[Substitution mode of rare and endangered Chinese medicinal materials and research strategy of multi-component replacement].

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.

[Research on artificial substitutes of rare and endangered animal medicinal materials and industrialization].

Rare and endangered animal medicine, a kind of important Chinese medicine, plays an irreplaceable role in the prevention and treatment of serious acute and chronic diseases and major diseases. Due to resource limitation and depletion and the increasing demand, rare and endangered medicinal animal resources have been drastically reduced or even extinct, which threatens the inheritance of traditional Chinese medicine, the integrity of clinical medicine, and the development of the traditional Chinese medicine industry. For the protection and sustainable utilization of Chinese medicinal resources, artificial substitutes came into being. However, there is still a lack of systematic research on the pharmacological effects and clinical applications of artificial substitutes and whether they can completely replace the original medicinal materials in clinical practice. Therefore, this study focuses on the status quo of rare and endangered animal medicinal materials and their artificial substitutes that have been marketed. To be specific, the two were compared and whether the artificial substitutes can completely replace the original medicinal materials was analyzed. In addition, constructive suggestions on the industrialization of artificial substitutes were put forward, which was expected to promote the sustainable development of Chinese medicinal resources.

[History and application of foreign medicinal resources serving healthcare industry].

Foreign medicinal resources have always been an important part of Chinese medicine and have made great contributions to the development of the Chinese medical and health industry. Since the opening of the Silk Road in the Han Dynasty, foreign medicinal resources have been introduced for different purposes, some of which have become Chinese medicine in clinical practice and are still in use today.Today, foreign medicinal resources also serve the Big Health industry in China. They are introduced and applied to the fields in the Big Health industry, such as food, cosmetics, health products, decoction pieces, and daily chemical products. With the integration and development of the "Healthy China" initiative, more foreign resources will enter the Big Health industry. This paper retrospectedthe history of foreign medicinal resources serving the ancient medical and health industry, reviewedits current development under the Big Health industry, summarizedthe experience of foreign medicinal resources serving the ancient medical and health industry, as well as the development and problems of new foreign medicinal resources, and put forward some suggestions to provide ideas for the development and application of foreign medicinal resources under the Big Health industry.

[Digestive properties of flavonoid components in Xiaoer Chiqiao Qingre Granules in simulated infant gastrointestinal environment].

This study aimed to elucidate the digestive characteristics of flavonoid components in Xiaoer Chiqiao Qingre Granules(XECQ) in the gastrointestinal environment of infants. An in vitro model was established to simulate the gastric and intestinal environment of infants. UPLC was used to analyze the content change of flavonoid components in XECQ, and their overall content was integrated through the mass fraction weight coefficient method. UPLC-Q-TOF-MS was employed to determine the digestive products of flavonoid components in gastrointestinal fluids and their metabolic pathways. The results showed that in the process of digestion, 11 digestion products were generated by oxidation, reduction, deglycosylation, methylation and other phase Ⅰ metabolism. From flavonoid content and component changes, it was found that the flavonoid components in XECQ were relatively stable in the gastric fluid, while their content in the intestinal fluid was first increased and then maintained stable. This was mainly because flavonoid components were released from proteins, polysaccharides and other macromolecular substances during gastrointestinal digestion. In addition, phase Ⅰ metabolism occurred, but with relatively low metabolic rate, resulting in their stable content. This study preliminarily explored the digestive characteristics of flavonoid components in XECQ in the infant gastrointestinal environment, which laid a foundation for further studying the absorption, transport and metabolism of pharmacodynamics components in XECQ, and facilitated the study of the biopharmaceutical pro-perties of pediatric Chinese medicine.

Enhancing the Biopharmacological Characteristics of Asperosaponin VI: Unveiling Dynamic Self-Assembly Phase Transitions in the Gastrointestinal Environment.

Purpose: Asperosaponin VI (ASP VI) as an active ingredient of Dipsacus asperoides, which has a wide range of biological and pharmacological activity. However, its development and application are restricted due to the poor gastrointestinal permeability and oral bioavailability. This investigation aims to reveal the influence of the self-assembled structure by the interaction between ASP VI and endogenous components NaTC and/or DOPC in the gastrointestinal environment on its biopharmaceutical properties, and novelty elucidated the molecular mechanism for the formation of self-assembled nanomicelles. Methods: This change in phase state in gastrointestinal fluids is characterized by dynamic light scattering (DLS) and transmission electron microscope (TEM). UPLC-Q-TOF-MS was used to analyze the composition of phase components and the exposure of nanomicelles in vivo. Molecular dynamics simulation (MDS) was applied to preliminarily elucidate the self-assembly mechanism of ASP VI in the gastrointestinal environment. Furthermore, theS8 promoting absorption mechanism of nanomicelles were investigated through in vivo pharmacokinetic experiments, parallel artificial membrane permeability assay (PAMPA), quadruple single-pass intestinal perfusion in rats, and Caco-2 cell monolayer model. Results: We demonstrated that the ASP VI could spontaneously form dynamic self-assembled structures with sodium taurocholate (NaTC) and dipalmitoyl phosphatidylcholine (DOPC) during gastrointestinal solubilization, which promoted the gastrointestinal absorption and permeability of ASP VI and increased its exposure in vivo, thus improving the biopharmacological characteristics of ASP VI. Moreover, ASP VI-NaTC-DOPC-self-assembled nanostructures (ASP VI-NaTC-DOPC-SAN) manifested higher cellular uptake in Caco-2 cells as evidenced by flow cytometry and confocal microscopy, and this study also preliminarily revealed the mechanism of self-assembly formation of ASP VI with endogenous components NaTC and DOPC driven by electrostatic and hydrogen bonding interactions. Conclusion: This study provides evidence that the dynamic self-assembled phase transition may play a key role in improving the biopharmacological characteristics of insoluble or low permeability active ingredients during the gastrointestinal dissolution of Chinese medicines.

Structural elucidation of a novel polysaccharide from Ophiopogonis Radix and its self-assembly mechanism in aqueous solution.

Ophiopogonis Radix polysaccharides with various bioactivities have caught people's attention in the pharmaceutical and functional food industries. It is necessary to reveal their structures, chain conformations, and solvent behaviors. A neutral polysaccharide named ORP-1 with molecular weight of 3667 Da was obtained from Ophiopogonis Radix. It was composed of d-fructofuranose and d-glucopyranose in the ratio of 0.85:0.15. Methylation, FT-IR and NMR analysis indicated ORP-1 consisted of 2,6-linked-Fruf units as the main chain and 1-linked-Glcp residue at the end. Congo red assay showed ORP-1 had no triple-helix structure. The observation of TEM and AFM found ORP-1 could self-assemble to form colloidal aggregate in water. This phenomenon was verified using CMC determination and MD simulation. Furthermore, intermolecular hydrogen bonds and hydrophobic interactions would be the main forces driving the aggregate. These results provided reference for the study of the chain conformation and behavior of polysaccharides in aqueous solution.

A review on the applications of Traditional Chinese medicine polysaccharides in drug delivery systems.

Traditional Chinese medicine polysaccharides (TCMPs) are plentiful and renewable resources with properties such as biocompatibility, hydrophilicity, biodegradability, and low cytotoxicity. Because the polysaccharide molecular chain contains a variety of active groups, different polysaccharide derivatives can be easily produced through chemical modification. They have been increasingly used in drug delivery systems (DDS). However, the potential of polysaccharides is usually ignored due to their structural complexity, poor stability or ambiguity of mechanisms of actions. This review summarized the applications of TCMPs in DDS around four main aspects. The general characteristics of TCMPs as drug delivery carriers, as well as the relationships between structure and function of them were summarized. Meanwhile, the direction of preparing multifunctional drug delivery materials with synergistic effect by using TCMPs was discussed. This review aims to become a reference for further research of TCMPs and their derivatives, especially applications of them as carriers in pharmaceutical preparation industry.

Palmatine from Mahonia bealei attenuates gut tumorigenesis in ApcMin/+ mice via inhibition of inflammatory cytokines.

Mahonia bealei is a Chinese folk medicine used to treat various ailments, in particular gastrointestinal inflammation­related illnesses, and palmatine is one of its active constituents. In this study, ApcMin/+ mice, a genetically engineered model, were used to investigate the effects of palmatine on the initiation and progression of gut inflammation and tumorigenesis enhanced by a high­fat diet. The in vitro antiproliferation and anti­inflammation effects of palmatine were evaluated on HT­29 and SW­480 human colorectal cancer cell lines. The concentration­related antiproliferative effects of palmatine on both cell lines (P<0.01) were observed. Palmatine significantly inhibited lipopolysaccharide­induced increase in cytokine interleukin (IL)­8 levels in the HT­29 cells (P<0.01). In the in vivo studies with ApcMin/+ mice, after 10 or 20 mg/kg/day oral palmatine treatment, tumor numbers were significantly reduced in the small intestine and colon in a dose­dependent manner (P<0.01 compared with the model group). The results were supported by tumor distribution data, body weight changes and organ index. The effect on survival was also dose­dependent. Both the low­ and high­dose palmatine treatments significantly increased the life span of the mice (P<0.01). The gut histology from the model group showed a prominent adenomatous change along with inflammatory lesions. With palmatine treatment, however, the dysplastic changes were greatly reduced in the small intestine and colon tissue. Reverse transcription­quantitative polymerase chain reaction analysis of interleukin (IL)­1α, IL1­ß, IL­8, granulocyte­colony stimulating factor and granulocyte macrophage colony­stimulating factor in the gut tissue showed that these inflammatory cytokines were reduced significantly following treatment (all P<0.01); serum cytokine levels were also decreased. Data suggests that palmatine has a clinical value in colorectal cancer therapeutics, and this action is likely linked to the inhibition of inflammatory cytokines.