Semaglutide

Semaglutide is a long-acting, selective, competitive GLP-1R agonist that can penetrate the blood-brain barrier. After activating GLP-1R, Semaglutide promotes insulin secretion, inhibits gastric emptying and appetite, and at the same time enhances autophagy, inhibits oxidative stress and apoptosis. Semaglutide also regulates mitochondrial function and lipid metabolism (such as reducing de novo lipogenesis in the liver). Semaglutide has activities such as lowering blood sugar, reducing weight, neuroprotection (such as improving motor function in Parkinson's disease models, reducing α-synuclein aggregation) and improving hepatic steatosis. Semaglutide can be used for the study of neurodegenerative diseases and liver diseases such as type 2 diabetes, obesity, Parkinson's disease, metabolic associated fatty liver disease (MASLD), and cancer^{[1][2][3][4][5]}. In Vitro: 1. Anti-Aβ_25-35 injury experiment:
Semaglutide (1-100 nM; 24 h) significantly increases the survival rate of SH-SY5Y cells, increases the expression of autophagy-related proteins such as LC3II, Atg7, Beclin-1 and P62, inhibits Bax and upregulated Bcl-2, and protectes neurons by enhancing autophagy, inhibiting apoptosis^[1][2].
2. Oral squamous cell carcinoma (OSCC) cell experiment:
Semaglutide (5-40 μM; 48 h) dose-dependently inhibits the proliferation, migration and invasion of Cal27 and HSC4 cells, upregulates E-cadherin and downregulates Vimentin, activates the P38 MAPK signaling pathway (increased p-P38 expression), and induces cell apoptosis^[3]. In Vivo: This product is not intended for oral administration. For animal studies, subcutaneous or intraperitoneal injection is recommended.
Oral squamous cell carcinoma (OSCC) xenograft model
Semaglutide (3 μmol/kg; subcutaneous injection; 3 times a week; 3 weeks) significantly inhibits the growth of tumor volume in nude mouse oral squamous cell carcinoma (OSCC) xenograft model, downregulates proliferation markers Ki67 and PCNA, upregulates pro-apoptotic protein Bax and downregulates anti-apoptotic protein Bcl-xL, and induces tumor cell apoptosis by activating the P38 MAPK pathway^[3].
Chronic MPTP-induced Parkinson's disease model
Semaglutide (25 nmol/kg; intraperitoneal injection; once every 2 days; 30 days) improves the chronic MPTP-induced Parkinson's disease model in mice and its motor dysfunction, increases the number of nigral tyrosine (TH)-positive neurons, reduces α-synuclein aggregation and glial activation, and reduces the level of oxidative stress marker 4-HNE^[4].
Metabolic dysfunction-associated fatty liver disease (MASLD) model
Semaglutide (25 μg/kg/week + 100 μg/kg/week; subcutaneous injection; once a week; 11 weeks) reduces body weight, blood glucose and serum liver enzymes (ALT, AST, AP), reduces hepatic triglyceride deposition, improves hepatic steatosis and hepatocyte ballooning, and downregulates the de novo lipogenesis markers Acaca and Scd1 in the mouse metabolic dysfunction-associated fatty liver disease (MASLD) model^[5].