Chemical Investigation of Tetradium ruticarpum Fruits and Their Antibacterial Activity against Helicobacter pylori

Myung Woo Na; Se Yun Jeong; Yoon-Joo Ko; Dong-Min Kang; Changhyun Pang; Mi-Jeong Ahn; Ki Hyun Kim

doi:10.1021/acsomega.2c02380

Chemical Investigation of Tetradium ruticarpum Fruits and Their Antibacterial Activity against Helicobacter pylori

ACS Omega. 2022 Jun 28;7(27):23736-23743. doi: 10.1021/acsomega.2c02380. eCollection 2022 Jul 12.

Authors

Myung Woo Na¹, Se Yun Jeong¹, Yoon-Joo Ko², Dong-Min Kang³, Changhyun Pang⁴, Mi-Jeong Ahn³, Ki Hyun Kim¹

Affiliations

¹ School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.
² Laboratory of Nuclear Magnetic Resonance, National Center for Inter-University Research Facilities (NCIRF), Seoul National University, Gwanak-gu, Seoul 08826, Republic of Korea.
³ College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju 52828, Republic of Korea.
⁴ School of Chemical Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Abstract

The fruit of Tetradium ruticarpum, known as Evodiae Fructus, is a traditional herbal medicine used to treat gastric and duodenal ulcers, vomiting, and diarrhea. The traditional usage can be potentially associated with the antibacterial activity of T. ruticarpum fruits against Helicobacter pylori. However, so far, the antibacterial activity of T. ruticarpum fruits and antibacterial components against H. pylori has not been investigated despite the traditional folk use. The current study was conducted to investigate the bioactive chemical components of T. ruticarpum fruits and evaluate their antibacterial activity against H. pylori. Phytochemical investigation of the EtOH extract of T. ruticarpum fruits led to the isolation and identification of nine compounds (1-9), including phellolactone (1), the absolute configuration of which has not yet been determined. The chemical structures of the isolated compounds were elucidated by analyzing the spectroscopic data from one-dimensional (1D) and two-dimensional (2D) NMR and high-resolution electrospray ionization mass spectrometry (HR-ESIMS) experiments. Specifically, the absolute configuration of compound 1 was established by the application of computational methods, including electronic circular dichroism (ECD) calculation and the NOE/ROE-based interproton distance measurement technique via peak amplitude normalization for the improved cross-relaxation (PANIC) method. In the anti-H. pylori activity test, compound 3 showed the most potent antibacterial activity against H. pylori strain 51, with 94.4% inhibition (MIC₅₀ and MIC₉₀ values of 22 and 50 μM, respectively), comparable to that of metronidazole (97.0% inhibition, and MIC₅₀ and MIC₉₀ values of 17 and 46 μM, respectively). Moreover, compound 5 exhibited moderate antibacterial activity against H. pylori strain 51, with 58.6% inhibition (MIC₅₀ value of 99 μM), which was higher than that of quercetin (34.4% inhibition) as a positive control. Based on the bioactivity results, we also analyzed the structure-activity relationship of the anti-H. pylori activity. Conclusion: These findings demonstrated that T. ruticarpum fruits had antibacterial activity against H. pylori and could be used in the treatment of gastric and duodenal ulcers. Meanwhile, the active compound, 1-methyl-2-(8E)-8-tridecenyl-4(1H)-quinolinone (3), identified herein also indicated the potential application in the development of novel antibiotics against H. pylori.