1.Research progress in mechanisms of traditional Chinese medicine polysaccharides in prevention and treatment of alcoholic liver disease.
Yu-Fan CHEN ; He JIANG ; Qing MA ; Qi-Han LUO ; Shuo HUANG ; Jiang QIU ; Fu-Zhe CHEN ; Zi-Yi SHAN ; Ping QIU
China Journal of Chinese Materia Medica 2025;50(2):356-362
Alcoholic liver disease(ALD), a major cause of chronic liver disease worldwide, poses a serious threat to human health. Despite the availability of various drugs for treating ALD, their efficacy is often uncertain, necessitating the search for new therapeutic approaches. Traditional Chinese medicine polysaccharides have garnered increasing attention in recent years due to their versatility, high efficiency, and low side effects, and they have demonstrated significant potential in preventing and treating ALD. Emerging studies have suggested that these polysaccharides exert their therapeutic effects through multiple mechanisms, including the inhibition of oxidative stress and the regulation of lipid metabolism, gut microbiota, and programmed cell death. This review summarizes the recent research progress in the pharmacological effects and regulatory mechanisms of traditional Chinese medicine polysaccharides in treating ALD, aiming to provide a scientific basis and theoretical support for their application in the prevention and treatment of ALD.
Humans
;
Liver Diseases, Alcoholic/metabolism*
;
Polysaccharides/administration & dosage*
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
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Oxidative Stress/drug effects*
;
Medicine, Chinese Traditional
;
Gastrointestinal Microbiome/drug effects*
;
Lipid Metabolism/drug effects*
2.Exploration of the Acupoint Selection Rules of Acupuncture for the Treatment of Tic Disorders in Children Based on Data Mining Techniques
Shan-Hong WU ; Zi-Han GONG ; Yan WANG ; Yang GAO ; Yi-Ming YUAN ; Ming-Yue ZHAO ; Zi-Wei ZHANG ; Tian-Yi LI ; Fei PEI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(4):1083-1090
Objective To analyze the acupoint selection rules of acupuncture for the treatment of tic disorders in children based on data mining techniques.Methods A computerized search was conducted for the clinical research literature on acupuncture treatment of tic disorders in children included in the CNKI,Wanfang,VIP,SinoMed,and PubMed databases from January 1992 to December 2022.A database was established by Excel 2019 to count the commonly used treatment methods and analyze the high-frequency application methods acupuncture(high-frequency acupoints,channel entry of acupoints,acupoint association rules,and acupoint clustering),auricular point seed-pressing(high-frequency auricular points,and acupoint association rules),and the high frequency division of cluster needling of scalp point.Results A total of 190 valid literature articles were included,involving 270 acupuncture prescriptions;among them,184 acupoints were counted in the acupuncture method,with a total application frequency of 1 906 times,and the high-frequency application of the acupoints in descending order were Baihui(DU20),Taichong(LR3),Fengchi(GB20),Hegu(LI4),Sanyinjiao(SP6),Neiguan(PC6),Shenmen(HT7),Zusanli(ST36),Yintang(EX-HN3),Sishencong(EX-HN1);and the high-frequency meridians were governor vessol,foot taiyang stomach meridian,foot taiyang stomach meridian,foot shaoyang gallbladder meridian,hand taiyang large intestine meridian,foot taiyang bladder meridian,foot jueyin gallbladder meridian;three sets of strong association rules and five clusters of acupoints were analyzed by SPSS modeler 18.0 and IBM SPSS Statistics 26.0 software.There were 29 acupoints of auricular point seed-pressing,application total frequency was 206 times,high-frequency application of auricular points in descending order of Shenmen(HT7),liver,heart,subcortex,kidney;four groups of acupoint strong association rules were obtained through the analysis of SPSS modeler 18.0 software.A total of 14 zones were involved in the application of cephalic acupoint plexus zoning,of which the high-frequency zones were parietal anterior temporal diagonal,parietal parietal 1,and chorea tremor control zone.Conclusion Acupuncture treatment of tic disorders in children,according to its pathogenesis(liver hyperactivity,kidney depletion,spleen deficiency,phlegm disturbance,etc.)and tic site,select acupoints compatibility,and mostly choose yang meridian acupoints,which is related to the nature and treatment characteristics of wind pathogen.Children's tic disorders are closely related to emotional disorders,therefore acupuncture and auricular acupoints all emphasize the method of soothing the liver and clearing the heart,and regulating the emotional state.Cluster needling of scalp point mostly used parietal temporal anterior oblique line,parietal 1 line,and dance tremor control area for the treatment of tic disorders.For children,auricular point seed-pressing and cluster needling of scalp point has the minimun of pain,the effect of treatment is long,and it is not easy to have dangerous situations such as bent needle,broken needle and so on.
3.Temporal trend of the global prevalence rate of tension-type headache in children and adolescents in 1990-2021
Ling-Zi YAO ; De-Nan JIANG ; Jing WU ; Guang-Dian SHEN ; Jin CAO ; Si-Qing CHENG ; Shi-Yi SHAN ; Ze-Yu LUO ; Jia-Li ZHOU ; Pei-Ge SONG
Chinese Journal of Contemporary Pediatrics 2024;26(10):1058-1065
Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.
4.Effects of electroacupuncture at "Jiaji" (EX-B 2) combined with neurodynamic mobilization on gastrocnemius muscle atrophy and expression of NF-κB and MuRF1 in rabbits after sciatic nerve injury.
Shan-Hong WU ; Yan WANG ; Dong-Liang XIANG ; Yi-Ming YUAN ; Ming-Yue ZHAO ; Xue-Wei ZHANG ; Zi-Han GONG
Chinese Acupuncture & Moxibustion 2023;43(11):1293-1299
OBJECTIVES:
To observe the effects of electroacupuncture (EA) at "Jiaji" (EX-B 2) combined with neurodynamic mobilization (NM) on the cross-sectional area of the gastrocnemius muscle fibers after sciatic nerve injury in rabbits, and the expression of nuclear factor κB (NF-κB) and muscle-specific ring-finger protein 1 (MuRF1).
METHODS:
A total of 180 common-grade New Zealand rabbits (half male and half female) were randomly divided into five groups, i.e. a normal control group, a model control group, a NM group, an EA group and a combined intervention group, 36 rabbits in each group. Except in the normal control group, clipping method was used to prepare the model of sciatic nerve injury in the rest groups. On the 3rd day of successful modeling, NM was delivered in the NM group. In the EA group, EA was exerted at bilateral "Jiaji" (EX-B 2) of L4 to L6, stimulated with disperse-dense wave and the frequency of 2 Hz/100 Hz. In the combined intervention group, after EA delivered at bilateral "Jiaji" (EX-B 2) of L4 to L6 , NM was operated. The intervention in each group was delivered once daily, for 6 days a week, and lasted 1, 2 or 4 weeks according to the collection time of sample tissue. After 1, 2 and 4 weeks of intervention, in each group, the toe tension reflex score and the modified Tarlov test score were observed; the morphology of the gastrocnemius muscle was observed by HE staining and the cross-sectional area of muscular fiber was measured; using Western blot method, the expression of NF-κB and MuRF1 of the gastrocnemius muscle was detected.
RESULTS:
After 1, 2 and 4 weeks of intervention, the toe tension reflex scores and the modified Tarlov scores in the model control group were lower than those of the normal control group (P<0.05), and these two scores in the NM group, the EA group and the combined intervention group were all higher than those of the model control group (P<0.05); the scores in the combined intervention group were higher than those in the EA group and the NM group (P<0.05). The gastrocnemius fibers were well arranged and the myocyte morphology was normal in the normal control group. In the model control group, the gastrocnemius fibers were disarranged, the myocytes were irregular in morphology and the inflammatory cells were infiltrated in the local. In the NM group, the EA group and the combined intervention group, the muscle fibers were regularly arranged when compared with the model control group. After 1, 2 and 4 weeks of intervention, the cross-sectional areas of the gastrocnemius muscle fibers in the model control group were smaller than those of the normal control group (P<0.05). The cross-sectional areas in the NM group, the EA group and the combined intervention group were larger than those of the model control group (P<0.05), and the cross-sectional areas in the combined intervention group were larger than those in the NM group and the EA group (P<0.05). After intervention for 1, 2 and 4 weeks, the protein expressions of NF-κB and MuRF1 in the gastrocnemius muscle were higher in the model control group in comparison of those in the normal control group (P<0.05). In the NM group, the EA group and the combined intervention group, the expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were lower when compared with those in the model control group (P<0.05). In the combined intervention group, the protein expressions of NF-κB after intervention for 1, 2 and 4 weeks and the expressions of MuRF1 after 2 and 4 weeks of intervention were decreased when compared with those in the NM group and the EA group (P<0.05).
CONCLUSIONS
Electroacupuncture at "Jiaji" (EX-B 2) combined with NM may increase the muscle strength and sciatic function and alleviate gastrocnemius muscle atrophy in the rabbits with sciatic nerve injury. The underlying mechanism is related to the inhibition of NF-κB and MuRF1 expression.
Animals
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Female
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Male
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Rabbits
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Electroacupuncture
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Muscle, Skeletal
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Muscular Atrophy/therapy*
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NF-kappa B/genetics*
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Peripheral Nerve Injuries
;
Rats, Sprague-Dawley
;
Sciatic Nerve
5.Effects of zhongfeng cutong moxibustion on motor function and corticospinal tract in the patients with motor dysfunction during the recovery period of cerebral infarction.
Zi-Long ZHU ; Tian-Yi SHEN ; Zheng SUN ; Hao LI ; Hua SHAN ; Lin-Li CAO ; Jian-Bin ZHANG
Chinese Acupuncture & Moxibustion 2023;43(12):1358-1362
OBJECTIVES:
To observe the effects of zhongfeng cutong moxibustion (moxibustion therapy for unblocking and treating stroke) on the motor function and the structure of corticospinal tract (CST) in the patients with motor dysfunction during the recovery period of cerebral infarction, and to explore the central mechanism of this moxibustion therapy for improving the motor function.
METHODS:
Fifty patients with motor dysfunction during the recovery period of cerebral infarction were randomly divided into an observation group (25 cases, 1 case dropped out) and a control group (25 cases, 1 case dropped out). The patients in both groups underwent the conventional basic treatment. In the control group, acupuncture was applied to Baihui (GV 20) and Shuigou (GV 26), as well as Chize (LU 5), Neiguan (PC 6), Weizhong (BL 40) and Sanyinjiao (SP 6) etc. on the affected side. Besides the intervention of the control group, in the observation group, zhongfeng cutong moxibustion therapy was combined at Baihui (GV 20), Shenque (CV 8) and bilateral Zusanli (ST 36). Both acupuncture and moxibustion therapies were delivered once daily, 5 times a week, for 2 weeks. The scores of Fugl-Meyer assessment scale (FMA) and National Institutes of Health stroke scale (NIHSS) were compared between the two groups before and after treatment. The diffusion tensor imaging technique was used to observe the fractional anisotropy (FA) of CST at the bilateral whole segment, the cerebral cortex, the posterior limb of the internal capsule and the cerebral peduncle before and after treatment in the two groups.
RESULTS:
The scores of the upper and the lower limbs of FMA, as well as the total FMA score swere increased after treatment when compared with those before treatment in the two groups (P<0.05), the upper limb FMA score and the total FMA score in the observation group were higher than those in the control group (P<0.05), and NIHSS scores of the two groups were dropped compared with those before treatment (P<0.01). FA of CST at the bilateral sides of the posterior limb of the internal capsule and the whole segment on the focal side was improved in comparison with that before treatment in the observation group (P<0.05), and FA of CST at the healthy side of the whole segment was higher than that before treatment in the control group (P<0.05).
CONCLUSIONS
Zhongfeng cutong moxibustion improves motor function and reduces neurological deficits in the patients with motor dysfunction during the recovery period of cerebral infarction, which may be related to enhancing the remodeling of white matter fiber bundles in the corticospinal tract on the focal side of the whole segment and the bilateral posterior limb of the internal capsule.
Humans
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Moxibustion
;
Pyramidal Tracts
;
Diffusion Tensor Imaging
;
Acupuncture Therapy
;
Cerebral Infarction/therapy*
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Stroke/therapy*
;
Acupuncture Points
;
Treatment Outcome
6.Reliability and validity of the Chinese version of adverse childhood experiences international questionnaire in parents of preschool children.
Xiao Yi MI ; Shan Shan HOU ; Zi Yuan FU ; Mo ZHOU ; Xin Xuan LI ; Zhao Xue MENG ; Hua fang JIANG ; Hong ZHOU
Journal of Peking University(Health Sciences) 2023;55(3):408-414
OBJECTIVE:
To test the reliability and validity of the Chinese version of adverse childhood experiences international questionnaire (ACE-IQ) in Chinese parents of preschool children.
METHODS:
The parents of preschool children in 6 kindergartens in Tongzhou District of Beijing were selected by stratified random cluster sampling, and the Chinese version of ACE-IQ after translation and adaptation was used for survey online. The collected data were randomly divided into two parts. One part of the data (n=602) was used for exploratory factor analysis (EFA), to screen items and evaluate structural validity, and then form the final Chinese version of ACE-IQ. The other part of the data (n=700) was used for confirmatory factor analysis (CFA), criterion validity analysis and reliability analysis. At the same time, experts investigation method was used to evaluate the content validity of the final Chinese version of ACE-IQ.
RESULTS:
After deleting four items of collective violence, the Chinese version of ACE-IQ with twenty-five items indicated good structural, criterion and content validity. Analysis results showed that the Chinese version of ACE-IQ presented a seven-factor model dimension, namely emotional neglect, physical neglect, family dysfunction, family violence, emotional and physical abuse, sexual abuse and violence outside the home, and the total score of the binary version of ACE-IQ Chinese version was positively correlated with the total score of childhood trauma questionaire-28 item short form (CTQ-SF, r=0.354, P < 0.001) and the center for epidemiological studies depression scale (CES-D, r=0.313, P < 0.001) respectively. Results from five experts showed that the item-level content validity index (I-CVI) of 25 items was between 0.80 and 1.00, and the average of all I-CVIs on the scale (S-CVI/Ave) of the scale was 0.984. At the same time, the internal consistency (Cronbach's α coefficient) of the whole scale was 0.818, and the split-half reliability (Spearman-Brown coefficient) was 0.621, which demonstrated good reliability.
CONCLUSION
This study has formed a Chinese version of ACE-IQ with 25 items and 7 dimensions, which has good reliability and validity among the parents of preschool children in China. It can be used as an evaluation instrument for measuring the minimum threshold of the adverse childhood experiences in the parents of preschool children in the cultural background of China.
Humans
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Child, Preschool
;
Adverse Childhood Experiences
;
Reproducibility of Results
;
Parents/psychology*
;
Surveys and Questionnaires
;
China
;
Psychometrics/methods*
7.Association of outdoor artificial light at night exposure with overweight and obesity among children and adolescents aged 9 to 18 years in China.
Jia Jia DANG ; Shan CAI ; Pan Liang ZHONG ; Ya Qi WANG ; Yun Fei LIU ; Di SHI ; Zi Yue CHEN ; Yi Hang ZHANG ; Pei Jin HU ; Jing LI ; Jun MA ; Yi SONG
Journal of Peking University(Health Sciences) 2023;55(3):421-428
OBJECTIVE:
To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China.
METHODS:
Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm2·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes.
RESULTS:
The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity.
CONCLUSION
There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.
Humans
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Adolescent
;
Child
;
Overweight/etiology*
;
Pediatric Obesity/etiology*
;
Light Pollution
;
Risk Factors
;
China/epidemiology*
8.An Anterior Cingulate Cortex-to-Midbrain Projection Controls Chronic Itch in Mice.
Ting-Ting ZHANG ; Su-Shan GUO ; Hui-Ying WANG ; Qi JING ; Xin YI ; Zi-Han HU ; Xin-Ren YU ; Tian-Le XU ; Ming-Gang LIU ; Xuan ZHAO
Neuroscience Bulletin 2023;39(5):793-807
Itch is an unpleasant sensation that provokes the desire to scratch. While acute itch serves as a protective system to warn the body of external irritating agents, chronic itch is a debilitating but poorly-treated clinical disease leading to repetitive scratching and skin lesions. However, the neural mechanisms underlying the pathophysiology of chronic itch remain mysterious. Here, we identified a cell type-dependent role of the anterior cingulate cortex (ACC) in controlling chronic itch-related excessive scratching behaviors in mice. Moreover, we delineated a neural circuit originating from excitatory neurons of the ACC to the ventral tegmental area (VTA) that was critically involved in chronic itch. Furthermore, we demonstrate that the ACC→VTA circuit also selectively modulated histaminergic acute itch. Finally, the ACC neurons were shown to predominantly innervate the non-dopaminergic neurons of the VTA. Taken together, our findings uncover a cortex-midbrain circuit for chronic itch-evoked scratching behaviors and shed novel insights on therapeutic intervention.
Mice
;
Animals
;
Gyrus Cinguli/physiology*
;
Pruritus/pathology*
;
Mesencephalon
;
Cerebral Cortex/pathology*
;
Neurons/pathology*
9.Effect of light intensity on growth, accumulation of ginsenosides, and expression of related enzyme genes of Panax quinquefolius.
Zi-Qi LIU ; Yi WANG ; Xiu WANG ; Na PENG ; Shan-Shan YANG ; Hui-Hui SHAO ; Xiao-Lin JIAO ; Wei-Wei GAO
China Journal of Chinese Materia Medica 2022;47(18):4877-4885
Appropriate light intensity is favorable for the photosynthesis, biomass accumulation, key enzyme activity, and secondary metabolite synthesis of medicinal plants. This study aims to explore the influence of light intensity on growth and quality of Panax quinquefolius. To be specific, sand culture experiment was carried out in a greenhouse under the light intensity of 40, 80, 120, and 160 μmol·m~(-2)·s~(-1), respectively. The growth indexes, photosynthetic characteristics, content of 6 ginsenosides of the 3-year-old P. quinquefolius were determined, and the expression of ginsenoside synthesis-related enzyme genes in leaves, main roots, and fibrous roots was determined. The results showed that the P. quinquefolius growing at 80 μmol·m~(-2)·s~(-1) light intensity had the most biomass and the highest net photosynthetic rate. The total biomass of P. quinquefolius treated with 120 μmol·m~(-2)·s~(-1) light intensity was slightly lower than that with 80 μmol·m~(-2)·s~(-1). The root-to-shoot ratio in the treatment with 120 μmol·m~(-2)·s~(-1) light intensity was up to 6.86, higher than those in other treatments(P<0.05),and the ginsenoside content in both aboveground and underground parts of P. quinquefolius in this treatment was the highest, which was possibly associated with the high expression of farnesylpyrophosphate synthase(FPS), squalene synthase(SQS), squalene epoxidase(SQE), oxidosqualene cyclase(OSC), dammarenediol-Ⅱ synthase(DS), and P450 genes in leaves and SQE and DS genes in main roots. In addition, light intensities of 120 and 160 μmol·m~(-2)·s~(-1) could promote PPD-type ginsenoside synthesis in leaves by triggering up-regulation of the expression of upstream ginsenoside synthesis genes. The decrease in underground biomass accumulation of the P. quinquefolius grown under weak light(40 μmol·m~(-2)·s~(-1)) and strong light(160 μmol·m~(-2)·s~(-1)) was possibly attributed to the low net photosynthetic rate, stomatal conductance, and transpiration rate in leaves. In the meantime, the low expression of SQS, SQE, OSC, and DS genes in the main roots might led to the decrease in ginsenoside content. However, there was no significant correlation between the ginsenoside content and the expression of synthesis-related genes in the fibrous roots of P. quinquefolius. Therefore, the light intensity of 80 and 120 μmol·m~(-2)·s~(-1) is beneficial to improving yield and quality of P. quinquefolius. The above findings contributed to a theoretical basis for reasonable shading in P. quinquefolius cultivation, which is of great significance for improving the yield and quality of P. quinquefolius through light regulation.
Farnesyl-Diphosphate Farnesyltransferase/metabolism*
;
Ginsenosides
;
Panax/metabolism*
;
Plant Roots/metabolism*
;
Sand
;
Squalene Monooxygenase
10.Liuwei Dihuangtang Alleviates Myelin Injury in Anterior Cingulate Cortex and Depression-like Behaviors of Rats with Diabetes Mellitus and Depression via Promoting Autophagy and Regulating Microglial Phenotype
Fang HUANG ; Zi-hu TAN ; Yi-miao CHEN ; Nan SHAN ; Wen-jing YAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(6):7-16
ObjectiveTo observe the effect of Liuwei Dihuangtang (LWDHT) on depression-like behaviors of rats with diabetes mellitus and depression (DD) and explore its mechanism. MethodThe diabetes mellitus (DM) model was induced by the high-fat diet and tail vein injection of low-dose streptozotocin (STZ) in 50 male Sprague-Dawley rats of SPF grade. Then the DD model was induced by chronic unpredictable mild stress (CUMS) for 28 days in DM rats. Fifty DD rats were randomly divided into model group, fluoxetine group (10 mg·kg-1·d-1), and low-, medium-, and high-dose LWDHT groups (3.375, 6.75, 13.5 g·kg-1·d-1), with 10 rats in each group. Another 10 healthy rats were assigned into a control group and received normal saline by gavage. After four weeks of drug intervention, the forced swimming assay was carried out to assess the depression-like behaviors of rats. The expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-4 (IL-4), and interleukin-10 (IL-10) in the anterior cingulate cortex (ACC) were detected by enzyme-linked immunosorbent assay (ELISA). Immunofluorescence was used to detect the expression of myelin basic protein (MBP) in ACC and the co-localization of ionized calcium-binding adapter molecule 1 (Iba1) with intracellular microtubule-associated protein 1 light chain 3 (LC3). The protein expression levels of MBP, myelin proteolipid protein (PLP), myelin oligodendrocyte glycoprotein (MOG), Beclin-1, LC3, p62, and microglia (MG) phenotypic protein-related inducible nitric oxide synthase (iNOS), and arginase 1 (Arg1) were detected by Western blot. ResultCompared with the control group, the model group showed shortened swimming time and prolonged immobility time (P<0.01). Compared with the model group, the medium- and high-dose LWDHT groups showed reduced immobility time (P<0.05, P<0.01). Compared with the control group, the model group showed decreased protein expression of MBP, PLP, and MOG in the ACC region (P<0.01). Compared with the model group, the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated protein expression of MBP, PLP, and MOG (P<0.05, P<0.01). Compared with the control group, the model group showed decreased MBP fluorescence intensity in the ACC region (P<0.01). Compared with the model group, the fluoxetine group and the medium- and high-dose LWDHT groups showed increased MBP fluorescence intensity in the ACC region (P<0.05, P<0.01). Compared with the control group, the model group showed increased expression of iNOS (P<0.01) and slightly increased Arg1 protein expression. Compared with the model group, the medium- and high-dose LWDHT groups and the fluoxetine group showed down-regulated iNOS expression and up-regulated Arg1 protein expression (P<0.05, P<0.01), but there was no significant difference between the fluoxetine group and the medium-,high-dose LWDHT groups. Compared with the control group, the model group showed increased expression levels of proinflammatory factors IL-1β and TNF-α in the ACC region (P<0.01) and slightly increased expression levels of anti-inflammatory factors IL-4 and IL-10. Compared with the model group, the fluoxetine group, and the medium- and high-dose LWDHT groups showed down-regulated expression of IL-1β and TNF-α (P<0.05, P<0.01) and up-regulated expression of IL-4 and IL-10 (P<0.05, P<0.01). Compared with the control group, the model group showed reduced expression levels of Beclin-1 and LC3Ⅱ (P<0.01) and increased expression level of p62 (P<0.01). Compared with the model group, the fluoxetine group and the medium- and high-dose LWDHT groups showed up-regulated Beclin-1 and LC3Ⅱ expression (P<0.01) and down-regulated p62 expression (P<0.01). Compared with the control group, the model group showed decreased LC3+Iba1+ cells in the ACC region (P<0.01). Compared with the model group, the fluoxetine group and the medium- and high-dose LWDHT groups showed increased LC3+Iba1+ cells (P<0.05, P<0.01). ConclusionLWDHT can alleviate the depression-like behaviors in DD rats presumedly by promoting MG autophagy, regulating MG phenotypic changes, and increasing MG clearance of myelin sheath fragments. Meanwhile, MG phenotypic transformation also inhibits ACC inflammation in DD rats, improves the local microenvironment of oligodendrocyte proliferation and differentiation, and ultimately promotes the repair and remyelination of damaged myelin sheath.

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