Ajugol

Ajugol is an orally active iridoid glycoside found in the traditional Chinese medicine Leonurus japonicus. Ajugol is an autophagy activator. Ajugol activates TFEB-mediated autophagy and lysosomal biogenesis. Ajugol also has anti-inflammatory effects. Ajugol has great potential in the research of asthma, non-alcoholic fatty liver disease (NAFLD), and osteoarthritis^[1][2][3][4]. In Vitro:Ajugol has antiprotozoal activity against Trypanosoma b. rhodesiense (IC₅₀: 31.8 μg/ml) and Trypanosoma b. rhodesiense (IC₅₀: 7.2 μg/ml)^[1].
Ajugol (0-100 μM, 0-72 h) in tert-butyl hydroperoxide (TBHP)-induced mouse primary chondrocytes restores TBHP-induced proliferation restriction and reduces chondrocyte apoptosis, ECM degradation and ROS accumulation without cytotoxicity (≤50 μM)^[2].
Ajugol (50 μM) in Palmitate (HY-N0830)-induced mouse hepatocytes significantly reduces cellular triglyceride (TG) and total cholesterol (TC) content and plays a protective role in Palmitate-induced lipid accumulation without cytotoxicity^[3].
Ajugol (25,50 μM) activates TFEB-mediated autophagy and promotes TFEB nuclear translocation by regulating mTOR dephosphorylation, enhancing lysosomal biogenesis, alleviating endoplasmic reticulum (ER) stress and lipid degradation in TBHP-induced mouse primary chondrocytes and Alpha Mouse Liver-12 (AML12) cells^[2][3].
Ajugol attenuates its protective effects against lipid accumulation and ER stress and ECM after autophagy is blocked by Chloroquine (HY-17589A), indicating that it is dependent on the autophagy pathway to exert its effects^[2][3].
In Vivo:Ajugol (25,50 mg/kg, i.p., once a day, 8 weeks) activates TFEB in vivo and improves the progression of osteoarthritis after DDM (Destabilization of the Medial Meniscus) surgery in an osteoarthritis mouse model^[2].
Ajugol (50 mg/kg, p.o., 12 weeks) improves HFD-induced hepatic steatosis and lipid metabolism disorders by promoting autophagic flux in a high-fat diet (HFD)-fed mouse model^[3].