Triple herbal extract DA-9805 exerts a neuroprotective effect via amelioration of mitochondrial damage in experimental models of Parkinson's disease.

Abstract

Moutan cortex, Angelica Dahurica root, and Bupleurum root are traditional herbal medicines used in Asian countries to treat various diseases caused by oxidative stress or inflammation. Parkinson's disease (PD) has been associated with mitochondrial dysfunction, but no effective treatment for mitochondrial dysfunction has yet been identified. In this study we investigated the neuroprotective effects of the triple herbal extract DA-9805 in experimental models of PD. DA-9805 was prepared by extracting three dried plant materials (Moutan cortex, Angelica Dahurica root, and Bupleurum root in a 1:1:1 mixture) with 90% ethanol on a stirring plate for 24 h at room temperature and fingerprinted using high-performance liquid chromatography. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its active metabolite 1-methyl-4-phenylpyridinium (MPP+), which both exert neurotoxic effects on dopaminergic neurons by inhibiting mitochondrial oxidative phosphorylation (OXPHOS) complex I, were used to make experimental models of PD. In MPP+-treated SH-SY5Y cells, DA-9805 ameliorated the suppression of tyrosine hydroxylase expression and mitochondrial damage on OXPHOS complex 1 activity, mitochondrial membrane potential, reactive oxygen species (ROS) generation, and oxygen consumption rate. In the MPTP-induced subacute PD model mice, oral administration of DA-9805 recovered dopamine content as well as bradykinesia, as determined by the rotarod test. DA-9805 protected against neuronal damage in the substantia nigra pars compacta (SNpc) and striatum. In both in vitro and in vivo models of PD, DA-9805 normalized the phosphorylation of AKT at S473 and T308 on the insulin signaling pathway and the expression of mitochondria-related genes. These results demonstrate that the triple herbal extract DA-9805 showed neuroprotective effects via alleviating mitochondria damage in experimental models of PD. We propose that DA-9805 may be a suitable candidate for disease-modifying therapeutics for PD.

• Authors: Jin Seok Jeong, Ying Piao, Sora Kang, Minuk Son, Young Cheol Kang, Xiao Fei Du, Jayoung Ryu, Young Woong Cho, Hai-Hua Jiang, Myung Sook Oh, Seon-Pyo Hong, Young J Oh, Youngmi Kim Pak
• Journal: Scientific reports (Sci Rep) Vol. 8 Issue 1 Pg. 15953 (10 29 2018) ISSN: 2045-2322 [Electronic] England
• PMID: 30374025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Drugs, Chinese Herbal
• Neuroprotective Agents
• Plant Extracts
• Reactive Oxygen Species
• moutan cortex
• Proto-Oncogene Proteins c-akt
• Dopamine

Topics

• Angelica (chemistry, metabolism)
• Animals
• Bupleurum (chemistry, metabolism)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Disease Models, Animal
• Dopamine (metabolism)
• Dopaminergic Neurons (drug effects, metabolism)
• Drugs, Chinese Herbal (chemistry, metabolism)
• Humans
• Male
• Membrane Potential, Mitochondrial (drug effects)
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Paeonia (chemistry, metabolism)
• Parkinson Disease (drug therapy, pathology)
• Plant Extracts (chemistry, pharmacology, therapeutic use)
• Proto-Oncogene Proteins c-akt (metabolism)
• Reactive Oxygen Species (metabolism)