Notopterol improves cognitive dysfunction and depression-like behavior via inhibiting STAT3/NF-ĸB pathway mediated
Zhengjun Zhou1, You Zhou2, Zhengxuan Huang1
1Department of Neurosurgery, The Affiliated Hospital of Southwest Medical University, Luzhou 646000, China; Southwest Medical University, Luzhou 646000, China.
Abstract:
Over the past few decades, clinicians and experts applied kinds of therapies for patients with malignant gliomas such as chemotherapy, radiation or surgical extraction. However, they used to ignore the real seriousness of neuropsychiatric symptoms after glioma, including cognitive dysfunction, anxiety, and depression, which severely impeded patients' recovery and prognosis. Interestingly, one of our previous clinical studies have found some behavioral symptoms in glioma patients were associated with systemic inflammation. Notopterol is one of the principal extracts of the traditional Chinese medicinal herb Notopterygium incisum having anti-tumour and anti-inflammatory activity. However, whether notopterol is beneficial to the treatment of glioma has not been reported. In this study, we found that notopterol inhibited growth and increased apoptosis of glioma via inhibiting STAT3 activity. In addition, notopterol treatment improved cognitive impairment and depression-like behavior in GL261 cell-based glioma mice via preventing the loss of dendritic spines and the reduction of synapse related proteins (PSD95 and Synapsin-1) in hippocampal neurons. Notopterol significantly reduced the levels of cytokines (iNOS, TNF-α, IL-6, and IL-β) and the activity of STAT3/NF-kB signalling pathway in peritumoural brain tissues and GL261 conditioned medium (GCM) treated microglial cell line (BV2 cells). These results demonstrated that notopterol not only exerted anti-glioma effects via inhibiting STAT3 activity, but improved neuropsychiatric symptoms via inhibiting tumour associated inflammation through modulation of the STAT3/NF-kB pathway in glioma-bearing mice.
Insights
Notopterol, a natural compound, combats glioma growth by inhibiting STAT3 activity. It also alleviates brain inflammation and improves cognitive and mood symptoms in glioma mice by modulating the STAT3/NF-kB pathway.
Area of Science:
- Neuro-oncology
- Pharmacology
- Neuroinflammation
Background:
- Malignant gliomas often present with severe neuropsychiatric symptoms, including cognitive dysfunction, anxiety, and depression, negatively impacting patient recovery.
- Systemic inflammation is increasingly recognized as a factor contributing to behavioral symptoms in glioma patients.
- Notopterol, an extract from Notopterygium incisum, possesses known anti-tumor and anti-inflammatory properties, but its efficacy in glioma treatment remains unexplored.
Purpose of the Study:
- To investigate the anti-glioma effects of notopterol.
- To evaluate notopterol's impact on glioma-associated neuropsychiatric symptoms.
- To elucidate the molecular mechanisms underlying notopterol's therapeutic actions in glioma.
Main Methods:
- Utilized a GL261 cell-based glioma mouse model.
- Assessed notopterol's effects on glioma cell growth, apoptosis, and STAT3 activity.
- Analyzed changes in dendritic spine density and synapse-related proteins (PSD95, Synapsin-1) in hippocampal neurons.
- Measured cytokine levels (iNOS, TNF-α, IL-6, IL-β) and STAT3/NF-kB pathway activity in brain tissue and microglial cells.
Main Results:
- Notopterol inhibited glioma cell growth and induced apoptosis by suppressing STAT3 activity.
- Notopterol treatment ameliorated cognitive impairment and depression-like behaviors in glioma-bearing mice.
- Notopterol prevented the loss of dendritic spines and reduced synapse-related proteins in hippocampal neurons.
- Notopterol significantly decreased pro-inflammatory cytokines and modulated the STAT3/NF-kB signaling pathway in peritumoral tissues and microglial cells.
Conclusions:
- Notopterol demonstrates dual therapeutic potential against malignant gliomas.
- It exerts direct anti-glioma effects through STAT3 inhibition.
- It improves neuropsychiatric symptoms by reducing tumor-associated inflammation via the STAT3/NF-kB pathway.
