Drug Design, Development and Therapy最新文献

{"title":"Intraoperative Non-Opiate Anesthesia for Patients Undergoing Arthroscopic Temporomandibular Joint Surgery: A Randomized Controlled Trial.","authors":"He Ma, Juan Perez, Julia Bertsch, Marissa L Albanese, Elizabeth G Korn, Ariel Mueller, Timothy Houle, Briana June Burris, Joseph McCain, Jingping Wang","doi":"10.2147/DDDT.S486134","DOIUrl":"10.2147/DDDT.S486134","url":null,"abstract":"<p><strong>Background: </strong>Pain intensity after temporomandibular joint (TMJ) surgery is often underestimated, and inadequate pain control may relate to poor recovery quality, increased opioid consumption, and longer hospital stay. This trial aims to evaluate whether non-opiate anesthesia provides a promising option of pain management for patients undergoing TMJ surgery.</p><p><strong>Methods: </strong>Sixty patients receiving TMJ surgery were randomly assigned to either the control group or the non-opiate group. Non-opiate anesthesia used lidocaine, dexmedetomidine, and ketamine infusion therapy for pain management. The primary outcome was the highest documented pain score while in the post-anesthesia care unit (PACU). Secondary outcomes included perioperative opioid consumption, utilization, dosage, and timing of rescue analgesia in the PACU, incidence of postoperative nausea and vomiting in the PACU and at home, pain satisfaction levels, occurrence of opioid-related adverse effects, duration of PACU and hospital stays, and total consumption of oxycodone-acetaminophen tablets at 24 and 48 hours post-surgery.</p><p><strong>Results: </strong>Patients were predominantly female (88.3%) and had a median age of 37.5 [IQR 26.0, 52.5] years. There were no significant differences observed in the highest documented pain scores (mean difference [MD] -0.36 points, 95% CI: -1.84, 1.12, p = 0.63), postoperative oxycodone-acetaminophen consumption (MD 6.68 mg, 95% CI: -2.48, 15.84, p = 0.15), pain satisfaction (odds ratio [OR] 0.81, 95% CI: 0.23, 2.81, p = 0.74), time to PACU discharge (hazard ratio [HR] 1.24, 95% CI: 0.67, 2.30, p = 0.49) or time to hospital discharge (HR 1.48, 95% CI: 0.80, 2.75, p = 0.21) between the two groups. Similarly, no significant difference was observed in time to rescue analgesia, calculated in minutes from the end of surgery (HR 1.69, 95% CI: 0.79, 3.61, p = 0.18).</p><p><strong>Conclusion: </strong>Non-opiate anesthesia for pain management shows a similar postoperative analgesia effect, compared to opioid-based anesthesia, in patients undergoing arthroscopic TMJ surgery.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4915-4925"},"PeriodicalIF":4.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11546274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Review of Microneedle Technology for Targeted Therapeutics in Vitiligo: Design Principles, Application Prospects.","authors":"Yihui Yu, Wei Li, Qian Li, Wenyan Liu, Sanquan Zhang, Xibao Zhang, Jingyao Liang","doi":"10.2147/DDDT.S449381","DOIUrl":"https://doi.org/10.2147/DDDT.S449381","url":null,"abstract":"<p><p>Vitiligo is a chronic autoimmune disorder characterized by depigmented patches of the skin. The treatment of vitiligo remains challenging, partly owing to the lack of efficient drug delivery system. Microneedles (MNs), an ideal transdermal drug delivery system, have emerged as promising drug delivery platform for vitiligo. Recently, the emergence of novel MNs with increased biocompatibility, including hydrogel and hollow MNs, further enhance the translational value of MNs in the treatment of vitiligo. However, up-to-date review of these advancements remains lacking. This review aims to summarize the most recent studies of MN-based drug delivery systems for vitiligo, highlighting the translational potential of MNs as a therapeutic platform for the treatment of vitiligo in the near future.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4901-4914"},"PeriodicalIF":4.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Detection of <i>SLCO1B1</i> Polymorphisms Using Duplex Fluorescence Melting Curve Analysis: Implications for Personalized Drug Dosing in Clinical Settings.","authors":"Zhikang Yu, Zifang Shang, Qingyan Huang, Heming Wu, Sandip Patil","doi":"10.2147/DDDT.S491972","DOIUrl":"https://doi.org/10.2147/DDDT.S491972","url":null,"abstract":"<p><strong>Objective: </strong>The polymorphism of the solute carrier organic anion transporter family member <i>1B1 (SLCO1B1)</i> gene exerts a marked influence on drug transport, thus playing a pivotal role in personalized drug dosing. This study endeavours to establish a rapid, precise, and straightforward method for detecting <i>SLCO1B1</i> genetic variants utilizing Duplex Fluorescence Melting Curve Analysis (DFMCA).</p><p><strong>Methods: </strong>Whole blood samples were collected from 54 individuals from Meizhou People's Hospital (2023.01-2023.03), with a mean age of 58.90 years (SD = 7.86), including 28 men and 26 women. DNA was extracted from these samples and subjected to PCR amplification targeting two allelic regions. Primers, fluorescent probes, and corresponding allelic target sequences were designed specifically for two common <i>SLCO1B1</i> polymorphisms (rs2306283 and rs4149056). The functionality of the fluorescent probes in binding to their respective allelic targets was verified using melting curve analysis, enabling the identification of distinct melting temperatures for different genotypes. Subsequently, DFMCA was employed to differentiate genotypes based on the melting temperature shifts of the corresponding fluorescent probes. The sensitivity, accuracy, and consistency of the method were evaluated, with sequencing validation performed on a subset of samples.</p><p><strong>Results: </strong>DFMCA facilitated the concurrent detection and accurate genotyping of both polymorphisms within 2 hours, demonstrating concordance with sequencing results from randomly selected samples. Importantly, stable detection performance was achieved for human genomic DNA at concentrations ≥ 3.125 ng. In a cohort comprising Han Chinese individuals from southern China, the allele frequencies for rs2306283 (A: 28.7%, G: 71.3%) and rs4149056 (T: 88.89%, C: 11.11%) concurred well with previous studies in the Han Chinese population.</p><p><strong>Conclusion: </strong>The SNP typing system utilizing DFMCA technology presents advantages in terms of speed, ease of use, accuracy, and cost-effectiveness, making it a suitable tool.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4889-4899"},"PeriodicalIF":4.7,"publicationDate":"2024-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Rapid and Simple HPLC-MS/MS Method for the Quantitative Determination of Colistin for Therapeutic Drug Monitoring in Clinical Practice.","authors":"Na Zhang, Yiran Xu, Beibei Liang, Jinru Zeng, Rui Wang, Yun Cai","doi":"10.2147/DDDT.S479329","DOIUrl":"10.2147/DDDT.S479329","url":null,"abstract":"<p><p>Colistin is the last-line option for the treatment of multidrug-resistant gram-negative bacterial infections with narrow therapeutic window. It is essential to ensure its efficacy and safety by therapeutic drug monitoring (TDM). Quantitative determination of colistin is difficult due to its complex ingredients. Previous determination methods demand intricate sample pre-treatment which are not only time-consuming but also costly, and is difficult to apply in clinical practice. Therefore, in order to carry out quantitative determination of colistin accurately and quickly, we establish a rapid high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) with simple sample pre-treatment process. The sample was purified by acetonitrile to remove the plasma protein. Then purified colistin was effectively separated from terfenadine, an internal standard (IS) using Phenomenex Kinetex C18 column (50.0×2.1mm, 5µm) with acetonitrile and water mobile phase at a flow rate of 0.5 mL/min and 40°C column temperature. Colistin and IS were monitored in positive ion mode. Our method expressed good linearity in 50.0~6000 ng/mL of colistin B and 28.31~3397.51 ng/mL of colistin A in plasma. Methodology validations, including selectivity, precision, accuracy, recovery, stability, matrix effect, and dilution integrity met acceptance criteria of <i>Bioanalytical Method Validation (M10)</i> of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH).</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4877-4887"},"PeriodicalIF":4.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537190/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Metabolomics and Network Pharmacology Study on the Mechanism of <i>Rehmanniae radix</i> Extract for Treating Thrombosis.","authors":"Hongling Du, Shunjie Zhang, Kezhu Yuan, Zhirui Yang, Mingquan Wu","doi":"10.2147/DDDT.S475838","DOIUrl":"10.2147/DDDT.S475838","url":null,"abstract":"<p><strong>Background: </strong><i>Rehmanniae Radix</i> (RR) has received attention for its antithrombotic effect. However, few studies have independently explored the bioactive components responsible for its antithrombotic bioactivity and the potential mechanism. We aimed to reveal the antithrombotic mechanisms of RR by using metabolomics integrated with network pharmacology.</p><p><strong>Methods: </strong>A thrombosis model was established by intraperitoneal injection of type I carrageenan in rats, and antithrombotic function was evaluated at different doses of RR. Metabolomics was used to identify the differential metabolites in the serum. Network pharmacology was then applied to identify the potential targets for the antithrombotic activity of the RR. An integrated network of metabolomics and network pharmacology was constructed using Cytoscape. Finally, key targets were verified using molecular docking.</p><p><strong>Results: </strong>RR at 5.4 g/kg significantly alleviated the thrombosis. Thirteen potentially significant metabolites were involved in the therapeutic effects of RR against thrombosis, most of which were regulated for recovery after RR treatment. An integrated analysis of metabolomics and network pharmacology showed that the antithrombosis effect of RR was closely associated with the regulation of PLA2G2A, PTGS1, ALOX5, and CYP2C9. Molecular docking showed high affinity between the key targets and components of RR. We speculated that the components of RR, such as catalpol, ferulic acid methyl ester, and methyl 4-hydroxycinnamate, might act on key proteins, including PLA2G2A, PTGS1, and ALOX5, to exert antithrombosis effects.</p><p><strong>Conclusion: </strong>This study confirmed the antithrombotic effect of high-dose RR, revealed the antithrombotic mechanism and potential material basis, and laid the foundation for the antithrombotic clinical application of RR. Furthermore, it provides a successful case reference for screening natural herbal components and exploring their potential pharmacological mechanisms.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4859-4875"},"PeriodicalIF":4.7,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11533886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rb1 Alleviates DSS-Induced Ulcerative Colitis by Protecting the Intestinal Barrier Through the Signal Network of VDR, PPARγ and NF-κB.","authors":"Yi Zhou, Xinyu Xiong, Zhe Cheng, Zekai Chen, Shizhen Wu, Yan Yu, Yujin Liu, Guang Chen, Lingli Li","doi":"10.2147/DDDT.S481769","DOIUrl":"10.2147/DDDT.S481769","url":null,"abstract":"<p><strong>Purpose: </strong>Ginseng (<i>Panax ginseng</i> Meyer) is an herbal medicine used in traditional Chinese medicine (TCM), has the effects of treating colitis and other diseases. Ginsenoside Rb1 (GRb1), a major component of ginseng, modulates autoimmunity and metabolism. However, the mechanism underlying GRb1 treatment of ulcerative colitis (UC) has not yet been elucidated. UC is a refractory inflammatory bowel disease (IBD) with a high recurrence rate, and researches on new drugs for UC have been in the spotlight for a long time.</p><p><strong>Methods: </strong>Mice with DSS-induced UC were treated with GRb1 or 0.9% saline for 10 days. Colon tissue of UC mice was collected to detect the levels of intestinal inflammatory cytokines and integrity of the intestinal barrier. RNA-seq and network pharmacology were used to predict the therapeutic targets of GRb1 during UC treatment.</p><p><strong>Results: </strong>GRb1 treatment alleviated intestinal inflammation and improved intestinal barrier dysfunction in UC mice. Specifically, GRb1 downregulated the levels of pro-inflammatory cytokines such as TNF-α and IL-6, while upregulating the level of the anti-inflammatory cytokine IL-10. Additionally, GRb1 treatment increased the levels of tight junction proteins including ZO-1, Occludin, and E-cadherin, which are crucial for maintaining intestinal barrier integrity. Further analyses using RNA-seq and network pharmacology suggested that these effects might involve the regulation of GRb1 in the signal transduction network of VDR, PPARγ, and NF-κB.</p><p><strong>Conclusion: </strong>The study demonstrated that GRb1 effectively alleviated UC by modulating intestinal inflammation and protecting the integrity of the intestinal barrier through the signal transduction network of VDR, PPARγ, and NF-κB.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4825-4838"},"PeriodicalIF":4.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Culprit Behind HBV-Infected Hepatocytes: NTCP.","authors":"Shenghao Li, Liyuan Hao, Jiali Deng, Junli Zhang, Fei Yu, Fanghang Ye, Na Li, Xiaoyu Hu","doi":"10.2147/DDDT.S480151","DOIUrl":"10.2147/DDDT.S480151","url":null,"abstract":"<p><p>Hepatitis B virus (HBV) is a globally prevalent human DNA virus responsible for over 250 million cases of chronic liver infections, leading to conditions such as liver inflammation, cirrhosis and hepatocellular carcinoma (HCC). Sodium taurocholate co-transporting polypeptide (NTCP) is a transmembrane protein highly expressed in human hepatocytes and functions as a bile acid (BA) transporter. NTCP has been identified as the receptor that HBV and its satellite virus, hepatitis delta virus (HDV), use to enter hepatocytes. HBV entry into hepatocytes is tightly regulated by various signaling pathways, and NTCP plays an important role as the initial stage of HBV infection. NTCP acts as an initiation signal, causing metabolic changes in hepatocytes and facilitating the entry of HBV into hepatocytes. Thus, a comprehensive understanding of NTCP's role is crucial. In this review, we will examine the regulatory mechanisms governing HBV pre-S1 binding to liver membrane NTCP, the role of NTCP in HBV internalization, and the transcriptional and translational regulation of NTCP expression. Additionally, we will discuss clinical drugs targeting NTCP, including combination therapies involving NTCP inhibitors, and consider the safety of NTCP as a therapeutic target.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4839-4858"},"PeriodicalIF":4.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11529284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topical hADSCs-HA Gel Promotes Skin Regeneration and Angiogenesis in Pressure Ulcers by Paracrine Activating PPARβ/δ Pathway.","authors":"Chaoying Jin, Ruolin Zhao, Weihang Hu, Xiaolong Wu, Li Zhou, Letian Shan, Huiling Wu","doi":"10.2147/DDDT.S474628","DOIUrl":"10.2147/DDDT.S474628","url":null,"abstract":"<p><strong>Background: </strong>Pressure ulcer is common in the bedridden elderly with high mortality and lack of effective treatment. In this study, human-adipose-derived-stem-cells-hyaluronic acid gel (hADSCs-HA gel) was developed and applied topically to treat pressure ulcers, of which efficacy and paracrine mechanisms were investigated through in vivo and in vitro experiments.</p><p><strong>Methods: </strong>Pressure ulcers were established on the backs of C57BL/6 mice and treated topically with hADSCs-HA gel, hADSCs, hyaluronic acid, and normal saline respectively. The rate of wound closure was observed continuously during the following 14 days and the wound samples were obtained for Western blot, histopathology, immunohistochemistry, and proteomic analysis. Human dermal fibroblasts (HDFs) and human venous endothelial cells (HUVECs) under normal or hypoxic conditions were treated with conditioned medium of human ADSCs (ADSC-CM), then CCK-8, scratch test, tube formation, and Western blot were conducted to evaluate the paracrine effects of hADSCs and to explore the underlying mechanism.</p><p><strong>Results: </strong>The in vivo data demonstrated that hADSCs-HA gel significantly accelerated the healing of pressure ulcers by enhancing collagen expression, angiogenesis, and skin proliferation. The in vitro data revealed that hADSCs strengthened the proliferation and wound healing capabilities of HDFs and HUVECs, meanwhile promoted collagen secretion and tube formation through paracrine mode. ADSC-CM was also proved to exert protective effects on hypoxic HDFs and HUVECs. Besides, the results of proteomic analysis and Western blot elucidated that lipid metabolism and PPARβ/δ pathway mediated the healing effect of hADSCs-HA gel on pressure ulcers.</p><p><strong>Conclusion: </strong>Our research showed that topical application of hADSCs-HA gel played an important role in dermal regeneration and angiogenesis. Therefore, hADSCs-HA gel exhibited the potential as a novel stem-cell-based therapeutic strategy of treating pressure ulcers in clinical practices.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4799-4824"},"PeriodicalIF":4.7,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bu Shen Huo Xue Formula Provides Neuroprotection Against Spinal Cord Injury by Inhibiting Oxidative Stress by Activating the Nrf2 Signaling Pathway.","authors":"Dan Luo, Yonghui Hou, Jiheng Zhan, Yu Hou, Zenglu Wang, Xing Li, Lili Sui, Shudong Chen, Dingkun Lin","doi":"10.2147/DDDT.S487307","DOIUrl":"10.2147/DDDT.S487307","url":null,"abstract":"<p><strong>Purpose: </strong>Spinal cord injury (SCI) is an irreversible neurological disease that can result in severe neurological dysfunction. The Bu Shen Huo Xue Formula (BSHXF) has been clinically shown to assist in the recovery of limb function in patients with SCI. However, the underlying mechanisms of BSHXF's therapeutic effects remain unclear. This study aimed to evaluate the effects of BSHXF in a mouse model of SCI and to identify potential therapeutic targets.</p><p><strong>Methods: </strong>The composition of BSHXF was analyzed using high-performance liquid chromatography (HPLC). In vivo, SCI was induced in mice following established protocols, followed by administration of BSHXF. Motor function was assessed using the Basso-Beattie-Bresnahan (BBB) and footprint tests. Levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were quantified with specific assay kits. Protein expression analysis was performed using Western blot and immunofluorescence. Additionally, reactive oxygen species (ROS) levels and apoptosis rates were evaluated with dedicated staining kits. In vitro, neurons were exposed to lipopolysaccharide (LPS) to investigate the effects of BSHXF on neuronal oxidative stress. The protective effects of BSHXF against LPS-induced neuronal injury were examined through RT-PCR, Western blot, and immunofluorescence.</p><p><strong>Results: </strong>The eight primary bioactive constituents of BSHXF were identified using HPLC. BSHXF significantly reduced tissue damage and enhanced functional recovery following SCI. Meanwhile, BSHXF treatment led to significant reductions in oxidative stress and apoptosis rates. It also reversed neuronal loss and reduced glial scarring after SCI. LPS exposure induced neuronal apoptosis and axonal degeneration; however, after intervention with BSHXF, neuronal damage was reduced, and the protective effects of BSHXF were mediated by the activation of the Nrf2 pathway.</p><p><strong>Conclusion: </strong>BSHXF decreased tissue damage and enhanced functional recovery after SCI by protecting neurons against oxidative stress and apoptosis. The effects of BSHXF on SCI may be related to the activation of the Nrf2 pathway.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4779-4797"},"PeriodicalIF":4.7,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nephroprotective Activity of <i>Angelica keiskei</i> (Miq). Koidz. on Cisplatin-Induced Rats: Reducing Serum Creatinine, Urea Nitrogen, KIM-1, and Suppressing NF-kappaB p65 and COX-2.","authors":"Ika Wahyuni, Diah Lia Aulifa, Aziiz Mardanarian Rosdianto, Jutti Levita","doi":"10.2147/DDDT.S481479","DOIUrl":"10.2147/DDDT.S481479","url":null,"abstract":"<p><strong>Background: </strong>The sap of <i>Angelica keiskei</i> (Miq). Koidz. has been reported for its abundance of chalcone contents. Chalcones have been known for their effective nephroprotective activity toward cisplatin-induced renal cells and mice.</p><p><strong>Purpose: </strong>To investigate the effect of <i>A. keiskei</i> sap extract (ASEE) on kidney function parameters (serum creatinine, urea nitrogen, and kidney injury molecule-1) and the expression of NF-kappaB p65 and COX-2 in cisplatin-induced Wistar rats.</p><p><strong>Methods: </strong>In vivo nephroprotective activity of ASEE at 1000 and 1500 mg/kg BW/day doses for 10 days on cisplatin (5 mg/kg BW) induced nephrotoxicity was evaluated on Wistar rats. Quercetin 20 mg/kg BW/day was used as the control drug. Cisplatin inducement was given on day 7. The BW was measured every day. On day 11, the rats were euthanized, and their blood was taken intracardially for creatinine and urea nitrogen analysis. Histopathological analysis was carried out on the right kidney, and KIM-1 levels in the left kidney were measured. The Western blot technique evaluated the NF-kappaB p65 and COX-2 expression in the kidney. All data obtained were compared to the cisplatin group (negative control). The total flavonoids and chalcones in ASEE were also determined.</p><p><strong>Results: </strong>Pretreatment with ASEE reduces the BW of Wistar rats, and significantly reduces creatinine and KIM-1 levels, but does not significantly reduce the levels of urea nitrogen, the expression of NF-kappaB p65, and COX-2 in the kidney of cisplatin-induced Wistar rats. The total flavonoid content in ASEE is 8.755 g QE/100 g extract and the total chalcone content is 5.532 g IBCE/100 g extract.</p><p><strong>Conclusion: </strong>The sap of <i>Angelica keiskei</i> (Miq). Koidz. reveal the potential to protect the kidneys against cisplatin-induced toxicity. The nephroprotective activity may be attributed to the antioxidant and anti-inflammatory properties of the flavonoids and the chalcones contained in the sap of <i>Angelica keiskei</i> (Miq). Koidz.</p>","PeriodicalId":11290,"journal":{"name":"Drug Design, Development and Therapy","volume":"18 ","pages":"4707-4721"},"PeriodicalIF":4.7,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}