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Ethnopharmacological Relevance: In vitro cultured calculus bovis (ICCB), which is produced based on the formation mechanism of bovine gallstones, is used to replace the natural bezoar. It has been used in the clinic to treat brain diseases, including stroke, Alzheimer's disease and depression., Aim of Study: ICCB is used to treat encephalopathy in the clinic. We explored the effects of ICCB on cerebral ischaemia-reperfusion injury (CIRI) and the potential associated mechanisms., Materials and Methods: Rats were subjected to middle cerebral artery occlusion for 90 min, followed by 24 h of reperfusion, after being given different concentrations of ICCB once a day for 3 days. Subsequently, the neurological scores, brain oedema and volume of cerebral infarction were measured, and the histopathological changes in the cortex neurons were observed by haematoxylin and eosin staining (H&E). Apoptosis was determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL). Ultrastructural changes in the mitochondria of the cortex were assessed by transmission electron microscopy (TEM). The apoptosis-related proteins Bax, Bcl-2, caspase-9, caspase-3, Mito-Cyt C and Cyto-Cyt C were detected by Western blotting., Results: Compared with those in the control group, the neurological scores, the volumes of cerebral infarction, and the brain water contents were significantly decreased in the ICCB groups at doses of 50 and 100 mg/kg. The ICCB treatment effectively decreased the neuronal apoptosis resulting from the CIRI-induced neuron injury. In addition, the histopathological damage and the mitochondria ultrastructure injury were partially improved in the CIRI rats after ICCB treatment. Western blotting analysis indicated that ICCB significantly decreased the expression of Bax, caspase-9, caspase-3 and Cyto-Cyt C protein levels while increasing the expression of Bcl-2 and Mito-Cyt C protein levels., Conclusion: The ICCB protected against CIRI by suppressing the mitochondria-mediated apoptotic signalling pathway., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Iridoid glycosides of Radix Scrophulariae (IGRS) are a group of the major bioactive components from Radix Scrophulariae with extensive pharmacological activities. The present study investigated the effects of IGRS on cerebral ischemia‑reperfusion injury (CIRI) and explored its potential mechanisms of action. A CIRI model in rats was established by occlusion of the right middle cerebral artery for 90 min, followed by 24 h of reperfusion. Prior to surgery, 30, 60 or 120 mg/kg IGRS was administered to the rats once a day for 7 days. Then, the neurological scores, brain edema and volume of the cerebral infarction were measured. The apoptosis index was determined by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling. The effects of IGRS on the histopathology of the cortex in brain tissues and the endoplasmic reticulum ultrastructure in the hippocampus were analyzed. Finally, the expression of endoplasmic reticulum stress (ERS)‑regulating mediators, endoplasmic reticulum chaperone BiP (GRP78), DNA damage‑inducible transcript 3 protein (CHOP) and caspase‑12, were detected by reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis. The volume of cerebral infarction and brain water content in the IGRS‑treated groups treated at doses of 60 and 120 mg/kg were decreased significantly compared with the Model group. The neurological scores were also significantly decreased in the IGRS‑treated groups. IGRS treatment effectively decreased neuronal apoptosis resulting from CIRI‑induced neuron injury. In addition, the histopathological damage and the endoplasmic reticulum ultrastructure injury were partially improved in CIRI rats following IGRS treatment. RT‑qPCR and western blot analysis data indicated that IGRS significantly decreased the expression levels of GRP78, CHOP and caspase‑12 at both mRNA and protein levels. The results of the present study demonstrated that IGRS exerted a protective effect against CIRI in brain tissue via the inhibition of apoptosis and ERS.