Zhengrong Li: Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, China.
Yuwen Liu: Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, China.
Kedi Liu: TANK Medicinal Biology Institute of Xi'an, Xi'an 710065, China.
Xingru Tao: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Naping Hu: Department of Pharmacy, General Hospital of Xinjiang Production and Construction Corps, Urumqi 830092, China.
Wangting Li: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Jialin Duan: Xi'an Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Medical Research, Northwestern Polytechnical University, Xi'an 710072, China; Shanghai Minhang Collaborative Innovation Center of Northwestern Polytechnical University, Shanghai 201108, China. Electronic address: duanjl@nwpu.edu.cn.
Aralia taibaiensi, widely distributed in western China, particularly in the Qinba Mountains, has been utilized as a folk medicine for treating diabetes, gastropathy, rheumatism, and cardiovascular diseases. Saponins from A. taibaiensis (sAT) have demonstrated protective effects against oxidative stress and mitochondrial dysfunction induced by ischemia/reperfusion (I/R). However, the underlying mechanisms remain unclear. In vivo, middle cerebral artery occlusion/reperfusion (MCAO/R) induced inflammatory infiltration, neuronal injury, cell apoptosis, mitochondrial dysfunction, and oxidative stress in the ischaemic penumbra, which were effectively mitigated by sAT. sAT increased the mRNA and protein expression levels of apelin and its receptor apelin/apelin receptors (ARs) both in vivo and in vitro. (Ala13)-Apelin-13 (F13A) and small interfering RNA (siRNA) abolished the regulatory effects of sAT on neuroprotection mediated by adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)/protein kinase B (Akt). Furthermore, sAT induced apelin/AR expression by simultaneously inhibiting P38 mitogen-activated protein kinase (P38 MAPK)/activating transcription factor 4 (ATF4) and upregulating hypoxia-inducible factor-1�� (HIF-1��). Our findings indicate that sAT regulates apelin/AR/AMPK by inhibiting P38 MAPK/ATF4 and upregulating HIF-1a, thereby suppressing oxidative stress and mitochondrial dysfunction.
