Therapeutic Potential of Camellia oleifera Flavonoids in Alleviating Mycoplasma pneumoniae-Induced Pneumonia

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Mycoplasma pneumoniae (M. pneumoniae) has emerged as a distinctive bacterial pathogen, primarily responsible for community-acquired pneumonia (CAP) in school-aged children and young adults [1]. This atypical pathogen induces inflammation in the respiratory tracts, leading to a spectrum of extrapulmonary syndromes [2,3,4,5].

Proinflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and IL-6, play a pivotal role in M. pneumoniae-induced pneumonia by mobilizing and activating immune cells such as macrophages and neutrophils [6,7]. The absence of a cell wall in M. pneumoniae highlights the significance of lipid-associated membrane proteins (LAMPs), particularly in their interaction with Toll-like receptor 2 (TLR2) on immune cells, triggering intracellular events and proinflammatory cytokine production [7,11,12].

Macrophages, in particular, are key players in the immune response to M. pneumoniae infection [8,9,10]. The delicate balance between mounting a defense against pathogens and preventing tissue damage underscores the need for a nuanced understanding of the molecular mechanisms involved [7].

Camellia oleifera (C. oleifera), a botanical treasure native to central and southern China, has a rich history beyond its industrial applications in oil production, dyeing, papermaking, and various other industries [15,16]. Recent research has explored the therapeutic potential of C. oleifera, focusing on its by-products, such as camellia seed cake and fruit shell.

The defatted seed pomace of C. oleifera is particularly rich in bioactive substances, including flavonoids, saponins, and polysaccharides [17,18,19,20,21]. The flavonoids, notably kaempferol glycosides, exhibit a diverse range of biological activities, including anti-inflammatory, antioxidant, anti-melanogenic, and anti-microbial properties [20,21,26,27,28].

Previous studies demonstrated the anti-inflammatory activities of C. oleifera defatted seed extracts in mitigating hepatotoxicity and nonalcoholic fatty liver disease in rats [29,30]. Moreover, flavonoids from C. oleifera defatted seeds were found to inhibit nitric oxide (NO) and proinflammatory cytokine production in lipopolysaccharide (LPS)-stimulated macrophages by suppressing the NF-κB signaling pathway [20,21].

Hypothesis and Research Objective

Building on this background, the present study hypothesized that the total flavonoids from the extract of defatted C. oleifera (TFCO) seeds could alleviate M. pneumoniae-induced pneumonia. The research aims not only to validate this hypothesis but also to explore the molecular intricacies underlying the therapeutic potential of C. oleifera flavonoids in the context of M. pneumoniae infection.

Methodology

The study employed a comprehensive methodology involving in vivo and in vitro experiments to assess the effects of TFCO on M. pneumoniae-induced pneumonia. Animal models were utilized to evaluate the anti-inflammatory properties of TFCO, while in vitro experiments focused on elucidating the molecular mechanisms involved, particularly the impact on the NF-κB signaling pathway.

Results

The research findings confirmed the hypothesis that TFCO could alleviate M. pneumoniae-induced pneumonia. In vivo experiments demonstrated a significant reduction in inflammatory markers and lung damage in animals treated with TFCO compared to control groups. In vitro experiments further revealed the suppression of proinflammatory cytokine production in macrophages exposed to M. pneumoniae in the presence of TFCO.

Molecular Mechanisms

The anti-inflammatory effects of TFCO were linked to its ability to modulate the NF-κB signaling pathway. TFCO was found to inhibit the activation of NF-κB, thereby reducing the production of proinflammatory cytokines induced by M. pneumoniae infection.

Discussion

M. pneumoniae Pathogenesis and Global Impact

Mycoplasma pneumoniae (M. pneumoniae) presents a significant health challenge as an obligate bacterial pathogen known for instigating respiratory diseases. Epidemiological data reveal that during outbreak seasons, M. pneumoniae contributes to 8% of community-acquired pneumonia (CAP) cases in pediatric populations and 2% in adults, highlighting its substantial burden [32].

Notably, the global reach of M. pneumoniae outbreaks poses a formidable challenge, with regions such as Asia, Europe, and North America experiencing escalating prevalence rates of macrolide-resistant strains. The pathogenicity of M. pneumoniae extends beyond the respiratory tract, implicating various extrapulmonary manifestations, including damage to the skin, nervous system, heart, and joints [32].

Therapeutic Potential of C. oleifera in Respiratory Infections

Camellia oleifera (C. oleifera), a plant with both medicinal and edible properties, has garnered attention for its therapeutic potential. The mature seeds of C. oleifera yield Camellia oil, traditionally used for treating gastrointestinal pain and skin burns. The by-products, particularly residues of C. oleifera seeds, are rich in bioactive compounds, including flavonoids, saponins, and polysaccharides [17,18,19,20,21]. Among these, kaempferol glycosides stand out for their diverse biological activities, including anti-inflammation, antioxidation, and antimicrobial properties [20,21,26,27,28].

Previous studies demonstrated the anti-inflammatory effects of C. oleifera defatted seed extracts, particularly in mitigating hepatic inflammation [29,30]. Kaempferol glycosides, the primary anti-inflammatory flavonoids in C. oleifera defatted seeds, have shown promising results in various models, including mouse asthma and rat transient focal stroke [33,34,35]. Building on this foundation, the current study investigated the protective effects of kaempferol glycosides against M. pneumoniae-induced lung injury in mice.

Immune Response and Molecular Mechanisms

M. pneumoniae’s unique biology, characterized by the absence of a traditional cell wall, directs attention to its lipid-associated membrane proteins (LAMPs), particularly in their interaction with Toll-like receptor 2 (TLR2) on immune cells [7,11,12]. This interaction triggers immune reactions and the release of inflammatory mediators, contributing to immune-mediated tissue damage [7]. The established in vivo and in vitro models in this study utilized M. pneumoniae nasal drops and LAMPs to simulate infection, respectively.

Proinflammatory cytokines, including TNF-α, IL-1β, and IL-6, play a pivotal role in the immune damage resulting from M. pneumoniae infection. Their excessive secretion correlates with the severity of diseases following M. pneumoniae infection [38,39,40]. The study demonstrated a significant reduction in these proinflammatory cytokines in both in vivo and in vitro models when treated with total flavonoids from C. oleifera (TFCO), supporting the anti-inflammatory effects of TFCO.

TLR2, as a crucial pattern recognition receptor for M. pneumoniae, activates immune responses and inflammatory reactions. TFCO treatment led to a dose-dependent decrease in TLR2 expression, suggesting a potential mechanism for alleviating pulmonary inflammation caused by M. pneumoniae infection.

Further exploration into the key mechanisms revealed the involvement of the NF-κB and MAPK signaling pathways. These pathways, activated by TLR2 recognition of LAMPs, play essential roles in regulating inflammatory responses. TFCO treatment significantly alleviated the phosphorylation of NF-κB and MAPK signaling pathway proteins in both in vivo and in vitro models.

Kaempferol Glycosides and Other Active Ingredients

While kaempferol glycosides constitute the primary component of TFCO, it is essential to acknowledge the potential influence of other active ingredients, including flavonoids, saponins, and polysaccharides [17-25]. Previous reports on saponins from C. oleifera have demonstrated in vivo anti-inflammatory activity, adding another layer to the potential mechanisms of TFCO [47,48]. Although no anti-inflammatory activity has been reported for polysaccharides from C. oleifera, literature on polysaccharides from other plants supports their anti-inflammatory properties [49].

Broader Therapeutic Implications

Beyond M. pneumoniae-induced pneumonia, the study suggests potential applications of TFCO in the treatment of conditions related to TLR2 activation, such as sepsis and Clostridium difficile infection [50]. Additionally, the anti-inflammatory effects of kaempferol glycosides in TFCO may extend to other inflammatory conditions, as demonstrated in asthma and stroke models [33,34].

In conclusion, the detailed investigation into the therapeutic potential of C. oleifera flavonoids, particularly TFCO, sheds light on its efficacy in alleviating M. pneumoniae-induced pneumonia. The study not only provides valuable insights into the molecular mechanisms involved but also opens avenues for further research on C. oleifera as a natural remedy for respiratory infections and inflammatory conditions. The multifaceted nature of the bioactive compounds in C. oleifera warrants continued exploration of its therapeutic applications.


reference link : https://www.mdpi.com/1420-3049/28/20/7077

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