Chinese herbal formula protects against hippocampal neurons death via non-classical estrogen 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 the 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.