Timosaponin A3 Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.

Acetylcorynoline Induces Apoptosis and G2/M Phase Arrest through the c-Myc Signaling Pathway in Colon Cancer Cells.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide, and despite advances in treatment, survival rates are still low; therefore, the development of novel drugs is imperative. Acetylcorynoline (ACN) is derived from Corydalis ambigua Cham. et Schltdl tubers. The effect of ACN on colon cancer is still unknown. Therefore, we investigated its potential effects. Our data showed that ACN inhibited cell viability and proliferation. Moreover, ACN induced apoptosis and cell cycle arrest by inhibiting cell growth. In the present study, we hypothesized that ACN regulates c-Myc through CNOT2 or MID1IP1. ACN reduced the protein expression of oncogenic genes, decreased c-Myc half-life, and rapidly inhibited the serum stimulation response. Moreover, knockdown of CNOT2 and MID1IP1 with ACN increased apoptosis and further reduced the expression of oncogenes. In addition, ACN exhibited a synergistic effect with low-dose 5-fluorouracil (5-FU) and doxorubicin (Dox). Collectively, our data demonstrate that ACN inhibited c-Myc expression through CNOT2 and MID1IP1, and induced apoptosis. These findings indicate the potential of ACN as a therapeutic agent against colon cancer.