[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.

[Antipyretic activity and potential mechanism of Indigo Naturalis on 2,4-dinitrophenol-induced fever rat model].

As an effective antipyretic medicine,Indigo Naturalis has a long history of application in the field of Chinese medicine.The content of organics,mainly indigo and indirubin,is about 10%. However,the active ingredients and mechanism of its antipyretic effect have not yet been fully elucidated. In view of this,they were investigated in this study with the rectal temperature change as an indicator and 2,4-dinitrophenol-induced fever rats as subjects. The content of PGE2 and c AMP in the hypothalamus and the serum levels of TNF-α,IL-1ß and IL-6 were determined by ELISA. Moreover,the plasma samples of fever rats were analyzed by metabonomics in combination with UPLC-Q-TOF-MS for the exploration of potential biomarkers and the discussion on the antipyretic mechanism of Indigo Naturalis and its active ingredients. The results showed that the rising trend of rectal temperature in rats was suppressed 0. 5 h after the treatment with Indigo Naturalis,organic matter,indigo or indirubin as compared with the rats of model group( P < 0. 05),among which Indigo Naturalis and organic matter had better antipyretic effect. ELISA results showed that organic matter and indigo can inhibit the expression of PGE2 and c AMP( P<0. 01),while Indigo Naturalis and organic matter were effective in curbing the increase in TNF-α( P<0. 05). A total of 21 endogenous metabolites were identified from the plasma samples of the Indigo Naturalis,organic matter,indigo and indirubin groups,which were mainly involved in glycerophospholipid metabolism.

[Preparation of hydrophilic Indigo Naturalis based on polyethylene glycol( PEG) surface film-forming method and evaluation].

Polyethylene glycol (PEG) surface film-forming method was used to prepare hydrophilic Indigo Naturalis decoction pieces with stable effect.The preparation process of modified Indigo Naturalis was optimized and its microscopic properties,hydrophilicity,antipyretic efficacy,and safety were systematically evaluated.With equilibrium contact angle as assessment index,the influence of modifier type,modifier dosage,dispersant dosage,and co-grinding time on water solubility of Indigo Naturalis was investigated by single factor test.The results showed that the optimal preparation process was as follows.The 6%PEG6000 is dissolved in 10%anhydrous ethanol solution by sonification and then the mixture is ground with Indigo Naturalis for 2 min.The resultant product is dried on a square tray in an oven at 60℃to remove ethanol and thereby the PEG-modified hydrophilic Indigo Naturalis decoction pieces are yielded.The morphological observation under scanning electron microscope (SEM) indicated that the modified Indigo Naturalis had smoother surface than Indigo Naturalis,and energy spectrometer measurement showed that the nitrogen (N),calcium(Ca),oxygen (O),and silicon (Si) on the surface of modified Indigo Naturalis powder were less than those of Indigo Naturalis powder.Modified Indigo Naturalis had the equilibrium contact angle 18.96°smaller,polar component 22.222 m J·m~(-2)more,and nonpolar component 7.277 m J·m~(-2)smaller than the Indigo Naturalis powder.Multiple light scattering technique was employed to evaluate the dispersion in water and the result demonstrated that the transmittance of Indigo Naturalis and modified Indigo Naturalis was about85%and 75%,respectively,suggesting the higher dispersity of modified Indigo Naturalis.The suspension rate of modified Indigo Naturalis in water was determined by reflux treatment.The result showed that 57%of Indigo Naturalis was not wetted after refluxing for1 h,while the modified Indigo Naturalis was all wetted and dispersed into water.The dissolution of indigo and indirubin of modified Indigo Naturalis increased and the process was more stable.Then,rats were randomized into the blank group,model group,acetaminophen group,Indigo Naturalis group,and hydrophilic Indigo Naturalis group.The temperature changes of rats were observed after administration and the concentration of IL-1ßand TNF-αin serum and IL-1ßand PGE_2in hypothalamus was measured.The results indicated that the temperature of Indigo Naturalis group and hydrophilic Indigo Naturalis group dropped and the IL-1ßlevel of the hydrophilic Indigo Naturalis group decreased (P<0.05) as compared with those in the model group.Thus,both Indigo Naturalis and hydrophilic Indigo Naturalis had antipyretic effect,particularly the hydrophilic Indigo Naturalis.The acute toxicity test of hydrophilic Indigo Naturalis verified that it had no toxicity to rats.In this study,the hydrophilic Indigo Naturalis decoction pieces were prepared with the PEG surface film-forming method,and the antipyretic efficacy and safety were evaluated,which expanded the technological means of powder modification for Chinese medicine and provided a method for clinical use of Chinese medicine.

Recent advances of novel technologies for quality consistency assessment of natural herbal medicines and preparations.

Quality consistency is one of the basic attributes of medicines, but it is also a difficult problem that natural medicines and their preparations must face. The complex chemical composition and comprehensive pharmacological action of natural medicines make it difficult to simply apply the commonly used evaluation methods in chemical drugs. It is thus urgent to explore the novel evaluation methods suitable for the characteristics of natural medicines. With the rapid development of analytical techniques and the deepening understanding of the quality of natural herbs, increasing numbers of researchers have proposed many new ideas and technologies. This review mainly focuses on the basic principles, technical characteristics and application examples of the chemical evaluation, biological evaluation methods and their combination in quality consistency evaluation of natural herbs. On the bases of chemical evaluation and clinical efficacy, new methods reflecting their pharmacodynamic mechanism and safety characteristics will be developed, and gradually towards accurate quality control, to achieve the goal of quality consistency. We hope that this manuscript can provide new ideas and technical references for the quality consistency of natural drugs and their preparations, thus better guarantee their clinical efficacy and safety, and better promote industrial development.

[Overview and prospects of traditional Chinese medicine blending technology oriented by quality consistency].

The consistency of drug quality is related to the clinical efficacy and safety,which is highly valued by the government and relevant industries. Compared with chemical medicine,traditional Chinese medicine originates from the nature,and is greatly influenced by natural factors,such as the place of origin,cultivation and processing technology,climate. The quality consistency of traditional Chinese medicine is poor. The quality consistency has become the pain point and difficulty of the development of the traditional Chinese medicine industry,which seriously affects the stability and controllability of clinical efficacy and the reproducibility or recognition of modern research results. It is also a bottleneck for Chinese patent medicine to enter the international market. Mixed batch blending technology is an effective method for the scientific guarantee of the quality consistency in other industries and disciplines,and widely applied in liquor making industry,tobacco industry and perfume industry. Overseas,mixed batch blending technology has been successfully applied in guaranteeing the quality consistency of Ginkgo biloba preparations Jinnado. It has been used in the production of Chinese formulations in Japan for more than 30 years. In recent years,mixed batch blending technology has been introduced into the pharmaceutical field to ensure the quality consistency of traditional Chinese medicine,and relevant research has gradually increased.This manuscript reviews the application of blending technology in other disciplines,summarizes the algorithm principles and software systems of mixed batch blending in traditional Chinese medicine or natural medicine,explains the specific implementation process of mixed batch blending technology,and looks forward to the application prospects of artificial intelligence and other new technologies,in the hope of providing new ideas and technologies for breaking through the problem of quality consistency,and boosting the high-quality and high-level development of Chinese medicine industry in the new era.

A Potential Anti-Tumor Herb Bred in a Tropical Fruit: Insight into the Chemical Components and Pharmacological Effects of Momordicae Semen.

Gac fruit (Momordica cochinchinensis Spreng) is a popular tropical fruit in southeast Asia. What is amazing is that its seeds (Momordicae Semen) and arils are traditional herbs with anti-tumor activity, and have protected human health for more than 1000 years. In recent years, its anti-tumor activity has received extensive attention and research. This manuscript summarized the chemical composition of saponins, fatty acids, volatile constituents, proteins, peptides, and other components from Momordicae Semen (MSE). The effect and mechanism of MSE and its extract on breast cancer, gastric cancer, lung cancer, esophagus cancer, melanomas, and human cervical epithelial carcinoma were discussed. In addition, its antioxidant, anti-inflammatory, and other pharmacological effects were also analyzed. We hope that this review will provide new ideas for the treatment of cancer and other diseases, and become a reference for the further research into complementary and alternative medicine.

Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities.

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two.