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The quality of Chinese materia medica (CMM) is a challenging and focused topic in the modernization of traditional Chinese medicine (TCM). A profound comprehension of the morphology, structure, active constituents, and dynamic changes during the whole process of CMM growth is essential, which needs highly precise contemporary techniques for in-depth elucidation. Magnetic resonance imaging (MRI) is a cutting-edge tool integrating the benefits of both nuclear magnetic resonance (NMR) spectroscopy and imaging technology. With real-time, non-destructive, and in situ detection capabilities, MRI has been previously used for monitoring internal and external structures of plants alongside compounds during physiological processes in vivo. Here, factors involved in the holistic quality evaluation of CMMs were investigated. Given the applications of MRI in various plants, several representative CMMs were used as examples to demonstrate a methodology of quality visualization by MRI, embodying holistically monitoring the real-time macroscopic morphology, mesoscopic structure, and microscopic metabolites non-destructively in situ. Taken together, the review not only presents a pioneering application mode for utilizing MRI for CMM quality visualization but also holds promise for advancing the quality control and evaluation of CMMs.

Backgrounds: Mature angiogenesis plays a critical role in improving cerebral ischemia-reperfusion injury (CIRI). Glycolysis serves as the primary energy source for brain microvascular endothelial cells (BMECs), whereas other vascular cells rely on aerobic respiration. Therefore, intercellular variations in energy metabolism could influence mature angiogenesis. Taohong Siwu Decoction (THSWD) has demonstrated efficacy in treating ischemic stroke (IS), yet its potential to promote mature angiogenesis through glycolysis activation remains unclear.Methods: In this study, we established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in vivo and an oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. We assessed neuroprotective effects using neurobehavioral scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxylin-eosin (HE) staining, and Nissl staining in MCAO/R rats. Additionally, we evaluated mature angiogenesis and glycolysis levels through immunofluorescence, immunohistochemistry, and glycolysis assays. Finally, we investigated THSWD’s mechanism in linking glycolysis to mature angiogenesis in OGD/R-induced BMECs.Results:In vivo experiments demonstrated that THSWD effectively mitigated cerebral damage and restored neurological function in MCAO/R rats. THSWD significantly enhanced CD31, Ang1, PDGFB, and PDGFR-β expression levels, likely associated with improved glucose, pyruvate, and ATP levels, along with reduced lactate and lactate/pyruvate ratios. In vitro findings suggested that THSWD may boost the expression of mature angiogenesis factors (VEGFA, Ang1, and PDGFB) by activating glycolysis, increasing glucose uptake and augmenting lactate, pyruvate, and ATP content, thus accelerating mature angiogenesis.Conclusion: THSWD could alleviate CIRI by activating the glycolysis pathway to promote mature angiogenesis. Targeting the glycolysis-mediated mature angiogenesis alongside THSWD therapy holds promise for IS treatment.

It is necessary to explore potent therapeutic agents via regulating gut microbiota and metabolism to combat Parkinson's disease (PD). Dioscin, a bioactive steroidal saponin, shows various activities. However, its effects and mechanisms against PD are limited. In this study, dioscin dramatically alleviated neuroinflammation and oxidative stress, and restored the disorders of mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). 16 S rDNA sequencing assay demonstrated that dioscin reversed MPTP-induced gut dysbiosis to decrease Firmicutes-to-Bacteroidetes ratio and the abundances of Enterococcus, Streptococcus, Bacteroides and Lactobacillus genera, which further inhibited bile salt hydrolase (BSH) activity and blocked bile acid (BA) deconjugation. Fecal microbiome transplantation test showed that the anti-PD effect of dioscin was gut microbiota-dependent. In addition, non-targeted fecal metabolomics assays revealed many differential metabolites in adjusting steroid biosynthesis and primary bile acid biosynthesis. Moreover, targeted bile acid metabolomics assay indicated that dioscin increased the levels of ursodeoxycholic acid, tauroursodeoxycholic acid, taurodeoxycholic acid and β-muricholic acid in feces and serum. In addition, ursodeoxycholic acid administration markedly improved the protective effects of dioscin against PD in mice. Mechanistic test indicated that dioscin significantly up-regulated the levels of takeda G protein-coupled receptor 5 (TGR5), glucagon-like peptide-1 receptor (GLP-1R), GLP-1, superoxide dismutase (SOD), and down-regulated NADPH oxidases 2 (NOX2) and nuclear factor-kappaB (NF-κB) levels. Our data indicated that dioscin ameliorated PD phenotype by restoring gut dysbiosis and regulating bile acid-mediated oxidative stress and neuroinflammation via targeting GLP-1 signal in MPTP-induced PD mice, suggesting that the compound should be considered as a prebiotic agent to treat PD in the future.

Nine major cell populations among 46,716 cells were identified in mouse intestinal ischemia‒reperfusion (II/R) injury by single-cell RNA sequencing. For enterocyte cells, 11 subclusters were found, in which enterocyte cluster 1 (EC1), enterocyte cluster 3 (EC3), and enterocyte cluster 8 (EC8) were newly discovered cells in ischemia 45 min/reperfusion 720 min (I 45 min/R 720 min) group. EC1 and EC3 played roles in digestion and absorption, and EC8 played a role in cell junctions. For TA cells, after ischemia 45 min/reperfusion 90 min (I 45 min/R 90 min), many TA cells at the stage of proliferation were identified. For Paneth cells, Paneth cluster 3 was observed in the resting state of normal jejunum. After I 45 min/R 90 min, three new subsets were found, in which Paneth cluster 1 had good antigen presentation activity. The main functions of goblet cells were to synthesize and secrete mucus, and a novel subcluster (goblet cluster 5) with highly proliferative ability was discovered in I 45 min/R 90 min group. As a major part of immune system, the changes in T cells with important roles were clarified. Notably, enterocyte cells secreted Guca2b to interact with Gucy2c receptor on the membranes of stem cells, TA cells, Paneth cells, and goblet cells to elicit intercellular communication. One marker known as glutathione S-transferase mu 3 (GSTM3) affected intestinal mucosal barrier function by adjusting mitogen-activated protein kinases (MAPK) signaling during II/R injury. The data on the heterogeneity of intestinal cells, cellular communication and the mechanism of GSTM3 provide a cellular basis for treating II/R injury.

The gut microbiota is inextricably linked to ulcerative colitis (UC). The therapeutic effect of Dendrobium huoshanense polysaccharides (DHP) on ulcerative colitis has been confirmed, but whether it acts through the intestinal flora is still unknown. The study aimed to investigate the potential mechanisms of DHP intervention in UC mice by combining metabolomics of intestinal contents and gut flora analysis. The results showed that DHP alleviated UC symptoms while improving colonic mucosal barrier function and inflammatory manifestations. A total of 12 potential biomarkers were significantly altered in metabolomics concerning tryptophan metabolism, vitamin B6 metabolism, regulation of sodium reabsorption by aldosterone, and steroid hormone biosynthesis. DHP reversed the abundance of Fusobacteriota, Deferribacterota and Bacteroidetes, and significantly increased Desulfobacteriota. DHP significantly decreased the relative abundance of Clostridioides, while increasing Alistipes, and Rikenella. In conclusion, through metabolomics and 16s RNA sequencing methods, we explored the mechanism of preventive effects of Dendrobium huoshanense on UC.

Objectives: To investigated the metrorrhagia volume-reduction activity, anti-inflammatory activity and repair-promoting activity of Clinopodium chinense (Benth.) O. Kuntze. Methods: An abnormal uterine bleeding (AUB) model was induced via oral administration of mifepristone and misoprostol to pregnant rats, which were treated with the total extract of C. chinense (TEC). After 7 days, the metrorrhagia volume was measured, the levels of TXB2, 6-keto-PGF1α, IL-6 and TNF-α were measured by ELISA, the pathological changes and micro vessel density (MVD) of the endometrium were evaluated using HE and immunofluorescence staining, and the expression of VEGF, MMP-2/9 and TGF-β were assessed by Western blotting. Preliminary phytochemicals were screened and identified by UPLC-Q-TOF-MS. Results: Eleven compounds in C. chinense were identified via comparison to standard substances. The results of animal experiment showed TEC could reduce metrorrhagia volume, alleviate pathological injury and increase MVD to promote recovery of the endometrium; TEC could also increase the levels of TXB2 and the expression of VEGF, TGF-β, decrease the levels of IL-6, TNF-α and the expression of MMP-2/9. Conclusions: TEC showed beneficial effects on treating AUB by reducing metrorrhagia volume, inhibiting the inflammatory response and promoting the repair of the endometrium. Additionally, TEC also showed great haemostatic potential in AUB. Keywords: Biomolecules, C. chinense, Abnormal uterine bleeding, Metrorrhagia, UPLC-Q-TOF-MS

It has been reported that ascorbic acid inhibits non-alcoholic fatty liver disease partially by activating fatty acid β-oxidation. However, little is known about the mechanism of ascorbic acid-mediated lipid synthesis. Western blot, qRT-PCR and immunofluorescent staining were used to determine if ascorbic acid can regulate expression of liver X receptor α (LXRα) and AMP-activated protein kinase α (AMPKα), which are key regulators of lipogenic genes. In hepatocytes, ascorbic acid decreased cellular lipid accumulation. Mechanistically, ascorbic acid inhibited expression of the genes for lipid synthesis by reducing LXRα nuclear translocation and activating AMPKα. In vivo, administration of ascorbic acid decreased triglyceride levels in serum and liver as well as FFA levels in the liver. Taken together, AMPKα/LXRα-mediated reduction of lipid accumulation in the liver is a novel activity of ascorbic acid on lipid metabolism, suggesting that ascorbic acid is an effective and safe dietary supplement to ameliorate hypertriglyceridemia.

C42H42F2N2O6, monoclinic, P21/c (no. 14), a = 20.159(3) Å, b = 8.3357(10) Å, c = 21.372(3) Å, β = 103.130(3)°, V = 3497.4(8) Å3, Z = 4, Rgt(F) = 0.0414, wRref(F2) = 0.1083, T = 113(2) K.

Our previous studies showed that the early use of calpain inhibitors reduces calpain activity in multiple brain regions, and that postnatal treatment with calpeptin may lead to cerebellar motor dysfunction. However, it remains unclear whether postnatal calpeptin application affects hippocampus-related behaviors. In this study, Sprague-Dawley rats were purchased from the Animal Center of Anhui Medical University of China. For the experiments in the adult stage, rats were intraperitoneally injected with calpeptin, 2 mg/kg, once a day, on postnatal days 7–14. Then on postnatal day 60, the Morris water maze test was used to evaluate spatial learning and memory abilities. The open field test was carried out to assess anxiety-like activities. Phalloidin staining was performed to observe synaptic morphology in the hippocampus. Immunohistochemistry was used to count the number of NeuN-positive cells in the hippocampal CA1 region. DiI was applied to label dendritic spines. Calpeptin administration impaired spatial memory, caused anxiety-like behavior in adulthood, reduced the number and area of apical dendritic spines, and decreased actin polymerization in the hippocampus, but did not affect the number of NeuN-positive cells in the hippocampal CA1 region. For the neonatal experiments, neonatal rats were intraperitoneally injected with calpeptin, 2 mg/kg, on postnatal days 7 and 8. Western blot assay was performed to analyze the protein levels of Akt, Erk, p-Akt, p-Erk1/2, Erk1/2, SCOP, PTEN, mTOR, p-mTOR, CREB and p-CREB in the hippocampus. SCOP expression was increased, and the phosphorylation levels of Akt, mTOR and CREB were reduced in the hippocampus. These findings show that calpeptin administration after birth affects synaptic development in neonatal rats by inhibiting the Akt/mTOR signaling pathway, thereby perturbing hippocampal function. Therefore, calpeptin administration after birth is a risk factor for neurodevelopmental defects.

Rheumatoid arthritis (RA) acts as one of the most common, agnogenic and chronic inflammatory-autoimmune disorder which is characterized by persistent synovitis, cartilage destruction, and joint deformities, leads to a wide range of disabilities, and increased mortality, thus imposing enormous burdens. Several drugs with anti-inflammatory and immunomodulatory properties such as celecoxib, diclofenac and methotrexate are being selected as conventional drugs in the allopathic system of medicine for the treatment of RA in clinic. However, there are some serious side effects more or less when using these drugs because of their short poor bioavailability and biological half-life for a long time. These shortcomings greatly promote the exploration and application of new low- or no-toxicity drugs for treating the RA. Meanwhile, a growing number of studies demonstrate that several herbs present certain anti-inflammatory and anti-arthritic activities through different enzymes and their derivatives, which indicate that they are promising therapeutic strategies when targeting these mediators based on herbal medicinal products in RA research. This review article summarizes the roles of the main enzymes and their derivatives during the pathogenesis of RA, and clearly clarifies the explicit and potential targeted actions of herbal medicinal products that have anti-RA activity. Our review provides timely and critical reference for the scientific rationale use of herbal medicinal products, with the increasing basic research and clinical application of herbal medicinal products by patients with RA.

Ischemic stroke is a common neurological disease that can lead to mortality and disability. The current curative effect remains unsatisfactory because drug accumulation in the diseased areas is insufficient as a result of the unique blood–brain barrier. Therefore, much attention has been paid to develop a novel therapeutic compound, paeonol-ozagrel conjugate (POC), for ischemic stroke. Then, POC was successfully synthesized by conjugating of paeonol and ozagrel as mutual prodrug. A series of in vitro characterizations and evaluations, including high - resolution mass spectroscopy, nuclear magnetic resonance spectroscopy, partition coefficient, and assessment of cytotoxicity against PC12 cells, were performed. Pharmacokinetic study demonstrated POC is eliminated quickly (t1/2 = 53.46 ± 19.64 min), which supported a short dosing interval. The neurological score, infarct volume, histopathological changes, oxidative stress, inflammatory cytokines levels, and TXA2 levels also were evaluated in vivo in middle cerebral artery occlusion (MCAO) rats. All results showed that POC had a significant curative and therapeutic effect on ischemic stroke, as evaluated by the middle cerebral artery occlusion. Overall, POC can be expected to become a new drug candidate for the treatment of ischemic stroke.

Objective: Taohong Siwu decoction (THSWD) is one of the classic prescriptions for promoting blood circulation and removing blood stasis, and it has a good therapeutic effect on ischemic stroke. We sought to explore the therapeutic effects of THSWD on pyroptosis in rats with middle cerebral artery occlusion-reperfusion (MCAO/R).Methods: MCAO/R model of rats were established by suture-occluded method. MCAO/R rats were randomly divided into five groups, which were model group, nimodipine group, THSWD high, medium and low dose group (18, 9, and 4.5 g/kg, respectively), rats of sham group without thread embolus. All rats were treated by intragastric administration for 7 days. We detected the level of inflammatory factors. NLRP3 and Caspase-1 were detected by immunofluorescence. Western blot was used to detect NLRP3, Caspase-1, ASC, and GSDMD in penumbra. Also, the expression of TXNIP, HMGB1, toll-like receptors (TLR4), NF-κB, and MAPK were detected.Results: THSWD treatment improved the behavioral function and brain pathological damage. These results showed that the levels of TNF-α, TGF-β, IL-2, IL-6, IL-1β, and IL-18 were significantly reduced in THSWD treatment groups. THSWD could significantly decrease the expression levels of NLRP3, Caspase-1, Caspase-1 p10, ASC, TXNIP, GSDMD, HMGB1, TLR4/NFκB, p38 MAPK, and JNK in penumbra.Conclusion: Our results showed that THSWD could reduce the activation level of NLRP3 inflammatory corpuscle, down-regulate GSDMD, and inhibit pyroptosis in MCAO/R rats. These may be affected by inhibiting HMGB1/TLR4/NFκB, MAPK signaling pathways.

Incomplete abortion, a procedure for terminating pregnancy, will lead to abnormal uterine bleeding (AUB), infections, and even death. Taohong Siwu decoction (TSD) is a traditional Chinese medicine (TCM) formula, which has been developed to treat AUB for hundreds of years. However, the mechanism of the protective effect of TSD against AUB is not clear. We performed mass spectrometry (MS) of uterine samples to observe metabolic profile resulting from the treatment with TSD. An integrated gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry based untargeted metabolomics approach combined with multivariate statistical analyses were used to investigate the metabolic profile of TSD against AUB. There was clear separation between pregnant and incomplete aborting rats as well as incomplete aborting and TSD administered rats. Based on random forest algorithm and receiver operator characteristic analysis, 12 biomarkers were optimized related to TSD administered. The effect of TSD on AUB are related to several pathways, such as AA metabolism, glyoxylate and dicarboxylate metabolism, alanine, aspartate, and glutamate metabolism. To our knowledge, this is the first uterine metabolomics study focusing on TSD on AUB and provide a new perspective for explaining the mechanism of TSD on AUB.

Diapause is one of the survival strategies of insects for confronting adverse environmental conditions. Bombyx mori displays typical embryonic diapause, and offspring diapause depends on the incubation environment of the maternal embryo in the bivoltine strains of the silkworm. However, the molecular mechanisms of the diapause induction process are still poorly understood. In this study, we compared the differentially expressed miRNAs (DEmiRs) in bivoltine silkworm embryos incubated at diapause- (25 °C) and non-diapause (15 °C)-inducing temperatures during the blastokinesis (BK) and head pigmentation (HP) phases using transcriptome sequencing. There were 411 known miRNAs and 71 novel miRNAs identified during the two phases. Among those miRNAs, there were 108 and 74 DEmiRs in the BK and HP groups, respectively. By the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of the predicted target genes of the DEmiRs, we found that aside from metabolism, the targets were also enriched in phototransduction-fly and insect hormone biosynthesis in the BK group and the HP group, respectively. Dual luciferase reporter assay illustrated that bmo-miR-6497-3p directly regulated Bmcycle and subsequently regulated the expression of circadian genes. These results imply that microRNAs, as vitally important regulators, respond to different temperatures and participate in the diapause induction process across species.

Background: Experimental and clinical studies have shown that Tao-Hong-Si-Wu decoction (THSWD) improved neurological deficits resulting from Middle Cerebral Artery Occlusion (MCAO). However, the mechanisms of action of THSWD in MCAO have not been characterized. In this study, the mRNA transcriptome was used to study various therapeutic targets of THSWD.Methods: RNA-seq was used to identify differentially expressed genes (DEGs). MCAO-induced up-regulated genes (MCAO vs. control) and THSWD-induced down-regulated genes (compared to MCAO) were identified. Intersection genes were defined as up-regulated differentially expression genes (up-DEGs) identified as MCAO-induced gene expression that were reversed by THSWD. Genes down-regulated by MCAO and up-regulated by THSWD were grouped as another series of intersections. Biological functions and signaling pathways were determined by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses. In addition, several identified genes were validated by RT-qPCR.Results: A total of 339 DEGs were filtered based on the 2 series (MCAO vs. control and MCAO vs. THSWD), and were represented by genes involved in cell cycle (rno04110), ECM–receptor interaction (rno04512), complement and coagulation cascades (rno04610), focal adhesion (rno04510), hematopoietic cell lineage (rno04640), neuroactive ligand–receptor interaction (rno04080), cocaine addiction (rno05030), amphetamine addiction (rno05031), nicotine addiction (rno05033), fat digestion and absorption (rno04975), glycerophospholipid metabolism (rno00564), and others. The protein–protein interaction (PPI) network consisted of 202 nodes and 1,700 connections, and identified two main modules by MOCDE.Conclusion: Cell cycle (rno04110), ECM–receptor interaction (rno04512), complement and coagulation cascades (rno04610), focal adhesion (rno04510), hematopoietic cell lineage (rno04640), and neuroactive ligand–receptor interactions (rno04080) are potential therapeutic targets of THSWD in MCAO. This study provided a theoretical basis for THSWD prevention of neurological deficits resulting from intracerebral hemorrhage.

C40H50N2O4, monoclinic, P21/c (no. 14), a = 10.355(2) Å, b = 17.809(4) Å, c = 8.9354(16) Å, β = 97.101(4)°, V = 1635.2(5) Å3, Z = 2, Rgt(F) = 0.0453, wRref(F2) = 0.1270, T = 113 K.

C42H42N2O6, monoclinic, P21/c (no. 14), a = 6.9848(14) Å, b = 20.816(4) Å, c = 11.543(2) Å, β = 99.745(5)°, V = 1654.1(6) Å3, Z = 2, Rgt(F) = 0.0377, wRref(F2) = 0.1019, T = 113(2) K.