An East-West team has created a potential anti-pain drug out of a traditional Chinese herbal medicine. The drug appears to be non-addictive, and eases both inflammatory and neuropathic pain. The latter is particularly intriguing, as no truly effective drugs exist to quell neuron pain.
The compound was concocted by the team of University of California Irvine neuropharmacology chair Olivier Civelli in the United States, alongside the crew of chemist Xinmiao Liang of the Dalian Institute of Chemical Physics (DICP) in China. In an upcoming Current Biology, the teams report rodent testing of the compound dehydrocorybulbine (DHCB), culled from the Corydalis yanhusuo root.
They found the compound lessened inflammatory pain caused by tissue damage and immune cell attack, and injury-associated neuropathic pain, prompted by nerve damage. They are working their way through an ancient “herbalome” collected and maintained by Liang at the Chinese institute.
“Yan Zhang, the first name on the paper, applied to my lab in 2007,” Civelli tells Drug Discovery. “I understood that the technologies developed at the DICP in China could be of use in our search for new ligands of GPCRs, which is the main research direction of my laboratory.” Between one third to one-half of all drugs act by binding to GPCRs, or G protein-coupled receptors, on cell surfaces.
“We established our collaboration at that time, but it took off when I visited the DICP in 2009,” Civelli says.
The two teams applied Civelli’s “reverse pharmacology” approach to 500 compounds from ten herbs in DICP’s herbalome before they found a reproducible effect in DHCB. Previously, the two groups isolated a peptide culled from scorpion venom, used for pain relief in China, although it is too weak to become a Western drug at this time.
Corydalis is an herbal flower native to Northern China, Japan and Siberia. Its root extract— which can be found now in health stores— has been used for centuries used to soothe menstrual, other stomach and chest pains.
Civelli says the main surprise for him was “to find [that] the analgesic property of this compound was mostly accounted for by its antagonism at the dopamine D2 receptor. The D2 receptor is dear to my heart because I cloned it in 1988. Yet, the D2 receptor is rarely implicated in pain perception, and if so, it is more through D2 agonists” – not antagonists, like DHCB. (In the brain, dopamine acts as a neurotransmitter, a communication chemical. It can play a major role in reward-motivated behaviors. Addictive drugs increase brain dopamine levels.)
Civelli will continue to study this unexpected mechanism of action. The compound will also be further evaluated for toxicity. If it is chemically modified, an even stronger potential drug might result.
The pharmaceutical industry has been running low on novel therapeutic compounds. Ancient Chinese remedies are starting to be considered a promising source. It is estimated that more than 10 million peptide toxins exist in 1,400 scorpion species; 400 snake species; 600 sea cone snail species; and 35,000 spider species. (These peptides can be analgesic, it is speculated, because some animals need to stun their prey before eating it.) Less than .02%of these and other natural drug stores have been raided by Western researchers for potential drug targeting.
By contrast, China has been harvesting medicines from these natural stores for over 7,000 years. Estimates find that traditional Chinese medicine encompasses 400,000 preparations, made out of 10,000 herbs and animal tinctures. But it is key, say Dalian researchers, to find and analyze the active ingredients in these ancient remedies, as their effects are uneven and unstudied— and sometimes a matter of myth.
The Herbalome Project is a multi-million dollar, 15-year-effort, led by the Dalian group.