Drug repurposing in alternative medicine: herbal digestive Sochehwan exerts multifaceted effects against metabolic syndrome

New drug development is a challenging process that requires high-risk, huge costs and long lead times. Therefore, drug repurposing is considered a strategic and economic way towards successful drug development. Sochehwan (SCH) is a herbal formula well known as a digestive aid in traditional oriental medicine, is referred to in classic medical texts, and is available as an over-the-counter drug for indications of digestive ailments. Interestingly, another medical text written in earlier age describes different indication of SCH yet to be examined. We conducted a series of investigations using maturated adipocytes, free fatty acid (FFA) induced hepatic steatosis model in vitro and high-fat diet (HFD) mice model in vivo. Exposure to SCH regulated expression of adipogenic genes and proteins, significantly inhibiting formation of lipid droplets in 3T3-L1 cells. Similarly, SCH treatment modulated proteins related with energy metabolism decreasing lipid accumulation in FFA induced HepG2 cells. Furthermore, HFD-fed c57BL/6 J mice supplemented with SCH exhibited significant changes in serum glucose and lipid profiles. Histologic analysis of mice liver and adipose tissue showed that SCH administration attenuated hepatic steatosis and hypertrophy of adipose tissue. In overall, the results show that SCH can potentially be used to treat metabolic syndrome (MetS) by enhancing glucose metabolism and inhibiting lipogenesis through activating AMP-activated protein kinase (AMPK) and its downstream signaling. Furthermore, it seems to be a feasible drug repurposing strategy for drugs originating from alternative medicine to revise the value for buried indications of some herbal prescription in old traditional Chinese Medicine (TCM) classics.