The traditional herb Polygonum hydropiper from China: a comprehensive review on phytochemistry, pharmacological activities and applications.

CONTEXT: Polygonum hydropiper L. (Polygonaceae) (PH) is a traditional Chinese traditional medicine with a pungent flavor and mild drug properties. PH is mainly distributed in the channel tropism in the stomach and large intestine. PH has multiple uses and can be used to treat a variety of diseases for a long time. OBJECTIVE: This review summarizes the phytochemical and pharmacological activities, and applications of PH from 1980 to 2022. We also provide suggestions for promoting further research and developing additional applications of PH. METHODS: The data and information on PH from 1980 to 2022 reviewed in this article were obtained from scientific databases, including Science Direct, PubMed, Science Citation Index, SciFinder Scholar (SciFinder), Springer, American Chemical Society (ACS) Publications, and China National Knowledge Infrastructure (CNKI), etc. Some information was obtained from classic literature on traditional Chinese medicines. The search terms were Polygonum hydropiper, phytochemistry compositions of Polygonum hydropiper, pharmacological activities of Polygonum hydropiper, and applications of Polygonum hydropiper. RESULTS: The comprehensive analysis of the literature resulted in 324 compounds being isolated, identified, and reported from PH. Regarding traditional uses, the majority of phytochemical and pharmacological studies have indicated the diverse bioactivities of PH extracts, flavonoids, and volatile oil elements, including antibacterial, antifungal, insecticidal, antioxidant, and anti-inflammatory. CONCLUSIONS: PH has a long history of diversified medicinal uses, some of which have been verified in modern pharmacological studies. Further detailed studies are required to establish scientific and reasonable quality evaluation standards and action mechanisms of active constituents from PH.

Axonal iron transport in the brain modulates anxiety-related behaviors.

Iron is essential for a broad range of biochemical processes in the brain, but the mechanisms of iron metabolism in the brain remain elusive. Here we show that iron functionally translocates among brain regions along specific axonal projections. We identified two pathways for iron transport in the brain: a pathway from ventral hippocampus (vHip) to medial prefrontal cortex (mPFC) to substantia nigra; and a pathway from thalamus (Tha) to amygdala (AMG) to mPFC. While vHip-mPFC transport modulates anxiety-related behaviors, impairment of Tha-AMG-mPFC transport did not. Moreover, vHip-mPFC iron transport is necessary for the behavioral effects of diazepam, a well-known anxiolytic drug. By contrast, genetic or pharmacological promotion of vHip-mPFC transport produced anxiolytic-like effects and restored anxiety-like behaviors induced by repeated restraint stress. Taken together, these findings provide key insights into iron metabolism in the brain and identify the mechanisms underlying iron transport in the brain as a potential target for development of novel anxiety treatments.

[Optimization of polysaccharide extraction from Hippocampus by deep neural network and Box-Behnken design-response surface methodology].

In this paper, the extraction rate of crude polysaccharides and the yield of polysaccharides from Hippocampus served as test indicators. The comprehensive evaluation indicators were assigned by the R language combined with the entropy weight method. The Box-Behnken design-response surface methodology(BBD-RSM) and the deep neural network(DNN) were employed to screen the optimal parameters for the polysaccharide extraction from Hippocampus. These two modeling methods were compared and verified experimentally for the process optimization. This study provides a reference for the industrialization of effective component extraction from Chinese medicinals and achieves the effective combination of modern technology and traditional Chinese medicine.

A Study Against Colon Cancer Mechanism of Xanthium Sibiricum Herba Based on Computer Simulation and Bioinformatics.

INTRODUCTION: Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs. AIM: This study aims to explores the bioactivity and the anti-cancer mechanism of XSH. METHODS: In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti-cancer mechanism of XSH. RESULTS: Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were ß-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted. DISCUSSION: Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with ß-sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells. CONCLUSION: This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis.

The Ghrelin/Growth Hormone Secretagogue Receptor System Is Involved in the Rapid and Sustained Antidepressant-Like Effect of Paeoniflorin.

Major depressive disorder (MDD) is a debilitating mental illness affecting people worldwide. Although significant progress has been made in the development of therapeutic agents to treat this condition, fewer than half of all patients respond to currently available antidepressants, highlighting the urgent need for the development of new classes of antidepressant drugs. Here, we found that paeoniflorin (PF) produced rapid and sustained antidepressant-like effects in multiple mouse models of depression, including the forced swimming test and exposure to chronic mild stress (CMS). Moreover, PF decreased the bodyweight of mice without affecting food intake and glucose homeostasis, and also reduced the plasma levels of total ghrelin and the expression of ghrelin O-acyltransferase in the stomach; however, the plasma levels of ghrelin and the ghrelin/total ghrelin ratio were unaffected. Furthermore, PF significantly increased the expression of growth hormone secretagogue receptor 1 alpha (GHSR1α, encoded by the Ghsr gene) in the intestine, whereas the levels of GHSR1α in the brain were only marginally downregulated following subchronic PF treatment. Finally, the genetic deletion of Ghsr attenuated the antidepressant-like effects of PF in mice exposed to CMS. These results suggested that increased GHSR1α expression in the intestine mediates the antidepressant-like effects of PF. Understanding peripheral ghrelin/GHSR signaling may provide new insights for the screening of antidepressant drugs that produce fast-acting and sustained effects.

Liver Soluble Epoxide Hydrolase Regulates Behavioral and Cellular Effects of Chronic Stress.

Major depression is a serious global health concern; however, the pathophysiology underlying this condition remains unclear. While numerous studies have focused on brain-specific mechanisms, few have evaluated the role of peripheral organs in depression. Here, we show that the liver activates an intrinsic metabolic pathway that can modulate depressive-like behavior. We find that chronic stress specifically increases the protein levels of monomeric and oligomeric soluble epoxide hydrolase (sEH), a key enzyme in epoxyeicosatrienoic acid (EET) signaling, in the liver. Hepatic deletion of Ephx2 (which encodes sEH) results in antidepressant-like effects, while the hepatic overexpression of sEH induces depressive phenotypes. The activity of sEH in hepatocytes modulates the plasma levels of 14,15-EET, which then interacts with astrocytes in the medial prefrontal cortex to mediate the effects of hepatic Ephx2 deletion. These results suggest that targeting mechanisms underlying the hepatic response to stress would increase our therapeutic options for the treatment of depression.

Down-Regulation of Neuregulin1/ErbB4 Signaling in the Hippocampus Is Critical for Learning and Memory.

Hippocampal function is important for learning and memory, and dysfunction of the hippocampus has been linked to the pathophysiology of neuropsychiatric diseases such as schizophrenia. Neuregulin1 (NRG1) and ErbB4, two susceptibility genes for schizophrenia, reportedly modulate long-term potentiation (LTP) at hippocampal Schaffer collateral (SC)-CA1 synapses. However, little is known regarding the contribution of hippocampal NRG1/ErbB4 signaling to learning and memory function. Here, quantitative real-time PCR and Western blotting were used to assess the mRNA and protein levels of NRG1 and ErbB4. Pharmacological and genetic approaches were used to manipulate NRG1/ErbB4 signaling, following which learning and memory behaviors were evaluated using the Morris water maze, Y-maze test, and the novel object recognition test. Spatial learning was found to reduce hippocampal NRG1 and ErbB4 expression. The blockade of NRG1/ErbB4 signaling in hippocampal CA1, either by neutralizing endogenous NRG1 or inhibiting/ablating ErbB4 receptor activity, enhanced hippocampus-dependent spatial learning, spatial working memory, and novel object recognition memory. Accordingly, administration of exogenous NRG1 impaired those functions. More importantly, the specific ablation of ErbB4 in parvalbumin interneurons also improved learning and memory performance. The manipulation of NRG1/ErbB4 signaling in the present study revealed that NRG1/ErbB4 activity in the hippocampus is critical for learning and memory. These findings might provide novel insights on the pathophysiological mechanisms of schizophrenia and a new target for the treatment of Alzheimer's disease, which is characterized by a progressive decline in cognitive function.

Astrocyte-derived ATP modulates depressive-like behaviors.

Major depressive disorder (MDD) is a cause of disability that affects approximately 16% of the world's population; however, little is known regarding the underlying biology of this disorder. Animal studies, postmortem brain analyses and imaging studies of patients with depression have implicated glial dysfunction in MDD pathophysiology. However, the molecular mechanisms through which astrocytes modulate depressive behaviors are largely uncharacterized. Here, we identified ATP as a key factor involved in astrocytic modulation of depressive-like behavior in adult mice. We observed low ATP abundance in the brains of mice that were susceptible to chronic social defeat. Furthermore, we found that the administration of ATP induced a rapid antidepressant-like effect in these mice. Both a lack of inositol 1,4,5-trisphosphate receptor type 2 and transgenic blockage of vesicular gliotransmission induced deficiencies in astrocytic ATP release, causing depressive-like behaviors that could be rescued via the administration of ATP. Using transgenic mice that express a Gq G protein-coupled receptor only in astrocytes to enable selective activation of astrocytic Ca(2+) signaling, we found that stimulating endogenous ATP release from astrocytes induced antidepressant-like effects in mouse models of depression. Moreover, we found that P2X2 receptors in the medial prefrontal cortex mediated the antidepressant-like effects of ATP. These results highlight astrocytic ATP release as a biological mechanism of MDD.