Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response
Abstract In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse m...
| المؤلفون الرئيسيون: | , , , , , , |
|---|---|
| التنسيق: | مقال |
| اللغة: | English |
| منشور في: |
Nature Portfolio
2023-11-01
|
| سلاسل: | Scientific Reports |
| الوصول للمادة أونلاين: | https://doi.org/10.1038/s41598-023-47226-1 |
| _version_ | 1827711155182764032 |
|---|---|
| author | Sandip Godse Lina Zhou Namita Sinha Sunitha Kodidela Asit Kumar Udai P. Singh Santosh Kumar |
| author_facet | Sandip Godse Lina Zhou Namita Sinha Sunitha Kodidela Asit Kumar Udai P. Singh Santosh Kumar |
| author_sort | Sandip Godse |
| collection | DOAJ |
| description | Abstract In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse model, we compared the biodistribution of EVG alone and in combination with CUR using intraperitoneal (IP) and intranasal (IN) routes. IN administration showed a significantly higher accumulation of EVG in the brain, while both IP and IN routes led to increased EVG levels in the lungs and liver. The addition of CUR further enhanced EVG brain delivery, especially when administered via the IN route. The expression of neural marker proteins, synaptophysin, L1CAM, NeuN, and GFAP was not significantly altered by EVG or CUR alone or their combination, indicating preserved neural homeostasis. After establishing improved brain concentration and safety of CUR-adjuvanted EVG in mice in acute treatment, we studied the effect of this treatment in HIV-infected U1 macrophages. In U1 macrophages, we also observed that the addition of CUR enhanced the intracellular concentration of EVG. The total area under the curve (AUCtot) for EVG was significantly higher in the presence of CUR. We also evaluated the effects of CUR on oxidative stress and antioxidant capacity in EVG-treated U1 macrophages. CUR reduced oxidative stress, as evidenced by decreased reactive oxygen species (ROS) levels and elevated antioxidant enzyme expression. Furthermore, the combination of CUR and EVG exhibited a significant reduction in proinflammatory cytokines (TNFα, IL-1β, IL-18) and chemokines (RANTES, MCP-1) in U1 macrophages. Additionally, western blot analysis confirmed the decreased expression of IL-1β and TNF-α in EVG + CUR-treated cells. These findings suggest the potential of CUR to enhance EVG permeability to the brain and subsequent efficacy of EVG, including HIV neuropathogenesis. |
| first_indexed | 2024-03-10T17:50:48Z |
| format | Article |
| id | doaj.art-53cc17566139497e835d1fcdf6a9be7c |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-10T17:50:48Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-53cc17566139497e835d1fcdf6a9be7c2023-11-20T09:22:34ZengNature PortfolioScientific Reports2045-23222023-11-0113111110.1038/s41598-023-47226-1Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory responseSandip Godse0Lina Zhou1Namita Sinha2Sunitha Kodidela3Asit Kumar4Udai P. Singh5Santosh Kumar6Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterDepartment of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science CenterAbstract In this study, we investigated the potential of using curcumin (CUR) as an adjuvant to enhance the delivery of antiretroviral drug elvitegravir (EVG) across the BBB, and alleviate oxidative stress and inflammatory response, which are the major hallmark of HIV neuropathogenesis. In a mouse model, we compared the biodistribution of EVG alone and in combination with CUR using intraperitoneal (IP) and intranasal (IN) routes. IN administration showed a significantly higher accumulation of EVG in the brain, while both IP and IN routes led to increased EVG levels in the lungs and liver. The addition of CUR further enhanced EVG brain delivery, especially when administered via the IN route. The expression of neural marker proteins, synaptophysin, L1CAM, NeuN, and GFAP was not significantly altered by EVG or CUR alone or their combination, indicating preserved neural homeostasis. After establishing improved brain concentration and safety of CUR-adjuvanted EVG in mice in acute treatment, we studied the effect of this treatment in HIV-infected U1 macrophages. In U1 macrophages, we also observed that the addition of CUR enhanced the intracellular concentration of EVG. The total area under the curve (AUCtot) for EVG was significantly higher in the presence of CUR. We also evaluated the effects of CUR on oxidative stress and antioxidant capacity in EVG-treated U1 macrophages. CUR reduced oxidative stress, as evidenced by decreased reactive oxygen species (ROS) levels and elevated antioxidant enzyme expression. Furthermore, the combination of CUR and EVG exhibited a significant reduction in proinflammatory cytokines (TNFα, IL-1β, IL-18) and chemokines (RANTES, MCP-1) in U1 macrophages. Additionally, western blot analysis confirmed the decreased expression of IL-1β and TNF-α in EVG + CUR-treated cells. These findings suggest the potential of CUR to enhance EVG permeability to the brain and subsequent efficacy of EVG, including HIV neuropathogenesis.https://doi.org/10.1038/s41598-023-47226-1 |
| spellingShingle | Sandip Godse Lina Zhou Namita Sinha Sunitha Kodidela Asit Kumar Udai P. Singh Santosh Kumar Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response Scientific Reports |
| title | Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| title_full | Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| title_fullStr | Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| title_full_unstemmed | Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| title_short | Curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| title_sort | curcumin enhances elvitegravir concentration and alleviates oxidative stress and inflammatory response |
| url | https://doi.org/10.1038/s41598-023-47226-1 |
| work_keys_str_mv | AT sandipgodse curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT linazhou curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT namitasinha curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT sunithakodidela curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT asitkumar curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT udaipsingh curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse AT santoshkumar curcuminenhanceselvitegravirconcentrationandalleviatesoxidativestressandinflammatoryresponse |