A systematic identification of anti-inflammatory active components derived from Mu Dan Pi and their applications in inflammatory bowel disease

Abstract

Mu Dan Pi (MDP), also known as Moutan Cortex Radicis, is a traditional Chinese medicine used to treat autoimmune diseases. However, the impact of MDP and its principal active compounds on inflammatory bowel disease (IBD) is uncertain. This study therefore systemically assessed the anti-inflammatory effects of MDP and its known active compounds in IBD. The anti-inflammatory activities of water extract and individual compounds were screened by NF-κB and interferon regulatory factor (IRF) reporter assays in THP-1 cells induced with either Toll-like receptor or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 activators and further verified in bone marrow-derived macrophages. MDP water extract significantly inhibited the activation of NF-κB and IRF reporters, downstream signaling pathways and the production of IL-6 and TNF-α, in a dose-dependent manner. Among 5 known active components identified from MDP (1,2,3,4,6-penta-O-galloyl-β-d-glucose [PGG], gallic acid, methyl gallate, paeoniflorin, and paeonol), PGG was the most efficient at inhibiting both reporters (with an IC50 of 5–10 µM) and downregulating IL-6 and TNF-α. Both MDP powder for clinical use and MDP water extract, but not PGG, reduced colitis and pathological changes in mice. MDP and its water extract show promise as a novel therapy for IBD patients.

Evaluations and Mechanistic Interrogation of Natural Products Isolated From Paeonia suffruticosa for the Treatment of Inflammatory Bowel Disease

“…Next, we screened MDP fractions using cell-based reporter assays to identify the most effective fractions contributing to the anti-inflammatory effects of MDP. The monocytic cell line THP-1, which stably expresses NF-κB reporter constructs, was used as the reporter cells as previously described ( Chen et al, 2020 ). NF-κB reporter activity, enabling verification of the inflammatory response to the TLR2 agonist, Pam3CSK4, was used to measure inhibitory activity of each MDP fraction ( Figure 2 ).…”

“…THP-1 cells and reporter cells were cultured according to a previously described protocol ( Chen et al, 2020 ). Bone marrow-derived macrophages (BMDMs) were isolated from mice and differentiated for 5–6 days, following standard procedures ( Hsu et al, 2015 ).…”

“…The relative signal response was also documented as a signature of MDP5 (Figure 7B). Paeoniflorin, gallic acid, and 1,2,3,4,6-penta-O-galloylβ-D-glucose (PGG) are reportedly active components with anti-inflammatory functions in MDP (Chen et al, 2020). Among these compounds, gallic acid and PGG are found in the MDP5 fraction (Table 1).…”

“…We have previously reported on the anti-inflammatory activity of our aqueous extraction of MDP ( Chen et al, 2020 ). We also compared this MDP aqueous extract with all reported anti-inflammatory compounds identified in MDP ( Chen et al, 2020 ).…”

“…We have previously reported on the anti-inflammatory activity of our aqueous extraction of MDP ( Chen et al, 2020 ). We also compared this MDP aqueous extract with all reported anti-inflammatory compounds identified in MDP ( Chen et al, 2020 ). However, the impact of MDP on IBD and its principal active compounds that contribute to the anti-inflammatory properties remain uncertain.…”