Levistilide A is a natural phthalide compound extracted from the traditional Chinese medicine Ligusticum chuanxiong, possessing multiple biological activities. Levistilide A can induce cancer cell apoptosis by activating PPARγ and inhibiting the GSK3α/β pathway, as well as promoting ROS generation. Levistilide A can be used in research related to Alzheimer's disease, tumors, and kidney diseases[1-4].
In vitro, Levistilide A (0–80μM) was used to treat MDA-MB-231 and MCF-7 breast cancer cells for 24–48 hours. Levistilide A significantly reduced cell viability and increased lactate dehydrogenase release in a dose-dependent manner, promoting cell damage and death. Levistilide A treatment significantly inhibited GPX4 protein expression while upregulating the mRNA expression of SLC7A11, SLC3A2, GCLC, GCLM, GSS, TFRC, SLC11A2, and NCOA4. Levistilide A treatment markedly increased the protein and mRNA expression levels of Nrf2 and HO-1[5]. Levistilide A (1–10μM) was co-treated with LPS (200ng/ml–1μg/ml) in BV-2 microglial cells and mouse primary microglial cells for 24 hours. Levistilide A significantly inhibited the expression of pro-inflammatory factors NO, IL-6, and TNF-α, reducing the inflammatory response[6].
In vivo, Levistilide A (3mg/kg and 6mg/kg; once daily) was intraperitoneally injected into CCl4-induced liver fibrosis Wistar rats for three weeks. Levistilide A improved the rats' serum liver function, alleviated liver fibrosis, and inhibited angiogenesis[7]. Levistilide A (20mg/kg; once daily) was administered orally to lauric acid-induced thromboangiitis obliterans Wistar rats, starting two days before surgery and continuing for 16 days. Levistilide A improved blood flow, reduced muscle inflammatory necrosis, and decreased serum levels of IL-1β, IL-6, and CRP, as well as NLRP3 expression[8].
References:
[1] Yang Y, Zhang Y, Wang L, et al. Levistolide A Induces Apoptosis via ROS-Mediated ER Stress Pathway in Colon Cancer Cells. Cell Physiol Biochem. 2017;42(3):929-938.
[2] Qu X, Guan P, Han L, et al. Levistolide A Attenuates Alzheimer's Pathology Through Activation of the PPARγ Pathway. Neurotherapeutics. 2021 Jan;18(1):326-339.
[3] Zeng W, Ren J, Li Z, et al. Levistolide A Inhibits PEDV Replication via Inducing ROS Generation. Viruses. 2022 Jan 27;14(2):258.
[4] Li S, Zhao W, Zhao Z, et al. Levistilide A reverses rat hepatic fibrosis by suppressing angiotensin II‑induced hepatic stellate cells activation. Mol Med Rep. 2020 Sep;22(3):2191-2198.
[5] Jing S, Lu Y, Zhang J, Ren Y, et al. Levistilide a Induces Ferroptosis by Activating the Nrf2/HO-1 Signaling Pathway in Breast Cancer Cells. Drug Des Devel Ther. 2022 Sep 7;16:2981-2993.
[6] Zhang M, Duan C, Lin W, et al. Levistilide A Exerts a Neuroprotective Effect by Suppressing Glucose Metabolism Reprogramming and Preventing Microglia Polarization Shift: Implications for Parkinson's Disease. Molecules. 2024 Feb 19;29(4):912.
[7] Zhao ZM, Liu HL, Sun X, et al. Levistilide A inhibits angiogenesis in liver fibrosis via vascular endothelial growth factor signaling pathway. Exp Biol Med (Maywood). 2017 May;242(9):974-985.
[8] Guo H, Sun L, Ling S, et al. Levistilide A Ameliorates NLRP3 Expression Involving the Syk-p38/JNK Pathway and Peripheral Obliterans in Rats. Mediators Inflamm. 2018 Aug 12;2018:7304096.