Mangiferin Against Respiratory Diseases: Pharmacological Targets and Prospects

Abstract

Respiratory diseases are associated with high mortality worldwide. Respiratory infections can lead to the emergence of chronic respiratory diseases. Scientists are constantly striving to identify new therapies with reduced side effects. The rise of antibiotic resistance and the scarcity of effective treatments further necessitate the development of novel therapeutics specific to respiratory diseases. Extensive research has been conducted on natural products that could be effective against respiratory diseases. Mangiferin, a polyphenol with a C-glycosyl xanthone structure, is a bioactive phytochemical that has potential applications in the treatment of respiratory tract infections. Mangiferin could be a therapeutic option against respiratory diseases because of its ability to target a variety of pharmacological pathways implicated in the development of these infections. It has been shown to limit infections, lower inflammation, control immune responses, and enhance host defense mechanisms. This review provides comprehensive insight into mangiferin's potential against various respiratory disorders, focusing on its pharmacological activity and therapeutic prospects. Despite the potential of mangiferin against respiratory problems-related pathobiology, additional scientific validation through clinical trials is required before the clinical application of mangiferin in the management of respiratory diseases.

Keywords: Mangiferin; fibrosis; infections; inflammation; oxidative stress; respiratory diseases.

FIGURE 1

Structure of mangiferin (PubChem CID 5281647).

FIGURE 2

PRISMA 2020 flow diagram for the systematic review of mangiferin effects against respiratory diseases.

FIGURE 3

Signaling pathways involved in the pathogenesis of respiratory damage. Under stress conditions (e.g., BLM, B(a)P, environmental pollutants), the respiratory cell can be damaged by immune‐mediated signaling pathways. NOX favors the conversion of NADPH to NADP+ by forming superoxide free radicals which in turn produce H₂O₂. Upregulated ROS causes MDA production that induces respiratory cell damage. Association of PRRs with PAMPs results in MYD88 and further NF‐κB stimulation, leading to the expression of the NLRP3 inflammasome complex. The NLRP3 inflammasome then induces caspase‐1 to convert pro‐IL‐1β, pro‐IL‐18, and GSDMD for producing IL‐1β, IL‐18, and GSDMD‐NT in a respective manner. As a result, pyroptosis occurs. Following cleavage of latent TGF‐β1, active TGF‐β1 binds with TGFβR‐II and activates TGFβR‐I, leading to the expression of phosphorylated Smad2 and Smad3. Following the attachment with Smad4 and in the presence of coactivators, gene expression occurs that incites respiratory fibrosis. Through the use of α‐SMA, TGF‐β1 creates myofibroblasts that cause elevated ECM and ultimately fibrosis. Active TGF‐β1 influences ROS generation, and redox imbalance in turn affects TGF‐β1 production. Redox imbalance further impels fibrosis. Nrf2 dissociates from Keap1 via ROS and helps in gene expression that generates antioxidants for suppressing cell damage. Nrf2 can inhibit cell damage by suppressing NF‐κB (induced by ROS) signaling that causes altered pro‐inflammatory cytokine levels and inflammasome complex inhibition.

FIGURE 4

Effects of mangiferin on respiratory tract infection. The diagram represents a variety of stress stimuli, for example, Bleomycin, LPS, B(a)P, environmental pollutants, etc. that mediate pyroptosis, inflammation, and oxidative stress, which ultimately lead to lung damage. Stress stimuli activate the NLRP3 inflammasome and NF‐κB pathway, which triggers tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐18, and MCP‐1, causing inflammation and eventually lung damage, and mangiferin acts by inhibiting NF‐κB and activation of the NLRP3 inflammasome. Mangiferin also activates the Nrf2/HO‐1 pathway and produces antioxidant enzymes like HO‐1, SOD, GPx, GST, CAT, GR, QR, and inhibits ROS production, eventually LPO, MDA release, thus inhibiting oxidative stress. In addition, TGF‐β1 causes accumulation of ECM and expressing α‐SMA. Thus, the lungs become protected by mangiferin, which is known to suppress the cascades of fibrosis.