By promoting insulin secretion and shielding pancreatic islets, it has been shown to lessen the symptoms of diabetes.
Through a standardized methanolic extract of deep red Aloe vera flowers (AVFME), this study explored its in-vitro antioxidant effect, acute oral toxicity, and possible in-vivo anti-diabetic activity, including examination of pancreas histology.
In order to ascertain the chemical composition, the procedure of liquid-liquid extraction and TLC was adopted. Total phenolics and flavonoids within AVFME were measured employing the Folin-Ciocalteu and AlCl3 procedures.
Colorimetric methods, in a respective manner. The present research sought to assess the antioxidant effect of AVFME in a laboratory setting, utilizing ascorbic acid as a reference point, and a subsequent acute oral toxicity study was undertaken on 36 albino rats treated with varying concentrations of AVFME (200 mg/kg, 2 g/kg, 4 g/kg, 8 g/kg, and 10 g/kg body weight). Using an in-vivo anti-diabetic approach, the study investigated alloxan-induced diabetic rats (120mg/kg, intraperitoneally), administering two doses of AVFME (200mg/kg and 500mg/kg, oral) alongside glibenclamide (5mg/kg, orally) as a control for hypoglycemic effect. A histological examination of the pancreas was undertaken.
The phenolic content of AVFME samples peaked at 15,044,462 milligrams of gallic acid equivalents per gram (GAE/g), exceeding all other samples, along with the remarkable flavonoid content of 7,038,097 milligrams of quercetin equivalents per gram (QE/g). Laboratory research on AVFME showed its antioxidant capabilities were on par with ascorbic acid's. The AVFME, across various dosages in in-vivo trials, exhibited no overt signs of toxicity or lethality in any group, highlighting the extract's safety and substantial therapeutic window. AVFME's antidiabetic properties resulted in a substantial decrease in blood glucose levels, comparable to glibenclamide, but without the accompanying risks of severe hypoglycemia or significant weight gain, a clear benefit of AVFME compared to glibenclamide. The histopathological assessment of pancreatic samples confirmed that AVFME safeguards pancreatic beta cells. The extract is expected to display antidiabetic effects by inhibiting -amylase, -glucosidase, and the enzyme dipeptidyl peptidase IV (DPP-IV). selleck inhibitor The investigation of possible molecular interactions with these enzymes was conducted using molecular docking studies.
The oral safety, antioxidant action, anti-hyperglycemic properties, and pancreatic protective qualities of AVFME position it as a promising alternative for diabetes mellitus. These data suggest that AVFME's antihyperglycemic activity is achieved through pancreatic preservation and a significant increase in insulin secretion, facilitated by an augmentation in functional beta cells. This finding suggests a promising avenue for utilizing AVFME as a novel antidiabetic agent, or a potential dietary enhancement for addressing type 2 diabetes (T2DM).
AVFME's potential as an alternative source for active constituents in the management of diabetes mellitus (DM) is bolstered by its demonstrated oral safety, antioxidant activity, anti-hyperglycemic effects, and protection of pancreatic function. These data highlight that AVFME's antihyperglycemic activity is contingent upon safeguarding the pancreas and concomitantly elevating insulin secretion through an increase in the number of functioning beta cells. This finding indicates that AVFME could be a groundbreaking new treatment option for type 2 diabetes (T2DM), either as a medication or a dietary supplement.
A frequently used Mongolian folk remedy, Eerdun Wurile, addresses a broad spectrum of health issues, encompassing cerebral nervous system disorders (including cerebral hemorrhage, cerebral thrombosis, nerve injury, and cognitive function), as well as cardiovascular diseases like hypertension and coronary heart disease. selleck inhibitor The effect of eerdun wurile on cognitive function after surgery is a subject of inquiry.
Based on a network pharmacology approach, this research investigates the molecular mechanisms through which the Mongolian medicine Eerdun Wurile Basic Formula (EWB) ameliorates postoperative cognitive dysfunction (POCD), specifically examining the contribution of the SIRT1/p53 signaling pathway, using a rodent model of POCD.
From the databases TCMSP, TCMID, PubChem, PharmMapper, GeneCards, and OMIM, collect disease-related targets and compounds, and identify genes shared between them. The functional enrichment of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was determined using R statistical software. A POCD mouse model, produced by intracerebroventricular lipopolysaccharide (LPS) injection, had its hippocampal tissue morphological alterations observed via hematoxylin-eosin (HE) staining, Western blotting, immunofluorescence, and TUNEL assays. These assays confirmed the conclusions of the network pharmacological enrichment analysis.
Through EWB's approach to improving POCD, 110 potential targets were discovered, 117 items enriched by GO, and 113 pathways enriched by KEGG. Among these KEGG enriched pathways, the SIRT1/p53 signaling pathway correlated with the development of POCD. selleck inhibitor Within EWB, quercetin, kaempferol, vestitol, -sitosterol, and 7-methoxy-2-methyl isoflavone exhibit stable conformational arrangements with low binding energy for core target proteins IL-6, CASP3, VEGFA, EGFR, and ESR1. Rodent studies revealed that, in comparison to the POCD model cohort, the EWB group exhibited a substantial enhancement in hippocampal apoptosis and a marked downregulation of Acetyl-p53 protein expression (P<0.005).
EWB's multifaceted effects, exhibiting multi-component, multi-target, and multi-pathway synergy, lead to enhanced POCD. Empirical evidence confirms that EWB's impact on gene expression within the SIRT1/p53 signaling pathway may increase the occurrence of POCD, providing a fresh therapeutic focus and basis for managing POCD.
EWB's improvement of POCD is facilitated by the combined actions of multiple components, targets, and pathways, exhibiting synergistic effects. Studies have underscored that EWB can positively affect the prevalence of POCD by influencing the expression of genes in the SIRT1/p53 signal transduction pathway, thereby presenting a novel therapeutic direction and basis for POCD.
Contemporary therapies for advanced castration-resistant prostate cancer (CRPC), employing agents like enzalutamide and abiraterone acetate focused on the androgen receptor (AR) transcription process, generally produce only a temporary benefit before the development of resistance becomes evident. Neuroendocrine prostate cancer (NEPC) is a lethal and AR pathway-independent form of prostate cancer, for which no standard therapeutic regimen is currently available. QDT, a traditional Chinese medicine formula, possesses a variety of pharmacological actions and has been frequently used to treat a broad spectrum of diseases, such as prostatitis, a condition possibly related to the development of prostate cancer.
The study aims to explore QDT's anti-tumor properties in prostate cancer and seeks to understand the potential mechanisms.
To facilitate research on CRPC prostate cancer, models involving cell lines and xenograft mice were established. To understand how TCMs affected cancer growth and spread, researchers used the CCK-8, wound-healing, and PC3-xenograft mouse model. To determine the toxicity of QDT in major organs, H&E staining was performed. The compound-target network was evaluated through the lens of network pharmacology. An analysis of QDT targets' correlation with prostate cancer prognosis was performed on multiple patient cohorts with prostate cancer. The detection of related proteins' and mRNA's expression was achieved through the combined use of western blotting and real-time PCR. The gene knockdown was facilitated by the CRISPR-Cas13 system.
Our comprehensive analysis, utilizing functional screening, network pharmacology, CRISPR-Cas13-directed RNA interference, and molecular validation in numerous prostate cancer models and clinical cohorts, revealed that Qingdai Decoction (QDT) inhibits cancer growth in advanced prostate cancer models in vitro and in vivo through a pathway not reliant on the androgen receptor, specifically modulating NOS3, TGFB1, and NCOA2.
This research not only discovered QDT as a novel therapeutic agent for lethal prostate cancer but also developed an extensive integrated research protocol for investigating the mechanisms and functions of Traditional Chinese Medicine in the treatment of other medical conditions.
The current study, besides unveiling QDT as a novel drug in lethal-stage prostate cancer treatment, further established a comprehensive integrative research model for exploring the functions and mechanisms of Traditional Chinese Medicines in treating various other diseases.
The consequences of ischemic stroke (IS) include significant illness and fatality. Previous studies by our team highlighted the pharmacological properties of the bioactive components found in the traditional medicinal and edible plant Cistanche tubulosa (Schenk) Wight (CT), particularly their effectiveness in managing nervous system ailments. Despite this, the consequences of computed tomography (CT) on the blood-brain barrier (BBB) post-ischemic stroke (IS) are presently unknown.
This study was undertaken to investigate the curative actions of CT on IS and the contributing mechanisms.
In a rat model of middle cerebral artery occlusion (MCAO), injury was observed. The gavage administration of CT, at 50, 100, and 200 mg/kg/day, occurred for seven days in a row. In order to predict the pathways and targets involved in CT's treatment of IS, network pharmacology was utilized, and follow-up studies confirmed the relevance of these targets.
In the MCAO group, the results demonstrated a more severe manifestation of neurological impairment as well as blood-brain barrier disruption. Ultimately, CT's impact was seen in the improvement of BBB integrity and neurological function, while providing defense against cerebral ischemia injury. Analysis via network pharmacology pointed to a potential role for microglia in the neuroinflammation associated with IS.