Polygonati Rhizoma: A review on the extraction, purification, structural characterization, biosynthesis of the main secondary metabolites and anti-aging effects.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizome (PR) is a plant that is extensively widespread in the temperate zones of the Northern Hemisphere. It is a member of the Polygonatum family of Asparagaceae. PR exhibits diverse pharmacological effects and finds applications in ethnopharmacology, serving as a potent tonic for more than two millennia. PR's compounds endow it with various pharmacological properties, including anti-aging, antioxidant, anti-fatigue, anti-inflammatory, and sleep-enhancing effects, as well as therapeutic potential for osteoporosis and age-related diseases. AIM OF THE STUDY: This review seeks to offer a thorough overview of the processing, purification, extraction, structural characterization, and biosynthesis pathways of PR. Furthermore, it delves into the anti-aging mechanism of PR, using organ protection as an entry point. MATERIALS AND METHODS: Information on PR was obtained from scientific databases (Google Scholar, Web of Science, ScienceDirect, SciFinder, PubMed, CNKI) and books, doctoral theses, and master's dissertations. RESULTS: In this investigation, 49 polysaccharides were extracted from PR, and the impact of various processing, extraction, and purification techniques on the structure and activity of these polysaccharides was evaluated. Additionally, 163 saponins and 46 flavonoids were identified, and three key biosynthesis pathways of secondary metabolites were outlined. Notably, PR and Polygonat Rhizomai polysaccharides (PRP) exhibit remarkable protective effects against age-induced injuries to the brain, liver, kidney, intestine, heart, and vessels, thereby promoting longevity and ameliorating the aging process. CONCLUSIONS: PR, a culinary and therapeutic herb, is rich in active components and pharmacological activities. Based on this review, PR plays a meaningful role in lifespan extension and anti-aging, which can be attributed to PRP. Future research should delve deeper into the structural aspects of PRP that underlie its anti-aging effects and explore potential synergistic interactions with other compounds. Moreover, exploring the potential applications of PR in functional foods and pharmaceutical formulations is recommended to advance the development of industries and resources focused on healthy aging.

Mechanisms of Cynarine for treatment of non-alcoholic fatty liver disease based on the integration of network pharmacology, molecular docking and cell experiment.

BACKGROUND: Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic Liver Disease prevalent all over the world. It has become more and more common in Japan, China and most western developed countries. The global prevalence rate is 25.24%, and the trend is increasing year by year. Related studies have shown that Cynarine has certain liver protection, lipid lowering and immune intervention effects. So, this study to systematically predict and analyze the mechanism of Cynarine in the treatment of non-alcoholic fatty liver disease (NAFLD) based on the integration of network pharmacology, molecular docking, and cell experiment. METHODS: We performed Heatmap and Venn diagram analyses to identify genes and targets in Cynarine treat NAFLD. The network of Cynarine-therapeutic targets and the protein-protein interaction network (PPI) was constructed. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. The Sybyl tool was used to dock the Cynarine with key therapeutic targets molecularly. Finally, cell experiments were applied to validate the role of Cynarine in the treatment of NAFLD. RESULTS: The Cynarine could act on 48 targets of NAFLD, and the role of CASP3, TP53, MMP9, ELANE, NOTCH1 were more important. The PPI network showed that immune and inflammation-related targets played a pivotal role. The KEGG analysis found that the PI3K-Akt signaling pathway, cell cycle and MAPK signaling pathway may be the main pathways for Cynarine to prevent and treat NAFLD. Molecular docking studies confirmed that Cynarine has good binding activity with therapeutic targets. Cynarine reduced the fat deposition ability of NAFLD model cells, and effectively reduced the levels of ALT and AST released by liver cells due to excessive lipid accumulation. We also found that Cynarine inhibited the expression of AKT1 and MAPK1. CONCLUSIONS: This study revealed that Cynarine could significantly reduce the fat deposition ability of NAFLD model cells, which may be closely related to the effective regulation of AKT1 and MAPK1 expression by Cynarine.

Investigation of Lonicera japonica Flos against Nonalcoholic Fatty Liver Disease Using Network Integration and Experimental Validation.

Background and objective: Lonicera japonica Flos (LJF) is a well-known traditional herbal medicine that has been used as an anti-inflammatory, antibacterial, antiviral, and antipyretic agent. The potent anti-inflammatory and other ethnopharmacological uses of LJF make it a potential medicine for the treatment of nonalcoholic fatty liver disease (NAFLD). This research is to explore the mechanisms involved in the activity of LJF against NAFLD using network integration and experimental pharmacology. Materials and methods: The possible targets of LJF involved in its activity against NAFLD were predicted by matching the targets of the active components in LJF with those targets involved in NAFLD. The analysis of the enrichment of GO functional annotations and KEGG pathways using Metascape, followed by constructing the network of active components-targets-pathways using Cytoscape, were carried out to predict the targets. Molecular docking studies were performed to further support the involvement of these targets in the activity of LJF against NAFLD. The shortlisted targets were confirmed via in vitro studies in an NAFLD cell model. Results: A total of 17 active components in LJF and 29 targets related to NAFLD were predicted by network pharmacology. Molecular docking studies of the main components and the key targets showed that isochlorogenic acid B can stably bind to TNF-α and CASP3. In vitro studies have shown that LJF down-regulated the TNF-α and CASP3 expression in an NAFLD cell model. Conclusions: These results provide scientific evidence for further investigations into the role of LJF in the treatment of NAFLD.

Genome-wide identification, molecular characterization, and gene expression analyses of honeysuckle NHX antiporters suggest their involvement in salt stress adaptation.

Background: Ion homeostasis is an essential process for the survival of plants under salt stress. Na+/H+ antiporters (NHXs) are secondary ion transporters that regulate Na+ compartmentalization or efflux reduce Na+ toxicity and play a critical role during plant development and stress responses. Methods and Results: To gain insight into the functional divergence of NHX genes in honeysuckle, a total of seven LjNHX genes were identified on the whole genome level and were renamed according to their chromosomal positions. All LjNHXs possessed the Na+/H+ exchanger domain and the amiloride-binding site was presented in all NHX proteins except LjNHX4. The phylogenetic analysis divided the seven NHX genes into Vac-clade (LjNHX1/2/3/4/5/7) and PM-clade (LjNHX6) based on their subcellular localization and validated by the distribution of conserved protein motifs and exon/intron organization analysis. The protein-protein interaction network showed that LjNHX4/5/6/7 shared the same putatively interactive proteins, including SOS2, SOS3, HKT1, and AVP1. Cis-acting elements and gene ontology (GO) analysis suggested that most LjNHXs involve in the response to salt stress through ion transmembrane transport. The expression profile analysis revealed that the expression levels of LjNHX3/7 were remarkably affected by salinity. These results suggested that LjNHXs play significant roles in honeysuckle development and response to salt stresses. Conclusions: The theoretical foundation was established in the present study for the further functional characterization of the NHX gene family in honeysuckle.

Interaction mechanism of flavonoids on bovine serum albumin: Insights from molecular property-binding affinity relationship.

The molecular structure properties-binding affinity relationship of a series of flavonoids and bovine serum albumin (BSA) was investigated in vitro from comparing the binding constants determined through the fluorescence method. As a result, the binding process was greatly influenced by different structural elements or substituents of flavonoids under analysis. The hydroxylation at the positions C3, C6, C4', C5' (for type I) and C5, C3' (for type II) were in favor of forming hydrogen bonds with the amino acids of BSA, which was of great importance in the binding and interaction between flavonoids and the protein. The decreased affinity could be realized by the methoxylation (C8, C3' and C4') and glycosylation (C3 and C7) of flavonoid type I. However, the adverse trend on binding affinity was observed when the methoxylation and glycosylation appeared at the sites C4' and C7, C4' of structure type II, respectively. Meanwhile, glycosylation at C7 mainly induced the decline in the affinity of flavonoids (type III), and the hydrogenation of the C2C3 double bond for type I was beneficial to increase the affinity on BSA. Moreover, part of flavonoids could mediate the conformational alteration of secondary structures of the protein during the interaction process, which was inferred by means of the synchronous fluorescence spectra. The determinations of ANS fluorescence probe suggested that hydrophobic interaction played an important role in the binding of a majority of flavonoids to BSA. Further evidences from the site-specific experiments revealed that the location of flavonoids 19, 29 and 34 binding on BSA mainly belonged to site I, while compound 3 bound to both sites I and II. Additionally, molecular modelling studies further confirmed the indispensable character of hydrophobic interaction and hydrogen bonds, and illustrated the preferred complex binding behaviors.

Studies on the structure-activity relationship and interaction mechanism of flavonoids and xanthine oxidase through enzyme kinetics, spectroscopy methods and molecular simulations.

In this study, some flavonoids were screened as potent xanthine oxidase (XO) inhibitors in vitro. Flavonoid 9 was demonstrated to exhibit the inhibitory activity through a ping-pong mechanism. Further structure-activity relationship revealed that different structural elements had greatly influenced the inhibition effect on XO and underlined the requirement of hydroxyl groups at C5 and C4' of flavonoid type I. Moreover, some bioactive flavonoids could efficiently quench the intrinsic fluorescence of XO by either static or static-dynamic mixed mechanism. The synchronous fluorescence, ANS-binding fluorescence, Fourier transform infrared spectra and circular dichroism suggested that active flavonoids could bind to the active center of XO, prevent the entrance of substrate, and induce the rearrangement and conformation change of its secondary structures, ultimately resulting in the significant inhibition effect. Additionally, molecular docking further confirmed these conclusions and highlighted the great importance of hydrophobic interactions and hydrogen bonds for the formation of stable complex conformation.

Exploring the structure-activity relationship and interaction mechanism of flavonoids and α-glucosidase based on experimental analysis and molecular docking studies.

α-Glucosidase (AG) has always been an indispensable drug target for the treatment of type 2 diabetes. Herein, an integrated method consisting of enzyme kinetics, multi-spectroscopy assay and molecular simulations was used to investigate the structure-activity relationship and interaction mechanism of flavonoids and AG. As a result, a small amount of flavonoids was found to present excellent inhibitory activity on AG, such as 3, 5, 6, 8, 10, 17, 19, 21, 22 and 34. Further analysis of the structure-activity relationship illustrated that hydroxylation at the positions C3, C6, C3' and C4' of flavonoids caused an increase in the inhibitory activity of AG, whereas the methoxylation at the corresponding positions would decrease the activity. Also, it was found that the glycosylation and hydrogenation of the C2[double bond, length as m-dash]C3 double bond would distinctly reduce the inhibition potency. Therefore, various groups at different positions of flavonoids exhibited an upward and downward tendency in the activity. According to the fluorescence quenching assay, all of the test flavonoids could effectively quench the intrinsic fluorescence of AG based on either the static or mixed static-dynamic mechanism. Besides, the thermodynamic parameters of the representative flavonoid 19 revealed the spontaneous characteristic of the binding process with AG, and highlighted the critical role of the hydrophobic interaction and hydrogen bonds. Moreover, the results obtained from the synchronous fluorescence, ANS-binding fluorescence, Fourier transform infrared and circular dichroism spectra illustrated that these active flavonoids could bind to the active site of AG and induce the rearrangement and conformation change of its secondary structures, which resulted in a significant inhibitory activity. Additionally, molecular modelling visualized the preferred binding conformation of flavonoids on AG, and further confirmed the great importance of the hydrophobic interaction and hydrogen bonds in the interaction. Such findings provided new insights for understanding the proposed interaction behavior between flavonoids and AG, and were helpful to develop novel AG inhibitors relying on the flavonoid scaffold for the treatment of type 2 diabetes.