Birch bark extract has been found to be able to treat many metabolic diseases in China

The sterol regulatory element binding protein (SREBP) family of transcription factors controls cell lipid homeostasis by regulating gene expression related to cholesterol, fatty acid and triglyceride synthesis and uptake Considering that hyperlipidemia is closely related to metabolic diseases, regulating the activity of SREBP represents a promising treatment strategy Recently, Chinese scientists have identified a specific small molecule inhibitor for the treatment of SREBP, which may be the beginning of the development of new therapies for type II diabetes and atherosclerosis The study was published in the recently published journal cell metabolism The activity of SREBP is regulated by sterols High levels of sterol stimulated the association between SREBP mitogen activator protein (SCAP) and insulin-induced gene 1 (INSIG1), which resulted in the retention of SREBP in the endoplasmic reticulum However, low levels of sterols stimulate the SCAP regulated transport of SREBP to Golgi complex, where it is divided and releases mature, nuclear form of SREBP Currently available SREBP treatment inhibitors cannot be used clinically because they activate the liver X receptor (LXR), which regulates cholesterol efflux but also upregulates srebp1c isoforms, which can lead to fatty acid synthesis Song Baoliang and colleagues from Shanghai Institute of life sciences, Chinese Academy of Sciences, therefore set the goal to identify a specific SREBP inhibitor and investigate its potential in the treatment of metabolic diseases First, using chemical screening, the researchers found that betulin can be used as an effective inhibitor of SREBP activity Betulin is a pentacyclic triterpenoid found in birch bark In the in vitro mechanism study, betulin was found to be able to bind directly to SCAP, and stimulate its association with INSIG1 by blocking SREBP treatment, down regulating genes related to cholesterol and fatty acid biosynthesis, and reducing cell lipid levels Importantly, birch alcohol has a specific effect on SREBP but no effect on LXR In order to evaluate the activity of betulin in vivo and to demonstrate the therapeutic potential of SREBP inhibition, mice fed a Western diet consisting of high fat and cholesterol were given daily gastric lavage with betulin or the control group After 6 weeks, mice treated with betulin gained less weight due to increased energy expenditure, which means that betulin can prevent diet induced obesity Consistent with in vitro studies, betulin reduces lipid levels in serum and tissues, and these effects can be regulated by the adjustment of the scap-srebp pathway In addition, betulin improved glucose tolerance and insulin sensitivity, and reduced the increase of fasting blood glucose level in the control group Moreover, gene expression related to cholesterol and fatty acid synthesis was reduced; conversely, the white adipose tissue genes known to have anti diabetes and anti-inflammatory effects were up-regulated Finally, in a mouse model of atherosclerosis, 14 weeks of betulin treatment reduced the size of the disease and improved plaque stability It is worth noting that betulin is as effective or even more effective as lovastatin in each in vivo study The latter is a widely used blood prescription drug against high cholesterol, which has different mechanisms to produce curative effects, with some side effects The researchers believe that these findings support the theory of treating hyperlipidemia and related metabolic diseases by inhibiting the SREBP pathway, and that this method will have more advantages than the existing treatment scheme.