Combination of Vinpocetine and Dexamethasone Alleviates Cognitive Impairment in Nasopharyngeal Carcinoma Patients following Radiation Injury

Abstract

<b><i>Background:</i></b> Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium. The most common treatments for NPC rT1–4 are radiotherapy and surgery. The pathogenesis of radiation-induced cognitive impairment is complex and includes oxidative stress, mitochondrial dysfunction, neuro-inflammation, and even apoptosis and cell death. Principally, toll-like receptors (TLRs) could regulate the inflammatory/anti-inflammatory balance in patients with radiation-induced brain injury. Vinpocetine has an anti-inflammatory effect as shown in both animal and in vitro studies. Also, dexamethasone is a widely used anti-inflammatory drug. Thus, it is important to test whether addition of vinpocetine could improve the anti-inflammatory properties of dexamethasone for the treatment of NPC patients with radiation-induced brain injuries. <b><i>Methods:</i></b> A total of 60 NPC patients with radiation-related brain injury were recruited for this study. All subjects were randomly and blindly assigned to the following groups: the dexamethasone group (D group, <i>n</i> = 30) and the vinpocetine and dexamethasone group (VD group, <i>n</i> = 30). Both medicine treatments were uninterrupted for 14 days of administration. <b><i>Results:</i></b> Combined administration of vinpocetine and dexamethasone lowered the expression levels of serum inflammatory cytokines, including TLR2, TLR4, interleukin (IL)-20, IL-8, tumor necrosis factor-α, interferon-γ, monocyte chemoattractant protein 2, and interferon-induced protein 20, when compared to dexamethasone monotherapy. Notably, combination therapy increased antioxidants (superoxide dismutase, glutathione, glutathione peroxidase, and glutathione reductase) and decreased oxidants (thiobarbituric acid reactive substances). Furthermore, combination therapy significantly increased the Mini Mental State Examination score, when compared to dexamethasone monotherapy. <b><i>Conclusion:</i></b> Administration of a combination of vinpocetine and dexamethasone may enhance the anti-inflammatory and anti-oxidative effects when compared to dexamethasone monotherapy, which leads to alleviated cognitive impairment in NPC patients with radiation injury.

Attenuated effects of topical vinpocetine in an imiquimod-induced mouse model of psoriasis

“…105 In light of these investigations, the co-administration of VNP and steroidal dexamethasone has been observed to ameliorate the synthesis of TNF-α, IL-8, IL-20, and IFN-γ, and to modulate the activity of TLR2 and TLR4, thus offering greater immunosuppressive, anti-inflammatory, and anti-oxidative benefits than corticoste-roids alone, and ameliorating mental deterioration in individuals with radiation-damaged nasopharyngeal cancer. 106 …”

Synthesis and pharmacological activity of vinpocetine derivatives

“…This reduction in cytokine expression alleviated cognitive deficits in nasopharyngeal carcinoma patients after radiotherapy. 36 Hu demonstrated that the combination of Vinpocetine and coenzyme CoQ10 ameliorated neuronal damage, promoted mitochondrial phagocytosis, and alleviated cognitive deficits in ischemia-reperfusion (IR) mice. 37 Park 38 found that both vincristine and ferulic acid improved memory function by reducing amyloid β-protein tangles in the hippocampus by enhancing insulin action induced in Alzheimer's disease in type 2 diabetic rats.…”

Treatment of Radiation‐Induced Brain Necrosis

“…Dexamethasone usually assists in quickly relieving the clinical symptoms caused by focal necrosis. 500 mg of dexamethasone was dissolved in 250 ml of 0.9% saline solution, and the dose was gradually reduced during the course of use until the end of 14 days of treatment [105]. Some cases after long-term application of corticosteroids showed a partial remission in imaging, but this remission remained temporary in most of the cases, and the patient eventually develops hormonal dependence.…”