BackgroundChina bears the highest global burden of esophageal cancer, with esophageal squamous cell carcinoma representing the predominant histological subtype. The poor clinical outcome of ESCC is largely attributable to its aggressive invasiveness and early metastatic spread. Currently, effective first-line targeted therapies remain limited, underscoring the need to identify actionable molecular targets and develop novel targeted agents for ESCC.MethodsXIAP expression was examined by Western blot analysis. Cell proliferation was assessed using CCK-8 assays, while cell migration and invasion were evaluated by wound-healing and Transwell assays. The interaction between W-1-32 and XIAP was investigated using drug affinity responsive target stability and cellular thermal shift assays. Molecular docking and molecular dynamics simulations were employed to explore the binding mode of W-1-32 to XIAP.ResultsA small-molecule compound, W-1-32, was identified as a modulator of XIAP. Computational analyses suggested a stable binding mode between W-1-32 and XIAP mediated by hydrogen bonding and noncovalent interactions, which was further supported by DARTS and CETSA assays. Treatment with W-1-32 reduced XIAP protein abundance in ESCC cells and was associated with decreased cell proliferation and migratory capacity. Notably, W-1-32 exhibited lower cytotoxicity toward normal esophageal epithelial cells compared with ESCC cells, indicating a degree of tumor selectivity in vitro.ConclusionOur results confirmed that W-1-32 significantly reduces ESCC cell proliferation and migration, which may be attributed to its binding to XIAP and the consequent reduction of XIAP protein levels. These findings identify W-1-32 as a XIAP-modulating compound with selective in vitro activity against ESCC cells, warranting further in vivo pharmacokinetic, efficacy, and safety evaluation before translational consideration.

Ethnopharmacological relevance Dahuang Mudan decoction (DMD) is a traditional Chinese prescription from Zhang Zhongjing's Synopsis of the Golden Chamber. In clinical practice, it is often used in the treatment of infectious diseases. Aim of the study To assess the therapeutic effect of DMD and its disassembled prescriptions on septic mice, and explore its potential mechanism. Materials and methods Cecal ligation and puncture (CLP) sepsis and endotoxemia mice models were established. The effects of DMD, its disassembled prescriptions and active compounds were studied. Xuebijing injection (XBJ) was used as positive drug. Mice 7-day survival rates, blood biochemical markers, hematoxylin and eosin (HE) staining and immune cell infiltration were used to evaluate the overall protective effect of the drugs on mice. Inflammatory cytokines and coagulation activation indicators were detected by enzyme-linked immunosorbent assay (ELISA). Results DMD, its Huoxue prescription, constituent drugs Mudanpi (MDP) and Taoren (TR) significantly protected mice with sepsis, improved the survival rate, reduced the degree of organ damage, and reduced the infiltration of immune cells in the lung tissues. The protective effect is comparable to that of XBJ. MDP and TR inhibited the levels of inflammatory factors and coagulation activation in septic mice. Paeonol and paeoniflorin in MDP showed significant protective effects on septic mice, and inhibited inflammatory cytokines level and coagulation activation. Conclusion These results confirm that DMD and its disassembled prescriptions have good therapeutic effect on septic mice, and the mechanism may be related to inhibition of the inflammatory response and coagulation activation.

Matrine, a component derived from traditional Chinese medicine, exhibits diverse pharmacological effects such as anti-hepatic fibrosis. Here we have investigated novel matrine tricyclic derivatives designed by a molecular fusion strategy for anti-fibrotic effects. Among these new compounds, ZM842 indicated potent inhibitory TGF-beta transcriptional activity in a dose-dependent manner by a TGF-beta/Smads reported gene assay. TGF-beta 1-stimulated LX-2 cells were treated with compound ZM842, resulting in a reduction of fibrosis markers, including collagen I and alpha-SMA, as observed at the protein level. Molecular docking disclosed that compound ZM842 may inhibit the activation of hepatic stellate cells (HSCs) by directly interacting with TGF-beta 1 and SMAD-3 proteins. In summary, our results suggest that compound ZM842 inhibits the TGF-beta 1 signaling pathway and HSC activation, indicating its potential as an anti-hepatic fibrosis agent.

Hepatic stellate cells (HSCs) activation is a key event in the development of liver fibrosis, and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Sophoridine, a bioactive alkaloid found in many Chinese herbs, exhibits a broad spectrum of pharmacological effects, but its activities are not strong. In this study, a series of structurally modified derivatives of sophoridine were designed and synthesized. Among them, sophoridine α-aryl propionamide derivative ZM600 displayed a significant inhibitory effect on the activation of HSCs. The in vivo experiment demonstrated that ZM600 markedly ameliorated carbon tetrachloride (CCl4) and bile duct ligation (BDL)-induced liver fibrosis with a significant improvement of extracellular matrix deposition. Mechanism investigations revealed that ZM600 specifically inhibited the activation of NF-κB, PI-3K/AKT, and TGF-β/Smads signaling pathways. These results suggest that ZM600 has a protective effect on liver fibrosis, which provides a new candidate for the treatment of liver fibrosis.

Background: The incidence of invasive fungal diseases (IFDs), represented by Candida albicans infection, is increasing year by year. However, clinically available antifungal drugs are very limited and encounter challenges such as limited efficacy, drug resistance, high toxicity, and exorbitant cost. Therefore, there is an urgent need for new antifungal drugs.Purpose: This study aims to find new antifungal compound from plants, which has ideal antifungal target.Methods: In vitro antifungal activities of compounds were investigated using broth microdilution method, spot assay, hyphal growth assay and biofilm formation assay. Synergistic effects were assessed using checkerboard broth microdilution method, disk diffusion assay and time-growth curve assay. In vivo antifungal activities were evaluated using Galleria mellonella and murine candidiasis models. Cytotoxicity was investigated using Cell Counting Kit-8 (CCK-8). Drug target discovery and validation were carried out using C. albicans monoallelic knockout library, haploinsufficiency profiling (HIP), thermal shift assay (TSA), molecular docking, and in vitro and in vivo antifungal studies.Results: 814 compounds from natural plant products were screened and petroselinic acid (PeAc) was found as an antifungal molecule. PeAc inhibited the growth of various pathogenic fungi, exhibited synergistic effects with fluconazole (FLC), inhibited the formation of C. albicans hyphae and biofilms, and showed antifungal effects in vivo. PeAc was relatively low cytotoxic to mammal cells. Fba1p was revealed the target of PeAc by using HIP, TSA and molecular docking methods. PeAc exerted antifungal effects more effectively on fba1Δ/FBA1 than wild-type (WT) strain both in vitro and in vivo.Conclusions: PeAc, a natural product of plants, is an effective and low toxic antifungal lead compound. The target of PeAc is Fba1p. Fba1p is a promising target for antifungal drug development.

MASM, a structurally modified derivative of matrine, exhibits superior efficacy in reducing inflammation and liver injury in rats when compared to matrine. This study aims to investigate the pharmacokinetic profile and acute toxicity of MASM. Pharmacokinetic results revealed that MASM exhibited rapid absorption, with a Tmax ranging from 0.21 ± 0.04 h to 1.31 ± 0.53 h, and was eliminated slowly, with a t1/2 of approximately 10 h regardless of the route of administration (intravenous, intraperitoneal, or intragastric). The absolute intragastric bioavailability of MASM in rats was determined to be 44.50%, which was significantly higher than that of matrine (18.5%). MASM was detected in all rat tissues including the brain, and through the utilization of stable isotope-labeled compounds and standard references, ten metabolites of MASM, namely sophocarpine, oxysophocarpine, and oxymatrine, were tentatively identified. The LD50 of MASM in mice was determined to be 94.25 mg/kg, surpassing that of matrine (83.21 mg/kg) based on acute toxicity results. Histopathological and biochemical analysis indicated no significant alterations in the primary organs of the low- to medium-dosage groups of MASM. These findings provide valuable insights into the efficacy and toxicity profile of MASM.

Background The incidence of invasive fungal diseases (IFDs), represented by Candida albicans infection, is increasing year by year. However, clinically available antifungal drugs are very limited and encounter challenges such as limited efficacy, drug resistance, high toxicity, and exorbitant cost. Therefore, there is an urgent need for new antifungal drugs. Purpose This study aims to find new antifungal compounds from plants, preferably those with good activity and low toxicity, and reveal their antifungal targets. Methods In vitro antifungal activities of compounds were investigated using broth microdilution method, spot assay, hyphal growth assay and biofilm formation assay. Synergistic effects were assessed using broth microdilution checkerboard technique. In vivo antifungal activities were evaluated using Galleria mellonella and murine candidiasis models. Cytotoxicity of compounds was investigated using Cell Counting Kit-8 (CCK-8). Discovery and validation of antifungal targets of compounds were conducted by using monoallelic knockout library of C. albicans, haploinsufficiency profiling (HIP), thermal shift assay (TSA), enzyme inhibitory effect assay, molecular docking, and in vitro and in vivo antifungal studies. Results 814 plant products were screened, among which petroselinic acid (PeAc) was found as an antifungal molecule. As a rare fatty acid isolated from coriander (Coriandrum sativum), carrot (Daucus carota) and other plants of the Apiaceae family, PeAc had not previously been found to have antifungal effects. In this study, PeAc was revealed to inhibit the growth of various pathogenic fungi, exhibited synergistic effects with fluconazole (FLC), inhibited the formation of C. albicans hyphae and biofilms, and showed antifungal effects in vivo. PeAc was less toxic to mammalian cells. Fructose-1,6-bisphosphate aldolase (Fba1p) was identified as a target of PeAc by using HIP, TSA, enzyme inhibitory effect assay and molecular docking methods. PeAc exerted antifungal effects more effectively on fba1Δ/FBA1 than wild-type (WT) strain both in vitro and in vivo. Conclusions PeAc is an effective and low toxic antifungal compound. The target of PeAc is Fba1p. Fba1p is a promising target for antifungal drug development.

Hepatic fibrosis is a pathological change caused by chronic liver injury and self-repair, and it is the inevitable stage of the development of chronic liver disease to cirrhosis or even liver cancer. Activation of hepatic stellate cells (HSCs) is a core event in the development of liver fibrosis and blockage of the activation of HSCs has been shown to alleviate liver fibrosis. Roxarsone, an organoarsenic additive, with antibiotic effect, growth promotion and improving feed efficiency, is widely used in livestock and animal production. The purpose of this study was to evaluate the therapeutic effect of Roxarsone on liver fibrosis and explore the possible mechanism. We found that Roxarsone could inhibit transforming growth factor-β1 (TGF-β1) induced the activation of HSCs and weaken the migration ability. Moreover, Roxarsone administration significantly ameliorated CCl4-induced liver fibrosis in mice with improvement of liver function and decreases of deposition of extracellular matrix (ECM). Mechanism investigations revealed that Roxarsone specifically inhibited the activation of TGF-β1/Smad signaling pathway, but had no effect on MAPK and PI3K/AKT pathways. These results suggest that Roxarsone has a protective effect on liver fibrosis which provides a new candidate for the treatment of liver fibrosis.

Cancer cachexia is a metabolic syndrome that is characterized by progressive loss of skeletal muscle mass, and effective therapeutics have yet to be developed. Saikosaponin D (SSD), a major bioactive component of Radix Bupleuri, exhibits antiinflammatory, anti-tumor, anti-oxidant, anti-viral, and hepatoprotective effects. In this study, we demonstrated that SSD is a promising agent for the treatment of cancer cachexia. SSD could alleviate TCM-induced myotube atrophy and inhibit the expression of E3 ubiquitin ligases muscle RING-finger containing protein-1 (MuRF1) and muscle atrophy Fbox protein (Atrogin-1/MAFbx) in vitro. Moreover, SSD suppressed the progression of cancer cachexia, with significant improvements in the loss of body weight, gastrocnemius muscle, and tibialis anterior muscle mass in vivo. Mechanism investigations demonstrated that SSD could directly bind to STAT3 and specifically inhibit its phosphorylation as well as its transcriptional activity. Overexpression of STAT3 partially abolished the inhibitory effect of SSD on myotube atrophy, indicating that the therapeutic effect of SSD was attributed to STAT3 inhibition. These findings provide novel strategies for treatment of cancer cachexia by targeting STAT3, and SSD may be a promising drug candidate for cancer cachexia.

Inflammatory bowel disease (IBD) is a chronic inflammatory bowel disease, which is characterized by inflammation, with many symptoms including diarrhea, abdominal pain, bloody stool, and weight loss. It is difficult to completely cure and promising therapeutic drug candidates are urgently needed. Citropten, a coumarin-like compound found in traditional Chinese medicine such as Finger Citron Fruit, notopterygium root and citrus peel, has been shown to inhibit the proliferation of tumor cells, protect against depression and suppress the production of inflammatory mediators. In this study, we demonstrated that citropten could alleviate dextran sulfate sodium (DSS)-induced acute and recurrent colitis in mice, with significant improvement in body weight loss, disease activity index, shortened colon length and histological changes. Moreover, citropten dramatically decreased the production of pro-inflammatory mediators in colon tissues and effectively suppressed the proportion of Th17 cells in spleen. Mechanism investigations revealed that citropten significantly inhibited the activation of NF-κB and JAK/STAT3 signaling pathways, thus leading to decreased inflammation, Th17 cells and alleviative colitis. These findings provide novel insights into the anti-colitis effect of citropten, which may be a promising drug candidate for treatment of IBD.

Blocking the interaction between Ras and Son of Sevenless homolog 1 (SOS1) has been an attractive therapeutic strategy for treating cancers involving oncogenic Ras mutations. K-Ras mutation is the most common in Ras-driven cancers, accounting for 86%, with N-Ras mutation and H-Ras mutation accounting for 11% and 3%, respectively. Here, we report the design and synthesis of a series of hydrocarbon-stapled peptides to mimic the alpha-helix of SOS1 as pan-Ras inhibitors. Among these stapled peptides, SSOSH-5 was identified to maintain a well-constrained alpha-helical structure and bind to H-Ras with high affinity. SSOSH-5 was furthermore validated to bind with Ras similarly to the parent linear peptide through structural modeling analysis. This optimized stapled peptide was proven to be capable of effectively inhibiting the proliferation of pan-Ras-mutated cancer cells and inducing apoptosis in a dose-dependent manner by modulating downstream kinase signaling. Of note, SSOSH-5 exhibited a high capability of crossing cell membranes and strong proteolytic resistance. We demonstrated that the peptide stapling strategy is a feasible approach for developing peptide-based pan-Ras inhibitors. Furthermore, we expect that SSOSH-5 can be further characterized and optimized for the treatment of Ras-driven cancers.

Excessive inflammatory response is a critical pathogenic factor for the tissue damage and organ failure caused by systemic inflammatory response syndrome (SIRS) and sepsis. In recent years, drugs targeting RIPK1 have proved to be an effective anti-inflammatory strategy. In this study, we identified a novel anti-inflammatory lead compound 4–155 that selectively targets RIPK1. Compound 4–155 significantly inhibited necroptosis of cells, and its activity is about 10 times higher than the widely studied Nec-1 s. The anti-necroptosis effect of 4–155 was mainly dependent on the inhibition of phosphorylation of RIPK1, RIPK3, and MLKL. In addition, we demonstrated that 4–155 specifically binds RIPK1 by drug affinity responsive target stability (DARTS), immunoprecipitation, kinase assay, and immunofluorescence microscopy. More importantly, compound 4–155 could inhibit excessive inflammation in vivo by blocking RIPK1-mediated necroptosis and not influence the activation of MAPK and NF-κB, which is more potential for the subsequent drug development. Compound 4–155 effectively protected mice from TNF-induced SIRS and sepsis. Using different doses, we found that 6 mg/kg oral administration of compound 4–155 could increase the survival rate of SIRS mice from 0 to 90

苦豆子是豆科槐属植物,为宁夏的道地药材之一.苦豆子有着丰富而复杂的活性成分,主要有生物碱、黄酮、挥发油、甾体、多糖、脂肪酸等.近年来,国内外对苦豆子生物碱开展了大量研究,该类生物碱具有抗肝炎、抗肝纤维化、抗肝硬化、抗肝衰竭、抗肝癌等药理作用,其中,苦参碱相关药物已经获批在临床用于治疗乙型肝炎病毒感染等疾病.鉴于苦豆子在肝脏疾病治疗中的药用价值,对苦豆子主要活性成分进行综述,重点阐述其治疗肝脏疾病的研究进展.

Ulcerative colitis (UC) is a chronically relapsing inflammatory disease in the intestinal tract. Current unsatisfactory treatments prompt people to seek for alternative therapies and drug candidates. Cryptotanshinone (CTS), a diterpene quinone extracted from the roots of Salvia miltiorrhiza, has recently been shown to inhibit acute colitis by reducing pro-inflammatory mediators. However, whether CTS can protect against chronic UC and its effect on T lymphocytes remain unknown. In this study, CTS (20, 60 mg/kg) showed potent inhibitory activity against dextran sulfate sodium (DSS)-induced acute UC, as determined by weight loss, disease activity, colon length and histology. Similarly, in a model of DSS-induced chronic colitis, the administration of CTS prevented the disease progression with longer colon length, lower histological scores, and less expression of fibrosis-related collagen and alpha-smooth muscle actin in the colon. CTS also reduced the proportion of CD4(+)IL-17A(+) Th17 cells in spleen and mesenteric lymph nodes of mice with acute or chronic colitis. However, CTS at 20 mg/kg had no effect on regulatory T cells (Tregs). In addition, CTS reduced the phosphorylation of signal transduction and transcription activator 3 (STAT3) in DSS-treated colon tissue. Further study showed that CTS concentration dependently suppressed the differentiation of naive CD4(+) T cells into Th17 cells. CTS could not inhibit the activation and proliferation of T lymphocytes or attenuate the secretion of cytokines including IL-10, IL-2, IL-6 and IFN-gamma, but could inhibit the production of IL-17A and TNF-alpha in Con A-stimulated splenocytes. CTS suppressed IL-6-induced phosphorylation and nuclear translocation of STAT3. In conclusion, our study demonstrated that CTS alleviated acute and chronic UC by suppressing STAT3 activation and Th17 cell differentiation, suggesting that it may be a promising candidate drug for the treatment of UC.

BACKGROUND:Sepsis is a life-threatening multi-organ dysfunction caused by the dysregulated host response to infection. Sepsis remains a major global concern with high mortality and morbidity, while management of sepsis patients relies heavily on early recognition and rapid stratification. This study aims to identify the crucial genes and biomarkers for sepsis which could guide clinicians to make rapid diagnosis and prognostication.METHODS:Preliminary analysis of multiple global datasets, including 170 samples from patients with sepsis and 110 healthy control samples, revealed common differentially expressed genes (DEGs) in peripheral blood of patients with sepsis. After Gene Oncology (GO) and pathway analysis, the Weighted Gene Correlation Network Analysis (WGCNA) was used to screen for genes most related with clinical diagnosis. Also, the Protein-Protein Interaction Network (PPI Network) was constructed based on the DEGs and the hub genes were found. The results of WGCNA and PPI network were compared and one shared gene was discovered. Then more datasets of 728 experimental samples and 355 control samples were used to prove the diagnostic and prognostic value of this gene. Last, we used real-time PCR to confirm the bioinformatic results.RESULTS:Four hundred forty-four common differentially expressed genes in the blood of sepsis patients from different ethnicities were identified. Fifteen genes most related with clinical diagnosis were found by WGCNA, and 24 hub genes with most node degrees were identified by PPI network. ARG1 turned out to be the unique overlapped gene. Further analysis using more datasets showed that ARG1 was not only sharply up-regulated in sepsis than in healthy controls, but also significantly high-expressed in septic shock than in non-septic shock, significantly high-expressed in severe or lethal sepsis than in uncomplicated sepsis, and significantly high-expressed in non-responders than in responders upon early treatment. These all demonstrate the performance of ARG1 as a key biomarker. Last, the up-regulation of ARG1 in the blood was confirmed experimentally.CONCLUSIONS:We identified crucial genes that may play significant roles in sepsis by WGCNA and PPI network. ARG1 was the only overlapped gene in both results and could be used to make an accurate diagnosis, discriminate the severity and predict the treatment response of sepsis.

Inflammatory bowel disease (IBD) is a non-specific chronic intestinal inflammatory disease, often presenting with abdominal pain, diarrhea, bloody stool, anorexia, and body loss. It is difficult to cure completely and a promising treatment is urgently needed. Natural compounds can offer promising chemical agents for treatment of diseases. Polydatin is a natural ingredient extracted from the dried rhizome of Polygonum cuspidatum, which has anti-inflammatory, anti-tumor, and dementia protection activities. The purpose of this study was to evaluate the therapeutic effect of polydatin on IBD and explore its possible mechanism. We found that polydatin could effectively suppress the differentiation of Th17 cells in vitro, but had no effect on the differentiation of Treg cells. Polydatin significantly alleviated colitis induced by dextran sulfate sodium (DSS) and 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) in mice, and dramatically decreased the proportion of Th17 cells in spleen and mesenteric lymph nodes. Mechanism investigations revealed that polydatin specifically inhibited signal transducer and activator of transcription 3 (STAT3) phosphorylation by directly binding to STAT3, leading to Th17 cell reduction and thereby alleviating colitis. These findings provide novel insights into the anti-colitis effect of polydatin, which may be a promising drug candidate for the treatment of IBD.

Elucidating the active components of traditional Chinese medicine (TCM) is essential for understanding the mechanisms of TCM and promote its rational use as well as TCM-derived drug development. Recent studies have shown that surface plasmon resonance (SPR) technology is promising in this field. In the present study, we propose an SPR-based integrated strategy to screen and analyze the major active components of TCM. We used Radix Paeoniae Alba (RPA) as an example to identify the compounds that can account for its anti-inflammatory mechanism via tumor necrosis factor receptor type 1 (TNF-R1). First, RPA extraction was analyzed using an SPR-based screening system, and the potential active ingredients were collected, enriched, and identified as paeoniflorin and paeonol. Next, the affinity constants of paeoniflorin and paeonol were determined as 4.9 and 11.8 μM, respectively. Then, SPR-based competition assays and molecular docking were performed to show that the two compounds could compete with tumor necrosis factor-α (TNF-α) while binding to the subdomain 1 site of TNF-R1. Finally, in biological assays, the two compounds suppressed cytotoxicity and apoptosis induced by TNF-α in the L929 cell line. These findings prove that SPR technology is a useful tool for determining the active ingredients of TCM at the molecular level and can be used in various aspects of drug development. The SPR-based integrated strategy is reliable and feasible in TCM studies and will shed light on the elucidation of the pharmacological mechanism of TCM and facilitate its modernization.

Astrocytes (AST) play an important role in the pathogenesis of neurological disorders, and their activation is involved in the progression of multiple sclerosis (MS). (6aS, 10S, 11aR, 11bR, 11cS)-10-methylaminododecahydro-3a, 7a-diaza-benzo (de) anthracene-8-thione (MASM), a novel derivative of matrine, exhibits vast pharmacological activities, such as anti-tumor, anti-fibrosis and immune regulation. In this study, we demonstrate that MASM is a promising agent for the treatment of experimental autoimmune encephalomyelitis (EAE). MASM not only inhibited inflammatory responses in LPS-stimulated astrocytes, but also suppressed the formation of reactive A1 astrocyte and maintained astrocytic functions, including the ability to promote synapse formation and phagocytose synapses and myelin debris. Importantly, MASM could significantly alleviate the development of EAE, with significant inhibition of inflammation, demyelination, axon loss and the body weight loss. Meanwhile, MASM also inhibited the activation of astrocytes and improved the function of BBB in vivo. These findings provide novel insights into the protective effect of MASM on EAE, which may be a promising drug candidate for treatment of EAE.

目的 基于表面等离子体共振(SPR)技术,筛选能与信号转导和转录激活因子3(STAT3)特异性结合并抑制其活性的小分子化合物.方法 使用基于SPR技术的Biacore T200生物分子互作分析系统,在最优pH富集条件下将纯化蛋白STAT3偶联到SPR系统的CM5芯片上,从50个中药单体中筛选出能够与STAT3结合且响应值较高的化合物,并对其结合特异性进行确认,然后运用生物学相关实验确证筛选所得化合物对STAT3的抑制作用,最后采用分子对接技术拟合化合物与STAT3的结合模式,明确其可能的作用位点.结果 初步筛选获得10多个高响应的候选分子,通过动力学测定发现其中仅有1个分子芹黄素显示特异性结合.Western-blot实验结果表明,芹黄素能够剂量依赖地抑制STAT3的磷酸化;双荧光素酶报告基因结果显示,芹黄素能够剂量依赖地抑制IL-6诱导的STAT3的转录活性.分子对接结果表明,芹黄素与STAT3蛋白的SH2结构域结合,与关键残基Glu638、Gln644、Gly656、Lys658形成氢键相互作用,与Tyr657残基形成π-π相互作用.结论 基于SPR技术筛选,发现芹黄素是STAT3的抑制剂.

Prostate cancer is the second most common malignant cancer in males. It involves a complex process driven by diverse molecular pathways that closely related to the survival, apoptosis, metabolic and metastatic characteristics of aggressive cancer. Prostate cancer can be categorized into androgen dependent prostate cancer and castration-resistant prostate cancer and cure remains elusive due to the developed resistance of the disease. Natural compounds represent an extraordinary resource of structural scaffolds with high diversity that can offer promising chemical agents for making prostate cancer less devastating and curable. Herein, those natural compounds of different origins and structures with potential cytotoxicity and/or in vivo anti-tumor activities against prostate cancer are critically reviewed and summarized according to the cellular signaling pathways they interfere. Moreover, the anti-prostate cancer efficacy of many nutrients, medicinal plant extracts and Chinese medical formulations were presented, and the future prospects for the application of these compounds and extracts were discussed. Although the failure of conventional chemotherapy as well as involved serious side effects makes natural products ideal candidates for the treatment of prostate cancer, more investigations of preclinical and even clinical studies are necessary to make use of these medical substances reasonably. Therefore, the elucidation of structure-activity relationship and precise mechanism of action, identification of novel potential molecular targets, and optimization of drug combination are essential in natural medicine research and development.