Full
Outline
To study the neurotoxicity of DH-004, a derivative of harmine (HM).
IL-1β, TNF-α, IL-12 and IL-6 in the brain of mice were determined by enzyme-linked immunosorbent assay (ELISA). Morphological changes of neurons in cerebral cortex of mice were detected by Nissl staining. Real-time fluorescence quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect ionized calcium binding adaptor molecule-1 (Iba-1) mRNA expression in brain tissue. Iba-1 protein expression in brain tissue was detected by Western-Blot.
ELISA results showed that except for the insignificant changes of IL-6 in each dose group, the expression levels of the other three inflammatory factors with HM-treated mice in the brain tissues were the highest. After the same dose of DH-004 was given, the expression levels of inflammatory factors in the cerebellum tissues were significantly decreased compared with HM-treated mice (P<0.01). The results of Nisier staining, qRT-PCR and Western-Blot showed that compared with the blank control group, HM group had serious and dose-dependent damage to the cortical nerve cells of mice. The expression levels of Iba-1 mRNA and Iba-1 protein in HM group were up-regulated compared with the corresponding blank control group (P<0.01), after the same dose of DH-004 was given, the expression levels of Iba-1 mRNA and Iba-1 protein in cerebellum tissues were significantly down-regulated compared with HM group (P<0.01).
HM can induce the activation of microglia cells in mice, then the activated microglia cells promote the release of inflammatory factors, leading to nerve tissue damage. While DH-004 can inhibit the activation of microglia cells, thus reducing the release of inflammatory factors and reducing neurotoxicity.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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