ABSTRACT
Pulmonary fibrosis is a key feature of COVID-19, Chinese herbal medicine Arenaria kansuensis has been used for curing pulmonary disease and antivirus for a long time and it has the potential against COVID-19. In this work, protective effect of A. kansuensis ethanol extract (AE) on pulmonary fibrosis was evaluated through paraquat (PQ)-induced pulmonary fibrosis animal model. Results showed that AE could significantly improve the survival rate, increase the body weight and reduce the lung index of mice at the raw drug doses of 700 and 350 mg/kg. Histopathological observation results showed that the destruction degree of lung tissue structure in mice was significantly improved with the increase of AE dosage. Collagen deposition in lung interstitium was significantly reduced. The marker protein alpha-SMA involved in PF were significantly inhibited through repressing TGF-beta1/Smads pathway. The degree of inflammatory infiltration was significantly reduced and inflammatory cytokines were significantly inhibited in mice through inhibiting the NF-kB-p65. Besides, oxidant stress level including upregulated ROS and down-regulated SOD and GSH was efficiently improved by AE through upregulation of Nrf2 and downregulation of NOX4. In summary, this study firstly showed that the protective effect of AE on pulmonary fibrosis was partly due to activation of Nrf2 pathway and the inhibition of NF-kB/TGF-beta1/Smad2/3 pathway.
Subject(s)
Arenaria Plant/chemistry , Drugs, Chinese Herbal/pharmacology , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/metabolism , Acute Lung Injury , Animals , Arenaria Plant/physiology , COVID-19/complications , COVID-19/pathology , Cytokines/metabolism , Disease Models, Animal , Drugs, Chinese Herbal/therapeutic use , Ethanol/chemistry , Female , Male , Mice , Mice, Inbred C57BL , NF-E2-Related Factor 2/metabolism , NF-kappa B/metabolism , Oxidative Stress/drug effects , Paraquat , Phytotherapy , Pulmonary Edema/drug therapy , Pulmonary Edema/pathology , Pulmonary Fibrosis/chemically induced , Pulmonary Fibrosis/pathology , SARS-CoV-2/drug effects , SARS-CoV-2/physiology , Signal Transduction/drug effects , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Survival Rate , Transforming Growth Factor beta1/metabolism , COVID-19 Drug TreatmentABSTRACT
Biogeographers claimed for more than a century that arctic plants survived glaciations in ice-free refugia within the limits of the North European ice sheets. Molecular studies have, however, provided overwhelming support for postglacial immigration into northern Europe, even from the west across the Atlantic. For the first time we can here present molecular evidence strongly favouring in situ glacial persistence of two species, the rare arctic-alpine pioneer species Sagina caespitosa and Arenaria humifusa. Both belong to the 'west-arctic element' of amphi-Atlantic disjuncts, having their few and only European occurrences well within the limits of the last glaciation. Sequencing of non-coding regions of chloroplast DNA revealed only limited variation. However, two very distinct and partly diverse genetic groups, one East and one West Atlantic, were detected in each species based on amplified fragment length polymorphisms (AFLPs), excluding postglacial dispersal from North America as explanation for their European occurrences. Patterns of genetic diversity and distinctiveness indicate that glacial populations existed in East Greenland and/or Svalbard (A. humifusa) and in southern Scandinavia (S. caespitosa). Despite their presumed lack of long-distance dispersal adaptations, intermixed populations in several regions indicate postglacial contact zones. Both species are declining in Nordic countries, probably due to climate change-induced habitat loss. Little or no current connectivity between their highly fragmented and partly distinct populations call for conservation of several populations in each geographic region.
