European journal of pharmacology
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In this study, the anti-inflammatory effects of flavonoids isolated from the roots of Glycyrrhiza uralensis (Leguminosae), namely, isoliquiritin (the glycoside of isoliquirigenin) and isoliquiritigenin (the aglycone of isoliquiritin) were evaluated on lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. Isoliquiritigenin (ILG) more potently inhibited LPS-induced nitric oxide (NO) and prostaglandin E(2) (PGE(2)) production than isoliquiritin (ILT). Consistent with these findings, ILG reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner, as determined by Western blotting and RT-PCR, respectively. ⋯ Moreover, ILG attenuated the LPS-induced DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this was associated with a decrease in inhibitory kappa B-alpha (IkappaB-alpha) phosphorylation and in the subsequent blocking of p65 and p50 protein translocations to the nucleus. Furthermore, ILG suppressed the phosphorylations of IkappaB kinase (IKK), ERK1/2, and p38, whereas the phosphorylation of JNK1/2 was unaffected. These results suggest that the anti-inflammatory properties of ILG are caused by iNOS, COX-2, TNF-alpha, and IL-6 down-regulation due to NF-kappaB inhibition via the suppression of IKK, ERK1/2 and p38 phosphorylation in RAW 264.7 cells.
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We have previously demonstrated synergy between morphine and Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in the expression of antinociception in acute pain models and in arthritic models of chronic pain. Our data has been extended to include acute pain in both diabetic mice and rats. In diabetic mice, Delta(9)-THC p.o. was more active in the tail-flick test in the diabetic mouse than in the non-diabetic mouse. ⋯ In the rat, the induction of the diabetic state decreased the antinociceptive effect of morphine, an effect temporally related to a decreased release of specific endogenous opioids. Conversely, Delta(9)-THC retained the ability to release endogenous opioids in diabetic rats and maintained significant antinociception. Extrapolation of such studies to the clinical setting may indicate the potential for use of Delta(9)-THC-like drugs in the treatment of diabetic neuropathic pain, alone or in combination with very low doses of opioids.
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The nonapeptide vasopressin acts both as a hormone and as a neurotransmitter/neuromodulator. As a hormone, its target organs include kidney, blood vessels, liver, platelets and anterior pituitary. As a neurotransmitter/neuromodulator, vasopressin plays a role in autonomic functions, such as cardiovascular regulation and temperature regulation and is involved in complex behavioral and cognitive functions, such as sexual behavior, pair-bond formation and social recognition. ⋯ Translation of peptide actions at the cellular level into autonomic, behavioral and cognitive effects requires an intermediate level of integration, i.e. the level of neuronal circuitry. Here, detailed information is lacking. Further progress will probably require the introduction of new techniques, such as targeted in vivo whole-cell recording, large-scale recordings from neuronal ensembles or in vivo imaging in small animals.