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Curcumin boosts brain delivery of HIV drug, curbing inflammation

Desk Report || risingbd.com

Published: 11:47, 16 November 2023  
Curcumin boosts brain delivery of HIV drug, curbing inflammation

In a recent study published in the journal Scientific Reports, researchers examined the use of curcumin as an adjuvant to improve the delivery of the antiretroviral elvitegravir across the blood-brain barrier and to reduce the inflammatory response and oxidative stress that constitutes the neuropathogenesis of human immunodeficiency virus (HIV) infection.

Although the use of antiretroviral therapy has significantly improved health outcomes for HIV patients and has been effective in controlling the replication of the virus, the neuronal complications that arise during HIV infections are yet to be addressed adequately, reports news-medical.net today.

Viral reservoirs persisting in the central nervous system in the microglia and macrophages allow latent HIV to hide in the body and replicate, triggering the release of cytokines causing chronic inflammation and cellular damage. The cumulative effect of these factors contributes to HIV-associated neurocognitive disorder (HAND).

Irrespective of the immunological and virological indicators of HIV suppression due to antiretroviral therapy, the neuronal damage caused during HAND continues to increase. The inability of current antiretrovirals to penetrate the blood-brain barrier and suppress the replication of HIV within the central nervous system can be observed in the detection of viral ribonucleic acid (RNA) in the brains of HIV patients who have completely suppressed viral loads in the plasma. The inadequate penetration of antiretroviral drugs across the blood-brain barrier presents a significant challenge in the eradication of HIV reservoirs from the central nervous system.

In the present study, the researchers investigated the efficacy of curcumin as an adjuvant in improving the transmigration of elvitegravir, an antiretroviral with a relatively better safety profile, across the blood-brain barrier, and in reducing the inflammation and oxidative stress that are the hallmarks of HAND and HIV neuropathogenesis. Curcumin is extracted from the rhizomes of Curcuma longa and is known to possess antimicrobial, antioxidant, and anti-inflammatory properties.

Studies have also shown curcumin to have antiviral and neuroprotective properties. Curcumin is also known to decrease neuroinflammation, have protective properties against oxidative damage, and prevent the formation of neurocognitive impairment-associated amyloid fibrils. The antiretroviral selected for the study was elvitegravir, an integrase strand transfer inhibitor approved by the United States (U.S.) Food and Drug Administration (FDA for treatment of HIV patients.

Although elvitegravir is considered safer than other antiretrovirals, it is not very effective at crossing the blood-brain barrier, and the researchers hypothesized that the inclusion of curcumin as the adjuvant and the intranasal delivery of elvitegravir and curcumin in mouse models would exhibit improved transmigration of the antiretroviral and adjuvant into rodent brains and macrophages. They also tested the ability of curcumin, by itself and in combination with elvitegravir, to decrease inflammation and oxidative stress.

The study also compared the in vivo biodistribution of the antiretroviral alone and in combination with the adjuvant curcumin when administered intranasally and intraperitoneally. The distribution of elvitegravir along and in the liver, plasma, lungs, and brain was compared 12 hours after intranasal and intraperitoneal administration.

Overall, the findings suggested that using curcumin as an adjuvant improved the delivery of the antiretroviral elvitegravir into the brain, liver, and lungs in mouse models and into U1 macrophages in vitro. Curcumin was also found to have a positive impact in lowering inflammation and oxidative stress, the two major events in the neuropathogenesis of HIV._Agencies.