Dengzhanxixin Injection Ameliorates Cognitive Impairment Through a Neuroprotective Mechanism Based on Mitochondrial Preservation in Patients With Acute Ischemic Stroke

Abstract

Acute ischemic stroke (AIS) is a global health burden and cognitive impairment is one of its most serious complication. Adequate interventions for AIS may have the potential to improve cognitive outcomes. In the present study, we selected Erigeron breviscapus (Vaniot) Hand.-Mazz. injection (Dengzhanxixin injection, DZXI), a widely used Chinese herbal injection, in contrast to edaravone as the positive control drug to test its potential to ameliorates neurological and cognitive impairments caused by AIS. We performed a 2-week randomized trial with these two drugs in AIS patients presenting mild to moderate cognitive impairments. Neuropsychological tests and MRI examinations showed that DZXI attenuated the neurological and cognitive impairments of patients and protected the grey matter in specific regions from ischemic damage. Notably, DZXI exerted better effects than edaravone in some neuropsychological tests, probably due to the protective effect of DZXI on grey matter. To explore the therapeutic mechanisms, we carried out an experiment with a middle cerebral artery occlusion rat model. We found that DZXI decreased the infarct volume and increased the survival of neuronal cells in the ischemic penumbra; furthermore, DZXI modulated the mitochondrial respiratory chain process and preserved the mitochondrial structure in the brain tissue. Overall, our data suggested that the administration of DZXI is effective at ameliorating neurological and cognitive impairments in AIS, and the underlying mechanisms are related to the protective effects of DZXI on cerebral neurons and neuronal mitochondria.

Natural products regulate mitochondrial function in cognitive dysfunction—A scoping review

“…The characteristics of the included studies are summarized in the Supplementary File . Of the 14 articles, one article was from the USA ( Gray et al, 2018 ), nine from China ( Pan et al, 2020 ; An et al, 2021 ; Huang et al, 2021 ; Sun et al, 2021 ; Yin et al, 2021 ; Liu et al, 2022b ; Ling et al, 2022 ; Ouyang et al, 2022 ; Yin et al, 2022 ), two from Korea ( Shin et al, 2019 ; Jang et al, 2020 ), and one from Taiwan ( Lu et al, 2021 ).…”

“…All articles used animal experiments except one, which was a mixed clinical trial ( An et al, 2021 ). Among the natural products investigated were DZXI ( An et al, 2021 ), CAW ( Gray et al, 2018 ; Lu et al, 2021 ), Chloroform fraction Actinidia arguta (CFAA) ( Ha et al, 2020 ), TMP from Ligusticum chuanxiong ( Huang et al, 2021 ), Schisandra chinensis extract (SCE), ascorbic acid (AA) ( Jang et al, 2020 ), (−)-Epicatechin (Epi) from Green tea ( Ling et al, 2022 ), GK from Ginkgo biloba ( Liu et al, 2022a ), Capsaicin from Capsicum ( Ouyang et al, 2022 ), CIN and ELA from Cinnamomum, Metabolite ( Pan et al, 2020 ), Red ginseng extract (RGE) ( Shin et al, 2019 ), SMYZD from Panax ginseng, Gastrodia elata ( Sun et al, 2021 ), Rheum ( Yin et al, 2022 ), and Rhein, emodin, aloe-emodin, chrysophanol, and physcion from Rheum ( Yin et al, 2021 ).…”

“…Among them, DZXI (Erigeron) treatment can protect mitochondrial functions and increase the resistance of neurons to neurodegeneration ( An et al, 2021 ). Asiatic acid ( Centella ) can not only prevent damage to the hippocampal synaptic mitochondrial structure in epileptic rats but can also affect mitochondrial proteins related to energy generation ( Gray et al, 2018 ; Lu et al, 2021 ).…”

“…injections (DZXI) (specifications: 5.32 mg scutellarin, 2.26 mg 3,4-O-dicaffeoylquinic acid, 1.10 mg 3,5-O-dicaffeoylquinic acid, 1.79 mg erigoster B, 2.70 mg 4,5-O-dicaffeoylquinic acid, and 11.26 mg erigeroster, 10 mL/ampoule, Lot No. 20180137) were provided by Yunnan Biovalley Pharmaceutical Co., Ltd. (Kunming, China), erigeroster (Lot No, 20190701, purity 93.3%) were provided by Yunnan Biovalley Pharmaceutical Co., Ltd. (Kunming, China) and Chengdu Pusi Biotechnology Co., Ltd. (Chengdu, China) ( An et al, 2021 ).…”

“…The natural products discussed here mainly refer to the natural ingredients extracted from botanical drugs. An et al (2021) reported Mitochondria are also involved in protein assembly and regulation and mediate cell proliferation, differentiation, and death. Mitochondria can initiate a protective program called the mitochondrial unfolded protein response (UPRmt) and use this protective mechanism to maintain normal mitochondrial function (Liu et al, 2022b).…”