Use of Network Pharmacology and Experiment Validation to Uncover the Mechanism of Jianshen Lishui Prescription in the Treatment of Intracerebral Hemorrhage.

BACKGROUND: As a Chinese medicinal formula, the Jianshen Lishui prescription has been clinically proven to be effective in treating intracerebral hemorrhage (ICH). Yet, the mechanisms involved are unknown. METHODS: (1) Network pharmacology analysis: It involved the screening of active components in the Jianshen Lishui prescription, identification of potential targets for these components, and the screening of ICH-related targets. Common targets for both disease and drug were identified. Protein- protein interaction networks were constructed, followed by further screening of core targets. Gene Ontology(GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes( KEGG) pathway enrichment analysis were performed on these core targets. Finally, molecular docking verification was carried out using the active components and core targets. (2) Experimental verification: It was conducted using a rat model of intracerebral hemorrhage. This involved observing neurological deficit scores in the rats and measuring cerebral water content. The effects of Jianshen Lishui prescription on the neurological function, cerebral water content, and brain tissue core targets were observed through HE staining, Western blot and qPCR. RESULTS: (1) In this study, 29 common targets were obtained by intersecting 256 potential drug targets and 642 genes associated with ICH. 9 core targets were obtained by employing the protein- protein interaction (PPI) construction system to screen more specific targets. In addition, the findings revealed that the molecular mechanism of Jianshen Lishui prescription in treating ICH was mainly related to cancer signaling pathways and signal transduction pathways, based on the results of GO and KEGG enrichment analysis. Molecular docking results showed that the active constituent of Jianshen Lishui prescription mannitol has the highest binding activity with KRAS, luteolin, and Poria sterol with AR, INS1 and KRAS, cerebrosterol with GNB1, INS and ESR1, and sitosterol with AR, INS1 and KRAS. (2) Animal experiments verified that Jianshen Lishui prescription significantly alleviated encephaledema and improved nerve functions of the rat model of ICH. And INS1 expression levels were upregulated and the expression levels of AR, KRAS, PTGS2, and ESR1 were down-regulated by the prescription. CONCLUSION: Jianshen Lishui prescription protects the nerve function of ICH patients by inhibiting inflammation and reducing cerebral edema. This study provides more supportive evidences for the clinical use of traditional Chinese prescriptions in ICH treatment.

Moxibustion modulates working memory in patients with amnestic mild cognitive impairment: a functional magnetic resonance imaging study.

OBJECTIVE: To investigate the correlation between changes in brain activity associated with working memory and assessment scales of memory scores in amnestic mild cognitive impairment (aMCI) before and after moxibustion therapy. METHODS: aMCI patients were randomized into the moxibustion treatment (MT) group and the placebo moxibustion (PM) group. Each group received either moxibustion therapy or a placebo moxibustion for eight weeks. Neuropsychological performance and functional brain responses to a working memory task were assessed at baseline and at the end of treatment. Memory function was evaluated individually by the Rivermead behavioral memory test (RBMT), and working memory was assessed by the N-back task. RESULTS: Compared with the PM group, RBMT score changes were significant ( < 0.05). In the MT group, the accuracy of the N-back texts increased compared with those before the intervention. After moxibustion intervention, the right insula, postcentral gyrus, precentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, calcarine sulcus, posterior cingulate gyrus, middle frontal gyrus and anterior frontal gyrus were significantly activated (= 0.01, Cluster-level Family-Wise Error = 0.05). Pearson correlation analysis showed that the insula, lingual gyrus and posterior cingulate gyrus were associated with changes in N-back score. Spearman correlation analysis showed that the postcentral gyrus, superior temporal gyrus, thalamus, lingual gyrus, and posterior cingulate gyrus were correlated with RBMT score changes. CONCLUSION: Moxibustion treatment improved memory in aMCI patients and was associated with the activation of the brain region of the insula, lingual gyrus, posterior cingulate gyrus, postcentral gyrus, superior temporal gyrus, and thalamus, which may be an important mechanism by which moxibustion improves the memory function.

Fetal exposure of Aristolochic Acid I undermines ovarian reserve by disturbing primordial folliculogenesis.

The primordial follicle pool established in early life determines the ovarian reserve in the female reproductive lifespan. Premature exhaustion of primordial follicles contributes to primary ovarian insufficiency (POI), that is dependent by the initial size of the primordial follicle pool and by the rate of its activation and depletion. AAI, a powerful nephrotoxin with carcinogenic potential, is present in the Aristolochiaceae species, which can release AAI into soil as a persistent pollutant. In order to assess the potential risk of Aristolochic Acid I (AAI) exposure on mammalian oogenesis, we uncovered its adverse effect on primordial folliculogenesis in the neonatal mouse ovary and its effect on female fertility in adulthood. Pregnant mice were orally administrated with doses of AAI without hepatic or renal toxicity during late-gestation. Ovaries from offspring of administered female displayed gross aberrations during primordial folliculogenesis. Also, unenclosed oocytes in germ-cell cysts showed increased DNA damage. Furthermore, several key factors, including NANOS3, SOX9, KLF4, that govern early gonad's differentiation were abnormally expressed in the exposed ovary, while the follicle formation was partially restored by knockdown of Nanos3 or sox9. In adulthood, these aberrations evolved into a significant reduction in offspring number and impaired ovarian reserve. Together, our results show that AAI influences primordial folliculogenesis and, importantly, affected female fertility. This study shows that administration of drugs herbs or consumption of vegetables that contain AAs during pregnancy may adversely influence the fertility of offspring.