AWARDEE OF MEDICAL SCIENCES AND MATERIA MEDICA PRIZE
JIN GUOZHANG
Jin Guozhang is a professor of neuropharmacology. He was born on Jun 6, 1927 in Yongkang, Zhejiang Province. After graduated from Zhejiang University School of Sciences in 1952, he joined the Shanghai Institute of Materia Medica, Chinese Academy of Sciences. He is now a professor of the institute. He was elected the academician of the Chinese Academy of Sciences in 2001.
Professor Jin has researched on the field of neuropharmacology and focused on the dopaminergic system more than 40 years. At first, he studied the traditional Chinese herb, Corydalis yanhusuo W.T. Wang in 1956-1964. And then he studied the neuropharmacology of tetrahydroprotoberberines (THPBs) isolated from the Chinese herbs on brain DA receptors in 1978-2002. He has ascertained that l-tetrahydropalmatine (l-THP or so-called rotundine) is the main active analgesic ingredient of Corydalis, which is neither a narcotic analgesic nor an antipyretic analgesic. Afterwards, l-THP was verified to be a DA receptor antagonist, which is consistence with its sedative-tranquillizing effect found in 1960-1964. Sequently, the analgesic mechanisin of l-THP has been elucidated to be mediated via D2 receptors in the nucleus accumbens, and thereby to promote the analgesic function through the nervous pathway from nucleus arcuate to periaqueduct of central gray in midbrain. Simultaneously, the l-THP can enhance the inhibition of brain stem on noxious stimulation ascending from the spinal cord. Therefore, the action of brain DA receptors is a main participatory factor in the analgesic mechanism of l-THP. Now, the l-THP has been written into almost all pharmacological textbooks in China since 1962, and listed in Chinese Pharmacopoeia since 1977. the l-THP is used a remedy of analgesic or sedative for more than 40 years. The study on Corydalis thus is a successful example of effort in modernization for the traditional Chinese medicine.
Based on the sedative-tranquillizing effect of l-THP, Professor Jin started a pioneer work of THPBs acting on dopamine receptors in the brain. Among THPBs, he has discovered l-stepholidine, isolated from Stephania intermedica LO, to possess dual dopamine D1 agonist and dopamine D2 antagonist actions. It means that l-stepholidine simultaneously acting on D1 and D2 receptors exhibits both inverse effects on different targets. That is a novel neuropharmacological action. Moreover, he found that the dihydroxy groups in the structure of l-stepholidine is the intrinsic chemical elements to contribute the dual actions and become the key factor in pharmacological creativity. Furthermore, the dual actions are not only found in l-stepholidine but also in the other dihydroxy-THPBs. l-Stepholidine is mere a leading compound of them. In other words, the unique characteristics of dual actions only belong to the dihydroxy-THPBs up-to-dately. More interestingly, the dual actions of l-stepholidine have the selective action targets in the brain, matching with a new hypothesis of schizophrenia pathogenesis. Its D1 agonist action selectively acts on the medial prefrontal cortex (mPFC), while its D2 antagonist action selectively on subcortex, such as nucleus accumbens and ventral tagmental area (VTA). This unique dual actions just match with the dysfucnction of D1 receptors is in the mPFC of schizophrenia patients and the hyperfunction of D2 receptors in the subcortex structures of patients. l-Stepholidine now is a first one of potential novel antipsychotic drug with dual D1 agonist and D2 antagonist actions on DA receptors. The role of the dual actions first discovered in DH-THPBs from traditional Chinese herbs, would lead more attractive compounds emerged.
Professor Jin has published more than 150 papers and 2 specialized research books regarding THPBs research topic. The book named Discoveries in the Voyage of Corydalis Research has first described the scientific findings concerned the actions of THPBs on DA receptors so far. He has won awards in recognition of his scientific achievements from the national state government (1964, 1991), Chinese Academy of Sciences (1980, 1989, 1998), and the Shanghai Municipal Government (2002).
