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1.
Inflammopharmacology ; 31(3): 1437-1447, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2258075

ABSTRACT

Acute lung injury (ALI) is a life-threatening condition usually associated with poor therapeutic outcomes and a high mortality rate. Since 2019, the situation has worsened due to the COVID-19 pandemic. ALI had approximately 40% of deaths before COVID-19, mainly due to the dysfunction of the blood-gas barrier that led to lung edema, failure of gas exchange, and dyspnea. Many strategies have been taken to mitigate the disease condition, such as diuretics, surfactants, antioxidants, glucocorticoids, heparin, and ventilators with concomitant sedatives. However, until now, there is no available effective therapy for ALI. Thus, we are presenting a new compound termed Arabincoside B (AR-B), recently isolated from Caralluma arabica, to be tested in such conditions. For that, the lipopolysaccharide (LPS) mice model was used to investigate the capability of the AR-B compound to control the ALI compared to standard dexamethasone. The results showed that AR-B had a significant effect on retrieving ALI. A further mechanistic study carried out in the serum, lung homogenate, histological, and immunohistochemistry sections revealed that the AR-B either in 50 mg/kg or 75 mg/kg dose inhibited pro-inflammatory cytokines such as IL-6, IL-13, NF-κB, TNFα, and NO and stimulated regulatory cytokines IL-10. Moreover, AR-B showed a considerable potential to protect the pulmonary tissue against oxidative stress by decreasing MDA and increasing catalase and Nrf2. Also, the AR-B exhibited an anti-apoptotic effect on the lung epithelium, confirmed by reducing COX and BAX expression and upregulating Bcl-2 expression. These results pave its clinical application for ALI.


Subject(s)
Acute Lung Injury , Apocynaceae , COVID-19 , Pneumonia , Mice , Animals , Humans , Lipopolysaccharides/pharmacology , Signal Transduction , Pandemics , COVID-19/metabolism , Lung , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , NF-kappa B/metabolism , Pneumonia/metabolism , Cytokines/metabolism , Apocynaceae/metabolism
2.
Steroids ; 165: 108759, 2021 01.
Article in English | MEDLINE | ID: covidwho-917434

ABSTRACT

Gastric ulcers are a very common public health problem affecting up to 10% worldwide. Russelioside B is a steroidal glycoside isolated from several Caralluma species. No study tested the ulcer healing potential of the compound. The current study aimed to assess the protective effect of russelioside B against ethanol-induced gastric mucosal injury in rats. Ulcer was induced on rats by a single intragastric dose of absolute ethanol (5 mL/kg). Rats were randomly assorted into four groups (n = 8) and given treatments (Antodine, 20 mg/kg or russelioside B, 50 mg/kg) by oral gavage 1 h before ulcer induction. Pretreatment with russelioside B (50 mg/kg) attenuated the gastric mucosal injury as proved by a decrease of ulcer index, and histological scores. It suppressed the gastric inflammation by a significant lowering the tumor necrosis factor-α and interleukin-6 levels with myeloperoxidase activity (which are also aggravating factors in the case of Covid-19 infection). In addition, administration of russelioside B halted the gastric oxidative stress via inhibition of lipid peroxides by maintaining reduced glutathione and by decreasing malondialdehyde. It was able also to restore the sharp drop in the levels of heat shock protein-70, vascular endothelial growth factor and prostaglandin E2 induced by ethanol. Additionally, it showed carbonic anhydrase inhibition activity. The gastroprotective action of russelioside B was umpired through multi mechanistic actions; suppression of gastric oxidative stress, inflammation, anti-apoptotic activities and enhanced gastric mucosal protection by up-regulation of endothelial growth factor, normalization of heat shock protein-70 and prostaglandin E2. These actions were comparable in part to some classical antiulcer drugs such as Antodine.


Subject(s)
Dinoprostone/genetics , Glycosides/pharmacology , HSP70 Heat-Shock Proteins/genetics , Pregnanes/pharmacology , Stomach Ulcer/drug therapy , Animals , Anti-Ulcer Agents/pharmacology , Apocynaceae/chemistry , COVID-19/genetics , COVID-19/virology , Disease Models, Animal , Ethanol/toxicity , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gene Expression Regulation/drug effects , Glycosides/chemistry , Humans , Interleukin-6/genetics , Oxidative Stress/drug effects , Peroxidase/genetics , Pregnanes/chemistry , Rats , SARS-CoV-2/genetics , SARS-CoV-2/pathogenicity , Stomach Ulcer/chemically induced , Stomach Ulcer/genetics , Stomach Ulcer/pathology , Tumor Necrosis Factor-alpha/genetics , COVID-19 Drug Treatment
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