2. Academic Validation
  3. Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity

Guarea microcarpa C. DC. extract inhibits NLRP3 inflammasome by suppressing its ATPase activity

  • J Ethnopharmacol. 2024 Jan 2:117711. doi: 10.1016/j.jep.2024.117711.
Sojung Lee 1,  Sojin Yun 2,  Hyeyun Yang 3,  Nahyun Lee 4,  YeJi Kim 5,  Sumin Lee 6,  Nelson A Zamora 7,  Silvia Soto Montero 8,  Dong-Keun Yi 9,  Soo-Yong Kim 10,  Sangho Choi 11,  Taesoo Choi 12,  Man S Kim 13,  Yoonsung Lee 14,  Yong Hwan Park 15
Affiliations

Affiliations

  • 1 Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea. Electronic address: lsj2209@naver.com.
  • 2 Department of Biomedical Science and Technology, Kyung Hee University, Seoul, 05278, Republic of Korea. Electronic address: cielyun98@khu.ac.kr.
  • 3 Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea. Electronic address: hynado@naver.com.
  • 4 Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, 05278, Republic of Korea. Electronic address: nahyun5407@gmail.com.
  • 5 Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea. Electronic address: ispy9806@icloud.com.
  • 6 Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea. Electronic address: sumin0038@ajou.ac.kr.
  • 7 Instituto Nacional de Biodiversidad (INBio), Santo Domingo de Heredia, 22-3100, Costa Rica. Electronic address: zamoravn@gmail.com.
  • 8 Instituto Nacional de Biodiversidad (INBio), Santo Domingo de Heredia, 22-3100, Costa Rica. Electronic address: sotomontero.silvia@gmail.com.
  • 9 International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. Electronic address: lydian78@gmail.com.
  • 10 International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. Electronic address: soodole@kribb.re.kr.
  • 11 International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea. Electronic address: decoy0@kribb.re.kr.
  • 12 Department of Urology, School of Medicine, Kyung Hee University, Seoul, 05278, Republic of Korea. Electronic address: taesoochoi85@daum.net.
  • 13 Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, 05278, Republic of Korea. Electronic address: manskim@khu.ac.kr.
  • 14 Clinical Research Institute, Kyung Hee University Hospital at Gangdong, School of Medicine, Kyung Hee University, Seoul, 05278, Republic of Korea. Electronic address: ylee3699@khu.ac.kr.
  • 15 Department of Microbiology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea; Department of Biomedical Sciences, Graduate School of Ajou University, Suwon, Republic of Korea. Electronic address: parky5@ajou.ac.kr.
PMID: 38176663 DOI: 10.1016/j.jep.2024.117711
Abstract

Ethnopharmacological relevance: Guarea genus comprises tropical and subtropical terrestrial herbs inhabiting Central and South America. These Plants, including Guarea guidonia (L.) Sleumer, have anti-inflammatory, analgesic, Antibacterial, Antiviral, and immune-enhancing properties.

Aim of the study: Although various species of the Guarea genus are known for their medicinal properties, comprehensive data on their anti-inflammatory effects remain limited. Therefore, we investigated the NLRP3 inflammasome-inhibiting effects of the Guarea genus in this study.

Materials and methods: To evaluate the anti-inflammatory activities of 18 members of the Guarea genus, we treated NLRP3 inflammasome activators with their extracts in LPS-primed J774A.1 and THP-1 cells. Cell viability was determined by WST (water soluble tetrazolium salt) and cytokine production, protein expression, and nuclear fractionation were determined by western blotting. ROS production and apoptosis-associated speck-like protein containing a Caspase recruitment domain (ASC) oligomerization were measured using confocal microscopic analysis. Inflammation-induced zebra fish was used in the in vivo experiments.

Results: Among the 18 Guarea members tested, Guarea microcarpa C. DC. extract (GM) exhibited no cytotoxicity and specifically suppressed the activation of the NLRP3 inflammasome, but not of the AIM2 or NLRC4 inflammasomes, by inhibiting the ATPase activity of NLRP3. This was achieved without affecting NF-κB signaling, potassium efflux, or intracellular Reactive Oxygen Species production, all of which are involved in NLRP3 activation. The reduced ATPase activity of NLRP3 led to decreased ASC oligomerization. Furthermore, GM exhibited anti-inflammatory effects in vivo. Additionally, GM treatment alleviated inflammation at the organismal level in an LPS-induced inflammation model using zebrafish embryos.

Conclusion: Our results demonstrate the anti-inflammatory effects of GM via suppressing the NLRP3 inflammasome. Therefore, GM can be a potential therapeutic candidate for various inflammatory diseases caused by aberrant NLRP3 inflammasome activation.

Keywords

Guarea microcarpa; Inflammation; Inflammatory diseases; Meliaceae family; NLRP3 inflammasome.

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