Inflammopharmacology最新文献

{"title":"NSAID-encapsulated nanoparticles as a targeted therapeutic platform for modulating chronic inflammation and inhibiting cancer progression: a review.","authors":"Srivarshini Sankar, Bharathi Kalidass, Janani Indrakumar, Gothandam Kodiveri Muthukaliannan","doi":"10.1007/s10787-025-01760-8","DOIUrl":"https://doi.org/10.1007/s10787-025-01760-8","url":null,"abstract":"<p><p>Recent advancements in nanotechnology have significantly advanced nanocarrier-mediated drug delivery systems, promoting therapeutic outcomes in mitigating chronic inflammation and cancer. Nanomaterials offer significant advantages over traditional small-molecule drugs, including a high surface-area-to-volume ratio, tunable structural features, and extended bloodstream circulation time. Chronic inflammation is a well-established mechanism for malignant initiation, progression, and metastasis, promoting the potent strategy for cancer prevention and therapy. Numerous studies revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have the therapeutic ability to manage disease progression via amolerating angiogenesis and inducing apoptosis. However, prolonged intake of NSAIDs is often limited by adverse side-effects and systemic toxicities. The encapsulation of NSAIDs in a nanocarrier have materialized as a dynamic approach to mitigate the limitations by improving pharmacokinetics and pharmacodynamics, reducing off-target effects, and enhancing the drug stability. This review encompasses recent progress in the development of NSAID-based nanotherapeutics, focusing on pivotal mechanisms underlying nanoparticle-mediated drug delivery, such as improved tumor-specific targeting and strategies to overcome drug resistance. The ability of these nano-cargoes to accommodate anti-inflammatory strategies with advanced drug delivery platforms is critically evaluated. This review also highlights the transformative potential of NSAID-encapsulated nanoparticles as a multifaceted therapeutic venue for addressing chronic inflammation and mitigating cancer progression.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of TRPV1⁺ and TRPA1⁺ nociceptive neurons in delayed-onset muscle soreness: inhibition by hesperidin methyl chalcone.","authors":"Giovana B Cortez, Mariana M Bertozzi, Amanda M Dionisio, Maiara Piva, Nayara R Morelli, Thacyana T Carvalho, Rubia Casagrande, Waldiceu A Verri, Sergio M Borghi","doi":"10.1007/s10787-025-01762-6","DOIUrl":"https://doi.org/10.1007/s10787-025-01762-6","url":null,"abstract":"<p><strong>Objective: </strong>Delayed-onset muscle soreness (DOMS) is a type of pain caused by muscle injury provoked by eccentric, high intensity, or long-duration exercise. Hesperidin methyl chalcone (HMC) is a flavonoid with analgesic and anti-inflammatory actions. We investigated the effects of HMC against DOMS.</p><p><strong>Methods: </strong>Mice received AMG9810 (100 nmol) or HC-030031 (10 μg) once intrathecally, or HMC twice (12 h plus 30 min before) intraperitoneally (1, 3, or 10 mg/kg) and were subjected to a single uninterrupted acute swimming session of 120 min to induce DOMS. Sham animals were subjected to swimming just for 30 s, and naïve mice were not exposed to water. Calcium imaging of dorsal root ganglia (DRG) neurons was used to assess nociceptive neuron activation. Muscle mechanical hyperalgesia was assessed 12-48 h later. Oxidative parameters (superoxide anion, lipid peroxidation, and antioxidant activity) and leukocyte recruitment (macrophages and neutrophils) were evaluated 2 and 24 h later, respectively.</p><p><strong>Results: </strong>DRG neurons from mice that underwent intense acute swimming showed higher levels of calcium at 24 h post-session relative to naïve mice. Capsaicin [transient receptor potential vanilloid 1 (TRPV1 agonist)] or AITC [transient receptor potential ankyrin 1 (TRPA1 agonist)] were used as agonists controls to identify the populations of responsive neurons positive for TRPV1/A1. KCl was used as a cell viability control. Counterproof pharmacologic functional tests targeting TRPV1 or TRPA1 with receptor antagonists reduce muscle mechanical hyperalgesia and DRG neuron increased activity. HMC (3 mg/kg) reduced muscle mechanical hyperalgesia, activation of DRG nociceptive neurons at 24 h post-swimming session and upon TRPV1 or TRPA1 agonists and inhibited oxidative stress and the recruitment of neutrophils and macrophages to muscle in DOMS mice.</p><p><strong>Conclusions: </strong>Thus, HMC prevented DOMS in mice caused by unaccustomed exercise. The underlying mechanisms of HMC involve targeting oxidative stress, inflammation, and reduced activity of TRPV1⁺ and TRPA1⁺ nociceptive neurons.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143994595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cassia fistula fruit pulp extracts mitigate collagen-induced arthritis via regulation of oxidative stress and inflammation.","authors":"Aashcharya U Mishra, Sumati Sen, Mridula Sahu, Meenu Devi, Dewasya P Singh, Aakriti Gupta, Abhishek K Rai, Ratnasekhar Ch, Ashutosh K Shukla, Dnyaneshwar U Bawankule, Daya N Mani","doi":"10.1007/s10787-025-01753-7","DOIUrl":"https://doi.org/10.1007/s10787-025-01753-7","url":null,"abstract":"<p><strong>Background: </strong>Rheumatoid arthritis (RA) is an autoimmune inflammation disorder affecting the joints, it has a complex pathophysiology including inflammatory cells (macrophages, CD4 + T and B-cells), oxidative markers (ROS, NO, MDA, GSH, and catalase). Inflammation promoting cytokines IL-1β, TNF-α, IL6, IL-17, and CRP create a feedback loop and irreversibly damage joints. NSAIDs and DMARDs treatments have adverse effects demanding for safer treatment options.</p><p><strong>Purpose: </strong>The study aimed to validate the anti-arthritic efficacy of Cassia fistula fruit pulp extracts (aqueous, hydro-ethanolic, and ethanolic).</p><p><strong>Methods: </strong>Extracts were prepared and chemically characterized through LC-MS. Chrysophanol and rhein present in extracts were evaluated for anti-inflammatory and anti-oxidant potential on LPS stimulated RAW 264.7 cell line. Extracts were evaluated for in-vivo anti-inflammatory (cytokine estimation), anti-oxidant potential (estimating oxidative stress markers) and micro-structural changes (histopathology of knee and ankle) in collagen-induced arthritis.</p><p><strong>Results: </strong>In-vitro study revealed significant anti-inflammatory potential against IL-1β, IL-6, TNF-α and ROS determination showed strong anti-oxidant potential of chrysophanol and rhein at 10 μM. In-vivo studies revealed that ethanolic extract significantly inhibited IL-1β, TNF-α, IL-6, IL-17 production and reduced NO, MDA and augmented GSH, catalase levels significantly. Combined efficacy of ethanolic extract against inflammation, and oxidative stress thus, significantly reduced cellular infiltration, bone, cartilage damage and improved joint space in knee and ankle joints assessed through histopathology. Improved joint micro-structure ameliorated paw swelling, paw volume and disease score significantly. Thus, ethanolic extract of C. fistula fruit pulp may be an alternate or complementary treatment for managing RA.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144009466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voclosporin promotes neurological function recovery by inhibiting inflammation and maintaining blood-brain barrier integrity following rtPA reperfusion after MCAO in mice.","authors":"Yangmin Zheng, Shubei Ma, Wei Sun, Feng Yan, Yumin Luo","doi":"10.1007/s10787-025-01757-3","DOIUrl":"https://doi.org/10.1007/s10787-025-01757-3","url":null,"abstract":"<p><p>Hemorrhagic transformation (HT) is the most serious complication after rtPA thrombolytic therapy in patients with acute ischemic stroke, which greatly limits the clinical application of rtPA. rtPA disruption of the blood-brain barrier (BBB) by inducing inflammation after cerebral ischemia may be an important mechanism for the development of HT, and maintaining BBB integrity can significantly reduce the risk of HT. Our study found that a new generation of calcineurin inhibitors, voclosporin can improve neurological function, reduce neuronal damage, and reduce cerebral infarction volume in mice. By Evans blue extravasation assay and cerebral water content measurement, it was found that voclosporin could improve BBB injury and reduce brain edema caused by rt-PA. The ELISA and immunofluorescence experiments further proved that voclosporin can reduce the expression of IL-1β/TNF-α, increase the expression of IL-10/IL-4, and protect the integrity of the BBB by promoting microglia/macrophage to M2 type polarization, providing new thinking for clinical rtPA combined therapy to alleviate BBB damage.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143985152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tetrylpyamethrazine alleviates hepatic fibrosis induced by experimental mansonic schistosomiasis.","authors":"Ana Carolina Campos Dos Santos, Daniel Figueiredo-Vanzan, Josiane Bentes, Juliana Maria Motta, Hilton Antônio Mata-Santos, Alexandre Dos Santos Pyrrho, Morgana Teixeira Lima Castelo-Branco","doi":"10.1007/s10787-025-01759-1","DOIUrl":"https://doi.org/10.1007/s10787-025-01759-1","url":null,"abstract":"<p><p>Hepatic fibrosis resulting from human mansonic schistosomiasis significantly impairs liver function and contributes substantially to morbidity associated with helminth infections. This pathological state develops following the deposition of helminth eggs within hepatic tissues, triggering a granulomatous inflammatory reaction. Schistosomiasis, a neglected tropical disease affecting approximately 240 million individuals globally, represents a major public health challenge. Although praziquantel (PZQ) is recommended by the World Health Organization (WHO) as the primary treatment for helminth infections, additional therapies are required to address the associated liver fibrosis. This study investigated the efficacy of tetramethylpyrazine (TMP), a natural compound known for its anti-inflammatory, antifibrotic, and hepatoprotective properties in various experimental models, in mitigating hepatic fibrosis induced by mansonic schistosomiasis. Our in vivo experiments demonstrated that TMP treatment significantly reduced hepatic granuloma size, as evidenced by histological analysis. Furthermore, our in vitro studies showed that TMP increased levels of the anti-inflammatory cytokine IL-10 while decreasing levels of the profibrotic cytokine IL-13 in a concentration-dependent manner. Immunofluorescence analysis also revealed that TMP effectively inhibited collagen deposition. Collectively, these findings suggest that TMP exhibits potential as an anti-inflammatory and antifibrotic agent for hepatic fibrosis resulting from Schistosoma mansoni infection.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ocimene mitigates pyroptosis through TLR4/NLRP3-mediated mechanisms in CFA-induced inflammation.","authors":"Iqra Laraib, Sumera Qasim, Ambreen Malik Uttra, Shaimaa R Ahmed","doi":"10.1007/s10787-025-01756-4","DOIUrl":"https://doi.org/10.1007/s10787-025-01756-4","url":null,"abstract":"<p><p>The monocyclic monoterpenoid ocimene (OC) has undergone pharmacological testing as a possible inhibitor of pyroptosis triggered by TLR4/NLRP3 pathway, involved in progression of several diseases, such as rheumatoid arthritis (RA), inflammation, and chronic pain. Arthritis was evaluated using formaldehyde-induced arthritis rat model. Potential targets of OC against adjuvant-induced arthritis (AIA) in rats were examined using pharmacological testing and an integrative research strategy. CFA (o.1 ml) was used to assess the anti-arthritic effects of OC during a 28-day study period. To ascertain the therapeutic effects and identify pharmacological mechanisms, a variety of techniques were used, including macroscopic examination, gene expression profiling using PCR, an estimate of PGE-2, anti-CCP, 5-LOX besides markers of oxidative stress via ELISA, as well as radiographic examination. Oral administration of OC (50, 100, and 200 mg/kg) significantly (p < 0.001) decreased paw edema in the formaldehyde-induced arthritis. Inhibition of the NLRP3 inflammasome led to a significant downregulation of NFκB, caspase-1, and ASC, a decrease in the release of IL-1β and IL-18, and a modulation of GSDMD-mediated pyroptosis, hence reducing bone erosion and joint inflammation by blocking TLR4/NLRP3/GSDMD signaling. Levels of IL-4 and IL-10 were elevated in comparison to the disease control group. In addition, ELISA revealed that levels of the primary mediators of inflammation PGE-2 and 5-LOX, as well as malondialdehyde (MDA), a marker of oxidative stress, were significantly lower in the treated rats. In contrast, other antioxidant markers, such as glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD), were upregulated following the treatment. In addition, OC altered the actions of the COX enzyme, which reduced inflammation and eased RA-related discomfort. Therefore, it can be concluded that OC exhibited anti-arthritic attributes via modulation of TLR4/NLRP3/GSDMD signaling-mediated pyroptosis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multifaceted roles of melatonin in oncology: an insight into its therapeutic potential in cancer management.","authors":"Hossein Maghsoudi, Farhad Sheikhnia, Nooshin Hajmalek, Fatemeh Dadash Gholipour, Shahriar Alipour, Mansour Ghorbanpour, Sara Farzanegan, Seyed Mostafa Mir, Mohammad Yousef Memar","doi":"10.1007/s10787-025-01751-9","DOIUrl":"https://doi.org/10.1007/s10787-025-01751-9","url":null,"abstract":"<p><p>Cancer remains the leading cause of death worldwide. The treatment of cancer has become increasing complex. Current treatment options for cancer include surgical resection, chemotherapy, radiotherapy, nanomedicine, and immunotherapy. Recent experimental and clinical studies have provided substantial evidence supporting the potential use of melatonin as a preventive and therapeutic agent in oncology. Melatonin (N-acetyl-5-methoxy-tryptamine), a pleiotropic and multitasking molecule, is secreted from the pineal gland during the night under normal light-dark conditions. Beyond its role in circadian regulation, melatonin exhibits antioxidant, anti-aging, immunomodulatory, and anti-cancer properties. Melatonin exerts significant apoptotic, angiogenic, oncostatic, and anti-proliferative effects on a variety of cancer cells. This review discusses the influence of melatonin on cancer cells through mechanisms involving cell cycle regulation, stimulation of apoptosis, autophagy induction, epigenetic modification, and transcriptional regulation.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dose-dependent effects of omega-3 polyunsaturated fatty acids on C-reactive protein concentrations in cardiometabolic disorders: a dose-response meta-analysis of randomized clinical trials.","authors":"Manoochehr Amin Amlashi, Atefeh Payahoo, Saber Jafari Maskouni, Elaheh Dehghani, Mahtab Karami Talandashti, Yeganeh Ghelichi, Mahya Nikoumanesh, Soroush Rezvani, Hossein Shahinfar, Farzad Shidfar","doi":"10.1007/s10787-025-01744-8","DOIUrl":"https://doi.org/10.1007/s10787-025-01744-8","url":null,"abstract":"<p><strong>Background: </strong>Based on current knowledge, omega-3 fatty acids help to reduce the concentration of C-reactive protein (CRP). However, the dose-response effect and the strength of this effect are not entirely clear.</p><p><strong>Methods: </strong>We systematically searched and screened databases to include eligible studies. This study incorporates a random effect, as well as dose-response meta-analyses using a restricted cubic spline model.</p><p><strong>Results: </strong>Forty randomized clinical trials were analyzed. Results demonstrated significant non-linear dose-response efficacy in the reduction of CRP concentration in patients with cardiovascular disease, metabolic syndrome, and hypertension up to 1200 mg/day of EPA and DHA. In addition, there was a linear decrease in CRP concentration in the dyslipidemia population. The meta-analysis results did not show any significant reduction of CRP in overweight and obese participants, and the dose-response analysis failed to show any apparent reduction. In type 2 diabetes, pooling the results revealed a significant reduction in CRP; however, the combination of EPA and DHA failed to show significant dose-response efficacy in changing CRP concentration.</p><p><strong>Conclusion: </strong>1200 mg/day of EPA and DHA may help to reduce CRP concentration in patients with cardiometabolic disorders. This reduction is clinically significant, and thus intervention with omega-3 fatty acids should be considered for this population.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic potential of NLRP3 inhibitors in Parkinson's Disease: a systematic review of in-vivo studies.","authors":"Najwane Said Sadier, Inaam Ali Hazimeh, Walaa Khazaal, Amani Al Khayat Al Sabouri, Abdulmajeed G Almutary, Abdullah M Alnuqaydan, Linda Abou-Abbas","doi":"10.1007/s10787-025-01733-x","DOIUrl":"https://doi.org/10.1007/s10787-025-01733-x","url":null,"abstract":"<p><strong>Background: </strong>Parkinson's disease is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. Although the exact etiology is unknown, the nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome-induced inflammation, plays a crucial role in the pathogenesis of Parkinson's disease. Many NLRP3 inhibitors are recognized for their role as potential therapeutic interventions for Parkinson's disease.</p><p><strong>Methods: </strong>A systematic literature search was performed in PubMed, Embase, and Science Direct databases for papers published during the 10 years prior to May 2023. All animal interventional studies assessing the effects of NLRP3 inhibitors on Parkinson's disease animal models were included. Primary outcomes included NLRP3 inflammasome inhibition, microglial activation reduction, oxidative stress, and anti-inflammatory marker reduction. The secondary outcomes included dopaminergic neuron loss alleviation and behavioral motor function attenuation. Quality assessment and narrative synthesis of the studies were performed.</p><p><strong>Results: </strong>Twenty-four studies out of 796 papers initially identified met the inclusion criteria. All the included studies, except one, found a reduction in NLRP3 inflammasome activation and anti-inflammatory markers in Parkinson's disease animal models after treatment with various NLRP3 inhibitors compared to control groups without inhibitors. Additionally, eighteen out of twenty-four inhibitors decreased microglial activation and behavioral deficits. Moreover, ten inhibitors attenuated oxidative stress, and twenty-two out of twenty-four alleviated dopaminergic neuron loss. The inhibitors utilized different mechanisms and pathways to exert their effects, including the NLRP3/Caspase-1 pathway, the NF-κB/NLRP3 pathway, inhibition of ROS and/or pyroptosis, as well as autophagy and mitophagy.</p><p><strong>Conclusion: </strong>NLRP3 inhibitors represent a prospective therapy for Parkinson's disease, demonstrating efficacy in lowering neuroinflammation and protecting against dopaminergic loss. However, constraints, such as a male animal focus, apparent regional bias from China-centric studies, and diversity in induction models, entail the results presented herein require cautious interpretation. Further research, including preclinical and clinical studies, is required to thoroughly examine the safety, effectiveness, and generalizability of NLRP3 inhibitors in Parkinson's disease.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143991868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phytochemical analysis of leaf extract of Piper nigrum and investigation of its biological activities.","authors":"Pankaj Barman, Srija Hazarika, Kallol Roy, Ravindra K Rawal, Rituraj Konwar","doi":"10.1007/s10787-025-01701-5","DOIUrl":"https://doi.org/10.1007/s10787-025-01701-5","url":null,"abstract":"<p><strong>Background: </strong>This study investigates the phytoconstituents of the less explored leaf of Piper nigrum, a common ethnomedicinal plant as an alternate source for multiple bioactivities.</p><p><strong>Methods: </strong>Hydro-ethanolic (1:4) extract of Piper nigrum leaves (PNLE) prepared and profiled using liquid chromatography and mass spectrometry for identification of phytomolecules. Anti-oxidant activity, intracellular reactive oxygen species (ROS) expression, phagocytosis activity, and cytokine expression were estimated using cell-free and cell-based assays. Anti-cancer activity was determined with cancer cell viability, migration inhibition and colony-formation assay. Apoptosis and membrane depolarization assay were done using fluorescent microscopic staining methods while network pharmacology, and molecular docking analysis were done using open source and online tools.</p><p><strong>Results: </strong>Major phytomolecules identified in PNLE were pentanamide N,N-didecyl, piperettine, curcumin, myristicin, pipernonaline, sesamin, and lupenone. PNLE exhibited anti-bacterial activity with higher activity against Gram-positive bacteria, Staphylococcus aureus. PNLE also showed anti-oxidant and anti-inflammatory activity through neutralization of free radicals; inhibition of intracellular ROS generation; inhibition of phagocytosis and reduction of cytokine (IL-6 and TNF-α) levels. PNLE showed anti-proliferative activity against human breast cancer cells (MDA-MB-231), rat mammary tumor cells (LA7), and mouse melanoma cells (B16-F10) with highest activity against MDA-MB-231 cells. The extract did not inhibit human kidney cells (HEK-293). Further, PNLE treatment significantly inhibited cell migration and colony formation of MDA-MB-231 cells. Fluorescent staining techniques confirmed induction of apoptosis in cancer cells by PNLE. Further, network pharmacology and molecular docking studies revealed that the identified PNLE phytomolecules share 97 targets of out of potential breast cancer and inflammation-related target genes with four best common target proteins among the top hub genes and sesamin showed the highest binding affinity with these important cellular targets.</p><p><strong>Conclusions: </strong>Overall, the phytochemical profile of PNLE showed clear presence of important phytomolecules and their association with critical human cellular mechanistic pathways responsible for exhibited bioactivities. This study further establishes the leaf of P. nigrum as an additional anatomical plant part with potent medicinal properties and  as a potential renewable source for bioactive phyomolecules.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144020566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}