Herbs-Phytochemicals-Fortunellin-Kumquat-Ameliorates-Acute-Lung-Injury-Possibly-Useful-For-Post-COVID

Herbs And Phytochemicals: Acute lung injury (ALI) and its more severe form, acute respiratory distress syndrome (ARDS), are significant causes of morbidity and mortality globally. These conditions are characterized by widespread inflammation in the lungs, leading to impaired gas exchange and respiratory failure. The ongoing COVID-19 pandemic has further highlighted the critical need for effective therapies targeting respiratory ailments. In this context, natural compounds like fortunellin derived from Kumquat (Fortunella margarita) have garnered attention for their potential therapeutic benefits, particularly in modulating inflammatory pathways implicated in ALI. This Herbs And Phytochemicals news report delves into the study by researchers from the Affiliated Hospital of Putian University-China and Wenzhou Medical University-China that explored the mechanisms underlying the therapeutic potential of fortunellin in ALI, its experimental evidence, and its implications for post-COVID-19 care.


Fortunellin From Kumquat (Fortunella margarita) Ameliorates Acute Lung Injury

Thailand Medical News had covered a study in August 2020 that showed fortunellin could also be used as an antiviral against SARS-CoV-2.

https://www.thailandmedical.news/news/breaking-covid-19-herbs-study-shows-that-fortunellin-found-in-kumquats-is-a-natural-dimerization-inhibitor-of-the-sars-cov-2-3cl-protein
 
Understanding Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS)
ALI and ARDS encompass a spectrum of acute respiratory disorders characterized by diffuse alveolar damage, inflammatory cell infiltration, increased vascular permeability, and impaired gas exchange. The pathophysiology involves an aberrant immune response leading to lung injury, often triggered by infections, sepsis, trauma, or inhalation of noxious substances. Despite advancements in critical care, the management of ALI/ARDS remains challenging, necessitating exploration into novel therapeutic modalities.
 
Fortunellin: An Overview of its Pharmacological Properties
Fortunellin is a flavonoid glycoside found in Kumquat, a citrus fruit known for its medicinal properties. Studies have highlighted fortunellin's diverse pharmacological effects, including anti-inflammatory, antioxidant, anti-cancer, and cardioprotective properties. Its ability to modulate inflammatory pathways makes it a promising candidate for respiratory conditions like ALI.
 
Mechanistic Insights: TLR4/NF-κB/NLRP3 Pathway
The Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway plays a central role in orchestrating inflammatory responses. Upon activation by pathogen-as sociated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), TLR4 triggers NF-κB signaling, leading to the production of pro-inflammatory cytokines. NLRP3, a component of the inflammasome, further amplifies the inflammatory cascade. Dysregulation of this pathway contributes significantly to ALI/ARDS pathogenesis.
 
Experimental Evidence of Fortunellin in ALI
Several preclinical studies have investigated the potential of fortunellin in ALI models induced by LPS or other inflammatory stimuli. These studies consistently demonstrate the protective effects of fortunellin against lung injury, inflammation, and oxidative stress. Fortunellin administration was associated with reduced lung histopathological damage, decreased inflammatory cell infiltration, and improved respiratory parameters in animal models.
 
Study Findings
The researchers found that fortunellin attenuated LPS-induced lung tissue damage and reduced the W/D ratio, the content of MPO in lung tissue, the total protein contents in BALF, and the neutrophils and leukocytes number. Besides, fortunellin alleviated LPS-stimulated lung tissue apoptosis, inflammatory response, and collagen deposition. Furthermore, Fortunellin repressed the activity of the Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway in the LPS-stimulated ALI model and LPS-induced RAW264.7 cells. Moreover, fortunellin attenuated LPS-stimulated tissue injury, apoptosis, inflammation, and collagen deposition of the lung via restraining the TLR4/NF-κB/NLRP3 pathway.
 
Anti-Inflammatory and Anti-Apoptotic Effects of Fortunellin
Fortunellin exerts potent anti-inflammatory effects by inhibiting NF-κB activation and subsequent cytokine production. It also modulates apoptotic pathways, reducing cell death in lung tissue. These dual mechanisms contribute to its overall protective effects in ALI by preserving lung integrity and function.
 
Modulation of Oxidative Stress and Antioxidant Defense
Oxidative stress is a hallmark of ALI/ARDS, contributing to tissue damage and inflammation. Fortunellin's antioxidant properties, including scavenging free radicals and enhancing antioxidant enzyme activity, play a crucial role in mitigating oxidative stress-induced lung injury. Studies have shown that fortunellin administration leads to decreased oxidative markers and improved antioxidant defense mechanisms in ALI models.
 
Collagen Deposition and Fibrosis: Implications for Long-Term Lung Function
One of the sequelae of ALI/ARDS is the development of pulmonary fibrosis characterized by excessive collagen deposition and tissue remodeling. Fortunellin has been shown to attenuate collagen accumulation, fibroblast activation, and fibrotic changes in lung tissue. This suggests a potential role in preventing long-term lung dysfunction post-ALI/ARDS.
 
Clinical Relevance and Translational Potential
While the bulk of evidence for fortunellin's efficacy in ALI/ARDS comes from preclinical studies, its translational potential holds promise. Clinical trials assessing the safety, efficacy, and optimal dosing of fortunellin in respiratory conditions are warranted. Furthermore, the post-COVID-19 era presents an opportune time to explore fortunellin as a therapeutic adjunct, given its anti-inflammatory and tissue-protective effects.
 
Challenges and Future Directions
Despite the encouraging findings, several challenges remain in translating fortunellin's therapeutic potential into clinical practice. These include standardizing extraction methods, ensuring bioavailability, determining optimal dosing regimens, and addressing potential drug interactions. Future research should focus on elucidating fortunellin's precise molecular targets, conducting robust clinical trials, and exploring combination therapies for synergistic effects.
 
Conclusion
Fortunellin from Kumquat emerges as a promising natural compound with multifaceted therapeutic effects in ALI/ARDS. Its ability to modulate the TLR4/NF-κB/NLRP3 pathway, reduce inflammation, inhibit apoptosis, and mitigate oxidative stress underscores its potential as a therapeutic agent. While preclinical studies provide compelling evidence, further research, including clinical trials, is imperative to validate fortunellin's efficacy, safety profile, and clinical utility in respiratory disorders. In the aftermath of the COVID-19 pandemic, fortunellin's role in post-viral lung complications warrants exploration, offering hope for improved outcomes in patients with acute and chronic respiratory conditions.
 
The study findings were published in the peer reviewed journal: Immunity, Inflammation and Disease (Wiley).
https://onlinelibrary.wiley.com/doi/10.1002/iid3.1164
 
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