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1.
Biomed Pharmacother ; 179: 117360, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39232387

RESUMEN

Macrophages undergo activation in response to multiple stimuli, including pathogens, growth factors and natural products. The inflammatory response and oxidative stress play critical roles in such macrophage activation. Some natural products reportedly promote immunoregulatory effects and the control of macrophage activation. Caryocar villosum (Cv), a native amazon plant, contains compounds that are an important source of molecules capable of macrophage activation. Herein, we demonstrate the immunomodulatory effects of oil obtained from Caryocar villosum (CvO) on macrophages. Macrophages were treated with varying concentrations of CvO, and resulting cellular morphological and functional changes were evaluated, including the production of nitric oxide (NO), reactive oxygen species (ROS), cytokines and phagocytic activity. Treatment of cells with 50 and 100 µg/mL CvO induced morphological and physiological alterations in the macrophages, such as increased cell surface and phagocytic activity. Additionally, treatment increased the productions of inflammatory cytokines (INF-γ, TNF-α, IL-6) and anti-inflammatory cytokines (IL-17 and IL-10) by macrophages, and significantly decreased ROS levels. In conclusion, these data suggest that, due to molecular diversity, CvO promoted an immunomodulatory effect on macrophages, mediated by an increased production of cytokines, and inhibition of ROS generation and phagocytic activity. Thus, CvO presents potential as a therapeutic agent for the treatment of inflammatory and non-inflammatory diseases.


Asunto(s)
Citocinas , Macrófagos , Óxido Nítrico , Fagocitosis , Aceites de Plantas , Especies Reactivas de Oxígeno , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Citocinas/metabolismo , Fagocitosis/efectos de los fármacos , Óxido Nítrico/metabolismo , Aceites de Plantas/farmacología , Células RAW 264.7 , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Factores Inmunológicos/farmacología , Activación de Macrófagos/efectos de los fármacos , Ericales/química
2.
Mar Drugs ; 22(9)2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39330307

RESUMEN

Marine natural products comprise unique chemical structures and vast varieties of biological activities. This review aims to summarize halichondrin, a marine natural product, and its synthetic analogs along with its therapeutic properties and mechanisms. Halichondrin and its analogs, derived from marine sponges, exhibit potent antineoplastic properties, making them promising candidates for cancer therapeutics. These compounds, characterized by their complex molecular structures, have demonstrated significant efficacy in inhibiting microtubule dynamics, leading to cell cycle arrest and apoptosis in various cancer cell lines. Several types of halichondrins such as halichondrins B, C, norhalichondrin B, and homohalichondrin B have been discovered with similar anticancer and antitumor characteristics. Since naturally available halichondrins show hurdles in synthesis, recent advancements in synthetic methodologies have enabled the development of several halichondrin analogs, such as E7389 (eribulin), which have shown improved therapeutic indices. Eribulin has shown excellent immunomodulatory properties by several mechanisms such as reprogramming tumor microenvironments, facilitating the infiltration and activation of immune cells, and inhibiting microtubule dynamics. Despite promising results, challenges remain in the synthesis and clinical application of these compounds. This review explores the mechanisms underlying the immunomodulatory activity of halichondrin and its analogs in cancer therapy, along with their clinical applications and potential for future drug development.


Asunto(s)
Antineoplásicos , Poríferos , Animales , Poríferos/química , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Neoplasias/tratamiento farmacológico , Productos Biológicos/farmacología , Productos Biológicos/química , Furanos/farmacología , Furanos/química , Furanos/aislamiento & purificación , Organismos Acuáticos , Cetonas/farmacología , Cetonas/química , Cetonas/aislamiento & purificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Macrólidos/farmacología , Macrólidos/química , Policétidos Poliéteres , Éteres Cíclicos
3.
Int J Med Mushrooms ; 26(11): 11-25, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39241160

RESUMEN

Polysaccharide fractions from the mycelium of the lion's mane medicinal mushroom Hericium erinaceus BP 16, cultivated on sterile grain substrates (barley, oats, wheat, rice, rye), were isolated and characterized. One percent solutions were prepared from the resulting fractions, mixed with blood, which was then subjected to cold stress at a temperature of 6°C for 3, 5 and 7 d. It has been shown that the fraction of H. erinaceus grown on rye is characterized by a high content of the protein fraction and arabinose monosaccharide and contributes to the preservation of higher phagocytic, bactericidal and antioxidant activity cells throughout the entire period of stress. Polysaccharide fractions of the fungus H. erinaceus, grown on various grain substrates, can serve as an immunomodulatory and antioxidant food additive and provide significant benefits in the daily life of people with stress and reduced immunity.


Asunto(s)
Antioxidantes , Hericium , Neutrófilos , Antioxidantes/farmacología , Hericium/química , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/metabolismo , Factores Inmunológicos/farmacología , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Micelio/química , Humanos , Estrés Fisiológico/efectos de los fármacos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/química
4.
Fitoterapia ; 178: 106174, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39122119

RESUMEN

Under the guidance of MS/MS-based molecular networking, five new clerodane diterpenoid glucosides, tinosinesides R-V (1-5), along with 15 known diterpenoids (6-20), were isolated from the stems of Tinospora sinensis. Compound 1 represents the first example of diterpenoid bearing a thio sugar and compound 5 is the first 18,19-dinor-clerodane with cis-fused A/B ring. The structures of the new compounds were elucidated by spectroscopic means, and their absolute configurations were established on the basis of time-dependent density functional theory (TD-DFT) based electronic circular dichroism (ECD) calculation and chemical methods. Selected compounds were evaluated for their immunomodulatory effect and several compounds could enhance the proliferation of B lymphocytes. Preliminary mechanistic studies disclosed that 3 could promote B cell generation and inhibit B cell differentiation.


Asunto(s)
Linfocitos B , Diterpenos de Tipo Clerodano , Fitoquímicos , Tinospora , Diterpenos de Tipo Clerodano/farmacología , Diterpenos de Tipo Clerodano/aislamiento & purificación , Diterpenos de Tipo Clerodano/química , Tinospora/química , Estructura Molecular , Linfocitos B/efectos de los fármacos , Animales , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Tallos de la Planta/química , China , Ratones , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Agentes Inmunomoduladores/química
5.
Int J Biol Macromol ; 278(Pt 2): 134757, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39151871

RESUMEN

Saussurea laniceps is a traditional medicinal herb. In our previous study, a pectin polysaccharide, SLP-4, was isolated from the petals of S. laniceps. In this study, the immunomodulatory activity of SLP-4 was studied by analyzing its effects on macrophage (RAW 264.7 cells) polarization. The immunomodulatory activity assays indicated that SLP-4 could significantly enhance the pinocytic and phagocytic capacity and promote the expression and secretion of cytotoxic molecules (nitric oxide, increased by 6.4 times when the SLP-4 concentration was 800 µg/mL) and cytokines (tumor necrosis factor-α and interleukin-6 increased by 7.7 and 11.9 times, respectively) in original macrophage. The possible mechanism could be attributed to the activation of the mitogen-activated protein kinase and nuclear factor-κB signaling pathways through Toll-like receptors 2 and 4. Moreover, SLP-4 significantly induced M1 polarization of original macrophages and transferred macrophages from M2 to M1, but had little effect on the conversion of M1 macrophages into M2 phenotype. Overall, these results demonstrate the potential of SLP-4 as an attractive immunomodulating functional supplement.


Asunto(s)
Macrófagos , Óxido Nítrico , Pectinas , Fagocitosis , Saussurea , Animales , Ratones , Pectinas/farmacología , Pectinas/química , Pectinas/aislamiento & purificación , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Saussurea/química , Fagocitosis/efectos de los fármacos , Óxido Nítrico/metabolismo , FN-kappa B/metabolismo , Citocinas/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 2/metabolismo , Flores/química , Receptor Toll-Like 4/metabolismo , Activación de Macrófagos/efectos de los fármacos , Pinocitosis/efectos de los fármacos , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Interleucina-6/metabolismo , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismo
6.
Int J Biol Macromol ; 278(Pt 3): 134947, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39173803

RESUMEN

This study aimed to optimize the extraction of Hericium erinaceus polysaccharides (HEP) using ultrasound-assisted enzymatic extraction combined with Plackett-Burman design (PBD) and response surface methodology (RSM). The optimal extraction conditions were identified as: 33 min extraction time, 30:1 liquid to material ratio, 38 °C extraction temperature, 9 g/kg cellulase amount, pH 4, and 20 % ethanol concentration. Under these conditions, the extraction yield of HEP was 5.87 ± 0.16 %, consistent with the predicted results. Additionally, the potential immunomodulatory activity of HEP on RAW 264.7 macrophage was evaluated. The results revealed that HEP improved the immunostimulatory activity of RAW264.7 cells, evident from increased production of IL-6 and TNF-α. These findings suggest that HEP is capable of enhancing the immune activity of RAW 264.7 macrophage.


Asunto(s)
Hericium , Macrófagos , Ratones , Animales , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Hericium/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/aislamiento & purificación , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Factor de Necrosis Tumoral alfa/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Interleucina-6/metabolismo
7.
Mar Drugs ; 22(7)2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-39057413

RESUMEN

From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology.


Asunto(s)
Organismos Acuáticos , Descubrimiento de Drogas , Humanos , Animales , Descubrimiento de Drogas/métodos , Productos Biológicos/farmacología , Productos Biológicos/química , Farmacopeas como Asunto , Océanos y Mares , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Factores Inmunológicos/farmacología , Factores Inmunológicos/química
8.
Int J Biol Macromol ; 273(Pt 2): 133206, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38885853

RESUMEN

The crude polysaccharide of Bletilla striata in this study was extracted by water extraction and alcohol precipitation and further purified by gel column to yield the purified component Bletilla striata polysaccharide (BSP). Its structure and innate immune regulation activity were studied. BSP mainly comprises mannose and glucose, with a monosaccharide molar ratio of 2.9:1 and a weight-average molecular weight of 28,365 Da. It is a new low-molecular-weight water-soluble neutral glucomannan. BSP contains a â†’ 6)-ß-Manp-(1→, →4)-ß-Glcp-(1→, →4)-ß-Manp-(1 â†’ and →3)-α-Manp-(1 â†’ linear main chain, containing ß-Glcp-(1 â†’ and ß-Manp-(1 â†’ two branched chain fragments were connected to the Man residue at position 4. BSP can enhance the anti-infection ability of Caenorhabditis elegans against Pseudomonas aeruginosa, significantly improve the phagocytic ability of RAW264.7 macrophages, stimulate the secretion of NO and TNF-α, and have good innate immune regulation activity. These findings guide the use of Bletilla striata polysaccharides with immunomodulatory action.


Asunto(s)
Inmunidad Innata , Mananos , Orchidaceae , Animales , Mananos/química , Mananos/farmacología , Mananos/aislamiento & purificación , Ratones , Orchidaceae/química , Células RAW 264.7 , Inmunidad Innata/efectos de los fármacos , Fagocitosis/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/inmunología , Peso Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación
9.
Int J Biol Macromol ; 276(Pt 1): 133459, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38945333

RESUMEN

A new polysaccharide, named SP40015A01, was obtained from Saposhnikoviae Radix by water extraction, isolation and purification. SP40015A01 (9.7 × 105 Da) is composed of Rhamnose (Rha), Galacturonic acid (GalA), Galactose (Gal), and Arabinose (Ara) with the proportion of 1.6:85.6:5.8:7.6. The backbone of SP40015A01 is composed of 3-α-GalAp, 2-α-GalAp, 2,3-ß-GalAp and 2,3-ß-Galp, and branched at C3 of 2,3-ß-GalAp, C3 of 2,3-ß-Galp. Zebrafish experiments were used to explore the immunomodulatory activity of SP40015A01. Results showed that SP40015A01 could significantly improve the neutrophils density of immunocompromised zebrafish and reduce the content of nitric oxide (NO) and interleukin-1ß (IL-1ß). This study demonstrated that SP40015A01 has significant immunomodulatory activity, which can improve the neutrophils density and reduce inflammatory factor content, suggesting SP40015A01 may be a potential immunomodulator in Saposhnikoviae Radix (SR) for treatment of hypoimmunity related disease. This study supplemented the research on the polysaccharide components in traditional Chinese medicine and provided a scientific explanation for the development and clinical applications of SR.


Asunto(s)
Apiaceae , Óxido Nítrico , Polisacáridos , Pez Cebra , Animales , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Apiaceae/química , Óxido Nítrico/metabolismo , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Interleucina-1beta/metabolismo , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Ácidos Hexurónicos
10.
Int J Biol Macromol ; 270(Pt 2): 132222, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38729468

RESUMEN

Fungal polysaccharides have been explored by many for both structural studies and biological activities, but few studies have been done on the extracellular polysaccharides of Dictyophora rubrovalvata, so a new exopolysaccharide was isolated from Dictyophora rubrovalvata and its structure and its immunological activity were investigated. The crude exopolysaccharide (EPS) was purified by DEAE52 cellulose and Sephadex G-200 to obtain a new acidic polysaccharide (DR-EPS). DR-EPS (2.66 × 103 kDa) was consisted mainly of mannose, glucose, galactose and glucuronic acid with a molar ratio of 1: 0.86: 0.20: 0.01. In addition, DR-EPS increased the phagocytic activity of RAW264.7 cells up to 2.67 times of the blank control group. DR-EPS improved intracellular nucleic acid and glycogen metabolism as observed by AO and PAS staining. DR-EPS(40 µg/mL) promoted NO production up to 30.66 µmol, enhanced acid phosphatase (ACP) and superoxide dismutase (SOD) activities, with activity maxima of 660 U/gprot and 96.27 U/mgprot, respectively, and DR-EPS (160 µg / mL) significantly increased the lysozyme content as 2.73 times of the control group. The good immunological activity of extracellular polysaccharides of Dictyophora rubrovalvata provides directions for the use of fermentation broths.


Asunto(s)
Polisacáridos Fúngicos , Ratones , Animales , Células RAW 264.7 , Polisacáridos Fúngicos/farmacología , Polisacáridos Fúngicos/química , Polisacáridos Fúngicos/aislamiento & purificación , Óxido Nítrico/metabolismo , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Fagocitosis/efectos de los fármacos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Superóxido Dismutasa/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Fosfatasa Ácida/metabolismo
11.
Molecules ; 29(9)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38731500

RESUMEN

A robust, well-functioning immune system is the cornerstone of good health. Various factors may influence the immune system's effectiveness, potentially leading to immune system failure. This review aims to provide an overview of the structure and action of immunomodulators isolated from African medicinal plants. The research was conducted according to PRISMA guidelines. Full-text access research articles published in English up to December 2023, including plant characteristics, isolated phytochemicals, and immuno-modulatory activities, were screened. The chemical structures of the isolated compounds were generated using ChemDraw® (version 12.0.1076), and convergent and distinctive signaling pathways were highlighted. These phytochemicals with demonstrated immunostimulatory activity include alkaloids (berberine, piperine, magnoflorine), polysaccharides (pectin, glucan, acemannan, CALB-4, GMP90-1), glycosides (syringin, cordifolioside, tinocordiside, aucubin), phenolic compounds (ferulic acid, vanillic acid, eupalitin), flavonoids (curcumin, centaurein, kaempferin, luteolin, guajaverin, etc.), terpenoids (oleanolic acid, ursolic acid, betulinic acid, boswellic acids, corosolic acid, nimbidin, andrographolides). These discussed compounds exert their effects through various mechanisms, targeting the modulation of MAPKs, PI3K-Akt, and NF-kB. These mechanisms can support the traditional use of medicinal plants to treat immune-related diseases. The outcomes of this overview are to provoke structural action optimization, to orient research on particular natural chemicals for managing inflammatory, infectious diseases and cancers, or to boost vaccine immunogenicity.


Asunto(s)
Fitoquímicos , Plantas Medicinales , Plantas Medicinales/química , Fitoquímicos/farmacología , Fitoquímicos/química , Humanos , Extractos Vegetales/química , Extractos Vegetales/farmacología , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , África , Animales
12.
Fitoterapia ; 176: 105988, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38703915

RESUMEN

Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.). Our study resulted in the isolation of new compound, 27-hydroxy octacosyl ferulate (1) along with eleven known compounds (2-12). The structures of the isolated compounds were characterized by combination of NMR (1D and 2D) and Mass spectroscopic methods. The hemisynthesis of compound 12 (ferulic acid) yielded (12a-12d and 12e-12 m) derivatives. Further, the isolated compounds and synthesized derivatives were assessed for their immunomodulatory potentials by evaluating their cytotoxicity and pro-inflammatory effects against macrophage cells (IL-6) and DC activation markers (CD 11c and 86). The biological results indicated that crude extract displayed potent immunomodulatory activity while isolated compounds and synthetic analogues showed moderate activity. Among the tested compounds, new compound (1), quercetin (10) and derivatives 12b, 12c found to be non-cytotoxic and displayed immunomodulatory potentials. Therefore, these compounds can be studied for autoimmunity and other immune suppressing conditions.


Asunto(s)
Agentes Inmunomoduladores , Fitoquímicos , Tinospora , Tinospora/química , Estructura Molecular , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Animales , Ratones , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Ácidos Cumáricos/farmacología , Ácidos Cumáricos/aislamiento & purificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/aislamiento & purificación , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Interleucina-6
13.
Inflammopharmacology ; 32(4): 2477-2491, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38717557

RESUMEN

Micromeria biflora (M.B) Benth has proven anti-inflammatory efficacy, thereby, the goal of the current investigation was to assess the anti-arthritic potential of M.B ethanolic extract and fractions as well as to investigate the likely mechanism of action. The effectiveness of M.B against acute arthritic manifestations was assessed using an arthritic model prompted by formaldehyde, whereas a chronic model was developed using an adjuvant called Complete Freund's in Sprague-Dawley rats. Weekly evaluations were conducted for parameters involving paw volume, body weight, and arthritic score; at the completion of the CFA model, hematological, biochemical and oxidative stress parameters as well as the level of various mediators (PGE2, IL-1ß, TNFα, IL6, MMP2, 3, 9, VEGF, NF-ĸB, IL-10, and IL-4) were evaluated. The results demonstrated the plant's ability to treat arthritis by showing a significant decrease in paw volume, arthritic score, and histological characteristics. The levels of NF-ĸB, MMP2, 3, 9, IL6, IL1ß, TNFα, and VEGF were all significantly reduced after treatment with plant extract and fractions. Plant extract and its fractions substantially preserved body weight loss, oxidative stress markers and levels of IL-4 and 1L-10. PGE2 levels were also shown to be reduced in the treatment groups, supporting the M.B immunomodulatory ability. Hematological and biochemical indicators were also normalized after M.B administration. Outcomes of the study validated the anti-arthritic and immunomodulatory attributes of M.B probably through modulating oxidative stress, inflammatory, pro-inflammatory and anti-inflammatory biomarkers.


Asunto(s)
Antiinflamatorios , Artritis Experimental , Citocinas , Estrés Oxidativo , Extractos Vegetales , Ratas Sprague-Dawley , Animales , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Ratas , Citocinas/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Masculino , Artritis Experimental/tratamiento farmacológico , Metaloproteasas , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Lamiaceae/química , Inflamación/tratamiento farmacológico , Femenino , Mediadores de Inflamación/metabolismo , Mediadores de Inflamación/antagonistas & inhibidores
14.
Artículo en Inglés | MEDLINE | ID: mdl-38810897

RESUMEN

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents.


Asunto(s)
Anuros , Catelicidinas , Animales , Ratones , Secuencia de Aminoácidos , Factores Inmunológicos/farmacología , Aeromonas hydrophila , Proteínas Anfibias/farmacología , Proteínas Anfibias/genética , Proteínas Anfibias/aislamiento & purificación , Antiinfecciosos/farmacología , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/aislamiento & purificación , Células RAW 264.7 , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Piel/efectos de los fármacos , Piel/metabolismo , Piel/inmunología , Pueblos del Este de Asia
15.
Molecules ; 29(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38731567

RESUMEN

A neutral Polygonatum cyrtonema polysaccharide (NPCP) was isolated and purified from Polygonatum cyrtonema by various chromatographic techniques, including DEAE-52 and Sephadex-G100 chromatography. The structure of NPCP was characterized by HPLC, HPGPC, GC-MS, FT-IR, NMR, and SEM. Results showed that NPCP is composed of glucose (55.4%) and galactose (44.6%) with a molecular weight of 3.2 kDa, and the sugar chain of NPCP was →1)-α-D-Glc-(4→1)-ß-D-Gal-(3→. In vitro bioactivity experiments demonstrated that NPCP significantly enhanced macrophages proliferation and phagocytosis while inhibiting the M1 polarization induced by LPS as well as the M2 polarization induced by IL-4 and IL-13 in macrophages. Additionally, NPCP suppressed the secretion of IL-6 and TNF-α in both M1 and M2 cells but promoted the secretion of IL-10. These results suggest that NPCP could serve as an immunomodulatory agent with potential applications in anti-inflammatory therapy.


Asunto(s)
Macrófagos , Fagocitosis , Polygonatum , Polisacáridos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Polygonatum/química , Ratones , Polisacáridos/farmacología , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Animales , Fagocitosis/efectos de los fármacos , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación , Células RAW 264.7 , Citocinas/metabolismo , Proliferación Celular/efectos de los fármacos , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Peso Molecular
16.
Molecules ; 29(8)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38675613

RESUMEN

Acne is a chronic inflammatory skin disease with a recurring nature that seriously impacts patients' quality of life. Currently, antibiotic resistance has made it less effective in treating acne. However, Paris polyphylla (P. polyphylla) is a valuable medicinal plant with a wide range of chemical components. Of these, P. polyphylla saponins modulate the effects in vivo and in vitro through antibacterial, anti-inflammatory, immunomodulatory, and antioxidant effects. Acne is primarily associated with inflammatory reactions, abnormal sebum function, micro-ecological disorders, hair follicle hyperkeratosis, and, in some patients, immune function. Therefore, the role of P. polyphylla saponins and their values in treating acne is worthy of investigation. Overall, this review first describes the distribution and characteristics of P. polyphylla and the pathogenesis of acne. Then, the potential mechanisms of P. polyphylla saponins in treating acne are listed in detail (reduction in the inflammatory response, antibacterial action, modulation of immune response and antioxidant effects, etc.). In addition, a brief description of the chemical composition of P. polyphylla saponins and its available extraction methods are described. We hope this review can serve as a quick and detailed reference for future studies on their potential acne treatment.


Asunto(s)
Acné Vulgar , Antibacterianos , Antiinflamatorios , Antioxidantes , Saponinas , Humanos , Acné Vulgar/tratamiento farmacológico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Antioxidantes/química , Saponinas/farmacología , Saponinas/química , Saponinas/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antibacterianos/química , Animales , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Factores Inmunológicos/farmacología , Factores Inmunológicos/uso terapéutico , Factores Inmunológicos/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/uso terapéutico , Agentes Inmunomoduladores/aislamiento & purificación , Melanthiaceae/química , Liliaceae/química
17.
Curr Top Med Chem ; 24(12): 1075-1100, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38551050

RESUMEN

BACKGROUND: Immunomodulation is the modification of immune responses to control disease progression. While the synthetic immunomodulators have proven efficacy, they are coupled with toxicity and other adverse effects, and hence, the efforts were to identify natural phytochemicals with immunomodulatory potential. OBJECTIVE: To understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach. METHODOLOGY: Several scientific database repositories were searched using different keywords: "Phytochemicals," "Alkaloids," "Polyphenols," "Flavonoids," "Lectins," "Glycosides," "Tannins," "Terpenoids," "Sterols," "Immunomodulators," and "Human Immune System" without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma. RESULTS: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS. CONCLUSION: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259 indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.


Asunto(s)
Biología Computacional , Fitoquímicos , Humanos , Fitoquímicos/farmacología , Fitoquímicos/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/aislamiento & purificación , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Echinacea/química , Extractos Vegetales/farmacología , Extractos Vegetales/química
18.
Curr Med Chem ; 31(36): 5969-5988, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38445701

RESUMEN

BACKGROUND: Punica granatum L. is well-known for its multifaceted therapeutic potential, including anti-inflammatory and immunomodulatory activities. AIM: This study aimed to characterize an immunomodulatory compound isolated from Punica granatum L. using a bioactivity-guided approach. METHODS: Chromatographic techniques were adopted for isolation and purification of secondary metabolites. In silico, in vitro, and in vivo methods were performed to characterize the therapeutic potential of the isolated compound. RESULTS: Using preparative thin-layer chromatography, rosmarinic acid was isolated from F4 (column chromatography product obtained from a butanolic fraction of the extract). The impact of rosmarinic acid was assessed in rats using the neutrophil adhesion test, DTH response, and phagocytic index. In immunized rats, rosmarinic acid demonstrated significant immunomodulatory potential. Computational experiments, like molecular docking and molecular dynamics, were also conducted against two targeted receptors, Cereblon (PDB ID: 8AOQ) and human CD22 (PDB ID: 5VKM). Computational studies suggested that an increase in phagocytic index by rosmarinic acid could be attributed to inhibiting Cereblon and CD22. Pharmacokinetics and toxicity prediction also suggested the drug-likeness of rosmarinic acid. CONCLUSION: Rosmarinic acid is a potential candidate, but extensive research needs to be done to translate this molecule from bench to bedside.


Asunto(s)
Cinamatos , Depsidos , Simulación del Acoplamiento Molecular , Granada (Fruta) , Ácido Rosmarínico , Cinamatos/química , Cinamatos/aislamiento & purificación , Cinamatos/farmacología , Depsidos/química , Depsidos/aislamiento & purificación , Depsidos/farmacología , Animales , Humanos , Ratas , Granada (Fruta)/química , Masculino , Agentes Inmunomoduladores/química , Agentes Inmunomoduladores/farmacología , Agentes Inmunomoduladores/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/aislamiento & purificación , Simulación por Computador , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Ratas Wistar , Simulación de Dinámica Molecular , Factores Inmunológicos/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/aislamiento & purificación
19.
Pharm Biol ; 60(1): 509-524, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35234563

RESUMEN

CONTEXT: Since the outbreak of SARS-CoV-2, researchers have been working on finding ways to prevent viral entry and pathogenesis. Drug development from naturally-sourced pharmacological constituents may be a fruitful approach to COVID-19 therapy. OBJECTIVE: Most of the published literature has focussed on medicinal plants, while less attention has been given to biodiverse sources such as animal, marine, and microbial products. This review focuses on highlighting natural products and their derivatives that have been evaluated for antiviral, anti-inflammatory, and immunomodulatory properties. METHODS: We searched electronic databases such as PubMed, Scopus, Science Direct and Springer Link to gather raw data from publications up to March 2021, using terms such as 'natural products', marine, micro-organism, and animal, COVID-19. We extracted a number of documented clinical trials of products that were tested in silico, in vitro, and in vivo which paid specific attention to chemical profiles and mechanisms of action. RESULTS: Various classes of flavonoids, 2 polyphenols, peptides and tannins were found, which exhibit inhibitory properties against viral and host proteins, including 3CLpro, PLpro, S, hACE2, and NF-κB, many of which are in different phases of clinical trials. DISCUSSION AND CONCLUSIONS: The synergistic effects of logical combinations with different mechanisms of action emphasizes their value in COVID19 management, such as iota carrageenan nasal spray, ermectin oral drops, omega-3 supplementation, and a quadruple treatment of zinc, quercetin, bromelain, and vitamin C. Though in vivo efficacy of these compounds has yet to be established, these bioproducts are potentially useful in counteracting the effects of SARS-CoV-2.


Asunto(s)
Antivirales/farmacología , Productos Biológicos/farmacología , Tratamiento Farmacológico de COVID-19 , Animales , Antiinflamatorios/administración & dosificación , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Antivirales/administración & dosificación , Antivirales/aislamiento & purificación , Productos Biológicos/aislamiento & purificación , COVID-19/virología , Desarrollo de Medicamentos/métodos , Sinergismo Farmacológico , Humanos , Agentes Inmunomoduladores/administración & dosificación , Agentes Inmunomoduladores/aislamiento & purificación , Agentes Inmunomoduladores/farmacología
20.
J Ethnopharmacol ; 289: 115087, 2022 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-35143934

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Aerva lanata Linn. (A. lanata) is traditionally used for cough, sore throat and asthma. AIM OF STUDY: The aim of the present study was to investigate the immunomodulatory and anti-inflammatory potentials of A. lanata in allergic asthmatic mice. MATERIALS AND METHODS: BALB/c mice were administered with three different (methanol, n-hexane and ethyl acetate) extracts of A. lanata two weeks after immunization with ovalbumin and continued for 7 days. Inflammatory cells count was estimated in blood and broncho-alveolar lavage fluid (BALF). RT-PCR was used to find out mRNA expression levels of inflammatory mediators. GC-MS analysis was also carried out. RESULTS: Among three extracts of A. lanata, ethyl acetate extract ameliorated (p < 0.001) count of inflammatory cells both blood and BALF remarkably. This study indicated that ethyl acetate extract of A. lanata lowered (p < 0.001) the level of inflammatory modulator TNF-α and IgE antibodies. A. lanata reduced (p < 0.001) interleukin 4, 5, 13 and enhanced (p < 0.001) expression levels of AQP1 and AQP5 in asthmatic mice. GC-MS analysis of ethyl acetate fraction indicated the presence of various anti-oxidant phyto-constituents. The groups treated with A. lanata improved inflammatory, goblet cells hyperplasia scoring and alveolar thickening. CONCLUSIONS: The anti-asthmatic effect of A. lanata might be contributed by the suppression of edema, pro-inflammatory cytokines and IgE antibodies, and elevation of aquaporin expression levels, suggesting future study and clinical trials to propose it as a candidate to treat allergic asthma. The anti-oxidant phytochemicals present in A. lanata might be responsible for such potential.


Asunto(s)
Amaranthaceae/química , Antiinflamatorios/farmacología , Asma/tratamiento farmacológico , Extractos Vegetales/farmacología , Animales , Antiasmáticos/aislamiento & purificación , Antiasmáticos/farmacología , Antiinflamatorios/aislamiento & purificación , Antioxidantes/aislamiento & purificación , Antioxidantes/farmacología , Citocinas/metabolismo , Agentes Inmunomoduladores/aislamiento & purificación , Agentes Inmunomoduladores/farmacología , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Ovalbúmina , Solventes/química
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