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Sepsis is a severe immune response to an infection. It is associated with multiple organ dysfunction syndrome (MODs) along with systemic and neuronal inflammatory response. This study focused on the acute neurologic dysfunction associated with sepsis by exploring the role of PPARγ/SIRT1 pathway against sepsis. We studied the role of this axis in ameliorating sepsis-associated encephalopathy (SAE) and its linked neurobehavioral disorders by using pioglitazone (PIO). This PPARγ agonist showed neuroprotective actions in neuroinflammatory disorders. Sepsis was induced in mice by LPS (10 mg/kg). Survival rate and MODs were assessed. Furthermore, behavioral deficits, cerebral oxidative, inflammatory, and apoptotic markers, and the cerebral expression level of SIRT1 were determined. In this study, we observed that PIO attenuated sepsis-induced cerebral injury. PIO significantly enhanced survival rate, attenuated MODs, and systemic inflammatory response in septic mice. PIO also promoted cerebral SIRT1 expression and reduced cerebral activation of microglia, oxidative stress, HMGB, iNOS, NLRP3 and caspase-3 along with an obvious improvement in behavioral deficits and cerebral pathological damage induced by LPS. Most of the neuroprotective effects of PIO were abolished by EX-527, a SIRT1 inhibitor. These results highlight that the neuroprotective effect of PIO in SAE is mainly SIRT1-dependent.

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Sepsis induces neuroinflammation, BBB disruption, cerebral hypoxia, neuronal mitochondrial dysfunction, and cell death causing sepsis-associated encephalopathy (SAE). These pathological consequences lead to short- and long-term neurobehavioural deficits. Till now there is no specific treatment that directly improves SAE and its associated behavioural impairments. In this review, we discuss the underlying mechanisms of sepsis-induced brain injury with a focus on the latest progress regarding neuroprotective effects of SIRT1 (silent mating type information regulation-2 homologue-1). SIRT1 is an NAD+ -dependent class III protein deacetylase. It is able to modulate multiple downstream signals (including NF-κB, HMGB, AMPK, PGC1α and FoxO), which are involved in the development of SAE by its deacetylation activity. There are multiple recent studies showing the neuroprotective effects of SIRT1 in neuroinflammation related diseases. The proposed neuroprotective action of SIRT1 is meant to bring a promising therapeutic strategy for managing SAE and ameliorating its related behavioural deficits.

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OBJECTIVE: Polycystic ovaries (PCO) is a hormonal disorder that is a leading cause of infertility. The formation of multiple persistent cysts and hormonal imbalance are hallmarks of PCO. Recent clinical studies reported a beneficial effect of the ketogenic diet (KD; high-fat, low-carbohydrate) on PCO. The aim of this study was to investigate the effect of the KD alone and in combination with metformin on letrozole-induced PCO in female rats. METHODS: Female rats were grouped into control and PCO (letrozole; 1 mg/kg for 21 days). The PCO group was subdivided into PCO (non-treated), PCO-metformin (300 mg/kg), PCO rats fed with KD only, and PCO rats treated with metformin and fed with KD. All groups continued to receive letrozole during the 21-day treatment period. At the end of the experiment, serum and ovaries were collected for further analysis. RESULTS: The untreated-PCO rats showed increased testosterone, LH/FSH ratio, and ovary weights. Disturbed apoptosis and proliferation balance were evident as a low caspase-3 activation and proliferating cell nuclear antigen expression and increased TGF-ß expression. The KD improved the letrozole-induced effects, which was comparable to the effect of metformin. Combining the KD with metformin treatment additively enhanced the metformin effect. CONCLUSION: Our results indicate that the KD has a protective role against PCO in rats, especially when combined with metformin. This study reveals a potential therapeutic role of the KD in PCO, which could prompt valuable future clinical applications.

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BACKGROUND: Recently, crop byproducts are considered a hot topic and can be converted into beneficial products. Cauliflower is well-known for its protective effects against oxidative stress-induced damage. The current study aimed to investigate the chemical profile and the ameliorative effects of cauliflower leaf extract (CL) on gentamicin-induced renal and hepatic injuries in rats. METHODS: Cauliflower leaf was extracted with methanol to give the total methanol extract (TME) followed by the determination of total phenolic contents (TPC). Rats were divided into five groups; Group I was assigned as the control group, while the other groups were injected with gentamicin for ten days. Group II was given distilled water. Rats in groups III and IV were treated with oral CL (200 mg/kg and 400 mg/kg, respectively). Group V received L-cysteine (as a positive control). The functions of the kidneys and liver; oxidative stress and morphological and apoptotic changes of renal and hepatic tissues were assessed. RESULTS: The TME was subjected to chromatographic techniques to yield ferulic acid, vanillic acid, p-coumaric acid and quercetin. TPC was 72.31 mg GAE/g of dried extract. CL treatment dose-dependently ameliorated gentamicin-induced impaired kidney and liver functions and improved the histopathological appearance of both organs. It also reduced gentamicin-induced oxidative stress. CL demonstrated downregulation of mRNA and protein expressions of IL-1ß and NF-κB compared to nontreated rats. In silico interaction of the isolated compounds with amino acid residues of IL-1ß and NF-κB might explain the current findings. CONCLUSION: Taken together, this study raises the waste-to-wealth potential of cauliflower to mitigate gentamicin-induced hepatorenal injury and convert the waste agromaterials into valuable products.