Advances in Pharmacological and Pharmaceutical Sciences最新文献

{"title":"Regulatory-Driven Pharmacokinetic and Immunogenicity Study of Siltartoxatug, a Recombinant Native Human Monoclonal Antibody Against Tetanus Toxin, in Cynomolgus Monkeys.","authors":"Xia Zhou, Fei Zhou, Zhenpeng Fu, Weijun Ye, Guo Li, Jason Li, Weihong Zheng, Hua-Xin Liao, Shaojie Wang, Xiaoyi Liu","doi":"10.1155/adpp/2804371","DOIUrl":"https://doi.org/10.1155/adpp/2804371","url":null,"abstract":"<p><p>Siltartoxatug-developed by Trinomab Pharmaceutical Co., Ltd., using its proprietary HitmAb® platform-is the first-in-class recombinant monoclonal antibody drug for urgent prophylaxis of tetanus approved by China National Medical Products Administration in February 2025, which addresses the critical unmet need to substitute blood-derived passive immunization preparations for prevention of tetanus. The nonclinical pharmacokinetic and immunogenicity study of siltartoxatug was designed and conducted in strict compliance with global regulatory guidelines for initiating the first-in-human clinical trials. Herein, we report the comprehensive findings from this study. Twenty-four naive cynomolgus monkeys (<i>Macaca fascicularis</i>) were randomly assigned to four groups each with 6 animals. Monkeys in Group 1 received intravenous infusion of siltartoxatug at 1 mg/kg. Monkeys in Groups 2, 3, and 4 received intramuscular injection of siltartoxatug at dose of either 1 mg/kg, 3 mg/kg, or 10 mg/kg. Blood samples were collected over 57 days post-administration, and serum drug concentrations and anti-drug antibody levels were determined with validated methods. Results showed that intramuscular administration of siltartoxatug exhibited favorable pharmacokinetic characteristics: primarily systemic distribution with high bioavailability (88.0% at 1 mg/kg) and low apparent volume of distribution (58.7-69.4 mL/kg), prolonged elimination half-life (11.7-12.4 days), short mean time to maximum concentration (1.2-2.7 days), and dose-dependent systemic exposure without significant sex differences. Additionally, minimal anti-drug antibody responses were observed. These findings underpinned greater predictability for its clinical translation and informed its first-in-human development.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"2804371"},"PeriodicalIF":2.9,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149223093","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":"Evaluation of Biological Effect of <i>Triticum vulgare</i> Extract Compared With Hyaluronic Acid in In Vitro Tissue Models.","authors":"Carlo Oliviero, Alessandra Fusco, Enrica Giustino, Roberta Palladino, Eugenia Romano, Barbara Maglione, Antonella D'Agostino, Chiara Schiraldi","doi":"10.1155/adpp/8857215","DOIUrl":"10.1155/adpp/8857215","url":null,"abstract":"<p><p>Plant extracts and microbial-derived molecules, particularly oligo- and polysaccharides, are known to promote tissue repair. <i>Triticum vulgare</i> extract (TVE), derived from germinated whole plants and utilized in medical devices, is rich in bioactive molecules comprised of oligo- and polysaccharides with diverse biological properties beneficial for wound repair. This study investigates the biochemical mechanisms underlying TVE's proregenerative activity in vitro effects, comparing it with hyaluronic acid (HA), a gold standard in wound healing. Preliminary results showed that TVE has scavenging properties/antioxidant activity also at lower concentrations with respect to HA that has long been recognized for these properties (Galvez-Martin et al.). In vitro assays evaluated cell proliferation, migration, extracellular matrix biomarkers, and responses to stress in 2D and 3D models. TVE significantly enhanced keratinocyte migration, reaching approximately 50% wound closure in less than 20 h, whereas the untreated control required about 30 h to achieve the same level of closure. Moreover, TVE performed better than HA at low concentrations, while both treatments improved HDF proliferation and ECM biomarker expression. More specifically, COL1 expression was upregulated by 2.3-fold relative to the control, showing an effect comparable to that induced by HA (2.8-fold). Conversely, ELS expression exhibited a 2.0-fold increase in response to TVE and a 2.6-fold increase following HA treatment compared with the control. In addition, the extract significantly increased HBD-2 expression by 2-fold relative to the control, a novel finding that may be relevant, given the role of this antimicrobial peptide in innate immunity, inflammation regulation, and wound repair. Under stressful conditions, including dehydration and exposure to reactive oxygen species, TVE showed protective effects comparable to HA in both HDF and HaCaT cells. 3D skin models, including those treated with LPS, confirmed the results of 2D assays, further validating TVE's biological properties. Overall, these studies demonstrate that this extract exerts biological effects comparable to pharmaceutical HA in several in vitro skin models. These findings further support the potential application of TVE in wound management and skin regenerative approaches.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"8857215"},"PeriodicalIF":2.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102767","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":"Dissolution Rate and Stability Improvement of Hydrochlorothiazide and Valsartan by Co-Amorphous Formulation.","authors":"Asal M Abdulraheem, Khouloud A Alkhamis, Suhair S Al-Nimry","doi":"10.1155/adpp/9387077","DOIUrl":"https://doi.org/10.1155/adpp/9387077","url":null,"abstract":"<p><p>The current study aimed to improve the dissolution rate and physical stability of two antihypertensive drugs, hydrochlorothiazide, and valsartan, through the development of a co-amorphous system. A co-amorphous system was successfully prepared at molar ratios of 1:1, 1:2, and 1:6 employing rotary evaporation technique. Characterization of the formulations was performed using powder X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and thermogravimetric analysis. Powder X-ray diffraction confirmed the amorphous nature of all samples, which remained physically stable under ambient dry conditions for at least 8 months. Differential scanning calorimetry confirmed the formation of a single-phase system. The experimental glass transition temperature values revealed a negative deviation from those calculated by the Gordon-Taylor equation, indicating nonideal mixing and intermolecular interactions. Fourier transform infrared spectroscopy spectra supported these findings, showing peak broadening in regions corresponding to the functional groups of the parent drugs. The thermogravimetric analysis demonstrated that the samples were thermally stable, with no degradation observed up to 100°C. Dissolution studies performed in phosphate buffer (pH 6.8, 25°C) revealed significant enhancements in the dissolution rates of both hydrochlorothiazide and valsartan from the co-amorphous formulations compared to their unprocessed forms and corresponding physical mixtures. A validated high-performance liquid chromatography method was developed for the simultaneous analysis of hydrochlorothiazide and valsartan using a Shimadzu LC-2030C 3D Plus system with a photodiode array detector. Separation was achieved on a Waters C18 column (250 × 4.6 mm, 5 μm) using a mobile phase of acetonitrile, methanol, and ammonium acetate buffer (20:50:30, v/v) at a flow rate of 0.70 mL/min. Detection wavelengths were set at 271 nm for hydrochlorothiazide and 249 nm for valsartan. The method showed good linearity in the range from 0.0033 to 0.0670 mM (3.3-67.0 μM), precision (RSD < 2%), and reproducibility, with hydrochlorothiazide and valsartan eluting at 3.5 and 7.2 min, respectively. At the first minute, hydrochlorothiazide release increased by approximately 8.5-, 8.7-, and 7.1-fold from the 1:1, 1:2, and 1:6 co-amorphous systems relative to the unprocessed drug, and by 4.5-, 4.8-, and 2.4-fold, respectively, compared to the corresponding physical mixtures. For valsartan, the co-amorphous systems showed 2.9-, 2.6-, and 1.9-fold improvements over the unprocessed drug, and 1.5-, 1.8-, and 1.5-fold improvements over the matching physical mixtures at the same molar ratios. Calcium carbonate was physically mixed with all samples to minimize gelation upon aqueous exposure. These results suggest that co-amorphous formulation is a promising strategy for enhancing the dissolution rate and physical stability of hydrochlorothiazide and valsartan.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"9387077"},"PeriodicalIF":2.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13626147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102750","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":"Total Glucosides of Paeony Alleviates Acute Kidney Injury by Inhibiting Dendritic Cells and T-Cell Communication.","authors":"Tingting Liu, Wei Liang, Yan Zhang, Xiaoqian Wu, Hongwei Zhang, Dongchun Zhu, Yukun Ma, Li Cao, Xiaohua Wang","doi":"10.1155/adpp/8877828","DOIUrl":"https://doi.org/10.1155/adpp/8877828","url":null,"abstract":"<p><strong>Aim: </strong>This study was designed to evaluate the renoprotective action of total glucosides of paeony (TGP) against cisplatin (Cis)-induced AKI and to delineate the molecular mechanisms.</p><p><strong>Methods: </strong>AKI was induced in mice via a single intraperitoneal injection of Cis (20 mg/kg). Renal morphological changes were examined using hematoxylin and eosin (H&E) staining, while kidney function and oxidative stress markers were quantitatively assessed. Flow cytometry (FCM) was employed to profile immune cell differentiation and functional status. The mRNA and protein levels of kidney injury-related biomarkers were measured by quantitative real-time PCR (qPCR) and Western blotting, respectively. To unravel the mechanistic basis, key signaling cascades were probed in both renal tissues and isolated immune cells.</p><p><strong>Results: </strong>Administration of TGP attenuated renal histological damage and diminished inflammatory cell infiltration in AKI mice. Notably, TGP recalibrated the function of bone marrow-derived dendritic cells (BMDCs), steering them away from a fully mature phenotype. This was evidenced by a marked reduction in the migratory marker C-C motif chemokine receptor 7 (CCR7) and a reciprocal elevation of the immunoinhibitory checkpoint programmed cell death ligand 1 (PD-L1). Importantly, this phenotypic shift was linked to TGP-induced metabolic reprogramming, as DCs from TGP-treated animals exhibited diminished mitochondrial membrane potential (MMP). The TGP-mediated DC reprogramming translated into a fundamentally rebalanced T-cell compartment: The cytotoxic CD8⁺ effector T cell was actively restrained, while the immunosuppressive regulatory T-cell (T_reg) subset was preferentially expanded. This modulation was further reinforced by elevated programmed cell death protein 1 (PD-1) surface expression on T cells. Mechanistic interrogation revealed that TGP concurrently dismantled two interconnected pro-inflammatory signaling nodes essential for DC-T cell communication. By attenuating TLR4/MyD88 recruitment, TGP curtailed the downstream nuclear translocation of NF-κB, thereby limiting the transcriptional output of DC-derived inflammatory cytokines that drive T-cell polarization. Concomitantly, TGP directly interfered with the JAK2/STAT3 module, not only diminishing its phosphorylation but also de-repressing the negative feedback regulator SOCS3. This dual blockade synergistically extinguished the inflammatory amplification loop instigated by Cis in the renal microenvironment.</p><p><strong>Conclusion: </strong>Collectively, these findings indicate that TGP exerts a protective effect against Cis-induced AKI by rebalancing immune cell homeostasis and interfering with pro-inflammatory signaling networks, positioning it as a promising candidate for future AKI pharmacotherapy.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"8877828"},"PeriodicalIF":2.9,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149102804","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":"Neuroprotective Effects of Huperzine B and <i>Huperzia carinata</i> Extract Against MPP⁺-Induced Oxidative Stress in SH-SY5Y Cells.","authors":"Kittikun Viwatpinyo, Poommaree Namchaiw, Pipob Suwanchaikasem, Sujira Mukda, Sudichhya Tamrakar, Amit Jaisi, Sakan Warinhomhoun","doi":"10.1155/adpp/6446024","DOIUrl":"10.1155/adpp/6446024","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a neurodegenerative disorder associated with dopaminergic neuronal loss, mitochondrial dysfunction, and redox imbalance. Huperzine B (HupB), an alkaloid derived from <i>Huperzia</i> species, has demonstrated antioxidant and acetylcholinesterase-inhibitory activity; however, its effects in toxin-induced cellular models of mitochondrial oxidative injury remain incompletely characterized. This study investigated the effects of HupB and an extract derived from <i>Huperzia carinata</i> (E1) in 1-methyl-4-phenylpyridinium (MPP⁺)-induced SH-SY5Y cells. LC-MS/MS analysis identified Huperzines A, B, and caffeic acid in E1. Cells were pretreated with HupB or E1 prior to exposure to 1 mM MPP⁺. Cell viability, nuclear morphology, reactive oxygen species (ROS), antioxidant enzyme activity, mitochondrial membrane potential (JC-1), apoptosis-related proteins (Bax/Bcl-2), and global proteomic profiles were evaluated. HupB and E1 attenuated MPP⁺-induced reductions in cell viability and ROS elevation, while partially improving glutathione levels and catalase and superoxide dismutase activities. MPP⁺ significantly decreased mitochondrial membrane potential, whereas pretreatments did not produce significant restoration. Similarly, Bax/Bcl-2 expression showed no significant modulation despite trends toward normalization at higher concentrations. Proteomic analysis revealed altered expression of proteins associated with negative regulation of apoptosis and cellular stress responses. These findings indicate that HupB and <i>H. carinata</i> extract are associated with modulation of oxidative and proteostasis-related responses in an MPP⁺-induced undifferentiated SH-SY5Y cellular injury model, supporting further investigation in more physiologically relevant systems.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"6446024"},"PeriodicalIF":2.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591997/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015132","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":"Artificial Intelligence in the Design and Development of Nanoparticle Drug Delivery Systems: A Systematic Review.","authors":"Razan Haddad","doi":"10.1155/adpp/5531134","DOIUrl":"10.1155/adpp/5531134","url":null,"abstract":"<p><strong>Background: </strong>Artificial intelligence (AI) has rapidly emerged as a powerful tool for accelerating the design and optimization of nanoparticle-based drug delivery systems (NDDSs). By analyzing complex multidimensional datasets, AI models can predict nanoparticle physicochemical properties, biodistribution, and safety profiles more efficiently than traditional experimental approaches.</p><p><strong>Methods: </strong>This systematic review was conducted following PRISMA 2020 guidelines and was registered in PROSPERO (ID: 1148160). Five electronic databases (PubMed, Scopus, Web of Science, ScienceDirect, and SpringerLink) were searched up to January 2025. Studies applying AI approaches, including machine learning, deep learning, and hybrid modeling to nanoparticle design, optimization, biodistribution prediction, or nanotoxicology, were included. Extracted data included nanoparticle platform, AI methodology, prediction targets, validation strategies, and reported performance metrics. Methodological quality was assessed using a framework integrating TRIPOD-AI and Joanna Briggs Institute (JBI) appraisal domains.</p><p><strong>Results: </strong>A total of 17 unique studies met the established eligibility criteria and were included in the final qualitative analysis. The applications of machine learning or deep-learning methods and models were demonstrated across the various nanoparticle-based platforms to predict the formulation properties, biodistribution, nano-bio interactions, therapeutic materials discovery, and nanoparticle toxicity. The models augmented by artificial intelligence (AI) technology in the physiologically based pharmacokinetic area manifested promising prediction ability for biodistribution, while the abilities differed among the datasets and the prediction endpoints. Nine studies incorporated in vitro or in vivo biological/experimental validation, whereas only four of the 17 included studies used independent external validation.</p><p><strong>Conclusions: </strong>AI has significant potential to enhance nanoparticle formulation optimization, biodistribution modeling, and toxicity prediction. Nevertheless, translation into clinical practice remains constrained by small datasets, limited external validation, and inconsistent reporting standards. Future research should prioritize standardized datasets, transparent AI models, and prospective validation to advance AI-enabled nanomedicine toward clinical implementation.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"5531134"},"PeriodicalIF":2.9,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149015227","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":"The Leaf Aqueous and Ethanolic Extracts of <i>Tricalysia okelensis</i> Hiern. (Rubiaceae) Reverse L-NAME-Induced Hypertension, Cardiac, and Vascular Remodeling in Rats.","authors":"Florence Nokam, Ariane Falone Goumtsa, Sahar Mofidi Tabatabaei, Cédric Wamba Koho, Cherif Mouhamed Moustapha Dial, Kevin Joseph Tidgewell, Pierre Watcho, Elvine Pami Nguelefack-Mbuyo","doi":"10.1155/adpp/8990646","DOIUrl":"10.1155/adpp/8990646","url":null,"abstract":"<p><p>Arterial hypertension is a worldwide challenging medical condition that continues to raise havoc despite existing treatments, prompting the need to develop new medicine. In a pilot study, we demonstrated that <i>Tricalysia okelensis</i> exhibits a vasorelaxant effect. This study evaluates the antihypertensive effect of the leaf aqueous (AETO) and ethanolic (EETO) extracts of <i>T. okelensis</i> against L-NAME-induced-hypertension, cardiac, and vascular remodeling. AETO and EETO underwent LC-MS/MS to identify potential metabolites responsible for the activity. Adult male Wistar rats were orally administered L-NAME (30 mg/kg/day) for 3 consecutive weeks. L-NAME administration was continued either alone or with captopril (20 mg/kg/day, p.o.), AETO, or EETO at doses of 85 and 170 mg/kg/day for another 3 consecutive weeks, while the naive group received the vehicle for 6 weeks. Blood pressure (BP) and heart rate were recorded before and weekly after the beginning of each treatment. Plasma angiotensin II (Ang II), serum nitric oxide (NO), lactate dehydrogenase (LDH), cardiac myeloperoxidase (MPO), and NO were assessed at the end of the experiment. Sections from the heart and aorta were analyzed for histological changes and immunohistochemical expression of atrial natriuretic peptide (ANP), endothelial (eNOS), and inducible (iNOS) nitric oxide synthases. AETO and EETO are rich in flavonoids and phenolic compounds. LC-MS/MS-based molecular networking enabled the putative annotation of several polyphenolic metabolites, including chlorogenic acid, neochlorogenic acid, rutin, quercetin derivatives, kaempferol derivatives, isorhamnetin, avicularin, and guaijaverin. L-NAME significantly increased BP and heart rate, Ang II, LDH, cardiac MPO, and heart weight (<i>p</i> < 0.05 - 0.001) while decreasing NO (<i>p</i> > 0.05). AETO and EETO reversed these alterations and also inhibited L-NAME-induced immune cell infiltration, fibrosis, cardiac and vascular eNOS downregulation, and iNOS overexpression, as well as ANP upregulation in heart tissue. AETO and EETO exhibit antihypertensive and anti-remodeling effects probably by modulating the renin-angiotensin system, improving endothelial function, and reducing inflammation and fibrosis.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"8990646"},"PeriodicalIF":2.9,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148904990","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":"Synergistic Combination of <i>Cryptolepis sanguinolenta (Lindl.)</i> Schlechter (Apocynaceae) and <i>Azadirachta Indica</i> (A. Juss) (Meliaceae) Against 3D7 and DD2 Strains of <i>Plasmodium Falciparum</i>.","authors":"Samuel Korsah, Nathaniel Nene Djangmah Nortey, Christian Akakpo, Felix Kwame Zoiku, Jessica Korsah, Miriam Tagoe, Joseph Kwao Amanor, Babu Jacob Yamba, Josephine Akosua Ofori-Asamoah","doi":"10.1155/adpp/1273876","DOIUrl":"10.1155/adpp/1273876","url":null,"abstract":"<p><strong>Introduction: </strong><i>Azadirachta indica</i> and <i>Cryptolepis sanguinolenta</i> are herbs commonly used together in polyherbal products in Ghana for the treatment of malaria.</p><p><strong>Aim: </strong>This research investigated the combined effects of <i>Azadirachta indica</i> and <i>Cryptolepis sanguinolenta</i> extracts against chloroquine-sensitive (3D7) and resistant (DD2) strains of <i>Plasmodium falciparum</i>.</p><p><strong>Methods: </strong>In vitro antimalarial activity was assayed on the aqueous extracts of both plants using a fluorescence-based SYBR Green assay. The combined effects of the two extracts were determined using computer-based software, CompuSyn.</p><p><strong>Results: </strong>Aqueous extracts of <i>Azadirachta indica</i> and <i>Cryptolepis sanguinolenta</i> exerted high antimalarial activities (IC₅₀ ≤ 10 μg/mL) against both 3D7 and DD2 strains of the <i>Plasmodium falciparum</i>. <i>Azadirachta indica</i> and <i>Cryptolepis sanguinolenta</i> displayed strong synergistic activity with combination index (CI) values ranging from 0.15 to 0.52 for 53%-99% inhibition of 3D7 <i>Plasmodium falciparum</i>. Also, CI values for the plants against DD2 were from 0.23 to 0.61 with corresponding 30%-97% parasitemia inhibitions. <i>Azadirachta indica</i> and <i>Cryptolepis sanguinolenta</i> exerted a dose reduction index (DRI) value greater than 1 (DRI > 1) in both strains.</p><p><strong>Conclusion: </strong><i>Cryptolepis sanguinolenta</i> and <i>Azadirachta indica</i> exerted synergistic interactions against 3D7 and DD2 strains of <i>Plasmodium falciparum</i>. The extracts are desirable when used in combination rather than alone.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"1273876"},"PeriodicalIF":2.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863152","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":"PCSK9-Mediated Inflammation in Foam Cell Formation and Exploring the Biologically Active Compounds Derived From Natural Resources.","authors":"Maharani Hestu Mukti Wisesa, Anisa Qisti Mathriul, Vicko Suswidiantoro, Meidi Utami Puteri, Mitsuyasu Kato, Muhd Hanis Md Idris, Fadlina Chany Saputri","doi":"10.1155/adpp/3005975","DOIUrl":"10.1155/adpp/3005975","url":null,"abstract":"<p><p>Atherosclerosis develops as a persistent inflammatory condition that gradually alters the vascular structure and condition, in which the formation of macrophage-derived foam cells plays a central role in disease initiation and progression. Although proprotein convertase subtilisin/kexin type 9 (PCSK9) is widely recognised for its involvement in low-density lipoprotein receptor regulation and systemic lipid homeostasis, growing evidence indicates that PCSK9 also exerts a direct influence on macrophage inflammatory responses and intracellular lipid metabolism. Within atherosclerotic lesions, PCSK9 accelerates foam cell development by promoting oxidised low-density lipoprotein uptake, impairing cholesterol efflux through ABCA1 downregulation and activating key inflammatory pathways, particularly those mediated by TLR4/NF-κB and the NLRP3 inflammasome. This review emphasises recent findings that identify natural bioactive compounds as a novel and biologically relevant approach to counteracting PCSK9-driven inflammatory foam cell formation. Compounds such as salvianolic acid B, curcumin, quercetin, fisetin and myricetin display broad antiatherogenic properties by concurrently regulating macrophage polarisation, limiting scavenger receptor expression, suppressing inflammasome activation and modulating PCSK9 expression or function. In contrast to monoclonal PCSK9 inhibitors, which primarily address lipid lowering, these natural agents offer integrated anti-inflammatory and lipid-modulatory effects at the cellular level. Collectively, the evidence discussed in this review positions PCSK9 modulation by natural compounds as an emerging therapeutic concept that links lipid dysregulation with vascular inflammation. This multitarget strategy may complement current lipid-lowering therapies and support the development of more accessible and inflammation-focused interventions for atherosclerosis.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"3005975"},"PeriodicalIF":2.9,"publicationDate":"2026-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13525378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857012","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":"<i>Annona muricata</i> Polyphenols Induce Cytoskeletal Alterations and Predicted Aldose Reductase Binding in <i>Giardia lamblia</i>.","authors":"Diana Valeria Govea-Flores, Mariana Garza-Ontiveros, Filiberto Gutiérrez-Gutiérrez, Ana Gabriela Gómez-Ibarra, Sendar Daniel Nery-Flores, Juan Alberto Ascacio-Valdés, Lizeth Guadalupe Campos-Múzquiz, Raúl Rodríguez-Herrera, Lissethe Palomo-Ligas","doi":"10.1155/adpp/4133207","DOIUrl":"10.1155/adpp/4133207","url":null,"abstract":"<p><p>Giardiasis has been classified as a neglected disease by the World Health Organization since 2004. Despite ongoing efforts, challenges such as drug resistance and treatment failures continue to hinder effective management. In recent years, the exploration of plant-derived compounds as antiparasitic agents has emerged as a promising strategy. This is supported by the discovery of plant-derived compounds such as quinine and artemisinin in antiparasitic pharmacology. The identification of specific molecular targets in <i>Giardia lamblia</i>, a protozoan with unique cytoskeletal and metabolic features, has further advanced drug discovery efforts. In this study, we evaluated the in vitro and in silico effects of a polyphenol-enriched extract from <i>Annona muricata</i> (soursop) leaves against <i>G. lamblia</i> trophozoites. The extract had a noticeable impact on parasite growth, cell adhesion, and morphology. Ultrastructural analyses revealed elongation, flagellar abnormalities, and damage to the ventral disk. Western blot and immunofluorescence assays demonstrated reduced <i>α</i>-tubulin expression and altered localization, indicating cytoskeletal alterations in treated trophozoites. Molecular docking analyses predicted favorable interactions between soursop polyphenols and <i>Giardia</i> aldose reductase, particularly involving the catalytic residues Y40 and K71. Collectively, these findings suggest that <i>A. muricata</i> polyphenols exert antigiardial effects through multiple cellular alterations and support the hypothesis that metabolic and cytoskeletal processes may both contribute to the observed biological effects. Further studies are required to experimentally validate the role of aldose reductase and its relationship with cytoskeletal disruption.</p>","PeriodicalId":7369,"journal":{"name":"Advances in Pharmacological and Pharmaceutical Sciences","volume":"2026 ","pages":"4133207"},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823988","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}