Liuwei Dihuang (LWDH), a Traditional Chinese Medicinal Formula, Protects against beta-Amyloid Toxicity in Transgenic Caenorhabditis elegans
Date
2012-08Author
Sangha, Jatinder S.
Sun, Xiaoli
Wally, Owen S. D.
Zhang, Kaibin
Ji, Xiuhong
Wang, Zhimin
Wang, Yanwen
Zidichouski, Jeffrey
Prithiviraj, Balakrishnan
Zhang, Junzeng
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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 beta-amyloid (A beta) 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 A beta induced paralysis in the
transgenic C. elegans (CL4176) model which expresses human A beta 1-42. 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 beta-amyloid
deposition in C. elegans strain CL2006 which constitutively expresses human A beta 1-42.
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 beta-amyloid induced toxicity, in part, through
up-regulation of heat shock protein, antioxidant activity and reduced ROS in C.
elegans.
Citation
Sangha, Jatinder S., Xiaoli Sun, Owen S. D. Wally, Kaibin Zhang, et al. 2012. "Liuwei Dihuang (LWDH), a Traditional Chinese Medicinal Formula, Protects against beta-Amyloid Toxicity in Transgenic Caenorhabditis elegans." Plos One 7(8): 43990-e43990. doi:10.1371/journal.pone.0043990
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