Ginkgolides and Huperzine A for complementary treatment of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by gradual deterioration of cognitive function, memory, and inability to perform daily, social, or occupational activities. Its etiology is associated with the accumulation of ß-amyloid peptides, phosphorylated tau protein, and neuroinflammatory and oxidative processes in the brain. Currently, there is no successful pharmacological treatment for AD. The few approved drugs are mainly aimed at treating the symptoms; however, due to the increasing discovery of etiopathological factors, there are great efforts to find new multifunctional molecules to slow down the course of this neurodegenerative disease. The commercial Ginkgo biloba formulation EGb 761® and Huperzine A, an alkaloid present in the plant Huperzia serrata, have shown in clinical trials to possess cholinergic and neuroprotective activities, including improvement in cognition, activities of daily living, and neuropsychiatric symptoms in AD patients. The purpose of this review is to expose the positive results of intervention with EGb 761® and Huperzine in patients with mild to moderate AD in the last 10 years, highlighting the pharmacological functions that justify their use in AD therapy.

Alleviation of spinal cord injury by Ginkgolide B via the inhibition of STAT1 expression.

Ginkgolide B has been known to inhibit cell apoptosis by modulating multiple cytokines and plays an important role in neuroprotection. Signal transducer and activator of transcription 1 (STAT1) has been studied in a spinal cord injury (SCI) model. However, the role of Ginkgolide B in SCI treatment remains unclear. This study investigated the potential mechanism of Ginkgolide B using an SCI rat model. SD rats were used to generate an SCI model followed by Ginkgolide B injection (4 mg/kg) for 14 days. Spinal cord tissue samples were examined using hematoxylin and eosin (H&E) staining. The expression of STAT1 was determined by western blot. Using a dyskinesia scale, intervention with Ginkgolide B significantly decreased the severity of SCI. H&E staining revealed less nuclear condensation and cell necrosis in SCI rats after treatment with Ginkgolide B. STAT1 expression was significantly increased in SCI model rats, but was lower after Ginkgolide B treatment. Therefore, Ginkgolide B can effectively inhibit STAT1 expression and alleviate SCI.

Role of platelet-activating factor in the pathogenesis of 5-fluorouracil-induced intestinal mucositis in mice.

PURPOSE: Gastrointestinal mucositis is a common side effect of cancer chemotherapy. Platelet-activating factor (PAF) is produced during gut inflammation. There is no evidence that PAF participates in antineoplastic-induced intestinal mucositis. This study evaluated the role of PAF in 5-fluorouracil (5-FU)-induced intestinal mucositis using a pharmacological approach and PAF receptor knockout mice (PAFR(-/-)). METHODS: Wild-type mice or PAFR(-/-) mice were treated with 5-FU (450 mg/kg, i.p.). Other mice were treated with saline or BN52021 (20 mg/kg, s.c.), an antagonist of the PAF receptor, once daily followed by 5-FU administration. After the third day of treatment, animals were sacrificed and tissue samples from the duodenum were removed for morphologic evaluation. In addition, myeloperoxidase activity and the cytokine concentration were measured. RESULTS: 5-FU treatment decreased the duodenal villus height/crypt depth ratio, increased MPO activity, and increased the concentration of TNF-α, IL-1ß and KC in comparison with saline-treated animals. In PAFR(-/-) mice and PAFR antagonist-treated mice, 5-FU-dependent intestinal damage was reduced and a decrease in duodenal villus height/crypt depth ratio was attenuated. However, the 5-FU-dependent increase in duodenum MPO activity was not affected. Without PAFR activation, 5-FU treatment did not increase the TNF-α, IL-1ß and KC concentration. CONCLUSIONS: In conclusion, our study establishes the role of PAFR activation in 5-FU-induced intestinal mucositis. This study implicates treatment with PAFR antagonists as novel therapeutic strategy for this condition.