Effects of Niaoduqing Particles () on Delaying Progression of Renal Dysfunction: A Post-trial, Open-Label, Follow-up Study.

OBJECTIVE: To follow up the participants of the randomized clinical trial "Efficacy and Safety of Niaoduqing Particles () for Delaying Moderate-to-Severe Renal Dysfunction", and assess the long-term effects of Niaoduqing Particles on delaying the progression of renal dysfunction. METHODS: Participants, who had previously been randomly assigned to receive Niaoduqing Particles or placebo for 24 weeks (146 cases in each group), were invited to follow-up and all were administered Niaoduqing Particles 5 g thrice daily and 10 g before bedtime for 24 weeks. The primary endpoints were changes in baseline serum creatinine (Scr) and estimated glomerular filtration rate (eGFR) after completion of the open-label treatment period. RESULTS: After the double-blind period, the median (interquartile range) changes in Scr were 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the Niaoduqing Particle and placebo groups, respectively (P=0.008), and the median changes in eGFRs were-0.2 (-4.3-2.7) and-2.21 (-5.7-0.8) mL•min-1•1.73 m-2, respectively (P=0.016). There were significant differences in the double-blind period changes in renal function between groups. After the open-label period, the median changes in Scr were 9.0 (-10.0-41.9) and 17.5 (-6.0-50.0) µmol/L for the Niaoduqing Particle and placebo groups according to baseline grouping, respectively (P=0.214), and the median changes in eGFRs were-2.3 (-6.4-1.9) and-3.7 (-7.5-1.1) mL•min-1•1.73 m-2, respectively (P=0.134). There were no statistical differences in the open-label period changes in renal function between groups. The eGFR reduction of participants who accepted Niaoduqing Particle treatment for 48 weeks was projected to 2.5 mL•min-1•1.73 m-2 per year. CONCLUSION: Niaoduqing Particles appear to have long-term efficacy for patients with moderate-to-severe renal dysfunction. Although there was no statistical difference, the early use of Niaoduqing Paticles seems to ameliorate the worsening of renal function. (Trial registration No. ChiCTR-TRC-12002448).

Efficacy and Safety of Niaoduqing Particles for Delaying Moderate-to-severe Renal Dysfunction: A Randomized, Double-blind, Placebo-controlled, Multicenter Clinical Study.

BACKGROUND: Chronic kidney disease (CKD) with moderate-to-severe renal dysfunction usually exhibits an irreversible course, and available treatments for delaying the progression to end-stage renal disease are limited. This study aimed to assess the efficacy and safety of the traditional Chinese medicine, Niaoduqing particles, for delaying renal dysfunction in patients with stage 3b-4 CKD. METHODS: The present study was a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial. From May 2013 to December 2013, 300 CKD patients with an estimated glomerular filtration rate (eGFR) between 20 and 45 ml·min-1·1.73 m-2, aged 18-70 years were recruited from 22 hospitals in 11 Chinese provinces. Patients were randomized in a 1:1 ratio to either a test group, which was administered Niaoduqing particles 5 g thrice daily and 10 g before bedtime for 24 weeks, or a control group, which was administered a placebo using the same methods. The primary endpoints were changes in baseline serum creatinine (Scr) and eGFR after completion of treatment. The primary endpoints were analyzed using Student's t-test or Wilcoxon's rank-sum test. The present study reported results based on an intention-to-treat (ITT) analysis. RESULTS: A total of 292 participants underwent the ITT analysis. At 24 weeks, the median (interquartile range) change in Scr was 1.1 (-13.0-24.1) and 11.7 (-2.6-42.9) µmol/L for the test and control groups, respectively (Z = 2.642, P = 0.008), and the median change in eGFR was -0.2 (-4.3-2.7) and -2.2 (-5.7-0.8) ml·min-1·1.73 m-2, respectively (Z = -2.408, P = 0.016). There were no significant differences in adverse events between the groups. CONCLUSIONS: Niaoduqing particles safely and effectively delayed CKD progression in patients with stage 3b-4 CKD. This traditional Chinese medicine may be a promising alternative medication for patients with moderate-to-severe renal dysfunction. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-TRC-12002448; http://www.chictr.org.cn/showproj.aspx?proj=7102.

Chronic curcumin treatment normalizes depression-like behaviors in mice with mononeuropathy: involvement of supraspinal serotonergic system and GABAA receptor.

RATIONALE: Comorbid depression is commonly observed in individuals who suffer from neuropathic pain, which necessitates improved treatment. Curcumin, a phenolic compound derived from Curcuma longa, possesses both antinociceptive and antidepressant-like activities in animal studies, suggesting its possible usefulness in treating this comorbidity. OBJECTIVE: We investigated the effect of curcumin on depressive-like behaviors in mice with mononeuropathy, and explored the mechanism(s). METHODS: Chronic constriction injury (CCI) was produced by loosely ligating the sciatic nerves in mice. The nociceptive behaviors were examined using Hargreaves test, and the depressive-like behaviors were determined by forced swim test (FST) and tail suspension test (TST). RESULTS: After CCI injury, the neuropathic mice developed nociceptive and depressive-like behaviors, as shown by thermal hyperalgesia in Hargreaves test and protracted immobility time in FST and TST. Chronic treatment of neuropathic mice with curcumin (45 mg/kg, p.o., twice per day for 3 weeks) corrected their exacerbated nociceptive and depressive-like behaviors, which was abolished by chemical depletion of brain serotonin rather than noradrenaline. The paralleled antinociceptive and antidepressant-like actions of curcumin seem to be pharmacologically segregated, since intrathecal and intracerebroventricular injection of methysergide, a nonselective 5-HT receptor antagonist, separately counteracted the two actions of curcumin. Further, this antidepression was abrogated by repeated co-treatment with 5-HT1A receptor antagonist WAY-100635 and greatly attenuated by acute co-treatment with GABAA receptor antagonist bicuculline. CONCLUSION: Curcumin can normalize the depressive-like behaviors of neuropathic mice, which may be independent of the concurrent analgesic action and possibly mediated via the supraspinal serotonergic system and downstream GABAA receptor.

[Effects of catgut embedding at "Zusanli" (ST 36) and "Shenshu" (BL 23) on morphine analgesic tolerance and locomotor sensitization in the rat].

OBJECTIVE: To compare effects of catgut embedding at "Zusanli" (ST 36) and "Shenshu" (BL 23) on Morphine analgesic tolerance and locomotor sensitization induced by chronic Morphine administration and the mechanism. METHODS: The rats were randomly divided into a model group, a non-acupoint group, a Shenshu group and a Zusanli group. The rats, except those in the model group, were pretreated with acupoint catgut-embedding 10 days before the first Morphine injection. The Morphine-tolerance model was established and the pain threshold was detected by hot-plate test every day. Locomotor activities were recorded after the first Morphine injection and Morphine-challenging 1 week after withdrawal of Morphine. The positive neurons of nitric oxide synthetase (NOS) were showed by NADPH-d histochemical method. RESULTS: Compared with the non-acupoint group, catgut embedding at "Zusanli" (ST 36) could attenuate the Morphine analgesic tolerance and the increase of locomotor activities in rats. Meanwhile, the expression of NOS positive neurons in nucleus accumbens septi and dorsal striatum decreased in the Zusanli group. There were no significant differences between the Shenshu group and the non-acupoint group in the analgesic threshold and locomotor sensitization, but the expression of NOS positive neurons in the striatum region significantly decreased. CONCLUSION: Catgut embedding at "Zusanli" (ST 36) can attenuate Morphine analgesic tolerance and reverse formation of locomotion sensitization induced by chronic Morphine administration, which are possibly related with inhibition of the expression of NOS positive neurons in nucleus accumbens septi and dorsal striatum.

[Effect of electroacupuncture on drug-seeking behaviors induced by heroin priming and FosB expression in relevant brain regions].

OBJECTIVE: To explore the effect of electroacupuncture on heroin seeking behavior and FosB expression in relevant brain regions. METHODS: Rat model of heroin relapse behaviors was developed with progressive fixed ratio program,and model rats were randomly divided into 3 groups: a restraint group, a needle retention group, and a electroacupuncture group. The heroin seeking behavior was elicited by a small dose of heroin. FosB expression in relevnt brain region was assessed with immunohistochemical technique. RESULTS: Tests on reinstatement of drug seeking behavior induced by heroin priming showed that compared with the restraint group, active pokes in the electroacupuncture group decreased significantly(P<0.05). Compared with the restraint group, the expression of FosB positive nuclei in Acd, Pcg and CeA of rats brain both in the electroacupuncture group and the needle retention group (P<0.05) decreased significantly. In LC, the expression of FosB positive nuclei in the needle retention group decreased significantly compared with the restraint group (P<0.05). CONCLUSION: Continuous acupuncture and needle retention attentuate the reinstatement of heroin-seeking behaviors induced by heroin priming, and the inhibitory effect may be mediated partially by the expression of FosB in relevant regions which are involved in the process of heroin addiction.

[Effects of electroacupuncture of low frequency on heroin-seeking behavior and FosB protein expression in relative brain regions].

OBJECTIVE: To observe effects of electroacupuncture (EA) of low frequency on heroin-seeking behavior and FosB protein expression in relative brain regions so as to explore the mechanism of EA. METHODS: Rat model of relapsing into heroin was established with progressive fixed ratio program, and model rats were randomly divided into 3 groups: a "Sanyinjiao" needle-retention control group, a low frequency and weak EA group, and a low frequency and strong EA group. Heroin-seeking behavior was elicited by conditional clue and small dose of heroin; FosB protein expression was investigated with immunohistochemical technique. RESULTS: After treatment, the heroin-seeking behavior induced by conditional clue decreased in the needle-retention control group and the weak EA group, and the heroin-seeking behavior induced by small dose of heroin in the weak EA group significantly reduced as compared with the control group, and FosB protein expression in the nucleus accumbens septi, globus pallidus, basolateral amygdaloid nucleus significantly decreased in the weak EA group, and did not significantly change in the strong EA group; the activity induced by heroin increased as compared with those in the control group and the weak EA group. CONCLUSION: EA of low frequency and low intensity can cure the heroin-seeking behavior, which is correlated with regulating nervous adaptation of nucleus accumbens septi, basolateral amygdaloid nucleus, etc..