AUTHOR=Wang Mo-Fei , Sun Tong , Chen Shi-Yu , Wang Xue , Li Hao , Wang Jia-Qi 

TITLE=Effects of Kalimeris indica on alcohol-induced liver injury through storing Nrf2/HO-1 pathway and gut microbiota

JOURNAL=Frontiers in Pharmacology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1502096

DOI=10.3389/fphar.2024.1502096

ISSN=1663-9812

ABSTRACT=<sec><title>Background</title><p><italic>Kalimeris indica (</italic>L.<italic>)</italic> Sch. Bip., (<italic>K. indica)</italic> is a plant classified under the genus Kalimeris within the Asteraceae family. The herb of <italic>K. indica</italic> has been historically utilized as a traditional medicine. The consumption of excessive amounts of alcohol represents a lifestyle choice that can induce tissue damage and contribute to the development of various health conditions.</p></sec><sec><title>Method</title><p>The HPLC-MS method was used to reveal the chemical composition of <italic>K. indica</italic> extract. HepG2 cells were used to test the <italic>in vitro</italic> oxidative stress. C57BL/6 mice were used to construct the <italic>in vivo</italic> alcohol-induced liver injury. H/E staining and serum ALT and AST levels were tested to assess the <italic>in vivo</italic> protective effect of ML (50 and 200 mg/kg). GSH, SOD, and CAT levels along with byproduct MDA levels were used to evaluate the <italic>in vivo</italic> oxidative stress. Immunohistochemical experiments were used to examine the <italic>in vivo</italic> Nrf2 and HO-1 levels. 16S rRNA gene-based profiling method was used to test the alteration in gut microbiota.</p></sec><sec><title>Results</title><p>16 compounds were identified from <italic>K. indica</italic> extract. <italic>K. indica</italic> treatment reduced oxidative stress in HepG2 cells treated with 5% alcohol. H/E staining results showed that <italic>K. indica</italic> (50 and 200 mg/kg) alleviated liver injury caused by alcohol administration, eliciting a similar protective effect to the positive drug silymarin. Serum ALT and AST examination gave a consistent result, showing that ML could restore serum ALT and AST levels in mice treated with alcohol. Furthermore, <italic>K. indica</italic> could also restore GSH, SOD, CAT, and MDA levels in alcohol-treated mice, showing a potent effect on oxidative stress alleviation. Immunohistochemical experiments indicated that <italic>K. indica</italic> showed the liver protective effect through Nrf2/HO-1 pathway. 16S rRNA gene-based profiling revealed that alcohol treatment caused the alteration in gut microbiota, while <italic>K. indica</italic> treatment could result in a significantly richer variety of microbial communities compared to the alcohol group.</p></sec><sec><title>Conclusion</title><p><italic>K. indica</italic> (ML) has a protective effect on liver injury caused by alcohol administration. The Nrf2/HO-1 pathway and gut microbiota regulation were involved in the ML-induced liver protection. All the results indicate that <italic>K. indica</italic> has a potential in the treatment of alcohol-induced liver injury.</p></sec>