Background: Tenuigenin (TEN), a major active component of the Chinese herb Polygala tenuifolia root, has been used to improve memory and cognitive function in Traditional Chinese Medicine for centuries.
Purpose: The present study was designed to explore the possible neuroprotective effect of TEN on the streptozotocin (STZ)-induced rat model of sporadic Alzheimer's disease (sAD).
Methods: STZ was injected twice intracerebroventrically (3 mg/kg, ICV) on alternate days (day 1 and day 3) in Rats. Daily treatment with TEN (2, 4, and 8 mg/kg) starting from the first dose of STZ for 28 days. Memory-related behaviors were evaluated using the Morris water maze test. Hyperphosphorylation of tau proteins in hippocampus were measured by western blot assay. Superoxide dismutase activities, malondialdehyde, glutathione peroxidase and 4-hydroxy-2-nonenal adducts contents were also measured in the hippocampus.
Results: Treatment with TEN significantly improved STZ-induced cognitive damage, markedly reduced changes in malondialdehyde and 4-hydroxy-2-nonenal adducts, and significantly inhibited STZ-induced reduction in superoxide dismutase and glutathione peroxidase activities in the hippocampus. In addition, TEN decreased hyperphosphorylation of tau resulting from intracerebroventricular STZ (ICV-STZ) injection, and Nissl staining results showed that TEN has protective effects on hippocampal neurons.
Conclusion: These results provide experimental evidence demonstrating preventive effect of TEN on cognitive dysfunction, oxidative stress, and hyperphosphorylation of tau in ICV-STZ rats. This study indicates that TEN may have beneficial effects in the treatment of neurodegenerative disorders such as AD.
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http://dx.doi.org/10.4103/bc.bc_2_17 | DOI Listing |
Brain Commun
December 2024
Division of Psychiatry, University College London, London W1T 7NF, UK.
Hyperphosphorylated tau accumulation is seen in the noradrenergic locus coeruleus from the earliest stages of Alzheimer's disease onwards and has been associated with symptoms of agitation. It is hypothesized that compensatory locus coeruleus-noradrenaline system overactivity and impaired emotion regulation could underlie agitation propensity, but to our knowledge this has not previously been investigated. A better understanding of the neurobiological underpinnings of agitation would help the development of targeted prevention and treatment strategies.
View Article and Find Full Text PDFEur J Med Chem
January 2025
Medical Research Center, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, Shandong, China. Electronic address:
The development of potent glycogen synthase kinase-3β (GSK-3β) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer's disease (AD). This study prepared various new pyrrolo[2,3-b]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-b]pyridine derivatives had strong GSK-3β inhibitory activities, particularly compounds 41, 46 and 54, with the half maximal inhibitory concentrations (IC) of 0.
View Article and Find Full Text PDFTransl Psychiatry
January 2025
Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, and Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
Long-term potentiation (LTP) and long-term depression (LTD) are widely used to study synaptic plasticity. However, whether proteins regulating LTP and LTD are altered in cognitive disorders and contribute to disease onset remains to be determined. Herein, we induced LTP and LTD in the hippocampal CA3-CA1 Schaffer collateral pathway, respectively, and then performed proteomic analysis of the CA1 region.
View Article and Find Full Text PDFJ Alzheimers Dis
January 2025
Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA.
RSC Med Chem
December 2024
Pharmaceutical Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology and Sciences Pilani Pilani Campus, Vidya Vihar Pilani 333031 RJ India +91 1596 244183 +91 1596 255 506.
Alzheimer's disease (AD) is a complex, incurable neurological condition characterized by cognitive decline, cholinergic neuron reduction, and neuronal loss. Its exact pathology remains uncertain, but multiple treatment hypotheses have emerged. The current treatments, single or combined, alleviate only symptoms and struggle to manage AD due to its multifaceted pathology.
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