Isosilybin

Isosilybin is a flavanolignan found in the extract of S. marianum fruits with antioxidant and anticancer activities.^1,2,3 It inhibits lipid peroxidation in rat liver microsomes (IC₅₀ = 32 μM) and reduces ADP/Fe³⁺-induced malondialdehyde (MDA) production and lactate dehydrogenase (LDH) release in rat hepatocytes.¹ Isosilybin inhibits the production of reactive oxygen species (ROS), MDA and LDH release, and reduction in total antioxidant capacity induced by amyloid-β (25-35) (Aβ25-35) in HT-22 hippocampal cells.² It also increases protein and mRNA expression of heme oxygenase-1 (HO-1), glutathione S-transferase (GST), and the aldo-keto reductases (AKCR) 1C1 and AKCR1C2 in HT-22 cells. In vivo, isosilybin (50 and 100 mg/kg) reduces tumor volume and increases tumor cell apoptosis in a DU145 prostate cancer mouse xenograft model.³ It also reduces expression of the tumor angiogenesis markers CD31, nestin, VEGF, VEGFR1, VEGFR2, phospho-Akt, and HIF-1α in tumor tissue without reducing blood vessel count in non-cancerous liver, lung, and kidney tissue in DU145 tumor-bearing mice.

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1. Bosisio, E., Benelli, C., and Pirola, O. Effect of the flavanolignans of Silybum marianum L. on lipid peroxidation in rat liver microsomes and freshly isolated hepatocytes. Pharmacol. Res. 25(2), 147-154 (1992).

2. Zhou, J., Chao, G., Li, Y., et al. Activation of NRF2/ARE by isosilybin alleviates Aβ₂5-35-induced oxidative stress injury in HT-22 cells. Neurosci. Lett. 632, 92-97 (2016).

3. Deep, G., Gangar, S.C., Rajamanickam, S., et al. Angiopreventive efficacy of pure flavonolignans from milk thistle extract against prostate cancer: Targeting VEGF-VEGFR signaling. PLoS One 7(4), e34630 (2012).