Astragalus polysaccharides combined with ibuprofen exhibit a therapeutic effect on septic rats via an anti-inflammatory cholinergic pathway

Zhang

Evidence-Based Complementary and Alternative Medicine

et al. 2022

Objective. The cholinergic anti-inflammatory pathway (CAP) has been shown to modulate cytokine release by activating alpha-7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. However, their association with proinflammatory factors and prognosis in patients with acute respiratory distress syndrome (ARDS) has not been clarified. Here, we explored the correlation between CAP activity, proinflammatory factors, and the prognosis of ARDS patients. Methods. The data of patients with ARDS (n = 65; underwent treatment) and healthy individuals (the control group; n = 65; underwent routine physical examination) at the Chongqing People's Hospital were investigated. Based on the survival status, ARDS patients were divided into a death ARDS group (n = 22) and a survival ARDS group (n = 43), and based on the diagnostic criteria of ARDS, the patients were also divided into a severe ARDS group (n = 30) and a mild-to-moderate ARDS group (n = 35). The levels of acetylcholine (ACh), acetylcholinesterase (AChE), and α7nAChR mRNA in peripheral blood monocytes were assessed. The levels of TNF-α and IL-6 in peripheral serum and peripheral monocytes were detected by ELISA and Western blot tests. The association between α7nAChR and inflammatory factors and prognosis was analyzed. The receiver-operating characteristic (ROC) curve was used to evaluate the reliability of CAP-related factors in predicting the survival status of ARDS patients. Results. Compared with the control group, the levels of ACh, AChE, and α7nAChR mRNA of the ARDS group were significantly decreased. And, the ACh, AChE, and α7nAChR mRNA levels in the death/severe ARDS group were significantly lower than in the survival/mild-to-moderate ARDS group. However, the levels of TNF-α and IL-6 were significantly higher in the severe/death ARDS group. Furthermore, we observed that CAP-related factors were negatively correlated with the levels of IL-6 and TNF-α in peripheral serum in the ARDS group. The ROC curve showed that CAP-related factors were reliable markers for predicting the survival status of ARDS patients. Conclusion. The related factors of the cholinergic anti-inflammatory pathway were significantly decreased in patients with ARDS, suggesting the ACh, AChE, and α7nAChR levels as potential indicators to evaluate the severity and prognosis status of ARDS patients.

Section: Discussionmentioning

confidence: 99%

Association of the Cholinergic Anti-Inflammatory Pathway Activity with Proinflammatory Factors and Prognosis of Patients with Acute Respiratory Distress Syndrome

Zhang

Evidence-Based Complementary and Alternative Medicine

et al. 2022

“…Another histological feature of AD is the present and accumulation of reactive astrocytes and microglia around plaque, which is called gliosis or neuroinflammation [ 22 ]. Previously, APS has been found to be a promising therapeutic strategy for reducing inflammatory response [ 23 ] and possess anti-inflammatory activity [ 24 , 25 , 26 , 27 ]. Gliosis was observed to evaluate the effect of APS on ameliorating HFSTZ-induced neuroinflammation in our present study.…”

Section: Discussionmentioning

confidence: 99%

Astragalus membranaceus-Polysaccharides Ameliorates Obesity, Hepatic Steatosis, Neuroinflammation and Cognition Impairment without Affecting Amyloid Deposition in Metabolically Stressed APPswe/PS1dE9 Mice

Huang

Tsay²,

et al. 2017

IJMS

Astragalus membranaceus is commonly used in traditional Chinese medicine for strengthening the host defense system. Astragalus membranaceus-polysaccharides is an effective component with various important bioactivities, such as immunomodulation, antioxidant, anti-diabetes, anti-inflammation and neuroprotection. In the present study, we determine the effects of Astragalus membranaceus-polysaccharides on metabolically stressed transgenic mice in order to develop this macromolecules for treatment of sporadic Alzheimer’s disease, a neurodegenerative disease with metabolic risk factors. Transgenic mice, at 10 weeks old prior to the appearance of senile plaques, were treated in combination of administrating high-fat diet and injecting low-dose streptozotocin to create the metabolically stressed mice model. Astragalus membranaceus-polysaccharides was administrated starting at 14 weeks for 7 weeks. We found that Astragalus membranaceus-polysaccharides reduced metabolic stress-induced increase of body weight, insulin and insulin and leptin level, insulin resistance, and hepatic triglyceride. Astragalus membranaceus-polysaccharides also ameliorated metabolic stress-exacerbated oral glucose intolerance, although the fasting blood glucose was only temporally reduced. In brain, metabolic stress-elicited astrogliosis and microglia activation in the vicinity of plaques was also diminished by Astragalus membranaceus-polysaccharides administration. The plaque deposition, however, was not significantly affected by Astragalus membranaceus-polysaccharides administration. These findings suggest that Astragalus membranaceus-polysaccharides may be used to ameliorate metabolic stress-induced diabesity and the subsequent neuroinflammation, which improved the behavior performance in metabolically stressed transgenic mice.

Analytical Cellular Pathology

“…Astragalus has a complex chemical composition, and its main active ingredients include astragaloside, flavonoids, and polysaccharides [ 13 ]. In the treatment of sepsis, studies have confirmed that Astragalus polysaccharides (APS) have anti-inflammatory, proliferative, and immune-regulating effects [ 14 – 16 ]. In the study of kidney disease, Ma et al found that APS pretreatment can prevent cisplatin-induced AKI by reducing oxidative damage and resisting apoptosis [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Astragalus Polysaccharide on Sepsis-Induced Acute Kidney Injury

Sun

Wei

Zhang

et al. 2021

Objective. To explore the protective roles of Astragalus polysaccharide (APS) on acute renal injury (AKI) induced by sepsis. Methods. Firstly, an animal model of sepsis-induced AKI was established by injecting lipopolysaccharide (LPS) into mice. The mice were pretreated with an intraperitoneal injection of 1, 3, and 5 mg/(kg·d) APS for 3 consecutive days. The severity of kidney injury was then scored by histopathological analysis, and the concentrations of serum urea nitrogen (BUN) and serum creatinine (SCr) and the levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were determined as well. In in vitro experiments, lipopolysaccharide (LPS) was used to induce HK-2 cell injury to establish a sepsis-induced AKI cell model, and the cell counting kit-8 (CCK-8) method was performed to determine the cytotoxicity and appropriate experimental concentration of APS. Then, cells were divided into the control, LPS, and APS+LPS groups. Cell apoptosis and inflammation-related TNF-α, IL-1β, IL-6, and IL-8 were determined by flow cytometry and enzyme-linked immunosorbent assay (ELISA), respectively. The microscope was used to observe the morphological changes of cells, and the cell migration ability was measured by wound healing assay. RT-qPCR and Western blot assay were used to determine the mRNA and protein levels of apoptosis-related factors including caspase-3, caspase-9, Bax, and Bcl-2; endoplasmic reticulum stress- (ERS-) related biomarkers including C/EBP homologous protein (CHOP) and glucose-regulated protein78 (GRP78); and epithelial-mesenchymal transition- (EMT-) related biomarkers including E-cadherin, Snail, α-smooth muscle actin (α-SMΑ), and Vimentin. Results. In vivo experiments in mice showed that APS can reverse LPS-induced kidney damage in a concentration-dependent manner ( P < 0.05 ); the concentrations of BUN and Scr were increased (all P < 0.05 ); similarly, the levels of TNF-α and IL-1β were increased as well (all P < 0.05 ). In in vitro experiments, the results showed that LPS can significantly cause HK-2 cell damage and induce apoptosis, inflammation, ERS, and EMT. When APS concentration was in the range of 0-200 μg/mL, it had no cytotoxicity in HK-2 cells, and 100 μg/mL APS pretreatment could significantly mitigate the decrease of cell activity induced by LPS ( P < 0.05 ). Compared with the LPS group, APS pretreatment could inhibit the expression of inflammatory factors including TNF-α, IL-1 β, IL-6, and IL-8 (all P < 0.05 ), reducing the number of apoptotic cells ( P < 0.05 ), suppressing the expression of caspase-3, caspase-9, and Bax, but upregulating the expression levels of Bcl-2. In ERS, APS pretreatment inhibited LPS-induced upregulation of CHOP and GRP78. Moreover, in EMT, APS pretreatment could inhibit the morphological changes of cells, downregulate the migration, decrease the expression of EMT biomarkers, and inhibit the process of EMT. Conclusion. APS could alleviate sepsis-induced AKI by regulating inflammation, apoptosis, ERS, and EMT.