Pregnane X receptor (PXR), a crucial member of the nuclear receptor superfamily, is predominantly expressed in the liver and intestine and serves as a key transcription factor regulating the expression of various drug-metabolizing enzymes and transporters. Beyond its classical role in xenobiotic detoxification, PXR also plays an important role in the metabolism of endogenous substances such as bile acids, lipids, and glucose. In recent years, extensive studies have demonstrated that PXR is closely associated with a variety of hepatic and intestinal diseases, including drug-induced liver injury, metabolic dysfunction-associated fatty liver disease, cholestasis, inflammatory bowel disease, and hepatointestinal malignancies. Multiple PXR agonists—including endogenous ligands, natural products, and synthetic small molecules—have shown significant potential in restoring metabolic homeostasis, regulating inflammation, and maintaining hepatic and intestinal functions. This review highlights the central role of PXR in metabolic regulation, systematically summarizes its mechanisms and recent advances in hepatic and intestinal diseases, and focuses on the development and clinical translation of PXR agonists, aiming to provide a theoretical basis for PXR-targeted therapeutic strategies against liver and intestinal disorders.

Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and is highly expressed mainly in the liver and intestine. As a transcription factor regulating the expression of multiple target genes, FXR not only regulates bile acid, glycolipid, and microbial metabolism through a number of different metabolic pathways, but also plays an important role in inflammation, cell proliferation, differentiation, apoptosis, and cancer growth. FXR is now recognized as a key component in the regulation of various digestive diseases such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), metabolic dysfunction-associated steatotic liver disease (MASLD) and inflammatory bowel disease (IBD). In recent years, significant progress has been made in the development of agonists and antagonists targeting FXR, but their clinical application still faces the challenge of balancing efficacy and safety. Based on the core physiological functions of FXR in regulating bile acid metabolism, glucose-lipid homeostasis and inflammatory response, this article systematically analyzes the mechanism of action and clinical translation of novel FXR agonists and antagonists, focusing on their therapeutic potential in digestive diseases such as PSC, PBC, MASLD and IBD, and the prospective development of drugs based on the precise regulation strategy of FXR.

Pregnane X receptor (PXR), an important member of the nuclear receptor superfamily, serves as a sensor for xenobiotics and regulates the expression of drug-metabolizing enzymes and transporters. Recent studies have revealed that PXR is not only involved in drug metabolism and detoxification but also plays a critical role in glucose metabolism, lipid metabolism, bile acid homeostasis, and inflammatory regulation. As a ligand-activated transcription factor, PXR regulates downstream target genes expression, thus defending the body from xenobiotic and endogenous toxin attacks. PXR is associated with the development of a number of metabolic diseases such as obesity, type 2 diabetes mellitus, metabolic dysfunction-associated fatty liver disease, cholestatic liver diseases, cardiovascular diseases, etc. However, the regulatory mechanism of PXR in the context of glucose, lipid, cholesterol, and bile acid metabolism are complex and vary depending on nutritional status, species, and tissues. Therefore, developing drugs that selectively regulate PXR and its downstream signaling pathways may represent a promising strategy for treating metabolic diseases in the future. We review the structural and functional characteristics of PXR in the article, its transcriptional regulatory mechanisms, and the research progress of PXR as a therapeutic target for metabolic diseases. We summarize the research progress of drugs targeting PXR for the treatment of metabolic diseases, aiming to provide insights for future drug development targeting the PXR receptor for metabolic diseases treatment.

Metabolic cardiovascular diseases are a category of cardiovascular conditions driven by metabolic risk factors, such as obesity, hypertension, metabolic-associated fatty liver disease (MAFLD), and diabetes, in which metabolism disturbance and inflammatory responses are key contributors. Peroxisome proliferator-activated receptor α (PPARα), a member of the nuclear receptor superfamily, plays a critical role in the maintenance of metabolic homeostasis. Recent studies have indicated that PPARα exerts beneficial effects on metabolic cardiovascular diseases via regulating lipid metabolism, inflammatory responses, and mitigating oxidative stress. This review summarized the molecular structure and biological functions of PPARα, with a focus on the underlying mechanisms in PPARα regulating metabolic cardiovascular diseases and translational significance of PPARα agonists in preclinical-clinical studies, aiming to establish novel therapeutic paradigms for these disorders.​

The pregnane X receptor (PXR) is a crucial member of the nuclear receptor superfamily and plays a pivotal role in regulating various biological processes. In recent years, significant progress has been made in the development of PXR antagonists and PXR-targeting proteolysis-targeting chimera (PROTAC). This review systematically summarizes recent advances in the study of PXR antagonists and PXR PROTAC drugs, with the aim of providing valuable insights and references for novel drug development and the exploration of new therapeutic targets in related fields.

With the advancement of industrialization in modern society, exposure to endocrine disrupting chemicals (EDCs) in daily environments is increasingly prevalent. These substances can interfere with physiological functions by activating nuclear receptors. The constitutive androstane receptor (CAR), a crucial member of the nuclear receptor family, serves as a key regulator in detoxifying endogenous substances and sensing exogenous EDCs, participating in the regulation of drug-metabolizing enzyme expression and energy metabolism. This study employed TCPOBOP (TC), a highly specific and potent agonist of CAR, to investigate the impact of exogenous EDC-activated nuclear receptors on mammary gland development and estrogen homeostasis in pubertal female mice. Using 3-week-old female mice as models, TC was administered via intraperitoneal injection at 0.5 mg·kg^-1 twice weekly. Mammary gland developmental morphology was observed, and serum estrogen levels were measured (all animal experiments conducted in this study were approved by the Institutional Animal Care and Use Committee of the Animal Experiment Center of Wuhan University, ethics number: WAEF-2023-0077). Results demonstrated that TC exposure significantly inhibited the developmental progression of the mammary ductal system through CAR activation. The underlying mechanism involved downregulating the expression of key estrogen-synthesizing enzymes while promoting estrogen metabolic conversion and inactivation, ultimately leading to reduced systemic estrogen levels. This study reveals the mechanism by which TC-activated nuclear receptor CAR suppresses mammary gland development and disrupts estrogen homeostasis in pubertal female mice. It provides insights for understanding how EDCs affect mammary development and endocrine balance in adolescent females via nuclear receptor pathways, and offers new research clues for exploring CAR's role in mammary development regulation.

Ritonavir (RTV) is widely used as an antiviral drug in clinical practice, but the mechanism underlying its hepatotoxicity remains incompletely understood. This study aimed to investigate the molecular mechanism by which pregnane X receptor (PXR) activation exacerbates RTV-induced hepatotoxicity. This study was approved by the Life Science Ethics Review Committee of Zhengzhou University (approval No.: ZZUIRB2022-142). Pxr gene knockout mice were constructed and treated with a PXR agonist and RTV, followed by evaluation of liver function indicators, hepatic pathological changes, expression of the metabolic enzyme, endoplasmic reticulum (ER) stress- and apoptosis-related genes, as well as the major active metabolites of RTV. Cellular experiments were further conducted for validation. The results demonstrated that PXR activation aggravated RTV-induced liver injury in mice, accompanied by upregulation of the relevant metabolic enzyme, accumulation of active RTV metabolites in the liver, elevated ER stress markers, and increased levels of molecules associated with cell death and tissue damage. In HepG2 cells, knockdown/overexpression of PXR respectively inhibited or enhanced rifampicin (RIF, a human PXR agonist)-induced expression of cytochrome P450 (CYP) 3A4. PXR overexpression combined with RIF increased the hepatotoxicity caused by RTV, which was reversed after CYP3A4 knockdown. Mechanistically, PXR activation accelerates the metabolism of RTV into toxic metabolites via upregulating CYP3A4, and these metabolites trigger ER stress, thereby promoting hepatotoxicity. This study reveals the central role of the PXR-CYP3A4 axis in RTV-induced hepatotoxicity by triggering ER stress, providing a novel strategy for mitigating drug-induced liver injury through targeted modulation of PXR.

This study focused on the medium- and long-chain acylcarnitines (MCACs/LCACs) metabolic axis regulated by peroxisome proliferator-activated receptor alpha (PPARα), aiming to elucidate its potential role in the hepatoprotective effects of herbal medicines. Initially, literature mining and database analysis were conducted to summarize the current research applications of PPARα agonists in liver diseases and the pathological implications of MCACs/LCACs accumulation across different liver disease models. Furthermore, published studies and animal experiments were integrated to validate the potential mechanism by which herbal medicines and herbal ingredients modulate liver disease via the PPARα-MCACs/LCACs pathway. Experimental results showed that co-administration of triptolide and celastrol (TP_Cel) significantly induced liver injury, accompanied by marked accumulation of MCACs/LCACs. In the TP_Cel model, Spearman analysis revealed moderately to strongly inverse correlations between plasma MCACs/LCACs abundances and the expression of hepatic PPARα-target genes, including Cpt1a, Cpt2, and Acox1, with most correlations reaching statistical significance (P < 0.05). In addition, plasma MCACs/LCACs abundances were significantly elevated in Ppara^-/- mice compared with wild-type 129 mice (P < 0.05). Based on these findings, a multi-stage screening strategy was established, resulting in the identification of 68 hepatoprotective herbal medicines (HpHMs) and 29 hepatoprotective herbal ingredients (HpHIs), both targeting PPARα with no documented hepatotoxicity. Finally, molecular docking was employed to preliminarily evaluate the binding capacity of HpHIs to PPARα. These findings provide mechanistic insights and potential resources for the development of herbal medicines and herbal ingredients targeting lipid metabolism disorders in liver diseases. All animal experiments were approved by the Animal Ethics Committee of West China Hospital, Sichuan University (approval No. 20220217001).

Rheumatoid arthritis (RA), a chronic autoimmune disease, has a complex interaction with glucose and lipid metabolism in pathological process. Glucose metabolism reprogramming disrupts the metabolic homeostasis of the microenvironment and activates aerobic glycolysis to drive synovial proliferation and inflammation; lipid metabolism dysfunction reshapes the inflammatory regulatory network through lipid-derived mediators. The interplay between glucose and lipid metabolism jointly drives the "metabolism-inflammation" vicious cycle, in which the metabolic hub role of acetyl coenzyme A, the bidirectional regulatory role of lactate, the synergistic regulation of metabolic signals, and the organelle interaction between mitochondria and lipid droplets collectively exacerbate the pathological progression of RA. This review systematically focuses on the abnormal characteristics and interaction mechanisms of the two core pathways of glucose and lipid metabolism in RA, proposes intervention strategies and research directions targeting metabolic homeostasis based on metabolic targets, and provides important scientific references for the in-depth analysis of the pathological mechanism of RA and the development of targeted metabolic intervention therapies.

Depression, a highly disabling psychiatric disorder, involves core disruptions in the epigenetic regulation (DNA methylation, histone modifications, non-coding RNA) of circadian clock genes (e.g., circadian locomotor output cycles kaput, brain and muscle ARNT-like protein 1, period, and cryptochrome). This dysregulation causes abnormal gene expression rhythms, leading to neurotransmitter imbalance, hypothalamic-pituitary-adrenal axis overactivation, and exacerbated neuroinflammation. We propose an "epigenetic-clock-neural circuit" interaction model, wherein suprachiasmatic nucleus master clock dysfunction disrupts synchronization of the hypothalamic-hippocampal-prefrontal circuit, constituting the core mechanism of emotional-cognitive comorbidity. Depression exhibits distinct circadian epigenetic signatures compared to epilepsy or dementia, revealing disease-specific mechanisms. Animal and clinical evidence converge on the pivotal role of circadian epigenetics. Diverse therapeutic strategies target this mechanism, including antidepressants, small-molecule inhibitors, behavioral interventions, gene editing/RNA therapies, and biomarker-guided personalized medicine. Treatment is evolving from generalized to personalized approaches, requiring novel targets and technologies. Despite challenges, this groundbreaking research opens new diagnostic and therapeutic avenues, advancing psychiatry into an era of "circadian medicine".

Due to the unique outer membrane barrier and their complex and diverse multidrug resistance mechanisms, the clinical resistance of Gram-negative bacteria is extremely severe, while the development of related new drugs has progressed slowly. This article systematically reviews representative anti-Gram-negative bacterial drugs that have been marketed in the past decade and those currently in clinical or preclinical research stages. It focuses on introducing drugs with novel targets/mechanisms of action and categorizes them based on intervention strategies targeting key stages of the Gram-negative bacterial life cycle, including: topoisomerase inhibition, protein synthesis disruption, protein transport obstruction, cell wall synthesis inhibition and damage, and bacterial cell division disruption. The content provides a comprehensive review of the structural information, mechanisms of action, antibacterial spectrum, clinical applications, as well as the applicational prospects and challenges of various classes of drugs.

Covalent inhibitors can realize specific binding by forming covalent bonds with the target, which can realize long-lasting inhibition of the target while reducing the dosage, and to a certain extent, they have overcome the traditional targets that are difficult to become drugs, and they have shown unique advantages in drug discovery and development. The binding characteristics of covalent inhibitors to plasma proteins are closely related to the efficacy, in vivo metabolism, and toxic side effects of these drugs, but the current research in this field is still limited, and there is a lack of systematic studies on the binding of covalent inhibitors of different warheads to high abundance proteins in human blood. Meanwhile, mass spectrometry has become an important tool to characterize the binding of covalent inhibitors to plasma proteins, and mass spectrometry-based proteomics can be used to comprehensively investigate the binding rate, binding reversibility, binding influencing factors, binding protein species, and binding sites of covalent inhibitors to plasma proteins. In this paper, the warheads of covalent inhibitors, the binding characteristics of covalent inhibitors to blood proteins and the research progress of mass spectrometry in the binding of covalent inhibitors to plasma proteins in recent years are reviewed to provide a reference for the study of binding of this class of drugs to plasma proteins.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by recurrent episodes and unbearable itching, imposing a heavy physical and psychological burden on patients. The pathogenesis of AD is complex, involving multiple factors such as environmental triggers, immune dysregulation, skin olfactory receptors, impaired epidermal barrier, and skin-gut microbiome imbalance. First-line clinical chemical drugs, such as glucocorticoids, can alleviate inflammation and itching to some extent, but relapse after discontinuation and drug resistance remain significant challenges, and effective treatments are still lacking. In recent years, research on essential oils extracted from natural plants for AD treatment has increased, demonstrating notable efficacy, high safety, and no drug resistance. This article explores the pathogenesis of AD, summarizes the therapeutic effects and mechanisms of plant essential oils in AD treatment, and discusses how drug delivery systems can improve the physical properties of essential oils, aiming to provide insights for developing novel AD therapies.

Small-angle neutron scattering (SANS) is a non-destructive structural characterization technique based on neutron-matter interactions, capable of providing microstructural information at the nanometer to micrometer scale (1-1 000 nm), including particle size distribution, morphological features, internal phase structures, and intermolecular interactions in pharmaceutical formulations. With the rapid development of nanodrug delivery systems (e.g., liposomes, polymeric micelles, lipid nanoparticles) and biologics (e.g., monoclonal antibodies, mRNA vaccines), conventional characterization techniques (e.g., electron microscopy, dynamic light scattering) face limitations in analyzing complex drug systems. Owing to its high sensitivity to light elements, exceptional penetration depth, and isotope discrimination capability, SANS offers unique advantages for probing the microstructure of pharmaceutical formulations. This review systematically summarizes recent advances in SANS applications for drug characterization, focusing on its pivotal role in elucidating the structure of nanodrug carriers, monitoring conformational dynamics of biologics, and investigating the self-assembly behavior of active pharmaceutical ingredients (APIs). Furthermore, the challenges of SANS in sample preparation, data analysis, and facility accessibility are discussed, along with future perspectives on integrating SANS with emerging technologies such as artificial intelligence and multiscale modeling. This review aims to provide new insights and technical support for the rational design and performance optimization of advanced drug formulations.

In recent years, the research of transdermal drug delivery systems (TDDS) represented by patches and gel plasters is in the ascendant. The interactions between drugs, pressure-sensitive adhesives, permeation enhancers and skin components, including hydrogen bonds, ionic interactions, dipole-dipole interactions, etc., play a key role in regulating the release and penetration of drugs in transdermal patches, thus affecting the efficiency of transdermal absorption of drugs. Infrared spectroscopy, molecular simulations or molecular docking, differential scanning calorimetry, Raman spectroscopy, nuclear magnetic resonance and other methods have been widely used to characterize multiple intermolecular interactions in patches. The aim of this review is to summary the molecular mechanisms of drug release from patches and transdermal permeation processes, provide useful theoretical guidance for the design and research of novel transdermal drug delivery systems.

The application of microneedle technology in biomedicine has attracted widespread attention due to its versatility in tissue sampling, biosensing and drug delivery. In particular, drug-loaded microneedle formulations can directly penetrate the stratum corneum to deliver drugs, enhance drug delivery efficiency, and achieve the purpose of disease treatment, which is characterized by high efficiency, portability, low trauma, and high controllability. When combined with smart responsive materials, microneedles enable precise drug delivery, improving targeting accuracy for diseases such as tumors while minimizing toxic side effects on normal tissues and cells. In this review, we introduce the history of microneedle technology and highlight its applications in smart-responsive systems for oncology therapy. We also discuss the current challenges and obstacles faced by microneedle technology in oncology therapy and clinical translation. Finally, we provide prospective recommendations on the current situation, aiming to inspire new ideas and directions for the development of related technologies.

Hair follicle is the organ of hair growth. Hair growth is highly associated with hair follicle cycle, which can be assessed by both promoting hair follicles from telogen to anagen and prolonging the anagen duration. In this study, according to the investigation of the hair follicle cycle in C57BL/6J mice, an evaluation model for the activity of hair follicles entering the anagen was established. Then, the hair follicle cycle was synchronized by beeswax-depilation, and the correspondence between the skin phenotypes and each phase of the hair follicle cycle was quantified, and the efficacy evaluation model for prolonging the anagen duration was innovatively constructed. Two mouse models established in this study can be utilized for active substances discovery and pharmacodynamic evaluation in vivo, which provides the methodology for development of hair growth promoting-drugs and health products. All animal experiments were approved by the Animal Care & Welfare Committee of Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (approval numbers: 00001932, 00001933, 00007786, and 00007787).

Nineteen compounds were isolated from the dichloromethane portion of the ethanol extract of Chinese Yam (Dioscorea opposita Thunb.) peel, using various chromatographic techniques including: silica gel column chromatography, medium-pressure liquid chromatography, Sephadex LH-20 gel column chromatography, and preparative high-performance liquid chromatography. Based on the physicochemical properties and spectral data, their structures were determined as follows: six phenanthrenes: 7′-hydroxybleformin E (1), 1,7-dihydroxy-5-methoxy-9,10-dihydrophenanthrene (2), 6-methoxycoelonin (3), 6-hydroxy-2,4,7-trimethoxyphenanthrene (4), 2,7-dihydroxy-4,6-dimethoxyphenanthrene (5), 5,7-dimethoxy-2,3-phenanthrenediol (6); three bibenzyls: dihydropinosylvin (7), 2′,3-dihydroxy-5-methoxybibenzyl (8), demethyl batatasin Ⅳ (9); eight diarylheptanoids: 1,7-bis(4-hydroxyphenyl)-1,5-epoxy-3-hydroxyheptane (10), engelheptanoxide C (11), diosniponol A (12), (+)-hannokinol (13), (3S,5S)-3,5-dihydroxy-1-(4-hydroxyphenyl)-7-(4-hydroxy-3-methoxyphenyl)heptane (14), (3S,5S)-3,5-dihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane (15), hexahydrocurcumin (16), (5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-3-heptanone (17); other compounds: one alkaloid, feruloyltyramine (18), and one fatty acid, octadecadienoic acid-2,3-dihydroxypropyl ester (19). Compound 1 is a new compound, whereas the ¹H NMR and ¹³C NMR spectral signals of 2 were fully attributed. compounds 2, 11, 16-19 were isolated from the Dioscoreaceae family for the first time, while compounds 3, 6, and 12 were the first to be reported from D. opposita. Among these, thirteen compounds showed differential inhibitory activities against α-glucosidase.

Thirteen compounds (1-13) were isolated from the ethanol extract of an endophytic fungus Cercophora sp. UJN-EF001 derived from Vaccinium bracteatum, using normal-phase silica gel column chromatography (CC), reversed-phase C₁₈ CC and high-performance liquid chromatography. The structures of these isolates were elucidated through spectroscopic methods including high-resolution mass spectrometry, nuclear magnetic resonance and electronic circular dichroism. Among them, two (1 and 2) were previously unreported molecules, two (3 and 4) were obtained for the first time as natural products, and nine (5-13) were isolated for the first time from the genus Cercophora. All 13 compounds were evaluated for their inhibitory activities against α-glucosidase and nitric oxide (NO) production. As a result, none of them exhibited significant inhibition toward α-glucosidase, while compound 13 displayed moderate inhibition against lipopolysaccharide-induced release of NO in RAW264.7 macrophages with an IC₅₀ value of 34.3 ± 3.8 μmol·L^-1.

Shexiang Tongxin Dropping Pill (STDP), a compound oral preparation of traditional Chinese medicine, has the therapeutic effects of improving myocardial ischemia and relieving chest tightness and pain. It is often used in combination with chemical drugs for cardiovascular diseases in clinical practice. In this paper, the inhibitory effects of STDP on 17 human transporters were studied by cellular accumulation experiments using overexpressing transgenic cell models, including important transporters in the intestine (PEPT1, OATP2B1, MDR1, BCRP), liver (OATP1B1, OATP1B3, OCT1, OAT2), kidney (OAT1, OAT3, OAT4, OCT2, MATE1, MATE2-K), and heart (OCTN1, OCTN2, OCT3). The results showed that STDP inhibited the renal cation transport system (OCT2, MATE1/2-K), but had no significant inhibitory effect on the other 14 transporters. Since the commonly co-administered drugs are not substrates of OCT2 and MATE1/2-K, atenolol and procainamide, the potential co-administered drugs of STDP, were selected as substrates for further study. The results reveled that STDP inhibited the transport of atenolol mediated by MATE1 and MATE2-K, as well as the transport of procainamide mediated by MATE1. Further study showed that the extracts of plasma, liver, and kidney from mice orally administered with STDP, even at 10-folds of clinical dose, merely inhibited MATE1-mediad transport of atenolol by 20%, without inhibiting MATE2-K-meidated transport of atenolol and MATE1/2-K-mediated transport of procainamide. It is speculated that at the clinical dose, STDP is unlikely to significantly affect the renal excretion of the two drugs. The above results suggest that at the clinical dose, STDP is unlikely to induce significant drug-drug interactions (DDIs) due to the inhibition of the above transporters. The animal experiments have been approved by the Animal Ethics Committee of Zhejiang University (approval number: ZJU20230086).

To explore the effects of Zhimu extract on the absorption and pharmacokinetic process of puerarin, thus to elucidate the scientific connotation of the compatibility application of Gegen-Zhimu herb pair from the perspective of P-glycoprotein (P-gp) regulation, a rapid and sensitive quantification method for puerarin in biological samples was established based on HPLC-UV technology. Combined with the rat single-pass intestinal perfusion model and pharmacokinetic experiments, with the classic P-gp inhibitor verapamil as control, the effects of Zhimu extract on the absorption and metabolism process of puerarin were investigated. The established HPLC method for puerarin in intestine perfusate and plasma samples met the requirements for quantitative analysis of biological samples. The K_a and P_app values of puerarin in the duodenal segment were significantly higher than those in the jejunal and ileal segments (P < 0.000 1). Co-administration with Zhimu extract or verapamil significantly increased the K_a and P_app values of puerarin in the duodenal segment (P < 0.000 1). Co-administration with high-dose Zhimu extract or verapamil significantly increased the C_max of puerarin in rats to (1.017 ± 0.25) µg·mL^-1 and (1.827 ± 0.87) µg·mL^-1 (P < 0.05), respectively, and AUC_0-∞ also significantly increased (P < 0.05), reaching 1.37-fold and 2.25-fold that of the puerarin group, respectively. Puerarin is best absorbed in the duodenal segment; by inhibiting the efflux of P-gp, Zhimu extract can promote the absorption of puerarin in the duodenal segment, increase its plasma concentration, and effectively improve the oral bioavailability of puerarin, which suggests the mechanism underlying the compatibility of Gegen-Zhimu herb pair. This experiment was approved by the Animal Ethics Committee of Naval Medical University (approval No.: NMUARE-21077).

The masking level of adverse taste of drugs, defined as taste-masking efficiency, directly affects the palatability of drugs, which in turn affects medication compliance. However, there is no effective and unified evaluation method. In this paper, three preparations with different dosage form and varied solubility, fexofenadine hydrochloride dry suspension, calcium carbonate D₃ particles and compound polyethylene glycol electrolyte powder, were selected to carry out simultaneous research on TS-5000Z, Astree Ⅱ V5 and iTongue20 electronic tongues. Through the determination of judgment criteria for reasonable solution preparation, effective sensor cleaning and repeatable sample testing, combined with high-dimensional data similarity discrimination methods such as principal component analysis and Euclidean distance, an evaluation method of taste-masking efficiency for drugs was established based on the design of reference solutions and determination of taste similarity between sample solution and reference solution. The above method was reproducible with comparable results among instruments, and with consistent results with human sensory evaluation. The above method is a standardized new method that can be used for multi-type drugs and multi-principle equipment, which provides technical support for the comparison of taste palatability between pharmaceutical preparations.