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Previous studies have revealed the microbial metabolism of dietary choline in the gut, leading to its conversion into trimethylamine (TMA). Polymethoxyflavones (PMFs), exemplified by tangeretin, have shown efficacy in mitigating choline-induced cardiovascular inflammation. However, the specific mechanism by which these compounds exert their effects, particularly in modulating the gut microbiota, remains uncertain. This investigation focused on tangeretin, a representative PMFs, to explore its influence on the gut microbiota and the choline–TMA conversion process. Experimental results showed that tangeretin treatment significantly attenuated the population of CutC–active bacteria, particularly Clostridiaceae and Lactobacillus, induced by choline chloride in rat models. This inhibition led to a decreased efficiency in choline conversion to TMA, thereby ameliorating cardiovascular inflammation resulting from prolonged choline consumption. In conclusion, tangeretin’s preventive effect against cardiovascular inflammation is intricately linked to its targeted modulation of TMA–producing bacterial activity.

Excessive reactive oxygen species (ROS) production contributes to brain ischemia/reperfusion (I/R) injury through many mechanisms including inflammation, apoptosis, and cellular necrosis. Chebulic acid (CA) isolated from Terminalia chebula has been found to have various biological effects, such as antioxidants. In this study, we investigated the mechanism of the anti-hypoxic neuroprotective effect of CA in vitro and in vivo. The results showed that CA could protect against oxygen-glucose deprivation/reoxygenation (OGD/R) induced neurotoxicity in SH-SY5Y cells, as evidenced by the enhancement of cell viability and improvement of total superoxide dismutase (T-SOD) in SH-SY5Y cells. CA also attenuated OGD/R-induced elevations of malondialdehyde (MDA) and ROS in SH-SY5Y cells. Nuclear factor-E2-related factor 2 (Nrf2) is one of the key regulators of endogenous antioxidant defense. CA acted as antioxidants indirectly by upregulating antioxidant-responsive-element (ARE) and Nrf2 nuclear translocation to relieve OGD/R-induced oxidative damage. Furthermore, the results showed that CA treatment resulted in a significant decrease in ischemic infarct volume and improved performance in the motor ability of mice 24 h after stroke. This study provides a new niche targeting drug to oppose ischemic stroke and reveals the promising potential of CA for the control of ischemic stroke in humans.

Current therapies for ischemic stroke are insufficient due to the lack of specific drugs. This study aimed to investigate the protective activity of polyphenol extracts from Terminalia chebula against cerebral ischemia-reperfusion induced damage. Polyphenols of ethyl acetate and n-butanol fractions were extracted from T. chebula. BV2 microglial cells exposed to oxygen-glucose deprivation/reoxygenation and mice subjected to middle cerebral artery occlusion/reperfusion were treated by TPE and TPB. Cell viability, cell morphology, apoptosis, mitochondrial membrane potential, enzyme activity and signaling pathway related to oxidative stress were observed. We found that TPE and TPB showed strong antioxidant activity in vitro. The protective effects of TPE and TPB on cerebral ischemia-reperfusion injury were demonstrated by enhanced antioxidant enzyme activities, elevated level of the nucleus transportation of nuclear factor erythroid 2-related factor 2 and expressions of antioxidant proteins, with a simultaneous reduction in cell apoptosis and reactive oxygen species level. In conclusion, TPE and TPB exert neuroprotective effects by stimulating the Nrf2 signaling pathway, thereby inhibiting apoptosis.

Abstract Background Understanding the process of relapse to abused drugs and ultimately developing treatments that can reduce the incidence of relapse remains the primary goal for the study of substance dependence. Therefore, exploring the metabolite characteristics during the relapse stage is valuable. Methods A heroin self-administered rat model was employed, and analysis of the 1H-nuclear magnetic resonance-based metabolomics was performed to investigate the characteristic metabolite profile upon reintroduction to the drug after abstinence. Results Sixteen metabolites in the serum of rats, including phospholipids, intermediates in TCA (Tricarboxylic Acid Cycle) cycle, keto bodies, and precursors for neurotransmitters, underwent a significant change in the reinstatement stage compared with those in the control group. In particular, energy production was greatly disturbed as evidenced by different aspects such as an increase in glucose and decrease in intermediates of glycolysis and the TCA cycle. The finding that the level of 3-hydroxybutyrate and acetoacetate increased significantly suggested that energy production was activated from fatty acids. The concentration of phenylalanine, glutamine, and choline, the precursors of major neurotransmitters, increased during the reinstatement stage which indicated that an alteration in neurotransmitters in the brain might occur along with the disturbance in substrate supply in the circulatory system. Conclusions Heroin reinforcement resulted in impaired energy production via different pathways, including glycolysis, the TCA cycle, keto body metabolism, etc. A disturbance in the substrate supply in the circulatory system may partly explain heroin toxicity in the central nervous system. These findings provide new insight into the mechanism underlying the relapse to heroin use.

Objective: To study the effect and mechanism of electroacupuncture at "Baihui, Yintang and Shuigou" acupoints on learning and memory in Post-Stroke Cognitive Impairment (PSCI) mice. Methods: 52 male C57BL/6 mice were used to establish a MACO model by using middle cerebral artery occlusion (n=38), while the Sham only ligated at the distal end of the external carotid artery (n=14). After 28 days, the MCAO was divided into three groups based on the escape latency of Morris water maze: non cognitive impairment (MNP), post-stroke cognitive impairment (MP), and electroacupuncture intervention group (MPEA). In the MPEA, electroacupuncture at "Baihui and Yintang" acupoints was performed for 20 minutes (density wave, 2/15HZ and 1mA) supplemented by acupuncture at "Shuigou" acupoints once a day with a 6-day course of treatment. The intervention last for 2 courses with a 1-day interval. Morris water maze was used to detect the cognitive function of mice in each group; Nissl staining was used to observe hippocampal neurons; Western blot was used to detect the expression of GluA1, Syp, and Syt-1 in the affected hippocampus; IHC was used to detect the expression of Syp in the CA1 region of the contralateral hippocampus. Conclusion: Acupuncture at points "Baihui, Yintang, and Shuigou" can improve the learning and memory abilities of PSCI mice, and its mechanism is related to synaptic plasticity of hippocampus. [ABSTRACT FROM AUTHOR]