Heterophyllin B, a cyclopeptide from Pseudostellaria heterophylla, enhances cognitive function via neurite outgrowth and synaptic plasticity

Abstract

Neurite outgrowth‐induced construction of neural circuits and networks is responsible for memory generalization, consolidation, and retrieval. In this study, we found that the traditional Chinese medicine Pseudostellaria heterophylla promoted neurite regrowth and enhanced cognitive function in normal mice. Further, we orally administered Pseudostellaria heterophylla water extracts (PHE) to ICR mice, and detected heterophyllin B (HET‐B), an important cyclopeptide, in the plasma and cerebral cortex. We demonstrated that neurites were significantly elongated after coculturing with HET‐B for 4 days. Next, the intraperitoneal injection of HET‐B on seven consecutive days in 3‐month‐old ICR mice significantly enhanced the object recognition memory and object location memory than that in control. Immunohistochemical analysis indicated significantly increased β3‐tubulin–positive neurite density, synaptophysin, and postsynaptic density 95 in the perirhinal cortex and hippocampus after administering HET‐B. Furthermore, the concentration of neurotransmitters was measured using HPLC analysis; HET‐B significantly increased five‐levels of HT in the hippocampus, and decreased metabolites of dopamine, dihydroxyphenylacetic acid, and homovanillic acid, in the prefrontal cortex and hippocampus. Taken together, HET‐B induces neurite elongation and neurotransmitter regulation and possibly enhances cognitive memory.

The Ethnopharmacological, Phytochemical, and Pharmacological Review of Euryale ferox Salisb.: A Chinese Medicine Food Homology

“…Due to specific properties, such as good target selectivity, binding affinity, and low toxicity, cyclic peptides have become attractive lead compounds for drug development [50]. Multiple bioactive activities have been reported including antimicrobial, anti-infection, anti-tumors, anti-chronic kidney diseases, anti-diabetes, and memory improvement [51,52]. Using thin-layer in situ chemical reactions, several cyclic dipeptides (13-18) have been isolated from EFS.…”

The Emerging Evidence for a Protective Role of Fucoidan from Laminaria japonica in Chronic Kidney Disease-Triggered Cognitive Dysfunction

“…To explore the effects of fucoidan on CKD-triggered recognition memory deficits, we performed a novel object recognition test, object location test, and passive avoidance memory test, as described previously [20]. In the novel object recognition memory test, the mice equally explored the identical objects A and A' (preferential index approximately In the locomotion test, adenine treatment dramatically decreased the moved distance compared with control mice, while the drug-treated groups failed to reverse it (Figure 1C).…”

“…To explore the effects of fucoidan on CKD-triggered recognition memory deficits, we performed a novel object recognition test, object location test, and passive avoidance memory test, as described previously [20]. In the novel object recognition memory test, the mice equally explored the identical objects A and A' (preferential index approximately 50%).…”

“…The open field test is used for evaluating the autonomous behavior, exploratory behavior, and anxiety of experimental animals in novel environments. The experimental method referred to a previous method with minor modification [20]. The object recognition test and object location test were established according to the principle that an animal possesses an innate tendency to explore new objects or novel located objects.…”

“…The object recognition test and object location test were established according to the principle that an animal possesses an innate tendency to explore new objects or novel located objects. The experiments were performed as described previously with minor modification [20]. In the passive avoidance test, the box was divided into a light and dark zone.…”