor erythroid 2-related factor 2 (Nrf2), leading to the suppression of reactive oxygen species (ROS) and nitric oxide generation (NO). In addition, DLA inhibited the activation of mitogen-activated protein kinases (MAPKs) and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, resulting in a decreased production of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and -6 (IL-6), as well as of monocyte chemoattractant protein-1 (MCP-1). In addition, DLA effectively inhibited the generation of nitric oxide (NO) and prostaglandin E2 (PGE2) by inhibiting the expression of the upstream genes inducible nitric oxidase (iNOS) and cyclooxygenase-2 (COX-2). DLA demonstrated powerful anti-inflammatory and antioxidant properties and thus appears as an intriguing prospective therapeutic treatment.