Effect of electroacupuncture on behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome. / ç”µé’ˆå¯¹æ ¢æ€§ç–²åŠ³ç»¼åˆå¾å¤§é¼ è¡Œä¸ºå­¦åŠæµ·é©¬ç‚Žæ€§å› å­çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.

Research progress on central mechanism of acupuncture treatment for chronic fatigue syndrome.

Chronic fatigue syndrome is a neurological disorder characterized by extreme fatigue that lasts for a long time and doesn't alleviate with rest. The number of the cases has been increasing during the era of COVID-19 pandemic. Acupuncture may have some effect on chronic fatigue syndrome, but its mechanism remains unclear. This article was to summarize the specific manifestations of abnormal central mechanism in patients with chronic fatigue syndrome through laboratory tests and neuroimaging. It was found from the laboratory evaluation that there were changes in the structure of the frontal cortex, thalamus and other brain tissues; factors, including IFN-α and IL-10 in cerebrospinal fluid were found abnormal; results of oxidative and nitrosative stress and changes in neurobiochemical substances, e.g. hypothalamus hormone levels and neurotransmitter concentrations, were observed. With magnetic resonance imaging and positron emission tomography, it was shown that the partial brain of persons with chronic fatigue syndrome had morphological changes with diminished grey matter and white; changes in cerebral blood flow velocity caused by decreased perfusion and functional activity with abnormal connectivity in brain were detected. In addition, there was significant decrease in glucose metabolism accompanied with neuroinflammatory response; metabolic disorders of serotonergic, cholinergic, glutamatergic and γ-aminobutyric acid energy neurotransmitters were also discovered. The regulatory effect of acupuncture on the above central neurological abnormalities in chronic fatigue syndrome model animals was elaborated, and the direction for further research was analyzed in order to provide ideas for further research on the central mechanism of acupuncture treatment for chronic fatigue syndrome.

Inflachromene attenuates seizure severity in mouse epilepsy models via inhibiting HMGB1 translocation.

Epilepsy is not well controlled by current anti-seizure drugs (ASDs). High mobility group box 1 (HMGB1) is a DNA-binding protein in the nucleus regulating transcriptional activity and maintaining chromatin structure and DNA repair. In epileptic brains, HMGB1 is released by activated glia and neurons, interacting with various receptors like Toll-like receptor 4 (TLR4) and downstream glutamatergic NMDA receptor, thus enhancing neural excitability. But there is a lack of small-molecule drugs targeting the HMGB1-related pathways. In this study we evaluated the therapeutic potential of inflachromene (ICM), an HMGB-targeting small-molecule inhibitor, in mouse epilepsy models. Pentylenetetrazol-, kainic acid- and kindling-induced epilepsy models were established in mice. The mice were pre-treated with ICM (3, 10 mg/kg, i.p.). We showed that ICM pretreatment significantly reduced the severity of epileptic seizures in all the three epilepsy models. ICM (10 mg/kg) exerted the most apparent anti-seizure effect in kainic acid-induced epileptic status (SE) model. By immunohistochemical analysis of brain sections from kainic acid-induced SE mice, we found that kainic acid greatly enhanced HMGB1 translocation in the hippocampus, which was attenuated by ICM pretreatment in subregion- and cell type-dependent manners. Notably, in CA1 region, the seizure focus, ICM pretreatment mainly inhibited HMGB1 translocation in microglia. Furthermore, the anti-seizure effect of ICM was related to HMGB1 targeting, as pre-injection of anti-HMGB1 monoclonal antibody (5 mg/kg, i.p.) blocked the seizure-suppressing effect of ICM in kainic acid-induced SE model. In addition, ICM pretreatment significantly alleviated pyramidal neuronal loss and granule cell dispersion in kainic acid-induced SE model. These results demonstrate that ICM is an HMGB-targeting small molecule with anti-seizure potential, which may help develop a potential drug for treating epilepsy.

Synthesis and biological evaluation of novel shikonin-benzo[b]furan derivatives as tubulin polymerization inhibitors targeting the colchicine binding site.

A novel series of shikonin-benzo[b]furan derivatives were designed and synthesized as tubulin polymerization inhibitors, and their biological activities were evaluated. Most compounds revealed the comparable anti-proliferation activities against the cancer cell lines to that of shikonin and simultaneously low cytotoxicity to non-cancer cells. Among them, compound 6c displayed powerful anti-cancer activity with the IC50 value of 0.18 µM against HT29 cells, which was significantly better than that of the reference drugs shikonin and CA-4. What's more, 6c could inhibit tubulin polymerization and compete with [3H] colchicine in binding to tubulin. Further biological studies depicted that 6c can induce cell apoptosis and cell mitochondria depolarize, regulate the expression of apoptosis related proteins in HT29 cells. Besides, 6c actuated the HT29 cell cycle arrest at G2/M phase, and influenced the expression of the cell-cycle related protein. Moreover, 6c displayed potent inhibition on cell migration and tube formation that contributes to the antiangiogenesis. These results prompt us to consider 6c as a potential tubulin polymerization inhibitor and is worthy for further study.

Design, synthesis and biological evaluation of resveratrol-cinnamoyl derivates as tubulin polymerization inhibitors targeting the colchicine binding site.

A novel series of resveratrol-cinnamoyl hybrids as tubulin polymerization inhibitors were designed and synthesized, and evaluated for their anti-proliferative activities against A549, MCF-7, HepG2, HeLa and MDA-MB-231 five cancer cell lines. Most designed compounds showed better anti-proliferative activities. Particularly, compound 6h exhibited the potent anti-proliferative activities with the IC50 value of 0.12, 0.016, 0.44, 0.37 and 0.78 µΜ against A549, MCF-7, HepG2, HeLa and MDA-231, respectively, which was superior to that of reference drug colchicine. Besides, compound 6h displayed a remarkable inhibition of tubulin polymerization and a great potency to compete with [3H] colchicine in binding to tubulin. Further studies indicated that compound 6h could induce the MCF-7 cells arrest in the G2/M phase. What' more, compound 6h induced cell apoptosis in a dose-dependent manner, and regulated the expression level of apoptosis-related proteins. These results revealed that compound 6h is a promising tubulin polymerization inhibitor for treatment of cancer and it is worthy of further exploitation.