Yujie Wan, Li Luo, Xinzhi Xu, Qihuan Fu, Ying Li, Kaifeng Huang, Hang Zhou, Fang Li
{"title":"Mesothelin-Mediated Paclitaxel Phase-Shifted Nanodelivery System for Molecular Ultrasound Imaging and Targeted Therapy Potential in Ovarian Cancer.","authors":"Yujie Wan, Li Luo, Xinzhi Xu, Qihuan Fu, Ying Li, Kaifeng Huang, Hang Zhou, Fang Li","doi":"10.2174/0115672018300502240530064139","DOIUrl":"10.2174/0115672018300502240530064139","url":null,"abstract":"<p><strong>Background: </strong>Ovarian cancer presents a substantial risk to women's health and lives, with early detection and treatment proving challenging. Targeted nanodelivery systems are viewed as a promising approach to enhance the effectiveness of ovarian cancer treatment and ultrasonic imaging outcomes.</p><p><strong>Objective: </strong>A phase-shifted nanodelivery system (NPs) loaded with paclitaxel (PTX) and further conjugated with avidin (Ab) was studied, with the goal of investigating the effects of targeted nanodelivery strategies on the <i>in vitro</i> therapeutic efficacy and ultrasonic imaging of ovarian cancer. This study provides a foundation for future <i>in vivo</i> treatments utilizing this approach.</p><p><strong>Methods: </strong>PTX-NPs were prepared using the single water-in-oil (O/W) emulsion solvent evaporation method, with avidin coupling achieved through biotin-avidin affinity. The encapsulation efficiency and release profile of PTX were analyzed using UV spectrophotometry. The phase-shift properties of the Ab-PTX-NPs delivery system were evaluated, and the targeting efficiency, cytotoxicity against SKOV3 cells, and <i>in vivo</i> biosafety of various nanodelivery systems were assessed.</p><p><strong>Results: </strong>The prepared nanodelivery system showed a stable and uniform structure with a good particle size distribution and exhibited favorable release characteristics under ultrasound exposure. <i>In vitro</i> experiments revealed that the nanodelivery system displayed excellent targeting and cytotoxic effects against SKOV3 cells, indicating the potential of the Ab-PTX-NPs delivery system for targeted ovarian cancer therapy. <i>In vivo</i> safety studies demonstrated the high biosafety of the prepared nanodelivery system.</p><p><strong>Conclusion: </strong>A novel nanodelivery system was developed, and the experimental results obtained provide a solid experimental basis for further research on <i>in vivo</i> ultrasound molecular imaging technology, offering new insights into targeted ultrasound molecular imaging and the treatment of ovarian cancer.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":"810-820"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141285709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Nanophase: An Effective Dispersion System for the Decoction of Kushen Huaihua for the Treatment of Ulcerative Colitis.","authors":"Jingrui Liu, Haixia Tang, Liansheng Yang, Haibo Wang, Xiuyan Li, Zhixin Yang","doi":"10.2174/0115672018351982250224062652","DOIUrl":"10.2174/0115672018351982250224062652","url":null,"abstract":"<p><strong>Introduction/objective: </strong>In traditional Chinese medicine, the decoction turns into a complex multiphase system following exposure to high temperatures and a complex chemical environment. However, the effective dispersion system of the decoction of Kushen Huaihua (DKH) for the treatment of ulcerative colitis (UC) has yet to be elucidated.</p><p><strong>Methods: </strong>DKH was separated into precipitated phase (DKH-P), nanophase (DKH-N), and solution phase (DKH-S) according to the particle size by ultracentrifugation dialysis, and the physicochemical properties of each phase group, such as particle size, morphology, chemical composition, and content, were analysed by TEM and HPLC. The anti-UC effects of the different phases were evaluated by ELISA and HE staining. Furthermore, the composition of the effective dispersion system and release characteristics were investigated by UV and HPLC.</p><p><strong>Results: </strong>The fingerprint analysis of DKH recognized 11 key components, namely Ru, Qu, Ka, Fo, Iso, Kur, SFG, OMT, OSC, MT, and SC. The content of these components in DKH-N was found to be 69.51%, 88.30%, 84.60%, 82.92%, 73.35%, 77.03%, 74.02%, 89.74%, 85.99%, 79.53%, and 85.24% of the corresponding levels in DKH, respectively. Pharmacodynamic results demonstrated that DKH-N exerted the same anti-UC effect as DKH, decreased DAI and CMDI scores, increased IL-4 and IL-10 activities, and reduced expression of IL-6, TNF-α, and MPO, which were significantly different from those of the model group (**P<0.01). Additionally, DKH-N was found to comprise 30.30% polysaccharides and 24.93% protein components. Furthermore, 11 components in DKH-N demonstrated more than 80% release in enzyme-containing simulated colonic fluid in 24 h.</p><p><strong>Conclusion: </strong>DKH-N may be an effective dispersion system for DKH treatment of UC.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":"821-836"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abhranil Bhuyan, Piyali Dey, Himanshu Gogoi, Santa Mandal
{"title":"Exploring Naturally-Derived Targeted Nano Delivery Therapy for Burn Wound Healing with Special Emphasis on Preclinical Outcomes.","authors":"Abhranil Bhuyan, Piyali Dey, Himanshu Gogoi, Santa Mandal","doi":"10.2174/0115672018343042241120072749","DOIUrl":"https://doi.org/10.2174/0115672018343042241120072749","url":null,"abstract":"<p><p>Plant bioactive are being used since the early days of medicinal discovery for their various therapeutic activities and are safer compared to modern medicines. According to World Health Organization (WHO), approximately 180,000 deaths from burns occur every year with the majority in countries. Recent years have witnessed significant advancements in this domain, with numerous plant bioactive and their various nanoformulations demonstrating promising preclinical burn wound healing activity and identified plant-based nanotechnology of various materials through some variations of cellular mechanisms. A comprehensive search was conducted on scientific databases like PubMed, Web of Science, ScienceDirect and Google Scholar to retrieve relevant literature on burn wound, plants, nano formulations and in vivo studies from 1990 to 2024. From a total of approximately 180 studies, 40 studies were screened out following the inclusion and exclusion criteria, which reported 40 different plants and plant extracts with their various nano-formulations (NFs) that were used against burn wounds preclinically. This study provides the current scenario of naturally-derived targeted therapy, exploring the impact of natural products on various nanotechnology in burn wound healing on a preclinical model. This comprehensive review provides the application of herbal nanoformulations (HBNF) for the treatment of burn wounds. Natural products and their derivatives may include many unidentified bioactive chemicals or untested nano-formulations that might be useful in today's medical toolbox. Mostly, nano-delivery system modulates the bioactive compound's effectiveness on burn wounds and increases compatibility by suppressing inflammation. However, their exploration remains incomplete, necessitating possible pathways and mechanisms of action using clinical models.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142776195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Innovative Nanocomposites for Drug Delivery: A Novel Approach for Diabetic Foot Ulcer.","authors":"Rubi Parveen, Faraat Ali, Shiv Dev Singh","doi":"10.2174/0115672018322140241023054041","DOIUrl":"https://doi.org/10.2174/0115672018322140241023054041","url":null,"abstract":"<p><p>Diabetic Foot Ulcer (DFU) is a chronic wound, and a person with diabetes has an increased lifetime risk of foot ulcers (19%-34%) and high morbidity (65% recurrence in 3-5 years, 20% lifetime amputation). Recent data have shown rising amputation rates, especially in the younger and minority populations. This abstract discusses innovative approaches for addressing this issue. This highlights the use of nanotechnology-based drug nanocomposite systems for natural wound healing therapies, with a focus on nanoparticles, nano-emulsions, and nanogels. This review also emphasizes the potential of hydrogels for drug delivery, highlighting their versatility in various medical applications. Furthermore, it delves into the use of silver nanoparticles (AgNP's) for treating diabetic wounds while acknowledging the need to address potential toxicity concerns. Finally, the abstract discusses the utilization of traditional herbal medicine and the integration of modern science to advance wound care, particularly focusing on wound microbiome, immune response, and controlled herbal medicine delivery. This study also highlights clinical trials conducted on DFU. Overall, these abstracts highlight the importance of exploring diverse and innovative solutions to chronic wound management.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ujjwal Kumar Biswas, Shreeja Sen, Susrita Sharma, Mohana Paul, Amit Kumar Nayak, Anindya Bose
{"title":"Nanostructured Lipid Carrier-based Topical Gels as Novel Drug Delivery System: A Comprehensive Overview.","authors":"Ujjwal Kumar Biswas, Shreeja Sen, Susrita Sharma, Mohana Paul, Amit Kumar Nayak, Anindya Bose","doi":"10.2174/0115672018335655241015062436","DOIUrl":"https://doi.org/10.2174/0115672018335655241015062436","url":null,"abstract":"<p><p>Nanostructured lipid carriers (NLCs) are lipidic nanocarriers that recover the permanency and capacity of drug payloads. NLCs are well-known as second-generation lipid nanocarriers with an unstructured matrix, presenting potentially advantageous nanocarrier systems with marketable opportunities because of reproducible production methodologies and biocompatible lipidic excipients. These (NLCs) are now recognized as a very promising nanocarrier structure for the efficient delivery of drugs via different administration routes. In recent years, several NLC-based gels have been developed and evaluated for topical delivery of many drugs and other therapeutic agents. This review article presents an overview of NLC-based topical gels investigated to deliver drugs via ocular, dermal, and transdermal routes. In addition, the classification, manufacturing, characterizations, advantages, and disadvantages of NLCs are addressed in this article. We also discussed different evaluations of NLC-based topical gels.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluconazole-loaded Hyaluronic Acid-modified Transfersomal Hydrogels Containing D-panthenol for Ocular Delivery in Fungal Keratitis Management.","authors":"Biswarup Das, Amit Kumar Nayak, Subrata Mallick","doi":"10.2174/0115672018342369241018050810","DOIUrl":"https://doi.org/10.2174/0115672018342369241018050810","url":null,"abstract":"<p><strong>Background: </strong>Fungal keratitis (mycotic keratitis) is an eye infection in which the cornea is infected by fungi and such fungal keratitis management can be effectively possible by ocular administration of antifungal drugs.</p><p><strong>Objective: </strong>The main objectives of the present research were to develop and evaluate fluconazoleloaded transfersomal hydrogels for ocular delivery in the effective management of fungal keratitis.</p><p><strong>Methods: </strong>A 23 factorial design-based approach was used for statistical optimization, where (A) the ratio of lipid to edge activators, (B) the amount of hyaluronic acid (% HA), and (C) the ratio of edge activators (sodium deoxycholate to Span 80) were taken as three factors. The average vesicle diameter (Z, nm) of transfersomes was taken as a response. Further, fluconazole-loaded transfersomes (FTO) were incorporated into 1% Carbopol 940-based hydrogel (OF1) and 2% HMPC K4M-based hydrogel (OF2) containing D-panthenol (5% w/w).</p><p><strong>Results: </strong>The optimal variable setting for the optimized formulations of FTO was (A) = 9.15, (B) = 0.30%, and (C) = 3.00. FTO exhibited 66.39 nm Z, 0.247 polydispersity index, - 33.10 mV zeta potential, and 65.38 ± 1.77 % DEE, and desirable elasticity. TEM image of FTO demonstrated a unilamellar vesicular structure. The ex vivo ocular permeation of fluconazole from transfersomal hydrogels was sustained over 24 h. All the transfersomal hydrogels showed good bioadhesion and excellent antifungal activity with respect to the zone of inhibition against Candida albicans than Aspergillus fumigates, in vitro. HET-CAM study results demonstrated that both the hydrogels were nonirritant and safe for ocular. Short-term physical stability study suggested the stability of the developed formulation.</p><p><strong>Conclusion: </strong>The current research demonstrated a new way to enhance the ocular penetration of fluconazole via transfersomal hydrogel formulations for ocular delivery in the effective management of fungal keratitis.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pooria M Arvejeh, Fatemeh A Chermahini, Amin Soltani, Zahra Lorigooini, Mahmoud Rafieian-Kopaei, Gholam Reza Mobini, Pegah Khosravian
{"title":"Improved Therapeutic Efficacy: Liposome-Coated Mesoporous Silica Nanoparticles Delivering Thymoquinone to MCF-7 Cells.","authors":"Pooria M Arvejeh, Fatemeh A Chermahini, Amin Soltani, Zahra Lorigooini, Mahmoud Rafieian-Kopaei, Gholam Reza Mobini, Pegah Khosravian","doi":"10.2174/0115672018317245241007044455","DOIUrl":"https://doi.org/10.2174/0115672018317245241007044455","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains a significant global health challenge, with thymoquinone showing promise as a therapeutic agent, but hindered by poor solubility.</p><p><strong>Objective: </strong>This study aimed to enhance TQ delivery to MCF-7 breast cancer cells using mesitylene- mesoporous silica nanoparticles coated with liposomes, designed for controlled drug release.</p><p><strong>Methods: </strong>Nanoparticles were synthesized using the sol-gel method and coated with phosphatidylserine- cholesterol liposomes. Different nanocharacterization techniques and in vitro assays were employed to assess the drug release kinetics, cellular uptake, cytotoxicity, and apoptosis.</p><p><strong>Results: </strong>The nanoparticles exhibited favorable properties, including a large pore size of 3.6 nm, a surface area of 248.96 m2/g, and a hydrodynamic size of 171.571 ± 8.342 nm with a polydispersity index of 0.182 ± 0.017, indicating uniformity and stability. The successful lipid bilayer coating was confirmed by a zeta potential shift from +6.25 mV to -5.65 mV. The coated nanoparticles demonstrated a slow and sustained drug release profile, with cellular uptake of FITC-formulated nanoparticles being approximately 5-fold higher than free FITC (P < 0.0001). Cytotoxicity assays revealed a significant reduction in cell viability (P < 0.0001), reaching an IC50 value of 25 μM at 48 hours. Apoptosis rates were significantly higher in cells treated with the formulated TQ compared to the free drug and control at both 24 and 48 hours (P < 0.0001).</p><p><strong>Conclusion: </strong>This nanoformulation significantly enhanced TQ delivery, offering a promising strategy for targeted breast cancer therapy. Further preclinical studies are recommended to advance this approach in cancer treatment.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Local Delivery of Ginger Extract <i>via</i> a Nanofibrous Membrane Suppresses Human Skin Melanoma B16F10 Cells Growth <i>via</i> Targeting Ras/ERK and PI3K/AKT Signaling Pathways: An <i>In vitro</i> Study.","authors":"Wenju Wei, Tianlu Zhang, Bo Yuan, Saeed Rohani","doi":"10.2174/0115672018319584241008075033","DOIUrl":"https://doi.org/10.2174/0115672018319584241008075033","url":null,"abstract":"<p><strong>Background: </strong>Metastatic melanoma poses a significant threat globally, with a distressingly low ten-year survival rate of only 10%. While FDA-approved treatments such as dacarbazine and high-dose IL-2 have been employed in clinical settings, their limitations underscore the urgent need for more effective therapies.</p><p><strong>Aims: </strong>This study aimed to develop a potential anticancer local treatment through the extraction of various amounts of ginger extract loaded unto Poly(vinyl alcohol) (PVA) nanofibers.</p><p><strong>Methods: </strong>The anticancer activity of the produced membranes was studied on human skin melanoma B16F10 cells. Other in vitro experiments such as cell migration assay, cell proliferation assay, cell viability assay, scanning electron microscopy assay, real-time PCR assay, and ant-inflammatory assay were performed for the in vitro characterization of the delivery system. Tissue toxicity of the developed patches was studied in a rat model.</p><p><strong>Results: </strong>The study showed that scaffolds loaded with 2%, 4%, 6%, 8%, and 0% of ginger extract had around 784.98 ± 202.31 nm, 771.86 ± 219.07 nm, 820.65 ± 242.43 nm, 785.19 ± 203.99 nm, and 671.29 ± 184.09 nm of mean fiber size, respectively. The ginger extract-loaded membranes suppressed the growth and migration activity of human skin melanoma B16F10 cells in a dose and time-dependent manner. Real-time PCR assay showed that the developed membranes modulated the expression levels of Ras/ERK and PI3K/AKT signaling pathways. Animal study results showed that our developed patches were not toxic against liver or skin tissues.</p><p><strong>Conclusion: </strong>Ginger extract-loaded PVA nanofibers exhibited promising anticancer potential against melanoma cells, suggesting a viable localized treatment option.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484989","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Alleviation of Tumor Invasion by the Development of Natural Polymerbased Low-risk Chemotherapeutic Systems - review on the Malignant Carcinoma Treatments.","authors":"Vignesh Natarajan","doi":"10.2174/0115672018349688241008220007","DOIUrl":"https://doi.org/10.2174/0115672018349688241008220007","url":null,"abstract":"<p><strong>Introduction/objective: </strong>The spread of tumors (48% in men and 51% in women), as well as the protection of malignant tumors by stromal cells and complex blood vessels, pose significant challenges to drug delivery to tumors. Modern chemotherapy, on the other hand, addresses tumor growth suppression by at least 60% through versatile formulation systems and numerous modifications to drug delivery systems. The renewable and naturally occurring polymers present invariably in all living cells form the fundamental foundation for most anticancer drug development. The review aims to discuss in detail the preparations of polysaccharide, lipid, and protein-based drug-loading vehicles for the targeted delivery of prominent anticancer drugs. It also provides an explanation of drug distribution in blood (cumulative releases of nearly 80% drug) and drug accumulation at tumor sites (1-5 mg/kg) due to enhanced permeability and retention (EPR).</p><p><strong>Methods: </strong>Specific delivery examples for treating colorectal and breast carcinomas have been presented to distinguish the varied drug administration, bioavailability, and tumor internalization mechanisms between sugar, fatty acid, and amino acid polymers. Current therapy possibilities based on cutting-edge literature are provided, along with drug delivery systems tailored to tumor location and invasive properties.</p><p><strong>Results: </strong>The unique combinations of the three natural polymers provide unparalleled solutions to minimize the toxicity (<20% drug release) of the chemotherapeutic drugs on normal tissues. Moreover, the development of a consolidated drug delivery system has contributed to a substantial reduction (dose reduction from 10.43 μM to 1.9 μM) in the undesirable consequences of higher dosages of chemotherapeutic drugs.</p><p><strong>Conclusion: </strong>The review extensively covers safe chemotherapeutic systems with significant advantages (tumor volume shrinkage of 4T1 cells from 1000 mm3 to 200 mm3) in clinical applications of carcinoma treatments using natural polymers.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fecal Microbiota Transplantation Induced by Wumei Pills Improves Chemotherapy-Induced Intestinal Mucositis in BALB/c Mice by Modulating the TLR4/MyD88/NF-κB Signaling Pathway.","authors":"Dongxue Lu, Lijiang Ji, Feng Liu, Haixia Liu, Zhiguang Sun, Jing Yan, Hua Wu","doi":"10.2174/0115672018304338241003095955","DOIUrl":"https://doi.org/10.2174/0115672018304338241003095955","url":null,"abstract":"<p><strong>Background: </strong>Our previous studies have found that Wumei Pills can regulate the intestinal flora to inhibit chemotherapy-induced intestinal mucositis (CIM). However, there is still insufficient evidence to confirm that intestinal flora is the main link in the regulation of CIM by Wumei Pills, and its downstream mechanism is still unclear.</p><p><strong>Method: </strong>We first obtained the signal pathway of the intervention of Wumei Pill on CIM through network pharmacological analysis and then transplanted the bacterial solution into CIM mice, combined with Western Blot, HE, ELISA and other biological technology-related proteins and inflammatory factors.</p><p><strong>Results: </strong>It showed that 97 kinds of effective ingredients and 205 kinds of targets of Wumei pills were screened out and the potential mechanism of Wumei Pills on CIM may be the NF-κB signaling pathway. In contrast with the control group, the results displayed that the weight, food intake, and mice's colon length were apparently decreased in the 5-Fu group, while the diarrhea score was increased. However, FMT reversed this change, and the difference was statistically significant. Additionally, FMT could improve the pathological state of inflammatory cell infiltration in mice, reduce histopathological scores of colon and jejunum, decrease the expression levels of IL-1β, MPO, TNF-α, and IL-6, reverse the activation of signaling pathway named TLR4/Myd88/ NF-κB and down-regulate protein expression, thereby exerting its anti-inflammatory activities. Further experiments have found that FMT could reverse the decreasing of tight junction proteins and mucins caused by 5-Fu, thereby repairing the intestinal mucosal barrier, and FMT could also increase the content of acetic acid, propanoic acid, and butanoic acid in the feces of 5-Fu group.</p><p><strong>Conclusion: </strong>FMT can defend the intestinal mucosal barrier integrality by increasing the content of exercise fatty acids, and its mechanism may be in connection with its inhibition of TLR4/My- D88/NF-κB signal pathway to relieve inflammation.</p>","PeriodicalId":94287,"journal":{"name":"Current drug delivery","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142484986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}