N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis

Ji Eun Kim; Changyu Kang; Phatcharaporn Budluang; Natpaphan Yawut; Il-Rae Cho; Yun Ju Choi; Jaejeong Kim; Sanghyun Ju; Beomgu Lee; Dong Hyun Sohn; Hyung-Soon Yim; Kyeong Won Lee; Jinsol Han; Youngmi Jung; Ho Young Kang; Jin Kyoon Park; Yunjin Jung; Dae Youn Hwang; Young-Hwa Chung

doi:10.3389/fphar.2023.1095955

N-benzyl-N-methyldecan-1-amine and its derivative mitigate 2,4- dinitrobenzenesulfonic acid-induced colitis and collagen-induced rheumatoid arthritis

Front Pharmacol. 2023 Apr 20:14:1095955. doi: 10.3389/fphar.2023.1095955. eCollection 2023.

Authors

Ji Eun Kim¹, Changyu Kang², Phatcharaporn Budluang³, Natpaphan Yawut³, Il-Rae Cho⁴, Yun Ju Choi¹, Jaejeong Kim², Sanghyun Ju², Beomgu Lee⁴, Dong Hyun Sohn⁴, Hyung-Soon Yim⁵, Kyeong Won Lee⁵, Jinsol Han⁶, Youngmi Jung⁶, Ho Young Kang⁷, Jin Kyoon Park⁶, Yunjin Jung², Dae Youn Hwang¹, Young-Hwa Chung^{3

4}

Affiliations

¹ Department of Biomaterials Science (BK21 FOUR Program), College of Natural Resources and Life Science, Pusan National University, Miryang, Republic of Korea.
² College of Pharmacy, Pusan National University, Busan, Republic of Korea.
³ Department of Cogno-Mechatronics Engineering, Optomechatronics Research Institute, Pusan National University, Busan, Republic of Korea.
⁴ Department of Microbiology and Immunology, College of Medicine, Pusan National University, Yangsan, Republic of Korea.
⁵ Korea Institute of Ocean Science and Technology, Marine Biotechnology Research Center, Busan, Republic of Korea.
⁶ Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan, Republic of Korea.
⁷ Department of Microbiology, Pusan National University, Busan, Republic of Korea.

Abstract

As our previous study revealed that N-benzyl-N-methyldecan-1-amine (BMDA), a new molecule originated from Allium sativum, exhibits anti-neoplastic activities, we herein explored other functions of the compound and its derivative [decyl-(4-methoxy-benzyl)-methyl-amine; DMMA] including anti-inflammatory and anti-oxidative activities. Pretreatment of THP-1 cells with BMDA or DMMA inhibited tumor necrosis factor (TNF)-α and interleukin (IL)-1β production, and blocked c-jun terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), MAPKAP kinase (MK)2 and NF-κΒ inflammatory signaling during LPS stimulation. Rectal treatment with BMDA or DMMA reduced the severity of colitis in 2,4-dinitrobenzenesulfonic acid (DNBS)-treated rat. Consistently, administration of the compounds decreased myeloperoxidase (MPO) activity (representing neutrophil infiltration in colonic mucosa), production of inflammatory mediators such as cytokine-induced neutrophil chemoattractant (CINC)-3 and TNF-α, and activation of JNK and p38 MAPK in the colon tissues. In addition, oral administration of these compounds ameliorated collagen-induced rheumatoid arthritis (RA) in mice. The treatment diminished the levels of inflammatory cytokine transcripts, and protected connective tissues through the expression of anti-oxidation proteins such as nuclear factor erythroid-related factor (Nrf)2 and heme oxygenase (HO)1. Additionally, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels did not differ between the BMDA- or DMMA-treated and control animals, indicating that the compounds do not possess liver toxicity. Taken together, these findings propose that BMDA and DMMA could be used as new drugs for curing inflammatory bowel disease (IBD) and RA.

Keywords: N-benzyl-N-methyldecane-1-amine; RA: rheumatoid arthritis; anti-inflammatory activity; anti-oxidative activity; rat colitis.

Grants and funding

This study received funding from Hayoung Meditech Inc. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or decision to submit it for publication. All authors declare no other competing interests. The work was also supported by Korea Institute for Advancement of Technology (KIAT) grant funded by the Korea Government (MOTIE) (P0008763, HRD Program for Industrial Innovation).