动物造模 z-bio 2022-07-21 325

　　Depression, also known as "emotional cold", is a common affective disorder characterized by persistent low mood. The clinical manifestations are depression, loss of various interests and pleasures, and are often accompanied by physical symptoms such as abnormal sleep, loss of appetite, weight loss, loss of libido, and even extreme behaviors such as suicide. At present, depression is the fourth leading disease in the world, and according to the WHO forecast, depression will become the second leading human disease after heart disease by 2020.

　　The pathogenesis of depression has not been clear so far. The most studied hypotheses of monoamine neurotransmitters and their receptors, the hypothesis of inflammatory response, the hypothesis of hypothalamic cluster adrenal gland (HPA axis) dysfunction, and the hypothesis of neurotrophic factors. Hypothesis and multi-factor comprehensive effect hypothesis, the main drugs for the treatment of depression: tricyclic antidepressants, monoamine oxidase inhibitors and reversible selective monoamine oxidase inhibitors, 5-hydroxytryptamine (SHIT) and norepinephrine (NE) ) reuptake inhibitor, NE and dopamine (DA) reuptake inhibitor, etc. Although these drugs can improve depression to varying degrees, the side effects of these drugs are relatively large, including apathy, fatigue, sleep disturbance, cognitive dysfunction, sexual dysfunction, and stroke. Natural medicines have low toxicity and side effects, and licorice has a long history of use as a traditional Chinese medicine. The "Administrative Measures for New Resource Foods" promulgated by the Ministry of Health of the People's Republic of China stipulates that licorice is both a food and a drug resource. It is listed as a safe and non-toxic substance. Scientific research has proved that licorice extract is an additive with various functions such as antibacterial, anti-inflammatory, detoxification, and deodorization. Symptoms, tuberculosis, dermatitis, bronchial asthma, etc. In recent years, it has been found that licorice has a significant effect on the treatment of depression. Now, the active ingredients in licorice are reviewed for the treatment of depression, in order to provide a theoretical basis for the development of new drugs for the treatment of depression in the future.

　　1 Biochemical properties of licorice

　　Licorice is the dried root and rhizome of the leguminous plant Ural licorice, licorice glabra or licorice. It has the functions of invigorating the spleen and nourishing qi, clearing heat and detoxifying, eliminating phlegm and relieving cough, relieving acute pain, and reconciling various medicines. It is the most widely used traditional Chinese medicine in clinical practice. old country". Modern pharmacological studies have shown that licorice has various activities such as hepatoprotective, anti-inflammatory, antibacterial, antiviral, antitussive, antimalarial, antioxidative, anticancer, immune regulation, hypoglycemic and antiplatelet aggregation.

　　The main components of licorice are three mushrooms and flavonoids, of which licorice is an important monomeric active ingredient in flavonoids, which has a good antidepressant effect.

　　2 The mechanism of action of licorice

　　2.1 To improve the behavioral indicators, the forced swimming test (FST) of rats and mice of Shanghai Xinsoft Information Technology Co., Ltd., the mouse tail suspension test (TST) of Shanghai Xinsoft Information Technology Co., Ltd. and the Shanghai Xinsoft Information Technology Co., Ltd. were used. The open field test (OFT) of rats and mice evaluated the anti-stress and depressive behavioral effects of total flavonoids of licorice root. The results showed that total flavonoids of licorice root at 100, 300 mg/kg could significantly shorten the immobility time of TST and FST in stressed rats, and increase the time in 0 FT. The number of horizontal activities, vertical activities and modification times of stressed rats, and the number of fecal particles decreased.

　　10, 20, and 40 mg/kg licorice in the 3-week treatment of depression model animals significantly increased the consumption of sugar and water, and the 20 and 40 mg/kg groups had returned to normal levels. Licorice can also significantly shorten the immobility time of chronically stressed rats in the forced swimming test, and the 20 mg "kg-' group has the strongest effect[[A]

　　2.2 Improve biochemical indicators

　　2.2.1 Regulation of monoamine components The low level of monoamine transmitters in the synaptic cleft of the brain is one of the main pathogenic mechanisms of depression. It is mainly depleted through four pathways: monoamine oxidase (MAO) degradation, presynaptic receptor reuptake, autoreceptor antagonism, and binding to postsynaptic receptors. The total flavonoid extract (LF) of licorice was given for 7 days, and each dose group had a good improvement effect on reserpine-induced ptosis and akinesia, but had no effect on the symptoms of hypothermia. Therefore, it is speculated that LF may have the enhancement effect of central SHITergic nerve function or dopaminergic nerve function, but has no agonistic effect of central a-adrenoceptor. Compared with the model group, each dose group of licorice can significantly antagonize the hypothermia, akinesia and ptosis caused by reserpine in mice (P<0.05, P<0.01), indicating that licorice has obvious anti-reserpine effect. , its effect may be related to monoamine transmitter antagonism.

　　2.2.2 Regulation of HPA axis Hyperfunction of HPA axis can lead to HPA axis dysregulation, which is also one of the important mechanisms of the pathogenesis of depression. The imbalance of HPA axis is mainly related to hippocampal glutamate and N-methyl-D-aspartate (NMDA) receptors and glucocorticoid receptors. Hyperactivity of HPA, increased secretion of corticotropin-releasing hormone (CRH), and elevated plasma (serum) and urinary free corticosterone concentrations. The hippocampus contains a large number of glucocorticoid receptors, and the increase in corticosterone can selectively damage the hippocampus, causing it to shrink and reduce the number of synapses. Through repeated stress, except the blank group, the rats in the other groups showed obvious symptoms of depression, and the interleukin and cortisol in the serum were significantly increased, and the interleukin was significantly decreased. After 21 days of drug treatment, the positive group and the middle-dose group of licorice (20 mg/kg) could reverse the increase of IL-1p and cortisol (P < 0.05) } IL-6 concentration increased (P < 0.05 ), no obvious effect on IL-2.

　　2.2.3 Anti-free radicals Decreased activity of antioxidant enzymes in vivo and increased lipid peroxide content is also one of the important mechanisms of the pathogenesis of depression. Superoxide dismutase is an important antioxidant enzyme in the body, which can effectively scavenge free radicals in the body. Malondialdehyde is a metabolite of lipid peroxidation. When it accumulates in large amounts in the brain, it can cross-link with proteins through the reaction of primary amino groups of proteins, destroy the lipid bilayer of the cell membrane, lead to changes in cell permeability, and eventually cause Neuronal degeneration and apoptosis. Animal experiments also found that the colonic superoxide dismutase activity decreased and the malondialdehyde content increased in chronic stress and depression model rats. licorice can be significantly

　　It can reverse the damage of chronic stress on rat behavior, and it may achieve antidepressant-like effect by increasing the activity of superoxide dismutase, scavenging free radicals, preventing lipid peroxidation, and reducing the production of malondialdehyde.

　　2.2.4 Protection of neurons The hyperactivity of the HPA axis and the increase of corticosterone levels caused by stress are closely related to the decline of cell regeneration ability including neurons in the hippocampus and the occurrence of depression. It has been confirmed from three aspects: experimental animal models, brain morphological and autopsy changes in patients with depression, and antidepressant drug treatment effects that the number of BrdU-labeled positive cells is restored during the occurrence and prognosis of depression. Hippocampal dentate gyrus granules Restoration of nerve regeneration capacity within the depression (SGZ) is critical [CI3-la7. The total flavonoid extract of licorice has anti-depressive behavioral effects in rats caused by CUS, and the antidepressant effect is related to the reduction of corticosterone levels and the protection of cell regeneration including neurons in the hippocampus. However, it is worth noting that some of the indicators observed in the experiment are effective at high doses, while medium and low doses are ineffective or statistically indistinguishable.

　　2.2.5 Anti-inflammatory effect The body releases inflammatory cytokines, leading to peripheral immune activation, which in turn causes neuroendocrine and immune system dysfunction, which is one of the reasons for depression. The study found that the inflammatory factor IL-6 can enhance the activity of SHIT and DA neurons in the hippocampus and prefrontal lobe of rats. These increased neuronal activity can accelerate the reuptake of central monoamine neurotransmitters and reduce neurotransmitter concentrations in the synaptic cleft. The inflammatory cytokine IL-6 can lead to excessive activation of the HPA axis by regulating the negative feedback inhibition of the HPA axis by peripheral circulating glucocorticoids. Nuclear transcription factor-KB (NF1kB) plays an important role in central nervous system cell survival. Especially in the hippocampus, NF1cB may activate nitric oxide (NO) synthase leading to increased NO synthesis, while excessive NO inhibits hippocampal neurogenesis. At the same time, NF1cB can also lead to increased synthesis of inflammatory cytokines, reactive oxides, and excitotoxins that lead to neurodegeneration, affecting changes in central nervous system processes, which are also thought to be closely related to depression. The total flavonoids of licorice root and licorice flavonoids can inhibit iNOS, cyclooxygenase (COX) gene and protein expression and the gene expression of inflammatory mediator IL-6, and can up-regulate peroxidation. Therefore, isoliquiritigenin may be the anti-inflammatory active component of total flavonoids of licorice [[I9] total saponin of licorice can significantly reduce LPS-induced RAW264.7 Cellular NO } ILK and tumor necrosis factor II (TNF}) release, and by inhibiting phospholipase Az ( PLAz ) enzymatic activity and COX} expression and reduce prostaglandin E2 ( PGEz ) synthesis.

　　3 Research and application of licorice antidepressant

　　Although licorice has a good therapeutic effect on behavioral and biochemical indicators in animal models of depression in experimental research, in clinical practice, licorice is generally not used alone for the treatment of patients with depression, but is mostly administered in combination.

　　3.1 The composition ratio of licorice in the antidepressant traditional Chinese medicine compound By reviewing the research on the treatment of depression with traditional Chinese medicine compound in recent years, the application of traditional Chinese medicine licorice in its prescription compatibility was summarized.

　　The vast majority of Chinese medicine prescriptions for the treatment of depression contain licorice, especially Ganmai Dazao Decoction.

　　3.2 Experimental study Chaihu Shugan Powder (Bupleurum chinensis, dried tangerine peel, Cyperus officinalis, Chuan peony root, white peony root, licorice root) can increase the content of monoamine neurotransmitters 5HT, NE and DA in hippocampus of depressed rats, and high The dose group improved significantly, and its antidepressant effect was similar to that of the western drug fluoxetine. Suanzaoren Decoction (Suanzaoren, Licorice, Anemarrhena, Hu, etc., Chuan Shao) can significantly improve the symptoms of psychomotor depression such as loss of interest and decreased activity in diffusely stressed rats. amine neurotransmitter content. Xiaoyao Powder (Bupleurum, Angelica, Baishao, Atractylodes, Huo, Ginger, Mint, Zhigancao) can increase the levels of neurotransmitters in the hippocampus, cortex and serum of depression model animals; it has positive effects on the expression levels of the hippocampus and cortex of model rats. The increasing trend has a tendency to inhibit the expression level, and the 7.5 g/kg dose of Xiaoyaosan significantly increases the expression level in the cortex.

　　3.3 Clinical application In clinical practice, depression is mainly divided into adolescent depression, postpartum depression, menopausal depression, postoperative depression and geriatric depression. Feng Zhenyu et al. applied Modified Ganmai Dazao Decoction (licorice, wheat, jujube) to treat 43 cases of female menopausal depression, 2 cases were cured, 24 cases were significantly improved, 11 cases were improved, and 6 cases were ineffective, with a marked rate of 88.4%. Xu Lei[25] observed Liujunzi Decoction (ginseng, Baizhu, Huo, etc., licorice, tangerine peel, Pinellia) combined with Banxia Houpu Decoction in the treatment of 29 patients with postoperative depression after gastric cancer, 0 cases were cured, 6 cases were significantly improved, and 15 cases were improved 8 cases of ineffectiveness, and the markedly effective rate was 72.4%. Feng Guangming et al. used Xiaoyao Powder to treat 62 cases of depression patients, and in 58 cases of effective cases, the patients were treated for 8 weeks, and 38 cases were cured, 14 cases were significantly improved, and 14 cases were improved. 4 cases and 2 cases were invalid, and the markedly effective rate was 90%.

　　4 Conclusion

　　The traditional Chinese medicine licorice was first seen in the "Shen Nong's Materia Medica", and it has been in use until now, and its role is still being excavated by people. The active ingredients in licorice include flavonoids, three mushrooms, polysaccharides, etc. The pharmacological research mainly focuses on compounds such as glycyrrhizic acid, glycyrrhetic acid, total flavonoids, single flavonoids and polysaccharides. In the treatment of depression, licorice total flavonoids and licorice are the main active substances. The main antidepressant mechanism of licorice involves the regulation of monoamine transmitters and their receptors; regulation of HPA axis; anti-free radicals; protection of neuronal cells; anti-inflammatory Cytokines and other effects, see Figure 1. In addition to the antidepressant effect, licorice also has the functions of protecting liver, anti-inflammatory, antibacterial, antiviral, antitussive, antimalarial, antioxidant, anticancer, immune regulation, hypoglycemic and antiplatelet aggregation. Liver, antibacterial and antiviral, anti-inflammatory and anti-allergic, treatment of cardiovascular and nephropathy, etc. Although the traditional Chinese medicine licorice is in the position of adjuvant and the dosage is small in the vast majority of traditional Chinese medicine compounds for the treatment of depression, it does not mean that the traditional Chinese medicine licorice is dispensable for the treatment of depression. Ganmai Dazao Decoction is a very Good evidence.