@article{oai:toyama.repo.nii.ac.jp:00005333, author = {Yokozawa, Takako and CHO, EunJu}, issue = {5}, journal = {和漢医薬学雑誌 = Journal of traditional medicines}, month = {Dec}, note = {application/pdf, Chinese prescription Kangen-karyu, comprised of six crude drugs, has received much attention due to its numerous biological activities. The present study reports the anti-aging potential of Kangen-karyu and its related mechanisms under in vivo conditions with senescence-accelerated mice (SAM) and aging rats, and in a cellular system with stress-induced premature senescence (SIPS). Kangen-karyu attenuated oxidative stress by the inhibition of free radical generation and lipid peroxidation under the SAM model, suggesting its anti-aging potential. In addition, investigation with the in vivo natural aging model also showed that Kangen-karyu and its main crude drug, Tanjin, played protective roles against protein modification and lipid peroxidation in serum and tissue with aging. In particular, Kangen-karyu exerted a stronger anti-aging effect than Tanjin, suggesting that Tanjin contributes synergistically to the anti-aging activity of Kangen-karyu. Kangen-karyu also regulated the glutathione redox cycle, working primarily to maintain mitochondrial function against the leakage of reactive oxygen species from mitochondria, and led to the inhibition of nuclear factor-kappa B (NF-κB) to nuclear translocation and regulation of related protein expressions such as cyclooxygenase-2, inducible nitric oxide synthase, heme oxygenase-1, bax, and bcl-2 proteins. Furthermore, under the SIPS cellular model, Kangen-karyu extract showed an anti-aging activity and led to increased longevity through the attenuation of oxidative damage with the inhibition of lipid peroxidation and cell cycle regulation. Its anti-aging activity results from modulations of NF-κB and the expressions of its related proteins. The present study suggests that Kangen-karyu has a promising anti-aging potential against oxidative stress-induced aging processes. 冠元顆粒は6種類の生薬からなる漢方方剤で,種々の生物活性を有することから注目されている。本研究では,冠元顆粒の抗老化の可能性とその機序について,老化促進モデルマウス(SAM)と加齢ラット,さらにstress-induced premature senescence(SIPS)を持った細胞系を用い検討した結果を報告する。SAMにおいて,冠元顆粒はフリーラジカル産生と脂質過酸化を抑制して酸化ストレス状態を緩和し,抗老化作用を有することが示唆された。生理的老化モデルを用いた実験においても,冠元顆粒とその主薬の丹参が,加齢によって生じる蛋白修飾や脂質過酸化に対し保護作用を示した。このような作用は,冠元顆粒の方が丹参より強い作用を示し,冠元顆粒の相乗作用が示唆された。冠元顆粒はまた,グルタチオンレドックスサイクルの調節やミトコンドリアからの活性酸素種の漏出を防御してミトコンドリア機能を維持し,NF-κBの核への移行の抑制とシクロオキシゲナーゼー2,誘導型一酸化窒素合成酵素,ヘムオキシゲナーゼー1,bax,bcl-2等の蛋白発現を制御していた。さらに,SIPS細胞モデルを用いた実験で,冠元顆粒が脂質過酸化の抑制による酸化傷害の改善や細胞周期を制御し,抗老化作用と細胞寿命の延長を示していたが,このような作用はNF-κBと蛋白発現の調節に起因していた。以上,本研究において冠元顆粒が酸化ストレスから誘導される老化過程に対し,抗老化作用を有する可能性が示唆された。, Article}, pages = {153--165}, title = {Contribution of Chinese prescription Kangen-karyu in the oxidative stress-related aging process}, volume = {23}, year = {2006} }