Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 16, Issue -, Pages 931-950Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S357061
Keywords
Huanglian Jiedu decoction; HLJDD; Alzheimer's disease; AD; sphingolipid metabolism; HPLC-QTOF-MS; HPLC-QTRAP-MS
Categories
Funding
- National Natural Science Foundation of China [81573635, 81873027]
- Qing-Lan Project of Jiangsu Province
- Open Project Program of Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica [JKLPSE201820]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Project of the Innovation Research Team of Nanjing University of Chinese Medicine
- Six Talent Project in Jiangsu Province
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The study investigates the therapeutic effect of Huanglian Jiedu decoction (HLJDD) on Alzheimer's disease (AD) in relation to sphingolipid metabolism. The results show that HLJDD can potentially treat AD by correcting the abnormal sphingolipid metabolism in AD mice and BV2 cells.
Background: Abnormal sphingolipid metabolism is closely related to the occurrence and development of Alzheimer's disease (AD). With heat-clearing and detoxifying effects, Huanglian Jiedu decoction (HLJDD) has been used to treat dementia and improve learning and memory impairments. Purpose: To study the therapeutic effect of HLJDD on AD as it relates to sphingolipid metabolism. Methods: The level of sphingolipids in the brains of APP/PS1 mice and in the supernatant of 0-amyloid (A beta)(25-35)-induced BV2 microglia was detected by HPLC-QTOF-MS and HPLC-QTRAP-MS techniques, respectively. The co-expression of ionized calcium-binding adapter molecule 1 (Iba1) and A beta as well as four enzymes related to sphingolipid metabolism, including serine palmitoyltransferase 2 (SPTLC2), cer synthase 2 (CERS2), sphingomyelin phosphodiesterase 1 (SMPD1), and sphingomyelin synthase 1 (SGMS1), in the brains of APP/PS1 mice were evaluated by immunofluorescence double labelling. In addition, realtime quantitative reverse transcription-polymerase chain reaction was conducted to determine the mRNA expression of SPTLC2, CERS2, SMPD1, SGMS1, galactosylceramidase (GALC), and sphingosine kinase 2 (SPHK2) in A beta(25-35)-stimulated BV2 microglia. Results: Abnormal sphingolipid metabolism was observed both in APP/PS1 mouse brain tissues and A beta(25-35)-stimulated BV2 cells. The levels of sphingosine, sphinganine, sphingosine-1-phosphate, sphinganine-1-phosphate and sphingomyelin were significantly reduced, while the levels of ceramide-1-phosphate, ceramide, lactosylceramide and hexosylceramide significantly increased in A beta(25-35)-stimulated BV2 cells. In AD mice, more microglia were clustered in the A0-positive region. The decreased level of SGMS1 and increased levels of CERS2, SPTLC and SMPD1 were also found. In addition, the expressions of SPTLC2, CERS2, and SMPD1 in A beta(25-35)-stimulated BV2 cells were increased significantly, while the expressions of GALC, SPHK2, and SGMS1 were decreased. These changes all showed a significant correction after HLJDD treatment. Conclusion: HLJDD is a good candidate for treating AD. This study provides a novel perspective on the potential roles of the sphingolipid metabolism in AD.
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