Search Results (205)

Background: Epilepsy comprises a range of disorders affecting the central nervous system (CNS) characterized by recurrent seizures, impacting approximately 60 million individuals globally. In this study, we designed and derived a series of peptide analogs 1–30 of 3,4,5-trimethoxycinnamic acid (TMCA) from the herbal combinations of Polygala tenuifolia and Gastrodia elata, recognized in Traditional Chinese Medicine (TCM). Methods: All the analogs were synthesized, and their anticonvulsant efficacy was subsequently assessed. The anticonvulsant activity of all TMCA analogs was evaluated using two acute seizure models in mice: the maximal electroshock (MES) and the sc-pentylenetetrazole (PTZ) models. Furthermore, we explored the electroencephalogram (EEG) and double-labeling immunofluorescence experiments were carried out as well. Results: Our findings indicated that compounds 11, 19, 22, and 23 demonstrated favorable anticonvulsant activities during the initial assessment. Compounds 19 and 23 also played roles in controlling the onset of epilepsy in EEG, modulating levels of GABA aminotransferase (GABA-AT)/gamma-aminobutyric acid type A receptor (GABA_AR), interacting with active sites of GABA-AT and GABA_AR obtained from docking simulation methods. Conclusions: Novel derivatives in this study provide new cores for further design and optimization inspired by TCM herb pair drugs P. tenuifolia and G. elata, with the aim of exploring new anticonvulsant agents. Full article

Background/Objectives: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are essential antidiabetic medications. However, their side effects warrant careful consideration. The search for novel SGLT2 inhibitors with high affinity remains an ongoing endeavor. Medicine food homology (MFH) herbs show promise for drug development due to their nutritional and medicinal value. Methods: This study aims to address the shortcomings of existing virtual screening models for SGLT2 inhibitors by optimizing feature selection and integrating multidimensional molecular fingerprints. Subsequently, an integrated virtual screening pipeline is constructed to identify potential SGLT2 inhibitors from eight selected MFH herbs. Results: The results indicate that the optimal model (LightGBM and RF) achieved an accuracy of 0.97 and an AUC of 0.98. Following rigorous filtering, a total of 44 potential SGLT2 inhibitors were identified, among which, Isoononin (from Gancao) and Ononin (from Huangqi, Gegen, and Gancao) exhibit favorable drug likeness and safety. Molecular docking demonstrate that both compounds can effectively bind to the SGLT2 active site, establishing stable hydrophobic interactions with critical residues such as Phe98 and Phe453. Furthermore, molecular dynamics simulations confirm the stability of the interactions between the two compounds and SGLT2. Conclusions: This study significantly enhances the accuracy and stability of SGLT2 inhibitor virtual screening models by addressing deficiencies in structural characterization and feature selection. It provides candidate molecules for the development of novel SGLT2 inhibitors and offers new scientific evidence for the application of MFH herbs in the prevention and treatment of chronic metabolic diseases. Full article

Fenugreek (Trigonella foenum-graecum) has attracted growing interest as a complementary agent in the management of hepatocellular carcinoma (HCC), a leading cause of cancer-related mortality worldwide. Its rich botanical and phytochemical profile, including key bioactive compounds such as diosgenin, trigonelline, saponins, and flavonoids, underpins a spectrum of biological activities relevant to liver cancer therapy. This review critically examines the risks, benefits, and molecular targets of fenugreek administration in HCC, synthesising current evidence on extraction methods, standardisation, pharmacokinetics, and mechanisms of action. Preclinical studies highlight fenugreek’s antitumor efficacy, mediated by apoptosis induction, cell cycle regulation, and modulation of oxidative stress and inflammatory pathways, while its hepatoprotective effects are supported by robust antioxidant and anti-inflammatory properties. However, the safety profile is nuanced, with potential risks including reproductive toxicity, rare hypersensitivity reactions, and herb–drug interactions, particularly in patients with compromised hepatic function or polypharmacy. The review identifies critical gaps in clinical evidence, especially regarding long-term safety and synergistic effects with conventional therapies and underscores the need for rigorous standardisation and patient monitoring. We describe the potential integration of fenugreek into multimodal HCC treatment strategies, if safety concerns are addressed. Future research should elucidate precise molecular targets, optimise formulations, and conduct well-controlled clinical trials to fully realise fenugreek’s therapeutic potential in HCC management. Full article

In recent years, dietary intervention has garnered significant attention for T2DM prevention and adjunctive treatment. Lentinula edodes (commonly known as shiitake mushroom), a common edible fungus, has been demonstrated to improve T2DM, primarily attributed to its main bioactive components like peptides and polysaccharides, while their synergistic characteristics are still not fully explained. Therefore, this study investigated the anti-T2DM molecular mechanisms of L. edodes peptides and polysaccharides by integrating network pharmacology and molecular docking. First, systematic searches of the PubMed and HERB databases using keywords such as “Lentinula edodes peptides”, “Lentinula edodes polysaccharides” and “T2DM” and “Lentinula edodes/shiitake mushroom” yielded 25 peptides and 14 polysaccharides. Second, network pharmacology analysis revealed 541 common interaction targets between these peptides/polysaccharides and T2DM. Topological analysis further identified nine core targets: ESR1, MAPK1, AKT1, SRC, EGFR, STAT3, JUN, PIK3CA, and PIK3R1. Third, pathway enrichment analysis showed that these core targets were significantly enriched within the PI3K-Akt signaling pathway and the AGE-RAGE signaling pathway in diabetic complications, suggesting potential anti-T2DM effects through regulation of these key pathways. Finally, molecular docking validation ensured strong binding affinities between peptides/polysaccharides and some core targets, with particularly prominent binding capacities observed for peptides VF and LDELEK with EGFR; peptides KIGSRSRFDVT, LDYGKL, and EDLRLP along with polysaccharides D-glucan and β-glucan with PIK3CA; and peptide DVFAHF with PIK3R1. In summary, this study revealed that L. edodes peptides and polysaccharides may exert synergistic anti-T2DM effects via the regulation of key signaling pathways, including the PI3K-Akt signaling pathway, EGFR tyrosine kinase inhibitor resistance, and the AGE-RAGE signaling pathway in diabetic complications, through their actions on critical targets such as ESR1, PIK3CA, and PIK3R1. These results offer a synergistic mechanism for the anti-T2DM effect of L. edodes, which could be helpful for the development of functional foods and drugs derived from L. edodes. Full article

Background/Objectives: Ginger (Zingiber officinale Roscoe) is a flowering plant widely used as a spice and natural medicine for millennia. Ginger demonstrates multiple protective effects, regulates cholesterol, and may reduce the risk of cancer and colitis. However, little attention has been paid to its potential to cause herb–drug interactions (HDIs). The aim of this study was to investigate the interaction of ginger extract and its major components [6]-gingerol and [6]-shogaol with clinically relevant uptake and efflux transporters in vitro. Methods: Transporter-overexpressing cell lines of 25 uptake transporters and inside-out membrane vesicles containing 8 efflux transporters were employed to measure potential interactions. Results: Zingiber officinale extract at 150 µg/mL interacted with 17 of 33 transporters examined. These were further investigated for interactions with the purified active components. Seven and 16 transporters interacted with pure [6]-gingerol (100 µM) and [6]-shogaol (100 µM), respectively. To evaluate the risk of in vivo inhibition, IC₅₀ values were determined for the affected transporters. Based on standard risk assessment calculations, we confirmed previously reported inhibitory effects of ginger components on MDR1 (67.64 µM) and BCRP (9.931 µM), and revealed novel potential interactions with renal OAT3 (0.956 µM) and URAT1 (5.887 µM), hepatic OCT1 (4.287 µM) and BSEP (25.45 µM), and the ubiquitously expressed ENT1 (11.62 µM) ([6]-shogaol IC₅₀ values are shown in parentheses). Strong and isoform-selective inhibition of OAT3 by [6]-shogaol is particularly intriguing. Additionally, via cell viability experiments on a set of human cervical, breast, and oropharyngeal cancer cell lines, we demonstrated the antiproliferative effect of [6]-shogaol in vitro. Conclusions: Prolonged consumption of high-dose ginger supplements may pose a risk of transporter-mediated HDIs when consumed concomitantly with conventional medications. Our study encourages follow-up of the suspected effects in vivo. Full article

Despite major advances in guideline-directed cardiovascular therapy, residual cardiovascular risk persists, partly driven by oxidative stress, chronic inflammation, endothelial dysfunction, and mitochondrial injury not fully addressed by current drugs. Translation of plant-based cardioprotectants is constrained by preparation-dependent variability in extract chemistry (plant part/cultivar/processing and extraction method), low and variable systemic exposure for key actives (notably curcuminoids and many polyphenols), and clinically relevant safety/interaction considerations (e.g., hepatotoxicity reports with concentrated green tea extracts and antiplatelet-related bleeding-risk considerations for some botanicals). We therefore provide a mechanism- and translation-oriented synthesis of evidence for cardioprotective botanicals, chosen for long-standing traditional use and scientific validation with reproducible experimental data and, where available, human studies, including Crataegus monogyna, Allium sativum, Olea europaea, Ginkgo biloba, Leonurus cardiaca, and Melissa officinalis. Across studies, polyphenols (especially flavonoids and phenolic acids) and organosulfur compounds are most consistently associated with cardioprotection, while terpene-derived constituents and secoiridoids contribute mechanistically in plant-specific settings (e.g., Ginkgo and Olea). Predominantly in experimental models, these agents engage redox-adaptive (Nrf2), mitochondrial (mPTP), endothelial, and inflammatory (NF-κB) pathways, with reported reductions in ischemia–reperfusion injury, oxidative damage, and apoptosis. Clinical evidence remains heterogeneous and is largely confined to short-term studies and surrogate outcomes (blood pressure, lipids, oxidative biomarkers, endothelial function), with scarce data on hard cardiovascular endpoints or event reduction. Priorities include standardized, chemotype-controlled formulations with PK/PD-guided dosing and adequately powered randomized trials that assess safety and herb–drug interactions. Full article

Psychotropic medicinal plants are commonly used among oncology patients, yet their relevance in the perioperative setting remains insufficiently characterized. We conducted a literature-based identification of 18 neuroactive plants and surveyed 123 cancer patients and 109 healthcare professionals at a tertiary hospital in Northern Thuringia, Germany. Seventy-five percent of patients reported using at least one psychotropic plant. Knowledge levels were high and similar across groups (median 11 plants), while professionals reported a broader usage spectrum (p = 0.042). Frequently known and applied species included Valeriana officinalis, Lavandula angustifolia, Hypericum perforatum, and Urtica. Women used more plants than men (p = 0.024), and higher usage rates were observed in breast cancer and head and neck cancer patients. Heat-map analyses showed substantial overlap in knowledge but differences for species such as Atropa, Cannabis, and Papaver somniferum. Given the potential interactions with anesthetic and analgesic medications, structured preoperative assessment of herbal use is warranted to enhance perioperative safety. Full article

Background: Doxorubicin (DOX) is a highly effective chemotherapy drug, but its use is limited by dose-dependent cardiotoxicity, driving the search for protective natural products. Although the herb Viscum coloratum (Kom.) Nakai is known for its cardiovascular benefits, the cardioprotective effects and mechanisms of its isolated compound, DHDK, remain unexplored. Methods: The protective effect of DHDK was first evaluated in DOX-injured H9c2 cardiomyocytes. Subsequently, an integrated network toxicology (incorporating DOX-induced toxicity targets and relevant chronic disease pathways such as aging and lipid metabolism) and pharmacology (DHDK) approach identified core targets, which were then refined through Protein–Protein Interaction (PPI) analysis and molecular docking. The underlying mechanism was investigated using lipidomics and validated through a series of in vitro assays, including CCK-8, q-PCR, biochemical tests, and flow cytometry, as well as in an in vivo rat model. Results: DHDK significantly alleviated DOX-induced cardiomyocyte toxicity. Integrated analysis identified 56 intersecting targets, with PPARG confirmed as the primary target via PPI and molecular docking. Lipidomics revealed that DHDK potently attenuated DOX-induced accumulation of pathogenic lipids (e.g., fatty acids, ceramides). Mechanistically, DHDK activated PPARG, which in turn upregulated CPT1B, a key regulator of fatty acid β-oxidation (FAO). This enhanced cell viability, ATP production, and mitochondrial membrane potential while reducing oxidative stress. These protective effects, which were abolished by the inhibition of PPARG or CPT1B, were further validated in vivo. Conclusion: This study demonstrates that DHDK exerts its cardioprotective effect by activating the PPARG-CPT1B-FAO axis, effectively correcting lipid metabolic disorders. Given that lipid dysregulation is a hallmark of various internal metabolic diseases, DHDK may also hold therapeutic potential for other heart conditions driven by metabolic disturbances, such as diabetic cardiomyopathy, highlighting its broad relevance to the field of internal diseases. Full article

Background/Objectives: Polygoni Cuspidati Rhizoma et Radix (PCRR) is an herb and a source of a resveratrol-containing dietary supplement. Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter involved in numerous drug-related pharmacokinetic interactions. This study used both in vivo and in vitro models to investigate the modulation effect of PCRR ingestion on BCRP. Methods: Three groups of rats were orally administered methotrexate (MTX), a probe substrate of BCRP, without and with PCRR at 1.0 g/kg and 2.0 g/kg in a parallel design, and the MTX pharmacokinetics were compared among three treatments. The modulation effects of PCRR and its serum metabolites (PCRRM) on BCRP were assayed by in vitro models. Results: PCRR at 1.0 g/kg and 2.0 g/kg significantly decreased the area under the serum level–time curve from 0 to 240 min (AUC_0-240) of MTX by 31% and 58%, respectively; 2.0 g/kg of PCRR markedly increased the area under the serum level–time curve from 240 to 2880 min (AUC_240-2880) and the mean residence time (MRT) of MTX by 39% and 74%, respectively. The results of in vitro assays indicated that PCRR enhanced the function of BCRP by 33~48%; on the contrary, PCRRM reduced the function of BCRP by 200~209%. Conclusions: PCRR activated BCRP, whereas PCRRM inhibited BCRP, thereby the coadministration of PCRR reduced both the absorption and excretion of MTX in rats. In clinical practice, the concurrent use of PCRR with critical BCRP substrate drugs should be avoided. Full article

Natural product (NP) use by patients alongside their conventional cancer therapies is ubiquitous. This common, yet often hidden, practice can potentially contribute to significant patient harm, given the narrow therapeutic window of most anticancer drugs. This review takes on this challenge directly, moving past theoretical concerns to summarize current clinical evidence on interactions between widely used NPs and modern cancer treatments, including chemotherapy, targeted therapy, and immunotherapy. We break down the key pharmacokinetic (PK) mechanisms, such as the disruption of cytochrome P450 enzymes, and the pharmacodynamic (PD) effects that can either help or hinder treatment. By examining both well-established clinical interactions and those supported by preliminary or preclinical findings, we highlight how NPs may alter the effectiveness of anticancer medications and where evidence remains uncertain. Lack of reliable safety information for NPs along with widespread use of these products by patient populations has the potential to impact clinical care and patient outcomes significantly, frequently causing harm. We advocate for improved patient-provider communication and additional evidence-based research to address this gap in literature. The majority of reported interactions are based on preclinical or limited clinical evidence. A more rigorous evidence base including real-world data and clinical trials is urgently needed to guide practice. Full article

Herbal medicinal products are increasingly used alongside conventional medicines, raising the risk of potential interactions such as pharmacodynamic drug–herb interactions (PD-DHIs) that can cause serious adverse drug reactions (ADRs). This review aims to present available pharmacological, clinical and pharmacoepidemiological literature regarding potential DHIs associated with serotonin syndrome or cardiac arrhythmias. Furthermore, it assesses the current evidence using the Oxford Centre for Evidence-Based Medicine (CEBM) 2009 framework. Serotonin syndrome most often results from combining serotonergic herbs (e.g., St. John’s wort) with antidepressants like serotonin reuptake inhibitors (SSRIs), as supported by repeated case reports and mechanistic plausibility (CEBM Level 3, Grade C). Other herbs such as black cohosh, ginseng, Syrian rue, turmeric, rhodiola, ashwagandha, and L-tryptophan/5-HTP have been linked to serotonin syndrome when used with SSRIs, serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase inhibitors (MAOIs), but evidence is limited (Levels 4–5, Grade D). For cardiac arrhythmias, PD-DHIs arise when herbs interact with drugs that alter cardiac electrophysiology—such as QT-prolonging agents, psychotropics, antiarrhythmics or digoxin—thereby amplifying arrhythmogenic risk. Ephedra with sympathomimetics is strongly associated with arrhythmias (Level 2–3, Grade B). Licorice may potentiate digoxin and QT-prolonging drugs via hypokalemia (Level 4, Grade C). Other related PD-DHIs include aconite with antiarrhythmics, bitter orange or caffeine with QT-prolonging psychotropics, yohimbine with cardiovascular agents, and aloe or senna with digoxin. Overall, the evidence for PD-DHIs varies from moderate to weak but large-scale pharmacoepidemiological data is scarce. Future approaches, including artificial intelligence with explainable machine learning and network pharmacology, may integrate mechanistic, clinical, and real-world data to improve early detection or prediction of PD-DHIs. However, several specific challenges must be addressed. Therefore, it is crucial for healthcare providers in both clinical and community settings to increase their awareness of these interactions and ADRs to ensure the safe use of herbal remedies alongside conventional therapies. Full article

The accurate prediction of herb–target interactions is essential for the modernization of traditional Chinese medicine (TCM) and the advancement of drug discovery. Nonetheless, the inherent complexity of herbal compositions and diversity of molecular targets render experimental validation both time-consuming and labor-intensive. We propose a graph neural network model, MAMGN-HTI, which integrates metapaths with attention mechanisms. A heterogeneous graph consisting of herbs, efficacies, ingredients, and targets is constructed, where semantic metapaths capture latent relationships among nodes. An attention mechanism is employed to dynamically assign weights, thereby emphasizing the most informative metapaths. In addition, ResGCN and DenseGCN architectures are combined with cross-layer skip connections to improve feature propagation and enable effective feature reuse. Experiments show that MAMGN-HTI outperforms several state-of-the-art methods across multiple metrics, exhibiting superior accuracy, robustness, and generalizability in HTI prediction and candidate drug screening. Validation against literature and databases further confirms the model’s predictive reliability. The model also successfully identified herbs with potential therapeutic effects for hyperthyroidism, including Vinegar-processed Bupleuri Radix (Cu Chaihu), Prunellae Spica (Xiakucao), and Processed Cyperi Rhizoma (Zhi Xiangfu). MAMGN-HTI provides a reliable computational framework and theoretical foundation for applying TCM in hyperthyroidism treatment, providing mechanistic insights while improving research efficiency and resource utilization. Full article

Irritable Bowel Syndrome (IBS) is a complex and multifactorial gastrointestinal disorder characterized by recurrent abdominal pain and altered bowel habits, impacting quality of life. Therapy is mainly based on relieving symptoms with specific drugs, whereas herbal and complementary remedies have gained attention in recent years. This review examines the current knowledge on herbal remedies in IBS management. Several herbal treatments, particularly peppermint oil and Iberogast, have demonstrated efficacy in randomized controlled trials. Preclinical studies have revealed promising anti-inflammatory and antispasmodic effects for herbs, e.g., curcumin, fennel oil, and cannabis derivatives. However, many studies suffer from some limitations, e.g., small sample sizes, short study durations, or methodological weaknesses. There is a lack of large-scale, long-term randomized controlled trials for most herbal remedies, and heterogeneity in study designs makes direct comparisons challenging. Moreover, limited evidence exists regarding herb–drug interactions and long-term safety profiles. Despite these limitations, certain herbal remedies may offer a valuable complementary approach for some IBS patients when used under medical supervision. Future research should focus on larger, well-designed clinical trials to establish efficacy, optimal dosing, and long-term safety, as well as elucidate specific mechanisms of action and identify patient subgroups that may benefit most from specific herbal treatments. Full article

Background: Epilepsy is a cluster of central nervous system (CNS) disorders identified by recurrent seizures, which affects about 60 million people around the world. In this research, a total of 40 types of 3,4,5-trimethoxycinnamic acid (TMCA) piperazine amide derivatives were designed and synthesized, inspired by the traditional Chinese medicine (TCM) herb pair drugs Polygala tenuifolia and Acori tatarinowii, followed by determination of their anticonvulsant potency. Methods: All the TMCA analogues were tested for their anticonvulsant potential through two acute models of seizures induced in mice: the maximal electroshock (MES) and sc-pentylenetetrazole (PTZ) models. In addition, the lactate dehydrogenase (LDH) inhibitory activity was determined in vitro. Results: The results showed that compounds A3, A9, A12, A14, B9, and B12 exhibited preferable anticonvulsant activity in the primary evaluation. In addition, the molecular docking results predicted good interactions of screened analogues with the LDH. Molecular dynamic simulation was used to reveal the consensual binding affinity between the most promising compound (B9) and active site interactions with LDH. Electroencephalogram (EEG) analysis and silver and immunofluorescence staining were performed to illustrate the anti-epilepsy potential of compound B9. Conclusions: Novel derivatives in this study provide new cores for the further design and optimization inspired by TCM herb pair drugs P. tenuifolia and A. tatarinowii, with the aim to explore new anticonvulsant agents. Full article

Background and purpose: Vulvovaginal candidiasis (VVC), caused by Candida albicans (C. albicans), is exacerbated by oxidative stress and uncontrolled inflammation. Pathogens like C. albicans generate reactive oxygen species (ROS) to enhance virulence, while host immune responses further amplify oxidative damage. This study investigates the antioxidant and antifungal properties of Hyssopus cuspidatus Boriss volatile extract (SXC), a traditional Uyghur medicinal herb, against fluconazole-resistant VVC. We hypothesize that SXC’s bioactive volatiles counteract pathogen-induced oxidative stress while inhibiting fungal growth and inflammation. Methods: GC-MS identified SXC’s major bioactive components, while broth microdilution assays determined minimum inhibitory concentrations (MICs) against bacterial/fungal pathogens, and synergistic interactions with amphotericin B (AmB) or fluconazole (FLC) were assessed via time–kill kinetics. Anti-biofilm activity was quantified using crystal violet/XTT assays, and in vitro studies evaluated SXC’s effects on C. albicans-induced cytotoxicity (LDH release in A431 cells) and inflammatory responses (cytokine production in LPS-stimulated RAW264.7 macrophages). A murine VVC model, employing estrogen-mediated pathogenesis and intravaginal C. albicans challenge, confirmed SXC’s in vivo effects. Immune modulation was assessed using ELISA and RT-qPCR targeting inflammatory and antioxidative stress mediators, while UPLC-MS was employed to profile metabolic perturbations in C. albicans. Results: Gas chromatography-mass spectrometry identified 10 key volatile components contributing to SXC’s activity. SXC exhibited broad-spectrum antimicrobial activity with MIC values ranging from 0.125–16 μL/mL against bacterial and fungal pathogens, including fluconazole-resistant Candida strains. Time–kill assays revealed that combinations of AmB-SXC and FLC-SXC achieved sustained synergistic bactericidal activity across all tested strains. Mechanistic studies revealed SXC’s dual antifungal actions: inhibition of C. albicans hyphal development and biofilm formation through downregulation of the Ras1-cAMP-Efg1 signaling pathway, and attenuation of riboflavin-mediated energy metabolism crucial for fungal proliferation. In the VVC model, SXC reduced vaginal fungal burden, alleviated clinical symptoms, and preserved vaginal epithelial integrity. Mechanistically, SXC modulated host immune responses by suppressing oxidative stress and pyroptosis through TLR4/NF-κB/NLRP3 pathway inhibition, evidenced by reduced caspase-1 activation and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Conclusions: SXC shows promise as a broad-spectrum natural antimicrobial against fungal pathogens. It inhibited C. albicans hyphal growth, adhesion, biofilm formation, and invasion in vitro, while reducing oxidative and preserving vaginal mucosal integrity in vivo. By disrupting fungal metabolic pathways and modulating host immune responses, SXC offers a novel approach to treating recurrent, drug-resistant VVC. Full article