Inflammopharmacology最新文献

{"title":"Esculin-loaded nanoparticles ameliorate adjuvant-induced polyarthritis via subduing inflammatory and oxidative stress biomarkers in Wistar rats.","authors":"Mehak Fatima, Ammara Saleem, Muhammad Furqan Akhtar, Kanwal Akhtar, Muhammad Imran Khan","doi":"10.1007/s10787-024-01621-w","DOIUrl":"https://doi.org/10.1007/s10787-024-01621-w","url":null,"abstract":"<p><p>Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed. ENPs were synthesized using the ion gelation method and their characterization was done. The formulated ENPs had a particle size of 205.1 nm, a polydispersity index of 0.574, zeta potential of 3.6 ± 0.1 mV, and entrapment efficiency of 68%, SEM analysis showed round spherical and irregularity from the outer surface, XRD revealed amorphous nature. Drug release from the carrier by erosion method. For anti-arthritic potential, 0.1 ml Complete Freund's Adjuvant was injected in the left hind paw of all Wistar rats except normal rats on day 1 and treatment with ENPS at 5, 10, 20, ESC and methotrexate (standard drug) was started at 8th day orally and continued for 21 days. Treatment with methotrexate, ESC, and ENPs revealed a significant reduction of paw edema and pain, restoration of body and immune organ weight, Treatment with ENPs 20 mg/kg remarkably (p < 0.0001) restored serotonin and noradrenaline level, oxidation status, hematological and biochemical parameters with significant down-regulation (p < 0.0001) of IL-6, COX-2, TNF-alpha, NF-κβ whereas, up-regulation of IL-4 and IL-10 in comparison to disease control group as obvious from histological examination of sciatic nerve, liver, and ankle joint. The LD₅₀ of ENPs was more than 2000 mg/kg in the acute toxicity study. The ENPs exhibited anti-inflammatory and anti-arthritic activities especially ENPs at 20 mg/kg.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894234","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":"Down-regulation of interlinked inflammatory signalling cascades by ethanolic extract of Suaeda fruticosa Forssk. ex J.F. Gmel. attenuated in vivo inflammatory and nociceptive responses.","authors":"Muhammad Fiaz, Mohamed Farouk Elsadek, Khalid S Al-Numair, Shafqat Rasul Chaudhry, Mohammad Saleem, Kashif Ur Rehman Khan, Ashwaq Hamid Salem Yehya, Muhammad Asif","doi":"10.1007/s10787-024-01624-7","DOIUrl":"https://doi.org/10.1007/s10787-024-01624-7","url":null,"abstract":"<p><p>Juice and decoction of leaves of Suaeda fruticosa, a halophytic medicinal plant of Cholistan desert, is traditionally used to treat rheumatism. The current study was carried out to probe into in vivo anti-nociceptive, anti-inflammatory, and anti-arthritic potential of ethanolic extract of the whole plant of S. fruticosa (Et-SF) and its bioactive molecules. GC-MS screening of Et-SF revealed presence of various bioactive compounds including phytol, thymol, n-hexadecanoic acid, farnesol, and 1-heptacosanol. DPPH in vitro radical scavenging assay demonstrated moderate antioxidant potential of Et-SF. Safety evaluation of Et-SF confirmed no lethal effects in female albino rats up to the single oral dose of 5000 mg/kg. In  all in vivo models, Et-SF was administered in three doses (125, 250, and 500 mg/kg) and a single dose of flurbiprofen (FP) (10 mg/kg). Et-SF significantly (p < 0.05) attenuated acute inflammation in carrageenan, histamine, and serotonin-induced rat paw oedema models in a time-dependent manner. Et-SF alleviated oedema, restored haematological parameters, and reduced severe pannus formation, inflammatory cell infiltration, and fibrous tissue proliferation in the paws of CFA-induced arthritic rats. Moreover, treatment with thymol, farnesol and n-hexadecanoic acid alone and in combination also attenuated the arthritic progression in the arthritic rats indicating involvement of these compounds towards anti-arthritic potential of Et-SF. Et-SF and FP significantly (p < 0.05) down-regulated IL-1β, TNF-α, IL-6, NF-κB, and COX-2 mRNA expression, and up-regulated IL-4 and IL-10 mRNA expression in arthritic rats. Hot plate and acetic acid-induced writhing models results indicated the analgesic attributes of Et-SF in mice models. This study suggests that S. fruticosa ethanol extract may regulate the expression of inflammatory markers involved in nociceptive, inflammatory, and arthritic disorders. Its phytochemicals could target multiple phases of these conditions at cellular and subcellular levels. Further research is needed to confirm this hypothesis.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894232","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":"Mechanisms and clinical applications of palmitoylethanolamide (PEA) in the treatment of neuropathic pain.","authors":"Ardra Das, Preetha Balakrishnan","doi":"10.1007/s10787-024-01623-8","DOIUrl":"https://doi.org/10.1007/s10787-024-01623-8","url":null,"abstract":"<p><p>Palmitoylethanolamide (PEA) is emerging as a promising therapeutic agent for neuropathic and other pain-related conditions. This naturally occurring fatty acid has drawn interest because of its ability to regulate pain and inflammation. Initially identified in food sources, PEA has been the subject of extensive research to elucidate its properties, efficacy, and clinical applications. PEA primarily exerts its effects through interaction with its primary receptor PPAR α, this interaction influences pain signalling pathways and neuroinflammatory processes by modulating the synthesis of pro-inflammatory cytokines, mast cell degranulation, microglial activation, and decrease of oxidative stress. PEA's interaction with endocannabinoid receptors decreases the inflammatory cytokine and chemokine production and thereby a descending pain sensation. The pharmacological and pharmacokinetic characteristics of PEA are examined in this paper, along with its potential for efficiency when used in in combination additional therapies in a variety of neurodegenerative disease models, including multiple sclerosis, Parkinson's disease, and Alzheimer's. Experimental evidence shows that PEA not only reduces pain and inflammation but also lowers the need for higher dosages of other drugs hence minimizing the risk of drug toxicity. The bioavailability of PEA has been enhanced by recent technological developments, which emphasize continuous research efforts to maximize PEA's therapeutic potential in pain treatment and associated medical sectors.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876955","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":"Across-the-board review on Omicron SARS-CoV-2 variant.","authors":"Rufaida Wasim, Sumaiya, Asad Ahmad","doi":"10.1007/s10787-024-01627-4","DOIUrl":"https://doi.org/10.1007/s10787-024-01627-4","url":null,"abstract":"<p><strong>Introduction: </strong>Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has resulted in a cataclysmic pandemic. Several SARS-CoV-2 mutations have been found and reported since the COVID-19 pandemic began. After the Alpha, Beta, Gamma, and Delta variants, the Omicron (B.1.1.529) is the most recently emerged variant of concern (VOC), which has evolved as a result of a high number of mutations, particularly in the spike protein, raising concerns about its ability to evade pre-existing immunity acquired through vaccination or natural infection.</p><p><strong>Methods: </strong>This is a review based on studies published from November 2021 to September 2024.</p><p><strong>Result and discussions: </strong>The current article discusses the advent of the SARS-CoV-2 Omicron variant, its key characteristics and significant global health concerns, as well as measures for dealing with it in the context of the continuing COVID-19 pandemic. Various mutations in Omicron have been discussed that contribute to increased transmissibility and immune evasion from vaccine-induced or natural immunity acquired after infection. To understand the similarities and differences between different VOCs and Omicron, we conducted a comparative investigation.</p><p><strong>Conclusion: </strong>Strengthening research, improving genomic surveillance and tracking, developing highly effective vaccines and immunotherapies, designing appropriate strategies, action plans, and future preparedness plans must all be prioritized and implemented quickly at global levels to mitigate the high global health concerns associated with the emergence of this new Omicron variant well before it causes large-scale COVID-19 outbreaks.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876925","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":"Berberine in rheumatoid arthritis: a comprehensive review and meta-analysis of its anti-inflammatory and immunomodulatory mechanisms in animal models.","authors":"Muhammad Muzammil Nazir, Iqra Farzeen, Shahla Fasial, Asma Ashraf","doi":"10.1007/s10787-024-01612-x","DOIUrl":"https://doi.org/10.1007/s10787-024-01612-x","url":null,"abstract":"<p><p>Berberine (BBR), an alkaloid derivative mostly found in Oregon grapes and barberry shoots, has several medical properties, including anti-microbial, anti-tumorigenic, and anti-inflammatory properties. As such, it is a superior alternative to presently recommended medications. From previous researches, which showed that BBR has anti-arthritic qualities by blocking a number of inflammatory signalling pathways. Furthermore, it has been demonstrated that BBR attenuates Beclin-1, which reduces autophagy-mediated survival of mature adipocytes. BBR has also been identified as an AhR inducer and a promoter of Treg differentiation. Berberine has been shown in earlier studies to be useful in treating rheumatoid arthritis (RA) in animal models. The pharmacological effects and possible action pathway of Berberine were evaluated in this study. We looked through three databases-PubMed, Web of Science, and Google Scholar-for pertinent research published from the time the databases were created and August 2024. This risk-of-bias measure was used to evaluate the methodological quality. Utilising RevMan 5.4, the statistical analysis was conducted. There were 12 studies in this research with 175 animals. The findings showed that Berberine lowers the levels of IL-1β, IL-17, IL-6, IL-10, and TNF-α), paw swelling, and histopathological scores. These connected to the anti-inflammatory, anti-oxidative stress, and osteoprotective qualities of berberine. Nonetheless, further superior animal research is required to evaluate berberine impact on rheumatoid arthritis (RA). Additionally, more research is needed to validate berberine safety. Considering the significance of the active component, further research is needed to determine the best dose and increase berberine bioavailability.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142876953","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":"Examining the role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease: a comprehensive review.","authors":"Mahmood Jawad, Subasini Uthirapathy, Farag M A Altalbawy, Enwa Felix Oghenemaro, Jasur Rizaev, Madan Lal, Mamdouh Eldesoqui, Naveen Sharma, Atreyi Pramanik, Ahmed Khudhair Al-Hamairy","doi":"10.1007/s10787-024-01622-9","DOIUrl":"https://doi.org/10.1007/s10787-024-01622-9","url":null,"abstract":"<p><p>Alzheimer's disease is a devastating neurodegenerative disorder that affects millions of people worldwide. One of the key pathological features of Alzheimer's disease is oxidative stress, which is characterized by an imbalance between the production of reactive oxygen species and the body's ability to neutralize them with antioxidants. In recent years, there has been growing interest in the potential role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease. This review paper aims to provide a comprehensive overview of the current research on antioxidant supplementation in Alzheimer's disease and its effects on oxidative stress markers. The paper will examine the underlying mechanisms of oxidative stress in Alzheimer's disease, the potential benefits of antioxidant supplementation, and the challenges and limitations of using antioxidants as a therapeutic strategy.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854060","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":"Carvone-loaded chitosan nanoparticles alleviate joint destruction by downregulating the expression of pro, inflammatory cytokines and MMP-13 in adjuvant-induced rat model.","authors":"Zartashia Kanwal, Bushra Akhtar, Bilal Aslam, Muhammad Imran Arshad","doi":"10.1007/s10787-024-01618-5","DOIUrl":"https://doi.org/10.1007/s10787-024-01618-5","url":null,"abstract":"<p><p>Rheumatoid arthritis is an autoimmune illness causing deformity, edema, and joint tenderness. Its long-term treatment burdens the healthcare system and leads to toxicity, and thus, finding safe, effective, and affordable therapies is essential. The current study aimed to exhibit the anti-arthritic activity of Carvone-loaded chitosan nanoparticles to treat Freund's complete adjuvant (FCA) arthritis in rats. Healthy albino rats (n = 35) were distributed into seven groups. The 1st group worked as normal control, while the 2nd was arthritic control. The 3rd group received methotrexate (10 mg/kg/week). The 4th group received Carvone (60 mg/kg/day), while the 5th (30 mg/kg/day), 6th (45 mg/kg/day), and 7th (60 mg/kg/day) groups received Carvone-C-NPs, respectively. Nanoparticles, prepared by the ion gelation method, were characterized by zeta size, potential, scanning electron microscopy, and Fourier transform infrared microscopy. NPs have zeta size (78.82 ± 0.02 nm) and potential (19.96 ± 0.02 mV). A significant reduction was shown in paw swelling (5.52 ± 0.05 mm), arthritic score (2.81 ± 0.23), and rheumatoid factor (14.56 ± 0.68 IU/L) by Carvone-C-NPs. qRT-PCR results showed significant down-regulation of pro-inflammatory cytokines [TNF-α (0.25 ± 0.03), IL-1β (0.21 ± 0.06), IL-17a (0.16 ± 0.12), and IL-33 (0.15 ± 0.01)] and up-regulation of anti-inflammatory cytokines [IL-4 (0.85 ± 0.06) and IL-10 (0.66 ± 0.04)] in ankle joint of Carvone-C-NPs treated group. The radiographical and histopathological findings showed reduced pannus formation, joint swelling, and synovial hyperplasia in the Carvone-C-NPs treated group. Overall, it is concluded that Carvone-C-NPs have remarkable anti-arthritic activity and promising anti-inflammatory properties.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846624","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":"Epidural injection of varying doses of capsaicin alleviates inflammatory pain in rats via the TLR4/AKT/NF-κB pathway.","authors":"Si Ri Gu Leng Sana, Chuanbao Lv, Shasha Yu, Xijin Deng, Yingwei Dong","doi":"10.1007/s10787-024-01617-6","DOIUrl":"https://doi.org/10.1007/s10787-024-01617-6","url":null,"abstract":"<p><strong>Background: </strong>Capsaicin (CAP) induces transient pain sensation by activating transient receptor potential vanilloid-1 (TRPV1). However, the initial neuronal excitation induced by CAP is followed by a prolonged refractory period, resulting in long-lasting analgesia. Although the effects of CAP on microglia in the dorsal root ganglion of neuropathic pain disorders have been reported, the regulatory pathways of CAP on microglia remain poorly defined.</p><p><strong>Methods: </strong>A chronic pain model was established via plantar injection of complete Freund's adjuvant (CFA), and different doses of CAP were administered to rats. Pain behavior, expression of pain-related factors, protein expression of TRPV1 in nerve cells, and the inflammatory activation of microglia were evaluated. In vitro experiments were conducted to explore the activation and migration ability of microglia, expression of inflammatory cytokines and pathway proteins, TRPV1 expression in nerve cells, and intracellular calcium concentration under different doses of CAP.</p><p><strong>Results: </strong>Different doses of CAP alleviated chronic pain in rats, reduced TRPV1 expression in nerve cells, and inhibited the activation of microglia; however, high doses of CAP were particularly effective in improving chronic pain. In vitro experiments confirmed that CAP reduces the secretion of inflammatory cytokines by microglia via inhibition of the TLR4/AKT/NF-κB signaling pathway. This mechanism reduced the injury and apoptosis of nerve cells, the expression of TRPV1, and the influx of calcium ions in nerve cells.</p><p><strong>Conclusions: </strong>CAP reduced inflammatory responses in microglia in a dose-dependent manner by inhibiting the TLR4/AKT/NF-κB signaling pathway, which consequently reduced TRPV1 expression on neuronal cells and reduced chronic pain.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142845934","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":"Anti-inflammatory effect of nestorone in a lipopolysaccharide-induced acute lung injury model through regulation of the TLR-4/Myd88/NF-κB signaling pathway.","authors":"Aying Ma, Jieyun Zhou, Hui Zou, Li Yuan, Ruihua Zhong, Yan Zhu, Chao Gao","doi":"10.1007/s10787-024-01625-6","DOIUrl":"https://doi.org/10.1007/s10787-024-01625-6","url":null,"abstract":"<p><p>Progesterone plays a crucial and indispensable role in regulating immunity and attenuating inflammation. Nestorone^® (NES, segesterone acetate) is a steroidal progestin and a 19-norprogesterone derivative with no -CH₃ group radical at the 6-position. Here, we showed that NES enhanced the viability of lipopolysaccharide (LPS)-stimulated THP-1 cell-derived macrophages, potently inhibiting both arms of the Toll-like receptor 4 (TLR-4) signaling cascade triggered by LPS, especially the TLR-4/MyD88/NF-κB pathway. In addition, NES exerted an anti-inflammatory effect by significantly decreasing the secretion of inflammatory cytokines and chemokines in type II alveolar epithelial A549 cells and THP-1 cell-derived macrophages stimulated by LPS. Furthermore, we evaluated the potential of NES pre-treatment, administered 2 h prior to LPS exposure, to mitigate acute lung injury induced by LPS, using an LPS-induced acute lung injury (ALI) mouse model. In this study, NES alleviated lung inflammation and damage by reducing leukocyte infiltration and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) and lung tissues of mice. Interestingly, our findings indicate that NES at a dosage of 1 mg/kg (91.67%) was more effective than at dosages of 0.1 mg/kg (70.83%) or 10 mg/kg (87.50%), as well as more effective than dexamethasone (DEX, 5 mg/kg, 83.34%), in extending survival in mice subjected to lethal LPS-induced injury. Additionally, this dosage was more successful in reducing acute lung inflammation and alleviating diffuse alveolar damage in the lungs of C57 mice. Our study indicates that concentration is a critical determinant of the anti-inflammatory efficacy of NES. Consequently, NES emerges as a potentially promising therapeutic agent for the treatment of pulmonary inflammatory conditions through the modulation of TLR-4 signaling pathways.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846623","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":"Mechanisms of action of ethyl acetate fractions of Liparis nervosa (Thunb.) Lindl. as potential central anti-nociceptive agents.","authors":"Jiachuan Li, Hu Hu, Xin Xu, Dan Zhu, Yisheng Chen, Laiming Li","doi":"10.1007/s10787-024-01620-x","DOIUrl":"https://doi.org/10.1007/s10787-024-01620-x","url":null,"abstract":"<p><p>Opioids/non-steroidal anti-inflammatory drugs are used to alleviate pain; however, they are expensive and can have adverse effects, especially when used over extended periods. Therefore, there is immense demand for innovative, non-addictive analgesics. Here, we report a novel plant-derived central anti-nociceptive agent, Liparis nervosa (Thunb.) Lindl. (LN), validated in animal pain models. Ethyl acetate fractions of L. nervosa (EALN) exhibited central anti-nociceptive activity in hot plate, tail immersion, formalin-induced paw oedema, and acetic acid-induced abdominal writhing tests. The chemical composition of the EALN was determined using ultra-high-performance liquid chromatography-mass spectrometry. Reserpine (monoamine transmitter-depleting agent) and naltrexone (opioid antagonist) partially suppressed the anti-nociceptive effect of EALN in both phases of the formalin test. Oral administration of EALN activated the endogenous opioid and central descending inhibitory systems by increasing β-endorphin, 5-hydroxytryptamine, and norepinephrine expression. EALN treatment increased the expression of γ-aminobutyric acid B; inhibited the expression of prostaglandin E2, substance P, calcitonin gene-related peptide, and c-Fos; and blocked the transmission of pain signals in the spinal cord. EALN treatment reduced the activity of nitric oxide and nitric oxide synthase in the central region and inhibited the nitric oxide-cyclic guanosine monophosphate signal transduction pathway, thereby attenuating the transmission of nociceptive information in the descending inhibitory pathways. The central anti-nociceptive effect of EALN was achieved by integrating these pathways. This study provides new insights into the pharmacologic action of LN and provide a therapeutic approach as a promising candidate for central anti-nociceptive agents.</p>","PeriodicalId":13551,"journal":{"name":"Inflammopharmacology","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142835614","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}