Eleven new chromane meroterpenoids (1-11), along with 24 known ones (12–35) were isolated from Rhododendron capitatum, a Tibetan medicine. Their structures were determined via extensive spectroscopic methods. The absolute configurations of 1 and 2 were determined by comparison of the experimental and theoretically calculated ECD data. For compounds 3–9, the absolute configurations at the C-2 were assigned according to the empirical chromane helicity rule. The stereochemistry of the chiral alcohols at C-13 in 3 and C-15 in 4 were determined using the Rh₂(OCOCF₃)₄-induced ECD spectra based on the bulkiness rule. Additionally, the absolute configurations of secondary alcohols at C-13 in 8 and 9 were unambiguously established by Mosher's method. Neuroprotection evaluations in vitro and in vivo revealed that compounds 1, 18, and 21 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions. Compound 21 also down-regulated MAPK signal pathway in BV-2 cells. The PC-12 cell damage induced by H₂O₂ and 6-hydroxydopamine (6-OHDA) was attenuated by compounds 1, 21, and 22, especially for 22. Moreover, compounds 3, 6, 22, 23, and 28 significantly enhanced NGF-induced neurite growth in PC-12 cells. Notably, compound 6 demonstrated the most potent neurite growth promotion with a rate of 22.93 ± 2.24 % at 10 μM, which was approximately 3-fold higher than that induced by nerve growth factor (NGF). In AD Caenorhabditis elegans CL4176 model, compounds 1 and 21 delayed Aβ-induced paralysis and reduced ROS expression levels. These studies provide new potential neuroprotective agents for the prevention and treatment of neurodegenerative diseases.

中文翻译：

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来自杜鹃花的结构多样化的色质硫萜类化合物，具有多功能神经保护作用


从藏药杜鹃花 （Rhododendron capitatum） 中分离出 11 种新的色质甲萜类化合物 （1-11） 以及 24 种已知的 （12-35）。它们的结构是通过广泛的光谱方法确定的。1 和 2 的绝对构型是通过比较实验和理论计算的 ECD 数据来确定的。对于化合物 3-9，C-2 处的绝对构型根据经验色质螺旋度规则分配。使用 Rh₂（OCOCF₃）₄ 诱导的基于体积法则的 ECD 光谱测定 C-13 在 3 和 C-15 在 4 处的手性醇的立体化学。此外，通过 Mosher 方法明确确定了 C-13 在 8 和 9 中的绝对构型。体外和体内神经保护评估显示，化合物 1、18 和 21 可显著抑制诱导型一氧化氮合酶 （iNOS） 和环氧合酶 2 （COX-2） 蛋白表达。化合物 21 还下调 BV-2 细胞中的 MAPK 信号通路。化合物 1 、 21 和 22 减轻了 H₂O₂ 和 6-羟基多巴胺 （6-OHDA） 诱导的 PC-12 细胞损伤，尤其是 22 。此外，化合物 3 、 6 、 22 、 23 和 28 显著增强 NGF 诱导的 PC-12 细胞神经突生长。值得注意的是，化合物 6 表现出最有效的神经突生长促进率，± 22.93 的比率。10μM 时为 24%，比神经生长因子 （NGF） 诱导的水平高约 3 倍。在 AD 秀丽隐杆线虫 CL4176 模型中，化合物 1 和 21 延迟了 Aβ诱导的麻痹并降低了 ROS 表达水平。这些研究为预防和治疗神经退行性疾病提供了新的潜在神经保护剂。