Hai-Xin Liu, Shuang He, Tian-Liang Xue, Shi-Yuan Wen, Yan Zhu
{"title":"Isoquercitrin Promotes Angiogenesis Through the Genomic Signaling Pathway of the Estrogen Receptor-Alpha.","authors":"Hai-Xin Liu, Shuang He, Tian-Liang Xue, Shi-Yuan Wen, Yan Zhu","doi":"10.1002/ptr.70082","DOIUrl":"https://doi.org/10.1002/ptr.70082","url":null,"abstract":"<p><p>Postmenopausal women's estrogen decline is a key factor for cardiovascular disease (CVD). Phytoestrogen may prevent CVD by protecting vascular endothelium and inhibiting vascular smooth muscle proliferation via receptor's genomic or nongenomic pathways, yet effective estrogen receptor α (ERα)-targeting phytoestrogens need further exploration. Molecular docking and thermal shift assay were used to verify compound binding to ERα. Effects of phytoestrogens on ERα nuclear translocation and transcription were evaluated in cells by high-content screening, luciferase assay, and ChIP. Tube formation assay illustrated phytoestrogen's role in angiogenesis in EAhy926 cells with different ERα forms. ERα gene or mutants were expressed in EAhy926 cell line to reveal genomic signaling. A hind-limb ischemia model of VEGFR2-Luc female mice with ovarian removal was established to demonstrate phytoestrogen's role on angiogenesis. Also, the effect of phytoestrogen on nuclear translocations of p-NF-κB, p-c-JUN, and p-p38 induced by ox-LDL or LPS in EAhy926 cells with different ERα forms was examined. Isoquercitrin (IQ) binds to ERα, promoting its nuclear translocation and transcription, and induces angiogenesis by activating ERα, enhancing VEGFR2 and VEGFA mRNA levels. Experiments show IQ activates ERα genomic signaling to promote angiogenesis, reversible by ICI 182780. IQ induces angiogenesis via ERα activation, increasing VEGFR2 and VEGFA protein expression in vivo. Also, IQ reduces nuclear translocation of p-NF-κB, p-c-JUN, and p-p38 in an ERα-dependent way and decreases their protein expression in ischemic hind-limb tissue. IQ binds to and activates ERα, promoting angiogenesis by regulating VEGF through ERα genomic signaling, showing potential for preventing and treating CVD in postmenopausal women.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astragaloside IV Pretreatment Alleviates Pulmonary Ischemia-Reperfusion Injury via the TLR4/MyD88/NF-κB p65 Pathway in Rats.","authors":"Xiao-Rui Tian, Jun-Hui Zhao, Xia-Hui Yin, Jia-Hui Lin, Si-Min Liang, Xiao-Qing Xu, Ke-Ying Li, Tian-Shuang Fan, Ping Xiong","doi":"10.1002/ptr.70039","DOIUrl":"https://doi.org/10.1002/ptr.70039","url":null,"abstract":"<p><p>Background and aim Our previous study confirmed that ASIV can protect the lung from ischemia-reperfusion injury. The aim of this study was to determine whether ASIV attenuates PIRI by inhibiting the activation of the TLR4/MyD88/NF-κBp65 pathway. Experimental procedure In vitro, the protection of ASIV, TAK-242, NAC, and DEX to OGD/R-induced cell injury was compared. In vivo, the PIRI model was induced in SD rats. The lung tissue W/D ratio and pathological morphology, as well as the markers of oxidative stress, were monitored. The mRNA and protein expression levels correlated to the TLR4/MyD88/NF-κB p65 pathway were evaluated. Furthermore, we performed molecular docking and binding affinity calculations of the interaction between ASIV and TLR4-MD-2, which was verified with SPR. Key results and conclusions and implications ASIV showed more effective protection than DEX or NAC, and exhibited a synergistic effect with TAK-242. After treatment with ASIV, lung tissue and cellular damage were obviously alleviated, and the levels of T-SOD and GSH-PX were significantly increased, while lung MDA and MPO decreased. Moreover, the ASIV groups showed a significant down-regulation of the TLR4, MyD88, NF-κBp65 and p-NF-κBp65 proteins when compared with the PIRI model group. The prediction showed that ASIV can enter the cavity of TLR4-MD-2 and exhibit strong binding, with a free binding energy of -8.0 kcal·mol<sup>-1</sup>. SPR further confirmed that ASIV rapidly bound to the rhTLR4-MD-2 complex with a K<sub>D</sub> of 2.17 × 10<sup>-6</sup> M. In conclusion, ASIV can specifically bind to rhTLR4-MD-2, thus alleviating PIRI by suppressing the activation of the TLR4/MyD88/NF-κB65-mediated inflammatory pathway.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"In Vivo Wound-Healing and Molecular Docking Studies Support the Traditional Use of Arisarum vulgare Aqueous Extract.","authors":"Zineb Bouafia, Amel Boudjelal, Souhila Bouaziz-Terrachet, Antonella Smeriglio, Mustapha Mounir Bouhenna, Ilyas Yıldız, Ibrahim Demirtas, Domenico Trombetta","doi":"10.1002/ptr.70087","DOIUrl":"https://doi.org/10.1002/ptr.70087","url":null,"abstract":"<p><p>In Algerian traditional medicine, Arisarum vulgare O. Targ. Tozz. (Araceae), locally known as \"Elbgouga,\" is widely used to treat eczema, wounds, and burns. The aim of this study was to investigate, for the first time and by using in vivo and in silico molecular docking techniques, the possible effects of A. vulgare ultrasound-assisted aqueous extract (AVAE) on wound healing. The phytochemical profile was elucidated by LC-ESI-MS/MS analysis. Wistar albino rats were used to evaluate the AVAE ointment's acute cutaneous toxicity and wound-healing potential (1%, 2%, and 5% AVAEO). Through in silico investigations, TNF-α, IL-1β, MMP-9, TGF-β, VEGF, and EGFR were examined as possible therapeutic targets. Twenty-seven phytochemicals, belonging mainly to the flavonoids and phenolic acids' class, were identified and semi-quantified. The 5% AVAEO-treated group showed a significantly greater (p < 0.001) wound contraction (8-20 days) with respect to untreated and petroleum jelly groups, whereas no statistically significant difference was observed with respect to the Madecassol-treated group. On the contrary, the two lower doses (1% and 2% AVAEO) showed no statistically significant effects. Docking studies showed that A. vulgare bioactive compounds may have therapeutic effects on wound healing by targeting with high affinity TNFα, IL-1β, MMP-9, TGF-βR1, VEGF, and EGFR, counteracting inflammation, angiogenesis, and oxidative unbalance, and promoting wound repair. This study demonstrated that AVAE possesses in vivo wound healing properties and no dermal toxicity, shedding light also on the potential therapeutic targets involved.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hye Jin Lee, Yu Jin So, Il-Joo Jo, Ji Yong Jang, Tae Han Yook, Jun Ho Lee, Sung Wook Kim, Kangwook Lee, Soo Jung Park, Gabsik Yang
{"title":"Harnessing Natural Compounds in Psoriasis: Targeting Cellular Pathways for Effective Therapy.","authors":"Hye Jin Lee, Yu Jin So, Il-Joo Jo, Ji Yong Jang, Tae Han Yook, Jun Ho Lee, Sung Wook Kim, Kangwook Lee, Soo Jung Park, Gabsik Yang","doi":"10.1002/ptr.70085","DOIUrl":"10.1002/ptr.70085","url":null,"abstract":"<p><p>Psoriasis is a persistent inflammatory dermatological condition, predominantly influenced by genetic factors, immune system dysfunction, and environmental stimuli. It presents as red papules and silvery-white scales, resulting in physical discomfort and contributing to various comorbidities, including mental health disorders, arthritis, and cardiovascular complications, which collectively impose considerable medical and socioeconomic burdens. Conventional treatments, such as immunosuppressants and biologics, may alleviate symptoms but frequently entail significant side effects and the potential for dependency. This review evaluates the therapeutic potential of natural compounds, emphasizing their capacity to influence critical cellular pathways involved in the pathogenesis of psoriasis. Natural compounds exhibit anti-inflammatory, keratinocyte-regulating, and antioxidant properties, influencing mechanisms like the Th17/IL-17 axis and oxidative stress. The results indicate that natural compounds may function as an adjunctive treatment, providing a safer alternative to existing therapies by mitigating side effects and improving symptom management.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Astragalin Inhibits Oxidative Stress-Induced Pyroptosis and Apoptosis in Mouse Models of Renal Ischemia/Reperfusion Injury by Activating the SIRT1/Nrf2 Pathway.","authors":"Qian Huang, Zilu Shi, Dandan Zheng, Huiqin Chen, Qiuhong Huang","doi":"10.1002/ptr.8527","DOIUrl":"https://doi.org/10.1002/ptr.8527","url":null,"abstract":"<p><p>Natural flavonoid astragalin (AST) has many pharmacological effects and has been reported to improve renal injury in diabetic kidney disease. This study aimed to investigate the role of AST in renal ischemia/reperfusion injury (RIRI) and elucidate related mechanisms. The RIRI mouse models were pre-treated with AST (25, 50, or 75 mg/kg) 24 h before ischemia/reperfusion surgery. The effects of AST on pathological renal injury in mice after I/R were determined using hematoxylin-eosin staining. HK-2 cells were pre-treated with AST (50, 100, or 200 μM) for 24 h before exposure to hypoxia/reoxygenation. The impact of AST on oxidative stress, apoptosis, and pyroptosis, as well as the Sirt1/Nrf2/HO-1 pathway in vivo and in vitro, was detected. The binding of AST with Sirt1 was verified using molecular docking and cellular thermal shift assay (CETSA). AST ameliorated pathological renal injury, reduced ROS production and MDA levels, increased SOD activity, and inhibited apoptosis and NLRP3-mediated pyroptosis in mice after I/R. AST attenuated H/R-induced oxidative stress, apoptosis, and pyroptosis in HK-2 cells. Mechanically, AST increased the levels of Sirt1, Nrf2, and HO-1 in the kidneys of mice undergoing I/R and in H/R-stimulated HK-2 cells. The inhibition of Sirt1 by EX725 or si-Sirt1 reversed the protective effects of AST on RIRI. AST exhibits renoprotective effects in RIRI by alleviating oxidative stress-induced pyroptosis and apoptosis by activating the SIRT1/Nrf2 pathway, suggesting that AST might be a novel therapeutic agent for RIRI.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144993374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shekhar Goyal, Surender K Beniwal, Pallavi Agarwal, Rajnish K Brar, Priyanka Jain, H S Kumar, Bhudev C Das
{"title":"Efficacy and Safety of Curcumin as an Adjuvant to Standard Chemotherapy in Advanced and Metastatic Breast Cancer Patients: A Randomized Controlled Study.","authors":"Shekhar Goyal, Surender K Beniwal, Pallavi Agarwal, Rajnish K Brar, Priyanka Jain, H S Kumar, Bhudev C Das","doi":"10.1002/ptr.70086","DOIUrl":"10.1002/ptr.70086","url":null,"abstract":"<p><p>The potential of the phytoconstituent, curcumin, as an adjuvant to chemoradiotherapy has been investigated because of its ameliorating effects, including the sensitization of cancer and cancer stem cells. Curcumin, a strong antioxidant with pharmacologically non-toxic effects, can be used as an adjuvant with enhanced bioavailability and administered along with chemotherapy to achieve better treatment outcomes. The present study was carried out with a total of 120 women with locally advanced/metastatic breast cancer, who were randomized to receive standard chemotherapy alone or chemotherapy with oral curcumin, a 500 mg capsule (1 g/day) containing 95% curcuminoid and 1% piperine given for 12 to 24 weeks. Primary outcomes were determined using the Response Evaluation Criteria in Solid Tumors (RECIST) to determine the objective response rate (ORR), progression-free survival (PFS), and time to tumor progression (TTP), including safety and adverse events, while the quality of life (QoL) and physical activity were secondary outcomes. ORR was significantly higher in the curcumin group than in those who received standard chemotherapy (38.33% vs. 8.33%, p < 0.01) at 4 weeks follow-up post-treatment, which further improved (43.40% vs. 10.64%, p < 0.0031) upon completion of 12 weeks post-treatment. Curcumin-treated women displayed higher physical performance, better prognosis and QoL, better tolerance to chemotherapy, fewer adverse effects, and better PFS. The study suggests that curcumin can be used as a safe adjuvant along with chemotherapeutic drugs for a better treatment outcome in breast cancer and also in other cancers.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144964950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phytotherapy ResearchPub Date : 2025-09-01Epub Date: 2025-07-16DOI: 10.1002/ptr.70046
Sinan Aktay, Yurixi Lopez-Miranda, Jaakko Parkkinen, Krishnan Raghavendran, Madathilparambil V Suresh
{"title":"Oral Administration of Water-Soluble Curcumin Complex Prevents ARDS With the Potential for COVID-19 Treatment.","authors":"Sinan Aktay, Yurixi Lopez-Miranda, Jaakko Parkkinen, Krishnan Raghavendran, Madathilparambil V Suresh","doi":"10.1002/ptr.70046","DOIUrl":"10.1002/ptr.70046","url":null,"abstract":"<p><p>Acute respiratory distress syndrome (ARDS)-a form of severe lung injury-is often caused by conditions such as pneumonia, sepsis, and COVID-19. COVID-19, which enters cells through the angiotensin-converting enzyme 2 (ACE2) receptor, has complications varying from mild infection to ARDS and death. Curcumin, a naturally occurring and safe anti-inflammatory compound, has previously been formulated as a water-soluble curcumin (CDC) to improve solubility and stability under physiologic conditions. CDC administration has been shown to improve cell survival and reduce inflammation, injury, and mortality in models of severe Klebsiella pneumoniae (KP) infection. This study aims to further evaluate the potential of CDC in treating COVID-19, particularly complicated by ARDS. Lung samples from post-mortem KP and COVID-19 patients were evaluated for relevant markers with immunohistochemistry. Separately, mice inoculated with KP with or without CDC were evaluated for injury, inflammation, and expression of ACE2, STAT-3, CXCL-10, and IFN-α. Mice treated with LPS with or without CDC were also evaluated similarly. Lung samples from KP patients had significantly higher ACE2 expression than normal lungs. Postmortem lung samples from COVID-19 patients exhibited intense ACE2 staining compared to normal human lungs. Administration of CDC substantially reduced ACE2 expression at serum, gene, and protein levels after KP and LPS infection. Furthermore, CDC administration reduced the levels of STAT-3, as well as the chemokine CXCL10, and interferon IFN-α in KP-infected mice. In vitro, data showed CDC administration reduced ACE2 and STAT3 expression in human lung epithelial cells following KP. Furthermore, administering CDC after LPS led to a significant decrease in injury, inflammation, and ACE2 levels. Based on the promising effects of CDC on these relevant markers, a proposal to use curcumin as a supportive therapy to treat ARDS and COVID-19 to save lives is being considered.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3924-3934"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144650134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phytotherapy ResearchPub Date : 2025-09-01Epub Date: 2025-08-03DOI: 10.1002/ptr.70014
Hong Qin, Jingmiao Chen, Zhuoya Xu, Jingfang Chen, Yansong Fu, Zhipeng Wang, Xi Liu, Wenya Zheng
{"title":"Liquiritigenin Alleviates Hepatic Metabolic Inflammation Through Regulation of Muscle-Liver Crosstalk Signal of Myonectin.","authors":"Hong Qin, Jingmiao Chen, Zhuoya Xu, Jingfang Chen, Yansong Fu, Zhipeng Wang, Xi Liu, Wenya Zheng","doi":"10.1002/ptr.70014","DOIUrl":"10.1002/ptr.70014","url":null,"abstract":"<p><p>Liquiritigenin (LQ), a flavonoid derived from the roots of licorice, exhibits diverse biological activities. However, the specific role of LQ in alleviating non-alcoholic fatty liver disease (NAFLD) and its correlated metabolic disorders remains to be further explored. This study aimed to investigate the effects and molecular mechanisms of LQ in modulating metabolic inflammation (meta-inflammation) and mainly focused on a systemic muscle-liver crosstalk mediated by myonectin. High-fat diet (HFD) male C57BL/6J mice were established to evaluate the effects of LQ on hepatic lipid accumulation, inflammation and secretion of myonectin. The effects of LQ and myonectin on meta-inflammation and the potential molecular mechanisms in vitro were assessed in C2C12 cells and HepG2 cells. In vivo findings indicated that LQ attenuated HFD-induced hepatic steatosis and meta-inflammation. LQ treatment downregulated the meta-inflammation-related protein expression levels of CD36 and TLR4, subsequently reducing the phosphorylation levels of c-Jun N-terminal kinase (JNK), c-jun, and NF-κB. Administration of LQ was associated with reduced levels of myonectin. Myonectin and PA exhibited synergistic effects on enhancing protein expressions of the CD36/TLR4 pathway, whereas LQ attenuated the activation of these protein expressions. Additionally, a pretreatment with LPS eliminated the protective effects of LQ and restored the effects of PA and myonectin. The mechanisms of LQ on reducing meta-inflammation might be mediated by muscle-liver crosstalk signaling of myonectin, and the CD36/TLR4 signaling pathway was essential in modulating meta-inflammation by LQ. These findings demonstrated the role and mechanisms of LQ in alleviating meta-inflammation, which was mediated through muscle-liver crosstalk signals of myonectin and its downstream CD36/TLR4 pathway. The results would provide novel insights into the potential of LQ as a phytotherapy for NAFLD.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4141-4155"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144776052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phytotherapy ResearchPub Date : 2025-09-01Epub Date: 2025-08-04DOI: 10.1002/ptr.70064
Ressin Varghese, Krishna Sayantika Deb, Kuntal Pal, Annapurna Jonnalagadda, Aswani Kumar Cherukuri, Mona Dawood, Joelle C Boulos, Thomas Efferth, Siva Ramamoorthy
{"title":"Harnessing the Potential of Carotenoids for Cancer Therapy: An Integrated Machine Learning and MST Based Approach.","authors":"Ressin Varghese, Krishna Sayantika Deb, Kuntal Pal, Annapurna Jonnalagadda, Aswani Kumar Cherukuri, Mona Dawood, Joelle C Boulos, Thomas Efferth, Siva Ramamoorthy","doi":"10.1002/ptr.70064","DOIUrl":"10.1002/ptr.70064","url":null,"abstract":"<p><p>Receptor tyrosine kinases (RTKs) are high-affinity membrane-anchored receptors involved in cellular communication via various ligands and manage numerous biological processes such as cell growth, differentiation, and metabolism. However, dysregulation of RTKs is a key instigating factor in the development of a vast array of cancers. Carotenoids are a major family of secondary plant metabolites known for their anti-cancer activities in various cancer models by targeting several molecular intermediates. We aimed to decipher the potential carotenoids as RTK inhibitors through an integrated workflow of in silico approaches and in vitro microscale thermophoresis. The kinase domains of nine RTKs were subjected to molecular docking with potential carotenoids, and the best-scoring carotenoids were selected. The molecular interactions of the best-scoring carotenoids and respective RTKs were validated through dynamics simulation. The selected carotenoid candidates were further validated through comparative analysis with clinically established drugs using various machine learning algorithms to establish the drug likeliness. Microscale thermophoresis was performed to prove the interaction of the best-scoring carotenoid with recombinant PDGFRA and VEGFR2 in vitro. The following five receptors and respective carotenoids were recognized through docking, MDS, and ML analysis: EGFR-fucoxanthin, FGFR2-peridinin, VEGFR2-canthaxanthin, PDGFRA-canthaxanthin, and ALK-crocin. MST experiments further underlined the high binding affinity of canthaxanthin with the targeted RTKs, underlining the possibilities of plant-based chemotherapy. Interestingly, carotenoids were recognized as potential plant-based alternatives for conventional drugs in RTK-targeted cancer therapy via an innovative ML-assisted drug discovery approach, and they provide novel insights into the discovery of phytochemicals as cancer drugs.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"4156-4170"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144785010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Natural Products in Regulating Mitophagy for the Intervention of Atherosclerosis and Its Risk Factors: Mechanisms and Therapeutic Potential.","authors":"Yu-Han Li, Hao Ma, Ying-Rui Wang, Si-Xiang Zhang, You-Min Zhao, Zheng Liu","doi":"10.1002/ptr.70041","DOIUrl":"10.1002/ptr.70041","url":null,"abstract":"<p><p>Atherosclerosis (AS) is a chronic systemic disease that poses a significant and escalating global challenge. The pathological process of AS involves multiple aspects. In addition to lipid-lowering therapy, therapeutic strategies such as anti-inflammatory and immunotherapy have been proposed, and attention has been paid to the intervention of its risk factors. However, the available drugs are still limited. Therefore, there is an urgent need to discover new pharmacological targets and drugs. Mitophagy is closely associated with AS and its risk factors, and it represents an important breakthrough in the intervention of AS and its risk factors. Natural products (NPs), with multiple pharmacological activities and lower toxicity, have caught attention as the new force in the treatment of AS and its risk factors. This review discusses the mechanisms and therapeutic potential of NPs in regulating mitophagy to alleviate AS and intervene in its risk factors. It also introduces the application prospects of the NPs, with the expectation of contributing to the treatment of AS and the development of innovative drugs.</p>","PeriodicalId":20110,"journal":{"name":"Phytotherapy Research","volume":" ","pages":"3966-3997"},"PeriodicalIF":6.3,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144691221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}