KCHO-1 is a novel product comprised of 30% ethanol extracts obtained from nine medical herbs, which are commonly used in traditional Korean and Chinese medicine. The nine herbs include Curcuma longa, Salvia miltiorrhiza, Gastrodia elata, Chaenomeles sinensis, Polygala tenuifolia, Paeonia japonica, Glycyrrhiza uralensis, Atractylodes japonica and processed Aconitum carmichaeli. Recent studies have reported the beneficial effects of these herbs. The present study aimed to investigate the direct neuroprotective effects of KCHO‑1 on HT22 mouse hippocampal cells, and to determine the possible underlying mechanisms. KCHO‑1 significantly suppressed glutamate‑ and hydrogen peroxide (H2O2)‑induced cell damage, and reactive oxygen species generation. In addition, KCHO‑1 increased the mRNA and protein expression levels of heme oxygenase (HO)‑1. Tin protoporphyrin, which is an inhibitor of HO activity, partially suppressed the effects of KCHO‑1. Furthermore, KCHO‑1 significantly upregulated nuclear factor erythroid‑derived 2‑related factor‑2 (Nrf2) nuclear translocation. Extracellular signal‑regulated kinase (ERK) activation also appeared to be associated with KCHO‑1‑induced HO‑1 expression, since the ERK inhibitor PD98059 suppressed HO‑1 expression and prevented KCHO‑1‑induced cytoprotection. The results of the present study suggested that KCHO‑1 may effectively prevent glutamate‑ or H2O2‑induced oxidative damage via Nrf2/ERK mitogen‑activated protein kinase‑dependent HO‑1 expression. These data suggest that KCHO‑1 may be useful for the treatment of neurodegenerative diseases.