Scutellarin alleviates lipopolysaccharide-provoked septic nephrotoxicity via attenuation of inflammatory and oxidative events and mitochondrial dysfunction.

BACKGROUND: Sepsis-associated acute kidney injury (AKI) is highlighted by high incidence of mortality and morbidity. Scutellarin is a flavone extracted from certain medicinal plants with anti-inflammatory and anti-oxidative properties. This research study was done to investigate the beneficial effect of scutellarin on lipopolysaccharide (LPS) murine model of AKI. MATERIALS AND METHODS: Five groups of mice were used including control (without LPS injection), LPS group (LPS injection, 10 mg/kg), and LPS + Scutellarin25, 50, and/or 100 groups (receiving scutellarin orally at different doses of 25, 50, or 100 mg/kg before LPS injection). RESULTS: Scutellarin pretreatment effectively lowered kidney function markers (BUN, creatinine, and cystatin C), improved superoxide dismutase (SOD) besides enhancement of level, and/or gene expression for nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase 1 (HO-1) and also reduced oxidative stress factors including reactive oxygen species (ROS) and malondialdehyde (MDA). In addition, scutellarin reduced tissue level and/or gene expression of inflammatory markers comprising toll-like receptor 4 (TLR4), nuclear factor-kappaB (NF-κB), and tumor necrosis factor α (TNF-α) and properly raised anti-inflammatory factor IL-10. Moreover, scutellarin enhanced mitochondrial membrane potential (MMP) and attenuated histopathological changes in renal tissue subsequent to LPS challenge. Beneficial effects of scutellarin was associated with improvement of gene expression regarding peroxisome proliferator-activated receptor gamma (PPARγ) and its coactivator PGC-1α as specific markers of mitochondrial biogenesis. CONCLUSION: These results indicate that scutellarin could protect against LPS-provoked AKI through restraining inflammation and oxidative stress and maintenance of mitochondrial health and biogenesis which is partly mediated through its regulation of Nrf2/PPAR-γ/PGC-1α/NF-kB/TLR4.

Therapeutic Potential of Isorhamnetin following Acetaminophen-Induced Hepatotoxicity through Targeting NLRP3/NF-κB/Nrf2.

Acetaminophen (APAP)-induced acute liver injury (ALI) is the principal cause of acute liver failure (ALF) in some countries including the United States and with few available treatments. Isorhamnetin is a bioflavonoid that is found in medicinal plants like Hippophae rhamnoides L. and Ginkgo biloba L. with promising potential to regulate inflammatory responses. In this study, we evaluated the possible effect of isorhamnetin in prevention of APAP-induced ALI and analyzed further the involvement of oxidative stress and inflammation-associated factors. Male C57BL/6 mice were given isorhamnetin (25 or 100 mg/kg b.w., p.o.) three times at 48, 24, and 1 h before APAP administration (300 mg/kg b.w., i.p.). Functional indicators of liver injury were measured as well as analysis of oxidative stress- and inflammation-associated indices and liver histopathology was also conducted. Isorhamnetin at the higher dose of 100 mg/kg significantly lowered serum levels of ALT, ALP, and AST in addition to reduction of ROS, TBARS, IL-6, TNFα, NF-kB, NLRP3, caspase 1, and MPO and significantly prevented reduction of GSH, SOD activity, sirtuin 1, and Nrf2. Additionally, isorhamnetin alleviated pathological changes of the liver tissue and suitably reversed NF-kB and Nrf2 immunoreactivity. These findings show protective effect of isorhamnetin against acetaminophen-induced liver injury through reducing oxidative stress, inflammation, and pyroptosis which is attributed to its regulation of NF-kB, Nrf2, NLRP3, and sirtuin 1.

S-allyl cysteine, an active ingredient of garlic, attenuates acute liver dysfunction induced by lipopolysaccharide/ d-galactosamine in mouse: Underlying mechanisms.

In the present study, beneficial effect of S-allyl cysteine (SAC) was evaluated in the lipopolysaccharide/d-galactosamine (LPS/d-Gal) model of acute liver injury (ALI). To mimic ALI, LPS and d-Gal (50 µg/kg and 400 mg/kg, respectively) were intraperitoneally administered and animals received SAC per os (25 or 100 mg/kg/d) for 3 days till 1 hour before LPS/d-Gal injection. Pretreatment of LPS/d-Gal group with SAC-lowered activities of alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase and partially reversed inappropriate alterations of hepatic oxidative stress- and inflammation-related biomarkers including liver reactive oxygen species, malondialdehyde, and hepatic activity of the defensive enzyme superoxide dismutase, ferric reducing antioxidant power (FRAP), toll-like receptor-4 (TLR4), cyclooxygenase 2, NLR family pyrin domain containing 3 (NLRP3), caspase 1, nuclear factor κB (NF-κB), interleukin 1ß (IL-1ß), IL-6, tumor necrosis factor-α, and myeloperoxidase activity. Additionally, SAC was capable to ameliorate apoptotic biomarkers including caspase 3 and DNA fragmentation. In summary, SAC can protect liver against LPS/d-Gal by attenuation of neutrophil infiltration, oxidative stress, inflammation, apoptosis, and pyroptosis which is partly linked to its suppression of TLR4/NF-κB/NLRP3 signaling.

Protective effect of sesamin in lipopolysaccharide-induced mouse model of acute kidney injury via attenuation of oxidative stress, inflammation, and apoptosis.

CONTEXT: Acute kidney injury (AKI) is considered a major public health concern in today's world. Sepsis-induced AKI is large as a result of exposure to lipopolysaccharide (LPS) that is the major outer membrane component of Gram-negative bacteria. Sesamin is the main lignan of sesame seeds with multiple protective effects. OBJECTIVE: In this research, we tried to demonstrate the protective effect of sesamin pretreatment in LPS-induced mouse model of AKI. METHODS: LPS was injected at a single dose of 10 mg/kg (i.p.) and sesamin was given p.o. at doses of 25, 50, or 100 mg/kg, one hour prior to LPS. RESULTS: Treatment of LPS-challenged mice with sesamin reduced serum level of creatinine and blood urea nitrogen (BUN) and returned back renal oxidative stress-related parameters including glutathione (GSH), malondialdehyde (MDA), and activity of catalase and superoxide dismutase (SOD). Moreover, sesamin alleviated inappropriate changes of renal nuclear factor-kappaB (NF-κB), toll-like receptor 4 (TLR4), cyclooxygenase-2 (COX2), tumor necrosis factor α (TNFα), interleukin-6, DNA fragmentation (an apoptotic index), and nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In addition, sesamin diminished magnitude of kidney tissue damage due to LPS. CONCLUSION: In summary, sesamin could dose-dependently abrogate LPS-induced AKI via attenuation of renal oxidative stress, inflammation, and apoptosis.

A review on potential roles of vitamins in incidence, progression, and improvement of multiple sclerosis.

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease, with unknown etiology. Vitamins, as important micronutrients playing different roles in body, seem to be important in MS pathogenesis. In vitro, in vivo and human studies, supports the protective role of some vitamins in MS occurrence or progression. Current study reviews recent insights and reports about the importance of vitamins in MS incidence or progression. In accordance, the importance of all water and fat-soluble vitamins in MS pathogenesis based on observational studies in human population and their role in the function of immune system as well as possible therapeutic opportunities are discussed in depth throughout this review.

Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects.

Systemic inflammation during infectious disorders usually accompanies chronic complications including cognitive dysfunction. Neuroinflammation and cognitive deficit are also observed in some debilitating neurological disorders like Alzheimer's and Parkinson's diseases. Genistein is a soy isoflavone with multiple beneficial effects including anti-inflammatory, anti-oxidative, and protective properties. In this research study, the effect of genistein in prevention of lipopolysaccharide (LPS)-induced cognitive dysfunction was investigated. LPS was given i.p. (500 µg/kg/day) and genistein was orally given (10, 50, or 100 mg/kg) for one week. Findings showed that genistein could dose-dependently attenuate spatial recognition, discrimination, and memory deficits. Additionally, genistein treatment of LPS-challenged group lowered hippocampal level of malondialdehyde (MDA) and increased activity of superoxide dismutase (SOD) and catalase and glutathione (GSH) level. Furthermore, genistein ameliorated hippocampal acetylcholinesterase (AChE) activity in LPS-challenged rats. Furthermore, genistein administration to LPS-injected group lowered hippocampal level of interleukin 6 (IL-6), nuclear factor-kappaB (NF-κB) p65, toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), cyclooxygenase-2 (COX2), inducible nitric oxide synthase (iNOS), glial fibrillary acidic protein (GFAP), and increased hippocampal level of antioxidant element nuclear factor (erythroid-derived 2)-like 2 (Nrf2). In conclusion, genistein alleviated LPS-induced cognitive dysfunctions and neural inflammation attenuation of oxidative stress and AChE activity and appropriate modulation of Nrf2/NF-κB/IL-6/TNFα/COX2/iNOS/TLR4/GFAP.