Abstract
Objectives: To evaluate the pharmacodynamical effects and pharmacological mechanism of Ginsenoside H dripping pills (GH) in chronic unpredictable mild stress (CUMS) model rats. Methods: First, the CUMS-induced rat model was established to assess the anti-depressant effects of GH (28, 56, and 112 mg/kg) by the changes of the behavioral indexes (sucrose preference, crossing score, rearing score) and biochemical indexes (serotonin, dopamine, norepinephrine) in Hippocampus. Then, the components of GH were identified by ultra-performance liquid chromatography-iron trap-time of flight-mass spectrometry (UPLC/IT-TOF MS). After network pharmacology analysis, the active ingredients of GH were further screened out based on OB and DL, and the PPI network of putative targets of active ingredients of GH and depression candidate targets was established based on STRING database. The PPI network was analyzed topologically to obtain key targets, so as to predict the potential pharmacological mechanism of GH acting on depression. Finally, some major target proteins involved in the predictive signaling pathway were validated experimentally. Results: The establishment of CUMS depression model was successful and GH has antidepressant effects, and the middle dose of GH (56 mg/kg) showed the best inhibitory effects on rats with depressant-like behavior induced by CUMS. Twenty-eight chemical components of GH were identified by UPLC/IT-TOF MS. Subsequently, 20(S)-ginsenoside Rh2 was selected as active ingredient and the PPI network of the 43 putative targets of 20(S)-ginsenoside Rh2 containing in GH and the 230 depression candidate targets, was established based on STRING database, and 47 major targets were extracted. Further network pharmacological analysis indicated that the cAMP signaling pathway may be potential pharmacological mechanism regulated by GH acting on depression. Among the cAMP signaling pathway, the major target proteins, namely, cAMP, PKA, CREB, p-CREB, BDNF, were used to verify in the CUMS model rats. The results showed that GH could activate the cAMP-PKA-CREB-BDNF signaling pathway to exert antidepressant effects. Conclusions: An integrative pharmacology-based pattern was used to uncover that GH could increase the contents of DA, NE and 5-HT, activate cAMP-PKA-CREB-BDNF signaling pathway exert antidepressant effects.
Highlights
Depression is a mental disorder illness with a high disability, morbidity and recurrence rate (Chen et al, 2008)
The sucrose preference of rats in low dose group of Ginsenoside H dripping pills (GH), middle dose group of GH, high dose group of GH, and Fluoxetine hydrochloride (Flu) group were obviously higher than the Chronic unpredictable mild stress (CUMS) group (p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively), showing the significant remission of depression symptoms
In the open field test, the crossing score and the rearing score of CUMS rat treated with middle dose of GH, high dose of GH, and Flu were markedly increased compared with the CUMS group (p < 0.01, p < 0.05, p < 0.01, respectively)
Summary
Depression is a mental disorder illness with a high disability, morbidity and recurrence rate (Chen et al, 2008). The main clinical features are decreased food-intake, low mood, anhedonia, activity decrease, irritability and other symptoms (Yang et al, 2018). In severe cases, they may have suicidal tendency (Zhu et al, 2020). There is no specific drug for the treatment of depression in cancer patients, and antidepressants are generally used. There are several Chinese herbal formulae for the treatment of depression including Chaihu Shugan powder, Xiaoyao Pill and Shugan Jieyu capsule (Du et al, 2014; Fu et al, 2014; Wang et al, 2014). The research on the treatment of depression with TCM has certain clinical value
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