Methyl rosmarinate

Methyl rosmarinate is an orally active hydroxycinnamic acid. Methyl rosmarinate exhibits an IC₅₀ of 24.70 μM and a K_i of 15.29 μM against PTP1B, an IC₅₀ of 41.46 μg/mL against BChE, a K_i of 0.61 mM against mushroom tyrosinase, and an IC₅₀ of 2.50 μM against SARS-CoV-2 3CLpro. Methyl rosmarinate downregulates the phosphorylation levels of ERK, JNK, p38, Smad2 and Smad3. Methyl rosmarinate activates erythrocyte BPGM and promotes the production of 2,3-BPG. Methyl rosmarinate induces apoptosis of fibroblasts. Methyl rosmarinate prolongs the survival time of hypoxic mice. Methyl rosmarinate improves insulin sensitivity. Methyl rosmarinate binds to SARS-CoV-2 3CLpro and inhibits viral replication. Methyl rosmarinate induces glioblastoma cell death. Methyl rosmarinate activates the TGR5/AMPK axis and reduces the levels of ROS and MDA. Methyl rosmarinate shows inhibitory activity against MMP-1. Methyl rosmarinate can be used in research related to pulmonary fibrosis, hypoxia-induced injury, type 2 diabetes, Alzheimer's disease, hyperpigmentation disorders, COVID-19, glioblastoma and myocardial ischemia-reperfusion injury^{[1][2][3][4][5][6][7][8][9]}. IC50 & Target:IC50: 0.28 mM (mushroom tyrosinase), a -glucosidase^[1] In Vitro:Methyl rosmarinate (10-160 μM; 48 h) exhibits cytotoxicity against L929 cells, with an IC₅₀ of 76.27 μM^[1].
Methyl rosmarinate (10-40 μM; 48 h) reduces extracellular matrix protein accumulation in TGF-β1-stimulated L929 cells^[1].
Methyl rosmarinate (20-40 μM; 12-72 h) inhibits the proliferation and migration of TGF-β1-stimulated mouse fibroblast L929 cells and increases the cellular apoptosis rate^[1].
Methyl rosmarinate (20-40 μM; 48 h) upregulates the expression levels of pro-apoptotic proteins Bax, cleaved caspase 3, and cleaved caspase 9, downregulates the expression level of anti-apoptotic protein Bcl-2, inhibits the phosphorylation of TGF-β1/Smad and MAPK signaling pathways, and alleviates the fibrotic response in TGF-β1-stimulated mouse fibroblast L929 cells^[1].
Methyl rosmarinate competitively and reversibly inhibits the activity of recombinant human PTP1B enzyme, with an IC₅₀ of 24.7 μM and a K_i of 15.29 μM^[3].
Methyl rosmarinate (6.25-25 μM; 24 h) acts as an insulin sensitizer, enhancing insulin-stimulated glucose uptake and glycogen synthesis in fully differentiated C2C12 myotubes. It activates the insulin signaling pathway and increases insulin-stimulated phosphorylation levels of IRS-1 and Akt, without altering the protein expression level of PTP1B^[3].
Methyl rosmarinate inhibits butyrylcholinesterase (BChE) with an IC₅₀ of 41.46 µg/mL, but exerts no significant inhibitory effect on acetylcholinesterase (AChE)^[4].
Methyl rosmarinate (0.01-0.4 mM; 2 min preincubation, 5 min reaction) inhibits the diphenolase activity of mushroom tyrosinase with a K_i of 0.61 mM, and inhibits yeast α-glucosidase activity^[5].
Methyl rosmarinate acts as an allosteric inhibitor of purified SARS-CoV-2 3CLpro, with an IC₅₀ of 2.5 μM, a K_i of 1.27 μM, and a K_d of 5.93 μM^[6].
Methyl rosmarinate (1-200 μM; 52 h total) inhibits the replication of SARS-CoV-2 replicons in Huh7 cells, with an EC₅₀ of 18.91 μM, and only exhibits moderate cytotoxicity at the concentration of 200 μM^[6].
Methyl rosmarinate (5-60 μM; 72 h) reduces the viability of human glioblastoma U87 (IC₅₀ = 9.8 μM) and T98 (IC₅₀ = 13 μM) cell lines in a dose-dependent manner^[7].
Methyl rosmarinate (9.8-19.6 μM in U87 cells; 13-26 μM in T98 cells; 72 h) induces subG0 and S phase arrest in U87 cells, and subG0 and G2/M phase arrest in T98 cells^[7].
Methyl rosmarinate (9.8-19.6 μM in U87 cells; 13-26 μM in T98 cells; 48 h) inhibits the migration of U87 and T98 cell lines in a dose-dependent manner^[7].
Methyl rosmarinate inhibits purified human MMP-1 with an IC₅₀ of 14.7 μM^[9]. In Vivo:Methyl rosmarinate (20 mg/kg; p.o.; daily; from day 3 to day 28) significantly attenuates Bleomycin (HY-108345)-induced pulmonary fibrosis in male C57BL/6 mice^[1].
Methyl rosmarinate (25-75 mg/kg, i.p.; once daily for 3 consecutive days) prolongs the survival time of mice under normobaric closed hypoxia. It protects mice from damage caused by high-altitude field hypoxia by reducing inflammatory factors, improving tissue oxidative stress, alleviating tissue pathological damage and relieving tissue hypoxia. Additionally, it enhances the glycolysis pathway activity of red blood cells in Mus musculus exposed to high-altitude field hypoxia, activates BPGM, and increases the level of 2,3-BPG, thereby improving the oxygen release capacity of red blood cells^[2].
Methyl rosmarinate (6.25-25 mg/kg; oral gavage; daily; 7 weeks) improves insulin sensitivity, restores glucose and lipid homeostasis, protects skeletal muscle and organ function, and enhances β-cell function in type 2 diabetic mice induced by high-fat diet/Streptozotocin (HY-13753)^[3].
Methyl rosmarinate (50-200 mg/kg; i.p.; single administration 3 hours before ligation) dose-dependently improves cardiac function, and alleviates myocardial injury, oxidative stress and mitochondrial damage in Mus musculus (mouse) models of myocardial ischemia-reperfusion injury by activating the TGR5/AMPK signaling axis^[8].