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.

New Insights into Sepsis Therapy Using Sepia Officinalis

“…Despite advances in critical care in human medicine, sepsis and septic shock due to infection play considerable roles in the morbidity and mortality of patients in intensive care units, which has been reported to be between 30% and 50% ( 23 ). Consistent with the finding of Liu et al ( 13 ), the present study showed 100% mortality following the CLP model in rats. The high mortality rate recorded here may be due to severe blood loss that caused impaired oxygen delivery, leading to tissue dysfunction and finally death ( 1 ).…”

“…It is therefore considered a gold standard tool for testing the success of CLP as a sepsis model, and for studying the efficacy of both SOBT and SOP extracts as novel antiseptic agents. In conjunction with the reports of Liu et al ( 13 ) and Tavares et al ( 27 ), data from the present investigation showed significantly increased PCT levels following CLP in rats. The increment of PCT in septic rats may be due to a continuous bulk-flow constitutive pathway, in which only limited conversion to mature calcitonin occurs ( 28 ).…”

“…Following the surgery, the rats were injected with normal saline (3 mL/kg b.wt) for fluid resuscitation. The CLP surgery was performed as described by Liu et al ( 13 ).…”

Echinochrome pigment extracted from sea urchin suppress the bacterial activity, inflammation, nociception, and oxidative stress resulted in the inhibition of renal injury in septic rats

“…Cecal ligation and puncture is considered the most clinically applicable in vivo model for sepsis. The cecal ligation and puncture surgery was performed as designated by Liu et al (2015). Briefly, rats were anesthetized with an intraperitoneal injection of sodium pentobarbital (50 mg/ kg body weight) (Ho et al, 2015).…”

Silver/Chitosan/Ascorbic Acid Nanocomposites Attenuates Bacterial Sepsis in Cecal Ligation and Puncture Rat Model

“…Experimental procedures: Rats were subjected to either Cecal Ligation and Puncture (CLP) or sham operation using aseptic techniques, according to Liu et al 32 Eighteen rats were divided into two main groups, the sham-operated control (6 rats) and the CLP group (12 rats). Sodium pentobarbital (50 mg kgG 1 b.wt.)…”