Abstract
 
Background: Hepatic fibrosis is a pre-pathologic state of cirrhosis, which plays a pivotal role in the pathogenesis of hepatocellular car-cinoma  (HCC).  This  study  was  carried  out  to  evaluate  the  hepatoprotective  effect  of Annona  muricata leaves  on  extracellular  matrix
(ECM) accumulation, lysosomal membrane integrity and liver damage in dimethylnitrosamine (DMN)-induced fibrotic rats.  
Methods: Healthy adult male wistar rats were divided into four groups. Group I rats received normal saline and served as control, Group
II  rats  were  administered  200mg/kg Annona  muricata,  Group  III  received  200mg/kg  Annona  muricata orally  simultaneously  with
10mg/kg DMN, Group IV received 10 mg/kg DMN without extract. DMN administered intraperitoneally was on first three days of each
week  for  two  weeks  while Annona  muricata was  administered  for  14  consecutive  days.  24  hours after  last  administration,  all  animals
were  sacrificed  and  blood  collected  for  serum  analysis.  Biochemical  parameters  such  as  lactate  dehydrogenase  (LDH),  total  bilirubin
(TB), total protein (TP), and albumin (ALB) were estimated to assess liver function and synthetic ability while hyaluronic acid (HA) was
determined to assess extracellular matrix (ECM) function. In addition, acid phosphatase (ACP) was estimated to assess lysosomal mem-brane stability/fragility.  
Results: Liver damage, decreased synthetic ability, lysosomal membrane fragility and altered ECM function were evident by an increase
in the levels of LDH,  TB,  ACP and HA as  well as  a decrease in level  of  TP and ALB in sera of rats administered DMN compared to
normal rats. However, simultaneous treatment with Annona muricata leaf extract significantly (p<0.05) reversed alterations in the above
indices.  
Conclusion: This study suggests that Annona muricata leaf functions as a potent  fibrosuppressant by suppressing ECM accumulation,
enhancing lysosomal membrane stability and liver synthetic ability