Terminalia chebula tannin-rich extract showed significant anxiolytic activity against picrotoxin and could be used as natural therapy in neurodegenerative disorders.
Background
IL‐5‐dependent residential and IL‐18‐transformed pathogenic eosinophils have been reported; however, the role of IL‐18‐transformed CD274‐expressing pathogenic eosinophils compared to IL‐5‐generated eosinophils in promoting airway obstruction in asthma has not yet been examined.
Methods
Eosinophils are detected by tissue anti‐MBP and anti‐EPX immunostaining, CD274 expression by flow cytometry, and airway resistance using the Buxco FinePointe RC system.
Results
We show that A. fumigatus‐challenged wild‐type mice, and different gene‐deficient mice including naïve CC10‐IL‐18‐transgenic mice, accumulate mostly peribronchial and perivascular CD274‐expressing eosinophils except naïve CD2‐IL‐5‐transgenic mice. Additionally, we show that CD2‐IL‐5 transgenic mice following rIL‐18 treatment accumulate high number of CD274‐expressing perivascular and peribronchial eosinophils with induced collagen, goblet cell hyperplasia and airway resistance compared to saline‐challenged CD2‐IL5 transgenic mice. Furthermore, we also show that even A. fumigatus‐challenged IL‐5
−/− mice and rIL‐18 given ΔdblGATA mice accumulate CD274‐expressing eosinophil‐associated asthma pathogenesis including airway obstruction. Most importantly, we provide evidence that neutralization of CD274 and IL‐18 in A. fumigatus‐challenged mice ameliorate experimental asthma. Taken together, the data presented are clinically significant in establishing that anti‐IL‐18 neutralization is a novel immunotherapy to restrict asthma pathogenesis.
Conclusions
We demonstrate that IL‐18 is critical for inducing asthma pathogenesis, and neutralization of CD274 is a potential immunotherapeutic strategy for asthma.
Reports indicate that accumulated macrophages in the pancreas are responsible for promoting the pathogenesis of chronic pancreatitis (CP). Recently, macrophage-secreted cytokines have been implicated in promoting pancreatic acinar-to-ductal metaplasia (ADM). This study aims to establish the role of accumulated macrophage-activated NLRP3-IL-18-eosinophil mechanistic pathway in promoting several characteristics of pancreatic malignancy in CP. We report that in a murine model of pancreatic cancer (PC), accumulated macrophages are the source of NLRP3-regulated IL-18, which promotes eosinophilic inflammation-mediated accumulation to periductal mucin and collagen, including the formation of ADM, pancreatic intraepithelial neoplasia (PanINs), and intraductal papillary mucinous neoplasm. Most importantly, we show improved malignant characteristics with reduced levels of oncogenes in an anti–IL-18 neutralized and IL-18 gene deficient murine model of CP. Last, human biopsies validated that NLRP3-IL-18–induced eosinophils accumulate near the ducts, showing PanINs formation in PC. Taken together, we present the evidence on the role of IL-18–induced eosinophilia in the development of PC phenotype like ADM, PanINs, and ductal cell differentiation in inflammation-induced CP.
Terminalia bellirica (Gaertn.) Roxb., Combretaceae, fruits are used in Indian system of medicine for multiple therapeutic applications. The present study was aimed to investigate the effect of gallic acid extract from T. bellirica fruits on chronic mild stress-induced depression-like activity in mice model. The results showed that administration of T. bellirica ameliorated chronic mild stress-induced depression-like behavior by increased sucrose preference and decreased immobility time. Further, T. bellirica treatment has significantly regulated hyperactivity of hypothalamic-pituitary-adrenal axis by decreasing serum corticosterone and acetylcholinesterase. In addition, T. bellirica treatment has significantly modulated monoaminergic system by elevating neurotransmitters and inhibiting monoamino oxidases. Terminalia bellirica treatment has effectively antagonized the chronic mild stress-induced oxidative stress and apoptotic cell death as evidenced by mRNA or protein expression studies. Thus, the study concluded that T. bellirica produces an antidepressant-like activity by regulating hypothalamic-pituitary-adrenal axis, monoaminergic systems, and apoptotic cell death.
Hexavalent chromium [Cr (VI)] is highly toxic compared to other valence states of chromium. In the process of metabolic reduction, Cr (VI) converts to trivalent chromium. Aegle marmelos (Bael), a sacred plant of India and its fruits are being consumed as traditional formulations against various diseases such as ulcer, gastric mucosal damage, inflammations, febrile delirium, acute bronchitis, anxiety, etc. The present study assessed the protective effects of marmelosin (MAR) from Aegle marmelos against K 2 Cr 2 O 7 -induced toxic effects in HepG2 cell line through its antiapoptotic mechanism. Results of the study revealed that pretreatment of MAR ameliorated cell viability, mitochondrial damage, and DNA damage induced by K 2 Cr 2 O 7 in HepG2 cell line as evidenced by cell morphology, MTT, LDH, and MMP assays. Pretreatment of MAR attenuated K 2 Cr 2 O 7 -induced oxidative stress by downregulating intracellular ROS and RNS. Further, pretreatment of MAR significantly downregulated K 2 Cr 2 O 7 -induced apoptotic markers, such as Bax, Caspase 3, and Gadd45. Our results suggested that application of marmelosin could be beneficial in ameliorating chromium-induced apoptotic cell death by suppressing oxidative stress and regulating excessive DNA damage.
Practical applicationsThe study focused on protective mechanism of marmelosin from Aegle marmelos against chromium-induced oxidative stress for the first time. In this research, we reported that marmelosin effectively ameliorated K 2 Cr 2 O 7 -induced morphological changes such as oxidative stress and apoptotic cell death by regulating Gadd45, Bcl-2, Bax, and Caspase 3 gene expressions, and inhibition of intracellular ROS and RNS.The study provides a better understanding of the pharmacological mechanisms of Aegle marmelos and its bioactive compound, that is, marmelosin in the management of intoxication of heavy metals associated with excessive DNA damage.
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