Pimaric Acid is a modulator of the large conductance Ca2+-activated K+ channel, which sensitizes the channel to voltage and stabilizes the open state in KV1.1-KV2.1[1]. Pimaric Acid can induce swelling of both mitochondria and endoplasmic reticulum by activating potassium channels, resulting in mitochondrial cristae becoming diffuse[2]. Pimaric Acid can be used to disrupt the plasma membrane of bacteria and inhibit the growth of Paenibacillus larvae [3].
In vitro, Pimaric Acid treatment for 24 hours significantly inhibited the production of NO in BV-2 cells under lipopolysaccharide (LPS) stress, with an IC50 value of 13.6μM[4]. Treatment with 20μM of Pimaric Acid for 48 hours significantly inhibited the viability of PA-1 cells and altered the morphology, promoting the upregulation of endoplasmic reticulum stress-related proteins, including p-PERK, PERK, AT-4, CHOP and IRE-1[5]. Treatment with 20μM of Pimaric Acid for 24 hours reduced the MMP-9 protein level in human aortic smooth muscle cells (HASMC) stimulated by TNF-α, accompanied by decreased expressions of p65, c-Fos, p-c-Jun, p-ATF2, and Jun-D, and inhibition of cell migration[6].
References:
[1] Sakamoto K, Suzuki Y, Yamamura H, et al. Molecular mechanisms underlying pimaric acid-induced modulation of voltage-gated K+ channels[J]. Journal of Pharmacological Sciences, 2017, 133(4): 223-231.
[2] Hoa N, Myers M P, Douglass T G, et al. Molecular mechanisms of paraptosis induction: implications for a non-genetically modified tumor vaccine[J]. PloS one, 2009, 4(2): e4631.
[3] Song H, Kim J, Shin Y K, et al. Antibacterial activity of pimaric acid against the causative agent of American foulbrood, Paenibacillus larvae[J]. Journal of Apicultural Research, 2022, 61(2): 219-226.
[4] Kim C S, Oh J, Subedi L, et al. Structural characterization of terpenoids from Abies holophylla using computational and statistical methods and their biological activities[J]. Journal of natural products, 2018, 81(8): 1795-1802.
[5] Li W, Xuemei G, Yilin Z, et al. Anticancer effects of Pimaric acid is mediated via endoplasmic reticulum stress, caspase-dependent apoptosis, cell cycle arrest, and inhibition of cell migration in human ovarian cancer cells[J]. Acta Biochimica Polonica, 2022, 69(1): 245-250.
[6] Suh S J, Kwak C H, Chung T W, et al. Pimaric acid from Aralia cordata has an inhibitory effect on TNF-α-induced MMP-9 production and HASMC migration via down-regulated NF-κB and AP-1[J]. Chemico-Biological Interactions, 2012, 199(2): 112-119.
Pimaric Acid是一种大电导钙激活钾通道的调节剂，能增强该通道对电压的敏感性，并稳定KV1.1-KV2.1的开放状态[1]。Pimaric Acid可通过激活钾通道诱导线粒体和内质网肿胀，导致线粒体嵴变得弥散[2]。Pimaric Acid可用于破坏细菌的质膜并抑制Paenibacillus larvae的生长[3]。
在体外，Pimaric Acid处理24小时显著抑制了脂多糖（LPS）应激下BV-2细胞中一氧化氮的产生，其IC50值为13.6µM[4]。使用20µM的Pimaric Acid处理48小时，显著抑制了PA-1细胞的活力并改变了细胞形态，促进了内质网应激相关蛋白的上调，包括p-PERK、PERK、ATF-4、CHOP和IRE-1[5]。使用20µM的Pimaric Acid处理24小时，降低了TNF-α刺激的人主动脉平滑肌细胞（HASMCs）中MMP-9蛋白水平，同时伴有p65、c-Fos、p-c-Jun、p-ATF2和Jun-D表达的下降，并抑制了细胞迁移[6]。