Role of HPA Axis Dysregulation in Cancer-related Fatigue Based on Principle of "Treating Overstrain with Warming" / 中国实验方剂学杂志

This paper discusses the theoretical basis of traditional Chinese medicine （TCM） for the treatment of cancer-related fatigue （CRF） based on the principle of treating overstrain with warming in the Huangdi's Internal Classic 《黄帝内经》 and the role of hypothalamic-pituitary-adrenal （HPA） axis dysregulation in CRF， aiming to provide new ideas for the clinical treatment of CRF. In the pulsatile regulation of the HPA axis， cortisol， which is synthesized and released by the adrenal cortex， plays an essential role in the life activities. The abnormal circadian rhythm and reduced serum level of cortisol are major factors leading to CRF. Therefore， increasing the serum level and stimulating the biological activity of cortisol and restoring the normal function of HPA axis are important targets for the treatment of CRF and also the key to the TCM treatment of this disease. According to the TCM principle of treating overstrain with warming， we interpreted the etiology and clinical manifestations of overstrain and further explored the causes of CRF. It is believed that the depletion of Qi and blood， Yin and Yang， and fluid in the kidney， spleen， and liver is the key of the disease， which results in symptoms such as fatigue. Further， we elaborated on the theoretical connotation of warming and summarized the two main treatment principles of tonifying with warm-natured herbs and relieving fever with sweet- and warm-natured herbs. According to the different characteristics of the organs affected by pathogen， we proposed the treatment method of warming kidney to cultivate essence， warming stomach and nourishing spleen to replenish Qi， nourishing liver and tonifying blood to promote Qi movement， and relieving fever with sweet- and warm-natured herbs to alleviate fatigue. The warming method can elevate the serum level and invigorate the biological functions of cortisol in CRF patients， which provides a new theoretical basis for alleviating the symptoms and improving the quality of life of cancer patients in clinical practice.

Protective Effect of Total Ginsenoside Ginseng Root on Learning and Memory Impairment and Anxiety in Rats Induced by Hindlimb Suspension / 中国实验方剂学杂志

Objective:To investigate the effect of total ginsenoside ginseng root on the learning and memory impairment and anxiety of hindlimb suspension rats by detecting the performance of rats in the water maze， elevated plus maze， and the expression of hypothalamic-pituitary-adrenal （HPA） axis， inflammatory factors and tryptophan pathway related factors through the intervention of ginsenosides in hindlimb suspension rats. Method:The Wistar male rats were divided into normal group， hindlimb suspension model group， Huperzine A group （0.1 mg·kg^-1）， and total ginsenoside ginseng root low and high dose groups （100， 200 mg·kg^-1）， with 8 rats in each group. Except for the normal group， the rats in the other groups maintained a -30° hindlimb suspension state for 24 h. The normal group and the model group received intragastric administration of 10 mL·kg^-1 pure water . After 28 days of continuous administration， the water maze and elevated plus maze behavioral tests were performed. After the tests， blood was taken from the abdominal aorta， and the rat brain cortex was peeled off on ice， quenched with liquid nitrogen， and stored at -80 ℃ for later use. LC-MS/MS was used to detect neurotransmitter levels of dopamine， acetylcholine， glutamate， <italic>γ</italic>-aminobutyric acid and tryptophan pathway metabolites （tryptophan， 5-hydroxytryptamine， 5-hydroxyindoleacetic acid， kynurenine， 3-hydroxykynurenine， and kynurenine） in rat brain cortex. An enzyme-linked immunosorbent assay （ELISA） kit was used to detect the levels of inflammatory factors interleukin-6 （IL-6）， interleukin-10 （IL-10， the HPA axis-related hormone corticotropin （ACTH）， and the level of corticosterone （CORT）. Result:Compared with the normal group， the escape latency in the water maze significantly increased， the number of crossings was significantly reduced， and the number of open-arm entry and the percentage of open-arm entry were significantly reduced in the elevated plus maze in model group （<italic>P</italic><0.05，<italic> P</italic><0.01）， the content of dopamine， acetylcholine， glutamic acid， and <italic>γ</italic>-aminobutyric acid in the cortex decreased， kynurenine and kynurenic acid showed an upward trend， 3-hydroxykynurenine， 5-hydroxytryptamine， 5-hydroxyindole acetic acid showed a downward trend， and the levels of IL-6， IL-10， ACTH， and CORT in the serum significantly increased （<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group of rats， total ginsenoside ginseng root low and high dose groups group reduced the avoidance latency in the water maze， and increased the number of crossings and the number of open arms of the elevated plus maze， dopamine， acetylcholine， glutamate， and <italic>γ</italic>-aminobutyl content increased， while kynurenine and kynurenic acid showed a downward trend， 3-hydroxykynurenine， serotonin， and 5-hydroxyindole acetic acid showed an upward trend， and IL-6， IL-10， ACTH， and CORT factor levels were down-regulated（<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Hindlimb suspension for 28 days in simulated microgravity can impair the learning and memory ability of rats and cause anxiety-like behaviors. Total ginsenoside ginseng root can improve their learning and memory impairment and anxiety-like behaviors. The mechanism may be mainly related to inhibiting body inflammation and regulating HPA axis imbalance.

Effects of heat-sensitive moxibustion on HPA axis in rats with irritable bowel syndrome / 中国针灸

<p><b>OBJECTIVE</b>To observe the effects of heat-sensitive moxibustion on corticotropin releasing hormone (CRH), adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) in rats with irritable bowel syndrome (IBS), and to explore the possible mechanism of heat-sensitive moxibustion on IBS.</p><p><b>METHODS</b>According to random number table, 56 SD male rats were randomly divided into a blank group (=8), a model group (=8), a moxibustion group (=32), and a mifepristone group (RU-486 group,=8). The rats in the blank group were treated with normal feeding; the rats in the model group, RU-486 group and moxibustion group were treated with chronic non-predictable stimulation for 21 days to establish IBS model. After model establishment, the rats in the moxibustion group were treated with moxibustion at "Mingmen" (GV 4) for 40 min, once a day for 14 days; the tail temperature was recorded every 5 min; according to the change of tail temperature, the rats were divided into a heat-sensitive moxibustion group and a non-heat-sensitive moxibustion group, and 8 rats were randomly selected in the two groups. The rats in the RU-486 group were treated with gastric administration of RU-486 for 14 days, while the rats in the blank group, model group and moxibustion groups were treated with identical volume of 0.9% NaCl. The rat general condition, body mass, behavioristics, intestinal propulsive rate and visceral sensitivity were observed in each group; ELISA method was used to detect serum CRH, ACTH and CORT; optical microscope was applied to observe the morphological changes of colon.</p><p><b>RESULTS</b>(1) After model establishment, rats were in rest state, fatigued, with withered hair and dim ear; the stool was dry or watery; the body mass were slowly increased; the number of crossed grid and standing frequency were significantly reduced; visceral sensitivity was increased and intestinal propulsion rate was decreased; no obvious inflammatory cell infiltration was observed under microscope. (2) After intervention, compared with the blank group, the body mass and visceral sensitivity in the RU-486 group were not significantly different (both>0.05), but the intestinal propulsion rate was decreased significantly (<0.01). Compared with the blank group, the body mass of heat-sensitive moxibustion group and non-heat-sensitive moxibustion group was lower (both<0.01), but the visceral sensitivity and intestinal propulsion rate were similar (both>0.05). Compared with the model group, the body mass and visceral sensitivity were improved in the RU-486 group (<0.05,<0.01), but the intestinal propulsion rate was similar (>0.05). The body mass, visceral sensitivity and intestinal propulsion rate of the heat-sensitive moxibustion group and the non-heat-sensitive moxibustion group were superior to those of the model group (<0.05,<0.01), and the body mass and intestinal propulsion rate of heat-sensitive moxibustion group were superior to those of non-heat-sensitive moxibustion group (both<0.05). (3) After intervention, compared with the blank group, the contents of CRH, ACTH and CORT in the model group were significantly increased (<0.05,<0.01). Compared with the model group, the contents of CRH, ACTH and CORT of the heat-sensitive moxibustion group were statistically reduced (<0.05,<0.01), and the contents of CRH and ACTH in the non-heat-sensitive moxibustion group were statistically reduced (<0.05,<0.01); the content of CRH in the RU-486 group was reduced (<0.05), but the contents of ACTH and CORT were increased (<0.05,<0.01). Compared with the non-heat-sensitive moxibustion group, the heat-sensitive moxibustion group was better in the improvement of CRH (<0.05), but there was no significant difference of ACTH and CORT between the two groups (both>0.05).</p><p><b>CONCLUSION</b>Heat-sensitive moxibustion could reduce the contents of CRH, ACTH and CORT through the HPA axis, and improve the function of gastrointestinal motility to treat IBS.</p>

Early-stage clinical characteristics and HPA axis alterations in first-episode and untreated the major de-pressive disorder patients with suicide / 中国神经精神疾病杂志

Objective To compare early-stage clinical features and hypothalamic-pituitary-adrenal (HPA) axis neuroendocrine function in first-episode and untreated major depressive disorders with suicide and without suicide. Methods Untreated patients who had a diagnosis as major depression according to ICD-10 were allocated to suicide with major depressive disorder group or non-suicide with major depressive disorder group according to whether the pa?tients had suicidal ideation or behaviours. Patients were assessed before treatment using the 17-item Hamilton Depres?sion Scale (HAMD-17), the Hamilton Anxiety Scale (HAMA), the Yale-Brown Obsessive Compulsive Scale (YBOCS) and the suicide assessment scale. The cortisol (CORT) and adrenocorticotropic hormone (ACTH) levels in serum were measured using a chemiluminescence immunoassay. Results There was no significant difference in demographic data be?tween the two groups (P>0.05). In early-stage clinical features, there were significant differences in changes of sexual ac? tivity and feeling of despair (P0.05). There were no significant differences in CORT or ACTH levels between two groups (P>0.05). There were no significant correlation of suicidal scores with early-stage clinical features, symptom scales scores, CORT or ACTH levels (P>0.05). Conclusion De?creased sexual desire and feeling of despair are more severe in depressed patients with suicide than those without. There is no correlation of early-stage clinical features or HPA axis functions with suicide in patients with depression.

Chronic Administration of Monosodium Glutamate under Chronic Variable Stress Impaired Hypothalamic-Pituitary-Adrenal Axis Function in Rats

The hypothalamic-pituitary-adrenal (HPA) axis is the primary endocrine system to respond to stress. The HPA axis may be affected by increased level of corticotrophin-releasing factors under chronic stress and by chronic administration of monosodium glutamate (MSG). The purpose of this study was to investigate whether chronic MSG administration aggravates chronic variable stress (CVS)-induced behavioral and hormonal changes. Twenty-four adult male Sprague-Dawley rats, weighing 200~220 g, were divided into 4 groups as follows: water administration (CON), MSG (3 g/kg) administration (MSG), CVS, and CVS with MSG (3 g/kg) administration (CVS+MSG). In addition, for the purpose of comparing the effect on plasma corticosterone levels between chronic stress and daily care or acute stress, 2 groups were added at the end of the experiment; the 2 new groups were as follows: naive mice (n=7) and mice exposed to restraint stress for 2 h just before decapitation (A-Str, n=7). In an open field test performed after the experiment, the CVS+MSG group significant decrease in activity. The increase in relative adrenal weights in the CVS and CVS+MSG group was significantly greater than those in the CON and/or MSG groups. In spite of the increase in the relative adrenal weight, there was a significant decrease in the plasma corticosterone levels in the CVS+MSG group as compared to all other groups, except the naive group. These results suggest that impaired HPA axis function as well as the decrease in the behavioral activity in adult rats can be induced by chronic MSG administration under CVS rather than CVS alone.