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Renal injury, a prevalent clinical outcome with multifactorial etiology, imposes a substantial burden on society. Currently, there remains a lack of effective management and treatments. Extensive research has emphasized the diverse biological effects of natural polysaccharides, which exhibit promising potential for mitigating renal damage. This review commences with the pathogenesis of four common renal diseases and the shared mechanisms underlying renal injury. The renoprotective roles of polysaccharides in vivo and in vitro are summarized in the following five aspects: anti-oxidative stress effects, anti-apoptotic effects, anti-inflammatory effects, anti-fibrotic effects, and gut modulatory effects. Furthermore, we explore the structure-activity relationship and bioavailability of polysaccharides in relation to renal injury, as well as investigate their utility as biomaterials for alleviating renal injury. The clinical experiments of polysaccharides applied to patients with chronic kidney disease are also reviewed. Broadly, this review provides a comprehensive perspective on the research direction of natural polysaccharides in the context of renal injury, with the primary aim to serve as a reference for the clinical development of polysaccharides as pharmaceuticals and prebiotics for the treatment of kidney diseases.
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Polisacáridos , Humanos , Polisacáridos/uso terapéutico , Polisacáridos/farmacología , Animales , Enfermedades Renales/tratamiento farmacológico , Enfermedades Renales/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/uso terapéutico , Sustancias Protectoras/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%-21.89% and 16.29%-22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.
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Lignanos , Vitex , Ratas , Animales , Osteoclastos , Vitex/metabolismo , Actinas/metabolismo , Linfocitos T , Lignanos/farmacología , Diferenciación CelularRESUMEN
Ensuring road safety, structural stability and durability is of paramount importance, and detecting road cracks plays a critical role in achieving these goals. We propose a GM-ResNet-based method to enhance the precision and efficacy of crack detection. Leveraging ResNet-34 as the foundational network for crack image feature extraction, we consider the challenge of insufficient global and local information assimilation within the model. To overcome this, we incorporate the global attention mechanism into the architecture, facilitating comprehensive feature extraction across the channel and the spatial width and height dimensions. This dynamic interaction across these dimensions optimizes feature representation and generalization, resulting in a more precise crack detection outcome. Recognizing the limitations of ResNet-34 in managing intricate data relationships, we replace its fully connected layer with a multilayer fully connected neural network. We fashion a deep network structure by integrating multiple linear, batch normalization and activation function layers. This construction amplifies feature expression, stabilizes training convergence and elevates the performance of the model in complex detection tasks. Moreover, tackling class imbalance is imperative in road crack detection. Introducing the focal loss function as the training loss addresses this challenge head-on, effectively mitigating the adverse impact of class imbalance on model performance. The experimental outcomes on a publicly available crack dataset emphasize the advantages of the GM-ResNet in crack detection accuracy compared to other methods. It is worth noting that the proposed method has better evaluation indicators in the detection results compared with alternative methodologies, highlighting its effectiveness. This validates the potency of our method in achieving optimal crack detection outcomes.
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Structural damage identification technology is of great significance to improve the reliability and safety of civil structures and has attracted much attention in the study of structural health monitoring. In this paper, a novel structural damage identification method based on transmissibility in the time domain is proposed. The method takes the discrepancy of transmissibility of structure response in the time domain before and after damage as the basis of finite element model updating. The damage is located and quantified through iteration by minimizing the difference between the measurements at gauge locations and the reconstruction response extrapolated by the finite element model. Taking advantage of the response reconstruction method based on empirical mode decomposition, damage information can be obtained in the absence of prior knowledge on excitation. Moreover, this method directly collects time-domain data for identification without modal identification and frequent time-frequency conversion, which can greatly improve efficiency on the premise of ensuring accuracy. A numerical example is used to demonstrate the overall damage identification method, and the study of measurement noise shows that the method has strong robustness. Finally, the present work investigates the method through a simply supported overhanging beam. The experiments collect the vibration strain signals of the beam via resistance strain gauges. The comparison between identification results and theoretical values shows the effectiveness and accuracy of the method.
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Vibración , Reproducibilidad de los ResultadosRESUMEN
Due to the coupling impacts of solar radiation, wind, air temperature and other environmental parameters, the temperature field of steel structures is significantly non-uniform during their construction and service stages. Corrugated web steel beams have gained popularity in structural engineering during the last few decades, while their thermal actions are barely investigated. In this paper, both experimental and numerical investigations were conducted to reveal the non-uniform features and time variation of the corrugated web steel beams under various environmental conditions. The heat-transfer simulation model was established and verified using the experimental temperature data. Both the experiment and simulation results demonstrate that the steel beam has a complicated and non-uniform temperature field. Moreover, 2-year continuous numerical simulations of steel beams' thermal actions regarding eight different cities were carried out to investigate the long-term temperature variations. Finally, based on the long-term simulation results and extreme value analysis (EVA), the representative values of steel beams' daily temperature difference with a 50-year return period were determined. The extreme temperature difference of the steel beam in Harbin reached up to 46.9 °C, while the extreme temperature difference in Haikou was 28.8 °C. The extreme temperature difference is highly associated with the steel beam's location and surrounding climate. Ideally, the outcomes will provide some contributions for the structural design regarding the corrugated web steel beam.
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The intelligent crack detection method is an important guarantee for the realization of intelligent operation and maintenance, and it is of great significance to traffic safety. In recent years, the recognition of road pavement cracks based on computer vision has attracted increasing attention. With the technological breakthroughs of general deep learning algorithms in recent years, detection algorithms based on deep learning and convolutional neural networks have achieved better results in the field of crack recognition. In this paper, deep learning is investigated to intelligently detect road cracks, and Faster R-CNN and Mask R-CNN are compared and analyzed. The results show that the joint training strategy is very effective, and we are able to ensure that both Faster R-CNN and Mask R-CNN complete the crack detection task when trained with only 130+ images and can outperform YOLOv3. However, the joint training strategy causes a degradation in the effectiveness of the bounding box detected by Mask R-CNN.
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Algoritmos , Redes Neurales de la ComputaciónRESUMEN
The suspended monorail (SM) vehicle-bridge system has been considered a promising modern transit mode due to its clear advantages: low pollution, high safety, convenient construction, and low cost. The wind-induced response can significantly affect the running safety and comfort of this type of vehicle due to its special suspended position from a fixed track. This study is the first to systematically investigate its aerodynamic characteristics and interference effects under various spacing ratios using wind tunnel tests and numerical simulations. A high level of agreement between the wind tunnel test and CFD (computational fluid dynamics) results was obtained, and the aerodynamic interference mechanism can be well explained using the CFD technique from a flow field perspective. A wireless wind pressure acquisition system is proposed to achieve synchronization acquisition for multi wind pressure test taps. The paper confirms that (1) the proposed wireless wind pressure acquisition system performed well; (2) the aerodynamic coefficients of the upstream vehicle and bridge were nearly unchanged for vehicle-bridge combinations with varying spacing ratios; (3) the aerodynamic interference effects were amplified when two vehicles meet, but the effects decrease as the spacing ratio increases; (4) the aerodynamic force coefficients, mean, and root mean square (RMS) wind pressure coefficients for the downstream vehicle and bridge are readily affected by the upstream vehicle; (5) the vortex shedding frequencies of vehicles and bridges can be readily obtained from the lift force spectra, and they decrease as the spacing ratio increases; and (6) a spacing ratio of 3.5 is suggested in the field applications to ensure the running safety and stability of the SM vehicle-bridge system under exposure to crosswinds.
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Digital image projection (DIP) with traditional vertical calibration cannot be used for measuring the water droplets/film on a curved surface, because significant systematic error will be introduced. An improved DIP technique with normal calibration is proposed in the present paper, including the principles, operation procedures and analysis of systematic errors, which was successfully applied to measuring the water droplets/film on a curved surface. By comparing the results of laser profiler, traditional DIP, improved DIP and theoretical analysis, advantages of the present improved DIP technique are highlighted.
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This paper focuses on the dynamic responses of a metro train-bridge system under train-braking. Experiments were performed on the elevated Metro Line 21 of Guangzhou (China). A continuous, three-span, rigid-frame bridge (42 m + 65 m + 42 m) and a standard B-type metro train were selected. The acceleration signals were measured at the center-points of the main span and one side-span, and the acceleration signals of the car body and the bogie frame were measured simultaneously. The train-bridge system's vibration characteristics and any correlations with time and frequency were investigated. The Choi-Williams distribution method and wavelet coherence were introduced to analyze the obtained acceleration signals of the metro train-bridge system. The results showed that the Choi-Williams distribution provided a more explicit understanding of the time-frequency domain. The correlations between different parts of the bridge and the train-bridge system under braking conditions were revealed. The present study provides a series of measured dynamic responses of the metro train-bridge system under train-braking, which could be used as a reference in further investigations.
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This study carries out a detailed full-scale investigation on the strong wind characteristics at a cable-stayed bridge site and associated buffeting response of the bridge structure during construction, using a field monitoring system. It is found that the wind turbulence parameters during the typhoon and monsoon conditions share a considerable amount of similarity, and they can be described as the input turbulence parameters for the current wind-induced vibration theory. While the longitudinal turbulence integral scales are consistent with those in regional structural codes, the turbulence intensities and gust factors are less than the recommended values. The wind spectra obtained via the field measurements can be well approximated by the von Karman spectra. For the buffeting response of the bridge under strong winds, its vertical acceleration responses at the extreme single-cantilever state are significantly larger than those in the horizontal direction and the increasing tendencies with mean wind velocities are also different from each other. The identified frequencies of the bridge are utilized to validate its finite element model (FEM), and these field-measurement acceleration results are compared with those from the FEM-based numerical buffeting analysis with measured turbulence parameters.
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The wind-sensitive long-span suspension bridge is a vital element in land transportation. Understanding the wind characteristics at the bridge site is thus of great significance to the wind- resistant analysis of such a flexible structure. In this study, a strong wind event from a landfall typhoon called Soudelor recorded at the Jiangyin Bridge site with the anemometer is taken as the research object. As inherent time-varying trends are frequently captured in typhoon events, the wind characteristics of Soudelor are analyzed in a non-stationary perspective. The time-varying mean is first extracted with the wavelet-based self-adaptive method. Then, the non-stationary turbulent wind characteristics, e.g.; turbulence intensity, gust factor, turbulence integral scale, and power spectral density, are investigated and compared with the results from the stationary analysis. The comparison highlights the importance of non-stationary considerations of typhoon events, and a transition from stationarity to non-stationarity for the analysis of wind effects. The analytical results could help enrich the database of non-stationary wind characteristics, and are expected to provide references for the wind-resistant analysis of engineering structures in similar areas.
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Anoectochilus roxburghii polysaccharides exhibit notable hepatoprotective effects, but the underlying substance basis and mechanisms remain unknown. In this study, four new polysaccharides named ARP-1a, ARP-1b, ARP-2a and ARP-2b, were isolated from A. roxburghii. Their structural characteristics were systematically analyzed using HPGPC, HPLC, GC-MS, IR and NMR analysis. ARP-1a, the leading polysaccharide isolated from A. roxburghii, was further evaluated for its hepatoprotective effects on acute liver injury mice induced by CCl4. ARP-1a significantly reduced the serum ALT, AST, TNF-α, IL-1ß and IL-6 levels, liver MDA content, and increased the SOD and CAT activities and GSH level in liver. H&E staining revealed that ARP-1a pretreatment could markedly relieve liver injury. Further mechanism exploration indicated that ARP-1a could relieve CCl4-induced oxidative damage through activating the Nrf2 signaling. In addition, metabolomics, lipidomics and 16S rRNA amplicon sequencing were used to elucidate the underlying mechanisms of ARP-1a. Multi-omics analysis indicated that ARP-1a exerted hepatoprotective effect against CCl4-induced acute liver injury by regulating lipid metabolism and modulating the gut microbiota. In conclusion, the above results suggest that ARP-1a can be considered a promising and safe candidate for hepatoprotective drug, as well as a potential prebiotic for maintaining intestinal homeostasis and promoting human intestinal health.
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ETHNOPHARMACOLOGICAL RELEVANCE: Anoectochilus elatus Lindl. was traditionally used for pain treatment and Gooderoside A (GA) was regarded as its principal constituent. AIM OF THE STUDY: To investigate whether GA can be responsible for the antinociceptive activity of A. elatus and explore its underlying mechanism. MATERIALS AND METHODS: Acetic acid-induced abdominal writhing and tail flick tests were employed to evaluate the antinociceptive activity of ethanolic extract of A. elatus (EEA) and GA. Formalin test was used to ascertain the antinociceptive pattern of GA. Entobarbital sodium induced sleep test was adopted to exclude its hypnotic effect, while open-field test was performed to rule out its motor impairment effect. Chronic constriction injury (CCI)-induced neuropathic pain in rats was developed to evaluate its efficacy on neuropathic pain, and BV-2 cells were used to explore the underlying mechanism. RESULTS: EEA and GA, significantly inhibited chemical and thermal nociception. GA suppressed nociception in formalin test in both phase I and II, whereas methylene blue and L-NAME partially reversed its efficacy. GA located inner and slightly blocked sodium channel current, and did not show any hypnotic effect or motor impairment effect. Crucially, GA markedly attenuated chronic neuropathic pain in rats, inhibited the phosphorylation of IRAK4, IRAK1 and TAK1, and suppressed MAPKs pathway in BV-2 cells. CONCLUSION: GA relieved acute and chronic pains in vivo. The mechanism of action involves the blocking of NO/cGMP and IRAK4/IRAK1/TAK1 pathways. These results suggested GA may be a promising candidate for antinociceptive drug development.
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Dolor Crónico , Neuralgia , Ratas , Animales , Dolor Crónico/tratamiento farmacológico , Analgésicos/farmacología , Analgésicos/uso terapéutico , Quinasas Asociadas a Receptores de Interleucina-1 , Neuralgia/tratamiento farmacológico , GMP Cíclico , Transducción de Señal , Hipnóticos y SedantesRESUMEN
BACKGROUND: Trichoderma species are rich source of bioactive secondary metabolites. In the past decades, a series of secondary metabolites were reported from different Trichoderma fungi, among which terpenoids possessing versatile structural diversities and extensive pharmacological activities are one of the particularly important categories. AIM OF REVIEW: The review aims to summarize the terpenoids isolated from Trichoderma species regarding their structural diversities, biological activities, and promising biosynthetic potentials. KEY SCIENTIFIC CONCEPTS OF REVIEW: So far, a total of 253 terpenoids, including 202 sesquiterpenes, 48 diterpenes, 2 monoterpenes and 1 meroterpenoid, were isolated and identified from Trichoderma species between 1948 and 2022. Pharmacological investigations of Trichoderma terpenoids mainly focused on their antibacterial activities, antifungal activities, inhibitory activities on marine plankton species and cytotoxic activities, indicating that Trichoderma species are important microbial agents for drug discovery and environmentally friendly agrochemicals development. Intriguing chemistry and enzymology involved in the biosynthesis of Trichoderma terpenoids were also presented to facilitate further precise genome mining-guided novel structure discovery. Taken together, the abundance of novel skeletons, bioactivities and biosynthetic potentials presents new opportunities for drug and agrochemicals discovery, genome mining and enzymology exploration from Trichoderma species. The work will provide references for the profound study of terpenoids derived from Trichoderma, and facilitate further studies on Trichoderma species in the areas of chemistry, medicine, agriculture and microbiology.
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Sesquiterpenos , Trichoderma , Terpenos/metabolismo , Trichoderma/química , Trichoderma/genética , Trichoderma/metabolismo , Suelo , Sesquiterpenos/química , Sesquiterpenos/metabolismo , Antifúngicos/farmacologíaRESUMEN
Anoectochilus elatus is a new record species from Yunnan province in China discovered by our group in 2018, used in folk as the most popular Anoectochilus species A. roxburghii for medicinal and culinary purposes. The crude polysaccharide of Anoectochilus elatus (AEP) exhibited significant antinociceptive effects against both chemical and thermal nociception in vivo. Bio-guided isolation identified GJXL-1 as the leading analgesic polysaccharide in AEP. Detailed structural analyses rationalized GJXL-1 (molecular weight: 10.3 kDa) as an α-D-1,4-linked glucan unexpectedly branched at O-3, and O-6 position. GJXL-1 dose-dependently suppressed acetic acid-induced writhing in mice and decreased the serum levels of NO, IL-6 and TNF-α, which also repressed the licking times in both the first and second phases in formalin test. Furthermore, only L-nitroarginine partly reversed the analgesic activity of GJXL-1, indicating that GJXL-1's efficacy was partially mediated by NO regulation, possibly through inhibiting IRAK4/TAK1/NF-κB signaling pathway, and modulating gut microbiota and short-chain fatty acids production. In addition, the motor impairment and hypnotic effects of GJXL-1 were excluded. Our study suggests that GJXL-1 can be regarded as a promising and safe drug candidate for diverse pain disorders, and also a promising prebiotic candidate to maintain intestinal homeostasis and promote human gut health.
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Analgésicos , Polisacáridos , Ratones , Humanos , Animales , China , Polisacáridos/química , Analgésicos/farmacología , Glucanos , Ácido Acético , Extractos Vegetales/químicaRESUMEN
A new species of Anoectochilus (Orchidaceae) from Guangxi, China, A.zhongshanensis, is described here, which was identified based on phylogenetic studies adopting combined plastid markers (rbcL-matK-trnL-F), morphological observation and chemical analysis. Molecular phylogenetic results support the systematic status of A.zhongshanensis as a new species in Anoectochilus genus. Morphologically, this new species is similar to A.zhejiangensis and A.malipoensis, but differs by its characteristic labellum and column, including the hastate or scalpel-shaped lobes of epichile, forward curved and pinnately divided cristate lobes at both sides of the mesochile and inverted triangle column wings. Furthermore, HPLC-ELSD analysis of these three species revealed the interesting chemotaxonomic difference that the principle and characteristic lactone glycoside in this new species was kinsenoside, rather than its diastereoisomer, goodyeroside A, a major glycoside in A.zhejiangensis and A.malipoensis.
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Two new polysaccharides, AZP-1a and AZP-1d, with molecular weights of 3.41 × 104 and 4568 Da, respectively, were extracted from Anoectochilus zhejiangensis and purified by column chromatography. Their structural characteristics were systematically explored and results indicated AZP-1a and AZP-1d shared a similar backbone consisted ofâ4)-Galp-(1â, â4)-Glcp-(1â, and â4,6)-Glcp-(1â, with a different terminal residue of Manp-(1 â and Glcp-(1â, respectively. In vivo experiments showed that the crude polysaccharide of A. zhejiangensis (AZP) exhibited significant hepatoprotective effects, decreasing the serum levels of ALT, AST and LDH in CCl4-treated mice, reducing MDA content, promoting SOD and CAT activities, and increasing GSH level in liver. Further in vitro investigation exhibited that AZP, AZP-1a and AZP-1d effectively protected liver cells against CCl4-stimulated oxidative damage, while AZP-1a and AZP-1d functioned mainly through the activation of Nrf2 signaling pathway. Our results suggest that A. zhejiangensis polysaccharides can be applied as a potential resource for the development of hepatoprotective drugs.
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PolisacáridosRESUMEN
The unprecedented COVID-19 pandemic has caused a traffic tie-up across the world. In addition to home quarantine orders and travel bans, the social distance guideline of about six feet was enacted to reduce the risk of contagion. However, with recent life gradually returning to normal, the crisis is not over. In this research, a moving train test and a Gaussian puff model were employed to investigate the impact of wind raised by a train running on the transmission and dispersion of SARS-CoV-2 from infected individuals. Our findings suggest that the 2 m social distance guideline may not be enough; under train-induced wind action, human respiratory disease-carrier droplets may travel to unexpected places. However, there are deficiencies in passenger safety guidelines and it is necessary to improve the quantitative research in the relationship between train-induced wind and virus transmission. All these findings could provide a fresh insight to contain the spread of COVID-19 and provide a basis for preventing and controlling the pandemic virus, and probe into strategies for control of the disease in the future.
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COVID-19 , Pandemias , Humanos , Cuarentena , SARS-CoV-2 , VientoRESUMEN
Chemical investigation on the solid rice culture of Chaetomium globosum D38, an endophytic fungus derived from Salvia miltiorrhiza, has afforded two new 19,20-seco-chaetoglobosins, salchaetoglobosins A (1) and B (2), along with three known analogues, chaetoglobosins E (3), Fex (4), and Vb (5). Their structures and absolute configurations were elucidated by a set of spectroscopy and single-crystal X-ray crystallography. Compounds 1-5 were evaluated for their cytotoxic activities against HCT-116 (colorectal carcinoma) and PC3 (prostate cancer) cells, as well as the NO production inhibitory effects in LPS-stimulated RAW264.7 cells.
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Antiinflamatorios/farmacología , Antineoplásicos/farmacología , Chaetomium/química , Alcaloides Indólicos/farmacología , Salvia miltiorrhiza/microbiología , Animales , Antiinflamatorios/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , China , Ensayos de Selección de Medicamentos Antitumorales , Células HCT116 , Humanos , Alcaloides Indólicos/aislamiento & purificación , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Células PC-3 , Células RAW 264.7RESUMEN
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.