Integrated network pharmacology analysis and experimental validation to investigate the mechanism of Flavan-3-ols and aromatic resins in depression.

The present investigation delved into the pharmacological mechanisms underlying the management of depression through Flavan-3-ols and Aromatic Resins, employing in silico and in vivo methodologies. Network pharmacology was utilized to identify targets associated with the antidepressant activity of Flavan-3-ols and Aromatic Resins. Protein-protein interaction and KEGG analyses were conducted to enrich and explore key pathways. Molecular docking and simulation studies were executed to assess the targets. The antidepressant effects were studied using the Forced Swim Test and Tail Suspension Test on both unstressed mice and those subjected to the chronic unpredictable mild stress (CUMS) paradigm. The Compound-Target network analysis revealed a substantial impact of the components on numerous targets, with 332 nodes and 491 edges. Protein-protein interaction analysis indicated significant interactions with targets implicated in depression. KEGG analysis highlighted major pathways, including neuroactive ligand-receptor interaction, dopaminergic synapse, and long-term depression. Docking studies on EGCG demonstrated binding energies of -7.2 kcal/mol for serotonin 1 A (5-HT1A), -7.9 kcal/mol for D2, and - 9.6 kcal/mol for MOA-A. Molecular dynamics simulation indicated minute fluctuation, hence suggesting stable complexes formed between small molecules and proteins. The combination of Flavan-3-ols and Aromatic Resins significantly increased mobility time (p < 0.05) in the Forced Swim Test and Tail Suspension Test, while significantly decreasing immobility time and time freezing (p < 0.05) in both unstressed and CUMS mice. This study demonstrated the antidepressant characteristics of Flavan-3-ols and Aromatic Resins, underscoring the need for further research to develop a novel antidepressant medication.

Network pharmacology combined with molecular docking and experimental verification to elucidate the effect of flavan-3-ols and aromatic resin on anxiety.

This study investigated the potential anxiolytic properties of flavan-3-ols and aromatic resins through a combined computational and experimental approach. Network pharmacology techniques were utilized to identify potential anxiolytic targets and compounds by analyzing protein-protein interactions and KEGG pathway data. Molecular docking and simulation studies were conducted to evaluate the binding interactions and stability of the identified targets. Behavioral tests, including the elevated plus maze test, open field test, light-dark test, actophotometer, and holeboard test, were used to assess anxiolytic activity. The compound-target network analysis revealed complex interactions involving 306 nodes and 526 edges, with significant interactions observed and an average node degree of 1.94. KEGG pathway analysis highlighted pathways such as neuroactive ligand-receptor interactions, dopaminergic synapses, and serotonergic synapses as being involved in anxiety modulation. Docking studies on EGCG (Epigallocatechin gallate) showed binding energies of -9.5 kcal/mol for MAOA, -9.2 kcal/mol for SLC6A4, and -7.4 kcal/mol for COMT. Molecular dynamic simulations indicated minimal fluctuations, suggesting the formation of stable complexes between small molecules and proteins. Behavioral tests demonstrated a significant reduction in anxiety-like behavior, as evidenced by an increased number of entries into and time spent in the open arm of the elevated plus maze test, light-dark test, open field center activity, hole board head dips, and actophotometer beam interruptions (p < 0.05 or p < 0.01). This research provides a comprehensive understanding of the multi-component, multi-target, and multi-pathway intervention mechanisms of flavan-3-ols and aromatic resins in anxiety treatment. Integrated network and behavioral analyses collectively support the anxiolytic potential of these compounds and offer valuable insights for future research in this area.

Anti-inflammatory effects of Chrozophora plicata uncovered using network pharmacology and in-vivo carrageenan paw edema model.

Chrozophora plicata has been extensively utilized in India for the management of numerous disorders. The effective Phytoconstituents derived from the Ethyl Acetate Fraction of Chrozophora plicata [EAFCP] have been identified as Camptothecin Agathisflavone, Rutin, Procynidine B, and Apigenin. These Phytoconstituents have been detected in the EAFCP through qualitative analysis using LC-Q-TOF-MS/MS. The anti-inflammatory properties of Chrozophora plicata are yet to be determined. Therefore, the aim of this study was to utilize a network pharmacology-based methodology to predict potential therapeutic targets of EAFCP in the setting of inflammation. The identification of inflammation targets was followed by the acquisition of verified targets of EAFCP. The key therapeutic targets of EAFCP against inflammation were found by creating a target-functional PPI network, GO studies were conducted on the core therapeutic targets in order to assess the essential signalling pathways involved in the anti-inflammatory effects of EAFCP. A total of 38 significant hub targets associated with EAFCP's anti-inflammatory effects were identified. The key proteins were retrieved for the docking investigation based on the findings, which aided in anticipating the potential interaction between components and targets. The in vivo study revealed that EAFCP had a notable efficiency in decreasing paw edema induced by carrageenan in rats. The evidence we have gathered collectively offers clarification about the anti-inflammatory activity of EAFCP, which is predominantly linked to the suppression of the Cox 1, 2 pathway. The aforementioned findings highlight potential therapeutic targets that could be utilized for the anti-inflammatory activity of EAFCP.

Neuroprotective effect of Feronia limonia on ischemia reperfusion induced brain injury in rats.

OBJECTIVES: Brain stroke is a leading cause of death without effective treatment. Feronia limonia have potent antioxidant activity and can be proved as neuroprotective against ischemia-reperfusion induced brain injury. MATERIALS AND METHODS: We studied the effect of methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) and Vitamin E as reference standard drug on 30 min induced ischemia, followed by reperfusion by testing the neurobehavioral tests such as neurodeficit score, rota rod test, hanging wire test, beam walk test and elevated plus maze. The biochemical parameters, which were measured in animals brain were catalase, superoxide dismutase (SOD), malondialdehyde and nitric oxide in control and treated rats. RESULTS: The methanolic extract of F. limonia fruit (250 mg/kg, 500 mg/kg body weight, p.o.) treated groups showed a statistically significant improvement in the neurobehavioral parameters such as motor performance (neurological status, significant increase in grasping ability, forelimb strength improvement in balance and co-ordination). The biochemical parameters in the brains of rats showed a significant reduction in the total nitrite (P < 0.01) and lipid peroxidation (P < 0.01), also a significant enhanced activity of enzymatic antioxidants such as catalase (P < 0.01) and SOD (P < 0.05). CONCLUSION: These observations suggest the neuroprotective and antioxidant activity of F. limonia and Vitamin E on ischemia reperfusion induced brain injury and may require further evaluation.