1.Acupuncture and moxibustion combined with umbilical therapy for 30 cases of anxiety and depression in patients with neurogenic bladder after spinal cord injury.
Dongli WANG ; Xueqian WANG ; Rui WANG ; Youzhi HAO ; Weiwei QIAO ; Chao LI ; Yinping ZUO
Chinese Acupuncture & Moxibustion 2025;45(7):923-926
OBJECTIVE:
To observe the clinical effect of acupuncture and moxibustion combined with umbilical therapy on anxiety and depression in patients with neurogenic bladder (NB) after spinal cord injury (SCI).
METHODS:
Thirty cases of NB after SCI with anxiety and depression were selected and treated with acupuncture and moxibustion combined with umbilical therapy. Acupuncture was applied at Baihui (GV20), Yintang (GV24+), Sanyinjiao (SP6), Shenmen (HT7), Hegu (LI4), Taichong (LR3), once a day, continuous treatment for 4 weeks. Ginger moxibustion was applied at the bladder meridian of foot taiyang and governor vessel, once a day, continuous treatment for 4 weeks. In treatment of umbilical therapy, Chaihu (Radix Bupleuri), Yujin (Radix Curcumae), Rougui (Cortex Cinnamomi) were ground and mixed with the same amount of honey, put into the application, and the application was placed on the navel after filling the navel with fine salt, once a day for 4 weeks. Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, urodynamic indexes (maximum urinary flow rate [Qmax], maximum detrusor pressure [Pdet-max], residual urine volume [RUV]), neurogenic bladder symptom score (NBSS), urinary symptom distress scale (USDS) score were compared before and after treatment, and the clinical efficacy was evaluated.
RESULTS:
After treatment, the scores of HAMA, HAMD, NBSS, USDS and RUVwere lower than those before treatment (P<0.05), and Qmax and Pdet-max were higher than those before treatment (P<0.05). The total effective rate was 93.3 (28/30).
CONCLUSION
Acupuncture and moxibustion combined with umbilical therapy can effectively relieve anxiety and depression symptoms, improve urination disorders in patients with NB after SCI.
Humans
;
Moxibustion
;
Male
;
Female
;
Adult
;
Middle Aged
;
Acupuncture Therapy
;
Spinal Cord Injuries/psychology*
;
Depression/etiology*
;
Anxiety/etiology*
;
Urinary Bladder, Neurogenic/etiology*
;
Young Adult
;
Aged
;
Combined Modality Therapy
;
Acupuncture Points
2.Protective effect of graphene heating film far-infrared hyperthermia against frostbite in mice.
Jinshui ZHANG ; Shuo LI ; Dongdong WEI ; Xin CHENG ; Yun DENG ; Youzhi ZHANG
Journal of Southern Medical University 2025;45(3):522-530
OBJECTIVES:
To investigate the protective effects of graphene heating film far-infrared (FIR) hyperthermia therapy against frostbite in mice and its impacts on microcirculation and coagulation function.
METHODS:
Seventy-six C57BL/6J mice were randomized into control, model, graphene-FIR, and carbon fiber-FIR groups. After 7-day FIR intervention (4 h/day), the mice were subjected to acute (4 ℃, 4 h) and intermittent (4 ℃, 4 h/day for 3 days) cold exposure and the changes in rectal temperature were monitored. In liquid nitrogen frostbite experiment, 24 ICR mice were divided into model, graphene-FIR, and carbon fiber-FIR groups, and after a 7-day FIR pretreatment (4 h/day), the liquid nitrogen frostbite models were established and apparent scores of the wounds were assessed on days 3 and 6 after modeling. In carrageenan-induced thrombosis experiment, 40 ICR mice were allocated to control, model, graphene-FIR, carbon fiber-FIR, and prazosin groups to test the effect of a 7-day FIR intervention on thrombosis induced by intraperitoneal carrageenan injection (2.5 mg/kg) by measuring thrombus length, blood perfusion, and serum biomarkers (6-keto-PGF1α, TXB2, t-PA, IL-6, IL-1β, TNF‑α) 24 h after the injection.
RESULTS:
The mice in graphene-FIR group showed significantly elevated rectal temperature in cold exposure tests. In mice with liquid nitrogen-induced frostbite, graphene-FIR treatment significantly reduced the wound scores and reduced frostbite area, producing better effects than carbon fiber. In mice with carrageenan-induced thrombosis, graphene-FIR treatment significantly decreased tail thrombosis length and thrombosis area, increased blood perfusion, lowered serum levels of TXB2, TNF-α and IL-6, and increased the levels of 6-keto-PGF1α and t-PA.
CONCLUSIONS
Graphene heating film FIR therapy can alleviate frostbite injury in mice by improving microcirculation, suppressing thrombosis and inflammatory responses, and reducing coagulation dysfunction.
Animals
;
Frostbite/therapy*
;
Graphite
;
Mice, Inbred C57BL
;
Mice
;
Infrared Rays
;
Mice, Inbred ICR
;
Hyperthermia, Induced/methods*
;
Male
;
Microcirculation
3.Cannabidiol regulates circadian rhythm to improve sleep disorders following general anesthesia in rats.
Xinshun WU ; Jingcao LI ; Ying LIU ; Renhong QIU ; Henglin WANG ; Rui XYE ; Yang ZHANG ; Shuo LI ; Qiongyin FAN ; Huajin DONG ; Youzhi ZHANG ; Jiangbei CAO
Journal of Southern Medical University 2025;45(4):744-750
OBJECTIVES:
To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder.
METHODS:
An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (n=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins.
RESULTS:
Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment.
CONCLUSIONS
CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
Animals
;
Rats, Sprague-Dawley
;
Male
;
Cannabidiol/therapeutic use*
;
Rats
;
Circadian Rhythm/drug effects*
;
Propofol/adverse effects*
;
Anesthesia, General/adverse effects*
;
Sleep Wake Disorders/chemically induced*
;
Hypothalamus/metabolism*
;
Electroencephalography
5.Research on Material Basis of Homologous and Heterogeneous Effect of Aurantii Fructus Immaturus and Aurantii Fructus Based on Total Statistical Moment Analysis and Molecular Connectivity Index
Xiao YUAN ; Yuefeng WU ; Shixiong LI ; Youzhi LIU ; Zhiqin YU ; Fuyuan HE ; Jin ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(3):161-168
ObjectiveTo investigate the material basis of homologous and heterogeneous effect of Aurantii Fructus Immaturus(AFI) and Aurantii Fructus(AF) based on the total statistical moment analysis and molecular connectivity index(MCI). MethodRelevant literature at home and abroad and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) were consulted to establish the chemical composition database of AFI and AF, and set up their fingerprints by ultra-high performance liquid chromatography(UPLC), and the total statistical moments and similarity parameters of the fingerprint were calculated. According to MCI, all components of AFI and AF were divided into different component groups, the average values of 0-8th order(0χ-8χ) MCI of the common component groups of AFI and AF were calculated. ResultThe values of total zero-order moment(AUCT) of AFI and AF were (10.57±2.45)×106, (5.09±0.89)×106 μV·s, the values of total first-order moment(MCRTT) were (11.57±1.58), (12.10±1.29) min, the values of total second-order moments(VCRTT) were(24.49±2.30), (26.49±2.54) min2, respectively. It showed that qualitative and quantitative parameters of AFI and AF were significantly different. The components with high similarity such as neohesperidin, hesperidin and narirutin were screened as the common potential pharmacodynamic components of AFI and AF. The non-common components of AFI, such as alysifolinone and imperatorin, and the non-common components of AF, such as neoeriocitrin and isosakuranin, with high similarity were screened out as potential heterogeneous components of AFI and AF. The composition groups of AFI and AF were classified into six categories, and the similarities between the composition groups of AFI and AF and the total constituents were 0.872-0.979 and 0.918-0.997, the average values of 0χ-8χ MCI of alkaloids in AFI and AF were 3.65 and 3.14, the average values of 0χ-8χ MCI of flavonoids were 8.47 and 8.47, the average values of 0χ-8χ MCI of volatile oils were 2.71 and 3.48, respectively. It showed that there were some differences in MCI of chemical constituents(groups) between AFI and AF. ConclusionThe chemical constituents(groups) of AFI and AF not only differ in content and species, but also in structural characteristics and structure-activity relationship, which can provide a basis for further explaining the scientific connotation of homologous and heterogeneous effect of AFI and AF.
6.ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor,exerts antidepressant effect via dual mechanism of monoamine enhancement and inflammation suppression
Jingwen ZHANG ; Qiongyin FAN ; Susu ZHANG ; Yang ZHANG ; Ya LUO ; Xinming SHEN ; Luyao LUO ; Beilei DONG ; Jincao LI ; Shuo LI ; Huajin DONG ; Xingzhou LI ; Yupeng HE ; Rui XUE ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(5):321-334
OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.
7.Improvement of sleep by Jiawei Tianwang Buxin Dan and its mechanisms in simulated model of plateau exposure in rats
Jiaying HUANG ; Jingcao LI ; Yongfang GU ; Yumeng LIU ; Renhong QIU ; Yang ZHANG ; Rui XUE ; Shuo LI ; Huajin DONG ; Yanxin WANG ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2024;38(6):401-409
OBJECTIVE To investigate the effect of Jiawei Tianwang Buxin Dan(JWBXD)on insomnia in rats exposed to simulated high-altitude conditions.METHODS ① Thirty SD rats were randomly divided into the normal control,model,model+Jiawei Tianwang Buxin Dan(JWBXD,9.6 mg·kg-1),model+Tianwang Buxin Dan(TWBXD,9.6 mg·kg-1),and model+diazepam(DZP,3 mg·kg-1)groups.Rats,except for the normal control group,were subjected to a low-pressure,low-oxygen animal experimental chamber simulating a 5000 m altitude.Respective drugs were ig administrated once daily at 9:00 for seven days,and signal acquisition and sleep analysis were conducted by a wireless physiological sig-nal telemetry system.②Forty rats were randomly divided into five groups as described in ①.Through-out the experiment,the general condition and body mass of the rats were observed daily.Drug adminis-tration lasted for seven days,and grip strength was tested one hour after the final administration.ELISA was used to measure the levels of corticotropin-releasing hormone(CRH),adrenocorticotropic hor-mone(ACTH),corticosterone(CORT),and melatonin(MLT)in serum.Western blotting was performed to measure the expression levels of core clock proteins period circadian regulator 2(Per2),circadian locomotor output cycles(Clock),cryptochrome 2(Cry2),brain-muscle arnt-like protein 1(Bmal1),nuclear receptor subfamily 1,group D member 1(NR1D1),glycogen synthase kinase-3β(GSK-3β),as well as acetylserotonin O-methyltransferase(ASMT)in the hypothalamus and pineal gland,respectively.RESULTS ① Compared with the normal control group,the model group exhibited a decrease in total sleep time(P<0.01),an increase in wakefulness(P<0.01),a significant reduction in slow wave sleep(SWS)(P<0.05)and the mean bouts duration(P<0.05).Compared with the model group,both DZP and JWBXD(P<0.01)prolonged sleep time and suppressed wakefulness(P<0.01)in the hypoxic envi-ronment.DZP and JWBXD prolonged SWS(P<0.05,P<0.01),while TWBXD had no significant effect.JWBXD improved the mean bouts duration of SWS in the model rats(P<0.01),whereas no such improvement was observed in model+DZP and model+TWBXD groups.② Compared with the normal control group,the model group showed a significant decrease in forelimb grip strength(P<0.01),increased levels of serum ACTH(P<0.05),CRH,and CORT(P<0.01),and decreased MLT levels(P<0.05).The expression levels of Per2,Cry2,GSK-3β,and NR1D1 in the hypothalamus were downregu-lated(P<0.05,P<0.01),while Bmal1 and Clock were upregulated(P<0.05,P<0.01).ASMT expression in the pineal gland was decreased(P<0.05).Compared with the model group,JWBXD and TWBXD enhanced forelimb grip strength(P<0.01),reduced serum CORT and ACTH levels(P<0.05),decreased CRH levels(P<0.01),and restored MLT levels(P<0.01).JWBXD upregulated the expression levels of Per2,Cry2,GSK-3β and NR1D1 in the hypothalamus(P<0.05,P<0.01),but downregulated Bmal1 and Clock expression(P<0.05,P<0.01).TWBXD downregulated Bmal1 expression in the hypothalamus(P<0.01)and increased NR1D1 expression(P<0.05).DZP significantly enhanced the expression levels of Per2,Cry2 and NR1D1 in the hypothalamus(P<0.01).JWBXD,TWBXD and DZP improved ASMT expression in the pineal gland(P<0.05).CONCLUSION JWBXD can improve sleep structure and prolong the duration of SWS in rats exposed to simulated high-altitude conditions.The mechanisms may involve the regulation of core clock protein expressions in the hypothalamus,promotion of mela-tonin secretion,and inhibition of HPA axis hyperactivity.
8.The efficacy of axillary and posterior approaches for lesion clearance, bone graft fusion, and internal fixation in the treatment of upper thoracic tuberculosis
Qishan LUO ; Weimin LUO ; Qiang SHI ; Yuanhong LI ; Youzhi HE ; Yuxia XU
Journal of Chinese Physician 2024;26(8):1157-1162
Objective:To compare the clinical efficacy of axillary transthoracic approach and posterior approach in the treatment of upper thoracic tuberculosis with vertebral clearance, bone graft fusion, and internal fixation surgery.Methods:Fifty five patients with upper thoracic tuberculosis admitted to Changsha Central Hospital, University of South China from March 2017 to March 2022 were selected and divided into axillary transthoracic group and posterior group according to different surgical approaches. The incision length, surgical time, intraoperative blood loss, and postoperative hospitalization time were compared between the two groups of patients. Two groups of patients were recorded for preoperative and postoperative pain visual analog scale (VAS) scores, Oswestry Disability Index (ODI) scores at 1 week, 3 months, and 12 months, preoperative and postoperative serum inflammatory indicators, CD4 + /CD8 + ratio of T lymphocyte subsets, and complications. Results:The incision length, operation time, and intraoperative blood loss in the axillary transthoracic group were significantly less than those in the posterior group, and the differences were statistically significant (all P<0.05). However, there was no statistically significant difference in postoperative hospitalization time between the two groups of patients ( P>0.05). The VAS and ODI scores of the two groups of patients showed significant improvement compared to preoperative levels at 1 week, 3 months, and 12 months after surgery (all P<0.05); And at 1 week and 3 months after surgery, the VAS scores of patients in the axillary transthoracic group were significantly lower than those in the posterior group (all P<0.05), and the ODI scores at 3 and 12 months after surgery were significantly lower than those in the posterior group (all P<0.05). The erythrocyte sedimentation rate and CRP levels of both groups of patients increased significantly one week after surgery compared with preoperative levels (all P<0.05), but the erythrocyte sedimentation rate and CRP levels basically returned to normal levels at three months after surgery. The CD4 + /CD8 + ratio of T lymphocyte subsets in both groups was lower than preoperative levels at one week after surgery, but with the continuation of treatment, the CD4 + /CD8 + ratio increased significantly at three months after surgery. Conclusions:Both axillary and posterior approaches can be used for surgical treatment of upper thoracic tuberculosis, but axillary and thoracic approaches have the advantages of less trauma, less bleeding, and faster recovery.
9.Analysis of reliability and validity of different methods for quantifying the proportion of shoulder glenoid defect
Huachen LIU ; Songyan LI ; Yiqi YANG ; Youzhi CAI ; Bin WANG
Chinese Journal of Orthopaedics 2024;44(21):1416-1423
Objective:To evaluate the reliability and validity of different quantitative methods based on CT images to evaluate the proportion of shoulder glenoid defect.Methods:Four shoulder joint specimens with no trauma, osteoarthritis or deformity were used, including 2 females and 2 males; the average age of death was 58±10 years old; all the specimens were prepared with a standard method with no bone defect occurring before preparation. A glenoid bone defect model was established with each specimen being cut into four defect gradient defects of approximately 8%, 16%, 24%, and 32% in proportion in sequence. A total of 16 samples were obtained. Physical photography and CT image reconstruction were performed on the 16 samples respectively. A total of 8 quantitative methods were used to quantify bone defects, which were surface area method, superimposed circle method, Barchilon method, Pico method, Shaha method, Griffith method, Sugaya method, and Giles method. Intraclass correlation (ICC) using a consistency model was used to evaluate reliability. Paired t-test was used to evaluate validity, with the physical measurement of the specimens using the surface area method as the reference standard. Result:The consistency ICC of each quantitative method was greater than 0.9, and all had high reliability. Combining the results of all bone defect gradients and imaging images, the surface area method had the best validity, which was 0.83%±0.75%; the Barchilon method came second, which was 0.91%±0.93%; the superimposed circle method and the Pico method had good validity, which were 0.99%±0.87% and 1.27%±1.09%, respectively; the Shaha method, the Griffith method, and the Sugaya method had poor validity, which were 6.11%±1.56%, 5.06%±1.35%, and 6.02%±1.61%, respectively; the Giles method had the worst validity, which was 8.40%±3.08%. Conclusion:In clinical practice, surface area method and superimposed circle method are the most reliable to quantify the proportion of bone defect if they can be performed. Otherwise, linear measurement of Barchilon method is the favored method while PICO method is the favored method for angle measurement.
10.Nuciferine,an aromatic ring-containing alkaloid,delivers sedative-hypnotic effects through serotoner-gic system
Luoxuan WANG ; Yumeng LIU ; Jingao LI ; Youzhi ZHANG
Chinese Journal of Pharmacology and Toxicology 2023;37(7):489-489
OBJECTIVE Insomnia is the most fre-quent sleep disorder worldwide and the clinical applica-tion of therapeutic drugs has various adverse effects.In recent years,drugs developed from natural herbs have become potential alternative therapies for insomnia.Nuciferine,one of the main bioactive components obtained from the lotus leaves,has been reported to possess extensive pharmacological activities.However,its hypnotic and sleep regulatory effects have rarely been reported.Hence,this study was intended to investigate the pharma-cological effects of nuciferine and its mechanisms of action in insomnia.METHODS The hypnotic and seda-tive effects of nuciferine were investigated using the eval-uation of locomotor activity test and pentobarbital-induced sleep test in normal and serotonin(5-HT)depletion-induced insomniac mice.Furthermore,the sleep regulatory effects,including sleep time,sleep architecture,and δ-wave power spectral density,were explored using elec-troencephalography/electromyogram(EEG/EMG)-based sleep profiling in normal rats.Finally,the mechanisms of the hypnotic and sedative effects of nuciferine were explored usingin vivoand in silico experiments.RESULTS Nuciferine reduced locomotor activity and prolonged pen-tobarbital-induced sleep time in a dose-dependent man-ner in normal and insomniac model mice.Nuciferine sig-nificantly increased the total sleep time and non-rapid eye movement(NREM)sleep time,inhibited NREM sleep fragmentation,and improved delta power between 0.5 Hz and 1 Hz in normal rats.The results of molecular experiments showed that nuciferine could increase the 5-HT content and 5-HT1A receptor level in the hypothala-mus of insomnia model mice.CONCLUSION This study combined network pharmacological prediction and experi-mental pharmacological techniques to discover the seda-tive-hypnotic effect of nuciferine for the first time Nucif-erine can ameliorate sleep disorder in mice with insom-nia,possibly via serotonergic system.Nuciferine may rep-resent a novel treatment that alleviate the insomnia-like symptoms by modulating 5-HT system.

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