The by-product of deer skin, which has mostly been used as a decorative material, is rich in collagen and amino acids that could bind to Ca²⁺. Therefore, the preparation process, stability, antioxidant activity and calcium transport capacity of deer skin collagen peptide calcium chelate (Ca-DSCP) were investigated. In addition, the structure of the new chelate was characterized. The preparation process of Ca-DSCP was optimized using one-way experiments and response surface methodology. The ideal conditions were pH 9, 48 °C, and a peptide-to-calcium mass ratio of 5:1. The chelation rate was (60.73 ± 1.54)%. Zeta potential, XRD, UV–vis and FTIR analyses yielded that deer skin collagen peptides (DSCP) underwent a chelating reaction with calcium ions to form new structures. The stability of Ca-DSCP and the fraction of bioavailability of calcium ions were determined using in vitro gastrointestinal digestion and a Caco-2 cell monolayer model. The results showed that fraction of bioavailability and stability of DSCP were improved by influencing the structural characterization. The antioxidant activities of DSCP and Ca-DSCP were evaluated by measuring relevant oxidative stress indicators, DPPH radical scavenging capacity and hydroxyl radical scavenging capacity. Finally, bioinformatics and molecular docking techniques were utilized to screen and study the antioxidant mechanism of DSCP.

Depression is a complex and common mental illness affecting physical and psychological health. Panax ginseng C. A. Mey is a traditional Chinese medicine with abundant pharmacological activity and applications in regulating mood disorders. 20 (S)-Protopanaxadiol is the major intestinal metabolite of ginsenoside and one of the active components in ginseng. In this study, we aimed to investigate the therapeutic effects of 20 (S)-Protopanaxadiol on neuronal damage and depression, which may involve mitochondrial dynamics. However, the mechanism underlying the antidepressant effects of 20 (S)-Protopanaxadiol is unelucidated. In the present study, we investigated the potential mechanisms underlying the antidepressant activity of 20 (S)-Protopanaxadiol by employing a corticosterone-induced HT22 cellular model and a chronic unpredicted mild stress (CUMS)-induced animal model in combination with a network pharmacology approach. In vitro, the results showed that 20 (S)-Protopanaxadiol ameliorated the corticosterone (CORT)-induced decrease in HT22 cell viability, decrease in 5-hydroxytryptamine (5-HT) levels, and increase in nitric oxide (NO) and malondialdehyde (MDA) levels. Furthermore, 20 (S)-Protopanaxadiol exerted improvement effects on the CORT-induced increase in HT22 cell mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and apoptosis. In vivo, the results showed that 20 (S)-Protopanaxadiol ameliorated depressive symptoms and hippocampal neuronal damage in CUMS mice, and sirtuin1 (SIRT1) and peroxisome proliferator-activated receptor-1-Alpha (PGC-1α) activity were activated in the hippocampus of mice, thereby alleviating mitochondrial dysfunction and promoting the clearance of damaged mitochondria. In both in vivo and in vitro models, after inhibiting SIRT1 expression, the protective effect of 20 (S)-Protopanaxadiol on mitochondria was significantly weakened, and dynamin-related protein 1 (DRP1)-mediated mitochondrial division was significantly reduced. These findings suggest that 20 (S)-Protopanaxadiol may exert neuroprotective and antidepressant effects by attenuating DRP1-mediated mitochondrial dysfunction and apoptosis by modulating the SIRT1/PGC-1α signaling pathway.

Depression is one of the most common neurological diseases, which imposes a substantial social and economic burden on modern society. The purpose of this study was to explore the mechanism of total ginsenoside ginseng root (TGGR) in the treatment of depression through a comprehensive strategy combining network pharmacology, transcriptomics, and in vivo experimental validation. The Traditional Chinese Medicine Systematic Pharmacology (TCMSP) database and literature were used to collect the main components and targets of TGGR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were applied to explore the underlying mechanisms. In addition, the chronic unpredictable mild stress (CUMS)-induced C57BL/6 mouse model was used to evaluate the antidepressant activity of TGGR. The results showed that TGGR improved depression-like behavior in mice and increased the decrease in serum 5-hydroxytryptamine (5-HT) and brain-derived neurotrophic factor (BDNF) levels caused by CUMS. Combined network pharmacology and transcriptomic analysis showed that the AMP-activated kinase (AMPK) signaling pathway mainly enriched the core target. Immunohistochemistry, Western blotting, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were used to confirm whether TGGR exerts antidepressant effects by regulating this pathway. The results showed that TGGR has a regulatory impact on related proteins in the AMPK pathway, and the regulatory effect of TGGR on proteins was inhibited after the administration of related pathway inhibitors. In summary, total ginsenosides may regulate the AMPK signaling pathway and activate the sirtuin 1 (SIRT1) peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1α) pathway to have therapeutic effects on depression.