Hippocampal neurons protected by geniposide via the non-classical estrogen signaling pathway
Amyloid-β (Aβ) plaques and neurofibrillary tangles are the main pathological hallmarks of Alzheimer's disease, as well as the loss of neurons and synapses.
Recent reports have shown that estrogen exerts neuroprotective effects. However, large clinical trials in postmenopausal women indicated adverse side-effects of estrogens, such as increased incidence of breast cancer and metrocarcinoma, thereby preventing clinical use of estrogen.
Tongluojiunao (TLJN) is an herbal medicine consisting of two main components, geniposide and ginsenoside Rg1. Prof. Qian Hua and team from Beijing University of Chinese Medicine in China pointed out that primary cultured hippocampal neurons treated with Aβ1-β significantly increased the release of lactate dehydrogenase, which was markedly reduced by TLJN, specifically by the component geniposide, but not ginsenoside Rg1. They also found that the estrogen receptor inhibitor did not block TLJN- or geniposide-mediated decrease of lactate dehydrogenase under Aβ1-β-exposed conditions. However, the non-classical estrogen pathway inhibitor blocked the decrease of lactate dehydrogenase mediated by TLJN or geniposide.
Therefore, these results, published in Neural Regeneration Research (Vol. 9, No. 5, 2014), suggest that the non-classical estrogen pathway (i.e., phosphatidyl inositol 3-kinase or mitogen-activated protein kinase) is involved in the neuroprotective effect of TLJN, specifically its component, geniposide, against Aβ1-β-mediated cell death in primary cultured hippocampal neurons.
Immunofluorescence staining showed hippocampal neurons under Aβ-exposed conditions presented with necrosis and neural network damage.
Credit: Neural Regeneration Research
Article: " Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-β peptide (1-42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway," by Jiao Li1, Feng Wang1, Haimin Ding2, Chunyan Jin2, Jinyan Chen2, Yanan Zhao1, Xiaojing Li2, Wenju Chen1, Ping Sun1, Yan Tan1, Qi Zhang1, Xu Wang1, Angran Fan1, Qian Hua1 (1 School of Preclinical Medicine, Beijing University of Chinese Medicine, Beijing, China; 2 School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, China)
Li J, Wang F, Ding HM, Jin CY, Chen JY, Zhao YN, Li XJ, Chen WJ, Sun P, Tan Y, Zhang Q, Wang X, Fan AR, Hua Q. Geniposide, the component of the Chinese herbal formula Tongluojiunao, protects amyloid-β peptide (1-42)-mediated death of hippocampal neurons via the non-classical estrogen signaling pathway. Neural Regen Res. 2014;9(5):474-480.