Sulfated polysaccharides with significant biological activities were widely applied in functional food, cosmetic, biomedical and pharmaceutical industries. In this study, we established a practical high-throughput screening workflow for sulfated polysaccharide-producing bacteria and applied it to natto-derived isolates. Using this approach, a sulfated polysaccharide produced by Bacillus subtilis var. natto GX10-35 with the yield of 0.86 mg/mL was isolated and a purified polysaccharide fraction, GX10-35-P1, was obtained from its fermentation broth. Chemical analyses showed the sulfate content of the sulfated polysaccharide GX10-35-P1 was 12.02
Hypertension remains a critical contributor to cardiovascular morbidity, driven largely by angiotensin II (Ang II)-mediated oxidative stress, inflammation, and hypertrophic remodelling. Although polyherbal formulations are valued for their multitargeted actions, systematic evidence at the cellular level is important. Thus, the present study explored the protective effects of a polyherbal formulation (Cardojith (CJ)) against Ang II-induced hypertensive injury in H9c2 cardiomyocytes. H9c2 cells were exposed to Ang II with or without CJ treatment. Cell viability was assessed by MTT assay, while oxidative stress parameters (ROS, TBARS, SOD, CAT) and hypertrophic/inflammatory mediators (ANP, BNP, IL-6, TNF-α) were quantified. Gene expression of AT1R, NF-κB, and COX-2 was evaluated by RT-PCR, and p38 MAPK activation was analysed by Western blotting. Apoptosis was evaluated using AO/EtBr fluorescence staining. Ang II triggered a pathological phenotype characterized by reduced cell viability, increased ROS and lipid peroxidation, and diminished antioxidant enzyme activity. These biochemical changes coincided with elevated ANP, BNP, IL-6, and TNF-α levels and increased apoptotic cell death. At the molecular level, Ang II significantly upregulated AT1R, NF-κB, and COX-2 expression and enhanced p38 MAPK phosphorylation, confirming activation of pro-hypertrophic and inflammatory pathways. In contrast, CJ treatment attenuated these alterations by restoring antioxidant enzyme activities, reducing ROS, TBARS and apoptotic cell death, while normalizing ANP and BNP levels. Importantly, CJ downregulated AT1R, NF-κB, and COX-2 and inhibited p38 MAPK phosphorylation, underscoring its capacity to modulate key signalling pathways. Therefore, Cardojith exerts its potent cardioprotective and antihypertensive effects by simultaneously attenuating oxidative stress, inflammation, apoptosis and hypertrophic signalling. These findings highlight its therapeutic potential as a multitargeted phytomedicine for managing hypertension-associated cardiac complications.
Garlic (Allium sativum) contains bioactive components with antioxidants and anti-inflammatory constituents with potential anticancer activity. We aimed to compare a petroleum-ether garlic extract (PEGE) versus an ethanolic garlic extract (EGE) in a DMBA-induced murine hepatic carcinogenesis model. Fresh garlic was extracted with petroleum ether or ethanol and chemically characterized by GC–MS. PEGE was enriched in long-chain fatty acids/derivatives, while EGE contained both lipids and more polar constituents. Male Swiss albino mice received DMBA and were assigned to concurrent (DMBA + extract) or post-DMBA (DMBA → extract) regimens; extract-only and vehicle groups served as toxicity controls. Biochemical parameters (ALT, AST, AFP), oxidative stress markers (MDA, GSH), inflammatory signaling (NF-κB by ELISA), apoptosis (caspase-3 gene expression by qPCR), proliferation (PCNA by flow cytometry), and histopathological changes (H E staining) were evaluated. Extract-only showed no significant differences compared to control groups, indicating no overt toxicity. DMBA administration resulted in significant hepatic injury, evidenced by elevated liver enzymes and AFP, increased lipid peroxidation and NF-κB levels, depleted GSH, enhanced cellular proliferation, and severe histopathological alterations. Across endpoints, the post-DMBA PEGE regimen produced the largest overall normalization, followed by EGE. Post-treatment outperforming concurrent dosing for both extracts. Histology aligned the biochemical trends, showing reduced necrosis, inflammation, vascular congestion, and dysplastic changes in treated groups. Both garlic extracts showed hepatoprotective effects in this preclinical model; they were well tolerated and mitigated DMBA-induced injury, with PEGE given after DMBA yielding the strongest biochemical, molecular, and histopathological improvements. Chemical differences between the lipid-rich PEGE and the more polar EGE likely contribute to their differential efficacy and merit further standardization and mechanistic study.
Purple aleurone1 (Pr1) gene plays vital role in anthocyanin biosynthesis in maize kernel. Here, accumulation pattern of anthocyanins and expression of Pr1 gene were analyzed during three kernel developmental stages (KDS) viz., 15, 30, and 45 days after pollination (DAP) among three wild-type (Pr1Pr1) and three mutant (pr1pr1) maize inbreds. Inbreds with dominant Pr1 allele produced blue-kernel, while inbreds with recessive pr1 allele possessed red-kernel. Total anthocyanin (TA) ranged from 36.5 to 514.2 ppm. Across genotypes, TA during 15 DAP was 59.2 ppm, while it increased to 205.4 ppm and 357.6 ppm at 30 and 45 DAP, respectively. Cyanidin-3-glucoside (C3G), cyanidin 3-(6´´-malonylglucoside) (C3MG), cyanidin-3,5-diglucoside (C3DG), pelargonidin-3-glucoside (P3G) and peonidin-3-glucoside (Pn3G) were components of anthocyanins. Of these, C3G (60
Oral infections remain a significant global health concern and are primarily associated with pathogenic microorganisms that contribute to dental caries, periodontal diseases, endodontic infections, and oral candidiasis. The increasing prevalence of antimicrobial resistance and the limitations of conventional antimicrobial agents have stimulated the search for alternative therapeutic strategies. Zinc oxide NPs (ZnO NPs) have attracted considerable attention due to their broad-spectrum antimicrobial activity, biocompatibility, chemical stability, and cost-effectiveness. ZnO NPs exhibit potent antimicrobial effects against a wide range of oral pathogens through multiple mechanisms. Recent studies have demonstrated that the antimicrobial performance of ZnO NPs can be significantly enhanced through modifications such as particle size reduction, morphology control, metal doping, surface functionalization, and incorporation into composite materials. These modifications improve microbial interactions, increase surface reactivity, and enhance overall antimicrobial efficacy against oral infection-associated microorganisms. In this review, we comprehensively discuss the antimicrobial activities of ZnO NPs against microorganisms associated with oral infections. Particular emphasis is placed on the influence of various modification strategies, including size-dependent effects, metal-ion doping, polymer incorporation, and hybrid nanocomposite formation, on antimicrobial performance. The underlying mechanisms responsible for enhanced antimicrobial activity are also summarized. We hope that this review will provide a valuable resource for researchers and clinicians interested in the development of advanced ZnO NP-based antimicrobial materials for the prevention and treatment of oral infections.
Burn wounds remain a significant clinical challenge due to delayed tissue regeneration and the high risk of microbial infections. Green-synthesized silver nanoparticles using medicinal plant extracts have emerged as promising candidates for wound management; however, the potential of Peucedanum officinale-mediated silver nanoparticles for burn wound healing has not been extensively investigated. In this study, silver nanoparticles were synthesized using an alcoholic extract of P. officinale seeds (Ag@POS NPs), and their physicochemical characteristics, antimicrobial, antioxidant, and wound healing properties were evaluated. The synthesis process was optimized based on silver nitrate concentration, reaction time, and temperature. The synthesized nanoparticles were characterized using XRD, FTIR, FESEM, TEM, and EDS analyses. The XRD results confirmed the crystalline structure of Ag nanoparticles, while FTIR analysis indicated the involvement of plant-derived functional groups in nanoparticle formation and stabilization. Morphological analysis revealed the formation of spherical nanoparticles with an average size of approximately 20–30 nm. The antimicrobial activity of Ag@POS NPs demonstrated effective inhibition and elimination of Gram-positive and Gram-negative bacterial strains as well as Candida albicans. Moreover, Ag@POS NPs exhibited significant antioxidant activity, achieving 91
Glucarpidase or carboxypeptidase G2 (CPG2) is an antidote for methotrexate (MTX) toxicity, but cannot penetrate cellular membranes. This study aims to clear intracellular MTX reservoirs and inhibit the MTX rebound effect. Therefore, two intracellular drug delivery approaches using the Tat-penetrating peptide, in the form of a Tat-CPG2 covalent conjugate and a Tat: CPG2 non-covalent complex, were compared. The native cpg2 gene from Pseudomonas sp. and the plasmid encoding tat-cpg2 conjugate were heterologously expressed in E. coli and purified using Ni-NTA. Tat: CPG2 complexes were formed by mixing 1 µM purified CPG2 with 0.5–80 µM Tat peptide. The HEK-293 cells were treated with both formulations to compare transduction efficiency by intracellular enzyme activity measurements at 320 nm and functional rescue of cells using 1-100 µM MTX. Molecular docking by ClusPro 2.0 revealed a distinct anionic patch on CPG2, facilitating electrostatic interactions through several salt bridges with the cationic Tat peptide. The highest transduction efficacy of the complex was observed at a Tat: CPG2 ratio of 20:1. While both formulations successfully delivered functional CPG2 into the cells, Tat-CPG2 conjugate displayed higher intracellular specific activity and retention, reaching approximately 2.6 ± 0.3 U/mg at 60 min compared with 1.9 ± 0.25 U/mg for the complex. In cytotoxicity assays, both forms protected HEK-293 cells from MTX; however, the conjugate provided statistically superior viability (94.8
The growing burden of antimicrobial resistance (AMR) and the persistence of biofilm-associated and quorum-sensing-mediated infections represent major public health challenges, highlighting the need for new anti-infective agents from natural sources. In this context, Allium atroviolaceum is recognized for its culinary and medicinal uses, remains relatively underexplored with respect to its anti-virulence potential, despite biological activities previously attributed to its organosulfur and phenolic constituents. In this study, ethanolic Allium atroviolaceum bulb extract (EAABE) was investigated for its antimicrobial, antibiofilm, and anti-quorum sensing (QS) activities. HR-LCMS analysis tentatively annotated 19 metabolites, including organic acids, phenolics, triterpenoids, fatty acids, glycosides, alkaloids, sphingolipids, steroid derivatives, and peptide-type compounds. EAABE demonstrated moderate antibacterial effects, with inhibition zones ranging from 6.00 to 7.33 mm and MIC values between 0.292 and 2.343 mg/mL. In contrast, a relatively enhanced antifungal activity was observed, with inhibition zones of 12.67–15.00 mm and MIC values of 0.292–0.585 mg/mL. The extract also inhibited biofilm formation in a dose-dependent manner, achieving up to a 56.91
Fungal pathogens and unsustainable fertilizer use pose a threat to global food security, driving demand for eco-friendly alternatives to conventional disease management and crop fertilization. This study characterizes Bacillus subtilis strain 55–7, isolated from a saline hot spring in Krabi, Thailand, as a dual-function bioinoculant for sustainable plant cultivation. Laboratory assays demonstrated potent antifungal activity against Curvularia lunata (91.9
Stable expression of γ-Glutamyltranspeptidase (GGT)-BPC157 and mScarlet-BPC157 in Bacillus licheniformis strain 2709 by chromosomal integration. Fermentation conditions were optimized using single-factor and orthogonal experiments to maximize yield. Under optimal conditions (2
Fabricated graphene quantum dots (FQD) are popularly used in biomedical applications, as well as for biosensing, drug administration, and anticancer therapy. Despite the promising biomedical applications of graphene quantum dots, their long-term biocompatibility and toxicological safety remain insufficiently understood. Therefore, this study aimed to develop a bioenhanced FQD nanocomposite and evaluate its biocompatibility, wound healing potential, and toxicity using in vitro endothelial cells and adult zebrafish models. In silico molecular docking confirmed favourable binding to the wound healing target protein (-3.526 kcal/mol), supporting the therapeutic potential of FQDs. The toxicity and safety of employing these materials, however, must be further evaluated due to their unfavourable side effects. The primary goal of the current investigation was to examine in adult Zebrafish (Danio rerio) the toxicities and wound-healing capacity of FQD. Cytotoxicity and scratch wound migratory assay demonstrated significant result with the concentration of 5 µg/ ml. The live model was exposed to different sample concentrations ranging from 1 to 25 µg/mL for the evaluation period of 14 days to examine the samples chronic effects. The acute toxicity in vital organs was examined and the result demonstrates defined morphology of cardiomyocytes, normal distribution of hepatocytes, densely packed parenchymal architecture of pancreatic artery and uniformly distributed neuronal cells. Up to the concentration of 5 µg results were closer to control groups with nil mortality. The end of 48 h observation concentration dependent efficacy was observed closer to control groups for exhibiting excellent wound healing percentage. Synthesis of GIQD using Spirulina platensis extract by autoclave method Highly biocompatibility FQD was formulated using ECM proteins from natural source The FQD formulation was optimized using BBD of RSM and ANOVA model was found significant with R2 = 0.9655 for p < 0.05 The FQD biocompatible, Cytotoxicity free and supports cell migration FQD favors angiogenesis the scope support wound healing process Evaluated by wound contraction, wound healing percentage and by histological examination Insillico Docking was performed to report protein interaction ability
A bioactive alkaloid derived from Piper nigrum is piperine (PIP); it exhibits significant anti-inflammatory properties, but the mechanistic basis remains incomplete. This study integrates zebrafish toxicity assays, antioxidant profiling and histopathology analysis along with a network pharmacology approach to elucidate system-level understanding of PIP’s therapeutic efficacy. Toxicity studies on zebrafish embryos indicated that PIP exhibits low toxicity at elevated dosages (LC50 = 160.25 µg/ml), with preserved hatching and cardiac function. In the DSS-induced intestinal inflammation model, PIP treatment significantly improved swimming behaviour and restored feeding activity. It also preserved lysosomal integrity, reduced apoptosis, and attenuated mucin hypersecretion and ROS (Reactive Oxygen Species) accumulation in a dose-dependent manner. In tissue homogenates, PIP effectively normalized DSS-induced changes in total protein, malondialdehyde (MDA), Glutathione (GSH), Superoxide Dimutase (SOD), catalase and nitric oxide (NO) levels, indicating restoration of redox homeostasis. Furthermore, network pharmacology analysis identified 2,142 PIP-associated targets, of which 55 overlapped with inflammation-related genes. Protein–protein interaction (PPI) network analysis identified key hub genes involved in immune and stress responses. Gene Ontology (GO) enrichment indicated significant involvement in apoptotic signalling, protein phosphorylation, and inflammatory processes, while Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted the role of PIP in modulating the PI3K–Akt, JAK–STAT, and MAPK signalling pathways, which are associated with the in vivo inflammatory phenotype. Molecular docking further demonstrated strong binding affinities of PIP with hub proteins, particularly MTOR (− 8.4 kcal/mol) and JAK2 (− 8.3 kcal/mol). Collectively, these findings correlate the observed in vivo phenotypic recovery with multi-target molecular mechanisms, supporting PIP as a promising anti-inflammatory compound for Inflammatory Bowel Diseae (IBD) and related disorders with significant bio-therapeutic potential.
Theranostic smart bionanosensors represent a revolutionary approach to solid tumor management, integrating accurate diagnostic functions with focused therapeutic strategies. This review thoroughly analyzes the progress of biosensors from traditional diagnostic tools to multifunctional theranostic systems, highlighting advancements in nanomaterials, surface functionalization, and tumor-targeting techniques that improve imaging contrast, payload delivery, and controlled release. Advanced bionanosensors comprising optical, electrochemical, magnetic, hydrogel-based, stimuli-responsive, and wearable platforms facilitate precise biomarker detection, real-time therapeutic monitoring, and minimally invasive diagnostics, presenting unmatched prospects for personalized cancer management. Despite these advancements, challenges persist, including inconsistent tumor uptake, prolonged biocompatibility, possible toxicity, scalability, reproducibility, and regulatory obstacles. The integration of nanomaterial studies, imaging, sensor technology, computational analytics, and clinical innovation offers a strategic framework for advancing smart theranostic bionanosensors from laboratory to clinical application, facilitating precision oncology and enhancing patient outcomes.
This study investigates the potential of niosomal drug delivery systems encapsulating L-DOPA and Rasagiline for Parkinson’s disease treatment. The aim is to enhance neuroprotective efficacy, reduce cytotoxic and genotoxic effects, and modulate PD-related gene expression. Niosomes were prepared using varying lipid-to-drug and Span 60-to-cholesterol ratios. Characterization included morphology, particle size, polydispersity index, and surface charge using Transmission electron microscopy and Zetasizer. Drug encapsulation efficiency was measured spectrophotometrically, and in vitro release was assessed in PBS (pH 7.4). Compared to free drugs, niosome-encapsulated L-DOPA and Rasagiline exhibited significantly reduced cytotoxicity and enhanced neuroprotective effects. Cytotoxicity of free and encapsulated drugs was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay in human dermal fibroblast cells (HDF). SH-SY5Y cells were differentiated into neuron-like cells using all-trans retinoic acid and exposed to methyl-4-phenylpyridinium (MPP+) to induce a PD model. Neuroprotective effects were assessed by comparing drug-loaded niosomes with free drugs. Genotoxicity was evaluated using Hoechst 33258 staining. Real-time quantitative polymerase chain reaction was performed to analyze PINK1 and LRRK2 gene expression. Niosomal formulations showed spherical morphology, nanoscale size, low polydispersity index, negative surface charge, high drug encapsulation, and sustained release. Drug-loaded niosomes exhibited reduced cytotoxicity in HDF cells and greater neuroprotection in MPP+-induced SH-SY5Y cells compared to free drugs, with minimal genotoxicity. PINK1 was upregulated, and LRRK2 was downregulated after treatment with the drug-loaded formulations. L-DOPA and Rasagiline-loaded niosomes demonstrated effective delivery, neuroprotection, and gene modulation with minimal toxicity. These findings demonstrate the potential of niosomal encapsulation of L-DOPA and Rasagiline in an in vitro Parkinson’s disease model, and indicate the necessity for further mechanistic and in vivo investigation. Niosomal drug delivery systems were successfully developed for delivery of L-DOPA and Rasagiline. Formulations showed spherical morphology, nanoscale size, high encapsulation efficiency, and sustained release profile. Drug-loaded niosomes reduced cytotoxicity in HDF cells and enhanced neuroprotection in MPP⁺-induced SH-SY5Y neuron-like cells. Minimal genotoxicity was observed, with favorable modulation of PD-related genes (PINK1 upregulation, LRRK2 downregulation).
The present study explores the therapeutic potential of Tiliacora acuminata, a traditional medicinal plant widely used in the treatment of jaundice. The root extract has antimicrobial efficacy, and the phytochemical analysis of the root extract showed the occurrence of proteins, alkaloids, flavonoids, phenols, saponins, steroids, tannins, and terpenoids. A cytotoxicity assay on HepG2 cells showed no significant cytotoxic effects, even at concentrations up to 30 µg/mL. GC–MS analysis identified bioactive compounds with high binding affinity for UDP-glucuronosyltransferase 1A1 (UGT1A1), a key enzyme involved in bilirubin glucuronidation. 3,5,24-trimethyltetracontane demonstrated the strongest binding affinity, suggesting its potential to enhance bilirubin glucuronidation. Tiliacora acuminata root extract was utilized to synthesise silver nanoparticles, to investigate their efficacy in the photocatalytic degradation of reactive red 120, reactive black 5, reactive brown 2, and mixed dyes. UV-DRS, FT-IR, XRD, SEM, and TEM analyses were employed to characterise the synthesised nanoparticles. Silver nanoparticles had a strong cytotoxic impact on HepG2 cells, with an IC50 value of 39.34 µg/mL using the MTT assay. The silver nanoparticle has antibacterial efficacy against Klebsiella pneumoniae (MTCC 109), Escherichia coli (MTCC 443), and Staphylococcus aureus (MTCC 7443), as well as two fungal strains, Candida albicans (MTCC 183), and Aspergillus brasiliensis (MTCC 1344). Degradation efficiencies of reactive red 120 were 52.63
Respiratory system diseases are currently the main cause of high incidence and mortality rates worldwide. Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. Currently, treatment outcomes are unsatisfactory. This is partly due to the incomplete elucidation of programmed cell death pathways. Ferroptosis is a lipid peroxidation-driven iron-dependent form of cell death. It has become a key mechanism in the study of respiratory system pathophysiology. We systematically explored the molecular basis of ferroptosis which includes core aspects such as iron metabolism disorders, lipid peroxidation and antioxidant defence. We also elaborate on the role of ferroptosis in COPD, pulmonary fibrosis, acute lung injury, lung cancer, asthma and pulmonary infections. We focus on summarizing emerging therapeutic targets and potential biomarkers via integrating new insights at the mechanism level and clinical significance. A deeper understanding of the above content will help promote the development of precise intervention strategies for respiratory system diseases.
Altered intestinal permeability is closely associated with gastrointestinal inflammation, and zonulin/pre-haptoglobin-2 has been investigated as a mediator and biomarker of tight junction regulation. This study describes the development of an aptamer-based electrochemical impedance spectroscopy (EIS) biosensor for zonulin measurement. A 40-nucleotide DNA aptamer candidate, ZON-Apt-40 (5’-GGTTGCGTACGATGGTAGCGTTGACCTGCGTACCAAGTTC-3’), was selected based on its length, balanced GC content, absence of long homopolymeric regions, predicted stem-loop formation, and compatibility with thiol-mediated immobilization. Mfold analysis predicted two low-energy secondary structures; the most stable had a Gibbs free energy of -5.63 kcal/mol and contained an exposed loop/bulge region spanning nucleotides 17–23. A DNA-like three-dimensional model of the aptamer was docked against a human zonulin model, and the predicted binding pose suggested that the exposed loop region interacted with polar and positively charged protein residues. Experimentally, a gold microelectrode was modified with thiolated poly(amidoamine) dendrimer (PAMAM-SH), followed by immobilization of AuNP-conjugated thiolated ZON-Apt-40 and blocking with human serum albumin. FTIR confirmed PAMAM-SH functionalization, whereas cyclic voltammetry and EIS verified stepwise electrode modification. Chronoimpedance measurements identified 200 s as a practical readout time. The sensor exhibited a concentration-dependent EIS response to zonulin, with the calibration equation y = 12.276x + 1509 and R² = 0.9981 ± 0.0012. The calculated limits of detection and quantification were 0.949 and 2.877 ng/mL, respectively. Zonulin-spiked serum samples yielded coefficients of variation of 5.1
Acute cerebral infarction (ACI), a severe neurological disorder, causes significant neuronal damage and brain injury, with cellular pyroptosis and abnormal activation of signaling pathways being key pathological contributors. This study aimed to investigate the protective effect and underlying mechanism of Thymosin β4 (Tβ4) against ACI. By establishing an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 mouse hippocampal neurons and a middle cerebral artery occlusion (MCAO) model in rat brains, the effects of Tβ4 on neuronal pyroptosis and the TLR4/NF-κB signaling pathway were systematically evaluated. Results demonstrated that Tβ4 significantly increased HT22 cell survival after OGD/R treatment, reduced lactate dehydrogenase (LDH) release, suppressed expression of pyroptosis-related proteins including NLRP3, ASC, cleaved caspase-1, and GSDMD-N, and decreased levels of inflammatory cytokines IL-18, IL-1β, and TNF-α. In the rat MCAO model, Tβ4 significantly reduced infarct volume, improved neurological function scores, decreased cerebral edema severity, and suppressed the expression of pyroptosis-related proteins and inflammatory cytokines in brain tissue. Mechanistically, Tβ4 inhibited the activation of the TLR4/NF-κB signaling pathway induced by OGD/R or cerebral ischemia both in vitro and in vivo, including suppression of p65 nuclear translocation as confirmed by immunofluorescence staining. Further gain- and loss-of-function experiments confirmed that Tβ4's anti-pyroptotic effects are mediated, at least partially, through inhibition of the TLR4/NF-κB pathway. In summary, Tβ4 exerts neuroprotective effects against ACI by suppressing the TLR4/NF-κB signaling pathway and mitigating neuronal pyroptosis, demonstrating potential clinical application value.
Parkinson’s disease (PD) is characterized by progressive dopaminergic neuronal degeneration and neuroinflammation. Traditional Chinese medicine (TCM) formulas exhibit potential neuroprotective effects, yet the active components and underlying mechanisms of Erjingwan (EJW) remain unclear. To elucidate the therapeutic mechanisms of EJW in PD by integrating network pharmacology with in vivo and in vitro experimental validation. PD mice were modeled using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Behavioral assessments, histological staining, immunohistochemistry, enzyme-linked immunosorbent assay (ELISA), and Western blotting were performed to evaluate neuronal injury, inflammation, and apoptosis. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify EJW components. Network pharmacology and machine learning were applied to screen potential targets. Molecular docking and molecular dynamics simulations were conducted to assess component-target interactions. Adeno-associated virus (AAV)-mediated peroxisome proliferator-activated receptor alpha (PPARA) knockdown in vivo and short hairpin RNA (shRNA) interference in vitro were used for mechanistic validation. EJW significantly improved motor dysfunction in PD mice. EJW attenuated dopaminergic neuronal loss in the substantia nigra, suppressed neuroinflammation, and decreased cell apoptosis. LC-MS/MS identified 10 bioactive compounds. Integrated analysis yielded 83 potential targets, with PPARA identified as a key target by machine learning. Molecular docking and dynamics simulations indicated stable binding between multiple bioactive compounds and PPARA. EJW upregulated PPARA expression and promoted autophagy. PPARA knockdown inhibited autophagy and diminished the neuroprotective effects of EJW. EJW alleviates PD by activating PPARA-mediated autophagy. PPARA may serve as a critical therapeutic target of EJW in PD. EJW improves motor deficits in MPTP-induced PD mice. EJW reduces α-syn accumulation and dopaminergic neuron loss. EJW suppresses neuroinflammation and cell apoptosis in PD models. PPARA identified as a key target via network pharmacology and Machine learning. EJW activates PPARA-mediated autophagy for neuroprotection.
Type 2 diabetes mellitus (T2DM) arises from the body's ineffective use or production of insulin. Recent research highlights the significant role of the gut microbiome in metabolism and immunity, indicating that microbial dysbiosis may be associated with T2DM development. This systematic review will explore the link between gut dysbiosis and Type 2 Diabetes Mellitus (T2DM), assess the impact of microbially-targeted therapies such as probiotics, prebiotics, dietary changes, and fecal microbiota transplantation (FMT) on glycaemic and metabolic outcomes in adults with T2DM, and determine if clinical trials validate the application of these therapies for T2DM treatment. An extensive literature search was conducted using PubMed up to January 2024, adhering to PRISMA 2020 guidelines, to identify eligible studies. The studies included were randomized controlled trials or observational studies reporting measurable outcomes related to metabolic health in adults aged 18 and older. A total of 25 studies show that individuals with Type 2 Diabetes Mellitus (T2DM) have lower gut microbial diversity, featuring fewer butyrate-producing bacteria and more inflammation-related bacteria. Probiotic supplementation and dietary fiber intake significantly improve hemoglobin A1c (HbA1c) levels and insulin sensitivity in T2DM patients. Gut microbiota dysbiosis is linked to Type 2 Diabetes Mellitus (T2DM), suggesting that the gut microbiome could be a therapeutic focus. However, while interventions like dietary changes, probiotics, and fecal microbiota transplantation show potential, current evidence does not support their routine clinical application. Recommendations for microbiome interventions should rely on strong evidence from effective longitudinal clinical trials verifying both efficacy and safety.
