beta-escin and Acute-Lung-Injury

Acute lung injury (ALI) represents the most severe form of the viral infection sustained by coronavirus disease 2019 (COVID-19). Today, it is a pandemic infection, and even if several compounds are used as curative or supportive treatment, there is not a definitive treatment. In particular, antiviral treatment used for the treatment of several viral infections (eg, hepatitis C, HIV, Ebola, severe acute respiratory syndrome-coronavirus) are today used with a mild or moderate effect on the lung injury. In fact, ALI seems to be related to the inflammatory burst and release of proinflammatory mediators that induce intra-alveolar fibrin accumulation that reduces the gas exchange. Therefore, an add-on therapy with drugs able to reduce inflammation, edema, and cell activation has been proposed as well as a treatment with interferon, corticosteroids or monoclonal antibodies (eg, tocilizumab). In this article reviewing literature data related to the use of escin, an agent having potent anti-inflammatory and anti-viral effects in lung injury, we suggest that it could represent a therapeutic opportunity as add-on therapy in ALI related to COVID-19 infection.

Topics: Acute Lung Injury; Anti-Inflammatory Agents; Antiviral Agents; Betacoronavirus; Coronavirus Infections; COVID-19; Drug Therapy, Combination; Escin; Humans; Immunologic Factors; Inflammation Mediators; Lung; Pandemics; Pneumonia, Viral; SARS-CoV-2

Sepsis-associated acute lung injury (ALI) is a critical condition characterized by severe inflammatory response and mitochondrial dysfunction. Coenzyme Q10 (CoQ10) and aescin (AES) are well-known for their anti-inflammatory activities. However, their effects on lipopolysaccharide (LPS)-induced lung injury have not been explored yet. Here, we asked whether combined pretreatment with CoQ10 and AES synergistically prevents LPS-induced lung injury. Fifty male rats were randomized into 5 groups: (1) control; (2) LPS-treated, rats received a single i.p. injection of LPS (8 mg/kg); (3) CoQ10-pretreated, (4) AES-pretreated, or (5) combined-pretreated; animals received CoQ10 (100 mg/kg), AES (5 mg/kg), or both orally for 7 days before LPS injection. Combined CoQ10 and AES pretreatment significantly reduced lung injury markers; 52.42% reduction in serum C-reactive protein (CRP), 53.69% in alkaline phosphatase (ALKP) and 60.26% in lactate dehydrogenase (LDH) activities versus 44.58, 37.38, and 48.6% in CoQ10 and 33.81, 34.43, and 39.29% in AES-pretreated groups, respectively. Meanwhile, combination therapy significantly reduced interleukin (IL)-1β and tumor necrosis factor (TNF)-α expressions compared to monotherapy (p < 0.05). Additionally, combination therapy prevented LPS-induced histological and mitochondrial abnormalities greater than separate drugs. Western blotting indicated that combination therapy significantly suppressed nucleotide-binding oligomerization domain (NOD)-like receptors-3 (NLRP-3) inflammasome compared to separate drugs (p < 0.05). Further, combination therapy significantly decreased the expression of signaling cascades, p38 mitogen-activated protein kinases (p38 MAPK), nuclear factor kappa B (NF-κB)-p65, and extracellular-regulated kinases 1/2 (ERK1/2) versus monotherapy (p < 0.05). Interestingly, combined pretreatment significantly downregulated high mobility group box-1 (HMGB1) by 72.93%, and toll-like receptor 4 (TLR4) by -0.93-fold versus 61.92%, -0.83-fold in CoQ10 and 38.67%, -0.70-fold in AES pretreatment, respectively. Our results showed for the first time that the enhanced anti-inflammatory effect of combined CoQ10 and AES pretreatment prevented LPS-induced ALI via suppression of NLRP-3 inflammasome through regulation of HMGB1/TLR4 signaling pathway and mitochondrial stabilization.

Topics: Acute Lung Injury; Animals; Escin; Lipopolysaccharides; Male; NF-kappa B; Rats; Sepsis; Ubiquinone

Topics: Acute Lung Injury; Animals; Escin; Inflammation; Interleukin-1beta; Interleukin-6; Lipid Peroxidation; Lipopolysaccharides; Lung; Male; Mice; Mice, Inbred C57BL; Random Allocation; Tumor Necrosis Factor-alpha

Endotoxin causes multiple organ dysfunctions, including acute lung injury (ALI). The current therapeutic strategies for endotoxemia are designed to neutralize one or more of the inflammatory mediators. Accumulating experimental evidence suggests that escin exerts anti-inflammatory and anti-edematous effects. The aim of this study was to evaluate the effect of escin on ALI induced by endotoxin in mice. ALI was induced by injection of lipopolysaccharide (LPS) intravenously. The mice were given dexamethasone or escin before injection of LPS. The mortality rate was recorded. Tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and nitric oxide (NO) were measured. Pulmonary superoxide dismutase (SOD), glutathione peroxidase (GPx) activity, glutathione (GSH), malondialdehyde (MDA) contents, and myeloperoxidase (MPO) activity were also determined. The expression of glucocorticoid receptor (GR) level was detected by Western blotting. Pretreatment with escin could decrease the mortality rate, attenuate lung injury resulted from LPS, down-regulate the level of the inflammation mediators, including NO, TNF-α, and IL-1β, enhance the endogenous antioxidant capacity, and up-regulating the GR expression in lung. The results suggest that escin may have potent protective effect on the LPS-induced ALI by inhibiting of the inflammatory response, and its mechanism involves in up-regulating the GR and enhancing the endogenous antioxidant capacity.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Blotting, Western; Escin; Glutathione Peroxidase; Interleukin-1beta; Lipopolysaccharides; Lung; Male; Mice; Nitric Oxide; Peroxidase; Superoxide Dismutase; Survival Analysis; Tumor Necrosis Factor-alpha

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with high rates of morbidity and mortality. Currently, several surfactant or anti-inflammatory drugs are under test as treatments for ALI. Sodium aescinate (SA) has been shown to exert anti-inflammatory and antiedematous effects. In the present work, the authors explored the effects of SA and the possible mechanisms of SA action in rats with ALI induced by oleic acid (OA) administration. Eight groups of rats received infusions of normal saline (NS) or OA. Rats exposed to OA were pretreated with 1 mg/kg of SA, or posttreated with SA at low (1 mg/kg), medium (2 mg/kg), or high (6 mg/kg) dose; a positive-control group received methylprednisolone. The pressure of oxygen in arterial blood (P(O(2))) levels, the pulmonary wet/dry weight (W/D) ratios, and indices of quantitative assessment (IQA) of histological lung injury were obtained 2 or 6 hours after OA injection (0.1 mL/kg, intravenously). The levels of superoxide dismutase (SOD), malondialdehyde (MDA), matrix metalloproteinase gelatinase B (MMP-9), and tissue inhibitor of metalloproteinase (TIMP-1) in both plasma and lung tissue were also determined. Both pre- and posttreatment with SA improved OA-induced pulmonary injury, increased P(O(2)) and SOD values, lowered IQA scores, and decreased the lung W/D ratio and MDA and MMP-9 levels in plasma and lung tissue. SA appeared to abrogate OA-induced ALI by modulating the levels of SOD, MDA, and MMP-9 in plasma and lung tissue.

Topics: Acute Lung Injury; Animals; Arteries; Blood Gas Analysis; Escin; Male; Malondialdehyde; Matrix Metalloproteinase 9; Oleic Acid; Oxygen; Rats; Rats, Sprague-Dawley; Sodium Compounds; Superoxide Dismutase; Tissue Inhibitor of Metalloproteinase-1

To explore the inhibitory effect and its mechanism of salviae miltiorrhizae and beta-aescinom natrium on the postburn acute lung injury in rats.. Forty-five rats were randomly divided into sham control (C, n = 9), sodium chloride group (S, n = 9), salviae miltiorrhizae group (M, n = 9), beta-aescinom natrium group (A, n = 9), and combination group (MA, n = 9). The rats in M, A and MA groups were subjected to 30% TBSA III degree scald on the back, and all the rats were sacrificed at 24 PBH. The blood and pulmonary tissue samples were harvested from the rats at 24 PBH for the determination of leukocyte adhesiveness/aggregation (LAA) in peripheral blood, myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD) contents, and the ratio of wet to dry weights (W/D) of lung tissue.. Compared with those in S group, the LAA in blood and the pulmonary tissue contents of MPO, MDA and W/D rate in M and A groups, and especially in MA group, were decreased significantly, but the SOD content in pulmonary tissue increased obviously in M and A groups, especially in MA group. Furthermore, blood LAA was positively correlated with pulmonary tissue MDA content.. Postburn intra-pulmonary agglutination and aggregation of PMNs and pulmonary injury by oxygen free radicals (OFRs) and their products could be inhibited by either Salviae Miltiorrhizae or beta-aescinom natrium. In addition, these agents could also increase the tissue content of antioxidant capacity and decrease pulmonary microvascular permeability and lung water content. The results indicated that all the agents used might be effective in prevention and treatment of postburn pulmonary injury, especially when used together.

Topics: Acute Lung Injury; Animals; Burns; Escin; Female; Free Radicals; Lung; Male; Nitric Oxide; Peroxidase; Phytotherapy; Rats; Rats, Sprague-Dawley; Salvia miltiorrhiza; Superoxide Dismutase