Alpinia oxyphylla Miq. (AOM) is a medicinal herb for improving cognitive functions in traditional Chinese medicine for poststroke treatment, but its efficacies and underlying mechanisms remain unknown. In the present study, we tested the hypothesis that AOM could induce adult hippocampal neurogenesis and improve poststroke cognitive impairment via inducing brain-derived neurotrophic factor (BDNF) signaling pathway. In order to test the hypothesis, we performed both in vivo rat experiments using transient middle cerebral artery occlusion (MCAO) model and in vitro neural stem cell (NSC) experiments using oxygen–glucose deprivation plus reoxygenation. First, AOM treatment significantly up-regulated the expression of BDNF, tropomycin receptor kinase B (TrkB), and phosphorylated AKT (p-AKT) in the hippocampus, enhanced adult hippocampal neurogenesis, and improved the spatial learning/memory and cognitive functions in the post-MCAO ischemic rats in vivo. Next, in vitro studies confirmed p-coumaric acid (P-CA) to be the most effective compound identified from AOM extract with the properties of activating BDNF/TrkB/AKT signaling pathway and promoting NSC proliferation. Cotreatment of BDNF/TrkB-specific inhibitor ANA12 abolished the effects of P-CA on inducing BDNF/TrkB/AKT activation and the NSC proliferation. Finally, animal experiments showed that P-CA treatment enhanced the neuronal proliferation and differentiation in the hippocampus, improved spatial learning and memory functions, and reduced anxiety in the transient MCAO ischemic rats. In conclusion, P-CA is a representative compound from AOM for its bioactivities of activating BDNF/TrkB/AKT signaling pathway, promoting hippocampal neurogenesis, improving cognitive functions, and reducing anxiety in post–ischemic stroke rats.
BackgroundCellular immune responses including lymphocyte functions and immune effector cells are critical for the control of coronavirus infection. Chinese herbal medicine (CHM) potentially has a therapeutic effect for treatment of coronavirus disease 2019 (COVID-19). Nevertheless, there are limited clinical practice suggestions on immunogenicity of the CHM against SARS-CoV-2. To assess the effect of oral CHM on immunogenicity and whether oral CHM improves the clinical parameters through the immunity profile during COVID-19, we performed the present study.MethodsFor this systematic review and meta-analysis, 11 databases were searched for relevant studies assessing oral CHM for COVID-19 on November 20, 2020 (updated March 9, 2021). Primary outcomes mainly included immunity profiles. Secondary outcomes included all-cause mortality; the remission time of fever, cough, chest tightness, and fatigue. The random effect was used to estimate the heterogeneity of the studies. Summary relative risks, weight mean difference and standardized mean difference were measured with 95% confidence intervals. Modified Jadad scale and Newcastle-Ottawa Scale were used to assess the risk of bias of randomized controlled trials (RCTs) and observational studies, respectively. The certainty of evidence was evaluated using the GRADE approach.ResultsWe analyzed findings from 3,145 patients in 30 eligible studies. Compared with routine treatment, oral CHM, as an adjuvant medicine, improved lymphocyte counts, CD4+, and CD4+/CD8+ ratio with low quality of evidence; improved CD3+ with moderate quality of evidence; and reduced TNF-α with low certainty of evidence. Besides, oral CHM, as an adjuvant medicine reduced the time to clinical symptoms remission with a lower risk of all-cause mortality, compared with routine treatment alone.ConclusionCHM may be recommended as an adjuvant immunotherapy for disease modification and symptom relief in COVID-19 treatment. However, large RCTs objectively assessing the efficacy of CHM on immune responses in COVID-19 are needed to confirm our findings.
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