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Published on: June 19, 2018
Effect of Melilotus suaveolens extract on pulmonary microvascular permeability by downregulating vascular endothelial
Ming-Wei Liu1, Mei-Xian Su2, Wei Zhang1
1Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
Abstract:
A typical indicator of sepsis is the development of progressive subcutaneous and body‑cavity edema, which is caused by the breakdown of endothelial barrier function, leading to a marked increase in vascular permeability. Microvascular leakage predisposes to microvascular thrombosis, breakdown of microcirculatory flow and organ failure, which are common events preceding mortality in patients with severe sepsis. Melilotus suaveolens (M. suaveolens) is a Traditional Tibetan Medicine. Previous pharmacological studies have demonstrated that an ethanolic extract of M. suaveolens has powerful anti‑inflammatory activity and leads to an improvement in capillary permeability. However, the mechanisms underlying its pharmacological activity remain elusive. The present study aimed to assess the impact of M. suaveolens extract tablets on pulmonary vascular permeability, and their effect on regulating lung inflammation and the expression of vascular endothelial growth factor (VEGF) in the lung tissue of rats with sepsis. A cecal ligation and puncture (CLP) sepsis model was established for both the control and treatment groups. ~2 h prior to surgery, 25 mg/kg of M. suaveolens extract tablet was administered to the treatment group. Polymerase chain reaction and western blot analyses were used to assess the expression of nuclear factor (NF)‑κB and VEGF in the lung tissue, and ELISA was applied to detect changes in serum tumor necrosis factor‑α as well as interleukins (IL) ‑1, ‑4, ‑6, and ‑10. The lung permeability, wet/dry weight ratio and lung pathology were determined. The results demonstrated that in the lung tissue of CLP‑rats with sepsis, M. suaveolens extract inhibited the expression of NF‑κB, reduced the inflammatory response and blocked the expression of VEGF, and thus significantly decreased lung microvascular permeability. The effects of M. Suaveolens extract may be of potential use in the treatment of CLP‑mediated lung microvascular permeability.
Insights
Melilotus suaveolens extract significantly reduces lung microvascular permeability in sepsis models. It inhibits nuclear factor-kappa B and vascular endothelial growth factor, decreasing inflammation and improving outcomes.
Area of Science:
- Pharmacology
- Traditional Medicine
- Sepsis Research
Background:
- Sepsis-induced edema results from endothelial barrier dysfunction and increased vascular permeability.
- Microvascular leakage in sepsis can lead to thrombosis, impaired blood flow, and organ failure.
- Melilotus suaveolens, a Tibetan medicine, shows anti-inflammatory properties and improves capillary permeability, but its mechanisms are unclear.
Purpose of the Study:
- To investigate the effects of Melilotus suaveolens extract on pulmonary vascular permeability in a rat sepsis model.
- To assess the extract's impact on lung inflammation and vascular endothelial growth factor (VEGF) expression.
- To elucidate the underlying mechanisms of Melilotus suaveolens in sepsis-induced lung injury.
Main Methods:
- A cecal ligation and puncture (CLP) model was used to induce sepsis in rats.
- Melilotus suaveolens extract (25 mg/kg) was administered prior to CLP surgery.
- Lung tissue analysis included polymerase chain reaction and western blot for NF-κB and VEGF; ELISA for cytokines (TNF-α, IL-1, IL-4, IL-6, IL-10); and assessment of lung permeability and pathology.
Main Results:
- Melilotus suaveolens extract significantly reduced lung microvascular permeability in CLP-induced sepsis.
- The extract inhibited the expression of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) in lung tissue.
- Reduced inflammatory responses and improved lung pathology were observed in the treatment group.
Conclusions:
- Melilotus suaveolens extract effectively mitigates lung microvascular permeability in a sepsis model.
- Inhibition of NF-κB and VEGF expression appears to be a key mechanism of action.
- The extract holds potential for treating sepsis-induced lung microvascular injury.
