title: Effect of Melilotus suaveolens extract on pulmonary microvascular permeability by downregulating vascular endothelial growth factor expression in rats with sepsis.
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.
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Liu
authors.affiliation: Surgical Intensive Care Unit, The Second Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650106, P.R. China.
authors.forename: Mei-Xian
authors.initials: MX
authors.lastname: Su
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Yun Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Lan-Fang
authors.initials: LF
authors.lastname: Qin
authors.affiliation: Department of Infectious Diseases, Yan'an Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650051, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Mao-Li
authors.initials: ML
authors.lastname: Tian
authors.affiliation: Department of Emergency, The First Hospital Affiliated To Kunming Medical University, Kunming, Yunnan 650032, P.R. China.
authors.forename: Chuan-Yun
authors.initials: CY
authors.lastname: Qian
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D029903:Melilotus / Q000737:chemistry*; D008833:Microcirculation / Q000187:drug effects* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D018805:Sepsis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D010936:Plant Extracts; D042461:Vascular Endothelial Growth Factor A