Since the efficiency in the transcription of the HIV genome contributes to the success of viral replication and infectivity, we investigated the downregulating effects of the spirobisindole alkaloids globospiramine (1), deoxyvobtusine (2), and vobtusine lactone (3) from the endemic Philippine medicinal plant, Voacanga globosa, during HIV gene transcription. Alkaloids 1–3 were explored for their inhibitory activity on TNF-α-induced viral replication in two latently HIV-infected cell lines, OM10.1 and J-Lat. The induction of HIV replication from OM10.1 and J-Lat cells elicited by TNF-α was blocked by globospiramine (1) within noncytotoxic concentrations. Furthermore, globospiramine (1) was found to target the NF-ĸB activation cascade in a dose-dependent manner when the transcriptional step at which inhibitory activity is exerted was examined in TNF-α-induced 293 human cells using transient reporter (luciferase) gene expression systems (HIV LTR-luc, ĸB-luc, and mutant ĸB-luc). Interrogation through molecular docking against the NF-ĸB p50/p65 heterodimer and target sites of the subunits comprising the IKK complex revealed high binding affinities of globospiramine (1) against the S281 pocket of the p65 subunit (BE = −9.2 kcal/mol) and the IKKα activation loop (BE = −9.1 kcal/mol). These findings suggest globospiramine (1) as a molecular inspiration to discover new alkaloid-based anti-HIV derivatives.
In this study we have examined the feasibility of a program based on the health belief model (HBM), for its effectiveness in improving lifestyle-related diseases in patients with schizophrenia (SZ) and bipolar disorder (BD), which are often complicated with physical conditions. In this model, we attempted to enable patients to identify a “threat” and to find “balance between benefits and disadvantages”. Subjects were carefully selected from among psychiatric patients by excluding any bias. Thus, the enrolled patients were 30 adult men and women with lifestyle-related diseases, or those with a body mass index (BMI) of over 24. Of these 30 subjects, 15 were randomly assigned to the intervention group and 10 the control group, since 5 subjects in the control voluntarily left from the study. Comparison of the intervention and control groups revealed significant improvement (p < 0.05) in HDL cholesterol in the intervention group. However, there were no significant changes in other variables. These findings support the usefulness and efficacy of HMB-based nutritional interventions for preventing lifestyle-related disorders among psychiatric patients. Further evaluation is needed with a larger sample size and a longer intervention period. This HMB-based intervention could be useful for the general population as well.
It has been previously documented that some antipsychotic medications could deteriorate the protective efficacy of vaccines. Likewise, we have initially observed that a significantly increased number of schizophrenic inpatients became ill irrespective of COVID-19 vaccination compared to healthy hospital workers. Thus, we examined the effects of anti-psychiatric medication on the COVID-19 incidence. A cohort study was conducted with 98 schizophrenia inpatients and 78 control hospital staff members, all of whom received the COVID-19 vaccine between July and September 2021. COVID-19 incidence and vaccine-related side effects were compared between these two groups. The schizophrenia group had a significantly higher incidence of COVID-19 (40.8%) compared to the control group (12.8%) ( P < 0.01). In particular, risperidone monotherapy was associated with a significant increase in COVID-19 incidence (65.6%), whereas aripiprazole use was linked to a significant reduction (0%) ( P < 0.01). No such difference in COVID-19 incidence was observed in patients using olanzapine. Risperidone administration appears to impair the immune responses and reduce vaccine effectiveness. Further studies with extended subjects and other vaccines are warranted to clarify the anti-vaccine effects associated with risperidone. IMPORTANCE: The vaccine efficacy in this study is significant because it sheds light on the potential impact of antipsychotic medications, particularly risperidone, on the effectiveness of COVID-19 vaccines in individuals with schizophrenia. The findings suggest that patients treated with risperidone have a significantly higher risk of incidence of COVID-19 despite vaccination, highlighting a possible interference with immune responses. In contrast, aripiprazole appears to have a protective effect, and the combined use of both medications results in an alarming increase in COVID-19 incidence. These results underscore the importance of further investigating the immunological mechanisms underlying these effects, especially through the dopamine receptor activity. Understanding these interactions could lead to more effective vaccination strategies and better healthcare management for patients with schizophrenia, ensuring better protection against COVID-19 and other infectious diseases.