Piscroside C, a novel iridoid glycoside isolated from Pseudolysimachion rotundum var. subinegrum suppresses airway inflammation induced by cigarette smoke.
BACKGROUND
Pseudolysimachion rotundum var. subintegrum (Speedwell, Plantaginaceae) is used as a traditional herbal medicine for treating bronchitis, cough and asthma in Korea, China, Russia, and Europe.


OBJECTIVE
In this study, we investigated the protective effects of the novel iridoid glycoside, piscroside C (compound 1) isolated from the methanolic extract of P. rotundum var. subintegrum against inflammatory responses using a cigarette smoke induced chronic obstructive pulmonary disease (COPD) and TNF-α-stimulated human airway epithelial NCI-H292 cells.


METHODS
The novel iridoid glycoside piscroside C was isolated from the methanolic extract of P. rotundum var. subintegrum. The chemical structure was established by NMR, HRESIMS, and optical rotation. In in vivo experiment, the mice received 1h of cigarette smoke for 3 days. Piscroside C was administered to mice by oral gavage 1h before cigarette smoke exposure for 3 days. In in vitro experiment, we evaluated the effect of piscroside C on proinflammatory mediators in H292 cells stimulated with TNF-α.


RESULTS
Piscroside C significantly reduced the neutrophil influx, reactive oxygen species production, IL-6, TNF-α, and elastase activity in bronchoalveolar lavage fluid in COPD animals. In addition, piscroside C attenuated NF-κB and IκB phosphorylation, leading to reduced recruitment of inflammatory cells into the lung tissue. Consistent with the results of in vivo experiment, piscroside C significantly inhibited the expression of inflammatory cytokines (IL-6, IL-8 and IL-1β) by inhibiting NF-κB activation, as resulting decrease in the phosphorylation of IKKβ, IκBα and TAK1 in TNF-α-stimulated H292 cells.


CONCLUSIONS
These findings indicate that piscroside C effectively inhibits inflammatory responses, which is an important process in the development of COPD through suppression of IKK/NF-κB activation. Our study suggest that piscroside C might represent a useful therapeutic for the treatment of inflammatory airway disease.
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Hyuk-Hwan
HH
Song
College of Veterinary Medicine, Chonnam National University, 77 Yongbong-ro, Buk-gu, Gwangju 500-757, Republic of Korea.
In-Sik
IS
Shin
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea; Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
So Yeun
SY
Woo
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Su Ui
SU
Lee
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Min Hee
MH
Sung
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Hyung Won
HW
Ryu
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Doo-Young
DY
Kim
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Kyung-Seop
KS
Ahn
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea.
Hyeong-Kyu
HK
Lee
Department of Biosystems and Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 136-713, Republic of Korea.
Dongho
D
Lee
Natural Medicine Research Center, Korea Research Institute of Bioscience & Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheong-ju, Chungbuk 363-883, Republic of Korea. Electronic address: seiryang@kribb.re.kr.
Sei-Ryang
SR
Oh
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D057889:Iridoid Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000209:etiology / Q000517:prevention & control*; D012906:Smoke / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage; D032264:Veronica / Q000737:chemistry*
D016207:Cytokines; D018836:Inflammation Mediators; D057889:Iridoid Glycosides; D016328:NF-kappa B; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; C000605653:piscroside C
Cigarette smoke; Inflammation; NF-κB; Piscroside C; Pseudolysimachion rotundum var. subintegrum