An Integrative Pharmacology-Based Pattern to Uncover the Pharmacological Mechanism of Ginsenoside H Dripping Pills in the Treatment of Depression

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.

Ginsenosides in central nervous system diseases: Pharmacological actions, mechanisms, and therapeutics

“…mediating the potential improvements of ginsenoside Rg1 in this CUMS-induced depression model Zhao et al (Zhao et al, 2020). adopted pharmacodynamics-network pharmacology mechanism verification found that ginsenoside H dripping pills significantly upregulated PKA activity and cAMP content in the hippocampus of CUMS model rats.…”

“…Thus, it appears that the ERK‐CREB‐BDNF signaling pathway within the PFC may be critically involved in mediating the potential improvements of ginsenoside Rg1 in this CUMS‐induced depression model. Zhao et al (Zhao et al, 2020) adopted pharmacodynamics‐network pharmacology mechanism verification found that ginsenoside H dripping pills significantly upregulated PKA activity and cAMP content in the hippocampus of CUMS model rats. Therefore, ginsenoside H dripping pills may exert anti‐depressant effects by regulating cAMP‐PKA‐CREB‐BDNF signaling transduction.…”

Methodology of network pharmacology for research on Chinese herbal medicine against COVID-19: A review

“…For instance, ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used for the chemical profiling of Isatis indigotica roots and leaves, and the active constituents present in I. indigotica were then screened using the prediction of gastrointestinal absorption and drug-likeness (DL) analysis in SwissADME (http://www.swissadme.ch) [9] . The active components in ginsenoside H dripping pills were identified by UPLC-Q-TOF-MS and then filtered based on oral bioavailability (OB) and DL [10] . To detect the volatile compounds from Scutellaria baicalensis , gas chromatography-MS (GC-MS) was performed.…”

Antidepressant Active Ingredients From Chinese Traditional Herb Panax Notoginseng: A Pharmacological Mechanism Review

“…The chief target proteins cAMP, PKA, CREB, p-CREB, and BDNF were verified in CUMS model rats in cAMP signaling pathway. It was found that GH can activate cAMP-PKA-CREB-BDNF signaling pathway ( Zhao et al, 2020 ).…”