Secoisolariciresinol diglucoside (SDG)

Secoisolariciresinol diglucoside (SDG) is a flaxseed lignan precursor with anti-inflammatory and antioxidant functions. Secoisolariciresinol diglucoside scavenges hydroxyl radicals and peroxyl radicals to inhibit lipid peroxidation, activates the Nrf2/HO-1 pathway and inhibits the NF-κB pathway, downregulates the expression of COX2, iNOS, TNF-α, IL-6 and MMP13, and affects hormone metabolism by regulating estrogen receptor signaling, aromatase and sex hormone-binding globulin. Secoisolariciresinol diglucoside can be used in the research of cardiovascular diseases, type 2 diabetes and obesity, hormone-related tumors such as breast cancer and prostate cancer, and osteoarthritis and oxidative stress inflammatory diseases^[1-4].

In vitro, 10-50µM Secoisolariciresinol diglucoside was used to treat 3T3-L1 preadipocytes for 48 hours. Secoisolariciresinol diglucoside reduced Oil Red O staining lipid accumulation, decreased the mRNA and protein expression of PPARγ, C/EBPα, adiponectin, aP2 and resistin, and increased the phosphorylation levels of LKB1 and AMPKα^[5]. 5-50µM Secoisolariciresinol diglucoside was used to treat HCT116 cells for 6-24 hours. Secoisolariciresinol diglucoside inhibited cell viability, caused cell shrinkage followed by swelling and rupture, increased LDH release and the proportion of PI-positive cells, upregulated cleaved caspase-1 and N-GSDMD expression, increased BAX and cytochrome c protein levels, decreased p-PI3K and p-AKT levels, and elevated intracellular ROS levels^[6]. H9c2 cardiomyocytes were pretreated with 500µM Secoisolariciresinol diglucoside for 24 hours and then treated with 50µM iron for 24 hours. Secoisolariciresinol diglucoside prevented iron-induced reduction in cell surface area, decreased ROS levels, prevented iron-induced decline in SOD concentration, and inhibited iron-induced increases in TNF-α, IL-10, MMP-2 and MMP-9 expression^[7].

In vivo, APP/PS1 mice and wild-type mice received daily intragastric administration of 70mg/kg Secoisolariciresinol diglucoside for 8 weeks. Secoisolariciresinol diglucoside improved spatial memory, recognition memory and working memory, increased PSD-95 and BDNF expression in the hippocampal dentate gyrus and cortex, activated the CREB/BDNF pathway, and reduced β-amyloid deposition in the hippocampal dentate gyrus and cortex^[8]. C57BL/6J mice received daily intragastric administration of 7-70mg/kg Secoisolariciresinol diglucoside for 8 weeks. Secoisolariciresinol diglucoside increased the number of secondary follicles and antral follicles, increased ovarian FSHR protein expression, improved ovarian amino acid transport, amino acid uptake and D-glucose uptake, reduced ROS production, increased ovarian mitochondrial DNA copy number, and slowed telomere shortening^[9]. Colitis model C57BL/6 mice received oral administration of 200mg/kg Secoisolariciresinol diglucoside for 7 days. Secoisolariciresinol diglucoside reduced colitis pathological severity, decreased colon macrophage infiltration, reduced colon IL-1β, IL-18 and TNF-α levels, and downregulated colon NLRP1, ASC and caspase-1 mRNA and protein expression^[10].

References:

[1] Kezimana P, Dmitriev AA, Kudryavtseva AV, et al. Secoisolariciresinol Diglucoside of Flaxseed and Its Metabolites: Biosynthesis and Potential for Nutraceuticals. Front Genet. 2018 Dec 12;9:641.

[2] Adolphe JL, Whiting SJ, Juurlink BH, et al. Health effects with consumption of the flax lignan secoisolariciresinol diglucoside. Br J Nutr. 2010 Apr;103(7):929-38.

[3] Scherbakov AM, Stasevich OV, Salnikova DI, et al. Antiestrogenic and antiproliferative potency of secoisolariciresinol diglucoside derivatives on MCF-7 breast cancer cells. Nat Prod Res. 2020 Oct 7; DOI: 10.1080/14786419.2020.1826479.

[4] Chen M, Zhu R, Wu T, et al. Amelioration of oxidative kidney damage in offspring by maternal trans-fatty acid exposure in mice by secoisolariciresinol diglucoside. J Cent South Univ(Med Sci). 2023;48(7):967-978.

[5] Kang J, Park J, Kim HL, et al. Secoisolariciresinol diglucoside inhibits adipogenesis through the AMPK pathway. Eur J Pharmacol. 2018; (in press; doi:10.1016/j.ejphar.2017.12.038).

[6] Chen T, Wang Z, Zhong J, et al. Secoisolariciresinol diglucoside induces pyroptosis by activating caspase-1 to cleave GSDMD in colorectal cancer cells. Drug Dev Res. 2022;83:1152-1166.

[7] Jia M, Ning F, Wen J, et al. Secoisolariciresinol diglucoside attenuates neuroinflammation and cognitive impairment in female Alzheimer's disease mice via modulating gut microbiota metabolism and GPER/CREB/BDNF pathway. J Neuroinflammation. 2024 Aug 12;21:201.

[8] Silva ACO, Bonfim M, Fontes JLM, et al. C57BL/6 Mice Pretreated With Alpha-Tocopherol Show a Better Outcome of Trypanosoma cruzi Infection With Less Tissue Inflammation and Fibrosis. Front Immunol. 2022 Jan 28;13:833560.

[9] He X, Wang Y, Wu M, et al. Secoisolariciresinol Diglucoside Improves Ovarian Reserve in Aging Mouse by Inhibiting Oxidative Stress. Front Mol Biosci. 2022 Jan 4;8:806412.

[10] Wang Z, Chen T, Yang C, et al. Secoisolariciresinol diglucoside suppresses Dextran sulfate sodium salt-induced colitis through inhibiting NLRP1 inflammasome. Int Immunopharmacol. 2020;78:105931.