Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ 42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.

Cadmium (Cd) accumulation in rice grains poses severe health risks. Conventional straw amendments exhibit inconsistent efficacy, likely because of variations in amendment types and soil sulfur deficiency. The pot experiment was evaluated in a Cd-contaminated paddy soil (3.18 mg Cd kg-1) to compare three treatments (1.0 % w/w) sources: WS (wheat straw), CW (wheat straw compost), and BW (wheat straw biochar) without or with sodium sulfate fertilization (30 mg sulfur kg-1). This experiment aimed to evaluate the Cd mobility, microbial diversity, and Cd accumulation in rice tissues. All treatments resulted in reduced Cd accumulation in brown rice at the maturity stage by 3 % (WS), 26 % (CW), and 60 % (BW), whereas sulfate co-application enhanced this reduction to 30 % (WS+S), 38 % (CW+S), and 66 % (BW+S). This could be attributed to decrease in soil Cd availability (17 %, 37 %, and 41 % for WS+S, CW+S, and BW+S, respectively, at the maturity stage), inhibition of Cd uptake by root iron plaque (-0.01 to -0.05), and decrease of Cd translocation in rice tissues (particularly phloem transfer). Microbial analysis revealed that biochar and compost preferentially increased bacterial alpha diversity and shifted microbial composition irrespective of sulfate supply, especially at the tillering and booting stages. Specifically, biochar and compost reduced Firmicutes (positively related to exchangeable Cd, P ≤ 0.01), and increased Bacteroidota and Proteobacteria (negatively related to exchangeable Cd, P ≤ 0.01) at these stages. These findings demonstrate that co-application of wheat straw biochar and sulfate offers a solution for remediating Cd-contaminated paddy soils while considering soil ecosystem health.

The ratio of soil dissolved organic carbon to nitrogen (DOC:N) influences mineralization and immobilization, consequently impacting soil nitrate nitrogen (NO3--N) accumulation and leaching. However, its relationship with soil NO3--N leaching remains ambiguous, especially in soil profiles. This study employed a soil column leaching experiment and a field investigation to elucidate the association between soil DOC:N ratios and potential leaching risk of NO3--N in fluvoaquic soil across three depths (0-20 cm, topsoil; 20-40 cm, subsoil; 40-60 cm, third-layer soil). Soil column demonstrated a positive linear correlation between both NO3--N concentration and the amount of leached NO3--N in soil leachate and soil NO3--N content extracted via cascade extraction methods. Within each soil layer, both parameters exhibited an exponential decrease with increasing soil DOC:N. Field validation confirmed robust negative exponential correlations between soil DOC:N and the corresponding NO3--N concentration in field soil solutions. High protease activity and high nitrogenase activity were respectively observed under low soil DOC:N ratio and high soil DOC:N ratio. Based on Groundwater Quality Standard (20 mg NO3--N L-1), critical DOC:N thresholds were established at 0.117 (topsoil), 0.145 (subsoil), and 0.137 (third-layer soil). The potential leaching risk of NO3--N was assessed by the DOC:N of soil collected from three depths in 2017. The potential risk for NO3--N leaching across all three layers showcased a consistent spatial distribution pattern: higher risks were identified around greenhouse land on the east bank of Chaobai River. These findings indicate that soil DOC:N can serve as an indicator for evaluating potential nitrate leaching risk.

Examining how hypoglycemic medications affect brain function is one of the best approaches to addressing cognitive impairment. In this study, trelagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, was utilized to assess memory loss in diabetic rats through fear conditioning tests. Trelagliptin restored fear memory in diabetic rats that had been disrupted over a relatively long period (24 h) or extended period (5 days). Moreover, trelagliptin treatment reduced the higher incidence of neuronal cell death in the cerebral cortex, as observed via Nissl or hematoxylin and eosin staining. Subsequent analyses revealed that diabetic rats exhibited elevated levels of inflammatory cytokines (p-IKKα and p-NFκB) and a trend toward oxidative damage, indicated by malondialdehyde (MDA), superoxide dismutase 2 (SOD2), and glutathione peroxidase 4 (GPX4) detection. However, administration of trelagliptin reversed these markers to baseline levels. Additionally, trelagliptin activated p-AMPK, p-AKT, and p-GSK-3β. Notably, trelagliptin upregulated the expression of postsynaptic density protein 95 (PSD95) and synaptotagmin 1 (SYT1) while downregulating amyloid precursor protein (APP) and beta-site amyloid precursor protein cleaving enzyme 1 (BACE1). These findings suggest that trelagliptin alleviates cognitive impairment in diabetic rats, likely through AMPK-AKT-GSK-3β-mediated mitigation of oxidative stress, enhancement of synaptic plasticity, and reduction of Aβ accumulation.

Sulfur (S) is essential for rice growth and plays a pivotal role in soil pollution remediation. Wheat straw (W) amendment and sulfate (SO42-) fertilization are common agricultural practices in rice cultivation, yet their combined effects on S transformation, including organic sulfur (OS), available sulfate (AS), and reduced inorganic sulfur (RIS), in waterlogged paddy soils remain poorly understood. We conducted a 162-day incubation experiment with different W levels (0 %, 0.1 %, 0.5 %, and 1.0 %, w/w) and S rates (0 and 30 mg center dot sulfur center dot kg-1, as SO42-) in flooded soil. The results demonstrated that both W and S applications alone enhanced RIS formation, and their coapplication exhibited synergistic effects. Compared to the control, the co-application of W and S increased the proportion of RIS in total S by 76 % (90 %), 70 % (54 %), and 94 % (65 %) with 0.1 %, 0.5 %, and 1.0 % W at the early (middle) stages of incubation, respectively. The increase of RIS was attributed to the enhanced reduction of iron oxides and SO42-, mediated by reducing bacteria (especially Fe reducing bacteria) under low pe + pH. Besides, W addition increased AS levels during the early stage irrespective of S application, especially at 1 % W, due to organic sulfate mineralization. In addition, the influence of W and S applications on S transformation diminished over time. These findings suggest that the co-application of W and S under waterlogged soil could optimize sulfate bioavailability and RIS formation, which could meet the demand of rice sulfur nutrition and contribute to soil pollution remediation.

Straw incorporation and sulfur fertilizer are considered promising agronomic practices for remediating cadmium (Cd)-contaminated soil. However, their combined effects on Cd availability and soil bacterial communities in paddy soil remain unclear and may vary depending upon initial soil Cd levels. In this study, we conducted a 162day incubation experiment under waterlogged conditions, applying wheat straw (0 and 1 % w/w) and sulfate (0 and 30 mg kg- 1) individually or in combination to soils with high Cd (3.18 mg Cd kg- 1) and low Cd (0.18 mg Cd kg- 1) contamination. At the early stage, straw alone (W) or in combination with sulfate (W + S) reduced dissolved Cd concentration in both the low- and high-Cd soils. However, an increase in exchangeable Cd was observed only in the low-Cd soil during this period. Sulfate application (S) alone had no significant effect on either dissolved or exchangeable Cd. Both W and W + S treatments reduced bacterial community alpha diversity in the low- and high-Cd soil, primarily effecting the relative abundance of Firmicutes, Bacteroidota, Proteobacteria, and Acidobacteriota. Change in bacterial communities and soil properties, including an increase in dissolved organic carbon and decreases in Eh and pH, were associated with shifts in Cd availability. The effect of straw and sulfate application on Cd availability and bacterial community diversity varied with Cd contamination levels. Overall, straw incorporation, either alone or with sulfate, may help reduce Cd availability and modulate microbial communities in high-Cd paddy soil.

Heart failure is a major health issue that threatens life and health. Previous studies have shown that heart failure is the terminal stage of arrhythmia, dilated cardiomyopathy, hypertension, hypertrophic cardiomyopathy and myocardial infarction. The pathological mechanisms through which cardiovascular diseases result in heart failure include myocardial fibrosis and hypertrophy, myocardial cell death, mitochondrial dysfunction, vascular remodeling and calcium dysregulation. However, the detailed molecular mechanisms of heart failure remain elusive because of its complexity, hindering the development of intervention approaches for heart failure. The present study reviewed recent research progress on heart failure and provided references and strategies for the prevention and treatment of heart failure.

Schisandrin A (SchA), a bioactive lignan that was isolated from the dried fruit of Schisandra chinensis, has attracted much attention because of its diverse spectrum of pharmacological effects. The aim of this study is to clarify the function of SchA in diabetes-related fear memory impairment and its molecular mechanisms. Rats are randomly assigned to 4 groups: the control group (Con group), the DM group, the DM + SchA group, and the Con + SchA group. The results demonstrate that SchA treatment improves insulin sensitivity, reduces blood glucose, and significantly reduces memory impairment. SchA treatment also prevents histological damage, enhances synaptic protein production, and significantly decreases Aβ 42 formation in the diabetic prefrontal cortex. Further research reveals that SchA therapy decreases microglial activation and the expression levels of variables linked to inflammation while increasing the phosphorylation of proteins implicated in the insulin resistance signaling pathway. Furthermore, in the prefrontal cortex of diabetic rats, SchA decreases ferroptosis by increasing the protein expressions of GPX4, SLC7A11, Nrf2, HO-1, and SIRT1. Overall, our findings suggest that SchA may lessen diabetes-associated fear memory impairment symptoms by, most likely, lowering ferroptosis and inflammatory responses in the prefrontal brain of diabetic rats. SchA may be a useful therapy for diabetes, including memory impairment.

The effects of straw incorporation on controlling the accumulation of cadmium (Cd) in brown rice are variable or even inconsistent, which could be attributed to the difference of straw application level, soil sulfur deficit, and Cd level. Herein, exposed to three levels of soil Cd (low Cd 0.13 mg kg−1, medium Cd 1.11 mg kg−1, and high Cd 2.99 mg kg−1), a pot experiment was carried out to examine the effects of three wheat straw levels (0

Lakes are integral to the carbon cycle through the processing of dissolved organic matter (DOM). However, the specific contributions of various aquatic plants to carbon emissions during their decomposition remain inadequately understood. In this study, decomposition experiments were performed on three aquatic plants-algae, Phragmites australis (PA), and Potamogeton crispus L. (PC)-using advanced techniques, including FT-ICR-MS and metagenomics, to investigate the mechanisms of carbon dioxide (CO2) and methane (CH4) emissions. The results indicate that algae exhibit a substantial potential for CO2 emissions, with emissions reaching up to 2193 μmol·g-1. Conversely, PA contributes the highest CH4 emissions, reaching up to 2397 μmol·g-1. Factors such as the protein-like content and aromaticity of DOM molecules significantly influence emission levels. DOM with lower aromaticity undergoes easier decomposition in the first 6 days, leading to increased CO2 production. Elevated C/N and C/P ratios in plants enhance the abundance of methanogenic bacteria and genes. Surplus carbon will be mineralized under anaerobic conditions, giving rise to mineralization of organics to CH₄. These findings elucidate the mechanisms underlying CO2 and CH4 emissions during the decomposition of different aquatic plants and provide valuable insights for lake water environment management.

The accurate identification and assessment of comprehensive risks associated with compound pollution in agricultural ecosystems remain significant challenges due to the complexity of pollution sources, soil heterogeneity, and spatial variability. In this study, bivariate local indicators of spatial association (LISA) were applied to analyze the spatial interaction between heavy metals (HMs) and polycyclic aromatic hydrocarbons (PAHs) in farmland soils in Hezhang County. The results revealed distinct clusters with elevated concentrations of both HMs and PAHs, predominantly in areas affected by long-standing lead-zinc mining and smelting activities. Positive matrix factorization (PMF) was utilized to identify mining and smelting activities, and associated coal consumption as common sources of both pollutants, contributing 53 % and 28 %, respectively. Ecological health risk assessment results indicated that the combined pollution in this area has led to particularly severe ecological and cancer risks, with the pollution coefficient (Pc) exceeding 3.0, and risk values for both adults and children surpassing the threshold of 10-4. Through the integration of advanced bivariate LISA mapping and thorough risk assessment, this study precisely delineated ecological risk zones (33.1 %) and more refined health risk zones (40.1 %) associated with combined pollution. The southwest of Hezhang was identified as a critical hotspot for combined pollution risks, primarily due to intensive mining and smelting activities in the region. Overall, this study underscores the utility of bivariate LISA as a robust approach for delineating spatial clustering patterns caused by combined pollutants. It provides crucial insights for identifying regions with heightened human health and ecological risks in rural settings.

ETHNOPHARMACOLOGICAL RELEVANCE:Salvia miltiorrhiza Bunge (S. miltiorrhiza) is an important Traditional Chinese herbal Medicine (TCM) used to treat cardio-cerebrovascular diseases. Based on the pharmacodynamic substance of S. miltiorrhiza, the aim of present study was to investigate the underlying mechanism of S. miltiorrhiza against cardiac fibrosis (CF) through a systematic network pharmacology approach, molecular docking and dynamics simulation as well as experimental investigation in vitro. MATERIALS AND METHODS:A systematic pharmacological analysis was conducted using the Traditional Chinese Medicine Pharmacology (TCMSP) database to screen the effective chemical components of S. miltiorrhiza, then the corresponding potential target genes of the compounds were obtained by the Swiss Target Prediction and TCMSP databases. Meanwhile, GeneCards, DisGeNET, OMIM, and TTD disease databases were used to screen CF targets, and a protein-protein interaction (PPI) network of drug-disease targets was constructed on S. miltiorrhiza/CF targets by Search Tool for the Retrieval of Interacting Genes/Proteins (STING) database. After that, the component-disease-target network was constructed by software Cytoscape 3.7. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the intersection targets between drug and disease. The relationship between active ingredient of S. miltiorrhiza and disease targets of CF was assessed via molecular docking and molecular dynamics simulation. Subsequently, the underlying mechanism of the hub compound on CF was experimentally investigated in vitro. RESULTS:206 corresponding targets to effective chemical components from S. miltiorrhiza were determined, and among them, there were 82 targets that overlapped with targets of CF. Further, through PPI analysis, AKT1 and GSK3β were the hub targets, and which were both enriched in the PI3K/AKT signaling pathway, it was the sub-pathways of the lipid and atherosclerosis pathway. Subsequently, compound-disease-genes-pathways diagram is constructed, apigenin (APi) was a top ingredients and AKT1 (51) and GSK3β (22) were the hub genes according to the degree value. The results of molecular docking and dynamics simulation showed that APi has strong affinities with AKT and GSK3β. The results of cell experiments showed that APi inhibited cells viability, proliferation, proteins expression of α-SMA and collagen I/III, phosphorylation of AKT1 and GSK3β in MCFs induced by TGFβ1. CONCLUSION:Through a systematic network pharmacology approach, molecular docking and dynamics simulation, and confirmed by in vitro cell experiments, these results indicated that APi interacts with AKT and GSK3β to disrupt the phosphorylation of AKT and GSK3β, thereby inhibiting the proliferation and differentiation of MCFs induced by TGFβ1, which providing new insights into the pharmacological mechanism of S. miltiorrhiza in the treatment of CF.

Biochar can serve as a soil amendment to immobilize soil nitrogen (N) and reduce N leaching from cropland without negative effect on crop yield. However, the interaction effect of biochar application and irrigation regimes on soil N status (N retention and N loss) and crop yield is rarely reported in the open perennial vegetable field. A two-years field trial (transplanting in first year and consecutive growth in second year) was conducted in citron daylily vegetable cropping system on a sandy brown alluvial soil. Two biochar application rates (0 and 30 t ha−1) and three irrigation regimes (CDI, conventional drip irrigation; WSDI, water-saving drip irrigation with 80% of full irrigation quota; APRDI, alternate partial root-zone drip irrigation with 80% of full irrigation quota) were included. The response of crop yield and soil N status to both biochar application and irrigation regimes varied across planting years for perennial citron daylily. After the first planting year's harvest, APRDI enhanced flower bud yield by 18–28% compared to CDI and WSDI, likely due to improved nitrate use efficiency evidenced by lower soil nitrate retention in the surface soil (0–20 cm) post-harvest. However, biochar application resulted in a reduction of yield by 27% under APRDI. Additionally, WSDI with reduced yields, decreased soil TN in the sub-surface layer (20–50 cm) with 9–19% by comparison with other two irrigation regimes, resulting in higher TN concentration in the soil solution (14–28%) in and thus an increased risk for N leaching. However, after the second harvest year, there were no variations in crop yield induced by biochar application and irrigation regimes. Irrigation regimes exhibited limited influence on soil N status, while biochar application mitigated soil nitrogen decline in the 0–50 cm layer by enhancing organic nitrogen retention capacity for nearly 16–85%. Furthermore, the lowest TN concentration in the soil solution in the sub-surface layer (20–50 cm) with biochar application under APRDI suggested a reduced risk for N leaching. We conclude that combining biochar application with the APRDI regime could help retain soil N, decrease the risk of N leaching, and enhance crop yield in total for two consecutive planting years. Therefore, this approach is recommended for sustainable N management in long-term planting of perennial crops.

Intensified industrial activities significantly threaten farmland soil integrity, particularly in salinized regions. However, comprehensive evaluations of soil fertility and contamination by polycyclic aromatic hydrocarbons (PAHs) remain limited. In this study, we assessed soil quality in China’s Yellow River Delta (YRD) by quantifying 13 indicators of soil physicochemical and biological properties, along with 11 PAHs. Our findings reveal that the minimum data set approach provides a robust and comprehensive representation of overall soil fertility. Salinity emerged as the primary limiting factor, with strong correlations between salinity and key ions, highlighting its adverse effects on soil structure and function. Additionally, significant PAH contamination was detected, particularly from benzo[a]anthracene (BaA), fluoranthene (Flu), and chrysene (Chr), as indicated by the Nemerov pollution index. A pronounced negative correlation between the soil quality index (SQI) and the soil environmental index (SEI) underscores the substantial role of PAH pollution in soil degradation. Notably, the SQI integrates both SEI and soil fertility, providing a holistic assessment of soil health. These findings highlight the utility of SQI as a diagnostic tool for evaluating soil degradation and emphasize the need for targeted remediation strategies to address salinity and PAH contamination, thereby promoting soil restoration and agricultural sustainability.

The impacts of biochar application on the carbon (C) and nitrogen (N) cycles in soil profiles in vegetable fields have rarely been reported. A three-year field experiment (CK, control; BC, biochar; N, nitrogen fertilizer; BCN, biochar and nitrogen fertilizer) was conducted in fluvo-aquic soil with a wild cabbage-Chinese cabbage rotation to investigate biochar effects on soil organic carbon (SOC) sequestration, N retention, and nitrate (NO3-) leaching in the soil profile (topsoil, 0-20 cm; subsoil, 20-50 cm; third-layer soil, 50-100 cm). The results showed that the biochar-induced increase in topsoil SOC under N fertilization was greater for Chinese cabbage season than for wild cabbage season. Excluding biochar-N, biochar application caused an extra increase in topsoil total nitrogen (TN) under N fertilization. Biochar decreased the NO3--N concentration of third-layer soil solution, particularly under N fertilization, indicating that biochar reduced the potential source of NO3- leaching. Under N fertilization, biochar reduced the abundances of carbon-degrading bacteria (Streptomyces, Bacillus, Mycobacterium, and Sphingomonas) and genes (sga, xylA, lig, and pgu) in the topsoil, as well as the abundances of ammonia-oxidizing bacteria (Nitrosospira and Nitrosomonas) and gene (amoA) in the third-layer soil. However, biochar increased the abundance of ammonia-assimilating bacteria (Rhodococcus) and gene (glnA) in the topsoil. Biochar inhibited the microbial function associated with C degradation by affecting soil TN, thus enhancing topsoil SOC sequestration. Biochar promoted the soil microbial function related to ammonia assimilation by affecting dissolved organic carbon (DOC), subsequently enhancing ammonia assimilation. Moreover, biochar initially inhibited ammonia oxidation in the third-layer soil by increasing soil DOC, subsequently affecting nitrite oxidation and ultimately reducing soil NO3- leaching. Biochar significantly increased the N use efficiency of vegetables in the last two years. This study provides insights into biochar effects on the changes in soil microbial function, which promoted SOC sequestration, enhanced N retention and mitigated nitrate leaching in a vegetable rotation field.

Activation of brown adipose tissue (BAT) thermogenesis increases energy expenditure and alleviates obesity. Here we discover that histone methyltransferase suppressor of variegation 4-20 homolog 2 (Suv420h2) expression parallels that of Ucp1 in brown and beige adipocytes and that Suv420h2 knockdown significantly reduces - whereas Suv420h2 overexpression significantly increases - Ucp1 levels in brown adipocytes. Suv420h2 knockout (H2KO) mice exhibit impaired cold-induced thermogenesis and are prone to diet-induced obesity. In contrast, mice with specific overexpression of Suv420h2 in adipocytes display enhanced cold-induced thermogenesis and are resistant to diet-induced obesity. Further study shows that Suv420h2 catalyzes H4K20 trimethylation at eukaryotic translation initiation factor 4E-binding protein 1 (4e-bp1) promoter, leading to downregulated expression of 4e-bp1, a negative regulator of the translation initiation complex. This in turn upregulates PGC1α protein levels, and this upregulation is associated with increased expression of thermogenic program. We conclude that Suv420h2 is a key regulator of brown/beige adipocyte development and thermogenesis.

Cardiovascular diseases (CVDs) are major public health problems that threaten the lives and health of individuals. The article has reviewed recent progresses about ferroptosis and ferroptosis-related intervention approaches for the treatment of CVDs and provided more references and strategies for targeting ferroptosis to prevent and treat CVDs. A comprehensive review was conducted using the literature researches. Many ferroptosis-targeted compounds and ferroptosis-related genes may be prospective targets for treating CVDs and our review provides a solid foundation for further studies about the detailed pathological mechanisms of CVDs. There are challenges and limitations about the translation of ferroptosis-targeted potential therapies from experimental research to clinical practice. It warrants further exploration to pursure safer and more effective ferroptosis-targeted thereapeutic approaches for CVDs.

Purpose. Type 2 diabetes mellitus is considered as one of the risk factors for cognitive impairment. DPP4 inhibitors are effective drugs for the treatment of type 2 diabetes mellitus. However, the relationship between DPP4 inhibitors and cognitive dysfunction remains unclear. Therefore, we used a meta-analysis to determine the association between DPP4 inhibitors and cognitive impairment in type 2 diabetes mellitus. Methods. We systematically searched PubMed, CNKI, and the Cochrane Library at the time of establishment, 2022, and then made inclusion criteria and screened strategies to identify studies with more precise correlations. Results. We included 10 studies with 5,583 participants. The data showed that DPP4 inhibitors significantly reduced the incidence rate of cognitive impairment in type 2 diabetes mellitus (SMD: 0.99; 95% CI [0.59, 1.38]). Furthermore, there was a linear correlation found between cognitive impairment in type 2 diabetes mellitus and fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. DPP4 inhibitors decreased fasting blood glucose (FPG) (SMD: 0.52; 95% CI [−0.68, −0.37]), blood glucose (2hPPG) at 2 hours after the meal (SMD: 0.82; 95% CI, [−1.2, −0.43]), and HbA1c (SMD: 0.34; 95% CI [−0.48, −0.21]). All data were statistically significant (P<0.0001). Furthermore, we conducted subgroup analyses of the following measures at various treatment durations and ages: cognitive scores, fasting blood glucose, glycosylated hemoglobin, and two-hour postprandial blood glucose. Conclusion. DPP4 inhibitors significantly improved type 2 diabetic mellitus individuals’ cognitive impairment and reduced fasting blood glucose, 2-hour postprandial blood glucose, and glycosylated hemoglobin. Subgroup analysis showed that people aged 60 to 70 years had better treatment effects at 0–180 days. This trial is registered with CRD42023399473.

Celastrol, the primary constituent of Tripterygium wilfordii, has demonstrated neuroprotective properties in rats with dementia by reducing inflammation. A high-fat diet and streptozotocin injection were utilized to establish a diabetic rat model, which was then employed to investigate the possible protective effect of celastrol against the development of diabetes-induced learning and memory deficits. Afterwards, the experimental animals received a dose of celastrol by gavage (4 mg/kg/d). An animal study showed that celastrol enhanced insulin sensitivity and glucose tolerance in diabetic rats. In the Morris water maze test, rats with diabetes performed poorly in terms of spatial learning and memory; treatment with celastrol improved these outcomes. Additionally, administration of celastrol downregulated the expression of inflammatory-related proteins (NF-κB, IKKα, TNF-α, IL-1β, and IL-6) and greatly reduced the generation of Aβ in the diabetic hippocampus tissue. Moreover, the insulin signaling pathway-related proteins PI3K, AKT, and GSK-3β were significantly upregulated in diabetic rats after celastrol was administered. Also, celastrol prevented damage to the brain structures and increased the synthesis of synaptic proteins like PSD-95 and SYT1. In conclusion, celastrol exerts a neuroprotective effect by modulating the insulin signaling system and reducing inflammatory responses, which helps to ameliorate the cognitive impairment associated with diabetes.