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Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE-/- mice model induced by high-fat diet. These pathological changes were evaluated by H&E and oil red O staining. The levels of pro-inflammatory cytokines in aortic tissue were measured by enzyme-linked immunosorbent assay kit. These protein expressions were detected by Western blot and immunohistochemistry. The results showed that PCP inhibited the serum inflammatory mediators (tumor necrosis factor-α, interleukin-6, and nitric oxide) and lipids (low-density lipoprotein-cholesterol, triglyceride, and total cholesterol) increase. Moreover, PCP also reduced the concentration of malondialdehyde, increased the activity of superoxide dismutase, and improved the pathological changes of the aorta. Finally, PCP inhibited the activation of the TLR4/NF-κB pathway in the aorta and blocked the expression of matrix metalloproteinase 2 and intercellular adhesion molecule 1 proteins. In short, PCP intervenes in AS by reducing inflammatory factors and blood lipid levels.

Acute kidney injury is a common clinical condition associated with increased morbidity and mortality. It is essential to find effective drugs with low side effects in the treatment of acute kidney injury. Harmine is one of the major active components of Peganum harmala L. Harmine possesses various pharmacological activities, including anti-inflammatory activity. Nevertheless, the protective effect of harmine in acute kidney injury induced by lipopolysaccharide (LPS) in mice is unknown. Therefore, we investigated the protective effect of harmine in LPS-induced renal inflammation and the involved molecular mechanisms. The results showed that pretreatment with harmine (25 or 50 mg/kg) markedly alleviated kidney injury by reducing the release of kidney biomarkers and inflammatory mediators and the formation of malondialdehyde (MDA) and myeloperoxidase (MPO) while increasing superoxide dismutase (SOD) and glutathione (GSH) activities and improving renal histopathological changes. In addition, immunohistochemistry staining and western blot analysis indicated that harmine treatment suppressed the expression of toll-like receptor 4 (TLR4) and the phosphorylation of nuclear factor-kappa B (NF-κB) p65 and inhibitor of κBα (IκBα) while inhibiting the expression of NLRP3, caspase-1 and interleukin-1β (IL-1β). In brief, harmine protects against acute kidney injury induced by LPS in mice through reducing oxidative stress and inflammation responses. The involved underlying mechanisms of harmine in LPS-induced acute kidney injury might be related to inhibition of the TLR4-NF-κB pathway and NLRP3 inflammasome pathway. Based on the above conclusion, it is possible for harmine to be used to clinically treat acute kidney injury.

Fraxin, the effective component of the Chinese traditional medicine Cortex Fraxini, is reported to have anti-inflammatory effects. This study assessed the anti-inflammatory effect of fraxin on the lipopolysaccharide (LPS)-induced inflammatory response in A549 cells and the protective efficacy on LPS-induced acute lung injury (ALI) in mice. Fraxin reduced LPS-induced TNF-α, IL-6 and IL-1β production in A549 cells and alleviated the LPS-induced wet/dry (W/D) weight ratio and the effects observed via histopathological examination of the lung in vivo. Furthermore, fraxin reduced the protein concentrations in the broncho-alveolar lavage (BAL) fluid and cytokine production in the sera. Fraxin also clearly attenuated the oxidation index, including the activity of myeloperoxidase (MPO), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione (GSH). Immunohistochemistry analysis showed that fraxin suppressed LPS-induced inflammatory damage. The expression of proteins involved in the NF-κB and NLRP3 inflammatory corpuscle signalling pathways was consistent between the lung tissues and cell samples. Overall, fraxin played a protective role in LPS-induced lung injury by inhibiting the NF-κB and NLRP3 signalling pathways.

Atherosclerosis (AS) is a common chronic inflammatory disease of the arteries, which is closely related to dyslipidemia, inflammatory factors, and oxidative stress. Poria cocos polysaccharides (PCP) are one of the main active ingredients of Poria, which has significant pharmacological effects. In this study, the potential protective mechanism of PCP on AS was discussed in the ApoE

Inflammation plays an important role in the process of atherosclerosis (AS). Inhibition of inflammation is an effective way to prevent AS. Imperatorin (IMP) is a kind of furan coumarin with various activities. In this study, the anti-inflammatory effect of IMP was explored in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs and high fat diet (HFD)-induced ApoE-/- mice. The results showed that IMP attenuated the elevation of TNF-α, IL-6, MCP-1 and NO induced by ox-LDL in supernatant of VSMCs. IMP has normalized the levels of serum lipids (TC, TG, LDL-C and HDL-C) and attenuated inflammatory cytokines in serum. IMP also improved pathological changes and lipid accumulation in aorta. Matrix metalloproteinase-2 (MMP-2) expression in aorta was down-regulated by IMP. IMP could inhibit the phosphorylation of MAPKs pathway in the aorta and VSMCs, resulting in a significant decrease in the contents of p-ERK 1/2, p-JNK and p-P38. Overall, IMP could exert anti-inflammatory effects in vivo and in vitro to interfere with AS.

Oxidative stress, inflammation, and foam cell formation in vascular smooth muscle cells (VSMCs) are considered to play crucial roles in the pathogenesis of atherosclerosis. Poria cocos polysaccharides (PCP) has been shown to possess anti-inflammatory, antitumor and anti-oxidative properties. In this study we explored the effects of PCP on ox-LDL-induced inflammation, oxidative stress and foam cell formation in VSMCs. PCP significantly attenuated ox-LDL-induced oxidative stress, as evidenced by the decreased reactive oxygen species (ROS) and MDA levels, and the increased SOD activity in VSMCs. PCP suppressed the induction effect of ox-LDL on inflammatory cytokines and inflammatory mediators. PCP also substantially inhibited VSMCs foam cell formation and intracellular lipids accumulation. Mechanistically, PCP suppressed ox-LDL-induced up-regulation of LOX-1, which is responsible for ox-LDL uptake. Western blotting suggested that PCP activated ERK1/2 signaling pathway, increased Nrf2 translocated from cytoplasm to nucleus and heme oxygenase-1 (HO-1) expression. Up-regulation of PCP on Nrf2/HO-1 signaling was reversed by pretreatment with ERK inhibitor PD98059, indicating the involvement of ERK in PCP activation of Nrf2/HO-1 signaling. In conclusion, these results demonstrated that PCP exerted its protection against oxidative stress and inflammation via the ERK/Nrf2/HO-1 signaling pathway and that PCP may be a promising candidate for the therapy of atherosclerosis.

Acute lung injury (ALI) is a common lung disease accompanied by acute and persistent pulmonary inflammatory response syndrome, which leads to alveolar epithelial cells and capillary endothelial cell damage. Yam glycoprotein, separated from traditional Chinese yam, has been shown to have anti-inflammatory and immunomodulatory effects. In this experiment, we mainly studied the therapeutic effect and mechanism of a glycoprotein on the lipopolysaccharide (LPS)-induced ALI mice. An oral glycoprotein method was used to treat the mouse ALI model induced by LPS injection in the peritoneal cavity. Afterward, we measured the wet/dry (W/D) ratio, the activity of myeloperoxidase (MPO), the oxidative index superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-PX) and the production of inflammatory cytokines interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) to evaluate the effect of yam glycoprotein on lung tissue changes. We examined the protein expression of TLR4, ASC, NF-κBp65, p-NF-κBp65, Caspase-1, IκB, NLRP3, p-IκB, and β-actin by western blot analysis. Immunohistochemical analyses of NLRP3 and p-p65 in lung tissue were carried out to assess the mechanism of glycoprotein action. This result suggests that glycoprotein markedly depressed LPS-induced lung W/D ratio, MPO activity, MDA content SOD and GSH-Px depletion, and the contents of inflammatory cytokines IL-1β, IL-6, and TNF-α. Moreover, glycoprotein blocked TLR4/NF-κBp65 signaling activation and NLRP3inflammasome expression in LPS-induced ALI mice. As this particular study shows, glycoprotein has a safeguarding effects on LPS-induced ALI mice, possibly via activating NLRP3inflammasome and TLR4/NF-κB signaling pathways.

Cinnamaldehyde is a flavor isolated from the bark of Cinnamomum cassia Presl and exerts anti-inflammation effects in various diseases. In our study, we investigated the protective effects and the potential mechanism of cinnamaldehyde on atherosclerosis (AS) by using a high fat diet (HFD)-fed ApoE−/− atherosclerotic mouse model. Here, we found that the serum LDL-C, TG and TC levels were elevated and the HDL-C level was decreased in HFD-fed ApoE−/− mice. Cinnamaldehyde treatment significantly decreased inflammatory cytokine (TNF-α, IL-6, NO and MCP-1) overproduction and the serum lipid level. Meanwhile, cinnamaldehyde increased the HDL-C level and down-regulated the activity of lipid peroxidation product MDA in serum. Moreover, cinnamaldehyde reduced the atherosclerotic plaque area in ApoE−/− mice. Furthermore, cinnamaldehyde reduced matrix metalloproteinase-2 (MMP-2) expression and attenuated the high phosphorylation level of IκBα and p65 NF-κB. Overall, our study indicates that cinnamaldehyde may achieve the anti-atherosclerotic effect via the IκB/NF-κB signaling pathway.

Fraxin, the effective component isolated from Cortex Fraxini, has been reported to have anti-inflammation effects. The aim of this study was to explore the effect of fraxin on lipopolysaccharide (LPS)-induced endotoxic shock in mice. We used Kunming male mice to establish the model, and we found that fraxin could improve the survival rate of the LPS-induced mice. Histopathological study showed that fraxin could mitigate the injuries in LPS-induced lung and liver tissues. The levels of tumour necrosis factor-α and interleukin-6 both in serum and lung, liver tissues, and the productions of nitric oxide (NO), aspartate transaminase and alanine transaminase in serum were decreased by fraxin. Western blot assay demonstrated that the pretreatment with fraxin could downregulate LPS-induced protein expressions of nuclear factor-kappa B (NF-κB) and NLRP3 inflammatory corpuscle signalling pathways. Overall, fraxin had protective effects on LPS-induced endotoxic shock mice and the possible mechanisms might activate through NF-κB and NLRP3 inflammatory corpuscle signalling pathways.

Vascular smooth muscle cells (VSMCs) lesions play an important role in atherosclerosis. The latest findings indicate that green tea extract has potential benefits for patients with atherosclerosis, but the components and mechanisms of action are unknown. (−)-Epicatechin gallate (ECG) is the main active ingredient extracted from green tea and has significant biological functions. However, the mechanism of ECG in atherosclerosis remains unclear. Therefore, we investigated the intervention of ECG on VSMCs induced by oxidized low-density lipoprotein (ox-LDL). The results show that ECG reduces the inflammatory response by preventing the overproduction of inflammatory mediators in VSMCs. ECG regulates the cell cycle and down-regulates the expression of proliferating cell nuclear antigen (PCNA) and cyclinD1, and then exerts an anti-proliferative effect. Furthermore, inhibition of the expression of matrix metalloproteinase 2 (MMP-2) and intercellular adhesion molecule 1 (ICAM-1) may be the mechanism by which ECG inhibits the migration of ox-LDL-induced VSMCs. Oil red O staining results show that ECG can improve cell foaming and reduce the content of total cholesterol (TC). In addition, ECG significantly reduces reactive oxygen species activity and also reduces the expression of p-p38, p-JNK, p-ERK1/2, p-IκBα, p–NF–κBp65, and TLR4. These results indicate that ECG has potential clinical applications for preventing atherosclerosis.

Abnormal proliferation, migration and foaming of vascular smooth muscle cells (VSMCs) are involved in atherosclerosis (AS) process. Imperatorin (IMP) is a coumarin compound mainly originated from angelica dahurica in natural plants. In this study, effects of IMP on proliferation, migration and foaming of oxidized low-density lipoprotein (ox-LDL)-induced VSMCs were investigated. The results showed that IMP regulated cell cycle in S ~ G2/M phase and down-regulated the proliferating cell nuclear antigen (PCNA), and then exerted anti-proliferation effect. IMP might have a repressive effect on migration in ox-LDL-stimulated VSMCs through inhibiting the metalloproteinase-2 (MMP-2). Oil red O staining showed IMP suppressed lipid accumulation in ox-LDL-induced-VSMCs. This was consistent with the determination of Lectin-like oxidation of lectin-like ox-LDL receptor-1 (LOX-1) and total cholesterol (TC). IMP also reduced the expression of p-PI3K, p-Akt and p-mTOR in ox-LDL-treated VSMCs. These results suggested that IMP might play an anti-lesion role in ox-LDL-stimulated-VSMCs by inhibiting the PI3K/Akt/mTOR pathway.