The computer-aided design was used to simulate the docking of PDGF receptor with known active compounds, and the active groups that can bind to key sites were identified by analyzing the key amino acid residue fragments that exerted active effects on the target proteins. The natural product oleanolic acid was used as the parent, and the active group was introduced into the 2-position, and the C-28 carboxyl group was esterified and amidated. A series of oleanolic acid analogues targeting PDGF receptor inhibitors were designed and synthesized. Their structures were confirmed by MS and NMR. Through MTT assay, SGC-7901 and A549 cells were selected for preliminary in vitro anti-tumor activity screening. PDGF receptor protein inhibition test was performed on Ⅰ₃ and Ⅱ₅ by FPIA. The activity tests showed that Ⅰ₃ and Ⅱ₅, compared with the positive control drug, had stronger inhibition. FPIA test showed that Ⅱ₅ and PDGF receptor protein had good binding ability. The newly synthesized oleanolic acid analogues have significantly higher antitumor activity than the parent compound and deserve further study.

Currently, single-target drugs are often difficult to achieve the desired results in the treatment of multifactorial diseases such as tumors, cardiovascular and endocrine diseases, and may also cause toxicity. Multi-target drugs can improve the efficacy, reduce side effect and drug resistance by regulating multiple links of the disease, showing good prospects for the application. The main aim of this article is to review the strategies of designing multi-target directed ligands (MTDLs) (including conjugated-pharmacophore, fused-pharmacophore and merged-pharmacophore) and the research progress in recent years. The existing problems and challenges of multi-target drugs are also discussed, to provide new ideas for the study of multi-target drugs.

Present study investigated the role of mesenchyme homeobox 2 (MEOX2) gene in neurovascular dysfunction in Alzheimer's disease (AD) model rats by bilateral intracerebroventricular injection of Aβ_1-42. One week after surgery, Morris water maze, immunohistochemistry, biochemical detection, Western blot and real-time PCR were used to detect the indexes. The animal studies were conducted in accordance with the Regulations of Experimental Animal Administration issued by the State Committee of Science and Technology of the People's Republic of China. Compared to the Sham-operated rats, Aβ_1-42-operated rats showed obviously cognitive dysfunction, accompanied by increased Aβ, glial fibrillary acidic protein (GFAP), allograft inflammatory factor 1 (AIF1), endothelial nitric oxide synthase (eNOS) and decreased neuron specific enolase (NSE), synaptophysin (SYN), CD34, vascular endothelial growth factor (VEGF) expressions of brain. Aβ_1-42-operated rats also increased the endothelin (ET) level and decreased nitric oxide (NO) level in brain tissue. Moreover, MEOX2 expression was decreased correlated with low density lipoprotein receptor-related protein 1 (LRP-1) decreasing and receptor for advanced glycation end products (RAGE) increasing in brain tissues of AD model rats. We found the correlation between MEOX2 gene expression and neurovascular dysfunction, in addition, the decreased MEOX2 may involve in increasing the accumulation of Aβ in brain by relating to the decreased LRP-1 and increased RAGE which is located in blood-brain barrier (BBB) in senescence-accelerated mice.

Naphthoquinones are a kind of important active ingredients in the traditional Chinese medicinal herb "Zicao". In recent years, researches on pharmacology and clinical application of naphthoquinones in Zicao have been gradually deepened and made extensive progress around the world. On the other hand, the plant origins of the herbal materials of Zicao in market are complex and their qualities are quite different, thus more and more studies have been focused on the quantitative determination and quality assessment of the medicinal herb as well as its products by using various naphthoquinones as quality chemical markers. In this paper, we review recent advances in the research on pharmacological actions and multi-components content determination of shikonin/alkannin and its derivatives in Zicao so as to provide a scientific guidance for further research and development of medicinal resource of Zicao, and to establish more comprehensive and systematic method for their quality control and evaluation.

Eighty percent of bacterial infections are related to the formation of bacterial biofilm. Compared with planktonic bacteria, bacterial biofilm is 10-1 000 times more resistant to antibiotics, which is the main cause of current bacterial drug resistance. A comprehensive understanding of the characteristics and resistance mechanisms of bacteria biofilm will help us treat the stubborn infections caused by the bacterial biofilm better and solve the problem of bacterial drug resistance. In this review, the composition and quorum sensing of bacterial biofilm, two major patterns of biofilm formation and drug resistance mechanisms were presented. Furthermore, representative compounds with anti-biofilm activity and compounds synergistic with antibiotics in anti-biofilm actions were introduced. Nano drug delivery strategies used for anti-biofilm in recent years as well as a novel drug delivery system-molecularly imprinted polymer was also introduced.

Lipopolysaccharide (LPS)-induced bone marrow-derived macrophages (BMDMs), treated with licochalcone A (LCA) and retreated with inflammasome inducers respectively (ATP and nigericin), were used to construct the inflammasome model of NLRP3 (NOD-like receptor family, pyrin domain containing 3), to investigate the inhibitory effect and the molecular mechanism of LCA on the activity of NLRP3 inflammasome. The secretion of mature interleukin (IL)-1β, tumor necrosis factor-α (TNF-α) and caspase-1 in the supernatants were analyzed by ELISA and the Caspase-Glo^® 1 Inflammasome Assay. Supernatants and cell lysates were analyzed for the expression of pro-caspase-1, pro-IL-1β, ASC, NLRP3, IL-1β, caspase-1 by immunoblotting. The study shows that LCA inhibited the activity of caspase-1 and the secretion of IL-1β, and suppressed the activity of NLRP3 inflammasome. There was also slight inhibition of NLRC4 inflammasome induced by Lfn-Flic, but no effect on poly(dA:dT)-induced the absent in melanoma 2 (AIM2) inflammasome. Western blot showed that LCA had no effect on the protein expression of NLRP3 and pro-IL-1β, which was mediated by NF-κB pathway. In summary, LCA can inhibit the cleavage of pro-caspase-1 and suppress the secretion of IL-1β to reduce the inflammation response. The study was carried out under the approval of the Scientific Investigation Board of 302 Hospital of PLA.

Depression is a common mental disorder. It is estimated that by 2020, the global incidence of depression will be about 20%, which will bring huge economic burden to society. The pathogenesis of depression is complicated, the diagnostic method is not objective, and the cure rate is low. Antidepressants are often associated with adverse reactions during treatment, and patient compliance is poor. Therefore, a single component with antidepressant effects in natural medicines or a compound Chinese medicine gradually shows an advantage in the treatment of depression. Berberine (C₂₀H₁₈NO₄) is one of the main components of traditional Chinese medicine Coptis. In recent years, a large amount of evidence indicates that berberine has a good antidepressant effect on different animal models of depression, and its mechanism may be related to the regulation of monoamines and metabolism, anti-inflammatory and anti-oxidation in the brain. This article describes the antidepressant effect and mechanism of berberine, and provides a basis for further exploration and research on the antidepressant effect of berberine.

The Nrf2-Keap1-ARE pathway is an important signaling axis that functions to protect cells against oxidative stress and harmful chemicals through the induction of cytoprotective genes. The maintenance and protective role of Nrf2 pathway has been recognized as a means for chemoprevention. On the other hand, constitutive activation of Nrf2, due to somatic mutations of genes that control Nrf2 degradation, promotes carcinogenesis and imparts chemoresistance to cancer cells. Autophagy is another tightly regulated complex cellular process that functions as a cellular quality control system to remove damaged proteins or organelles. Recently, these two cellular pathways were shown to intersect through the direct interaction between p62 (an autophagy adaptor protein) and Keap1. Dysregulation of autophagy was shown to result in prolonged activation of Nrf2 in a p62-dependent manner, which is associated with the pathogenesis and therapies of several human diseases including cancer. In this review, we discuss the molecular mechanisms of p62-mediated Nrf2 signaling pathway, with a special emphasis on their impact on nervous system disease, cardiovascular disease and cancer.

Based on the integrity and systematicness of Chinese medicine, the components preparation simplifies the complex problems of multi-components of Chinese medicine, provides an effective and feasible model for the development of Chinese medicine preparation. It has become a hot topic in the research of prep-aration, and is also considered as one of the effective ways to realize the modernization of Chinese medicine. Based on the previous research on multi-components and the work of our research group, the research frontiers of multi-components are elucidated, including the properties and characterization techniques of components, the construction of components release unit, and the multiple drug delivery system. The purpose of this paper is to explore the technical basis and key problem of components preparation, and then bring some inspiration and thought to the relevant researchers.

The development and metabolism of medicinal plant is affected by many factors, among which the effect from endophytic fungi has been noticed recently and has become one of hot fields. In order to explore the effect of endophytic fungi on gene expression in R. crenulata, RNA-sequencing was used to find genes involved in metabolic pathways, and the differential genes were verified by real-time fluorescent quantitative PCR. The method of 2^-△△Ct was used to analyze the relative expression levels of genes in related metabolic pathways, which was used to verify the result of transcriptomics sequencing. The results showed that the endophytic fungus, P. fortinii, could up-regulate the gene expression in lipid metabolic pathway of R. crenulata. In signal transduction pathway, the genes were influenced at different level but the gene expressions were significantly increased under control of Notch signaling pathway, which was 34 times of that in control. The gene expressions of environmental adaption pathway were up-regulated in R. crenulata after inoculation of P. fortinii. This study could provide help for further understanding on mechanism of plant-fungus interaction, root cause of geoherbalism of medicinal plant and exploring bio-function of endophytic fungi.