Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2025-12-29DOI: 10.1080/13880209.2025.2606959
Zhongfu Tang, Lili Cheng, Ming Li, Junjie Chen, Chuanbing Huang
{"title":"Jianpi Zishen Decoction ameliorates renal damage induced by systemic lupus erythematosus through inhibition of the TLR4/MAPK pathway.","authors":"Zhongfu Tang, Lili Cheng, Ming Li, Junjie Chen, Chuanbing Huang","doi":"10.1080/13880209.2025.2606959","DOIUrl":"10.1080/13880209.2025.2606959","url":null,"abstract":"<p><strong>Context: </strong>Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. Jianpi Zishen Decoction (JZD) is a TCM formula used to improve proteinuria in SLE, which has been widely used in the treatment of renal damage in SLE.</p><p><strong>Objective: </strong>To investigate the potential targets and action mechanisms of JZD in ameliorating renal damage in SLE through network pharmacology and <i>in-vivo</i> and <i>in-vitro</i> experiments.</p><p><strong>Methods: </strong>The main components of JZD were determined using UPLC-Q-TOF-MS/MS. The potential targets and action mechanisms of JZD were explored using network pharmacology and molecular docking techniques. MRL/lpr mice were used as animal models, and their renal pathological changes were observed by HE staining, periodic acid-Schiff staining, and Masson staining. Additionally, mouse glomerular ultrastructure was observed using TEM. The level of urinary protein, immunoinflammatory indicators, and TLR4/MAPK pathway-related molecules were detected through a variety of experimental methods. Furthermore, the effects of JZD on LPS-stimulated HMCs were evaluated.</p><p><strong>Results: </strong>A total of 27 prototype components were identified in the blood-entered component of JZD. Animal experiments showed that JZD effectively ameliorated renal damage and immune disorders, reduced glomerular scores and vascular wall scores, as well as attenuated IgG and C3 deposition in the kidneys of MRL/lpr mice. Network pharmacological analysis and molecular docking identified TLR4 as a core potential target of JZD's efficacy. JZD inhibited the expression of TLR4, p38, JNK, AP-1, and pro-inflammatory factors in the kidneys of MRL/lpr mice. <i>In-vitro</i> experiments further showed that JZD inhibited LPS-induced HMC proliferation.</p><p><strong>Conclusion: </strong>JZD could ameliorate SLE renal damage and its active ingredients exerted therapeutic effects by inhibiting the TLR4/MAPK pathway, highlighting the therapeutic potential of JZD in modulating immunoinflammation.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"108-129"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145857363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-02-23DOI: 10.1080/13880209.2026.2631826
Bill J Gurley, Catherine M Gurley, Kumar Katrugunta, Bharathi Avula, Ikhlas A Khan, Amar Chittiboyina, Philip W Melchert, John S Markowitz
{"title":"Formulation-dependent dissolution and bioaccessibility of curcuminoids and (S)-ar-turmerone from eight commercial turmeric extract- and curcumin-containing dietary supplements.","authors":"Bill J Gurley, Catherine M Gurley, Kumar Katrugunta, Bharathi Avula, Ikhlas A Khan, Amar Chittiboyina, Philip W Melchert, John S Markowitz","doi":"10.1080/13880209.2026.2631826","DOIUrl":"10.1080/13880209.2026.2631826","url":null,"abstract":"<p><strong>Context: </strong>Curcumin-containing dietary supplements are widely marketed with claims of enhanced bioavailability, despite well-recognized limitations related to poor aqueous solubility, chemical instability, and extensive first-pass metabolism. Comparisons among commercially available products using physiologically relevant performance metrics remain limited.</p><p><strong>Objective: </strong>To systematically evaluate disintegration, dissolution, and bioaccessibility of curcuminoids and (S)-ar-turmerone from a cross section of commercially available turmeric dietary supplements under fasted- and fed-state biorelevant conditions.</p><p><strong>Materials and methods: </strong>Eight marketed turmeric supplements representing diverse formulation strategies were assessed for disintegration and dissolution using USP-aligned methods in fasted- and fed-state simulated gastric and intestinal media (FaSSGF, FaSSIF, FeSSGF, FeSSIF). Bioaccessible concentrations, quantities, and dose fractions of curcuminoids and (S)-ar-turmerone were quantified after 3 h.</p><p><strong>Results: </strong>All products exhibited poor dissolution overall, with no formulation achieving greater than 40% total release. Dissolution was lowest under fasted-state conditions and improved modestly in fed-state gastric media, reflecting the influence of lipid content. Products with higher curcuminoid loads per capsule generated greater absolute bioaccessible concentrations despite poor release efficiency, whereas a phytosome formulation achieved superior release despite a lower dose. Several products marketed as \"enhanced\" formulations demonstrated poor disintegration and low bioaccessibility.</p><p><strong>Discussion: </strong>These findings indicate that bioaccessible concentration is governed jointly by dosage-form performance and curcuminoid dose loading, and that plasma exposure metrics dominated by conjugated metabolites may not reliably reflect formulation performance.</p><p><strong>Conclusion: </strong>Commercial turmeric supplements exhibit substantial limitations in biorelevant disintegration and dissolution. Superior <i>in vitro</i> release is a prerequisite - but not a guarantee - for enhanced systemic exposure, underscoring the need for cautious interpretation of bioavailability claims.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"334-350"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Majoon Ushba alleviated IL-17A sensitized keratinocyte ferroptosis via JAK-2-STAT-3 signaling axis and reversed imiquimod induced psoriasiform inflammation.","authors":"Arulkumaran Rithvik, Shangomitra Bhattacharjee, Gouri H Illanad, Pawan Kumar, Ghazala Javed, Ritu Karwasra, Zaheer Ahmed, Mahaboobkhan Rasool","doi":"10.1080/13880209.2026.2654904","DOIUrl":"10.1080/13880209.2026.2654904","url":null,"abstract":"<p><strong>Context: </strong>Psoriasis is a relapsing autoimmune disease exacerbated by aberrant interleukin (IL)-17 A activity. Majoon Ushba, a unani polyherbal formulation implicated in clinical cases of psoriasis lacks immunopharmacological validation.</p><p><strong>Objective: </strong>The study aims to investigate the pre-clinical efficacy of Majoon Ushba and its therapeutic role in mitigating IL-17A-induced keratinocytes ferroptosis <i>via</i> ablation of JAK-2/STAT-3 pathway.</p><p><strong>Materials and methods: </strong>HaCaT cells were stimulated with IL-17A to assess the activation of the JAK-2-STAT-3 pathway. The STAT-3 inhibitor, S3I-201, was used to confirm the role of the STAT-3 axis in keratinocyte ferroptosis. Majoon Ushba pretreatment was assessed to determine its efficacy in alleviating keratinocyte ferroptosis. An imiquimod (IMQ)-induced psoriasis mouse model was used to evaluate the pre-clinical efficacy of Majoon Ushba. Furthermore, prior high-performance liquid chromatography (HPLC) profiling was leveraged for in-silico docking analysis to identify the binding affinities of key phytoconstituents with IL-17RA and STAT-3.</p><p><strong>Results: </strong>Majoon Ushba alleviated the IL-17A/JAK-2-STAT-3 axis, improved GPX4 expression, and regulated lipid peroxidation. Subsequently, Majoon Ushba also reversed the expression of pathogenic mediators and led to a reduction in serum cytokine levels of IL-17A, IL-23, and IFN-γ. An in-silico docking analysis suggested favorable binding affinities for key phytoconstituents of Majoon Ushba against IL-17RA and STAT-3. Aligned with pre-clinical and <i>in vitro</i> results, the computational findings offer initial evidence that the polyherbal formulation may influence the IL-17A/JAK-2-STAT-3 signaling pathway.</p><p><strong>Discussion and conclusion: </strong>In conclusion, our preliminary findings reveal a plausible mechanistic basis for the anti-psoriatic efficacy of Majoon Ushba, warranting larger clinical trials in psoriasis patient cohorts.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"575-598"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-03-01DOI: 10.1080/13880209.2026.2629622
Diana I Saavedra, Dakota T Carter, Joseph T Dawson, Sara A Shah, Nicole Stevens, Ambika Poudel, Prabodh Satyal, Cécile Bascoul
{"title":"Turmeric (<i>curcuma longa</i>) rhizome essential oil: analytical profile of authenticated and commercial samples, safety and pharmacology review.","authors":"Diana I Saavedra, Dakota T Carter, Joseph T Dawson, Sara A Shah, Nicole Stevens, Ambika Poudel, Prabodh Satyal, Cécile Bascoul","doi":"10.1080/13880209.2026.2629622","DOIUrl":"10.1080/13880209.2026.2629622","url":null,"abstract":"<p><strong>Context: </strong>Turmeric (<i>Curcuma longa</i>) rhizome essential oil is the volatile and aromatic fraction of turmeric rhizome. Despite increasing commercial availability and scientific interest, variability in production practices and oil composition has created challenges for quality, safety, and pharmacological interpretation.</p><p><strong>Objective: </strong>This work provides a comprehensive overview of turmeric rhizome essential oil including an assessment of the composition of authentic oils, and commercial oils, and a review of safety and pharmacology.</p><p><strong>Materials and methods: </strong>Authentic samples from India (<i>n</i> = 35) and Nepal (<i>n</i> = 15), and market samples (<i>n</i> = 25) were analyzed by GC-MS. A review of published toxicological and pharmacological studies was conducted.</p><p><strong>Results: </strong>Authenticated oils were primarily composed of turmerones. Sesquiterpenes were more abundant in the oil from ground material, whereas monoterpenes were more prevalent in the oil from fresh rhizomes. Most market samples also exhibited the large dominance of turmerones, with some showing compositional variability, dilution, or adulteration, including 4/25 samples containing adulteration markers. Toxicological studies indicate no genotoxicity or dermal toxicity, minimal systemic toxicity, and good tolerability in humans. The pharmacology data supports anti-inflammatory, antimicrobial, neuroprotective, antioxidant, and anticancer properties, with synergistic effects when turmerones and curcuminoids are combined.</p><p><strong>Discussion and conclusion: </strong>Turmeric rhizome essential oil demonstrated a favorable safety profile and diverse bioactivities with therapeutic potential. However, compositional variation in commercial products with adulteration highlights the need for production standards. Authentic and consistent essential oil composition is key to ensure reproducible research findings, validate therapeutic potential, guarantee safety and provide the desirable outcomes when used.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"379-397"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12954815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147326621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-03-19DOI: 10.1080/13880209.2026.2640678
Ilma Imtiaz, Janet Schloss, Andrea Bugarcic
{"title":"Low, plasma level‑informed native curcumin concentrations fail to induce cell death in human lung and colorectal cancer cells.","authors":"Ilma Imtiaz, Janet Schloss, Andrea Bugarcic","doi":"10.1080/13880209.2026.2640678","DOIUrl":"10.1080/13880209.2026.2640678","url":null,"abstract":"<p><strong>Background/objectives: </strong>Curcumin, a dietary polyphenol derived from turmeric, has been widely studied for its anti-cancer properties, yet its effects at clinically relevant concentrations remain unclear. This study investigates the anti-cancer effects of curcumin at low <i>in vitro</i> concentrations selected based on reported plasma ranges using <i>in vitro</i> lung and CRC models, with a focus on underlying cellular mechanisms.</p><p><strong>Methods: </strong>Curcumin was tested at 4, 10, 20, and 50 µg/mL in two CRC cell lines (Caco-2 and HT29) and two lung cancer cell lines (A549 and H460).</p><p><strong>Results: </strong>MTS assays showed that at a low concentration of Curcumin 4 µg/mL, cell viability remained above 100% across all cell lines (A549: 102.1%, H460: 101.1%, Caco-2: 103.6%, HT29: 104.9%, <i>n</i> = 3, <i>p</i> > 0.05) and had no significant effect on cell death. Immunofluorescence analysis showed increased nuclear Cyclin D1 levels at 4 µg/mL curcumin in H460 and HT29 cells (<i>p</i> < 0.001), and no change in Caco-2 cells (<i>p</i> = 0.17), and a significant reduction in A549 cells (<i>p</i> < 0.001), suggesting promotion of cell cycle progression in H460 and HT29 cells only. Western blotting analysis showed higher levels of procaspase-3 without evidence of cleavage at 4 µg/mL, indicating the absence of apoptosis. A reduction in procaspase 3 levels were observed at 20 µg/mL (Caco-2, <i>p</i> < 0.05) and 50 µg/mL (H460, <i>p</i> < 0.05; A549, and HT29, <i>p</i> > 0.05).</p><p><strong>Conclusions: </strong>These findings suggest that at low. plasma level-informed concentrations, curcumin may support cancer cell survival rather than induce cytotoxicity. This study highlights the need for further pre-clinical evaluation of polyphenols at clinically relevant concentrations.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"471-486"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007458/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147487098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-04-28DOI: 10.1080/13880209.2026.2659421
Catherine Mahony, Arianna Bartlett, Suzanne Fitzpatrick, Corrado Galli, Piper Hunt, Amy Inselman, Jessica Jimenez, Julie Krzykwa, Jacob Larson, Cynthia Rider, John Rogers, Vicki Sutherland, Kevin Welch, Constance A Mitchell
{"title":"A screening strategy for identifying the developmental and reproductive toxicity potential of botanicals.","authors":"Catherine Mahony, Arianna Bartlett, Suzanne Fitzpatrick, Corrado Galli, Piper Hunt, Amy Inselman, Jessica Jimenez, Julie Krzykwa, Jacob Larson, Cynthia Rider, John Rogers, Vicki Sutherland, Kevin Welch, Constance A Mitchell","doi":"10.1080/13880209.2026.2659421","DOIUrl":"10.1080/13880209.2026.2659421","url":null,"abstract":"<p><strong>Context: </strong>Botanicals are widely consumed as dietary supplements and traditional medicines, yet their developmental and reproductive toxicity (DART) potential is often inadequately characterized. Botanicals are chemically complex and variable, complicating traditional <i>in vivo</i> testing and interpretation. There is a need for fit-for-purpose new approach methodologies (NAMs) to evaluate DART hazards of complex mixtures while reducing reliance on mammalian models.</p><p><strong>Objective: </strong>This review describes the Botanical Safety Consortium (BSC) DART Working Group strategy to evaluate a battery of NAMs for screening botanical extracts and outlines the botanicals selected as case studies to assess assay suitability for complex mixtures.</p><p><strong>Methods: </strong>Available NAMs relevant to DART were identified and reviewed, including human induced pluripotent stem cell assays (e.g., devTox Quick Predict), zebrafish embryos, <i>Caenorhabditis elegans</i>, transcriptomics with Connectivity Map analysis, <i>in vitro</i> pharmacology profiling, and selected <i>in silico</i> tools. Assays were selected to provide complementary functional, mechanistic, and biomarker coverage across biological levels. Eighteen botanicals were chosen based on published <i>in vivo</i>, mechanistic, livestock, or <i>in vitro</i> evidence indicating no concern, uncertain effects, or established DART hazards.</p><p><strong>Results: </strong>The selected NAM battery captures diverse mechanisms relevant to DART. The case study botanicals span clear positives (e.g., locoweed, poison hemlock, cottonseed), suspected positives based on limited data (e.g., bitter melon, goldenseal, rue), and low concern examples (e.g., Asian ginseng), enabling evaluation of assay performance for complex mixtures.</p><p><strong>Conclusions: </strong>This strategy paper lays the groundwork to assess the suitability of integrated NAMs for screening botanical DART potential and establishes the foundation for subsequent testing and case study evaluation.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"639-667"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147778116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-10-11DOI: 10.1080/13880209.2026.2743419
Amy L Roe, Igor Koturbash
{"title":"From tradition to translational medicine: advances and controversies in turmeric and curcumin research.","authors":"Amy L Roe, Igor Koturbash","doi":"10.1080/13880209.2026.2743419","DOIUrl":"10.1080/13880209.2026.2743419","url":null,"abstract":"","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1062-1065"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149168286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2026-10-14DOI: 10.1080/13880209.2026.2740863
Roy T Upton
{"title":"Concise ethnobotanical review and botanical pharmacognosy of turmeric rhizome (<i>Curcuma longa</i> L.).","authors":"Roy T Upton","doi":"10.1080/13880209.2026.2740863","DOIUrl":"10.1080/13880209.2026.2740863","url":null,"abstract":"<p><strong>Context: </strong>Turmeric (<i>Curcuma longa</i> L. Zingiberaceae) is a highly valued botanical medicine worldwide and has emerged as among the best-selling herbal products in North America.</p><p><strong>Objective: </strong>Presented an ethnobotanical record of turmeric use to present a context for this edition on turmeric.</p><p><strong>Methods: </strong>Information was primarily compiled from online sources including PubMed, Web of Science, Google Scholar, and Science Direct using 'turmeric', 'curcuma', and 'curcuma longa' as search terms; No time limit was specified. The primary goal was to mine ethnobotanical literature regarding turmeric use of various cultures. Online searches were augmented by hardcopy searches of ethnobotanical, and pharmacognosy literature from the first century.</p><p><strong>Results and conclusion: </strong>Turmeric is used in an array of preparations. It is listed among the top ten spices in the world and is used as a dye, medicine, object of cultural and religious significance, and coloring agent. Turmeric is used in African, Ayurvedic, Korean, Malaysian, Siddha, Chinese, Persian, Unani, and Western herbal traditions though India remains the largest producer and consumer of turmeric. Turmeric is universally used to support healthy gastrointestinal, circulatory, respiratory, and renal systems. The treatment of jaundice was one of turmeric's primary historical indications. In combination with other botanicals, turmeric is used for treating almost any condition. Following is an ethnobotanical review of its traditional uses and select botanical pharmacognostic characteristics used for ensuring authenticity of raw material, including a discussion of some of the most common adulterants of turmeric products.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"1087-1107"},"PeriodicalIF":6.0,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13670277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149183862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pharmaceutical BiologyPub Date : 2026-12-01Epub Date: 2025-12-23DOI: 10.1080/13880209.2025.2605571
Chao Zhao, Xiaodan Bai, Yi Ding, Aiguo Zeng, Aidong Wen, Qiang Fu, Jingwen Wang
{"title":"The role of salvianolic acid B and benzoylpaeoniflorin in enhancing angiogenesis through Nrf2/HO-1/VEGFA signaling axis in ischemic stroke recovery.","authors":"Chao Zhao, Xiaodan Bai, Yi Ding, Aiguo Zeng, Aidong Wen, Qiang Fu, Jingwen Wang","doi":"10.1080/13880209.2025.2605571","DOIUrl":"10.1080/13880209.2025.2605571","url":null,"abstract":"<p><strong>Context: </strong>Angiogenesis is one of the essential protective mechanisms that promote neural repair and regeneration after ischemic stroke (IS). Salvianolic Acid B (SAB) and Benzoyl paeoniflorin (BP) are compounds extracted from the Chinese medicines <i>Salvia miltiorrhiza</i> Bunge and <i>Paeonia suffruticosa</i> Andrews, respectively.</p><p><strong>Objective: </strong>We investigated whether SAB combined with BP alleviated IS by promoting micrangium angiogenesis and determined the potential molecular mechanisms.</p><p><strong>Materials and methods: </strong>The impact of SAB-BP on angiogenesis after IS was investigated in middle cerebral artery occlusion (MCAO) rat model, ponatinib-induced ischemic stroke in zebrafish, and human umbilical vein endothelial cells (HUVECs). The neuroprotective effect of SAB-BP in rats was assessed using behavior tests and histopathological staining. The cerebral thrombosis assessment and angiogenesis assay were performed in the zebrafish model. Cell proliferation and angiogenesis in oxygen-glucose deprivation and reperfusion (OGD/R) HUVECs were assessed through cell viability, tube formation, migration, and invasion assays. Western blot analysis and immunofluorescence staining were used to determine the protein expression levels of Nrf2, HO-1, and VEGFA.</p><p><strong>Results: </strong>The findings indicated that SAB-BP significantly reduced neurological impairment following IS and promoted the formation of functional vessels in the cerebral ischemic penumbra. Furthermore, SAB-BP up-regulated the protein expression of Nrf2, HO-1, HIF-1α, and VEGFA. Intriguingly, the pro-angiogenic effect of SAB-BP markedly restrained by adding the inhibitor of Nrf2 (ML385).</p><p><strong>Discussion and conclusion: </strong>Our study demonstrates that SAB-BP enhances angiogenesis following IS by modulating the Nrf2/HO-1/VEGFA signaling axis both <i>in vivo</i> and <i>in vitro</i>. SAB-BP could serve as a promising therapeutic agent for IS recovery.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"67-86"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145820455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Xijiaqi Formula attenuates myocardial infarction-induced chronic heart failure by inhibiting TGF-β1/Smads-mediated fibroblast activation.","authors":"Qian Zhang, Jie Chen, Lin-Nan Zhou, Xue-Fen Wu, Yu-Zhuo Wu, Wan-Ting Li, Gui-Yang Xia, Huan Xia, Hong-Cai Shang, Xiao-Hong Wei, Sheng Lin","doi":"10.1080/13880209.2025.2602234","DOIUrl":"10.1080/13880209.2025.2602234","url":null,"abstract":"<p><strong>Context: </strong>Chronic heart failure (CHF) is the common concern following myocardial infarction. Xijiaqi Formula (XJQ) effectively treats CHF clinically while the underlying mechanism remains unclarified.</p><p><strong>Objective: </strong>This study was designed to investigate the effect and mechanism of XJQ on CHF in rats following MI.</p><p><strong>Materials and methods: </strong>UHPLC-Q-TOF-MS/MS was utilized to analyze the constituents of XJQ. Post-MI CHF was induced in rats by permanent ligation of the left anterior descending coronary artery. Cardiac function was assessed by echocardiogram and hemodynamic. Myocardial morphology, fibrosis, and ultrastructure were evaluated through HE staining, Masson staining, and transmission electron microscopy, respectively. Myocardial transcriptomics were employed to identify genes that may be altered in response to XJQ treatment. Consistently, XJQ inhibited TGF-β1-induced myofibroblast activation <i>in vitro</i>.</p><p><strong>Results: </strong>XJQ significantly improved cardiac function and structure, mitigating fibrosis, edema, and mitochondrial damage, while reducing key biomarkers (BNP, NT-proBNP, cTnT, Ang II). Transcriptomic analysis indicated that the differentially expressed genes influenced by XJQ were predominantly associated with extracellular matrix (ECM) remodeling. Notably, XJQ inhibited the upregulation of ECM proteins, including <i>Adamts2</i>, <i>Fbln1</i>, <i>Itgbl1</i>, and <i>Ltbp3</i> mRNAs, as well as the proteins TGF-β1, P-Smad2/3, and MMP2. Additionally, <i>in vitro</i> experiments revealed that XJQ significantly suppressed the activation of myofibroblasts induced by TGF-β1.</p><p><strong>Conclusions: </strong>XJQ significantly attenuated the progression from MI to CHF by inhibiting fibroblast activation mediated by TGF-β1/Smads signaling. The molecular mechanisms underlying this effect appear to be intricately linked to its regulation of ECM remodeling proteins, specifically <i>Adamts2</i>, <i>Itgbl1</i>, <i>Fbln1</i>, and <i>Ltbp3</i>.</p>","PeriodicalId":19942,"journal":{"name":"Pharmaceutical Biology","volume":"64 1","pages":"46-66"},"PeriodicalIF":4.8,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12777859/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145843833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}