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1.
Biomacromolecules ; 25(6): 3345-3359, 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38700942

RESUMO

The management of diabetic ulcers poses a significant challenge worldwide, and persistent hyperglycemia makes patients susceptible to bacterial infections. Unfortunately, the overuse of antibiotics may lead to drug resistance and prolonged infections, contributing to chronic inflammation and hindering the healing process. To address these issues, a photothermal therapy technique was incorporated in the preparation of wound dressings. This innovative solution involved the formulation of a self-healing and injectable hydrogel matrix based on the Schiff base structure formed between the oxidized Bletilla striata polysaccharide (BSP) and hydroxypropyltrimethylammonium chloride chitosan. Furthermore, the introduction of CuO nanoparticles encapsulated in polydopamine imparted excellent photothermal properties to the hydrogel, which promoted the release of berberine (BER) loaded on the nanoparticles and boosted the antibacterial performance. In addition to providing a reliable physical protection to the wound, the developed hydrogel, which integrated the herbal components of BSP and BER, effectively accelerated wound closure via microenvironment regulation, including alleviated inflammatory reaction, stimulated re-epithelialization, and reduced oxidative stress based on the promising results from cell and animal experiments. These impressive outcomes highlighted their clinical potential in safeguarding the wound against bacterial intrusion and managing diabetic ulcers.


Assuntos
Quitosana , Hidrogéis , Polissacarídeos , Cicatrização , Quitosana/química , Quitosana/análogos & derivados , Quitosana/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Hidrogéis/química , Hidrogéis/farmacologia , Polissacarídeos/química , Polissacarídeos/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Terapia Fototérmica/métodos , Camundongos , Humanos , Berberina/farmacologia , Berberina/química , Ratos , Diabetes Mellitus Experimental/tratamento farmacológico , Cobre/química , Cobre/farmacologia , Masculino , Polímeros/química , Polímeros/farmacologia , Indóis/química , Indóis/farmacologia , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/microbiologia , Nanopartículas/química , Staphylococcus aureus/efeitos dos fármacos , Nanopartículas Metálicas/química
2.
Ecotoxicol Environ Saf ; 260: 115059, 2023 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-37257344

RESUMO

Thermal processing is one of the important techniques for most of the plant-based food and herb medicines before consumption and application in order to meet the specific requirement. The plant and herbs are rich in amino acids and reducing sugars, and thermal processing may lead to Maillard reaction, resulting as a high risk of acrylamide pollution. Acrylamide, an organic pollutant that can be absorbed by the body through the respiratory tract, digestive tract, skin and mucous membranes, has potential carcinogenicity, neurological, genetic, reproductive and developmental toxicity. Therefore, it is significant to conduct pollution determination and risk assessment for quality assurance and security of medication. This review demonstrates state-of-the-art research of acrylamide focusing on the toxicity, formation, contamination, determination, and mitigation in taking food and herb medicine, to provide reference for scientific processing and ensure the security of consumers.


Assuntos
Acrilamida , Temperatura Alta , Acrilamida/toxicidade , Reação de Maillard , Manipulação de Alimentos/métodos , Extratos Vegetais , Contaminação de Alimentos/análise
3.
Environ Toxicol ; 38(5): 1196-1210, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36880448

RESUMO

One of the important monitoring indicators of the air pollution is atmospheric fine particulate matter (PM2.5 ), which can induce lung inflammation after inhalation. Coelonin can alleviate PM2.5 -induced macrophage damage through anti-inflammation. However, its molecular mechanism remains unclear. We hypothesized that macrophage damage may involve the release of inflammatory cytokines, activation of inflammatory pathways, and pyrosis induced by inflammasome. In this study, we evaluated the anti-inflammation activity of coelonin in PM2.5 -induced macrophage and its mechanism of action. Nitric oxide (NO) and reactive oxygen species (ROS) production were measured by NO Assay kit and dichlorofluorescein-diacetate (DCFH-DA), and apoptosis were measured by Flow cytometry and TUNEL staining. The concentration of inflammatory cytokines production was measured with cytometric bead arrays and ELISA kits. The activation of NF-κB signaling pathway and NLRP3 inflammasome were measured by immunofluorescence, quantitative reverse transcription-polymerase chain reaction and western blot. As expected, coelonin pretreatment reduced NO production significantly as well as alleviated cell damage by decreasing ROS and apoptosis. It decreased generation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in PM2.5 -induced RAW264.7 and J774A.1 cells. Moreover, coelonin markedly inhibited upregulating the expression of toll-like receptor (TLR)4 and cyclo-oxygenase (COX)-2, blocked activation of p-nuclear factor-kappa B (NF-κB) signaling pathway, and suppressed expression of NLRP3 inflammasome, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, the results showed that coelonin could protect against PM2.5 -induced macrophage damage via suppressing TLR4/NF-κB/COX-2 signaling pathway and NLRP3 inflammasome activation in vitro.


Assuntos
Inflamassomos , NF-kappa B , NF-kappa B/metabolismo , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ciclo-Oxigenase 2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais , Macrófagos/metabolismo , Citocinas/metabolismo , Interleucina-6 , Anti-Inflamatórios/farmacologia , Material Particulado/toxicidade
4.
Int J Mol Sci ; 24(22)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38003478

RESUMO

The healing process of a diabetic wound (DW) is often impeded by a series of interrelated factors, including severe infection, persistent inflammation, and excessive oxidative stress. Therefore, it is particularly crucial to develop a medical dressing that can address these issues simultaneously. To this end, different ratios of Bletilla striata polysaccharide (BSP) and berberine (BER) were physically blended with Carbomer 940 (CBM940) to develop a composite hydrogel as a medical dressing. The BSP/BER hydrogel was characterized using SEM, FTIR, rheological testing and other techniques. The anti-inflammatory, antioxidant, and antibacterial properties of the hydrogel were evaluated using cell and bacterial models in vitro. A DW model of ICR mice was established to evaluate the effect of the hydrogel on DW healing in vivo. The hydrogel exhibited excellent biocompatibility and remarkable antibacterial, anti-inflammatory, and antioxidant properties. In addition, animal experiments showed that the BSP/BER hydrogel significantly accelerated wound healing in DW mice. Among the different formulations, the LBSP/BER hydrogel (2% BSP, mBER:mBSP = 1:40) demonstrated the most remarkable efficacy. In conclusion, the BSP/BER hydrogel developed exhibited immense properties and great potential as a medical dressing for the repair of DW, addressing a crucial need in clinical practice.


Assuntos
Berberina , Diabetes Mellitus , Animais , Camundongos , Hidrogéis/farmacologia , Berberina/farmacologia , Berberina/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Camundongos Endogâmicos ICR , Cicatrização , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Bandagens , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia
5.
Prep Biochem Biotechnol ; 52(4): 383-393, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34339343

RESUMO

The optimization of extraction of Tetrastigma hemsleyanum Diels et Gilg polysaccharides (THP) using ultrasonic with enzyme method and its monosaccharide compositions and antioxidant activity were investigated in this work. Single-factor experiments and response surface methodology (RSM) were performed to optimize conditions for extraction, and the independent variables were (XA) dosage of cellulase, (XB) extraction time, (XC) ultrasonic power, and (XD) ratio of water to the material. The extraction rate of THP was increased effectively under the optimum conditions, and the maximum (4.692 ± 0.059%) was well-matched the predicted value from RSM. THP was consisted of mannose, glucuronic acid, rhamnose, galacturonic acid, glucose, galactose, and arabinose, while glucose was the dominant (26.749 ± 0.634%). According to the total antioxidant capacity assay with the FRAP method, DPPH, and hydroxyl radical scavenging assay, THP showed strong antioxidant activity with a dose-dependent behavior. The results indicated that THP has the potential to be a novel antioxidant and could expand its application in food and medicine.


Assuntos
Antioxidantes , Vitaceae , Antioxidantes/química , Glucose , Monossacarídeos , Polissacarídeos/química , Vitaceae/química
6.
Neurochem Res ; 46(6): 1423-1434, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33675461

RESUMO

A growing number of studies have shown that air fine particulate matter (PM2.5) pollution is closely associated with neuroinflammation in humans. Militarine, a glucosyloxybenzyl 2-isobutylmalate compound isolated from Bletilla striata, has been found to exert significant neuroprotective effects. However, the anti-inflammatory, antioxidant and antiapoptotic effects of militarine on PM2.5-stimulated BV-2 microglial cells have not been reported. This study aimed to investigate the protective effects of militarine against PM2.5-induced cytotoxicity and its mechanism in BV-2 microglial cells. Our results revealed that pretreatment with 0.31-1.25 µg/mL militarine reversed the morphological changes caused by PM2.5 and decreased proinflammatory cytokine generation and gene expression in PM2.5-treated BV-2 cells. In particular, tumor necrosis factor-α and interleukin-6 expression was inhibited in a dose-dependent manner. Notably, militarine markedly inhibited the upregulation of Toll-like receptor 4, Toll-like receptor 2, and cyclo-oxygenase-2 expression at both the mRNA and protein levels and reduced NF-κB pathway-associated protein expression. Immunofluorescence analysis showed that militarine suppressed NF-κB activity through inhibiting p65 nuclear translocation. Our data suggested that militarine alleviated neuroinflammation in BV-2 microglial cells, possibly by inhibiting the expression of neuroinflammatory cytokines through the TLR/NF-κB signaling pathway. Additionally, militarine significantly reduced PM2.5-mediated reactive oxygen species (ROS) generation and cell apoptosis and restored the mitochondrial membrane potential (MMP; ΔΨm). Collectively, these findings demonstrate that militarine played a protective role against PM2.5-induced damage in BV-2 cells by exerting anti-inflammatory, antioxidant, and antiapoptotic effects.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Material Particulado/toxicidade , Succinatos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Citocinas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição RelA/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 41(1): 106-111, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-28845650

RESUMO

Chrysin is an active flavonoid wildly presented in many herbs. It has the effect to reduce serum lipid. To investigate the effect of chrysin on the adipogenic differentiation of mouse embryonic fibroblasts, methyl thiazolyl tetrazolium (MTT) and crystal violet were used to detect the cytotoxic effect of chrysin on Immortalized mouse embryonic fibroblasts (iMEFs). Propidium iodide (PI) staining combined with flow cytometry (FCM) was employed to detect the effects of different concentrations of chrysin on iMEFs cell cycle. The effect of chrysin on adipogenic differentiation ability of iMEFs was determined by oil red O staining. Semi-quantitative PCR was employed to detect the effect of chrysin on mRNA transcriptional levels of adipogenic differentiation markers, including perilipin 2, adiponectin (adipoq), Fabp4, LPL, MCP-1 and adipogenic differentiation key transcription factor peroxisome proliferators-actiated receptor-gamma 2(PPAR-γ2). Results indicated that chrysin had certain cytotoxic effect for iMEFs in a dose-dependent manner, and the IC50 was identified nearly to 30 µmol•L⁻¹. FCM analysis showed that chrysin could affect the cell-cycle distribution of iMEFs, increasing the ratio of cells in G1 phase. Adipogenic differentiation inducing experiment showed that 30 µmol•L⁻¹ chrysin significantly reduced lipid drops accumulation induced by insulin and dexamethasone. In addition, the mRNA transcriptional levels of PPAR-γ2 and LPL were significantly decreased and mRNA levels of fabp 4, MCP-1, adipoq were also affected after chrysin treatment. The experiment results suggest that chrysin attenuates the adipogenic differentiation capacity of mesenchymal stem cells.


Assuntos
Adipócitos/citologia , Adipogenia/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Flavonoides/farmacologia , Camundongos/embriologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adiponectina/genética , Adiponectina/metabolismo , Animais , Células Cultivadas , Proteínas de Ligação a Ácido Graxo/genética , Proteínas de Ligação a Ácido Graxo/metabolismo , PPAR gama/genética , PPAR gama/metabolismo
8.
Int J Biol Macromol ; 265(Pt 2): 131015, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38521298

RESUMO

The anti-inflammatory activity of polysaccharides derived from Melastoma dodecandrum Lour. was evaluated in pyretic mice and HEK-Blue™ hTLR4 cells. The testing led to the identification of MDP2-1, which was then investigated for its structural characteristics and anti-inflammatory effects. Results showed that MDP2-1 had a molecular weight of 29.234 kDa and primarily consisted of galactose, arabinose, rhamnose, glucose, glucuronic acid, and galacturonic acid. Its main backbone was composed of →4)-α-D-GalpA-(1→, →2)-α-L-Rhap-(1→, →3,4)-α-D-GalpA-(1→, →2,4)-α-D-GlcpA-(1→, and its side chains were connected by →4)-α-D-Galp-(1→, α-D-Galp-(1→, →4)-ß-D-Glcp-(1→, and α-L-Araf-(1→. In vivo experiments on mice demonstrated that MDP2-1 attenuated LPS-induced acute lung injury, and in vitro experiments on RAW264.7 cells showed that MDP2-1 reduced the levels of inflammatory mediators and mitigated LPS-induced inflammatory damage by inhibiting the activation of the TLR4 downstream NF-κB/MAPK pathway. These findings suggest that MDP2-1 is a novel anti-inflammatory agent for therapeutic interventions.


Assuntos
Lipopolissacarídeos , Polissacarídeos , Camundongos , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Galactose , Glucose , Anti-Inflamatórios/farmacologia
9.
J Ethnopharmacol ; 319(Pt 3): 117361, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38380574

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bletilla striata polysaccharides (BSP) extracted from the B. striata tuber, have been demonstrated to possess anti-inflammatory properties. However, their potential protective effect against ARDS and their role in regulating cell pyroptosis remained unexplored. AIM OF THE STUDY: The aim of this study was to investigate the therapeutic effect of BSP in the alleviation of lipopolysaccharide (LPS)-induced ARDS, and to explore its mechanism of action. METHODS: The effect of BSP was assessed by LPS injection into the intraperitoneal cavity in vivo; pathological changes of ARDS mice were gauged by immunohistochemical, hematoxylin and eosin staining, and immunofluorescence assays. MH-S cells were used to model the pyroptosis in vitro. Finally, the pyroptosis of alveolar macrophage was detected by western blots, qPCR, and flow cytometry for NLRP3/caspase1/GSDMD and HMGB1/TLR4 pathway-associated proteins and mRNA. RESULTS: BSP could significantly increase the weight and survival rate of mice with ARDS, alleviate the cytokine storm in the lungs, and reduce lung damage in vivo. BSP inhibited the inflammation caused by LPS/Nigericin significantly in vitro. Compared with the control group, there was a remarkable surge in the incidence of pyroptosis observed in ARDS lung tissue and alveolar macrophages, whereas BSP significantly diminished the pyroptosis ratio. Besides, BSP reduced NLRP3/caspase1/GSDMD and HMGB1/TLR4 levels in ARDS lung tissue and MH-S cells. CONCLUSIONS: These findings proved that BSP could improve LPS-induced ARDS via inhibiting pyroptosis, and this effect was mediated by NLRP3/caspase1/GSDMD and HMGB1/TLR4, suggesting a therapeutic potential of BSP as an anti-inflammatory agent for ARDS treatment.


Assuntos
Proteína HMGB1 , Síndrome do Desconforto Respiratório , Animais , Camundongos , Macrófagos Alveolares , Lipopolissacarídeos/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Receptor 4 Toll-Like , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Pulmão
10.
J Ethnopharmacol ; 323: 117732, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38218501

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Tetrastigma hemsleyanum Diels et Gilg, is one of the perennial evergreen plants with grass vine, which has obvious curative effect on severe infectious diseases. Although Tetrastigma hemleyanum has long been recognized for its capacity of antipyretic and antitoxic, its specific mechanism is unknown. AIM OF THE STUDY: To evaluate the antipyretic effect of Tetrastigma hemleyanum polysaccharide (THP) on mice with dry yeast-induced fever, and to explore its specific antipyretic mechanism. METHODS: In this study, THP was administered by aerosol in febrile mice. The rectal temperatures of treated animals were monitored at different time points. Histopathological evaluation and various inflammatory indexes were used to assess inflammatory damage. The concentration variations of the central neurotransmitter, endocrine system, substance and energy metabolism indicators were measured to explore the physiological mechanism. Quantitative real-time PCR, Western bolt and Immunohistochemistry were performed to identify the correlation between antipyretic and TLR4/NF-κB signaling pathway. RESULTS: THP reduced the body temperature of febrile mice induced by dry yeast, as well as the levels of thermogenic cytokines and downregulated the contents of thermoregulatory mediators. THP alleviated the pathological damage of liver and hypothalamus caused by fever. In addition, THP decreased the secretion of thyroid hormone, substance and energy metabolism related indicators. Furthermore, THP significantly suppressed TLR4/NF-κB signaling pathway-related indicators. CONCLUSIONS: In conclusion, our results suggest that inhaled THP exerts antipyretic effect by mediating the thermoregulatory mediator, decreasing the content of pyrogenic factors to lower the body temperature, and eventually restoring the high metabolic level in the body to normal via inhibiting TLR4/NF-κB signaling pathway. The study provides a reasonable pharmacodynamic basis for the treatment of polysaccharide in febrile-related diseases.


Assuntos
Antipiréticos , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Antipiréticos/farmacologia , Antipiréticos/uso terapêutico , Saccharomyces cerevisiae , Receptor 4 Toll-Like/metabolismo , Transdução de Sinais , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/química , Febre/tratamento farmacológico , Metabolismo Energético
11.
Carbohydr Polym ; 333: 121922, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38494202

RESUMO

A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 105 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.


Assuntos
Receptor 4 Toll-Like , Vitaceae , Animais , Camundongos , Vitaceae/química , Polissacarídeos/química , Macrófagos , Células RAW 264.7
12.
Int J Biol Macromol ; 275(Pt 1): 133424, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945330

RESUMO

The absence of effective therapeutic targets poses considerable obstacles to the treatment of triple-negative breast cancer (TNBC). This study aimed to explore the function and mechanism of polysaccharides derived from the aerial parts of Tetrastigma hemsleyanum (THP) for the treatment of TNBC. THP exerts notable anti-TNBC effects when used alone, and its combination with Doxorubicin (DOX) effectively augments the sensitivity of TNBC cells to DOX. Through RNA sequencing, Fe2+ assays, western blotting, and transmission electron microscopy, THP was identified as a natural inducer of ferroptosis and ferritinophagy through the xCT/GSH/GPX4 and Nrf2/NCOA4/FTH1 pathways. Further research revealed that the THP branched-chain hexose directly binds to the xCT protein to inhibit its expression and promotes ferroptosis. In vivo experiments confirmed the role of THP in inducing ferroptosis and showed that THP improves the tumor microenvironment and immune function by increasing the ratio of CD4+ and CD8+ T cells to regulatory T cells and modulating cytokine levels. As demonstrated by electrocardiography, blood chemistry, and histological analyses, THP alleviates organ toxicity caused by DOX. Overall, these results suggest that THP has significant clinical potential as a natural macromolecular drug and may provide a safe and effective treatment strategy for TNBC when combined with DOX.

13.
Int J Biol Macromol ; 275(Pt 1): 133427, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38936586

RESUMO

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an disease characterized by pulmonary edema and widespread inflammation, leading to a notably high mortality rate. The dysregulation of both pro-inflammatory and anti-inflammatory systems, results in cytokine storm (CS), is intricately associated with the development of ALI/ARDS. Tetrastigma hemsleyanum polysaccharide (THP) exerts remarkable anti-inflammatory and immunomodulatory effects against the disease, although its precise role in pathogenesis remains unclear. In the present study, an ALI/ARDS model was established using bacterial lipopolysaccharides. THP administration via aerosol inhalation significantly mitigated lung injury, reduced the number of inflammatory cells, and ameliorated glycerophospholipid metabolism. Furthermore, specific CS-related pathways were investigated by examining the synergy between tumor necrosis factor-α and interferon-γ used to establish CS models. The results indicated that THP effectively decreased inflammatory damage and cell death. The RNA sequencing revealed the involvement of the Janus kinase (JAK) 2-signal transducers and activators of transcription (STAT) signaling pathway in exerting the mentioned effects. Additionally, THP inhibited the activation of the JAK-STAT pathway, thereby alleviating the CS both in vivo and in vitro. Overall, THP exhibited marked therapeutic potential against ALI/ARDS and CS, primarily by targeting the IFN-γ-JAK2/STAT signaling pathway.

14.
Int Immunopharmacol ; 137: 112404, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-38851163

RESUMO

Ulcerative colitis (UC) is characterized by a chronic and protracted course and often leads to a poor prognosis. Patients with this condition often experience postoperative complications, further complicating the management of their condition. Tetrastigma hemsleyanum polysaccharide (THP) has demonstrated considerable potential as a treatment for inflammatory bowel disease. However, its underlying mechanism in the treatment of UC remains unclear. This study systematically and comprehensively investigated the effects of THP on dextran sulfate-induced UC mice and illustrated its specific mechanism of action. The colon and spleen in UC mice were restored after THP treatment. The levels of key markers, such as secretory immunoglobulin A, ß-defensin, and mucin-2 were increased, collagen deposition and epithelial cell apoptosis were decreased. Notably, THP administration led to increased levels of Ki67 and tight junction proteins in colon tissue and reduced colon tissue permeability. THP contributed to the restored balance of intestinal flora. Furthermore, THP downregulated the expressions of the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-17 and promoted those of the regulatory factors forkhead box protein P3. It also exerted anti-inflammatory effects by promoting suppressor of cytokine signaling (SOCS1) expression and inhibiting the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Our results demonstrated that THP had an efficacy comparable to that of JAK inhibitor in treating UC. In addition, THP might play a role in UC therapy through modulation of the SOCS1/JAK2/STAT3 signaling pathway and remodeling of the intestinal mucosal barrier.


Assuntos
Colite Ulcerativa , Função da Barreira Intestinal , Mucosa Intestinal , Polissacarídeos , Transdução de Sinais , Vitaceae , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colo/efeitos dos fármacos , Colo/patologia , Citocinas/metabolismo , Sulfato de Dextrana , Modelos Animais de Doenças , Função da Barreira Intestinal/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/patologia , Janus Quinase 2/metabolismo , Camundongos Endogâmicos C57BL , Polissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 1 Supressora da Sinalização de Citocina/genética , Vitaceae/química
15.
Environ Sci Pollut Res Int ; 30(2): 2665-2675, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35931855

RESUMO

Pyrethroid insecticides are ubiquitously detected in environmental media, food, and urine samples. Our previous epidemiological study reported a correlation between increased pyrethroid exposure and delayed pubertal development in Chinese girls. In this study, we further investigated the effects of perinatal exposure to low doses of cypermethrin (CP) on pubertal onset and hypothalamic-pituitary-ovarian axis in the female mice offspring. The treatment of CP with 60 µg/kg/day from gestation day 6 (GD6) to postnatal day 21 (PND21) significantly decreased the time to puberty in the female offspring. Exposure of CP increased the serum levels of gonadotropin-releasing hormone (GnRH) and the expression of GnRH genes in a dose-dependent manner in the female offspring. CP also induced the serum levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as the expression of gonadotropin subunit genes [LHß, FSHß, and chorionic gonadotropin α (Cgα)]. Furthermore, CP induced serum estradiol (E2) levels and the expression of steroidogenesis-related genes [steroidogenic acute regulatory (StAR) and Cytochrome p 450, family 11, subfamily A, polypeptide 1 (CYP11A1)] in the ovary. In accordance with the in vivo tests, administration of CP (6.7, 20, and 60 µg/L) stimulated a dose-dependent increase in the synthesis and secretion of the puberty-related hormones in the explants of hypothalamus, pituitary, and ovary. The interference with calcium channels in the ovary may be responsible for CP-induced pubertal onset. Our study provided evidence that perinatal exposure to low doses of CP induced puberty-related hormones and decreased the time to puberty in the female offspring.


Assuntos
Piretrinas , Maturidade Sexual , Feminino , Camundongos , Animais , Hormônio Foliculoestimulante , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/farmacologia , Piretrinas/toxicidade
16.
J Biomater Appl ; 38(3): 424-437, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37599387

RESUMO

Diabetic wounds impose enormous distress and financial burden on patients, and finding effective dressings to manage wounds is critical. As a Chinese herbal medicine with a long history of Clinical application, Bletilla striata has significant medicinal effects in the therapy of various wounds. In this study, PLA and the pharmacodynamic substances of Bletilla striata were prepared into fibrous scaffolds by emulsion electrospinning technology for the management of diabetic wounds in mice. The results of scanning electron microscopy showed that the core-shell structure fibre was successfully obtained by emulsion electrospinning. The fibre membrane exhibited excellent water absorption capability and water vapor transmission rate, could inhibit the growth of Staphylococcus aureus and Pseudomonas aeruginosa, had good compatibility, and achieved excellent healing effect on diabetic wounds. Especially in the in vivo wound healing experiment, the wound healing rate of composite fibre membrane treatment reached 98.587 ± 2.149% in 16 days. This work demonstrated the good therapeutic effect of the developed fibrous membrane to diabetic wound, and this membrane could be potentially applied to chronic wound healing.


Assuntos
Diabetes Mellitus , Nanofibras , Animais , Camundongos , Emulsões , Nanofibras/uso terapêutico , Cicatrização , Microscopia Eletrônica de Varredura , Pseudomonas aeruginosa
17.
Folia Microbiol (Praha) ; 68(1): 121-133, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35982376

RESUMO

Biocontrol fungi are widely used to promote plant growth and pest control. Four fungi were isolated from Cremastra appendiculata tubers and screened for plant growth-promoting and antagonistic effects. Based on the morphological characterization and ITS, 18S rRNA and 28S rRNA gene sequencing analysis, the fungi were identified to be related to Colletotrichum gloeosporioides (DJL-6), Trichoderma tomentosum (DJL-9), Colletotrichum godetiae (DJL-10) and Talaromyces amestolkiae (DJL-15). The growth inhibition tests showed that the four isolates had different inhibitory effects on Colletotrichum fructicola, Alternaria alternata and Alternaria longipes, among which DJL-9 showed the highest inhibitory activity. Their culture filtrates (especially that of DJL-15) can also inhibit pathogens. Four isolates were positive for the production of indole-3-acid (IAA) and ß-1,3-glucanase and possessed proteolytic activity but were negative for the production of iron siderophore complexes. The four fungi showed strong nitrogen fixation and potassium dissolution abilities. In addition to DJL-9 being able to solubilize phosphate, DJL-10 was able to produce chitinase and cellulase. Pot experiments indicated that the four fungi increased the germination rate of C. appendiculata and soybean seeds and increased soybean radicle growth and plant biomass. Among them, DJL-6 had a better growth-promoting effect. Therefore, we successfully screened the biocontrol potential of endophytes from C. appendiculata, with a focus on preventing fungal diseases and promoting plant growth, and selected strains that could provide nutrients and hormones for plant growth.


Assuntos
Fungos , Desenvolvimento Vegetal , Endófitos , Fosfatos , Sementes , Doenças das Plantas/microbiologia
18.
Int J Biol Macromol ; 241: 124419, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37080409

RESUMO

The intestinal mucosal barrier is one of the important barriers to prevent harmful substances and pathogens from entering the body environment and to maintain intestinal homeostasis. This study investigated the reparative effect and possible mechanism of Tetrastigma hemsleyanum polysaccharides (THP) on ceftriaxone-induced intestinal mucosal damage. Our results suggested that THP repaired the mechanical barrier damage of intestinal mucosa by enhancing the expression of intestinal tight junction proteins, reducing intestinal mucosal permeability and improving the pathological state of intestinal epithelial cells. Intestinal immune and chemical barrier was further restored by THP via the increment of the body's cytokine levels, intestinal SIgA levels, intestinal goblet cell number, intestinal mucin-2 levels, and short-chain fatty acid levels. In addition, THP increased the abundance of probiotic bacteria (such as Lactobacillus), reduced the abundance of harmful bacteria (such as Enterococcus) to repair the intestinal biological barrier, restored intestinal mucosal barrier function, and maintains intestinal homeostasis. The possible mechanisms were related to sphingolipid metabolism, linoleic acid metabolism, and D-glutamine and D-glutamate metabolism. Our results demonstrated the potential therapeutic effect of THP against intestinal flora disorders and intestinal barrier function impairment caused by antibiotics.


Assuntos
Antibacterianos , Microbiota , Animais , Camundongos , Antibacterianos/efeitos adversos , Antibacterianos/metabolismo , Mucosa Intestinal/metabolismo , Polissacarídeos/química , Metaboloma
19.
Int J Biol Macromol ; 250: 126167, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37558022

RESUMO

In this study, the therapeutic effects of Tetrastigma hemsleyanum polysaccharide (THP) on inflammatory bowel disease (IBD) and its possible mechanisms were investigated based on the IBD mouse model induced by dextran sodium sulfate (DSS) and the lipopolysaccharide (LPS)-stimulated Caco-2 cell model. THP significantly alleviated the signs and symptoms of DSS-induced IBD mice, including the reduced weight, shortened colonic length, and increased colitis disease activity index. In vivo, THP significantly reduced inflammatory cell infiltration and oxidative damage, promoted intestinal mucus secretion, and restored the integrity of the intestinal epithelial barrier and mucus barrier. Furthermore, THP reversed the changes in the intestinal flora of colonized mice and restored the levels of short-chain fatty acids (SCFAs) by increasing the abundance of potentially beneficial bacteria and increasing the abundance of butyrate-producing bacteria. In addition, THP upregulated the expression of G-protein-coupled receptors (GPR41 and GPR43) both in vivo and in vitro. In summary, the current investigation showed that THP effectively protected against intestinal inflammation and impairment in the intestinal barrier in the setting of DSS-induced IBD, possibly by regulating gut microbiota structure and corresponding SCFA metabolites, and the pathway of SCFAs action may be related to SCFA-GPR41/43 signaling pathway.

20.
Front Pharmacol ; 13: 838873, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370633

RESUMO

Tetrastigma hemsleyanum Diels et Gilg (Sanyeqing, SYQ) has traditionally been used to treat inflammation, high fever and improve immune function of patients. Polysaccharides have been proved to be one of the important components of SYQ. Previous studies have confirmed the antipyretic and antitumor effects of polysaccharides from SYQ (SYQP), and clarified that SYQP could enhance immunity through TLR4 signalling pathway. However, there were more possibilities for the mechanism by which SYQP exerted immunomodulatory effects and the role of SYQP in acute respiratory distress syndrome (ARDS) is elusive. The purpose of this study was further to explain the bidirectional modulation of immunity mechanism of SYQP in vitro and its effect in LPS-induced ARDS in vivo. Experimental results showed that SYQP significantly stimulated gene expressions of TLR1, TLR2 and TLR6 and secretion of cytokines in RAW264.7 cells. Individual or combined application of TLR2 antagonist C29 and TLR4 antagonist TAK-242 could reduce SYQP-mediated stimulation of cytokine secretion in RAW264.7 cells and mouse peritoneal macrophages (MPMs) to varying degrees. On the other hand, SYQP markedly inhibited the expression levels of inflammatory cytokines, NO, iNOS and COX-2 in LPS-treatment RAW264.7 cells. Moreover, in vivo results indicated that SYQP significantly reduced LPS-induced damage in ARDS mice through alleviating LPS-induced pulmonary morphological damage, inhibiting myeloperoxidase (MPO) expression levels, ameliorating the inflammatory cells in bronchoalveolar lavage fluid (BALF) and improving hematological status. Meanwhile, SYQP evidently reduced IL-6, TNF-α and IFN-γ secretion, the overexpression levels of TLR2 and TLR4, as well as the phosphorylation of NF-κB p65. In addition, SYQP reduced the phosphorylation of JAK2 and STAT1 and the overexpression of NLRP3, caspase-1, caspase-3 and caspase-8 in lung tissues of ARDS mice. In summary, our study confirmed that SYQP induced bidirectional immunity and ameliorated LPS-induced acute respiratory distress syndrome in mice through TLR2/TLR4-NF-κB, NLRP3/caspase and JAK/STAT signaling pathways, which provided a theoretical basis for further use of SYQP.

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