RESUMEN
To explore the network pharmacological mechanisms of four anti-vitiligo Uyghur medicines based on the Phlegmatic temperament theory. First, The anti-vitiligo Uyghur medicine formulas based on Phlegmatic temperament theory were collected. The pharmacokinetic characteristic of main compounds in four anti-vitiligo Uyghur medicines were obtained by using admetSAR. The targets of active compounds were predicted via bSDTNBI (balanced substructure-drug-target network-based inference model) method. Then, biological process (BP) and molecular function (MF) enrichment analysis of targets were analysed via DAVID database. Constructing anti-vitiligo Uyghur medicine formula-Uyghur medicines network model (FMI network) and Uyghur medicines-active compounds-targets-BP-Hilit network model (MCTBHI network), we utilized closeness centrality to analyse key Uyghur medicines, active compounds, key targets as well as Hilit. Finally, the in vitro melanin production model of C57BL/6 mice was used to verify the ability of the active compounds to improve melanogenesis. The results showed that Psoralea corylifolia, Vernonia anthelmintica, Syzygium aromaticum and Anacyclus pyrethrum were the key Uyghur medicines in the FMI network. There were 22 active compounds with a relatively higher bioavailability interacted with 58 therapeutic targets. These active compounds were mainly composed of coumarins and flavonoids. In the MCTBHI network, the MF of 58 therapeutic targets was related to steroid hormone receptor activity, heme binding and enzyme binding functhon. Classification of the Hilit according to the BP of 58 therapeutic targets, the first place was the blood, followed by the lymph, the cerebrospinal fluid and digestive juice. It was found that the expression of some targets located in the skin was closed to the heart muscle, lymph node, spleen, cerebral cortex and so on, which were the main places for Hilit. In particular, ESR1, PTGS2, PPARA, PPARG, PTGS1 and CA2 were regulated by the flavonoids (kaempferide and isorhamnetin). The in vitro melanin production model showed that kaempferide and isorhamnetin could promote the melanin production in C57BL/6 mice ear skin. Based on admetSAR and bSDTNBI, we used network pharmacological method to construct a systematic means of studying anti-vitiligo Uyghur medicines, providing clues for the further study of the modern molecular mechanisms of Phlegmatic temperament.
RESUMEN
Objective To investigate the effects of Abnormal Phlegmatic Temperament Granules on spatial learning and memory, histopathology morphological change in hippocampus CA1 zone; To discuss its mechanism of action.Methods Three-month-old APP/PS1 transgenic mice were randomly divided into 5 groups: model control group, positive control (donepezil 0.92 mg/kg) group, Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups (3, 2, 1.5 g/kg), 18 mice in each group. Another 18 three-month-old C57BL/ 6J mice were chosen as normal control group. All administration groups received relevant medicine for successive 6 months. Then the changes in learning and memory ability of mice were detected by Morris water maze test; pathomorphism in hippocampus CA1 zone was detected by HE staining method; changes of myelin sheath, microtubule, and microfilament in myelinated nerve of hippocampus CA1 zone were detected by electron microscope. Results Morris water maze test results showed that escape incubation period of APP/PS1 transgenic mice was significantly longer than the normal control group (P<0.01), and the original platform time was significantly shorter than normal control group (P<0.01); compared with model control group, Abnormal Phlegmatic Temperament Granules treatment groups escape latency time was significantly reduced (P<0.05, P<0.01). Space experiments and escape incubation period of Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups were significantly shortened (P<0.05, P<0.01), and spatial searching test showed that the times of mice in Abnormal Phlegmatic Temperament Granules high-, medium-, low-dose groups passing through effective area increased (P<0.01). The integrity of HE staining pyramidal cell layer in the hippocampus CA1 zones of Abnormal Phlegmatic Temperament Granules high-, medium-, and low-dose groups was relatively good; cells arranged orderly; distribution was normal. Electron microscopic observation showed that compared with model control group, the hippocampus neurons nuclear had irregular shape; nuclear membrane was clear and complete; chromatin was clear; nucleolus was obvious; cell matrix was uniform; organelles were abundant; mitochondrial cristae was obvious; endoplasmic reticulum and free ribosomes were obvious. Conclusion Abnormal Phlegmatic Temperament Granules can improve spatial learning and memory in APP/PS1 mice, alleviate neuronal ultrastructure damage and ultimately improve cognitive function.