Paeoniflorin induces apoptosis of lymphocytes through a redox-linked mechanism.
Paeoniflorin (PF), isolated from paeony root, has been used as a herbal medicine for more than 1,200 years in China, Korea, and Japan for its anti-allergic, anti-inflammatory, and immunoregulatory effects. In this study, we found that PF induces apoptosis in both murine T-lineage cells and human T-cell leukemia Jurkat cells. This apoptosis was mediated through the reduction of mitochondrial membrane potential, activation of caspase, and fragmentation of DNA. Interestingly, PF induced generation of reactive oxygen species (ROS) and a reducing agent, dithiothreitol (DTT), and a ROS scavenger, N-acetyl cysteine (NAC), successfully attenuated the PF-induced apoptosis. Additionally, PF induced the phosphorylation of three mitogen-activated protein (MAP) family kinases, extracellular signal-regulated kinase, c-Jun amino-terminal kinase (JNK), and p38 MAP kinase. Curcumin, an anti-oxidant and JNK inhibitor, inhibited PF-induced apoptosis, suggesting the possible involvement of curcumin-sensitive JNK or other redox-sensitive elements in PF-induced apoptosis. These results partially explain the action mechanism of PF-containing paeony root as a herbal medicine.
Tsuboi
Hideo
H
Department of Immunology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Hossain
Khaled
K
Akhand
Anwarul A
AA
Takeda
Kozue
K
Du
Jun
J
Rifa'i
Muhaimin
M
Dai
Yan
Y
Hayakawa
Akemi
A
Suzuki
Haruhiko
H
Nakashima
Izumi
I
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001565:Benzoates / Q000494:pharmacology*; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D019169:Jurkat Cells / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D039821:Monoterpenes; D010084:Oxidation-Reduction; D029596:Paeonia / Q000737:chemistry; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D006027:Glycosides
D000111:Acetylcysteine; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001565:Benzoates; D001952:Bridged-Ring Compounds; D020169:Caspases; D003474:Curcumin; D004229:Dithiothreitol; D004791:Enzyme Inhibitors; D005960:Glucosides; D020928:Mitogen-Activated Protein Kinases; D039821:Monoterpenes; D017382:Reactive Oxygen Species; C015423:peoniflorin; D006027:Glycosides