Advancement in Beneficial Effects of AVE 0991: A Brief Review.

AVE 0991, a non-peptide analogue of Angiotensin-(1-7) [Ang-(1-7)], is orally active and physiologically well tolerated. Several studies have demonstrated that AVE 0991 improves glucose and lipid metabolism, and contains anti-inflammatory, anti-apoptotic, anti-fibrosis, and anti-oxidant effects. Numerous preclinical studies have also reported that AVE 0991 appears to have beneficial effects on a variety of systemic diseases, including cardiovascular, liver, kidney, cancer, diabetes, and nervous system diseases. This study searched multiple literature databases, including PubMed, Web of Science, EMBASE, Google Scholar, Cochrane Library, and the ClinicalTrials.gov website from the establishment to October 2022, using AVE 0991 as a keyword. This literature search revealed that AVE 0991 could play different roles via various signaling pathways. However, the potential mechanisms of these effects need further elucidation. This review summarizes the benefits of AVE 0991 in several medical problems, including the COVID-19 pandemic. The paper also describes the underlying mechanisms of AVE 0991, giving in-depth insights and perspectives on the pharmaceutical value of AVE 0991 in drug discovery and development.

Post-COVID-19 pulmonary fibrosis: the rationale of mesenchymal stem cell transplantation for lung regeneration

Coronavirus disease 2019 (COVID-19) has caused nearly 15 million deaths worldwide. The rapid development of COVID-19 vaccines and anti-viral drugs significantly decreased the level of mortality related to COVID-19. However, post-COVID-19 pulmonary fibrosis has become a severe problem for some COVID-19 patients. The previous articles present the results of mesenchymal stem cell (MSC) transplantation to treat COVID-19 patients;in this article, we would like to discuss the potential of MSC transplantation to treat and improve post- COVID-19 pulmonary fibrosis. MSCs exhibit immune modulation and anti-inflammation that can control the inflammation caused by coronavirus 2 infection and the cytokine storm that some patients experience during COVID-19. The anti-fibrotic qualities of MSCs have also been demonstrated both in vitro and in vivo. Based on the current information about the anti-fibrotic effects of MSCs, MSC transplantation can be used to improve post-COVID-19 pulmonary fibrosis.

Bioavailability Enhancement of Cepharanthine via Pulmonary Administration in Rats and Its Therapeutic Potential for Pulmonary Fibrosis Associated with COVID-19 Infection.

Cepharanthine (CEP) has excellent anti-SARS-CoV-2 properties, indicating its favorable potential for COVID-19 treatment. However, its application is challenged by its poor dissolubility and oral bioavailability. The present study aimed to improve the bioavailability of CEP by optimizing its solubility and through a pulmonary delivery method, which improved its bioavailability by five times when compared to that through the oral delivery method (68.07% vs. 13.15%). An ultra-performance liquid chromatography tandem-mass spectrometry (UPLC-MS/MS) method for quantification of CEP in rat plasma was developed and validated to support the bioavailability and pharmacokinetic studies. In addition, pulmonary fibrosis was recognized as a sequela of COVID-19 infection, warranting further evaluation of the therapeutic potential of CEP on a rat lung fibrosis model. The antifibrotic effect was assessed by analysis of lung index and histopathological examination, detection of transforming growth factor (TGF)-ß1, interleukin-6 (IL-6), α-smooth muscle actin (α-SMA), and hydroxyproline level in serum or lung tissues. Our data demonstrated that CEP could significantly alleviate bleomycin (BLM)-induced collagen accumulation and inflammation, thereby exerting protective effects against pulmonary fibrosis. Our results provide evidence supporting the hypothesis that pulmonary delivery CEP may be a promising therapy for pulmonary fibrosis associated with COVID-19 infection.

Hypothesis: The potential therapeutic role of nicorandil in COVID-19.

At present, there is yet no specific antiviral treatment or immunization against the newly identified human severe acute respiratory syndrome virus (SARS-CoV2) that results in a rapidly progressive pandemic coronavirus disease 2019 (COVID-19). We believe in a crucial need for a clinical strategy to counteract this viral pandemic based on the known pathogenesis throughout the disease course. Evidence suggests that exaggerated patient's inflammatory response and oxidative stress are likely to aggravate the disease pathology. The resulting endothelial dysfunction further induces fibrosis and coagulopathy. These disturbances can generate severe acute respiratory distress syndrome (ARDS) that can progress into respiratory and circulatory failure. Nicorandil is an anti-anginal vasodilator drug acts by increasing nitric oxide bioavailability and opening of the KATP channel. Recently, nicorandil has been recognized to possess multiple protective effects against tissue injury. Here, we address a possible modulatory role of nicorandil against COVID-19 pathogenesis. We hypothesise nicorandil would be an effective form of adjuvant therapy against COVID-19.