Search Results (387)

Tilia americana var. mexicana is a medicinal species whose reported pharmacological effects primarily target the central nervous system, including anxiolytic, antidepressant, and anticonvulsant activities, attributed in part to flavonoids such as tiliroside (8). In this study, 14 compounds were isolated and identified from the methanolic extract (Ta-MeOH) and evaluated by molecular docking against the monoamine oxidases MAO-A and MAO-B, enzymes implicated in Parkinson’s disease (PD) due to their involvement in dopamine metabolism. Chemical analysis identified six terpenes: α- and β-amyrine (1–2), β-sitosterol (3), stigmasterol (4), ursolic acid (5), and β-sitosterol glucoside (6); the novel diglycosylated monoterpene 4α-terpineol sambubioside (7), characterized through its hexaacetate derivative (7a); the flavonoids tiliroside (8) and rutin (9); sucrose (10); and four phenolic compounds: scopoletin (11), caffeic acid (12), coumaric acid (13), and chlorogenic acid (14). Molecular docking against monoamine oxidases A and B (MAO-A and MAO-B) was used as a computational strategy to prioritize isolated metabolites for biological evaluation. β-Sitosterol glucoside (6), 4α-terpineol sambubioside (7), tiliroside (8) and rutin (9) exhibited the most favorable docking scores toward MAO-B, with predicted binding energies of −10.8733, −11.1434, −12.16986 and −12.9474 kcal/mol, respectively. Considering the docking results together with phytochemical and experimental criteria, (6) and (8) (1 mg/kg) were prioritized for biological evaluation, together with Ta-MeOH extract (100 mg/kg) and selected fractions (25 mg/kg), in a reserpine-induced mouse model of parkinsonism using L-DOPA (150 mg/kg) as a positive control. In the open field test, spontaneous locomotor activity was assessed by total crossings and expressed as AUC. Ta-MeOH significantly increased locomotor activity compared with the reserpine-treated group (AUC: 1281.8 vs. 551.7, respectively; p < 0.05). Tiliroside (8) also increased locomotor activity (AUC: 858). In the Rota-Rod test, fine motor coordination was assessed by latency to fall and expressed as AUC. Ta-MeOH showed the greatest recovery, with AUC values of 431, 89, and 34 at 4, 10, and 20 rpm, respectively. In addition, treatments derived from T. americana attenuated behavioral alterations induced by reserpine in the Irwin test. Overall, this study demonstrates that integrating phytochemical isolation, molecular docking, and in vivo pharmacological evaluation provides a useful strategy for prioritizing bioactive metabolites from T. americana. These findings support further pharmacological investigation of this medicinal species and its isolated metabolites, while additional studies are required to establish their molecular targets and mechanisms of action. Full article

Background/Objectives: Tryptophol and tyrosol are prominent secondary metabolites with diverse biological activities. Acetylation has been proposed as a strategy to modify the physicochemical properties of these compounds. Despite the proven neuroprotective and adaptogenic activity of tyrosol, in vivo studies, particularly concerning the anxiolytic effects of its acetylated forms, are currently limited. Materials and Methods: This study aimed to compare the behavioral effects of tryptophol, tryptophol acetate, and tyrosol acetate in mice using the chloral hydrate sleep model, the Open Field Test (OFT), and the Forced Swim Test (FST). Results: In the chloral hydrate sleep model, both tryptophol acetate and tyrosol acetate (100 mg/kg, i.g.) significantly prolonged sleep duration without affecting sleep latency, whereas none of the tested compounds induced sleep after single administration (100 mg/kg, i.p.). In the OFT, tyrosol acetate (100 mg/kg, i.g.) significantly increased exploratory activity, as reflected by increased time spent in the central zone and number/duration of verticalizations, indicating an anxiolytic-like behavioral profile. In the FST, tyrosol acetate (100 mg/kg, i.g.) significantly reduced immobility time, suggesting an effect on behavioral responses to acute inescapable stress. Conclusions: Overall, the tested compounds exhibited distinct behavioral profiles, with tyrosol acetate producing the most consistent behavioral effects across the experimental models. These findings suggest that acetylation modifies the neuropharmacological properties of naturally occurring aromatic alcohols and support further investigation of tyrosol acetate, including studies of its mechanisms of action and evaluation in additional anxiety-specific behavioral models. Full article

Background: Minor phytocannabinoids engage CB₁ and CB₂ receptors, as well as broader receptors and ion-channel targets. However, fragmented evidence limits translation into central nervous system (CNS) therapeutics. This review introduces pharmacological switching, defined as a dose-, state-, or model-dependent shift in the dominant determinant of a compound’s net effect that reverses the direction, rather than merely the magnitude, of that effect on a defined functional endpoint, as a framework for compound–indication matching. Unlike biased agonism, which redistributes downstream coupling without reversing direction, switching requires directional reversal between or within receptor systems. Methods: This narrative review integrates receptor pharmacology, preclinical CNS disease-model data, early-phase clinical evidence, and pharmacokinetics identified through a structured literature search. Results: Three mechanistic axes recurred: PPARγ/CB₂/Nrf2-linked neuroinflammatory modulation; TRP/GABA_A/5-HT₁A-linked control of neuronal excitability; and low-efficacy CB₁ antagonism with 5-HT₁A potentiation. Their expression was context-dependent: tetrahydrocannabivarin is reported to shift from CB₁ antagonism toward partial agonism as receptor occupancy rises, cannabidiolic acid shows stress-conditional anxiolytic and antiemetic activity, and cannabigerolic acid displays seizure-model-dependent bidirectionality. No instance yet meets all five defining criteria; each is graded provisional or proposed pending systematic testing. Human evidence remains limited: inconclusive cannabidivarin efficacy in epilepsy and neuropathic pain, proof-of-mechanism neuroimaging in autism, and early tetrahydrocannabivarin safety data. Conclusions: Minor phytocannabinoids are pharmacologically diverse but clinically underdeveloped. A tiered, biomarker-guided framework is proposed to match compound–indication pairs to the doses, formulations, and subgroups most likely to express their therapeutic pharmacology. Full article

Background/Objectives: Chronic stress and neuroinflammation (promoted by micro- and astroglia) represent key factors in affective pathogenesis. Complementing rodent models, zebrafish (Danio rerio) are widely used in experimental modeling of affective disorders. Here, we examined the effects of chronic treatment with two distinct anti-inflammatory drugs, minocycline and nimesulide, on behavior and neuroinflammation-related biomarker genes in the zebrafish chronic unpredictable stress (CUS) model. Methods: Following two-week CUS with or without drug treatment, fish were assessed using the novel tank test for anxiety-like behavior, and the zebrafish tail immobilization (ZTI) test for depression-like behavior. Results: A 14-day treatment with minocycline (50 mg/L) reduced general motor activity and brain expression of both pro-inflammatory (nos2a) and anti-inflammatory (arg1) microglial biomarker genes, as well as upregulated the anti-inflammatory astrocytic marker s100a10. In CUS-exposed fish, this treatment attenuated depression-like ZTI immobility behavior and downregulated both pro-inflammatory (nos2a, cox2) and anti-inflammatory (arg1, ptx) glial biomarkers compared to the stress-only control. In contrast, one-week nimesulide treatment during CUS produced an anxiolytic-like effect and normalized the expression of stress-induced pro-inflammatory glial biomarkers cox2 and il1β. Conclusions: Overall, our findings suggest that the two anti-inflammatory drugs tested modulate behavioral and molecular responses to chronic stress in zebrafish, with minocycline demonstrating broader anti-neuroinflammatory and antidepressant-like effects, and nimesulide exhibiting more specific anxiolytic-like properties in this model. Full article

Background: Obesity-linked anxiety may involve leptin resistance, impairing serotonin (5-hydroxytryptamine; 5-HT) signaling. In addition to drugs, nutraceuticals have been explored for their potential to address this pathophysiology. Herein, natural honey and its glycoproteins were assessed for their roles in modulating the leptin–serotonin axis to alleviate metabolic and anxiety-related disturbances. Methodology: Sixty Wistar rats were allocated to two groups (n = 30 each), one on a normal diet (ND) and the other on a high-fat diet (HFD), for four weeks to induce obesity. Each group was further divided into five sub-groups (n = 6 each) as follows: saline, low honey dose (LHD, 1 g/kg), high honey dose (HHD, 2 g/kg), low protein dose (LPD, 0.25 mg/kg), and high protein dose (HPD, 0.5 mg/kg), while continuing on the ND or HFD. The interventions were administered for four weeks. Body weight and behavioral activities were measured weekly, whereas serum leptin and triglycerides, and brain 5-HT and its primary metabolite, 5-hydroxyindoleacetic acid (5-HIAA), were measured at sacrifice. Statistical analyses were performed using ANOVA, Tukey’s post hoc test, and correlation analyses. Results: The HFD induced leptin-driven metabolic dysfunction and serotonergic disruption, exacerbating anxiety-like behavior and locomotor deficits compared with the ND rats (p < 0.05). HHD produced a dual metabolic–neurochemical improvement by reducing hyperleptinemia, elevating 5-HT, and restoring locomotor activity while reducing anxiety-like behavior. In contrast, HPD increased 5-HIAA without altering 5-HT, reflecting an imbalanced serotonin turnover that yielded only partial anxiolytic effects. Overall, HHD partially reversed HFD-induced pathology through leptin–serotonin crosstalk, whereas HPD provided more targeted neurochemical modulation. Conclusions: Natural honey and its glycoproteins attenuate HFD-induced metabolic dysregulation and anxiety-like behavior by counteracting hyperleptinemia and enhancing serotonin synthesis. These findings highlight the potential of diet-personalized, honey-based interventions for metabolic–CNS comorbidities, warranting validation through clinical trials. Full article

The genus Annona is scarcely investigated for its neuropharmacological and toxicological activities, especially regarding its seeds. To explore the effects on the central nervous system (CNS) and the acute toxicity (LD₅₀) of the polar extracts and fractions obtained from the A. macroprophyllata seeds, their potential as a possible source of anxiolytic drugs was evaluated. After determining LD₅₀, one or two doses were selected to evaluate the neuronal activity using electrocorticographic (ECoG) recordings, and the anxiolytic-like behavior in mice treated with the crude extracts or some of their fractions was assessed in the experimental models of anxiety, such as the open-field, hole-board, and plus-maze tests. Phytochemical analysis was carried out to identify the most abundant constituents, whose possible mechanism of action was also evaluated by in silico analysis. Results showed CNS depressant activity associated with an anxiolytic-like behavior, in which cherimolacyclopeptide D and squamins C and D were identified. According to a docking analysis, the inhibitory receptors GABA_A and 5-HT_1A of serotonin are possible mechanisms of action involved in the anxiolytic-like effects of these cyclopeptides, which, in conclusion, might be potential molecules for anxiety therapy. Full article

Salvia guaranitica A.St.-Hil. Ex Benth. (Lamiaceae) is native from South America, traditionally used for releasing tension and treating gastrointestinal cramps. It was evaluated for the presence of flavonoids and isoflavones in the extract, and the hypothesis of being cardioprotective under ischemia and reperfusion (I/R), antidiarrheal, antispasmodic and anxyolitic in respective models. For phytochemistry, GC-MS and HPLC-DAD methodologies were used. Cardiac performance after subchronic oral administration of S. guaranitica tincture (S.g-T, 0.95 mg extract/mL) was evaluated in rat isolated perfused hearts exposed to I/R, and mechanisms were characterized. Antispasmodic effects of S.g-T were evaluated on contractile concentration–response curves (CRCs) of carbachol (CCh) and calcium (Ca²⁺) in rat isolated intestinal tissue. In vivo tests of ricin-oil diarrhea models, open-field (OFT), novel-suppressed feeding (NFT) and tail suspension (TST) tests were performed on mice. Phenolic acids, genistin, luteolin, kaempferol and quercetin glycosides, genins, loliolide, dodecane, farnesene, phytol and isochiapin B were identified. Post-ischemic cardiac recovery was improved by S.g.-T, associated to activation of phosphatidylinositol-3-kinase and β-estrogenic receptor. S.g.-T also induced antispasmodic effects, as a non-competitive inhibitor of the CCh-CRC and Ca²⁺-CRC in the intestine. In vivo, S.g.-T showed antidiarrheal activity (95 mg extract/kg) and anxiolytic-like effects (0.95–9.5 mg extract/kg) without sedation or antidepressant-like effects. Therefore, S. guaranitica leaves have potential therapeutic cardioprotective, antidiarrheal, antispasmodic and anxiolytic effects. Full article

Sideritis species (Lamiaceae), the aromatic mountain teas of the Mediterranean and Balkans, accumulate a phytochemically rich array of bioactive compounds—phenylethanoid glycosides (notably verbascoside), flavonoid aglycones and glycosides, phenolic acids, and terpenoids—whose pharmacological relevance is increasingly defined at the molecular level. This review synthesizes current evidence on the molecular mechanisms through which these constituents act in human health and disease, integrating in vitro, in vivo, in silico, and clinical data. Anti-inflammatory activity is attributed to modulation of the NF-κB and NLRP3 inflammasome pathways; direct verbascoside binding to both targets has been demonstrated in vitro by microscale thermophoresis (nanomolar-to-micromolar Kd), with suppression of TNF-α and IL-1β observed in cell-based and animal models. Neuroprotective effects are proposed to operate through amyloid-β clearance via ADAM10 upregulation and enhanced microglial phagocytosis in transgenic mouse models, together with in vitro triple monoamine (serotonin, noradrenaline, dopamine) reuptake inhibition, and are supported at the functional level by small randomized clinical trials reporting cognitive and anxiolytic benefits. Antioxidant and cytoprotective actions reflect radical scavenging, metal chelation, and restoration of SOD/CAT/GSH with attenuation of lipid peroxidation, underpinning documented hepatoprotective and gastroprotective outcomes. Preliminary cardiometabolic findings from small clinical trials include cholesterol modulation and sex-dependent effects on insulin sensitivity that remain to be confirmed in larger, adequately powered cohorts. We further evaluate structure–activity relationships, species- and tissue-level chemical variability, and green extraction strategies relevant to standardized bioactivity-preserving preparations. Critical gaps—in vivo validation of antiproliferative effects documented only in cell-based and in silico studies so far, systematic toxicological assessment, and bioavailability characterization—are identified to guide translation. Collectively, Sideritis-derived phytochemicals, exemplified by S. scardica, represent a mechanistically coherent group of plant bioactives with defined molecular targets in inflammatory, neurodegenerative, and metabolic disorders. Full article

Jujuboside is an active saponin with anxiolytic and sedative effects, but its oral bioavailability is extremely low. This study prepared an oral film to achieve rapid absorption through the oral mucosa. Using jujuboside as the raw material, the mass ratio of vinyl alcohol polymer to microbial polysaccharide, the ratio of propylene glycol to glycerol and the amount of cellulose ether were selected as influencing factors. On the basis of single-factor experiments, the response surface method was employed to optimize the preparation process of jujuboside oral films, and the effects of these factors on disintegration time and flexibility of the films were investigated. Meanwhile, the content uniformity of jujuboside A and γ-aminobutyric acid in the films was determined by high-performance liquid chromatography. Results showed that the optimized jujuboside oral film had complete molding, a smooth surface, good flexibility, a disintegration time of 25 s in simulated oral environment, and acceptable content uniformity of jujuboside A and γ-aminobutyric acid. The oral film can disintegrate rapidly and release the drug in the oral cavity, and is designed for oromucosal delivery. This oral film is convenient to take, particularly suitable for children, the elderly and patients with dysphagia, providing a new strategy for the clinical application of jujuboside. Full article

Essential oils are multicomponent natural products with potential neurobehavioral activity, but integrated comparative studies remain limited. This study compared the essential oils of Satureja brevicalyx, Peperomia dolabriformis, and Rosmarinus officinalis in relation to their chemical profiles, predicted target interactions, preliminary acute oral safety, anxiolytic-like and antidepressant-like effects, antagonist-sensitive behavioral patterns, and exploratory serum biomarkers. Oils were characterized by GC-MS, and their constituents were screened by molecular docking against anxiety-, depression-, sleep-, and stress-related targets. Independent cohorts of male BALB/c mice received oral essential oils (25–100 mg/kg) and were assessed in anxiety-related, depression-related, and locomotor behavioral paradigms, including the elevated plus maze, light–dark box, marble burying, tail suspension, forced swim, and open field tests. Flumazenil and WAY-100635 were used to examine whether the behavioral responses were sensitive to γ-aminobutyric acid type A (GABA-A)/benzodiazepine- and serotonin 1A (5-HT1A)-related pharmacological modulation, respectively. In a preliminary 24-h acute oral toxicity screen, no mortality was observed up to 5000 mg/kg. The three oils produced anxiolytic-like and antidepressant-like effects without reducing spontaneous locomotor activity. Within its experimental block, S. brevicalyx showed the most consistent flumazenil-sensitive anxiolytic-like pattern and FDR-significant reductions in corticosterone and TNF-α, together with increased IL-4. P. dolabriformis showed a broader predicted multitarget docking profile and antagonist-sensitive behavioral attenuation compatible with mixed pathway participation. R. officinalis produced significant but more moderate behavioral effects. WAY-100635 partially attenuated the antidepressant-like effects of all three oils. These findings support differentiated but convergent functional neurobehavioral profiles among the oils. The docking, antagonist, and biomarker results should be interpreted as hypothesis-generating evidence of possible pathway involvement, supporting further validation in chronic stress models, receptor-specific assays, pharmacokinetic studies, and expanded safety evaluations. Full article

Psilocybin, a psychedelic drug with reported anxiolytic and antidepressant potential, is rapidly metabolized to its active metabolite psilocin. However, a lack of adequate toxicity studies and tissue distribution studies currently restricts its development and application. This study combined behavioral assays in zebrafish with desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to systematically evaluate the acute neurotoxicity of psilocybin and characterize the in vivo spatial distribution of its active metabolite, psilocin. The novel tank test was used to evaluate zebrafish following a 4 h exposure to psilocybin at three different doses (20, 40, and 80 μM; n = 6 per group). Statistical analysis of the data was performed using ANOVA. Behavioral analyses revealed that exposure to psilocybin induced pronounced neurobehavioral alterations, including hyperactivity and disrupted swimming patterns, as evidenced by significant increases in the number of zone transitions and shuttle frequency. We established a DESI-MSI-based method for quantitative mapping and visualization of psilocin in zebrafish tissues. Methodological validation indicated that a linear relationship between ion intensity, spotted amount (R² = 0.9947), and reproducibility (RSD < 15%) is suitable for quantitative analysis of psilocin in zebrafish tissues. Spatial distribution maps showed that following continuous exposure for 4 h, psilocin was widely distributed across multiple tissues, such as the eye, brain, heart, liver, and kidney, with marked accumulation in the brain and the periportal regions of the liver. Relative psilocin signal intensity revealed a dose-dependent increase in tissue drug levels. The dose-dependent increase in both behavioral hyperactivity and brain psilocin levels points to a consistent relationship, in line with a central site of action. Collectively, these findings demonstrate that DESI-MSI provides a visual and efficient strategy for studying drug distribution in biological tissues from exposed animals. The neurobehavioral toxicity phenotypes and distinct tissue distribution patterns of psilocin uncovered in this study offer critical insights into the biological effects and potential risks of this psychoactive substance. Full article

Anxiety disorders are characterized by dysregulation of monoaminergic signaling and remain a significant therapeutic challenge due to limitations associated with current pharmacological treatments. In this context, the essential oil of Morisonia flexuosa (Capparaceae) seeds was chemically characterized and evaluated for anxiolytic-like activity in adult zebrafish. Chemical profiling by GC–MS and GC–FID revealed a predominance of isothiocyanates, particularly butyl isothiocyanate (42.60%) and isobutyl isothiocyanate (42.28%). Acute toxicity assessment demonstrated no lethality at the tested doses. Behavioral analyses showed a significant increase in light preference in the light/dark paradigm, with moderate locomotor reduction insufficient to account for the behavioral shift solely by sedation. Pharmacological antagonism assays indicated that the anxiolytic-like effect was predominantly mediated by 5-HT1 and 5-HT2A/2C receptors. Chemometric analyses (PCA, HCA, and heatmap) revealed statistical association between compound abundance and behavioral endpoints, supporting the contribution of major isothiocyanates within the tested model. Notably, the strongest behavioral response was observed at the lowest concentration, suggesting an ideal effective concentration range. Collectively, these findings provide the first evidence that an isothiocyanate-rich essential oil from M. flexuosa exerts serotonergic-involved anxiolytic-like effects in zebrafish and supports further mechanistic investigation of its neuropharmacological potential. Full article

Background/Objectives: Insomnia is a prevalent sleep disorder with substantial public health implications, yet epidemiological data from Serbia remain limited. This study aimed to assess the prevalence of clinically significant insomnia symptoms in the adult population of Serbia and to examine associated sociodemographic, comorbidity, psychosocial, and lifestyle factors. Materials and methods: A cross-sectional study was conducted from September 2023 to September 2025, including 2577 adults aged 18–89 years across Serbia. Insomnia symptom severity was measured using the Insomnia Severity Index (ISI), with scores ≥ 15 indicating clinically significant insomnia symptoms. Sociodemographic, comorbidity, psychosocial, and lifestyle factors were assessed via self-reported questionnaires. Multivariable logistic regression with LASSO variable selection was used to identify factors independently associated with clinically significant insomnia symptoms. Results: The prevalence of clinically significant insomnia symptoms (ISI ≥ 15) was 10.9%. Independent factors associated with clinically significant insomnia symptoms included being single (OR = 1.54) or divorced (OR = 1.75), lower educational attainment (OR = 0.71 per level increase), being retired (OR = 1.83) or a student (OR = 1.66), dermatological comorbidities (OR = 2.99), use of anxiolytic medications (OR = 2.44), exposure to stressful life events (OR = 1.88), engagement in late-night activities (OR = 1.37), consumption of coffee/tea (OR = 2.22), energy drink consumption (OR = 1.52), and late-night eating habits (OR = 1.27). Conclusions: Clinically significant insomnia symptoms among adults in Serbia are influenced by a complex interplay of sociodemographic, comorbidity, psychosocial, and lifestyle factors. These findings underscore the need for integrated approaches that address both medical and modifiable behavioral determinants in the prevention and management of insomnia symptoms. Full article

Delta-3-carene (CAR), a monoterpene derived from plant essential oils, exhibits promising biological properties, including anti-inflammatory, antioxidative, anxiolytic, and antimicrobial activities. Therefore, this study aimed to investigate the anti-inflammatory effects of CAR by analyzing the activity of this terpene on leukocyte activation through the evaluation of cell migration in in vitro and in vivo models. Cell viability analysis demonstrated that CAR (3, 10, 30, and 90 μg/mL) exerted no cytotoxic effects and significantly reduced in vitro neutrophil chemotaxis toward N-formylmethionyl-leucyl-phenylalanine (fMLP). Furthermore, CAR decreased phagocytosis in zymosan-stimulated neutrophils in vitro. In Swiss mice, oral CAR treatment, at doses of 25, 50, and 100 mg/kg, reduced inflammatory and antinociceptive parameters in zymosan-induced peritonitis, carrageenan-induced paw edema and mechanical hyperalgesia, and nociception induced by acetic acid and formalin models. In the persistent inflammation model (for 21 days) induced by complete Freund’s adjuvant (CFA), daily CAR treatment (50 mg/kg) reduced paw edema and mechanical hyperalgesia in all evaluated times at 6, 11, 16, and 21 days after CFA-induced inflammation. In conclusion, our data demonstrated that CAR modifies acute and chronic inflammatory responses, highlighting its potential therapeutic application in managing inflammation and pain. Full article

Dihydrosanguinarine (DHSA) is a naturally occurring benzo[c]phenanthridine alkaloid primarily isolated from plants of the Papaveraceae family. DHSA exhibits broad pharmacological activities, including antitumor, anti-inflammatory, hypoglycemic, neuroprotective, analgesic, anxiolytic, antiarrhythmic, and antimicrobial effects. Mechanistically, DHSA regulates multiple signaling pathways and molecular targets, including TMEM16A, p53, Ras/Raf/MEK/ERK, PI3K/AKT, NF-κB, PPARγ, GABA_A receptors, and voltage-gated sodium channels. Compared with its biosynthetic precursor sanguinarine (SA), DHSA exhibits a comparatively favorable safety profile while retaining considerable biological activity. Pharmacokinetic studies further suggest that DHSA possesses acceptable membrane permeability, gastrointestinal absorption potential, enterohepatic circulation characteristics, and sustained systemic exposure. In addition, structure–activity relationship (SAR) and electrostatic surface potential (ESP) analyses indicate that the chemically accessible C6 position may provide opportunities for rational structural optimization. Nevertheless, the clinical translation of DHSA still faces several challenges. Therefore, this review systematically summarizes the physicochemical properties, pharmacological activities, molecular mechanisms, SAR characteristics, ESP distribution, toxicity, pharmacokinetic behavior, and clinical prospects of DHSA, aiming to provide a theoretical basis for its future drug development and translational application. Full article