We used Box-Behnken design-based (BBD) response surface methodology (RSM) in this research to optimize the extraction process of Traditional medicine Majun Mupakhi Ela (MME) and evaluate its effect on hydrocortisone-induced kidney yang deficiency. Three independent parameters were applied to evaluate the maximum phosphodiesterase type 5 (PDE5) inhibition activity of MME extracts in vitro. The optimal processing conditions (extraction time 2 h, solid-liquid ratio 1:16, extraction once) gave a maximum PDE5 inhibition rate of 84.10%, flavonoid content of 0.49 mg/ml, icariin content of 0.028 mg/ml and targeted extraction yield of 26.50%. In animal experiments, MME extracts significantly increased the adrenal mass index, semen weight index, preputial gland weight index, and penis weight index in mice; in the middle and high dose group, the level of serum testosterone increased by 7664.29% and 14207.14% respectively, compared with the model group, and the level of PDE5 decreased by 67.22% and 74.69% respectively compared with the control group. These results indicate that MME has a significant positive effect on the hypothalamus-pituitary-gonadal axis, improve mating ability and not only has inhibits PDE5 activity but also significantly inhibits the expression of PDE5 in penile tissues, potential to become erectile dysfunction (ED) therapies for the clinical management of patients with kidney yang deficiency.
This paper aims to study the potential biological mechanism of Üstikuddus Sherbiti (ÜS) in the treatment of ischemic cerebrovascular diseases (ICVD) by the network pharmacology method. Traditional Chinese Medicine Systems Pharmacology (TCMSP) database was used to obtain effective constituents of ÜS by screening eligible oral utilization, drug similarity, and blood-brain barrier permeability threshold. By drug target prediction and stroke treatment target mining, 2 target data sets were analyzed to find intersection targets and the corresponding constituents were used as active constituents. An active constituent target network and an effective constituent target network were constructed by using Cytoscape 3.7.2 software. Degree parameters of the effective constituent target network were analyzed to find important effective constituents and targets. Through protein-protein interaction (PPI) analysis/Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, potential signaling pathways of ÜS in ischemic stroke were found out. AutoDock was used for molecular docking verification. A total of 90 active constituents of ÜS were screened out. There were 10 active constituents against ICVD, including quercetin, luteolin, kaempferol, and naringenin, and 10 important targets for anticerebral ischemia, namely, PIK3CA, APP, PIK3R1, MAPK1, MAPK3, AKT1, PRKCD, Fyn, RAC1, and NF-κB1. Based on the protein interaction network, the important targets of ÜS were significantly enriched in PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction pathway, Ras signaling pathway, etc. ÜS in ICVD has characteristics like multiple targets, multiple approaches, and multiple pathways. Results of molecular docking showed that the active components in ICVD had a good binding ability with the key targets. Its main biological mechanism may be related to the PI3K-Akt and Ras-MAPK centered signaling pathway. Our study demonstrated that ÜS exerted the effect of treating ICVD by regulating multiple targets and multiple channels with multiple components through the method of network pharmacology and molecular docking.
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