Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury
Toxoplasma gondii, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-T. gondii activity and reduces depression-like behaviors induced by T. gondii infection. This study...
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Elsevier
2025-04-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320724000563 |
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| author | Jing-Mei Lu Guang-Nan Jin Yan Xin Jing-Wen Ma Xin-Yu Shen Yan-Zhu Quan Yi-Ming Liu Jin-Yi Zhou Bing-Zhe Wang Ying-Biao Li Xiang Xu Lian-Xun Piao |
| author_facet | Jing-Mei Lu Guang-Nan Jin Yan Xin Jing-Wen Ma Xin-Yu Shen Yan-Zhu Quan Yi-Ming Liu Jin-Yi Zhou Bing-Zhe Wang Ying-Biao Li Xiang Xu Lian-Xun Piao |
| author_sort | Jing-Mei Lu |
| collection | DOAJ |
| description | Toxoplasma gondii, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-T. gondii activity and reduces depression-like behaviors induced by T. gondii infection. This study aimed to enhance AG's brain-targeting and therapeutic efficacy by developing lactoferrin-modified nanoemulsions loaded with AG (Lf-AG-NEs). Lf-modified nanoemulsions were prepared and assessed using in vivo and in vitro infection models with the T. gondii RH strain, and a co-culture system of BV2 microglia and primary neuron cells. The effects of Lf-AG-NEs on T. gondii-induced neuronal injury were examined, and potential molecular mechanisms were elucidated through real-time quantitative PCR, western blotting, immunofluorescence, flow cytometry, immunohistochemistry, and Nissl staining. In vitro assessments showed significant increases in cellular uptake and blood-brain barrier penetration by Lf-AG-NEs. These nanoemulsions notably inhibited T. gondii proliferation in brain tissue and BV2 cells, surpassing the effects of free AG or AG-NEs alone. Additionally, Lf-AG-NEs substantially alleviated neuropathological changes and reduced microglial activation and neuroinflammation by downregulating the TLR4/NF-κB and TNFR1/NF-κB signaling pathways. Co-culturing BV2 cells with primary cortical neurons indicated that Lf-AG-NEs, similarly to CLI-095 and R7050, attenuated T. gondii-induced microglial activation and subsequent neuronal injury. In conclusion, the successfully prepared Lf-AG-NEs not only enhanced the anti-T. gondii effect but also strengthened the protective impact against neuronal injury induced by T. gondii, through the modulation of microglial signaling pathways. |
| format | Article |
| id | doaj-art-edc553f0978f4e4d8aff7d34b5f6c69d |
| institution | DOAJ |
| issn | 2211-3207 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj-art-edc553f0978f4e4d8aff7d34b5f6c69d2025-08-20T03:05:21ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072025-04-012710057510.1016/j.ijpddr.2024.100575Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injuryJing-Mei Lu0Guang-Nan Jin1Yan Xin2Jing-Wen Ma3Xin-Yu Shen4Yan-Zhu Quan5Yi-Ming Liu6Jin-Yi Zhou7Bing-Zhe Wang8Ying-Biao Li9Xiang Xu10Lian-Xun Piao11Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaKey Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, ChinaDepartment of Neurology, Yanbian University Hospital, Yanbian University, Yanji, 133000, Jilin Province, China; Corresponding author.Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China; Corresponding author.Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Molecular Medicine Research Center, College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China; Corresponding author.Toxoplasma gondii, a neurotropic protozoan parasite, affects the central nervous system and causes various neurological disorders. Previous studies have demonstrated that Arctigenin (AG) exhibits anti-T. gondii activity and reduces depression-like behaviors induced by T. gondii infection. This study aimed to enhance AG's brain-targeting and therapeutic efficacy by developing lactoferrin-modified nanoemulsions loaded with AG (Lf-AG-NEs). Lf-modified nanoemulsions were prepared and assessed using in vivo and in vitro infection models with the T. gondii RH strain, and a co-culture system of BV2 microglia and primary neuron cells. The effects of Lf-AG-NEs on T. gondii-induced neuronal injury were examined, and potential molecular mechanisms were elucidated through real-time quantitative PCR, western blotting, immunofluorescence, flow cytometry, immunohistochemistry, and Nissl staining. In vitro assessments showed significant increases in cellular uptake and blood-brain barrier penetration by Lf-AG-NEs. These nanoemulsions notably inhibited T. gondii proliferation in brain tissue and BV2 cells, surpassing the effects of free AG or AG-NEs alone. Additionally, Lf-AG-NEs substantially alleviated neuropathological changes and reduced microglial activation and neuroinflammation by downregulating the TLR4/NF-κB and TNFR1/NF-κB signaling pathways. Co-culturing BV2 cells with primary cortical neurons indicated that Lf-AG-NEs, similarly to CLI-095 and R7050, attenuated T. gondii-induced microglial activation and subsequent neuronal injury. In conclusion, the successfully prepared Lf-AG-NEs not only enhanced the anti-T. gondii effect but also strengthened the protective impact against neuronal injury induced by T. gondii, through the modulation of microglial signaling pathways.http://www.sciencedirect.com/science/article/pii/S2211320724000563ArctigeninLactoferrinNanoemulsionsToxoplasma gondiiNeuronMicroglia |
| spellingShingle | Jing-Mei Lu Guang-Nan Jin Yan Xin Jing-Wen Ma Xin-Yu Shen Yan-Zhu Quan Yi-Ming Liu Jin-Yi Zhou Bing-Zhe Wang Ying-Biao Li Xiang Xu Lian-Xun Piao Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury International Journal for Parasitology: Drugs and Drug Resistance Arctigenin Lactoferrin Nanoemulsions Toxoplasma gondii Neuron Microglia |
| title | Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury |
| title_full | Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury |
| title_fullStr | Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury |
| title_full_unstemmed | Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury |
| title_short | Lactoferrin-modified nanoemulsions enhance brain-targeting and therapeutic efficacy of arctigenin against Toxoplasma gondii-induced neuronal injury |
| title_sort | lactoferrin modified nanoemulsions enhance brain targeting and therapeutic efficacy of arctigenin against toxoplasma gondii induced neuronal injury |
| topic | Arctigenin Lactoferrin Nanoemulsions Toxoplasma gondii Neuron Microglia |
| url | http://www.sciencedirect.com/science/article/pii/S2211320724000563 |
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