Sparganii Rhizoma alleviates pulmonary fibrosis by inhibiting fibroblasts differentiation and epithelial-mesenchymal transition mediated by TGF-ß1/ Smad2/3 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Pulmonary fibrosis (PF), a lethal lung disease, can lead to structural destruction of the alveoli until death. Sparganii Rhizoma (SR), primarily distributed in East Asia, has been used clinically for hundreds of years against organ fibrosis and inflammation. AIM OF THE STUDY: We intended to verify the effect of SR alleviate PF and further explore mechanisms. METHODS: Murine model of PF was established by endotracheal infusion of bleomycin. We detected the anti-PF effect of SR through lung coefficient, hydroxyproline content, lung function and pathological staining. Then, we used Western Blot and RT-PCR to verify the mechanism. In vitro experiments, MRC-5 and BEAS-2B were induced to phenotypic transformation by TGF-ß1 and then RT-PCR, WB and IF were conducted to verify the effect of SR. RESULTS: SR significantly reduced BLM-induced PF in mice, improved lung function, slowed the degree of lung tissue lesions, and reduced collagen deposition. SR alleviated PF by inhibiting fibroblasts differentiation and epithelial-mesenchymal transition. In vivo studies explored the mechanism and found that it was related to TGF-ß1/Smad2/3 pathway. CONCLUSIONS: Our research proved SR could effectively treat PF, providing a fresh idea and approach for the treatment of PF with traditional Chinese medicine.

Qingfei Litan Decoction Against Acute Lung Injury/Acute Respiratory Distress Syndrome: The Potential Roles of Anti-Inflammatory and Anti-Oxidative Effects.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is an acute respiratory failure syndrome characterized by progressive arterial hypoxemia and dyspnea. Qingfei Litan (QFLT) decoction, as a classic prescription for the treatment of acute respiratory infections, is effective for the treatment of ALI/ARDS. In this study, the compounds, hub targets, and major pathways of QFLT in ALI/ARDS treatment were analyzed using Ultra high performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) and systemic pharmacology strategies. UHPLC-MS identified 47 main components of QFLT. To explore its anti-inflammatory and anti-oxidative mechanisms, gene ontology (Go) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and network pharmacological analysis were conducted based on the main 47 components. KEGG enrichment analysis showed that TNF signaling pathway and Toll-like receptor signaling pathway may be the key pathways of ALI/ARDS. We explored the anti-inflammatory and anti-oxidative pharmacological effects of QFLT in treatment of ALI/ARDS in vivo and in vitro. QFLT suppressed the levels of proinflammatory cytokines and alleviated oxidative stress in LPS-challenged mice. In vitro, QFLT decreased the levels of TNF-α, IL-6, IL-1ß secreted by LPS-activated macrophages, increased GSH level and decreased the LPS-activated reactive oxygen species (ROS) in lung epithelial A549 cells. This study suggested that QFLT may have anti-inflammatory and anti-oxidative effects on ALI/ARDS, combining in vivo and in vitro experiments with systemic pharmacology, providing a potential therapeutic strategy option.

Integrated multicomponent analysis based on UHPLC-Q-Exactive Orbitrap-MS and network pharmacology to elucidate the potential mechanism of Baoyuan decoction against idiopathic pulmonary fibrosis.

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a serious lung disease with a high mortality rate. Baoyuan decoction (BYD), a classic medicinal food homology recipe, has anti-apoptotic effects, enhances immune function, and alleviates fibrosis, suggesting that it may be a potential therapeutic drug for IPF. OBJECTIVES: We aimed to identify the main active ingredients of BYD, determine the basis of its efficacy, prove its anti-IPF effects, and explore the mechanisms underlying its anti-IPF effects. MATERIALS AND METHODS: In this study, the active components of BYD were detected and analysed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). A network pharmacology analysis was performed to determine the potential targets and relevant pathways of BYD in treating IPF. Western blotting and quantitative real-time polymerase chain reaction (qPCR) were conducted to verify the efficacy of BYD against IPF. Finally, molecular docking and qPCR were performed to identify the central targets of BYD. RESULTS: A total of 39 components of BYD were identified. After performing the network pharmacology analysis, 35 active components and eight presumptive targets of BYD were found to play a central role in its anti-IPF effects. The molecular docking results indicated that most of the active components of BYD exhibited good binding activity with these eight central target proteins. In addition, the expression of collagen, α-SMA, and these eight targets in human pulmonary fibroblast (HPF) cells was suppressed from treatment with BYD. CONCLUSION: This study determined the efficacy of BYD against IPF and clarified its multiple-target and multiple-pathway mechanisms. Furthermore, the study also provides a new method for exploring the chemical and pharmacological bases of other traditional Chinese medicine (TCM).

Network Pharmacology Prediction and Molecular Docking-Based Strategy to Discover the Potential Pharmacological Mechanism of Wen-Yu-Jin against Pulmonary Fibrosis in a Mouse Model.

BACKGROUND: Pulmonary fibrosis (PF) is a devastating lung disease, resulting in gas exchange dysfunction until death. The two drugs approved by the FDA, pirfenidone and nintedanib, have obvious side effects. Wen-yu-jin (WYJ), one of the commonly used herbs in China, can treat respiratory diseases. The potential effects and the underlying mechanism of WYJ against PF are unclear. PURPOSE: Employing network pharmacology, molecular docking, and in vivo and in vitro experiments to explore the potential effects and underlying mechanisms of WYJ in the treatment of PF. METHODS: Ultra-high pressure liquid chromatography combined with linear ion trap-orbital tandem mass spectrometry (UHPLC-LTQ-orbital trap) was used to identify compounds of WYJ. We got PF-related targets and WYJ compounds-related targets from public databases and further completed critical targets exploration, network construction, and pathway analysis by network pharmacology. Molecular docking predicted binding activity of WYJ compounds and critical targets. Based on the above results, in vivo and in vitro experiments validated the potential effects and mechanisms of WYJ against PF. RESULTS: 23 major compositions of WYJ were identified based on UHPLC-LTQ-Orbitrap. According to the results of network pharmacology, STAT3, SRC, IL6, MAPK1, AKT1, EGFR, MAPK8, MAPK14, and IL1B are critical therapeutic targets. Molecular docking results showed that most of the compounds have good binding activities with critical targets. The results of in vivo and in vitro experiments showed that WYJ alleviated the process of fibrosis by targeting MAPK and STAT3 pathways. CONCLUSION: Network pharmacology, molecular docking, and in vivo and in vitro experiments showed the potential effects and mechanisms of WYJ against PF, which provides a theoretical basis for the treatment of WYJ with PF.

Silicon nanowires decorated with platinum nanoparticles were applied for photothermal-enhanced sonodynamic therapy.

Sonodynamic therapy (SDT) triggered by ultrasound (US) can overcome pivotal limitations of photo-therapy owing to its high depth-penetration and low phototoxicity. However, there is still a need to develop more efficient sonosensitizes to enhance the therapy efficiency. Methods: In this study, Pt nanoparticles (Pt NPs) are reduced on silicon nanowires (SiNWs) by in situ reduction to prepare Si-Pt nanocomposites (Si-Pt NCs). Results: Si-Pt NCs can produce reactive oxygen radicals (ROS) under ultrasound (US) irradiation, which have sonodynamic therapy (SDT) effect. Meanwhile, Si-Pt NCs can convert excess hydrogen peroxide (H2O2) into ROS in the tumor microenvironment, which endow strong chemodynamic therapy (CDT) effect. Taking the advantages of the mesoporous structure of SiNWs, the SDT and CDT effects of Si-Pt NCs are stronger than those of the pure Pt NPs and SiNWs. Besides, the mild photothermal effect of Si-Pt NCs further improves the SDT&CDT activity and realizes the combined cancer therapy. Conclusion: The developed Si-Pt NCs with the ability of photothermal enhanced SDT/CDT combined therapy play a momentous role in the novel cancer treatment.

Sini powder ameliorates the inflammatory response in rats with stress-induced non-alcoholic fatty liver disease by inhibiting the nuclear factor kappa-B / pyrin domain-containing protein 3 pathway.

OBJECTIVE: To evaluate the effectiveness of Sini powder for the treatment of non-alcoholic fatty liver disease (NAFLD) in rats and the molecular mechanisms involved. METHODS: A rat model of stress-induced NAFLD was established by a combination of long-term tethering and feeding of a high-fat, high-calorie diet. These rats were then intragastrically administered with either simvastatin, Sini powder, or vehicle for 1 week. The body mass and field test scores for each group were recorded weekly. Serum aspartate aminotransferase and alanine aminotransferase activities, and triglyceride, total cholesterol, and free fatty acid concentrations were measured. Liver tissue histopathology was examined on hematoxylin and eosin-stained paraffin sections and oil red O-stained frozen sections. The hepatic mRNA expression of nuclear factor kappa-B (NF-κB), NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 were measured by reverse transcription-polymerase chain reaction (RT-PCR). The hepatic protein concentrations of NF-κB and NLRP3, ASC, caspase-1, interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and the serum concentrations of IL-1ß and IL-6 were measured by enzyme-linked immunosorbent assay. RESULTS: Compared with the Blank group, rats in the Compound model group showed significant pathologic manifestations of NAFLD, and the expression of NF-κB, NLRP3, ASC, caspase-1, IL-1ß and IL-6 were significantly higher (all P < 0.01). Both simvastatin and Sini powder significantly ameliorated the NAFLD pathology and the abnormal expression of NF-κB, NLRP3, ASC, caspase-1, IL-1ß, and IL-6 (all P < 0.01). CONCLUSION: Sini powder inhibits the inflammatory response in rats with NAFLD, which is mediated by NF-κB/NLRP3, IL-1ß, and IL-6, reduces the effects of psychological stress, and improves lipid metabolism. Therefore, Sini powder may be effective for the treatment of stress-related NAFLD through multiple mechanisms.

Effect of traditional Chinese medicine formula Sinisan on chronic restraint stress-induced nonalcoholic fatty liver disease: a rat study.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) represents one of the most common forms of liver disease worldwide, and it is always regarded as a consequence of a sedentary, food-abundant lifestyle, sitting for an extended time, and a low physical activity level, which often coincide with chronic and long-lasting psychological stress. A Chinese medicine Sinisan (SNS) may be a potential formula for treating this kind of disease. METHODS: In this study, a long-term chronic restraint stress protocol was used to investigate the mechanism underlying stress-induced NALFD. To investigate the effect of SNS treatment on stress-induced NAFLD, we measured the liver and serum values of total cholesterol (TC), triglyceride (TG), liver free fatty acids (FFA), low-density lipoprotein, superoxide dismutase, tumor necrosis factor-α, malondialdehyde, interleukin (IL)-6, and serum values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase. Results are shown as a mean ± standard deviation. Significant differences between the groups were evaluated using the Student t-test. For multiple comparisons, one-way analysis of variance (ANOVA) was used. If the results of ANOVA indicated significant differences, post hoc analysis was performed with the Tukey test or Dunnett test, and p < 0.05 was considered statistically significant. RESULTS: Long-term chronic stress led to steatosis and non-alcoholic steatohepatitis. Additionally, SNS treatment significantly increased body weight gain (p < 0.01) and sucrose preference (p < 0.001), and it reduced the liver values of TC, TG, and FFA (p < 0.05). SNS also reduced the serum values of AST and ALT (p < 0.001), and the liver value of IL-6 (p < 0.01). CONCLUSIONS: This study's results demonstrate that psychological stress may be a significant risk factor of NAFLD. Furthermore, the traditional Chinese medicine formula SNS may have some beneficial effect in antagonizing psychological stress and stress-related NAFLD.

New Perspectives on Specific Immune-Depletion Technique Using Monoclonal Antibodies against Small Active Molecules in Herbs.

One of the main focuses in Chinese Medicine research is the identification of efficacious components in Chinese herbal medicine (CHM). Studies in such area are difficult due to the complexity and the synergistic characteristics of CHM. Current methods to track and separate active components are not adequate to meet the needs of revealing effects and identify substances and pharmacological mechanisms, which directly restrict the modernization and globalization of CHM. In this paper, a new methodology to deplete a single active component via immunoassay was introduced. The specific active component in a CHM mixture can then be identified and studied through comparative analyses of the pharmacological effects before and after immune depletion. With this new methodology, degree of contribution of a particular component to the whole complex herbal mixture can be elucidated, and its synergistic property with other components can be determined. The new method can reflect not only the overall combined pharmacological effects of CHM but also the effect of individual component. It is an effective way to explain the degree of contribution of one specific component to the overall activity of a CHM prescription.