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

Kun-Chang Wu; Der-Yen Lee; Jeh-Ting Hsu; Chi-Fang Cheng; Joung-Liang Lan; Shao-Chih Chiu; Der-Yang Cho; Jye-Lin Hsu

doi:10.3389/fphar.2021.696158

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

Front Pharmacol. 2021 Dec 6:12:696158. doi: 10.3389/fphar.2021.696158. eCollection 2021.

Authors

Kun-Chang Wu¹, Der-Yen Lee², Jeh-Ting Hsu³, Chi-Fang Cheng⁴, Joung-Liang Lan^{5

6}, Shao-Chih Chiu^{4

7

8}, Der-Yang Cho^{4

7

8

9}, Jye-Lin Hsu^{4

7}

Affiliations

¹ School of Pharmacy, College of Pharmacy, China Medical University, Taichung, Taiwan.
² Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan.
³ Department of Information Management, Hsing Wu University, New Taipei, Taiwan.
⁴ Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan.
⁵ Division of Rheumatology and Immunology and Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
⁶ College of Medicine, China Medical University, Taichung, Taiwan.
⁷ Drug Development Center, China Medical University, Taichung, Taiwan.
⁸ Translational Cell Therapy Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁹ Department of Neurosurgery, China Medical University Hospital, Taichung, Taiwan.

Abstract

Mu Dan Pi (MDP), a traditional Chinese medicine derived from the root bark of Paeonia suffruticosa Andrews, is used to treat autoimmune diseases due to its anti-inflammatory properties. However, the impact of MDP on inflammatory bowel disease (IBD) and its principal active compounds that contribute to the anti-inflammatory properties are uncertain. Thus, this study systemically evaluated the anti-inflammatory effects of fractionated MDP, which has therapeutic potential for IBD. MDP fractions were prepared by multistep fractionation, among which the ethyl acetate-fraction MDP5 exhibited the highest potency, with anti-inflammatory activity screened by the Toll-like receptor (TLR)-2 agonist, Pam3CSK4, in a cell-based model. MDP5 (at 50 μg/ml, p < 0.001) significantly inhibited nuclear factor kappa-B (NF-κB) reporters triggered by Pam3CSK4, without significant cell toxicity. Moreover, MDP5 (at 10 μg/ml) alleviated proinflammatory signaling triggered by Pam3CSK4 in a dose-dependent manner and reduced downstream IL-6 and TNF-α production (p < 0.001) in primary macrophages. MDP5 also mitigated weight loss, clinical inflammation, colonic infiltration of immune cells and cytokine production in a murine colitis model. Index compounds including paeoniflorin derivatives (ranging from 0.1 to 3.4%), gallic acid (1.8%), and 1,2,3,4,6-penta-O-galloyl-β-D-glucose (1.1%) in MDP5 fractions were identified by LC-MS/MS and could be used as anti-inflammatory markers for MDP preparation. Collectively, these data suggest that MDP5 is a promising treatment for IBD patients.

Keywords: Paeonia suffruticosa; anti-inflammation; inflammatory bowel disease; moutan radicis cortex; mu dan pi; traditional Chinese medicine.