Senkyunolide I

Catalog	BBC94596288
CAS	94596-28-8
Structure
Description	Senkyunolide I, isolated from Ligusticum chuanxiong Hort, is an anti-migraine compound. Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3.
Synonyms	(3Z,6R,7R)-rel-3-Butylidene-4,5,6,7-tetrahydro-6,7-dihydroxy-1(3H)-isobenzofuranone
IUPAC Name	(3Z,6S,7S)-3-butylidene-6,7-dihydroxy-4,5,6,7-tetrahydro-2-benzofuran-1-one
Molecular Weight	224.25
Molecular Formula	C12H16O4
Canonical SMILES	CCC/C=C\1/C2=C([C@@H]([C@H](CC2)O)O)C(=O)O1
InChI	InChI=1S/C12H16O4/c1-2-3-4-9-7-5-6-8(13)11(14)10(7)12(15)16-9/h4,8,11,13-14H,2-3,5-6H2,1H3/b9-4-/t8-,11+/m0/s1
InChI Key	DQNGMIQSXNGHOA-JXQVETIVSA-N
Purity	98%
Density	1.28 g/ml
Appearance	Powder
Storage	4°C, protect from light*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light).

Case Study

Role of Senkyunolide I in Promoting Neural Stem/Progenitor Cell Proliferation

Wang, Min, et al. Biomedicine & Pharmacotherapy 168 (2023): 115683.

Senkyunolide I (SEI) is a bioactive compound extracted from traditional Chinese medicines Ligusticum chuanxiong Hort. and Angelica sinensis (Oliv.) Diels, and has been shown to have protective effects against ischemic stroke. This study investigated the impact of SEI on the proliferation and neuronal lineage differentiation of neural stem/progenitor cells (NS/PCs).
The results indicated that SEI exposure significantly enhanced NS/PC proliferation. An increase in cell numbers was observed in neurospheres treated with SEI for 3 days. However, NS/PC differentiation was reduced after 5 days of SEI treatment. Additionally, SEI treatment upregulated pAkt/Akt and active-β-catenin signaling, promoting NS/PC proliferation. The proliferation effect of SEI was reversed by the phosphatidylinositol 3-kinase inhibitor LY294002, which also downregulated differentiation processes. Therefore, SEI effectively stimulates NS/PC proliferation while suppressing their differentiation into neurons and astrocytes, suggesting its potential as a promising candidate for stimulating neural stem cells.

Senkyunolide I Ameliorates Thoracic Aortic Aneurysm and Dissection in Mice

Zhao, K., Zhu, H., He, X., Du, P., Liang, T., Sun, Y., ... & Zhou, J. (2023). Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1869(7), 166819.

Thoracic aortic aneurysm and aortic dissection (TAAD) are among the most fatal cardiovascular diseases. Senkyunolide I (SEI), a bioactive compound from traditional Chinese medicine, is known for its potent anti-inflammatory properties and protective effects. However, its potential impact on TAAD remains unclear. This study aimed to investigate the role of SEI in a murine model of TAAD and explore the underlying immunopharmacological mechanisms.
The structure of SEI is shown in Fig. A, while Fig. B illustrates the TAAD induction and administration protocols. As seen in Fig. C, body weight was significantly reduced in the TAAD model group, but SEI treatment alleviated the weight loss (on day 33, model + DMSO vs. model + SEI: 15.5 ± 1.3 g vs. 19.0 ± 1.5 g, p < 0.001, n = 10 per group). The Kaplan-Meier survival curve revealed a statistically higher overall survival probability in the SEI-treated group compared to the model group (p < 0.01) (Fig. D). Representative samples from all four groups are shown in Fig. E.
In conclusion, SEI treatment alleviates BAPN/AngII-induced TAAD in mice through the PI3K/AKT/NF-κB signaling pathway. Additionally, SEI administration protects endothelial cells (ECs) from oxidative stress and apoptosis.

Senkyunolide I Attenuates Oxygen-Glucose Deprivation/Reoxygenation-Induced Inflammation in Microglial Cells

Hu, Yang-ye, et al. Brain Research 1649 (2016): 123-131.

Over-activated microglia during stroke have been shown to exacerbate brain damage. Our previous studies indicated that senkyunolide I (SEI) has anti-inflammatory effects in response to endotoxin insult in vitro and ameliorates cerebral ischemia/reperfusion (I/R) injury in vivo. In this study, we investigated the anti-inflammatory effects of SEI on microglial cells using oxygen-glucose deprivation/reoxygenation (OGD/R) to model stroke, and explored the underlying mechanisms.
OGD for 3 hours followed by 12 hours of reoxygenation significantly increased the release of pro-inflammatory cytokines and the expression of inflammation-related enzymes in BV-2 cells. This effect was inhibited by pretreatment with SEI. To understand the mechanisms, we examined its impact on upstream signaling pathways. We found that SEI suppressed the activation of the NF-κB pathway induced by OGD/R, while the MAPK pathway was not involved. Furthermore, SEI down-regulated the TLR4/MyD88 pathway and specifically increased the levels of inducible Hsp70 by enhancing HSF-1/DNA binding activity. These regulatory effects were attenuated by transfecting Hsp70 siRNA and HSF-1 decoy ODNs. SEI had a similar effect on the Hsp70/TLR4/NF-κB pathway in rat primary microglial cells.
In conclusion, SEI demonstrates potent anti-inflammatory effects against stroke-induced neuroinflammation by suppressing the TLR4/NF-κB pathway through the upregulation of Hsp70, a process dependent on HSF-1.