The effect of the herbal combination Flasil on liver-lung axis pathologies in a CCl₄-induced precirrhotic model

Abstract

Background: Plant combinations in functional diets can synergistically enhance therapeutic efficacy, but unstandardized consumption of potent bioactives poses physiological risks. Flasil is an investigational herbal mixture of Helichrysum rubicundum and Silybum marianum. This combination of active botanical components is proposed as a dual-therapy approach for liver cirrhosis. Objective: This study aimed to investigate the effects of Flasil on histopathological and morphometric alterations in the liver-lung axis within the context of organ-systemic pathologies during the progression of toxic liver cirrhosis. Methods:  Hepatic injury was induced using CCl4 (2 mL/kg, i.p.). Animals received Flasil (300 mg/kg, p.o., 3×/week) or served as controls. Biweekly histopathological (H&E) and morphometric changes in the liver and lung tissues were assessed over 8 weeks. Results: Flasil administration significantly mitigated histopathological changes induced by CCl4 intoxication, suppressing fibrous septa formation and demonstrating multisystemic efficacy across hepatic and pulmonary tissues. Specifically, Flasil normalized the cellular profile, increasing the proportion of hepatocytes with intact nuclear structures from 27.8% [24.5%; 37.3%] to 47.5% [44.3%; 48.8%] (padj= 0.008) by week 8 post-CCl4 injury. By comparison, this cell population decreased to 17.5% [10.8%; 18.8%] in the untreated control group. Concurrently, Flasil attenuated acute pulmonary exudative lesions and structural consolidation, reducing the semiquantitative injury score by 2.5 [1.5; 3.0] points relative to controls at 8 weeks (padj = 0.008). Conclusion: The current research indicates that the herbal combination Flasil mitigates CCl₄-induced histological alterations in liver and lung in a rodent model. Structural analyses indicate that Flasil shows potential in alleviating tissue damage and structural changes associated with toxic liver injury and related pulmonary complications; nevertheless, further research is required to evaluate its underlying molecular mechanisms and clinical significance. Novelty of the Study: This work is the first to demonstrate the systemic therapeutic dynamics of Flasil herbal mixture along the liver-lung axis, proving its capacity to simultaneously restore hepatic and pulmonary histological architectures during toxic cirrhosis progression.  Keywords: bioactive compounds, carbon tetrachloride, hepatotoxicity, pulmonary injury, histopathology, silymarin, Helichrysum rubicundum.