Figure 2. Main mechanisms of TCM therapies against MRSA infections. (A) Targets of immune responses in the lung and mucosa. 1a. Acting on PMNs; 1b. Acting on promoting or inhibiting inflammation; 1c. Acting on adaptive immune responses. 2. Acting on mucosal immunity. (B) Targets of immune responses in MRSA immune evasion strategies. PMN, polymorphonuclear leukocyte. ICAM-1, Intercellular adhesion molecule 1. GL, glycyrrhizin. 18-β -GA, 18-β -glycyrrhetinic acid. RUS, Ruscogenin. CSE, C. sinensis extract. AO-I,Atractylenolide I. APS, Astragalus polysaccharides. SMS (SA), Shengmai San (Schisantherin A ). Cor, cordycepin. GOP, Ginseng oligopeptides. CVT-E002, a patented aqueous extract fromPanax quinquefolium (P. quinquefolius ). OPS, Ophiopogon polysaccharide. AMPS, A. macrocephala polysaccharides. Mφ, macrophage. HET, Hochuekkito. YPF-PS, polysaccharides derived from Yupingfeng San. Green arrows represent promotion. Red arrows represent inhibition.
Briefly, MRSA infection is closely associated with neutrophil function, inflammation, immune responses, and MRSA immune evasion. In this section, the main mechanisms of TCM immune therapies for anti-MRSA infection are summarized and analyzed, suggesting that they can regulate multiple biological processes to modulate the host’s immune responses and MRSA immune evasion (Fig. 2). As is shown in Fig 2. 1a, regarding the aspects of regulating the function of PMNs, GL and 18-β-GA inhibit PMN adhesion and recruitment [67, 72]. RUS, CSE, AO-I and APS inhibit PMN infiltration by reducing MPO levels[68, 94, 101, 110]. With respects to modulating inflammation, various TM therapies exert their therapeutic effect on MRSA infection by regulating TLR4/NF-κB signaling (Fig. 2. 1b). Ginsenoside, AMPS, CVT-E002 and other therapies increase the phagocytic functions of immune cells to promote inflammation through activating TLR4/NF-κB signaling. OPS also contributes to enhancing the functions of macrophages. GL, Cor, CSE, RUS, SMS and other active compounds inhibit excessive inflammation by blocking this signaling. In addition, RUS inhibits cell apoptosis by blocking this signaling to improve MRSA clearance and alleviate lung injuries. Cor also inhibits excessive inflammation by activating Nrf2/HO-1 signaling. These herbs and formulae exhibit anti-MRSA infection functions by regulating inflammation (Fig 2. 1b). Besides innate immune responses, TM therapies act on the adaptive immune response (Fig 2. 1c). For example, GOP plays immunomodulatory activities by stimulating the secretion of cytokines and the production of antibodies. YPF-PS significantly enhances T lymphocyte proliferation to potentiate cell immune responses. Moreover, ginsan and HET act on mucosal immunity to promote SIgA formation and secretion, significantly preventing MRSA invasion (Fig. 2. 2). Apart from regulating host immunity, TCM therapies act on MRSA virulence factors (Fig 2. 1d). 18-β-GA directly inhibits MRSA virulence factors. Ginsenoside can disrupt MRSA-BF structure and inhibit MRSA immune evasion against MRSA infection.