Pharmaceuticals (Basel, Switzerland)最新文献

{"title":"Flavonoids from <i>Piper</i> Species as Promising Antiprotozoal Agents against <i>Giardia intestinalis</i>. Structure-Activity Relationship and Drug-Likeness Studies.","authors":"Juan C Ticona,&nbsp;Pablo Bilbao-Ramos,&nbsp;Ángel Amesty,&nbsp;Ninoska Flores,&nbsp;M Auxiliadora Dea-Ayuela,&nbsp;Isabel L Bazzocchi,&nbsp;Ignacio A Jiménez","doi":"10.3390/ph15111386","DOIUrl":"https://doi.org/10.3390/ph15111386","url":null,"abstract":"<p><p>Diarrhea diseases caused by the intestinal protozoan parasite <i>Giardia intestinalis</i> are a major global health burden. Moreover, there is an ongoing need for novel anti-<i>Giardia</i> drugs due to drawbacks with currently available treatments. This paper reports on the isolation and structural elucidation of six new flavonoids (<b>1</b>-<b>6</b>), along with twenty-three known ones (<b>7</b>-2<b>9</b>) from the <i>Piper</i> species. Their structures were established by spectroscopic and spectrometric techniques. Flavonoids were tested for in vitro antiprotozoal activity against <i>Giardia intestinalis</i> trophozoites. In addition, structure-activity relationship (SAR) and in silico ADME studies were performed to understand the pharmacophore and pharmacokinetic properties of these natural compounds. Eight flavonoids from this series exhibited remarkable activity in the micromolar range. Moreover, compound <b>4</b> was identified as having a 40-fold greater antiparasitic effect (IC₅₀ 61.0 nM) than the clinical reference drug, metronidazole (IC₅₀ 2.5 µM). This antiprotozoal potency was coupled with an excellent selectivity index (SI 233) on murine macrophages and in silico drug-likeness. SAR studies revealed that the substitution patterns, type of functional group, and flavonoid skeleton played an essential role in the activity. These findings highlight flavonoid <b>4</b> as a promising candidate to develop new drugs for the treatment of <i>Giardia</i> infections.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9695682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40455670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Cytoskeleton, Protein Trafficking, and Signaling Pathways by Metabolites from <i>Cucurbitaceae</i>, <i>Ericaceae,</i> and <i>Rosaceae</i> Plant Families.","authors":"Ankit Patel,&nbsp;Aliyah Rasheed,&nbsp;Isiah Reilly,&nbsp;Zil Pareek,&nbsp;Mattia Hansen,&nbsp;Zayn Haque,&nbsp;Daniela Simon-Fajardo,&nbsp;Chloe Davies,&nbsp;Akash Tummala,&nbsp;Karlyn Reinhardt,&nbsp;Alexandria Bustabad,&nbsp;Maxwell Shaw,&nbsp;Jasmine Robins,&nbsp;Karolaent Vera Gomez,&nbsp;Thitisuda Suphakorn,&nbsp;Mariana Camacho Gemelgo,&nbsp;Ashley Law,&nbsp;Kristina Lin,&nbsp;Elizabeth Hospedales,&nbsp;Harrison Haley,&nbsp;Jean Pierre Perez Martinez,&nbsp;Saifullah Khan,&nbsp;Jessica DeCanio,&nbsp;Malcolm Padgett,&nbsp;Artem Abramov,&nbsp;Meera Nanjundan","doi":"10.3390/ph15111380","DOIUrl":"https://doi.org/10.3390/ph15111380","url":null,"abstract":"<p><p>One promising frontier within the field of Medical Botany is the study of the bioactivity of plant metabolites on human health. Although plant metabolites are metabolic byproducts that commonly regulate ecological interactions and biochemical processes in plant species, such metabolites also elicit profound effects on the cellular processes of human and other mammalian cells. In this regard, due to their potential as therapeutic agents for a variety of human diseases and induction of toxic cellular responses, further research advances are direly needed to fully understand the molecular mechanisms induced by these agents. Herein, we focus our investigation on metabolites from the <i>Cucurbitaceae, Ericaceae,</i> and <i>Rosaceae</i> plant families, for which several plant species are found within the state of Florida in Hillsborough County. Specifically, we compare the molecular mechanisms by which metabolites and/or plant extracts from these plant families modulate the cytoskeleton, protein trafficking, and cell signaling to mediate functional outcomes, as well as a discussion of current gaps in knowledge. Our efforts to lay the molecular groundwork in this broad manner hold promise in supporting future research efforts in pharmacology and drug discovery.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40455668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can Essential Oils Provide an Alternative Adjuvant Therapy for COVID-19 Infections and Pain Management at the Same Time?","authors":"Roxana Damiescu,&nbsp;David Y W Lee,&nbsp;Thomas Efferth","doi":"10.3390/ph15111387","DOIUrl":"https://doi.org/10.3390/ph15111387","url":null,"abstract":"<p><p>The active compounds from essential oils have been an important asset in treating different diseases for many centuries. Nowadays, there are various available formulations used as food supplements to stimulate the immune system. In light of the current pandemic and the large amount of fake news circulating the internet, it is important to analyze which of the active compounds from essential oils can be successfully used in the treatment of COVID-19 infections. We analyzed the current literature on the effects of essential oils against the new SARS-CoV-2 virus to gain a better understanding of the underlying mechanisms of these compounds and establish their possible antiviral efficacy. The available studies have highlighted the antiviral potential of active compounds from essential oils, indicating that they could be used as adjuvants in treating various viral infections, including COVID-19, leading to a milder course of the disease, and improving patients' outcomes. At the same time, these compounds relieve pain and lift the mood in comorbid patients suffering from opioid addiction. Essential oils might be useful as adjuvant tools, not only against SARS-CoV-2 but also for a subset of especially vulnerable patients affected with both COVID-19 and opioid addiction. However, randomized clinical trials are needed to determine their efficacy and develop standardized high-quality preparations that can be safely administered to the general population.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40455669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant Administration of Capecitabine and Folate Supplements: Need to Encourage Medication Reconciliation.","authors":"Berenice Stefanelli,&nbsp;Carmine Sellitto,&nbsp;Emanuela De Bellis,&nbsp;Martina Torsiello,&nbsp;Nicola Bertini,&nbsp;Angelo Maria Pezzullo,&nbsp;Graziamaria Corbi,&nbsp;Francesco Sabbatino,&nbsp;Stefano Pepe,&nbsp;Angela Tesse,&nbsp;Valeria Conti,&nbsp;Amelia Filippelli","doi":"10.3390/ph15111388","DOIUrl":"https://doi.org/10.3390/ph15111388","url":null,"abstract":"<p><p>Hand-Foot syndrome (HFS) and diarrhoea are dose-limiting Adverse Drug Reactions (ADRs) of capecitabine-based chemotherapy. Four polymorphisms in the <i>dihydropyrimidine dehydrogenase</i> (<i>DPYD</i>) gene, encoding the DPD enzyme responsible for the metabolism of fluoropyrimidines, such as capecitabine, are strongly associated with severe ADRs, and their screening should be performed before starting treatment. Moreover, capecitabine-related toxicity may worsen due to drug-drug and drug-supplement interactions. Here we investigated factors responsible for severe HFS and diarrhoea presented by two patients, non-carriers of the recommended <i>DPYD</i> single nucleotide polymorphisms (SNPs) but carriers of other genetic variants suggested to increase the risk of capecitabine-related ADRs. Through careful therapy recognition, we demonstrated that, unbeknownst to the oncologists, the patients were taking folic acid during the treatment with capecitabine at a dosage higher than 2000 mg/m², which is the maximum tolerated dose when folate is administered. To resolve the ADRs, the therapy had to be drastically changed. In one case, dose reduction of capecitabine and discontinuation of lipid-lowering agents were carried out. In the other case, discontinuation of capecitabine and folic acid and capecitabine re-administration were performed after a month. Genetic and environmental factors should be considered good predictors of severe capecitabine-related toxicity. Medication reconciliation should be encouraged to avoid the harmful consequences of inappropriate treatments.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9693983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40457678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alginate-Chitosan Hydrogel Formulations Sustain Baculovirus Delivery and VEGFA Expression Which Promotes Angiogenesis for Wound Dressing Applications.","authors":"Sabrina Schaly,&nbsp;Paromita Islam,&nbsp;Ahmed Abosalha,&nbsp;Jacqueline L Boyajian,&nbsp;Dominique Shum-Tim,&nbsp;Satya Prakash","doi":"10.3390/ph15111382","DOIUrl":"https://doi.org/10.3390/ph15111382","url":null,"abstract":"<p><p>Hydrogel wound dressings are effective in their ability to provide a wound-healing environment but are limited by their ability to promote later stages of revascularization. Here, a biosafe recombinant baculovirus expressing VEGFA tagged with EGFP is encapsulated in chitosan-coated alginate hydrogels using ionic cross-linking. The VEGFA, delivered by the baculovirus, significantly improves cell migration and angiogenesis to assist with the wound-healing process and revascularization. Moreover, the hydrogels have an encapsulation efficiency of 99.9%, no cytotoxicity, antimicrobial properties, good blood compatibility, promote hemostasis, and enable sustained delivery of baculoviruses over eight days. These hydrogels sustain baculovirus delivery and may have clinical implications in wound dressings or future gene therapy applications.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9698055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40455665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preparation of Transdermal Patch Containing Selenium Nanoparticles Loaded with Doxycycline and Evaluation of Skin Wound Healing in a Rat Model.","authors":"Dhiya Altememy,&nbsp;Moosa Javdani,&nbsp;Pegah Khosravian,&nbsp;Anita Khosravi,&nbsp;Elham Moghtadaei Khorasgani","doi":"10.3390/ph15111381","DOIUrl":"https://doi.org/10.3390/ph15111381","url":null,"abstract":"<p><p>The present study aimed to prepare and evaluate a controlled-release system based on a chitosan scaffold containing selenium nanoparticles loaded with doxycycline. Its topical application in skin wound healing in rats was investigated. Therefore, 80 female rats were used and, after creating experimental skin defects on their back, were randomly divided into four equal groups: the control group without any therapeutic intervention; the second group received a chitosan transdermal patch (Ch); the third group received chitosan transdermal patch loaded with selenium nanoparticles (ChSeN), and the last group received chitosan transdermal patch containing selenium nanoparticle loaded by doxycycline (ChSeND). Morphological and structural characteristics of the synthesized patches were evaluated, and in addition to measuring the skin wound area on days 3, 7, and 21, a histopathological examination was performed. On the third day of the study, less hemorrhage and inflammation and more neo-vascularization were seen in the ChSeND group. Moreover, on day 7, less inflammation and collagen formation were recorded in the ChSeN and ChSeND groups than in the other groups. At the same time, more neo-vascularization and re-epithelialization were seen in the ChSeND group on days 7 and 21. In addition, on day 21 of the study, the most collagen formation was in this group. Examination of the wound area also showed that the lowest area belonged to the ChSeND group. The results showed that the simultaneous presence of selenium nanoparticles and doxycycline in the ChSeND group provided the best repair compared to the control, Ch and ChSeN groups.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory Effects of an Aqueous Extract of Black Radish on Mouse Macrophages via the TLR2/4-Mediated Signaling Pathway.","authors":"Hyungsik Jeon,&nbsp;Soyeon Oh,&nbsp;Eunjoo Kum,&nbsp;Sooyeong Seo,&nbsp;Youngjun Park,&nbsp;Giok Kim","doi":"10.3390/ph15111376","DOIUrl":"https://doi.org/10.3390/ph15111376","url":null,"abstract":"<p><p>Here, we determined the immunostimulatory effects of black radish (<i>Raphanus sativus</i> ver niger) hot water extract (BRHE) on a mouse macrophage cell line (RAW 264.7) and mouse peritoneal macrophages. We found that BRHE treatment increased cell proliferation, phagocytic activity, nitric oxide (NO) levels, cytokine production, and reactive oxygen species synthesis. Moreover, BRHE increased the expression of the following immunomodulators in RAW 264.7 cells and peritoneal macrophages: pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), iNOS, and COX-2. BRHE treatment significantly up-regulated the phosphorylation of components of the mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), Akt, and STAT3 signaling pathways. Further, the effects of BRHE on macrophages were significantly diminished after the cells were treated with the TLR2 antagonist C29 or the TLR4 antagonist TAK-242. Therefore, BRHE-induced immunostimulatory phenotypes in mouse macrophages were reversed by multiple inhibitors, such as TLR antagonist, MAPK inhibitor, and Akt inhibitor indicating that BRHE induced macrophage activation through the TLR2/4-MAPK-NFκB-Akt-STAT3 signaling pathway. These results indicate that BRHE may serve as a potential immunomodulatory factor or functional food and provide the scientific basis for the comprehensive utilization and evaluation of black radish in future applications.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9697478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Danazol in Refractory Autoimmune Hemolytic Anemia or Immune Thrombocytopenia: A Case Series Report and Literature Review.","authors":"Hsu-En Huang,&nbsp;Ko-Ming Lin,&nbsp;Jing-Chi Lin,&nbsp;Yu-Ting Lin,&nbsp;Hsiao-Ru He,&nbsp;Yu-Wei Wang,&nbsp;Shan-Fu Yu,&nbsp;Jia-Feng Chen,&nbsp;Tien-Tsai Cheng","doi":"10.3390/ph15111377","DOIUrl":"https://doi.org/10.3390/ph15111377","url":null,"abstract":"<p><p>Danazol is a treatment option for autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). Three patients with AIHA and eight patients with ITP between 2008 and 2022 were enrolled in the Rheumatology Outpatient Clinic of Chang Gung Memorial Hospital, Kaohsiung. Those patients were refractory or intolerant to conventional therapy and were treated with danazol. All the patients received an initial dose of danazol (200-400 mg). The observation period was 6 months. Three patients (100%) with AIHA and six (75%) with ITP achieved treatment response after 6 months of danazol therapy. The dose of glucocorticoid for responders could be reduced to ≤5 mg/day of prednisolone, and the immunosuppressants, except hydroxychloroquine and azathioprine for systemic lupus erythematosus, could be discontinued. Adverse events were acne in two (18.2%) patients and transient dose-related liver function impairment in one (9.1%) patient in the current series. Danazol therapy appears to be a favorable alternative for refractory AIHA and ITP by altering the erythrocyte membrane to resist osmotic lysis and protecting platelets against complement-mediated lysis. In this report, we also performed a literature review and searched the PubMed/Cochrane Library for articles published from 1984 to January 2022 on danazol therapy for patients with AIHA and ITP.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9692819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological Properties of <i>Jaeumgeonbi-Tang</i> on Redox System and Stress-Related Hormones in Chronic Subjective Dizziness: A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Trial.","authors":"Chan-Young Kim,&nbsp;Hyeong-Geug Kim,&nbsp;Hye Won Lee,&nbsp;In-Chan Seol,&nbsp;Yoon-Sik Kim,&nbsp;Hyung Il Choi,&nbsp;Miso S Park,&nbsp;Ho-Ryong Yoo","doi":"10.3390/ph15111375","DOIUrl":"https://doi.org/10.3390/ph15111375","url":null,"abstract":"<p><p><i>Jaeumgeonbi-Tang</i> (JGT), a traditional herbal medicine, has been used to treat dizziness and vertigo in Korea and China for hundreds of years. The purpose of this study was to evaluate the pharmacological properties of JGT in chronic subjective dizziness (CSD) patients. A randomized, double-blind, parallel-group and placebo-controlled trial was performed with a total of 50 CSD patients. The patients were randomly assigned to one of two groups: JGT or placebo (<i>n</i> = 25 for each). All participants received the treatment (placebo or JGT, 24 g/day) for 4 weeks. We analyzed the serum levels of oxidative stressors, antioxidants, and stress hormones. Serum levels of lipid peroxidation, but not nitric oxide, were significantly decreased in the JGT group. JGT not only prevented the decline of serum total glutathione contents and total antioxidant capacity, but it also increased superoxide dismutase and catalase activities. Serum levels of stress hormones including cortisol, adrenaline, and serotonin were notably normalized by JGT treatment, but noradrenaline levels were not affected. Regarding the safety and tolerability of JGT, we found no allergic, adverse, or side effects in any of the participants. JGT showed beneficial effects on CSD patients by improving redox status and balancing psycho-emotional stress hormones.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9696700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"2-Butoxytetrahydrofuran and Palmitic Acid from <i>Holothuria scabra</i> Enhance <i>C. elegans</i> Lifespan and Healthspan via DAF-16/FOXO and SKN-1/NRF2 Signaling Pathways.","authors":"Prapaporn Jattujan,&nbsp;Sirin Srisirirung,&nbsp;Warisra Watcharaporn,&nbsp;Kawita Chumphoochai,&nbsp;Pichnaree Kraokaew,&nbsp;Tanatcha Sanguanphun,&nbsp;Prachayaporn Prasertsuksri,&nbsp;Salinthip Thongdechsri,&nbsp;Prasert Sobhon,&nbsp;Krai Meemon","doi":"10.3390/ph15111374","DOIUrl":"https://doi.org/10.3390/ph15111374","url":null,"abstract":"<p><p>Extracts from a sea cucumber, <i>Holothuria scabra</i>, have been shown to exhibit various pharmacological properties including anti-oxidation, anti-aging, anti-cancer, and anti-neurodegeneration. Furthermore, certain purified compounds from <i>H. scabra</i> displayed neuroprotective effects against Parkinson's and Alzheimer's diseases. Therefore, in the present study, we further examined the anti-aging activity of purified <i>H. scabra</i> compounds in a <i>Caenorhabditis elegans</i> model. Five compounds were isolated from ethyl acetate and butanol fractions of the body wall of <i>H. scabra</i> and characterized as diterpene glycosides (holothuria A and B), palmitic acid, bis (2-ethylhexyl) phthalate (DEHP), and 2-butoxytetrahydrofuran (2-BTHF). Longevity assays revealed that 2-BTHF and palmitic acid could significantly extend lifespan of wild type <i>C. elegans</i>. Moreover, 2-BTHF and palmitic acid were able to enhance resistance to paraquat-induced oxidative stress and thermal stress. By testing the compounds' effects on longevity pathways, it was shown that 2-BTHF and palmitic acid could not extend lifespans of <i>daf-16</i>, <i>age-1</i>, <i>sir-2.1</i>, <i>jnk-1</i>, and <i>skn-1</i> mutant worms, indicating that these compounds exerted their actions through these genes in extending the lifespan of <i>C. elegans</i>. These compounds induced DAF-16::GFP nuclear translocation and upregulated the expressions of <i>daf-16</i>, <i>hsp-16.2</i>, <i>sod-3</i> mRNA and SOD-3::GFP. Moreover, they also elevated protein and mRNA expressions of GST-4, which is a downstream target of the SKN-1 transcription factor. Taken together, the study demonstrated the anti-aging activities of 2-BTHF and palmitic acid from <i>H. scabra</i> were mediated via DAF-16/FOXO insulin/IGF and SKN-1/NRF2 signaling pathways.</p>","PeriodicalId":520747,"journal":{"name":"Pharmaceuticals (Basel, Switzerland)","volume":" ","pages":""},"PeriodicalIF":4.6,"publicationDate":"2022-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9699485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40464712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}