Journal of Holistic Integrative Pharmacy最新文献

{"title":"Formulation and evaluation of carbamazepine loaded ethosomal nasal in-situ gel for brain targeted drug delivery","authors":"Arjun Bilapatte ,&nbsp;Anjali More ,&nbsp;Kranti Satpute ,&nbsp;Shoaeb Mohammad Syed","doi":"10.1016/j.jhip.2025.03.002","DOIUrl":"10.1016/j.jhip.2025.03.002","url":null,"abstract":"<div><h3>Objective</h3><div>This study aimed to develop a novel intranasal drug delivery system for carbamazepine, an antiepileptic drug, to enhance its therapeutic efficacy through targeted and sustained delivery. The goal was to evaluate the suitability of various polymers and excipients for formulating an effective and mucoadhesive nasal gel.</div></div><div><h3>Methods</h3><div>Ethosomes were prepared using the cold method and evaluated for particle size, zeta potential, entrapment efficiency, and drug release. Gels were formulated using poloxamer 407 and carbopol 934 and characterized for their physicochemical properties. The optimized ethosomal gel was further assessed for mucoadhesive properties and <em>in vitro</em> drug release. Nasal in-situ gels were also prepared using carbopol and HPMC k 100, and their spreadability and drug release profiles were compared.</div></div><div><h3>Results</h3><div>The optimized ethosomal batch (ET3) exhibited a particle size of 200.7 ​nm, a zeta potential of −54.8 ​mV, and a high drug entrapment efficiency of 93%. The <em>in vitro</em> drug release from ET3 was 88.64%. Among the nasal in-situ gels, the carbopol-based batches demonstrated better spreadability compared to HPMC k 100. The optimized in-situ gel batch (G2) showed a gelation temperature of 33.7 ​°C and an <em>in vitro</em> drug release of 94.05%.</div></div><div><h3>Conclusion</h3><div>The developed ethosomal gel and in-situ gel formulations demonstrated sustained drug release, enhanced mucoadhesion, and targeted delivery, making them promising alternatives for the treatment of epilepsy. This intranasal delivery system could improve patient compliance and therapeutic outcomes by providing a non-invasive and effective route for carbamazepine administration.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 57-63"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686161","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":"Protective potential of Carduus marianus extract against p-dimethylaminoazobenzene (pDAB) induced hepatocarcinogenesis in mice through apoptosis induction and antioxidant pathway","authors":"Saili Paul ,&nbsp;Anisur Rahman Khuda-Bukhsh","doi":"10.1016/j.jhip.2025.02.005","DOIUrl":"10.1016/j.jhip.2025.02.005","url":null,"abstract":"<div><h3>Objective</h3><div>In homeopathy, ethanolic extract of <em>Carduus marianus</em> (EECM)<em>,</em> is used against various liver disorders including cancer. This investigation aims at evaluating hepatoprotective potential of EECM, if any, against p-dimethylaminoazobenzene (pDAB)-induced hepatocarcinogenesis in mouse models <em>in vivo</em> and elucidating its possible underlying mechanism(s).</div></div><div><h3>Methods</h3><div>Randomized sets of inbred mice were chronically fed with different food regimens for varying periods of time and divided accordingly, 6 mice in each group, into control (Normal I and Alcohol II) and treated groups (III-V); group I: fed Normal diet, group II: Normal diet ​+ ​Alcohol, group III: pDAB ​+ ​Phenobarbital (PB), group IV: pDAB ​+ ​PB ​+ ​Alcohol, group V: pDAB ​+ ​PB ​+ ​EECM. They were sacrificed at day 30, 60, 90 and 120. All routine protocols were deployed for cytogenetical, enzymatic, and histopathological studies. Expressions of B-cell lymphoma 2 (Bcl-2), B-cell lymphoma-extra large (Bcl-xl), Bcl-2 associated X protein (Bax), Cysteine aspartic acid protease-3 (Caspase-3), and Matrix metalloproteinase 9 (MMP-9) were evaluated at day 90 and 120 only. The DPPH free-radical scavenging activity of EECM was estimated to determine the antioxidant properties.</div></div><div><h3>Results</h3><div>No mice of groups I and II developed tumors in liver at any fixation intervals while all mice of groups (III-IV) developed liver tumors at three fixation intervals. But in group V mice, 4 each of 6 mice at 90 and 120 days, did not show tumor nodules in their livers, signifying that feeding of EECM could combat carcinogenesis. EECM reduced genotoxic effects and favorably modulated expression of Caspase 3 and MMP-9 as compared to control.</div></div><div><h3>Conclusion</h3><div>The treatment of EECM clearly demonstrated protective action against pDAB induced hepatocarcinogenesis in mice for delaying tumor progression, decreasing total tumor load and genotoxic effects, and also evidenced by favourable modulations of the apoptotic signal proteins like Bcl2, Bcl-xl. Bax, Caspase 3 and other marker enzymes AST (Aspartate amino transferase), ALT (Alanine amino transferase) etc. However, the molecular mechanism of this protective action still needs to be further elucidated.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 64-73"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686151","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":"Oral pH-triggered colon-specific ketoprofen loaded microspheres for the better management of early morning symptoms associated with rheumatoid arthritis. Part II: Pharmacokinetic and pharmacodynamic assessment in rats","authors":"Krishna Sanka ,&nbsp;Prabhakar Reddy Veerareddy ,&nbsp;Rajeswara Rao Pragada","doi":"10.1016/j.jhip.2025.03.001","DOIUrl":"10.1016/j.jhip.2025.03.001","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the effectiveness of oral pH-triggered colon-specific ketoprofen-loaded microspheres (C-SKLMs) in managing early morning symptoms of rheumatoid arthritis (RA) through pharmacokinetic and pharmacodynamic assessments.</div></div><div><h3>Methods</h3><div>Pharmacokinetic parameters, including T_max, C_max, and mean residence time (MRT), were analyzed in animals treated with C-SKLMs and compared with pure ketoprofen. Pharmacodynamic evaluations assessed the ability of C-SKLMs to address early morning RA symptoms effectively by aligning drug release with the body's circadian rhythm.</div></div><div><h3>Results</h3><div>The T_max for the C-SKLMs group (9.33 ​± ​1.63 ​h) was significantly prolonged compared to pure ketoprofen (2 ​h), indicating delayed drug release tailored to circadian needs. The C_max for C-SKLMs (5.94 ​± ​1.20 ​μg/mL) was lower than that of pure ketoprofen (12.4 ​± ​3.00 ​μg/mL), demonstrating a controlled-release profile. Additionally, the MRT for C-SKLMs (12.96 ​± ​1.42 ​h) was approximately 1.4 times longer than for pure ketoprofen (9.44 ​± ​0.69 ​h), emphasizing extended drug release. Pharmacodynamic evaluations supported the superior effectiveness of C-SKLMs in managing early morning RA symptoms compared to pure ketoprofen.</div></div><div><h3>Conclusion</h3><div>C-SKLMs demonstrated significant potential to improve the management of early morning symptoms associated with RA through controlled, extended, and circadian-tailored drug release, making them a promising therapeutic approach.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 83-90"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725790","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":"Mitochondrial function: A new direction for the targeted treatment of cardiovascular diseases with Chinese herbal medicine","authors":"Lin Yang ,&nbsp;Liang Wang ,&nbsp;Baofeng Yang ,&nbsp;Yue Zhang","doi":"10.1016/j.jhip.2025.03.003","DOIUrl":"10.1016/j.jhip.2025.03.003","url":null,"abstract":"<div><div>Mitochondria play a central role in cardiovascular diseases, primarily by providing cellular energy and facilitating various cardiac functions. Excessive fat accumulation, circadian rhythm disturbances, viral infections, and persistent inflammation can lead to myocarditis, fibrosis, and infarction, thereby exacerbating the progression of cardiovascular diseases. As essential organelles for energy production, mitochondria exhibit remarkable dynamic adaptability and can integrate diverse cellular signaling pathways, endowing myocardial cells with both bioenergetic and biosynthetic versatility. Consequently, targeting mitochondria for cardiovascular disease therapy has gained increasing attention and is applicable to various cardiovascular conditions. Numerous mitochondrial adaptive mechanisms, including dynamics, metabolic processes, and apoptosis regulation, have emerged as promising therapeutic targets. Nevertheless, contemporary investigations into mitochondrial biology have unveiled their intricate structural and functional characteristics, as well as their complex roles within cellular systems, which present obstacles to the clinical implementation of mitochondria-focused cardiovascular therapies. Recent studies have found that traditional Chinese medicine (TCM) possesses the potential to effectively address cardiovascular diseases while enhancing the structural integrity and functional capacity of mitochondria. This review aims to offer a comprehensive analysis of the modulatory effects of TCM on cardiac mitochondria and its therapeutic ramifications for cardiovascular conditions.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 91-104"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143725794","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":"Kalanchoe crenata decoction and infusion improve insulin resistance and fasting glycemia of diabetic obese rats MACAPOS 2","authors":"Ngakou Mukam Joseph ,&nbsp;Mvongo Clémence ,&nbsp;Mfopa Adamou ,&nbsp;Kamgang Tchawou Armel Georges ,&nbsp;Nkoubat Tchoundjwen Sandrine ,&nbsp;Fankem Gaëtan Olivier ,&nbsp;Noubissi Paul Aimé ,&nbsp;Fokam Tagne Michel Archange ,&nbsp;Kamgang René ,&nbsp;Essame Oyono Jean-Louis","doi":"10.1016/j.jhip.2025.02.006","DOIUrl":"10.1016/j.jhip.2025.02.006","url":null,"abstract":"<div><h3>Objective</h3><div><em>Kalanchoe crenata</em> is a medicinal plant traditionally used in diabetes management. Type 2 diabetes is a metabolic disorder characterized by abnormally high glycemia and insulin resistance. We investigated the effects of <em>Kalanchoe crenata</em> aqueous extracts on diabetic rats.</div></div><div><h3>Methods</h3><div>Six-week-old normal rats were fed a high-fat diet for 16 weeks. Then, selected obese rats intravenously received a unique dose of streptozotocin (22.5 ​mg/kg b.w.). One week later, the obtained diabetic rats received <em>K. crenata</em> decoction (DKc) or infusion (IKc) once daily, respectively, at 37.5, 75.0, or 150.0 ​mg/kg b.w., or Metformin(70 ​mg/kg) once daily for 42 days, during which the fasting glycemia, urine volume, and water intake were recorded. At the end of the treatment, animals were subjected to oral glucose tolerance and insulin tolerance tests. They were then sacrificed; serum and pancreas were collected for insulinemia evaluation and histological analysis, respectively.</div></div><div><h3>Results</h3><div>Obese diabetic animals had fasting glycemia &gt; 200 ​mg/dL. The DKc, IKc, and Metformin reduced (<em>P</em> ​&lt; ​0.05) glycemia with the maximum effect (<em>P</em> ​&lt; ​0.01) in the 6th week and improved glucose tolerance and insulin resistance. The extracts decreased 24-h urine volume as well as water intake and reduced insulinemia (<em>P</em> ​&lt; ​0.01): IKc75 (−66.4%) and IKc150 (−59.3%). This result was associated with decreased results of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The extracts improved the size of Langerhans islets. Infusion improved diabetes parameters to a greater extent than decoction.</div></div><div><h3>Conclusion</h3><div><em>Kalanchoe crenata</em> aqueous extracts improved glucose tolerance and insulin resistance in diabetic rats. This study contributed to justifying the empirical use of this plant for diabetes management.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 50-56"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686160","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":"Unravelling the gut-liver axis: The role of gut microbiota-mitochondria interactions in the pathogenesis and management of metabolic-associated fatty liver disease (MAFLD)","authors":"Binzhi Zhang ,&nbsp;Xia Luo ,&nbsp;Song Lei ,&nbsp;Wenbo Gao ,&nbsp;Zhipeng Chen ,&nbsp;Qing Zhu ,&nbsp;Lizheng Huang ,&nbsp;Qinqiang Long","doi":"10.1016/j.jhip.2025.02.001","DOIUrl":"10.1016/j.jhip.2025.02.001","url":null,"abstract":"<div><div>Metabolic-associated fatty liver disease (MAFLD) has emerged as a prevalent chronic liver disease. Our review of the existing literature reveals that the interplay between gut microbiota, mitochondria, and the liver is a key mechanism in the development of MAFLD. This paper distills the pathogenic role of gut microbiota in MAFLD through its influence on mitochondria and outlines the therapeutic mitochondrial mechanisms of MAFLD that leverage gut microbiota. It also touches on the traditional Chinese medicine perspective on the liver-intestine connection and the concept of ''<em>qi</em>'' in relation to mitochondria, as well as its modern medical counterpart. We conclude that the gut microbiota and their metabolites can directly or indirectly affect the intestinal mitochondria, leading to structural and functional changes. These changes include shifts in mitochondrial membrane potential, changes in permeability, and dysregulation of signaling pathways. As a result, the permeability of intestinal epithelial cells may be increased, and the integrity of the intestinal barrier may be compromised. The gut microbiota and their metabolites can then influence hepatic mitochondria through the hepatic-intestinal axis, triggering liver pathology. When liver damage occurs, their metabolites can enter the intestine and affect intestinal mitochondria and microbiota, which in turn can lead to a disrupted intestinal barrier and microbiota and a dysregulated homeostatic balance. Our extensive literature review suggests that the gut microbiota may mediate the treatment of MAFLD through mitochondrial pathways. The therapeutic approach of modulating the gut microbiota to regulate mitochondrial function and restore liver health is promising. Traditional Chinese medicine diets are particularly well suited for this strategy. Further research is warranted to fully elucidate the underlying mechanisms. By protecting the body's own mitochondrial function through the gut microbiota, we can effectively combat liver injury, providing a novel therapeutic avenue for the treatment of liver disease.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"6 1","pages":"Pages 23-40"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143686152","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":"Anticancer flavonoids producing endophytic fungi: A review","authors":"Kirti G. Sahu ,&nbsp;Deepak S. Khobragade ,&nbsp;Shriniwas P. Patil","doi":"10.1016/j.jhip.2024.11.002","DOIUrl":"10.1016/j.jhip.2024.11.002","url":null,"abstract":"<div><div>Plants living in different environments inhabit endophytic microbes. The relationship between plants and endophytic microbes may be symbiotic or parasitic. Transmission of endophytes varies when they are obtained through roots or cracks on bark or airborne spores from soil or originated from seeds or pollens. Endophytes could be bacteria or fungi. So far, actual flavonoids have been detected from endophytic fungi only. Several flavonoids like rutin, quercetin, kaempferol, naringenin, vitexin, apigenin, luteolin, chrysin, and silymarin are isolated from endophytic fungi. These flavonoids are tested for their anticancer activity on different cell lines and their mechanisms were determined. This review focuses on endophytic fungi from which anticancer flavonoids have been reported.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 4","pages":"Pages 305-313"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174791","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":"Visual analysis of drug research and development based on artificial intelligence","authors":"Wei Wei ,&nbsp;Chao Song ,&nbsp;Changxing Qi ,&nbsp;Xin Zhang ,&nbsp;Xiaoyi Zhang ,&nbsp;Run Pu ,&nbsp;Yi Ao","doi":"10.1016/j.jhip.2024.12.002","DOIUrl":"10.1016/j.jhip.2024.12.002","url":null,"abstract":"<div><div>The iteration of artificial intelligence (AI) technology provides new opportunities for drug research and experimental development. In recent years, AI-based drug research has continuously made new progress and has garnered widespread attention. This study retrieved data from a total of 23,096 papers in AI-based drug research and development from the Web of Science up to May 14, 2024, and conducted bibliometric analysis using VOSviewer software. The results indicated that the AI-based drug research and development is a globally recognized hotspot, and the United States holds a certain authority in this field, while China ranks second in total publication output. The integration of AI technology with drug development primarily involves four stages: drug discovery, preclinical research, clinical trials, and drug manufacturing. So, AI technology has been applied throughout the entire process of drug development. AI-based virtual drug screening and structure-activity relationship analysis started early, while graph neural networks, pre-trained models (Transformer), interpretable AI technology, ChatGPT, and large language models were significantly highlighted in the last 3 years. Moreover, since 2020, AI-based drug repurposing, molecular dynamics simulation, 3D printing, and drug delivery system design have emerged as research hotspots and have been mainly applied to, particularly, on COVID-19, disease prognosis, liver cancer, lung cancer, and immunotherapy.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 4","pages":"Pages 323-332"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174795","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":"Study on the application of Aloe vera in cosmetology and clinical treatment of skin diseases","authors":"Jiajun Zhu ,&nbsp;Yuanru Zheng ,&nbsp;Yanhui Ge","doi":"10.1016/j.jhip.2024.11.006","DOIUrl":"10.1016/j.jhip.2024.11.006","url":null,"abstract":"<div><div>The medicinal value of <em>Aloe vera</em> (AV) has been continuously explored and utilized in recent years, becoming a research hotspot. Some basic studies have found that AV had cosmetic effects such as whitening, sun protection, antioxidant, anti-aging, and moisturizing. Some clinical trials have found that AV had medical effects such as antibacterial, anti-damage, and promoting wound healing. In this work, we summarized the indications and therapeutic efficacy of AV in cosmetology and clinical treatment of dermatosis, in order to provide certain inspiration for the development of new AV-based skincare products and new medicines for skin diseases.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 4","pages":"Pages 299-304"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174793","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":"Human Epididymis Protein 4 (HE4) as a promising biomarker and therapy target in fibrotic diseases: A review","authors":"Huiqun Tian,&nbsp;Li Chen","doi":"10.1016/j.jhip.2024.12.001","DOIUrl":"10.1016/j.jhip.2024.12.001","url":null,"abstract":"<div><div>The treatment of fibrosis faces a significant challenge due to the lack of effective therapies that can reverse established fibrosis. Early detection is vital for intervention, yet distinguishing fibrosis from normal tissue repair is complex. Human Epididymis Protein 4 (HE4), a traditional tumor marker, has been found to be increased in some non-neoplastic conditions, such as fibrosis related diseases. According to properties analysis, HE4 has been characterized as a highly stable cross-class protease inhibitor, which interacts with key fibrotic proteins (such as MMP2 and PRSS family members) and potentially involves in the progression of fibrosis by inhibiting the enzymatic activity of these proteins. Meanwhile, studies indicated that HE4 may be involved in fibrosis through PI3K/AKT, NF-κB, MAPK, and other signaling pathways. Here we summarized the latest research progress of HE4 in pulmonary fibrosis, renal fibrosis, myocardial fibrosis, liver fibrosis, and autoimmune diseases induced fibrosis. As reported in this review, HE4 was closely related to disease severity and prognosis, and also was a promising prognostic evaluation marker and therapeutic intervention target for fibrotic diseases.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"5 4","pages":"Pages 291-298"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174789","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}