Journal
EUROPEAN JOURNAL OF PHARMACOLOGY
Volume 899, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ejphar.2021.174008
Keywords
Neuropathic pain; Chronic constriction injury; Pharmacological improvement; Anti-inflammatory effect; Curcumin and CurDDG
Categories
Funding
- 90th Anniversary of Chulalongkorn University Fund
- Ratchadaphiseksomphot Endowment Fund [GCUGR1125623097M]
- Chulalongkorn University Graduate Scholarship
- National Research Council of Thailand [IRN FY2020 507/2563]
- Thailand Science Research and Innovation (TSRI) Fund [CU_FRB640001_01_33_3]
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The study demonstrated that the potential ester prodrug of curcumin, CurDDG, showed stronger analgesic effects than curcumin in a mouse model of chronic constriction injury. Additionally, CurDDG exhibited superior anti-inflammatory effects compared to curcumin in an in vitro study.
Neuropathic pain is a debilitating chronic pain condition, and its treatment remains a clinical challenge. Curcumin, a naturally occurring phenolic compound, possesses diverse biological and pharmacological effects but has not yet been approved as a drug due to its low bioavailability. In order to overcome this limitation, we synthesized a potential ester prodrug of curcumin, curcumin diethyl diglutarate (CurDDG). In this study, we evaluated the pharmacological advantages of CurDDG over curcumin in a mouse model of chronic constriction injury (CCI), and the anti-inflammatory effect of CurDDG in LPS-induced RAW 264.7 macrophage cells was accessed to clarify the underline mechanism. Mice were treated with various oral doses of curcumin (25, 50, 100 and 200 mg/kg/day, daily for 14 days) or equimolar doses of CurDDG. CurDDG at all doses tested significantly attenuated CCI-induced thermal hyperalgesia and mechanical allodynia compared with the CCI-control group. CurDDG at 25, 50 and 100 mg/kg demonstrated significantly greater efficacy on both mechanical and thermal hypersensitivities compared to that of curcumin. The effect of CurDDG correlated well with the inhibition of TNF-? and IL-6 levels in both the sciatic nerve and the spinal cord, as compared to its respective control groups. Similarly, in the in vitro study, CurDDG significantly reduced the LPS-induced expression of TNF-? and IL-6. Moreover, CurDDG significantly decreased COX-2 and iNOS levels and attenuated p38, JNK, and ERK1/2 phosphorylation as compared to the curcumin-treated cells. Altogether, this study demonstrated the improved pharmacological effects of curcumin by its diglutarate conjugate, CurDDG.
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