Tuberculosis (TB) remains one of the deadliest infectious diseases worldwide. The substantial reservoir of latent infections, the emergence of multidrug-resistant and extensively drug-resistant TB (MDR/XDR-TB), and the prolonged duration and toxicity of current therapeutic regimens underscore the urgent need for novel treatment strategies. Therapeutic vaccines, an innovative immunotherapeutic approach, are designed to be administered alongside standard pharmacological treatments. By enhancing pathogen-specific immune responses in the host, these vaccines aim to eradicate persistent bacteria, reduce treatment duration, and prevent disease recurrence, thus representing a promising strategy for addressing MDR-TB. This review systematically summarizes the leading therapeutic vaccine candidates currently in clinical trials, detailing the associated mechanisms of action and preclinical and clinical efficacy data. Additionally, the review critically examines existing challenges and outlines future research directions. Overall, this comprehensive analysis seeks to enhance understanding of the potential and development pathways of therapeutic vaccines for TB treatment, contributing to the global effort against this widespread health threat.
Medicinal plants have long been used to manage hyperuricemia (HUA) and gout, with flavonoids identified as key bioactive components. However, the therapeutic effects of flavonoids on HUA remain inadequately characterized. Thus, we conducted a systematic review and meta-analysis to evaluate the impact of flavonoids on serum uric acid (UA) and xanthine oxidase (XOD) activity in animal models. A comprehensive literature search of the PubMed and Web of Science databases (January 2007–December 2024) identified 21 eligible studies involving 550 male mice. A random-effects meta-analysis revealed that flavonoid administration significantly reduced serum UA (standardized mean difference [SMD] = –2.22, 95% confidence interval (CI): –2.80 to –1.64; p < 0.001) and XOD activity (SMD = –1.79, 95% CI: –2.50 to –1.08; p < 0.001). Subgroup analyses indicated that chalcones, flavonols, and flavones exerted the most pronounced hypouricemic effects. Molecular docking of 28 flavonoids to XOD yielded binding affinities ranging from –8.4 to –10.9 kcal/mol, with molecular dynamics simulations confirming stable ligand–enzyme complexes; flavones exhibited the highest stability. Collectively, these data provide robust preclinical evidence that flavonoids ameliorate hyperuricemia via dual mechanisms of UA reduction and XOD inhibition, and support the further clinical development of flavonoids as potential natural agents for managing HUA.
The therapeutic potential of herbal and natural compounds has long been recognized; meanwhile, the role of these compounds in neuropharmacology is gaining increasing attention due to their promising biochemical effects. The rising prevalence of neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and depression, has underscored the need for novel, effective treatments with minimal side effects. Notably, natural products derived from plants, fungi, and other organisms offer a vast array of bioactive molecules that can interact with neuronal pathways to modulate cognitive function, neuroprotection, and synaptic plasticity. Furthermore, recent advancements in neuropharmacology have revealed the molecular mechanisms underlying the therapeutic efficacy of herbal compounds, such as flavonoids, alkaloids, terpenoids, and phenolic acids, in mitigating oxidative stress, inflammation, and neuroinflammation. Moreover, these compounds have shown promise in enhancing neurotransmitter systems, such as serotonin, dopamine, and acetylcholine. The integration of cutting-edge technologies, including high-throughput screening, metabolomics, and molecular docking, has facilitated the discovery of novel natural neuroprotective agents. Artificial Intelligence (AI) and nanotechnology are transforming the use of phytobioactive compounds in modern neuropharmacology by enabling precise prediction of molecular targets, optimizing drug-likeness, and enhancing mechanistic understanding. Additionally, nanocarriers such as polymeric nanoparticles, liposomes, and nanoemulsions, are improving the brain delivery, stability, and bioavailability of plant-derived molecules that traditionally suffer from poor pharmacokinetics. Together, these technologies can accelerate the development of next-generation neuroprotective therapeutics from natural products with greater efficiency, specificity, and translational potential. This review provides a comprehensive overview of the latest biochemical innovations in herbal and natural compounds for neuropharmacology, emphasizing the potential of these compounds as safe and effective alternatives or adjuncts to conventional neurotherapeutics.
Background: Dioscorea dumetorum (bitter yam) is an underutilized West African species valued for its nutritional and ethnomedicinal importance. While its tubers have been extensively studied, the essential oils of its aerial parts remain largely unexplored. This study investigated the chemical composition, antimicrobial activity, and antioxidant potential of essential oils extracted from the leaves and stems of Dioscorea dumetorum, to provide scientific insight into their bioactive properties and industrial relevance.Methods: Leaves and stems were air-dried, pulverized, and hydro distilled using a Clevenger-type apparatus. Oil yields and physicochemical properties were determined, while chemical constituents were characterized by Gas Chromatography-Mass Spectrometry (GC-MS). Antimicrobial activity was evaluated against selected bacterial (Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Salmonella typhi, Pseudomonas aeruginosa, Klebsiella pneumoniae) and fungal (Candida albicans, Aspergillus niger, Penicillium notatum, Rhizopus stolonifer) pathogens using the agar well diffusion method. Antioxidant potential was assessed by Ferric Reducing Antioxidant Power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays.Results: The leaf and stem oils yielded 0.50% and 1.07%, respectively. GC-MS analysis revealed 23 and 20 compounds dominated by 2-pentadecanone (20.64%) and phytol (16.74%) in the leaf oil, and di-n-octyl phthalate (34.43%) and eicosanoic acid esters (15.97%) in the stem oil. Both oils exhibited broad-spectrum antimicrobial effects, with leaf oil showing larger inhibition zones (18-26 mm) than stem oil (14-24 mm). Antioxidant assays demonstrated concentration-dependent activities: leaf oil showed stronger ferric-reducing power, whereas stem oil displayed higher radical-scavenging potential.Conclusions: These findings demonstrated that Dioscorea dumetorum essential oils possess significant antimicrobial and antioxidant properties with distinct phytochemical profiles, supporting their potential applications as natural sources of bioactive compounds in nutraceutical, pharmaceutical, and cosmetic formulations.
Background: The incidence of altitude-related diseases has increased as more and more people have begun living in places at high altitudes. High-altitude polycythemia (HAPC) is a very widespread disease in high-altitude areas. Salvia miltiorrhiza has high medicinal value, with anti-tumor, anti-inflammatory, anti-myocardial ischemia, anti-oxidative stress, anti-thrombosis, and vascular dilation effects, as well as anti-atherosclerosis effects, thereby protecting against brain tissue damage, improving microcirculation, and activating the immune system. This study aimed to predict the latent molecular mechanisms through which the main active ingredients of Salvia miltiorrhiza treat HAPC disease using bioinformatics methods, including network pharmacology and molecular docking.Methods: The Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen for effective compounds and protein targets of Danshen, and the chemical structures of these compounds were downloaded. Using 'high-altitude polycythemia' as the keyword, the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases were searched for potential disease targets, and the overlapping targets were identified through an intersection analysis. The protein-protein interaction (PPI) network was analyzed using Cytoscape 3.80. The Metascape database was utilized for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. 3D structures of the major proteins were obtained from the Protein Data Bank (PDB) database, and molecular docking was conducted between the main compounds and the core proteins, after which binding energies were plotted as a heatmap. The binding scenarios of the top two binding energies were visualized.Results: Danshen has anti-HAPC effects on the major compounds MOL000006, MOL007154, MOL007145, MOL007100, MOL007041, MOL007049, MOL007108, and MOL007088; the core targets are RAC-alpha serine/threonine-protein kinase (AKT1), interleukin-6 (IL6), tumor necrosis factor (TNF), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-9 (MMP9), nitric oxide synthase 3 (NOS3), estrogen receptor (ESR1), peroxisome proliferator-activated receptor gamma (PPARG), and interleukin-10 (IL10). The GO and KEGG results revealed that Danshen may exert anti-HAPC activity by regulating the binding of ligand-activated transcription factors, nuclear receptor activity, signaling receptor regulator activity, and the binding of certain other molecules to cellular compounds such as receptor complexes, the side of the membrane, the endoplasmic reticulum lumen, and the response to hormones, thereby achieving the regulation of epithelial cell migration, blood pressure, and other biological process (BP) entries. The signaling pathways related to the mechanism of action of Danshen mainly include the cancer pathway, the Hypoxia-inducible factor 1 (HIF-1) signaling pathway, and the Phosphatidyqinositol-3 kinase-RAC-alpha serine/threonine-protein kinase (PI3K-Akt) signaling pathway. The molecular docking results showed that the active components bound more stably to the targets, especially NOS3, TNF, and AKT1.Conclusion: This research predicted the primary active compounds, targets of action, and signaling pathways involved in predicting the efficacy of Danshen in treating HAPC, using network pharmacology and molecular docking methods. This research provides the theoretical basis for subsequent experimental studies on the use of Danshen in clinical practice.
Background and Objective: Renal interstitial fibrosis (RIF) is a prevalent and irreversible process that drives the progression of chronic kidney disease (CKD) to end-stage renal failure and is characterized by significant deposition of fibrotic matrix proteins. The unilateral ureteral obstruction (UUO) model induces rapid tubulointerstitial fibrosis and is widely used to study antifibrotic interventions. Scutellarin, an active flavonoid derived from Erigeron breviscapus, has demonstrated efficacy in alleviating symptoms of various chronic diseases, including stroke, neurodegenerative disorders, and cardiovascular and renal diseases. However, the impact of scutellarin on renal fibrosis in obstructive nephropathy remains unclear. Thus, this study evaluated the effects of scutellarin on fibrosis and renal function in a UUO mouse model.Materials and Methods: Male C57BL/6 mice underwent UUO surgery and received oral scutellarin (21 mg/kg/day) for 3 days before and 5 days after surgery. Renal fibrosis was assessed by immunohistochemistry (IHC; collagen I) and Western blotting (WB; alpha-smooth muscle actin (alpha-SMA), fibronectin (FN), collagen I). Kidney function was evaluated by urinary protein (BCA assay), serum blood urea nitrogen (BUN), and serum creatinine (Scr). Data were analyzed using GraphPad Prism 8; p < 0.05 was considered statistically significant.Results: UUO induced significant interstitial fibrosis, as evidenced by increased collagen I deposition and elevated protein levels of alpha-SMA, FN, and collagen I. Scutellarin treatment significantly attenuated these changes, reducing the collagen I IHC-positive area to 0.63-fold and the alpha-SMA, FN, and collagen I protein levels (WB, normalized to glyceraldehyde-3-phosphate dehydrogenase) to 0.21-, 0.45-, and 0.54-fold of UUO levels, respectively (all p < 0.01). Concurrently, scutellarin significantly lowered proteinuria, BUN, and Scr compared with the UUO group (all p < 0.0001).Conclusion: Scutellarin ameliorated renal fibrosis and dysfunction in the UUO mouse model, associated with downregulation of key fibrosis-related proteins. These findings support further preclinical investigation of scutellarin as a potential antifibrotic agent in kidney disease.
Background: Subarachnoid hemorrhage (SAH) is a cerebrovascular disease with high mortality and long-term neurological sequelae, largely driven by early brain injury, inflammation, neuronal apoptosis, and oxidative stress. Umbelliferone (7-hydroxycoumarin) exhibits notable antioxidant and anti-inflammatory properties. This study aimed to investigate the neuroprotective effect of umbelliferone in a mouse model of SAH and explore the underlying mechanisms.Materials and Methods: Following SAH induction, mice received the oral administration of umbelliferone (2.5, 5, or 10 mg/kg). Body weight, brain weight, and brain water content were measured to assess cerebral edema and neurological injury. Tight junction protein levels were quantified to assess blood brain barrier (BBB) integrity; meanwhile, antioxidant markers, inflammatory cytokines, and apoptosis-related parameters were also evaluated. Furthermore, mRNA expression levels in brain tissue were analyzed to elucidate the underlying molecular mechanisms.Results: Umbelliferone significantly improved body weight and enhanced brain weight (p < 0.001). Umbelliferone also altered the level of tight junction parameters (occludin, claudin-5, zonula occludens-1 (ZO-1)); oxidative stress parameters (glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), malonaldehyde (MDA)); mitogen-activated protein kinase (MAPK) parameters (phosphorylated c-Jun N-terminal kinase(p-JNK), phosphorylated extracellular signal-regulated kinase (p-ERK), phosphorylated p38 MAPK (p-38)); inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-18 (IL-18)); inflammatory parameters (cyclooxygenase-2 (COX-2), nuclear factor kappa B (NF-kappa B), transforming growth factor-beta (TGF-beta)); apoptosis parameters (Bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), caspase-3, Bax/Bcl-2 ratio). Umbelliferone also significantly (p < 0.001) altered the mRNA expression of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), basigin (BSG2), TNF-alpha, IL-6, monocyte chemoattractant protein-1 (MCP-1), claudin-5, occludin, phosphoinositide 3-kinase (PI3K), protein kinase B (AkT), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4).Conclusion: Umbelliferone exerts neuroprotective effects against SAH in mice, at least in part, by modulating the TLR2/TLR4-NF-kappa B-MMP-9 and PI3K/Akt signaling pathways.
Background: Hepatic fibrosis (HF) is a major global health burden with limited effective therapies. Ferroptosis, an iron-dependent form of cell death, and inflammatory pathways are implicated in HF progression. Salvia miltiorrhiza (Danshen) has demonstrated antifibrotic effects, but its underlying mechanisms remain unclear. Objective: To elucidate the mechanisms of Danshen in treating HF through network pharmacology and experimental validation, focusing on the JAK/STAT pathway, iron metabolism, and ferroptosis. Methods: Using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, we identified 92 common targets among Danshen components, HF-related genes, and iron metabolism genes. A CCl4-induced HF rat model was established (n = 70) and treated with Danshen (3 or 6 g/kg/d) for 4 weeks. Hepatic fibrosis was assessed by Masson staining. Serum markers including Fe2+, transferrin (TRF), ferritin (SF), type III procollagen (PCIII), hydroxyproline (HyP), malondialdehyde (MDA), and glutathione (GSH) were measured. Western blotting evaluated hepatic expression of IL-6, P-JAK2, p-STAT3, and GPX4. Results: Network pharmacology revealed JAK2/STAT3 as top hub genes among 92 intersection targets. High-dose Danshen decreased IL-6, P-JAK2, and p-STAT3 expression by 45-60% (p < 0.05), increased serum Fe2+ and TRF by 1.8-fold, and reduced SF, HyP by >40% and PCIII by >15% (p < 0.05). Additionally, Danshen restored GPX4 protein expression and suppressed ferroptosis by decreasing MDA while increasing GSH (p < 0.01). Masson staining showed 55% reduction in collagen deposition with high-dose treatment. Conclusion: Danshen alleviates hepatic fibrosis by modulating the JAK/STAT-iron-ferroptosis axis, establishing a novel multi-target therapeutic strategy for HF.
Background: Tirzepatide (TZP), a dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide 1 (GLP-1) receptor agonist, has shown potential in improving glycemic control. However, its effects on diabetes mellitus (DM)-related systemic complications remain less defined. This study investigated the impact of TZP on metabolic, cardiovascular, renal, and thyroid parameters in a rat model of DM.Methods: Experimental DM was induced in rats via a single intraperitoneal injection of streptozotocin (50 mg/kg). Animals were allocated into four groups: control (saline), DM, TZP alone (1.35 mg/kg, cyclic dosing), and DM+TZP (streptozotocin followed by five TZP injections). Survival, body-weight, and serum biochemical markers were monitored, including glucose, insulin, troponin I, Creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), blood urea nitrogen (BUN), creatinine, cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), thyroid-stimulating hormone (TSH), thyroxine (T4), and triiodothyronine (T3).Results: Survival was preserved in the control, TZP alone, and DM+TZP groups, whereas mortality reached 10% in the DM group. Body weight decreased significantly in the DM and DM+TZP groups, with a modest reduction in the TZP alone group. TZP markedly increased hyperglycemia and LDH levels without altering troponin I or CK-MB levels. DM-associated elevations in BUN and creatinine were partially attenuated by TZP, suggesting renoprotective effects. TZP had no impact on cholesterol or LDL-C, but significantly decreased triglycerides and increased HDL-C. Additionally, TZP modulated thyroid hormone levels, as reflected by increased T4 and decreased T3 concentrations compared with diabetic rats.Conclusions: In this experimental DM model, TZP improved glycemic control, ameliorated renal dysfunction, and favorably modulated lipid metabolism and thyroid axis activity, with no evidence of overt myocardial necrosis observed based on troponin I and CK-MB; additional studies incorporating histology and/or functional assessments are needed to evaluate subclinical cardiac effects. These findings indicate the therapeutic potential of TZP in mitigating DM-associated complications beyond glucose regulation.
Background: Alcohol consumption exerts toxic effects on the central nervous system, causing neurodegeneration and behavioral disorders. The neuroprotective potential of disulfiram (DSF), a widely used treatment for alcohol dependence, remains unclear. Thus, this study aimed to evaluate the effects of DSF on ethanol-induced neurodegeneration, behavioral impairments, and cardiovascular alterations.Materials and Methods: A total of 28 rats were randomly assigned to four groups: control, ethanol (EtOH), EtOH + DSF, and DSF. Ethanol (5 g/kg) was administered orally three times per week for 14 days. The EtOH + DSF group received ethanol plus DSF (100 mg/kg, intraperitoneally, i.p.) while the DSF group received DSF alone. Blood pressure was measured using tail-cuff plethysmography. Behavioral alterations were analyzed through the open field test (OFT), elevated plus maze (EPM), and forced swim test (FST). Brain tissues were examined histopathologically using hematoxylin-eosin and toluidine blue staining. Data were analyzed by analysis of variance (ANOVA) and the Kruskal-Wallis test.Results: In the EPM, no significant differences were found among the groups in open-arm activity or risk-assessment behaviors. The OFT showed a significant reduction in locomotor activity in the EtOH group (p < 0.0001). In the FST, ethanol increased immobility (p < 0.0001) and decreased the latency to immobility (p = 0.0014). Ethanol markedly lowered systolic, diastolic, and mean arterial pressures, whereas DSF elevated systolic and mean arterial pressures without affecting heart rate. DSF treatment affects systolic and mean arterial blood pressures. So for systolic blood pressure p = 0.002. For mean arterial blood pressure p = 0.024. Histological analysis revealed neuronal damage in the EtOH group, while DSF significantly reduced the number of degenerating neurons (p < 0.001).Conclusion: Ethanol exposure was associated with depression-like behavior, reduced locomotor activity, and hypotension. DSF treatment may improve behavioral outcomes, partially counteract ethanol-induced hypotension, and confer neuroprotective effects.
Background: As a major metabolic organ, the liver is constantly exposed to toxic substances. Although the flesh and seeds of Ajwa dates have been established to have antioxidant and anti-inflammatory properties, the hepatoprotective potential of Ajwa seed oil (ASO) against CCl4-induced damage has yet to be ascertained. Methods: Twenty-four adult male mice were randomly assigned to one of four groups (n = 6 per group): control (oral saline for 12 days), CCl4-treated [saline for 12 days plus a single dose of CCl4 dissolved in corn oil 1:1 (1 mL/kg)], CCl4 + ASO (100 mg/kg ASO administered daily for 12 days, followed by CCl4), and CCl4 + silymarin (100 mg/kg silymarin administered daily for 12 days, followed by CCl4). Blood and liver samples were collected 24 h after CCl4 administration for biochemical and histological analyses. Results: ASO treatment substantially reduced CCl4-induced liver damage by restoring normal serum liver enzyme levels (alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase; p < 0.05), lowering elevated levels of cholesterol and triglycerides, and increasing albumin levels (p < 0.05). The treatment significantly reduced lipid peroxidation, as evidenced by decreased malondialdehyde levels (p < 0.0001), and concurrently restored the total antioxidant capacity. Histological analysis revealed the preservation of liver architecture, reduced collagen deposition, and maintenance of glycogen storage (p > 0.05). Conclusion: Our findings in this study revealed that ASO has beneficial hepatoprotective effects against CCl4-induced injury, which can be attributed largely to its antioxidant properties, as evidenced by restored total antioxidant capacity and reduced lipid peroxidation. Anti-inflammatory mechanisms may also contribute, as suggested by the histological reduction in inflammatory cell infiltration; however, direct measurement of inflammatory biomarkers warrants investigation in future studies.
Background: Berberine represents a promising supplement with several health benefits. Thus, this study aimed to investigate the efficacy of berberine in reducing mammary carcinoma induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female mice.Materials and Methods: A total of 40 virgin female mice were segregated into four groups: an untreated control group, a group treated with a daily oral dose of berberine (BBR) extract (25 mg/kg), a group injected with a single dose of 50 mg/kg DMBA in the breast fat pad, and a group treated with DMBA, similar to the third group. After 1 week of injections, the animals were treated with BBR extract, as in the second group.Results: Animals treated with DMBA for mammary carcinoma induction showed increases in liver enzymes (ALT, AST, and ALP), kidney biomarkers (BUN, UA, and CRT), and an oxidative stress marker (MDA). Meanwhile, DMBA also promoted a decrease in the antioxidant marker (GSH) and a minor elevation in estrogen levels. Conversely, the progesterone levels increased significantly, along with those of proinflammatory cytokines (interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha)). The histopathological analysis revealed carcinoma cells in the breast tissue, with a marked desmoplastic response. Meanwhile, the uterus showed hyperplasia and dysplasia of endometrial epithelia. The immunohistochemical analysis for Ki-67 expression revealed an intense immunoreaction associated with carcinoma proliferation in the breast. In contrast, the treatment with BBR extraction one week after the induction of mammary carcinoma by DMBA resulted in a significant decrease in liver enzymes and kidney biomarkers, as well as a reduced MDA level and a higher GSH level due to oxidative stress reduction, along with a variance in female hormone levels and a decrease in cytokines. Furthermore, the histopathological analysis showed a decline in the occurrence of carcinoma and desmoplastic response in the breast, as well as less hyperplasia and dysplasia of endometrial epithelia, and a lower incidence of Ki-67 expression in the breast.Conclusion: This study observed that berberine extract possessed a potent effect in reducing the mammary carcinoma induced by DMBA in female mice.
Background: Patients with acute coronary syndrome (ACS) who also have chronic myelocytic leukemia (CML) or gastrointestinal stromal tumor (GIST) may receive a concurrent therapy of imatinib and ticagrelor. The absorption and transport of both drugs are influenced by organic anion transporting polypeptides (OATPs), P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Furthermore, both are primarily metabolized by CYP3A4 enzymes. Thus, co-administration may lead to pharmacokinetic interactions. Therefore, this study aimed to investigate the effect of ticagrelor on imatinib pharmacokinetics in rats.Methods: A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups: a control group (imatinib 30 mg/kg), a low-dose experimental group (imatinib 30 mg/kg, ticagrelor 10 mg/kg), and a high-dose experimental group (imatinib 30 mg/kg, ticagrelor 20 mg/kg). All rats received the appropriate drugs once daily for 14 consecutive days. Venous blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose on days 1 and 14, and the plasma was isolated. Pharmacokinetic parameters were calculated using DAS 2.0 software.Results: On day 1, no significant changes were observed in the pharmacokinetic parameters of either imatinib or any associated active metabolite, N-desmethyl imatinib. However, after 14 days, the high-dose experimental group showed a significant decrease in the area under the plasma concentration time curve for imatinib from 0 to 24 hours (area under the curve, AUC0-24) and from 0 to infinity (AUC0-infinity). Similarly, the AUC0-24, AUC0-infinity, and maximum concentration (Cmax) of N-desmethyl imatinib were also significantly reduced in the high-dose experimental group. In contrast, administering 10 mg/kg ticagrelor did not significantly affect the pharmacokinetics of imatinib or N-desmethyl imatinib. The trough plasma concentrations (Cmin) of both imatinib and N-desmethyl imatinib were not significantly altered in any group.Conclusions: Repeated administration of 20 mg/kg ticagrelor significantly inhibited imatinib absorption in rats. These results suggest that clinical symptoms and imatinib plasma concentration should be monitored when ticagrelor and imatinib are used concomitantly.
Background: Aging is a critical global public health challenge, and natural products represent a key area in anti-aging research. Therefore, this study aimed to explore the chemical composition and anti-aging efficacy of the lotus seed coat.Methods: Ultra-high-performance liquid chromatography-Orbitrap mass spectrometry (UHPLC/Orbitrap-MS) was used to analyze chemical components. The lifespan of Caenorhabditis elegans (C. elegans) treated with lotus seed coat extract was measured, along with oxidative stress markers and antioxidant enzyme activity. Network pharmacology and molecular dynamics simulations were employed to predict any associated anti-aging mechanisms.Results: A total of 67 compounds were tentatively identified in the lotus seed coat, including 14 alkaloids, 19 flavonoids, and 6 phenolic acids. Lotus seed coat extract prolonged the lifespan of C. elegans (p < 0.05), reduced lipofuscin and reactive oxygen species (ROS) levels (p < 0.001), increased superoxide dismutase (SOD) and catalase (CAT) activity, and decreased malondialdehyde (MDA) content. Network pharmacology linked the anti-aging effects of the lotus seed coat extract to the regulation of SRC, PIK3R1, AKT1, IL6, and TNF genes expression and implicated the phosphatidylinositol 3-kinase/protein kinase B pathway (PI3K-Akt), mitogen-activated protein kinase (MAPK), hypoxia-inducible factor 1 (HIF-1), forkhead box O (FOXO), tumor necrosis factor (TNF), and mammalian target of rapamycin (mTOR) signaling pathways. Molecular simulations confirmed that neferine strongly binds to phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), histone acetyltransferase p300 (EP300), and RAC-alpha serine/threonine-protein kinase (AKT1).Conclusion: Lotus seed coat is rich in bioactive compounds and exhibits significant anti-aging potential.
Background: Aging and menopause accelerate bone loss, increasing susceptibility to osteoporotic vertebral compression fractures (OVCFs), which cause severe pain, compromise respiratory function, and elevate mortality risk. Therefore, to mitigate this risk, various 10 medications have been used to prevent secondary fractures. However, a comprehensive summary of the efficacy of these medications remains limited, prompting our systematic review and meta-analysis of randomized controlled trials (RCTs) to elucidate the effects of these medications on the prevention of subsequent OVCFs.Materials and Methods: A comprehensive systematic search was conducted across five electronic databases-PubMed, EMBASE, Scopus, Web of Science (WOS), and the Cochrane Library-to identify peer-reviewed studies published in English. Eligible studies were included in a quantitative synthesis. Pooled effect estimates were calculated as odds ratios (ORs) or risk ratios (RRs), along with the associated 95% confidence intervals (CIs). Additionally, heterogeneity was assessed using the Cochrane Q statistic and quantified with the I-2 metric, and meta-analytic procedures were performed using Review Manager (RevMan) software, version 5.4 (The Cochrane Collaboration, Copenhagen, Denmark). The systematic review protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD420251176522), and the full protocol is available at: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251176522.Results: High- to moderate-quality evidence from pooled randomized controlled trials indicates that most bisphosphonates (zoledronate, alendronate, risedronate, etidronate, and ibandronate) and non-bisphosphonate therapies (denosumab, teriparatide, bazedoxifene, estrogen, calcitonin, and parathyroid hormone) are associated with a significant reduction in fracture risk. Overall, most bisphosphonates demonstrated an approximate 40-60% reduction in fracture risk (risk ratio [RR] range: 0.40-0.60; 95% confidence intervals [CIs] spanning 0.23-0.77), while non-bisphosphonates were associated with a 30-50% reduction (RR range: 0.30-0.50; 95% CIs: 0.19-0.71), acknowledging that individual agents exhibited varying magnitudes of effect. Pooled analyses also showed that both drug classes increased bone mineral density, with bisphosphonates producing an approximate 3-7% increase (odds ratio [OR] range: 0.33-0.54; 95% CI: 0.19-0.74) and non-bisphosphonates a 3-5% increase (OR range: 0.36-0.57; 95% CI: 0.23-0.83). Furthermore, safety data synthesized from the included trials indicated a low incidence of adverse events for both treatment classes, with bisphosphonates showing RRs ranging from 0.19 to 0.44 (95% CI: 0.09-0.81) and non-bisphosphonates from 0.23 to 0.49 (95% CI: 0.12-0.89).Conclusion: High- to moderate-quality evidence supports the efficacy of zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone (PTH), denosumab, and selective estrogen receptor modulators (SERMs) in preventing secondary OVCFs. Zoledronate, risedronate, and PTH reduced both vertebral and non-vertebral fractures. Denosumab outperformed alendronate, and PTH surpassed risedronate, although with increased risk of adverse events.
Background: Despite nephrotoxicity concerns, liposomal amphotericin B (L-AMB) remains essential for treating invasive fungal infections in immunocompromised patients. Therefore, this study aimed to evaluate the incidence of L-AMB-associated nephrotoxicity, assess the effectiveness of nephroprotective premedication, determine treatment efficacy, and identify risk factors for adverse outcomes. Methods: A retrospective analysis was conducted on adult hematology-oncology patients who received intravenous L-AMB for >= 7 days between January 2017 and December 2020. Patients with pre-existing dialysis dependency or acute kidney injury were excluded. The primary endpoint was the incidence of acute kidney injury within two weeks of L-AMB administration. Secondary endpoints included treatment efficacy, biomarker associations, predictors of nephrotoxicity, and the effectiveness of nephroprotective strategies. Results: Among the 90 analyzed patients, 46.7% (42/90) developed nephrotoxicity within two weeks of L-AMB treatment, whereas 53.3% (48/90) did not experience nephrotoxicity. Treatment efficacy was high, with 83.3% of patients avoiding breakthrough fungal infections. Median serum creatinine levels were significantly higher in the nephrotoxicity group both before and after treatment (p < 0.001). Logistic regression identified advancing age as significantly associated with higher odds of nephrotoxicity (odds ratio (OR) = 1.032; p = 0.017). Concomitant use of colistin (OR = 10.10; p = 0.008) and cyclosporine (OR = 9.01; p = 0.027) significantly increased nephrotoxicity risk. No significant association was found between the galactomannan/beta-D-glucan results and breakthrough infections (p = 0.131) or between nephroprotective premedication protocols and nephrotoxicity prevention (p = 0.798). Conclusions: L-AMB-associated nephrotoxicity affected 46.7% of the included hematology-oncology patients while maintaining acceptable antifungal efficacy (83.3% without breakthrough infections). Advancing age, colistin, and cyclosporine were identified as independent risk factors with additive nephrotoxic mechanisms. The absence of demonstrable benefits from premedication strategies likely reflects methodological limitations. These findings support enhanced renal monitoring for patients receiving concurrent nephrotoxic agents and highlight the need for prospective studies to optimize nephroprotective strategies.
Background and Objective: Aloe vera gel is well-known as a beauty product, nutrient and herbal medicine due to its therapeutic properties. The current research aimed to make a comparative study of natural Aloe vera gel (AG), sitagliptin (SIAG) and glibenclamide (GLIB) as diabetes medications on streptozotocin (STZ)-induced albino Wistar male rat models.Materials and Methods: Rat models (60) were grouped equally into control, diabetic, normal+AG, STZ+AG, STZ+GLIB and STZ+SIAG. After 3 weeks of treatments, body weights, fasting blood glucose levels, blood analyses, fat profile and biochemical and antioxidant enzymes were evaluated. Data were analyzed in SPSS and all values are reported as Mean +/- SD. The post hoc multiple comparison tests revealed significant differences among rat groups at p <= 0.05.Results: The oral administration of Aloe vera gel was efficient in the STZ+AG group compared to STZ+GLIB and STZ+SIAG. Treatments of the STZ+AG group caused a remarkable reduction of fasting blood glucose level 100.01 mg/dL. The STZ+AG group and STZ+GLIB group detected the same hemoglobin and glycosylated hemoglobin values. The STZ+GLIB group reported the lowest values for Homeostatic Model Assessment of Insulin Resistance (HOMA IR and beta cell) 46.73 and 474.02, respectively.Conclusion: The effect of Aloe vera gel was more pronounced for the biochemical and antioxidant enzymes. These results involved that, when compared to sitagliptin and glibenclamide as diabetes medications, Aloe vera gel ingestion significantly enhanced the diabetic rat' antioxidant defense system.
Objective: The present study aimed to elucidate the mechanism of action of the dried roots of Vladimiriae Radix against benign prostatic hyperplasia (BPH) using network pharmacology, molecular docking, and cell-level experimental verification technologies, thereby providing experimental evidence for basic research, clinical application, and the modernization research of Tibetan-Chinese medicine integrated medication.Methods: Firstly, the active components of Vladimiriae Radix were screened using the TCM Systems Pharmacology Database and Analysis Platform (TCMSP) and PubChem, with the criteria of oral bioavailability (OB) >= 30% and drug-likeness (DL) >= 0.18. Subsequently, the SwissTargetPrediction database was used to identify potential targets for the components, and an overlap analysis was conducted on the BPH-related targets from GeneCards, Online Mendelian Inheritance in Man (OMIM), and the Therapeutic Target Database (TTD) to identify the common targets. Then, STRING and Cytoscape 3.10.3 analyses were used to construct the protein-protein interaction (PPI) network and the "Chinese medicine-component-target-disease" network for screening core targets. Gene ontology (GO)/kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database and bioinformatics platforms. Discovery Studio 2019 was used to verify the binding between components and targets, and AutoDockTools1-2 was employed to calculate the binding energy. Cell-level experiments (CCK-8 assay and RT-PCR) were conducted using BPH-1 cells to validate the effect of the representative component oleanolic acid. Results: A total of 235 common targets were identified between Vladimiriae Radix and BPH, and 6 core targets, including AR, CYP17A1, CYP19A1, ACHE, F2, and HMGCR, were further screened. These core targets are mainly involved in biological functions such as steroid hormone response, cellular response to nutrient levels, and regulation of membrane potential, and are enriched in BPH-related pathways including lipid and atherosclerosis, cholinergic synapse, and AGE-RAGE. Molecular docking verification found that the active components form stable bindings with the core targets. Cell experiments found that oleanolic acid significantly inhibits BPH-1 cell proliferation and regulates the mRNA expression of the six core targets at concentration of 10 mu M, 20 mu M, 40 mu M (significantly downregulated the mRNA expression of AR and HMGCR (p < 0.05), significantly upregulated the mRNA expression of CYP17A1, CYP19A1, and ACHE (p < 0.05), and had no significant effect on F2).Conclusion: Costunolide, dehydrocostus lactone, luteolin, quercetin, taraxasterol and oleanolic acid are the main bioactive ingredients in Vladimiriae Radix. Among them, oleanolic acid exhibited the highest binding energy with 6 core targets and exhibits anti-BPH properties. The present study fills the research gap in the anti-BPH mechanism of Vladimiriae Radix, validates the efficacy of the active components in Vladimiriae Radix at the cellular level, and provides clear targets and theoretical support for subsequent pharmacological verification, active component development, and clinical translation.
Background and Objective: There is no universally accepted understanding of the complex pathogenesis of Benign Prostatic Hyperplasia (BPH). Precision prostate artery embolization (PPAE) is performed under the guidance of digital subtraction angiography and can alleviate clinical symptoms caused by BPH. This research assessed the effectiveness of PPAE combined with highly specific alpha 1 blockers for elderly BPH patients.Materials and Methods: The 144 elderly BPH patients were split into two groups: 80 for observation and 64 for control. The study treated all participants with alpha 1 blockers, while the observation group additionally received precise prostatic artery embolization (PPAE). Changes in clinical symptoms before and after therapy were monitored.The statistical assessment was done by SPSS 22.00. Count data were reported as a percentage (%), while data were expressed as the Mean +/- Standard Deviation (SD). The threshold of significance was p < 0.05.Results: The treatment led to a significantly greater overall effective rate in the observation group than in the control group (p < 0.05). Both groups had lower international prognostic scoring system (IPSS) and urinary symptom distress (BS) levels than before therapy (p < 0.05), with the observation group also having lower scores. After 2 weeks, 1 month, 6 months and 1 year of therapy, both groups saw substantial increases in Qmax, while the fraction of residual urine volume (RU), prostate volume (PV) and ischemia were reduced. The observation group improved more significantly than the control group. The observation group was considerably lower than the control group (p < 0.05).Conclusion: High selectivity alpha 1-receptor blockers have good feasibility in the treatment of elderly BPH and combined with precise PAE can improve the treatment effect, with good safety and reliability.
Background: Plants have played a crucial role in human health since ancient times, serving as reliable and significant sources of biologically active compounds used to treat numerous disorders. Thus, the potential of these compounds to treat various diseases, including cancer and cardiovascular conditions, is being extensively researched. Notably, the diverse mechanisms of action associated with these compounds make them promising candidates for future drug development. Meanwhile, 7-hydroxyflavone (7-HF), a natural flavonoid, has demonstrated notable biological properties; however, the therapeutic potential of 7-HF for pain remains unexplored. Threfore, this study aimed to investigate the potential role of 7-HF in alleviating pain in rats.Materials and Methods: This prospective experimental study employed healthy Swiss albino rats with Institutional Animal Ethical Committee (IAEC) approval. Rats were divided in to four groups: control group, which received normal saline; the standard group, which received morphine 2 mg/kg; and two test group, which received 7-HF at doses of 5 & 10 mg/kg/rat. Behavioral analysis was performed after treatment to assess the central and peripheral analgesic effects using the hot plate, tail flick analgesiometer, tail immersion, and acetic acid-induced writhing, a validated animal model for screening analgesic effects in a preclinical laboratory. All animals were sacrificed after the writhing test and screened for oxidative stress markers as well as antioxidants level.Results: At 30-240 min, the administration of a 10 mg/kg test dose notably showed prolonged response time in the hot plate test, tail flick test and tail immersion method. In the acetic acid writhing test, 7-HF at 10 mg/kg significantly inhibited writhing in experimental animals. Moreover, 7-HF at a dose of 10 mg/kg restored superoxide dismutase (SOD) and glutathione (GSH) levels, and conversely reduced elevated lipid peroxidation (LPO) levels.Conclusion: This study provides the first evidence that 7-HF effectively mitigates pain in rats, likely through the associated antioxidant, anti-inflammatory, and analgesic effects. These results support the therapeutic potential of 7-HF as a novel candidate for a management pain in various chronic disorders.
