Malvidin 3-galactoside chloride

Malvidin 3-galactoside chloride (CAS 30113-37-2) exerts its core effects through multiple molecular targets, encompassing inflammatory regulatory pathways (NF-κB), tumor-associated pathways (PTEN/AKT, JNK/p38 MAPK, VEGF/MMP-2/9), and antioxidant pathways (Nrf2/Keap1). It also targets molecules related to oxidative stress (ROS, lipid peroxidase) and cell cycle regulatory proteins (cyclin D1/B/E).

In terms of anti-inflammatory activity, M3G targets the NF-κB pathway in a concentration-dependent manner. At a concentration of 1 μM, it inhibits TNF-α-induced release of monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), with inhibition rates of 35.9%, 54.4%, and 44.7%, respectively. The mRNA expression levels of these molecules are also significantly downregulated (p<0.05). At 50 μM, M3G inhibits IκBα degradation by 84.8% and blocks p65 nuclear translocation. When used in combination with Malvidin-3-glucoside, a synergistic anti-inflammatory effect is observed.

In the field of anti-tumor activity, M3G targets the PTEN/AKT and JNK/p38 MAPK pathways in HepG2 cells. At a concentration of 200 μg/mL, it induces S phase cell cycle arrest, downregulates the expression of cyclin D1, cyclin B, and cyclin E, and upregulates Bax and cleaved caspase-3 protein levels, resulting in a cell apoptosis rate of 32% (p<0.01). Additionally, M3G targets the VEGF/MMP-2/9 pathway, significantly downregulating their expression and inhibiting tumor migration and invasion.

Regarding antioxidant activity, although M3G does not have a clearly defined IC50 value, it effectively targets the lipid peroxidation process at concentrations of 2–10 μM. It inhibits Fe²⁺/ascorbic acid- or H₂O₂-induced lipid peroxidation in mouse brain/testicular tissues, reducing TBARS levels (p=0.021). At 10 μM, M3G scavenges intracellular ROS, decreases AAPH-induced ROS production in mouse erythrocytes (p=0.001), and protects hemoglobin from oxidative damage.

In vivo, M3G targets oxidative stress response genes (sod1, nrf2) and lipid metabolism genes (bmm, Lip3) in Drosophila melanogaster. At concentrations of 1–100 μM, it extends the lifespan of male flies by up to 5% (p<0.05). At 100 μM, it significantly enhances resistance to paraquat (oxidative stress), 35°C heat shock, and 300 Gy γ-radiation, increasing median survival by 13% (p<0.01), 10% (p<0.05), and 12% (p<0.05), respectively.

In a mouse hepatocellular carcinoma model, oral administration at 40–80 mg/kg body weight targets tumor cell proliferation and apoptosis pathways. In the 80 mg/kg group, tumor volume is reduced by 35% compared to the control group. TUNEL staining indicates increased apoptosis, and immunohistochemistry confirms upregulation of cleaved caspase-3 and downregulation of Ki-67 (a proliferation marker), along with upregulation of PTEN and inhibition of p-AKT (p<0.05). These effects are superior to those observed with 20 mg/kg 5-fluorouracil.

It should be noted that sex differences exist: in female Drosophila, high concentrations (10 μM) of M3G result in reduced lifespan and decreased stress resistance.

References:

[1] Huang WY, Liu YM, Wang J, Wang XN, Li CY. Anti-inflammatory effect of the blueberry anthocyanins malvidin-3-glucoside and malvidin-3-galactoside in endothelial cells. Molecules. 2014 Aug 21;19(8):12827-41. doi: 10.3390/molecules190812827. PMID: 25153881; PMCID: PMC6271830.

[2] Wang Y, Lin J, Tian J, Si X, Jiao X, Zhang W, Gong E, Li B. Blueberry Malvidin-3-galactoside Suppresses Hepatocellular Carcinoma by Regulating Apoptosis, Proliferation, and Metastasis Pathways In Vivo and In Vitro. J Agric Food Chem. 2019 Jan 16;67(2):625-636. doi: 10.1021/acs.jafc.8b06209. Epub 2019 Jan 7. PMID: 30586992.

[3] Golubev D, Platonova E, Zemskaya N, Shevchenko O, Shaposhnikov M, Tumaeva P, Patov S, Moskalev A. Sex-dependent geroprotective effects of malvidin in Drosophila melanogaster. Biogerontology. 2025 Jul 13;26(4):144. doi: 10.1007/s10522-025-10285-0. PMID: 40652411.