In vivo Immunomodulatory Effect and Histopathological Features of Mouse Liver and Kidney Treated with Neolignans Isolated from Red Betel (Piper crocatum Ruiz & Pav) Leaf

Purpose: To investigate in vivo immunomodulatoryeffect and histopathological feature of mouse liver and kidney following treatment with 2 neolignans (Pc-1 and Pc-2) 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 Pc-1 and Pc-2 significantly increased the activity and the capacity of macrophages (p < 0.05). Both Pc-1 and Pc-2 significantly increased phagocytic activity of macrophage by 25% and 23%, respectively, and phagocytic index to 38 and 52, respectively at a dose of 5 mg/kg body weight. Increases in nitric oxide production due to Pc-1 and Pc2 (at doses of 2.5, 5, and, 10 mg/kg body weight) were also observed although no lymphocyte proliferation effect was observed. Histopathological examination of liver and kidney of mice given Pc-1 demonstrated normal features. On the other hand, hydropic degeneration and liver necrosis were seen in mice given Pc-2 treatment. Based on this result and the structure similarity of the two compounds (Pc-1 and Pc-2), an interesting presumption was made that the –OH functional group (Pc-2) was responsible for the toxicity that caused liver damage. Conclusion: The two neolignans (Pc-1 and Pc-2) 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 Pc-2 demonstrate hydropic degeneration and necrosis, possibly due to the –OH group on Pc-2.