Mycoplasma Pneumonia: Flavonoids Of Camellia Oleifera Prevents Lung Injury In ‘White Lungs’ Via Inhibition Of TLR2-Mediated NF-κB And MAPK Pathways!

Mycoplasma Pneumonia: Mycoplasma pneumoniae (M. pneumoniae) stands as a formidable atypical bacterial pathogen, exerting its influence as the primary agent responsible for community-acquired pneumonia (CAP) predominantly in school-aged children and young adults. The intricate interplay between M. pneumoniae and the host's immune system often results in a cascade of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β and IL-6, leading to a complex immune response. Recognizing the need for innovative therapeutic approaches, researchers from Hengyang Medical College at the University of South China explored the potential of total flavonoids from Camellia oleifera (C. oleifera) in mitigating Mycoplasma Pneumonia-induced lung injury.
 

Camellia oleifera

Understanding Mycoplasma Pneumoniae-Induced Lung Injury
M. pneumoniae's ability to induce inflammation in both the upper and lower respiratory tracts contributes to a range of extrapulmonary syndromes. Proinflammatory cytokines, known for their dual role in fine-tuning immune responses and potentially causing tissue damage if unregulated, play a pivotal role in M. pneumoniae-induced pneumonia. Macrophages, particularly sensitive to M. pneumoniae due to its lack of a cell wall, respond to lipid-associated membrane proteins (LAMPs) through Toll-like receptor 2 (TLR2), initiating cascades such as NF-κB and MAPK.
 
The Therapeutic Potential of Camellia Oleifera
Camellia oleifera, renowned for its historical use in high-quality oil production, has garnered attention for its therapeutic potential. The residual defatted seed pomace of C. oleifera emerges as a rich source of bioactive substances, notably flavonoids, including kaempferol glycosides. Previous studies have hinted at the anti-inflammatory effects of C. oleifera defatted seed extracts, prompting researchers to delve deeper into the potential of total flavonoids from C. oleifera (TFCO) seed extract.
 
Identification of Key Components in TFCO
Employing advanced chromatography methods, researchers identified five kaempferol glycosides as the major components of TFCO. These compounds exhibited notable anti-inflammatory activities, laying the foundation for a thorough exploration of their therapeutic potential.
 
The five identified flavonoids were:
-Kaempferol-3-O-[2-O-β-D-glucopyranosyl-6-O-L-rhamnopyranosyl]-β-D-glucopyranoside (compound 1)
-Kaempferol-3-O-β-D-glucopyranosyl-(1→4)-α-L-rhamnopyranosyl-7-O-α-L-rhamnopyranoside (compound 2)
-Kaempferol-3-O-[2-O-β-D-xylopyranosyl-6-O-α-L-rhamnopyranosyl]-β-D-glucopyranoside (compound 3)
-Kaempferol-3-O-[4″″-O-acetyl-α-L-rhamnopyranosyl-(1→6)]-[&beta ;-D-glucopyranosyl-(1→2)]-β-D-glucopyranoside (compound 4)
-Kaempferol-3-O-[4″″-O-acetyl-α-L-rhamnopyranosyl-(1→6)]-[β-D-xylopyranosyl-(1→2)]-β-D-glucopyranoside (compound 5)
 
TFCO Alleviates Lung Injury in Mice
In a meticulously designed mouse model of M. pneumoniae pneumonia, TFCO showcased its ability to significantly reduce lung damage. Histological examinations revealed improvements, including looser alveolar structures, reduced inflammatory cell infiltration, and ameliorated alveolar walls and bronchial tubes, all in a dose-dependent manner. The histology score echoed these findings, highlighting TFCO's efficacy in mitigating lung tissue injury induced by M. pneumoniae infection.
 
In Vitro Evidence of TFCO's Anti-Inflammatory Effects
Expanding their investigation to RAW264.7 macrophage cells stimulated by LAMPs, researchers observed that TFCO suppressed the generation of proinflammatory cytokines and TLR2 expression. Crucially, TFCO exhibited these anti-inflammatory effects without compromising cell viability. Furthermore, TFCO was found to inhibit the phosphorylation of key proteins involved in both NF-κB and MAPK pathways, including IκBα, JNK, ERK, p38, and p65 nuclear translocation.
 
Molecular Mechanisms Unveiled
The study not only underscores the potential of C. oleifera flavonoids but also delves into the molecular intricacies behind their anti-inflammatory effects. By inhibiting TLR2-mediated NF-κB and MAPK pathways, TFCO emerges as a potent candidate for therapeutic intervention against M. pneumoniae-induced lung damage.
 
Discussion and Implications
M. pneumoniae's impact extends beyond the respiratory tract, with extrapulmonary manifestations contributing to its pathogenic repertoire. Furthermore, the rise of macrolide-resistant M. pneumoniae strains adds another layer of complexity to the treatment landscape. C. oleifera, a plant historically valued for its industrial utility, now emerges as a source of medicinal compounds with significant potential.
 
The study raises intriguing possibilities regarding the multifaceted benefits of C. oleifera. Beyond its industrial applications, C. oleifera holds promise in the realm of therapeutics. The identified kaempferol glycosides in TFCO, constituting 98.44% of its composition, take center stage in the anti-inflammatory effects observed. However, the potential influence of other active ingredients, including saponins and polysaccharides, should not be overlooked.
 
Moreover, the absence of a traditional cell wall in M. pneumoniae directs attention towards its LAMPs, particularly in the context of TLR2 activation. TFCO's ability to suppress TLR2 expression and modulate downstream NF-κB and MAPK pathways presents a broader therapeutic implication beyond M. pneumoniae-induced lung inflammation. Conditions associated with TLR2 activation, such as sepsis and Clostridium difficile infection, may also benefit from the anti-inflammatory effects of TFCO.
 
Conclusion
In conclusion, the research conducted at Hengyang Medical College provides a comprehensive exploration of the potential of total flavonoids from Camellia oleifera in mitigating Mycoplasma pneumoniae-induced lung injury. The identified kaempferol glycosides in TFCO emerge as key players in inhibiting TLR2-mediated NF-κB and MAPK pathways, demonstrating robust anti-inflammatory effects. This not only positions TFCO as a promising therapeutic agent for M. pneumoniae-induced lung inflammation but also opens avenues for broader applications in inflammatory conditions associated with TLR2 activation. The study, enriched with molecular insights, serves as a stepping stone for future research and clinical applications in the domains of respiratory and inflammatory diseases.
 
The study findings were published in the peer reviewed journal: Molecules.
https://www.mdpi.com/1420-3049/28/20/7077
 
For the latest on Mycoplasma Pneumonia, keep on logging to Thailand Medical News.