Catalpol

Catalpol (CAS No. 2415-24-9) is a natural iridoid glycoside compound derived from the traditional Chinese medicinal herb Rehmannia, with core biological functions covering neuroprotection, anti-osteoporosis, anti-ischemic stroke, anti-liver fibrosis, anti-depression, etc.; it has diverse targets and modes of action: activates the TrkB receptor (forming hydrophobic binding and promoting BDNF secretion), the SDF-1α/CXCR4 pathway, the VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 pathways, and inhibits the NF-κB signaling pathway (blocking phosphorylation and nuclear translocation), the EphA2/FAK/Src pathway (directly targeting EphA2 and reducing its binding to FAK), NLRP3 inflammasome activation, and oxidative stress-mediated neuroinflammation; it is commonly used for treatment in animal models, with common models including the LPS-induced sepsis-associated encephalopathy (SAE) model, ovariectomy (OVX)-induced postmenopausal osteoporosis model, permanent middle cerebral artery occlusion (pMCAO)-induced ischemic stroke model, carbon tetrachloride (CCl₄)-induced liver fibrosis model, and chronic unpredictable mild stress (CUMS)-induced depression model.

Common applications and concentrations: in cell culture, BV2 microglia and PC12 neuronal cells 3-30 μM, LX-2 hepatic stellate cells 20-80 μM, RAW264.7 osteoclast precursor cells 25-100 μM, neural stem cells (NSCs) and brain microvascular endothelial cells (BMECs) 2-100 μM; in animal experiments, SAE model intraperitoneal injection 2.5-10 mg/kg/d, osteoporosis model oral gavage 5-20 mg/kg/d, ischemic stroke model intravenous injection 2.5-10 mg/kg/d, liver fibrosis model oral gavage 20-80 mg/kg/d, depression model intraperitoneal injection 20 mg/kg/d.

Effects corresponding to effective therapeutic concentrations: at the animal level, 10 mg/kg/d can improve cognitive impairment in SAE mice, 20 mg/kg/d can alleviate bone loss in OVX rats, 10 mg/kg/d can reduce cerebral infarct volume in pMCAO rats, 80 mg/kg/d can inhibit CCl₄-induced liver fibrosis, and 20 mg/kg/d can improve depression-like behaviors in CUMS mice; at the cellular level, 30 μM can inhibit M1 polarization of BV2 cells, 100 μM can promote apoptosis of RAW264.7 cells, 50 μM can promote NSC proliferation and migration, and 80 μM can inhibit aerobic glycolysis in LX-2 cells.

References:

[1] Bai Y, Zhu R, Tian Y, Li R, Chen B, Zhang H, Xia B, Zhao D, Mo F, Zhang D, Gao S. Catalpol in Diabetes and its Complications: A Review of Pharmacology, Pharmacokinetics, and Safety. Molecules. 2019 Sep 11;24(18):3302. doi: 10.3390/molecules24183302. PMID: 31514313; PMCID: PMC6767014.

[2] Wang YL, Wu HR, Zhang SS, Xiao HL, Yu J, Ma YY, Zhang YD, Liu Q. Catalpol ameliorates depressive-like behaviors in CUMS mice via oxidative stress-mediated NLRP3 inflammasome and neuroinflammation. Transl Psychiatry. 2021 Jun 8;11(1):353. doi: 10.1038/s41398-021-01468-7. PMID: 34103482; PMCID: PMC8187638.

[3] Chen H, Deng C, Meng Z, Meng S. Effects of Catalpol on Alzheimer's Disease and Its Mechanisms. Evid Based Complement Alternat Med. 2022 Jun 30;2022:2794243. doi: 10.1155/2022/2794243. PMID: 35815283; PMCID: PMC9262514.

[4] Wang HJ, Ran HF, Yin Y, Xu XG, Jiang BX, Yu SQ, Chen YJ, Ren HJ, Feng S, Zhang JF, Chen Y, Xue Q, Xu XY. Catalpol improves impaired neurovascular unit in ischemic stroke rats via enhancing VEGF-PI3K/AKT and VEGF-MEK1/2/ERK1/2 signaling. Acta Pharmacol Sin. 2022 Jul;43(7):1670-1685. doi: 10.1038/s41401-021-00803-4. Epub 2021 Nov 18. PMID: 34795412; PMCID: PMC9253350.

[5] Zhang Z, Dai Y, Xiao Y, Liu Q. Protective effects of catalpol on cardio-cerebrovascular diseases: A comprehensive review. J Pharm Anal. 2023 Oct;13(10):1089-1101. doi: 10.1016/j.jpha.2023.06.010. Epub 2023 Jun 21. PMID: 38024856; PMCID: PMC10657971.

[6] Hu W, Zou L, Yu N, Wu Z, Yang W, Wu T, Liu Y, Pu Y, Jiang Y, Zhang J, Zhu H, Cheng F, Feng S. Catalpol rescues LPS-induced cognitive impairment via inhibition of NF-Κb-regulated neuroinflammation and up-regulation of TrkB-mediated BDNF secretion in mice. J Ethnopharmacol. 2024 Jan 30;319(Pt 3):117345. doi: 10.1016/j.jep.2023.117345. Epub 2023 Nov 4. PMID: 37926114.

[7] Chen S, Jin J, Xu Z, Han H, Wu L, Li Z. Catalpol attenuates osteoporosis in ovariectomized rats through promoting osteoclast apoptosis via the Sirt6-ERα-FasL axis. Phytomedicine. 2024 Jan;123:155262. doi: 10.1016/j.phymed.2023.155262. Epub 2023 Dec 5. PMID: 38100921.

[8] Zhang MF, Wang JH, Sun S, Xu YT, Wan D, Feng S, Tian Z, Zhu HF. Catalpol attenuates ischemic stroke by promoting neurogenesis and angiogenesis via the SDF-1α/CXCR4 pathway. Phytomedicine. 2024 Jun;128:155362. doi: 10.1016/j.phymed.2024.155362. Epub 2024 Jan 15. PMID: 38522312.

[9] Nie W, Zhu H, Sun X, Zhou J, Xu H, Yu Z, Lu M, Jiang B, Zhou L, Zhou X. Catalpol attenuates hepatic glucose metabolism disorder and oxidative stress in triptolide-induced liver injury by regulating the SIRT1/HIF-1α pathway. Int J Biol Sci. 2024 Aug 1;20(10):4077-4097. doi: 10.7150/ijbs.97362. PMID: 39113710; PMCID: PMC11302874.

[10] Zhang Q, Ran T, Li S, Han L, Chen S, Lin G, Wu H, Wu H, Feng S, Chen J, Zhang Q, Zhao X. Catalpol ameliorates liver fibrosis via inhibiting aerobic glycolysis by EphA2/FAK/Src signaling pathway. Phytomedicine. 2024 Dec;135:156047. doi: 10.1016/j.phymed.2024.156047. Epub 2024 Sep 13. PMID: 39321687.

[11] Laurindo LF, Rodrigues VD, Guiguer EL, Laurindo LF, de Campos Zuccari DAP, Detregiachi CRP, Araújo AC, da Silva Camarinha Oliveira J, Maria DA, Dias JA, Rici REG, Lamas CB, Direito R, Barbalho SM. Catalpol: An Iridoid Glycoside With Potential in Combating Cancer Development and Progression-A Comprehensive Review. Phytother Res. 2025 Oct;39(10):4950-4971. doi: 10.1002/ptr.70057. Epub 2025 Sep 23. PMID: 40985933; PMCID: PMC12504809.