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.