Antioxidant and anti-inflammatory activity through inhibition of NF-κB and sEH of some citrus peel and phytoconstituent characteristics.

In Indonesia, there are many types of citrus where parts of the fruit, leaves, and peel can be utilized as food, drinks, spices, and medicine. This research aims to determine the phytochemical characteristics, antioxidant activities, and anti-inflammatory activity through inhibition of NF-κB and sEH, and the main phytoconstituents of three types of citrus fruits that are commonly used as herbs in Indonesia. The flesh and peel of Citrus amblycarpa/CAm, C. aurantiifolia/CAu, and C. hystrix/CH were extracted by Ultrasound-Assisted Extraction (UAE) with 70 % ethanol and then concentrated. All extracts were tested for total flavonoid content (TFC), total polyphenolic content (TPC), chemical constituents using LCMS, and DPPH radical scavenging activity. Molecular docking tests of 33 compounds containing CAm, CAu, and CH fruit peels from the literature study against NF-κB (Nuclear Factor Kappa Beta) and sEH (Soluble Epoxide Hydrolase) were also conducted. The TFC in fruit peels was 13.47-17.34 mg QE/g extract, and in flesh was 1.35-2.51 mg QE/g extract. The TPC in fruit peels was 4.28-6.3 mg GAE/g extract, and in flesh was 0.85-2.09 mg GAE/g extract. The IC50 values of antioxidant activity on fruit peel were 74.01-168.54 µg/mL; and flesh 185.62-2669 µg/mL. CAu peels provided the highest antioxidant activity and polyphenol content. The LC-MS/MS test on citrus peels shows the main chemical compounds: naringin (C27H32O14), naringenin (C15H12O5), hesperidin (C28H34O15), and hesperitin (C16H14O6). Molecular docking shows that naringin and neohesperidin predicted inhibit NF-κB, and hesperidin, neohesperidin, narirutin, naringin, apigenin, kaempferol, quercetin, rutin, eriocitrin, sinensetin, and vitamin A predicted can inhibit sEH enzyme. All citrus peel has stronger antioxidant activity and more flavonoids and phenolics than the flesh. Naringin and neohesperidin can inhibit NF-κB and sEH enzymes. The main flavonoid contents of the citrus peels and presumed to have activity are hesperidin and naringin. These flavonoids and their glycosides can be used as marker phytoconstituents in the quality assurance of pharmaceutical products.