Ameliorative efficacy of Syzygium aromaticum ethanolic extract and Silymarin® upon carbon tetrachloride-induced liver fibrosis: antioxidant, antibacterial and anti-inflammatory activities.

Liver cirrhosis is associated with high morbidity and mortality rates and poses a serious threat to global health due to its rapid progression to cirrhosis and hepatocellular carcinoma. This study aims to assess the anti-fibrotic effect of combination of clove (Syzygium aromaticum) ethanolic extract (CEE) with Silymarin® on carbon tetrachloride (CCl)-induced liver fibrosis in an effort to advance their synergistic clinical application as well as their antibacterial and anti-inflammatory activities. Adult rats were divided into six groups (10 animals each) as follows: group (1) included normal rats as control, group (2) included normal rats daily CEE, group (3) comprise of CCl-induced liver fibrosis and acts as positive control, group (4) CCl-induced liver fibrosis rats those were treated with CEE, (5) CCl-induced liver fibrosis rats those were treated with Silymarin® and group (6) CCl₄-induced liver fibrosis rats those were treated CEE and Silymarin® for six weeks. By using HPLC analysis, eleven significant constituents were identified, including four flavonoids and seven phenolic acids. The combination of CEE and Silymarin® exhibited potent antibacterial activity against Streptococcus mutans, Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli with MIC values ranging from 182.32 to 201.63 μg/mL. The combination of CEE and Silymarin® significantly reduced nitric oxide levels and increased superoxide dismutase activity in lipopolysaccharide (LPS)-inflamed HepG-2 cells more than CEE and Silymarin® alone, thereby this combination acting as a potent anti-inflammatory and antioxidant candidate. The results indicated that the combination of CEE and Silymarin® was successfully reduced CCl-induced liver fibrosis as approved by a large increase in serum CD4 and albumin levels and the activity of hepatic antioxidant enzymes. These consequences boosted by reduction in several hepatic inflammation markers and distressed the structural restoration of the liver's histological images. In conclusion, the combination of CEE and Silymarin® exert a hepatoprotective complement manner as attributed to the synergistic effect of CEE and Silymarin®.