Archives of Pharmacal Research最新文献

{"title":"Anti-osteoporosis effects of triterpenoids from the fruit of sea buckthorn (Hippophae rhamnoides) through the promotion of osteoblast differentiation in mesenchymal stem cells, C3H10T1/2","authors":"Da Eun Lee,&nbsp;Kun Hee Park,&nbsp;Joo-Hyun Hong,&nbsp;Seon Hee Kim,&nbsp;Ki-Moon Park,&nbsp;Ki Hyun Kim","doi":"10.1007/s12272-023-01468-9","DOIUrl":"10.1007/s12272-023-01468-9","url":null,"abstract":"<div><p>In a previous study, we discovered that the ethanolic extract of sea buckthorn (<i>Hippophae rhamnoides</i>) fruits exhibited anti-osteoporosis effects both in vitro and in vivo. Through bioassay-guided fractionation, we identified the hexane fraction (HRH) as the active fraction, which was further fractionated using preparative HPLC. Among the resulting six fractions, HRHF4 showed significant activity. In the present study, we focused on the bioassay-guided isolation of bioactive compounds from the HRHF4 fraction. We successfully identified the active HRHF43 fraction, which led us to the isolation of potential bioactive compounds (<b>1–6</b>). The chemical structures of these compounds were determined using NMR data, LC-MS analysis, and HR-ESI-MS data as four triterpenes, ursolic acid (<b>1</b>), uvaol (<b>2</b>), oleanolic aldehyde (<b>3</b>), and ursolic aldehyde (<b>4</b>), together with two fatty acids, methyl linoleate (<b>5</b>) and ethyl oleate (<b>6</b>). To evaluate the efficacy of promoting osteoblast differentiation and the expression of mRNA biomarkers related to osteogenesis, we tested the isolated compounds in the mouse mesenchymal stem cell line, C3H10T1/2. Alkaline phosphate staining demonstrated that triterpenes (<b>1–4</b>) displayed osteogenic activity. Particularly noteworthy, ursolic aldehyde (<b>4</b>) exhibited the most potent effect, showing an 11.2-fold higher activity at a concentration of 10 μg/mL compared to the negative control. Moreover, ursolic aldehyde (<b>4</b>) upregulated the gene expression of bone formation-related biomarkers, including Runx2, Osterix, Alp, and Osteopontin. These findings suggest that the fruit extract of <i>H. rhamnoides</i> may have potential as a nutraceutical for promoting bone health, with ursolic aldehyde (<b>4</b>) identified as an active constituent.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"771 - 781"},"PeriodicalIF":6.7,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 mitochondrial dysfunction in diseases: from powerhouses to saboteurs","authors":"Surapriya Surendranath Prabhu,&nbsp;Aathira Sujathan Nair,&nbsp;Saiprabha Vijayakumar Nirmala","doi":"10.1007/s12272-023-01465-y","DOIUrl":"10.1007/s12272-023-01465-y","url":null,"abstract":"<div><p>The fact that mitochondria play a crucial part in energy generation has led to the nickname “powerhouses” of the cell being applied to them. They also play a significant role in many other cellular functions, including calcium signalling, apoptosis, and the creation of vital biomolecules. As a result, cellular function and health as a whole can be significantly impacted by mitochondrial malfunction. Indeed, malignancies frequently have increased levels of mitochondrial biogenesis and quality control. Adverse selection exists for harmful mitochondrial genome mutations, even though certain malignancies include modifications in the nuclear-encoded tricarboxylic acid cycle enzymes that generate carcinogenic metabolites. Since rare human cancers with mutated mitochondrial genomes are often benign, removing mitochondrial DNA reduces carcinogenesis. Therefore, targeting mitochondria offers therapeutic options since they serve several functions and are crucial to developing malignant tumors. Here, we discuss the various steps involved in the mechanism of cancer for which mitochondria plays a significant role, as well as the role of mitochondria in diseases other than cancer. It is crucial to understand mitochondrial malfunction to target these organelles for therapeutic reasons. This highlights the significance of investigating mitochondrial dysfunction in cancer and other disease research.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"723 - 743"},"PeriodicalIF":6.7,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41096445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review on pharmacological effects of gastrodin","authors":"Guirong Xiao,&nbsp;Rong Tang,&nbsp;Nan Yang,&nbsp;Yanhua Chen","doi":"10.1007/s12272-023-01463-0","DOIUrl":"10.1007/s12272-023-01463-0","url":null,"abstract":"<div><p><i>Gastrodia elata</i> Blume is a well-known traditional Chinese medicine that is mainly used to treat diseases related to the nervous system, such as stroke, epilepsy, and headache. Gastrodin is the main bioactive component of <i>Gastrodia elata</i> Blume, and studies have shown that it has extensive pharmacological activity. This narrative review aims to systematically review relevant studies on the pharmacological effects of gastrodin to provide researchers with the latest and most useful information. Studies have shown that gastrodin has prominent neuroprotective effects and can treat or improve epilepsy, Tourette syndrome, Alzheimer’s disease, Parkinson’s disease, emotional disorders, cerebral ischemia-reperfusion injury, cognitive impairment, and neuropathic pain. Gastrodin can also improve myocardial hypertrophy, hypertension, and myocardial ischemia-reperfusion injury. In addition, gastrodin can mitigate liver, kidney, and bone tissue damage caused by oxidative stress and inflammation. In short, gastrodin is expected to treat many diseases, and it is worth investing more effort in research on this compound.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 9-10","pages":"744 - 770"},"PeriodicalIF":6.7,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41106272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperoside attenuates pyrrolizidine alkaloids-induced liver injury by ameliorating TFEB-mediated mitochondrial dysfunction","authors":"Jie Xu,&nbsp;Aizhen Xiong,&nbsp;Xunjiang Wang,&nbsp;Xing Yan,&nbsp;Yilin Chen,&nbsp;Xuanling Ye,&nbsp;Zhengtao Wang,&nbsp;Lili Ding,&nbsp;Li Yang","doi":"10.1007/s12272-023-01460-3","DOIUrl":"10.1007/s12272-023-01460-3","url":null,"abstract":"<div><p>Pyrrolizidine alkaloids (PAs) are potent hepatotoxins that can cause liver damage. Hyperoside (Hyp), a natural flavonoid, can be extracted from medicinal plants. Hyp displays hepatoprotective activity in various liver diseases. However, the potential effect and mechanism of action of Hyp in ameliorating PA-induced liver injury remain obscure. This study aimed to explore the protective effect of Hyp against PA-induced hepatotoxicity and its underlying mechanism. We established an in vitro model of PAs in mouse primary hepatocytes and developed a mouse model of acute PA toxicity to investigate the protective effect of Hyp. We found that Hyp notably attenuated PA-induced hepatotoxicity. RNA-sequencing showed that the beneficial effect of Hyp against PA-induced hepatotoxicity was associated with the transcription factor EB (TFEB)-peroxisome proliferator-activated receptor-γ coactivator-1-α (PGC1α) pathway. Our results confirmed that both the autophagy-lysosomal pathway and mitochondrial biogenesis were induced by Hyp through TFEB nuclear translocation in PA-induced liver injury. Furthermore, we demonstrated that activation of the mechanistic target of rapamycin complex 1 (mTORC1) by MHY 1485 decreased TFEB nuclear translocation and abrogated the protective effect of Hyp against PA-induced liver injury in mice. In contrast, inhibition of mTORC1 activity increased the level of TFEB and reduced hepatotoxicity induced by PAs in mouse livers. Likewise, Hyp-induced TFEB activation was validated in vitro. In conclusion, Hyp can activate the TFEB-mediated autophagy-lysosomal pathway and mitochondrial biogenesis through inhibition of mTORC1 activity, alleviating the liver injury induced by PAs, thus suggesting the potential value of Hyp in the treatment of PA-induced hepatotoxicity.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"694 - 712"},"PeriodicalIF":6.7,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41102997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of CYP2D6 and CYP2C19 genetic polymorphisms and cigarette smoking on the pharmacokinetics of tolperisone","authors":"Ji-Young Byeon,&nbsp;Chang‑Keun Cho,&nbsp;Pureum Kang,&nbsp;Se-Hyung Kim,&nbsp;Choon-Gon Jang,&nbsp;Seok-Yong Lee,&nbsp;Yun Jeong Lee","doi":"10.1007/s12272-023-01462-1","DOIUrl":"10.1007/s12272-023-01462-1","url":null,"abstract":"<div><p>Tolperisone, a muscle relaxant used for post-stroke spasticity, is metabolized to its main metabolite by CYP2D6 and to a lesser extent by CYP2C19 and CYP1A2. We investigated the effects of <i>CYP2D6</i> and <i>CYP2C19</i> genetic polymorphisms and cigarette smoking on tolperisone pharmacokinetics. A 150 mg oral dose of tolperisone was given to 184 healthy Korean subjects and plasma concentrations of tolperisone were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A 3.14-fold significant increase in AUC_0–∞ was observed in the <i>CYP2D6*10/*10</i> group compared with the <i>CYP2D6*wt/*wt</i> group, whereas a 3.59-fold increase in AUC_0–∞ was observed in CYP2C19PMs compared to CYP2C19EMs. Smokers had a 38.5% decrease in AUC_0–∞ when compared to non-smokers. When these effects were combined, <i>CYP2D6*10/*10</i>-CYP2C19PM-Non-smokers had a 25.9-fold increase in AUC_0–∞ compared to <i>CYP2D6*wt/*wt</i>-CYP2C19EM-Smokers. Genetic polymorphisms of <i>CYP2D6</i> and <i>CYP2C19</i> and cigarette smoking independently and significantly affected tolperisone pharmacokinetics and these effects combined resulted in a much greater impact on tolperisone pharmacokinetics.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"713 - 721"},"PeriodicalIF":6.7,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41098822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Androgen receptor and hyaluronan-mediated motility receptor as new molecular targets of baicalein: new molecular mechanisms for its anticancer properties","authors":"Mingyue Jiang,&nbsp;Suman Poudel,&nbsp;Kyung Song","doi":"10.1007/s12272-023-01461-2","DOIUrl":"10.1007/s12272-023-01461-2","url":null,"abstract":"<div><p>Natural compounds known as phytochemicals have served as valuable resources for the development of new anti-cancer drugs and treatment of malignancies. Among these phytochemicals, baicalein is an emerging anti-tumor flavonoid obtained from <i>Scutellaria baicaleinsis</i> (Lamiaceae), but its underlying mechanisms of action and molecular targets have not yet been completely elucidated. Here, we identified new mechanisms for the anti-tumor activities of baicalein, providing evidence that hyaluronan-mediated motility receptor (HMMR) and androgen receptor (AR) are new molecular targets of baicalein in human cancer cells. We observed that HMMR, known to be highly associated with poor prognosis in a wide range of human cancers, was substantially downregulated by baicalein at mRNA and protein levels. Reporter assays further revealed that the suppression of HMMR by baicalein might occur through a transcriptional regulatory mechanism with the participation of Egr-1, E2F3α, and serum response factor (SRF). We also found that baicalein significantly inhibits androgenic responses in hormone-responsive prostate cancer cells, indicating that this might be attributed to the downregulation of AR promoter activity by baicalein. Additionally, baicalein markedly induced the expression of tumor suppressive miR-30C, which might be partly involved in baicalein-mediated autophagy and anti-cancer effects. Overall, our study sheds light on new diverse mechanisms of the anti-cancer effects exhibited by baicalein, implying that baicalein could be a potential therapeutic agent against human cancers and function as an inhibitor of HMMR and AR.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"679 - 693"},"PeriodicalIF":6.7,"publicationDate":"2023-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10199766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Au–Ag bimetallic nanoparticles using Korean red ginseng (Panax ginseng Meyer) root extract for chemo-photothermal anticancer therapy","authors":"Gayeon Lee,&nbsp;You Jeong Lee,&nbsp;Yeon-Jeong Kim,&nbsp;Youmie Park","doi":"10.1007/s12272-023-01457-y","DOIUrl":"10.1007/s12272-023-01457-y","url":null,"abstract":"<div><p>Green synthesis strategies have been widely applied for the preparation of versatile nanomaterials. Gold nanospheres with an average size of 6.95 ± 2.25 nm were green synthesized by using a 70% ethanol extract of Korean red ginseng (<i>Panax ginseng</i> Meyer) root as a reducing agent. A seed-mediated synthesis was conducted to prepare Au–Ag bimetallic nanoparticles using gold nanospheres as seeds. Remarkably, Au–Ag bimetallic nanoparticles with an average size of 80.4 ± 11.9 nm were synthesized. Scanning transmission electron microscopy, energy dispersive X-ray spectroscopy and elemental mappings revealed bimetallic nanoparticles with Au–Ag alloy core and Au-rich shells. A face-centered cubic structure of Au–Ag bimetallic nanoparticles was confirmed by X-ray diffraction analysis. For Au–Ag bimetallic nanoparticles, the ratio of Ag/Au was 0.20 which was detected and analyzed by inductively coupled plasma-mass spectrometry. Gold nanospheres and Au–Ag bimetallic nanoparticles were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Finally, docetaxel was loaded for evaluating the in vitro cell viability on cancer cells. Successful functionalization was confirmed by Fourier-transform infrared spectra. The anticancer activity of the docetaxel-loaded nanoparticles was higher than that of their non-docetaxel-loaded counterparts. The highest anticancer activity on human gastric adenocarcinoma cells (AGS) was observed in the docetaxel-loaded gold nanospheres that were functionalized by PEGylation, folic acid conjugation and grafting onto graphene oxide. Additionally, grafting onto graphene oxide and docetaxel loading induced high intracellular reactive oxygen species generation. For chemo-photothermal (PTT) anticancer therapy, cell viability was investigated using near-infrared laser irradiation at 808 nm. The highest chemo-PTT anticancer activity on AGS cells was observed in the docetaxel-loaded Au–Ag bimetallic nanoparticles. Therefore, the newly prepared docetaxel-loaded Au–Ag bimetallic nanoparticles in the current report have potential applications in chemo-PTT anticancer therapy.\u0000</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 8","pages":"659 - 678"},"PeriodicalIF":6.7,"publicationDate":"2023-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01457-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10023622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilization of RNA G-quadruplexes in the SARS-CoV-2 genome inhibits viral infection via translational suppression","authors":"Maria Razzaq,&nbsp;Ji Ho Han,&nbsp;Subramaniyam Ravichandran,&nbsp;Jaehyun Kim,&nbsp;Joon-Yong Bae,&nbsp;Man-Seong Park,&nbsp;Shrute Kannappan,&nbsp;Woo-Chang Chung,&nbsp;Jin-Hyun Ahn,&nbsp;Moon Jung Song,&nbsp;Kyeong Kyu Kim","doi":"10.1007/s12272-023-01458-x","DOIUrl":"10.1007/s12272-023-01458-x","url":null,"abstract":"<div><p>The G-quadruplex (G4) formed in single-stranded DNAs or RNAs plays a key role in diverse biological processes and is considered as a potential antiviral target. In the genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 25 putative G4-forming sequences are predicted; however, the effects of G4-binding ligands on SARS-CoV-2 replication have not been studied in the context of viral infection. In this study, we investigated whether G4-ligands suppressed SARS-CoV-2 replication and whether their antiviral activity involved stabilization of viral RNA G4s and suppression of viral gene expression. We found that pyridostatin (PDS) suppressed viral gene expression and genome replication as effectively as the RNA polymerase inhibitor remdesivir. Biophysical analyses revealed that the 25 predicted G4s in the SARS-CoV-2 genome formed a parallel G4 structure. In particular, G4-644 and G4-3467 located in the 5′ region of ORF1a, formed a G4 structure that could be effectively stabilized by PDS. We also showed that PDS significantly suppressed translation of the reporter genes containing these G4s. Taken together, our results demonstrate that stabilization of RNA G4s by PDS in the SARS-CoV-2 genome inhibits viral infection via translational suppression, highlighting the therapeutic potential of G4-ligands in SARS-CoV-2 infection.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"598 - 615"},"PeriodicalIF":6.7,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin–proteasome system as a target for anticancer treatment—an update","authors":"Yeon Jung Kim,&nbsp;Yeonjoo Lee,&nbsp;Hyungkyung Shin,&nbsp;SuA Hwang,&nbsp;Jinyoung Park,&nbsp;Eun Joo Song","doi":"10.1007/s12272-023-01455-0","DOIUrl":"10.1007/s12272-023-01455-0","url":null,"abstract":"<div><p>As the ubiquitin–proteasome system (UPS) regulates almost every biological process, the dysregulation or aberrant expression of the UPS components causes many pathological disorders, including cancers. To find a novel target for anticancer therapy, the UPS has been an active area of research since the FDA’s first approval of a proteasome inhibitor bortezomib in 2003 for treating multiple myeloma (MM). Here, we summarize newly described UPS components, including E3 ubiquitin ligases, deubiquitinases (DUBs), and immunoproteasome, whose malfunction leads to tumorigenesis and whose inhibitors have been investigated in clinical trials as anticancer therapy since 2020. We explain the mechanism and effects of several inhibitors in depth to better comprehend the advantages of targeting UPS components for cancer treatment. In addition, we describe attempts to overcome resistance and limited efficacy of some launched proteasome inhibitors, as well as an emerging PROTAC-based tool targeting UPS components for anticancer therapy. </p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"573 - 597"},"PeriodicalIF":6.7,"publicationDate":"2023-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12272-023-01455-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10030468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals","authors":"Le Zhang,&nbsp;Yuxing Wang,&nbsp;Dayong Wang","doi":"10.1007/s12272-023-01459-w","DOIUrl":"10.1007/s12272-023-01459-w","url":null,"abstract":"<div><p>Paeoniflorin is the major active compound of total glycoside of paeony in <i>Paeonia lactiflora</i> Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in <i>Caenorhabditis elegans</i> induced by <i>Pseudomonas aeruginosa</i> infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of <i>P. aeruginosa</i> infected nematodes at the immunosuppression stage could be significantly increased by 25–100 mg/L paeoniflorin treatment. <i>P. aeruginosa</i> accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of <i>bar-1</i>, <i>pmk-1</i>, and <i>egl-1</i> inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the <i>P. aeruginosa</i> accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (<i>lys-1</i> and <i>lys-8</i>) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.</p></div>","PeriodicalId":8287,"journal":{"name":"Archives of Pharmacal Research","volume":"46 7","pages":"616 - 628"},"PeriodicalIF":6.7,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10405702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}