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Osteoarthritis (OA), which is characterized as a common degenerative joint disease, is presently the most prevalent chronic degenerative joint disease. Accumulating evidence has shown a biological function for Garcinol in a variety of diseases; however, whether it could be used to treat OA remains unclear. In this study, we explored the protective effects of garcinol on the progression of OA and explored the underlying mechanism. In vitro, garcinol reduced the expression of pro-inflammatory cytokines, such as IL-6 and tumor necrosis factor alpha (TNF-α). It also decreased the expression of inducible nitric oxide synthase (iNOS), as well as cyclooxygenase-2 (COX-2). Furthermore, garcinol inhibited the expression of thrombospondin motifs 5(ADAMTS5) and metalloproteinase (MMPs), both of which regulate extracellular matrix degradation. These changes could be attributed to garcinol-related suppression of the IL-1β-induced NF-κB signaling pathway. Moreover, we investigated the protective effects of garcinol on the surgical destabilization of the medial meniscus (DMM) of the mouse, an in vivo model of OA. Taken together, our data suggest garcinol as a potential future agent for the treatment of OA.

Background: This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats.Methods: Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were tested by QT-PCR and Western blot, and levels of 5-hydroxytryptamine (5-HT), KYN, TRY, 3-hydroxykynurenine (3-HK), and kynurenic acid (KA) in different brain regions were estimated using HPLC. Effects of the IDO direct inhibitor 1-methyl-L-tryptophan (1-MT) on cognitive, anxiety, and depressive-like behavior were evaluated in bile duct ligation (BDL) rats.Results: Increased serum TNF-α, IL-1β, and IL-6 levels were shown in rats 7 days after BDL, and these increases were observed earlier than those in the brain, indicating peripheral immune activation may result in central upregulation of proinflammatory cytokines. Moreover, BDL rats showed a progressive decline in memory formation, as well as anxiety and depressive-like behavior. Further study revealed that IDO expression increased after BDL, accompanied by a decrease of 5-HT and an increase of KYN, as well as abnormal expression of 3-HK and KA. The above results affected by BDL surgery were reversed by IDO inhibitor 1-MT treatment.Conclusion: Taken together, these findings indicate that (1) behavioral impairment in BDL rats is correlated with proinflammatory cytokines; (2) TRY pathway of KYN metabolism, activated by inflammation, may play an important role in HE development; and (3) 1-MT may serve as a therapeutic agent for HE. [ABSTRACT FROM AUTHOR]

The original version of this article contained mistakes, and the authors would like to correct them. [ABSTRACT FROM AUTHOR]

Patients suffering from chronic neuropathic pain are at high risk of co-morbid depression, which burdens healthcare. Trans-astaxanthin has been shown in our previous studies to exert antidepressant-like effect. This work aimed to investigate the effects of trans-astaxanthin on pain-related depressive-like behaviors in mice and explored the mechanism(s). Chronic constriction injury (CCI) model was used in this research. Chronic pain was evaluated by thermal hyperalgesia in Hargreaves test and mechanical allodynia in von Frey test, depressive-like behaviors were evaluated by immobility time in forced swim test and tail suspension test. Chronic trans-astaxanthin treatment ameliorated mechanical allodynia and thermal hyperalgesia, as well as decreasing immobility time in forced swim test and tail suspension test in CCI mice, and these actions were abolished by co-treatment with P-Chlorophenylalanine (PCPA). Subsequent study indicated that indoleamine 2,3-dioxygenase (IDO) expression increased after CCI surgery in hippocampus and spinal cord, accompanied by increase of kynurenine (KYN)/tryptophan (TRY) ratio, decrease of serotonin (5-HT)/TRY ratio and decrease of 5-HT/5-HIAA ratio. The above results affected by CCI surgery were reversed by trans-astaxanthin treatment. Moreover, trans-astaxanthin at 80 mg/kg was demonstrated to effectively antagonize IL-1β, IL-6 and TNF-α expression in hippocampus and spinal cord of CCI mice. Taken together, chronic trans -astaxanthin administration exerts therapeutic effects on thermal hyperalgesia and co-morbid depressive-like behaviors in CCI mice. These effects of trans-astaxanthin involves the serotonergic system, and also may be owing to its potent anti-inflammatory property. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated neuroinflammation and increased cytokine levels are associated with depression. Aware of the efficacy the potential anti-inflammatory and antioxidative activity of proanthocyanidin, the present study was designed to investigate the effects of proanthocyanidin on lipopolysaccharide (LPS)-induced depressive-like behavior in mice. In depressive behavior tests, the immobility time of forced swimming test (FST) and tail suspension test (TST) was increased when mice were administrated a single dose of LPS (0.83 mg/kg, i.p.), whereas these alterations were reversed by proanthocyanidin treatment (80 mg/kg, p.o.). In anxiety behavior tests, all the anxiety-related parameters, such as number of buried marble, time spent in the open arm and close arm did not show statistical differences between LPS and control groups. However, anxiolytic effects were observed in marble-burying test and elevated plus maze test in single proanthocyanidin treatment and proanthocyanidin treatment together with LPS group. Further assays indicated that LPS-induced overexpression of pro-inflammatory cytokines in the hippocampus, prefrontal cortex (PFC) and amygdala were reversed by proanthocyanidin treatment. Furthermore, proanthocyanidin inhibited the LPS-induced iNOS and COX-2 overexpression, via the modulation of NF-κB in the hippocampus, PFC and amygdala. Taken together, proanthocyanidin may be an effective therapeutic agent for LPS-induced depressive-like behaviors via its potent anti-inflammatory property. [ABSTRACT FROM AUTHOR]