Targeting sickle cell pathobiology and pain with novel transdermal curcumin

被引：0

作者：

Goel, Yugal ^{[1
]}

Arellano, Mya A. ^{[1
]}

Fouda, Raghda T. ^{[1
]}

Garcia, Natalie R. ^{[1
]}

Lomeli, Reina A. ^{[1
]}

Kerr, Daniel ^{[2
,3
]}

Argueta, Donovan A. ^{[1
]}

Gupta, Mihir ^{[4
]}

Velasco, Graham J. ^{[5
]}

Prince, Richard ^{[6
]}

Banerjee, Probal ^{[2
,3
]}

Jana, Sirsendu ^{[7
]}

Alayash, Abdu, I

Friedman, Joel M. ^{[8
]}

Gupta, Kalpna ^{[1
,9
]}

机构：

[1] Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92697 USA

[2] CUNY Coll Staten Isl, Dept Chem, Staten Isl, NY 10314 USA

[3] Coll Staten Isl CUNY, Ctr Dev Neurosci, Staten Isl, NY 10314 USA

[4] Yale Sch Med, Dept Neurosurg, New Haven, CT 06520 USA

[5] VA Long Beach Med Ctr, Pathol Dept, Long Beach, CA 90822 USA

[6] Vascarta Inc, Summit, NJ 07446 USA

[7] US FDA, Lab Biochem & Vasc Biol, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA

[8] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA

[9] Univ Minnesota, Dept Med, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA

来源：

PNAS NEXUS | 2025年 / 4卷 / 02期

关键词：

curcumin; inflammation; pain; red blood cell; sickle cell disease; OXIDATIVE STRESS; SUBSTANCE-P; DISEASE; MICE; ACTIVATION; HEMOLYSIS; MODEL; INFLAMMATION; CONTRIBUTES; HEMOGLOBIN;

D O I：

10.1093/pnasnexus/pgaf053

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Several comorbidities of sickle cell disease (SCD) originate from red blood cell (RBC) instability, chronic inflammation, and oxidative stress. Development of scalable, cost-effective therapeutics suitable for chronic administration to prevent, attenuate, and perhaps reverse the consequences of RBC instability is needed. Curcumin has many of these attributes as a safe compound with antisickling, antiinflammatory, and antioxidant properties, but its translational potential has been constrained due to limited bioavailability from oral administration. The present study demonstrates the rapid and high bioavailability of a novel topical/transdermal (TD) curcumin gel formulation in the plasma and blood cells and its effectiveness in humanized sickle cell mice in: (i) ameliorating features of sickle cell pain hypersensitivity and axonal injury; (ii) reducing multiple manifestations of RBC instability including evidence of decreased hemolysis (reduced lactate dehydrogenase levels), enhanced RBC ATP levels along with decreased oxidative damage; (iii) decreasing multiple proinflammatory cytokines including interleukin-6, monocyte chemoattractant protein-1, granulocyte-macrophage colony-stimulating factor, and activation, normal T cell expressed and secreted protein in skin secretome; and (iv) reducing mast cell degranulation and activation. Our data suggest that an easy-to-use novel TD curcumin gel formulation has the potential to ameliorate chronic pain, improve RBC stability, and reduce inflammatory consequences of SCD.

引用

页数：13

共 78 条

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