Search Results (176)

Oral anticoagulants, including warfarin, a vitamin K antagonist, have been used for anticoagulation therapy, but their limitations, such as drug interactions and complex dosing, have prompted the development of direct oral anticoagulants (DOACs) like rivaroxaban, apixaban, dabigatran, and edoxaban. This study reviews the interactions of both warfarin and DOACs, particularly those influenced by cytochrome P450 enzymes and P-glycoprotein. Warfarin is metabolized by various cytochrome P450 isoforms, making it vulnerable to interactions with medications and herbs that modulate these enzymes. In contrast, DOACs, while having fewer interactions, are still affected by strong inducers or inhibitors of cytochrome 3A4 and P-glycoprotein, depending on the specific drug. Some herbs may also interfere with these pathways. Continuous monitoring of these interactions is crucial to ensure the safe use of oral anticoagulants. The findings underscore the importance of identifying and understanding these interactions to improve patient safety and guide appropriate anticoagulant therapy. Full article

Traditional Chinese medicine (TCM), a holistic medical system rooted in dialectical theories and natural product-based therapies, has served as a cornerstone of healthcare systems for millennia. While its empirical efficacy is widely recognized, the polypharmacological mechanisms stemming from its multi-component nature remain poorly characterized. The conventional trial-and-error approaches for bioactive compound screening from herbs raise sustainability concerns, including excessive resource consumption and suboptimal temporal efficiency. The integration of artificial intelligence (AI) and multi-omics technologies with network pharmacology (NP) has emerged as a transformative methodology aligned with TCM’s inherent “multi-component, multi-target, multi-pathway” therapeutic characteristics. This convergent review provides a computational framework to decode complex bioactive compound–target–pathway networks through two synergistic strategies, (i) NP-driven dynamics interaction network modeling and (ii) AI-enhanced multi-omics data mining, thereby accelerating drug discovery and reducing experimental costs. Our analysis of 7288 publications systematically maps NP-AI–omics integration workflows for natural product screening. The proposed framework enables sustainable drug discovery through data-driven compound prioritization, systematic repurposing of herbal formulations via mechanism-based validation, and the development of evidence-based novel TCM prescriptions. This paradigm bridges empirical TCM knowledge with mechanism-driven precision medicine, offering a theoretical basis for reconciling traditional medicine with modern pharmaceutical innovation. Full article

Lung cancer is the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) is the major subtype, accounting for more than 85% of all lung cancer cases. Recent advances in precision oncology have allowed NSCLC patients bearing specific oncogenic epidermal growth factor receptor (EGFR) mutations to respond well to EGFR tyrosine kinase inhibitors (TKIs). Due to the high EGFR mutation frequency (up to more than 50%) observed particularly in Asian NSCLC patients, EGFR-TKIs have produced unprecedented clinical responses. Depending on their binding interactions with EGFRs, EGFR-TKIs are classified as reversible (first-generation: gefitinib and erlotinib) or irreversible inhibitors (second-generation: afatinib and dacomitinib; third-generation: osimertinib). While the discovery of osimertinib represents a breakthrough in the treatment of NSCLC, most patients eventually relapse and develop drug resistance. Novel strategies to overcome osimertinib resistance are urgently needed. In Asian countries, the concomitant use of Western medicine and traditional Chinese medicine (TCM) is very common. Ganoderma lucidum (Lingzhi) and Coriolus versicolor (Yunzhi) are popular TCMs that are widely consumed by cancer patients to enhance anticancer efficacy and alleviate the side effects associated with cancer therapy. The bioactive polysaccharides and triterpenes in these medicinal mushrooms are believed to contribute to their anticancer and immunomodulating effects. This review presents the latest update on the beneficial combination of Lingzhi/Yunzhi and EGFR-TKIs to overcome drug resistance. The effects of Lingzhi/Yunzhi on various oncogenic signaling pathways and anticancer immunity, as well as their potential to overcome EGFR-TKI resistance, are highlighted. The potential risk of herb–drug interactions could become critical when cancer patients take Lingzhi/Yunzhi as adjuvants during cancer therapy. The involvement of drug transporters and cytochrome P450 enzymes in these herb–drug interactions is summarized. Finally, we also discuss the opportunities and future prospects regarding the combined use of Lingzhi/Yunzhi and EGFR-TKIs in cancer patients. Full article

Lobelia nummularia Lam. is a traditional medicinal herb of which the anticancer mechanisms remain largely unexplored. Here, we demonstrated that its ethanolic extract (LNE) exerts potent anti-breast cancer activity by inducing ROS-dependent mitochondrial apoptosis in MDA-MB-231 cells, a mechanism confirmed via rescue experiments with the antioxidant N-acetylcysteine (NAC). This pro-apoptotic program is driven by a dual mechanism: potent suppression of the pro-survival EGFR/PI3K/AKT signaling pathway and simultaneous activation of the TP53-mediated apoptotic cascade, culminating in the cleavage of executor caspase-3. Phytochemical analysis identified numerous flavonoids, and quantitative HPLC confirmed that key bioactive compounds, including luteolin and apigenin, are substantially present in the extract. These mechanisms translated to significant in vivo efficacy, where LNE administration suppressed primary tumor growth and lung metastasis in a 4T1 orthotopic model in BALB/c mice. Furthermore, a validated molecular docking protocol provided a plausible structural basis for these multi-target interactions. Collectively, this study provides a comprehensive, multi-layered validation of LNE’s therapeutic potential, establishing it as a mechanistically well-defined candidate for natural product-based anticancer drug discovery. Full article

This study aimed to evaluate the antinociceptive effect of Salvia hispanica L. seeds, Citrus × latifolia (Lime) juice, and the interaction of their combination in rats using the writhing test. Dose–response curves were constructed for an n-hexane extract of S. hispanica seeds (100–300 mg/kg; p.o.) and C. × latifolia juice (10–300 mg/kg; p.o.) administered individually or in combination to rats subjected to 1% acetic acid-induced writhing. Isobolographic analysis was used to assess the interaction between the combinations. Results showed that both medicinal plants exhibited dose-dependent antinociceptive effects. The antinociceptive effect of C. × latifolia (ED₅₀ = 43.95 ± 1.9 mg/kg) exhibited greater potency than S. hispanica (ED₅₀ = 112.9 ± 2.0 mg/kg). Their combination (1:1 ratio) showed a synergistic antinociceptive effect (Z_exp = 4.9 ± 0.6 mg/kg vs. Z_add = 83.5 ± 1.7 mg/kg). Both extracts were non-toxic, according to the OECD-423 test. Antioxidant activity may have contributed to the observed antinociceptive synergy. This study demonstrates that the synergistic antinociceptive effects suggest that combining S. hispanica and C. × latifolia may be a promising therapeutic approach for managing inflammatory and visceral pain with potential clinical utility. Full article

Food components and herbal substances can inhibit or enhance the therapeutic effects of drugs, thus influencing their efficacy and safety. As relatively little in known of these interactions, the aim of this review is to shed further light on the potentially dangerous influences that food and herbs may have on cytochrome P450 enzyme (CYP) and monoamine oxidase (MAO) activity in the first stage of drug biotransformation. The review includes documented cases in which such interactions have led to health complications in patients. For example, fruit juices, such as grapefruit juice, cranberry juice, and pomegranate juice, have been found to interact with drugs, and to particularly inhibit CYP450 activity, and commonly used herbs are known to inhibit (e.g., Astragalus membranous) or induce (e.g., Hypericum perforatum) CYP enzymes involved in drug metabolism. CYP is also induced by polycyclic aromatic hydrocarbons (PAHs), found in grilled meat and tobacco smoke. The paper also discusses the toxic effects of tyramine, present in inter alia blue cheese, resulting from interactions with MAO-metabolised drugs. Most importantly, while the quantity of food and herbs consumed plays a significant role in the described drug interactions, it is possible for toxic effects to be observed even after the consumption of relatively small amounts. Patients are encouraged to consult a healthcare provider about any potential drug interactions that may occur when starting a new medication. Full article

Rehmannia glutinosa (RG), a fundamental herb in traditional Chinese medicine belonging to the Orobanchaceae family, has been widely used for centuries due to its diverse therapeutic properties, including promoting blood circulation, enhancing immunity, managing diabetes, reducing inflammation, and supporting kidney function. Despite its traditional significance, scientific studies on RG’s therapeutic mechanisms remain limited, and its underlying pharmacological pathways are not extensively elucidated. This study employed network pharmacology and molecular docking to identify RG’s active compounds and investigate their therapeutic potential in allergy, anemia, diabetes, and menopause. From an initial pool of 122 compounds, 50 bioactive compounds were screened based on bioavailability and drug-likeness, resulting in 40 active compounds and 11 target proteins closely associated with these conditions. Key active compounds identified included iridoid glycosides (rehmaglutin A, B, C, D, jioglutin A, B, C, jioglutolide) and other bioactive molecules such as caffeic acid, geraniol, 5-hydroxytryptamine, melatonin, and rhodioloside. Molecular docking technology was employed to verify the stable binding of target proteins with active compounds. Protein–protein interaction (PPI) analysis revealed that RG’s core target proteins are central to pathways regulating inflammation, cell survival, apoptosis, and immune response. Enrichment analyses demonstrated that RG’s target proteins intersect significantly with pathways including the AGE-RAGE signaling pathway in diabetic complications, IL-17, HIF-1 signaling, and neuroactive ligand-receptor interactions, all of which are essential in managing diabetes and menopause symptoms. These findings underscore RG’s multi-target therapeutic potential, particularly in modulating immunity, metabolism, and inflammation. This study highlights RG’s potential as a therapeutic agent and provides a framework for future research to further elucidate its mechanisms and support the development of targeted drugs based on RG’s active compounds. Full article

Artificial intelligence (AI) has emerged as a powerful tool in medical sciences that is revolutionizing various fields of drug research. AI algorithms can analyze large-scale biological data and identify molecular targets and pathways advancing pharmacological knowledge. An especially promising area is the assessment of drug interactions. The AI analysis of large datasets, such as drugs’ chemical structure, pharmacological properties, molecular pathways, and known interaction patterns, can provide mechanistic insights and identify potential associations by integrating all this complex information and returning potential risks associated with these interactions. In this context, an area where AI may prove valuable is in the assessment of the underlying mechanisms of drug interactions with natural products (i.e., herbs) that are used as dietary supplements. These products pose a challenging problem since they are complex mixtures of constituents with diverse and limited information regarding their pharmacological properties, especially their pharmacokinetic data. As the use of herbal products and supplements continues to grow, it becomes increasingly important to understand the potential interactions between them and conventional drugs and the associated adverse drug reactions. This review will discuss AI approaches and how they can be exploited in providing valuable mechanistic insights regarding the prediction of interactions between drugs and herbs, and their potential exploitation in experimental validation or clinical utilization. Full article

Background/Objectives: The interaction of bioactive compounds derived from plants with drugs has become a significant area of investigation due to its potential to improve, reduce, or have no effect on therapeutic outcomes. Due to the dual effect of these interactions, elucidating the underlying mechanisms is essential for establishing a therapeutic strategy. This study emphasizes the significant findings, mechanisms, and clinical implications of drug–plant bioactive interactions. It calls for more studies to seek safe and effective incorporation into clinical practice. Methods: To identify relevant studies, we performed a systematic literature search based on various scientific databases from 11 August 2024 to 30 December 2024. The search will be based on relevant keywords such as synergy, antagonism, plant bioactive compounds, and drug interactions supplemented with secondary terms such as phytochemicals, herb-drug interactions, pharmacokinetics, and pharmacodynamics. Results: Plant bioactives, including polyphenols, flavonoids, alkaloids, and terpenoids, display valuable biological activities that can interact with medications in three principal ways: synergy, additive effects, and antagonism. Synergy occurs when the combined effects of plant chemicals and pharmaceuticals outweigh the sum of their separate effects, increasing therapeutic effectiveness or allowing dosage decrease to reduce adverse effects. Additive effects occur when the combined impact equals the total individual effects, resulting in better outcomes without increasing risk. Antagonism occurs when a plant ingredient reduces or counteracts the effects of a medicine, thereby jeopardizing treatment. In addition, specific interactions may have no discernible effect. The chemical makeup of bioactive chemicals, medication pharmacokinetics, and individual patient characteristics such as genetics and metabolism all impact the intricacy of these interactions. Conclusions: Pharmacokinetics and pharmacodynamics of drugs can be considerably modulated through their interactions with plant bioactive components, which may cause a significant decrease in efficacy or increase in toxicity of therapeutic agents. More studies are needed to clarify mechanisms of action, prove clinical relevance, and create guidelines for safe co-administration. This integrative approach can mitigate those risks and allow for therapeutic optimization by introducing pharmacogenomics and personalized medicine approaches. Full article

Background/Objectives: Fexofenadine hydrochloride is a widely prescribed drug for treating histamine-mediated allergic reactions. This review systematically collates existing research on the clinical pharmacokinetics (PK) of fexofenadine, with a copious emphasis on examining the impact of stereoisomerism, disease states, and drug interactions. Methods: The search engines PubMed, Science Direct, Google Scholar, and Cochrane were scanned systematically for articles concerning the clinical PK of fexofenadine in humans. The extensive literature search yielded 85 articles meeting the inclusion standards. Results: The PK parameters of fexofenadine showed a linear correlation between increasing doses and proportional elevations in PK parameters such as area under the curve from time 0 to infinity (AUC_0–∞) and maximum plasma concentration (C_max). Under fed conditions, its bioavailability was reduced by approximately 50%. Findings from patients with end-stage renal disease (ESRD) displayed a 63% decline in oral clearance (CL/F) of fexofenadine. A drug–food interaction study has displayed that grapefruit juice decreased C_max (201 ng/mL vs. 128 ng/mL), accompanied by a 30% reduction in the bioavailability of fexofenadine. Furthermore, a drug–herb interaction study with St John’s Wort (SJW) has reported a reduction in CL/F by 10% after a single dose, but long-term administration reversed this effect, resulting in elevated CL/F by 17% of fexofenadine. Conclusions: Since no prior systematic review on the PK of this drug exists, this review amalgamates all pertinent PK parameters in humans by pooling up-to-date data from published studies. This detailed literature review can be advantageous for researchers who want to develop and assess PK models. Full article

Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan’s team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent. In this research, computational chemical analysis was employed, incorporating the “TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)” algorithm to systematically explore 139 active small molecules from thunder god vine. These compounds were classified into six categories, with a particular focus on Category 1 molecules for their exceptional binding affinity to obesity-related targets, offering new avenues for therapeutic development. Using advanced molecular docking techniques and Cytoscape prediction models, six representative Celastrol-like molecules were identified, namely 3-Epikatonic Acid, Hederagenin, Triptonide, Triptotriterpenic Acid B, Triptotriterpenic Acid C, and Ursolic Acid. These compounds demonstrated superior binding affinity and specificity toward two key obesity targets, PPARG and PTGS2, suggesting their potential to regulate fat metabolism and mitigate inflammatory responses. To further substantiate these findings, molecular dynamics simulations and MM-PBSA free-energy calculations were applied to analyze the dynamic interactions between these small molecules and the enzymatic active sites of their targets. The results provide robust theoretical evidence that support the feasibility of these molecules as promising candidates for anti-obesity therapies. This study underscores the power of the 3DHFC-TRS algorithm in uncovering bioactive compounds from natural sources, such as thunder god vine, and highlights the therapeutic promise of PPARG and PTGS2 as novel obesity-related targets. Furthermore, it emphasizes the essential role of computational science in expediting drug discovery, paving the way for personalized and precision-based treatments for obesity and heralding a future of more effective healthcare solutions. Full article

This study aimed to scientifically validate the traditional use of Garrya laurifolia (Gl) leaves as an antidiabetic agent attributed to a community in Mexico. The descriptive ethnobotanical study was conducted in San Miguel Tecpan, a municipality of Jilotzingo, State of Mexico, Mexico, where a structured questionnaire was applied to 44 inhabitants. In vivo studies evaluated the acute oral toxicity of Gl leaves in murine and the effects of a leaf infusion on glycemia in normoglycemic and diabetic rats; in addition, the interaction between Gl and metformin (Met) was also evaluated. The in vitro antioxidant activity of Gl was determined. The phytochemical screening and quantification of phenolic and flavonoid content of Gl leaves were performed. Gl had a high relative frequency of citation (0.68) among respondents. Gl had a low acute toxicity risk with LD₅₀ > 5000 mg/kg. The extract had no hypoglycemic effect in normoglycemic rats, but it did have hypoglycemic and antihyperglycemic effects (250 and 500 mg/kg) in diabetic rats. The interaction between Gl (500 mg/kg) + Met (300 mg/kg) resulted in antidiabetic synergism. Gl showed strong antioxidant activity (93.1 ± 0.4%). Phytochemical screening revealed the presence of alkaloids, flavonoids, and some other phenolic compounds. The total phenol content was 77.9 ± 0.6 mg EQ/g and 87.7 ± 0.7 mg EAG/g, and the flavonoids content was 5.32 ± 0.2 mg EQ/g. UHPLC-MS/MS analysis identified chlorogenic acid, rutin, aucubin, luteolin 7-O-neohesperoside, and myricitrin. The findings support the potential use of Gl as a safe and effective antidiabetic agent. Full article

Background/Objectives: Products from various parts of Crataegus species are traditionally applied as a cardiotonic. In Europe and the USA, mainly Crataegus monogyna Jacq. (Lindm.) and Crataegus laevigata (Poir.) DC (synonym Crataegus oxyacantha L.) are used, but worldwide, other Crataegus species are also used. Phytotherapeutic preparations with a standardised content of flavonoids and/or oligomeric procyanidins are commercially available. The products are generally considered as safe and are at most associated with minor and atypical adverse reactions. The aim of this study was to critically assess the information about the safety of Crataegus-containing products in humans. Methods: A scoping review of the literature about adverse reactions associated with Crataegus-containing products was performed. Next, individual case safety reports (ICSRs) were assessed, which were included in VigiBase (the World Health Organisation’s global database of adverse event reports for medicines and vaccines) and in the database of the Netherlands Pharmacovigilance Centre Lareb. The findings are discussed in relation to the literature. Results: The scoping review yielded 23 clinical studies with single-herb and 14 with multi-herb preparations, from which only a few minor gastrointestinal and cardiac events had been reported. A total of 1527 reports from VigiBase, from 1970 to 2023, were analysed, as well as 13 reports from Lareb. The most frequently reported adverse reactions belonged to the system organ classes ‘gastrointestinal disorders’, ‘skin and subcutaneous tissue disorders’, ‘general disorders and administration site conditions’, ‘cardiac disorders’ or ‘nervous system disorders’. In 277 reports of VigiBase, a single-herb product was the only suspect for causing the adverse reaction(s). Of these, 12.6% were graded as serious. Conclusions: The results of our study provide deeper insight in the adverse reaction profile of Crataegus-containing products and should contribute to their safe application in the treatment of less severe forms of cardiac failure. Full article

Background/Objectives: One of the major risks associated with the concomitant use of herbal products and therapeutic drugs is herb–drug interactions (HDIs). The most common mechanism leading to HDIs is the inhibition and/or induction of transport proteins and drug-metabolizing enzymes by herbal ingredients, causing changes in the pharmacokinetic disposition of the victim drug. The present study aimed to determine the potential interactions of Uncaria tomentosa (UT) (cat’s claw), a popular herb due to its supposed health benefits. Methods: The effect of UT extract and its major oxindole alkaloids was investigated on multispecific solute carrier (SLC) and ATP-binding cassette (ABC) drug transporters, using SLC transporter-overexpressing cell lines and vesicles prepared from ABC transporter-overexpressing cells. Results: UT extract significantly inhibited all ABC transporters and the majority of the SLC transporters tested. Of the investigated oxindole alkaloids, isopteropodine significantly inhibited OATP, OCT1 and OCT2, OAT3, ENT4, MDR1, and BCRP transporters. OCTs, OCTN1-, ENT1-, and MDR1-mediated substrate accumulation was below 50% in the presence of mitraphylline. Conclusions: Based on the calculated intestinal concentration of UT extract, interactions with intestinal transporters, especially OATP2B1, ENTs, MRP1, MRP2, MDR1, and BCRP could be relevant in vivo. Our data can help to predict the clinical consequences of UT co-administration with drugs, such as increased toxicity or altered efficacy. In conclusion, the use of these in vitro models is applicable for the analysis of transporter-mediated HDIs similar to drug–drug interaction (DDI) prediction. Full article

Cirsium japonicum, a traditional herb, exhibits significant anti-inflammatory activity. However, the main components and potential mechanisms of C. japonicum remain unclear. The aim of this study is to investigate the anti-inflammatory mechanism of Cirsium japonicum through network pharmacology and cellular experiments. The effective components of and potential targets for the anti-inflammatory activity of C. japonicum were identified using a traditional Chinese medicine systematic pharmacology database, the TCMSP analysis platform, and the GeneCards database. The drug–component–target–disease network diagram was constructed using Cytoscape 3.8.0 software, while the protein interaction network diagram was created using the STRING database and Cytoscape 3.8.0 software. Gene ontology (GO) enrichment and KEGG pathway enrichment analysis were carried out using the DAVID database. Molecular docking between key targets and active components was constructed with AutoDock 4.2.6 software to determine the best binding target. The results revealed that 14 active components of C. japonicum targeted 171 anti-inflammatory proteins. GO function enrichment analysis yielded 173 items, while KEGG pathway enrichment analysis identified 48 signaling pathways related to inflammation regulation. Molecular docking showed a strong affinity of sitosterol, stigmasterol, and other components with key targets such as peroxisome proliferator-activated receptor α recombinant protein (PPARA) and cyclooxygenase-2 (PTGS2). Vanillin, one active ingredient of C. japonicum, inhibited the release of lipopolysaccharide (LPS)-induced inflammatory factors in RAW264.7 cells. These findings suggest that C. japonicum may exert its anti-inflammatory effects by modulating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signal pathway (PI3K-Akt) and apoptin signal pathway, highlighting the multi-component, multi-target, and multi-channel molecular mechanism underlying its anti-inflammatory properties. Finally, the anti-inflammatory effect of vanillin, an effective component of C. japonicum, was verified by cell experiments. This study provides a new understanding of the pharmacological mechanisms of C. japonicum in the treatment of inflammatory conditions. Full article