Renal fibrosis progression is closely associated with aging, which ultimately leads to renal dysfunction. Salidroside (SAL) is considered to have broad anti-aging effects. However, the roles and mechanisms of SAL in aging-related renal fibrosis remain unclear. The study aimed to evaluate the protective effects and mechanisms of SAL in SAMP8 mice. SAMP8 mice were administered with SAL and Ferrostatin-1 (Fer-1) for 12 weeks. Renal function, renal fibrosis, and ferroptosis in renal tissue were detected. The results showed that elevated blood urea nitrogen (BUN) and serum creatinine (SCr) levels significantly decreased, serum albumin (ALB) levels increased, and mesangial hyperplasia significantly reduced in the SAL group. SAL significantly reduced transforming growth factor-β (TGF-β) and α-smooth muscle actin (α-sma) levels in SAMP8 mice. SAL treatment significantly decreased lipid peroxidation in the kidneys, and regulated iron transport-related proteins and ferroptosis-related proteins. These results suggested that SAL delays renal aging and inhibits aging-related glomerular fibrosis by inhibiting ferroptosis in SAMP8 mice.

Background. Beta-amyloid (Aβ) peptide is a widely recognized pathological marker of Alzheimers disease (AD). Salidroside and Hedysari Radix polysaccharide (HRP) were extracted from Chinese herb medicine Rhodiola rosea L and Hedysarum polybotrys Hand-Mazz, respectively. The neuroprotective effects and mechanisms of the combination of salidroside and Hedysari Radix polysaccharide (CSH) against Aβ_25–35 induced neurotoxicity remain unclear. Objective. This study aims to investigate the neuroprotective effects and pharmacological mechanisms of CSH on Aβ_25–35-induced HT22 cells. Materials and Methods. HT22 cells were pretreated with various concentrations of salidroside or HRP for 24h, followed by exposed to 20μm Aβ_25–35 in the presence of salidroside or RHP for another 24h. In a CSH protective assay, HT22 cells were pretreated with 40μm salidroside and 20μg/mL HRP for 24h. The cell viability assay, cell morphology observation, determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and cell apoptosis rate were performed. The mRNA expression of protein kinase C-beta (PKCβ), Bax, and Bcl-2 were measured by qRT-PCR. The protein expression levels of cleaved caspase-3, Cyt-C, PKCβ, phospho-ERK1/2, Bax, and Bcl-2 were measured by Western blot. Results. CSH treatment increased cell viability, MMP, and decreased ROS generation in Aβ_25–35-induced HT22 cells. PKCβ and Bcl-2 mRNA expression were elevated by CSH while Bax was decreased. CSH increased the protein expression levels of PKCβ, Bcl-2, and phospho-ERK1/2, and decreased those of Bax, Cyt-C, and cleaved caspase-3. Conclusions. CSH treatment have protective effects against Aβ_25–35-induced cytotoxicity through decreasing ROS levels, increasing MMP, inhibiting early apoptosis, and regulating PKC/ERK pathway in HT22 cells. CSH may be a potential therapeutic agent for treating or preventing neurodegenerative diseases.

Background. Traditional Chinese herbal medicine draws more attention to explore an effective therapeutic strategy for Alzheimers disease (AD). Shenqi Yizhi granule (SQYG), a Chinese herbal recipe, has been applied to ameliorate cognitive impairment in mild-to-moderate AD patients. However, the overall molecular mechanism of SQYG in treating AD has not been clarified. Objective. This study aimed to investigate the molecular mechanism of SQYG on AD using an integration strategy of network pharmacology and molecular docking. Methods. The active compounds of SQYG and common targets between SQYG and AD were screened from databases. The herb-compound network, compound-target network, and protein-protein interaction network were constructed. The enrichment analysis of common targets and molecular docking were performed. Results. 816 compounds and 307 common targets between SQYG and AD were screened. KEGG analysis revealed that common targets were mainly enriched in lipid metabolism, metal ion metabolism, IL-17 signaling pathway, GABA receptor signaling, and neuroactive ligand-receptor interaction. Molecular docking analysis showed high binding affinity between ginsenoside Rg1 and Aβ_1–42, tanshinone IIA and BACE1, baicalin, and AchE. Conclusions. The therapeutic mechanisms of SQYG on AD were associated with regulating lipid metabolism, metal ion metabolism, IL-17 signaling pathway, and GABA receptor signaling. Ginsenoside Rg1, tanshinone IIA, baicalin, astragaloside IV, and folic acid may play an important role in AD treatment.

Background. Sjögrens syndrome (SS) is a chronic autoimmune disease characterized by progressive oral and ocular dryness that correlates poorly with autoimmune damage to the glands. CheReCunJin (CRCJ) formula is a prescription formulated according to the Chinese medicine theory for SS treatment. Objective. This study aimed to explore the underlying mechanisms of CRCJ against SS. Methods. The databases, including Traditional Chinese Medicine System Pharmacology, Encyclopedia of Traditional Chinese Medicine, Bioinformatics Analysis Tool for the molecular mechanism of Traditional Chinese Medicine, and Traditional Chinese Medicine Integrated Databases, obtained the active ingredients and predicted targets of CRCJ. Then, DrugBank, Therapeutic Target Database, Genecards, Comparative Toxicogenomics Database, and DisGeNET disease databases were used to screen the predicted targets of SS. Intersected targets of CRCJ and SS were visualized by using Venn diagrams. The overlapping targets were uploaded to the proteinprotein interaction network analysis search tool. Cytoscape 3.8.2 software constructed a compound-targets-disease network. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes analyses characterized potential targets biological functions and pathways. AutoDock Vina 1.1.2 software was used to research and verify chemical effective drug components and critical targets. Results. From the database, we identified 878 active components and 2578 targets of CRCJ, and 827 SS-related targets. 246 SS-related genes in CRCJ were identified by intersection analysis, and then ten hub genes were identified as crucial potential targets from PPI, including ALB, IL-6, TNF, INS, AKT1, IL1B, VEGFA, TP53, JUN, and TLR4. The process of CRCJ action against SS was mainly involved in human cytomegalovirus infection and Th17 cell differentiation, as well as the toll-like receptor signaling and p53 signaling pathways. Molecular docking showed that the bioactive compounds of CRCJ had a good binding affinity with hub targets. Conclusions. The results showed that CRCJ could activate multiple pathways and treat SS through multiple compounds and targets. This study lays a foundation for better elucidation of the molecular mechanism of CRCJ in the treatment of SS, and also provides basic guidance for future research on Chinese herbal compounds.

Background/Objectives: Alzheimer’s disease (AD) involves amyloid and tau pathology with neuroimmune dysregulation, and Yixin Yangshen Granules (YXYS) shows neuroprotective promise, though mechanisms remain unclear. This study aimed to elucidate the multi-target mechanisms of YXYS in AD. Methods: The study began by analyzing a public human AD hippocampal snRNA-seq dataset to identify cell-type-specific pathological pathways and profiled YXYS constituents by UPLC-QTOF-MS. In vitro, YXYS cytoprotection against mitochondrial dysfunction and oxidative stress was tested in Aβ_25–35-challenged HT22 cells; in vivo efficacy was assessed in Aβ_1–42-induced mice via behavioral and histopathological analyses. Integrated transcriptomic and proteomic profiling of brain tissue, with ELISA, qRT-PCR, and Western blot validation, confirmed pathway targets. Using the intersection of transcriptomic and proteomic targets as biological input, the DTIAM deep learning framework was employed to prioritize active YXYS constituents. Finally, molecular docking and 100-ns dynamics simulations demonstrated direct binding of Ganosporelactone A to HIF−1α. Results: AD snRNA-seq analysis highlighted HIF−1 and AGE-RAGE signaling as prominent pathways in the AD hippocampus, particularly enriched in brain microvascular endothelial cells, implicating neurovascular hypoxic and inflammatory stress. In Aβ-induced mice, YXYS improved cognition, reduced Aβ pathology, suppressed neuroinflammation, and promoted neuronal survival, consistent with in vitro evidence of restored mitochondrial function. Multi-omics confirmed convergence on HIF−1 and AGE-RAGE pathways, with YXYS rebalancing the neuroimmune microenvironment by reducing pro-inflammatory M0 macrophages. Screening against these consensus signaling hubs, deep learning analysis prioritized Ganosporelactone A as the top-ranked modulator, and molecular further demonstrated the stable binding of Ganosporelactone A to HIF−1α, linking YXYS to mitigation of hypoxic stress. Conclusions: Guided by multi-omics and deep learning, our findings suggest that YXYS may alleviate AD-related phenotypes through multi-target modulation of the HIF−1 and AGE-RAGE pathways, with associated improvements in neuro-immune homeostasis and reductions in oxidative stress, neuroinflammation, and hypoxia.