lipopolysaccharide

Despite advancements in antimicrobial and anti-inflammatory treatments, inflammation and its repercussions continue to pose a considerable challenge in medicine. Acute inflammation may cause life-threatening conditions like septic shock, while chronic inflammation leads to tissue degeneration and impaired function. Lipopolysaccharides (LPS), a well-known pathogenic trigger contributing to several dysfunctions, is a crucial part of the outer membrane of gr-negative bacteria. LPS are well-known for eliciting acute inflammatory responses by activating a pathogen-associated molecular pattern (PAMP), which stimulates the innate immune system and triggers local or systemic inflammatory responses. LPS also activate numerous intracellular molecules that modulate the expression of a wide range of inflammatory mediators. These mediators subsequently initiate or exacerbate various inflammatory processes. Beyond immune cells, LPS can also activate non-immune cells, leading to inflammatory reactions. These excessive inflammatory responses are often detrimental and typically result in chronic and progressive inflammatory diseases, including neurodegenerative, cardiovascular diseases, and cancer. This review delves into the mechanisms by which the bacterial endotoxin LPS contribute to multiple inflammatory diseases. These insights into LPS signaling pathways could inform the design of new treatment strategies such as TLR4, NLRP3, HMGA1, MAPK, and NF-kB inhibitors. This enables precise targeting of inflammation-related processes in disease management.

Acute lung injury (ALI) is characterized by severe hypoxia and alveolar damage, often caused by oxidative stress, endoplasmic reticulum stress (ERS), and apoptosis. Fluvoxamine (FLV), an antidepressant, has tissue-protective properties through various intracellular mechanisms. This study investigates the anti-inflammatory effects of  FLV used as an antidepressant in a lipopolysaccharide (LPS)-induced ALI model.

Thirty-two female Wistar Albino rats aged 14–16 weeks and weighing 300–350 g, with 8 animals in each group, were divided into four groups: control, LPS, LPS+FLV, and FLV. After LPS administration, rats were euthanized, and histopathological analysis, immunohistochemistry for tumor necrosis factor-α (TNF-α) and caspase-3 (Cas-3), ELISA for oxidative stress markers, and PCR for CHOP, Cas-12, and Cas-9 gene expressions were conducted.

In the LPS group, lung tissue damage, increased inflammatory cell infiltration, increased Cas-3 and TNF-α expressions, increased oxidative stress markers, and increased CHOP, Cas-9, and Cas-12 mRNA expressions were observed compared to the control group. FLV treatment in the LPS+FLV group significantly reversed these effects in the LPS group.

FLV exhibits protective effects against ALI by mitigating inflammation, ERS, and apoptosis via the CHOP/Cas-9/Cas-12 pathway. Further studies are needed to explore additional pathways and potential clinical applications of FLV.

 Evidence declared lipopolysaccharide (LPS) initiates inflammatory responses by stimulating the abandon of cytokines, which may perturb organ function. On the other side, it has been suggested Cedrol has potential properties, including anti-inflammatory and anti-oxidative activities. Herein, this study was done to assess the protective effect of Cedrol against LPS-associated heart damage.

 Thirty-five rats (200-250 g) were sorted into five groups, including control, LPS, LPS-Cedrol 7.5 mg/kg, LPS-Cedrol 15 mg/kg, and LPS-Cedrol 30 mg/kg groups. Cedrol was administrated through injected intra-peritoneally for two weeks. The heart tissues were removed and malondialdehyde (MDA) as a lipid peroxidation marker, superoxide dismutase (SOD), and catalase (CAT) as antioxidant markers were assessed. Furthermore, the interleukin (IL)-6 level in cardiac tissue was measured and Masson’s trichrome methods were employed to appraise cardiac inflammation and fibrosis, respectively.

 Inflammation induced by LPS was significantly accompanied by myocardial fibrosis which was shown by Masson’s trichrome staining (P<0.001). In addition, LPS administration enhanced the MDA level while it diminished the activity of anti-oxidant markers such as CAT and SOD (P<0.001 for all cases). In the histological results, Cedrol improved LPS-induced inflammation and cardiac fibrosis (P<0.01 to P<0.001). Cedrol also enhanced CAT and SOD activities, whereas declined MDA level in the cardiac tissue (P<0.01 to P<0.001).

 The current findings proposed that the administration of Cedrol exerted a protective role in LPS-associated heart damage by reducing inflammation, cardiac fibrosis, and oxidative stress.

Probiotic administration can be an effective treatment against intestinal inflammation. This study aimed to assess the potential effects of spores isolated from probiotic strains Bacillus subtilis natto and Bacillus coagulans Hammer on inflammation induced by lipopolysaccharide (LPS) in human colon epithelial cells in vitro.

The viability of HT-29 cells treated with spores derived from B. subtilis natto and B. coagulans Hammer (MOI 10, 100, 1000), as well as LPS (10 μg/ml) was assessed. The anti-inflammatory effects of spores were examined on HT-29 cells that were pre-stimulated with LPS. The expression level of IL-6 and TLR4 genes in HT-29 cells was quantified after 24 h using RT-qPCR.

There was no significant reduction in the viability of HT-29 cells after exposure to LPS and various MOIs of probiotic spores. Stimulation of HT-29 cells with LPS significantly increased the expression level of IL-6 and TLR4 in comparison to control (P < 0.0001). Spores isolated from both probiotic strains, B. subtilis natto and B. coagulans Hammer, caused a significant reduction in the gene expression of IL-6 and TLR4 in HT-29 cells compared to LPS control (P < 0.0001).

The findings of this study suggest that probiotics-derived spores may exert anti-inflammatory effects through interference with the LPS signaling pathway in colon cancer HT-29 cell line.

Toll-like receptor (TLR) 4 is involved in neuroinflammatory processes in peripheral tissues and central nervous system. Pro-inflammatory cytokines production, due to over activation of TLR4, interfere with insulin signaling elements lead to insulin resistance. Regarding the critical roles of TLR4 and insulin in the pathogenesis of Parkinson’s disease (PD), in the present study the TLR4/insulin receptor interaction was assessed in a neuroinflammation model of PD.

LPS was injected into the right striatum of male Wistar rats (20µg/rat). Insulin (2.5IU/ day), insulin receptor antagonist (S961; 6.5nM/kg), or TLR4 antibody (Resatorvid (TAK242); 0.01µg/rat) were administered intracerebroventricularly (ICV) for 14 days. Insulin and TAK242 were also simultaneously injected in a distinct group. Behavioral assessments were performed using rotarod, apomorphine-induced rotation, and cylinder tests. The levels of α-synuclein, TLR4, and elements of the insulin signaling pathway were measured in the striatum.

LPS impaired motor performance of the animals and increased the levels of α-synuclein and TLR4. Furthermore, it reduced mRNA levels of IRS1 and IRS2 and enhanced GSK3β mRNA and protein levels, indicating the development of insulin resistance. Treatment with insulin and TAK 242 improved motor deficits, restored insulin signaling pathway, and reduced α-synuclein and TLR4 levels.

The findings indicate that LPS impaired motor function, at least in part, via α-synuclein and TLR4 overexpression, leading to insulin resistance. Suppression of TLR4 and activation of insulin receptors attenuated motor deficits, suggesting that TLR4 and insulin receptors are promising therapeutic targets for PD modification.

The protective impacts of physical activity against inflammatory and oxidative stress conditions have been demonstrated. In this study, the impacts of moderate-intensity exercise on oxidative stress-associated factors and proinflammatory cytokines levels as well as the count of white blood cells (WBC) were assessed in a lipopolysaccharide (LPS)-triggered model of inflammation. Wistar rats were randomized into these groups (8 rats in each): (1) control; (2) LPS; (3) moderate exercise (EX); and (4) moderate exercise + LPS (EX+LPS). Exercise groups were trained for 8 weeks (30 min, 6 days/week) at 15 m/min speed. During the final week of the experiment, 1 mg/kg/day of intraperitoneal LPS was administered for 5 days. On day 56, from the rats’ hearts, peripheral blood was taken for biochemical evaluation. LPS enhanced serum levels of C-reactive protein (CRP), interleukin (IL)- 1β, tumor necrosis factor-α (TNF-α), metabolites of nitric oxide, and malondialdehyde (MDA), as well as the counts of total WBC, monocytes, neutrophils, and eosinophils, but decreased serum levels of thiol as well as superoxide dismutase (SOD) and catalase (CAT) activity versus the control rats. Moderate exercise reduced the levels of thiol, CAT, and SOD, but increased TNF-α level, and total WBC, neutrophils, eosinophils, and monocytes counts versus the control group. In the EX+LPS group, moderate exercise decreased cell counts and diminished MDA, TNF-α, IL-1β, and CRP levels, while increasing thiol level, CAT, and SOD versus the LPS group. In our study, exercise preconditioning reduced inflammation induced by LPS by ameliorating inflammatory cytokine levels, WBC counts, and oxidative damage, while improving antioxidant defenses.

Carvacrol is a phenolic monoterpenoid compound that has antibacterial, antifungal, anti-cancer, and anti-inflammatory effects. Lipopolysaccharide (LPS) is derived from the outer cell wall of gram-negative bacteria and is responsible for acute kidney injury. In this research, the protective effect of carvacrol on lipopolysaccharide-induced acute kidney injury was studied. For this purpose, 40 male Wistar rats (200-250 g) were used. Animals were randomly divided into 5 equal groups: 1) control, 2) LPS group, 3) LPS+carvacrol (25 mg kg-1), 4) LPS+carvacrol (50 mg kg-1) and 5) LPS+carvacrol (100 mg kg-1). To induce acute renal injury, daily 1 mg kg-1 LPS for 2 weeks was injected intraperitoneally. Carvacrol was administered intraperitoneally daily for 30 minutes before LPS injection. LPS-induced kidney injury was evaluated by blood urea nitrogen (BUN), serum creatinine, and nitric oxide levels in kidney tissue by spectrophotometric methods. The level of the interleukin 1 beta was detected by ELISA in the kidney. Our results showed that LPS injection increased BUN, creatinine, nitric oxide, and IL-1β levels (P <0.001). Pretreatment with carvacrol reduced BUN at 25 mg kg-1 (P <0.001), 50 mg kg-1 (P <0.01), and 100 mg kg-1 (P <0.001) doses, nitric oxide at 25 mg kg-1 (P <0.05), 50 mg kg-1(P <0.01) and 100 mg kg-1(P <0.001) doses, and IL-1β levels (P <0.001) at all doses significantly but did not affect serum creatinine. These results indicate that carvacrol has an anti-inflammatory effect and protects kidneys against LPS by reducing pro-inflammatory mediators such as IL-1β and nitric oxide.

The mechanism of action of Crinum glaucumbulb (Cgb) A. Chev (Amaryllidaceae) is enigmatic. Therefore, this study aimed at investigating the possible modulating properties of an aqueous extract of Cgb on endogenous antioxidant enzymes during lipopolysaccharide (LPS)-induced oxidative stress in a rat model.

Experimental: 

25 male and 25 female rats were divided into five groups (n=5) each: control group; treatment group, rats were given an aqueous extract of Cgb for 7 days; induced-oxidative stress group, rats were injected with LPS for 4 hours; post-Cgb group, rats were injected with LPS for 4 hours and treated with an aqueous extract of Cgb; and pre-Cgb group, rats were given an aqueous extract of Cgb for 7 days, injected with LPS for 4 hours, and treated with an aqueous extract of Cgb for 7 days. The blood, brain, heart, lungs, liver, and kidneys were harvested for the biochemical analysis. The endogenous antioxidant enzymes (catalase, superoxide dismutase, and glutathione-S-transferase) were analysed spectrophotometrically.

The hallmark of LPS is its ability to decrease the activity of oxidative stress marker enzymes, as observed in this study. The pre- and post-administration of an aqueous extract of Cgb significantly (P≤0.05) reversed the damaging effect of LPS by increasing the activities of catalase and superoxide dismutase in the blood and organs of male and female rats, respectively, while plasma glutathione-S-transferase activity was inhibited.

Recommended applications/industries: 

The aqueous extract of Cgb has modulating properties to reduce the action of LPS-induced oxidative stress on endogenous antioxidant enzymes in male and female rats.

Salidroside (SAL), an active ingredient purified from the medicinal plant Rhodiola rosea, has anti-inflammatory, anti-oxidant, anticancer, and neuroprotective properties. The study aims to examine SAL’s protective role in liver damage brought on by lipopolysaccharide (LPS).  Six to eight-week-old male C57BL/6 wild-type mice were intraperitoneally treated with 10 mg/kg LPS for 24 hr and 50 mg/kg SAL two hours before  LPS administration. Mice were categorized into control, LPS, and LPS + SAL groups. To evaluate liver injury, biochemical and TUNNEL staining test studies were performed. The Elisa assay analyzed interleukin- 1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) pro-inflammatory cytokine expression levels. RT-qPCR and western blotting measured mRNA and protein expression of SIRT1, NF-кB, NLRP3, cleaved caspase-1, and GSDMD, respectively. Analysis of the serum alanine/aspartate aminotransferases (ALT/AST), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) revealed that SAL protected against hepatotoxicity induced by LPS. The pathological evaluation of the liver supported the protection provided by SAL. SAL treatment reversed IL-1β, TNF-α, and IL-6 pro-inflammatory cytokines after being induced by LPS (all, P<0.001). The western blotting examination results demonstrated that SAL increased the levels of Sirtuin 1 (SIRT1) expression but markedly reduced the phosphorylation of Nuclear Factor Kappa B (NF-B) and the expressions of NLRP3, cleaved caspase-1, and gasdermin D (GSDMD) induced by LPS (all, P<0.001). Our results speculated that by inhibiting the SIRT1- NF-κB pathway and NLRP3 inflammasome, SAL defends against LPS-induced liver injury and inflammation.

The present study aims to investigate the role of breast cancer-susceptibility gene 1 (BRCA1) protein in the β-Glucan (βG) molecule mediated regulation of lipopolysaccharide (LPS)-induced liver genotoxicity.

In this experimental study, totally, 32 male Swiss Albino mice were randomly divided into 4 equal groups: control (C), LPS-administered (LPS), βG-administered (βG) and βG-pre-administered/LPS-administered (βG+LPS). The βG was injected at the dose of 150 mg/kg/day intraperitoneally (i.p.) for 3 days. A single dose of 4 mg/ kg (i.p.) LPS was administered 24 hours after the last βG injection. BRCA1 expression was determined by western blot analysis and confirmed by quantitative immunofluorescence. Proliferating cell nuclear antigen (PCNA), nuclear factor erythroid 2–related factor (Nrf2) and 8-OHdG protein levels were also determined by the immunofluorescence analysis. The alkaline comet assay was performed. superoxide dismutase (SOD), catalase (CAT) and membrane lipid peroxidation were biochemically measured, and light microscopic histology was evaluated.

The BRCA1 expression level was significantly decreased in the LPS group. However, in the βG+LPS group, expression of BRCA1 protein was over 2 folds higher than the control. After the LPS induction, the DNA strand breaks, oxidative DNA lesions and abnormal proliferation of the liver cells were almost entirely suppressed in βG preadministrated animals, indicating the BRCA1 mediated ubiquitination of PCNA and activation of the DNA damage repair pathways. Activation of Nrf2 in the βG+LPS group resulted in an increase in the levels of Nrf2 pathway dependent antioxidant enzymes SOD and CAT, prevented the peroxidation of membrane lipids and maintained the histological architecture of the liver.

The results manifested that the βG is a strong inducer of the BRCA1 protein expression in the LPSinduced hepatic stress and the protein constitutes the key component of a βG mediated liver protection against an LPS-induced genotoxic and pathological damage.

Liver is an important player in regulation of body homeostasis. Study investigated the effects of hydro-alcohol extract of Zataria multiflora (ZM) on oxidative damage, level of IL-6 and enzymes of liver in lipopolysaccharide (LPS)-treated rats. The rats were distributed into 5 groups: 1) Control; 2) LPS; and 3-5) ZM-Extract (Ext) 50, ZM-Ext 100, and ZM-Ext 200. ZM-Ext groups received 50, 100 and 200 mg/kg of extract 30 min before LPS. Drugs were injected intraperitoneally. The entire period of this project was 17 days. In first three days, only extract was injected and then, ZM was injected along with LPS. LPS increased the level of ALT (Alanine aminotransferase), AST (Aspartate aminotransferase ), ALK-P (Alkaline Phosphatase), IL-6, malondialdehyde (MDA), and nitric oxide (NO) metabolites and lowered thiol, superoxide dismutase (SOD) and catalase (CAT) concentration. ZM extract not only reduced ALT, AST, ALK-P, IL-6, MDA, and NO metabolites concentrations but also increased thiol content, and SOD and CAT levels. Extract of ZM prevented LPS-induced hepatotoxicity. This protective effect was associated with reduction in inflammation and oxidative stress.

 Inflammation and oxidative stress are contributed to cardiovascular diseases. Vitamin D (Vit D) has antioxidant and anti-inflammatory properties. In the current research, the effect of Vit D on cardiac fibrosis and inflammation, and oxidative stress indicators in cardiovascular tissues was studied in lipopolysaccharides(LPS) injected rats.

 Rats were distributed into 5 groups and were treated for 2 weeks. Control: received vehicle(saline supplemented with tween-80) instead of Vit D and saline instead of LPS, LPS: treated by 1 mg/kg of LPS and was given vehicle instead of Vit D, LPS-Vit D groups: received 3 doses of Vit D (100, 1000, and 10000 IU/kg) of Vit D in addition to LPS. Vit D was dissolved in saline supplemented with tween-80 (final concentration 0.1%) and LPS was dissolved in saline. The white blood cell (WBC) was counted. Oxidative stress markers were determined in serum, aorta, and heart. Cardiac tissue fibrosis was also estimated using Masson’s trichrome staining method.

 WBC and malondialdehyde (MDA) were higher in the LPS group than the control group, whereas the thiol content, superoxide dismutase (SOD), and catalase (CAT) were lower in the LPS group than the control group (P<0.01 and P<0.001). Administration of Vit D decreased WBC (P<0.001) and MDA (P<0.05 and P<0.001) while enhanced thiol (dose 10000 IU/Kg) (P<0.001), SOD (dose 10000 IU/kg) (P<0.001), and CAT (P<0.05 and P<0.001) compared to the LPS group. All doses of Vit D also decreased cardiac fibrosis compared to the LPS group (P<0.001).

 Vit D protected the cardiovascular against the detrimental effect of LPS. This cardiovascular protection can be attributed to the antioxidant and anti-inflammatory properties of Vit D.

 Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are 2 common liver diseases that currently lack effective treatment options.

 This study aimed to investigate the effect of lipopolysaccharide (LPS)-stimulated adipose-derived stem cells (ADSCs) on NAFLD treatment in an animal model.

 Male Wistar rats were fed a high-fat diet (HFD) to induce NAFLD for 7 weeks. The rats were then categorized into 3 groups: Mesenchymal stem cell (MSC), MSC + LPS, and fenofibrate (FENO) groups. Liver and body weight were measured, and the expression of genes involved in fatty acid biosynthesis, β-oxidation, and inflammatory responses was assessed.

 Lipopolysaccharide-stimulated ADSCs were more effective in regulating liver and body weight gain and reducing liver triglyceride (TG) levels compared to the other groups. Treatment with LPS-stimulated ADSCs effectively corrected liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased transforming growth factor β (TGF-β) and genes associated with inflammatory responses. Additionally, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS.

 Lipopolysaccharide-stimulated ADSCs showed potential in alleviating NAFLD by reducing inflammatory genes and ROS levels in HFD rats, demonstrating better results than treatment with ADSCs and FENO groups alone.

Sepsis-mediated acute lung injury (ALI) is a critical clinical condition. Artesunate (AS) is a sesquiterpene lactone endoperoxide that was discovered in Artemisia annua, which is a traditional Chinese herb. AS has a broad set of biological and pharmacological actions; however, its protective effect on lipopolysaccharide (LPS)-induced ALI remains unclear.

LPS-mediated ALI was induced in rats through bronchial LPS inhalation. Then NR8383 cells were treated with LPS to establish an in vitro model. Further, we administered different AS doses in vivo and in vitro.

AS administration significantly decreased LPS-mediated pulmonary cell death and inhibited pulmonary neutrophil infiltration. Additionally, AS administration increased SIRT1 expression in pulmonary sections. Administration of a biological antagonist or shRNA-induced reduction of SIRT1 expression significantly inhibited the protective effect of AS against LPS-induced cellular injury, pulmonary dysfunction, neutrophil infiltration, and apoptosis. This demonstrates that enhanced SIRT1 expression is crucially involved in the observed protective effects.

Our findings could suggest the use of AS for treating lung disorders through a mechanism involving SIRT1 expression.

Lipopolysaccharide (LPS) has been shown to cause depression by activating microglia and inducing pro-inflammatory factors in the brain. Citrus medica (CM) is a plant with known therapeutic effects. In this study, depression was induced in mice using intraperitoneal (IP) LPS (1 mg/kg). Two days later, behavioral tests were conducted. Mice were divided into nine groups of seven, including the control group, LPS group, CM extract groups (at different doses), L-arginine (L-Arg, alone and with an effective 1.dose of CM extract), aminoguanidine (AG, with an ineffective dose of CM extract), L-NAME (with an ineffective dose of CM extract), and fluoxetine 30 minutes before LPS. In the behavioral tests, the duration of immobility in mice treated with CM extract was reduced compared to the control and LPS groups. Treatment with L-Arg increased the duration of immobility, which was reversed by CM extract. The concurrent administration of L-NAME and AG with CM extract demonstrated synergistic antidepressant effects.