Combination use of tolfenamic acid with curcumin improves anti‐inflammatory activity and reduces toxicity in mice

Abstract

Long‐term use of tolfenamic acid inevitably causes side effects, including gastric ulcer and hepatotoxicity. Curcumin is generally recognized to be anti‐inflammatory, hepatoprotective, and gastroprotective. Herein, we investigated the combinational effects of tolfenamic acid and curcumin and possible mechanism in a TPA‐induced inflammation mouse model. Combinational use of tolfenamic acid (100 mg/kg) and curcumin (100 mg/kg) by oral administration reduced dermal inflammation represented by ear edema and lymphocytic infiltration. Moreover, curcumin dispersed in polyvinyl pyrrolidone showed stronger synergistic effect. The beneficial effect of the coadministration was also reproduced in PKC/Akt/IKK/NF‐κB signaling pathways. Notably, hepatoprotective and gastroprotective effect was exhibited by the reverse of body weight loss and NF‐κB downregulation in the liver, and by increased Spleen Index of mice. These results suggested combination administration of tolfenamic acid with curcumin enhances anti‐inflammatory efficacy and reduces hepatic/gastric toxicity, which indicates dietary uptake of curcumin may facilitate the function of tolfenamic acid. Practical applications Curcumin, a representative polyphenolic compound, is one of the main constituents of dietary spice turmeric which has been widely consumed throughout the world, especially in Asia. The beneficial aspect of combination use of curcumin in enhancing anti‐inflammatory effect and reducing hepatic/gastric toxicity of NSAID drug tolfenamic acid in mice has been explored. It might be anticipated as a potential naturally derived bioactive constituent in functional food and pharmaceutical applications.

Nano‐Derived Therapeutic Formulations with Curcumin in Inflammation‐Related Diseases

“…In a clinical study with anterior uveitis-baring patients, 2 weeks of CUR administration triggered a significant disease remission [ 4 ]. Also, it was proven that tolfenamic acid and CUR coadministration enhances tolfenamic acid AIF effects while reducing its toxic effects on the stomach and liver [ 70 ]. Moreover, CUR has been proposed to alleviate chronic inflammation after chemotherapy or radiotherapy [ 57 ].…”

Comparison of Analysis Methods for Curcumin Determination: A Literature Review

“…For centuries, curcumin has primarily been used in the food industry because of its vibrant color. However, the pharmaceutical industry has recently shown great interest in this compound due to its various pharmacological effects, such as its ability to fight cancer (Tamaddoni et al, 2020), reduce cellular aging (Aggarwal et al, 2007), antioxidant (Abrahams et al, 2019), anti-inflammatory (Zhou et al, 2020), anti-diabetic (Pivari et al, 2019), antibacterial, antiviral, andantifungal benefits (Zorofchian et al, 2014).…”

Tolfenamic acid inhibits ROS-generating oxidase Nox1-regulated p53 activity in intrastriatal injection of malonic acid rats

“…Tolfenamic acid, a nonsteroidal anti-inflammatory drug, shows anti-inflammatory effects through cyclooxygenase inhibition mechanisms [ 1 ]. It regulates the protein kinase C (PKC)/protein kinase B (Akt)/IkappaB kinase (IKK)/noncanonical nuclear factor-κB (NF-κB) signalling pathways to improve anti-inflammatory activity and reduce toxicity in mice [ 2 ]. Tolfenamic acid also shows antioxidative effects.…”