Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex

Yan Qin; Qingqing Liu; Saiying Wang; Qinhui Wang; Yaya Du; Jingyue Yao; Yue Chen; Qi Yang; Yumei Wu; Shuibing Liu; Minggao Zhao; Gaofei Wei; Le Yang

doi:10.1021/acsptsci.3c00282

Santacruzamate A Alleviates Pain and Pain-Related Adverse Emotions through the Inhibition of Microglial Activation in the Anterior Cingulate Cortex

ACS Pharmacol Transl Sci. 2024 Feb 16;7(4):1002-1012. doi: 10.1021/acsptsci.3c00282. eCollection 2024 Apr 12.

Authors

Yan Qin¹, Qingqing Liu¹, Saiying Wang¹, Qinhui Wang¹, Yaya Du¹, Jingyue Yao¹, Yue Chen¹, Qi Yang¹, Yumei Wu², Shuibing Liu², Minggao Zhao¹, Gaofei Wei³, Le Yang¹

Affiliations

¹ Precision Pharmacy and Drug Development Center, Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi 710038, China.
² Department of Pharmacology, School of Pharmacy, Air Force Medical University, Xi'an 710072, China.
³ Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, China.

PMID: 38633586
PMCID: PMC11019733 (available on 2025-02-16)
DOI: 10.1021/acsptsci.3c00282

Abstract

Chronic pain is a complex disease. It seriously affects patients' quality of life and imposes a significant economic burden on society. Santacruzamate A (SCA) is a natural product isolated from marine cyanobacteria in Panama. In this study, we first demonstrated that SCA could alleviate chronic inflammatory pain, pain-related anxiety, and depression emotions induced by complete Freund's adjuvant in mice while inhibiting microglial activation in the anterior cingulate cortex. Moreover, SCA treatment attenuated lipopolysaccharide (LPS)-induced inflammatory response by downregulating interleukin 1β and 6 (IL-1β and IL-6) and tumor necrosis factor-α (TNF-α) levels in BV2 cells. Furthermore, we found that SCA could bind to soluble epoxide hydrolase (sEH) through molecular docking technology, and the thermal stability of sEH was enhanced after binding of SCA to the sEH protein. Meanwhile, we identified that SCA could reduce the sEH enzyme activity and inhibit sEH protein overexpression in the LPS stimulation model. The results indicated that SCA could alleviate the development of inflammation by inhibiting the enzyme activity and expression of sEH to further reduce chronic inflammatory pain. Our study suggested that SCA could be a potential drug for treating chronic inflammatory pain.