Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against β-amyloid toxicity in transgenic caenorhabditis elegans
; Sangha, Jatinder S.
; Sun, Xiaoli
; Wally, Owen S. D.
; Zhang, Kaibin
; Ji, Xiuhong
; Wang, Zhimin
; Wang, Yanwen
; Zidichouski, Jeffrey
; Prithiviraj, Balakrishnan
NRC Institute for Nutrisciences and Health; National Research Council Canada
Liuwei Dihuang; LWDH; beta-amyloid
Liuwei Dihuang (LWDH), a classic Chinese medicinal formula, has been used to improve or restore declined functions related
to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. Here, we report on the
effect and possible mechanisms of LWDH mediated protection of b-amyloid (Ab) induced paralysis in Caenorhabditis elegans
using ethanol extract (LWDH-EE) and water extract (LWDH-WE). Chemical profiling and quantitative analysis revealed the
presence of different levels of bioactive components in these extracts. LWDH-WE was rich in polar components such as
monosaccharide dimers and trimers, whereas LWDH-EE was enriched in terms of phenolic compounds such as gallic acid
and paeonol. In vitro studies revealed higher DPPH radical scavenging activity for LWDH-EE as compared to that found for
LWDH-WE. Neither LWDH-EE nor LWDH-WE were effective in inhibiting aggregation of Ab in vitro. By contrast, LWDH-EE
effectively delayed Ab induced paralysis in the transgenic C. elegans (CL4176) model which expresses human Ab1–42.
Western blot revealed no treatment induced reduction in Ab accumulation in CL4176 although a significant reduction was
observed at an early stage with respect to b-amyloid deposition in C. elegans strain CL2006 which constitutively expresses
human Ab1–42. In addition, LWDH-EE reduced in vivo reactive oxygen species (ROS) in C. elegans (CL4176) that correlated
with increased survival of LWDH-EE treated N2 worms under juglone-induced oxidative stress. Analysis with GFP reporter
strain TJ375 revealed increased expression of hsp16.2::GFP after thermal stress whereas a minute induction was observed
for sod3::GFP. Quantitative gene expression analysis revealed that LWDH-EE repressed the expression of amy1 in CL4176
while up-regulating hsp16.2 induced by elevating temperature. Taken together, these results suggest that LWDH extracts,
particularly LWDH-EE, alleviated b-amyloid induced toxicity, in part, through up-regulation of heat shock protein,
antioxidant activity and reduced ROS in C. elegans.