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Hospital, Sichuan University","award":["25NSFSC0261"],"award-info":[{"award-number":["25NSFSC0261"]}]},{"name":"Innovative Chinese Medicine Preclinical Research Fund of \u201cLiqing No. 2\u201d, West China Hospital, Sichuan University","award":["25NSFSC2221"],"award-info":[{"award-number":["25NSFSC2221"]}]},{"name":"Innovative Chinese Medicine Preclinical Research Fund of \u201cLiqing No. 2\u201d, West China Hospital, Sichuan University","award":["25NSFSC2246"],"award-info":[{"award-number":["25NSFSC2246"]}]},{"name":"Innovative Chinese Medicine Preclinical Research Fund of \u201cLiqing No. 2\u201d, West China Hospital, Sichuan University","award":["25QNJJ3824"],"award-info":[{"award-number":["25QNJJ3824"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["HXYS19001"],"award-info":[{"award-number":["HXYS19001"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["HXYS19002"],"award-info":[{"award-number":["HXYS19002"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["ZYXY21002"],"award-info":[{"award-number":["ZYXY21002"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["161200012"],"award-info":[{"award-number":["161200012"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["25NSFSC0261"],"award-info":[{"award-number":["25NSFSC0261"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["25NSFSC2221"],"award-info":[{"award-number":["25NSFSC2221"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["25NSFSC2246"],"award-info":[{"award-number":["25NSFSC2246"]}]},{"name":"Natural Science Foundation of Sichuan Province","award":["25QNJJ3824"],"award-info":[{"award-number":["25QNJJ3824"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Radix Paeoniae Rubra (RPR), an edible and medicinal Traditional Chinese Medicine (TCM), is extensively employed in therapeutic interventions of cardiovascular and cerebrovascular diseases. However, the curative effect of RPR on ischemic stroke remains ambiguous. This work integrated network pharmacology, molecular docking, and experimental validation to explore the mechanisms of RPR in treating ischemic stroke. Methods: In this study, we preliminarily elucidated the therapeutic effect and mechanism of RPR on ischemic stroke through network pharmacology, molecular docking analysis, and experimental verification. Results: The results indicated that RPR improved the neurological deficit scores, decreased the size of infarcts, and reduced brain edema symptoms in the tMCAO mice model. Furthermore, through network pharmacology and molecular docking, four core targets (MAPK3, TNF-\u03b1, MAPK14, and JNK) closely related to RPR\u2019s treatment of ischemic stroke were identified, exhibiting strong affinity with two key active components of RPR: albiflorin (AF) and \u03b2-sitosterol (BSS). The Western blot showed the potential mechanism of RPR treatment for ischemic stroke by regulating the MAPK signaling pathway. Moreover, RPR and its main active ingredients exhibited a significant inhibitory effect on platelets. Conclusion: In conclusion, this study revealed that RPR alleviates ischemic injury by activating the MAPK signaling pathway, and its protective effect may partly stem from inhibiting platelet activation. This work may provide a scientific basis for the development and utilization of RPR as a natural edible material to prevent ischemic stroke and anti-platelet therapy.<\/jats:p>","DOI":"10.3390\/nu16244409","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T09:13:38Z","timestamp":1734945218000},"page":"4409","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Investigation into the Potential Mechanism of Radix Paeoniae Rubra Against Ischemic Stroke Based on Network Pharmacology"],"prefix":"10.3390","volume":"16","author":[{"given":"Tingyu","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guang","family":"Xin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qilong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8955-416X","authenticated-orcid":false,"given":"Tao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuxian","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanceng","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Natural and Biomimetic Medicine Research Center, Tissue-Orientated Property of Chinese Medicine Key Laboratory of Sichuan Province, West China School of Medicine, West China Hospital, Sichuan University, Chengdu 610000, 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(2020). Protective effect and mechanism of Qishiwei Zhenzhu pills on cerebral ischemia-reperfusion injury via blood-brain barrier and metabonomics. Biomed. Pharmacother., 131.","DOI":"10.1016\/j.biopha.2020.110723"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Gao, L., Xia, X.W., Shuai, Y.Q., Zhang, H., Jin, W., Zhang, X.Y., and Zhang, Y. (2023). Gut microbiota, a hidden protagonist of traditional Chinese medicine for acute ischemic stroke. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1164150"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wang, Z.J., Jiang, A.A., Xiao, H.M., Yuan, X.F., Zhang, S.R., and Qin, X.Y. (2022). Exploring the potential mechanism of Fritiliariae Irrhosae Bulbus on ischemic stroke based on network pharmacology and experimental validation. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1049586"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Stegner, D., Klaus, V., and Nieswandt, B. (2019). Platelets as modulators of cerebral ischemia\/reperfusion injury. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02505"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1182\/bloodadvances.2020002888","article-title":"Platelets as drivers of ischemia\/reperfusion injury after stroke","volume":"5","author":"Shaik","year":"2021","journal-title":"Blood Adv."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13105-021-00841-w","article-title":"The progress of research on histone methylation in ischemic stroke pathogenesis","volume":"78","author":"Su","year":"2022","journal-title":"J. Physiol. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Huajuan, J., Xulong, H., Bin, X., Yue, W., Yongfeng, Z., Chaoxiang, R., and Jin, P. (2023). Chinese herbal injection for cardio-cerebrovascular disease: Overview and challenges. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1038906"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.jpba.2013.04.029","article-title":"The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC-DAD-ESI-IT-TOF-MS technique: A novel strategy for the systematic screening and identification of absorbed constituents and metabolites from traditional Chinese medicines","volume":"83","author":"Liang","year":"2013","journal-title":"J. Pharmaceut. Biomed."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"117987","DOI":"10.1016\/j.jep.2024.117987","article-title":"A systematic review and meta-analysis of the anti-tumor effects of Paeoniae Radix Rubra in animal models","volume":"326","author":"Wang","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"117729","DOI":"10.1016\/j.jep.2024.117729","article-title":"Dendrobium huoshanense in the treatment of ulcerative colitis: Network pharmacology and experimental validation","volume":"323","author":"Yao","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, H., Jiang, X., Shen, X., Sun, Y., Jiang, N., Zeng, J., Lin, J., Yue, L., Lai, J., and Li, Y. (2021). TMEA, a polyphenol in sanguisorba officinalis, promotes thrombocytopoiesis by upregulating PI3K\/Akt signaling. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.708331"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Hsin, K.Y., Ghosh, S., and Kitano, H. (2013). Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0083922"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"924541","DOI":"10.1155\/2013\/924541","article-title":"Electroacupuncture could regulate the NF-\u03baB signaling pathway to ameliorate the inflammatory injury in focal cerebral ischemia\/reperfusion model rats","volume":"2013","author":"Qin","year":"2013","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"154934","DOI":"10.1016\/j.phymed.2023.154934","article-title":"Elucidation of the mechanism of Yiqi Tongluo Granule against cerebral ischemia\/reperfusion injury based on a combined strategy of network pharmacology, multi-omics and molecular biology","volume":"118","author":"Yuan","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Wang, Y., Guo, W., Liu, Y., Wang, J., Fan, M., Zhao, H., Xie, S., and Xu, Y. (2019). Investigating the protective effect of gross saponins of tribulus terrestris fruit against ischemic stroke in rat using metabolomics and network pharmacology. Metabolites, 9.","DOI":"10.3390\/metabo9100240"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Zhou, X., Yu, X., Wan, C., Li, F., Wang, Y., Zhang, K., Feng, L., Wen, A., Deng, J., and Li, S. (2023). NINJ1 Regulates Platelet activation and PANoptosis in septic disseminated intravascular coagulation. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24044168"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nian, K.Q., Harding, I.C., Herman, I.M., and Ebong, E.E. (2020). Blood-brain barrier damage in ischemic stroke and its regulation by endothelial mechanotransduction. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.605398"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dithmer, S., Blasig, I.E., Fraser, P.A., Qin, Z.H., and Haseloff, R.F. (2024). The basic requirement of tight junction proteins in blood-brain barrier function and their role in pathologies. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25115601"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/B978-0-12-388448-0.00025-5","article-title":"Time-resolved luminescence resonance energy transfer imaging of protein-protein interactions in living cells","volume":"505","author":"Rajapakse","year":"2012","journal-title":"Methods Enzymol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1089\/ars.2013.5288","article-title":"Highly Conserved cysteines are involved in the oligomerization of occludin-redox dependency of the second extracellular loop","volume":"20","author":"Bellmann","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1089\/ars.2014.6162","article-title":"Redox regulation of cell contacts by tricellulin and occludin: Redox-sensitive cysteine sites in tricellulin regulate both tri- and bicellular junctions in tissue barriers as shown in hypoxia and ischemia","volume":"23","author":"Cording","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1083\/jcb.200302070","article-title":"Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice","volume":"161","author":"Nitta","year":"2003","journal-title":"J. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1182\/blood-2018-11-882993","article-title":"Thromboinflammation: Challenges of therapeutically targeting coagulation and other host defense mechanisms","volume":"133","author":"Jackson","year":"2019","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41582-019-0221-1","article-title":"Thrombo-inflammation in acute ischaemic stroke- implications for treatment","volume":"15","author":"Stoll","year":"2019","journal-title":"Nat. Rev. Neurol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.blre.2009.04.001","article-title":"Platelet \u03b1-granules: Basic biology and clinical correlates","volume":"23","author":"Blair","year":"2009","journal-title":"Blood Rev."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1182\/blood-2012-04-420745","article-title":"Mechanism of platelet dense granule biogenesis: Study of cargo transport and function of Rab32 and Rab38 in a model system","volume":"120","author":"Ambrosio","year":"2012","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1055\/s-0042-1758800","article-title":"Gelsolin modulates platelet dense granule secretion and hemostasis via the actin cytoskeleton","volume":"123","author":"Paul","year":"2023","journal-title":"Thromb Haemost."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1182\/blood-2004-04-1257","article-title":"Integrins: Dynamic scaffolds for adhesion and signaling in platelets","volume":"104","author":"Shattil","year":"2004","journal-title":"Blood"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1016\/S1474-4422(16)30073-4","article-title":"Global burden of stroke and risk factors in 188 countries, during 1990\u20132013: A systematic analysis for the Global Burden of Disease Study 2013","volume":"15","author":"Feigin","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e1808361","DOI":"10.1002\/adma.201808361","article-title":"Microthrombus-targeting micelles for neurovascular remodeling and enhanced microcirculatory perfusion in acute ischemic stroke","volume":"31","author":"Lu","year":"2019","journal-title":"Adv. Mater."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Bhaskar, S., Stanwell, P., Cordato, D., Attia, J., and Levi, C. (2018). Reperfusion therapy in acute ischemic stroke: Dawn of a new era?. BMC Neurol., 18.","DOI":"10.1186\/s12883-017-1007-y"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sun, X.Q., Fang, J., and Fang, N.Y. (2024). Chishao alleviates intra-hepatic cholestasis by modulating NTCP in rats. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1341651"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2016.01.016","article-title":"Metabolomics study on the effects of Buchang Naoxintong capsules for treating cerebral ischemia in rats using UPLC-Q\/TOF-MS","volume":"180","author":"Liu","year":"2016","journal-title":"J. Ethnopharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s11655-019-2701-y","article-title":"Asymmetric dimethylarginine predicts one-year recurrent cardiovascular events: Potential biomarker of \u201ctoxin syndrome\u201d in coronary heart disease","volume":"25","author":"Xu","year":"2019","journal-title":"Chin. J. Integr. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1161\/CIRCULATIONAHA.108.812537","article-title":"Ligand-activated peroxisome proliferator-activated receptor-\u03b3 protects against ischemic cerebral infarction and meuronal apoptosis by 14-3-3\u2208 upregulation","volume":"119","author":"Wu","year":"2009","journal-title":"Circulation"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.pneurobio.2017.10.001","article-title":"Blood-brain barrier dysfunction and recovery after ischemic stroke","volume":"163\u2013164","author":"Jiang","year":"2018","journal-title":"Prog. Neurobiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"116306","DOI":"10.1016\/j.jep.2023.116306","article-title":"Network pharmacology, a promising approach to reveal the pharmacology mechanism of Chinese medicine formula","volume":"309","author":"Zhao","year":"2023","journal-title":"J. Ethnopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1074\/jbc.M110.158675","article-title":"Calcineurin\/nuclear factor of activated T cells and MAPK signaling induce TNF-\u03b1 gene expression in pancreatic islet endocrine cells","volume":"286","author":"Lawrence","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.jphs.2017.11.009","article-title":"Acacetin protects against cardiac remodeling after myocardial infarction by mediating MAPK and PI3K\/Akt signal pathway","volume":"135","author":"Chang","year":"2017","journal-title":"J. Pharmacol. Sci."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Belmellat, N., Semerano, L., Segueni, N., Damotte, D., Decker, P., Ryffel, B., Quesniaux, V., Boissier, M.C., and Assier, E. (2017). Tumor necrosis factor-alpha targeting can protect against arthritis with low sensitization to infection. Front. Immunol., 8.","DOI":"10.3389\/fimmu.2017.01533"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1161\/STROKEAHA.115.012166","article-title":"Inflammatory markers and outcomes after lacunar stroke levels of inflammatory markers in treatment of stroke study","volume":"47","author":"Boehme","year":"2016","journal-title":"Stroke"},{"key":"ref_42","first-page":"209","article-title":"The importance of selected markers of inflammation and blood-brain barrier damage for short-term ischemic stroke prognosis","volume":"70","author":"Student","year":"2019","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Lin, S.Y., Wang, Y.Y., Chang, C.Y., Wu, C.C., Chen, W.Y., Liao, S.L., and Chen, C.J. (2021). TNF-\u03b1 receptor inhibitor alleviates metabolic and inflammatory changes in a rat model of ischemic stroke. Antioxidants, 10.","DOI":"10.3390\/antiox10060851"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"4888","DOI":"10.1073\/pnas.95.9.4888","article-title":"Mechanism of platelet inhibition by nitric oxide: Phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase","volume":"95","author":"Wang","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4969","DOI":"10.1038\/s41467-018-07409-1","article-title":"A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis","volume":"9","author":"Wen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Bladowski, M., Gawrys, J., Gajecki, D., Szahidewicz-Krupska, E., Sawicz-Bladowska, A., and Doroszko, A. (2020). Role of the platelets and nitric oxide biotransformation in ischemic stroke: A translative review from bench to bedside. Oxidative Med. Cell. Longev., 2020.","DOI":"10.1155\/2020\/2979260"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1146\/annurev-biochem-030222-120000","article-title":"The Art and Science of Molecular Docking","volume":"93","author":"Paggi","year":"2024","journal-title":"Annu. Rev. Biochem."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1021\/acs.jmedchem.6b00725","article-title":"When Does Chemical Elaboration Induce a Ligand to Change Its Binding Mode?","volume":"60","author":"Malhotra","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1016\/j.chembiol.2019.06.001","article-title":"Analyzing Resistance to Design Selective Chemical Inhibitors for AAA Proteins","volume":"26","author":"Pisa","year":"2019","journal-title":"Cell Chem. Biol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ahmed, M., Khan, K.U., Ahmad, S., Aati, H.Y., Ovatlarnporn, C., Rehman, M.S., Javed, T., Khursheed, A., Ghalloo, B.A., and Dilshad, R. (2022). Comprehensive Phytochemical Profiling, Biological Activities, and Molecular Docking Studies of Pleurospermum candollei: An Insight into Potential for Natural Products Development. Molecules, 27.","DOI":"10.3390\/molecules27134113"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/24\/4409\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:58:10Z","timestamp":1760115490000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/24\/4409"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":50,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["nu16244409"],"URL":"https:\/\/doi.org\/10.3390\/nu16244409","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}