Identification of Target Proteins of Mangiferin in Mice with Acute Lung Injury Using Functionalized Magnetic Microspheres Based on Click Chemistry

Abstract

Prevention of the occurrence and development of inflammation is a vital therapeutic strategy for treating acute lung injury (ALI). Increasing evidence has shown that a wealth of ingredients from natural foods and plants have potential anti-inflammatory activity. In the present study, mangiferin, a natural C-glucosyl xanthone that is primarily obtained from the peels and kernels of mango fruits and the bark of the Mangifera indica L. tree, alleviated the inflammatory responses in lipopolysaccharide (LPS)-induced ALI mice. Mangiferin-modified magnetic microspheres (MMs) were developed on the basis of click chemistry to capture the target proteins of mangiferin. Mass spectrometry and molecular docking identified 70 kDa heat-shock protein 5 (Hspa5) and tyrosine 3-monooxygenase (Ywhae) as mangiferin-binding proteins. Furthermore, an enzyme-linked immunosorbent assay (ELISA) indicated that mangiferin exerted its anti-inflammatory effect by binding Hspa5 and Ywhae to suppress downstream mitogen-activated protein kinase (MAPK) signaling pathways. Thoroughly revealing the mechanism and function of mangiferin will contribute to the development and utilization of agricultural resources from M. indica L.

Natural product derived phytochemicals in managing acute lung injury by multiple mechanisms

“…In addition, mangiferin obviously prevented lung inflammation via inhibiting proinflammatory mediators and enzyme production (TNF-α, IL-6, IL-8, COX-2, iNOS, PGE2 and NO), inhibited oxidative stress via promoting antioxidant enzyme levels (SOD, GSH and CAT) and attenuated apoptosis via regulating Bax/Bcl-2, Caspase 9 and Caspase 8. Concerning the underlying mechanism, this compound obviously suppressed MAPK and NF-κB signaling and up-regulated the Nrf2-HO-1 signaling pathway [ [133] , [134] , [135] , [136] ]. Additionally, these protective effects of mangiferin were also associated with Hspa5 and Ywhae, which could subsequently down-regulate the MAPK signaling pathway.…”

“…Additionally, these protective effects of mangiferin were also associated with Hspa5 and Ywhae, which could subsequently down-regulate the MAPK signaling pathway. Interestingly, 30 mg/kg mangiferin gave slightly stronger lung protection than 1 mg/kg DEX in LPS-induced ALI mice [ 133 ].…”

Mangiferin: A xanthonoid with multipotent anti‐inflammatory potential

“…Another study showed that mangiferin exhibits its anti‐inflammatory activity by activating superoxide dismutase and reducing the levels of malonaldehyde and COX‐2 mRNA along with some other cytokines in animals with lung injury . Moreover, in acute lung injury, mangiferin is capable in alleviating the inflammatory responses by down regulating the MAP kinase signaling pathways . In addition, mangiferin also exhibits antispasmodic effects by activating the nitric oxide‐cyclic GMP pathway and thereby preventing tracheal contractions is guinea pig .…”

Mangiferin modulation of metabolism and metabolic syndrome

“…Using a DNA hybridization array, Leiro et al found that MGF had significant impacts on the profiles of a large number of NF‐κB related cytokine genes that are critical for regulation of inflammation . More recent studies reported MGF's ability to suppress IKK‐β/NF‐κB and/or MAPK/ERK/JNK signaling pathways in lymphoid organs , leucocytes , diabetic kidneys , and heart , acutely injured liver , colon and lungs , and to inhibit NF‐kB DNA binding and IKK activity in HepG2 cells .…”