Paeonol ameliorates monosodium urate-induced arthritis in rats through inhibiting nuclear factor-κB-mediated proinflammatory cytokine production.

Moutan Cortex has been widely used to treat various types of arthritis in traditional Chinese medicine. Paeonol is isolated as an active ingredient from Moutan Cortex. However, the effect and potential mechanism of paeonol on gouty arthritis have not been evaluated. In this study, rats were treated intragastrically with paeonol for consecutive 7 days. On Day 5, rats were intra-articularly injected with monosodium urate (MSU) crystals in the ankle joints to induce MSU-induced arthritis (MIA). Paw volume was detected at various time points. Gait score was measured at 24 hr after MSU crystal injection. Ankle joints were collected for evaluation of histological score and expression of proinflammatory cytokines using hematoxylin and eosin staining and immunohistochemistry staining, respectively. Nuclear level of nuclear factor (NF)-κBp65 in synovial tissues was analyzed by western blot assay. NF-κB DNA-binding activity was measured by enzyme linked immunosorbent assay. Paeonol markedly lowered the paw volume, gait score, and histological score in MIA rats. Mechanistically, paeonol markedly reduced the expression of TNF-α, IL-1ß, and IL-6 in synovial tissues of MIA rats. In addition, the elevated level of p65 in nucleus and NF-κB DNA-binding activity in synovial tissues of MIA rats were reduced significantly by paeonol treatment. These findings suggest that paeonol exerts anti-inflammatory effect in MIA rats through inhibiting expression of proinflammatory cytokines and NF-κB activation.

[Estrogen protects the dopaminergic neurons in substantia nigra against damage induced by 6-hydroxydopamine].

Substantial evidence strongly implies that sensory gating P50 (also called P50 auditory evoked potential, P50) and dopaminergic neurotransmitters are related. In animal experiment, P50 can be recorded in an awake and quiet state with freedom of movement. Until now there is lack of animal experimental data on the supportive effect of estrogen on function of dopaminergic neurons in substantia nigra (SN) in physiological state. In the present study, female Sprague-Dawley (SD) rats were used as subjects. The animals were divided randomly into four groups: (1) control group (normal animals); (2) Parkinson's disease (PD) model group: the right SN was lesioned with 6-hydroxydopamine (6-OHDA); (3) PD model with bilateral ovariectomized group (OVX-PD): bilateral ovariectomy was performed before administration with 6-OHDA; (4) estrogen + PD model with bilateral ovariectomized group (OVX-E(2)-PD): physiological dose of estrogen was given to the bilateral ovariectomy animals before administration with 6-OHDA. P50 induced by two brief acoustic stimuli were recorded in the right SN and the number of TH(+) dopaminergic neurons in the SN stained by immunohistochemistry was calculated after the determination of P50. The results showed that in the PD model group, the testing/conditioning (T/C) ratio of P50 decreased by 40.60% and the number of TH(+) cells in the right SN decreased by 64.74% as compared with that in the control group (P<0.01); In the OVX-PD group, the T/C ratio of P50 decreased by 45.88% and the number of TH(+) cells was reduced by 57.26% as compared with that in the PD group (P<0.01). Administration with 6-OHDA into the SN pars compacta of ovariectomized rats caused more decrease in the number of TH(+) cells as well as more damage to the function of sensory gating in SN. While in OVX-E(2)-PD group, intramuscular injection with estrogen at physiological dose 3 d before 6-OHDA administration decreased the degree of damage to the SN functionally and morphologically, and its degree of injury corresponded to PD group. These results indicate that the mechanism of protection of dopaminergic neurons in the SN provided by physiological level of estrogen is by promoting the resistibility of the neurons to harmful stimulation. If the gonads are resected resulting in a lack of estrogen, the degree of injury to the function and morphology of dopaminergic neurons in SN induced by 6-OHDA increases. Replacement of estrogen at physiological level on time is necessary. Sensory gating P50 in SN may reflect dynamically the protection of estrogen against dopaminergic neurons depletion in vivo.

[Sexual dimorphisms of dopaminergic neurons in rat substantia nigra].

There are sex differences in some brain areas in mammalians. Parkinson's disease (PD), caused by the mesencephalic substantia nigra (SN) dopaminergic neuronal loss, displays sexual difference, i.e., the incidence is higher and the symptoms are more intense in males than that in females. However, it has not been known whether sexual dimorphisms exist in the SN. Sixty adult Sprague-Dawley rats were randomly divided into 5 groups: (1) Female intact group (F-INT group); (2) Male intact group (M-INT group); (3) Ovariectomized group (OVX group); (4) Castration group (CAST group); (5) Ovariectomized + estrogen-replaced group (OVX-E(2) group): The rats received sequentially physiological dose of estrogen for 3 d from the 7th day after ovariectomization. P50 auditory evoked potential (P50) was recorded for 14 d from electrodes inserted in the rat right SN in quiet and awake state. After recording, the brain tissues were dissected and the tyrosine hydroxylase (TH)-expressing neurons in the compact zone of the SN were counted using immunohistochemical method. The results showed that the number of TH-positive (TH(+)) cells in the SN of normal male animals was less than that in normal female rats (P<0.05), and the T/C ratio of P50 in normal males was significantly less than that in normal females (P<0.01), indicating that there exists sexual difference in function and structure in the SN. No differences in the T/C ratio of P50 or the number of TH(+) cells were found between M-INT and CAST groups. The T/C ratio of P50 and the number of TH(+) cells in the SN in OVX group were reduced significantly compared with those in F-INT group (P<0.01). There was no significant difference in the T/C ratio of P50 and the number of TH(+) cells in the SN between OVX- E(2) and F-INT groups 15-20 d after estrogen replacement, suggesting that estrogen can promote the survival and functional recovery of dopaminergic neurons in the SN. The results suggest that there exist sex-specific differences in the dopaminergic neurons in the SN structurally and functionally. The difference of estrogen level in cerebra between male and female animals may account for the sexual differences. Endogenous estrogen plays an important role in maintaining the integrity and modulating the functional activity of dopamine system in the SN.

The protective effect of coptisine on experimental atherosclerosis ApoE-/- mice is mediated by MAPK/NF-κB-dependent pathway.

Coptisine is one of main bioactive compounds extracted from the traditional Chinese herbal medicine Rhizoma Coptidis. It is reported that coptisine can attenuate obesity-related inflammation and oxidant damage in Syrian golden hamsters. Therefore，coptisine may exhibit beneficial effects for the treatment of atherosclerosis (AS) due to its hypolipidemic and anti-inflammation activities. The present study investigated the anti-atherosclerotic and anti-inflammatory properties of coptisine using apoE-/- mice as AS model. The atherosclerotic plaque area of aorta, serum lipid profile and the expression of inflammatory cytokines were determined. After coptisine treatment, the serum level of TC, TG and LDL-C decreased; the serum level of IL-6, IL-1ß and TNF-α were decreased; the mRNA levels of NF-κBp65, VCAM-1, ICAM-1, IL-6 and IL-1ß in both aorta and liver were down-regulated; the p-p38 and p-JNK1/2 protein expression level were decreased. Coptisine decreased atherosclerotic plaque area significantly through both anti-inflammation and lipid lowering effect. The anti-inflammatory effect of coptisine is achieved through inhibiting activation of MAPK signaling pathways and NF-κB nuclear translocation. Therefore，the combined anti-inflammation and lipid lowering effect of coptisine attributed the decreased atherosclerotic plaque area in coptisine treated apoE-/- mice. The results of this study will afford a novel application for coptisine in the treatment of atherosclerosis and other chronic inflammatory disease.

Nitric oxide inhibits excitatory vagal afferent input to nucleus tractus solitarius neurons in anaesthetized rats.

OBJECTIVE: Endogenous nitric oxide (NO) has been implicated in the regulation of neuronal activity which mediates cardiovascular reflexes. However, there is controversy concerning the role of NO in the nucleus tractus solitarius (NTS). The present study aims to elucidate the possible physiological role of endogenous NO in modulating the excitatory vagal afferent input to NTS neurons. METHODS: All the experiments in the rat were conducted under anaesthetic conditions. Ionophoresis method was used for the application of NO donor or nitric oxide synthase (NOS) inhibitor, and single unit recording method was employed to detect the effects of these applications on vagal afferent- or cardio-pulmonary C-fibre reflex-evoked neuronal excitation in NTS. RESULTS: Ionophoresis applications of L-arginine (L-Arg), a substrate of NOS, and sodium nitroprusside (SNP), a NO donor, both attenuated the vagal afferent-evoked discharge by (51.5+/-7.6)% (n = 17) and (68.3+/-7.1)% (n = 9), respectively. In contrast, application of D-Arg at the same current exerted no overall effect on this input. Also, both L-Arg and SNP inhibited spontaneous firing of most of the recorded neurons. In contrast, ionophoresis application of N(G)-nitro-L-arginine methyl ester (L-NAME) enhanced vagal afferent-evoked excitation by (66.3+/-11.4)% (n = 7). In addition, ionophoresis application of L-Arg and SNP significantly attenuated cardio-pulmonary C-fibre reflex-induced excitation in the tested NTS neurons. CONCLUSION: Activation of local NO pathway in the NTS could suppress vagal afferent-evoked excitation, suggesting that NO is an important neuromodulator of visceral sensory input in the NTS.