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Journal of Ethnopharmacology Jan 2024The flowers of Inula japonica (Inulae Flos) can be used to treat cough and asthma and remove phlegm in traditional Chinese medicine (TCM).
ETHNOPHARMACOLOGICAL RELEVANCE
The flowers of Inula japonica (Inulae Flos) can be used to treat cough and asthma and remove phlegm in traditional Chinese medicine (TCM).
AIM OF THE STUDY
Our research aimed to obtain active components with the inhibition of inflammation and MUC5AC production to alleviate asthma symptoms from I. japonica.
MATERIALS AND METHODS
These compounds were separated from the MeOH extract of Inulae Flos by column chromatography over silica gel, AB-8 macroporous resin column, MPLC, and semipreparative HPLC. Their structures were elucidated by detailed spectroscopic data analysis, ECD calculations, and chemical methods. NO production was determined to evaluate anti-inflammatory activity in RAW 264.7 cells. The expression of MUC5AC, IL-1β, and IL-4 were measured in NCI-H292 cells by qRT-PCR. The anti-asthma activity assessments in vivo were performed through H & E and PAS staining, pulmonary function analysis, and cytokines determination by qRT-PCR or ELISA. The expression levels of PI3K, p-PI3K, AKT, p-AKT, MEK, p-MKE, ERK, p-MEK, and IL-1β were analyzed through western blotting.
RESULTS
One undescribed 1,10-seco-eudesmanolide derivative (1), two previously unreported 1,10-seco-eudesmanolide glycosides (2 and 3), and thirty-two known compounds (4-35) were obtained from Inulae Flos. Compound 11 had the most inhibitory effect against LPS-induced NO production in RAW 264.7 murine macrophages. Meanwhile, compound 11 also attenuated the increase in MUC5AC, IL-1β, and IL-4 mRNA expression in NCI-H292 cells. The results of the animal experiment confirmed that compound 11 significantly ameliorated OVA-induced asthma in a murine model of allergic asthma demonstrated by elevated pulmonary function, reduced inflammatory cell infiltration and mucus production. In addition, compound 11 significantly inhibited the levels of OVA-specific IgE in serum, of IL-4 and IL-6 in BALF, and of MUC5AC, IL-1β , IL-4, IL-5, IL-6 and IL-13 in lung tissue. Finally, compound 11 suppressed PI3K/AKT/MEK/ERK signaling pathway in lung tissue of mice.
CONCLUSION
This study indicated that compound 11 might be a potential therapeutic candidate ameliorating airway inflammation and mucus hypersecretion via PI3K/AKT/MEK/ERK signaling pathway in allergic asthma.
Topics: Animals; Mice; Inula; Interleukin-4; Interleukin-6; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Anti-Inflammatory Agents; Asthma; Inflammation; Mitogen-Activated Protein Kinase Kinases
PubMed: 37597674
DOI: 10.1016/j.jep.2023.117052 -
Journal of Traditional Chinese Medicine... Oct 2023To preliminary investigate the distribution of Traditional Chinese Medicine (TCM) constitution among patients with allergic rhinitis (AR) and reveal the related factors...
OBJECTIVE
To preliminary investigate the distribution of Traditional Chinese Medicine (TCM) constitution among patients with allergic rhinitis (AR) and reveal the related factors with anxiety and depression.
METHODS
Between July 2020 and June 2021, specialist doctor recruited AR patients in Beijing and Shanghai. A total of 630 patients admitted to participate in the survey, and 516 (81.9%) (male 54.3%, female 45.7%) participants completed the questionnaires. Three scales including Constitution in Chinese Medicine Questionnaire (CCMQ), Generalized Anxiety Disorder Questionnaire (GAD-7) and The Patient Health Queationaire-9 (PHQ-9) were applied. The χ and the Fisher's exact test were used to evaluate the classification data, multivariate logistic regression was used to explore the related factors of anxiety and depression.
RESULTS
According to 516 AR patients, the most commonly first-constitution was deficiency (22.1%) and frequent of all constitutions was inherited-special (21.6%). One third of AR patients (33.5%) suffered from anxiety, nearly half of AR patients (46.5%) were found to be depressive. Inherited-special (27.7%) was the most common constitution in patients with anxiety whereas deficiency (26.7%) was most common constitution in patients with depression. Sex, duration of symptoms, balanced, deficiency, phlegm-dampness, stagnation, and inherited-special constitutions were related with anxiety; Sex, income, duration of symptoms, balanced, deficiency, deficiency, phlegm-dampness, stagnation, and inherited-special constitutions were related with depression.
CONCLUSIONS
According to our study, the commonly constitution types of AR were deficiency and inherited-special. We found that the prevalence value of anxiety and depression were high. People with deficiency, phlegm-dampness, stagnation, and inherited-special constitutions were more likely to have mental problems than the others. Controlling these influential factors might be beneficial for clinical health management of AR patients, and the government should apply appropriate mental health treatment services to offer psychiatric support.
Topics: Humans; Male; Female; Medicine, Chinese Traditional; Depression; Body Constitution; China; Yang Deficiency; Anxiety; Anxiety Disorders
PubMed: 37946488
DOI: 10.19852/j.cnki.jtcm.20230919.001 -
Journal of Ethnopharmacology Nov 2023Salvia miltiorrhiza Bge. mixed with porcine cardiac blood (PCB-DS) is mainly employed for the treatment of brain ischemia-induced mental disturbances, palpitations and...
Porcine cardiac blood - Salvia miltiorrhiza root alleviates cerebral ischemia reperfusion injury by inhibiting oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway.
ETHNOPHARMACOLOGICAL RELEVANCE
Salvia miltiorrhiza Bge. mixed with porcine cardiac blood (PCB-DS) is mainly employed for the treatment of brain ischemia-induced mental disturbances, palpitations and phlegm confusion based on the traditional principle of Menghe medical sect. PCB is the guide to DS and enhances the effect of DS. However, the potential mechanism of PCB-DS preventing cerebral ischemia/reperfusion injury (CIRI) from the perspective of oxidative stress induced cell apoptosis remains unknown.
AIM OF THE STUDY
To investigate the pharmacological activity and molecular mechanism of PCB-DS against CIRI.
MATERIALS AND METHODS
DS samples processed with different methods were prepared and UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the respective processing product. The middle cerebral artery occlusion reperfusion model was then established to investigate the pharmacological activities of PCB-DS. Pathological changes in the rat brain were observed by triphenyl tetrazolium chloride (TTC), hematoxylin-eosin, and TUNEL staining. The levels of IL-6, IL-1β, and TNF-α were detected by ELISA to evaluate the inflammatory damage. Metabolomics of cerebrospinal fluid was further used to explore the potential mechanism of PCB-DS in preventing CIRI. Based on this, the levels of oxidative stress-related lactate dehydrogenase (LDH), reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD) were determined. The protein levels of PI3K, AKT, Bcl-2, Bax, cleaved-caspase-3, and cleaved-caspase-9 proteins of the cerebral infarct zone were finally measured by western blotting.
RESULTS
Forty-seven components were identified in four processing products. Compared to DS, the content of total aqueous components in PCB-DS was significantly increased including salvianolic acid B isomer, salvianolic acid D, salvianolic acid F, and salvianolic acid H/I/J. Among the DS, DS processed with wine, DS processed with pig blood, and DS processed with porcine cardiac blood, PCB-DS best alleviated the CIRI through the neurological score, brain infarct volume, brain histopathology and the levels of inflammatory factors in the brain. Twenty-five significant metabolites in the cerebrospinal fluid were screened out between the sham and I/R groups. They were mainly involved in the beta-alanine metabolism, histidine metabolism, and lysine degradation, which indicated that PCB-DS may inhibit oxidative stress-induced apoptosis to achieve treating ischemic stroke. The results of biomedical examination showed that PCB-DS could alleviate oxidative damage, significantly downregulate the expression of Bax, cleaved caspase-3 and cleaved caspase-9, and upregulate the expression of p-PI3K, p-AKT, and Bcl-2.
CONCLUSION
In summary, this study demonstrated that PCB-DS alleviated CIRI and the molecular mechanism may be related to inhibiting the oxidative stress induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway.
Topics: Rats; Animals; Swine; Proto-Oncogene Proteins c-akt; bcl-2-Associated X Protein; Caspase 3; Caspase 9; Phosphatidylinositol 3-Kinases; Rats, Sprague-Dawley; Tandem Mass Spectrometry; Signal Transduction; Reperfusion Injury; Brain Ischemia; Oxidative Stress; Apoptosis
PubMed: 37286116
DOI: 10.1016/j.jep.2023.116698 -
Journal of Ethnopharmacology Mar 2024The occurrence and development of atherosclerosis, a common chronic inflammatory vascular disease, are closely related to cardiovascular and cerebrovascular diseases....
ETHNOPHARMACOLOGICAL RELEVANCE
The occurrence and development of atherosclerosis, a common chronic inflammatory vascular disease, are closely related to cardiovascular and cerebrovascular diseases. Banxia Baizhu Tianma Decoction (BBTD) is a representative traditional Chinese medicine formula that resolves phlegm, disperses wind, invigorates the spleen and eliminates dampness and is also a commonly used clinical medication for treating vascular diseases.
AIM OF THE STUDY
To explore the pharmacological mechanisms of BBTD in alleviating atherosclerosis, the present study was carried out by conducting an integrative analysis of aortic and perivascular adipose tissue (PVAT) proteomics and metabolomics.
MATERIALS AND METHODS
Eight-week-old ApoE-/- mice were randomly divided into the BBTD group and the model group, and nine age-matched C57BL/6J (C57) mice were used as the control group (n = 9). The C57 mice were fed a standard diet, while the ApoE mice were fed a high-fat, high-cholesterol diet for 12 weeks. Mice in the BBTD group were transgastrically administered BBTD at a dose of 17.8 g/kg/day for 8 weeks, while the model group and control group mice received an equivalent volume of saline by gavage. Histomorphology of the aortas and PVAT was assessed by HE staining, oil red O staining, Masson staining, and α-SMA and CD68 immunohistochemical methods. An integrative analysis of aortic proteomics, PVAT proteomics and PVAT metabolomics was conducted to study the pharmacological mechanisms of BBTD.
RESULTS
Compared to the model group, mice treated with BBTD had thicker fibrous caps, increased collagen content, less erosion of smooth muscle cells and infiltration of macrophages, as well as a relatively low inflammatory response level, suggesting that BBTD treatment reduced plaque vulnerability. Omics analysis suggested that BBTD treatment demonstrated anti-atherosclerotic effects and increased plaque stability in the aorta by activating the TGF-beta pathway. Simultaneously, BBTD inhibited PVAT inflammation levels (decreased the levels of MCP and IL-6). Proteomics and metabolomics of PVAT suggested that the targets of BBTD included upregulation of the α-linolenic acid metabolic pathway and downregulation of multiple inflammatory pathways, such as the NF-kappa B signalling pathway, primary immunodeficiency and Th17 cell differentiation in PVAT.
CONCLUSIONS
BBTD reduces the vulnerability of atherosclerotic plaques and inhibits the inflammatory phenotype of perivascular adipose tissue.
Topics: Mice; Animals; Mice, Knockout, ApoE; Mice, Inbred C57BL; Atherosclerosis; Plaque, Atherosclerotic; Adipose Tissue; Obesity; Apolipoproteins E; Drugs, Chinese Herbal
PubMed: 38103846
DOI: 10.1016/j.jep.2023.117575 -
Postgraduate Medicine Nov 2023Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic... (Review)
Review
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality globally. In the major revision of the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2023 report, the scientific committee concluded that the use of long-acting β-agonist/inhaled corticosteroids (LABA/ICS) is not encouraged in patients with COPD. However, current prescribing patterns reveal significant use of LABA/ICS. In this paper, the evidence behind the current practice and the latest treatment recommendations is reviewed. We compare the efficacy and safety of combination therapy with long-acting muscarinic antagonist (LAMA) and LABA vs LABA/ICS and note that LAMA/LABA combinations have reduced the annual rate of moderate/severe exacerbations, delayed the time to first exacerbation, and increased post-dose FEV vs ICS-based regimens. The GOLD 2023 report recommends treatment with LABA and LAMA combination (preferably as a single inhaler) in patients with persistent dyspnea, with initiation of ICS in patients based on the symptoms (dyspnea and exercise intolerance as indicated by modified Medical Research Council [mMRC] score ≥ 2 and COPD Assessment Test [CAT™] > 20), blood eosinophil count (≥ 300 cells/µL), and exacerbation history (history of hospitalizations for exacerbations of COPD and ≥ 2 moderate exacerbations per year despite appropriate long-acting bronchodilator maintenance therapy). We describe practical recommendations for primary care physicians to optimize therapy for their patients and prevent overuse of ICS-based regimens. We advocate adherence to current recommendations and a greater focus on effective treatments to successfully control symptoms, minimize exacerbation risk, preserve lung function, maximize patient outcomes, and reduce the burden of drug-related adverse events.
Topics: Humans; Adrenergic beta-2 Receptor Agonists; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Administration, Inhalation; Drug Therapy, Combination; Adrenal Cortex Hormones; Dyspnea; Bronchodilator Agents
PubMed: 38032494
DOI: 10.1080/00325481.2023.2284650 -
Journal of Ethnopharmacology Dec 2023A traditional Chinese medicine experience compound known as Yipibushen (YPBS) decoction stimulates qi and nourishes yin, stimulates the kidney and solid essence,...
ETHNOPHARMACOLOGICAL RELEVANCE
A traditional Chinese medicine experience compound known as Yipibushen (YPBS) decoction stimulates qi and nourishes yin, stimulates the kidney and solid essence, dissolves phlegm and eliminates stasis. YPBS decoction has proven to be successful in treating obese type 2 diabetes mellitus with oligoasthenotspermia in clinical settings. Nevertheless, the pharmacological mechanism is not understood.
AIM OF THE STUDY
Investigating the mechanism of action of YPBS decoction in enhancing the obese type 2 diabetes mellitus with oligoasthenotspermia involved network pharmacology and animal validation techniques.
METHODS AND MATERIALS
The YPBS Decoction' active components were found in the TCMSP database and their targets were identified using UniProtKB. Additionally, targets for the obese type 2 diabetes mellitus with oligoasthenotspermia were found in the GeneCard, DisGeNet, TTD and OMIM databases. The intersection of active ingredients, the obese type 2 diabetes mellitus with oligoasthenotspermia was chosen as the intersection target. The protein-protein interaction (PPI) network of the intersection target was built with the aid of Cytoscape 3.9.1, the core target of PPI was obtained through software analysis in R-project, GO enrichment and KEGG enrichment analysis was carried out on the core target. Finally, animal experiments were used to verify the intersection target.
RESULTS
The research revealed 74 intersection targets of YPBS decoction active ingredients in the obese type 2 diabetes mellitus with oligoasthenotspermia. There were also 18 PPI core targets, GO enrichment analysis of PPI core targets involving response to oxidative stress, membrane raft, DNA-binding transcription regulator complex and other biological processes; KEGG involving endocrine resistance, PI3K/AKT signaling pathway, apoptosis and other signal pathways. In the obese type 2 diabetes mellitus with oligoasthenotspermia mice, animal studies have shown that YPBS decoction group could decrease blood glucose levels and improve insulin resistance; improve testicular function, enhance sperm count, sperm motility, sperm viability, and decrease the malformation rate. It could increase the levels of T-SOD and GSH-Px, and decrease the MDA level. In addition to this, it could improve the amount of testosterone hormone, and enhance the expression of PI3K, p-AKT and Bcl-2.
CONCLUSION
By controlling the degree of oxidative stress and the PI3K/AKT/Bcl-2 pathway, YPBS decoction may enhance the obese type 2 diabetes mellitus with Oligoasthenotspermia, provide a scientific basis for clinical diagnosis and therapy.
Topics: Male; Animals; Mice; Diabetes Mellitus, Type 2; Network Pharmacology; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Semen; Sperm Motility; Drugs, Chinese Herbal; Molecular Docking Simulation
PubMed: 37369336
DOI: 10.1016/j.jep.2023.116738 -
Frontiers in Public Health 2023The clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis...
OBJECTIVE
The clinical manifestations of tuberculosis (TB) range from asymptomatic to disseminated depending on the microbiological and immunological status, making the diagnosis challenging. To improve our understanding of the disease progression mechanism, we aimed to identify the characteristics of subclinical TB and important predictors of symptom development.
METHODS
From July 2018 to June 2019, we systemically collected data from the National Surveillance System of South Korea on patients with pulmonary TB, and compared the characteristics of subclinical and active symptomatic TB patients.
RESULTS
A total of 4,636 patients with pulmonary TB were included, and the prevalence of subclinical TB was 37.1% (1,720/4,636). In subclinical TB patients, the positivity rates of acid-fast bacilli (AFB) smear and culture were 16.2 and 50.2%, respectively. Subclinical TB patients were younger (55.6 ± 19.2 vs. 60.7 ± 19.5, < 0.001), had a higher body mass index (21.7 ± 3.1 vs. 21.0 ± 3.5, < 0.001), less under Medicaid support, and had lower rates of chronic lung disease, AFB smear and culture positivity, and bilateral disease. Regarding the characteristic differences of individual TB-related symptoms, age was positively associated with dyspnoea and general weakness but negatively associated with chest pain, haemoptysis, and weight loss. Male patients were more prone to weight loss. Chronic lung disease was related to symptoms including cough/phlegm, dyspnoea, and haemoptysis, while autoimmune diseases were associated with fever and weight loss.
CONCLUSIONS
The development of TB-related symptoms was associated with microbiological burden and clinical characteristics including underlying comorbidities, which should be evaluated carefully.
Topics: Humans; Male; Prospective Studies; Hemoptysis; Tuberculosis; Registries; Dyspnea; Weight Loss
PubMed: 38125851
DOI: 10.3389/fpubh.2023.1275125 -
Health Information Science and Systems Dec 2023Dyslipidemia is a prominent risk factor for cardiovascular diseases and one of the primary independent modifiable factors of diabetes and stroke. Statins can...
BACKGROUNDS
Dyslipidemia is a prominent risk factor for cardiovascular diseases and one of the primary independent modifiable factors of diabetes and stroke. Statins can significantly improve the prognosis of dyslipidemia, but its side effects cannot be ignored. Traditional Chinese Medicine (TCM) has been used in clinical practice for more than 2000 years in China and has certain traits in treating dyslipidemia with little side effect. Previous research has shown that Mutual Obstruction of Phlegm and Stasis (MOPS) is the most common dyslipidemia type classified in TCM. However, how to compose diagnostic factors in TCM into diagnostic rules relies heavily on the doctor's experience, falling short in standardization and objectiveness. This is a limit for TCM to play its advantages of treating dyslipidemia with MOPS.
METHODS
In this study, the syndrome diagnosis in TCM was transformed into the prediction and classification problem in artificial intelligence The deep learning method was employed to build the classification prediction models for dyslipidemia. The models were built and trained with a large amount of multi-centered clinical data on MOPS. The optimal model was screened out by evaluating the performance of prediction models through loss, accuracy, precision, recall, confusion matrix, PR and ROC curve (including AUC).
RESULTS
A total of 20 models were constructed through the deep learning method. All of them performed well in the prediction of dyslipidemia with MOPS. The model-11 is the optimal model. The evaluation indicators of model-11 are as follows: The true positive (TP), false positive (FP), true negative (TN) and false negative (FN) are 51, 15, 129, and 9, respectively. The loss is 0.3241, accuracy is 0.8672, precision is 0.7138, recall is 0.8286, and the AUC is 0.9268. After screening through 89 diagnostic factors of TCM, we identified 36 significant diagnosis factors for dyslipidemia with MOPS. The most outstanding diagnostic factors from the importance were dark purple tongue, slippery pulse and slimy fur, etc.
CONCLUSIONS
This study successfully developed a well-performing classification prediction model for dyslipidemia with MOPS, transforming the syndrome diagnosis problem in TCM into a prediction and classification problem in artificial intelligence. Patients with dyslipidemia of MOPS can be accurately recognized through limited information from patients. We also screened out significant diagnostic factors for composing diagnostic rules of dyslipidemia with MOPS. The study is an avant-garde attempt at introducing the deep-learning method into the research of TCM, which provides a useful reference for the extension of deep learning method to other diseases and the construction of disease diagnosis model in TCM, contributing to the standardization and objectiveness of TCM diagnosis.
PubMed: 37035723
DOI: 10.1007/s13755-023-00215-0 -
Journal of Ethnopharmacology Jan 2024Mai Men Dong decoction (MMDD), a traditional Chinese medicine formula, is relevant to ethnopharmacology due to its constituents and therapeutic properties. The formula...
ETHNOPHARMACOLOGICAL RELEVANCE
Mai Men Dong decoction (MMDD), a traditional Chinese medicine formula, is relevant to ethnopharmacology due to its constituents and therapeutic properties. The formula contains herbs like Ophiopogon japonicus (Thunb.) Ker Gawl., Pinellia ternata (Thunb.) Makino, Panax ginseng C.A.Mey, Glycyrrhiza uralensis Fisch, and Ziziphus jujuba Mill, Oryza sativa L., which have been used for centuries in Chinese medicine. These herbs provide a comprehensive approach to treating respiratory conditions by addressing dryness, cough, and phlegm. Ethnopharmacological studies have explored the scientific basis of these herbs and identified active compounds that contribute to their medicinal effects. The traditional usage of MMDD by different ethnic groups reflects their knowledge and experiences. Examining this formula contributes to the understanding and development of ethnopharmacology.
AIM OF THE STUDY
In the case of pulmonary fibrosis (PF), treating it can be challenging due to the limited treatment options available. This study aimed to assess the potential of MMDD as a treatment for PF by targeting macrophages and the PI3K/Akt/FOXO3a signaling pathway.
MATERIALS AND METHODS
In a mouse model of PF, we investigated the effects of MMDD on inflammation, fibrosis, and M2 macrophage infiltration in lung tissue. Additionally, we examined the modulation of pro-fibrotic factors and key proteins in the PI3K/Akt/FOXO3a pathway. In vitro experiments involved inducing M2-type macrophages and assessing the impact of MMDD on fibroblast activation and the PI3K/Akt/FOXO3a pathway.
RESULTS
Results demonstrated that MMDD improved weight, reduced inflammation, and inhibited M2 macrophage infiltration in mouse lung tissue. It downregulated pro-fibrotic factors, such as TGF-β1 and PDGF-RB, as well as markers of fibroblast activation. MMDD also exhibited regulatory effects on key proteins in the PI3K/Akt/FOXO3a signaling pathway.
CONCLUSIONS
MMDD inhibited M2 macrophage polarization and released profibrotic factors that inhibited pulmonary fibrosis. As a result, the PI3K/Akt/FOXO3a signaling pathway is suppressed. MMDD is proving to be a successful treatment for PF. However, further research is needed to validate its effectiveness in clinical practice.
Topics: Male; Humans; Animals; Mice; Pulmonary Fibrosis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Inflammation; Macrophages; Signal Transduction; Fibroblasts
PubMed: 37865276
DOI: 10.1016/j.jep.2023.117308 -
Journal of Ethnopharmacology Jan 2024Alzheimer's disease (AD) belongs to the category of "senile dementia" in traditional Chinese medicine. AD is associated with brain emptiness or collaterals blocked by...
ETHNOPHARMACOLOGICAL RELEVANCE
Alzheimer's disease (AD) belongs to the category of "senile dementia" in traditional Chinese medicine. AD is associated with brain emptiness or collaterals blocked by phlegm-heat. "Fumanjian" from Jingyue Quanshu treats dementia by promoting qi circulation, alleviating depression, eliminating turbidity, cultivating positivity, and dispelling evil spirits. Qingxin Kaiqiao Fang (QKF), derived from Fumanjian, is effective in treating AD owing to previously mentioned clinical effects. Elucidating the mechanism(s) of action of QKF on AD associated with phlegm-heat may be beneficial for therapeutic management; however, further research is needed.
AIM OF THE STUDY
This study aimed to determine the role of the PI3K/Akt pathway in AD, especially the specific effector protein involved, and explore the efficacy of QKF in treating AD by modulating the PI3K/Akt signal.
MATERIALS AND METHODS
High-performance liquid chromatography-Q-orbitrap-mass spectrometry was used to analyze the chemical components of QKF. Subsequently, APP/PS1 double-transgenic mice were used for behavioral tests, and hematoxylin-eosin and Nissl staining were used to assess the neuroprotective and cognitive effects of QKF. Cerebrospinal fluid pharmacology was used in in vitro validation, and Aβ was used to induce PC12 cells to establish the AD cell model. Various methods, including immunohistochemistry, Western blotting, quantitative real-time polymerase chain reaction, morphological assay, cell counting kit-8(CCK-8) assay, and terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL)staining, were used to evaluate the effect of QKF on Tau hyperphosphorylation and anti-apoptosis. These methods also assessed the influence of QKF on the PI3K/Akt/GSK3β pathway involving the mRNA and protein expressions. Finally, the inhibitor - LY294002 was used for reverse validation.
RESULTS
We identified 295 chemical components in the water extract of QKF.QKF improved spatial cognition and learning memory in APP/PS1 mice, protected PC12 cell morphology, improved cell survival, reduced Aβ-induced apoptosis, and inhibited the hyperphosphorylation of Tau protein via the PI3k/Akt/GSK3β signaling pathway. Furthermore, this protective effect of QKF was reduced by LY294002 in vitro.
CONCLUSIONS
QKF can improve spatial cognition, learning, and memory abilities in APP/PS1 mice and protect PC12 cells. Decreasing the Tau hyperphosphorylation in AD exhibits curative efficacy on AD via the PI3K/Akt/GSK3β pathway in vitro and in vivo.
Topics: Rats; Mice; Animals; Alzheimer Disease; tau Proteins; Proto-Oncogene Proteins c-akt; Phosphatidylinositol 3-Kinases; Glycogen Synthase Kinase 3 beta; Amyloid beta-Peptides; Phosphorylation; Mice, Transgenic; Maze Learning
PubMed: 37579924
DOI: 10.1016/j.jep.2023.117031