Arrhythmia is the abnormal heart-beat frequency and/or rhythm caused by the origin of cardiac activity and/or conduction disorder. Arrhythmia disease has various manifestations and complex etiology, which can occur alone or complicated with other cardiovascular diseases. A sudden arrhythmic onset may lead to sudden death, whereas a sustained onset may lead to heart failure. In cardiomyocytes, calcium overload induces apoptosis and leads to arrhythmia. Calcium channel blockers have been widely used in clinic as a routine cardiovascular drug to regulate calcium signal, but their efficacy on different arrhythmia complications vary, and they also have potential therapeutic risks. Therefore, it is of great significance to seek calcium signal modulators targeting new mechanisms from plants and other natural product resources and develop them into anti-arrhythmia drugs with higher safety and better curative effect. This review focuses on the calcium signal regulatory effects of plant-derived natural calcium channel antagonists in arrhythmia models, highlights the research progress in recent years, and summarizes the effects and mechanisms of various natural drugs such as alkaloids, saponins, quinones and flavonoids, which regulate Ca²⁺ homeostasis, to provide a theoretical basis for the drug development of natural calcium channel antagonists to prevent and treat arrhythmia in the future.

The enteric-hepatic axis plays an important role in the occurrence, progression and regression of nonalcoholic fatty liver disease (NAFLD). Obeticholic acid (OCA) is a farnesoid X receptor agonist. In this study, C57BL/6 mice were fed with methionine and choline deficient (MCD) diet for 8 weeks with OCA (6.5 mg·kg^-1·d^-1) administration by gavage at the same time. The effects of OCA on serum lipid and bile acid metabolomics and ileal gut microbiota (GM) of MCD mice were studied by UPLC-MS and 16S rDNA sequencing. The results were as follows: (1) OCA decreased the activities of alanine aminotransferase and aspartate aminotransferase in serum and the contents of triglyceride (TG) and malondialdehyde in liver, alleviated the accumulation of liver fat and inflammation of MCD mice. OCA down-regulated the contents of 2 eicosanoids (12, 13-EPOME, 9, 10-EPOME) and 4 free fatty acids (FFA16∶1, FFA18∶1, FFA16∶2, FFA18∶3) and TG (16∶1_16∶1_18∶2) in serum, and up-regulated the content of 1 eicosanoid thromboxanes B3. KEGG differential metabolite pathway analysis showed that fatty acid biosynthesis might be the main way that OCA ameliorated lipid metabolism disorder of MCD mice. OCA reduced the relative abundance of Christensenellaceae and Lachnospiraceae_UCG-006 in the GM of MCD mice; OCA decreased the serum levels of 23-deoxycholic acid, porcine deoxycholic acid, 3-deoxycholic acid, glycine deoxycholic acid, glycine cholic acid, taurine deoxycholic acid, taurocholic acid and taurine. These results suggest that the alleviating effect of OCA on NAFLD of MCD mice may be related to its above-mentioned regulation of the metabolism of the free fatty acids, oxidized lipids, 12α-hydroxylated bile acids and the abundance of GM. The animal experiments were approved by the Experimental Animal Ethics Committee of Hubei University (No. 20220036).

A new [7, 10∶1, 5]-patchoulane-type sesquiterpenoid was isolated and purified by silica gel column chromatography, medium pressure liquid chromatography, and semi-preparative high performance liquid chromatography. Based on IR, HR-ESI-MS, NMR, and X-single crystal diffraction data analyses, compound 1 was determined to be (-)-(3S, 4R, 5R, 7R, 10R)-[7, 10∶1, 5]patchoul-1(2)-en-3, 4-diol. It showed an inhibitory effect on LPS-induced NO production in RAW264.7 cells.

In this study, we investigated the effect of aspirin on tumor biological effects mediated by hepatocyte growth factor/cellular-mesenchymal-epithelial transition factor (HGF/c-Met) axis, and preliminarily explored the molecular mechanism of inhibiting tumor metastasis by aspirin. The binding of aspirin to c-Met was predicted by molecular docking; cellular thermal shift assay (CETSA) was used to verify the binding of aspirin to c-Met at the cellular level. The inhibitory effect of aspirin on c-Met kinase was detected by kinase activity; Western blot, cell scattering test, cell branching morphogenesis and Transwell test were used to evaluate the cell signal transduction, morphological changes and migration and invasion ability. The results showed that aspirin could effectively inhibit the kinase activity of c-Met with a half inhibitory concentration of 0.95 mmol·L^-1. The results of docking showed that aspirin could bind to the ATP pocket of c-Met protein, and the main binding sites were Tyr1230, Tyr1159 and Met1229. The CETSA test also showed that aspirin could form binding complex with c-Met protein. Western blot results showed that aspirin could inhibit the up-regulation of phosphorylated Met stimulated by HGF in a concentration-dependent manner. The results of cell scattering test showed that aspirin could block HGF/c-Met promoted cell scattering in a concentration dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L^-1, and this effect was independent of HGF. Similarly, the results of MDCK cell branching morphogenesis experiment showed that aspirin could inhibit HGF/c-Met mediated invasive growth in a concentration dependent manner. The results of Transwell test showed that aspirin could block HGF/c-Met mediated cell migration and invasion in a concentration-dependent manner. Aspirin could almost completely block the biological function mediated by c-Met activation at the concentration of 4 mmol·L^-1, and this effect was independent of HGF. The above results indicate that aspirin can bind to c-Met, thereby blocking the biological effects mediated by HGF/c-Met, and inhibiting tumor metastasis. This study revealed the new biological function of aspirin, and provided a new theoretical basis for a comprehensive understanding of the anti-metastatic effect of aspirin.

Doxorubicin (DOX) is an anthracycline antibiotic widely used in the treatment of certain types of tumors. However, DOX have some serious side effects in the body after long-term use, especially acute and chronic cardiotoxicity. This study explored the protective effect of tanshinone I (Tan I) on acute cardiotoxicity induced by DOX and its underlying molecular mechanisms. In vivo and in vitro acute cardiotoxicity models were established by injecting DOX (6 mg·kg^-1, twice per week) into the tail vein of C57 mice and stimulating H9C2 cardiomyocytes with DOX. In in vivo experiments, Tan I (10 mg·kg^-1) was administered daily by oral 5 days before the tail vein injection, till the end of the experiment. The effects of Tan I on mice heart function, myocardial tissue morphology and serological indicators were detected. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Beijing University of Traditional Chinese Medicine. In in vitro experiments, the specific mechanism of Tan I against oxidative stress was further studied. Immunofluorescence was used to detect the expression of Nrf2 and its transcription into the nucleus. In addition, the levels of oxidative stress related proteins, protein kinase B (Akt), nuclear erythroid factor 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1), were detected by Western blot. Finally, AutoDock software was used for molecular docking verification. The results showed that Tan I significantly improved cardiac function in mice. Meanwhile, the expression levels of creatine kinase-MB (CK-MB) and lactic dehydrogenase (LDH) in serum were decreased. Immunofluorescence results indicated that Tan I could increase Nrf2 expression level in H9C2 cells and promote Nrf2 entry into the nucleus. Western blot results also indicated that the levels of oxidative stress related proteins, P-Akt, Nrf2, HO-1 and NQO1 in DOX plus Tan I group were significantly increased compared with DOX group. These results suggest that Tan I can alleviate DOX-induced acute cardiotoxicity by inhibiting oxidative stress through up-regulating the Akt-Nrf2 pathway, thereby alleviating DOX-induced acute myocardial injury.

Alangium chinense is a commonly used medicinal plant of Alangiaceae Alangium, one of the characteristic Miao medicines in Guizhou. The genus is strongly differentiated and has complex morphological variation, with significant differences in active ingredients and potency among herbs. In this paper, we sequenced the chloroplast genomes of Alangium chinense subsp. Pauciflorum, Alangium chinense subsp. Strigosum and Alangium kurzii Craib using Illumina high-throughput sequencing technology. The genomes of Alangium chinense subsp. Pauciflorum, Alangium chinense subsp. Strigosum and Alangium kurzii Craib chloroplasts were sequenced, their assembly annotation and structural characterization were completed, and the genomes of the congeners Alangium chinense and Alangium alpinum were downloaded from NCBI for comparative analysis. Finally, the phylogenetic tree was constructed by selecting published species with close affinity to Alangium chinense family from NCBI. The results were as follows: Alangium chinense subsp. Pauciflorum, Alangium chinense subsp. Strigosum and Alangium kurzii Craib chloroplast genomes were 156 670, 156 672 and 156 871 bp in length, with a typical four-segment structure, all containing one long single copy region (LSC), one short single copy region (SSC) and two inverted repeat regions (IRa and IRb). All of them were annotated to 133 genes, including 88 protein-coding genes, 37 tRNA genes and 8 rRNA genes. Three types of long repeat sequences and SSR loci, forward repeats, palindrome repeats and reverse repeats, were found in all chloroplast genomes. Comparative genomic analysis showed that there was diversity in the boundary transition regions of the five species, no rearrangements or inversions were found in the chloroplast genome, and there were significant differences in the coding regions of ndhA, ycf1, rpl16, ycf2, and petD genes, which provided new loci for molecular identification of Patagonia. In the phylogenetic analysis, Alangium kurzii var. kurzii clustered as a single species, and Alangium chinense subsp. Pauciflorum and Alangium chinense subsp. Strigosum clustered as a single species, with a support rate of 93 and close affinity, indicating that the phylogenetic tree can be used for the species identification. This paper can provide a basis for the taxonomic identification of Alangium, ensure the safety of clinical use of anise herbs and regulate the market of Alangium chinense herbs.

Depression is a psychiatric disease characterized by long-lasting low mood, accompanied by symptoms such as cognitive, sleep and social disturbances. In the theory of traditional Chinese medicine, depression is included in the categories of "depression syndrome" and "madness", and the main syndrome type is liver stagnation and spleen deficiency. Xiaoyao san, Sini san and Chaihushugan san are commonly used prescriptions for clinical treatment of depression, and flavonoids are the common active ingredients. Clinical and basic studies have shown that the flavonoids derived from antidepressant compound prescription have pharmacological effects such as anti-inflammatory, antioxidant, neuroprotective, and intestinal flora regulation which could prevent the occurrence and development of depression from different pathways. Based on this, this review focuses on the pathogenesis of depression, summarizes the common flavonoids in antidepressant prescriptions, and summarizes their regulatory mechanisms and effects in order to provide ideas for the prevention and treatment of depression.

Heterotrimeric G proteins are classes of signal-transducing proteins that bind to guanine nucleotides and possess GTP hydrolase activity. G proteins are composed of three subunits α, β, and γ, and are considered as the "molecular switch" in the GPCR signaling pathway. The abnormal activation of G protein is strongly related to diseases such as uveal melanoma, asthma, et al., making directly targeting G protein as an promising strategy for combating diseases. In this review, the classification and physiological functions of G protein are briefly described, and the research progress of G proteins in diseases, G protein modulators are reviewed.

To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg^-1 group, oxiracetam groups (30, 100 and 200 mg‧kg^-1), S-oxiracetam groups (30, 100 and 200 mg‧kg^-1) and R-oxiracetam 200 mg‧kg^-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.

4-(Cytidine 5′-diphospho)-2-C-methyl-D-erythritol kinase (CMK) was one of the key enzymes in the methylerythritol-4-phosphate (MEP) pathway to generate terpenoids. In this study, based on the transcriptome data of Atractylodes lancea, the sequence of the CMK gene was cloned, named AlCMK (GenBank accession number OM283293). The results showed that AlCMK contains a 1 230 bp open reading frame (ORF) encoding 409 amino acids. The deduced protein had a theoretical molecular weight of 44 752.53 and an isoelectric point of 6.67. Transmembrane structure analysis showed that there was no transmembrane structure, and the secondary structure of AlCMK was predicted to be mainly composed of random coil. Homologous alignment revealed that AlCMK shared high sequence identity with the CMK proteins of Tanacetum cinerariifolium, Osmanthus fragrans, Eucommia ulmoides, Lonicera japonica and Salvia miltiorrhiza. Phylogenetic analysis indicated that AlCMK protein had the higher homology with CMK protein of Compositae. The pET-32a-AlCMK prokaryotic expression vector was constructed and a fusion protein with molecular mass of about 65 kDa was expressed in the E. coli BL21 (DE3). The qRT-PCR was used to analyze the expression pattern of AlCMK gene in different tissues and after MeJA treatment. Meanwhile, the enzyme activity was determined by ELISA kit. The results showed that AlCMK gene was tissue-expressed in different origins and its expression was induced by MeJA, and the results of the enzyme activity assay showed that the AlCMK enzyme activity in different regions was higher in the leaves. The subcellular localization showed that AlCMK was located in the chloroplast. This study provides a reference for further elucidating the biological function of AlCMK gene in terpenoid synthesis pathway in Atractylodes lancea.