title: Src/Syk-Targeted Anti-Inflammatory Actions of Triterpenoidal Saponins from Gac (Momordica cochinchinensis) Seeds.
abstract: Momordica cochinchinensis Spreng (family Cucurbitaceae), also known as gac, or red melon, is an edible Southeast Asian fruit valued for its nutritional and medicinal properties. Specifically, Momordicae Semen, the seeds of the gac fruit, is used in traditional Chinese medicine to treat boils, rheumatic pain, muscle spasm, hemorrhoids, and hemangiomas. In this study, a chemical investigation into a gac seed ethanol (EtOH) extract resulted in the identification of three triterpenoidal saponins (1-3), which were investigated for their anti-inflammatory effects. Among the saponins, momordica saponin I (compound 3) reduced the production of nitric oxide (NO) in LPS-activated RAW264.7 cells without inducing cytotoxicity. The mRNA levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by momordica saponin I. Additionally, the translocation of p65 and p50 (subunits of the transcription factor NF-[Formula: see text]B) into the nucleus was remarkably inhibited. Furthermore, the phosphorylation levels of inflammatory signaling proteins (I[Formula: see text]B[Formula: see text], Src, and Syk) known to be upstream regulatory molecules of p65 were decreased under momordica saponin I-treated conditions. The molecular targets of momordica saponin I were confirmed in overexpression experiments and through immunoblot analyses with Src and Syk. This study provides evidence that momordica saponin I could be beneficial in treating inflammatory diseases, and should be considered a bioactive immunomodulatory agent with anti-inflammatory properties.
authors.affiliation: * School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Sik
authors.initials: JS
authors.lastname: Yu
authors.affiliation: † Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jun Ho
authors.initials: JH
authors.lastname: Kim
authors.affiliation: * School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Seulah
authors.initials: S
authors.lastname: Lee
authors.affiliation: ‡ Institute of Pharmaceutical Sciences, College of Pharmacy, CHA University, Seongnam 13488, Republic of Korea.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Jung
authors.affiliation: * School of Pharmacy, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Ki Hyun
authors.initials: KH
authors.lastname: Kim
authors.affiliation: † Department of Genetic Engineering, Sungkyunkwan University, Suwon 440-746, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D051379:Mice; D029775:Momordica / Q000737:chemistry*; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000067996:RAW 264.7 Cells; D012503:Saponins / Q000302:isolation & purification / Q000494:pharmacology*; D012639:Seeds / Q000737:chemistry*; D000072377:Syk Kinase / Q000378:metabolism*; D014315:Triterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D016328:NF-kappa B; D009363:Neoplasm Proteins; D029543:Nucleocytoplasmic Transport Proteins; D012503:Saponins; D014315:Triterpenes; C063447:p65 oncofetal mRNA transport protein, rat; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D000072377:Syk Kinase; D019061:src-Family Kinases
keywords: Anti-inflammatory activity; Momordica cochinchinensis; NF-B, Src, Syk; Triterpenoidal saponins