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Background: Diabetic nephropathy (DN) is one of the most common and serious chronic complications in the clinic. Cornus officinalis has the effects of replenishing qi and nourishing yin , tonifying liver and kidney, and it is one of the main traditional Chinese medicines used clinically to treat diabetes and its complications. However, the effect and mechanism of Cornus officinalis before and after processing on intestinal flora of diabetic nephropathy need to be further elucidated. Methods: SD rats were randomly divided into a blank group (10 rats) and DN groups (70 rats). After 4 weeks of high-sugar and high-fat diet, the DN rat model was established by intraperitoneal injection of streptozotocin. After successful modeling, the rats were randomly divided into DN model group, irbesartan group (1.35 mg·kg −1 ), Cornus officinalis group (281.25 mg·kg −1 ), wine Cornus officinalis group (281.25 mg·kg −1 ), wine honey Cornus officinalis group (281.25 mg·kg −1 ), auxiliary wine group (10 ml·kg −1 ), auxiliary wine honey group (10 ml·kg −1 ). During the observation of the rats’ general state, after 6 weeks of continuous administration, the fasting blood glucose of rats in each group was detected, and the kidney index was calculated. The serum creatinine levels, urea nitrogen and 24 h urinary microalbumin were detected by enzyme-linked immunosorbent assay. The expression levels of YKL-40, Wnt4, β -catenin and TGF- β 1 mRNA in renal tissue were detected by fluorescence quantitative PCR. Hematoxylin-eosin staining was used to observe the changes in renal pathological injury in each group; GC-MS detected the changes of short chain fatty acid content. Feces were collected for 16 s high-throughput sequencing to analyze the effects of Cornus officinalis on the diversity of intestinal flora in DN before and after processing. Results: Compared with the blank group, the serum creatinine, urea nitrogen, 24 h urinary microalbumin, kidney index and fasting blood glucose in the DN model group were significantly increased ( p < 0.05). The renal tissue morphology was disordered and a large number of inflammatory cells were infiltrated. The expression of YKL-40, Wnt4, β -catenin and TGF- β 1 mRNA was significantly increased ( p < 0.05). Compared with the DN model group, the serum creatinine, urea. Nitrogen, 24 h urine microalbumin, kidney index and fasting blood glucose of rats in each administration group were significantly decreased ( p < 0.05), and the general condition and pathological renal damage of DN rats were improved. The effect of wine honey Cornus officinalis was the best, and the expression of YKL-40, Wnt4, β -catenin and TGF- β 1 mRNA was significantly decreased ( p < 0.05). In each administration group, the improvement of the above indicators in the wine honey Cornus officinalis group was significantly better than that in the raw Cornus officinalis group and wine Cornus officinalis group ( p < 0.05), There was no significant difference compared with the irbesartan group ( p > 0.05). Each administration group had a significant callback effect on the content of short-chain fatty acids in rat feces, with increased intestinal beneficial bacteria and decreased pathogenic bacteria. Compared with the blank group, the abundance of Firmicutes in the DN model group increased, the abundance of Bacteroidetes decreased, and the ratio showed an upward trend in the DN model group decreased. Each administration group could improve the relative abundance of the above intestinal flora in the model group to varying degrees. Conclusion: The processing of Cornus officinalis may improve the renal injury of DN rats by blocking the activation of Wnt/β-catenin signaling pathway, regulating the structural composition of intestinal microorganisms, and ultimately playing a role in renal protection.

Cornus officinalis (CO) is a traditional herbal medicine renowned in Traditional Chinese Medicine (TCM) for its properties of tonifying the liver and kidney and replenishing vital essence. Meanwhile, wine‐processed CO (pCO) exhibits superior pharmacological effects, including anti‐inflammatory, antioxidant and anti‐fibrotic activities. However, the immunomodulatory mechanism of pCO in osteoarthritis (OA) remains unclear. OA models were established in Sprague–Dawley rats via anterior cruciate ligament transection (ACLT). Network pharmacology and molecular docking were used to predict potential targets of pCO against OA, which were validated through behavioural tests, histomorphological staining and immunohistochemistry. HPLC‐Q‐Orbitrap‐MS analysis identified key differential compounds between raw and wine‐processed CO. The immunomodulatory effects of pCO were further confirmed by ELISA, immunofluorescence staining and RT‐qPCR. pCO ameliorated joint pain and cartilage damage in OA rats by reducing pro‐inflammatory factors (IL‐1β, COX‐2, IL‐12) and promoting anti‐inflammatory factors (IL‐10, TGF‐β1) in serum and synovial fluid. Network pharmacology combined with in vivo experiments revealed that pCO attenuated chondrocyte degeneration and apoptosis. Mechanistically, pCO modulated macrophage polarization by suppressing the M1 phenotype (CD86, iNOS) while promoting the M2 phenotype (CD206, TGF‐β1, Arg‐1), which revealed the key mechanism underlying its therapeutic effects against OA. pCO improved joint function and attenuated cartilage degeneration and synovial lesions, which were associated with the promotion of articular cartilage protection via the modulation of M1/M2 macrophage polarization.

Cornus officinalis Sieb. et Zucc. is part of the genus Cornus of the family Cornaceae . Ripening and dry fruits ( Corni Fructus ) are recognized as an essential herb medicine in the traditional Chinese medicine (TCM) and have been widely used for over 2000 years. This review provides a comprehensive summary of Corni Fructus (CF), including the botany, phytochemistry, traditional use, and current pharmacological activities. According to the basic theory of TCM, CF usually participates in various Chinese medicinal formulae to exert the essential roles in replenishing liver and kidney, arresting seminal emission and sweat. Based on modern pharmacological studies, about 90 compounds have been isolated and identified from CF. In vivo and in vitro experimental studies indicate that CF exhibits extensive pharmacological activities including hypoglycemic, antioxidant, anti-inflammatory, anticancer, neuroprotective, hepatoprotective, and nephroprotective activities. However, only about 18% of chemical constituents in CF were tested. It means the potential pharmacological activities and clinical values of CF need to be further investigated.

Autophagy plays an increasingly significant role in diabetic nephropathy (DN), but the mechanism by which autophagy participates in DN injury is not well understood. Our previous studies have shown that (AM-CO) improves DN lipid metabolism disorders, however, the exact mechanism of which is also not well defined. The aim of this study was to investigate the therapeutic effects of AM-CO officinalis on DN and the mechanism of action on DN using lipidomic techniques and network pharmacological approaches. The experiments were carried out using the KKAy mice model with the intervention of AM-CO. Analysis of kidney and serum samples from KKAy mice treated with AM-CO using lipidomic technology to obtain biomarkers for the treatment of DN and to identify the main targets associated with DN; Analyse potential signalling pathways for the treatment of DN using network pharmacology methods. experiments were performed with PA-induced HK-2 cells and results verified by protein blotting and immunofluorescence. Lipidomic analysis revealed 363 differential metabolites in serum and 195 differential metabolites in kidney tissue, which were compared and analysed to find their common differential metabolites belonging to the phosphatidylethanolamine (PE) classes, respectively. In addition, PE plays a vital functiona in the process of autophagy. And the network analysis results speculated that Calycosin (Cal), a major component of AM-CO, could ameliorate DN injury by regulating autophagy through modulating the PI3K-AKT signaling pathway. experiments showed that AM-CO could induce autophagy, an increase in LC3II expression and a decrease in P62 expression. Meanwhile, experiments showed that Cal could also increase the expression of LC3II and inhibit the protein expression levels of p62, PI3K, P-AKT and AKT. The addition of a PI3K activator resulted in a reversal of protein expression. In conclusion, Cal can ameliorate the injury in DN by regulating autophagy, and PI3K-AKT is the main pathway for its regulation of autophagy and a key pathway for the action of AM-CO.

This study investigates the degradation characteristics, pathways, and mechanisms of ochratoxin A (OTA) by CGMCC 9951 ( CGMCC 9951), as well as its detoxification effect on pulp through fermentation. The strain efficiently degraded 300 ng/mL of OTA within 72 h (98% degradation) under optimal conditions of 37 °C, pH 5.0, and 180 rpm. Active degradation substances were primarily localized in the cell-free supernatant (CF). The degradation activity was significantly inhibited by heat treatment, proteinase K, EDTA, Cu , and organic reagents, suggesting an enzymatic mechanism. UHPLC-MS and MS/MS analysis indicated that OTA appears to be degraded to a product consistent with ochratoxin α (OTα). Based on homology to known OTA-degrading carboxypeptidases, the gene encoding WGU28473.1 was selected, expressed in , and confirmed to possess OTA-degrading activity. Molecular docking suggested potential interactions between the enzyme and OTA. Under optimal conditions, co-fermentation with pulp contaminated with 300 ng/mL OTA for 96 h resulted in a 74% degradation of OTA. The fermentation process increased the pulp's sugar content and ABTS free radical scavenging capacity, reduced acidity, and improved the safety of the pulp. These findings demonstrate that CGMCC 9951 efficiently degrades OTA and improves pulp quality, highlighting its potential as a starter culture for detoxifying OTA-contaminated food.

Cornus officinalis fruits have long been used to treat many ailments such as kidney dysfunction, pain, and diabetes in Asia; however, the seeds of Cornus officinalis are discarded. In this study, activity-guided isolation of Cornus officinalis seeds led to the isolation and characterization of five compounds: betulinic acid ( 1 ), ursolic acid ( 2 ), gallic acid ( 3 ), 1,2,3,6-tetra- O -galloyl-β-D-glucose ( 4 ), and 1,2,6-tri- O -galloyl-β-D-glucose (5). The DPPH radical-scavenging, tyrosinase-inhibiting, and elastase-inhibiting activities of these five compounds, in addition to their effects on the proliferation of human dermal fibroblasts were assessed. Compounds 3 , 4 , and 5 showed the most potent anti-oxidative activities. Gallotannins (compounds 4 and 5 ) had relatively potent whitening activity. Compounds 1 and 2 showed the most potent elastase inhibition. This is the first known study to demonstrate the cosmetic effects of compounds isolated from Cornus officinalis seeds.

As a traditional nourishing Chinese herbal medicine, Cornus officinalis Sieb. et Zucc. has a long history of application. At present, only the flesh of the fruit of Cornus officinalis is used as a medicine, which wastes a large quantity of ingredients in the nutlet. To improve the comprehensive utilization efficiency of the fruit’s nutlet, which could be used when there is a shortage of the plant’s fruit in the market, this study used Fourier transform-infrared spectroscopy (FT-IR), gas chromatography-mass spectrometry (GC-MS), thermogravimetric (TG) analysis, pyrolysis-gas chromatography-mass spectrometry (PY-GC-MS), and nuclear magnetic resonance (NMR) techniques to analyze the Cornus officinalis nutlet. The results showed that the active ingredients of Cornus officinalis nutlet have great medicinal value and could become a substitute for the fruit. After extracting the active ingredients, the residue can be used as a good biomass liquid fuel, providing reference for the future to replace fossil fuels. This study provides the scientific basis for the comprehensive utilization of high-quality resources for Cornus officinalis.

Background Shanzhuyu (the dried mature sarcocarp of Cornus officinalis Sieb. et Zucc., DMSCO) is a Chinese herb that can be used for the treatment of Alzheimer’s disease (AD), but its mechanism remains unknown. The present study aimed to investigate the active ingredients and effective mechanisms of DMSCO for the treatment of AD based on a network pharmacology approach. Methods The active components of DMSCO were collected from the TCMSP and ETCM databases and the target proteins of these compounds were predicted using TCMSP, SwissTargetPrediction and the STITCH database. The AD-related target proteins were identified from the OMIM, DisGeNet, GEO and GeneCards databases. The network interaction model of the compound-target-disease was established and was used to obtain the key targets of DMSCO on AD through network topology analysis. Subsequently, gene enrichment in Gene Ontology (GO) and KEGG pathways were conducted using the David 6.8 online tool. Results A total of 30 DMSCO effective compounds and 209 effective drug targets were obtained. A total of 172 AD-related genes and 37 shared targets of DMSCO and AD were identified. A total of 43 key targets for the treatment of AD were obtained from the topological analysis of the DMSCO-AD target network. These key targets were involved in a variety of biological processes, including amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress and pathways, such as the PI3K-AKT, MAPK and TNF pathways. Three key compounds, namely ursolic acid, anethole and β-sitosterol were obtained from the analysis of the key targets. Conclusions Ursolic acid, anethole and β-sitosterol may be the main active components of DMSCO in the treatment of AD. DMSCO can treat AD by regulating amyloid deposition, apoptosis, autophagy, inflammatory response and oxidative stress via the PI3K-AKT, MAPK and other signaling pathways.

This study evaluated the effects of Cornus officinalis extract (1.5% DM) on growth performance, blood serum biochemical parameters, rumen fermentation and microbial composition in Hu lambs fed diets with different concentrate:forage ratio. Thirty-two lambs were assigned to a 2 × 2 factorial design receiving either a common basal diet or a high-concentrate diet with (CPC, HPC groups) or without (CBD, HCD groups) Cornus officinalis extract supplementation respectively. The results showed that lambs in CPC group had shown enhanced average daily gain and feed efficiency ( P  < 0.05). Blood serum biological parameters remained similar across all the treatments ( P  > 0.05), except for blood urea nitrogen (BUN) showing significant group differences ( P  < 0.05). Concentrations of tumor necrosis factor-alpha (TNF-α), lipopolysaccharide-binding protein (LBP), lipopolysaccharide (LPS), serum amyloid A (SAA), and Toll-like receptor 4 (TLR4) ( P  < 0.10) were significantly reduced in HPC, while TLR4 was notably decreased in CBD group ( P  < 0.05). Cornus officinalis extract significantly increased (P < 0.05) pH, total volatile fatty acids (TVFAs) and lactic acid levels under high concentrate diet. Furthermore, high-concentrate diets decreased the relative abundance of Bacteroidota and increased those of Firmicutes compared with the basal diet. While, HPC diet slightly decreased Firmicutes abundance and reduced α-diversity indices ( P  < 0.10). Correlation analysis between genus-level biomarkers and PICRUSt2-predicted enzymes revealed that enzymes related to lactate synthesis and the Embden-Meyerhof-Parnas (EMP) pathway were slightly increased in HPC group while antioxidation-related enzymes were more enriched in CPC group. Enzymes associated with volatile fatty acid synthesis were higher in HCD while carbohydrate hydrolysis–related enzymes were relatively higher in CBD group. Key genera, including Succinivibrio and Prevotella , remained stable across all treatments, whereas the abundance of Rikenellaceae_RC9_gut_group decreased under high-concentrate diet but was not affected by Cornus officinalis extract supplementation. Overall, supplementation with 1.5% Cornus officinalis extract promoted growth performance and positively altered composition and functional potential of ruminal microbiota ultimately contributing to improved metabolic balance in Hu lambs.

Alcoholic liver injury (ALI) is a major global public health issue, with oxidative stress imbalance as its core pathological mechanism. The Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–heme oxygenase-1/glutathione peroxidase 4 signaling pathway (Keap1–Nrf2–HO-1/GPX4) signaling pathway is a key target for regulating hepatic antioxidant defense. This study integrated Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS), Global Natural Products Social Molecular Networking (GNPS) molecular networking, network pharmacology, and animal experiments to systematically explore the hepatoprotective effect and mechanism of Cornus officinalis yeast-fermentation (COF). Component characterization identified 25 bioactive components, including flavonoids, triterpenic acids, and other fermentation-derived metabolites. Network pharmacology identified 441 common targets and 36 core targets of COF and ALI, which were enriched in oxidative stress regulation, inflammatory response, and the Keap1–Nrf2 pathway via Gene Ontology (GO)/Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Molecular docking showed that icariin and other components had stable interactions with Keap1 and Nrf2 (binding energy < −5 kcal/mol). Animal experiments confirmed that COF reduced the liver index of ALI mice, downregulated serum Alanine Aminotransferase (ALT)/Aspartate Aminotransferase (AST) activities, and ameliorated liver pathological damage. Western blot verified that COF inhibited Keap1 expression, promoted Nrf2 nuclear translocation, and upregulated HO-1/GPX4 expression. In conclusion, COF alleviates hepatic oxidative stress by regulating the Keap1–Nrf2–HO-1/GPX4 pathway, providing a scientific basis for its development as a functional food or candidate drug against ALI and a technical paradigm for fermentation-enhanced medicinal plant research.