20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.

Platycodin D stimulates AMPK activity to inhibit the neurodegeneration caused by reactive oxygen species-induced inflammation and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) was considered to be a neurodegenerative disease that caused cognitive impairment. Reactive Oxidative stress (ROS) was considered to be one of a major cause of the onset and progression of AD. Platycodin D (PD), a representative saponin from Platycodon grandiflorum, has conspicuous antioxidant activity. However, whether PD could protect nerve cell against oxidative injury remains unknown. AIM OF STUDY: This study investigated the regulatory effects of PD on neurodegeneration caused by ROS. To determine whether PD could play its own antioxidant role in neuronal protection. MATERIALS AND METHODS: First, PD(2.5, 5 mg/kg) ameliorated the memory impairment induced by AlCl3 (100 mg/kg) combined with D-galactose (D-Gal) (200 mg/kg) in mice, using the radial arm maze (RAM) test, and neuronal apoptosis in the hippocampus was evaluated by hematoxylin and eosin staining (HE). Next, the effects of PD (0.5, 1, and 2 µM) on okadaic-acid (OA) (40 nM) -induced apoptosis and inflammation of HT22 cells were investigated. Mitochondrial ROS production was measured by fluorescence staining. The potential signaling pathways were identified through Gene Ontology enrichment analysis. The role of PD in regulating AMP-activated protein kinase (AMPK) was assessed using siRNA silencing of genes and an ROS inhibitor. RESULTS: In vivo, PD improved memory in mice, and recovered the morphological changes of brain tissue and nissl bodies. In vitro experiment, PD increased cell viability (p < 0.01; p < 0.05;p < 0.001), decreased apoptosis (p < 0.01), reduced excessive ROS and MDA, rised SOD and CAT content(p < 0.01; p < 0.05). Morover, it can block the inflammatory response caused by ROS. Be important, PD strengthen antioxidant ability by elevating AMPK activation both in vivo and in vitro. Furthermore, molecular docking suggested a good likelihood of PD-AMPK binding. CONCLUSION: AMPK activity is vital for the neuroprotective effect of PD, suggesting that PD may be a potential pharmaceutical agent to treat ROS-induced neurodegeneration.

Exploring the mechanism of active components from ginseng to manage diabetes mellitus based on network pharmacology and molecular docking.

A large body of literature has shown that ginseng had a role in diabetes mellitus management. Ginsenosides are the main active components of ginseng. But what ginsenosides can manage in diabetic are not systematic. The targets of these ginsenosides are still incomplete. Our aim was to identify which ginsenosides can manage diabetes mellitus through network pharmacology and molecular docking. To identify the targets of these ginsenosides. In this work, we retrieved and screened ginsenosides and corresponding diabetes mellitus targets across multiple databases. PPI networks of the genes were constructed using STRING, and the core targets were screened out through topological analysis. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed by using the R language. Finally, molecular docking was performed after bioinformatics analysis for verification. Our research results showed that 28 ginsenosides in ginseng might be against diabetes mellitus by modulating related proteins such as VEGFA, Caspase 3, and TNF-α. Among the 28 ginsenosides, 20(R)-Protopanaxatriol, 20(R)-Protopanaxadiol, and Ginsenoside Rg1 might play a significant role. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis showed that the management of diabetes mellitus by ginsenosides may be related to the positive regulation of reactive oxygen metabolic processes, associated with the insulin signaling pathway, TNF signaling pathway, and AMPK signaling pathway. Molecular docking results and molecular dynamics simulation showed that most ginsenosides could stably bind to the core target, mainly hydrogen bonding and hydrophobic bond. This study suggests the management of ginseng on diabetes mellitus. We believe that our results can contribute to the systematic study of the mechanism of ginsenosides for the management of diabetes mellitus. At the same time, it can provide a theoretical basis for subsequent studies on the management of ginsenosides in diabetes mellitus.

Arginyl-fructosyl-glucose, a major Maillard reaction product of red ginseng mitigates cisplatin-evoked intestinal toxicity in vivo and in vitro.

Cisplatin-evoked profound gastrointestinal symptomatology is one of the most common side effects of chemotherapy drugs, further causing gastrointestinal cell damage, diarrhea and vomiting. Panax ginseng C. A. Meyer, a widely used medicinal and edible plant in China, shows many pharmacological activities. Nevertheless, the role of non-saponin is less known and has great potential in the treatment of severe toxic side effects related to the cisplatin treatment. The present work evaluates the efficiency of a major Maillard reaction product (MRP) of red ginseng, arginyl-fructosyl-glucose (AFG), against cisplatin-evoked intestinal toxicity in vivo and vitro, and the underlying possible mechanisms are also explored. The cisplatin-treated mice (a dose of 20 mg kg-1 for one time) showed serious intestinal mucosa damage accompanied by increased indicators of diamine oxidase (DAO) and decreased expression of tight junction proteins zonula occludens-1 (ZO-1) and occludin. Moreover, cisplatin exposure increased intestinal cell apoptosis with decreased expression of Bcl-2 and increased expression of Bax and cleaved-caspase 3/9 as well as NF-κB related proteins. Interestingly, the supplements of AFG at doses of 40 and 80 mg kg-1 day-1 for 10 days significantly ameliorated these changes. It was also demonstrated in cultured IEC-6 cells that AFG enhanced the expression levels of apoptotic proteins during cisplatin exposure and reduced the sensitivity of IEC-6 cells to cisplatin by inhibiting the activation of GSK3ß and up-regulating the protein expression of ß-catenin. In conclusion, AFG exerted protective effects against cisplatin-induced intestinal toxicity, at least partially by the inhibition of NF-κB-mediated apoptosis, via regulating Wnt/ß-catenin signaling pathway.