Supplementation with Tetrahydrocurcumin Enhances the Therapeutic Effects of Dexamethasone in a Murine Model of Allergic Asthma

Abstract

<b><i>Background:</i></b> Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from <i>Curcuma</i> species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma. <b><i>Methods:</i></b> BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed. <b><i>Results:</i></b> THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A). <b><i>Conclusions:</i></b> Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.

The Effects of Curcumin on Inflammasome: Latest Update

“…THC and DEX have comparable therapeutic potential in various pathological contexts. Interestingly, when compared to monotherapy with either THC or DEX alone, the combination of both agents significantly reduced nasal rubbing frequency, mucus hypersecretion, and Th2 and Th17 cell count, and it reduced the related cytokines IL-4, IL-5, and IL-17involved in inflammasome activation and pyroptosis in pulmonary infectious diseases [ 70 , 71 ]. Further research is needed to improve curcumin’s low bioavailability and to investigate the use of dry powder inhalation for asthma to overcome solubility and dissolution issues.…”

The role of tetrahydrocurcumin in disease prevention and treatment

“…181 In addition, the combination of 0.08% THC and 2.5 mg kg −1 dexamethasone significantly reduced the nasal rubbing frequency, mucus hyperproduction, the number of Th2, Th17 cells and the cytokine levels of IL-4, IL-5 and IL-17A in ovalbumin-induced asthmatic mice. 95 In cancer treatment, THC combined with 5-fluorouracil significantly suppressed the proliferation of TE-1 cells to treat esophageal squamous cell carcinoma, while only 5-fluorouracil did not. 182 These results indicated that THC played a synergistic role in inhibiting squamous cell carcinoma, whose effect was different from 5-fluorouracil.…”

Dietary Polyphenols—Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions

“…Recent experimental studies provided strong evidence that certain flavonoids such as quercetin, luteolin, cyanidin, and baicalin exert an anti-allergic effect by upregulating the number of Tregs and restoring the balance between Th17/Treg [164,[168][169][170]. Similarly, curcumin showed a modulatory effect on Th17/Treg imbalance, effectively reducing the differentiation of Th17 cells while significantly increasing the number of Treg subtypes in a murine model of asthma [171][172][173].…”

“…Importantly, evidence suggested that curcumin, by inhibition of the Notch1-GATA3 signaling pathway, is capable of not only attenuating the severity of airway inflammation, but also preventing the development of an allergic inflammatory response when administered before the OVA challenge [272]. Curcumin has also been reported to be efficacious in the reduction in airway remodeling in asthma, with the effect of curcumin on histopathological features being dose-dependent and, at the highest doses, comparable to that of dexamethasone [171,271,273]. Moreover, Wu et al showed that supplementation of curcumin in asthmatic mice could increase the therapeutic efficacy of dexamethasone and even prevent adverse effects caused by glucocorticoid treatment, suggesting potential employment as an add-on therapy in asthma [171].…”

“…Curcumin has also been reported to be efficacious in the reduction in airway remodeling in asthma, with the effect of curcumin on histopathological features being dose-dependent and, at the highest doses, comparable to that of dexamethasone [171,271,273]. Moreover, Wu et al showed that supplementation of curcumin in asthmatic mice could increase the therapeutic efficacy of dexamethasone and even prevent adverse effects caused by glucocorticoid treatment, suggesting potential employment as an add-on therapy in asthma [171]. Indeed, a randomized control study involving patients with mild to moderate asthma demonstrated significant enhancement in the mean FEV1 values in patients treated with oral curcumin in addition to standard therapy compared to a group receiving only standard inhaled therapy for asthma.…”