Amomum tsaoko (AT) is a dietary botanical with laxative properties; however, the active ingredients and mechanisms are still unclear. The active fraction of AT aqueous extract (ATAE) for promoting defecation in slow transit constipation mice is the ethanol-soluble part (ATES). The total flavonoids of ATES (ATTF) were the main active component. ATTF significantly increased the abundance of Lactobacillus and Bacillus and reduced the dominant commensals, such as Lachnospiraceae, thereby changing the gut microbiota structure and composition. Meanwhile, ATTF changed the gut metabolites mainly enriched in pathways such as the serotonergic synapse. In addition, ATTF increased the serum serotonin (5-HT) content and mRNA expression of 5-hydroxytryptamine receptor 2A (5-HT_2A), Phospholipase A2 (PLA2), and Cyclooxygenase-2 (COX2), which are involved in the serotonergic synaptic pathway. ATTF increased Transient receptor potential A1 (TRPA1), which promotes the release of 5-HT, and Myosin light chain 3(MLC3), which promotes smooth muscle motility. Notably, we established a network between gut microbiota, gut metabolites, and host parameters. The dominant gut microbiota Lactobacillus and Bacillus, prostaglandin J2 (PGJ2) and laxative phenotypes showed the most significant associations. The above results suggest that ATTF may relieve constipation by regulating the gut microbiota and serotonergic synaptic pathway and has great potential for laxative drug development in the future.

Neurological disorders cause untold human disability and death each year. For most neurological disorders, the efficacy of their primary treatment strategies remains suboptimal. Microglia are associated with the development and progression of multiple neurological disorders. Targeting the regulation of microglia polarization has emerged as an important therapeutic strategy for neurological disorders. Their pro-inflammatory (M1)/anti-inflammatory (M2) phenotype microglia are closely associated with neuronal apoptosis, synaptic plasticity, blood-brain barrier integrity, resistance to iron death, and astrocyte regulation. LncRNA, a recently extensively studied non-coding transcript of over 200 nucleotides, has shown great value to intervene in microglia polarization. It can often participate in gene regulation of microglia by directly regulating transcription or sponging downstream miRNAs, for example. Through proper regulation, microglia can exert neuroprotective effects, reduce neurological damage and improve the prognosis of many neurological diseases. This paper reviews the progress of research linking lncRNAs to microglia polarization and neurological diseases.

Amomum tsaoko is an important homologous medicinal and food plant, and its fruit is rich in flavonoids. However, few studies have reported the preparation and bioactivity of flavonoids in A. tsaoko (ATF). In this study, the optimal conditions for ultrasound-assisted extraction of ATF were identified through response surface optimization. HPD300 was identified as the best resin for the purification of ATF, as it exhibited a Freundlich model-conformative adsorption isotherm. Among the different concentrations of ethanol, 20 % and 30 % resulted in higher flavonoid purity (>90 %) and stronger antioxidant and α-glucosidase inhibition activities. A widely targeted metabolomics assay revealed that the relative abundance of flavonoids in a mixture of 20 % and 30 % ethanol eluates was greater than 73 %, which mainly contained (+)-epicatechin, isoquercitrin, astragalin kaempferol-3-O-rutinoside, and procyanidin B2. These findings provide a theoretical basis for the in-depth development and potential use of ATF in the functional food, cosmetic and pharmaceutical industries.

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Constipation is a prodromal symptom of PD. It is important to investigate the pathogenesis of constipation symptoms in PD. Rotenone has been successfully used to establish PD animal models. However, the specific mechanism of rotenone-induced constipation symptoms is not well understood. In this work, we found that constipation symptoms appeared earlier than motor impairment in mice gavaged with a low dose of rotenone (30 mg/kg·BW). Rotenone not only caused loss of dopaminergic neurons and accumulation of α-synuclein, but also significantly reduced serum 5-HT levels and 5-HTR4 in the striatum and colon. The mRNA expression of aquaporins, gastrointestinal motility factors (c-Kit, Cx43, smMLCK and MLC-3) in mouse colon was also significantly regulated by rotenone. In addition, both colon and brain showed rotenone-induced inflammation and barrier dysfunction; the PI3K/AKT pathway in the substantia nigra and colon was also significantly inhibited by rotenone. Importantly, the structure, composition and function of the gut microbiota were also significantly altered by rotenone. Some specific taxa were closely associated with motor and constipation symptoms, inflammation, and gut and brain barrier status in PD mice. Akkermansia, Staphylococcus and Lachnospiraceae_UCG—006 may play a role in exacerbating constipation symptoms, whereas Acinetobacter, Lactobacillus, Bifidobacterium, Solibacillus and Eubacterium_xylanophilum_groups may be beneficial in stimulating gastrointestinal peristalsis, maintaining motor function and alleviating inflammation and barrier damage in mice. In conclusion, low-dose rotenone can cause parkinsonism with constipation symptoms in mice by disrupting the intestinal microecosystem and inhibiting the PI3K-AKT pathway and gastrointestinal motility.

Ulcerative colitis (UC) is a global disease for which there is little of effective treatment options, thus creating an urgent need for the development of new drug candidates from natural and functional foods. Amomum tsaoko Crevost et Lemarie is a kind of medicinal and food herb that is rich in flavonoids. However, the pharmacological effects of Amomum tsaoko flavonoids (ATF) on UC have not yet been reported. The present study established a mouse model of UC using 3% dextran sulfate sodium (DSS), and modern molecular biology techniques such as IHC, RT-qPCR, Western blot, and 16S rRNA gene analysis were used to investigate the effect of ATF in UC mice. The results demonstrated that a high dose of ATF (100 mg/kg) led to a significant restoration of body weight, disease activity index score, and colon length, in addition to ameliorating colonic tissue damage in UC mice. ATF reduced the serum levels of lipopolysaccharides (LPS), inhibited the activation of the colonic TLR4/NF-κB/NLRP3 signaling pathway, and increased the mRNA expression of tight junction proteins such as ZO-1, Occludin, and Claudin4. Furthermore, ATF was found to reduce the relative abundance of the DSS-induced conditional pathogenic (Escherichia-Shigella, Colidextribacter, and Oscillibacter), increase the potential probiotic taxa (Akkermansia, Bifidobacterium and unclassified_f__Atopobiaceae). Interestingly, these genera were found to be significantly correlated with the UC core phenotypic indicators. These findings indicated that ATF may alleviate UC symptoms by modulating the gut microbiota-LPS/TLR4/NF-κB/NLRP3 axis. The present study has the potential to serve as a valuable reference point for understanding the role of natural flavonoids in the prevention of inflammatory diseases, and to expand the future applications of ATF in the fields of food and medicine.

Vidarabine (VID) is an antiviral medication that is commonly utilized to treat conditions such as hand, foot, and mouth disease and herpes. Constipation is a prevalent complication of these diseases. Could VID treat these diseases by influencing defecation behavior? To date, no studies have been conducted on the potential of VID to relieve constipation. Therefore, a systematic investigation was conducted into the laxative effects and mechanisms of VID using loperamide-induced functional constipated mice. The findings indicate that the oral administration of VID promoted gastrointestinal peristalsis, improved fecal properties, facilitated defecation, and demonstrated a significant laxative effect on functional constipated mice. It has been demonstrated that VID may increase the water content of feces by regulating the expression of aquaporins (AQP3, AQP4, and AQP8) in the colon and promote intestinal motility by regulating the expression of neurotransmitters (AChE and VIP) and the adenosine A2A receptor–myosin light chain (A2AR-MLC) signaling pathway in constipated mice. Concurrently, VID may also reduce colonic inflammation in constipated mice, reinforce the gut barrier function, and alter the composition and structure of the gut microbial community. Some microbial taxa, including Firmicutes and Lactobacillus, were found to be associated with the alleviation of constipation, while other taxa, including Bacteroidetes, Proteobacteria, Muribaculaceae, Muribaculum, norank__f__Desulfovibrionaceae, and Parasutterella, were found to be associated with constipation. These results indicate that the gut microbiota may play a significant role in the alleviation of constipation by VID. These findings confirm the efficacy of VID in a constipated animal model, which justifies further investigation into its potential clinical applications.