Search Results (1,117)

Background: Abemaciclib (ABM) in combination with tamoxifen (TAM) is an extremely significant treatment regimen for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. It is approved for patients to reduce the risk of cancer recurrence. A bioanalytical method for the simultaneous determination of this new anti-breast cancer combination and its pharmacokinetic application has not yet been reported. Methods: An ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) method was developed for quantifying ABM, TAM, and its metabolites, including abemaciclib active metabolites M2, M18, and M20 and tamoxifen active metabolite N-desmethyl tamoxifen (NDTAM), in rat plasma using econazole as the internal standard (IS). Chromatographic separation was achieved on a Kinetex C18 column (100 × 2.1 mm ID, 2.6 µm) using gradient elution with 5 mM ammonium formate in water (eluent A) and 5 mM ammonium formate in water/methanol (1:9, v/v, eluent B) at a flow rate of 0.4 mL/min. Detection was performed on a TSQ Fortis Plus mass spectrometer employing multiple reaction monitoring mode under positive electrospray ionization. Results: The developed method was validated according to the guidance of the FDA. Linearity in rat plasma (ng/mL) was achieved from 1 to 1000 for ABM, TAM, and M20; 3 to 1000 for M2; 5 to 500 for M18; and 1 to 500 for NDTAM; with correlation coefficients ranging from 0.9991 to 0.9931 for all analytes using a weighting factor of 1/X². The lower limit of detection (LLOD) ranged between 0.3 and 1.5 ng/mL for all drugs. The accuracy ranged from 96 to 108% and the precision was less than 7.6% RSD for all analytes. For the first time, the newly developed approach was effectively used in a pharmacokinetic study on the simultaneous oral administration of ABM and TAM in rats that received 30.0 mg/kg of ABM and 8.0 mg/kg of TAM. Conclusions: To the best of our knowledge, this is the first reported UPLC–MS/MS method for the assay of ABM, TAM, and its active metabolites in plasma. This method offers a bioanalytical tool for assessing the pharmacokinetics of ABM and TAM. Therefore, this study makes a definite significant contribution to the field of bioanalytical research. Further validation in human plasma is required for future clinical or therapeutic drug monitoring applications, as the approach was developed in an animal model. Full article

Intervertebral disc degeneration (IDD) is a fundamental pathological basis of low back pain, yet its pathogenic mechanisms remain incompletely understood. Infection by low-virulence anaerobic bacteria has recently been recognized as a potential etiological factor. In this study, Cutibacterium acnes (C. acnes) was detected in 13.7% of degenerated intervertebral disc (IVD) tissues, and its presence was significantly associated with younger patients and Modic changes. In vitro experiments demonstrated that C. acnes supernatant induces oxidative stress, apoptosis, and extracellular matrix (ECM) degradation in nucleus pulposus (NP) cells in a dose-dependent manner. RNA sequencing and functional validation further indicated that these pathological effects are mediated through activation of the p38 MAPK signaling pathway. Pharmacological inhibition of p38 with the specific inhibitor BIRB-796 effectively reversed the observed cellular damage. Wogonin exhibited negligible cytotoxicity toward NP cells and significantly attenuated C. acnes supernatant-induced oxidative stress, apoptosis, and ECM metabolic imbalance by inhibiting the phosphorylation of p38, JNK, and ERK1/2 within the MAPK pathway. Furthermore, in vivo experiments confirmed that Wogonin alleviated disc height loss, reduced T2-weighted signal attenuation, and mitigated histological damage induced by C. acnes in rat models, thereby restoring the balance between ECM synthesis and degradation. Collectively, this study demonstrates for the first time that C. acnes supernatant exacerbates IDD through activation of the p38 MAPK signaling pathway. It further shows that Wogonin can specifically inhibit this pathway and effectively ameliorate C. acnes-mediated IDD damage in both in vitro and in vivo models. These findings expand the theoretical framework of infection-related mechanisms underlying IDD and identify potential therapeutic targets and candidate agents for the treatment of IDD associated with C. acnes infection. Low back pain is a common health issue affecting populations worldwide, with intervertebral disc degeneration as its core etiology. However, the pathogenic causes in some patients, especially young individuals, remain incompletely understood. This study found that Cutibacterium acnes, a low-virulence bacterium commonly colonizing human skin and mucous membranes, produces metabolic products that can induce damage to the core cells of the intervertebral disc, exacerbate disc degeneration, and this process is associated with the abnormal activation of specific cellular signaling pathways. Through clinical sample detection, cell experiments, and animal model validation, we confirmed that infection with this bacterium is closely related to young patients and specific spinal imaging changes. Meanwhile, we identified Wogonin, a natural compound extracted from Scutellaria baicalensis, which can effectively inhibit the aforementioned abnormal signaling pathways, alleviate cell damage caused by bacterial metabolic products, and improve the pathological state of intervertebral disc degeneration. This study not only reveals the role of low-virulence bacterial infection in intervertebral disc degeneration and provides a new explanation for the pathogenic mechanism in young patients but also offers a natural antibiotic-free candidate for addressing bacterial resistance. It holds significant reference value for the clinical diagnosis and treatment of spinal diseases as well as the development of related drugs. Full article

Tripterygium glycosides extract (TGE), the primary active component of tripterygium glycosides tablets, is widely used for immune-related disorders but raises significant clinical concerns regarding cholestatic drug-induced liver injury. As conventional models fail to fully recapitulate the complex pathogenesis of traditional Chinese medicine toxicity, this study aimed to elucidate the mechanisms of TGE-induced cholestatic injury using a biomimetic microfluidic liver-on-a-chip platform. The chip integrated rat precision-cut liver slices (PCLSs) and human endothelial cells (EA.hy926) to simulate the hepatic sinusoidal microenvironment. Following TGE exposure (15–135 μg/mL for 12 and 24 h), vascular barrier integrity was maintained, while liver injury markers (ALT, AST, TBA, DBIL) significantly increased in a dose- and time-dependent manner, accompanied by progressive histopathological deterioration in PCLSs. Mechanistically, TGE triggered severe oxidative stress (decreased SOD/GSH/GSH-Px and increased MDA) and upregulated pro-inflammatory cytokines (IL-4 and IL-1β). Consequently, the expression of the bile acid receptor FXR and transporters (BSEP and MRP2) was significantly downregulated. In conclusion, TGE induces cholestatic liver injury via a sequential pathway: oxidative stress initiates an immune-inflammatory response, which subsequently suppresses the FXR/BSEP/MRP2 axis. Future studies should focus on developing fully humanized liver-on-a-chip systems to further validate these mechanisms and improve clinical translational significance. Full article

Background/Objectives: The oral administration of donepezil has been shown to have common side effects due to systemic drug delivery, with fluctuations in blood and brain donepezil concentrations. Therefore, we obtained nanostructured lipid carriers loaded with donepezil (donepezil–NLC) for nose-to-brain targeting. Methods: The obtained NLCs were characterized by measurements of particle size, the polydispersity index, zeta potential, encapsulation efficiency, atomic force microscopy, Differential Scanning Calorimetry, Fourier transform infrared spectroscopy, X-ray diffraction, and in vitro release studies. Plasma and brain pharmacokinetic studies in Wistar rats were carried out to determine brain targeting. Results: Donepezil–NLC showed low polydispersity and nanometric size, high zeta potential, and high drug entrapment efficiency. Microscopy images showed spherical particles with regular surfaces. Thermal analysis, X-ray diffraction, and FTIR-ATR suggested the formation of an amorphous lipid matrix and the incorporation of donepezil molecularly dispersed within the lipid matrix. In vitro drug release studies demonstrated a biphasic drug release pattern with an initial burst followed by sustained release, with results better fitted to the Korsmeyer–Peppas model (n-value > 0.5). Following the nasal administration of donepezil–NLC, brain pharmacokinetic studies in Wistar rats demonstrated a significant improvement in bioavailability. Compared to the intravenous injection of donepezil, the AUC^0–ꝏ value was 10.5-fold higher. Drug targeting efficiency and direct transport percentage showed extremely higher values, suggesting nose-to-brain targeting after donepezil–NLC intranasal administration. Conclusions: Donepezil–NLC has proven to be an efficient drug delivery system for the nose to the brain, which may reduce systemic toxicity and improve Alzheimer’s therapy with low doses of donepezil and fewer adverse effects. Full article

Celastrol (CSL), a natural triterpenoid extracted from Tripterygium wilfordii, demonstrates a wide range of biological activities. In this study, we explored whether CSL alleviates kidney damage in spontaneously hypertensive rats (SHRs) through the modulation of the Nrf2/Ho-1 pathway, a crucial target in renal injury models. A total of 40 male SHRs, aged 6–8 weeks, were randomly allocated to four groups: the control group (CON, serving as the healthy control), the spontaneously hypertensive rat group (SHR), the SHR group treated with low-dose CSL (L-CSL + SHR, 0.5 mg/kg/d), and the SHR group treated with high-dose CSL (H-CSL + SHR, 1 mg/kg/d). All drugs were formulated using physiological saline as the solvent and administered via intraperitoneal injection. The control group received an equivalent volume of physiological saline via intraperitoneal injection, and all groups underwent continuous daily administration for 6 weeks. The results indicated that, in comparison with the control group, the serum levels of angiotensin, angiotensin-converting enzyme, and aldosterone in the SHR group were relatively high, and CSL treatment further downregulated these indices. Simultaneously, CSL downregulated pro-inflammatory factors (tumor necrosis factor-α and interleukin-1β) and upregulated interleukin-6. Regarding renal function-related indicators, CSL reduced malondialdehyde levels and enhanced the activities of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase, and catalase. Moreover, CSL inhibited the overexpression of Keap1. Significantly, the mRNA levels of Nrf2, Nqo1, and Ho-1 in the CSL-treated groups were notably higher than those in the SHR group. These findings suggest that CSL mitigates renal pathological damage in SHR by activating the Nrf2/Ho-1 pathway, offering a potential therapeutic approach for hypertension-induced renal injury. Full article

Empagliflozin (EMPA), a sodium-glucose cotransporter 2 inhibitor, has garnered attention for its cardiovascular benefits beyond glycemic control. Ferroptosis, a novel form of regulated cell death, contributes to the pathogenesis of diabetic cardiomyopathy (DCM). However, whether EMPA mitigates DCM by suppressing ferroptosis remains unclear. Here, Type 2 diabetic db/db mice were used to establish a DCM model and treated with EMPA (10 mg/kg/day) for 12 weeks. EMPA significantly improved cardiac function, reduced myocardial fibrosis, and attenuated ferroptosis, concomitant with upregulated silent information regulator 3 (SIRT3) expression. In the rat cardiomyocytes (H9c2 cells) exposed to high glucose and palmitic acid, EMPA treatment or SIRT3 overexpression alleviated oxidative stress, mitochondrial dysfunction, and ferroptosis. Mechanistically, molecular docking, molecular dynamics simulation, cellular thermal shift assay and drug affinity responsive target stability assay confirmed that SIRT3 is the drug target of EMPA, stabilizing its protein levels and reducing acetylated p53 expression. Notably, SIRT3 silencing abolished EMPA’s beneficial effects on oxidative stress and ferroptosis. Our findings demonstrate that EMPA exerts cardioprotective effects by inhibiting oxidative stress and ferroptosis in cardiomyocytes, which is mediated by SIRT3. This study provides novel insights into the mechanisms underlying EMPA’s therapeutic effects in DCM. Full article

Background/Objectives: Rebamipide is a gastroprotective agent with poor aqueous solubility and rapid gastrointestinal clearance, leading to reduced therapeutic efficiency. This study aimed to enhance the solubility, mucoadhesion, and sustained oral delivery of Rebamipide through the development of a deep eutectic mixture (DEM)-based bioadhesive controlled-release granule formulation. Methods: In silico hydrogen-bonding interactions between Rebamipide, malonic acid, and urea were analyzed using CCDC tools. A thermodynamically stable DEM (1:3:1) was prepared and incorporated into bioadhesive granules using chitosan and HPMC. Physicochemical characterization was conducted using FTIR, DSC, TGA, and PXRD. Solubility, in vitro dissolution, ex vivo mucoadhesion (sheep gastric mucosa), and in vivo gastric retention (BaSO₄-loaded granules in rats) were evaluated. Results: The optimized DEM significantly enhanced Rebamipide solubility (10.08 mg/mL vs. 0.045 mg/mL). Solid-state analyses confirmed hydrogen-bond formation and reduced crystallinity. DEM granules exhibited sustained drug release over 24 h (99.7 ± 0.8%) with improved dissolution efficiency compared to the marketed tablet (Mucosta®, 100 mg; T₅₀%: 5.03 h vs. 0.82 h). Kinetic modeling indicated non-Fickian anomalous transport (n = 0.47). The bioadhesive force of DEM granules (0.29 ± 0.02 N) was significantly higher than that of the pure drug and physical mixture. In vivo radiographic studies confirmed prolonged gastric retention. Conclusions: The DEM-based bioadhesive granule system effectively improves solubility, dissolution rate, mucoadhesion, and gastric retention of Rebamipide. This approach represents a promising platform for once-daily gastroretentive oral delivery, pending further pharmacokinetic evaluation. Full article

Background: Autonomic side effects are a major determinant of tolerability for many psychotherapeutic drugs. While often attributed to receptor-mediated mechanisms, the potential contribution of direct modulation of smooth muscle excitability remains poorly characterized at a comparative pharmacological level. Methods: A systematic comparative pharmacological profiling of a broad panel of psychotherapeutic drugs (antidepressants, antipsychotics, and anxiolytics) was conducted using a standardized ex vivo model. Potassium chloride (KCl, 105 mM) was used to induce depolarization-dependent contraction in three isolated smooth muscle preparations (rat uterus, rat vas deferens, and guinea-pig ileum). Inhibitory potency (IC₅₀), dose-dependency, and tissue consistency were integrated to define functional inhibitory profiles. Results: Psychotherapeutic drugs exhibited marked heterogeneity in their ability to inhibit K⁺-induced smooth muscle contraction. Integrative analysis stratified compounds into four distinct functional profiles: (i) High Inhibitory Liability (e.g., nortriptyline, paroxetine), characterized by low micromolar IC₅₀ values and dose-dependent inhibition across multiple tissues; (ii) Non-Selective Inhibition (e.g., flunarizine, cinnarizine), showing consistent but dose-independent inhibition; (iii) Tissue-Dependent Inhibition (e.g., risperidone, reboxetine); and (iv) Minimal Inhibition (e.g., moclobemide). Agents classified within the High Inhibitory Liability profile correspond to drugs known to carry a higher clinical burden of autonomic adverse effects. Conclusions: This study reveals a previously underrecognized pharmacodynamic dimension of psychotherapeutic drugs and establishes a comparative functional taxonomy based on their direct, non-receptor-mediated inhibition of smooth muscle excitability. The identified profiles provide a mechanism-informed framework for contextualizing autonomic side-effect liability and may support improved safety evaluation in psychotherapeutic drug development. Full article

Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We hypothesized that combining these modalities would yield superior outcomes. Accordingly, we investigated whether a lidocaine-loaded alginate–carboxymethyl cellulose–polyethylene oxide (ACPE) electrospun film could more effectively reduce both postoperative pain and adhesion formation than either component alone. Materials and Methods: An electrospun nanofiber film composed of ACPE containing lidocaine was prepared. Its effects were evaluated in rats using an incisional pain and a peritoneal adhesion model. Four groups were compared: saline control, free lidocaine, drug-free ACPE film, and lidocaine-loaded ACPE film. Fifteen rats were allocated to each group. The primary outcome was the mechanical withdrawal threshold (MWT) after plantar incision, while secondary outcomes included histological changes and adhesion scores assessed by the Moreno system. Results: The lidocaine–ACPE film significantly increased MWT compared with all other groups, demonstrating a stronger and longer-lasting analgesic effect than free lidocaine. Adhesion scores were also lowest in the film group. Histological analysis confirmed a reduction in inflammatory cell infiltration and collagen deposition. Conclusions: A lidocaine-loaded ACPE nanofiber film effectively reduced both postoperative pain and adhesion formation in a rodent model. The combination of sustained local drug release and physical barrier function provides a promising strategy to address two major postoperative complications. Further preclinical studies are warranted before clinical application. Full article

Skin wound management in veterinary medicine requires therapies able to control inflammation, limit microbial burden, and support tissue repair. This study evaluated the anti-inflammatory, wound-healing, and immunomodulatory effects of four novel topical formulations combining synthetic anti-inflammatory drugs, antibiotics, and plant extracts in rat experimental models. Burn injury was induced in male Wistar rats for wound-healing assessment, while kaolin- and dextran-induced paw edema models were used to assess anti-inflammatory activity. The tested formulations were meloxicam, dexamethasone, and levofloxacin; thyme extract with meloxicam and dexamethasone; burdock extract with dexamethasone and levofloxacin; and thyme extract combined with burdock extract. Wound evolution was monitored macroscopically, edema was quantified by plethysmometry, and selected inflammatory mediators were measured by immunoassay. In the burn model, the thyme-containing formulation with meloxicam and dexamethasone, and the thyme–burdock formulation, achieved complete wound closure by the end of follow-up, whereas the reference product did not. In the acute inflammation models, all innovative formulations significantly reduced edema at the main early time points compared with the negative control and outperformed the reference product. The thyme–burdock formulation also showed the most favorable immunomodulatory profile, including normalization of interleukin-10 and marked reduction in interleukin-1 beta in both models. These results support the potential of multi-component topical formulations, particularly plant extract-based combinations, as promising candidates for veterinary wound care. Full article

The dextran sodium sulfate (DSS) colitis model is the most widely used experimental model of inflammatory bowel disease (IBD) due to its simplicity and versatility, with over 7000 PubMed entries in the last decade and an exponential rise in recent years. Since its initial description in 1985, DSS colitis has been extensively evaluated across species, most notably in mice and rats, and has yielded substantial insights into IBD pathogenesis. However, the model’s multifactorial nature poses a dual challenge: it offers an opportunity but complicates study design, interpretation, and translational relevance. This complexity is worsened by inconsistent reporting, which hampers reproducibility and comparability across studies. The broad use of the DSS-induced colitis model yields numerous insights about the model, which help better understand its complexity, characteristics and limitations. Although DSS colitis is induced locally, inflammation in the colon and gut barrier destruction may also affect other organs (such as the liver and brain) and their metabolism and molecular responses, which, in turn, may interfere with colitis-underlying mechanisms and drug response, and may influence the interpretation of results. These intrinsic (intra-experimental) characteristics of the DSS model are summarised in the paper (colitis, gut–brain axis, gut–liver axis). In addition, the DSS model is heavily influenced by numerous extrinsic (inter-experimental) factors (environmental, microbiological, genetic), which may further complicate the colitis model, the study outcomes, and data interpretation, and these are also discussed in the paper. As science advances and new data accumulate, understanding the intricate interplay among internal mechanisms, external factors, and technical variables becomes increasingly essential for the accurate interpretation of DSS outcomes. This review synthesises the complexity and interdependence of factors shaping the DSS model, emphasising the need for meticulous reporting and consideration of methodological nuances to enhance reproducibility, interpretation, and translational value in DSS colitis research. In addition, the review provides practical guidance through a “traps and tricks” subsection and checklist table designed to provide a framework and practical recommendations to better understand, apply, and interpret DSS model results in the context of broader systemic and methodological considerations. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

Background/Objectives: Research has shown a high prevalence of co-occurring trauma-related disorders and cocaine use disorder (CUD). However, there remains a need for preclinical studies to determine how traumatic event exposure influences vulnerability to CUD development and relapse. In this study, we assessed the impact of traumatic event exposure using a threat conditioning (TC) paradigm, which models traumatic event exposure through associative threat learning on cocaine-seeking behavior in adult male and female rats. Methods: Adult male and female rats were exposed to a single TC session. After TC, the rats underwent cocaine self-administration (SA), extinction training, cue-primed reinstatement, and cocaine-primed reinstatement testing. A parallel cohort was subjected to a sucrose SA cohort to assess whether TC altered non-drug reward seeking in the form of sucrose SA. Results: In the cocaine cohort, stressed male rats exhibited greater cue- and cocaine-primed reinstatement relative to non-stressed males, whereas no reinstatement differences emerged in female rats. In the sucrose cohort, stressed females displayed increased sucrose pellet delivery during self-administration compared to non-stressed females, but no differences were observed during sucrose reinstatement in either male or female rats. Conclusions: These findings indicate that trauma exposure prior to cocaine use influences cocaine relapse-related behavior, as well as non-drug reward reinforcement earning, in a sex-specific manner. Overall, these results highlight the value of associative stress models such as TC for studying trauma–addiction comorbidity and the need to investigate the neurobiological mechanisms driving these sex-specific outcomes. Full article

Drug resistance remains a major challenge in epilepsy, and overexpression of ATP-binding cassette transporters, particularly P-glycoprotein (P-gp), at the blood–brain barrier (BBB) has been consistently implicated in limiting central nervous system drug exposure. Genetic experimental models suitable for investigating molecular regulation and functional alterations of P-gp in epilepsy remain scarce. This study evaluated P-gp expression and functional alterations in the Wistar Audiogenic Rat (WAR), a genetic model of epilepsy exhibiting phenotypic heterogeneity. WAR animals were classified into refractory epilepsy (WAR-RE) or temporal lobe epilepsy (WAR-TLE) phenotypes and compared with non-epileptic Wistar controls. Fexofenadine, a well-established in vivo P-gp probe substrate, was administered orally, and plasma pharmacokinetic parameters were determined. P-gp expression at the BBB was assessed by immunohistochemistry in hippocampal regions. WAR-RE animals exhibited significantly increased systemic exposure to fexofenadine, characterized by higher area under the curve and prolonged half-life, alongside reduced apparent clearance, compared with control animals (p < 0.05). In contrast, WAR-TLE animals showed greater interindividual variability without statistically significant differences. Immunohistochemical analysis revealed increased P-gp expression in hippocampal microvessels in both WAR phenotypes. These findings demonstrate that the WAR model displays molecular upregulation of P-gp at the BBB, accompanied by functional alterations in the disposition of a prototypical P-gp substrate. Although direct brain drug concentrations were not assessed, the integration of systemic pharmacokinetics with transporter expression supports the use of WAR as a genetic proof-of-concept model for studying P-gp regulation and transporter-mediated drug disposition in epilepsy. This model provides a valuable molecular framework for future investigations addressing transporter modulation and mechanisms underlying pharmacoresistance. Full article

Background/Objectives: Ulcerative colitis is a chronic inflammatory bowel disease marked by a disrupted intestinal barrier and consequent aberrant immune responses. Pseudoginsenoside RT2, an ocotillol-type ginsenoside abundant in Panax herbs, represents a potential therapeutic candidate, yet its anti-ulcerative colitis efficacy and pharmacokinetic profile remain unclear. This study aimed to elucidate RT2’s therapeutic potential for ulcerative colitis through a parallel evaluation of pharmacodynamic efficacy and pharmacokinetic properties. Methods: The anti-ulcerative colitis efficacy and in vivo disposition of RT2 were investigated in a trinitrobenzene sulfonic acid-induced rat colitis model. An ultra-performance liquid chromatography–tandem mass spectrometry method was employed to delineate its pharmacokinetic characteristics and quantify its distribution in various tissues following oral administration. Results: Pharmacodynamically, RT2 demonstrated significant efficacy in the UC rat model by repairing the intestinal barrier (by promoting goblet cell regeneration and upregulating tight junction proteins and mucin) and restoring immune homeostasis (by correcting T-helper 17/regulatory T-cell imbalance and reducing pro-inflammatory cytokines while elevating anti-inflammatory cytokines). Pharmacokinetically, RT2 exhibited rapid absorption, slow elimination, and high colonic accumulation, with concentrations in the inflamed colon being significantly higher than those in healthy rats. Furthermore, the biphasic concentration–time profile may account for its prolonged systemic residence time and enhanced local exposure. In summary, through parallel efficacy and pharmacokinetic studies, this work systematically reveals its characteristics as a therapeutic agent that exhibits high colonic accumulation and acts via barrier repair and immunomodulation. Conclusions: These findings provide a theoretical foundation for the development of RT2 as a novel gut-selective drug candidate for UC. Full article