Anthocyanins Extracted from Oryza sativa L. Prevent Fluorouracil-Induced Nuclear Factor-κB Activation in Oral Mucositis: In Vitro and In Vivo Studies

Abstract

This study aims to investigate the immunomodulatory effect of anthocyanins (ANTs) from Oryza sativa L. extracts on 5-fluorouracil (5-FU)-induced oral mucositis, using a rat model and oral keratinocytes. ANTs were detected by high-performance liquid chromatography (HPLC)-electrospray ionization mass spectrometry. Animals were randomly given varying doses of ANT-rich extract treatment (500 mg/kg and 1000 mg/kg) in the absence or presence of 5-FU-induced mucositis. Buccal mucosae were photographed and scored for macroscopic analysis and incisional biopsies of cheek pouches were collected for microscopic examination of oral mucositis. 5-FU caused marked hemorrhage, extensive ulcerations and abscesses compared to non-treated animals with slight erythema. Histologically, a loss of collagen bundles and inflammatory cell infiltrates was observed. After 29 days of ANT treatment, lesions resolved, and abundant collagen fibers were evident in the lamina propria. Buccal mucosa of 5-FU-injected rats showed increased Nuclear factor-kappa B (NF-κB) p50 and p65 in oral keratinocytes. The administration of ANT reduced NF-κB-positive cells in 5-FU rats (p < 0.001) compared to the non-treatment group. In oral keratinocytes, ANT treatment significantly restored 5-FU-induced growth inhibition and impaired the nuclear accumulation of NF-κB p50 and p65. Our study demonstrated that ANT from Oryza sativa L. exhibited effective anti-inflammatory properties against 5-FU-induced oral mucositis by inhibiting NF-κB activation.

Antioxidant and Anti-Inflammatory Properties of Anthocyanins Extracted from Oryza sativa L. in Primary Dermal Fibroblasts

“…The total phenolic content was ~30 ± 1.5 mM gallic acid equivalent (gFW). Our results of the levels of C3G and the antioxidant properties of ANT extracted from O. sativa L. were lower than the levels in a previous study [26]. The differences in the C3G content and antioxidant capacity between the previous study and our findings probably stem from the diversity of rice cultivars, as well as the variety of extraction methods and analyses.…”

“…Our investigation is in agreement with an in vivo study that demonstrated the anti-inflammatory role of ANT from Thai black rice using a 5-FU-induced oral mucositis model. This study indicated that ANT reduced the lesions induced by 5-FU in the oral mucosa via NF- κ B-mediated biological manipulations [26]. Furthermore, ANT suppressed the H 2 O 2 -induced IL-6 production and NF- κ B activation, which is in agreement with a previous study on normal human dermal fibroblasts exposed to UVB [62].…”

“…Black rice was obtained from Chachoengsao Province, Thailand, and subjected to ANT extraction as previously reported [26]. ANT were extracted in ethanol (60/40, v / v %), concentrated using a Büchi B-490 rotary evaporator (Büchi Labortechnik AG, Flawil, Switzerland) and lyophilized with a freeze dryer (Labconco Corp., Kansas City, MO, USA).…”

HMGB1: meeting the need for new tools in the box

“…9,10 Lastly, treatment of cells with anthocyanins, compounds with a similar action to NecroX-7, decreases HMGB1 release from cells and OM in mice treated with 5-FU. 11 Taken together with the report from Im et al, a model emerges in which OM results from epithelial cell death and release of pro-inflammatory proteins, such as HMGB1, from the dying cells.…”

New Innovations in Wound Healing and Repair

“…It includes articles that outline new approaches to reduce wound infection [1,2] as well as studies aimed at developing new in vitro chronic wound models as alternatives to animal experimentation [3]. The interest in natural products as potential wound agents is evidenced through three articles that investigated healing responses to honey [4], deoxyshikonin [5], and anthocyanins extacted from Oryza sativa L [6]. Understanding cytoskeletal interactions in keratinocytes and fibroblasts [7] as well as neutrophil proteome signatures [8] also provide important new information that may inform researchers with the development of new therapeutic approaches to improve healing responses.…”