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OBJECTIVE@#To examine the anti-inflammatory effects and potential mechanisms of polypeptide from Moschus (PPM) in lipopolysaccharide (LPS)-induced THP-1 macrophages and BALB/c mice.@*METHODS@#The polypeptide was extracted from Moschus and analyzed by high-performance liquid chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Subsequently, LPS was used to induce inflammation in THP-1 macrophages and BALB/c mice. In LPS-treated or untreated THP-1 macrophages, cell viability was observed by cell counting kit 8 and lactate dehydrogenase release assays; the proinflammatory cytokines and reactive oxygen species (ROS) were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively; and protein and mRNA levels were measured by Western blot and real-time quantitative polymerase chain reaction (qRT-PCR), respectively. In LPS-induced BALB/c mice, the proinflammatory cytokines were measured, and lung histology and cytokines were observed by hematoxylin and eosin (HE) and immunohistochemical (IHC) staining, respectively.@*RESULTS@#The SDS-PAGE results suggested that the molecular weight of purified PPM was in the range of 10-26 kD. In vitro, PPM reduced the production of interleukin 1β (IL-1β), IL-18, tumor necrosis factor α (TNF-α), IL-6 and ROS in LPS-induced THP-1 macrophages (P<0.01). Western blot analysis demonstrated that PPM inhibited LPS-induced nuclear factor κB (NF-κB) pathway and thioredoxin interacting protein (TXNIP)/nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain containing 3 (NLRP3) inflammasome pathway by reducing protein expression of phospho-NF-κB p65, phospho-inhibitors of NF-κB (Iκ Bs) kinase α/β (IKKα/β), TXNIP, NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1 (P<0.05 or P<0.01). In addition, qRT-PCR revealed the inhibitory effects of PPM on the mRNA levels of TXNIP, NLRP3, ASC, and caspase-1 (P<0.05 or P<0.01). Furthermore, in LPS-induced BALB/c mice, PPM reduced TNF-α and IL-6 levels in serum (P<0.05 or P<0.01), decreased IL-1β and IL-18 levels in the lungs (P<0.01) and alleviated pathological injury to the lungs.@*CONCLUSION@#PPM could attenuate LPS-induced inflammation by inhibiting the NF-κB-ROS/NLRP3 pathway, and may be a novel potential candidate drug for treating inflammation and inflammation-related diseases.
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Xiao Xumingtang in The Catalogue of Famous Ancient Classics (The First Batch) issued by the National Administration of Traditional Chinese Medicine is derived from the Important Prescriptions Worth a Thousand Gold for Emergency (Bei Ji Qian Jin Yao Fang) written by SUN Si-miao in the Tang dynasty. The present study systematically explored the origin, development, historical evolution, and clinical application of Xiao Xumingtang. As revealed by the results, Xiao Xumingtang as well as its analogues are primary prescriptions indicated for apoplexy before the Tang and Song dynasties and serve as the benchmark for the treatment of apoplexy. After the Song dynasty, due to the changes in the understanding of the pathogenesis of apoplexy and the limitations of the understanding of Xiao Xumingtang, its clinical application to apoplexy gradually decreased. In modern times, it has been re-recognized and applied, during which its clinical applications have undergone great changes. Its clinical applications are extensive, involving a variety of diseases related to the brain and nervous systems, such as stroke and its sequelae, peripheral facial paralysis, rheumatoid arthritis, hypertension, and other diseases related to the motor nervous system. Its primary indications are stroke and its sequelae, followed by peripheral facial paralysis. Other new indications are gradually found. This study is expected to provide references for the clinical application of Xiao Xumingtang and the transformation of new drugs.
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Malignant tumors are currently seriously endangering human health and life, which has become one of the main causes of death in China. In modern Western medicine, they are mainly tackled by surgery, chemotherapy, and radiotherapy, but the death toll continues to rise year by year. At present, most of the anti-tumor chemotherapeutics used in clinical practice have toxic and side effects, affecting the anti-tumor efficacy and the conditions after treatment. Long-term medication will also induce drug resistance, making the good anti-tumor effect difficult to be achieved. With the vigorous development of traditional Chinese medicine (TCM), it has played a crucial role in the fight against tumors. It is believed in TCM that "heat toxin" is one of the important causes of tumors. Therefore, the methods of clearing away heat and removing toxin are often emphasized in the treatment of tumors, and the resulting outcomes are satisfactory. There are many Chinese herbs and Chinese herbal compounds classified into the heat-clearing and toxin-removing type. Xihuangwan, a classic heat-clearing prescription, is composed of Calculus Bovis, Moschus, Olibanum, and Myrrh and has the effects of clearing away heat, removing toxin, eliminating edema, and dissipating mass, which is mainly used to treat carbuncle, pustule, scrofula, multiple abscess, and cancer caused by heat-toxin obstruction. In modern clinical practice, it has been employed in patients with lung cancer, breast cancer, gastric cancer, liver cancer, colorectal cancer, and other malignant tumors, especially during the advanced stage, as a routine or adjuvant treatment for alleviating their clinical symptoms and improving their quality of life. The main active components of Xihuangwan are pentacyclic triterpenoids (such as masticinic acids), volatile oils, steroids (like porcine deoxycholic acid), and bilirubin, which have been proved effective in anti-tumor. This paper reviewed the prescription source, pharmaceutical research, clinical anti-tumor research, and pharmacological mechanisms of Xihuangwan, which has provided reference for further expanding the anti-tumor applications of Xihuangwan and enhancing its secondary development.
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Aim To evaluate the effect of E-se extract on insulin resistance in KK-Ay mice with spontaneous type 2 diabetes anrl explore its mechanism.Methods Ten C57/6J mice were assigned to a normal control group.Fifty KK-Ay model mice were randomly divided into model group, positive control group ( rosiglita- zone, 2.67 mg • kg 1 ), and low- ( 0.75 g • kg 1 ) , medium- ( 1.50 g • kg 1 ) , and high-dose ( 3.00 g • kg ') E-se groups, with 10 mice in each group.All mice were measured for body weight and fasting blood glucose weekly, insulin tolerance on the 32nd day, and insulin after the last administration on the 35th day, and the insulin resistance/sensitivity indexes were calculated.The pancreas was stained by hematoxylin- eosin ( HE ).Islet cell apoptosis was detected by TUNEL staining.Glucagon-like peptide-1 ( GLP-1 ) was detected by immunohistochemistry.Results j j Compared with the model group, the E-se groups showed reduced body weight, fasting blood glucose, serum insulin concentration, and insulin resistance in¬dex, elevated insulin sensitivity index, decreased le¬sion grading score of pancreatic tissues and apoptosis percentage of islet cells, and increased content of GLP- 1 protein in pancreatic tissues.Conclusions E-se ex¬tract can improve insulin resistance by reducing serum insulin level, inhibiting islet cell apoptosis, and in¬creasing the sensitivity of the body to insulin.
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Objective:To investigate the pharmaceutical idiosyncratic hepatotoxicity effect of Xanthii Fructus on the immune-sensitive rat model induced by endotoxin lipopolysaccharide (LPS). Method:The SD rats were randomly divided into five groups: control group, model group, and three Xanthii Fructucs groups. The immune-sensitive rat model was established by LPS (iv. 0.7 mg·kg-1, twice every 7 days). Then, the rats in control and model groups received the equal volume of distilled water, while the rats in Xanthii Fructus groups were administrated with water extract of Xanthii Fructus intragastrically (1.67, 5.01, 16.7 g·kg-1, respectively) for 14 days. The serum and liver of the rats were collected on the 7th and 14th day to examine the levels of hepatotoxic biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), alkaline phosphatase (ALP), and total bile acids (TBA), and liver histopathology. In addition, inflammatory factors, including interleukin-1β(IL-1β), interleukin-2(IL-2), interleukin-6(IL-6), interleukin-10(IL-10)and tumor necrosis factor-α(TNF-α)of the idiosyncratic hepatotoxicity rats, were determined by enzyme-linked immunosorbent assay(ELISA). Result:The immune-sensitive model rats showed elevated levels of IL-1β, IL-6(P<0.05,P<0.01), and mild inflammatory cells infiltrated in portal area of liver significantly (P<0.05), with no significant changes in hepatotoxic biomarkers. Meanwhile, there was no significant change between Xanthii Fructus groups and model rats in the levels of hepatotoxic biomarkers, inflammatory factors and hepatic lesions. Conclusion:Water extract of Xanthii Fructus intragastrically does not affect the levels of hepatotoxic biomarkers, inflammatory factors and hepatic lesions in rats induced by LPS intravenously. That is to say, Xanthii Fructus does not induce pharmaceutical idiosyncratic hepatotoxicity.