Purpose: To investigate in vivo immunomodulatory effect and histopathological feature of mouse liver and kidney following treatment with 2 neolignans (croactidin  and deasetil crocatidin) isolated from red betel (Piper crocatum Ruiz & Pav) leaf.

Methods: Balb/c mice immune response was induced with Listeria monocytogenes. Immunomodulatory effect was tested by using macrophage phagocytic, nitric oxide, and lymphocyte proliferation assays. The morphological features of liver and kidney were observed with light microscope and then compared with the liver and kidney of control group.

Results: At the dose of 5 and 10 mg/kg body weight, both crocatidin and deacetyl crocatidin significantly increased the activity and the capacity of macrophages (p < 0.05). Crocatidin and deacetyl crocatidin increase phagocytic activity of macrophage, respectively for 25 % and 23 % at the dose of 5 mg/kg body weight, and increase the phagocytic index respectively for 38 and 52.   Increasing nitric oxide production due to crocatidin and deacetyl crocatidin (2.5, 5, and, 10 mg/kg body weight) was also observed although no lymphocyte proliferation effect was observed. Histopathological examination of liver and kidney of mice given crocatidin demonstrated normal features. On the other hand, hydropic degeneration and liver necrosis were seen in mice given deacetyl crocatidin treatment. Based on this result and the structure similarity of the two compounds (crocatidin and deacetyl crocatidin), an interesting presumption can be made that the –OH functional group (deacetyl crocatidin) was responsible for the toxicity that caused liver damage.

Conclusion: The two neolignans (crocatidin and deacetyl crocatidin) isolated from the leaves of P. crocatum Ruiz & Pav. are capable of increasing macrophage phagocytosis as well as nitric oxide production but not lymphocyte proliferation. Histophatological features of liver given deacetyl crocatidin demonstrate hydropic degeneration and necrosis, possibly due to the –OH group on deacetyl crocatidin.