TCM2COVID: A resource of anti-COVID-19 traditional Chinese medicine with effects and mechanisms.

In China, traditional Chinese medicine (TCM) has been widely used for coronavirus infectious disease 2019 (COVID-19) prevention, treatment, and recovery and has played a part in the battle against the disease. A variety of TCM treatments have been recommended for different stages of COVID-19. But, to the best of our knowledge, a comprehensive database for storing and organizing anti-COVID TCM treatments is still lacking. Herein, we developed TCM2COVID, a manually curated resource of anti-COVID TCM formulas, natural products (NPs), and herbs. The current version of TCM2COVID (1) documents over 280 TCM formulas (including over 300 herbs) with detailed clinical evidence and therapeutic mechanism information; (2) records over 80 NPs with detailed potential therapeutic mechanisms; and (3) launches a useful web server for querying, analyzing and visualizing documented formulas similar to those supplied by the user (formula similarity analysis). In summary, TCM2COVD provides a user-friendly and practical platform for documenting, querying, and browsing anti-COVID TCM treatments, and will help in the development and elucidation of the mechanisms of action of new anti-COVID TCM therapies to support the fight against the COVID-19 epidemic. TCM2COVID is freely available at http://zhangy-lab.cn/tcm2covid/.

[Exploration on rationality evaluation approach of drug combination medication based on sequential analysis and machine learning].

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.

Identification of Antifungal Bisphosphocholines from Medicinal Gentiana Species.

Gentiana species including G. crassicaulis, G. macrophylla, G. dahurica, and G. straminea are used in traditional Chinese medicine as "Qinjiao" for the treatment of rheumatism, hepatitis, and pain. Four antifungal bisphosphocholines [irlbacholine (2) and three new analogues, gentianalines A-C (1, 3, and 4)] were identified from G. crassicaulis by a bioassay-guided fractionation and structure elucidation approach. Subsequent chemical analysis of 56 "Qinjiao" samples (45 from G. crassicaulis, five from G. macrophylla, three from G. dahurica, and three from G. straminea) showed that bisphosphocholines were present in all four Gentiana species, with irlbacholine as the major compound ranging from 2.0 to 6.2 mg per gram of dried material. Irlbacholine exhibited potent in vitro antifungal activity against Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans, and Candida glabrata with minimum inhibitory concentration (MIC) values of 0.63, 1.25, 10.0, and 5.0 µg/mL, respectively. Identification of the bisphosphocholines, a rare class of antifungal natural products, in these medicinal plants provides scientific evidence to complement their medicinal use. The bisphosphocholines carrying a long aliphatic chain possess amphiphilic molecule-like properties with a tendency of retention in both normal and reversed-phase silica gel column chromatography and thereby may be neglected in natural products discovery. This report may stimulate interest in this class of compounds, which warrant the further study of other biological activities as well.

New Triterpenoid Saponins from Green Vegetable Soya Beans and Their Anti-Inflammatory Activities.

Ten compounds were isolated and identified from green vegetable soya beans, of which five are new triterpenoid saponins (1-5) and five are known compounds (6-10). The chemical structures of the five triterpenoid saponins (1-5) were elucidated to be 3ß,24-dihydroxy-22ß,30-epoxy-30-oxoolean-12-en 3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-d-xylopyranosyl-(1 → 2)-ß-d-glucuronopyranoside, 1; 3ß,24-dihydroxy-22ß,30-epoxy-30-oxoolean-12-en 3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-d-(3″-O-formyl)-galactopyranosyl-(1 → 2)-ß-d-glucuronopyranoside, 2; 22-keto-3ß,24-dihydroxy oleanane-12-ene 3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-d-(3″-O-formyl)-galactopyranosyl-(1 → 2)-ß-d-glucuronopyranoside, 3; 3ß,22ß,24-trihydroxy oxyolean-18(19)-ene-29-acid 3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-d-galactopyranosyl-(1 → 2)-ß-d-glucuronopyranoside, 4; and punicanolic acid 3-O-α-l-rhamnopyranosyl-(1 → 2)-ß-d-galactopyranosyl-(1 → 2)-ß-d-glucuronopyranoside, 5 from the spectroscopic data (IR, GTC/FID, HR-ESI-MS, and 1D and 2D NMR). The nitric oxide release inhibitions of compounds 1-10 in LPS-stimulated RAW264.7 cells were evaluated, and the data suggested that compounds 1, 2, and 5 might possess moderate anti-inflammatory activities, with IC50 values of 18.8, 16.1, and 13.2 µM, respectively.

Modulating AtDREB1C Expression Improves Drought Tolerance in Salvia miltiorrhiza.

Dehydration responsive element binding proteins are transcription factors of the plant-specific AP2 family, many of which contribute to abiotic stress responses in several plant species. We investigated the possibility of increasing drought tolerance in the traditional Chinese medicinal herb, Salvia miltiorrhiza, through modulating the transcriptional regulation of AtDREB1C in transgenic plants under the control of a constitutive (35S) or drought-inducible (RD29A) promoter. AtDREB1C transgenic S. miltiorrhiza plants showed increased survival under severe drought conditions compared to the non-transgenic wild-type (WT) control. However, transgenic plants with constitutive overexpression of AtDREB1C showed considerable dwarfing relative to WT. Physiological tests suggested that the higher chlorophyll content, photosynthetic capacity, and superoxide dismutase, peroxidase, and catalase activity in the transgenic plants enhanced plant drought stress resistance compared to WT. Transcriptome analysis of S. miltiorrhiza following drought stress identified a number of differentially expressed genes (DEGs) between the AtDREB1C transgenic lines and WT. These DEGs are involved in photosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis, ribosome, starch and sucrose metabolism, and other metabolic pathways. The modified pathways involved in plant hormone signaling are thought to be one of the main causes of the increased drought tolerance of AtDREB1C transgenic S. miltiorrhiza plants.

Application of 12S rRNA gene for the identification of animal-derived drugs.

PURPOSE. Animal-derived drugs are the major source of biological products and traditional medicine, but they are often difficult to identify, causing confusion in the clinical application. Among these medicinal animals, a number of animal species are endangered, leading to the destruction of biodiversity. The identification of animal-derived drugs and their alternatives would be a first step toward biodiversity conservation and safe medication. Until now, no effective method for identifying animal-derived drugs has been demonstrated; DNA-based species identification presents a brand-new technique. METHODS. We designed primers to amplify a 523-bp fragment of 12S rRNA and generated sequences for 13 individuals within six medicinal animal species. We examined the efficiency of species recognition based on this sequence, and we also tested the taxonomic affiliations against the GenBank database. RESULTS. All the tested drugs were identified successfully, and a visible gap was found between the inter-specific and intra-specific variation. We further demonstrated the importance of data exploration in DNA-based species identification practice by examining the sequence characteristics of relative genera in GenBank. This region of the 12S rRNA gene had a 100% success rate of species recognition within the six medicinal animal species. CONCLUSIONS. We propose that the 12S rRNA locus might be universal for identifying animal-derived drugs and their adulterants. The development of 12S rRNA for indentifying animal-derived drugs that share a common gene target would contribute significantly to the clinical application of animal-derived drugs and the conservation of medicinal animal species. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

Antioxidant activities of Dracocephalum tanguticum maxim extract and its up-regulation on the expression of neurotrophic factors in a rat model of permanent focal cerebral ischemia.

The aim of this study was to investigate the effect of a BuOH-soluble fraction from Dracocephalum tanguticum Maxim (DME), which contained 52% of total flavonoid, on the cerebral ischemia injury induced by permanent middle cerebral artery occlusion (pMCAO) in rats. RT-PCR and Western blot analysis showed that DME (30 mg/kg/day for seven days) by intragastric administration modulated the mRNA expression and protein synthesis of two neurotrophic factors: brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). DME was effective in stimulating BDNF mRNA expression and protein synthesis in the ipsilateral frontal cortex (IFC) of both the sham-operated and pMCAO rats and this effect was also observed in the hippocampus of the pMCAO rats. DME significantly increased NT-3 mRNA expression and protein synthesis in the IFC and hippocampus of the pMCAO rats, although it had no effect on NT-3 expression in the sham-operated groups. Meanwhile, DME also decreased the malondialdehyde contents in the hippocampus of the sham-operated and pMCAO groups, and significantly attenuated the decrease of endogenous antioxidant (superoxide dismutase, glutathione peroxidase and catalase) activities in both the IFC and hippocampus of the rats after ischemia insult injury. Moreover, DME facilitated the neurobehavioral recovery after the cerebral ischemia. These findings suggested that DME has potential for treatment of ischemia-induced brain damage through stimulation of antioxidant activity and neurotrophic factor synthesis.

[Identification, characterization and utilization of simple sequence repeat markers derived from Salvia miltiorrhiza expressed sequence tags].

Despite Salvia miltiorrhiza being one of the most important medicine plants in China, there is a limited availability of genomic resources, especially of the expressed sequence tag-based markers. In this study, we selected and characterized functional markers in S. miltiorrhiza, which consisted of 4,192 non-redundant expressed sequence tags (ESTs) from 10,288 identified S. miltiorrhiza ESTs in dbEST data bank. Among them, 159 simple sequence repeats (SSR) were detected, which amounted to 3.79% of the non-redundant starting sequence population. This incidence was equivalent to one EST-SSR in every 12.74 kb of S. miltiorrhiza ESTs. Among the different motifs ranging from 1 bp to 6 bp, di-nucleotide repeat motif was the most abundant (77, 48.43%), followed by tri-nucleotide (41, 25.79%), hexa-nucleotide (23, 14.47%), penta-nucleotide (12, 7.55%) and tetra-nucleotide (6, 3.77%). In 47 identified motif types, the detected frequency above 5% were GA/CT (16.35%), AG/TC (15.09%), TCA/AGT (10.69%), AT/TA (6.29%), GAAAAG/CAAAAC (6.29%) and TA/AT (5.03%). Based on flank sequence of detected SSR, a total of 83 EST-SSR primer pairs were designed and tested for the amplification efficiency, polymorphism and transferability in thirteen S. mihiorrhiza samples and other ten species from the genus Salvia. The results showed that 72 primer pairs were successfully amplified in S. miltiorrhiza samples to yield and 279 loci with an average of 3.88 loci per primer pair. The cross-transferability of S. miltiorrhiza EST-SSR markers to other ten Salvia plants was very high, ranging from 60% to 100% with an average of 85%. Further analysis of the genetic similarity based on the polymorphic bands showed the EST-SSR could detect the genetic diversity on different levels among the whole test samples and distinguish the S. miltiorrhiza from other Salvia plants effectively. It is expected that the potential markers described here would add to the repertoire of DNA markers needed for genetic analysis, linkage mapping and comparative genomics studies in S. miltiorrhiza and related Salvia genus plants.