Tanshinone I: Pharmacological activities, molecular mechanisms against diseases and future perspectives.

BACKGROUND: Tanshinone I (Tan I) is known as one of the important active components in Salvia miltiorrhiza. In recent years, Tan I has received a substantial amount of attention from the research community for various studies being updated and has been shown to possess favorable activities including anti-oxidative stress, regulation of cell autophagy or apoptosis, inhibition of inflammation, etc. PURPOSE: To summarize the investigation progress on the anti-disease efficacy and effect mechanism of Tan I in recent years, and provide perspectives for future study on the active ingredient. METHOD: Web of Science and PubMed databases were used to search for articles related to "Tanshinone I" published from 2010 to 2022. Proteins or genes and signaling pathways referring to Tan I against diseases were summarized and classified along with its different therapeutic actions. Protein-protein interaction (PPI) analysis was then performed, followed by molecular docking between proteins with high node degree and Tan I, as well as bioinformactic analysis including GO, KEGG and DO enrichment analysis with the collected proteins or genes. RESULTS: Tan I shows multiple therapeutic effects, including protection of the cardiovascular system, anti-cancer, anti-inflammatory, anti-neurodegenerative diseases, etc. The targets (proteins or genes) affected by Tan I against diseases involve Bcl-2, Bid, ITGA2, PPAT, AURKA, VEGF, PI3K, AKT, PRK, JNK, MMP9, ABCG2, CASP3, Cleaved-caspase-3, AMPKα, PARP, etc., and the regulatory pathways refer to Akt/Nrf2, SAPK/JNK, PI3K/Akt/mTOR, JAK/STAT3, ATF-2/ERK, etc. What's more, AKT1, CASP3, and STAT3 were predicted as the key action targets for Tan I by PPI analysis combined with molecular docking, and the potential therapeutic effects mechanisms against diseases were also further predicted by bioinformatics analyses based on the reported targets, providing new insights into the future investigation and helping to facilitate the drug development of Tan I.

Identification of pharmacokinetic markers for safflower injection using a combination of system pharmacology, multicomponent pharmacokinetics, and quantitative proteomics study.

Safflower injection (SI), a water-extract preparation from safflower (Carthamus tinctorius L.), has been widely used for the treatment of cardio-cerebrovascular diseases. This work aims to develop an approach for identifying PK markers of cardiovascular herbal medicines using SI as a case study. Firstly, qualitative and quantitative analyses were performed to reveal ingredients of the preparation via HPLC-MS. Subsequently, multiple PK ingredients and integrated PK investigations were carried out to ascertain ingredients with favorable PK properties (e.g., easily detected at conventional PK time points and high system exposure) for the whole preparation. Next, ingredients against cardiovascular diseases (CVDs) in the preparation were predicted with target fishing and system pharmacology studies. Finally, ingredients with favorable PK properties, satisfactory PK representativeness for the preparation, and high relevance to CVDs were considered as potential PK markers. Their therapeutic effect was further evaluated using the H2O2-induced H9c2 cardiomyocyte-injured model and a proteomics study to identify objective PK markers. As results, it disclosed that SI mainly contains 11 ingredients. Among them, five ingredients, namely, hydroxysafflor yellow A (HSYA), syringin (SYR), p-coumaric acid (p-CA), scutellarin (SCU), and p-hydroxybenzaldehyde (p-HBA), showed favorable PK properties. HSYA, SYR, and rutin (RU) were predicted to show high relevance to CVDs and screened as potential PK markers. However, only HSYA and SYR were confirmed as therapeutic ingredients against CVDs. Combined with these findings, only HSYA demonstrated satisfactory representativeness on PK properties and therapeutic effects of multiple ingredients of the preparation, thereby indicating that HSYA is a potential PK marker for the SI. The results of this study can provide a reference for the characterization of PK markers for traditional Chinese medicines.

Synthesis, biological evaluation, pharmacokinetic studies and molecular docking of 4'''-acetyl-delicaflavone as antitumor agents.

Structural modification of natural products is the effective option to improve their pharmacological effects and drug properties. DLF is a lead compound of antitumor drug, which is a broad-spectrum, low toxic and high-efficient component isolated from Selaginella doederleinii Hieron by our research group. Here, we report the structural modification method of this component, and find that the acetylated product of C4'''- OH (C4'''-acetyl-delicaflavone, 4'''ADLF) has better inhibitory effect on the selected cancer cell lines, including, lung, liver, colon and cervical cancer cell lines. Since the increased water solubility of 4'''ADLF may lead to higher absorption rate and activity, we evaluate the pharmacodynamics in vitro and in vivo, and the pharmacokinetic of 4'''ADLF. It shows that 4'''ADLF inhibit the proliferation and induce cycle arrest in tumor cells, and had better anticancer activity and bioavailability than DLF.

Recent progress (2015-2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer.

Ginsenoside Rb1 (Rb1), one of the most important ingredients in Panax ginseng Meyer, has been confirmed to have favorable activities, including reducing antioxidative stress, inhibiting inflammation, regulating cell autophagy and apoptosis, affecting sugar and lipid metabolism, and regulating various cytokines. This study reviewed the recent progress on the pharmacological effects and mechanisms of Rb1 against cardiovascular and nervous system diseases, diabetes, and their complications, especially those related to neurodegenerative diseases, myocardial ischemia, hypoxia injury, and traumatic brain injury. This review retrieved articles from PubMed and Web of Science that were published from 2015 to 2020. The molecular targets or pathways of the effects of Rb1 on these diseases are referring to HMGB1, GLUT4, 11ß-HSD1, ERK, Akt, Notch, NF-κB, MAPK, PPAR-γ, TGF-ß1/Smad pathway, PI3K/mTOR pathway, Nrf2/HO-1 pathway, Nrf2/ARE pathway, and MAPK/NF-κB pathway. The potential effects of Rb1 and its possible mechanisms against diseases were further predicted via Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and disease ontology semantic and enrichment (DOSE) analyses with the reported targets. This study provides insights into the therapeutic effects of Rb1 and its mechanisms against diseases, which is expected to help in promoting the drug development of Rb1 and its clinical applications.

Recent Research Progress (2015-2021) and Perspectives on the Pharmacological Effects and Mechanisms of Tanshinone IIA.

Tanshinone IIA (Tan IIA) is an important characteristic component and active ingredient in Salvia miltiorrhiza, and its various aspects of research are constantly being updated to explore its potential application. In this paper, we review the recent progress on pharmacological activities and the therapeutic mechanisms of Tan IIA according to literature during the years 2015-2021. Tan IIA shows multiple pharmacological effects, including anticarcinogenic, cardiovascular, nervous, respiratory, urinary, digestive, and motor systems activities. Tan IIA modulates multi-targets referring to Nrf2, AMPK, GSK-3ß, EGFR, CD36, HO-1, NOX4, Beclin-1, TLR4, TNF-α, STAT3, Caspase-3, and bcl-2 proteins and multi-pathways including NF-κB, SIRT1/PGC1α, MAPK, SREBP-2/Pcsk9, Wnt, PI3K/Akt/mTOR pathways, TGF-ß/Smad and Hippo/YAP pathways, etc., which directly or indirectly influence disease course. Further, with the reported targets, the potential effects and possible mechanisms of Tan IIA against diseases were predicted by bioinformatic analysis. This paper provides new insights into the therapeutic effects and mechanisms of Tan IIA against diseases.

Deciphering the potential anti-COVID-19 active ingredients in Andrographis paniculata (Burm. F.) Nees by combination of network pharmacology, molecular docking, and molecular dynamics.

Currently, coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 has posed an enormous threat to public health worldwide. An andrographolide sulfonates preparation, named Xiyanping injection in Chinese, which was prepared from the aqueous extract of Andrographis paniculata (Burm. F.) Nees, showed favorable therapeutic effectiveness on COVID-19, suggesting A. paniculata could contain powerful therapeutic ingredients against COVID-19. In this study, to search for the potential drug candidates for COVID-19 in the herb, 68 potential target proteins and 24 active ingredients from A. paniculata were screened out using TCMSP, STP, Genecards and TTD databases firstly. A. paniculata-Compound-Target network constructed by cytoscape software showed that the protein targets PTGS2, EGFR, MAPK14, etc. had a high network relevance value. GO and KEGG enrichment analysis indicated that the 24 compounds in A. paniculata might exert their therapeutic effects by the biological processes, cellular response to biotic stimulus, response to lipopolysaccharide, response to molecule of bacterial origin, etc. And AGE-RAGE signaling pathway in diabetic complications (hsa04933), Kaposi sarcoma-associated herpesvirus infection (hsa05167), Human cytomegalovirus infection (hsa05163), etc. were predicted as the most significant effect pathways. Andrographidine C (MOL008223) and andrographolide (MOL008232) were found with strong binding affinity to the target active sites of the potential targets by molecular docking. Ultimately, the application of molecular dynamics simulations demonstrated that andrographidine C could bind well to the ACE2 and PIK3CG proteins. This research identified novel molecules against COVID-19 for developing natural medicines from A. paniculate and also provides a possible explanation for the molecular mechanisms of Xiyanping Injection against COVID-19.

Comparison of the complete mitochondrial genome of Phyllophorus liuwutiensis (Echinodermata: Holothuroidea: Phyllophoridae) to that of other sea cucumbers.

Sea cucumber species are abundant (>1400 species) and widely distributed globally. mtDNA sequencing is frequently used to identify the phylogenetic and evolutionary relationships among species. However, there are no reports on the mitochondrial genome of Phyllophorus liuwutiensis. Here, we performed mtDNA sequencing of P. liuwutiensis to examine its phylogenetic relationships with other echinoderms. Its mitochondrial genome (15 969 bp) contains 37 coding genes, including 13 protein-coding genes, 22 tRNA genes and 2 rRNA genes. Except for one protein-coding gene (nad6) and five tRNA genes encoded on the negative strand, all other genes were encoded on the positive strand. The mitochondrial bases of P. liuwutiensis were composed of 29.55% T, 22.16% C, 35.64% A and 12.64% G. The putative control region was 703 bp in length. Seven overlapping regions (1-10 bp) were found. The noncoding region between the genes ranged from 1 to 130 bp in length. One putative control region has been found in the P. liuwutiensis mitogenome. All of the tRNA genes were predicted to fold into a cloverleaf structure. In addition, we compared the gene arrangements of six echinoderms, revealing that the gene order of P. liuwutiensis was a new arrangement.

Spatiotemporal pattern analysis of schistosomiasis based on village level in the transmission control stage in lake and marshland areas in China.

Hubei Province is one of the endemic regions with severe schistosomiasis in China. To eliminate schistosomiasis in lake and marshland regions, this study detected hotspots of schistosomiasis cases both spatially and spatiotemporally on the basis of spatial autocorrelation; clustering and outlier, purely spatial and spatiotemporal cluster analyses at the village level from 2013 to 2017 in Hubei Province. The number of cases confirmed positive by an immunodiagnostic test and etiological diagnosis and advanced schistosomiasis cases dramatically declined during the study period. Significant global spatial autocorrelation of schistosomiasis patients was found at the village level in the whole province in 5 years. Clustering and outlier analysis showed that most HH villages were mainly concentrated along the Yangtze River, especially in Jianghan Plain. Spatial and spatiotemporal cluster analyses showed that significant clusters of the schistosomiasis cases were detected at the village level. In general, space and spatiotemporal clustering of schistosomiasis cases at the village level demonstrated a downward trend from 2013 from 2017 in Hubei Province. High-risk regions included Jianghan Plain along the middle reach of Yangtze River and Yangxin County in the lower reaches of the Yangtze River in Hubei Province. To eliminate schistosomiasis, precise control and management of schistosomiasis cases should be strictly implemented. Moreover, comprehensive prevention and control measures should be continuously strengthened in these regions.

Administrative village-based spatial distribution specificity of Oncomelania hupensis and its relationship with water systems in Hubei Province / 中国血吸虫病防治杂志

Objective To investigate the spatial distribution of Oncomelania hupensis snail habitats at the administrative village scale in schistosomiasis-endemic areas of Hubei Province, so as to provide scientific bases for precise control of O. hupensis snails in the province. Methods Data regarding snail distribution at the village level in Hubei Province in 2017 were collected to create a spatial analysis database of snail distribution in Hubei Province. The spatial aggregations of O. hupensis distribution were analyzed using Moran’s I index and Local Moran’s I index. In addition, the distances from schistosomiasis-endemic villages to the Yangtze River were captured using the software ArcGIS 13.0, and their correlations with area of snail habitats were examined with the Spearman correlation method. Results O. hupensis snails were mainly distributed in 5 450 endemic villages from 63 counties of 13 cities in Hubei Province in 2017. The global spatial autocorrelation analysis showed spatial aggregations in the areas of historically accumulated snail habitats, current areas of snail habitats, areas of snail habitats outside the embankment and snail habitats inside the embankment (all Z Scores > 0, all P values < 0.05), and no spatial aggregation was seen in the areas of snail habitats in hilly areas (Z Score > 0, P > 0.05). There were four types of spatial distribution of historically accumulated areas of snail habitats, areas of current snail habitats, areas of snail habitats outside the embankment and snail habitats inside the embankment, including the high-high type (H-H type), high-low type (H-L type), low-high type (L-H type) and random distribution type, and a high percentage of the H-H type was found. There were 340, 125 and 110 endemic villages with the H-H type of areas of historically accumulated snail habitats, current areas of snail habitats and areas of snail habitats outside the embankment, and these villages were mainly concentrated in Wuhan and Jingzhou cities, with almost consistent spatial aggregation locations. There were 319 endemic villages with the H-H type of distribution of snail habitats inside the embankment, which were mainly distributed in Jingzhou, Xiaogan and Huangshi cities. In addition, the areas of historically accumulated snail habitats, current areas of snail habitats and areas of snail habitats outside the embankment negatively correlated with the distance from the endemic villages to the Yangtze River (r = −0.094, P < 0.01; r = −0.225, P < 0.01; r = −0.177, P < 0.01). Conclusion The clustering areas of snail habitats along the Yangtze River Basin, notably the villages near the Yangtze River are key regions for snail monitoring and control in Hubei Province.

[Research on competency building standards of institutions of schistosomiasis prevention and control in Hubei Province I Investigation of institution management].

OBJECTIVE: To investigate the current situation of management of institutions of schistosomiasis prevention and control in Hubei Province, so as to explore the probable competency building standards for these institutions at the county and township levels. METHODS: By using a combination of quantitative and qualitative methods, the institutions of schistosomiasis prevention and control at county and township levels were investigated for the institutional setup, staffing and fulfillment functions since the reform of 2004. RESULTS: Among 63 schistosomiasis endemic counties (cities, districts) of Hubei Province, there were 26 independent schistosomiasis control institutions (41.27%), there were 24 institutions which were incorporated into CDC (38.10%), and there were no institutions in 13 counties (20.63%). Among 518 endemic towns, there were 299 institutions (57.72%). The total staffing size were 1 932, but there were 1 586 (82.09%) people actually working in the post, and therefore there were 346 (17.91%) empty positions. The average rates of carrying out the six functions were 91.48%-71.19%, but only 19.23% of the institutions participated in the comprehensive schistosomiasis control management project and its effect assessment. CONCLUSION: According to the management model for schistosomiasis control institutions under the current institutional mechanisms, we need a rigorous industry standard to constrain, guide and standardize the management and capacity-building of the institutions in different historical periods.

[Research on competency building standards of institutions of schistosomiasis prevention and control in Hubei Province. II. Investigation of human resources].

OBJECTIVE: To understand the human resources of the grassroots institutions of schistosomiasis control and prevention, so as to provide the evidence for formulating the standards of institutional capacity-building. METHODS: By using the combination of quantitative and qualitative methods, the hierarchy of schistosomiasis control institution workers, structural features of workers, and benefits of workers were investigated and the results were analyzed statistically after the 2004 reform. RESULTS: The constituent ratios of personnel ≤ 30 years old, 30 to 45 years old, and ≥ 45 years old were 6.8%, 64.0% and 29.2% respectively, with an average age of 43.1 years. For education levels, 61.35% of the personnel had secondary or high school levels. At the city level, the structural proportion of the senior professional; medium professional and primary professional titles was 1.4 : 5.6 : 3.0, and at the county level, the proportion was 0.5 : 6.1 : 3.4. There was 14 200 yuan per capita at the township schistosomiasis control institutions. CONCLUSION: The technology of the personnel in schistosomiasis institutions of Hubei Province is weak, the average age of personnel is old, and the salary is low.