산수유

BACKGROUND: Recurrent pneumonia in the elderly can repeatedly damage lung function and reduce quality of life, posing certain challenges to clinical treatment. OBJECTIVE: To analyze the synergistic immune regulatory effects of Cistanche deserticola, Schisandra chinensis and Cornus officinalis on elderly patients with recurrent pneumonia. METHODS: A total of 165 patients with recurrent pneumonia from Chengde Medical University from January 2024 to January 2025 were recruited, 158 were enrolled after exclusions, 8 lost to follow-up, and 150 finally analyzed. The 150 patients were divided into MC group (n=75) and MA group (n=75). Both groups were treated with Ma Xing Shi Gan Tang and Azithromycin, while the MC group was additionally treated with Cistanche deserticola, Schisandra chinensis and Cornus officinalis. The main evaluation includes the Traditional Chinese Medicine Syndrome Score (TCMSS), lung function indicators, inflammation indicators, immune indicator levels and clinical efficacy of two groups. Secondary outcomes include quality of life scores, incidence of complications and adverse reactions. RESULTS: After treatment, the lung function indicators, immune indicators and clinical efficacy in MC group were higher than in the CC group; the TCMSS and inflammatory indicators were lower in the CC group (P>0.05). No significant difference in quality of life score, incidence of complications and adverse reactions between the two groups (P<0.05). CONCLUSION: This method has a good immunomodulatory effect on elderly patients with recurrent pneumonia and is worthy of further promotion and application.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix (RR) and Cornus officinalis (CO) are two traditional Chinese medicines widely used in China for treating diabetes mellitus and its complications, such as diabetic nephropathy. Iridoid glycoside of Cornus officinalis (IGCO), triterpenoid acid of Cornus officinalis (TACO) and iridoid glycoside of Rehmanniae Radix (IGRR) formed an innovative formula named combinatorial bioactive parts (CBP). The aims of the present study were to investigate the renoprotective effects of CBP on DN through the inhibition of AGEs/RAGE/SphK1 signaling pathway activation, and identify the advantage of CBP compared with IGCO, TACO, IGRR. MATERIALS AND METHODS: The db/db diabetic renal injury model was used to examine the renoprotective effects of CBP, IGCO, TACO and IGRR. For mechanistic studies, diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGEs/RAGE/SphK1 pathway were determined. RESULTS: CBP, IGCO, TACO and IGRR inhibited the decrease in serum insulin levels and the increases in urine volume, food consumption, water intake, TC, TG, glycated serum protein, fasting blood glucose levels, 24h urine protein levels, and serum levels of urea nitrogen and creatinine. It also prevented ECM accumulation and improved the histology of pancreas and kidney, and alleviated the structural alterations in mesangial cells and podocytes in renal cortex. Moreover, CBP, IGCO, TACO and IGRR down-regulated the elevated staining, protein levels of RAGE, SphK1, TGF-β and NF-κB. Among the treatment groups, CBP produced the strongest effects. CONCLUSIONS: These findings suggest that the inhibitory effect of CBP, IGCO, TACO and IGRR on the activation of AGEs/RAGE/SphK1 signaling pathway in db/db diabetic mice kidney is a novel mechanism by which CBP, IGCO, TACO and IGRR exerts renoprotective effects on DN. Among all the groups, CBP produced the strongest effect while IGCO, TACO and IGRR produced weaker effects.

Obesity is a medical condition that presents excessive fat accumulation with high risk of serious chronic diseases. The aim of this clinical trial is to investigate the anti-obesity effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) on body fat reduction in Korean overweight women. A total of 147 overweight female participants enrolled in double-blinded clinical trial for 12 weeks and 76 participants completed the clinical study. Participants were treated with four CO and RF mixture (COEC; 400 mg per tablet) or four placebo tablets once a day. Obesity associated parameters (body weight, body mass index (BMI), waist circumference, waist-to-hip ratio, body fat percentage and body fat mass) and safety assessment were analyzed. After 12 weeks of COEC treatment, primary outcomes such as body fat percentage (0.76% vs. 0.01%; p = 0.022) and mass (1.1 kg vs. 0.5 kg; p = 0.049) were significantly decreased. In addition, the results were statistically significant between the COEC and placebo groups, strongly indicated that COEC had anti-obesity effects on overweight women. Secondary outcomes-including body weight, waist and hip circumference, waist-to-hip ratio, body mass index and computed tomography measurement of visceral fat area, subcutaneous fat area, total abdominal fat area and visceral-to-subcutaneous fat ratio-were reduced in COEC-treated group, but no statistical differences were found between the COEC and placebo groups. The safety assessment did not differ between the two groups. These results suggest that treatment of COEC extract reduces body fat percentage and mass in Korean overweight women, indicating it as a protective functional agent for obesity.

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. © 2026 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

This study investigated the effects and mechanisms of Cornus officinalis Siebold & Zucc. ethanol extract (COEE) on primary dysmenorrhea (PD). COEE administration dose-dependently reduced writhing times, prolonged writhing latency, decreased uterine prostaglandin F2α (PGF2α) levels and pro-inflammatory mediators, and improved histopathological signs of uterine inflammation. Furthermore, COEE suppressed the activation of the TLR4/MyD88/NF-κB/NLRP3 signaling axis. In ex vivo experiments, COEE inhibited spontaneous and agonist-induced uterine contractions, attenuated CaCl2-induced contractile recovery, and reduced Bay K 8644 evoked Ca2+-mediated contractions. Collectively, our findings suggested that COEE alleviates PD by attenuating uterine inflammation and abnormal calcium-dependent contractions, supporting its potential use as a functional food source for managing PD.

Cognitive impairment induced by chronic neuropathic pain (CNP-CI) is a severe complication that markedly compromises patients' quality of life, functional independence, and overall disease burden. However, current pain management strategies demonstrate limited efficacy in preventing or reversing this cognitive decline. Cornuside, an active flavonoid glycoside isolated from the traditional Chinese herb Cornus officinalis, demonstrates potent anti-inflammatory and antioxidative stress properties, however, its therapeutic potential for the treatment of neuropathic pain remains to be elucidated. In this study, we demonstrated that cornuside effectively alleviated microglial inflammation and improved cognitive impairment induced by chronic neuropathic pain. Mechanistically, cornuside ameliorated microglia-mediated neuroinflammation through activation of the Nrf2/Sirt3 signaling pathway and enhancement of mitophagy. Notably, pharmacological inhibition of Sirt3 markedly counteracted the therapeutic effects of cornuside on microglial inflammation and CNP-CI. Our findings provide new insights into the pharmacological mechanisms of cornuside and suggest its potential as a viable therapeutic approach for CNP-CI.

Mild cognitive impairment (MCI) represents an intermediate stage between normal aging and Alzheimer's disease. This study investigated the neuroprotective effects of a combined extract of Mentha piperita (MP) and Cornus officinalis (CO) (MC) using in vitro and in vivo models. In SK-N-SH cells, pretreatment with MC (50-150 μg/mL) significantly attenuated H2O2-induced cellular injury, as evidenced by a reduction in Annexin V-positive cells and an increase in brain-derived neurotrophic factor (BDNF) mRNA expression. Rosmarinic acid and loganin, the marker compounds of MP and CO, alone or combined at a 6:4 ratio, mitigated H2O2-induced decreases in cell viability and BDNF mRNA. In the in vivo study, male Sprague-Dawley rats were orally administered MC (50, 100, or 200 mg/kg/day) for 28 days, with phosphatidylserine (50 mg/kg/day) serving as a positive control. MC administration significantly improved cognitive performance in rats with scopolamine-induced memory impairment, as demonstrated by increased step-through latency in the passive avoidance test and reduced escape latency in the Morris water maze. Furthermore, in the probe trial, MC-treated rats spent significantly more time in the target quadrant, indicating enhanced spatial memory retention. Mechanistically, MC restored hippocampal acetylcholine levels and reversed the scopolamine-induced decrease in BDNF and its downstream signaling. Specifically, MC upregulated hippocampal BDNF expression and enhanced the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (AKT), and cAMP response element-binding protein (CREB). In conclusion, these results demonstrate that the MC extract possesses potent neuroprotective and learning- and memory-enhancing effects, highlighting its potential as a therapeutic candidate for managing age-related cognitive decline and MCI.

Ischemic stroke (IS) remains a major cause of global mortality and disability, with neuroinflammation driven by microglial pyroptosis representing a key pathological mechanism. This study examined the neuroprotective efficacy of morroniside-an iridoid glycoside from Cornus officinalis-in experimental model of IS, focusing on its regulation of microglial inflammasome activation, pyroptosis and associated signaling cascades. Using a transient middle cerebral artery occlusion/reperfusion (tMCAO/R) model in Sprague-Dawley rats and an oxygen-glucose deprivation/reperfusion (OGD/R) model in BV2 microglia, morroniside was administered at 270 mg/kg intragastrically in vivo and at concentrations of 1-100 μmol/L in vitro. Protein expression was assessed by Western blotting, cellular markers by immunofluorescence, cytokine levels by enzyme-linked immunosorbent assay (ELISA), and pathway alterations by transcriptomic profiling. Morroniside treatment significantly attenuated microglial activation, as evidenced by reduced ionized calcium-binding adapter molecule 1 (IBA-1) expression, and suppressed pyroptosis through downregulation of gasdermin D (GSDMD), NOD-like receptor family pyrin domain containing 3 (NLRP3), caspase-1, interleukin-1β (IL-1β), and interleukin-18 (IL-18) in both models. Transcriptomic analysis revealed marked enrichment in inflammatory and immune response pathways, with notable suppression of interleukin-17 (IL-17) signaling. Mechanistic analyses showed that morroniside concurrently suppressed IL-17 expression, nuclear factor-κB (NF-κB) phosphorylation, and NLRP3 inflammasome assembly, implicating coordinated inhibition of the IL-17/NF-κB/NLRP3 cascade. Functional in vitro assays confirmed the pathway's essential role: recombinant IL-17 partially reversed, whereas selective IL-17 blockade enhanced, morroniside-mediated suppression of pyroptosis, demonstrating that IL-17 signaling is both necessary and targetable in this cascade. Collectively, these findings identify morroniside as a regulator of IS-associated neuroinflammation that mitigates microglial pyroptosis by interrupting the IL-17/NF-κB/NLRP3 axis, underscoring its potential as a therapeutic candi

Hepatocellular carcinoma (HCC) represents a highly aggressive malignancy with limited treatment options. While the traditional herb Cornus officinalis Sieb. et Zucc. (C. officinalis, commonly called Asiatic dogwood or "Shanzhuyu" in Chinese) is known for its hepatoprotective properties, the structural features and anti-HCC potential of polysaccharides from its leaves remain largely unexplored. Therefore, we hypothesized that the leaf-derived polysaccharides with uncharacterized structure may exhibit anti-HCC activity. In this study, a homogeneous anti-HCC polysaccharide, designated PCL-2I (Mw = 67.0 kDa), was isolated from C. officinalis leaves, and its structure was characterized by monosaccharide composition, methylation analysis, partial acid hydrolysis, and NMR spectra. PCL-2I is a pectic polysaccharide with a backbone repeating unit: →[6,3)-β-Glcp-(1 → 6)-α-Galp-(1 → 6)-α-Galp-(1]x → [4)-α-GalpA-(1 → 4)-β-GalpA-OMe-(1]y → [4)-α-GalpA-(1 → 2,4)-α-Rhap-(1 → 4)-α-GalpA-(1 → 2)-α-Rhap-(1]z→. Its branched side chains include →6)-α-Galp-(1→, →3)-α-Araf-(1→, →3,5)-α-Araf-(1→, and →2)-α-Rhap-(1→, with substitutions at C-3 of the Glc residue and C-4 of Rha residue, respectively. PCL-2I suppressed HCC growth in vivo and induced apoptosis in vitro by targeting pyruvate kinase M2 (PKM2), thereby attenuating glycolysis and disrupting hypoxia-inducible factor-1α oncogenic signaling. These effects may be attributed to PCL-2I's high content of arabinose and galactose. This study provides a theoretical foundation for utilizing PCL2I, a pectic polysaccharide from C. officinalis leaves, as a potential therapeutic agent against HCC by targeting PKM2.

Microglia monitor disease stimulation, neuronal apoptosis, and neural repair, and their overactivation-induced inflammation plays a key role in the pathogenesis of Alzheimer's disease (AD). Morroniside (Mor), an iridoid glycoside compound in Cornus officinalis, is one of the effective active components. The effects of Mor on antioxidant stress, antiapoptosis, and nerve repair function have been widely studied, but the mechanism of Mor in AD treatment remains unclear. To study the neuroprotective effects of Mor and elucidate the molecular mechanisms underlying its improvement of AD symptoms, we used ApoE4 transgenic mice and ApoE4-transfected BV2 cells as models of AD, focusing on microglia phenotype, function, and neuroinflammation. The 10-month-old mice were randomly divided into the ApoE3 control group (ApoE3 + Veh), the ApoE4 model group (ApoE4 + Veh), and the ApoE4 + Mor 10, 20, and 40 mg/kg groups as in vivo models. The in vitro BV2-ApoE model was constructed via lentiviral transfection. The effects of Mor on cognitive function of AD models were assessed through behavioral tests, western blot, immunofluorescence staining, and ELISA to measure changes of related pathological and inflammatory factors. Mor improved the cognitive function of ApoE4 transgenic mice by reducing Aβ plaques in the brain, improving the structural lesions of hippocampal neurons, and increasing synaptic plasticity in the brain of AD mice. In addition, Mor promoted the transformation of microglia from the M1 to the M2 phenotype, inhibited the activation of the CX3CR1/PU.1 signaling axis, and alleviated the dysfunction of microglia both in vitro and in vivo. CX3CR1 siRNA and PU.1 siRNA were used further to verify the regulatory effect of Mor on microglia phenotype. Our findings indicate that Mor can inhibit neuroinflammation, reduce Aβ accumulation, and improve synaptic damage in ApoE4 mice via the CX3CL1/CX3CR1/PU.1 pathway regulating the phenotype and function of microglia. This study provides a new therapeutic candidate for the prevention and treatment of AD. © 2026 John Wiley & Sons, Ltd.

OBJECTIVE: Cardiac ischemia/reperfusion (I/R) injury is characterized by excessive inflammation and aberrant activation of intracellular signaling pathways, including JAK/STAT. Cornus officinalis total glycosides (COTG) possess anti-inflammatory properties, but their role in myocardial I/R injury remains incompletely defined. This study aimed to investigate the cardioprotective effects of COTG against I/R -induced injury and clarify its pathway-dependent mechanism involving JAK1/STAT3 signaling. METHODS: A myocardial I/R injury model was established in male Sprague-Dawley rats, which were randomly divided into Sham control, I/R control, and COTG-treated groups (200, 400, and 600 mg/kg). Cardiac function was evaluated by echocardiography, and myocardial histopathology was assessed by hematoxylin and eosin staining. Serum myocardial injury markers were measured by ELISA. Inflammatory cytokine expression and macrophage polarization were analyzed using qRT-PCR and immunofluorescence, respectively. JAK1/2 and STAT3 phosphorylation was detected by Western blotting. An in vitro hypoxia/reoxygenation (H/R) model combined with a pharmacological JAK inhibitor was further employed to verify pathway dependency. RESULTS: COTG treatment significantly improved cardiac function, as evidenced by increased left ventricular ejection fraction and fractional shortening and reduced ventricular dilation. Histological damage and serum levels of cardiac troponin I, cardiac troponin T, and creatine kinase-MB were markedly attenuated. COTG suppressed pro-inflammatory markers (iNOS, IL-1β, IL-6) while enhancing anti-inflammatory mediators (Arg-1, IL-10). Mechanistically, COTG dose-dependently inhibited JAK1, JAK2, and STAT3 phosphorylation without altering total protein levels. Pharmacological inhibition experiments confirmed that JAK/STAT suppression by COTG was pathway-dependent. Moreover, COTG reduced myocardial apoptosis by increasing Bcl-2 and decreasing Bax and cleaved caspase-3 expression. CONCLUSION: COTG protects against myocardial I/R injury by pathway-dependent inhibition of JAK/STAT signaling, modulation of inflammatory responses, and attenuation of cardiomyocyte apoptosis, hig

BACKGROUND: Cornus officinalis, traditionally used for its kidney-tonifying and waist-protecting properties, has recently shown potential therapeutic effects in neurological disorders. However, its mechanisms in Parkinson's disease (PD) remain unclear. METHODS: This study employed a network pharmacology approach combined with molecular docking to systematically explore the active components of Cornus officinalis and their associated signaling pathways in PD. RESULTS: A total of 11,663 PD-related targets were identified from multiple databases, with 185 overlapping targets obtained from active components of Cornus officinalis using SwissTargetPrediction. Protein-protein interaction (PPI) network analysis identified EGFR, TP53, HIF1A, ESR1, PPARG, TNF, HSP90AA1, PTGS2, and SRC as the core targets of Cornus officinalis in PD. Gene Ontology (GO) enrichment analysis revealed that Cornus officinalis primarily modulates pathways such as MAPK signaling, synaptic function, and lipid metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted the involvement of target genes in the neuro-endocrine-immune network. Molecular docking confirmed strong binding affinities between active components and core targets, with binding energies below -5 kcal/mol. Reactome pathway enrichment analysis further identified the IL-4 and IL-13 signaling pathway as the most significant, suggesting a critical role in regulating immune responses and neuroinflammation. Molecular dynamics simulations further confirmed the stability of the binding between Cornus officinalis and the targets. CONCLUSION: Cornus officinalis exhibits potential therapeutic effects against PD through multi-target and multi-pathway mechanisms, including anti-inflammatory actions, regulation of synaptic function regulation, and metabolic modulation. These findings provide a theoretical foundation for further experimental and clinical validation of Cornus officinalis as a promising candidate for PD treatment.

Cornus officinalis (C. officinalis) is an important plant resource with a long history and a wide range of uses in medicine and food. Polysaccharides are one of the main active components of C. officinalis. Because of its unique and significant anti-tumor, antioxidant, immunomodulatory, and many other biological activities, it has received extensive attention from researchers, and its study has become more and more in-depth. Although the phytochemical and bioactive aspects of C. officinalis polysaccharides (COPs) have been extensively studied, a systematic and comprehensive summary of these polysaccharides has not yet been compiled. This lack of summary hinders their full utilization and development. This paper reviews the extraction, purification, structural features, and biological activities, as well as applications of COPs. It also discusses the potential development and future research directions of COPs in the food, pharmaceutical, and cosmeceutical fields. This paper may provide direction and a theoretical basis for the development of COPs as novel functional foods.

Inflammation is known to exacerbate depressive symptoms. Loganin, a major iridoid glycoside derived from Cornus officinalis Sieb. et Zucc., exhibits antidepressant-like properties and anti-inflammatory effects; however, the mechanisms underlying these actions remain unclear. Given the involvement of the Sigma-1 receptor (Sigma-1R) in both depression and neuroinflammation, this study aimed to investigate whether loganin can ameliorate inflammation-related depression by modulating Sigma-1R. Experimental models of social isolation and lipopolysaccharide (LPS)-induced depressive-like behaviors were employed. The effects of loganin on behavioral outcomes, neurons, astrocytes, and microglia, oxidative stress levels, and the NLRP3 inflammasome were assessed. Molecular docking analysis and cellular thermal shift assay were conducted to evaluate the binding affinity of loganin to Sigma-1R. Additionally, the impact of a Sigma-1R inhibitor (BD1047) on loganin's effects was investigated. Loganin improved social isolation- and LPS-induced depressive-like behaviors. It also reduced astrocyte and microglia reactivity and decreased oxidative stress levels. Furthermore, loganin downregulated the expression of IRE1α, TXNIP, and the NLRP3 cascade. Molecular docking and cellular thermal shift assays confirmed strong binding of loganin to Sigma-1R. Loganin increased Sigma-1R expression in the hippocampus in response to LPS or social isolation. The antidepressant-like effects of loganin, as well as its inhibition of the NLRP3 inflammasome and oxidative stress, were reversed by BD1047. These findings suggest that loganin alleviates inflammation-associated depressive-like behaviors by inhibiting the NLRP3 inflammasome and oxidative stress via the Sigma-1R/IRE1α/TXNIP pathway, highlighting its potential as a therapeutic agent for inflammation-related depression. © 2025 John Wiley & Sons Ltd.

BACKGROUND: Diabetic nephropathy (DN) is a common microvascular complication of diabetes. Liuwei Dihuang Pills (LW) has significant clinical efficacy in the treatment of DN, but its pharmacological mechanism and material basis remain poorly understood. OBJECTIVE: This study aimed to explore the substance basis and mechanism of action of LW in treating DN. DESIGN: The potential mechanism of LW was investigated through UPLC/LTQ-Orbitrap-MS and network pharmacology. The activity of LW and its constituent herbs was evaluated in human renal glomerular endothelial cells (HRGEC) and HK2 cells. Key pathways and targets were identified by transcriptomics and validated by qRT-PCR. Molecular docking was employed to screen for active ingredients of LW. RESULTS: The results showed that LW, Cornus Officinalis (CO), Moutan Cortex (MC), Rhizoma Dioscoreae (RD), and Alismatis Rhizoma (AR) mitigated oxidative damage in HRGEC cells. LW primarily targeted VEGFA and EGR1, thereby modulating the AGE-RAGE signaling pathway in diabetic complications. LW also reduced fibrosis in HK2 cells by up-regulating BMP4 and modulating the TGF-beta signaling pathway. Rehmanniae Radix Praeparata (RRP), CO, MC, RD, and Poria Cocos (PC) were identified as key contributors to improving renal fibrosis. Additionally, 43 potential active ingredients were identified in LW, 13 of which exhibited favorable ADMET properties. Six key ingredients, including taxifolin, cianidanol, gallic acid, caffeic acid, 5-hydroxymethylfurfural, and paeonol were found to be primarily responsible for the effects of LW on microvascular endothelial injury and renal fibrosis. CONCLUSION: In summary, these findings reveal the material basis and mechanism of LW against DN, providing a foundation for its clinical application. © 2025 Chaoqun Liu et al.

To screen for anti-PMO active components in Cornus officinalis based on ERβ enzyme activity using affinity ultrafiltration and molecular docking techniques.ERβ enzyme and UHPLC-Q-Exactive Orbitrap MS were employed to analyze the anti-PMO activity and predict the components of different concentrations of ethanol extracts of C. officinalis. Molecular docking was used to verify the interaction mechanism between small molecule ligands and ERβ. The anti-PMO activity of the predicted components was further verified using MC3T3-L1 cells. The results showed that the ERβ enzyme can serve as a target enzyme for screening anti-PMO components. The 50% ethanol extract exhibited the best activity. UHPLC-Q-Exactive Orbitrap MS identified and analyzed 17 potential active components. Based on the binding rate and molecular docking results, the following three active components were identified: sweroside, 4-hydroxycinnamic acid, and cornuside. In vitro activity validation confirmed that these components have potential anti-PMO effects. The ERβ enzyme can be used as a potential target enzyme for screening anti-PMO active components in traditional Chinese medicine. The combination of affinity ultrafiltration and molecular docking provides an effective and rapid method for active component screening, offering valuable references for the targeted therapy, mechanism exploration, and quality control of traditional Chinese medicine. © 2025 John Wiley & Sons Ltd.

Four previously undescribed compounds, including two dihydroisocoumarin glycosides (1 and 2), a truxillic acid derivative (4), and a cadinane-type sesquiterpene (5), were isolated from the fruits of Cornus officinalis Sieb. et Zucc., along with seven known ones (3, 6-11). Their chemical structures were determined by extensive spectroscopic methods and computational analyses. All isolated compounds were evaluated for the effects on glucose consumption in insulin-resistant (IR) HepG2 cells. The compounds exhibited no significant cytotoxicity at 10.0 μM in the CCK-8 assay. Compounds 2, 3, and 8 significantly increased glucose consumption (P < 0.05) at 5.0 and 10.0 μM. The 2-NBDG labeling indicated that compounds 2 and 8 significantly increased glucose uptake at 10 μM. Moreover, compounds 2 and 8 also significantly increased insulin receptor (INSR) expression, indicating their potential to upregulate the INSR in the cytomembrane and enhance glucose uptake.

Cornus officinalis Sieb. et Zucc. (C. officinalis) has been widely utilized as a traditional Chinese medicine and food ingredient in China. C. officinalis polysaccharides (COPs) is one of the key bioactive components of C. officinalis, which has attracted much attention due to their decent pharmacological activities, such as anti-aging, antioxidant, anti-tumor, antidiabetic, neuroprotective effects and anti-atherosclerotic efficacy. COPs can be extracted via diverse methods with the extraction yields ranging from 3.42 % to 30.43 %. Although significant progress has been made in the extraction and purification technologies, the structure-activity relationships between COPs structures and their pharmacological effects remain to be fully elucidated. To address this, the present review systematically summarizes recent advances in COPs research, including extraction methods, purification techniques, structural characteristics, bioactivities, and safety assessment. In addition, the structure-activity relationships of COPs were critically analyzed and their potential applications, current challenges, and future research directions were discussed, which would provide theoretical reference and practical guidance for the follow-up studies.

Hyperuricemia, characterized by elevated serum uric acid levels, is a major risk factor for gout and kidney disease. This study evaluated the antihyperuricemic effects of Cornus officinalis extract (COE) using urate transporter 1 (URAT1)-expressing oocytes and a hyperuricemia rat model. COE effectively inhibited uric acid absorption by modulating URAT1, with an IC50 value of 3.24 µg/mL. In the hyperuricemia model, COE administration (100 and 200 mg/kg) significantly reduced serum uric acid levels and increased urinary uric acid excretion. The primary constituents of COE, morroniside (MO) and loganin (LO) exerted similar effects, with MO exhibiting potent inhibition of uric acid absorption even at low concentrations. Kidney tissue analysis revealed a reduction in blood urea nitrogen (BUN) levels, indicating improved renal function. Liver function parameters (ALT, AST, and LDH) remained unchanged, suggesting an absence of hepatotoxicity. Ultra-high-performance liquid chromatography with charged aerosol detection (UHPLC-CAD) analysis identified MO (17.8 mg/g), LO (9.8 mg/g), and cornin (1.4 mg/g) as the principal components of COE. These findings suggest that COE enhances uric acid excretion via URAT1 regulation and exerts renoprotective effects, highlighting its potential as an antihyperuricemic agent. Furthermore, MO and LO were identified as the primary active constituents, and COE appears to be a promising therapeutic candidate with a favorable safety profile.

Cornus officinalis, a plant used in traditional medicine and as a food, has anti-inflammatory and immune-enhancing properties. This study investigated the structure and anti-infection capabilities of a polysaccharide (COP-60a) from its leaves under microgravity stress. COP-60a was a homogeneous heteropolysaccharide (13,774 Da) composed of arabinose, galactose, xylose, and glucose. Its backbone structure included α-Araf-(1→, →4,6)-β-Galp-(1→, →5)-β-Araf-(1→, →3,6)-α-Galp-(1→, →6)-β-Glcp-(1→ with branches at specific C4/C3 positions. Functionally, COP-60a activated the p38 MAPK pathway (nsy-1, sek-1, pmk-1) and the mitochondrial unfolded protein response (UPRmt), upregulated immune genes (irg-1, hsf-1, lys-1, spp-1, abf-1), and repaired mitochondrial dysfunction, enhancing C. elegans' anti-infection capacity under microgravity. Additionally, microgravity weakens lung immunity and disrupts lung microbiota homeostasis in mice, but COP-60a restored these imbalances. These findings provided valuable insights into the structure-activity relationship of COP-60a and highlighted its potential as a protective strategy against infection risks in microgravity environments.

We aimed to identify and isolate the metabolically active compounds from Cornus officinalis (C. officinalis) that underlie the biological effects previously observed in our in vitro and in vivo studies. Our prior findings demonstrated that C. officinalis promoted activation of the Keap1/Nrf2 pathway in a pancreatic β-cell line and delayed the onset of type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. To characterize the metabolically active compounds within C. officinalis, the concentrated extract was fractionated by column chromatography, and evaluated for their effect on β-cell metabolic activity and expression of Nrf2 targets such as heme oxygenase-1 (HO1) and superoxide dismutase 2 (SOD2). Highly concentrated compounds of interest within metabolically active fractions were isolated using high performance liquid chromatography (HPLC). Elucidation of a highly abundant compound within C. officinalis extract was identified by mass spectrometry and nuclear magnetic resonance (NMR) as 5-hydroxymethylfurfural (5-HMF) which was demonstrated by immunoblotting to significantly increase SOD2 expression. Quantitative proteomics was performed on 5-HMF treated murine non-obese diabetic (NOD) islets and revealed increased expression of Nrf2 and downstream targets such as SOD2, GSTA3, GSTA4 and GCLC. Our findings suggest that 5-HMF is a highly abundant and metabolically active compound within C. officinalis that stimulates partial activation of the Keap1/Nrf2 pathway.

BACKGROUND: This study investigated the pharmacological potential of volatile organic compounds (VOCs) extracted from the leaves of Cornus officinalis, with the aim of elucidating their interactions with human olfactory receptors and transport proteins, and assessing their applicability in functional foods and aroma-based therapies. Using solid-phase microextraction coupled with gas chromatography-mass spectrometry (SPME-GC-MS), 22 representative VOCs were identified from age-stratified samples. Seven small bioactive molecules were selected for integrated analysis involving absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction, network pharmacology, molecular docking, and spectroscopic validation. Network pharmacology analysis identified 243 predicted targets, with β-ionone emerging as a key compound interacting with multiple olfactory receptors - olfactory receptor 1A1 (OR1A1), olfactory receptor 2W1 (OR2W1), and olfactory receptor 10S1 (OR10S1) - as well as transport proteins including human serum albumin (HSA), α-lactalbumin (α-La), and β-lactoglobulin (β-LG). RESULTS: Functional enrichment analysis highlighted that β-ionone-related targets were involved significantly in olfactory transduction, cytochrome P450 metabolism, and neuroactive ligand-receptor interaction pathways. Molecular docking demonstrated the highest binding affinities for β-ionone across multiple protein classes, which was further validated by fluorescence and ultraviolet-visible (UV-visible) spectroscopy. Thermodynamic analysis confirmed that the binding process was spontaneous, mainly driven by hydrophobic and electrostatic forces. The novel contribution of this study lies in its systematic investigation of C. officinalis leaf VOCs and their interactions with human olfactory and transport proteins, an area not previously explored. CONCLUSION: This study elucidated the mechanisms of VOC-protein interactions and highlighted their potential applications in functional foods and aroma therapies. The integrated computational and experimental approach established a solid scientific basis for future screening of natural bioactive compounds with high bioavailability and s

Sevoflurane, a commonly used inhalational anesthetic, is implicated in neuroinflammation and postoperative cognitive dysfunction (POCD) pathogenesis. This study investigated the neuroprotective potential of loganin, a principal iridoid glycoside from Cornus officinalis, against sevoflurane-induced cognitive impairment in aged mice. An aged mouse POCD model was established by exposing 18-month-old C57BL/6 J mice to 3% sevoflurane. Cognitive and motor functions were assessed using the Morris water maze and open field tests. Hippocampal neuronal integrity, microglial activation, and neuroinflammation were evaluated via Nissl staining, immunofluorescence, and molecular analyses. Complementary in vitro studies employed primary hippocampal neuron cultures and a microglia-neuron transwell co-culture system. Neuronal viability, apoptosis, inflammatory responses, and the SIRT1/NF-κB signaling pathway were investigated using CCK-8, flow cytometry, ELISA, and Western blot. Loganin pretreatment significantly improved spatial learning and memory in sevoflurane-exposed aged mice. It attenuated sevoflurane-induced neuronal loss in the hippocampus, suppressed microglial activation, and reduced levels of hippocampal pro-inflammatory cytokines. Mechanistically, loganin reversed the sevoflurane-induced downregulation of SIRT1 and activation of NF-κB in vivo. In vitro, loganin directly protected neurons via the SIRT1/NF-κB pathway, an effect blocked by the SIRT1 inhibitor EX-527. Moreover, the microglia-neuron co-culture experiment demonstrated that loganin's neuroprotection is also mediated by its direct action on microglia: it suppressed sevoflurane-induced dysregulation of the SIRT1/NF-κB pathway and cytokine secretion, which in turn preserved neuronal viability and reduced apoptosis. This microglia-mediated protection was similarly abolished by EX-527. Our findings demonstrate that loganin effectively ameliorates sevoflurane-induced cognitive impairment in aged mice. It confers neuroprotection by by activating SIRT1 and subsequently inhibiting NF-κB signaling in hippocampal neurons, and by suppressing microglial activation and neuroinflammation via the same SIRT1/NF-κB axis. ©

Cornin, a bioactive iridoid glycoside isolated from Cornus officinalis, has been reported to exhibit cardioprotective and pro-apoptotic activities. However, its antitumor mechanism in cervical cancer remains largely unknown. In this study, we investigated the antiangiogenic and anti-invasive effects of Cornin, focusing on the CNOT2-VEGF signaling axis. Cornin showed limited cytotoxicity in SiHa, HeLa, and CaSki cervical cancer cells but significantly downregulated CNOT2, N-cadherin, VEGF, and Snail expression in HeLa and SiHa cells. Functional analyses revealed that CNOT2 silencing suppressed wound healing activity, while Cornin treatment markedly inhibited cell migration, invasion, and VEGF secretion in HeLa cells. VEGF luciferase reporter and cycloheximide chase assays confirmed that Cornin reduced VEGF transcription and protein stability in a time-dependent manner. Furthermore, Cornin inhibited tube formation in HUVECs and angiogenesis in the chick chorioallantoic membrane (CAM) model. TCGA analysis showed that CNOT2 expression was elevated in cervical cancer tissues and positively correlated with VEGF expression (r = 0.35). This association was further supported by immunoprecipitation analysis demonstrating a physical interaction between CNOT2 and VEGF in HeLa cells. Mechanistically, ectopic CNOT2 expression upregulated VEGF, whereas its depletion suppressed VEGF expression. Collectively, these findings highlight the CNOT2-VEGF axis as a crucial mediator in antiangiogenic and anti-invasive effects of Cornin in cervical cancer, suggesting Cornin as a potent natural inhibitor of tumor angiogenesis and invasion. © 2026. The Author(s).

Allelopathic interactions between associated tree species can shape seedling establishment, resource acquisition, and long-term coexistence. However, the mechanisms underlying such interactions in endangered plants remain underexplored. In this study, we aimed to elucidate whether and how aqueous litter extracts from Cornus controversa Hemsl. influence the growth performance and nutrient acquisition in Davidia involucrata Baill., a relict and endangered tree species in China. Seedlings were treated with distilled water (control), branch litter extract, leaf litter extract, or a mixture of both at natural concentrations. Across all treatments, litter extracts increased plant height, total leaf area, dry mass, and tissue nitrogen (N) and phosphorus (P) content, with branch litter extract exerting the strongest growth-promoting effects. Notably, this treatment was associated with a marked increase in soil phosphatase activity, while root phosphatase activity remained unchanged. Soil phosphatase activity showed significant positive relationships with most growth traits of D. involucrata seedlings. Metabolite profiling identified 35 shared compounds and multiple organ-specific metabolites among the extracts, with branch litter extracts exhibiting the highest abundance of indole-related compounds, suggesting a potential biochemical basis for the observed positive allelopathic effects. These findings reveal a previously underappreciated positive allelopathic interaction involving an endangered tree species and demonstrate that organ-specific litter inputs can enhance nutrient acquisition by activating soil enzymes. This study offers novel mechanistic insights into how associated tree species may sustain ecological interactions under nutrient-limited conditions, with implications for the conservation and management of endangered forest species. © The Author(s) 2026. Published by Oxford University Press. All rights reserved. For commercial re-use, please contact [email protected] for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further inform

Cornus officinalis Siebold & Zucc. 1839 is a medicinally important species of Cornaceae, yet mitochondrial genomic information for this genus has remained unavailable. In this study, we assembled and annotated the mitochondrial genome of C. officinalis using PacBio HiFi sequencing data. The mitogenome comprises three circular molecules totaling 556,620 bp with similar GC contents of approximately 45%. A total of 70 genes were identified, including 43 protein-coding genes, 23 transfer RNA genes, and four ribosomal RNA genes. Phylogenetic analysis based on mitochondrial protein-coding genes placed C. officinalis in a well-supported clade with Hydrangeaceae, Ericaceae, and Primulaceae. This first mitochondrial genome reported for Cornaceae provides a useful resource for mitochondrial genome evolution and angiosperm phylogenetic studies. © 2026 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

Microglia-mediated neuroinflammation in the central nervous system is a hallmark of both multiple sclerosis (MS) and the animal model experimental autoimmune encephalomyelitis (EAE). Current immunosuppressive therapies for MS have limited efficacy and notable side effects. This study aimed to investigate mechanisms underlying anti-neuroinflammatory effects of morroniside, an iridoid glycoside derived from Cornus officinalis, which is used in Chinese herbal medicine. Morroniside treatment significantly attenuated lipopolysaccharide-induced alterations and mitochondrial dysfunction in BV2 microglia cells. In vivo, morroniside treatment improved clinical scores and ameliorated pathological findings and neurological deficits in a mouse EAE model. Mechanistic investigations revealed that morroniside activated the Nrf2/HO-1 signaling axis, promoted Nrf2 nuclear translocation and elevated HO-1 expression. This activation also upregulated p62, thereby enhancing LC3-II/PINK1/Parkin-mediated mitophagosome formation. The resultant mitophagy suppressed p65 phosphorylation leading to anti-inflammatory effects. Collectively, our findings suggest that morroniside ameliorates EAE by increasing anti-inflammatory microglial activation through upregulating the Nrf2/HO-1/p62 axis to mitigate mitochondrial oxidative stress and enhance mitophagy. These results identify morroniside as a promising therapeutic candidate for MS and emphasize the importance of the Nrf2-p62-mitophagy axis in resolving neuroinflammation and maintaining mitochondrial homeostasis. © The Author(s) 2026. Published by Oxford University Press on behalf of American Association of Neuropathologists, Inc.

Cornus officinalis Sieb. et Zucc. (CF), a dual-purpose medicinal and edible herb in Traditional Chinese Medicine, requires stringent quality control to ensure therapeutic efficacy and safety. This study developed a comprehensive multi-criteria evaluation system integrating Analytic Hierarchy Process (AHP) with 4 main criteria (appearance characteristics, quality parameters, characteristic components, and pharmacological activities), which are further subdivided into 18 measurable indicators. Through single-factor experiments and Response Surface Methodology (RSM), optimal processing parameters were established, achieving a comprehensive quality score of 54.143 (on a normalized 0-100 scale with only 0.70% validation error. To further elucidate the biological mechanisms of quality deterioration during storage, ITS sequencing analysis elucidated microbial community succession under varying storage conditions (4-36 °C, 35-75% RH), demonstrating that low-temperature/low-humidity storage (4 °C, 35% RH) significantly suppressed fungal proliferation while maintaining >95% retention of morroniside and loganin, whereas only ≈78% retention of morroniside under high-temperature/high-humidity conditions (36 °C, 75% RH). This work establishes a potential methodological framework and offers practical technical insights toward the standardization of processing, storage, and quality assessment of CF. © 2026. The Author(s).

Salicylic acid enhances cadmium tolerance in plants by modulating antioxidant defenses and promoting cadmium immobilization in cell walls. However, its potential to mitigate cadmium-induced growth inhibition and physiological disturbances in the woody species Cornus alba L. remains unexplored. Cornus alba L. seedlings were used in the pot experiment with four treatments: control (CK); 40 mg·kg-1 cadmium treatment (Cd); 100 µmol·L-1 salicylic acid treatment (SA); and both salicylic acid and cadmium treatment (SACd). The results showed that salicylic acid reduced lipid peroxidation in cell membranes by enhancing root cadmium sequestration and reconfiguring the antioxidant enzyme system, thus demonstrating a synergistic protective effect. By inhibiting cadmium transport to the shoots, it thereby mitigated the cadmium-induced inhibition of photosynthesis and reproductive development. Transcriptome analysis indicated that salicylic acid upregulates key genes in sucrose and starch metabolism pathways (e.g., TPS, GN1_2_3, otsB), leading to enhanced carbon assimilation and energy supply. Furthermore, it upregulates the key terpenoid biosynthesis genes (including HMGR and GGPS), leading to a coordinated modulation of primary and secondary metabolic flux and an increased output of the related pathways. The results reveal a potential mechanism by which salicylic acid alleviates cadmium stress in Cornus alba L., offering new insights into its role in plant heavy metal stress responses.

Fungal pathogens have dramatically altered forests worldwide, yet the mechanisms of virulence remain poorly understood. From the 1970s to the early 2000s, dogwood anthracnose, caused by Discula destructiva, devastated North American flowering and Pacific dogwoods (Cornus florida and C. nuttallii, respectively), causing one of the most destructive forest tree epidemics of the modern era. Despite its ecological impacts, genomic resources for D. destructiva and related Diaporthales pathogens remain limited, thus hindering efforts to resolve the mechanisms of pathogenicity. Here, we present the telomere-to-telomere genome assembly of D. destructiva, complemented by transcriptome profiling to investigate gene expression shifts across its hemibiotrophic life cycle. The 46.655-Mb assembly comprised eight chromosomes with 99.47% BUSCO completeness, along with 10,373 predicted gene models with 97.40% BUSCO completeness. To profile life cycle-specific gene expression, we conducted RNA sequencing of sporulating (reproductive) and nonsporulating (vegetative) tissue and identified 240 differentially expressed genes (Padj < 0.05). Of those, 162 upregulated sporulation genes were associated with plant cell wall degradation and sugar metabolism, whereas 78 downregulated sporulation genes were associated with oxidative stress response and metal ion homeostasis. Of the 240 sporulation genes, 117 genes also encoded predicted virulence factors, including signal peptides, carbohydrate-active enzymes (CAZymes), and effectors. These patterns suggest a metabolic reallocation accompanying the transition to sporulation, which reflects physiological adaptation in response to environmental factors. Together, these findings illuminate the hemibiotrophic adaptation of D. destructiva and provide high-quality genomic tools for future comparative and functional studies. [Formula: see text] Copyright © 2026 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Acute kidney injury (AKI) is a critical condition with high morbidity and mortality, often caused by ischemia/reperfusion (I/R) injury. Morroniside (MOR), derived from Cornus officinalis, has anti-inflammatory and antioxidant properties. This study investigates its effects on AKI induced by hypoxia/reoxygenation (H/R) in renal tubular epithelial cells. H/R-induced HK-2 cells were treated with MOR (0.5, 1.0, and 2.0 ‍μM). Cell viability was assessed using CCK-8, and oxidative stress was evaluated via reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) levels. Ferroptosis was examined through GPX4 and ACSL4 expression. The Nrf2/HO-1 signaling pathway was analyzed by Western blotting. Results show that MOR alleviates H/R-induced cell damage and oxidative stress by increasing cell viability, reducing lactate dehydrogenase (LDH) release, ROS, and MDA levels, while enhancing SOD and GSH activities. It also inhibits ferroptosis by upregulating GPX4 and downregulating ACSL4. Additionally, MOR activates the Nrf2/HO-1 signaling pathway. These findings suggest that MOR protects renal tubular epithelial cells from H/R injury by reducing oxidative damage and inhibiting ferroptosis, potentially through the Nrf2/HO-1 pathway.

Cornus mas L. is traditionally used for various medicinal purposes, although systematic data on its pharmacognostic properties are still limited. Considerable variation was observed among plant organs, so phenolic and flavonoid content varied by plant part, with location-related differences among samples, with the highest in leaf and fruit from Bijeljina and the lowest in leaf from Sarajevo. Antioxidant activity was much better in leaf and bark than in fruit. Extracts inhibited ESBL-producing Escherichia coli, with MICs mainly at 125 µg/mL; bark extract (Tuzla) showed 250 µg/mL and reduced biofilm formation. Leaf and bark extracts showed dose-dependent cytotoxicity against PC-9, MCF-7, and MDA-MB-231 cells, while fruit extracts were weaker. In human lymphocytes, bark (Bileća) and leaf (Tuzla) extracts decreased nuclear division and induced micronuclei at 200 µg/mL. Molecular docking indicated strong bacterial target binding for loganin and cornuside, supporting the antibacterial and antitumor potential of C. mas.

Although renowned for its ornamental value and extensive adaptability to heterogeneous environments, particularly in coastal saline-alkali region, the mechanism of salt tolerance in Cornus hongkongensis subsp. tonkinensis remains insufficiently explored. This study is to investigate the phenotypic, physiological, and transcriptomic responses of its seedlings exposure to a 0.3% salt solution for 55 days. Under the short-term salt stress (0-5 days), a significantly increment in proline content, while no significant responding in photosynthetic properties, were observed compared to the control (CK). However, after salt stress exceeded 30 days, superoxide dismutase (SOD) and the contents of osmotic regulators (soluble sugar, soluble protein and proline) significantly increased, along with a decline in photosynthetic efficiency. Through GO, KEGG, and WGCNA analyses, 12 candidate genes involved in chlorophyll synthesis, carotenoid biosynthesis, light-dependent reactions, Calvin cycle, and photorespiration were identified and found to be upregulated in the initial phase of salt stress. Amongst, transgenic Arabidopsis thaliana overexpressing chtSGAT exhibited enhanced seed germination rate and seedling growth under salt stress. The enhancement of Fv/Fm and Fv/F0 ratios, antioxidant system, and osmotic regulators in transgenic lines, were alleviated ROS accumulation. These results suggest that chtSGAT tend to be a promising candidate gene for enhancing salt tolerance of C. hongkongensis subsp. tonkinensis. Our study provides theoretical support for the large-scale cultivation of dogwood seedlings in saline-alkali areas.

BACKGROUND: Cornus officinalis is an important Chinese medicinal herb with high economic value. Carposina coreana Kim (Lepidoptera: Carposinidae) is a severe fruit-boring pest that inflicts devastating damage on C. officinalis. There is an urgent need to develop attractants to monitor and control this pest. RESULTS: Using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-electroantennogram detection (GC-EAD), we identified (Z)-7-eicosen-11-one and (Z)-7-tricosene as the female-produced sex pheromone components of C. coreana to attract its conspecific males. Field experiments showed that rubber septa dispenser baited with a blend of 1000 μg (Z)-7-eicosen-11-one and 500 μg (Z)-7-tricosene is the optimal lure formulation for attracting the male moths. Further experiments revealed that the most efficient traps are green Delta sticky traps, hung at 1.5-2.0 m aboveground from tree branches and ≈15-20 m from the forest edge. Finally, we validated the trap effectiveness in a 2-month monitoring survey conducted in three major C. officinalis production regions, and the identity of the captured insects was confirmed by DNA barcoding. CONCLUSION: We identified the sex pheromone components of C. coreana, which provide technical support for the monitoring and control of this pest. Our findings establish a foundation for developing sustainable pest management strategies to improve C. officinalis production. © 2026 Society of Chemical Industry. © 2026 Society of Chemical Industry.

This study aimed to investigate the effects of L-borneol on the molecular, biochemical, and histological damage caused by acrylamide (ACR) in the hippocampus of adult male Wistar rats. It also examined the impact of L-borneol on spatial memory and anxiety-like behaviors in these animals. Animals were divided into four groups: control, L-borneol, ACR, and ACR + L-borneol. ACR (25 mg/kg) and L-borneol (50 mg/kg) were administered orally for 21 consecutive days. L-borneol reduced levels of malondialdehyde and nitric oxide, increased glutathione content, and enhanced superoxide dismutase activity in the hippocampus of rats treated with ACR. In addition, L-borneol lowered the expression of pro-inflammatory markers, nuclear factor-κB, and inducible nitric oxide synthase in the hippocampus. It effectively prevented changes in the expression of apoptosis-related genes, which are associated with decreased neuronal death in the cornus ammonis 1 and dentate gyrus regions. Moreover, L-borneol increased the expression of sirtuin 1 (SIRT1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), brain-derived neurotrophic factor, and alpha 7-nicotinic acetylcholine receptors, while reducing the expression and activity of acetylcholinesterase. Finally, L-borneol improved spatial memory and reduced anxiety-like behaviors. In conclusion, L-borneol enhances behavioral performance in ACR-exposed animals by decreasing oxidative and nitrosative stress, as well as inhibiting inflammation and apoptosis. It appears that the upregulation of the SIRT1/Nrf2/HO-1 signaling pathway and the stimulation of acetylcholine signaling are crucial for mitigating ACR-induced neurotoxicity. © 2026. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Background: Mitochondrial dysfunction is a fundamental driver of skin aging, making the enhancement of cellular bioenergetics an important strategy in dermocosmetic innovation. Cornus officinalis fruit extract (COFE), standardized for iridoid glycosides, was investigated for its ability to modulate mitochondrial function and counteract photo-oxidative stress associated with skin aging. Methods: Human dermal fibroblasts were treated with COFE to evaluate mitochondrial bioactivation. Transcriptomic changes were assessed using RNA sequencing (RNA-seq), with key mitochondrial genes validated by qPCR. AMPK phosphorylation, intracellular ATP content, NAD+/NADH ratio, and mitochondrial membrane potential (ΔΨm) were quantified as functional indicators of mitochondrial performance. To examine anti-aging relevance, a reconstructed human epidermis model was challenged with UVA and retinol to induce photo-oxidative stress. COFE's effects on inflammatory (IL-1α), hydration (AQP3), proliferation (Ki67), and barrier-related (PKCα) markers were subsequently analyzed. Results: COFE was associated with activation of AMPK signaling and coordinated upregulation of OXPHOS-related genes in dermal fibroblasts, increasing ATP by 30.00%, the NAD+/NADH ratio by 158.71%, and ΔΨm by 158.82%. It also reduced IL-1α and upregulated AQP3, Ki67, and PKCα in a UVA/retinol-challenged epidermis model. In vivo, a 1% COFE eye cream produced statistically significant improvements across hydration, barrier function, redness, skin tone, wrinkles, elasticity, and periorbital contour after 28 days. Conclusions: COFE functions as an AMPK-associated mitochondrial bioenergetic modulator that enhances cellular energy metabolism and mitigates photo-oxidative stress in skin-relevant experimental models. The concordance between mechanistic findings and clinical outcomes supports COFE as a promising anti-aging active ingredient for dermocosmetic applications.

The big-bracted (Benthamidia) dogwood clade consists of small- to medium-sized deciduous trees within the genus Cornus, known for their showy spring-time floral bract display. Cornus is within the family Cornaceae and order Cornales, and as Cornales is one of the earliest diverging asterids, these taxa have been important for phylogenetic research. Three species within the big-bracted clade, flowering (Cornus florida), kousa (C. kousa), and Pacific (C. nuttallii) dogwoods, are popular ornamental landscape plants in North America, with more than 130 cultivars released. Despite their commercial popularity, numerous research gaps have limited the expansion of fundamental research and dogwood breeding programs. In this present review, we aim to provide a thorough overview of our current understanding of 1) the phylogenetic and biogeographic context, 2) plant biology and major pests and pathogens impacting commercialization, 3) historical commercialization and propagation methods, and 4) genetic and genomic resources and how they have been implemented to understand these species. Research gaps and future directions to advance basic research and breeding of big-bracted ornamental dogwoods are discussed throughout. This work is authored in part by Trinity P. Hamm, Robert N. Trigiano, Marcin Nowicki, Erin L. P. Moreau, Thomas J. Molnar, Q.Y. Jenny Xiang, Sarah L. Boggess, Tarek Hewezi, William E. Klingeman, Denita Hadziabdic, and Margaret E. Staton, © 2026 Battelle Energy Alliance, LLC.