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Sepsis is a serious disease with high mortality and has been a hot research topic in medical research in recent years. With the continuous reporting of in-depth research on the pathological mechanisms of sepsis, various compounds have been developed to prevent and treat sepsis. Natural small-molecule compounds play vital roles in the prevention and treatment of sepsis; for example, compounds such as resveratrol, emodin, salidroside, ginsenoside, and others can modulate signaling through the NF-κB, STAT3, STAT1, PI3K, and other pathways to relieve the inflammatory response, immunosuppression, and organ failure caused by sepsis. Here, we discuss the functions and mechanisms of natural small-molecule compounds in preventing and treating sepsis. This review will lay the theoretical foundation for discovering new natural small-molecule compounds that can potentially prevent and treat sepsis.
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Investigación Biomédica , Emodina , Ginsenósidos , Sepsis , Humanos , Sepsis/tratamiento farmacológico , Sepsis/prevención & control , Terapia de InmunosupresiónRESUMEN
Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ failure. Biological macromolecules are drugs produced using modern biotechnology to prevent or treat diseases. Indeed, antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan have been used to prevent and treat sepsis. In vitro, biological macromolecules can significantly ameliorate the inflammatory response, apoptosis, and multiple organ failure caused by sepsis. Several biological macromolecules have entered clinical trials. This review summarizes the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in the prevention and treatment of sepsis.
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Insuficiencia Multiorgánica , Sepsis , Humanos , Sepsis/tratamiento farmacológico , Sepsis/prevención & control , Anticuerpos , Anticoagulantes , Péptidos Antimicrobianos , Sustancias Macromoleculares/uso terapéuticoRESUMEN
Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.
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Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Sistemas de Liberación de Medicamentos , Control Glucémico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
Treatment for sepsis and its complications in the clinic is primarily in the forms of antibiotics, anti-inflammatory agents, and antioxidant drugs. Kombucha, a traditional fermented beverage rich in tea polyphenols and organic acids, offers several benefits including bacteriostasis, anti-inflammation ability, and boosting the immune system. Currently, research on kombucha is primarily focused on its antibacterial and antioxidant properties; however, in-depth exploration of the involved mechanisms is lacking. Herein, turmeric, Paeoniae alba, and black tea were used as fermentation substrates to detect the bacteriostatic and antioxidant activities of the fermentation broth and evaluate its anti-inflammatory effects on RAW264.7 cells stimulated by lipopolysaccharides (LPSs). The results showed that fermentation enhanced the antibacterial activity of turmeric against E. coli and S. aureus and that of Paeoniae alba against S. aureus. Turmeric black tea exhibited the highest antioxidant activity. The fermentation broth of turmeric and turmeric black tea significantly reduced the expression of inflammatory cytokines induced by LPSs. Our results showed that using turmeric and Paeoniae alba culture media as substrates can enhance the anti-inflammatory effects of fermentation broth and provide a new strategy for developing anti-inflammatory substances.
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Decoy receptor 3 (DcR3), a soluble glycosylated protein in the tumor necrosis factor receptor superfamily, plays a role in tumor and inflammatory diseases. Sepsis is a life-threatening organ dysfunction caused by the dysregulation of the response to infection. Currently, no specific drug that can alleviate or even cure sepsis in a comprehensive and multi-level manner has been found. DcR3 is closely related to sepsis and considerably upregulated in the serum of those patients, and its upregulation is positively correlated with the severity of sepsis and can be a potential biomarker for diagnosis. DcR3 alone or in combination with other markers has shown promising results in the early diagnosis of sepsis. Furthermore, DcR3 is a multipotent immunomodulator that can bind FasL, LIGHT, and TL1A through decoy action, and block downstream apoptosis and inflammatory signaling. It also regulates T-cell and macrophage differentiation and modulates immune status through non-decoy action; therefore, DcR3 could be a potential drug for the treatment of sepsis. The application of DcR3 in the treatment of a mouse model of sepsis also achieved good efficacy. Here, we introduce and discuss the progress in, and suggest novel ideas for, research regarding DcR3 in the diagnosis and treatment of sepsis.
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Sepsis , Animales , Ratones , Sepsis/diagnóstico , Sepsis/tratamiento farmacológico , Adyuvantes Inmunológicos , Apoptosis , Modelos Animales de Enfermedad , Transducción de SeñalRESUMEN
To improve patient survival in sepsis, it is necessary to curtail exaggerated inflammatory responses. Fucoxanthin (FX), a carotenoid derived from brown algae, efficiently suppresses pro-inflammatory cytokine expression via IRF3 activation, thereby reducing mortality in a mouse model of sepsis. However, the effects of FX-targeted IRF3 on the bacterial flora (which is disrupted in sepsis) and the mechanisms by which it impacts sepsis development remain unclear. This study aims to elucidate how FX-targeted IRF3 modulates intestinal microbiota compositions, influencing sepsis development. FX significantly reduced the bacterial load in the abdominal cavity of mice with cecal ligation and puncture (CLP)-induced sepsis via IRF3 activation and increased short-chain fatty acids, like acetic and propionic acids, with respect to their intestines. FX also altered the structure of the intestinal flora, notably elevating beneficial Verrucomicrobiota and Akkermansia spp. while reducing harmful Morganella spp. Investigating the inflammation-flora link, we found positive correlations between the abundances of Morganella spp., Proteus spp., Escherichia spp., and Klebsiella spp. and pro-inflammatory cytokines (IL-6, IL-1ß, and TNF-α) induced by CLP. These bacteria were negatively correlated with acetic and propionic acid production. FX alters microbial diversity and promotes short-chain fatty acid production in mice with CLP-induced sepsis, reshaping gut homeostasis. These findings support the value of FX for the treatment of sepsis.
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Microbioma Gastrointestinal , Microbiota , Sepsis , Humanos , Animales , Ratones , Xantófilas/farmacología , Xantófilas/uso terapéutico , Sepsis/tratamiento farmacológico , Citocinas , Factor 3 Regulador del InterferónRESUMEN
Sepsis remains a major challenge owing to its severe adverse effects and high mortality, against which specific pharmacological interventions with high efficacy are limited. Mitigation of hyperactive inflammatory responses is a key factor in enhancing the likelihood of survival in patients with sepsis. The Aloe genus has several health benefits, including anti-inflammatory properties. The toxicological implications of aloe-emodin (AE), extracted from various Aloe species, remain uncertain in clinical contexts. However, AE has been shown to inhibit inflammatory responses in lipopolysaccharide-induced mice, indicating its potential as a therapeutic approach for sepsis treatment. Nonetheless, there is a paucity of data regarding the therapeutic benefits of AE in the widely recognized cecal ligation and puncture (CLP)-induced sepsis model, which is commonly used as the gold standard model for sepsis research. This study demonstrates the potential benefits of AE in the treatment of CLP-induced sepsis and investigates its underlying mechanism, along with the efficacy of postoperative AE treatment in mice with CLP-induced sepsis. The results of this study suggest that AE can mitigate sepsis in mice by diminishing systemic inflammation and regulating the gut microbiota. The study provides novel insights into the molecular mechanisms underlying the anti-inflammatory effects of AE.
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Aloe , Emodina , Sepsis , Ratones , Animales , Emodina/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Punciones/efectos adversos , Ligadura/efectos adversos , Sepsis/tratamiento farmacológico , Sepsis/etiología , Ciego/cirugía , Modelos Animales de EnfermedadRESUMEN
The Aloe species is known for its medicinal and cosmetic properties. Aloin is an active ingredient found in the leaves of medicinal plants of the genus Aloe. Aloin has attracted considerable interest for its antiinflammatory, anticancer, antibacterial, and antioxidant activities. However, since its clinical application is restricted by its unclear mechanism of action, a deeper understanding of its pharmacological activity is required. This review provides an overview of current pharmacological and toxicological studies published in English from February 2000 to August 2021. Herein, we summarized the sources and potential health benefits of aloin from a clinical application perspective to guide for further studies on the sources of aloin, aimed at efficiently increasing aloin production. Importantly, the function and mechanism of action of aloin remain unclarified. In future research, it is necessary to develop new approaches for studying the pharmacological molecular mechanisms underlying the activity of this compound against various diseases.
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Aloe , Emodina , Plantas Medicinales , Emodina/análogos & derivados , Emodina/farmacología , Hojas de la PlantaRESUMEN
Huperzine A (HupA) is an effective inhibitor of acetylcholinesterase and has attracted great interest as a therapeutic candidate for Alzheimer's disease. However, the use of HupA is limited by resource scarcity as well as by its low yields from Huperzia serrata, its primary plant source. Recent studies have shown that this compound is produced by various endophytic fungi, thereby providing a promising alternative source, as fungi are much more amenable than plants owing to their simpler genetics and the ease of manipulation. In this review, we summarize the progress in research on the methods to increase HupA production, including fermentation conditions, fungal elicitors, gene expression, and the activation of key enzymes. This review provides guidance for further studies on HupA-producing endophytic fungi aimed at efficient HupA synthesis and accumulation, and offers new approaches for studies on the regulation of high-value bioactive secondary metabolites.
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Alcaloides/biosíntesis , Endófitos/metabolismo , Hongos/metabolismo , Microbiología Industrial/tendencias , Endófitos/genética , Fermentación , Hongos/genética , Huperzia/metabolismo , Huperzia/microbiología , SesquiterpenosRESUMEN
Sepsis is defined as "a life-threatening organ dysfunction caused by a host's dysfunctional response to infection". Although the treatment of sepsis has developed rapidly in the past few years, sepsis incidence and mortality in clinical treatment is still climbing. Moreover, because of the diverse manifestations of sepsis, clinicians continue to face severe challenges in the diagnosis, treatment, and management of patients with sepsis. Here, we review the recent development in our understanding regarding the cellular pathogenesis and the target of clinical diagnosis of sepsis, with the goal of enhancing the current understanding of sepsis. The present state of research on targeted therapeutic drugs is also elaborated upon to provide information for the treatment of sepsis.
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Biomarcadores/sangre , Sepsis/sangre , Sepsis/tratamiento farmacológico , Autofagia , Trastornos de la Coagulación Sanguínea , Estrés del Retículo Endoplásmico , Humanos , Incidencia , Inflamación , Enfermedades Mitocondriales , Células Neuroendocrinas/inmunología , Sepsis/diagnóstico , Sepsis/mortalidad , VirulenciaRESUMEN
Acetylcholinesterase inhibitors (AChEIs) are an attractive research subject owing to their potential applications in the treatment of neurodegenerative diseases. Fungi and bacteria are major producers of AChEIs. Their active ingredients of fermentation products include alkaloids, terpenoids, phenylpropanoids, and steroids. A variety of in vitro acetylcholinesterase inhibitor assays have been developed and used to measure the activity of acetylcholinesterases, including modified Ellman's method, thin layer chromatography bioautography, and the combined liquid chromatography-mass spectrometry/modified Ellman's method. In this review, we provide an overview of the different detection methodologies, the microbe-derived AChEIs, and their producing strains.
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Bacterias , Inhibidores de la Colinesterasa , Cromatografía Liquida , Cromatografía en Capa Delgada , Hongos , Espectrometría de Masas , Acetilcolinesterasa/metabolismo , Alcaloides/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Bacterias/metabolismo , Inhibidores de la Colinesterasa/análisis , Inhibidores de la Colinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/uso terapéutico , Cromatografía Liquida/métodos , Cromatografía en Capa Delgada/métodos , Hongos/metabolismo , Espectrometría de Masas/métodosRESUMEN
Diabetes, one of the world's top ten diseases, is known for its high mortality and complication rates and low cure rate. Prediabetes precedes the onset of diabetes, during which effective treatment can reduce diabetes risk. Prediabetes risk factors include high-calorie and high-fat diets, sedentary lifestyles, and stress. Consequences may include considerable damage to vital organs, including the retina, liver, and kidneys. Interventions for treating prediabetes include a healthy lifestyle diet and pharmacological treatments. However, while these options are effective in the short term, they may fail due to the difficulty of long-term implementation. Medications may also be used to treat prediabetes. This review examines prediabetic treatments, particularly metformin, glucagon-like peptide-1 receptor agonists, sodium glucose cotransporter 2 inhibitors, vitamin D, and herbal medicines. Given the remarkable impact of prediabetes on the progression of diabetes mellitus, it is crucial to intervene promptly and effectively to regulate prediabetes. However, the current body of research on prediabetes is limited, and there is considerable confusion surrounding clinically relevant medications. This paper aims to provide a comprehensive summary of the pathogenesis of pre-diabetes mellitus and its associated therapeutic drugs. The ultimate goal is to facilitate the clinical utilization of medications and achieve efficient and timely control of diabetes mellitus.
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Diabetes, a metabolic disease caused by abnormally high levels of blood glucose, has a high prevalence rate worldwide and causes a series of complications, including coronary heart disease, stroke, peripheral vascular disease, end-stage renal disease, and retinopathy. Small-molecule compounds have been developed as drugs for the treatment of diabetes because of their oral advantages. Insulin secretagogues are a class of small-molecule drugs used to treat diabetes, and include sulfonylureas, non-sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, and other novel small-molecule insulin secretagogues. However, many small-molecule compounds cause different side effects, posing huge challenges to drug monotherapy and drug selection. Therefore, the use of different small-molecule drugs must be improved. This article reviews the mechanism, advantages, limitations, and potential risks of small-molecule insulin secretagogues to provide future research directions on small-molecule drugs for the treatment of diabetes.
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Hipoglucemiantes , Insulina , Humanos , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Animales , Insulina/metabolismo , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/metabolismo , Compuestos de Sulfonilurea/uso terapéutico , Compuestos de Sulfonilurea/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Secretagogos/uso terapéutico , Secretagogos/farmacología , Secreción de Insulina/efectos de los fármacos , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Secretagogos de InsulinaRESUMEN
Carrimycin (CA), sanctioned by China's National Medical Products Administration (NMPA) in 2019 for treating acute bronchitis and sinusitis, has recently been observed to exhibit multifaceted biological activities, encompassing anti-inflammatory, antiviral, and anti-tumor properties. Despite these applications, its efficacy in sepsis treatment remains unexplored. This study introduces a novel function of CA, demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide (LPS) and cecal ligation and puncture (CLP) in mice models. Our research employed in vitro assays, real-time quantitative polymerase chain reaction (RT-qPCR), and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines, namely tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1ß), and interleukin 6 (IL-6), in response to LPS stimulation. Additionally, Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B (NF-κB) activation in LPS-stimulated RAW264.7 cells. Complementing these findings, in vivo experiments demonstrated that CA effectively alleviates LPS- and CLP-triggered organ inflammation in C57BL/6 mice. Further insights were gained through 16S sequencing, highlighting CA's pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways, particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP. Notably, a comparative analysis revealed that CA's anti-inflammatory efficacy surpasses that of equivalent doses of aspirin (ASP) and TIENAM. Collectively, these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment. This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.
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Lipopolisacáridos , Sepsis , Espiramicina/análogos & derivados , Ratones , Animales , Lipopolisacáridos/efectos adversos , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Punciones , Sepsis/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Despite the high mortality rate, sepsis lacks specific and effective treatment options. Conventional antibiotics, such as TIENAM (TIE; imipenem and cilastatin sodium for injection), face challenges owing to the emergence of bacterial resistance, which reduces their effectiveness and causes adverse effects. Addressing resistance and judicious drug use is crucial. Our research revealed that aloin (Alo) significantly boosts survival rates and reduces inflammation and bacterial load in mice with sepsis, demonstrating strong antimicrobial activity. Using a synergistic Alo + TIE regimen in a cecal ligation and puncture (CLP)-induced sepsis model, we observed a remarkable increase in survival rates from 10 % to 75 % within 72 h compared with the CLP group alone. This combination therapy also modulated inflammatory markers interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α, mitigated tissue damage, regulated immune cells by lowering NK, activated CD8+ and CD4+ T cells while increasing peritoneal macrophages, and decreased the bacterial load in the peritoneal cavity. We noted a significant shift in the abdominal cavity microbiota composition post-treatment, with a decrease in harmful bacteria, such as Lachnospiraceae_NK4A136_group, Klebsiella, Bacillus, and Escherichia, and an increase in beneficial bacteria, such as Lactobacillus and Mucispirillum. Our study emphasizes the efficacy of combining Alo with TIE to combat sepsis, and paves the way for further investigations and potential clinical applications aiming to overcome the limitations of TIE and enhance the therapeutic prospects of Alo.
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Despite the high mortality associated with sepsis, effective and targeted treatments remain scarce. The use of conventional antibiotics such as TIENAM (imipenem and cilastatin sodium for injection, TIE) is challenging because of the increasing bacterial resistance, which diminishes their efficacy and leads to adverse effects. Our previous studies demonstrated that ulinastatin (UTI) exerts a therapeutic impact on sepsis by reducing systemic inflammation and modulating immune responses. In this study, we examined the possibility of administering UTI and TIE after inducing sepsis in a mouse model using cecal ligation and puncture (CLP). We assessed the rates of survival, levels of inflammatory cytokines, the extent of tissue damage, populations of immune cells, microbiota in ascites, and important signaling pathways. The combination of UTI and TIE significantly improved survival rates and reduced inflammation and bacterial load in septic mice, indicating potent antimicrobial properties. Notably, the survival rates of UTI+TIE-treated mice increased from 10 % to 75 % within 168 h compared to those of mice that were subjected to CLP. The dual treatment successfully regulated the levels of inflammatory indicators (interleukin [IL]-6, IL-1ß, and tumor necrosis factor [TNF]-α) and immune cell numbers by reducing B cells, natural killer cells, and TNFR2+ Treg cells and increasing CD8+ T cells. Additionally, the combination of UTI and TIE alleviated tissue damage, reduced bacterial load in the peritoneal cavity, and suppressed the NF-κB signaling pathway. Our findings indicate that UTI and TIE combination therapy can significantly enhance sepsis outcomes by reducing inflammation and boosting the immune system. The results offer a promising therapeutic approach for future sepsis treatment.
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Despite the high mortality rate associated with sepsis, no specific drugs are available. Decoy receptor 3 (DcR3) is now considered a valuable biomarker and therapeutic target for managing inflammatory conditions. DcR3-SUMO, an analog of DcR3, has a simple production process and high yield. However, its precise underlying mechanisms in sepsis remain unclear. This study investigated the protective effects of DcR3-SUMO on lipopolysaccharide (LPS)-induced inflammatory cells and septic mice. We evaluated the effects of DcR3 intervention and overexpression on intracellular inflammatory cytokine levels in vitro. DcR3-SUMO significantly reduced cytokine levels within inflammatory cells, and notably increased DcR3 protein and mRNA levels in LPS-induced septic mice, confirming its anti-inflammatory efficacy. Our in vitro and in vivo results demonstrated comparable anti-inflammatory effects between DcR3-SUMO and native DcR3. DcR3-SUMO protein administration in septic mice notably enhanced tissue morphology, decreased sepsis scores, and elevated survival rates. Furthermore, DcR3-SUMO treatment effectively lowered inflammatory cytokine levels in the serum, liver, and lung tissues, and mitigated the extent of tissue damage. AlphaFold3 structural predictions indicated that DcR3-SUMO, similar to DcR3, effectively interacts with the three pro-apoptotic ligands, namely TL1A, LIGHT, and FasL. Collectively, DcR3-SUMO and DcR3 exhibit comparable anti-inflammatory effects, making DcR3-SUMO a promising therapeutic agent for sepsis.
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Citocinas , Lipopolisacáridos , Miembro 6b de Receptores del Factor de Necrosis Tumoral , Sepsis , Animales , Sepsis/metabolismo , Sepsis/tratamiento farmacológico , Miembro 6b de Receptores del Factor de Necrosis Tumoral/metabolismo , Miembro 6b de Receptores del Factor de Necrosis Tumoral/genética , Ratones , Citocinas/metabolismo , Inflamación/metabolismo , Masculino , Humanos , Proteínas Recombinantes de Fusión/farmacología , Antiinflamatorios/farmacología , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Ratones Endogámicos C57BLRESUMEN
Sepsis, characterized by high mortality rates, causes over 50 % of acute lung injury (ALI) cases, primarily due to the heightened susceptibility of the lungs during this condition. Suppression of the excessive inflammatory response is critical for improving the survival of patients with sepsis; nevertheless, no specific anti-sepsis drugs exist. Huperzine A (HupA) exhibits neuroprotective and anti-inflammatory properties; however, its underlying mechanisms and effects on sepsis-induced ALI have yet to be elucidated. In this study, we demonstrated the potential of HupA for treating sepsis and explored its mechanism of action. To investigate the in vivo impacts of HupA, a murine model of sepsis was induced through cecal ligation and puncture (CLP) in both wild-type (WT) and α7 nicotinic acetylcholine receptor (α7nAChR) knockout mice. Our results showed that HupA ameliorates sepsis-induced acute lung injury by activating the α7nAChR. We used the CLP sepsis model in wild-type and α7nAChR -/- mice and found that HupA significantly increased the survival rate through α7nAChR, reduced the pro-inflammatory cytokine levels and oxidative stress, ameliorated histopathological lung injury, altered the circulating immune cell composition, regulated gut microbiota, and promoted short-chain fatty acid production through α7nAChR in vivo. Additionally, HupA inhibited Toll-like receptor NF-κB signaling by upregulating the α7nAChR/protein kinase B/glycogen synthase kinase-3 pathways. Our data elucidate HupA's mechanism of action and support a "new use for an old drug" in treating sepsis. Our findings serve as a basis for further in vivo studies of this drug, followed by application to humans. Therefore, the findings have the potential to benefit patients with sepsis.
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Despite its high mortality, specific and effective drugs for sepsis are lacking. Decoy receptor 3 (DcR3) is a potential biomarker for the progression of inflammatory diseases. The recombinant human DcR3-Fc chimera protein (DcR3.Fc) suppresses inflammatory responses in mice with sepsis, which is critical for improving survival. The Fc region can exert detrimental effects on the patient, and endogenous peptides are highly conducive to clinical application. However, the mechanisms underlying the effects of DcR3 on sepsis are unknown. Herein, we aimed to demonstrate that DcR3 may be beneficial in treating sepsis and investigated its mechanism of action. Recombinant DcR3 was obtained in vitro. Postoperative DcR3 treatment was performed in mouse models of lipopolysaccharide- and cecal ligation and puncture (CLP)-induced sepsis, and their underlying molecular mechanisms were explored. DcR3 inhibited sustained excessive inflammation in vitro, increased the survival rate, reduced the proinflammatory cytokine levels, changed the circulating immune cell composition, regulated the gut microbiota, and induced short-chain fatty acid synthesis in vivo. Thus, DcR3 protects against CLP-induced sepsis by inhibiting the inflammatory response and apoptosis. Our study provides valuable insights into the molecular mechanisms associated with the protective effects of DcR3 against sepsis, paving the way for future clinical studies. IMPORTANCE: Sepsis affects millions of hospitalized patients worldwide each year, but there are no sepsis-specific drugs, which makes sepsis therapies urgently needed. Suppression of excessive inflammatory responses is important for improving the survival of patients with sepsis. Our results demonstrate that DcR3 ameliorates sepsis in mice by attenuating systematic inflammation and modulating gut microbiota, and unveil the molecular mechanism underlying its anti-inflammatory effect.
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Ciego , Modelos Animales de Enfermedad , Miembro 6b de Receptores del Factor de Necrosis Tumoral , Sepsis , Animales , Sepsis/tratamiento farmacológico , Sepsis/microbiología , Ratones , Miembro 6b de Receptores del Factor de Necrosis Tumoral/genética , Miembro 6b de Receptores del Factor de Necrosis Tumoral/metabolismo , Ciego/cirugía , Humanos , Ligadura , Punciones , Masculino , Ratones Endogámicos C57BL , Microbioma Gastrointestinal , Citocinas/metabolismo , Lipopolisacáridos , Apoptosis/efectos de los fármacos , InflamaciónRESUMEN
Kombucha is a customary tea-based beverage that is produced through the process of fermenting a mixture of tea and sugar water with symbiotic culture of bacteria and yeast (SCOBY). Traditional kombucha has various beneficial effects and can improve immunity. The significant market share of Kombucha can be attributed to the growing consumer inclination towards healthy foods within the functional beverage industry. The research focus has recently expanded from the probiotics of traditional black tea kombucha to encompass other teas, Chinese herbs, plant materials, and alternative substrates. There is a lack of comprehensive literature reviews focusing on substance transformation, functional, active substances, and efficacy mechanisms of alternative kombucha substrates. This article aimed to bridge this gap by providing an in-depth review of the biological transformation pathways of kombucha metabolites and alternative substrates. The review offers valuable insights into kombucha research, including substance metabolism and transformation, efficacy, pharmacological mechanism, and the purification of active components, offering direction and focus for further studies in this field.