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1.
Front Bioeng Biotechnol ; 12: 1320337, 2024.
Article in English | MEDLINE | ID: mdl-38468688

ABSTRACT

Objective: Patients with chronic stroke capable of independent gait were classified into functional ambulation category (FAC) 4 or 5, and the kinetic and kinematic data on their lower limb joints on the affected and unaffected sides were compared with that of healthy individuals. Finally, the qualitative changes in the gait of patients with stroke were investigated based on the differences in FAC scores. Methods: Twelve healthy participants and 19 patients with stroke capable of independent gait were included. The three-dimensional (3D) motion analysis and conventional assessment were conducted for all patients with stroke. Results: The FAC 5 group exhibited a larger range of motion (ROM) than the FAC 4 group in knee and hip joints on the affected side and only in the hip on the unaffected side. In the FAC 5 group, ROM differences in the healthy group on either the affected or unaffected side were absent. The peak of the hip flexion moment on the affected side in both the FAC 4 and 5 groups was smaller than that in the healthy group and in the FAC 4 group on the unaffected side. The absorption power minimum on the affected side was smaller only in the FAC 4 group than that in the healthy group and was larger in the FAC 5 group than that in the FAC 4 group. On the unaffected side, the absorption power minimum was smaller only in the FAC 4 group than that in the healthy group. Conclusion: Functional differences in gait were found in patients classified based on conventional evaluation capable of independent gait after post-stroke rehabilitation. Patients may not exhibit complete recovery in the kinetic indices even if they are judged to be normal in the conventional evaluation, and the kinematic gait indices indicate recovery. Evaluating kinetic indices in addition to kinematic indices is necessary, and joint power may be an especially useful index.

2.
Int Immunopharmacol ; 141: 113018, 2024 Nov 15.
Article in English | MEDLINE | ID: mdl-39216235

ABSTRACT

Turmeric (Curcuma longa L.) extract (CLE) has been shown to elicit several pharmacological properties and is widely used in Asian traditional medicine. Herein, we assessed the impact of CLE on airway inflammation in BALB/c mice and A549 cells to clarify the underlying mechanism. An asthmatic mouse model was established by administering ovalbumin (OVA). CLE (100 or 300 mg/kg/day) was orally administered daily from days 18 to 23, with dexamethasone (3 mg/kg/day) used as the positive control. Human airway epithelial cells, A549, were stimulated using recombinant tumor necrosis factor-α. The CLE100 and CLE400 groups exhibited a significant downregulation in eosinophil counts, cytokine levels, and immunoglobulin-E levels. Moreover, CLE administration dose-dependently suppressed oxidative stress and airway inflammation in the lung tissue. CLE administration inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) and the expression and activity of matrix metalloproteinase (MMP)-9. In vitro, CLE treatment reduced mRNA levels of proinflammatory cytokines, MAPK phosphorylation, and the expression and activity of MMP-2 and MMP-9. Additionally, 50 µg/mL CLE and 2.5 µg/mL curcumin showed similar anti-inflammatory effects. Collectively, our findings revealed that CLE could suppress airway inflammation in asthmatic mice and A549 cells via oxidative stress-driven MAPK/MMPs signaling, suggesting that CLE could be developed as a potential treatment option for patients with asthma.


Subject(s)
Anti-Inflammatory Agents , Asthma , Curcuma , Matrix Metalloproteinase 9 , Mice, Inbred BALB C , Oxidative Stress , Plant Extracts , Animals , Humans , Oxidative Stress/drug effects , Asthma/drug therapy , Asthma/metabolism , Asthma/immunology , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Curcuma/chemistry , A549 Cells , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Matrix Metalloproteinase 9/metabolism , Matrix Metalloproteinase 9/genetics , Mice , Cytokines/metabolism , Mitogen-Activated Protein Kinases/metabolism , Ovalbumin/immunology , Disease Models, Animal , Female , Lung/drug effects , Lung/pathology , Lung/metabolism , Lung/immunology , Immunoglobulin E/blood , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 2/genetics , MAP Kinase Signaling System/drug effects
3.
Nutrients ; 16(14)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39064710

ABSTRACT

Ageratum conyzoides, an annual herbaceous plant that inhabits tropical and subtropical regions, has been traditionally used in Asia, Africa, and South America for phytotherapy to treat infectious and inflammatory conditions. However, the pharmacological effects of standardized ethanolic extract of Ageratum conyzoides (ACE) on benign prostatic hyperplasia (BPH) remain unexplored. The objective of this research is to examine the potential physiological impacts of ACE, a traditionally utilized remedy for inflammatory ailments, in a rat model with BPH induced by testosterone propionate (TP). Rats were subcutaneously administered TP (3 mg/kg) to induce BPH and concurrently orally administered ACE (20, 50, and 100 mg/kg) daily for 42 days. ACE markedly improved BPH characteristics, including prostate weight, prostate index, and epithelial thickness, while also suppressing androgens and related hormones. The findings were supported by a decrease in androgen receptor and downstream signals associated with BPH in the prostate tissues of the ACE groups. Furthermore, increased apoptotic signals were observed in the prostate tissue of the ACE groups, along with heightened detection of the apoptotic nucleus compared to the BPH alone group. These changes seen in the group that received finasteride were similar to those observed in this group. These findings suggest that ACE shows promise as an alternative phytotherapeutic agent for treating BPH.


Subject(s)
Ageratum , Apoptosis , Cell Proliferation , Plant Extracts , Prostate , Prostatic Hyperplasia , Rats, Sprague-Dawley , Male , Animals , Prostatic Hyperplasia/drug therapy , Prostatic Hyperplasia/chemically induced , Prostatic Hyperplasia/pathology , Plant Extracts/pharmacology , Apoptosis/drug effects , Prostate/drug effects , Prostate/pathology , Rats , Ageratum/chemistry , Cell Proliferation/drug effects , Testosterone/blood , Testosterone Propionate , Disease Models, Animal , Inflammation/drug therapy , Phytotherapy
4.
Pharmaceuticals (Basel) ; 17(8)2024 Jul 29.
Article in English | MEDLINE | ID: mdl-39204106

ABSTRACT

Fritillariae thunbergii Bulbus (FTB), a member of the Liliaceae family, has a long history of use in many herbal formulations for traditional and modern clinical applications to treat various infections and inflammation. To understand FTB's diverse physiochemical properties, it is important to determine the pharmacokinetic properties of its active constituents, the steroidal alkaloids. The aim of the present study was to investigate the pharmacokinetic alterations of the alkaloids, the active components of FTB, in the presence of colitis. A single oral dose of FTB (1 g/kg) was treated to a 2,4-dinitrobenzene sulfonic acid (DNBS)-induced colitis rat model to assess whether the colitis condition could influence the pharmacokinetics of the major alkaloids present in FTB. Among the four major alkaloids, peimisine exhibited a significantly increased systemic exposure, approximately five times higher, under the colitis condition compared with the normal state. Meanwhile, peimine, peiminine, and sipeimine exhibited shorter half-lives in the DNBS group without significant changes in systemic absorption. As herbal medicine may contain active substances with different or opposing efficacies, careful consideration of pharmacokinetic changes in individual components due to diseases is necessary. Further experiments on peimisine are required to ensure the effectiveness and safety of FTB's clinical application in the presence of colitis.

5.
Redox Biol ; 73: 103193, 2024 07.
Article in English | MEDLINE | ID: mdl-38781728

ABSTRACT

Obesity is associated with an increased incidence of asthma. However, the mechanisms underlying this association are not fully understood. In this study, we investigated the role of thioredoxin-interacting protein (TXNIP) in obesity-induced asthma. Asthma was induced by intranasal injection of a protease from Aspergillus oryzae in normal diet (ND)- or high fat diet (HFD)-fed mice to investigate the symptoms. We measured TXNIP expression in the lungs of patients with asthma and in ND or HFD asthmatic mice. To explore the role of TXNIP in asthma pathogenesis, we induced asthma in the same manner in alveolar type 2 cell-specific TXNIP deficient (TXNIPCre) mice. In addition, the expression levels of pro-inflammatory cytokines were compared based on TXNIP gene expression in A549 cells stimulated with recombinant human tumor necrosis factor alpha. Compared to ND-fed mice, HFD-fed mice had elevated levels of free fatty acids and adipokines, resulting in high reactive oxygen species levels and more severe asthma symptoms. TXNIP expression was increased in both, asthmatic patients and HFD asthmatic mice. However, in experiments using TXNIPCre mice, despite being TXNIP deficient, TXNIPCre mice exhibited exacerbated asthma symptoms. Consistent with this, in vitro studies showed highest expression levels of pro-inflammatory cytokines in TXNIP-silenced cells. Overall, our findings suggest that increased TXNIP levels in obesity-induced asthma is compensatory to protect against inflammatory responses.


Subject(s)
Asthma , Carrier Proteins , Diet, High-Fat , Obesity , Thioredoxins , Animals , Asthma/metabolism , Asthma/etiology , Asthma/pathology , Asthma/genetics , Mice , Humans , Obesity/metabolism , Obesity/genetics , Obesity/etiology , Carrier Proteins/metabolism , Carrier Proteins/genetics , Diet, High-Fat/adverse effects , Thioredoxins/metabolism , Thioredoxins/genetics , Alveolar Epithelial Cells/metabolism , Reactive Oxygen Species/metabolism , Cytokines/metabolism , Disease Models, Animal , Male , A549 Cells , Mice, Knockout
6.
Front Pharmacol ; 15: 1415670, 2024.
Article in English | MEDLINE | ID: mdl-39050759

ABSTRACT

Introduction: Cissus quadrangularis is a vining plant widely used as a traditional herbal remedy for various ailments. In this study, the therapeutic effects of C. quadrangularis extract (CQR-300) on type 2 diabetes mellitus (T2DM) were investigated in a leptin receptor-mutated db/db mouse model. Methods: CQR-300 was orally administered to db/db mice (n = 6/group) at different doses (50, 100, and 200 mg/kg) for 8 weeks. Blood glucose levels and oral glucose tolerance were assessed using the AccuCheck glucometer. Enzyme-linked immunosorbent assay was performed to evaluate insulin and hemoglobin A1c (HbA1c) levels in the blood of db/db mice. Liver and pancreatic tissues from db/db mice were examined by hematoxylin and eosin (H&E) and immunohistochemical staining. The protein levels of gluconeogenesis-, lipogenesis-, and oxidative stress-related factors were evaluated using western blotting. Results and discussion: CQR-300 treatment effectively reduced body weight, blood glucose, and insulin levels. HbA1c levels were increased by leptin receptor mutation. Additionally, in the oral glucose tolerance tests, the CQR-300 treated group had a faster blood glucose recovery rate than the db/db group. H&E and Oil red-O staining of the liver showed decreased lipid accumulation in the CQR-300 treated group than the db/db group. Western blot analysis confirmed that CQR-300 effectively inhibited gluconeogenesis, lipogenesis, and oxidative stress-related factors. Our findings suggest that CQR-300 has the potential to be used as a T2DM supplement.

7.
Front Immunol ; 15: 1362404, 2024.
Article in English | MEDLINE | ID: mdl-38745671

ABSTRACT

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.


Subject(s)
Asthma , Epithelial Cells , Matrix Metalloproteinase 9 , Oxidative Stress , Plant Extracts , Animals , Female , Humans , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Asthma/drug therapy , Asthma/immunology , Asthma/metabolism , Cytokines/metabolism , Disease Models, Animal , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Matrix Metalloproteinase 9/metabolism , Mice, Inbred BALB C , Mitogen-Activated Protein Kinases/metabolism , Ovalbumin/immunology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Respiratory Mucosa/metabolism , Respiratory Mucosa/drug effects , Respiratory Mucosa/immunology , Respiratory Mucosa/pathology , Signal Transduction/drug effects
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