Department of Pharmacy, Chia-Nan University of Pharmacy and Science, Tainan.
Int J Immunopathol Pharmacol. 2012 Jan-Mar;25(1):39-48. doi: 10.1177/039463201202500106.
β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-a gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-α were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-κB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicty, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-α production as well as iNOS, COX2, and NF- κB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-α production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-α and iNOS production. β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications. β-thujaplicin, an active constituent from Chamaecyparis obtusa, has been shown to have acaricidal and antimicrobial effects. Very few studies have focused on the potential of the anti-inflammatory effect of β-thujaplicin. Moreover, its capability of inhibiting inflammatory mediators e.g. TNF-alpha gene transcription, nitric oxide (NO) and prostaglandin E2, remains unknown. Besides those molecular mechanisms behind the anti-inflammatory effect of β-thujaplicin, solid proof of its effectiveness in vivo has not yet been studied. In our study, in vitro effects of β-thujaplicin were verified on RAW 264.7 macrophages which were stimulated by LPS. Indomethacin was used as a positive control. The inducible NO production after stimulation was measured by Griess reagent. PGE2, IL-6 and TNF-alpha were measured by ELISA methods. Protein expressions of iNOS, COX2, and NF-kB were evaluated by Western blotting. Septic ICR mice were administered 20 mg/kg of LPS and then the mortality rate was monitored. Within the concentration range which was devoid of cytotoxicty, β-thujaplicin exhibited a clear dose-dependent inhibition on LPS-induced NO production. Furthermore, β-thujaplicin inhibited LPS-induced PGE2, IL-6, and TNF-alpha production as well as iNOS, COX2, and NF-kB protein expression more substantially potent than indomethacin. In agreement with the in vitro study, β-thujaplicin was shown to be effective in vivo for inhibiting LPS-induced NO and TNF-alpha production and a significant decrease in mortality rate of mice suffering from septic shock was observed. This study demonstrates the potential of β-thujaplicin in treatment of inflammation and sepsis. These effects occur through an efficient blockage of TNF-alpha and iNOS production. β-thujaplicin efficacy is comparable to that of indomethacin thus it can be a substitution but bear less depletion of PGE2, making this compound very promising in clinical applications.
β-雪松醇是柏科柏木属植物中的一种活性成分，具有杀螨和抗菌作用。很少有研究关注β-雪松醇的抗炎作用潜力。此外，其抑制炎症介质如 TNF-a 基因转录、一氧化氮（NO）和前列腺素 E2 的能力仍不清楚。除了β-雪松醇抗炎作用背后的这些分子机制外，其在体内的有效性尚未进行研究。在我们的研究中，体外实验验证了β-雪松醇对 LPS 刺激的 RAW264.7 巨噬细胞的作用。吲哚美辛被用作阳性对照。通过格里斯试剂测量刺激后诱导型 NO 的产生。通过 ELISA 方法测量 PGE2、IL-6 和 TNF-α。通过 Western blot 评估 iNOS、COX2 和 NF-κB 的蛋白表达。给感染性 ICR 小鼠注射 20mg/kg 的 LPS，然后监测死亡率。在无细胞毒性的浓度范围内，β-雪松醇对 LPS 诱导的 NO 产生表现出明显的剂量依赖性抑制作用。此外，β-雪松醇对 LPS 诱导的 PGE2、IL-6 和 TNF-α产生以及 iNOS、COX2 和 NF-κB 蛋白表达的抑制作用比吲哚美辛更显著。与体外研究一致，β-雪松醇在体内对抑制 LPS 诱导的 NO 和 TNF-α产生有效，并观察到感染性休克小鼠的死亡率显著降低。这项研究表明了β-雪松醇在治疗炎症和败血症方面的潜力。这些作用是通过有效阻断 TNF-α和 iNOS 的产生而产生的。β-雪松醇的疗效与吲哚美辛相当，因此它可以作为替代品，但对 PGE2 的消耗较少，这使得该化合物在临床应用中非常有前途。
