ABSTRACT
Kangfuxin has been widely recognized for its use in treating ulcerative conditions and mucositis, primarily due to its anti-inflammatory properties, which promote cell proliferation, granulation tissue growth, and angiogenesis. However, the exact mechanisms underlying these effects remain poorly understood. In this study, we employed high-throughput mass spectrometry to identify 11 compounds in Kangfuxin, including uracil, hypoxanthine, xanthine, inosine, glutamic acid, glycine, alanine, valine, isoleucine, leucine, and lysine. Notably, the antipyretic and anti-inflammatory properties of inosine, one of these compounds, have not been well characterized. To address this gap, we induced fever in vivo using lipopolysaccharide (LPS) and conducted various experiments, including the analysis of endogenous mediators, inflammatory factors, quantitative polymerase chain reaction (QPCR), Western blotting, and hematoxylin and eosin (HE) staining. Our findings indicate that inosine significantly reduces LPS-induced fever, inhibits the expression of inflammatory factors, and alleviates the inflammatory response. These results suggest that inosine may serve as a potential therapeutic target for inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents , Inosine , Lipopolysaccharides , Inosine/pharmacology , Animals , Mice , Anti-Inflammatory Agents/pharmacology , Antipyretics/pharmacology , Male , Inflammation/drug therapy , Fever/drug therapy , Disease Models, Animal , Inflammation Mediators/metabolism , Cytokines/metabolism , Drugs, Chinese Herbal/pharmacologyABSTRACT
A comparative assessment of radioprotective properties of inosine nucleoside (riboxin) and recognized radioprotector indralin was carried out. We analyzed survival of male ICR CD-1 mice weighting 32.2±0.2 g exposed to external X-ray radiation at doses 6.5 and 6.75 Gy and receiving indralin at a dose of 100 or 150 µg/g body weight or riboxin (inosine) at a dose of 100 or 200 µg/g body weight before irradiation. The survival analysis was carried out by the Kaplan-Meier method. The significance was assessed by using the log-rank-test. Inosine showed a significant difference from the irradiated control only at a dose of 100 µg/g body weight at a radiation dose of 6.75 Gy. The survival of animals treated with indralin was significantly higher in comparison with not only the irradiated control group, but also with the groups receiving inosine.
Subject(s)
Inosine , Radiation-Protective Agents , Animals , Inosine/pharmacology , Radiation-Protective Agents/pharmacology , Male , Mice , Mice, Inbred ICR , X-Rays , PhenolsABSTRACT
BACKGROUND: It has been clinically confirmed that the Shexiang Baoxin Pill (SBP) dramatically reduces the frequency of angina in patients with stable coronary artery disease (SCAD). However, potential therapeutic mechanism of SBP has not been fully explored. PURPOSE: The study explored the therapeutic mechanism of SBP in the treatment of SCAD patients. METHODS: We examined the serum metabolic profiles of patients with SCAD following SBP treatment. A rat model of acute myocardial infarction (AMI) was established, and the potential therapeutic mechanism of SBP was explored using metabolomics, transcriptomics, and 16S rRNA sequencing. RESULTS: SBP decreased inosine production and improved purine metabolic disorders in patients with SCAD and in animal models of AMI. Inosine was implicated as a potential biomarker for SBP efficacy. Furthermore, SBP inhibited the expression of genes involved in purine metabolism, which are closely associated with thrombosis, inflammation, and platelet function. The regulation of purine metabolism by SBP was associated with the enrichment of Lactobacillus. Finally, the effects of SBP on inosine production and vascular function could be transmitted through the transplantation of fecal microbiota. CONCLUSION: Our study reveals a novel mechanism by which SBP regulates purine metabolism by enriching Lactobacillus to exert cardioprotective effects in patients with SCAD. The data also provide previously undocumented evidence indicating that inosine is a potential biomarker for evaluating the efficacy of SBP in the treatment of SCAD.
Subject(s)
Coronary Artery Disease , Drugs, Chinese Herbal , Inosine , Lactobacillus , Myocardial Infarction , Purines , Animals , Coronary Artery Disease/drug therapy , Male , Humans , Drugs, Chinese Herbal/pharmacology , Inosine/pharmacology , Middle Aged , Rats , Lactobacillus/drug effects , Female , Disease Models, Animal , Rats, Sprague-Dawley , Aged , Gastrointestinal Microbiome/drug effects , Fecal Microbiota TransplantationABSTRACT
Periventricular leukomalacia (PVL) is a neurological condition observed in premature infants, characterized by hypomyelination and activation of microglia. Maternal inflammation-induced brain injury in offspring significantly contributes to the development of PVL. Currently, there are no clinical pharmaceutical interventions available for pregnant women to prevent maternal inflammation-mediated brain injury in their offspring. Inosine has been shown to modulate the immune response in diverse stressful circumstances, such as injury, ischemia, and inflammation. The aim of this investigation was to examine the potential prophylactic impact of inosine on offspring PVL induced by maternal inflammation. This was accomplished by administering a 1â¯mg/ml inosine solution (40â¯ml daily) to pregnant Sprague-Dawley (SD) rats for 16 consecutive days prior to their intraperitoneal injection of lipopolysaccharide (350⯵g/kg, once a day, for two days). The results showed that maternal inosine pretreatment significantly reversed the reduction in MBP and CNPase (myelin-related markers), CC-1 and Olig2 (oligodendrocyte-related markers) in their PVL pups (P7), suggesting that inosine administration during pregnancy could improve hypomyelination and enhance the differentiation of oligodendrocyte precursor cells (OPCs) in their PVL pups. Furthermore, the protective mechanism of inosine against PVL is closely associated with the activation and polarization of microglia. This is evidenced by a notable reduction in the quantity of IBA 1-positive microglia, a decrease in the level of CD86 (a marker for M1 microglia), an increase in the level of Arg 1 (a marker for M2 microglia), as well as a decrease in the level of pro-inflammatory factors TNF-α, IL-1ß, and IL-6, and an increase in the level of anti-inflammatory factors IL-4 and IL-10 in the brain of PVL pups following maternal inosine pretreatment. Taken together, inosine pretreatment of pregnant rats can improve hypomyelination in their PVL offspring by triggering the M1/M2 switch of microglia.
Subject(s)
Inflammation , Inosine , Microglia , Rats, Sprague-Dawley , Animals , Female , Pregnancy , Microglia/drug effects , Microglia/metabolism , Rats , Inosine/pharmacology , Inflammation/metabolism , Lipopolysaccharides/pharmacology , Leukomalacia, Periventricular/metabolism , Myelin Sheath/metabolism , Myelin Sheath/drug effects , Animals, Newborn , Prenatal Exposure Delayed EffectsABSTRACT
Adenosine (Ado) drives immune suppression in the tumor microenvironment. In this issue of Cancer Cell, Klysz et al. investigate Ado-mediated immunosuppression. Overexpression of Ado deaminase (ADA-OE), metabolizing Ado to inosine (INO), induces stemness and improves CAR T cell functionality. Likewise, exposure to INO enhances CAR T cells' function and induces stemness features.