Search Results (1,041)

The occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD) are closely related to intestinal flora imbalance, intestinal barrier damage, and gut-liver axis dysfunction. Due to their multi-target regulatory effects and advantages in intestinal microecological intervention, Chinese herbal monomers have shown promising application prospects in the prevention and treatment of MASLD. However, basic research on their toxicity still lags behind, and issues related to safety and clinical translation urgently need attention. This article systematically reviews the research progress on how flavonoids, triterpenoids, alkaloids, and polysaccharides improve hepatic steatosis, inflammatory responses, and metabolic disorders from a toxicological perspective by reshaping the intestinal microbiota, repairing the intestinal mucosal barrier, regulating short-chain fatty acid and bile acid metabolism, and synergistically acting on signaling pathways such as TLR4/NF-kB, FXR, TGR5, SIRT1, and the NLRP3 inflammasome. Furthermore, by combining methods such as 16S rRNA sequencing, metagenomics, metabolomics, and multi-omics integration, the article analyzes their application value and limitations in toxicological mechanism research, and discusses the translational bottlenecks faced by Chinese herbal monomers in pharmacokinetics, bioavailability, quality standardization, targeted delivery, and toxicological safety. Existing evidence indicates that Chinese herbal monomers have a three-in-one intervention advantage of microecological remodeling-metabolic regulation-inflammation inhibition, but their long-term medication safety, toxic target organs, dose-effect/toxicity relationships, and potential drug interactions still need further clarification. This article aims to provide a systematic reference for the safety evaluation and clinical translational research of Chinese herbal monomers in the prevention and treatment of MASLD. Full article

Glioma, the most common and aggressive primary brain tumor, presents significant clinical management challenges due to difficulties in blood–brain barrier penetration, high tumor heterogeneity, and susceptibility to drug resistance and recurrence, leading to an extremely poor prognosis. Traditional Chinese Medicine (TCM), particularly its derived active ingredients and herbal formulations, with its advantages of multi-component, multi-target, and holistic regulation, demonstrates significant potential in the comprehensive treatment of this disease. This review systematically outlines the research progress in TCM for combating glioma. Regarding mechanisms of action, active TCM components not only directly inhibit tumors by inducing cell apoptosis but also exert synergistic therapeutic effects via multiple pathways. These include remodeling the immunosuppressive microenvironment, activating novel cell death programs such as ferroptosis and immunogenic cell death, intervening in tumor metabolic reprogramming, and reversing chemotherapy resistance. In terms of overcoming delivery barriers, drug delivery systems represented by nanocarriers, liposomes, and extracellular vesicles, combined with the penetration-enhancing effects of aromatic orifice-opening herbs (a class of TCM medicinals traditionally used to “open the orifices” and awaken the mind, now recognized to transiently enhance BBB permeability), have significantly improved the brain-targeting efficiency and bioavailability of TCM components. For clinical translation, a number of innovative drugs derived from TCM, such as elemene, cinobufagin, and ACT001, are currently under clinical investigation, with initial results showing efficacy in prolonging survival and improving quality of life. In the future, by integrating the analysis of multi-target synergistic mechanisms, promoting the clinical translation of intelligent drug delivery systems, and conducting high-quality clinical research on integrated Chinese and Western medicine, TCM is expected to provide a new generation of integrated treatment strategies for glioma that combines holistic and precision medicine. Full article

Background and Objectives: Drug-induced liver injury (DILI) is increasingly associated with the use of herbal medicines. Ephedra sinica (ES) occasionally induces hepatocellular injury, yet therapeutic strategies for herb-induced liver injury are limited. This study investigated the potential mechanisms of a multicomponent pharmacopuncture formulation (VP) in ES-associated hepatotoxicity. Materials and Methods: Bioactive constituents of VP were collected from pharmacological databases and literature. The physicochemical properties were evaluated using SwissADME. Compound–target interactions were identified using the STITCH database and integrated with DILI–related genes retrieved from GeneCards (relevance score ≥ 5.0). Protein–protein interaction network analysis, Gene Ontology enrichment, and KEGG pathway analyses were performed. Results: A total of 22 overlapping targets were identified. A nine-gene module—comprising TNF, IL6, STAT3, CASP3, PINK1, PRKN, NFE2L2, HMOX1, and ABCB11—was associated with key biological processes, including inflammatory signaling, mitochondrial quality control, oxidative stress regulation, and hepatobiliary transport. Conclusions: These findings suggest that VP may modulate multiple biological processes relevant to hepatotoxic stress, including inflammatory signaling, mitochondrial quality control, and bile acid transport. These results provide a plausible mechanistic framework for further investigation, pending experimental validation. Full article

The Wannachawee Recipe (WCR) is a traditional Thai herbal formulation with a clinical history of use in psoriasis. An observational study conducted at Prapokklao Hospital reported that 93% of psoriasis patients showed good clinical responses. However, the absence of standardized quality control parameters remains a critical barrier to its pharmaceutical reproducibility, safety, and integration into mainstream clinical practice. This study established robust quality specifications and a phytochemical profiling for WCR, in accordance with the Thai Herbal Pharmacopoeia (THP) guidelines, to support its development from traditional use to a standardized therapeutic agent. A multimodal analytical approach was employed, integrating microscopic characterization, physicochemical evaluation, and advanced instrumental techniques. Phytochemical characterization was conducted using High-Performance Liquid Chromatography (HPLC) fingerprinting and Compact Mass Spectrometry (CMS). A validated HPLC method was developed to quantify trans-p-coumaryl alcohol, a key bioactive marker. Anti-inflammatory activity was further assessed by measuring inhibition of nitric oxide production. Physicochemical analysis established rigorous benchmarks, including ethanol-soluble extractive (8.73 ± 0.15% w/w), water-soluble extractive (18.89 ± 0.09% w/w), and loss on drying (<10%), which ensure long-term stability and microbial safety. CMS analysis successfully identified key chemical constituents, including alpha-amyrin, stemone, protocatechuic acid, and trans-p-coumaryl alcohol. HPLC fingerprinting demonstrated high batch-to-batch consistency, while quantitative analysis determined a trans-p-coumaryl alcohol content of 8.77 mg/g extract. Critically, biological evaluation showed that WCR exhibited potent anti-inflammatory activity by inhibiting nitric oxide production, with a superior inhibitory effect compared with the reference drug indomethacin. This study provides a preliminary scientific framework for the standardization of WCR. It defines precise quality specifications and a potential bioactive marker, establishing the rigor needed for regulatory certification and industrial production. This work connects traditional Thai medicine with evidence-based pharmaceutics, positioning WCR as a promising therapy for psoriasis. Full article

Novel psychoactive substances (NPSs) exhibit extremely strong pharmaco-toxicological activity, often leading to severe adverse effects that pose a serious risk to consumers’ health. Among these, synthetic cannabinoids (SCs) currently represent the majority of drug seizures in Europe. One such compound, AKB-48 (also known as APINACA), was first identified in Japanese herbal smoking blends in 2012. Although it mimics the effects of Δ9-THC, the primary psychoactive component of Cannabis sativa, AKB-48 can induce more severe and potentially life-threatening outcomes. Several in vivo studies investigating the acute administration of AKB-48 have reported profound behavioral, neurological, and neurochemical alterations, including disruptions of neurotransmission across multiple brain regions, thus confirming its neurotoxic potential. Given the recognized vulnerability of the cerebellum to NPS, and its critical role in integrating neural circuits affected by psychostimulant drugs, the present study evaluated the toxic effects of repeated AKB-48 exposure on the cerebellar cortex of adult male and female ICR-CD1^® mice. Particular attention was paid to the modulation of cell death pathways, alongside assessments of sensorimotor responses. The results demonstrate, for the first time, that repeated AKB-48 administration induces significant morphological, immunohistochemical, and ultrastructural changes in both male and female mice. These alterations included pronounced disruption of cerebellar architecture and marked modulation of cell death pathways, further corroborated by TEM-detected ultrastructural damage and a substantial reduction in the basal visual placing response. Overall, the findings provide clear evidence of AKB-48’s sex-independent neurotoxicity, leading to cerebellar alterations that ultimately result in neuroplasticity impairment. Full article

Honey and propolis from the stingless bees Tetragonula drescheri and Tetragonula pagdeni remain underexplored for their health-promoting application. This study investigated the bioactive compounds, and antiviral and anticancer activities of honey and propolis extracts against herpes simplex virus (HSV), and human papillomavirus (HPV-16/18)-positive cervical cancer cells. Water and ethanol extracts were prepared and evaluated for anti-HSV activity using plaque assay, and for anticancer effects on CaSki and HeLa cells using apoptosis, colony formation, cell migration, and candidate gene expression analysis. Propolis water extract most potentially inhibited HSV wild-type and drug-resistant strains. Propolis ethanol extract from T. drescheri markedly suppressed CaSki and HeLa cell growth, induced apoptosis, downregulated HPV-16/18 E6, and upregulated BAX expression. Chemical profiles were identified by electrospray ionization quadrupole time-of-flight mass spectrometry. Most candidate compounds displayed preferable drug-likeness properties. Prototype herbal soup formulations containing selected extracts significantly inhibited HSV-1 drug-resistant strain and HPV-16 E6 expression. These findings demonstrated the high antiviral and anticancer potential of the extracted compounds from T. drescheri and T. pagdeni propolis, supporting their application in health-promoting products against HSV and HPV infection. Full article

The skin represents the largest organ in the body and functions to protect internal tissues from damage and infection. When wounds in small animals do not receive proper management, they may progress to chronic conditions, resulting in pain, delayed healing, and impaired well-being. Although conventional treatment mainly includes the use of topical antimicrobial agents and anti-inflammatory drugs, integrative veterinary medicine has been considered a promising complementary approach to enhance tissue repair. In this context, this study aimed to review non-conventional therapies applied to wound management in small animals, focusing on ozone therapy, light therapy that stimulates cellular activity, herbal medicine, and apitherapy, especially propolis. Overall, the analyzed studies indicate that ozone may contribute to microbial control and modulation of the immune response; light therapy may stimulate cellular activity and collagen production, promoting healing; medicinal plants present antioxidant and anti-inflammatory effects; and propolis demonstrates antimicrobial and regenerative properties. Thus, when responsibly applied and supported by scientific evidence, these approaches may complement conventional therapy, broaden clinical possibilities, and contribute to improved recovery and quality of life in animals. Full article

Aging is a multifactorial process characterized by progressive physiological changes, including cellular senescence, cellular loss, and organ decline, which collectively accelerate the development of metabolic syndrome (MetS) in older adults. MetS, in turn, not only significantly increases the risk of cardiovascular disease (CVD) but also contributes to decreased functional and cognitive capacity, partly due to diminished ability to adapt to metabolic stress. While genetic predisposition has a substantial influence on the risk of developing MetS, other intrinsic factors, including chronic inflammation, insulin resistance (InsR), and altered neurohormonal activation, also play crucial roles. Targeted therapies, lifestyle interventions, and pharmacotherapy can decelerate the progression of CVD, improving the likelihood of survival with favorable neurological and functional outcomes in older individuals with MetS. However, adverse drug reactions and the lack of adequate interventions for cognitive decline have led to the emergence of self-medication with nonprescription products. The anti-inflammatory, antioxidant, anti-channelopathy, antiaging, and neuroprotective properties of flavonoids, alkaloids, polysaccharides, and polyphenols found in key traditional medicines have shown promising potential in the treatment of MetS-induced cognitive decline. This narrative review summarizes current evidence on bioactive compounds and herbal medicines that may offer cognitive benefits in elderly patients with MetS. Full article

Bitter compounds may function not only as taste substances but also as important active constituents mediating therapeutic effects. Their recognition is primarily mediated by bitter taste receptors (TAS2Rs), which exert pharmacological effects, such as regulating glucose metabolism, anti-inflammatory properties, and immune modulation, aligning closely with the therapeutic effects of bitter Chinese herbal medicine (BCHM). Contemporary pharmacological research has increasingly underscored the therapeutic potential of bitter traditional Chinese medicine (TCM), particularly through their bioactive constituents in the prevention and treatment of diverse pathological conditions. Here, we systematically review the diversity of bitter compounds from TCM and features of TAS2Rs, including their tissue distribution, physiological functions, structural characteristics, signal transduction mechanisms, and single-nucleotide polymorphisms. While numerous bitter phytochemicals have been characterized as agonists of TAS2Rs, the precise physiological functions and underlying molecular mechanisms mediated by TAS2R activation remain incompletely elucidated. This knowledge gap is largely attributable to several methodological and biological challenges, including the widespread tissue distribution of TAS2Rs, the complexity of their downstream signaling cascades, and the structural and functional heterogeneity of bitter compounds. This review outlines theoretical foundations, future perspectives and challenges for the drug development of TAS2R from BCHM. Full article

Herbal melanin (HM), previously reported for its antiproliferative and pro-apoptotic properties, has garnered interest as a promising anti-colorectal cancer drug. However, HM’s biological effects and underlying molecular mechanisms and the related signaling pathways in colorectal cancer (CRC) cell motility are poorly investigated. To evaluate the impact of various concentrations (50, 100, and 200 μg/mL) of HM on cell migration, invasion, and tumorigenicity on human HT29 and SW620 CRC cell lines, a real-time cell analyzer instrument and colony formation assays were employed, respectively. An angiogenesis-related protein array was also used, and the levels of protein expression contributing to colony formation and extracellular proteolysis-driven cell migration and invasion, such as E-cadherin, N-cadherin and urokinase-type plasminogen activator receptor (uPAR), were monitored using Western blotting and RT-qPCR technologies. HM significantly decreased CRC cell motility, invasiveness, and formation of colonies, associated with E-cadherin upregulation and N-cadherin downregulation. In addition, HM specifically inhibited uPAR expression levels, which were also decreased by the pharmacological mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor UO126 and Jun N-terminal kinase (JNK) inhibitor SP600125, in both CRC cell lines, including metastatic CRC (mCRC) SW620 cell line. Addition of HM to cells pretreated with JNK and MEK inhibitors attenuated the blockade of JNK and ERK phosphorylation and alleviated HM-downregulated uPAR expression and HM-inhibited mCRC cell migration. In conclusion, our in vitro studies demonstrate that HM exhibits an inhibitory effect on CRC migration and invasiveness, associated with uPAR downregulation through JNK and ERK pathways. Full article

Background: The introduction of targeted therapy in oncology has led to several challenges. These medicines are relatively new in clinical practice and are not well known to specialists with regard to adverse drug reactions (ADRs) and potential drug–drug interactions (pDDIs). In addition, cancer affects multiple body systems, including weight loss, anemia, liver and kidney function, depression, and pain. Patients frequently have comorbidities, leading to polypharmacy and the use of special foods, nutritional supplements, and herbal products for self-medication. Identification of pDDIs is essential, as concomitant use of multiple medicinal products increases the risk of ADRs and may compromise treatment. Objective: This study aims to retrospectively review and analyze data on ADRs and pDDIs in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors and to evaluate the relationship between them. Method: EudraVigilance and UpToDate^® Lexidrug™ application were used to screen suspected ADRs and pDDIs, respectively. Descriptive statistical analysis was performed. Results: After reviewing Line Listing Reports (LLRs) from 2021 to 2023 in EudraVigilance, the number of suspected adverse drug reactions (ADRs) reported was higher when drug interactions classified as risk categories D and X were identified, compared with cases involving EGFR inhibitor monotherapy or other drug combinations. Of the 144 cases involving category D and/or X interactions, 63 demonstrated a possible association with the reported ADRs of EGFR inhibitors. The most common pDDIs detected were erlotinib–ranitidine (14 cases, category D) and osimertinib–amiodarone (13 cases, category D). Conclusions: Although EGFR inhibitors improve overall and progression-free survival in NSCLC, screening for pDDIs before treatment is essential to improve safety and quality of life. Full article

Background/Objectives: Cholestasis is a clinically intractable liver disorder. Da-Huang-Xiao-Shi Decoction (DHXSD), a classic traditional Chinese medicine formula, demonstrates notable efficacy, yet the mechanistic basis for its multi-herb synergy remains unclear. The purpose of this study was to decipher the pharmacokinetic interaction underlying the synergy of DHXSD. Methods: A cholestatic rat model was established in male Sprague Dawley rats. Hepatoprotective efficacy was evaluated, and the pharmacokinetics of anthraquinones were profiled. Key interaction mechanisms were investigated using the everted intestinal sac model, the breast cancer resistance protein (BCRP)-overexpressing MDCKII cells, and molecular docking simulations. Results: DHXSD provided significantly stronger hepatoprotection than its principal herb Rheum palmatum L. (DaHuang, DH) alone. This enhanced efficacy correlated with an approximate 2-fold increase in the systemic exposure of rhein compared to DH monotherapy. We identified berberine from Phellodendron amurense Rupr. (Huang Bo, HB) as the key synergist, which potently inhibited the BCRP efflux transporter, thereby enhancing rhein absorption. In contrast, geniposide from Gardenia jasminoides Ellis (Zhi Zi, ZZ) showed minimal effects. Conclusions: This work elucidates a concrete, transporter-mediated pharmacokinetic interaction as the core mechanism underlying herbal synergy in DHXSD. Our findings offer a rational strategy—targeted efflux transporter modulation—for improving the oral bioavailability of challenging drug molecules. Full article

It is necessary to understand the complicated interplay between diseases and medicinal plants to find new curing agents that may be used in natural sources. Nevertheless, the state of interaction between diseases and plants today is not fully developed yet, and the potentially productive plant-based treatment can hardly be identified rationally. In order to elaborate on this challenge, we will offer a heterogeneous network approach to the prediction of novel disease–plant associations by using the Random Walk with Restart (RWR) algorithm. The framework combines three significant relational networks, including (i) a disease–plant association network, which has been built using curated literature and biological databases, (ii) a disease–disease similarity net, which is constructed using shared symptoms and therapeutic profiles, and (iii) a plant–plant similarity net using phytochemical and functional similarities. These elements are integrated into a homogeneous graph that is heterogeneous in nature, and thus, information flows through related nodes. The model begins by finding RWR between known disease or plant nodes and develops the network by exploring the graph further to make estimates of the probability of association between disease and plant networks that were not previously connected. Experimental tests show that the proposed model has an excellent predictive ability, ROC-AUC of 0.9987, PR-AUC equal to 0.915, and Precision = 10 of 1.0, significantly better than the results of the base models, including Random- and Degree-based models. The bootstrap analysis supported the strength of the model as the mean ROC-AUC was 0.9987 with a standard deviation of 0.00051. The suggested structure offers an effective computational methodology to systematically explore disease–plant interactions to aid in finding novel herbal drugs to treat diseases and speed up the drug discovery process by means of inference based on networks. Full article

Ashwagandha (Withania somnifera L.) root powder and extracts have long been used in Ayurvedic medicine to improve sleep and anxiety. Recent scientific investigations into its efficacy have shown promise for relief from anxiety, insomnia and stress and for improving the immune system. It has also been suggested that oxygen uptake in the cardiovascular system, muscle strength, cognitive function, the reproductive system and the aging process significantly benefit from ashwagandha treatment. Since the herbal remedy is taken daily by millions of people in India, China and parts of the West, it is interesting that there are very few case reports of side effects directly attributed to the treatment, suggesting that the administration of ashwagandha preparations may be safe. Currently, neither the European Medicines Agency nor the FDA considers ashwagandha as a drug or general health supplement. Therefore, ashwagandha products are marketed in the West as dietary supplements so that users may be exposed to unscrupulous vendors. In this narrative/literature review, scientific findings from basic research and human clinical trials on herbal remedies, spanning the period from 1994 to date, were critically evaluated for the purpose of highlighting knowledge gaps to provide context for new research. Such investigations will provide evidence for the efficacy and safety of ashwagandha treatment, thus making the herbal preparations more accessible to a wider audience. Full article

Hepatic cirrhosis is a progressive chronic liver disease driven by sustained inflammation, cell death, and tissue remodeling, and effective disease-modifying options remain limited. Here, we applied a multiscale interactome framework to prioritize candidate herbs and active compounds for hepatic cirrhosis. Herb–compound associations were collected from the OASIS database and mapped to experimentally supported compound–target interactions (DrugBank/TTD/STITCH), while cirrhosis-related proteins were curated from DisGeNET. Using a biased random-walk algorithm, we generated disease and herb/compound diffusion profiles on the multiscale network and ranked candidates by profile similarity and target overlap. Among the top-ranked herbs, Magnoliae Cortex, Notoginseng Radix et Rhizoma, Polygoni Cuspidati Rhizoma et Radix, and Capsici Fructus were supported by prior literature, whereas several high-ranking herbs lacked curated evidence and were highlighted as underexplored candidates, including Saposhnikoviae Radix and Fritillariae Cirrhosae Bulbus. Enrichment analyses indicated convergence on inflammatory and innate-immune pathways (TNF, Toll-like receptor, NF-κB) and apoptosis-related processes, with additional signals involving HIF-1 and PI3K–Akt pathways. Disease-focused subnetworks suggested mechanistic hypotheses for evidence-lacking compounds, including bergapten, oleic acid, and octadecanoic acid. Overall, we systematically prioritize herbal candidates and provides a mechanistic basis for follow-up validation in hepatic cirrhosis. Full article