Jiawei Tan , Yichao Li , Peixin Chen , Xiaowen Huang , Tianyu Tang , Yingsong Chao , Mingxi Chen , Quanxing Liao , Yan Zhang , Junfeng Ban , Xiaofang Li
{"title":"Study of tea bran: comprehensive chemical profiling by UPLC-Q-TOF-MS/MS linked to antibacterial and antioxidant activities for potential high-value applications","authors":"Jiawei Tan , Yichao Li , Peixin Chen , Xiaowen Huang , Tianyu Tang , Yingsong Chao , Mingxi Chen , Quanxing Liao , Yan Zhang , Junfeng Ban , Xiaofang Li","doi":"10.1016/j.jhip.2026.05.005","DOIUrl":"10.1016/j.jhip.2026.05.005","url":null,"abstract":"<div><h3>Objective</h3><div>Tea bran, also referred to as tea residue or tea seed cake, is the residual by-product generated after the extraction and pressing of tea oil. As a traditional agricultural waste product, the high-value utilization of tea bran plays a significant role in promoting the development of a green circular economy. Therefore, determining its chemical composition and biological activity is fundamental to realizing such high-value applications.</div></div><div><h3>Methods</h3><div>This study aimed to optimize the extraction process of tea bran extract and to quantitatively determine its tea saponin (TS) and total flavonoid (TF) contents using ultraviolet-visible (UV) spectrophotometry. The phytochemical composition of the extract was systematically characterized via ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Furthermore, its <em>in vitro</em> biological activities were evaluated, including antibacterial effects against <em>Staphylococcus aureus</em> (<em>S. aureus</em>) and methicillin-resistant <em>Staphylococcus aureus</em> (MRSA) by determining the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) using the broth dilution method, as well as antioxidant potential via DPPH and ABTS radical scavenging assays.</div></div><div><h3>Results</h3><div>This study established an optimal method for extracting tea bran extract using reflux extraction with 80% ethanol-water as the solvent, involving two extraction cycles of 90 min each. UV spectroscopic analysis revealed that tea saponins were the predominant constituents of the extract, with a content of (130.44 ± 0.54) mg/g, whereas the total flavonoid content was only (50.75 ± 2.21) mg/g. A total of 51 compounds were preliminarily identified in the extract using UPLC-Q-TOF-MS/MS. Furthermore, <em>in vitro</em> bioactivity assays demonstrated that the tea bran extract exhibited significant antibacterial activity against Gram-positive bacteria, including <em>S. aureus</em> and MRSA. The extract also exhibited notable antioxidant activity, with half-maximal inhibitory concentration (IC<sub>50</sub>) values of (131.94 ± 7.79) μg/mL for the DPPH radical and (299.21 ± 3.64) μg/mL for the ABTS radical.</div></div><div><h3>Conclusion</h3><div>As the primary constituent of tea bran extract, tea saponin is a naturally occurring antimicrobial agent that also exhibits antioxidant properties. The present study provides fundamental guidance for the comprehensive development and utilization of tea bran.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 293-302"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189489","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":"Ethnobotanical survey and evaluation of antioxidant and angiotensin-converting enzyme inhibitory activities of selected medicinal plants","authors":"Cherish Blessing Ordia , Mubo Adeola Sonibare , Akingbolabo Daniel Ogunlakin","doi":"10.1016/j.jhip.2026.05.006","DOIUrl":"10.1016/j.jhip.2026.05.006","url":null,"abstract":"<div><h3>Objective</h3><div>The pathophysiology of several diseases, including hypertension, is linked to oxidative stress. Natural antioxidants play a crucial role in maintaining the balance between pro- and antioxidant levels. Angiotensin-converting enzyme inhibitors (ACEIs) are a class of drugs that treat high blood pressure, also known as hypertension. The limitations of orthodox antihypertensive medications, including side effects and high costs, emphasize the need for alternative therapies. This study investigates the ethnobotanical relevance, antioxidant properties, and antihypertensive potential of selected medicinal plants.</div></div><div><h3>Methods</h3><div>Seven plants, including <em>Picralima nitida, Securidaca longipedunculata, Tetracera alnifolia, Senna fistula, Peperomia pellucida, Kigelia africana</em>, and <em>Mangifera indica,</em> were selected for the study from an ethnobotanical survey conducted in Ibadan, Nigeria. The plant samples were collected, authenticated, air-dried, and pulverized. 200 g of the powdered samples were extracted using 70% ethanol at room temperature for 72 h. The extracts were concentrated using a rotary evaporator at 40 °C. Phytochemical screenings were conducted to detect the presence and absence of secondary metabolites. The antioxidant activities were evaluated using 2,2-Diphenyl-1-Picrylhydrazyl (DPPH), Ferric Reducing Antioxidant Power (FRAP), and Nitric Oxide (NO) assays. Ascorbic acid, Trolox, and sodium nitrite were used as standards. Four plants with the highest antioxidant activity were selected for <em>in vitro</em> antihypertensive activity, which was assessed through an angiotensin-converting enzyme (ACE) inhibition assay using hippuryl-L-histidyl-L-leucine (HHL) as the substrate. Captopril was used as the standard. Absorbance was read at 208 nm. Experiments were conducted in triplicate, and the values were expressed as percentage inhibition, using version 5.01 for Windows, GraphPad Software, San Diego, California, USA. <em>P</em>-values that were less than 0.05 were deemed significant.</div></div><div><h3>Results</h3><div>Phytochemical screening revealed the presence of saponin, flavonoid, tannin, cardiac glycosides, anthraquinones, and alkaloids in <em>Picralima nitida</em>, <em>Senna fistula,</em> and <em>Kigelia africana</em>. Alkaloids were absent in <em>Securidaca longipenduculata</em> and <em>Mangifera indica</em>. <em>Kigelia africana</em> (94.55% ± 0.11%) and <em>Mangifera indica</em> (95.20% ± 0.03%) showed the strongest DPPH scavenging ability, while <em>Picralima nitida</em> (82.88% ± 0.57%) and <em>Securidaca longipedunculata</em> (72.59% ± 1.61%) had moderate activity. <em>Kigelia africana</em> and <em>Securidaca longipedunculata</em> had ferric reducing antioxidant capacities of 5.50 ± 0.41 μg TE/mg and 5.39 ± 0.20 μg TE/mg, respectively. <em>Securidaca longipedunculata</em> (82.13% ± 2.82%) and <em>Tetracera alnifolia</em> (80.72% ± 4.45%) excelled as NO scavenging agents,","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 260-269"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189785","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}
Wanying Jia , Jiao Li , Xiaoshuang Chen , Weiya Zhang , Mingge Geng , Fang Cao , Songji Song , Xia Xu , Lingbo Qu
{"title":"From components to mechanisms: study on the anti-inflammatory effects and mechanisms of active compounds in Phoebe zhennan","authors":"Wanying Jia , Jiao Li , Xiaoshuang Chen , Weiya Zhang , Mingge Geng , Fang Cao , Songji Song , Xia Xu , Lingbo Qu","doi":"10.1016/j.jhip.2026.05.008","DOIUrl":"10.1016/j.jhip.2026.05.008","url":null,"abstract":"<div><h3>Objective</h3><div>To analyse the chemical components of <em>Phoebe zhennan</em> and preliminarily investigate its anti-inflammatory mechanism based on network pharmacology and cell experiments, thereby providing a scientific basis for the utilisation and development of traditional timber resources.</div></div><div><h3>Methods</h3><div>The chemical components of the essential oil and wood of <em>Phoebe zhennan</em> were analyzed using GC-Orbitrap-HRMS and UPLC-Q-Exactive-MS, respectively. The compounds were identified by spectral library matching and accurate molecular mass determination, and their relative contents were calculated using the peak area normalization method. Component targets were predicted by TCMSP, PharmMapper and other databases, and inflammation targets were obtained by combining with GeneCards and OMIM databases; protein-protein interactions (PPI) network was constructed by STRING, core targets were screened by Cytoscape, and enriched by DAVID database, and molecular docking was verified by Autodock. Finally, an <em>in vitro</em> inflammation model was established using LPS-induced RAW264.7 cells to evaluate the effects of <em>Phoebe zhennan</em> extract and its active components, alantolactone and farnesol, on the release of NO, TNF-<em>α</em> and IL-6. Reverse transcription quantitative real-time PCR (RT-qPCR) was also employed to detect the mRNA expression of IL-17A, IL-17RA and ACT1 in the IL-17 signalling pathway.</div></div><div><h3>Results</h3><div>A total of 65 compounds were identified from essential oil by GC-Orbitrap-HRMS, 99 compounds from wood by UPLC-Q-Exactive-MS, and 41 compounds by GNPS complementary analysis, with terpenoids dominating all the components. Network pharmacology analysis revealed 48 common targets between the active components and inflammation; enrichment analysis indicated that these targets are mainly involved in biological processes such as regulation of cell apoptosis, modulation of inflammatory response, and xenobiotic stimulus response, exerting anti-inflammatory, immunomodulatory, and cell apoptosis-regulating effects through signaling pathways including IL-17, PI3K-AKT, and cancer-related pathways; molecular docking demonstrated that alantolactone exhibits the optimal binding activity with the core targets. <em>In vitro</em> cell experiments demonstrated that <em>Phoebe zhennan</em> extract, alantolactone and farnesol, within safe concentration ranges, significantly inhibited LPS-induced release of NO, TNF-<em>α</em> and IL-6, and downregulated the mRNA expression of IL-17A, IL-17RA and ACT1.</div></div><div><h3>Conclusion</h3><div><em>Phoebe zhennan</em> extract and its active components, alantolactone and farnesol, exhibit good anti-inflammatory activity, and the mechanism may be related to the inhibition of the IL-17 signalling pathway.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 280-292"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189784","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":"Cannabidiol as a modulator of NLRP3 inflammasome: Mechanistic insights and therapeutic potential","authors":"Dharshini Jaisankar, Nandhini Jayaprakash","doi":"10.1016/j.jhip.2026.05.003","DOIUrl":"10.1016/j.jhip.2026.05.003","url":null,"abstract":"<div><div>Dysregulated activation of the NLRP3 inflammasome is a central driver of chronic inflammatory, neurodegenerative, metabolic, and autoimmune diseases, contributing significantly to the global burden of disease and reduced quality of life. Cannabidiol (CBD), a non-psychoactive phytocannabinoid derived from <em>Cannabis sativa</em>, has emerged as a promising complementary and integrative therapeutic agent due to its broad anti-inflammatory and immunomodulatory properties. This narrative review synthesizes current mechanistic and translational evidence demonstrating that CBD modulates NLRP3 inflammasome activity through multiple interconnected pathways. These include suppression of NF-<em>κ</em>B–mediated priming, attenuation of mitochondrial dysfunction and reactive oxygen species generation, regulation of ionic fluxes, and enhancement of autophagic clearance of inflammasome activators. Collectively, these actions lead to reduced caspase-1 activation and decreased release of interleukin-1<em>β</em> and interleukin-18, conferring protective effects in preclinical models of neuroinflammation, colitis, metabolic dysfunction, and organ injury. Despite robust preclinical support, clinical translation of CBD remains constrained by poor oral bioavailability, extensive first-pass metabolism, and formulation-dependent pharmacokinetics highlighting the need for innovative, affordable, and accessible pharmaceutical technologies. Emerging pharmaceutical strategies, including nano-delivery systems and advanced formulations, offer potential solutions to these limitations. Viewed through a systems-oriented pharmacological framework, CBD represents a plant-based, multi-target modulator capable of regulating complex inflammatory networks rather than single molecular targets. While existing evidence supports its therapeutic promise, biomarker-driven clinical trials are essential to establish its efficacy and clinical relevance in inflammasome-driven diseases.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 338-349"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148242870","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}
Yaxiong Liu, Xuan Zhang, Jiaxin Wen, Zhuoya Luo, Hua Li, Zhiye Yang
{"title":"Rapid identification of lingnan traditional Chinese medicinal materials via headspace-gas chromatography-ion mobility spectrometry combined with deep learning","authors":"Yaxiong Liu, Xuan Zhang, Jiaxin Wen, Zhuoya Luo, Hua Li, Zhiye Yang","doi":"10.1016/j.jhip.2026.05.004","DOIUrl":"10.1016/j.jhip.2026.05.004","url":null,"abstract":"<div><h3>Objective</h3><div>To develop a rapid, accurate, and non-destructive authentication method for Lingnan traditional Chinese medicinal materials (TCMMs), this study integrated headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) with deep learning technology.</div></div><div><h3>Methods</h3><div>A total of 4755 HS-GC-IMS fingerprint samples were collected from 11 types of medicinal materials, including 9 types of Lingnan TCMMs (e.g., <em>Amomum villosum</em>, agarwood, <em>Citrus reticulata</em>) and 2 types of non-Lingnan TCMMs (<em>Cordyceps sinensis</em> and its weight-increased adulterants), to construct a dataset in Portable Network Graphics (PNG) and comma-separated values (CSV) formats. Three convolutional neural network models (ResNet18, MobileNetV2, and EfficientNet-B0) were trained for multi-class classification, with the ArcFace loss function applied to enhance inter-class separability. Model performance was evaluated using accuracy, precision, recall, and F1-score.</div></div><div><h3>Results</h3><div>The EfficientNet-B0 model exhibited the optimal performance, achieving an average accuracy of 99.56%, precision of 97.62%, recall of 99.42%, and F1-score of 98.49%. It successfully distinguished geographical origins of Lingnan TCMMs, verified authenticity of genuine vs. counterfeit samples, and achieved high-accuracy identification of non-Lingnan <em>Cordyceps sinensis</em>. Notably, PNG-format spectral images showed 140-fold higher training efficiency and 12-fold higher inference efficiency than CSV data.</div></div><div><h3>Conclusion</h3><div>This study first established an HS-GC-IMS fingerprint dataset covering Lingnan and non-Lingnan TCMMs. The proposed method not only provides a reliable and efficient solution for quality control of Lingnan TCMMs but also demonstrates strong extended application potential, offering a technical innovation for traditional Chinese medicine inspection and promoting its modernization.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 303-311"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189354","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}
Yaxing Zhou , Yakun Hao , Qing Liu , Xiaoqun Shen , Xiaoqian Zhang , Shengguo Ji
{"title":"Characterization of Alismatis Rhizoma and its salt-processed products via near-infrared spectroscopy with partial least squares regression","authors":"Yaxing Zhou , Yakun Hao , Qing Liu , Xiaoqun Shen , Xiaoqian Zhang , Shengguo Ji","doi":"10.1016/j.jhip.2026.05.001","DOIUrl":"10.1016/j.jhip.2026.05.001","url":null,"abstract":"<div><h3>Objective</h3><div>Alismatis Rhizoma (AR) is the dried rhizome of <em>Alisma orientale</em> (Sam.) Juzep. and <em>Alisma plantago-aquatica</em> Linn., as recorded in the Chinese Pharmacopoeia (2025 Edition, Part I). This study aimed to develop a rapid and reliable quality evaluation strategy for AR and its salt-processed product, Salt-processed Alismatis Rhizoma (SAR), by integrating near-infrared spectroscopy (NIRS) with partial least squares (PLS) regression. Quantitative and qualitative models were established to support routine quality control and geographical origin identification.</div></div><div><h3>Methods</h3><div>Reference values for alisol B 23-acetate, alisol C 23-acetate, moisture, alcohol-soluble extract, and total ash were obtained through high-performance liquid chromatography (HPLC) and pharmacopoeial methods. Corresponding NIR spectra were collected and subjected to preprocessing, wavelength optimisation, and multivariate modelling. Quantitative PLS models and qualitative discriminant models were constructed and validated.</div></div><div><h3>Results</h3><div>Twelve quantitative calibration models exhibited strong predictive performance, with high correlation coefficients and low RMSEC/RMSEP values across all indicators. The qualitative models accurately differentiated AR and SAR from different production regions, achieving 100% classification accuracy for calibration samples. The optimized preprocessing methods and spectral regions significantly enhanced model robustness.</div></div><div><h3>Conclusion</h3><div>NIRS combined with PLS regression provides an efficient, nondestructive, and high-throughput approach for assessing the quality of AR and SAR. The established models support rapid batch screening and origin discrimination, offering scientific evidence for standardized quality control and practical application in traditional Chinese medicine.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 270-279"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189490","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}
Yuchen Wang, Shuo Fu, Xiaoyue Zhao, Guiquan Ding, Ye Wang, Wen Zhang, Junke Song, Guanhua Du
{"title":"Isoliquiritin apioside, a natural product from Glycyrrhizae radix et rhizoma, alleviates cerebral ischemia-reperfusion injury by suppressing TXNIP/NLRP3-mediated pyroptosis","authors":"Yuchen Wang, Shuo Fu, Xiaoyue Zhao, Guiquan Ding, Ye Wang, Wen Zhang, Junke Song, Guanhua Du","doi":"10.1016/j.jhip.2026.06.002","DOIUrl":"10.1016/j.jhip.2026.06.002","url":null,"abstract":"<div><h3>Objective</h3><div>Cerebral ischemia-reperfusion (I/R) injury contributes substantially to neuronal damage after stroke. Recent studies have demonstrated the efficacy of <em>Glycyrrhizae</em> radix et rhizoma in I/R injury, yet the underlying mechanism remains unclear. Therefore, the present study investigated whether isoliquiritin apioside (ISLA), a bioactive compound derived from it, protected against cerebral I/R injury.</div></div><div><h3>Methods</h3><div>Rats subjected to middle cerebral artery occlusion/reperfusion were treated with ISLA (5, 10, or 20 mg/kg). Neurological outcomes and infarct volume were evaluated, histopathological and apoptotic changes were assessed by H&E and TUNEL staining, oxidative stress was determined by MDA and SOD assays, the expression of proteins related to TXNIP/NLRP3 signaling, pyroptosis, and inflammation was examined by western blotting and immunofluorescence methods.</div></div><div><h3>Results</h3><div>ISLA significantly reduced infarct volume, improved neurological function, preserved cortical morphology, and decreased TUNEL-positive cells in the ischemic brain. ISLA also attenuated oxidative stress, as evidenced by reduced MDA levels and restored SOD activity. Mechanistically, ISLA downregulated TXNIP and NLRP3 expressions, suppressed cleaved caspase-1 and cleaved GSDMD production, and reduced IL-1<em>β</em> and IL-18 levels.</div></div><div><h3>Conclusion</h3><div>These findings indicated that ISLA alleviated cerebral I/R injury, at least in part, by reducing oxidative stress and inhibiting TXNIP/NLRP3-associated pyroptotic and inflammatory signaling.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 365-374"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148539896","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":"Flavone scaffold: A polypharmacological strategy in multifactorial disease","authors":"Nilotpal Choudhury, Haradeep Nath, Nilanjana Medhi, Rajdeep Bhuyan, Debaprotim Dasgupta, Bhargab Jyoti Sahariah, Deijy Choudhury, Babita Deka, Pooja Patowary","doi":"10.1016/j.jhip.2026.06.004","DOIUrl":"10.1016/j.jhip.2026.06.004","url":null,"abstract":"<div><div>Flavones are a subclass of flavonoids, the plant-derived polyphenolic compounds that are biologically constructed in terms of chemical structure and are constructed around a 2-phenylchromen-4-one nucleus which can be considered to be a class of evolutionarily privileged natural products designed to fit into various biological systems. The conventional \"one drug, one target\" approach to the treatment of the various complex multifactorial diseases that afflict mankind, like cancer, diabetes and neurodegenerative diseases, has been increasingly found wanting and attention has re-focused on multi-target therapeutics, i.e., polypharmacology, which seeks to effect simultaneous multi-point modulations of the various abnormalities associated with these diseases via the use of a single chemical entity. The current review gives a comprehensive analysis of the new developments that are reported in the use of flavone derivatives as multi-target therapeutic agents. This includes both the chemical and biological rationale for their suitability for use as polypharmacological agents. There is a detailed assessment of the important approaches that are possible, including inspiration from natural products, synthetic modifications of these compounds (thionation, halogenation, carbamoylation) to overcome pharmacokinetic limitations, and the rational design of novel hybrid molecules incorporating two or more pharmacophores to give synergistic results. The therapeutic effects of these new derivatives are considered in some detail covering their effects in Alzheimer's Disease, Parkinsonism, cancers and diabetes mellitus where they would seem to modulate pathological processes in inflammation, oxidative stress, cell signalling and metabolism at one and the same time. Finally, the review deals with some of the crucial translational aspects such as bioavailability and possible toxicity and gives a critical account of future possibilities such as the introduction of new advanced delivery systems and the harvesting of artificial intelligence in the considerations of drug design.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 388-403"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148539959","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":"Gut microbiota and radiotherapy: towards enhancing radiotherapy efficacy and mitigating toxicities","authors":"Rourong Li, Jiayuan Huang","doi":"10.1016/j.jhip.2026.05.007","DOIUrl":"10.1016/j.jhip.2026.05.007","url":null,"abstract":"<div><div>Radiotherapy (RT) is a principal modality for cancer treatment; however, its clinical benefit is often limited by treatment-associated toxicities, particularly radiation enteritis (RE), which can reduce patients’ quality of life and treatment adherence. Increasing evidence indicates that the gut microbiota, an emerging pharmacological target and essential regulator of epithelial barrier integrity, metabolism, and immune homeostasis, plays an important role in both RT-induced intestinal injury and tumor radiosensitivity. RT disrupts microbial diversity and metabolic functions, leading to dysbiosis, impaired epithelial barrier repair, altered metabolite networks, and exaggerated inflammatory responses. Conversely, specific microbial taxa and their metabolites, especially short-chain fatty acids (SCFAs), can modulate antitumor immunity, DNA damage response and repair pathways, microbial metabolite signaling, and mucosal resilience, thereby influencing both tumor radiosensitivity and host susceptibility to intestinal injury. This review summarizes the bidirectional interactions between RT and the gut microbiota, with emphasis on mechanisms underlying radiation-induced microbial alterations and microbiota-mediated modulation of RT efficacy and toxicity. We further discuss microbiota-targeted therapeutic strategies, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation (FMT), antibiotic modulation, dietary interventions, and traditional Chinese medicine (TCM)-derived compounds and formulae, as promising approaches to mitigate RE and improve therapeutic outcomes. Understanding these microbiota-RT interactions may support microbiota-guided precision radiotherapy and facilitate the development of microbiota-based drugs for enhancing RT efficacy and reducing toxicities.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 350-359"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148242871","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":"miR-221-3p mediates T-cell differentiation through repressing DYRK1A","authors":"Hongqiong Wang, Jieming Hu, Jia Chen, Wenkai Shi, Huishan Zhong, Hongwei Shao, Wenfeng Zhang, Fenglin Wu","doi":"10.1016/j.jhip.2026.05.010","DOIUrl":"10.1016/j.jhip.2026.05.010","url":null,"abstract":"<div><h3>Objective</h3><div>This study aims to comprehensively investigate the role and underlying molecular mechanism of hsa-miR-221-3p in regulating the differentiation and effector functions of distinct T cell subpopulations, and to further explore the potential implication of modulating miR-221-3p activity for optimizing CAR-T cell therapy persistence.</div></div><div><h3>Methods</h3><div>Based on miRNA expression profiles of four T cell subpopulations [naïve T cells (TN), stem cell-like memory T cells (TSCM), central memory T cells (TCM), and effector memory T cells (TEM)] obtained by high-throughput sequencing in a previous study, differential expression analysis was performed between TN and other subpopulations to identify hsa-miR-221-3p. Computational prediction was used to screen putative targets of miR-221-3p, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A dual luciferase reporter assay was conducted to verify the direct binding of miR-221-3p to <em>DYRK1A</em>. Functional experiments were performed to assess the effects of miR-221-3p overexpression on T cell proliferation, apoptosis, cell death, cytokine secretion (TNF-<em>α</em> and IFN-<em>γ</em>), and expression of differentiation-related genes. Flow cytometry was used to analyze the changes in T cell subsets (marked by CD62L and CD45RO) after miR-221-3p overexpression.</div></div><div><h3>Results</h3><div>GO and KEGG analyses revealed that miR-221-3p target genes were enriched in transcription regulatory pathways. Dual-luciferase assays confirmed direct binding of miR-221-3p to <em>DYRK1A</em>, suppressing its expression in T cells. Functionally, miR-221-3p overexpression reduced T cell proliferation, increased apoptosis, and enhanced TNF-<em>α</em> and IFN-<em>γ</em> secretion. Mechanistically, it downregulated early differentiation genes while upregulating late differentiation/effector genes (<em>Blimp-1</em>, <em>T-bet</em>, <em>GZMB</em>, <em>GNLY</em>). Flow cytometry confirmed a shift from TN toward TEM/TEFF subsets.</div></div><div><h3>Conclusion</h3><div>miR-221-3p drives terminal effector differentiation of T cells by repressing <em>DYRK1A</em>. Inhibition of miR-221-3p preserves early memory subsets, offering a potential strategy to enhance CAR-T cell persistence.</div></div>","PeriodicalId":100787,"journal":{"name":"Journal of Holistic Integrative Pharmacy","volume":"7 2","pages":"Pages 312-325"},"PeriodicalIF":0.0,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148189783","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}