Chinese scientists have identified the chemical mechanism of celastrol, which they call one of the most potent natural weight-loss agents, marking another step toward its possible future development into a major weight-loss drug.

The compound is extracted from the roots of thunder god vine, a toxic herb used in traditional Chinese medicine for centuries to cure arthritis and autoimmune diseases. In TCM, however, it is used in tiny amounts, mainly to treat severe diseases, because of its potentially dangerous side effects.

A research team led by Zhang Xiaokun, the Dean of School of Pharmaceutical Sciences, Xiamen University, found celastrol can change a cell's metabolism by eliminating inflamed mitochondria, leading to weight loss. Mitochondria are the cell's "energy factory".

"This is a huge step in turning celastrol into a feasible and safe medicine for humans," he said. "Celastrol could be a powerful tool to treat patients suffering from obesity and associated complications, such as Type 2 diabetes, heart disease and fatty liver."

Celastrol has long been a hot subject in biomedicine. In 2007, Cell, a prestigious science journal, listed celastrol with the discovery of antimalarial drug artemisinin - which won chemist Tu Youyou the Nobel Prize in 2015 - among five natural herbal compounds with the most potential for modern medicine.

In 2015, scientists at Boston Children's Hospital and Harvard Medical School discovered celastrol can help obese mice lose up to 45 percent of their body fat by enhancing a cell's reaction to an appetite-suppressing hormone called leptin.

However, scientists did not know exactly how celastrol affects a cell's bioactivities. Since celastrol and the plant it comes from are extremely toxic, "some people were very skeptical or even objected to the idea that people can eat such a thing", Zhang said. "After all, the vine has a scary, centuries-old nickname: gut-cutting grass."

Terrifying as it may sound, on a cellular level, "celastrol may be beneficial" because it acts on an orphan receptor called Nur77, which induces inflamed mitochondria to dissolve, effectively taking out the root cause of many chronic inflammation diseases such as obesity, tumors and metabolic diseases, he said.

Mitochondria play a key role in cellular death, immunity and inflammation. By killing the malfunctioning mitochondria, celastrol can help control cell metabolism and increase a cell's sensitivity to leptin, a hormone that inhibits hunger, thus leading to weight loss, Zhang added.

Zhang said his team, whose findings were published this month by Molecular Cell, an international science journal, will now focus on how celastrol regulates metabolism in greater detail and find ways to reduce the substance's toxicity while keeping its weight loss potency.

Also, scientists are looking for other receptors for celastrol that may affect cells differently and possibly offer new solutions to chronic metabolic or autoimmune diseases such as rheumatoid arthritis, tumors and AIDS, he added.

zhangzhihao@chinadaily.com.cn