<br>Santacruzamate A 通过抑制前扣带皮层小胶质细胞的激活来减轻疼痛和疼痛相关的不良情绪,ACS Pharmacology & Translational Science

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Santacruzamate A 通过抑制前扣带皮层小胶质细胞的激活来减轻疼痛和疼痛相关的不良情绪
ACS Pharmacology & Translational Science ( IF 4.9 ) Pub Date : 2024-02-16 , DOI: 10.1021/acsptsci.3c00282
Yan Qin ₁ , Qingqing Liu ₁ , Saiying Wang ₁ , Qinhui Wang ₁ , Yaya Du ₁ , Jingyue Yao ₁ , Yue Chen ₁ , Qi Yang ₁ , Yumei Wu ₂ , Shuibing Liu ₂ , Minggao Zhao ₁ , Gaofei Wei ₃ , Le Yang ₁

Affiliation

慢性疼痛是一种复杂的疾病。严重影响患者的生活质量，给社会带来重大的经济负担。 Santacruzamate A (SCA) 是从巴拿马海洋蓝藻中分离出来的天然产物。在本研究中，我们首次证明SCA可以减轻弗氏完全佐剂引起的小鼠慢性炎症性疼痛、疼痛相关的焦虑和抑郁情绪，同时抑制前扣带皮层小胶质细胞的激活。此外，SCA 治疗通过下调 BV2 细胞中白细胞介素 1β 和 6（IL-1β 和 IL-6）以及肿瘤坏死因子-α（TNF-α）水平来减弱脂多糖（LPS）诱导的炎症反应。此外，我们通过分子对接技术发现SCA可以与可溶性环氧化物水解酶（sEH）结合，并且SCA与sEH蛋白结合后sEH的热稳定性得到增强。同时，我们发现SCA可以降低LPS刺激模型中sEH酶的活性并抑制sEH蛋白的过度表达。结果表明，SCA可以通过抑制sEH的酶活性和表达来减轻炎症的发展，从而进一步减轻慢性炎症疼痛。我们的研究表明，SCA 可能是治疗慢性炎症性疼痛的潜在药物。

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

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.

更新日期：2024-02-16

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