Search Results (159)

Background: Temporal lobe epilepsy (TLE), a prevalent refractory focal epilepsy frequently complicated by comorbid anxiety and depression, poses significant therapeutic challenges due to the inadequate efficacy of current antiepileptic drugs in seizure control. Carbon dots (CDs) demonstrate notable biological activities and represent a promising class of nanomedicines for TLE intervention. Methods: This study established an eco-friendly calcination protocol to synthesize a novel suspension of Crinis Carbonisatus-derived carbon dots (CC-CDs) as a candidate therapeutic for TLE. Results: In a TLE mouse model, the CC-CDs suspension significantly inhibited phosphorylation of the MAPK pathway (p-JNK, p-ERK, p-p38; p < 0.01, p < 0.05), leading to reduced levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α; p < 0.01, p < 0.05), upregulation of TGF-β1 (p < 0.01, p < 0.05), and restoration of antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01, p < 0.05). These modifications subsequently regulated the Glu/GABA balance, alleviating excitotoxicity (p < 0.05), attenuating neuronal damage and Nissl body loss in hippocampal CA1/CA3 regions, and improving cognitive function alongside reducing anxiety-like behaviors (p < 0.01, p < 0.05). In vitro, the CC-CDs suspension suppressed LPS-induced apoptosis in BV2 cells. Conclusions: The CC-CDs suspension ameliorates TLE by inhibiting MAPK signaling, thereby reducing neuroinflammation and oxidative stress, rectifying Glu/GABA imbalance, attenuating excitotoxicity, and ultimately improving behavioral deficits. These findings underscore the therapeutic potential of CC-CDs suspension for TLE treatment. Full article

Background/Objectives: Rutin (RT), a promising bioflavonoid, faces clinical limitations due to its poor solubility and bioavailability. In this study, we formulated RT-loaded phytosome nanoparticles (RT-PNPs) via thin-layer hydration and characterized their morphology, size distribution, and zeta potential. Methods: We established a mouse model of Ehrlich ascites carcinoma (EAC), randomly allocating ninety female Swiss albino mice into six groups: untreated controls, RT-treated, RT-PNP-treated, EAC, EAC + RT, and EAC + RT-PNPs. Tumor induction and treatment protocols were controlled, with the oral administration of 25 mg/kg/day of RT or RT-PNPs for 20 days. We comprehensively assessed survival, body weight, ascitic fluid/tumor volume, and cell viability and performed detailed hematological, serum biochemical, and tumor marker analyses. Multiorgan (liver and kidney) function and redox homeostasis were evaluated through enzymatic assays for SOD, CAT, GSH-Px, and GSH, as well as lipid peroxidation assessment. Proinflammatory cytokines and tumor markers (AFP, CEA, CA19-9, CA125, and CA15-3) were quantified via ELISA. Results: Gene expression profiling (TP53, Bax, and Bcl-2) and flow cytometry (p53 and Ki-67) elucidated the modulation of apoptosis. Histopathological scoring documented organ protection, while advanced multivariate (heatmap and principal component) analyses revealed distinct treatment clusterings. The RT-PNPs demonstrated potent anti-tumor, antioxidant, anti-inflammatory, and apoptosis-inducing effects, outperforming free RT in restoring physiological markers and tissue integrity. Conclusions: The current results underscore the potential of RT-PNPs as a multifaceted therapeutic approach to EAC, leveraging nanoparticle technology to optimize efficacy and systemic protection. Full article

Calcium oxalate (CaOx) stones account for 90% of uroliths in cats and contribute to ureteral inflammation and fibrosis, although the underlying mechanism remains unclear. Apoptosis inhibitor of macrophage (AIM) is known to play a protective role against tubular injury in feline kidney disease. This study investigated whether AIM contributes to ureteral fibrosis by using AIM-felinized mice subjected to CaOx bead-induced ureteral injury. Male C57BL/6 mice (n = 54), including wild-type mice (mA), AIM-knockout (koA) mice, and AIM-felinized mice (fA), were assigned to either a unilateral ureteral obstruction (UUO; U) group or a UUO plus CaOx implantation (C) group. Ureters were collected 14 days after the procedure for histopathological analysis. The severity of ureteral injury followed the order of koA-C ≥ fA-C > mA-C, indicating AIM’s involvement in the injury process. Furthermore, fA exhibited more severe fibrosis than mA mice (p < 0.05), suggesting that mouse AIM may have stronger anti-fibrotic effects than feline AIM. These results suggest that AIM-felinized mice could serve as a useful model for investigating feline-specific ureteral pathology. To our knowledge, this is the first experimental study to explore the role of feline AIM in ureteral injury and fibrosis. Further studies are warranted to validate the utility of this model. Full article

Cushing’s disease (CD) is a rare neuroendocrine disorder caused by ACTH-secreting pituitary adenomas, presenting significant diagnostic and therapeutic challenges. Given the evolutionary conservation of the hypothalamic–pituitary–adrenal axis, this review explores the translational value of spontaneous CD forms in dogs, horses, cats, small mammals, and rats, as well as of experimental models in mice, rats, and zebrafish. Dogs are the most studied, showing strong molecular and clinical similarities with human CD, making them valuable for preclinical drug and diagnostic research. While equine and feline CD are less characterized, they may provide insights into dopaminergic therapies and glucocorticoid resistance. Nevertheless, practical and ethical challenges limit the experimental use of companion animals. In preclinical research, mouse models are widely used to study hypercortisolism and test therapeutic agents via transgenic and xenograft strategies. Conversely, few studies are available on a zebrafish transgenic model for CD, displaying pituitary corticotroph expansion and partial resistance to glucocorticoid-negative feedback at the larval stage, while adults exhibit hypercortisolism resembling the human phenotype. Future transplantable systems in zebrafish may overcome several limitations observed in mice, supporting CD research. Collectively, these animal models, each offering unique advantages and limitations, provide a diverse toolkit for advancing CD research and improving human clinical outcomes. Full article

Background: Schizophrenia is a complex neuropsychiatric disorder whose pathophysiology may involve oxidative stress-induced neuronal damage and inflammation. We conducted a cross-species study to elucidate oxidative stress dysregulation in schizophrenia. Methods: We measured peripheral oxidative stress biomarkers (malondialdehyde [MDA], nitric oxide [NO], reduced glutathione [GSH], superoxide dismutase [SOD], catalase [CAT], advanced protein oxidation products [APOP]), and C-reactive protein (CRP) in antipsychotic-naïve schizophrenia patients and matched controls. We also assayed liver enzymes (ALP, ALT, AST) as indicators of systemic metabolic stress. In parallel, we re-analyzed published single-cell RNA-sequencing data from a Setd1a^+/–^ mouse model of schizophrenia, focusing on prefrontal cortex (PFC) cell types and oxidative stress-related gene expression. Results: Patients with schizophrenia showed markedly elevated MDA and NO (indicators of lipid and nitrosative stress) and significantly reduced antioxidant defenses (GSH, SOD, CAT) versus controls (p < 0.01 for all comparisons). Notably, urban patients exhibited higher oxidative stress biomarker levels than rural patients, implicating environmental contributions. Liver function tests revealed increased ALT, AST, and ALP in schizophrenia, suggesting hepatic/metabolic dysregulation. Single-cell analysis confirmed dysregulated redox pathways in the schizophrenia model; PFC neurons from Setd1a^+/–^ mice displayed significantly lower expression of key antioxidant genes (e.g., Gpx4, Nfe2l2) compared to wild-type, indicating impaired glutathione metabolism. Conclusions: Our integrative data identify convergent oxidative stress imbalances in schizophrenia across species. These findings advance a mechanistic understanding of schizophrenia as a disorder of redox dysregulation and inflammation. They also have translational implications as augmenting antioxidant defenses (for example, with N-acetylcysteine or vitamins C/E) could mitigate oxidative injury and neuroinflammation in schizophrenia, representing a promising adjunct to antipsychotic therapy. Full article

Selenium is an important trace element with certain antioxidant effects. Nano-selenium, as a novel selenium source, has the advantages of strong biological activity, high absorption efficiency, and low toxicity. The aim of the present study was to compare the protective effects of sodium selenite and nano-selenium on intestinal oxidative stress induced by hydrogen peroxide (H₂O₂) in mice. A total of 60 female mice were randomly divided into 6 groups with 10 replicates per group and 1 mouse per replicate (n = 10). The first three groups were as follows: the Control group (C), fed with basal diet; the sodium selenite group (SS), basal diet + 0.3 mg·kg⁻¹ sodium selenite; and the nano-selenium group (NS), basal diet + 0.3 mg·kg⁻¹ nano-selenium. The latter three groups (CH, SSH, NSH) were fed the same diet as the former three groups, but the last 10 days of the experiment were fed with drinking water containing 0.3% H₂O₂ to induce oxidative stress. The results showed that under normal conditions, the supplementation with sodium selenite or nano-selenium decreased the spleen index of mice; sodium selenate up-regulates GPX3 expression in the ileum, and increases T-SOD in the colon of mice; and nano-selenium up-regulated GPX1 expression but decreased T-AOC in the jejunum. After drinking water treated with H₂O₂, H₂O₂ increased the expression of intestinal inflammatory factors and selenium proteins, such as IL-1β and SOD in jejunum, IL-1β, NF-κB, IL-10, TXNRD1, TXNRD2, GPX1, GPX3, GPX4, and CAT in ileum, and IL-1β and SOD in colon. At the antioxidant level, H₂O₂ decreased T-AOC in the jejunum. In the H₂O₂ treatment, sodium selenite and nano-selenium increased the ratio of VH to CD (VH/CD) in jejunum; sodium selenite up-regulated the expression of TXNRD1 in jejunum, down-regulated the expression of GPX3 in ileum, at the antioxidant level, decreased the T-SOD and T-AOC in colon, and increased the content of MDA in ileum; and nano-selenium down-regulated the expression of TXNRD1 in colon. At the same time, the expression of IL-1β, NF-κB, IL-10, TXNRD1, TXNRD2, GPX1, GPX4, and CAT can be restored to normal levels by selenium supplementation. According to the results, drinking H₂O₂ induced intestinal oxidative stress in mice to a certain extent, and selenium supplementation mitigated the destructive effect of H₂O₂ on the intestinal morphology of mice jejunum and restored the level of related inflammatory factors, and had a positive effect on antioxidants. Full article

Oxidative stress plays a key role in tissue damage during inflammation, highlighting the need for effective antioxidant interventions. This study investigates the antioxidant potential of argan oil (AO)—obtained from Argania spinosa (L.) Skeels almonds—in comparison with olive oil (OO), cactus seed oil (CSO), and colza oil (CO). Quantitative analyses of total polyphenols and pigments—including chlorophylls, carotenoids, and xanthophylls—were conducted alongside antioxidant capacity assessments via DPPH, ABTS, and FRAP assays. The methanolic fraction consistently demonstrated the highest phenolic concentration and antioxidant efficacy across all oils. To establish in vivo relevance, a male C57BL/6J mouse model of acute oxidative stress was induced by lipopolysaccharide (LPS) administration. Pretreatment with oils significantly modulated key oxidative stress biomarkers—SOD, CAT, GPx activities, GSH levels, and lipid peroxidation (MDA)—in both heart and kidney. LPS challenge induced marked oxidative imbalance, notably increasing enzymatic activity and MDA levels, while depleting GSH in the heart and elevating it in the kidney. However, pretreatment with oils effectively restored redox homeostasis, with AO showing particularly potent effects and a stronger regulatory effect observed in the kidney. Hierarchical clustering of z-score-normalized heatmaps revealed distinct oxidative stress signatures, clearly separating LPS-treated heart and kidney tissues from other groups due to heightened oxidative markers. In contrast, oil-treated and oil-combined-with-LPS groups clustered closer to the control, underscoring the protective effect of oils against LPS-induced oxidative stress, with efficiency varying by oil type. Pearson correlation analysis, complemented by multivariate principal component analysis (PCA), further emphasized strong positive associations between antioxidant enzymes (SOD, CAT, GPx) and MDA levels, while GSH exhibited tissue-specific behavior—negatively correlated in the heart but positively in the kidney—highlighting divergent redox regulation between organs. Collectively, AO demonstrated robust cardioprotective and nephroprotective properties, supporting its potential as a natural dietary strategy against inflammation-induced oxidative stress. Full article

Hyperlipidemia, oxidative stress, and excessive inflammatory cytokine production are risk factors for depression. The potential preventive effects of essential oils (EOs) such as cumin and fennel EOs on depression may stem from their hypolipidemic, antioxidant, and anti-inflammatory activities. This work aimed to investigate the effects of cumin and fennel EO nanocapsules in a mouse model of depression caused by a high-fat diet (HFD) and chronic mild stress (CMS) using both in silico and in vivo studies. The cumin and fennel EOs were extracted, analyzed by GC-MS, and encapsulated in nano-form using gum Arabic and maltodextrin as wall materials. The freeze-dried nanocapsules were evaluated in HFD/CMS-treated mice. Molecular docking was used to examine the significance of the oils’ compounds in blocking the active sites of hydroxymethylglutaryl-CoA (HMG-CoA) and indoleamine 2,3-dioxygenase (IDO). According to the molecular docking results, the interactions between EO components and HMG-CoA or IDO indicate that these EOs may have hypercholesterolemic and antidepressive effects. Cumin and fennel EO nanocapsules showed hypolipidemic, antioxidant, and anti-inflammatory effects in vivo. This was demonstrated by the down-regulation of oxidants (ROS, MDA, and NO) and inflammatory markers (TLR4, TNF-α, and IL-6) in the brain, changes in lipid profile parameters, and the up-regulation of antioxidant enzymes (SOD, CAT, and GSH). The in silico and in vivo outputs revealed the potential preventive impact of cumin and fennel EO nanocapsules against depression-like states in the mouse model through the prevention of dyslipidemia, neuroxidation, and neuroinflammation. More human studies are needed to fully understand the antidepressive effects of cumin and fennel EO nanocapsules. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

Previously, research adopted an ultrasound-assisted extraction method to isolate crude polysaccharide from blackened jujube, followed by preliminary structural identification of the purified polysaccharide (BJP). This manuscript analyzed the accurate structure and immunomodulatory activity of BJP. Further structural identification indicated that BJP was mainly composed of →3)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →3)-β-D-GalpA-(1→, →2,4)-β-D-Galp-(1→, →4)-β-D-GalpA-(1→, →3)-α-L-Rhap-(1→ and →3,4)-α-L-Rhap-(1→. The immunomodulatory effects of BJP were examined using a mouse model with immunosuppression induced by cyclophosphamide. The findings suggested that BJP could relieve the condition of immunosuppressed mice. BJP could inhibit decreases in the body weight and organ index of mice, and HE staining showed that BJP could alleviate the harm to spleen and thymus tissues. BJP enhanced the secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), immunoglobulin A (IgA), and immunoglobulin G (IgG) in serum. It also reduced liver oxidative stress by increasing superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activities, while lowering malondialdehyde (MDA) levels. Moreover, BJP contributed to the maintenance of gut homeostasis by stimulating the generation of short-chain fatty acids in the cecal contents. The study aims to establish a solid basis for the comprehensive development of blackened jujube and furnish a theoretical framework for its polysaccharides’ role in immune modulation. Full article

Liver injury caused by the irrational use of acetaminophen (APAP) represents a significant challenge in the field of public health. In clinical treatment, apart from N—acetylcysteine (NAC), the only approved antidote, there are extremely limited effective intervention measures for APAP-induced hepatotoxicity. Therefore, exploring novel liver-protecting drugs and elucidating their mechanisms of action is of great scientific significance and clinical value. Rosmarinic acid (RA), as a natural polyphenolic compound, has been proven to have significant antioxidant activity. Previous studies have shown that it has a protective effect against drug-induced liver injury. Nevertheless, the precise protective mechanism of RA in APAP-induced acute liver injury (AILI) has not been fully defined. This study was based on an AILI mouse model to systematically explore the liver-protecting effect of RA and its underlying molecular mechanisms. The research results showed that pretreatment with RA could notably mitigate liver pathological injury. It could decrease the activities of ALT and AST in the serum, suppress the liver inflammatory reaction, and reverse the decline in the levels of CAT, T-AOC, SOD, and GSH caused by APAP. Meanwhile, RA could enhance antioxidant defense capabilities by activating the Keap1/Nrf2/HO-1 signaling pathway, regulate the xCT/GPX4 axis to inhibit lipid peroxidation, and thus block the process of ferroptosis. In conclusion, this study confirmed that RA exerts a protective effect against AILI by regulating the Keap1/Nrf2/HO-1 axis to enhance antioxidant capacity and inhibit ferroptosis through the xCT/GPX4 pathway. Our research provides a theoretical basis for RA as a potential therapeutic agent for APAP-induced liver injury. Full article

Background: Under oxidative stress conditions, the increased levels of reactive oxygen species (ROS) within cells disrupt the intracellular homeostasis. Tartary buckwheat peptides exert their effects by scavenging oxidative free radicals, such as superoxide anion and hydrogen peroxide, thereby reducing oxidative damage within cells. Meanwhile, these peptides safeguard mitochondria by maintaining the mitochondrial membrane potential, decreasing the production of mitochondrial oxygen free radicals, and regulating mitochondrial biogenesis and autophagy to preserve mitochondrial homeostasis. Through these mechanisms, Tartary buckwheat peptides restore the intracellular redox balance, sustain cellular energy metabolism and biosynthesis, and ensure normal cellular physiological functions, which is of great significance for cell survival and adaptation under oxidative stress conditions. Objectives: In this experiment, a classical cellular oxidative stress model was established. Indicators related to antioxidant capacity and mitochondrial membrane potential changes, as well as pathways associated with oxidative stress, were selected for detection. The aim was to elucidate the effects of Tartary buckwheat oligopeptides on the metabolism of cells in response to oxidative stress. Methods: In this study, we established an oxidative damage model of mouse skeletal muscle myoblast (SOL8) cells using hydrogen peroxide (H₂O₂), investigated the pre-protective effects of Tartary buckwheat oligopeptides on H₂O₂-induced oxidative stress damage in SOL8 cells at the cellular level, and explored the possible mechanisms. The CCK-8 method is a colorimetric assay based on WST-8-[2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodiumsalt], which is used to detect cell proliferation and cytotoxicity. Results: The value of CCK-8 showed that, when the cells were exposed to 0.01 mmol/L H₂O₂ for 1 h and 10 mg/mL Tartary buckwheat oligopeptides intervention for 48 h, these were the optimal conditions. Compared with the H₂O₂ group, the intervention group (KB/H₂O₂ group) showed that the production of ROS was significantly reduced (p < 0.001), the malondialdehyde (MDA) content was significantly decreased (p < 0.05), and the activity of catalase (CAT) was significantly increased (p < 0.01); the mitochondrial membrane potential in the KB/H₂O₂ group tended to return to the level of the control group, and they all showed dose-dependent effects. Compared with the H₂O₂ group, the mRNA expression of KEAP1 in the KB/H₂O₂ group decreased, while the mRNA expression of NRF2α, HO-1, nrf1, PGC-1, P62, and PINK increased. Conclusions: Therefore, Tartary buckwheat oligopeptides have a significant pre-protective effect on H₂O₂-induced SOL8 cells, possibly by enhancing the activity of superoxide dismutase, reducing ROS attack, balancing mitochondrial membrane potential, and maintaining intracellular homeostasis. Full article

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) associated with recurrent inflammation and ulceration of the colonic mucosa. Conventional treatments, including corticosteroids, have significant side effects, driving the need for safer, effective alternatives. The present study aimed to investigate the mitigating effects of Epilobium angustifolium extract (EAE) in a Dextran sulfate sodium (DSS)-induced colitis mouse model, in a comparative manner to the reference drug dexamethasone (DXM). The severity and progression of colitis were evaluated through disease activity indices and a range of inflammatory and oxidative stress markers, assessed using multiple analytical methods. EAE treatment significantly reduced colonic inflammation, as indicated by decreased myeloperoxidase (MPO) activity, lower levels of malondialdehyde (MDA), and reduced white blood cell counts. EAE also enhanced antioxidant defenses, increasing glutathione (GSH) levels by 64%, and boosting catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities by 36%, 53%, and 70%, respectively. Histopathological analysis confirmed EAE’s efficacy in attenuating colonic injury and inflammation. The blood parameters hemoglobin, erythrocytes, and hematocrit were also improved. Our study shows that EAE has potential as a natural therapeutic candidate for the treatment of UC, demonstrating efficacy comparable to that of conventional pharmacological treatments. Full article

Suk-SaiYasna (SSY) is a well-documented traditional Thai herbal formula in the Royal Scripture of King Narai’s Traditional Medicine. SSY contains Cannabis sativa leaves as a key ingredient and has traditionally been used to promote sleep, alleviate stress-related symptoms, and stimulate appetite. This study aimed to investigate the neuroprotective effects of SSY in a mouse model of unpredictable chronic mild stress (UCMS)-induced cognitive impairment and explore the underlying mechanisms, particularly antioxidant enzyme pathways. Behavioral tests, including the Y-maze test, novel object recognition test, and Morris water maze test, demonstrated that UCMS-exposed mice exhibited cognitive impairment compared to non-stress mice. However, SSY treatment significantly improved learning and memory performance in UCMS-exposed mice. Mechanistic studies revealed that SSY reduced lipid peroxidation in the hippocampus and frontal cortex, key brain regions affected by chronic stress. Furthermore, UCMS significantly reduced the activity of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), whereas SSY treatment restored their activity, indicating antioxidative and neuroprotective effects in vivo. Gene expression analysis further revealed that SSY regulates oxidative stress via the Nrf2/Keap1 signaling pathway. In vitro studies using 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay confirmed the radical scavenging activities of SSY and its herbal components, demonstrating significant antioxidant potential. Phytochemical analysis identified delta-9-tetrahydrocannabinol, delta-9-tetrahydrocannabinolic acid A, and cannabinoids as bioactive compounds in SSY, along with potent antioxidants such as gallic acid, myricetin, myristicin, piperine, costunolide, and gingerol. These findings suggest that the SSY formula mitigates UCMS-induced cognitive function through its antioxidant properties via multiple pathways, including radical scavenging activities, modulating the Nrf2-Keap1 pathway, inducing the expression of HO-1, NQO1 mRNAs, and other antioxidant enzymes. This work bridges traditional Thai medicine with modern neuropharmacology. Full article

Background/Objectives: Previous studies have shown that unformulated extracts of Passiflora ligularis leaves exhibit promising antidiabetic activity. This research aimed to demonstrate that formulating the extract into a self-emulsifying drug delivery system (PLE-SEDDS) enhanced its antidiabetic activity in a high-fat-diet/streptozotocin-induced diabetic mouse model. Methods: Blood glucose levels (BGLs) of diabetic mice were monitored during 21 days of oral administration of P. ligularis extract (PLE) and PLE-SEDDS. Control groups included metformin (positive control), vehicle, and SEDDS vehicle (negative controls). The animals underwent an oral glucose tolerance test (OGTT). The oxidative stress markers superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation quantified by malondialdehyde (MDA) levels were measured in the kidney, liver, and pancreas, complemented with histopathological analysis. Additionally, plasma lipid profile parameters were evaluated. Results: The PLE-SEDDS formulation demonstrated superior efficacy compared to the PLE extract in improving antidiabetic outcomes. Animals treated with PLE-SEDDS exhibited a minimal increase in blood glucose levels (11.5%) during the OGTT, compared to 27.4% with PLE and over 77% in the vehicle groups. PLE-SEDDS also showed greater enhancement of SOD and CAT activity, along with a more pronounced reduction in MDA levels, indicating stronger protection against oxidative stress. Histological analysis revealed significant preservation of pancreatic islets, and lipid profile analysis showed greater reductions in triglycerides, cholesterol, and LDL-C, alongside increased HDL-C levels. Conclusions: Altogether, these findings suggest that PLE-SEDDS exhibits superior antihyperglycemic, hypolipidemic, and antioxidant effects compared to the unformulated extract, making this novel formulation a promising option for treating type 2 diabetes mellitus. Full article