Chen Pang, Jie Zhang, Yujin Gu, Qili Zhang, Yanfang Zhao
{"title":"The biological roles of exosome-encapsulated traditional Chinese medicine monomers in neuronal disorders.","authors":"Chen Pang, Jie Zhang, Yujin Gu, Qili Zhang, Yanfang Zhao","doi":"10.1016/j.jpha.2024.101131","DOIUrl":"10.1016/j.jpha.2024.101131","url":null,"abstract":"<p><p>A traditional Chinese medicine (TCM) monomer is a bioactive compound extracted from Chinese herbal medicines possessing determined biological activity and pharmacological effects, and has gained much attention for treating neuronal diseases. However, the application of TCM monomers is limited by their low solubility and poor ability to cross the blood-brain barrier (BBB). Exosomes are small extracellular vesicles (EVs) ranging in size from 30 to 150 nm in diameter and can be used as drug delivery carriers that directly target cells or tissues with unique advantages, including low toxicity, low immunogenicity, high stability in blood, and the ability to cross the BBB. This review discusses the biogenesis, components, stability, surface modification, isolation technology, advantages, and disadvantages of exosomes as drug carriers and compares exosomes and other similar drug delivery systems. Furthermore, exosome-encapsulated TCM monomers exert neuroprotective roles, such as anti-inflammation, anti-apoptosis, anti-mitophagy, and anti-oxidation, in various neuronal diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and cerebral ischemia and reperfusion (CI/R) injury, as well as anti-drug resistance, anti-tumorigenesis, anti-angiogenesis, and promotion of apoptosis in brain tumors, providing more inspiration to promote the development of an exosome-based delivery tool in targeted therapy for neuronal diseases.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101131"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144259818","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}
Caiyi Yang, Kehan Chen, Yunliang Chen, Xuting Xie, Pengcheng Li, Meng Zhao, Junjie Liang, Xueqian Xie, Xiaoyun Chen, Yanping Cai, Bo Xu, Qing Wang, Lian Zhou, Xia Luo
{"title":"Liquiritin improves macrophage degradation of engulfed tumour cells by promoting the formation of phagolysosomes via NOX2/gp91phox.","authors":"Caiyi Yang, Kehan Chen, Yunliang Chen, Xuting Xie, Pengcheng Li, Meng Zhao, Junjie Liang, Xueqian Xie, Xiaoyun Chen, Yanping Cai, Bo Xu, Qing Wang, Lian Zhou, Xia Luo","doi":"10.1016/j.jpha.2024.101093","DOIUrl":"10.1016/j.jpha.2024.101093","url":null,"abstract":"<p><p>The incomplete degradation of tumour cells by macrophages (Mϕ) is a contributing factor to tumour progression and metastasis, and the degradation function of Mϕ is mediated through phagosomes and lysosomes. In our preliminary experiments, we found that overactivation of NADPH oxidase 2 (NOX2) reduced the ability of Mϕ to degrade engulfed tumour cells. Above this, we screened out liquiritin from <i>Glycyrrhiza uralensis Fisch</i>, which can significantly inhibit NOX2 activity and inhibit tumours, to elucidate that suppressing NOX2 can enhance the ability of Mϕ to degrade tumour cells. We found that the tumour environment could activate the NOX2 activity in Mϕ phagosomes, causing Mϕ to produce excessive reactive oxygen species (ROS), thus prohibiting the formation of phagolysosomes before degradation. Conversely, inhibiting NOX2 in Mϕ by liquiritin can reduce ROS and promote phagosome-lysosome fusion, therefore improving the enzymatic degradation of tumour cells after phagocytosis, and subsequently promote T cell activity by presenting antigens. We further confirmed that liquiritin down-regulated the expression of the NOX2 specific membrane component protein gp91 phox, blocking its binding to the NOX2 cytoplasmic component proteins p67 phox and p47 phox, thereby inhibiting the activity of NOX2. This study elucidates the specific mechanism by which Mϕ cannot degrade tumour cells after phagocytosis, and indicates that liquiritin can promote the ability of Mϕ to degrade tumour cells by suppressing NOX2.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101093"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268263","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":"Polyphyllin VII promotes hepatic stellate cell ferroptosis via the HIC1/CX3CL1/GPX4 axis.","authors":"Feng Jiang, Xinmiao Li, Mengyuan Li, Weizhi Zhang, Yifei Li, Lifan Lin, Lufan He, Jianjian Zheng","doi":"10.1016/j.jpha.2024.101147","DOIUrl":"10.1016/j.jpha.2024.101147","url":null,"abstract":"<p><p>Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of <i>Paris polyphylla</i>, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (<i>Hic1</i>), which binds to the <i>Cx3cl1</i> promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis <i>in vivo</i>. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101147"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268264","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":"A review of research methods for elucidating the microstructure of pharmaceutical preparations.","authors":"Peng Yan, Zhiyuan Hou, Jinsong Ding","doi":"10.1016/j.jpha.2024.101156","DOIUrl":"10.1016/j.jpha.2024.101156","url":null,"abstract":"<p><p>The microstructures of pharmaceutical preparations play a pivotal role in determining their critical quality attributes (CQAs), such as drug release, content uniformity, and stability, which greatly impact the safety and efficacy of drugs. Unlike the inherent molecular structures of active pharmaceutical ingredients (APIs) and excipients, the microstructures of pharmaceutical preparations are developed during the formulation process, presenting unique analytical challenges. In this review, we primarily focus on presenting the research methods used to elucidate the microstructures of pharmaceutical preparations, including X-ray imaging (XRI), scanning electron microscopy (SEM), atomic force microscopy (AFM), Raman spectroscopy, infrared (IR) spectroscopy, and rheometer technology. Subsequently, we highlight the applications, advantages, and limitations of these methods. Finally, we discuss the current challenges and future perspectives in this field. This review aims to provide a comprehensive reference for understanding the microstructures of pharmaceutical preparations, offering new insights and potential advancements in their development.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101156"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12150094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268257","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}
Zeshan Ali, Aqsa Ayub, Yawen Lin, Sonam Anis, Ishrat Khan, Shoaib Younas, Rana Adnan Tahir, Shulin Wang, Jianrong Li
{"title":"<i>Lycium</i> <i>b</i> <i>arbarum</i>'s diabetes secrets: A comprehensive review of cellular, molecular, and epigenetic targets with immune modulation and microbiome influence.","authors":"Zeshan Ali, Aqsa Ayub, Yawen Lin, Sonam Anis, Ishrat Khan, Shoaib Younas, Rana Adnan Tahir, Shulin Wang, Jianrong Li","doi":"10.1016/j.jpha.2024.101130","DOIUrl":"10.1016/j.jpha.2024.101130","url":null,"abstract":"<p><p>Diabetes, a metabolic disease stemming from impaired or defective insulin secretion, ranks among the most severe chronic illnesses globally. While several approved drugs exist for its treatment, they often come with multiple side effects. Therefore, there is a pressing need for safe and effective anti-diabetic medications. Traditional Chinese medicine has recognized <i>Lycium barbarum</i> (LB; goji berry) plant, commonly known as \"wolfberry fruit\" in China, for over 2,000 years. Natural compounds derived from LB show promise in reducing diabetes levels. Although research on the impact of LB on diabetes is still limited, our review aims to explore the potential of LB in reducing the risk of diabetes and examine the underlying mechanisms involved. LB can modulate diabetes through various pathways, such as inhibiting α-amylase and α-glucosidase activities, promoting β-cell proliferation, stimulating insulin secretion, inhibiting glucagon secretion, improving insulin resistance and glucose tolerance, and enhancing antioxidant and anti-inflammatory activities. Additionally, LB improves gut flora and immunomodulation, further aiding diabetes management. These findings highlight the potential clinical utility of LB in managing diabetes and its complications within the framework of evidence-based modern medicine.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 5","pages":"101130"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12151213/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268343","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":"Thalidomide mitigates Crohn's disease colitis by modulating gut microbiota, metabolites, and regulatory T cell immunity.","authors":"Chao-Tao Tang, Yonghui Wu, Qing Tao, Chun-Yan Zeng, You-Xiang Chen","doi":"10.1016/j.jpha.2024.101121","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101121","url":null,"abstract":"<p><p>Thalidomide (THA) is renowned for its potent anti-inflammatory properties. This study aimed to elucidate its underlying mechanisms in the context of Crohn's disease (CD) development. Mouse colitis models were established by dextran sulfate sodium (DSS) treatment. Fecal microbiota and metabolites were analyzed by metagenomic sequencing and mass spectrometry, respectively. Antibiotic-treated mice served as models for microbiota depletion and transplantation. The expression of forkhead box P3<sup>+</sup> (FOXP3<sup>+</sup>) regulatory T cells (Tregs) was measured by flow cytometry and immunohistochemical assay in colitis model and patient cohort. THA inhibited colitis in DSS-treated mice by altering the gut microbiota profile, with an increased abundance of probiotics <i>Bacteroides fragilis</i>, while pathogenic bacteria were depleted. In addition, THA increased beneficial metabolites bile acids and significantly restored gut barrier function. Transcriptomic profiling revealed that THA inhibited interleukin-17 (IL-17), IL-1β and cell cycle signaling. Fecal microbiota transplantation from THA-treated mice to microbiota-depleted mice partly recapitulated the effects of THA. Specifically, increased level of gut commensal <i>B. fragilis</i> was observed, correlated with elevated levels of the microbial metabolite 3alpha-hydroxy-7-oxo-5beta-cholanic acid (7-ketolithocholic acid, 7-KA) following THA treatment. This microbial metabolite may stable FOXP3 expression by targeting the receptor FMR1 autosomal homolog 1 (FXR1) to inhibit autophagy. An interaction between FOXP3 and FXR1 was identified, with binding regions localized to the FOXP3 domain (aa238-335) and the FXR1 domain (aa82-222), respectively. Conclusively, THA modulates the gut microbiota and metabolite profiles towards a more beneficial composition, enhances gut barrier function, promotes the differentiation of FOXP3<sup>+</sup> Tregs and curbs pro-inflammatory pathways.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101121"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144016089","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}
Zhe Yu, Teng Li, Zhi Zheng, Xiya Yang, Xin Guo, Xindi Zhang, Haoying Jiang, Lin Zhu, Bo Yang, Yang Wang, Jiekun Luo, Xueping Yang, Tao Tang, En Hu
{"title":"Tailoring a traditional Chinese medicine prescription for complex diseases: A novel multi-targets-directed gradient weighting strategy.","authors":"Zhe Yu, Teng Li, Zhi Zheng, Xiya Yang, Xin Guo, Xindi Zhang, Haoying Jiang, Lin Zhu, Bo Yang, Yang Wang, Jiekun Luo, Xueping Yang, Tao Tang, En Hu","doi":"10.1016/j.jpha.2025.101199","DOIUrl":"https://doi.org/10.1016/j.jpha.2025.101199","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) exerts integrative effects on complex diseases owing to the characteristics of multiple components with multiple targets. However, the syndrome-based system of diagnosis and treatment in TCM can easily lead to bias because of varying medication preferences among physicians, which has been a major challenge in the global acceptance and application of TCM. Therefore, a standardized TCM prescription system needs to be explored to promote its clinical application. In this study, we first developed a gradient weighted disease-target-herbal ingredient-herb network to aid TCM formulation. We tested its efficacy against intracerebral hemorrhage (ICH). First, the top 100 ICH targets in the GeneCards database were screened according to their relevance scores. Then, SymMap and Traditional Chinese Medicine Systems Pharmacology (TCMSP) databases were applied to find out the target-related ingredients and ingredient-containing herbs, respectively. The relevance of the resulting ingredients and herbs to ICH was determined by adding the relevance scores of the corresponding targets. The top five ICH therapeutic herbs were combined to form a tailored TCM prescriptions. The absorbed components in the serum were detected. In a mouse model of ICH, the new prescription exerted multifaceted effects, including improved neurological function, as well as attenuated neuronal damage, cell apoptosis, vascular leakage, and neuroinflammation. These effects matched well with the core pathological changes in ICH. The multi-targets-directed gradient-weighting strategy presents a promising avenue for tailoring precise, multipronged, unbiased, and standardized TCM prescriptions for complex diseases. This study provides a paradigm for advanced achievements-driven modern innovation in TCM concepts.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101199"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12036049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144040554","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}
Yangyang Wang, Yizhou Rong, Liangce Chen, Qi Cui, Haixue Kuang, Bo Yang
{"title":"Hypothalamic lipidomics reveals that AMPK-FA metabolism mediates the energy-balancing effect of the four typical \"hot\" herbs on hypothyroidism.","authors":"Yangyang Wang, Yizhou Rong, Liangce Chen, Qi Cui, Haixue Kuang, Bo Yang","doi":"10.1016/j.jpha.2024.101151","DOIUrl":"https://doi.org/10.1016/j.jpha.2024.101151","url":null,"abstract":"<p><p>Image 1.</p>","PeriodicalId":94338,"journal":{"name":"Journal of pharmaceutical analysis","volume":"15 4","pages":"101151"},"PeriodicalIF":0.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11999588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047590","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}