Transcriptomic and Metabolomic Profiling Reveals the Protective Effect of Acanthopanax senticosus (Rupr. & Maxim.) Harms Combined With Gastrodia elata Blume on Cerebral Ischemia-Reperfusion Injury.

The effects of current treatment strategies used in ischemic stroke are weakened by cerebral ischemia-reperfusion (CIR) injury. Suitable treatment regimens targeting CIR injury are still lacking. Two herbs, namely, Acanthopanax senticosus (Rupr. & Maxim.) Harms (ASE) and Gastrodia elata Blume (GEB), have been used as traditional Chinese medicine and are indicated in the treatment of stroke and cerebrovascular diseases. However, there are no studies that report the effects of ASE combined with GEB in the treatment of CIR injury. In this study, we used the Zea Longa method to induce CIR injury in male Wistar rats. Results of the pharmacodynamic studies revealed that co-administration of ASE and GEB may improve neuronal injury and prevent neuronal apoptosis by reducing oxidative stress and inflammation, and also help prevent CIR injury. On the basis of our hypothesis, we combined the results from transcriptomic and metabonomic analyses and found that ASE and GEB could prevent CIR injury by targeting phenylalanine, pyrimidine, methionine, and sphingolipid metabolism. Therefore, our study provides the basis for the compatibility and efficacy of ASE and GEB.

Studies on effect of Tongfengxiaofang in HUM model mice using a UPLC-ESI-Q-TOF/MS metabolomic approach.

Hyperuricemia (HUM) is a major risk factor for the development of gout. The traditional Chinese medicine (TCM) complex prescription Tongfengxiaofang (TFXF) is composed of a variety of TCMs. To study the therapeutic effect of TFXF on HUM mice and the mechanisms by which it exerts a therapeutic effect, the biochemical indices were measured and qPCR technique was used. In addition, plasma metabolomics analysis was carried out based on UPLC-Q-TOF/MS to evaluate the characteristics of the metabolic spectrum changes. TFXF significantly downregulated the contents of uric acid, urea nitrogen and creatinine in serum and the concentration of xanthine oxidase in liver of HUM mice. In addition, TFXF significantly inhibited the overexpression of uric acid transporter 1 and glucose transporter 9 and upregulated the expression of organic anion transporter 1 in the kidney. A total of 152 metabolites were identified and 11 key biomarkers were further selected from these pathways to understand the mechanism of TFXF on the arginine biosynthesis, galactose metabolism, pyrimidine metabolism, glycerophospholipid metabolism, tryptophan metabolism and the citrate cycle (TCA cycle). The results of this confirmed the effect of TFXF on HUM and revealed the metabolic activity mechanism.

Effects of Acanthopanax senticosus (Rupr. & Maxim.) Harms on cerebral ischemia-reperfusion injury revealed by metabolomics and transcriptomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Cerebral ischemia-reperfusion (CIR) injury is one of the main diseases leading to death and disability. Acanthopanax senticosus (Rupr. & Maxim.) Harms (AS), also known as Panax ginseng, has neuroprotective effects on anti-CIR injury. However, the underlying molecular mechanism of its therapeutic effects is not clear. AIM OF THE STUDY: To systematically study and explore the mechanism of Acanthopanax senticosus (Rupr. & Maxim.) Harms extract (ASE) in the treatment of CIR injury based on metabolomics and transcriptomics. MATERIALS AND METHODS: The pharmacological basis of ASE in the treatment of CIR was evaluated, and samples were used in plasma metabolomics and brain tissue transcriptomics to reveal potential biomarkers. Finally, according to online database, we analyzed biomarkers identified by the two technologies, explained reasons for the therapeutic effect of ASE, and identify therapeutic targets. RESULTS: A total of 53 differential metabolites (DMs) were identified in plasma and 3138 differentially expressed genes (DEGs) were identified in brain tissue from three groups of rats, including sham, ischemia-reperfusion (I/R), and ASE groups. Enrichment analysis showed that Nme6, Tk1, and Pold1 that are involved in the production of deoxycytidine and thymine were significantly up-regulated and Dck was significantly down-regulated by the intervention with ASE. These findings indicated that ASE participates in the pyrimidine metabolism by significantly regulating the balance between dCTP and dTTP. In addition, ASE repaired and promoted the lipid metabolism in rats, which might be due to the significant expression of Dgkz, Chat, and Gpcpd1. CONCLUSIONS: The findings of this study suggest that ASE regulates the significant changes in gene expression in metabolites pyrimidine, and lipid metabolism in CIR rats and plays an active role in the treatment of CIR injury through multiple targets and pathways.

The chemical profile of active fraction of Kalimeris indica and its quantitative analysis.

Kalimeris indica (L) Sch-Bip is a medicinal plant used by the Miao ethnic group in the Guizhou province of China. It is widely used as a fresh vegetable to treat colds, diarrhea and gastric ulcers. However, few studies have been conducted on the mechanism of its effect on colds, and its quality control. The anticomplement and antitussive activities of different polar extracts of K. indica were evaluated. Fifty-nine compounds, mainly including phenols and flavonoids, were identified in K. indica extract by ultra-high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. A method was established through ultra-high-performance liquid chromatography with a photodiode array to simultaneously determine the anticomplement and antitussive activity of five compounds in K. indica combining chemical identification with chemometrics for discrimination and quality assessment. Also, 3,5-dicaffeoylquinic acid and 4,5-dicaffeoylquinic acid exhibited significantly higher anticomplementary activity than the other three compounds. The quantitative data were further analyzed by principal component analysis and orthogonal partial least-squares discriminant analysis. Heatmap visualization was conducted to clarify the distribution of the major compounds in different geographical origins. Screening pharmacological activities by a combination of chemometrics and chemical identification might be an effective method for the quality control of K. indica.

Exploring the effects of Gastrodia elata Blume on the treatment of cerebral ischemia-reperfusion injury using UPLC-Q/TOF-MS-based plasma metabolomics.

Gastrodia elata Blume (Orchidaceae, GEB) is a medicinal plant that has been widely used in the treatment of cerebrovascular disease. This study explored the protective effects of GEB against cerebral ischemia-reperfusion using Information-Dependent Acquisition (IDA)-mediated UPLC-Q/TOF-MS-based plasma metabolomics. Cerebral ischemia-reperfusion (IR) injury was induced in male Wistar rats using the Zea Longa method. Biochemical and histological assays were performed to evaluate the therapeutic effects of GEB on IR rats. We found that the neurobehavioral scores and infarction areas of GEB and nimodipine treated groups were dramatically lower than those of the IR groups. Hematoxylin and Eosin (HE) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) showed that GEB significantly improved neuronal injury and prevented neuronal apoptosis. Biochemical analysis revealed that GEB prevented cerebral ischemia-reperfusion injury by regulating inflammation and oxidative injury. Through ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-metabolomics-based approaches, 43 plasma metabolites related to GEB treatment were detected, 6 of which significantly differed (p < 0.05) between the model and GEB groups. The levels of l-histidine, sphinganine, thymine, spermidine and deoxycytidine in the IR group were significantly higher than those in the sham group, but decreased following GEB treatment. Arachidonic acid levels were lower in the IR group, but dramatically increased in response to GEB. Pharmacodynamics and metabolomics confirmed that the mechanism of GEB in the treatment of cerebral ischemia was not only related to the reduction of inflammation, oxidation, neurotoxicity, and apoptosis, but also mediated through arachidonic acid metabolism, histidine metabolism, pyrimidine metabolism, arginine and proline metabolism, sphingolipid metabolism, and glycerophospholipid metabolism in vivo.

Lomatogonium Rotatum for Treatment of Acute Liver Injury in Mice: A Metabolomics Study.

Lomatogonium rotatum (L.) Fries ex Nym (LR) is used as a traditional Mongolian medicine to treat liver and bile diseases. This study aimed to investigate the hepatoprotective effect of LR on mice with CCl4-induced acute liver injury through conventional assays and metabolomics analysis. This study consisted of male mice (n = 23) in four groups (i.e., control, model, positive control, and LR). The extract of whole plant of LR was used to treat mice in the LR group. Biochemical and histological assays (i.e., serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), and histological changes of liver tissue) were used to evaluate LR efficacy, and metabolomics analysis based on GC-MS and LC-MS was conducted to reveal metabolic changes. The conventional analysis and metabolomic profiles both suggested that LR treatment could protect mice against CCl4-induced acute liver injury. The affected metabolic pathways included linoleic acid metabolism, α-linolenic acid metabolism, arachidonic acid metabolism, CoA biosynthesis, glycerophospholipid metabolism, the TCA cycle, and purine metabolism. This study identified eight metabolites, including phosphopantothenic acid, succinic acid, AMP, choline, glycerol 3-phosphate, linoleic acid, arachidonic acid, and DHA, as potential biomarkers for evaluating hepatoprotective effect of LR. This metabolomics study may shed light on possible mechanisms of hepatoprotective effect of LR.