The stemwood of dracaena cochinchinensis, a Thai herb, exerts neuroprotection in cultured neuronal cells : potential development of herbal treatment for Alzheimer's disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by the deposition of amyloid plaques in the brain. Neuroinflammation plays a pivotal role in the pathogenesis of AD, contributing to disease development and progression. Targeting amyloid beta (Aβ) aggregation, Aβ-induced neuronal toxicity, and neuroinflammatory are crucial therapeutic approaches for AD treatment. Regulation of neuronal differentiation is an essential therapeutic strategy for enhancing cochinchinensis stemwood (DCS), a Thai medicinal plant named Chan-Daeng, has been traditionally used for its antipyretic, and anti-inflammatory effects. However, the potential of DCS in inhibiting Aβ aggregation, promoting neuroprotection, and modulating neuroinflammation remains unexplored. This study revealed that DCS effectively disrupted Aβ aggregation, protected Aβ fibril-induced cell toxicity, stimulated neuronal differentiation, and suppressed LPS-induced inflammation. In addition, the combination of DCS with a low dose of nerve growth factor (NGF) synergistically promoted neurite outgrowth and neuronal differentiation, as indicated by increased neurofilament expressions in cultured PC12 cells. Furthermore, DCS exhibited anti-inflammatory properties by reducing the mRNA expression of pro-inflammatory mediators, including IL-1β, TNF-α, and iNOS, and by increasing mRNA expression of anti-inflammatory biomarker Arg1 in LPS-activated BV2 microglia and RAW264.7 macrophages. DCS could modulate excessive microglial phagocytosis of beads and Aβ fibrils. The anti-inflammatory effects of DCS were associated with the reduction of p38, JNK, and Akt activities in the LPS-activated BV2 microglial cells. These findings indicate that DCS could be a promising natural product for complementary and intervention therapy in AD, targeting Aβ fibril formation, promoting neuron regeneration, and suppressing neuroinflammation. Besides, the synergistic interactions between DCS and Ardisia elliptica fruit (AEF), another Thai herb used for treating diarrhea with fever, at a specific ratio of 1:9 w/w, showed optimized pharmacological activities in neuroprotection. The combination of DCS and AEF extract synergistically enhanced neuronal differentiation, inhibited Aβ aggregation, and prevented Aβ fibril-induced cell death. In addition, the synergy between DCS and AEF exerted anti-inflammation by attenuating pro-inflammatory markers and inducing morphological changes in activated microglia. Embelin and pterostilbene, the major compounds in the herbal mixture, partially accounted for the neuroprotective activities. These results suggest the potential application of combining the herbal extract of DCS and AEF as a neuroprotective agent, as well as a complementary treatment for AD.

Date of Award	2024
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Karl Wah Keung TSIM (Supervisor)