Investigation Of The Biological Effects And Mechanisms Of Dendrobium Officinale Based On Multi-Omics

Dendrobium officinale,known as Tiepi Shihu,is enriched with various bioactive compounds,including flavonoids,bibenzyls,polysaccharides,and alkaloids.These compounds exhibit a spectrum of pharmacological activities,such as antioxidative,anti-inflammatory,and anticancer effects.The precise biological impacts and underlying mechanisms of Dendrobium officinale,however,remain a topic of debate and are not completely elucidated.Consequently,investigating its biological effects through multi-omics studies to clarify these mechanisms holds scientific value.In this study,a naturally aging C57BL/6J mouse model was selected and segregated into a control group and a Dendrobium officinale treatment group.Utilizing a multi-omics approach,including DNA methylation techniques,16SrDNA gut microbiota profiling,and transcriptomics,the study investigates the influence of Dendrobium officinale on DNA methylation age,gut microbiome composition,and gene expression in mice.Moreover,UPLC-TOF-MS technology combined with network pharmacological analysis was employed to identify the bioactive components and their molecular targets in Dendrobium officinale.At the cellular level,the study employs techniques such as RT-qPCR,Western Blot,flow cytometry,and electron microscopy to examine the modulatory effects of quercetin—a principal component in Dendrobium officinale—on PTGS2,and to explore its potential mechanisms in antioxidation and the suppression of cellular inflammation.The principal findings include:（1）DNA methylation techniques revealed that the DNA methylation age,calculated based on Prima1,Hsf4,and Kcns1 blood DNA methylation levels in mice,reduced by3.49 weeks,1.99 weeks,and 2.72 weeks,respectively,at 22,33,and 48 weeks in the Dendrobium officinale-treated group.An optimized age prediction formula further reduced these values to 2.49 weeks,1.26 weeks,and 2.03 weeks,indicating that Dendrobium officinale can delay aging.（2）Using 16SrDNA sequencing,it was revealed that Dendrobium officinale significantly influenced the β-diversity of gut microbiota in mice and adjusted their microbial community structure.Compared with the control group,in the mice treated with Dendrobium officinale,the abundance of strains such as g＿norank＿f＿Lachnospiraceae,g＿Lachnospiraceae＿UCG-001,g＿Lachnospiraceae＿UCG-010,g＿Odoribacter,and g＿Blautia notably decreased.On the contrary,strains like g＿Eubacterium＿coprostanoligenes＿group,g＿Ruminococcus＿1,g＿Paraprevotella,g＿Faecalibaculum,o＿Enterobacteriales,and g＿Ruminococcaceae＿UCG-013 experienced a significant increase in abundance.Furthermore,Dendrobium officinale reduced the correlations between microbial strains in the mouse gut.（3）Transcriptomics revealed 522 differentially expressed genes in the mouse brain post-treatment,with 176 genes upregulated and 346 downregulated.PTGS2 was identified as a pivotal gene integrating gut microbiota and transcriptomic analysis.（4）Using the UPLC-TOF-MS technique,468 compounds from Dendrobium officinale were detected in the positive ion mode and 245 in the negative ion mode.These compounds mainly consisted of polysaccharides,terpenoids,flavonoids,and alkaloids.Ultimately,379 compounds with potential activity were selected for subsequent target analysis.（5）Utilizing network pharmacology methods,511 targets associated with the components of Dendrobium officinale were identified.The core active ingredients were determined to be Quercetin,3,5-Dimethoxy-4-hydroxybenzaldehyde,Vanillic acid,Apigenin,Icaritin,Iristectorigenin B,4-Methylcatechol,Quinic acid and Capsaicin;The primary target proteins were SRC,AKT1,PIK3R1,GSK3β,PTGS2,HSP90AA1,GRB2,SLC18A3,EGFR,and EP300.Molecular docking results revealed a stable conformational binding between Quercetin and PTGS2.（6）Quercetin has been shown to effectively diminish the levels of Reactive Oxygen Species（ROS）in cells,augment the Mitochondrial Membrane Potential（MMP）,and sustain the equilibrium of intracellular Ca²⁺.Western Blot analyses reveal that Lipopolysaccharides（LPS）significantly elevate the expression of PTGS2,NLRP3,and associated inflammatory factors in BV-2 cells.Conversely,quercetin markedly reduces the expression of PTGS2,NLRP3,and related inflammatory factors.These results underscore quercetin’s role in modulating the PTGS2/NLRP3 pathway,which contributes to the attenuation of inflammation and cellular damage in BV-2 cells.In conclusion,this research comprehensively investigates the biological impacts of Dendrobium officinale on naturally aging mice.Utilizing multi-omics approaches,it was discovered that Dendrobium officinale could decrease the DNA methylation age in mice,thereby slowing down the aging process.It also modulates the composition of the gut microbiome and alters gene expression patterns in the brain.PTGS2 has been pinpointed as a pivotal target,with quercetin identified as the primary active ingredient in Dendrobium officinale.Studies at the cellular level indicate that quercetin can efficaciously mitigate cell inflammation and damage by regulating oxidative stress and the PTGS2/NLRP3 signaling pathway.These insights provide critical scientific evidence to clarify the biological effects and action mechanisms of Dendrobium officinale and its active components.