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BACKGROUND: PRG is derived from Phellinus ribis and is a homogeneous polysaccharide with well-defined structural information. PRG was found to have significant in vitro neurotrophic and neuroprotective activities. Thus, PRG might be a potential treatment for Alzheimer's disease. However, the related mechanisms of action are still unclear, so deeper in vivo experimental validation and the potential mechanisms need to be investigated. PURPOSE: The effects of PRG on AD mice were investigated using Senescence-accelerated SAMP8 mice as an AD model to elucidate the crucial molecular mechanisms. METHODS: PRG was obtained from Phellinus ribis by water-alcohol precipitation, column chromatography, and ultrafiltration. The Morris water maze and novel object recognition behavioral assays were used to evaluate the effects of PRG in AD mice. Nissl staining, the TUNEL apoptosis assay, and Golgi staining were used to assess brain neuronal cell damage, apoptosis, and neuronal status. Enzyme-linked immunosorbent assays, Western blotting, and immunofluorescence were used to explore the impacts of correlated factors and protein pathways under relevant mechanisms. RESULTS: The findings suggest that PRG improved learning ability and spatial memory capacity in SAMP8 mice. PRG hastened the disintegration of ß-amyloid, reduced the content and abnormal accumulation of the toxic Aß1-42 protein, and decreased apoptosis. PRG activated the BDNF/ERK/CREB signaling pathway through a cascade, exerted neurotrophic effects, regulated cell proliferation and differentiation, increased neuronal dendritic branching and spine density, and improved synaptic plasticity. CONCLUSION: PRG promoted ß-amyloid degradation to reduce neuronal damage and apoptosis. It exerted neurotrophic effects by activating the BDNF/ERK/CREB pathway, promoting neuronal dendritic branching and dendritic spine growth, regulating cell proliferation and differentiation, and improving synaptic plasticity, which improved AD. Taken together, as a novel natural active polysaccharide with a well-defined structure, PRG affected AD symptoms in senescence-accelerated mice by interacting with multiple targets. The results indicate that PRG is a promising potential anti-AD drug candidate.
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Doença de Alzheimer , Peptídeos beta-Amiloides , Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Sistema de Sinalização das MAP Quinases , Animais , Masculino , Camundongos , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Apoptose/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Modelos Animais de Doenças , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Memória Espacial/efeitos dos fármacosRESUMO
Ribisin A has been shown to have neurotrophic activity. The aim of this study was to evaluate the neuroprotective effect of ribisin A on injured PC12 cells and elucidate its mechanism. In this project, PC12 cells were induced by H2O2 to establish an injury model. After treatment with ribisin A, the neuroprotective mechanism of ribisin A was investigated by methyl tetrazolium (MTT) assay, Enzyme-linked immunosorbent assay (ELISA), flow cytometric analysis, fluorescent probe analysis, and western blot. We found that ribisin A decreased the rate of lactate dehydrogenase (LDH) release, increased cellular superoxide dismutase (SOD) level, decreased the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), Ca2+ expression and reactive oxygen species (ROS). Moreover, ribisin A significantly increased mitochondrial membrane potential (MMP) and inhibited apoptosis of PC12 cells. Meanwhile, ribisin A activated the phosphorylation of ERK1/2 and its downstream molecule CREB by upregulating the expression of Trk A and Trk B, the upstream molecules of the ERK signaling pathway.
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Catecóis , Peróxido de Hidrogênio , Fármacos Neuroprotetores , Ratos , Animais , Células PC12 , Peróxido de Hidrogênio/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Fármacos Neuroprotetores/farmacologia , Apoptose , Estresse Oxidativo , Sobrevivência CelularRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifolia is used in a variety of Chinese medicine prescriptions for the classic dementia treatment, and polysaccharide is an important active component in the herb. AIM OF THE STUDY: This study investigated the in vivo anti-Alzheimer's disease (AD) activity of the polysaccharide PTPS from Polygala tenuifolia using the senescence-accelerated mouse/prone8 (SAMP8) model and explored its molecular mechanism to lay the foundation for the development of polysaccharide-based anti-AD drugs. MATERIALS AND METHODS: The Morris water maze test (MWM)was used to detect changes in the spatial cognitive ability of mice, and Nissl staining was applied to observe the state of neurons in the classic hippocampus. The levels of acetylcholine (ACh) and acetylcholinesterase (AChE) were measured by ELISA. Immunofluorescence was used to reflect ß-amyloid (Aß) levels in brain tissue. Apoptosis was evaluated by TdT-mediated dUTP Nick-End Labeling (TUNEL) method. The status of dendritic branches and spines was observed by Golgi staining. Meanwhile, the expression levels of recombinant human insulin-degrading enzyme (IDE), brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), extracellular regulated protein kinases (ERK), and cAMP-response element binding protein (CREB) proteins were determined by Western blotting. RESULTS: PTPS improves spatial cognitive deficits in AD mice, reduces cellular damage in the CA3 region of the hippocampus, maintains the balance of the cholinergic system, and exerts an anti-AD effect in vivo. The molecular mechanism of its action may be related to the reduction of Aß deposition as well as the activation of ERK pathway-related proteins with enhanced synaptic plasticity. CONCLUSIONS: PTPS is able to exert anti-AD activity in vivo by mitigating Aß damage and targeting the ERK pathway.
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Doença de Alzheimer , Disfunção Cognitiva , Polygala , Camundongos , Humanos , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Polygala/química , Proteínas Quinases/metabolismo , Sistema de Sinalização das MAP Quinases , Acetilcolinesterase/metabolismo , Hipocampo , Peptídeos beta-Amiloides/metabolismo , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/metabolismo , Modelos Animais de DoençasRESUMO
ETHNOPHARMACOLOGIC RELEVANCE: Rehmannia glutinosa (Gaertn.) DC. (RG) is a widely used herb for clearing heat and cooling the blood. Polysaccharides from Rehmannia glutinosa (Gaertn.) DC. (RGPs) have a variety of biological activities, including antioxidation, hypoglycemia, immune enhancement, hematopoiesis promotion, and antianxiety. AIM OF THE STUDY: This review provides up-to-date and comprehensive information on the extraction and separation methods, structural characteristics, and pharmacological activities of RGPs. A more in-depth study on the structure and clinical pharmacology of the RGPs was investigated. To further explore the pharmacological effects of RGPS, and lay a foundation for the safe clinical application and expansion of application scope. MATERIALS AND METHODS: Use Google Scholar, Scifinder, PubMed, Springer, Elsevier, Wiley, Web of Science and other online database search to collect the literature on extraction, separation, structural analysis and pharmacological activity of RGPs published before December 2022. The key words are "extraction", "isolation", "purification" and "pharmacological action" and "Rehmanniae polysaccharide". RESULTS: Rehmannia glutinosa has been widely used in the treatment of diabetes since ancient times, and is known as one of the "Four Sacred Medicines" for the treatment of diabetes, along with Ginseng, Psidium Guajava and Pueraria Mirifica. The active ingredients of Rehmannia glutinosa that have been studied more in the treatment of diabetes are Rehmannia glutinosa polysaccharide and Rehmannia glutinosa oligosaccharide. The content of polysaccharides varies due to different extraction methods, and separation and purification methods. RGPs have a wide range of pharmacological activities, including antitumor, immunomodulatory, neuroprotective effect, hypoglycemic activity, cardioprotective and antioxidant activities. These pharmacological properties lay a foundation for the treatment of tumors, inflammation, hyperglycemia, myocardial ischemia, oxidative stress and other diseases with RGPs. CONCLUSION: Based on its effects of promoting hematopoiesis, antitumor and enhancing immunity, RGPs have been clinically applied in the treatment of chronic aplastic anemia and esophageal cancer, but other effects of RGPs have not been reflected in the clinical practice. In the future, more in-depth research can be conducted on the molecular structure analysis, toxicity, side effects and clinical pharmacological effects of RGPs to further explore the pharmacological effects of RGPs and to lay the foundation for safe clinical application and expansion of application scope.
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Rehmannia , Rehmannia/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Oligossacarídeos , Hipoglicemiantes , Antioxidantes/farmacologia , Antioxidantes/uso terapêuticoRESUMO
A novel styrylpyrone derivative, named phelliribsin B (1), as well as four biogenetically related known compounds, phellifuropyranoneâ A (2), inoscavinâ C (3), inoscavinâ A (4), and inoscavinâ D (5) were separated and purified from the medicinal fungus Phellinus ribis. The structure of phelliribsinâ B was determined by spectroscopic analysis, and the absolute configuration was assigned by experimental and calculated ECD data. Additionally, the plausible biosynthetic pathway of 1 was also proposed. Compoundâ 1 showed moderately cytotoxic activity against HepG2 and SKOV-3 tumor cell lines with IC50 values of 32.71 and 57.89â µM, respectively. Based on the results of cytotoxicity against HepG2 tumor cells, the structure-activity relationship of compoundsâ 1-4 with similar skeletons was discussed. The styrylpyrone derivatives with similar skeletons have moderately cytotoxic activity and have the potential to play an important role in the anti-tumor treatment.
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Phellinus , Pironas , Antineoplásicos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Fungos/química , Estrutura Molecular , Phellinus/química , Relação Estrutura-Atividade , Pironas/química , Pironas/farmacologiaRESUMO
Alzheimer's disease (AD) is a complex neurodegenerative disorder. The pathology is characterized by the generation of amyloid plaques and neuronal fiber tangles in the brain. Although decades of research have been conducted, there is still a lack of effective treatments and countermeasures. Polysaccharide components of natural origin obtained by extraction and isolation possess a variety of pharmacological activities and medicinal values, and they are receiving increasing attention. Polysaccharides have shown good promise in the field of AD prevention and treatment, and polysaccharides ameliorate AD in multiple ways by targeting different mechanisms with almost no toxic side effects. In this paper, we review the research on polysaccharides of natural sources regulation in AD in recent years and list systematically the possible intervention pathways of polysaccharides targeting different mechanisms.
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Doença de Alzheimer , Doença de Alzheimer/metabolismo , Humanos , Neurônios/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêuticoRESUMO
OBJECTIVES: Crataegus pinnatifida (C. pinnatifida), including C. pinnatifida Bge. and its variant C. pinnatifida Bge. var. major N, E. Br., has traditionally been used as a homologous plant for traditional medicine and food in ethnic medical systems in China. Crataegus pinnatifida, especially its fruit, has been used for more than 2000 years to treat indigestion, stagnation of meat, hyperlipidemia, blood stasis, heart tingling, sores, etc. This review aimed to provide a systematic summary on the botany, traditional uses, phytochemistry, pharmacology and clinical applications of C. pinnatifida. KEY FINDINGS: This plant contains flavonoids, phenylpropanoids, terpenoids, organic acids, saccharides and essential oils. Experimental studies showed that it has hypolipidemic, antimyocardial, anti-ischemia, antithrombotic, anti-atherosclerotic, anti-inflammatory, antineoplastic neuroprotective activity, etc. Importantly, it has good effects in treating diseases of the digestive system and cardiovascular and cerebrovascular systems. SUMMARY: There is convincing evidence from both in vitro and in vivo studies supporting the traditional uses of C. pinnatifida. However, multitarget network pharmacology and molecular docking technology should be used to study the interaction between the active ingredients and targets of C. pinnatifida. Furthermore, exploring the synergy of C. pinnatifida with other Chinese medicines to provide new understanding of complex diseases may be a promising strategy.
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Botânica , Crataegus , Crataegus/química , Simulação de Acoplamento Molecular , Flavonoides/química , Frutas/química , Medicina Tradicional ChinesaRESUMO
The present study was to isolate and purify Bombyx batryticatus cocoonase inhibitor (BBCI) and to evaluate its inhibitory effect on the proliferation of SMCC-7721 cells. BBCI was purified from the crude proteins of Bombyx batryticatus using affinity chromatography with cocoonase as the ligand, its N-terminal amino acid sequence was determined using the Edman degradation method, and its inhibiting activity on SMCC-7721 cell proliferation was detected in vitro using the MTT method and in vivo in tumor-bearing nude mice. The purified BBCI presented as a single band in SDS-PAGE, the molecular weight determined by time-of-flight mass spectrometry was 13,973.63 Da, and its N-terminal amino acid sequence was VRNKRQSNDD. BBCI was a noncompetitive cocoonase inhibitor with an average Michaelis constant of 76.50, and it inhibited cocoonase activity with an inhibition ratio of 1 : 1 (molar). BBCI could inhibit the proliferation of SMCC-7721 cells in vitro with the IC50 being about 260.52 µg/ml within 36 h of treatment and inhibit the SMCC-7721 tumor growth in nude mice by subcutaneous injection of BBCI around the tumor, where the tumor inhibitory effect was dose dependent. BBCI did not significantly influence the spleen coefficient of the mice. In conclusion, to the best of our knowledge, the present study is the first to report that BBCI, which was purified from Bombyx batryticatus, was a serine proteinase inhibitor with antitumor activity.
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INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3ß (GSK3ß)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3ß, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3ß/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.
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Humulus , Sobrecarga de Ferro , Animais , Flavonoides , Glicogênio Sintase Quinase 3 beta/metabolismo , Glicogênio Sintase Quinase 3 beta/farmacologia , Heme Oxigenase-1/metabolismo , Heme Oxigenase-1/farmacologia , Humulus/metabolismo , Ferro/farmacologia , Sobrecarga de Ferro/tratamento farmacológico , Camundongos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/farmacologia , Estresse Oxidativo , Extratos Vegetais/farmacologia , Propiofenonas , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Depression, one of the most common psychiatric disorders, is the fourth leading cause of long-term disability worldwide. A series of causes triggered depression, including psychological stress and conflict, as well as biological derangement, among which stress has a pivotal role in the development of depression. Traditional herbal medicine has been used for the treatment of various disorders including depression for a long history with multi-targets, multi-levels and multi-ways, attracting great attention from scholars. Recently, natural products have been commercialized as antidepressants which have become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated and updated vast amount of data associated with natural products in antidepressant-like activity. AIMS OF THE REVIEW: This review aims to briefly discuss the pathological mechanism, animal models of stress-induced depression, traditional use of herbal medicines and especially recapitulate the natural products with antidepressant activity and their pharmacological functions and mechanism of action, which may contribute to a better understanding of potential therapeutic effects of natural products and the development of promising drugs with high efficacy and low toxicity for the treatment of stress-induced depression. MATERIALS AND METHODS: The contents of this review were sourced from electronic databases including PubMed, Sci Finder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wan Fang, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM). Additional information was collected from Yao Zhi website (https://db.yaozh.com/). Data were obtained from April 1992 to June 2021. Only English language was applied to the search. The search terms were 'stress-induced depression', 'pathological mechanism' in the title and 'stress', 'depression', 'animal model' and 'natural products' in the whole text. RESULTS: Stress-induced depression is related to the monoaminergic system, hypothalamic-pituitary-adrenal (HPA) axis, neuronal plasticity and a series of inflammatory factors. Four main types of animal models of stress-induced depression were represented. Fifty-eight bioactive phytochemical compounds, fifty-six herb medicines and five formulas from traditional Chinese medicine were highlighted, which exert antidepressant effects by inhibiting monoamine oxidase (MAO) reaction, alleviating dysfunction of the HPA axis and nerve injury, and possessing anti-inflammatory activities. CONCLUSIONS: Natural products provide a large number of compounds with antidepressant-like effects, and their therapeutic impacts has been highlighted for a long time. This review summarized the pathological mechanism and animal models of stress-induced depression, and the natural products with antidepressant activity in particular, which will shed light on the action mechanism and clinical potential of these compounds. Natural products also have been a vital and promising source for future antidepressant drug discovery.
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Antidepressivos/farmacologia , Produtos Biológicos/farmacologia , Depressão , Fitoterapia/métodos , Plantas Medicinais/classificação , Estresse Psicológico/complicações , Animais , Depressão/tratamento farmacológico , Depressão/etiologia , Depressão/imunologia , Depressão/metabolismo , Descoberta de Drogas , Humanos , Medicina Tradicional Chinesa/métodosRESUMO
OBJECTIVES: Xanthohumol (XAN) is a unique component of Humulus lupulus L. and is known for its diverse biological activities. In this study, we investigated whether Xanthohumol could ameliorate memory impairment of APP/PS1 mice, and explored its potential mechanism of action. METHODS: APP/PS1 mice were used for in vivo test and were treated with N-acetylcysteine and Xanthohumol for 2 months. Learning and memory levels were evaluated by the Morris water maze. Inflammatory and oxidative markers in serum and hippocampus and the deposition of Aß in the hippocampus were determined. Moreover, the expression of autophagy and apoptosis proteins was also evaluated by western blot. KEY FINDINGS: Xanthohumol significantly reduced the latency and increased the residence time of mice in the target quadrant. Additionally, Xanthohumol increased superoxide dismutase level and reduced Interleukin-6 and Interleukin-1ß levels both in serum and hippocampus. Xanthohumol also significantly reduced Aß deposition in the hippocampus and activated autophagy and anti-apoptotic signals. CONCLUSIONS: Xanthohumol effectively ameliorates memory impairment of APP/PS1 mice by activating mTOR/LC3 and Bax/Bcl-2 signalling pathways, which provides new insight into the neuroprotective effects of Xanthohumol.
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Peptídeos beta-Amiloides/metabolismo , Flavonoides/farmacologia , Hipocampo/efeitos dos fármacos , Humulus/química , Transtornos da Memória/metabolismo , Propiofenonas/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Proteína X Associada a bcl-2/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Apoptose , Autofagia , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Memória/efeitos dos fármacos , Transtornos da Memória/tratamento farmacológico , Camundongos Transgênicos , Proteínas Associadas aos Microtúbulos/metabolismo , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Extratos Vegetais/farmacologia , Presenilina-1/metabolismo , Transdução de SinaisRESUMO
Three new benzofuran derivatives, namely ribisin E (1) ribisin F (2) along with ribisin G (3) were isolated from the MeOH extract of the fruiting bodies of Phellinus ribis. Their structures were elucidated based on the NMR analysis. Furthermore, the absolute configuration of ribisin E (1) and ribisin G (3) were deduced by the CD calculations, and the absolute configuration of ribisin F (2) was determined by comparing its CD spectrum and specific rotation with the data of known analogues. All compounds (1-3) exhibited the activity of promoting neurite outgrowth in nerve growth factor (NGF)-ediated PC 12 cell at concentrations ranging from 1 to 30 µM.
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Benzofuranos , Fator de Crescimento Neural , Animais , Benzofuranos/farmacologia , Neuritos , Células PC12 , Phellinus , RatosRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal plant widely distributed in India, Malaysia, Thailand, and the southeastern coastal areas of China including Fujian, Guangdong, and Guizhou. It has been used for centuries for the treatment of wind-cold cough, fever, rheumatism arthralgia, diarrhea dysentery, postpartum foot swelling, stomachache, toothache, diabetes, and traumatic injury. AIMS OF THE REVIEW: To critically anayze the literature for the botany, traditional uses, phytochemistry, pharmacology, toxicity, and clinical trials of P. sarmentosum in order to provide a scientific consensus for further research and discovery of potential candidate drugs. MATERIALS AND METHODS: The contents of this review were sourced from electronic databases including PubMed, SciFinder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wanfang, Chinese Scientific and Technological Periodical Database (VIP), Chinese Biomedical Database (CBM), Cochrane Controlled register of Clinical Trials, Clinical Trials. gov, and Chinese Clinical Trial Registry. Chinese medicine books published over the years were used to elucidate the traditional uses of P. sarmentosum and additional information was also collected from Yao Zhi website (https://db.yaozh.com/). RESULTS: Phytochemical analyses of the chemical constituents of P. sarmentosum include essential oil, alkaloids, flavonoids, lignans, and steroids. The literature supports the ethnomedicinal uses of P. sarmentosum for the treatment of cold, gastritis, and rheumatoid joint pain, and further confirms its relatively new pharmacological activities, including anti-inflammatory, antineoplastic, and antipyretic activities. Other biological roles such as anti-osteoporosis, antibacterial, antidepressant, anti-atherosclerotic, and hypoglycemic activities have also been reported. However, the methodologies employed in individual studies are limited. CONCLUSIONS: There is convincing evidence from both in vitro and in vivo studies supporting the traditional use of P. sarmentosum and it is imperative that natural bioactive compounds are examined further. More efforts should be focused on the pharmacodynamic constituents of P. sarmentosum to provide practical basis for quality control, and additional studies are needed to understand the mechanism of their action. Further studies on the comprehensive evaluation of medicinal quality and understandings of serum chemistry, multi-target network pharmacology, and molecular docking technology of P. sarmentosum are of great importance and should be considered.
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Medicamentos de Ervas Chinesas/uso terapêutico , Etnobotânica/métodos , Etnofarmacologia/métodos , Medicina Tradicional Chinesa/métodos , Compostos Fitoquímicos/uso terapêutico , Piper , Animais , Anti-Infecciosos/química , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/uso terapêutico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Etnobotânica/tendências , Etnofarmacologia/tendências , Humanos , Medicina Tradicional Chinesa/tendências , Simulação de Acoplamento Molecular/métodos , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Fitoterapia/métodos , Fitoterapia/tendênciasRESUMO
Previous studies have demonstrated that the sulfated polysaccharide named PRP-S16 could inhibit the proliferation, migration, and tube formation of endothelial cells in vitro. Here, its anti-angiogenic effect and mechanism in vivo were investigated by Lewis lung carcinoma (LLC) mice model. PRP-S16 significantly reduced the microvessel density (MVD) of tumor, exhibiting a high tumor growth inhibitory effect in LLC mice. All designed assays including quantitative real-time PCR, immunohistochemistry, enzyme-linked immunosorbent assay and western blotting showed that PRP-S16 reduced the mRNA and the protein expression of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR-2) in serum or tumor tissue of mice. Western blotting also detected decreased phosphorylated (p)-VEGFR-1, p-VEGFR-2, hypoxia-inducible factor-1α (HIF-1α), protein kinase B (Akt), and matrix metalloproteinases-9 (MMP-9). PRP-S16 had no adverse effects on angiogenesis in non-target organs. These findings suggested that the mechanism of anti-angiogenesis of PRP-S16 in vivo was due to inhibition of VEGF/VEGFR signaling pathway and it might be a promising candidate for tumor by anti-angiogenic therapy.
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Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Phellinus/química , Sulfatos/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Inibidores da Angiogênese/química , Inibidores da Angiogênese/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Transdução de Sinais/efeitos dos fármacos , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cynanchum bungei Decne. (CB) (Asclepiadaceae) and its two related species Cynanchum auriculatum Royle ex Wight. (CA) and Cynanchum wilfordii (Maxim.) Hemsl. (CW) are well known Chinese herbal medicines known by the name Baishouwu. Among them, CB has long been used for nourishing the kidney and liver, strengthening the bones and muscles, and regulating stomachache. However, to date, no comprehensive review on Baishouwu has been published. AIM OF THE REVIEW: This review aims to provide a comprehensive summary on traditional uses, phytochemistry, pharmacology, and toxicology of the three herbal components of Baishouwu with the ultimate objective of providing a guide for future scientific and therapeutic potential use of Baishouwu. MATERIAL AND METHODS: A literature search was undertaken on CB, CA and CW by analyzing the information from scientific databases (SciFinder, Pubmed, Elsevier, Google Scholar, Web of Science, and Baidu Scholar). Information was also gathered from local classic herbal literatures and conference papers on ethnopharmacology and the information provided in this review has been obtained from peer-reviewed papers. RESULTS: Comparative analysis of literature search indicate that ethnopharmacological use of CB was recorded in China, however, CA and CW have been used in China, Korea and Japan. To date, 151 chemical compounds have been isolated from these species, and the major chemical constituents have been revealed to be acetophenones, C21-steroids, terpenoids, and alkaloids. These compounds and extracts have been proven to exhibit significant pharmacological activities, including anti-tumor, anti-inflammatory, immunomodulatory, hypolipidemic, anti-obesity, hepatoprotective, antifungal, antiviral, anti-depressant, vasodilating and estrogenic activities. CONCLUSIONS: CB, CA and CW collectively known as Baishouwu are valuable medicinal herbs with multiple pharmacological activities. The traditional use for nourishing liver is closely associated with the hepatoprotective activity. The available literature performs that various of the activity of Baishouwu can be attributed to acetophenones and C21-steroids. It is high time that more efforts should be focused on the underlying mechanisms of their beneficial bioactivities and the structure activity relationship of the constituents, as well as their potential synergistic and antagonistic effects. The proper toxicology evaluation is crucial to guarantee the safety, efficacy, and eligibility for medical use. Further research on the comprehensive evaluation of medicinal quality and the understanding of multi-target network pharmacology of Baishouwu is in great request.
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Cynanchum , Medicamentos de Ervas Chinesas , Animais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , FitoterapiaRESUMO
Phellinus linteus is a popular medicinal mushroom that is widely used in China, Korea, Japan, and other Asian countries. P. linteus comprises various bioactive components, such as polysaccharides, triterpenoids, phenylpropanoids, and furans, and has proven to be an effective therapeutic agent in traditional Chinese medicine for the treatment and the prevention of various diseases. A number of studies have reported that P. linteus possesses many biological activities useful for pharmacological applications, including anticancer, anti-inflammatory, immunomodulatory, antioxidative, and antifungal activities, as well as antidiabetic, hepatoprotective, and neuroprotective effects. This review article briefly presents the recent progress made in understanding the bioactive components, biological activities, pharmacological applications, safety, and prospects of P. linteus, and provides helpful references and promising directions for further studies of P. linteus.
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Agaricales/química , Basidiomycota/química , Produtos Biológicos/farmacologia , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Humanos , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Estrutura Molecular , Propanóis/química , Propanóis/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/farmacologia , Terpenos/química , Terpenos/farmacologiaRESUMO
Phylloporia ribis is an edible fungus in China. Its fermented mycelia have been approved by the National Health and Family Planning Commission (NHFPC) of PR China for use as a novel food material, but little information on its safety is available. The present research was the first to evaluate acute and subchronic toxicity in experimental animals of fermented Phylloporia ribis mycelia (FPM) following standard procedures. In acute toxicity study, FPM was orally administered to male and female mice twice a day at single dose of 10 g/kg bw. The Maximum Tolerated Dose (MTD) of FPM for mice of both sexes was over 10 g/kg bw. No death and abnormal behaviors occurred during 14 days study except for an increased locomotor activity in three animals. In 90-day feeding study, male and female Sprague-Dawley rats were fed diets containing 10.0%, 5.0%, 2.5%, 1.25% and 0% (control) FPM for 90 days. The treatment caused no effects on mortality, gross pathology, histology, hematology, and blood chemistry, no dose-dependent changes in food consumption, but caused effect on body weight gain compared with control group. The No Observed Adverse-Effect Level (NOAEL) of FPM was greater than 8.7 g/kg bw/day in both sexes of rats.
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Análise de Perigos e Pontos Críticos de Controle/métodos , Lonicera , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Fermentação , Lonicera/genética , Masculino , Dose Máxima Tolerável , Camundongos Endogâmicos ICR , Micélio , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Testes de Toxicidade Aguda , Testes de Toxicidade SubcrônicaRESUMO
Two sulfated derivatives (PRP-S1 and PRP-S2) of a ß-glucan from Phellinus ribis with different degrees of substitution were obtained by chlorosulfonic acid method. The derivatives could block formation of new vessels in zebrafish and inhibit the proliferation of human umbilical vein endothelial cells (HUVECs). The two sulfated derivatives had remarkably high antitumor activities in vivo (in BALB/c mice inoculated with H22 hepatocellular carcinoma) as well as in vitro (against human ovary cancer SKOV-3 cells), without producing any overt signs of general toxicity. The results of immunohistochemistry assay indicated that the derivatives significantly reduced the average number of microvessel density (MVD) and inhibited the expression of vascular endothelial growth factor (VEGF) in tumor. Thus, these derivatives exhibit pronounced antiangiogenic and antitumoral properties. Except for cytotoxic effects on tumor cells, it is reasonable to expect that the antitumoral effects of PRP-S1 and PRP-S2 are mediated via their antiangiogenic properties.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos/farmacologia , Basidiomycota/metabolismo , Glucanos/farmacologia , Neovascularização Patológica/prevenção & controle , beta-Glucanas/química , Inibidores da Angiogênese/química , Animais , Antineoplásicos/química , Basidiomycota/crescimento & desenvolvimento , Sequência de Carboidratos , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Glucanos/química , Células Endoteliais da Veia Umbilical Humana , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Dados de Sequência Molecular , Neoplasias Ovarianas/irrigação sanguínea , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra/crescimento & desenvolvimento , Peixe-Zebra/metabolismoRESUMO
OBJECTIVE: To study the genetic diversity of rDNA ITS sequences in different species of Bai Shouwu, utilize the molecular diversity of ITS sequences to authenticate the different species of Bai Shouwu. METHOD: Firstly, total DNA was extracted from the different species of Bai Shouwu. Secondly, the ITS sequence was amplified by PCR with universal primer of ITS and sequenced after cloning and purification. RESULT: From four species the complete sequence of ITS and 5.8 S rDNA, the partial sequences of 18S rDNA and 26S rDNA were obtained. The rDNA ITS sequences of Cynanchum bungei (sign in No. GU198970 and No. GU479037) were obtained. Ten variable sites among the sequences were found. CONCLUSION: ITS sequence could be used to authenticate the species. The method could be used to identify germplasm resources and authenticate.
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Cynanchum/genética , DNA Espaçador Ribossômico/genética , Cynanchum/classificação , DNA de Plantas/genética , Dados de Sequência MolecularRESUMO
The present study was undertaken with the objective of finding out the comparative analgesic effect of Ligusticum chuanxiong (LC) pieces decoction, LC formula granule decoction, liquored LC pieces decoction and liquored LC formula granule decoction. The analgesic effects were analyzed using the hot plate and acetic-induced writhing test in mice, and antidysmenorrheic effect was observed with primary dysmenorrhea model. The results showed that four kinds of LC decoction had definite effect in delaying incubation period and decreasing the writhing frequency within 30 min. They also effectively relieved dysmenorrhea. Moreover, liquored LC had better analgesic effect than crude LC in four decoctions.