To investigate the mechanism of Dazao (Ziziphi Jujubae Fructus) in reducing Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity based on network pharmacology and animal experiments.

The toxic components of Fuzi (Aconiti Lateralis Radix) and active constituents of Dazao (Ziziphi Jujubae Fructus) were screened through literature retrieval and database searches. Potential targets of toxic components were predicted using Swiss Target Prediction and PharmMapper databases, followed by construction of a comprehensive target library. A disease target library was established by retrieving “nerve toxicity” and “toxic encephalopathy”-related genes from biomedical databases. The intersection targets between component-related and disease-related targets were subsequently subjected to protein-protein interaction (PPI) network analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment. Comparative analysis of the identified detoxification pathways [from Dazao (Ziziphi Jujubae Fructus)] and neurotoxicity pathways [from Fuzi (Aconiti Lateralis Radix)] was performed to predict the underlying detoxification mechanisms. Using SD rats as the animal model, a quantitative real-time polymerase chain reaction (qRT-PCR) was employed to investigate the effects of Fuzi (Aconiti Lateralis Radix) and Dazao (Ziziphi Jujubae Fructus) combination therapy on mRNA expression levels of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and hypoxia inducible factor-1α(HIF-1α) in the brain tissues of the rats.

Through network pharmacology analysis, it identified 21 potential toxic components and 1169 potential toxic targets in Fuzi (Aconiti Lateralis Radix), including 570 neurotoxic targets. There were 29 active components in Dazao (Ziziphi Jujubae Fructus) with 680 corresponding targets. Venn analysis identified 76 overlapping targets as the potential detoxification targets through which Dazao (Ziziphi Jujubae Fructus) counteracted Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity. PPI network pharmacology identified quercetin, saponins and specific alkaloids as the primary mediators of Dazao (Ziziphi Jujubae Fructus) detoxification effects against Fuzi (Aconiti Lateralis Radix) neurotoxicity. The KEGG pathway analysis identified enrichment in 171 pathways, primarily involving signaling pathways such as the PI3K-AKT signaling pathway and HIF-1 signaling pathway. In vivo studies revealed that Fuzi (Aconiti Lateralis Radix) disrupted redox homeostasis in the rat brain, promoting oxidative stress, whereas co-administration with Dazao (Ziziphi Jujubae Fructus) effectively counteracted these pro-oxidative effects, q RT-PCR experiment results demonstrated that, compared with those of the control group, the mRNA levels of PI3K, AKT and HIF-1α in the cerebral cortex and hippocampal tissues of the rats in the Fuzi (Aconiti Lateralis Radix) group were significantly increased. Compared with those in the Fuzi (Aconiti Lateralis Radix) group, the mRNA expression levels of PI3K, AKT and HIF-1α in the cerebral cortex and hippocampus of rats in the Fuzi (Aconiti Lateralis Radix)-Dazao (Ziziphi Jujubae Fructus) combination group were significantly decreased.

The neuroprotective effect of Dazao (Ziziphi Jujubae Fructus) against Fuzi (Aconiti Lateralis Radix)-induced neurotoxicity is mediated through modulation of the PI3K/AKT/HIF-1 signaling pathway, thereby alleviating Fuzi (Aconiti Lateralis Radix)-triggered oxidative stress damage in rat brain tissues. These findings provide a novel perspective for network pharmacology research on toxic traditional Chinese herbs and offer new insights into the mechanism of toxicity reduction through herbal compatibility.

To investigate and analyze the protective effect of triptolide (TPL) on bleomycin (BLM)-induced pulmonary fibrosis in mice induced by integrin-mediated extracellular matrix remodeling.

Sixty male C57BL/6 mice were randomly divided into control group, model group, dexamethasone group (DXM group), TPL low and high dose groups, with 12 mice in each group. Blood gas analysis was performed in whole blood of abdominal aorta, oxygen partial pressure (PO₂) and blood oxygen saturation (SO₂) were recorded, the pulmonary histology was observed by HE staining, and the contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in mice sample in each group were detected. The interaction between triptolide and integrin β1 (ITG-β1) was confirmed by cell thermal migration assay (CESTA) and surface plasmonresonance assay (SPR), and the relative expression levels of ITG-β1, transforming growth factor-β1 (TGF-β1) and Smad3 were detected by Western blot.

The lung tissue integrity of mice in TPL low and high dose groups and DXM group was better, and the interstitial expansion of the lungs was reduced in these groups. At the same time, it was observed that the loss and fusion between the alveoli of the mice in TPL groups and DXM group were repaired, and the samples did not show significant interstitial inflammatory infiltration, effectively alleviating fibrosis. Compared with those in the control group, the levels of PO₂, SO₂, SOD and GSH-Px in the model group were significantly decreased, and MDA content was significantly increased (P<0.01). Compared with those in the model group, the levels of PO₂, SO₂, SOD and GSH-Px in the DXM group, TPL low and high dose groups were significantly increased, while the content of MDA was significantly decreased (P<0.05). Compared with those in the TPL low dose group, the effect of TPL high dose group was more obvious, and the levels of PO₂, SOD and GSH-Px were increased more significantly (P<0.05). The results of CESTA and SPR experiments indicated that triptolide interacted with ITG-β1 and was a possible anti-pulmonary fibrosis target. Compared with those of the control group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of the model group were increased (P<0.01). The protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the DXM group, TPL low and high dose groups were lower than those in the model group (P<0.05), and compared with those in the DXM group and TPL low dose group, the protein expression levels of ITG-β1, TGF-β1 and Smad3 in lung tissue of mice in the TPL high dose group were decreased (P<0.05).

TPL can protect pulmonary fibrosis induced by bleomycin through extracellular matrix remodeling mediated by integrin, and the fibrosis-related change protein induced by integrin can be used as the target of TPL in the treatment of pulmonary fibrosis.

It aimed to investigate the potential causal relationship between eye-image features and CHD, as examined by coronary angiography (CAG).

The study selected the patients hospitalized in the Department of Cardiology from November 15, 2021 to February 27, 2022. The selected patients were divided into two groups based on their CAG findings: the CHD group (at least one coronary lesion stenosis≥50%) and the control group (lesion stenosis<50%).

The final analysis included 342 patients out of a total of 426 participants, and 165 (48.2%) were diagnosed with CHD among these participants. The study found that certain characteristics in the left region 5 (L5) and right region (R5) were associated with CHD, including L5 pink dark speckle (OR: 4.143, 95%CI[1.135, 15.124], P=0.031), L5 vascular tortuosity (OR: 0.234, 95%CI[0.077, 0.71], P=0.010), R5 dark red blood vessels (known as blood meridian in TCM)(OR: 1.683, 95%CI[1.035, 2.738], P=0.036) and R5 yellowish mounds (OR: 2.083, 95%CI[1.221, 3.554], P=0.007). Multivariate regression analyses showed that L5 vascular tortuosity had a negative correlation with CHD.

The study revealed that four types of eye-image features, namely pink dark speckle, vascular tortuosity, dark red blood vessels and yellowish mounds, were associated with CHD. A-mong these features, vascular tortuosity showed a negative correlation with CHD, which could potentially aid in the diagnosis of the disease.

To observe the effects of Kangxian Yixin Decoction (抗纤益心方, KYD) on cardiomyocyte apoptosis and endoplasmic reticulum stress-related factors glucose regulated protein 78 (GRP78), activating transcription factor 6 (ATF6) and C/EBP homologous protein (CHOP) in mice with dilated cardiomyopathy (DCM), and to explore the mechanism of KYD regulating GRP78/ATF6 signaling pathway to improve the apoptosis of DCM cardiomyocytes.

According to the random number table method, 40 cTnT^R141W transgenic DCM mice were divided into model group, KYD high and low dose (5.4 g/kg, 2.7 g/kg) groups and captopril (0.01 g/kg) group, with 10 mice in each group. Another C57BL/6J mice were set up as the normal group. Left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), ejection fraction (EF) and reduction rate (FS) were detected by ultrasonography in small animals. Myocardial pathological morphology was observed by HE staining, endoplasmic reticulum ultrastructure was observed by electron microscopy, and myocardial apoptosis was detected by TUNEL method. The expression levels of GRP78 and ATF6 in myocardial tissue of mice were detected by immunohistochemistry (IHC) method. The mRNA and protein expressions of GRP78, ATF6, CHOP, Bax and Bcl-2 were detected by Real-time PCR and Western blot, respectively.

Compared with those in the normal group, the levels of LVESD and LVEDD were increased in the model group, the levels of FS and EF were decreased (P<0.05), myocardial pathological injury and apoptosis number increased (P<0.01), endoplasmic reticulum structure was damaged and enlarged. The expressions of GRP78 and ATF6 were increased by IHC (P<0.05). The mRNA expressions of GRP78, ATF6 and CHOP were increased (P<0.05). The expressions of GRP78, ATF6, CHOP and Bax were increased, while the expression of anti-apoptotic factor Bcl-2 was decreased (P<0.05). Compared with those in the model group, the levels of LVESD and LVEDD were decreased, the levels of FS and EF were increased (P<0.05), myocardial injury was alleviated, the apoptosis was decreased, the endoplasmic reticulum was damaged and enlarged, and IHC results showed that the expressions of GRP78 and ATF6 were decreased (P<0.05、P<0.01) in the KYD groups. The mRNA expressions of GRP78, ATF6 and CHOP were decreased (P<0.05, P<0.01). The expressions of GRP78, ATF6, CHOP and Bax were decreased (P<0.05, P<0.01), while the expressions of anti-apoptotic factor Bcl-2 were increased (P<0.05, P<0.01).

KYD can inhibit DCM cardiomyocyte apoptosis and improve the cardiac function in mice, and its mechanism may be related to inhibiting endoplasmic reticulum stress and down-regulating ATF6/GRP78 signaling pathway.