Development of natural products as drugs acting on central nervous system

Abstract

We have recently studied several natural product constituents which have effects on the CNS. (1) Tetrahydropalmatine (THP) and its analogues were isolated from Corydalis ambigua and various species of Stephania. (+)-THP and (-)-THP possess not only analgesic activity, but also exert sedative-tranquilizing and hypnotic actions. Results of receptor binding assay and their pre- and post-synaptic effects on dopaminergic system indicate that (-)-THP and (-)-stepholidine are dopamine receptor antagonists while (+)-THP is a selective dopamine depletor. (2) 3-Acetylaconitine (AAC) is an alkaloid isolated from Aconitum flavum. The relative potency of analgesic action of AAC was 5.1-35.6 and 1250-3912 times that of morphine and aspirin, respectively. The analgesic effect of AAC was not antagonized by naloxone, but was eliminated by reserpine. In monkeys, after AAC was injected for 92 days, no abstinence syndrome was seen after sudden AAC withdrawal or when challenged with nalorphine. (3) Huperzine A (Hup-A) is an alkaloid isolated from Huperzia serrata which was found to be a selective ChE inhibitor and could improve learning and retrieval processes. Preliminary clinical studies showed that Hup-A improve short- and long-term memory in patients of cerebral arteriosclerosis with memory impairment. (4) Ranamargarin is a new tetradecapeptide isolated from the skin of the Chinese frog Rana margaratae. This peptide may mainly act on NK-1 receptor.

Influence of Vinegar and Wine Processing on the Alkaloid Content and Composition of the Traditional Chinese Medicine Corydalis Rhizoma (Yanhusuo)

“…Wine processing elevated the content of tetrahydropalmatine (8) in the water decoction of JLZS, while vinegar processing increased its content in the water decoction of Corydalis Rhizoma. Tetrahydropalmatine (8) is one of the main alkaloids responsible for the pharmacological properties of Yanhusuo which include analgesic, anxiolytic and cardiovascular effects [33][34][35].…”

Effects of Tetrahydropalmatine (THP) on PTSD-induced Changes in Rat Neurobehavior

“…Corydalis yanhusuo is a traditional Chinese herbal medicine that has speculated analgesic properties (Hu, Xie, Zhang, Wang, & Chen, 1994), antiseizure activity (Chang & Lin, 2001;Lin, Wang, & Young, 2002); antihypertensive effects (Chan, Chiu, Chen, Wu, & Cheng, 1999;Lin, Chueh, Hsieh, & Chen, 1996); and sedative/hypnotic effects (Zhu, 1991). It appears that tetrahydropalmatine (THP) is the biologically active extract (Hong et al, 2006) and has been demonstrated to have antiseizure properties by reducing the seizure activity of kindled rats (Lin et al, 2002).…”

Utility of Nutraceutical Products Marketed for Cognitive and Memory Enhancement

“…The Chinese research indicates positive findings for the use of huperzine in the treatment of multi-infarct dementia (R. Zhang et al, 1991) and for patients with short-term and long-term memory loss caused by cerebral arteriosclerosis (Zhu, 1991). In addition, Huperzin A capsules were found to enhance the memory and learning performance of adolescent students (Sun, Xu, Pan, Guo, & Cao, 1999).…”