Polygala tenuifolia willd. Extract alleviates LPS-induced acute lung injury in rats via TLR4/NF-κB pathway and NLRP3 inflammasome suppression.

BACKGROUND: Acute lung injury (ALI) has received considerable attention in the field of critical care as it can lead to high mortality rates. Polygala tenuifolia, a traditional Chinese medicine with strong expectorant properties, can be used to treat pneumonia. Owing to the complexity of its composition, the main active ingredient is not yet known. Thus, there is a need to identify its constituent compounds and mechanism of action in the treatment of ALI using advanced technological means. PURPOSE: We investigated the anti-inflammatory mechanism and constituent compounds with regard to the effect of P. tenuifolia Willd. extract (EPT) in lipopolysaccharide (LPS)-induced ALI in vivo and in vitro. METHODS: The UHPLC-Q-Exactive Orbitrap MS technology was used to investigate the chemical profile of EPT. Network pharmacology was used to predict the targets and pathways of action of EPT in ALI, and molecular docking was used to validate the binding of polygalacic acid to Toll-like receptor (TLR) 4. The main compounds were determined using LC-MS. A rat model of LPS-induced ALI was established, and THP-1 cells were stimulated with LPS and adenosine triphosphate (ATP) to construct an in vitro model. Pathological changes were observed using hematoxylin and eosin staining, Wright-Giemsa staining, and immunohistochemistry. The expression of inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) was determined using enzyme-linked immunosorbent assay, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The LPS + ATP-induced inflammation model in THP-1 cells was used to verify the in vivo experimental results. RESULTS: Ninety-nine compounds were identified or tentatively deduced from EPT. Using network pharmacology, we found that TLR4/NF-κB may be a relevant pathway for the prevention and treatment of ALI by EPT. Polygalacic acid in EPT may be a potential active ingredient. EPT could alleviate LPS-induced histopathological lung damage and reduce the wet/dry lung weight ratio in the rat model of ALI. Moreover, EPT decreased the white blood cell and neutrophil counts in the bronchoalveolar lavage fluid and decreased the expression of genes and proteins of relevant inflammatory factors (NE, MPO, Ly-6 G, TNF-α, IL-1ß, IL-6, and iNOS) in lung tissues. It also increased the expression of endothelial-type nitric oxide synthase expression. Western blotting confirmed that EPT may affect TLR4/NF-κB and NLRP3 signaling pathways in vivo. Similar results were obtained in THP-1 cells. CONCLUSION: EPT reduced the release of inflammatory factors by affecting TLR4/NF-κB and NLRP3 signaling pathways, thereby attenuating the inflammatory response of ALI. Polygalacic acid is the likely compounds responsible for these effects.

Effects of comprehensive nursing intervention on quality of life, Self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy.

Objective: To assess the effects of comprehensive nursing intervention on quality of life, self-efficacy, gastrointestinal reaction and immune function of patients with breast cancer undergoing chemotherapy. Methods: This was a retrospective study. One hundred and twenty patients receiving chemotherapy after breast cancer surgery were randomly divided into the experimental group and the control group(n=60) from January 2021 to January 2023. Patients in the perioperative period, the experimental group were given comprehensive nursing intervention, while those in the control group were given conventional specialist nursing intervention. The differences in quality of life, self-efficacy, gastrointestinal reaction, immune function and patient satisfaction between the two groups were compared and analyzed. Results: After the intervention, the SF-36 scores in the experimental group were significantly higher than those in the control group (P=0.00), the efficacy indicators were significantly improved compared to the control group(P=0.00); the scores of gastrointestinal symptoms in the experimental group were significantly lower than those in the control group after the intervention(P<0.05). The indexes of CD3+, CD4+ and CD4+/CD8+ in the experimental group after the intervention were significantly higher than those in the control group(P=0.00); The patient satisfaction in the experimental group was 100%, which was significantly higher than 92% in the control group, with statistically significant differences(P=0.02). Conclusion: Comprehensive nursing intervention leads to a variety of benefits in the treatment of patients with breast cancer during postoperative chemotherapy, such as relieving patients' gastrointestinal reactions, improving their immune function and quality of life, besides effectively improving their self-efficacy, which is worthy of clinical application.

Compression Therapy after Thermal Ablation of Varicose Veins: A Meta-Analysis.

OBJECTIVE: To investigate whether compression therapy after thermal ablation of varicose veins can improve the prognosis of patients. METHODS: Systematic research were applied for Chinese and English electronic databases(PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP Databases). Eligible prospective studies that comparing the efficacy of compression therapy and non-compression therapy on patients after thermal ablation of varicose veins were included. The interest outcome such as pain, quality of life (QOL), venous clinical severity score (VCSS), time to return to work and complications were analyzed. RESULTS: 10 studies were of high quality, and randomized controlled trials involving 1,545 patients met the inclusion criteria for this study. At the same time, the meta-analysis showed that the application of compression therapy improved pain (SMD: -0.51, 95% CI: -0.95, -0.07) but exhibited no statistically significant effect on QOL (SMD: 0.04, 95% CI: -0.08, 0.16), VCSS (MD: -0.05, 95% CI: -1.19, 1.09), time to return to work (MD: -0.43, 95% CI: -0.90, 0.03), total complications (RR: 0.54, 95% CI: 0.27, 1.09), and thrombosis (RR: 0.71, 95% CI: 0.31, 1.62). CONCLUSION: Compression therapy after thermal ablation of varicose veins can slightly relieve pain, but it has not been found to be associated with improvement in other outcomes.

Shiwei Qingwen decoction regulates TLR4/NF-κB signaling pathway and NLRP3 inflammasome to reduce inflammatory response in lipopolysaccharide-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear. AIM OF THE STUDY: To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia. MATERIALS AND METHODS: First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model. RESULTS: HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1ß, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1ß) in vivo and vitro. CONCLUSIONS: The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.

The synthetic cannabinoid WIN55212-2 ameliorates traumatic spinal cord injury via inhibition of GAPDH/Siah1 in a CB2-receptor dependent manner.

The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases. Therefore, the present study aimed to investigate whether WIN55212-2 could promote functional recovery after traumatic SCI via inhibition of the GAPDH/Siah1 signaling. The traumatic SCI was induced by dropping a 10-g impactor from 25mm on the dorsal surface of T9 and T10. Our results showed that WIN55212-2 alleviated the activation of GAPDH/Siah1 signaling pathway after SCI, as indicated by the reduction in GAPDH nuclear expression, GAPDH-Siah1 complex formation and iNOS protein expression. Furthermore, WIN55212-2 reduced apoptosis, production of IL-1ß and TNF-α and activation of NF-κB signaling in the spinal cord after SCI. The behavioral tests showed that WIN55212-2 improved the functional recovery after traumatic SCI as indicated by sustained increase in the locomotor scores. However, these neuroprotective effects of WIN55212-2 were blocked in the presence of the combined treatment of AM630 (an antagonist of CB2) rather than AM251 (an antagonist of CB1). In conclusion, our study indicates that, WIN55212-2 improves the functional recovery after SCI via inhibition of GAPDH/Siah1 cascades in a CB2 receptor dependent manner, indicative of its therapeutic potential for traumatic SCI or other traumatic conditions.

Neuroprotective effect of endogenous cannabinoids on ischemic brain injury induced by the excess microglia-mediated inflammation.

Increasing evidence has demonstrated the role of endogenous cannabinoids system (ECS) on protecting brain injury caused by ischemia (IMI). Papers reported that microglia-mediated inflammation has become one of the most pivotal mechanisms for IMI. This study was aimed to investigate the potential roles of ECS on neuron protection under microglia-mediated inflammation. Inflammatory cytokines level both in vitro (BV-2 cells) and in vivo (brain tissue from constructed IMI model and brain-isolated microglia) was detected. ECS levels were detected, and its effects on inflammations was also analyzed. Influence of microglia-mediated inflammation on neuron injury was analyzed. Moreover, the effects of ECS on protecting neuron injury were also analyzed. Our results showed that the levels of inflammatory cytokines including TNFα and IL-1ß were higher while IKBα was lower in IMI model brain tissue, brain-isolated microglia and BV-2 cells compared to the control. Inflammation was activated in microglia, as well as the activation of ECS characterized by the increasing level of AEA and 2-AG. Furthermore, the activated microglia-mediated self-inflammation performed harmful influence on neurons via suppressing cell viability and inducing apoptosis. Moreover, ECS functioned as a protector on neuron injury though promoting cell proliferation and suppressing cell apoptosis which were caused by the activated BV-2 cells (LPS induced for 3 h). Our data suggested that ECS may play certain neuroprotective effects on microglia-mediated inflammations-induced IMI through anti-inflammatory function.