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Background: Huanshaodan (HSD) is a Chinese Herbal Compound which has a definite clinical effect on Alzheimer's disease (AD), however, the underlying mechanism remains unclear. The aim of this study is to preliminarily reveal the mechanism of HSD in the treatment of AD model of SAMP8 mice. Methods: Chemical composition of HSD and its drug-containing serum were identified by Q-Orbitrap high resolution liquid mass spectrometry. Six-month-old SAMP8 mice were treated with HSD and Donepezil hydrochloride by gavage for 2 months, and Wogonin for 28 days. Behavioral test was performed to test the learning and memory ability of mice. Immunofluorescence (IF) or Western-blot methods were used to detect the levels of pSer404-tau and β-amyloid (Aβ) in the brain of mice. Hematoxylin–eosin (H&E) staining and Transmission electron microscopy (TEM) assay was applied to observe the pathological changes of neurons. Proteomic technology was carried out to analyze and identify the protein network of HSD interventions in AD. Then the pathological process of the revealed AD-related differential proteins was investigated by IF, Q-PCR, Western-blot, Fluorescence in situ hybridization (FISH) and 16S rRNA sequencing methods. Results: The results showed that HSD and Wogonin, one of the components in its drug-containing serum, can effectively improve the cognitive impairments of SAMP8 mice, protect hippocampal neurons and synapses, and reduce the expression of pSer404-tau and Aβ. HSD and Wogonin reduced the levels of fibrinogen β chain (FGB) and γ chain (FGG), the potential therapeutic targets revealed by proteomics analysis, reduced the colocalization of FGB and FGG with Aβ, ionized calcium binding adaptor molecule 1 (Iba-1), glial fibrillary acidic protein (GFAP), increased level of and myelin basic protein (MBP). Meanwhile, HSD and Wogonin increased ZO-1 and Occludin levels, improved brain microvascular injury, and reduced levels of bacteria/bacterial DNA and lipopolysaccharide (LPS) in the brain of mice. In addition, 16S rRNA sequencing indicated that HSD regulated the structure of intestinal microbiota of mice. Conclusion: The effects of HSD on AD may be achieved by inhibiting the levels of fibrinogen and the interactions on glia cells in the brain, and by modulating the structure of intestinal microbiota and improving the blood–brain barrier function. [ABSTRACT FROM AUTHOR]

Objective To explore the active components, targets and possible mechanism of Yishen Tongluo (Kidney-boosting Collateral-unblocking) Formula (YSTLF) in the treatment of diabetic kidney disease (DKD) based on network pharmacology. Methods The effective components and related targets of YXTLF were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform ( TCMSP), The Encyclopedia of Traditional Chinese Medicine ( ETCM) and A Bioinformatics Analysis Tool for Molecular mechanism of Tradition Chinese Medicine (BATMAN-TCM), and further supplemented with literature research. Then these components and targets were associated with the target information related to DKD in GeneCards, OMIM, TTD and DrugBank databases. Based on the protein-protein interaction (PPI) network constructed by String11. 0 software, the key targets corresponding to the main active components in YSTLF were obtained. The "component-disease-target" regulatory network diagram with TCM compounds was constructed by cytoscape 3. 8. 0, and the pharmacodynamic mechanism of YSTLF in the treatment of DKD was preliminarily predicted. At the same time, gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) enrichment analysis were carried out using R language BioConductor and pathview software to reveal the functions of related target genes and pathways. With the mesangial cells ( SV40-MES-13) of mice induced by high glucose as the main research object, the effects of YSTLF on the expression of key target genes and the regulation of related pathways were verified by luciferase reporter gene detection, RT-qPCR and western blot. Results 108 active components of YSTLF with potential therapeutic effect of DKD and 417 corresponding targets were screened. The " component-disease-target" network diagram suggested that kaempferol and astragaloside were the main active components in YSTLF in the treatment of DKD, and Akt and IL-6 were the key targets of the above-mentioned chemical components. The result of GO functional annotation and KEGG pathway enrichment showed that the selected key targets were mainly involved in a series of biological reactions, such as drug immune response, oxidative stress response, inflammatory response, and signal transduction, etc., and were mainly involved in the regulation of AGE-RAGE and PI3K/ AKT signal pathways. The result showed that YSTLF could effectively improve the activation of inflammation related indexes TNF-α and IL-6 and fibrosis related indexes TGF-β1, α-SMA and Col-I in SV40-MES-13 cells in mice induced by high glucose. Conclusion Yishen Tongluo Formula seems to be multi-component, multi-target and multi-pathway in the treatment of DKD. It may play a role in the treatment of DKD by regulating AGE-RAGE and PI3K/ AKT signal pathways, thus inhibiting inflammatory reaction and renal tissue fibrosis. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common cause of dementia. The emerging data suggest that cognitive decline occurred in the setting of A β accumulation with synaptic dysfunction, which started to happen at preclinical stages. Then, presymptomatic intervention is more critical to postponing AD processing. Traditional Chinese medicine has a long history of treating and preventing dementia. Findings have shown that the decoction of Panax notoginseng and Gardenia jasminoides Ellis enhances memory functions in patients with stroke, and their main components, Panax notoginseng saponins (PNS) and geniposide (GP), improved memory abilities in experimental AD models. Since herbal medicine has advantages in protection with few side effects, we wish to extend observations of the NeuroProtect (NP) formulation for reducing amyloid- β and restoring synaptic structures in APP/PS1 transgenic mice. Methods: APP/PS1 transgenic mice and their wild-type littermates were fed with control, NP, and their components from 4 to 7 months of age. We assessed the synaptic structure by Golgi staining, analyzed the amyloid deposits by Thioflavin-S staining, and measured related protein levels by Western blot or ELISA. We used the Morris water maze and shuttle box test to evaluate cognitive functions. Results: Compared to WT mice, APP/PS1 mice are characterized by the accumulation of amyloid plaques, reducing synaptic structure richness and memory deficits. NP prevents these changes and ameliorates cognitive deficits. These effects may have been due to the contribution of its components by inhibition of insoluble amyloid- β deposition and restoration of synaptic structures. Conclusion: These findings reveal a beneficial effect of NP on AD progression under an early intervention strategy and provide a food supplement for AD prevention. [ABSTRACT FROM AUTHOR]

Background: Chinese Herbal Medicines (CHMs), as an important and integral part of a larger system of medicine practiced in China, called Traditional Chinese Medicine (TCM), have been used in stroke therapy for centuries. A large body of studies suggest that some Chinese herbs can help reverse cognitive impairment in stroke patients, while whether these herbs also exert therapeutic benefits for Alzheimer's disease remains to be seen.Objective: To address this issue, we selected four types of CHMs that are commonly prescribed for stroke treatment in clinical practice, namely DengZhanXiXin (D1), TongLuoJiuNao (T2), QingKaiLing (Q3), and HuangQinGan (H4), and tested their effects on amyloid-β protein precursor (AβPP) processing in vitro.Methods: AβPP, β-secretase (BACE1), and 99-amino acid C-terminal fragment of AβPP (C99) stably transfected cells were used for the tests of AβPP processing. The production of Aβ, activity of BACE1, neprilysin (NEP), and γ-secretase were assessed by ELISA, RT-PCR, and western blot.Results: By upregulating BACE1 activity, D1 increased Aβ production whereas decreased the ratio of Aβ42/Aβ40; by downregulating BACE1 activity and modulating the expression of γ-secretase, T2 decreased Aβ production and the ratio of Aβ42/Aβ40; by downregulating BACE1 activity, Q3 decreased Aβ production; H4 did not change Aβ production due to the simultaneously downregulation of BACE1 and NEP activity.Conclusion: Our study indicates that these four anti-stroke CHMs regulate AβPP processing through different mechanisms. Particularly, T2 with relatively simple components and prominent effect on AβPP processing may be a promising candidate for the treatment of AD. [ABSTRACT FROM AUTHOR]

Objectives: To measure the expression of matrix metalloproteinase (MMP)-2, tissue inhibitor of matrix metalloproteinase inhibitor (TIMP)-2, and CD147 in mice with chronic liver injury induced by carbon tetrachloride after treatment with the traditional Chinese medicine (TCM) "Compound T11". Method: Sixty male ICR mice were divided randomly into 6 groups of 10: control (C), model (M), low-dose treatment (LT; 50 mg/mL of Compound T11), medium-dose treatment (MT, 100 mg/mL), high-dose treatment (HT, 150 mg/mL), and positive drug treatment (YT, 67.5 mg/mL). Each group was modeled for 7 weeks. Groups M, LT, MT, HT, and YT were injected (s.c.) with 20% carbon tetrachloride diluted with olive oil, and group C was given olive oil in the same way twice a week. After modeling, the treatment groups were administered Compound T11 at the concentrations shown above by oral gavage daily for 2 weeks, while group C was given 0.5% carboxymethyl cellulose sodium. After the final treatment, mice were killed and their liver tissues were excised. Immunohistochemical staining was performed to measure the protein expression of MMP-2, TIMP-2, and CD147, and western blotting was used to measure the protein expression of MMP-2, TIMP-2, CD147, and α-smooth muscle actin (SMA). MMP-2, TIMP-2, and CD147 mRNA expression was determined by quantitative fluorescence real-time PCR. Results: Compound T11 increased the protein expression of MMP-2 and CD147 and decreased the protein expression of TIMP-2 and α-SMA. Conclusions: Treatment of chronic liver injury by TCM Compound T11 may be associated with changes to the expression of MMP-2 and CD147, and the inhibition of TIMP-2 expression. [ABSTRACT FROM AUTHOR]

Excessive sulfur dioxide (SO₂) disturbs physiology of lysosomes causing diseases and threatening human health. A fluorescent probe has been regarded as one of the most attractive approaches, which is compatible with living cells and possesses high sensitivity. However, most of fluorescent probes' reaction sites are activated before they reach the destination. In this work, an acid‐activatable fluorescent probe PT1 was synthesized, characterized, and used for SO2 detection. The introduction of oxazolines in PT1 enables the intelligent response of probe to release the activation stie for SO2 derivatives through Michael addition upon exposure to acid. In vitro studies showed a remarkable selectivity of PT1 to SO₂ derivatives than other biothiols with a limit of detection as low as 62 nM. By using this acidic pH‐controlled fluorescence responsiveness to SO₂, precise spatiotemporal identification of lysosomal SO2 fluctuations has been successfully performed. Furthermore, probe PT1 can be applied for monitoring SO₂ derivatives in traditional Chinese medicines. [ABSTRACT FROM AUTHOR]

Kai Xin San (KXS), first proposed by Sun Simiao during the Tang Dynasty, has been utilized to treat dementia by tonifying qi and dispersing phlegm. This study aimed to elucidate the mechanism by which KXS exerts its therapeutic effects on Alzheimer's disease (AD) by targeting ferroptosis, using a combination of network pharmacology, bioinformatics, and experimental validation strategies. The active target sites and the further potential mechanisms of KXS in protecting against AD were investigated through molecular docking, molecular dynamics simulation, and network pharmacology, and combined with the validation of animal experiments. Computational and experimental findings provide the first indication that KXS significantly improves learning and memory defects and inhibits neuronal ferroptosis by repairing mitochondria damage and upregulating the protein expression of ferroptosis suppressor protein 1 (FSP1) in vivo APP/PS1 mice AD model. According to bioinformatics analysis, the mechanism by which KXS inhibits ferroptosis may involve SIRT1. KXS notably upregulated the mRNA and protein expression of SIRT1 in both vivo APP/PS1 mice and in vitro APP -overexpressed HT22 cells. Additionally, KXS inhibited ferroptosis induced by APP- overexpression in HT22 cells through activating the SIRT1-FSP1 signal pathway. Collectively, our findings suggest that KXS may inhibit neuronal ferroptosis through activating the SIRT1/FSP1 signaling pathway. This study reveals the scientific basis and underlying modern theory of replenishing qi and eliminating phlegm, which involves the inhibition of ferroptosis. Moreover, it highlights the potential application of SIRT1 or FSP1 activators in the treatment of AD and other ferroptosis-related diseases. Schematic representation of proposed mechanism of KXS on the protective effect of AD. [Display omitted] • Kai-Xin-San inhibits the neuronal ferroptosis in APP/PS1 transgenic AD mice and APP -overexpressed HT22 cells. • SIRT1 is the core of Kai-Xin-San's protein-protein interaction networks regulating ferroptosis. • Kai-Xin-San inhibits the neuronal ferroptosis through activating SIRT1-FSP1 signal pathway. [ABSTRACT FROM AUTHOR]

Shenmai injection (SMI), a traditional Chinese herbal medicine is widely used for the clinical treatment of cerebral infarction in China. Aim of the study: Tight junctions (TJs) are major components of the blood-brain barrier (BBB) that physically restrict the paracellular diffusion of blood-borne substances between endothelial cells into the CNS. TJ proteins are associated with cholesterol-enriched regions of plasma membrane known as lipid rafts, which are critical for the trafficking, positioning and function of TJ proteins. In this study, we investigated the effect of SMI on the expression and trafficking of the key TJ-associated protein, occludin, in lipid rafts. Using a neutral pH, rat cerebral microvessels were subjected to detergent-free density-gradient fractionation to isolate lipid rafts containing occludin. Transmission electron microscopy (TEM) was performed to study the effects of drug administration on ultrastructural changes to TJs. Western blotting (WB), immunofluorescence (IF), and co-immunoprecipitation (COIP) were used to observe the localization and function of TJ-associated proteins. We successfully isolated cerebral microvessels and separated lipid rafts from plasma membranes. With SMI treatment, extravasation of FITC-albumin decreased around the cerebral vessels by IF, the tight junctions were found to still be intact and the basement membrane appeared to be of uniform thickness in TEM. Compared with the untreated group, the co-expression of flotillin-1 and occludin in microvascular endothelial cells was increased and distributed continuously in SMI treatment as shown in double label IF. SMI significantly increased the translocation of occludin to lipid raft fractions by WB and COIP. SMI helps maintain the proper assembly of the TJ multiprotein complex in lipid rafts, thereby helping to preserve BBB functional integrity during focal cerebral ischemic insult. Our findings enhance our understanding of the mechanisms underlying the neuroprotective effect of SMI in cerebral ischemia. Image 1 [ABSTRACT FROM AUTHOR]

Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect. Aim of the study : To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway. WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis. ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN , HMGCR , etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond. Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism. [Display omitted] [ABSTRACT FROM AUTHOR]