The health benefits of dietary polyphenols on pediatric intestinal diseases: Mechanism of action, clinical evidence and future research progress.

Pediatric intestinal development is immature, vulnerable to external influences and produce a variety of intestinal diseases. At present, breakthroughs have been made in the treatment of pediatric intestinal diseases, but there are still many challenges, such as toxic side effects, drug resistance, and the lack of more effective treatments and specific drugs. In recent years, dietary polyphenols derived from plants have become a research hotspot in the treatment of pediatric intestinal diseases due to their outstanding pharmacological activities such, as anti-inflammatory, antibacterial, antioxidant and regulation of intestinal flora. This article reviewed the mechanism of action and clinical evidence of dietary polyphenols in the treatment of pediatric intestinal diseases, and discussed the influence of physiological characteristics of children on the efficacy of polyphenols, and finally prospected the new dosage forms of polyphenols in pediatrics.

[Comparative analysis of efficacy of different forms of Galli Gigerii Endothelium Corneum on functional dyspepsia in rats based on composition-pharmacodynamics].

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.

The investigation of thermal stability and GC-MS analysis of Acorus tatarinowii and Atractylodes lancea volatile oils treated by ß cyclodextrin inclusion and Pickering emulsion technologies.

Objective: To investigate the stability of Acorus tatarinowii and Atractylodes lancea essential oils (ATaAL-EO) under a hot environment at 60 °C, and to analyze the differences in component, quantity, and quality changes, as well as variations in the main components, under different treatment methods of crude oil, ß-cyclodextrin inclusion of ATaAL-EO, and Pickering emulsion, to improve the stability and quality of ATaAL-EO. Methods: The stability of the ATaAL-EO group, the ß-cyclodextrin inclusion ATaAL-EO group, and the Pickering emulsion group were investigated under a 60 °C heat environment. Volatile oil retention rate and peroxide value were collected and measured. The volatile oil components of each group were determined by GC-MS, and t-tests were used to screen for differential components. PCA plots for each group were constructed using the OmicShare online platform. Line plots were generated using the Rmisc and reshape2 packages. Upset Venn diagrams under different hot environments were created using the OmicShare online platform to identify quantitative and qualitative changing components and heat map stack plots for newly generated compounds and connected line plots for disappearing compounds were produced for each group. Boxplots for the main component compounds under different hot environments were generated using the reshape2 and ggplot2 packages. Results: In a hot environment of 60 °C, the ß-cyclodextrin inclusion ATaAL-EO and Pickering emulsion group with 1, 3, and 8 h of placement showed higher retention and lower oxidation degree compared to the stability of the ATaAL-EO group. GC-MS analysis results showed that the stability of volatile components in the Pickering emulsion group and ß-cyclodextrin inclusion ATaAL-EO group was significantly improved compared to the crude oil group. Conclusion: ß-cyclodextrin inclusion complexes with ATaAL-EO, as well as Pickering emulsions, can significantly enhance the stability and quality of ATaAL-EO. Pickering emulsions have more advantages.

[Research progress on structure, structure-activity relationship, and biological activity of Aconiti Lateralis Radix Praeparata polysaccharides].

Aconiti Lateralis Radix Praeparata polysaccharides(AP) are a class of bioactive macromolecules extracted from the herbs of Aconiti Lateralis Radix Praeparata and its various processed products. Since the AP was first separated in 1986, its pharmacological effects include immune regulation, anti-tumor, anti-depression, organ protection, hypoglycemia, and anti-inflammatory had been found. In recent years, with the development of polysaccharide extraction, separation, and structure identification technologies, more than 20 kinds of AP have been separated from Aconiti Lateralis Radix Praeparata and its processed products, and they have ob-vious differences in relative molecular weight, monosaccharide composition, glycosidic bond, structural characteristics, and biological activities. In particular, AP may be dissolved, degraded, or allosteric under the complex processing environment of fermentation, soaking, cooking, etc., leading to the diversified structure of AP, which provides a possibility for further understanding of the structure-activity relationship of AP. Therefore, this study systematically reviewed the research progress on the structure and structure-activity relationship of AP, summarized the biological activity and potential action mechanism of AP, and discussed the technical challenges in the development and application of AP, so as to promote the quality control and further development and utilization of AP.

[Technology and principle of improving solubility of Dioscoreae Rhizoma formula granules based on powder modification].

The powder modification technology was used to improve the powder properties and microstructure of Dioscoreae Rhizoma extract powder, thereby solving the problem of poor solubility of Dioscoreae Rhizoma formula granules. The influence of modifier dosage and grinding time on the solubility of Dioscoreae Rhizoma extract powder was investigated with the solubility as the evaluation index, and the optimal modification process was selected. The particle size, fluidity, specific surface area, and other powder properties of Dioscoreae Rhizoma extract powder before and after modification were compared. At the same time, the changes in the microstructure before and after modification was observed by scanning electron microscope, and the modification principle was explored by combining with multi-light scatterer. The results showed that after adding lactose for powder modification, the solubility of Dioscoreae Rhizoma extract powder was significantly improved. The volume of insoluble substance in the liquid of modified Dioscoreae Rhizoma extract powder obtained by the optimal modification process was reduced from 3.8 mL to 0 mL, and the particles obtained by dry granulation of the modified powder could be completely dissolved within 2 min after being exposed to water, without affecting the content of its indicator components adenosine and allantoin. After modification, the particle size of Dioscoreae Rhizoma extract powder decreased significantly, d_(0.9) decreased from(77.55±4.57) µm to(37.91±0.42) µm, the specific surface area and porosity increased, and the hydrophilicity improved. The main mechanism of improving the solubility of Dioscoreae Rhizoma formula granules was the destruction of the "coating membrane" structure on the surface of starch granules and the dispersion of water-soluble excipients. This study introduced powder modification technology to solve the solubility problem of Dioscoreae Rhizoma formula granules, which provided data support for the improvement of product quality and technical references for the improvement of solubility of other similar varieties.

[Physicochemical properties and anti-inflammatory and immunomodulatory effects of Shengfupian polysaccharides].

In this study, the crude polysaccharides was extracted from Shengfupian and purified by Sevag deproteinization. Then, the purified neutral polysaccharide fragment was obtained by the DEAE-52 cellulose chromatography column and Sephadex G-100 co-lumn. The structure of polysaccharides was characterized by ultraviolet spectroscopy, infrared spectroscopy, ion chromatography, and gel permeation chromatography. To investigate the anti-inflammatory activity of Shengfupian polysaccharides, LPS was used to induce inflammation in RAW264.7 cells. The expression of the CD86 antibody on surface of M1 cells, the function of macrophages, and the content of NO and IL-6 in the supernatant were examined. An immunodepression model of H22 tumor-bearing mice was established, and the immunomodulatory activity of Shengfupian polysaccharides was evaluated based on the tumor inhibition rate, immune organ index and function, and serum cytokine levels. Research indicated that Shengfupian polysaccharides(80 251 Da) was composed of arabinose, galactose, glucose, and fructose with molar ratio of 0.004∶0.018∶0.913∶0.065. It was smooth and lumpy under the scanning electron microscope. In the concentration range of 25-200 µg·mL~(-1), Shengfupian polysaccharides exhibited little or no toxicity to RAW264.7 cells and could inhibit the polarization of cells to the M1 type and reduce the content of NO and IL-6 in the cell supernatant. It could suppress the phagocytosis of cells at the concentration of 25 µg·mL~(-1), while enhancing the phagocytosis of RAW264.7 cells within the concentration range of 100-200 µg·mL~(-1). The 200 mg·kg~(-1) Shengfupian polysaccharides could alleviate the spleen injury caused by cyclophosphamide, increase the levels of IL-1ß and IL-6, and decrease the level of TNF-α in the serum of mice. In conclusion, Shengfupian polysaccharides has anti-inflammatory effect and weak immunomodulatory effect, which may the material basis of Aconm Lateralis Radix Praeparaia for dispelling cold and relieving pain.

The material basis of astringency and the deastringent effect of polysaccharides: A review.

Astringency is a feeling of dryness in the mouth. Microscopically, it is manifested in the diversity of ingredients and mechanisms that can cause astringency, astringent components are mainly flavonoids, phenolic acids, tannin and other polyphenols components. Macroscopically, it is manifested in the rich variety of foods with astringent taste, because polyphenols are common secondary metabolites of plants. With the improvement of people's living standards, the demand for reducing or removing astringency in food and medicine is also increasing, and polysaccharides, as commonly used flavoring agents and food additives, have become the ideal choice for decreasing astringency. In this paper, the material basis, molecular mechanism, possible pathways and related cases of polysaccharides moderating of astringency are mainly reviewed, so as to illustrate the feasibility of polysaccharides decreasing of astringency and provide a reference for reducing the astringency of food and drugs.

[Combined anti-bitterness strategy for extremely bitter characteristics of Andrographis Herba decoction and mechanism].

Three kinds of excipients were selected to investigate the anti-bitterness effect on the extremely bitter characteristics of Andrographis Herba decoction, and the optimal combined anti-bitterness formula was obtained. The preparation principle of different excipients was clarified by virtual screening and experimental verification to explore the advantages of the three kinds of excipients in the combined anti-bitterness effect. Sensory evaluation showed that mPEG_(2000)-PLLA_(2000), γ-cyclodextrin(γ-CD), and aspartame all had good anti-bitterness effect, which reduced the bitterness intensity of Andrographis Herba decoction by 0.5, 6, and 3 points, respectively. The anti-bitterness effect was superior when 0.15% mPEG_(2000)-PLLA_(2000), 1.60% γ-CD, and 0.04% aspartame were combined, and the taste score of the Andrographis Herba decoction decreased from 8 points(severe bitterness) to 1 point(almost no bitterness). Quantum chemistry calculations showed that mPEG_(2000)-PLLA_(2000) reduced the electrostatic potential of bitter groups, which spontaneously combined with it and formed a physical barrier, hindering the binding of bitter components to receptors. The interaction between γ-CD and bitter components was studied. It was found that the surface area and free energy of γ-CD decreased and the dipole moment increased, indicating that γ-CD included bitter components and self-assembled to form supramolecules. Molecular docking showed that hydroxy at position 14 and carbonyl at position 16 of andrographolide, and hydroxy at position 3 and 4, carbonyl at position 14, and five-membered lactone ring of dehydrated andrographolide were possibly the main bitter groups. The binding free energies of aspartame to bitter receptors TAS2 R10, TAS2 R14, and TAS2 R46 were-3.21,-1.55, and-2.52 kcal·mol~(-1), respectively, indicating that aspartame competed to inhibit the binding of bitter groups to bitter receptors. The results of content determination showed that the free amounts of andrographolide and dehydrated andrographolide in Andrographis Herba decoction were 0.23% and 0.28% respectively, while after adding flavor masking excipients, the dissociation amount of andrographolide and dehydrated andrographolide in the decoction decreased to 0.13% and 0.20%, respectively. The above results show that mPEG_(2000)-PLLA_(2000) involves some bitter components into it through micellar self-assembly to reconcile the entrance bitterness, and γ-CD includes the remaining bitter components in the real solution to control the main bitter taste. Aspartame further competes to inhibit the combination of bitter components and bitter receptors, and improves the taste to be sweet. Multi-excipients combined with anti-bitterness strategy significantly reduces the free concentration of bitter substances in Andrographis Herba decoction, and optimizes the taste of the decoction.

[Comparison of odor and quality of Galli Gigerii Endothelium Corneum derived from domestic chickens and broilers].

Galli Gigerii Endothelium Corneum(GGEC) is commonly used for the clinical treatment of indigestion, vomiting, diarrhea, and infantile malnutrition with accumulation. In recent decades, omnivorous domestic chickens, the original source of GGEC, has been replaced by broilers, which may lead to significant changes in the quality of the yielding GGEC. Through subjective and objective sensory evaluation, biological evaluation, and chemical analysis, this study compared the odor and quality between GGEC derived from domestic chickens and that from broilers. The odor intensity between them was compared by odor profile analysis and it was found that the fishy odor of GGEC derived from domestic chickens was significantly weaker than that of GGEC from broilers. Headspace-solid phase microextraction-gas chromatography-triple quadrupole tandem mass spectrometry(HS-SPME/GC-QQQ-MS/MS) suggested that the overall odor-causing chemicals were consistent with the fishy odor-causing chemicals. According to the odor activity va-lue and the orthogonal partial least squares discriminant analysis(OPLS-DA) result, dimethyl trisulfide, 2-methoxy-3-isobutylpyrazine, and 2-methylisoborneol were responsible for the fishy odor(OAV≥1) and the content of fishy odor-causing chemicals in GGEC derived from broilers was 1.12-2.13 folds that in GGEC from domestic chickens. The average pepsin potency in GGEC derived from broilers was 15.679 U·mg~(-1), and the corresponding figure for the medicinal from domestic chickens was 26.529 U·mg~(-1). The results of pre-column derivatization reverse-phase high-performance liquid chromatography(RP-HPLC) assay showed that the content of total amino acids and digestion-promoting amino acids in domestic chickens-derived GGEC was 1.12 times and 1.15 times that in GGEC from broilers, and the bitter amino acid content was 1.21 times folds that of the latter. In conclusion, GGEC derived from domestic chickens had weaker fishy odor, stronger enzyme activity, higher content of digestion-promoting amino acids, and stronger bitter taste than GGEC from broilers. This study lays a scientific basis for studying the quality variation of GGEC and provides a method for identifying high-quality GGEC. Therefore, it is of great significance for the development and cultivation of GGEC as both food and medicine and breeding of corresponding varieties.

[Material basis of stench of animal medicine: a review].

Despite the distinctive characteristics and remarkable efficacy, animal medicine is stenchy, which decreases the comp-liance of patients. At the moment, the research on the method for deodorizing animal medicines lags behind. To be specific, the components related to the odor and the basic properties transformation of the components are unclear and there is a lack of specific deodorizing method. This study aims to clarify the main components related to the stench of animal medicine, such as aldehydes, amines, trimethylamines and sulfur compounds, and their basic properties, and to explore their metabolism and transformation in vivo and in vitro, which is expected to serve as a reference for the research on deodorization of animal medicine and development of new techniques.

[Connotation and mitigation of polyphenolic astringency in Chinese medicine].

Taste is one of the important factors in the design of oral drug preparations. Polyphenols are the secondary metabolites produced in the growth process of Chinese medicine with a variety of physiological activities. However, astringency perceived from polyphenols tastes uncomfortable. As one of the true taste of Chinese medicine, astringency with drying, rough, and wrinkled sensation, seriously affects the texture of Chinese medicine and the compliance of patients. Due to the universality of polyphenolic astringency in Chinese medicine and the weakness of modern research, this study systematically reviewed and summarized the latest research on the mechanism of polyphenolic astringency, the astringency evaluation method, and the astringency-mitigation technology. Through comprehensively analyzing the quantification methods, such as sensory evaluation, animal preference evaluation, chemical evaluation, bionic evaluation, and polyphenol-protein interaction evaluation, the direction of overall astringency assessment with "unified dimension" was proposed. Since the characteristics of Chinese medicine and the mechanism of polyphenolic astringency did not reach a consensus, this study proposed the idea of astringency mitigation suitable for Chinese medicine. This study is intended to deepen the understanding of astringency associated with Chinese medicine, and establish a real and objective astringency evaluation method for Chinese medicine, thus promoting the technique of astringency mitigation of polyphenolic Chinese medicine preparations from trial and error to science.

[Main spicy components, mechanism and masking technology for spicy flavor of Chinese medicine: a review].

Many Chinese medicinal materials, vegetable oils and extracts, and even Chinese patent medicines are spicy, which influences the medication compliance of patients, especially children. Different from the sour, sweet, bitter, salty, and umami tastes, it is a painful sensation formed when the spicy substances stimulate the nerve endings. At the moment, there are a few studies on the spicy components and mechanism and masking technology for the spicy flavor of Chinese medicine in the pharmaceutical industry, and the findings in food science are usually taken as a reference, which fail to guide the masking of the spicy flavor in Chinese medicine preparations. According to literature research, the exterior-releasing medicine, dampness-resolving medicine, and interior-warming medicine are spicy, especially some vegetable oils and extracts. Taking Zingiberis Rhizoma and prescriptions containing this medicinal as an example, the spicy components in Chinese medicine and the structure-activity characteristics were analyzed to reveal the mechanism for the spicy flavor: spicy components activate the transient receptor potential vanilloid subfamily member 1(TRPV1). The advantages and disadvantages of separation, neutralization with sugar, and inclusion for the masking of the spicy flavor were summarized and the applicability in Chinese medicine was analyzed. Moreover, the future development direction was put forward. This study is expected to promote the development of spicy masking technology for Chinese medicine prescriptions for children.

Dual role of the nasal microbiota in neurological diseases-An unignorable risk factor or a potential therapy carrier.

Recently, comparative studies have rapidly increased with the closer correlation between microbiota and neurological diseases. However, most insights about the association between microbiota and neurological diseases still focus on the gut-brain axis and ignore that nasal microbiota could form a complex and essential link with the nervous system via the nose-to-brain pathway, suggesting the role in modulating the immune system, metabolic system, and nervous system development, which influence the physiopathology of neurological diseases. Due to the complex interactions between nasal microbiota and the brain, the nasal microbiota may have a particular pathogenic effect and therapeutic potential on neurological diseases. Therefore, this review aims to deeply analyze the dual effects of nasal microbiota on neurological diseases, focusing on pathogenic and therapeutic effects to provide a new perspective for preventing and treating neurological diseases by altering nasal microbiota. This review concludes the bidirectional effects of nasal microbiota on neurological diseases, including the pathogenicity and potential treatment on Alzheimer's disease, Parkinson's disease, Multiple sclerosis, and Stroke. Furthermore, modern medical technology combined with artificial intelligence, including implantable sensors, modeling software, and nanofluid techniques, may further study the complex effects between nasal microbiota and the brain, thereby providing new options for treating neurological diseases.

Traditional Uses, Pharmacological Effects, and Molecular Mechanisms of Licorice in Potential Therapy of COVID-19.

The current Coronavirus disease 2019 (COVID-19) pandemic has become a global challenge, and although vaccines have been developed, it is expected that mild to moderate patients will control their symptoms, especially in developing countries. Licorice, not only a food additive, but also a common traditional Chinese herbal medicine, which has several pharmacological effects, such as anti-inflammation, detoxification, antibacterial, antitussive, and immunomodulatory effects, especially in respiratory diseases. Since the outbreak of COVID-19, glycyrrhizin, glycyrrhizin diamine and glycyrrhizin extract have been widely studied and used in COVID-19 clinical trials. Therefore, it is a very interesting topic to explore the material basis, pharmacological characteristics and molecular mechanism of licorice in adjuvant treatment of COVID-19. In this paper, the material basis of licorice for the prevention and treatment of COVID-19 is deeply analyzed, and there are significant differences among different components in different pharmacological mechanisms. Glycyrrhizin and glycyrrhetinic acid inhibit the synthesis of inflammatory factors and inflammatory mediators by blocking the binding of ACE 2 to virus spike protein, and exert antiviral and antibacterial effects. Immune cells are stimulated by multiple targets and pathways to interfere with the pathogenesis of COVID-19. Liquiritin can prevent and cure COVID-19 by simulating type I interferon. It is suggested that licorice can exert its therapeutic advantage through multi-components and multi-targets. To sum up, licorice has the potential to adjuvant prevent and treat COVID-19. It not only plays a significant role in anti-inflammation and anti-ACE-2, but also significantly improves the clinical symptoms of fever, dry cough and shortness of breath, suggesting that licorice is expected to be a candidate drug for adjuvant treatment of patients with early / mild COVID-19.

[Research progress of Phyllanthi Fructus and prediction of its Q-markers].

Phyllanthi Fructus, a unique Chinese and Tibetan medicinal plant with both edible and medical values, has high potential of cultivation and development. The resources of Phyllanthi Fructus in China are rich, mainly distributed in Yunnan, Sichuan, Fujian, Guangdong, Guangxi, etc. Phyllanthi Fructus is widely used in the clinical practice of Chinese medicine and plays an important role in Tibetan medicine, Uyghur medicine, Yi medicine, and Mongolian medicine. Phyllanthi Fructus mainly contains phenolic acids,tannins, terpenes, sterols, fatty acids, flavonoids, amino acids and other compounds. Modern pharmacological studies show that Phyllanthi Fructus has antioxidant, anticancer, blood lipid-lowering, liver protective, antimicrobial, anti-inflammatory, and immune regulatory activities. In this paper, the research status of Phyllanthi Fructus was reviewed from the aspects of herbal textual research,chemical composition, and pharmacological action. The quality markers(Q-markers) of Phyllanthi Fructus were predicted and analyzed from the aspects of biogenic pathway, specificity and measurability of chemical components, efficacy, properties, new clinical uses, drug-food homology, and transformation of polyphenols. The results will provide a scientific basis for the quality control, quality evaluation, and standard formulation of Phyllanthi Fructus.

Screening S protein - ACE2 blockers from natural products: Strategies and advances in the discovery of potential inhibitors of COVID-19.

The Coronavirus disease, 2019 (COVID-19) is caused by severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), which poses a major threat to human life and health. Given its continued development, limiting the spread of COVID-19 in the population remains a challenging task. Currently, multiple therapies are being tried around the world to deal with SARS-CoV-2 infection, and a variety of studies have shown that natural products have a significant effect on COVID-19 patients. The combination of SARS-CoV-2 S protein with Angiotensin converting enzyme II(ACE2) of host cell to promote membrane fusion is an initial critical step for SARS-CoV-2 infection. Therefore, screening natural products that inhibit the binding of SARS-CoV-2 S protein and ACE2 also provides a feasible strategy for the treatment of COVID-19. Establishment of high throughput screening model is an important basis and key technology for screening S protein-ACE2 blockers. Based on this, the molecular structures of SARS-CoV-2 and ACE2 and their processes in the life cycle of SARS-CoV-2 and host cell infection were firstly reviewed in this paper, with emphasis on the methods and techniques of screening S protein-ACE2 blockers, including Virtual Screening (VS), Surface Plasmon Resonance (SPR), Biochromatography, Biotin-avidin with Enzyme-linked Immunosorbent assay and Gene Chip Technology. Furthermore, the technical principle, advantages and disadvantages and application scope were further elaborated. Combined with the application of the above screening technologies in S protein-ACE2 blockers, a variety of natural products, such as flavonoids, terpenoids, phenols, alkaloids, were summarized, which could be used as S protein-ACE2 blockers, in order to provide ideas for the efficient discovery of S protein-ACE2 blockers from natural sources and contribute to the development of broad-spectrum anti coronavirus drugs.

[Challenges and strategies of high-quality development of Indigo Naturalis industry].

Traditional Chinese medicine( TCM) processing is a traditional pharmaceutical technology unique to China,which is an important means to ensure the safety and effectiveness of clinical medication. As China' s intangible cultural heritage,it contains a wealth of wisdom. With the evolution and optimization of processing methods,Indigo Naturalis,an ancient dye,has gradually become an effective medicine for the treatment of high fever in children,colitis,psoriasis,and leukemia. However,the quality of Indigo Naturalis pieces is difficult to be fundamentally improved due to the unique traditional processing method,complex technology,unclear principle,and outdated equipment. After spending 20 years in exploring the inheritance,innovation,and transformation of ancient lawtheory-principle-technology-equipment-quality control in Indigo Naturalis processing,our research group has basically expounded the processing principle and realized the modern expression and industrial transformation of traditional technology. As China enters a new era,the TCM industry has begun to undergo the high-quality transformation. It is urgent to carry out new excavations and improve the processing,quality,and clinical application of Indigo Naturalis pieces,to better inherit and innovate traditional processing technologies and meet people's demand for high-quality TCM health services.

[Microbial community structure and transformation of indoles in soaking and fermentation of Indigo Naturalis].

The soaking and fermentation of Baphicacanthus cusia( Nees),the important intermediate link of Indigo Naturalis processing,facilitates the synthesis of indigo and indirubin precursors and the dissolution of endogenous enzymes and other effective components,while the role of microorganisms in the fermentation is ignored. The present study investigated the changes of microbial community structure in Indigo Naturalis processing based on 16 S amplicon sequencing and bioinformatics. Meanwhile,the contents of indigo,indirubin,isatin,tryptanthrin,indole glycoside,etc. were determined to explore the correlation between the microorganisms and the alterations of the main components. As demonstrated by the results,the microbial diversity decreased gradually with the fermentation,which bottomed out after the addition of lime. Proteobacteria,Bacteroidetes,and Firmicutes were the main dominant communities in the fermentation. The relative abundance of Proteobacteria declined gradually with the prolongation of fermentation time,and to the lowest level after the addition of lime. The relative abundance of Firmicutes increased,and that of Bacteroidetes decreased first and then increased. The contents of effective substances in Indigo Naturalis also showed different variation tendencies. As fermentation went on,indole glycoside decreased gradually; indigo first increased and then decreased; indirubin and isatin first decreased and then increased; tryptanthrin gradually increased. Those changes were presumedly related to the roles of microorganisms in the synthesis of different components. This study preliminarily clarified the important role of microorganisms in the soaking and fermentation and provided a scientific basis for the control of Indigo Naturalis processing and the preparation of high-quality Indigo Naturalis.

[Changes in forms of Indigo Naturalis slices in ancient and modern times: a systematic study on quality of purified Indigo Naturalis and crude Indigo Naturalis].

Indigo Naturalis has a long history of medicinal use with particularity and complexity in its processing. Before the Ming dynasty,Indigo Naturalis was extracted from the top layer of zymotic fluid,called " purified Indigo Naturalis". In modern processing,the precipitate " crude Indigo Naturalis" is dried to produce Indigo Naturalis after impurity removal. The form of Indigo Naturalis slices has undergone significant changes in ancient and modern times. In view of this,the quality comparison between crude Indigo Naturalis and purified Indigo Naturalis was conducted in this study with modern analytical techniques. Firstly,chemical composition was analyzed with UPLC-Q-TOF-MS,and the chemical composition of scent with HS-SPME/GC-MS/MS. The content of indigo,indirubin,total ash,and water-soluble extract was determined as well as the inorganic composition in crude Indigo Naturalis and purified Indigo Naturalis. Then,their microscopic morphology was observed and the surface element composition was investigated. Finally,the antipyretic activities of crude Indigo Naturalis and purified Indigo Naturalis were compared in the fever rat model induced by lipopolysaccharide and 2,4-dinitrophenol. The results demonstrated that the purified Indigo Naturalis had a faster and more lasting antipyretic effect,while the crude Indigo Naturalis had almost no antipyretic effect. This study is of great significance to the research on processing technology of Indigo Naturalis and provides reference for the formulation of its quality standards,production specifications and calibration procedures.

[Key to Indigo Naturalis' oral effectiveness: in vivo and in vitro verification of bile action].

Indigo Naturalis( IN) is mainly composed of 10% organic matter and 90% inorganic matter,with a poor wettability and strong hydrophobicity. Indigo,indirubin and effective ingredients are almost insoluble in water. And how it exerts its effect after oral administration still needs to be revealed. For this reason,this study put forward the hypothesis that " Indigo Naturalis forms a slightly soluble calcium carbonate carrier in a strong acid environment of gastric fluid,and organic substances are solubilized in the bile environment of intestinal fluid",and then verified the hypothesis. First,the dissolution apparatus was used to simulate the change process of IN in different digestive fluid,and the effects of low-dose and normal bile on the dissolution of inorganic substances and the release of organic substances were compared. After the surface morphology and element changes of IN in different digestive fluid were observed,it was found that bile is the key to promoting the dissolution of organic and inorganic substances in IN. Furthermore,the rat fever model induced by 2,4-dinitrophenol was used to study the antipyretic effect of IN in normal rats and bile duct ligation rats. It was found that the antipyretic effect of IN on normal rats was better than that of bile duct ligation rats. The above results indicated that after oral administration of IN,the calcium carbonate carrier was transformed into a slightly soluble state in acidic gastric fluid,and a small amount of organic matter was released. When IN entered the intestinal fluid mixed with bile,the carrier dissolved in a large amount,and indigo and indirubin were dissolved in a large amount,so as to absorb the blood and exert the effect. This study has a certain significance for guiding clinical application of IN. For patients with insufficient bile secretion( such as bile duct resection),oral administration with IN may not be effective and shall be paid attention.