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Nutrients Jun 2024Saikosaponin D (SSD), derived from L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies...
Saikosaponin D (SSD), derived from L., has various pharmacological properties, including immunoregulatory, anti-inflammatory, and anti-allergic effects. Several studies have investigated the anti-tumor effects of SSD on cancer in multiple organs. However, its role in colorectal cancer (CRC) remains unclear. Therefore, this study aimed to elucidate the suppressive effects of SSD on CRC cell survival and metastasis. SSD reduced the survival and colony formation ability of CRC cells. SSD-induced autophagy and apoptosis in CRC cells were measured using flow cytometry. SSD treatment increased LC3B and p62 autophagic factor levels in CRC cells. Moreover, SSD-induced apoptosis occurred through the cleavage of caspase-9, caspase-3, and PARP, along with the downregulation of the Bcl-2 family. In the in vivo experiment, a reduction in the number of metastatic tumor nodules in the lungs was observed after the oral administration of SSD. Based on these results, SSD inhibits the metastasis of CRC cells to the lungs by inducing autophagy and apoptosis. In conclusion, SSD suppressed the proliferation and metastasis of CRC cells, suggesting its potential as a novel substance for the metastatic CRC treatment.
Topics: Saponins; Oleanolic Acid; Autophagy; Colorectal Neoplasms; Apoptosis; Humans; Lung Neoplasms; Animals; Cell Line, Tumor; Cell Proliferation; Mice; Mice, Inbred BALB C; Antineoplastic Agents, Phytogenic; Xenograft Model Antitumor Assays; Cell Survival; Mice, Nude
PubMed: 38931199
DOI: 10.3390/nu16121844 -
Plants (Basel, Switzerland) Jun 2024Blueberries ( L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate...
Chemical Composition, Antioxidant Activities, Antidepressant Effect, and Lipid Peroxidation of Peruvian Blueberry: Molecular Docking Studies on Targets Involved in Oxidative Stress and Depression.
Blueberries ( L.) are cultivated worldwide and are among the best dietary sources of bioactive compounds with beneficial health effects. This study aimed to investigate the components of Peruvian blueberry using high-performance liquid chromatography coupled to electrospray ionization and quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS/MS), identifying 11 compounds. Furthermore, we assessed in vitro the antioxidant activity and in vivo the antidepressant effect using a rat model and protective effect on lipid peroxidation (in the serum, brain, liver, and stomach). We also conducted molecular docking simulations with proteins involved in oxidative stress and depression for the identified compounds. Antioxidant activity was assessed by measuring total phenolic and flavonoid contents, as well as using 1,1-diphenyl-2-picrylhydrazin (DPPH), 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS), and ferric-reducing antioxidant power (FRAP) assays. Peruvian blueberries demonstrated higher antioxidant activity than fruits from Chile, Brazil, the United States, Turkey, Portugal, and China. The results showed that oral administration of Peruvian blueberries (10 and 20 mg/kg) for 28 days significantly ( < 0.001) increased swimming and reduced immobility in the forced swimming test (FST). Additionally, at doses of 40 and 80 mg/kg, oxidative stress was reduced in vivo ( < 0.001) by decreasing lipid peroxidation in brain, liver, stomach, and serum. Molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions were performed. In the molecular docking studies, quercitrin and 3,5-di-O-caffeoylquinic acid showed the best docking scores for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, superoxide dismutase, and xanthine oxidase; while 3,5-dicaffeoylquinic acid methyl ester and caffeoyl coumaroylquinic acid had the best docking scores for monoamine oxidase and serotonin receptor 5-HT. In summary, our results suggest that the antidepressant and protective effects against lipid peroxidation might be related to the antioxidant activity of Peruvian L.
PubMed: 38931078
DOI: 10.3390/plants13121643 -
Plants (Basel, Switzerland) Jun 2024The treatment and management of diabetes mellitus (DM) with conventional therapies, such as insulin injections and oral hypoglycemic agents, present significant... (Review)
Review
The treatment and management of diabetes mellitus (DM) with conventional therapies, such as insulin injections and oral hypoglycemic agents, present significant challenges due to their side effects and burdensome administration. Therapies often manage symptoms rather than addressing insulin regulation, akin to medications like thiazolidinediones and glinides, which resemble many medicinal plants. Medicinal plants offer potential alternative treatments due to bioactive compounds targeting diabetes causes. We aimed to explore the antidiabetic potential of two medicinal plants, and L., by investigating their phytochemical constituents, medicinal uses, pharmacological actions, and mechanisms. This review followed specific guidelines and searched databases including PubMed, Scopus, ScienceDirect, and Web of Science for studies on medicinal plants and DM. Eligible studies underwent quality assessment and were categorized based on their design and interventions for data synthesis. This review identified the phytochemical constituents in and L., including tannins, flavonoids, phenols, and steroids, exerting antidiabetic effects through various mechanisms like antioxidant activity, anti-inflammatory effects, stimulation of insulin secretion, glucose regulation, and inhibition of carbohydrate-digesting enzymes. and L. exhibit promising antidiabetic potential, offering alternative approaches to diabetes management. Polyherbalism, combining multiple plant extracts, may enhance therapeutic efficacy in diabetes treatment. Comprehensive research is needed to explore the combined therapeutic effects of these plants and develop more effective antidiabetic treatments. This review highlights the importance of harnessing natural resources to combat the global burden of DM. Further research is warranted to fully explore the combined therapeutic effects of these plants and develop novel treatments.
PubMed: 38931040
DOI: 10.3390/plants13121608 -
Molecules (Basel, Switzerland) Jun 2024Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated...
Cisplatin, a platinum-based chemotherapeutic, is effective against various solid tumors, but its use is often limited by its nephrotoxic effects. This study evaluated the protective effects of trametinib, an FDA-approved selective inhibitor of mitogen-activated protein kinase kinase 1/2 (MEK1/2), against cisplatin-induced acute kidney injury (AKI) in mice. The experimental design included four groups, control, trametinib, cisplatin, and a combination of cisplatin and trametinib, each consisting of eight mice. Cisplatin was administered intraperitoneally at a dose of 20 mg/kg to induce kidney injury, while trametinib was administered via oral gavage at 3 mg/kg daily for three days. Assessments were conducted 72 h after cisplatin administration. Our results demonstrate that trametinib significantly reduces the phosphorylation of MEK1/2 and extracellular signal-regulated kinase 1/2 (ERK1/2), mitigated renal dysfunction, and ameliorated histopathological abnormalities. Additionally, trametinib significantly decreased macrophage infiltration and the expression of pro-inflammatory cytokines in the kidneys. It also lowered lipid peroxidation by-products, restored the reduced glutathione/oxidized glutathione ratio, and downregulated NADPH oxidase 4. Furthermore, trametinib significantly inhibited both apoptosis and necroptosis in the kidneys. In conclusion, our data underscore the potential of trametinib as a therapeutic agent for cisplatin-induced AKI, highlighting its role in reducing inflammation, oxidative stress, and tubular cell death.
Topics: Animals; Cisplatin; Acute Kidney Injury; Pyridones; Oxidative Stress; Mice; Pyrimidinones; Disease Models, Animal; Inflammation; Male; Cell Death; Apoptosis; Kidney Tubules; Lipid Peroxidation; Cytokines; MAP Kinase Signaling System
PubMed: 38930946
DOI: 10.3390/molecules29122881 -
Molecules (Basel, Switzerland) Jun 2024Achyranthes bidentata (AR) is a traditional Chinese herb used for the treatment of hypertension and cerebral ischemia, but its pharmacological effects are not known.
Characterization of the Components and Metabolites of Achyranthes Bidentata in the Plasma and Brain Tissue of Rats Based on Ultrahigh Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UHPLC-HR-MS).
BACKGROUND
Achyranthes bidentata (AR) is a traditional Chinese herb used for the treatment of hypertension and cerebral ischemia, but its pharmacological effects are not known.
AIM OF STUDY
We aimed to detect and accurately identify the components and metabolites of AR in the plasma and brain tissue of Sprague Dawley rats.
METHODS
We employed ultrahigh performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HR-MS) to detect AR components in the plasma and brain tissue of rats. The absorption and metabolites in the plasma and brain tissue of normal control rats and rats that underwent middle cerebral artery occlusion (MCAO) were characterized and compared.
RESULTS
A total of 281 compounds, including alkaloids, flavonoids, terpenoids, phenylpropanes, sugars and glycosides, steroids, triterpenes, amino acids, and peptides, was identified in samples of Achyranthes bidentata (TCM-AR). Four types of absorbable prototype components and 48 kinds of metabolites were identified in rats in the normal control plasma group which were given AR (AR plasma group), and five kinds of metabolites were identified in rats of the normal control brain tissue group which were given AR (AR brain group). Three absorbed prototype components and 13 metabolites were identified in the plasma of rats which underwent MCAO and were given AR (MCAO + AR plasma group). Six absorbed prototype components and two metabolites were identified in the brain tissue of rats who underwent MCAO and were administered AR (MCAO + AR brain group). These results showed that, after the oral administration of AR, the number of identified components in plasma was more than that in brain tissue. The number of prototype components in the AR plasma group was higher than that in the MCAO + AR plasma group, which may indicate that metabolite absorption in rats undergoing MCAO was worse. The number of prototype components in the MCAO + AR brain group was higher than that in the AR brain group, indicating that the blood-brain barrier was destroyed after MCAO, resulting in more compounds entering brain tissue.
CONCLUSIONS
UHPLC-HR-MS was used to rapidly analyze the components and metabolites of AR in the blood and brain of rats under normal and pathologic conditions, and to comprehensively characterize the components of TCM-AR. We also analyzed and compared the absorbable components and metabolites of normal rats under cerebral ischemia-reperfusion injury to explore the potential mechanism of action. This method could be applied to various Chinese herbs and disease models, which could promote TCM modernization.
Topics: Animals; Achyranthes; Chromatography, High Pressure Liquid; Rats; Brain; Rats, Sprague-Dawley; Male; Mass Spectrometry; Drugs, Chinese Herbal; Infarction, Middle Cerebral Artery; Flavonoids; Alkaloids
PubMed: 38930905
DOI: 10.3390/molecules29122840 -
Microorganisms Jun 2024CRL1505 possesses immunomodulatory activities in the gastrointestinal and respiratory tracts when administered orally. Its adhesion to the intestinal mucosa does not...
CRL1505 possesses immunomodulatory activities in the gastrointestinal and respiratory tracts when administered orally. Its adhesion to the intestinal mucosa does not condition its beneficial effects. The intranasal administration of CRL1505 is more effective than the oral route at modulating immunity in the respiratory tract. Nonetheless, it has not yet been established whether the adherence of the CRL1505 strain to the respiratory mucosa is needed to provide the immune benefits to the host. In this study, we evaluated the role of adhesion to the respiratory mucosa of the mucus-binding factor (mbf) knock-out CRL1505 mutant ( CRL1505) in the context of a Toll-like receptor 3 (TLR3)-triggered innate immunity response. In vitro adhesion studies in porcine bronchial epitheliocytes (PBE cells) indicated that CRL1505 adhered weakly compared to the wild-type strain. However, in vivo studies in mice demonstrated that the CRL1505 also reduced lung damage and modulated cytokine production in the respiratory tract after the activation of TLR3 to a similar extent as the wild-type strain. In addition, the mutant and the wild-type strains modulated the production of cytokines and antiviral factors by alveolar macrophages in the same way. These results suggest that the Mbf protein is partially involved in the ability of CRL1505 to adhere to the respiratory epithelium, but the protein is not necessary for the CRL1505 strain to exert its immunomodulatory beneficial effects. These findings are a step forward in the understanding of molecular interactions that mediate the beneficial effects of nasally administered probiotics.
PubMed: 38930591
DOI: 10.3390/microorganisms12061209 -
Microorganisms Jun 2024Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to (MP) infection. The pathogenic mechanisms involved remain largely...
Plastic bronchitis (PB) constitutes a life-threatening pulmonary disorder, predominantly attributed to (MP) infection. The pathogenic mechanisms involved remain largely unexplored, leading to the absence of reliable approaches for early diagnosis and clear treatment. Thus, the present investigation aimed to develop an MP-induced mouse model of PB, thereby enhancing our understanding of this complex condition. In the first stage, healthy BALB/c mice were utilized to investigate the optimal methods for establishing PB. This involved the application of nebulization (15-20 min) and intratracheal administration (6-50 μL) with 2-chloroethyl ethyl sulfide (CEES) concentrations ranging from 4.5% to 7.5%. Subsequently, the MP model was induced by administering an MP solution (2 mL/kg/day, 10 CFU/50 μL) via the intranasal route for a duration of five consecutive days. Ultimately, suitable techniques were employed to induce plastic bronchitis in the MP model. Pathological changes in lung tissue were analyzed, and immunohistochemistry was employed to ascertain the expression levels of vascular endothelial growth factor receptor 3 (VEGFR-3) and the PI3K/AKT/mTOR signaling pathway. The administration of 4.5% CEES via a 6 µL trachea was the optimal approach to establishing a PB model. This method primarily induced neutrophilic inflammation and fibrinous exudate. The MP-infected group manifested symptoms indicative of respiratory infection, including erect hair, oral and nasal secretions, and a decrease in body weight. Furthermore, the pathological score of the MP+CEES group surpassed that of the groups treated with MP or CEES independently. Notably, the MP+CEES group demonstrated significant activation of the VEGFR-3 and PI3K/AKT/mTOR signaling pathways, implying a substantial involvement of lymphatic vessel impairment in this pathology. This study successfully established a mouse model of PB induced by MP using a two-step method. Lymphatic vessel impairment is a pivotal element in the pathogenetic mechanisms underlying this disease entity. This accomplishment will aid in further research into treatment methods for patients with PB caused by MP.
PubMed: 38930514
DOI: 10.3390/microorganisms12061132 -
Microorganisms May 2024Periodontitis is a destructive inflammatory response triggered by dysbiosis. LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the...
Periodontitis is a destructive inflammatory response triggered by dysbiosis. LA5 (LA5) may impair microbial colonization and alter the host. Thus, we evaluated the effect of LA5 on alveolar bone loss in a periodontitis murine model and investigated its effect on the oral and gut microbiomes. and were inoculated in C57BL/6 mice (P+), with LA5 (L+). SHAM infected controls (P- and/or L- groups) were also evaluated. After 45 days, alveolar bone loss in the maxilla and oral and gut microbiomes were determined. The administration of LA5 controlled the microbial consortium-induced alveolar bone loss. Periodontopathogens infection resulted in shifts in the oral and gut microbiomes consistent with dysbiosis, and LA5 reshaped these changes. The oral microbiome of P+L- group showed the increased abundance of , , , and , which were attenuated by the administration of LA5 to the infected group (P+L+). The administration of LA5 to otherwise non-infected mice resulted in the increased abundance of the superphylum Patescibacteria and the family in the gut. These data indicate LA5 as a candidate probiotic for the control of periodontitis.
PubMed: 38930439
DOI: 10.3390/microorganisms12061057 -
Journal of Clinical Medicine Jun 2024Gastric fluid volume has been used as a surrogate marker for pulmonary aspiration risk in studies evaluating fasting protocol safety. This study measured residual...
Gastric fluid volume has been used as a surrogate marker for pulmonary aspiration risk in studies evaluating fasting protocol safety. This study measured residual gastric fluid volume in children using a protocol in which diluted oral contrast medium was administered up until one hour before anesthesia. This was a single-center prospective observational cohort trial of 70 children for elective abdominal/pelvic computed tomography (CT). Imaging was performed after diluted enteral contrast medium administration, beginning two hours before and ending at least one hour before induction. For each patient, gastric fluid volume was calculated using an image region of interest. The primary outcome measure was gastric fluid volume measured using the computed tomography image. The median time from the end of contrast administration to imaging was 1.5 h (range: 1.1 to 2.2 h). Residual gastric volume, measured using CT was <0.4 mL/Kg in 33%; ≥0.4 mL/Kg in 67%; and ≥1.5 mL/Kg in 44% of patients. Residual gastric volumes measured using CT and aspiration were moderately correlated (Spearman's correlation coefficient = 0.41, = 0.0003). However, the median residual gastric volume measured using CT (1.17, IQR: 0.22 to 2.38 mL/Kg) was higher than that of aspiration (0.51, IQR: 0 to 1.58 mL/Kg, = 0.0008 on differences in paired measures). Three cases of vomiting were reported. No evidence of pulmonary aspiration was identified. Children who receive large quantities of clear fluid up to one hour before anesthesia can have a significant gastric residual volume.
PubMed: 38930113
DOI: 10.3390/jcm13123584 -
Journal of Clinical Medicine Jun 2024: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic...
: The introduction of biological drugs in the management of chronic rhinosinusitis with nasal polyps (CRSwNP) is allowing new and increasingly promising therapeutic options. This manuscript aims to provide a multicenter trial in a real-life setting on Mepolizumab treatment for severe uncontrolled CRSwNP with or without comorbid asthma. : A retrospective data analysis was jointly conducted at the Otolaryngology-Head and Neck Surgery departments of La Sapienza University and San Camillo Forlanini Hospital in Rome. Both institutions participated by sharing clinical information on patients with CRSwNP treated with Mepolizumab. Patients were evaluated before starting Mepolizumab, at six months and at twelve months from the first drug administration. During follow-up visits, patients underwent endoscopic evaluation, quality of life assessment, nasal symptoms assessment, and blood tests to monitor mainly neutrophils, basophils, eosinophils, and IgG, IgA, and IgE assay. : Twenty patients affected by CRSwNP and treated with Mepolizumab were enrolled (12 females and 8 males with a mean age of 63.7 years). Sixteen patients (80%) had concomitant asthma. During follow-up, a gradual improvement in nasal polyp score, quality of life and nasal symptoms, assessed by SNOT-22 and VAS and loss of smell measured by olfactory VAS, was found. Regarding blood tests, eosinophils decreased gradually, while other blood parameters showed no statistically significant changes. : Mepolizumab has been shown to be effective in the therapeutic management of patients with CRSwNP. Further studies are needed to support our findings and better understand the underlying immune pathways to predict patients' response to biological treatment in CRSwNP.
PubMed: 38930104
DOI: 10.3390/jcm13123575