Front Pharmacol [JOURNAL]
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200 papers
Editorial: Innovative approaches and molecular mechanisms in cardiovascular pharmacology.
Silva MLS, Toghi CJ, Dias-Junior CAC
Front Pharmacol · 2026 · PMID 42375622 · Full text
Abstract loading — click title to view on PubMed.
Case Report: Successful multimodal management of a lethal cyanide poisoning - insights into the role of early blood purification and potential bedside monitoring indicators.
Xie H, Zhang Y, Luo X … +4 more , Xu J, Chen C, Qu Y, Wang L
Front Pharmacol · 2026 · PMID 42375621 · Full text
This article reports a rare and lethal case of cyanide poisoning, aiming to explore its early diagnosis and successful treatment strategies. Upon admission, the patient presented with cardiac and respiratory arrest, deep...
This article reports a rare and lethal case of cyanide poisoning, aiming to explore its early diagnosis and successful treatment strategies. Upon admission, the patient presented with cardiac and respiratory arrest, deep coma, and severe metabolic acidosis. The core resuscitation measures included early mechanical ventilation, vasoactive drug support, bicarbonate therapy, and the early initiation of continuous blood purification as part of a multimodal strategy. We observed that a combination of elevated central venous partial pressure of carbon dioxide (PvCO) and elevated lactate provided potential bedside clues for early suspicion of cyanide poisoning. During treatment, a rise in PvCO accompanied by a decrease in lactate was noted, which may serve as a hypothesis-generating observation for treatment response, acknowledging the influence of multiple concurrent interventions. The patient recovered substantially after comprehensive treatment. This case provides valuable experience for the treatment of cyanide poisoning.
Comparative evaluation for small molecule somatostatin 4 receptor agonists: , , and approaches.
Biskup D, Ganbold M, Nehr-Majoros AK … +10 more , Tékus V, Hajna Z, Fülöp B, Szőke É, Hetényi C, Crider AM, Daryaei I, Helyes Z, Börzsei R, Pintér E
Front Pharmacol · 2026 · PMID 42375620 · Full text
INTRODUCTION: The treatment of neuropathic pain with traditional and adjuvant analgesics is limited in efficacy and associated with severe adverse effects. Our group has previously shown that somatostatin, released from...
INTRODUCTION: The treatment of neuropathic pain with traditional and adjuvant analgesics is limited in efficacy and associated with severe adverse effects. Our group has previously shown that somatostatin, released from capsaicin-sensitive peptidergic sensory nerve terminals, mediates analgesic and anti-inflammatory effects at the peripheral and central levels via the somatostatin receptor subtype 4 (SST4). The therapeutic use of native somatostatin is limited by its numerous biological actions mediated by the five somatostatin receptors and its short elimination half-life. Therefore, the development of SST4-selective agonists may be an effective approach for treating neuropathic pain. METHODS: In this comparative study, the receptor binding and activation properties of four small molecules were compared with those of somatostatin and the SST4 receptor superagonist, J-2156, through in silico drug-likeness investigation, pharmacokinetic prediction, molecular docking calculations, in vitro cAMP accumulation assays, and in vivo assessment of their antihyperalgesic effects in the partial sciatic nerve ligation mouse model of traumatic neuropathy. RESULTS AND DISCUSSION: Docking calculations showed that all compounds interact with the conserved Asp126 of SST4, which is suggested to play a key role in ligand binding. cAMP assays confirmed that all molecules activate the SST4 receptor with comparable potency to that of J-2156. All examined compounds reversed PSNL-induced mechanical hyperalgesia. Their antihyperalgesic effects ranged from 20% to 70% and depended on both the time and the applied dose. These results suggest that the tested compounds could be potentially effective in the treatment of neuropathic pain.
Correction: Discovery of potent bisindole-based pyrazolopyridine derivatives as topoisomerase inhibitors: DNA damage induction and synergistic antileukemic activity.
Eldehna WM, Tawfik HO, Veselá D … +9 more , Peřina M, Negmeldin AT, Elsayed ZM, Majrashi TA, Vojáčková V, Elbadawi MM, Shaldam MA, Kryštof V, Abdel-Aziz HA
Front Pharmacol · 2026 · PMID 42375619 · Full text
[This corrects the article DOI: 10.3389/fphar.2026.1745220.].
[This corrects the article DOI: 10.3389/fphar.2026.1745220.].
Water intake during drinking does not alleviate hangover symptoms.
Imai H, Kushio S, Matsuura K … +5 more , Nakamura A, Mori K, Kadowaki M, Oikawa I, Uemura N
Front Pharmacol · 2026 · PMID 42375618 · Full text
BACKGROUND: Hangovers can impair the ability to drive a car or work in industrial settings, in addition to causing unpleasant symptoms such as headaches and fatigue. As for reducing hangover symptoms, the effect of consu...
BACKGROUND: Hangovers can impair the ability to drive a car or work in industrial settings, in addition to causing unpleasant symptoms such as headaches and fatigue. As for reducing hangover symptoms, the effect of consuming water between drinks, often referred to as a "chaser," has been empirically recognized; however, this effect has not been verified to date. The purpose of this study was to clarify whether intermittent drinking of water during alcohol consumption affects the ethanol and acetaldehyde kinetics in the body and whether it alleviates hangover symptoms with the psychomotor function test and subjective symptoms on the following day. METHODS: Thirteen healthy Japanese adult males with wild-type aldehyde dehydrogenase (ALDH)2 ( */*) were included in this study. The trial design was a randomized, 2×2 crossover study in which subjects drank (1) equivalent to 1.3 g/Kg body weight of pure alcohol (Control group) and (2) the same amount of and 15 mL/Kg body weight of water (Water group) intermittently, each at a constant pace over 1 hour. Before drinking, immediately after drinking, and at various times up to 15 hours after, we measured ethanol and acetaldehyde concentrations in the expired air, administered the Digit Symbol Substitution Test (DSST), and evaluated the subjective intoxication symptom score (VAS). Breath ethanol and acetaldehyde concentrations were determined by sensor gas chromatography. Differences in breath concentrations and pharmacodynamic indices between the two groups were evaluated using a linear mixed-effects model with fixed effects for the test beverages and the number of administrations, and random effects for the subjects. RESULTS: No differences were observed between the two groups in the kinetics of exhaled ethanol and acetaldehyde. The DSST scores were similar between them. The VAS assessed subjective symptoms of facial flushing, headache, nausea, concentration, sleepiness, and mood elevation, and no differences were found between the two groups. CONCLUSION: The intermittent addition of drinking water during ethanol consumption did not significantly alter ethanol disposition or pharmacodynamic parameters, suggesting it did not affect hangover symptoms.
Glucosamine/platelet-rich plasma/bone marrow MSC-loaded GelMA hydrogel supports cartilage endplate repair in mice and is associated with reduced inflammation- and oxidative stress-related readouts.
Bao Y, Hu B, Bai Y … +4 more , Zhang Y, Meng H, Wang H, Fang F
Front Pharmacol · 2026 · PMID 42375617 · Full text
OBJECTIVE: In this study, we developed a gelatin methacryloyl (GelMA) hydrogel composite for the simultaneous delivery of glucosamine (GlcN), platelet-rich plasma (PRP), and bone marrow-derived mesenchymal stem cells (BM...
OBJECTIVE: In this study, we developed a gelatin methacryloyl (GelMA) hydrogel composite for the simultaneous delivery of glucosamine (GlcN), platelet-rich plasma (PRP), and bone marrow-derived mesenchymal stem cells (BMMSCs). We systematically investigated its effects on cartilage endplate (CEP) cell behavior, inflammation, and oxidative stress, and evaluated its reparative efficacy in a murine caudal CEP injury model. METHODS: GlcN/PRP/BMMSC@GelMA was fabricated and comprehensively characterized in terms of its microarchitecture, compressive and rheological properties, enzymatic degradability, swelling, and the sustained release profile of GlcN and platelet-derived growth factor (PDGF). Additionally, primary CEP cells were treated with either GelMA or GlcN/PRP/BMMSC@GelMA to evaluate cell viability, proliferation, apoptosis, and the expression of chondrogenic markers (COL2A1, ACAN, and SOX9) using RT-qPCR and Western blot. Under lipopolysaccharide (LPS) challenge, cytokines (IL-1β, IL-6, TNF-α, IL-10) were quantified using ELISA. Under HO exposure, reactive oxygen species (ROS) levels and oxidative stress markers (MDA, SOD, GSH) were assessed. , male BALB/c-nu nude mice underwent caudal disc puncture at the Co5/6 level using a 30G needle, followed by intradiscal injection of either GelMA or GlcN/PRP/BMMSC@GelMA. Tissue analyses were performed at 8 weeks post-procedure. RESULTS: The composite formed a stable three-dimensional network with higher elastic and storage moduli than GelMA alone and supported the sustained release of GlcN and PDGF. The composite also improved CEP cell viability and proliferation, reduced apoptosis, and increased the expression of collagen II, aggrecan, and SOX9. In addition, it reduced LPS-induced inflammatory cytokines and mitigated HO-induced oxidative stress-related changes . , treatment was associated with improved CEP structural continuity, higher cartilage-related marker expression, and favorable inflammation- and oxidative stress-related readouts. CONCLUSION: GlcN/PRP/BMMSC@GelMA showed favorable and effects and supports the therapeutic potential of this combined local delivery platform for CEP repair.
Effects of the glucagon-like peptide-1 receptor agonist liraglutide on retinal endothelial function and oxidative stress during sepsis.
Böhm EW, Kouchek Zadeh J, Omran W … +9 more , Arad T, Pfeiffer N, Wagner FM, Patzak A, Oelze M, Daiber A, Helmstädter J, Steven S, Gericke A
Front Pharmacol · 2026 · PMID 42375616 · Full text
PURPOSE: To test the hypothesis that the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide improves retinal vascular function in mice with polymicrobial sepsis. METHODS: Three groups of mice were studied. Two...
PURPOSE: To test the hypothesis that the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide improves retinal vascular function in mice with polymicrobial sepsis. METHODS: Three groups of mice were studied. Two groups underwent cecal ligation and puncture to induce polymicrobial sepsis. One received vehicle and the other liraglutide via intraperitoneal injection starting 24 h before the procedure and continuing twice daily until euthanasia. A third group underwent sham surgery and served as control. Forty-eight hours after sepsis induction, mice were euthanized and retinas were isolated for assessment of vascular function by videomicroscopy. In addition, reactive oxygen species (ROS) formation and gene expression were evaluated using dihydroethidium staining, quantitative real-time PCR, and immunostaining of NADPH oxidase (NOX)1 and NOX2, respectively. RESULTS: Endothelium-dependent vasodilation to acetylcholine was markedly impaired in retinal arterioles of septic, vehicle-treated mice but was partially preserved in liraglutide-treated septic mice. In contrast, vasodilation to the endothelium-independent vasodilator sodium nitroprusside was similar across all groups. Dihydroethidium staining revealed increased ROS signals in retinal arterioles, the ganglion cell layer, the inner and outer nuclear layers, and the optic nerve of septic, vehicle-treated mice. These increases were attenuated by liraglutide treatment. Furthermore, retinal mRNA expression of NOX1 was significantly upregulated in septic, vehicle-treated mice but remained at control levels in liraglutide-treated septic mice. . In addition, mRNA levels of SOD2, nNOS, and PAI-1 were increased, whereas NOX4, COX-2, and UCP-2 were decreased in septic, vehicle-treated mice. Liraglutide treatment was associated with increased mRNA expression for the antioxidant enzymes SOD1 and SOD3, reduced expression for MCP-1, ICAM-1 and PAI-1 mRNA levels and restoration of UCP-2 mRNA expression. Immunoreactivity for NOX1, but not NOX2, was increased in retinal blood vessels of septic mice. CONCLUSION: Treatment with liraglutide attenuates endothelial dysfunction, reduces oxidative stress, and suppresses NOX1 upregulation in the retina during polymicrobial sepsis. These findings highlight the preventive and therapeutic potential of GLP-1 receptor agonists for retinal vascular complications associated with sepsis and systemic inflammation.
Lessons from the STOPPCog criteria: prevalence of potentially inappropriate medications for cognition and their association with a cognitive status - a cross-sectional study.
Szoszkiewicz M, Szafarkiewicz Z, Szkudelski F … +4 more , Grabowski S, Deskur-Śmielecka E, Neumann-Podczaska A, Wieczorowska-Tobis K
Front Pharmacol · 2026 · PMID 42375615 · Full text
INTRODUCTION: Potentially inappropriate medications (PIMs), are common among residents of long-term care institutions (LTCIs) and may contribute to cognitive impairment (CIm). STOPPCog criteria, developed in 2025, suppor...
INTRODUCTION: Potentially inappropriate medications (PIMs), are common among residents of long-term care institutions (LTCIs) and may contribute to cognitive impairment (CIm). STOPPCog criteria, developed in 2025, support the identification of PIMs relevant to cognition and accuracy of dementia treatment. OBJECTIVES: The study aimed to identify PIMs according to the STOPPCog criteria among residents of long-term care institutions in Poland, and to assess the association between CIm and exposure to specific drug classes. PATIENTS AND METHODS: This is a multicenter cross-sectional study in four LTCIs. Medication lists were reviewed using STOPPCog criteria and anticholinergic burden scales. Cognitive status was assessed with the Mini-Mental State Examination (MMSE), and CIm was defined using a conventional cut-off. We compared exposure frequencies between residents with and without CIm and explored factors associated with MMSE using regression models adjusted for key demographic and clinical variables and facility effects. RESULTS: Of 204 residents, 133 (65.2%) had at least one STOPPCog-listed medication on their medication list. Drugs with anticholinergic burden (ACB) (54.9%), especially one subgroup - antipsychotics (39.2%), were most frequently used within the study sample. Antipsychotics were the only drug class significantly associated with CIm independently of sex, age, comorbidity burden, and facility (p < 0.001). The majority of residents with a previous diagnosis of dementia in their medical records and consequently dementia-specific pharmacotherapy had severe CIm. CONCLUSION: There is a high prevalence of PIMs among LTCIs residents. Antipsychotic deprescribing and early diagnosis of CIm should be further evaluated in future prospective studies and clinical practice.
Soyeom-Jetong mixture attenuates NLRP3 inflammasome-mediated inflammation.
Ye Q, Lee S, Park YC … +18 more , Kim MS, Kim W, Jin JS, Kim DK, Jang S, Lee S, Lee N, Lee S, Seo BK, Kim MS, Kim Y, An D, Seo S, Lee D, Kim H, Park YH, Lee Y, Baek YH
Front Pharmacol · 2026 · PMID 42375614 · Full text
BACKGROUND: Soyeom-Jetong (SJ) is a traditional East Asian polyherbal formulation composed of Pallas, Batal, and W.T. Wang, traditionally used for treating inflammatory disorders. Given the central role of the NLRP3 i...
BACKGROUND: Soyeom-Jetong (SJ) is a traditional East Asian polyherbal formulation composed of Pallas, Batal, and W.T. Wang, traditionally used for treating inflammatory disorders. Given the central role of the NLRP3 inflammasome in inflammation-related pathologies, SJ is of particular interest as a potential anti-inflammatory modulator. However, the molecular mechanisms underlying the anti-inflammatory effects remain unclear. This study aimed to evaluate the anti-inflammatory efficacy of SJ in a lipopolysaccharide (LPS)-induced zebrafish model and determine its regulatory effects on the NLRP3 inflammasome . METHODS: Inflammation was induced in zebrafish embryos via LPS exposure and tail amputation. The anti-inflammatory effects of SJ were assessed through Sudan Black B staining and whole-mount hybridization to detect neutrophil infiltration. assays were performed to investigate the regulatory effects of SJ on NLRP3 inflammasome activation. RESULTS: SJ significantly reduced neutrophil accumulation in the caudal hematopoietic tissue of LPS-exposed zebrafish and the injury site of zebrafish embryos with amputated tails. It also modulated inflammatory gene expression, including NLRP3 and proinflammatory cytokines. SJ suppressed NLRP3 inflammasome activation. CONCLUSION: SJ exhibits anti-inflammatory activity by modulating neutrophil inflammation and suppressing NLRP3 inflammasome activation . These findings provide experimental support for the pharmacological activity of SJ and suggest its potential as an anti-inflammatory candidate for further investigation.
Activation of BK channels ameliorates cardiac injury Via NFκB-NLRP3 signaling in angiotensin II-induced hypertension mouse model.
Zhao L, Wu X, Luo X … +10 more , Zheng A, Yue Q, Wang H, Ishida J, Romero CA, Eaton DC, Klein JD, Wang XH, Xu Y, Cai H
Front Pharmacol · 2026 · PMID 42375613 · Full text
BACKGROUND: Hypertension-induced cardiac fibrosis leads to heart failure. Large-conductance calcium-activated potassium (BK) channels regulate vascular tone, and their activation may mitigate fibrosis. This study explore...
BACKGROUND: Hypertension-induced cardiac fibrosis leads to heart failure. Large-conductance calcium-activated potassium (BK) channels regulate vascular tone, and their activation may mitigate fibrosis. This study explores the impact of BK channel activation on angiotensin II (Ang II)-induced hypertension and cardiac fibrosis and its effects on nuclear factor-kappa B (NFκB) signaling. METHODS: Male C57BL/6 J mice were infused with Ang II for 4 weeks to induce hypertension and cardiac fibrosis. The BK channel activator BMS-191011 was administered via intraperitoneal injection. Cardiac tissue was analyzed using histology, Western blotting and qPCR. Single channel recordings were used to analyze the activation of BKα channels. A dihydroethidium (DHE) Assay was used to detect superoxide (ROS) production. Superoxide Dismutase (SOD) was measured using a colorimetric activity kit. , macrophages (RAW 264.7) were stimulated with Ang II, to detect NFκB activation and macrophage polarization. RESULTS: The expression of BKα mRNA and protein abundance was decreased while markers of cardiac fibrosis (fibronectin, vimentin, αSMA and TGF-β) and ROS production were increased in the hearts of Ang II-induced hypertensive mice. In addition, macrophage infiltration was significantly increased along with inflammatory cytokines IFNγ, IL-6, IL-4, IL-10 and TNFα. The BK channel opener, BMS-191011, significantly reduced hypertension, cardiac fibrosis, and ROS production, but restored SOD in the hearts of Ang II-treated mice. In cultured macrophages, we found that Ang II increased inflammatory cytokines through NFκB-NLRP3-caspase-1 signaling. After Ang II treatment, BK channel activation inhibited NFκB, NLRP3 and caspase-1 expression. BK channel activation also suppressed NFκB-NLRP3 signaling, leading to reduced ROS accumulation and restored SOD activity. CONCLUSION: BK channel activation reduces Ang II-induced hypertension and cardiac fibrosis by modulating oxidative stress, inflammation and macrophage polarization through the NFκB-NLRP3 pathway. These findings implicate BK channel activators as a potential novel therapeutic strategy for hypertensive cardiomyopathy.
Randomized controlled trials of major oral traditional Chinese medicine preparations for postherpetic neuralgia: an evidence map.
Li K, Liu M, He B … +5 more , Cheng H, Lv J, Wang J, Song P, Chen S
Front Pharmacol · 2026 · PMID 42375612 · Full text
OBJECTIVE: To identify and synthesize randomized controlled trials (RCTs) of oral traditional Chinese medicine (TCM) for postherpetic neuralgia (PHN), map the volume, methodological quality, and evidence distribution, id...
OBJECTIVE: To identify and synthesize randomized controlled trials (RCTs) of oral traditional Chinese medicine (TCM) for postherpetic neuralgia (PHN), map the volume, methodological quality, and evidence distribution, identify evidence gaps, and inform future research. METHODS: We systematically searched PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, VIP Database, the Chinese Clinical Trial Registry (ChiCTR), and China Biomedical Literature Database (CBM). RCTs published from database inception to 1 August 2025 were included. The evidence was summarized using evidence maps and narrative synthesis. Risk of bias in the included RCTs was assessed using the Cochrane Risk of Bias tool (RoB 1.0). RESULTS: A total of 357 RCTs were included, most were small studies with sample sizes ranging from 50 to 100 participants. Most studies reported diagnostic criteria and inclusion/exclusion criteria, however, limited attention was paid to TCM syndrome differentiation and its standardization. The main outcomes were pain degree, clinical effective rate, adverse reactions, sleep quality, negative emotions, and quality of life, however, outcomes such as recurrence and TCM syndrome scores were infrequently reported. Overall methodological quality was low, as assessed using the RoB 1.0. CONCLUSION: Although many included studies reported favourable findings, the formulas and preparations differed substantially in composition, and high-quality evidence remains limited. Future trials should better incorporate key features of TCM (e.g., syndrome differentiation), use standardized and clinically meaningful outcome measures, and strengthen trial design and reporting to reduce risk of bias and improve the credibility of evidence. SYSTEMATIC REVIEW REGISTRATION: URL: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251110786, identifier CRD420251110786.
Editorial: Advancements and strategies in predicting and managing clinical drug-drug interactions.
Subash S, Lai Y, Tsang A … +1 more , Li C
Front Pharmacol · 2026 · PMID 42375611 · Full text
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Safety profile of upadacitinib in inflammatory Bowel disease: a dual-source pharmacovigilance study integrating FAERS signal detection and real-world clinical cohort analysis.
Tan W, Wang H, Guo H … +4 more , Song X, Lei W, Liu Y, Xiang L
Front Pharmacol · 2026 · PMID 42375610 · Full text
BACKGROUND: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated efficacy in inflammatory bowel disease (IBD). However, safety data in real-world Asian populations remain limited. This study aimed...
BACKGROUND: Upadacitinib, a selective Janus kinase 1 (JAK1) inhibitor, has demonstrated efficacy in inflammatory bowel disease (IBD). However, safety data in real-world Asian populations remain limited. This study aimed to characterize the adverse event (AE) profile of upadacitinib by integrating large-scale pharmacovigilance data with real-world clinical evidence. METHODS: We conducted a dual-source analysis comprising spontaneous reports from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS; Q1 2018-Q3 2025) and a retrospective single-center clinical cohort in China (April 2023-September 2025). In the FAERS database, disproportionality analyses were performed using four algorithms (ROR, PRR, EBGM, and IC) to detect safety signals. In the clinical cohort, we assessed AE incidence, severity, timing, and management strategies. Subgroup analyses were descriptive, and Kaplan-Meier methods were used to estimate the time to the first AE. RESULTS: The clinical cohort included 183 patients, of whom 85 (46.4%) experienced at least one AE. The most common events were laboratory abnormalities, infections, and dermatologic conditions. Serious events, including intestinal perforation and venous thrombosis, were rare. A distinct early clustering of toxicity was observed: 38.8% of first events occurred within 30 days and 67.0% within 60 days of treatment initiation. Male reproductive safety appeared favorable; one patient experienced transient semen discoloration, which resolved following dose reduction. The FAERS analysis identified rare signals absent in the clinical cohort, notably Pneumocystis jirovecii pneumonia (PJP) and pseudostroke, highlighting potential high-risk scenarios. Signal classification revealed strong signals for herpes zoster and acne, moderate signals for venous thrombosis and laboratory abnormalities, and weak signals for rare events. AE patterns varied by age, disease type, and induction dose, consistent with the mechanistic expectations of JAK1 inhibition. CONCLUSION: Upadacitinib demonstrates a manageable safety profile in patients with IBD, with most AEs controllable through vigilant monitoring and individualized management. The integration of clinical cohort data with FAERS pharmacovigilance provides a comprehensive view of both common and rare risks. These findings offer critical real-world evidence from an Asian population, complementing global data to inform clinical decision-making.
Breaking the barrier: from biosynthetic inhibition to multidimensional modulation of the mycobacterial cell wall in tuberculosis therapy.
Li P, Liao Y, Zhu L … +7 more , Zhang M, Wang Y, Liao L, Wu T, Chen X, Xia Y, Han X
Front Pharmacol · 2026 · PMID 42375609 · Full text
Tuberculosis remains a leading cause of global mortality, with the rise of multidrug resistant and extensively drug-resistant strains highlighting an urgent need for novel therapeutics. The mycobacterial cell wall has l...
Tuberculosis remains a leading cause of global mortality, with the rise of multidrug resistant and extensively drug-resistant strains highlighting an urgent need for novel therapeutics. The mycobacterial cell wall has long served as a validated drug target, owing to its unique architecture comprising arabinogalactan, peptidoglycan, and mycolic acids. This review provides a comprehensive overview of recent advances in cell wall targeting anti tuberculosis drug discovery, encompassing both established and emerging targets within the major biosynthetic pathways. Beyond conventional enzymatic inhibition, a multidimensional framework is explored that includes disrupting cell wall integrity through alternative mechanisms, interfering with energy metabolism and regulatory networks, blocking the secretion and transport of cell wall components, harnessing host-directed therapies and antimicrobial peptides, and leveraging nanotechnology-based delivery systems. By integrating discoveries across these diverse fronts, this review highlights evolving strategies and offers a forward looking perspective on the development of ultra short, highly effective, and resistance proof tuberculosis regimens.
Lysosome-dependent cell death in hepatocellular carcinoma: unlocking the therapeutic potential of natural products.
Xu Y, Wang R, Xie X … +2 more , Fan H, Peng F
Front Pharmacol · 2026 · PMID 42375608 · Full text
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and the available targeted therapies (e.g., sorafenib, lenvatinib) have limited options and frequent drug resistance. Lysosome-depende...
Hepatocellular carcinoma (HCC) is one of the deadliest malignant tumors in the world, and the available targeted therapies (e.g., sorafenib, lenvatinib) have limited options and frequent drug resistance. Lysosome-dependent cell death (LDCD), characterized by increased lysosomal membrane permeabilization (LMP) and the release of proteases, has attracted considerable attention as a non-apoptotic mechanism that can circumvent drug resistance. In recent years, researchers have used natural compounds in the treatment of HCC, which effectively induce LDCD through a variety of mechanisms, such as acid sphingomyelinase inhibition, lysosomal-iron-ferroptosis axis activation, lysosomal pH regulation, PI3K/AKT/mTOR-TFEB pathway inhibition and so on. These compounds synergize with conventional targeted agents to overcome drug resistance through direct cytotoxicity or targeting hypertrophic lysosomal drug release. This article reviews the regulation of LDCD and the role of natural products in HCC based on PubMed, Web of Science and CNKI databases, aiming to providing a reference for the treatment of drug-resistant liver cancer.
Fucoxanthin attenuates carbonyl stress and neuroinflammation by modulating MGO/RAGE/NF-κB axis in Aβ-induced models.
Lee N, Youn K, Kwon H … +3 more , Kim DH, Ho CT, Jun M
Front Pharmacol · 2026 · PMID 42375607 · Full text
INTRODUCTION: Amyloid-β (Aβ) accumulation is a central pathological feature of Alzheimer's disease (AD) and a major driver of disease progression. Recent evidence suggests that carbonyl stress associated with Aβ plays a...
INTRODUCTION: Amyloid-β (Aβ) accumulation is a central pathological feature of Alzheimer's disease (AD) and a major driver of disease progression. Recent evidence suggests that carbonyl stress associated with Aβ plays a critical role in AD pathology by promoting neuroinflammation and neuronal damage. In particular, methylglyoxal (MGO), a highly reactive carbonyl compound, contributes to activation of the receptor for advanced glycation end products (RAGE) and NF-κB-dependent inflammatory signaling, leading to synaptic dysfunction. The present study investigated whether fucoxanthin, a marine-derived carotenoid, attenuates Aβ-induced carbonyl stress and inflammatory responses associated with MGO/RAGE/NF-κB-related signaling. METHODS: PC12 neuronal cells were pretreated with fucoxanthin (0.1-5 μM) and exposed to aggregated Aβ (10 μM) to assess its effects on carbonyl stress-associated inflammatory signaling. In parallel, an Aβ intracerebroventricular injection mouse model was used to validate the findings. Mice were orally administered fucoxanthin (100 or 200 mg/kg/day) for 15 days and assessed for serum MGO levels, hippocampal RAGE/NF-κB activation, microglial activation, and synaptic marker expression. RESULTS: Fucoxanthin significantly reduced the expression of pro-inflammatory mediators, including COX-2, iNOS, IL-1β, and TNF-α in Aβ-exposed neuronal cells. This anti-inflammatory effect was associated with inhibition of NF-κB nuclear translocation and downregulation of RAGE expression. Consistent with these findings, fucoxanthin treatment in Aβ-injected mice alleviated systemic and hippocampal carbonyl stress, as evidenced by decreased serum MGO levels and suppression of hippocampal RAGE/NF-κB activation. These effects were accompanied by reduced microglial activation (Iba-1) across hippocampal subregions and significant restoration of both presynaptic and postsynaptic markers, indicating preservation of synaptic integrity. CONCLUSION: These findings demonstrate the neuroprotective role of fucoxanthin in mitigating Aβ-induced carbonyl stress by targeting the MGO/RAGE/NF-κB axis, thereby suppressing neuroinflammation and preserving synaptic integrity in Aβ-induced cellular and mouse models. Fucoxanthin emerges as a promising pharmacological candidate targeting carbonyl stress-associated mechanisms in AD.
flower inhibits lipopolysaccharide-induced acute lung injury in mice by regulating the gut-lung axis and inflammatory response.
Fu S, Liao W, He B … +3 more , Wu H, Huang J, Jiang W
Front Pharmacol · 2026 · PMID 42375606 · Full text
BACKGROUND: flower (HUF), the dried flower of (Haw.) Britton and Rose, was first recorded in the Lingnan Record of Medicinal Herbs and is now listed in the Dictionary of Traditional Chinese Medicines. As an established...
BACKGROUND: flower (HUF), the dried flower of (Haw.) Britton and Rose, was first recorded in the Lingnan Record of Medicinal Herbs and is now listed in the Dictionary of Traditional Chinese Medicines. As an established traditional remedy, HUF is primarily used to treat various pulmonary conditions, including pneumonia, asthma, and tuberculosis. Acute lung injury (ALI) represents a critical and common pathological manifestation underlying severe respiratory disorders. However, the potential protective effects of HUF against ALI, and the specific mechanisms involved, remain unelucidated. PURPOSE: To systematically evaluate the protective effects of HUF extract on ALI and the pharmacological mechanisms involved. METHODS: Using a lipopolysaccharide-induced mouse model of ALI, we investigated the effects of HUF on the intestinal microbiota of ALI mice via microbial sequencing, metabolomics sequencing, and fecal microbiota transplantation (FMT). We explored the targets and signaling pathways of HUF intervention using transcriptomics and network pharmacology methods and then validated our results using immunological experiments and polymerase chain reaction analysis (PCR). RESULTS: HUF reduced lung indices and wet-dry ratios associated with pulmonary edema, alleviated inflammatory responses, and mitigated the severity of pulmonary pathological damage. HUF also increased the expression of intestinal tight junction protein (ZO-1), modulated the structure and relative abundance of the gut microbiota, and elevated the levels of certain short-chain fatty acids (SCFAs). FMT experiments confirmed that the HUF-mediated remodeling of the microbiota played a significant role in alleviating ALI. Transcriptomics and network pharmacology analyses suggested that the mechanism underling the interventional effect of HUF on ALI is related to inflammatory pathways. Immunological and PCR experiments further confirmed an association with the P38 mitogen-activated protein kinase (MAPK) pathway. CONCLUSION: HUF is associated with attenuation of ALI, correlating with modulation of the gut-lung axis and the inflammatory pathways, and HUF may be a candidate for the treatment of ALI.
RANKL-RANK signaling promotes cigarette smoke-induced emphysema with MMP-9 upregulation in alveolar macrophages.
Zhou L, Zhang B, Wang H … +2 more , Huang F, Miao L
Front Pharmacol · 2026 · PMID 42375605 · Full text
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading global health problem, with pulmonary emphysema as one of its hallmark pathological features. Matrix metalloproteinase-9 (MMP-9), predominantly derive...
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a leading global health problem, with pulmonary emphysema as one of its hallmark pathological features. Matrix metalloproteinase-9 (MMP-9), predominantly derived from alveolar macrophages, has been implicated in extracellular matrix degradation. However, the upstream regulatory signals responsible for MMP-9 induction in cigarette smoke (CS)-related COPD remain incompletely understood. We investigated whether receptor activator of nuclear factor-κB ligand (RANKL) and its receptor RANK are involved in this process. METHODS: We localized RANKL and RANK in lung tissues of mice subjected to long-term CS exposure. Emphysema was evaluated in CS-exposed mice that received intraperitoneal injections of either an anti-mouse RANKL monoclonal antibody or a rat IgG2a kappa isotype control antibody. Next, we examined their expression under cigarette smoke extract (CSE) stimulation in the MH-S mouse alveolar macrophage cell line. Finally, we evaluated the functional role of RANKL in regulating CS-induced MMP-9 production using neutralizing antibodies. RESULTS: , chronic CS exposure resulted in alveolar enlargement, structural destruction, and decline in lung function, accompanied by increased expression of RANKL, RANK, and MMP-9 in lung tissue. These molecules were predominantly localized to alveolar macrophages. Neutralization of RANKL was associated with reduced MMP-9 expression, attenuated alveolar damage, and improved pulmonary function. , CSE stimulation of MH-S cells upregulated RANKL and RANK and induced MMP-9 expression, while RANKL blockade partially inhibited this effect. CONCLUSION: RANKL-RANK signaling is associated with increased MMP-9 expression in alveolar macrophages and contributes to CS-induced emphysema. Targeting this pathway attenuates structural damage and functional impairment and may represent a potential therapeutic strategy in COPD-related emphysema.
Comparative cardiovascular outcomes of renin-angiotensin system inhibitors in patients receiving maintenance hemodialysis: a large real-world cohort study.
Wu JY, Lee KW, Huang SC … +2 more , Chang HY, Lin YM
Front Pharmacol · 2026 · PMID 42375604 · Full text
BACKGROUND: The comparative cardiovascular effectiveness of different renin-angiotensin system (RAS) inhibitors in patients receiving maintenance hemodialysis remains uncertain, and current guideline recommendations larg...
BACKGROUND: The comparative cardiovascular effectiveness of different renin-angiotensin system (RAS) inhibitors in patients receiving maintenance hemodialysis remains uncertain, and current guideline recommendations largely assume therapeutic equivalence between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB). METHODS: Using the TriNetX multi-institutional database, we identified adults with ESKD who newly initiated ARB or ACEI therapy from 2006 to 2025. An active-comparator new-user design and 1:1 propensity score matching were applied. The primary outcome was 1-year major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, or all-cause mortality). Secondary outcomes included individual MACE components and hyperkalemia. Hazard ratios (HRs) were estimated using Cox models, and negative-control analyses assessed residual confounding. RESULTS: After matching, 55,894 patients were included. ARB was associated with a lower risk of MACE compared with ACEI users (30.3% vs. 35.0%; HR 0.85; 95% CI 0.83-0.88). Stroke (HR 0.90; 95% CI 0.86-0.94) and all-cause mortality (HR 0.75; 95% CI 0.71-0.78) were also associated with a lower risk, while MI risk was similar (HR 0.99; 95% CI 0.94-1.03). Hyperkalemia rates were comparable. Subgroup findings consistently favored ARBs across age, sex, diabetes, heart failure, CAD, and PAD strata. Negative-control outcomes showed no significant associations. CONCLUSION: In this large real-world cohort of patients receiving maintenance hemodialysis, initiation of ARB was associated with lower risks of major adverse cardiovascular events, stroke, and all-cause mortality compared with ACEI. These findings suggest a potential difference in observed cardiovascular outcomes between ARBs and ACEIs in the hemodialysis population; however, causal inference is limited by the observational design.
Cyproheptadine enhances weight gain and modulates appetite-regulating peptides in children with failure to thrive and food allergies.
Zhang Y, Ma N, Lan J … +6 more , Zhang X, Li Z, Zhao Q, Jin C, Li C, Yang M
Front Pharmacol · 2026 · PMID 42375603 · Full text
BACKGROUND: Cyproheptadine hydrochloride (CH) possesses both antihistaminic and appetite-stimulating properties, suggesting therapeutic potential for children with failure to thrive (FTT) and food allergies. This study e...
BACKGROUND: Cyproheptadine hydrochloride (CH) possesses both antihistaminic and appetite-stimulating properties, suggesting therapeutic potential for children with failure to thrive (FTT) and food allergies. This study evaluated the effects of CH on growth parameters, clinical manifestations, and serum levels of appetite-regulating peptides Nesfatin-1 and NUCB2 in children aged 1-3 years with FTT and food allergy. METHODS: In this non-randomized controlled real-world study, participants were assigned to either the treatment group (T-group, n = 25), receiving CH at 0.15 mg/kg twice daily for 12 weeks, or the control group (NT-group, n = 19). Primary outcomes were anthropometric indices: body weight, weight-for-age Z-score (WAZ), height, weight-for-length Z-score (WLZ), body mass index (BMI), and length-for-age Z-score (LAZ). Secondary outcomes included clinical symptom scores and changes in Nesfatin-1 and NUCB2 levels. RESULTS: After 12 weeks, the T-group showed significantly greater improvements in body weight (10.32 ± 0.28 kg vs. 9.05 ± 0.23 kg, = 0.002), WAZ ( < 0.001), WLZ ( < 0.001), and BMI ( = 0.001) compared to the NT-group. No significant differences were observed in height or LAZ. Within the T-group, significant improvements from baseline to week 12 were observed for all weight-based indices ( < 0.001). CH treatment was also associated with significant reductions in serum Nesfatin-1 ( = 0.000) and NUCB2 ( = 0.043) levels. At baseline, reduced food intake and sleep disturbances were negatively correlated with WAZ and LAZ, respectively. CONCLUSION: CH treatment significantly enhances weight gain and improves key anthropometric indices in young children with FTT and food allergy, potentially mediated by the downregulation of anorexigenic peptides Nesfatin-1 and NUCB2. These findings suggest that CH may be a promising pharmacotherapeutic option for this complex patient population.
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