Nikhil Prasad Fact checked by:Thailand Medical News Team Jun 19, 2024 1 week, 5 days, 2 hours, 21 minutes ago
Sepsis is a life-threatening condition triggered by an excessive immune response to infection, leading to organ failure and high mortality rates. A groundbreaking study by researchers from China has discovered that a compound called Isaridin E (ISE), derived from marine fungi, can significantly protect against
Sepsis by targeting a specific protein pathway. This exciting discovery could pave the way for new, effective treatments for sepsis, a condition that claims millions of lives worldwide each year.
Isaridin E(ISE) From Marine Fungus Yields Promising Sepsis Treatment
ISE significantly improved pulmonary endothelial permeability. (A) Representative images of lungs from mice treated via the tail vein with Evans blue staining. (B) Evans blue dye contents in the lungs. (C,D) The levels of cell count and protein content in bronchoalveolar lavage fluid. (E,F) The plasma levels of endoglin and syndecan-1 were determined by ELISA. (G–I) Western blot results of VE-cadherin and occludin expression in mouse lung tissue. (J) The IC50 value of ISE for the increased endothelial permeability induced by 10 ng/mL LPS is 21.5 μM. (K–M) Western blot results of VE-cadherin and occludin expression in LPS-stimulated HUVECs. n = 6 independent experiments. *** p < 0.001 vs. the sham group (animal) or the control group (cell); # p < 0.05; ## p < 0.01, ### p < 0.001 vs. the vehicle + CLP group (animal) or LPS group (cell).
Understanding Sepsis
Sepsis occurs when the body's response to infection becomes overwhelming, causing widespread inflammation and damage to organs. This can lead to conditions like acute lung injury, which makes breathing difficult and can be fatal. Traditional treatments have often fallen short, highlighting the urgent need for new approaches.
The Role of von Willebrand Factor (vWF)
One of the key players in the development of sepsis is a protein called von Willebrand factor (vWF). This protein, produced by the cells lining blood vessels and by platelets, helps blood to clot. However, during sepsis, the levels of vWF can become excessively high, causing blood vessels to become leaky and leading to inflammation and clotting problems. This makes vWF a prime target for new sepsis treatments.
Isaridin E: A Promising Marine-Derived Compound
Researchers have turned to the ocean, a vast and largely untapped source of medicinal compounds, in their search for new treatments. They identified Isaridin E (ISE), a compound produced by a marine fungus named Amphichorda felina, as a potential anti-sepsis agent. Previous studies showed that ISE has strong anti-clotting properties, making it a promising candidate for further research.
Breakthrough Study on ISE
The Chinese researchers explored the effects of ISE on mice with sepsis induced by a surgical procedure known as cecal
ligation and puncture (CLP). This procedure mimics the human condition of sepsis by causing a severe infection in the abdomen. The results were remarkable:
-Improved Survival Rates: Mice treated with ISE had significantly higher survival rates compared to those that did not receive the treatment.
-Reduced Lung Injury: The compound helped to prevent the severe lung damage typically seen in sepsis, making breathing easier and improving overall health.
-Lower Inflammation: ISE reduced levels of inflammatory markers in the blood, indicating a decrease in the severe immune response that characterizes sepsis.
-Protection Against Vascular Leakage: One of the most significant findings was that ISE helped maintain the integrity of blood vessels, preventing the leakage that can lead to multiple organ failure.
How Does ISE Work?
The study revealed that ISE works by inhibiting the release of vWF from platelets and endothelial cells (the cells lining blood vessels). It does this by blocking specific molecular pathways, particularly those involving integrin αvβ3, a protein that helps vWF bind to blood vessels. By preventing this binding, ISE helps keep blood vessels intact and reduces inflammation and clot formation.
ISE was found to reduce the secretion of vWF by suppressing the overexpression of proteins such as vesicle-associated membrane protein 8 (VAMP-8) and soluble N-ethylmaleimide-sensitive factor attachment protein 23 (SNAP-23) in septic mice. This suppression resulted in decreased platelet adhesion to the endothelial cells, further preventing the harmful effects of sepsis.
Insights from the Study
Researchers administered different doses of ISE (25, 50, and 100 mg/kg) to mice and monitored their survival over seven days. The mice treated with the highest dose of ISE showed a survival rate of 60%, compared to only 20% in the untreated group. Moreover, ISE-treated mice exhibited less weight loss and quicker recovery, indicating an overall improvement in health.
Histological analysis of lung tissues from treated mice showed significantly less damage compared to untreated mice. The treated mice had reduced signs of inflammation, such as thickening of the alveolar walls and hemorrhage, which are indicative of acute lung injury. Additionally, the levels of pro-inflammatory cytokines like TNF-α and IL-1β were significantly lower in the blood of ISE-treated mice.
Potential Clinical Implications
The discovery of ISE’s protective effects against sepsis is a major breakthrough. Not only does it offer a potential new treatment for a condition with limited options, but it also highlights the vast potential of marine-derived compounds in medicine. Further research is needed to confirm these findings in human trials, but the future looks promising.
ISE's ability to inhibit the vWF-integrin αvβ3 pathway and reduce endothelial hyperpermeability could be particularly beneficial in managing sepsis-induced complications. Its low bleeding risk makes it a safer alternative to conventional anti-clotting medications, which often come with a significant risk of bleeding.
Conclusion
Sepsis remains a major medical challenge, but discoveries like ISE offer new hope. By targeting specific pathways involved in the disease, researchers are opening the door to more effective treatments. As we continue to explore the natural world, particularly the oceans, we may find even more compounds that can help combat deadly diseases like sepsis.
The study findings were published in the peer reviewed journal: Marine Drugs.
https://www.mdpi.com/1660-3397/22/6/283
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https://www.thailandmedical.news/news/covid-19-viral-sepsis-unveiling-the-hidden-dangers-of-coagulation-and-platelet-dysfunction
https://www.thailandmedical.news/news/chinese-researchers-uncover-the-critical-role-of-adaptor-proteins-in-sepsis-regulation
