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Background: Neuroglobin (Ngb) and growth-associated protein (GAP) 43 in neurons are associated with axonalregeneration. Korean Red Ginseng Extract (KRGE) enhances glial fibrillary acidic protein (GFAP)-positive astrocytesand hypoxia-inducible factor-1α (HIF-1α) protein activation in normoxic astrocytes. However, crosstalkbetween neural stem cell (NSC) differentiation and astrocytic HIF-1α in the KRGE-treated normoxic brain andretina remains unclear. We investigated whether KRGE-treated astrocytic HIF-1α can enhance NSC differentiationand increase the mature neurons expressing Ngb and GAP43.

Methods: Mature neuronal markers such as neuronal nuclei (NeuN) or microtubule-associated protein 2 (MAP2)were tested with Ngb in the mouse brain or retinal tissues post-KRGE administration. Direct KRGE treatment ofNSCs or astrocytes was evaluated for Ngb levels. The KRGE-treated astrocyte conditioned media (ACM) weretransferred to NSCs and HIF-1α levels were reduced using small interfering RNA transfection (si-HIF-1α) in astrocytes.

si-HIF-1α-ACM with KRGE was tested for NSC differentiation.

Results: KRGE-administered mice showed significantly enhanced co-expression of Ngb with NeuN in the brainand MAP2 in the retina, along with the NSC marker Nestin, than water-administered mice. The KRGE treatmentdid not increase Ngb levels in NSCs, but stimulated astrocytes to secrete factors affecting NSCs’ differentiate intomature neurons and astrocytes. The KRGE-treated mouse retinas showed GFAP- and HIF-1α double-positive cells.

Co-treatment with si-HIF-1α-transfected KRGE–ACM blocked KRGE–ACM-induced NSC differentiation into astrocytesor Ngb-expressing neurons.

Conclusion: KRGE stimulates astrocytic HIF-1α, which regulates NSC differentiation into mature neuronsexpressing Ngb, thereby promoting regeneration by enhancing NSC–astrocyte crosstalk in the physiologicalretina and brain.

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Antiviral potential of ginseng : targeting human pathogenic viruses with compounds derived from ginseng Chen Huo, Jihye Baek, Ki Hyun Kim p. 105-117
(A) narrative review of Panax notoginseng : unique saponins and their pharmacological activities Wenbiao Li, Hailian Shi, Xiaojun Wu p. 118-133
Total saponins from Panax Japonicus regulate the ferritin heavy chain to reduce inflammation in aging adipose tissue by mediating iron metabolism Leiqi Zhu, Jihong Zhang, Yaqi Hu, Yifan Zhang, Shuwen Wang, Rui Wang, Qi Yuan, Yiyang Luo, Ding Yuan, Yumin He, Chengfu Yuan p. 134-144
Synergistic effects of ginsenoside Rb1 and peroxiredoxin 6 in enhancing myocardial injury treatment through anti-inflammatory, anti-oxidative, and anti-apoptotic mechanisms Runhong Mu, Yupeng Li, Yunhe Cui, Chuanbo Feng, Tingyu Li, Tengda Liu, Mingzhu Chang, Xiao Guo, Xingcheng Yi p. 145-155
Rare ginsenosides transformed from stems and leaves of Panax ginseng reverse obesity by promoting browning of white fat through PKA/CREB pathway via REGγ negative regulation Jianbo Chen, Jiyue Sha, Xiaohui Huo, Zhiman Li, Di Qu, Xueqing Li, Meijia Li p. 156-165
Korean red ginseng relieves the inflammation and oxidative stress induced by pseudo-typed SARS-CoV-2 Hyeon Jin Kim, Yena Oh, Sohee Moon, Jieun Oh, Ji Hye Kim, Seung Ho Lee, Sun Hee Hyun, Ji Hye Park, Hun-kun Ko, Jaehyeon Hwang, Han Gyung Kim, Dae-Hyuk Kweon, Jae Youl Cho p. 166-178
Ginsenoside Rg1 exerts antidepressant effect by regulating hepatic kynurenine metabolism through promoting the interaction between HNF4α and PGC1α Keke Jia, Shuman Pan, Wenyuan Wu, Yiming Sun, Qingyu Zhang p. 179-188
Korean red ginseng-induced astrocytic HIF-1α : a key regulator of neuroglobin derived from neural stem cell differentiation in physiologic retina and brain Sunhong Moon, Jinseo Park, Sueun Kim, Minsu Kim, Hui Su Jeon, Hyungsu Kim, Young-Myeong Kim, Ji-Yoon Kim, Yoon Kyung Choi p. 189-196
Panax ginseng exerts cardioprotective effect post myocardial infarction by attenuating myocardial fibrosis and inflammation through SIRT1 signaling pathways Honglin Xu, Mingjie Pang, Changlei Hu, Tong Xu, Guanghong Chen, Guoyong Zhang, Xin Han, Yue Hua, Yuting Wu, Jiayi Zhang, Yiming Bi, Bin Liu, Yingchun Zhou p. 197-207
(The) molecular mechanism of ginsenoside Rh2 and its octyl ester derivative on antiangiogenesis in cancer treatment : the battle between PI3K and ROS Qi-Rui Hu, Xin-Yi Zhong, Hua Feng, Xu-Chu Li, Zhi-Hong Zhang, Yao Pan, Ting Luo, Ze-Yuan Deng, Fang Chen p. 208-222

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