Multi-omic analysis revealed the therapeutic mechanisms of Alpinia oxyphylla fructus water extract against bladder overactivity in spontaneously hypertensive rats.

OBJECTIVE: Alpinia oxyphylla fructus without impurities and shells is called "Yi-Zhi-Ren" (YZR) in Chinese, and traditionally used to alleviate enuresis. The aim of this study was to investigate the effects and underlying mechanisms of YZR in the treatment of overactive bladder (OAB) in spontaneously hypertensive rats (SHR), a vascular disorder-related OAB model. METHODS: A 3-week administration of YZR water extract (p.o.) was done, followed by urodynamics to measure bladder parameters. Changes in bladder structure were observed through H&E staining and Masson's staining. An integrated approach involving network pharmacology, transcriptomics and metabolomics was employed to elucidate the potential mechanisms of YZR, and the key proteins involved in the mechanisms were validated by Western blotting. Additionally, network pharmacology was used to predict the relationship between YZR's active components and validated proteins. RESULTS: YZR treatment significantly improved the bladder storage parameters, tightened the detrusor layer, reduced inflammatory infiltration, and decreased collagen proportion in the SHR bladder. These results indicated that YZR water extract can alleviate OAB symptoms and improve bladder structure. Integrated analysis suggested that YZR may affect extracellular matrix-receptor interaction and calcium signaling pathway. Western blotting results further confirmed that the reduction in key proteins, such as TGFß1, p-SMAD3, collagen III, Gq and PLCß1, involved in collagen synthesis and calcium signaling pathways after YZR treatment. Network pharmacology predicted that sitosterol, chrysin, and nootkatone were potential components responsible for YZR's therapeutic effect on OAB. CONCLUSION: YZR's mechanisms of action in treating OAB involved the TGFß1-SMAD3 signaling pathway-related collagen synthesis and Gq-PLCß1 calcium signaling pathway, which are associated with detrusor contraction frequency and strength, respectively.

Combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus ameliorates aluminum-induced Alzheimer's disease via reducing BACE1 expression.

Being the most common form of dementia, Alzheimer's disease (AD) has a series of modifiable risk factors, including metal ions represented by aluminium. Aluminium (Al) exhibits its neurotoxic effects, especially mainly by affecting amyloid-ß protein (Aß) aggregation and Tau hyperphosphorylation. As reported in our previous study, the combination of Alpinia Oxyphylla Fructus and Schisandra Chinensis Fructus (AS) had a neuroprotective effect. This study aimed to evaluate the anti-AD effect of AS and the mechanism by which AS reduces the neurotoxic effect of Al. Firstly, we used aluminium-maltol (Al(mal)3) to construct a mouse model of AD and performed oral administration of AS, followed by behavioral experiments, and we collected the mouse brain for immunohistochemistry analysis. In vivo results showed that AS significantly improved Al-induced cognitive decline in mice, and reduced the levels of Aß1-42 and P-Tau in the brain, which further proved the anti-AD effect of AS. Then, in order to explore the mechanism by which AS reduced Aß1-42, Al-induced PC12 cells were used for the in vitro experiments. Compared with other ratios, the ratio of Alpinia Oxyphylla Fructus: Schisandra Chinensis Fructus (AO:SC) = 1:2 could better improve the cell viability and reduce the Aß1-42 level. According to western blot and quantitative real-time polymerase chain reaction (qPCR) results, AS ameliorated the pathological process by downregulating the expression of ß-secretase (BACE1), rather than by reducing the expression of amyloid precursor protein (APP) or Tau. These results suggest that AS ameliorated Al-induced AD by affecting the expression of BACE1 and reducing the level of Aß1-42, thereby exerting a neuroprotective effect. Combined with previous studies, this study shows that AS has potential for further research and development in AD treatment.

Effects of Alpinia oxyphylla fructus on learning-memory and expression of related signal proteins in hippocampus of brain aging mice / 中华行为医学与脑科学杂志

Objective To investigate the effects and mechanisms of Alpinia oxyphylla fructus (AOF) on learning and memory in D-galactose induced brain aging mice. Methods The brain aging model was induced by s. c D-galactose. Learning-memory ability was tested by passive avoidance test and Morris water maze test, and the expression of synapsin ( Syn), mitogen-activated protein kinase (MAPK) and protein kinase ( PKC ) in hippocampus were examined by Western blot. Results ① Passive avoidance test:the latency in brain aging group( ( 119.80 ±101.80)s) significantly decreased,and the number of errors (4.4 ± 1.3 ) significantly increased compared with the control group( latency: (279.30 ± 31.64) s; number of errors: ( 1. 8 ±0.9), P＜0. 01 ) ). The latency in low dose, middle dose and high dose AOF group( ( 170.25 ± 68.31 ) s, (226.31 ± 73.25 ) s, (263.20 ± 70.55 ) s) significantly increased, and the number of errors in middle dose and high dose AOF group ( ( 2.8 ± 1.2 ), ( 2.3 ±0. 9 ) ) significantly decreased compared with brain aging group (P ＜ 0. 05, P ＜ 0. 0 1 ). ② Morris water maze test:the escape latency in brain aging group was significantly longer, and the time spent in the original quadrant that previously contained the platform was significantly shorter compared with the control group (P＜0. 01 ). The escape latency in 3 AOF groups was significantly shorter (P＜ 0. 05 ), and the time spent in the original quadrant that previously contained the platform in middle and high dose AOF groups was significantly longer compared with brain aging group (P＜0. 05, P＜0. 01 ). ③ Western blot test:the expression of Syn,MAPK and PKC in hippocampus of brain aging group was significantly weakened than that of the control group. In contrast, the expression of Syn,MAPK, PKC were significantly enhanced in all AOF groups. Conclusion AOF could significantly improve the ability of learning and memory in brain aging mice. Its effects might be related to the increase of the expression of Syn, MAPK and PKC in hippocampus.