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1.
Sci Total Environ ; 926: 171934, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38527536

RESUMEN

Climate change can significantly alter phytoplankton growth and proliferation, which would counteract restoration efforts to control algal blooms. However, the knowledge is limited about the quantitative evaluation of the causal effect of algal biomass resurgence in large shallow lakes where there is no significant improvement after long term lake restoration. Here, a bucket process-based phytoplankton dynamic model is developed to quantify the contributions of climate change and nutrients concentration changes to phytoplankton biomass resurgence after 2014 in hypereutrophic Lake Taihu, China. Compared to 2008-2014, the mean water temperature (WT) and the mean phosphate are higher, the mean photosynthetically active radiation (PAR), the mean total suspended solids (TSS), and the mean dissolved inorganic nitrogen (DIN) are lower, during 2015-2020. Their contribution to algal biomass resurgence during 2015-2020 is WT (+58.7 %), PAR (-2.6 %), TSS (+23.2 %), DIN (-22.1 %) and phosphate (+42.7 %), respectively. Climate change (WT, PAR, and TSS), which contributed +64.9 % to the phytoplankton biomass resurgence, underscores the urgent need to continuously take more effective measures to reduce nutrient emissions to offset the effects of climate change in Lake Taihu and in other eutrophic lakes.


Asunto(s)
Cambio Climático , Lagos , Biomasa , Monitoreo del Ambiente , Fitoplancton , Eutrofización , China , Fosfatos , Nitrógeno , Fósforo/análisis
2.
Carbohydr Polym ; 327: 121668, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38171659

RESUMEN

The great structural and functional diversity supports polysaccharides as favorable candidates for new drug development. Previously we reported that a drug candidate pectin-like natural polysaccharide, RN1 might target galectin-3 (Gal-3) to impede pancreatic cancer cell growth in vivo. However, the quality control of polysaccharide-based drug research faces great challenges due to the heterogeneity. A potential solution is to synthesize structurally identified subfragments of this polysaccharide as alternatives. In this work, we took RN1 as an example, and synthesized five subfragments derived from the putative repeating units of RN1. Among them, pentasaccharide 4 showed an approximative binding affinity to Gal-3 in vitro, as well as an antiproliferative activity against pancreatic BxPC-3 cells comparable to that of RN1. Further, we scaled up pentasaccharide 4 to gram-scale in an efficient synthetic route with a 6.9 % yield from D-galactose. Importantly, pentasaccharide 4 significantly suppressed the growth of pancreatic tumor in vivo. Based on the mechanism complementarity of galactin-3 inhibitor and docetaxel, the combination administration of pentasaccharide 4 and docetaxel afforded better result. The result suggested pentasaccharide 4 was one of the functional structural domains of polysaccharide RN1 and might be a leading compound for anti-pancreatic cancer new drug development.


Asunto(s)
Carcinoma , Neoplasias Pancreáticas , Humanos , Pectinas/química , Docetaxel , Polisacáridos/farmacología , Neoplasias Pancreáticas/tratamiento farmacológico , Oligosacáridos , Galectina 3/metabolismo
3.
Chin J Nat Med ; 21(12): 886-901, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38143103

RESUMEN

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-ß-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain ß-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of ß-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in ß-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.


Asunto(s)
Glicósidos , Manósidos , Glicosilación , Estereoisomerismo
4.
Int J Biol Macromol ; 248: 125785, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37451376

RESUMEN

Achyranthes bidentata (A. bidentata) is a famous traditional Chinese medicine (TGM) for treatment osteoporosis. Polysaccharides, a major factor for shaping the gut microbiota, are the primary ingredients of A. bidentata. However, bioactivity of A. bidentata polysaccharide on human gut microbiota (HGM) remains unknown. Here, a homogeneous pectic polysaccharide A23-1 with average molecular weight of 93.085 kDa was extracted and purified from A. bidentata. And A23-1 was compsed of rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose in a molar ratio of 7.26: 0.76: 5.12: 2.54: 23.51: 60.81. GC-MS, partial acid hydrolysis and NMR results indicated the backbone of A23-1 was composed of 1, 2, 4-Rhap and 1, 4-GlapA, while the branches were composed of galactose, arabinose, glucose and glucuronic acid. Further, A23-1 was found to be degraded into monosaccharides and fragments. Taking Bacteroides thetaiotaomicron (BT) as a model, we suggested three polysaccharide utilization loci (PULs) might be involved in the A23-1 degradation. Degraded products generated by BO might not support the growth of probiotics. Besides, acetate and propionate as the main end products were generated by Bacteroides spp. and probiotics utilizing A23-1. These findings suggested A23-1 was possible one of food sources of human gut Bacteroides spp.


Asunto(s)
Achyranthes , Bacteroides thetaiotaomicron , Humanos , Pectinas , Achyranthes/química , Galactosa , Arabinosa/metabolismo , Polisacáridos/química , Bacteroides thetaiotaomicron/metabolismo , Glucosa , Ácido Glucurónico
5.
Fitoterapia ; 169: 105552, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37257698

RESUMEN

The accumulation of amyloid ß (Aß) containing senile plaques is one of the key histopathological hallmarks of Alzheimer's disease (AD). Increasing evidences demonstrated the important role of autophagy in Aß clearance. Recent studies implied that extracts from Semiaquilegia adoxoides (DC.) Makino could ameliorate the memory of D-galactose induced aging mice. However, the bioactive substance and underlying mechanism remains unknown. Thus, the present study sought to explore the effects of a novel homogenous peptidoglycan on Aß42 secretion and the underlying mechanism. Briefly, we extracted a novel peptidoglycan named SA02C using hot water extraction and alcohol precipitation with the Mw of 13.72 kDa. SA02C contains 73.33% carbohydrate and 27.83% protein. The structure characterization revealed that its glycan part might mainly composed of galacturonic acid with minor rhamnose in backbone, and branched with glucose, galactose, arabinose, xylose and galacturonic acid. The protein or peptide moiety in SA02C was bonded to the polysaccharide via threonine. Bioactivities test showed that SA02C could reduce Aß42 production in a dose dependent manner with no obvious cytotoxicity. Mechanism study demonstrated that SA02C could modulate APP processing by upregulating the expression of ADAM10, sAPPα and downregulating BACE1, sAPPß. Furthermore, SA02C also could stimulate autophagy by promoting the expression of the markers of autophagy such as LC3B and ATG5, resulting in the promotion of Aß42 phagocytosis.


Asunto(s)
Enfermedad de Alzheimer , Semiaquilegia , Ratones , Animales , Péptidos beta-Amiloides , Secretasas de la Proteína Precursora del Amiloide , Peptidoglicano , Ácido Aspártico Endopeptidasas/metabolismo , Estructura Molecular , Enfermedad de Alzheimer/tratamiento farmacológico , Autofagia , Polisacáridos
6.
Carbohydr Polym ; 310: 120725, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-36925250

RESUMEN

Age-related bone loss is unavoidable and effective safe drugs are in great need. The fruit of Lycium barbarum was recorded to strengthen bones in the "Ben Cao Gang Mu (Compendium of Materia Medica)". However, there lacks scientific explanation. Herein, we investigated L. barbarum water extract (LBE), L. barbarum polysaccharides (LBP) and the homogeneous polysaccharide LBP1C-2 on the bone loss in adult mouse, aging mouse and ovariectomized mouse models. LBE, LBP and LBP1C-2 all markedly increased bone mass and bone strength in these models and promoted osteoblast proliferation, differentiation and ossification. Mechanistic studies showed that LBP1C-2 binds directly to the BMP receptors (BMPRIA and BMPRII) and noggin, activates the phosphorylation of Smad and disrupts the interaction between noggin and BMPs. Our results clearly elucidate the mechanism, the critical component and the direct targets of L. barbarum and provide potentially safe natural products and new drug candidate against age-related bone loss.


Asunto(s)
Medicamentos Herbarios Chinos , Lycium , Osteoporosis , Ratones , Animales , Polisacáridos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Modelos Animales de Enfermedad , Osteoporosis/tratamiento farmacológico
7.
Int J Biol Macromol ; 234: 123673, 2023 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-36801222

RESUMEN

Polysaccharide is one of the major factors for shaping the gut microbiota. However, bioactivity of polysaccharide isolated from Semiaquilegia adoxoides on human gut microbiota remains unclear. Thus, we hypothesize gut microbes may act on it. Herein, pectin SA02B from the roots of Semiaquilegia adoxoides with molecular weight 69.26 kDa was elucidated. The backbone of SA02B was composed of alternate 1, 2-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 4-, 1, 3- and 1, 3, 6-linked ß-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf and T-, 1, 4-linked-ß-Xylp substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity screening showed SA02B promoted the growth of Bacteroides spp. which deconstructed it into monosaccharide. Simultaneously, we observed competition might exist between Bacteroides spp. and probiotics. Besides, we found that both Bacteroides spp. and probiotics could generate SCFAs grown on SA02B. Our findings highlight SA02B may deserve as a prebiotic to be explored to benefit the health gut microbiota.


Asunto(s)
Microbioma Gastrointestinal , Semiaquilegia , Humanos , Pectinas/química , Polisacáridos/química , Raíces de Plantas/química
8.
Food Funct ; 14(3): 1627-1635, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36688462

RESUMEN

Antibiotic associated diarrhea (AAD) is a common side effect of antibiotic therapy in which gut microbiota plays an important role in the disease. However, the function of gut microbiota in this disease is still not entirely clear. Polysaccharides have shown strong activity in shaping gut microbiota. Whether the polysaccharide can intervene with the microbiota to improve ADD has not been determined. In this study, we extract crude polysaccharides from Nemacystus decipiens (N. decipiens), a traditional Chinese medicine (TCM), named NDH0. The crude polysaccharide NDH0 might significantly relieve the symptom of mice with AAD, including a reduction in body weight, shortening of cecum index and the infiltration of inflammatory cells into the colon. NDH0-treated mice exhibited more abundant gut microbial diversity; significantly increased the abundance of Muribaculum, Lactobacillus, and Bifidobacterium and decreased the abundance of Enterobacter and Clostridioides at genus level. NDH0 treatment down-regulated the level of pro-inflammatory cytokines, including IL-1ß and IL-6 in colon tissue. NDH0 protected the integrity of colon tissues and partially inactivated the related inflammation pathway by maintaining occludin and SH2-containing Inositol 5'-Phosphatase (SHIP). NDH0 could alleviate symptoms of diarrhea by modulating gut microbiota composition, improving intestinal integrity and reducing inflammation. The underlying protective mechanism was to reduce the abundance of opportunistic pathogens and maintain SHIP protein expression. Collectively, our results demonstrated the role of NDH0 as a potential intestinal protective agent in gut dysbiosis.


Asunto(s)
Colitis , Diarrea , Ratones , Animales , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Diarrea/metabolismo , Colitis/inducido químicamente , Antibacterianos/efectos adversos , Colon/metabolismo , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Inflamación/tratamiento farmacológico , Inflamación/inducido químicamente , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
9.
J Agric Food Chem ; 70(32): 9908-9918, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35924862

RESUMEN

The fruit of Fructus Mori is food and medicine, which has been demonstrated to have a significant neuroprotective effect. However, the effective constituent remains unknown. We speculate that the glycopeptide in the extract of the fruit has similar activity. To address this hypothesis, we isolated a novel pectin-like glycopeptide (FMP-6-S4) with a molecular weight of 11.23 kDa from the fruit. It contains about 20% of peptide comprising 17 amino acids and 80% glycan consisting of L-rhamnose (L-Rha), D-galactose (D-Gal), D-galacturonic acid (D-GalA), L-arabinose (L-Ara) and d-glucose (D-Glc) in molar ratios of 7.25:4.62:77.66:5.62:4.85. The backbone of the glycan part consisted of 1,4-linked α-D-GalpA and 1, 2-linked α-L-Rhap, while the branches were composed of hexenuronic acid (HexA) substituted at the C-3 position of partial galacturonic acid, and traces of galactose, glucose, and arabinose were substituted at the C-4 position of rhamnose. The in vitro experiments revealed that FMP-6-S4 might inhibit Aß42 (ß-amyloid peptides 42) aggregation and decrease Aß42 production by modulating APP (amyloid precursor protein) processing.


Asunto(s)
Frutas , Pectinas , Arabinosa/química , Frutas/química , Galactosa/química , Glicopéptidos , Pectinas/química , Polisacáridos/química , Ramnosa
10.
Glycoconj J ; 39(1): 131-141, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35286528

RESUMEN

Antibiotic-associated diarrhea (AAD) is a common side-effect of antibiotic treatment resulting from an imbalance in the colonic bacteria. The hypothesis of this study is to ask whether polysaccharide from the rhizome of Dioscorea opposita which is recorded as conventional herbs and food for diarrhea treatment in Southeast Asia, may be an active compound against diarrhea induced by antibiotics. To address, firstly, a homogenous polysaccharide, DOP0.2-S-3 was characterized as a homogalacturonan containing linear repeating units of → 4)-α-D-GalAp(1 → 4)-α-D-GalAp(1 → with the average molecular weight of 14 kDa. DOP0.2-S-3 significantly reduced the water content and defecation times caused by AAD in mice, while it also remarkably attenuated the cytokines of IL-1ß and IL-6 expression in mice colon tissues. DOP0.2-S-3 decreased potential pathogen and increased Bacteroidetes in the mice gut. These results suggested DOP0.2-S-3 might be a new leading compound for the functional foods or drug candidate development against AAD partially through regulating gut flora.


Asunto(s)
Dioscorea , Animales , Diarrea/inducido químicamente , Diarrea/tratamiento farmacológico , Interleucina-1 , Interleucina-6/genética , Ratones , Pectinas
11.
Carbohydr Polym ; 276: 118772, 2022 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-34823789

RESUMEN

Renal fibrosis is the final common result of a variety of progressive injuries leading to chronic renal failure. However, there are no effective clinical available drugs for the treatment. Notoginsenoside from Panax notoginseng could ameliorate renal fibrosis. We hypothesized that polysaccharide from this herb might have similar bioactivity. Here, we elucidated structure of a novel pectin-like polysaccharide designed SQD4S2 with a netty antenna backbone of glucogalacturonan substituted by glucoarabinan, glucurogalactan and galactose residues from this herb. Interestingly, SQD4S2 could reverse the morphological changes of human renal tubular HK-2 cells induced by TGF-ß. Mechanism study suggested that this bioactivity might associate with N-cadherin (CDH2), Snail (SNAI1), Slug (SNAI2) depression and E-cadherin (CDH1) enhancement. In addition, SQD4S2 could impede critical fibrogenesis associated molecules such as α-SMA, fibronectin, vimentin, COL1A1, COL3A1, FN1 and ACTA2 expression induced by TGF-ß in HK-2 cells. Current findings outline a novel leading polysaccharide for against renal fibrosis new drug development.


Asunto(s)
Enfermedades Renales/metabolismo , Túbulos Renales/metabolismo , Panax notoginseng/química , Pectinas/farmacología , Factor de Crecimiento Transformador beta/metabolismo , Actinas/metabolismo , Cadherinas/metabolismo , Línea Celular , Células Epiteliales/metabolismo , Transición Epitelial-Mesenquimal/efectos de los fármacos , Fibronectinas/metabolismo , Fibrosis/metabolismo , Humanos , Riñón/metabolismo , Riñón/patología , Pectinas/análisis , Pectinas/química , Vimentina/metabolismo
12.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5123-5129, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34738410

RESUMEN

The systematic collation and mining of ethnic medicine literature is the key to the screening and textual research of classic prescriptions. This study focused on the textual research of such key issues as the source of prescriptions, the translation of minority languages into Chinese characters and their corresponding medical terms, the original plants of drugs, and the standard dosage. It is believed that the methods and experience of textual research of classic prescriptions in traditional Chinese medicine(TCM) can be utilized by the ethnic medicine. At the same time, the prominent problems unique to ethnic medicine cannot be neglected.(1)Attention should be paid to extraterritorial traditional medical literature in the textual research of the source of prescriptions. For instance, Indian medical literature is the source of many classic prescriptions in Tibetan medicine, Ibn Sina's Canon of Medicine the source of those in Uygur and Hui medicine, and ancient Indian Buddhist classics the source of those in Dai medicine.(2)The translation and comparison of medical terms in different language systems requires the cooperation of linguists, historians, and medical experts, the combination of historical research, historical linguistics and clinical research methods, and the use of cross-language comparison. In recent years, the related research achievements like multiple translated and annotated versions of classical literature in ethnic medicine and their respective terminology standards have been constantly emerging.(3)In textual research of the original plants of drugs, the following two points deserve attention: one is that the same drug is used in different ethnic medical systems, but there are differences in the understanding of drug properties and active parts; the other is that the original plants of the same drug vary in different ethnic medical systems.(4)The derivation of some classic prescriptions in ethnic medicine from foreign classics results in the difference among measurement systems. In addition, the detailed dosage fails to be covered in some ethnic literature, so the dosage standard should be determined depending on clinical practice and expert consensus.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Medicina Tradicional Tibetana , Prescripciones , Publicaciones
13.
Carbohydr Polym ; 272: 118534, 2021 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-34420703

RESUMEN

Although the polysaccharide utilization loci (PULs) activated by pectin have been defined, due to the complex of side-chain structure, the degradative mechanisms still remain vague. Thus, we hypothesize that there may have other specific PULs to target pectin. Here, we characterize loci-encoded proteins expressed by Bacteroides thetaiotaomicron (BT) that are involved in the pectin capturing, importation, de-branching and degradation into monosaccharides. Totally, four PULs contain ten enzymes and four glycan binding proteins which including a novel surface enzyme and a surface glycan binding protein are identified. Notably, PUL2 and PUL3 have not been reported so far. Further, we show that the degradation products support the growth of other Bacteroides spp. and probiotics. In addition, genes involved in this process are conservative in other Bacteroides spp. Our results further highlight the contribution of Bacteroides spp. to metabolism the pectic network.


Asunto(s)
Bacteroides thetaiotaomicron , Glicósido Hidrolasas , Cristalografía por Rayos X , Sitios Genéticos , Pectinas , Polisacáridos
14.
Carbohydr Polym ; 267: 118172, 2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34119144

RESUMEN

The fruit of Lycium ruthenicum Murr is used as traditional medicine and functional food. Previously we reported that one RG-I pectin from this fruit might inhibit pancreatic cancer cells growth. We further hypothesized that there might be other type of polysaccharides in this fruit also have anti-tumor effect. Here, we showed novel structure of a homogeneous polysaccharide named LRP1-S2 from this fruit and its anti-pancreatic cancer effect. Structure analyses suggested that LRP1-S2 was a novel arabinogalactan with the molecular weight (Mw) of 17.0 kDa. Bioactivity test showed that LRP1-S2 might attenuate the proliferation of pancreatic cancer cells in vitro and in vivo without significant cytotoxicity to normal pancreatic HPDE6-C7 cells and LO2 liver cells. Mechanism study indicated that it might induce apoptosis of BxPC-3 by inactivating P38 MAPK/NF-κB and GSK-3ß/ß-Catenin signaling pathways. These results suggested that LRP1-S2 could be a potential anti-tumor leading compound for functional food and new drug development. CHEMICAL COMPOUNDS: arabinogalactan, pectin, galactan, arabinan, RN-1, HH1-1, LRP1-S2, LRP3-S1.


Asunto(s)
Antineoplásicos/uso terapéutico , Galactanos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antineoplásicos/toxicidad , Apoptosis/efectos de los fármacos , Secuencia de Carbohidratos , Línea Celular , Proliferación Celular/efectos de los fármacos , Frutas/química , Galactanos/química , Galactanos/aislamiento & purificación , Galactanos/toxicidad , Humanos , Lycium/química , Ratones Endogámicos BALB C , Ratones Desnudos , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Int J Biol Macromol ; 181: 357-368, 2021 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-33774071

RESUMEN

Inflammatory bowel disease (IBD) afflicted individual and most medications have side-effects. Crataegus pinnatifida (Hawthorn), which is a safe medicine and food homolog plant, has been reported to prevent colitis in murine. Yet the bioactivity component and the underlying molecular mechanism remain unclear. Here, we established a direct link between colitis induced by dextran sulphate sodium (DSS) in mice and polysaccharide HAW1-2 isolated from hawthorn. Our results showed HAW1-2 restored the pathological lesions in colon and inhibited the expression of inflammatory cytokines including IL-1ß, IL-6 and TNF-α. Meanwhile, IKKα/ß, IκBα, NF-κB and the phosphorylation levels were inhibited significantly. These findings suggested HAW1-2 could alleviate the inflammation of colon. Further, we found the composition of gut microbiota was modified and Bacteroides including Alistipes and Odoribacter were significantly enriched. Besides, we showed Alistipes and Odoribacter were positively co-related with acetic acid and propionic acid while were negatively co-related with inflammatory cytokines. Finally, we demonstrated the anti-inflammation activity of HAW1-2 might be induced by acetic acid. Together, the present data revealed HAW1-2 could directly modify the gut microbiota, especially for Bacteroides, and generate SCFAs to inhibit colitis. It also implies microbiota-directed intervention in IBD patients should be particularly given more attention.


Asunto(s)
Colitis/tratamiento farmacológico , Colitis/microbiología , Crataegus/química , Ácidos Grasos Volátiles/metabolismo , Microbioma Gastrointestinal , Polisacáridos/uso terapéutico , Ácido Acético/farmacología , Animales , Antiinflamatorios/farmacología , Bacteroides/efectos de los fármacos , Bacteroides/crecimiento & desarrollo , Línea Celular , Colitis/inducido químicamente , Colitis/patología , Colon/efectos de los fármacos , Colon/microbiología , Colon/patología , Sulfato de Dextran , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación/patología , Masculino , Metaboloma , Ratones Endogámicos C57BL , Modelos Biológicos , FN-kappa B/metabolismo , Polisacáridos/farmacología , Ratas , Transducción de Señal/efectos de los fármacos
16.
Food Funct ; 11(8): 6961-6970, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32696775

RESUMEN

Pancreatic cancer is a highly lethal and malignant solid tumor. Treatments for pancreatic cancer are seriously limited because it is highly drug-resistant and immunosuppressive. Hence, it is urgent to explore novel approaches for anti-pancreatic cancer therapy. In this study, we show that S1, a crude polysaccharide from corn silk, may significantly inhibit pancreatic cancer cell proliferation in vitro and in vivo. Further studies reveal that S1 can induce pancreatic cancer cell apoptosis, arrest the cell cycle in S phase and impede pancreatic cancer cell migration and invasion. Moreover, S1 may block the EGFR/PI3K/AKT/CREB signaling pathway to exert its anti-pancreatic cancer activity. However, S1 has almost no toxicity either in vitro or in vivo. These results provide evidence that S1 is a new functional food component that can be developed to fight pancreatic cancer.


Asunto(s)
Antineoplásicos/farmacología , Mezclas Complejas/farmacología , Neoplasias Pancreáticas/terapia , Extractos Vegetales/farmacología , Polisacáridos/farmacología , Zea mays/química , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Receptores ErbB/metabolismo , Alimentos Funcionales/análisis , Humanos , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos
17.
Int J Biol Macromol ; 162: 107-115, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32531363

RESUMEN

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignant carcinomas, which is characterized by apoptosis- and autophagy-dependent tumorigenic growth. Autophagy constitutes a stress adaptation that suppresses apoptosis. To explore new leading compound against PDAC, a pectin-like polysaccharide named RP02-1, was purified from roots of Polygala tenuifolia. Bioactivity test showed that RP02-1 might inhibit pancreatic cancer cells growth in vitro and in vivo. RP02-1 could inhibit pancreatic cancer cell (AsPC-1 and BxPC-3) proliferation, migration and colony formation. Mechanism study suggested that RP02-1 induced pancreatic cancer cells apoptosis, which was detected by Bcl-2 down-regulation, Bax up-regulation and conversion from Caspase 3 to Cleaved Caspase 3. Interestingly, autophagy was suppressed by RP02-1 treatment concentration-dependently through affenuatingBeclin-1, ATG5 and LC3B expression in BxPC-3 cells. In addition, RP02-1 could inhibit autophagy induced by Pennogenin 3-O-beta-chacotrioside. However, RP02-1 had almost no toxicity both in vitro and in vivo. The above results suggested that RP02-1 might be a potential leading compound for new drug candidate development for human PDAC treatment via inducing apoptosis and against autophagy.


Asunto(s)
Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Neoplasias Pancreáticas/tratamiento farmacológico , Polygala/química , Polisacáridos/farmacología , Animales , Caspasa 3/metabolismo , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Humanos , Inmunohistoquímica , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Pancreáticas/metabolismo , Pectinas/farmacología , Pectinas/uso terapéutico , Polisacáridos/aislamiento & purificación , Polisacáridos/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto
18.
Chin J Nat Med ; 18(5): 345-355, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32451092

RESUMEN

Cordycepin (3'-deoxyadenosine) from Cordyceps militaris has been reported to have anti-tumor effects. However, the molecular target and mechanism underlying cordycepin impeding pancreatic cancer cell growth in vitro and in vivo remain vague. In this study, we reported functional target molecule of cordycepin which inhibited pancreatic cancer cells growth in vitro and in vivo. Cordycepin was confirmed to induce apoptosis by activating caspase-3, caspase-9 and cytochrome c. Further studies suggested that MAPK pathway was blocked by cordycepin via inhibiting the expression of Ras and the phosphorylation of Erk. Moreover, cordycepin caused S-phase arrest and DNA damage associated with activating Chk2 (checkpoint kinase 2) pathway and downregulating cyclin A2 and CDK2 phosphorylation. Very interestingly, we showed that cordycepin could bind to FGFR2 (KD = 7.77 × 10-9) very potently to inhibit pancreatic cancer cells growth by blocking Ras/ErK pathway. These results suggest that cordycepin could potentially be a leading compound which targeted FGFR2 to inhibit pancreatic cells growth by inducing cell apoptosis and causing cell cycle arrest via blocking FGFR/Ras/ERK signaling for anti-pancreatic cancer new drug development.


Asunto(s)
Cordyceps/química , Desoxiadenosinas/administración & dosificación , Medicamentos Herbarios Chinos/administración & dosificación , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/fisiopatología , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Animales , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética
19.
Int J Biol Macromol ; 161: 35-43, 2020 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-32473218

RESUMEN

More and more evidences show that pectin polysaccharide may have impact on Aß42, one important molecule implicated in Alzhemer's disease pathology. We speculate special structural motif of pectin might have better bioactivity on Aß42. To address this hypothesis, we reported structure and impact of a novel pectin RP02-1 with the molecular weight of 116.0 kDa from roots of Polygala tenuifolia on Aß42 aggregation and production and the underlying mechanism. Its structure is characterized as a backbone of alternate 1, 2, 4-linked α-Rhap and 1, 4-linked α-GalpA, with branches of terminal (T) -, 1, 3-,1, 4-, 1, 6- and 1, 3, 6-linked ß-Galp, T-, 1, 5- and 1, 3, 5-linked α-Araf substituted at C-4 of 1, 2, 4-linked α-Rhap. Bioactivity study shows that this pectin may significantly block the aggregation of Aß42. We further show that RP02-1 suppresses Aß42 production with no apparent cytotoxicity in both CHO/APPBACE1 and HEK293-APPsw cells. Mechanism study demonstrates that RP02-1 may enhance the expression of insulin-degradation enzyme (IDE) and neprilysin (NEP), which are the main enzymes involved in Aß degradation. These results suggest that RP02-1 may be a candidate leading compound for anti-Alzheimer's disease new drug development by attenuating Aß42 production and inhibiting Aß42 aggregation.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Insulisina/genética , Neprilisina/genética , Pectinas/farmacología , Polygala/química , Agregado de Proteínas/efectos de los fármacos , Línea Celular , Hidrólisis , Insulisina/metabolismo , Espectroscopía de Resonancia Magnética , Peso Molecular , Neprilisina/metabolismo , Pectinas/química , Pectinas/aislamiento & purificación , Proteolisis/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier
20.
Zhen Ci Yan Jiu ; 45(2): 152-6, 2020 Feb 25.
Artículo en Chino | MEDLINE | ID: mdl-32144927

RESUMEN

OBJECTIVE: To observe the effect contralateral needling of in improving pain, edema and limb dysfunction in stroke patients with shoulder-hand syndrome. METHODS: A total of 62 patients with post-stroke shoulder-hand syndrome were divided into a control group and an observation group, 31 cases in each one. The routine treatment with internal medicine and rehabilitation manipulation was adopted in the two groups. Additionally, the routine acupuncture treatment was used in the control group and the contralateral needling techniques was applied in the observation group. The needles were retained for 30 min. The treatment was given once a day for 5 days a week and consecutively for 4 weeks. Before and after treatment, the score of the modified Fugl-Meyer assessment scale (FMA scale), the score of the visual analogue scale (VAS), the score of the hand edema rating and the score of the modified Barthel index (ADL score) were evaluated. RESULTS: The total effective rate was 90.32% (28/31) in the observation group and was 67.74% (21/31) in the control group. The effective rate in the observation group was higher than that in the control group (P<0.05). VAS score, the score of the hand edema rating, FMA score and ADL score were obviously improved as compared with those before treatment in each group and the scores in the observation group were better than those of the control group (P<0.05). CONCLUSION: The contralateral needling therapy of acupuncture is effective for relieving pain and edema as well as improving the motor function of the affected limb in the patients with post-stroke shoulder-hand syndrome.


Asunto(s)
Terapia por Acupuntura , Distrofia Simpática Refleja , Accidente Cerebrovascular , Puntos de Acupuntura , Humanos , Distrofia Simpática Refleja/terapia , Resultado del Tratamiento
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