Osteoarthritis (OA) is a chronic and debilitating disease of the knee joint. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by an exaggerated inflammation leading to cartilage damage. Currently, no effective and safe therapeutic option capable of restoring articular cartilage tissue and joint architecture is available. We here report a novel and highly bioavailable formulation of curcumin, labeled as Next Generation Ultrasol Curcumin (NGUC), which was 64.7 times more bioavailable than natural 95% curcumin extract as demonstrated in rat bioavailability studies. We further investigated the protective effect of NGUC against monosodium iodoacetate (MIA)‐induced knee OA in rats. Analysis of X-ray and histopathological images revealed that NGUC supplementation restored joint architecture and reduced swelling of joints induced by MIA. NGUC treatment caused a significant reduction in the levels of inflammatory mediators such as TNF-α, IL-1β, IL-6, COMP, and CRP, and expressions of MMP-3, 5-LOX, COX-2, and NFκB in synovial tissue of rats with MIA-induced OA. NGUC also decreased serum MDA level and increased the levels of antioxidant enzymes SOD, CAT, and GPX. Thus, our results indicate that a novel formulation of curcumin with enhanced bioavailability effectively ameliorates the pathophysiology of OA.

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice.

In this study, the effects of L-Carnitine supplementation on the lipid peroxidation and expression of PPAR-γ and glucose transporters in the liver and muscles of chronically and acutely exercised rats were investigated. A total of 42 male Wistar Albino rats (8-week-old) were divided into six groups as follows: Control, L-Carnitine, Chronic Exercise (CE), Chronic Exercise + L-Carnitine, Acute Exercise (AE) and L-Carnitine + Acute Exercise. Chronic exercise consists of 30 m/min, 30 min/day, and 5 days/week for 6 weeks. Rats in the acute exercise groups were run on the treadmill at 30 m/min until exhaustion. L-Carnitine was given at the level of 300 mg per kilogram of diet for 6 weeks. There was no significant difference in the levels of serum ALT, AST, urea, creatinine and glucose levels between the exercise and L-Carnitine groups (P > 0.05). Cholesterol and triglyceride levels decreased by L- carnitine supplementation and chronic exercise in control groups but increased in the AE groups compared to the control group without reinforcement (P < 0.05). Serum, muscle, heart, and liver malondialdehyde (MDA) concentrations were lower in CE and higher in the AE groups (P < 0.001). However, L-Carnitine supplementation reduced MDA levels (P < 0.05). Liver and muscle PPAR-γ, liver GLUT-2 and muscle GLUT-4 mRNA expressions were lower in AE group than in all other groups (P < 0.001). Both chronic exercise and supplemental L-Carnitine increased liver and muscle PPAR-γ, GLUT-2 and GLUT-4 mRNA expression (P <0.05). As a result, although acute exercise increased oxidative stress, chronic exercise reduced oxidative stress by lowering lipid peroxidation level. L-Carnitine supplementation decreased oxidative stress and improved glucose and lipid metabolism by regulation of PPAR-γ, GLUT-2 and GLUT-4 mRNA expression in rats.