Inflammatory factors play an important role in the pathogenesis of Alzheimer’s disease (AD). Byu d Mar 25 (BM25) has been suggested to have protective effects in the central nervous system. However, the effect of BM25 on AD has not been determined. This study aims to investigate the neuroprotective effect of BM25 in AD. A total of 40 AD model mice were randomly assigned to the following five groups (n = 8 per group): the AD + NS group, the AD + donepezil group, and three AD + BM25 groups treated with either 58.39 mg/kg (AD + BM25-L), 116.77 mg/kg (AD + BM25-M), or 233.54 mg/kg BM25 (AD + BM25-H). The Morris water maze test was performed to assess alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuronal damage. The expression of IL-1β and TNF-α was evaluated by ELISA. The protein expression of P-P38, P38, P-IκBα, caspase 1, COX2, and iNOS was determined by western blotting. The expression of Aβ, p-Tau, and CD11b was measured by immunohistochemistry. The mRNA expression levels of IL-1β, TNF-α, COX2, and iNOS were measured by qRT-PCR. Spatial memory significantly improved in the AD + BM25-M and AD + BM25-H groups compared with the AD + NS group ( p < 0.05 ). The expression of Aβ and p-Tau significantly decreased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). The neuron density and hierarchy and number of pyramidal neurons significantly increased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). In addition, the expression levels of CD11b, IL-1β, TNF-α, COX2, iNOS, caspase 1, p-IκBα, and p-P38 significantly decreased in the AD + BM25-M and AD + BM25-H groups ( p < 0.05 ). In conclusion, our findings suggest that BM25 may exert anti-inflammatory and neuroprotective effects in AD model mice by suppressing the activity of microglia and inhibiting the phosphorylation of IκBα and p38 MAPK.

Background: The unique geographical environment at high altitudes may cause a series of diseases, such as acute altitude reaction, cerebral edema, and pulmonary edema. Gymnadenia conopsea (L.) R. Br. has been reported to have an effect on high-altitude hypoxia. However, the molecular mechanism, especially the expression of long noncoding RNAs (lncRNAs), is not yet clear. Methods: The expression profiles of lncRNAs in high-altitude hypoxia-induced brain injury mice treated with Gymnadenia conopsea (L.) R. Br. by using a microarray method. Results: A total of 226 differentially expressed lncRNAs, 126 significantly dysregulated mRNAs and 23 differentially expressed circRNAs were detected (>2.0-fold, p<0.05). The expression of selected lncRNAs, mRNAs and circRNAs was validated by qRT-PCR. KEGG analysis showed that the mRNAs coexpressed with lncRNAs were involved in inflammation and hypoxia pathways, including the HIF-1, PI3K-Akt, and NF-kappa B signaling pathways. The lncRNA-TF network analysis results indicated that the lncRNAs were regulated mostly by HMGA2, SRY, GATA4, SOX5, and ZBTB16. Conclusion: This study is the first to report the expression profiles of lncRNAs, mRNAs and circRNAs in mice with high-altitude hypoxia-induced brain injury treated with Gymnadenia conopsea (L.) R. Br. and may improve the understanding of the molecular mechanism of Gymnadenia conopsea (L.) R. Br. in treating high altitude hypoxia-induced brain injury.