RESUMO
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.
Assuntos
Organismos Aquáticos , Descoberta de Drogas , Humanos , Animais , Descoberta de Drogas/métodos , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Farmacopeias como Assunto , Oceanos e Mares , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Fatores Imunológicos/farmacologia , Fatores Imunológicos/químicaRESUMO
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-(1â, â4)-ß-Glcp-(1â, â4)-ß-Manp-(1 â and â3)-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.
Assuntos
Imunidade Inata , Mananas , Orchidaceae , Animais , Mananas/química , Mananas/farmacologia , Mananas/isolamento & purificação , Camundongos , Orchidaceae/química , Células RAW 264.7 , Imunidade Inata/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Caenorhabditis elegans/efeitos dos fármacos , Caenorhabditis elegans/imunologia , Peso Molecular , Pseudomonas aeruginosa/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Fator de Necrose Tumoral alfa/metabolismo , Óxido Nítrico/metabolismo , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificaçãoRESUMO
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.
Assuntos
Apiaceae , Óxido Nítrico , Polissacarídeos , Peixe-Zebra , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Apiaceae/química , Óxido Nítrico/metabolismo , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Interleucina-1beta/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Ácidos HexurônicosRESUMO
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.
Assuntos
Anti-Inflamatórios , Artrite Experimental , Citocinas , Estresse Oxidativo , Extratos Vegetais , Ratos Sprague-Dawley , Animais , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificação , Ratos , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Masculino , Artrite Experimental/tratamento farmacológico , Metaloproteases , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Lamiaceae/química , Inflamação/tratamento farmacológico , Feminino , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/antagonistas & inibidoresRESUMO
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.
Assuntos
Anuros , Catelicidinas , Animais , Camundongos , Sequência de Aminoácidos , Fatores Imunológicos/farmacologia , Aeromonas hydrophila , Proteínas de Anfíbios/farmacologia , Proteínas de Anfíbios/genética , Proteínas de Anfíbios/isolamento & purificação , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Células RAW 264.7 , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/imunologia , População do Leste AsiáticoRESUMO
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 â1)-α-D-Glc-(4â1)-ß-D-Gal-(3â. 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.
Assuntos
Macrófagos , Fagocitose , Polygonatum , Polissacarídeos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Polygonatum/química , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Animais , Fagocitose/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Células RAW 264.7 , Citocinas/metabolismo , Proliferação de Células/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Peso MolecularRESUMO
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.
Assuntos
Compostos Fitoquímicos , Plantas Medicinais , Plantas Medicinais/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , África , AnimaisRESUMO
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 (2.66â¯×â¯103â¯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⯵g/mL) promoted NO production up to 30.66⯵mol, enhanced acid phosphatase (ACP) and superoxide dismutase (SOD) activities, with activity maxima of 660â¯U/gprot and 96.27â¯U/mgprot, respectively, and DR-EPS (160⯵g / 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.
Assuntos
Polissacarídeos Fúngicos , Camundongos , Animais , Células RAW 264.7 , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/isolamento & purificação , Óxido Nítrico/metabolismo , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Fatores Imunológicos/isolamento & purificação , Fagocitose/efeitos dos fármacos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Superóxido Dismutase/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Fosfatase Ácida/metabolismoRESUMO
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.
Assuntos
Agentes de Imunomodulação , Compostos Fitoquímicos , Tinospora , Tinospora/química , Estrutura Molecular , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Animais , Camundongos , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/isolamento & purificação , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/isolamento & purificação , Células RAW 264.7 , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Interleucina-6RESUMO
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.
Assuntos
Acne Vulgar , Antibacterianos , Anti-Inflamatórios , Antioxidantes , Saponinas , Humanos , Acne Vulgar/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/química , Saponinas/farmacologia , Saponinas/química , Saponinas/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Antibacterianos/química , Animais , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Fatores Imunológicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/uso terapêutico , Agentes de Imunomodulação/isolamento & purificação , Melanthiaceae/química , Liliaceae/químicaRESUMO
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.
Assuntos
Biologia Computacional , Compostos Fitoquímicos , Humanos , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Agentes de Imunomodulação/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Fatores Imunológicos/farmacologia , Fatores Imunológicos/química , Echinacea/química , Extratos Vegetais/farmacologia , Extratos Vegetais/químicaRESUMO
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.
Assuntos
Antivirais/farmacologia , Produtos Biológicos/farmacologia , Tratamento Farmacológico da COVID-19 , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antivirais/administração & dosagem , Antivirais/isolamento & purificação , Produtos Biológicos/isolamento & purificação , COVID-19/virologia , Desenvolvimento de Medicamentos/métodos , Sinergismo Farmacológico , Humanos , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologiaRESUMO
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.
Assuntos
Amaranthaceae/química , Anti-Inflamatórios/farmacologia , Asma/tratamento farmacológico , Extratos Vegetais/farmacologia , Animais , Antiasmáticos/isolamento & purificação , Antiasmáticos/farmacologia , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Citocinas/metabolismo , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Solventes/químicaRESUMO
Sesquiterpene lactones (SL), characterized by their high prevalence in the Asteraceae family, are one of the major groups of secondary metabolites found in plants. Researchers from distinct research fields, including pharmacology, medicine, and agriculture, are interested in their biological potential. With new SL discovered in the last years, new biological activities have been tested, different action mechanisms (synergistic and/or antagonistic effects), as well as molecular structure-activity relationships described. The review identifies the main sesquiterpene lactones with interconnections between immune responses and anti-inflammatory actions, within different cellular models as well in in vivo studies. Bioaccessibility and bioavailability, as well as molecular structure-activity relationships are addressed. Additionally, plant metabolic engineering, and the impact of sesquiterpene lactone extraction methodologies are presented, with the perspective of biological activity enhancement. Sesquiterpene lactones derivatives are also addressed. This review summarizes the current knowledge regarding the therapeutic potential of sesquiterpene lactones within immune and inflammatory activities, highlighting trends and opportunities for their pharmaceutical/clinical use.
Assuntos
Anti-Inflamatórios/farmacologia , Agentes de Imunomodulação/farmacologia , Lactonas/farmacologia , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Asteraceae/química , Descoberta de Drogas , Humanos , Agentes de Imunomodulação/química , Agentes de Imunomodulação/isolamento & purificação , Lactonas/química , Lactonas/isolamento & purificação , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificaçãoRESUMO
The growing number of deaths related to sepsis has become a major concern for past few years. Sepsis is a complex pathological reactions that is explained by series of host response to microbial insult. The resulted systemic reactions are manifested by early appearance of proinflammatory cytokines leading to hyperinflammatory phase which is followed by septic shock and death of the patient. The present study has revealed that antibiotics are not self-sufficient to control the complex mechanism of sepsis. Moreover prolonged and unnecessary administration of antibiotics may lead to antibiotic resistance to pathogens. In addition to this, immunosuppressive medications are selective and have targeted approach to certain study population. Drugs from herbal origin have shown to possess a mammoth of immunomodulatory potential by suppressing proinflammatory and anti-inflammatory cytokines exhibiting no or minimal unwanted secondary responses. Concomitantly, herbal plants tend to modulate oxidative stress level and haematological imbalance during inflammatory diseased conditions. Natural compounds have gained much attention for the treatment of several clinical complications. Considering the promising responses of medicinal plants with less/no side effects and easy procurement, comprehensive research on herbal plants to treat sepsis should be contemplated.
Assuntos
Anti-Inflamatórios/uso terapêutico , Agentes de Imunomodulação/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Sepse/tratamento farmacológico , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/uso terapêutico , Anti-Inflamatórios/isolamento & purificação , Antioxidantes/isolamento & purificação , Antioxidantes/uso terapêutico , Humanos , Agentes de Imunomodulação/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Sepse/imunologia , Sepse/metabolismo , Sepse/microbiologiaRESUMO
Lactarius volemus Fr. is an edible mushroom widely consumed in China. Polysaccharide is an important nutritional component of L. volemus. This research aimed to isolate the polysaccharide from L. volemus and study its structure and bioactivities. A purified polysaccharide was identified and named as LVF-I whose primary structure was proposed considering the comprehensive results of monosaccharide composition, periodate oxidation-smith degradation, methylation analysis, FT-IR and 1D/2D NMR spectroscopy. Then the immunomodulation of LVF-I and its inhibition effect on H1299 and MCF-7 cells were investigated. Results showed that LVF-I (12,894 Da) contained fucose, mannose, glucose and galactose. It had a backbone consisting of â4)-α-D-Glcp-(1â, â6)-ß-D-Manp-(1â, â6)-α-D-Galp-(1 â and â4)-ß-D-Manp-(1â. And its side chains were branched at C2 of â4)-ß-D-Manp-(1 â by â6)-α-D-Galp-(1â, α-D-Glcp-(1â, α-D-Galp-(1 â and α-L-Fucp-(1â. LVF-I (250-1000 µg/mL) could inhibit the proliferation of H1299 and MCF-7 cells, while enhance the proliferative response of splenocyte and the phagocytic ability of RAW264.7. Furthermore, LVF-I (250-1000 µg/mL) significantly induced the secretion of nitric oxide, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by up-regulating their mRNA expression in macrophages. These results suggested that LVF-I had the potential to be developed as antitumor or immunomodulatory agents by inhibiting the proliferation of tumor cells and stimulating macrophages-mediated immune responses.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Basidiomycota/química , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Agentes de Imunomodulação/química , Agentes de Imunomodulação/farmacologia , Animais , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Fenômenos Químicos , Testes Imunológicos de Citotoxicidade , Polissacarídeos Fúngicos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Agentes de Imunomodulação/isolamento & purificação , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Peso Molecular , Células RAW 264.7 , Espectroscopia de Infravermelho com Transformada de Fourier , Relação Estrutura-AtividadeRESUMO
The link between diabetes and cognitive dysfunction has been reported in many recent articles. There is currently no disease-modifying treatment available for cognitive impairment. Boswellia serrata (B. serrata) is used traditionally to treat chronic inflammatory diseases such as type 2 diabetes (T2D), insulin resistance (IR), and Alzheimer's disease (AD). This review aims to highlight current research on the potential use of boswellic acids (BAs)/B. serrata extract in T2D and AD. We reviewed the published information through June 2021. Studies have been collected through a search on online electronic databases (Academic libraries as PubMed, Scopus, Web of Science, and Egyptian Knowledge Bank). Accumulating evidence in preclinical and small human clinical studies has indicated that BAs/B. serrata extract has potential therapeutic effect in T2D and AD. According to most of the authors, the potential therapeutic effects of BAs/B. serrata extract in T2D and AD can be attributed to immunomodulatory, anti-inflammatory, antioxidant activity, and elimination of the senescent cells. BAs/B. serrata extract may act by inhibiting the IκB kinase/nuclear transcription factor-κB (IKK/NF-κB) signaling pathway and increasing the formation of selective anti-inflammatory LOX-isoform modulators. In conclusion, BAs/B. serrata extract may have positive therapeutic effects in prevention and therapy of T2D and AD. However, more randomized controlled trials with effective, large populations are needed to show a definitive conclusion about therapeutic efficacy of BAs/B. serrata extract in T2D and AD.
Assuntos
Boswellia/química , Extratos Vegetais/farmacologia , Triterpenos/farmacologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/prevenção & controle , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diabetes Mellitus Tipo 2/prevenção & controle , Humanos , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Triterpenos/isolamento & purificaçãoRESUMO
BACKGROUND: Mesenchymal stem cells-derived adipose tissue (AT-MSCs) are recognized for the treatment of inflammatory diseases including multiple sclerosis (MS). Hypericum perforatum (HP) is an anti-inflammatory pharmaceutical plant with bioactive compounds. Plant tissue culture is a technique to improve desired pharmacological potential. The aim of this study was to compare the anti-inflammatory and proliferative effects of callus with field-growing plant extracts of HP on AT-MSCs derived from MS patients. MATERIALS AND METHODS: AT-MSCs were isolated and characterized. HP callus was prepared and exposure to light spectrum (blue, red, blue-red, and control). Total phenols, flavonoids, and hypericin of HP callus and plant extracts were measured. The effects of HP extracts concentrations on proliferation were evaluated by MTT assay. Co-culture of AT-MSCs: PBMCs were challenged by HP plant and callus extracts, and Tregs percentage was assessed by flow cytometry. RESULTS: Identification of MSCs was performed. Data showed that blue light could stimulate total phenols, flavonoids, and hypericin. MTT test demonstrated that plant extract in concentrations (0.03, 1.2, 2.5 and 10 µg/ml) and HP callus extract in 10 µg/ml significantly increased. Both HP extracts lead to an increase in Tregs percentage in all concentrations. In particular, a comparison between HP plant and callus extracts revealed that Tregs enhanced 3-fold more than control groups in the concentration of 10 µg/ml callus. CONCLUSIONS: High concentrations of HP extracts showed effectiveness on AT-MSCs proliferation and immunomodulatory properties with a certain consequence in callus extract. HP extracts may be considered as supplementary treatments for the patients who receiving MSCs transplantation.
Assuntos
Hypericum/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Esclerose Múltipla/tratamento farmacológico , Extratos Vegetais/farmacologia , Tecido Adiposo/citologia , Adulto , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Proliferação de Células/efeitos dos fármacos , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Feminino , Humanos , Agentes de Imunomodulação/administração & dosagem , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Células-Tronco Mesenquimais/citologia , Esclerose Múltipla/imunologia , Extratos Vegetais/administração & dosagemRESUMO
The study aimed, by integrating transcriptomics and metabolomics, to reveal novel biomarkers caused by overdosed acetaminophen (APAP) and liver protection substances procured by pre-administration of ginseng shoots extract (GSE). Totally 4918 genes and 127 metabolites were identified as differentially expressed genes and differential metabolites, respectively. According to KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment, such pathways as primary bile acid biosynthesis, bile secretion, retinol metabolism, histidine and several other amino-related metabolism were significantly altered by GSE and disturbed by subsequent overdosed APAP at the transcriptomic as well as metabolomic levels. Fifteen key biomarker metabolites related to these pathways were up-regulated in APAP-treated vs GSE-pretreated liver tissues, and were reported exerting anti-oxidant, anti-inflammatory, anti-apoptotic and/or immunomodulate functions, three of which even possessed direct hepatoprotection effects. Twenty five vital unigenes modulating these metabolites were further verified by correlation analysis and expression levels of fifteen of them were examined by qRT-PCR. Our findings indicate that GSE may be an effective dietary supplement for preventing the liver damage caused by the overdosed APAP.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Perfilação da Expressão Gênica , Fígado/efeitos dos fármacos , Metaboloma , Metabolômica , Panax , Extratos Vegetais/farmacologia , Transcriptoma , Acetaminofen , Aminoácidos/metabolismo , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Biomarcadores/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Overdose de Drogas , Agentes de Imunomodulação/isolamento & purificação , Agentes de Imunomodulação/farmacologia , Mediadores da Inflamação/metabolismo , Fígado/metabolismo , Fígado/patologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Panax/química , Extratos Vegetais/isolamento & purificação , Brotos de Planta , Vapor , Vitamina A/metabolismoRESUMO
Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.