Table 2.

The mechanisms of immunomodulatory effects of several bioactive metabolites present in Phyllanthus species.

Compound No.	Name of compounds	Species	Mechanism of action	Reference
1	Corilagin	P. amarus, P. emblica, P. niruri, P. urinaria, P. reticulatus, P. virgatus	Inhibits MPO, MDA, and translocation of NF-κB and inhibits ROS and NO production Inhibits fMLP-induced chemotaxis in human PMN cells	(Jantan et al., 2014)
2	Geraniin	P. amarus, P. urinaria, P. emblica, P. wightianus	Inhibits production of ROS and NO Inhibits pro-inflammatory cytokine release, Inhibits PHA-induced lymphocyte proliferation in human PBMCs	(Jantan et al., 2014)
3	Gallic acid	P. amarus, P. urinaria, P. emblica	Inhibits production of ROS and NO Inhibits pro-inflammatory cytokine release Inhibits PHA-induced lymphocyte proliferation in human PBMCs	(Jantan et al., 2014)
4	Phyllanthin	P. amarus, P. niruri, P. urinaria	Inhibits cellular and humoral immune response in Balb/C mice Inhibits ROS and NO release, inhibits fMLP-induced neutrophil migration Inhibits pro-inflammatory cytokine release Inhibits MyD88-dependent signaling pathways (NF-κB and MAPK)	(Ilangkovan et al., 2016a; Harikrishnan et al., 2018c)
5	Hypophyllanthin	P. amarus P. urinaria	Inhibits production of ROS and NO Inhibits pro-inflammatory cytokine release, Inhibits PHA-induced lympocyte proliferation in human PBMCs Inhibits protein and gene levels of COX-2 and downstream signaling products of PGE2, TNF-α, and IL-1β. Suppresses the inhibitors of IκB, Ikkα/β, NF-κB phosphorylation, and IκB degradation human PBMCs	(Jantan et al., 2014; Harikhrisnan et al., 2018)
6	Ellagic acid	P. amarus, emblica, P. niruri, P. urinaria	Inhibits fMLP-induced chemotaxis in human PMN cells Inhibits PMA and zymosan-induced ROS release and LPS-induced NO release in macrophages Reduces phagocytic activity of human PMN cells	(Jantan et al., 2014)
7	Phyltetralin	P. amarus	Decreased the specific binding of [3H]-PAF in mouse cerebral cortex membranes. Inhibited the increase of myeloperoxidase activity induced by PAF injection in the mouse paw	(Kassuya et al., 2006)
8	Niranthin	P. amarus, P. niruri	Enables the switching from a Th2- to a Th1-type immune response in Leishmania BALB/c mice infected by Leishmania donovani Inhibits protein and gene levels of COX-2 and downstream signaling products of PGE2, TNF-α, and IL-1β. Suppresses the inhibitors of IκB, Ikkα/β, NF-κB phosphorylation, and IκB degradation and suppresses JNK and ERK	(Chowdhury et al., 2012; Harikrishnan et al., 2018c)
9	Catechin	P. niruri, P. orbicularis	Inhibits ROS release Augments expression of ICAM-1 and VCAM-1 Inhibits COX-2 and iNOS release in human chondrocytes	(El-Aziz et al., 2012)
10	Quercetin	P. emblica, P. urinaria, P. virgatus	Inhibits in vitro LPS-induced TNF-α	(Comalada et al., 2005)
11	Astragalin	P. urinaria	Inhibits NO release, IL-6, and PGE-2 by LPS-stimulated RAW 264.7 cells	(Lee et al., 2011)
12	Chebulagic acid	P. emblica, P. myrtifolius	Inhibits T-cell proliferation and the killing activity of CD8+ CTL, inhibits VEGFA-induced vascular permeability	(Hamada et al., 1997)