[Exosome and prevention of Alzheimer's disease: based on theory of kidney storing essence].

The theory of kidney storing essence storage, an important part of the basic theory of traditional Chinese medicine(TCM), comes from the Chapter 9 Discussion on Six-Plus-Six System and the Manifestations of the Viscera in the Plain Questions, which says that "the kidney manages closure and is the root of storage and the house of Jing(Essence)". According to this theory, essence is the fundamental substance of human life activities and it is closely related to the growth and development of the human body. Alzheimer's disease(AD) is one of the common neurodegenerative diseases, with the main pathological features of Aß deposition and Tau phosphorylation, which activate neurotoxic reactions and eventually lead to neuronal dysfunction and cell death, severely impairing the patient's cognitive and memory functions. Although research results have been achieved in the TCM treatment of AD, the complex pathogenesis of AD makes it difficult to develop the drugs capable of curing AD. The stem cell therapy is an important method to promote self-repair and regeneration, and bone marrow mesenchymal stem cells(BMSCs) as adult stem cells have the ability of multi-directional differentiation. By reviewing the relevant literature, this paper discusses the association between BMSCs and the TCM theory of kidney storing essence, and expounds the material basis of this theory from the perspective of molecular biology. Studies have shown that TCM with the effect of tonifying the kidney in the treatment of AD are associated with BMSCs. Exosomes produced by such cells are one of the main substances affecting AD. Exosomes containing nucleic acids, proteins, and lipids can participate in intercellular communication, regulate cell function, and affect AD by reducing Aß deposition, inhibiting Tau protein phosphorylation and neuroinflammation, and promoting neuronal regeneration. Therefore, discussing the prevention and treatment of exosomes and AD based on the theory of kidney storing essence will provide a new research idea for the TCM treatment of AD.

Ginsenoside Rg1 treats ischemic stroke by regulating CKLF1/CCR5 axis-induced neuronal cell pyroptosis.

BACKGROUND: Ischemic stroke, a severe and life-threatening neurodegenerative condition, currently relies on thrombolytic therapy with limited therapeutic window and potential risks of hemorrhagic transformation. Thus, there is a crucial need to explore novel therapeutic agents for ischemic stroke. Ginsenoside Rg1 (Rg1), a potential neuroprotective agent, exhibits anti-ischemic effects attributed to its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. Nevertheless, the precise underlying mechanism of action remains to be fully elucidated. PURPOSE: This study aimed to explore whether Rg1 exerts anti-ischemic stroke effects by inhibiting pyroptotic neuronal cell death through modulation of the chemokine like factor 1 (CKLF1)/ C-C chemokine receptor type 5 (CCR5) axis. METHODS: In this study, the MCAO model was used as an ischemic stroke model, and experimental tests were performed after 6 hours of ischemia. The anti-ischemic effect of Rg1 was examined by TTC staining, nissl-staining and neurobehavioral tests. In the in vitro experiments, PC12 cells were subjected to stimulation with CKLF1's mimetic peptide C27 to assess the potential of CKLF1 to induce focal neuronal cell death. Additionally, the impact of CKLF1 mimetic peptide C27, antagonistic peptide C19, and CCR5 inhibitor MVC on PC12 cells subjected to oxygen-glucose deprivation (OGD) and subsequently treated with Rg1 was investigated. In vivo, Rg1 treatment was examined by quantitative real-time PCR (qPCR), ELISA, immunohistochemistry (IHC), immunofluorescence (IF), western blot (WB), and co-immunoprecipitate (Co-IP) assays to perspective whether Rg1 treatment reduces CKLF1/CCR5 axis-induced pyroptotic neuronal cell death. In addition, to further explore the biological significance of CKLF1 in ischemic stroke, CKLF1-/- rats were used as the observation subjects in this study. RESULTS: The in vitro results suggested that CKLF1 was able to induce neuronal cells to undergo pyroptosis. In vivo pharmacodynamic results showed that Rg1 treatment was able to significantly improve symptoms in ischemic stroke rats. In addition, Rg1 treatment was able to inhibit the interaction between CKLF1 and CCR5 after ischemic stroke and inhibited CKLF1/CCR5 axis-induced pyroptosis. The results of related experiments in CKLF1-/- rats showed that Rg1 lost its therapeutic effect after CKLF1 knockdown. CONCLUSION: Our findings indicate that the activation of the NLRP3 inflammasome is initiated by the CKLF1/CCR5 axis, facilitated through the activation of the NF-κB pathway, ultimately resulting in the pyroptosis of neuronal cells. Conversely, Rg1 demonstrates the capability to mitigate neuronal cell damage following CKLF1-induced effects by suppressing the expression of CKLF1. Thus, CKLF1 represents a crucial target for Rg1 in the context of cerebral ischemia treatment, and it also holds promise as a potential target for drug screening in the management of ischemic stroke.

Paeoniae Radix Rubra extract attenuates cerebral ischemia injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Paeoniae Radix Rubra (PRR), the root of Paeonia lactiflora Pall. or Paeonia veitchii Lynch, has been widely used to promote blood circulation and eliminate blood stasis in Chinese clinical practice, but its effect on cerebral ischemia is still rarely reported. AIM OF THE STUDY: The present study aimed to assess the potential therapeutic possibilities of the extract of PRR (PRRE) on cerebral ischemia, further exploring the underlying mechanism, and preliminary screening of the corresponding active components. MATERIALS AND METHODS: The neuroprotective effects of PRRE in Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO) injury and mouse hippocampal neuronal cells (HT22 cell line) following oxidative stress were confirmed. The mechanism was investigated using immunohistochemical staining, western blotting, transmission electron microscopy (TEM), and immunofluorescence. The active components of PRRE were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and molecular docking. RESULTS: The in vivo study showed that PRRE reduced infarct volume and improved neurological deficits in rats, and the expression of GPX4, FTH1, Beclin1, LC3 II, and p-Akt was upregulated in the rat hippocampi. In addition, the vitro research indicated that PRRE can also alleviate H2O2-induced HT22 cell damage by regulating cytokines such as malondialdehyde (MDA), reduced glutathione (GSH) and reactive oxygen species (ROS), and the expressions of GPX4 and Beclin1 were observed to be elevated. The PI3K/Akt signalling pathway was inhibited by LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K). Furthermore, the effective components of PRRE in regulating ferroptosis and autophagy are mainly defined as albiflorin, paeoniflorin, benzoyl paeoniflorin, oleanolic acid, and hederagenin. CONCLUSION: PRRE exerts neuroprotective effects against cerebral ischaemic injury by inhibiting ferroptosis and activating autophagy through the PI3K/Akt signalling pathway. This study provides an experimental basis for the potential application of PRRE as a novel therapeutic drug, and PI3K/Akt-associated ferroptosis and autophagy as therapeutic targets for cerebral ischemia.

Neurotrophic basis to the pathogenesis of depression and phytotherapy.

Depression is a major neuropsychiatric disease that considerably impacts individuals' psychosocial function and life quality. Neurotrophic factors are now connected to the pathogenesis of depression, while the definitive neurotrophic basis remains elusive. Besides, phytotherapy is alternative to conventional antidepressants that may minimize undesirable adverse reactions. Thus, further research into the interaction between neurotrophic factors and depression and phytochemicals that repair neurotrophic factors deficit is highly required. This review highlighted the implication of neurotrophic factors in depression, with a focus on the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and detailed the antidepressant activities of various phytochemicals targeting neurotrophic factors. Additionally, we presented future opportunities for novel diagnostic and therapeutic strategies for depression and provided solutions to challenges in this area to accelerate the clinical translation of neurotrophic factors for the treatment of depression.

New Therapeutic Approaches to and Mechanisms of Ginsenoside Rg1 against Neurological Diseases.

Neurological diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), stroke, cerebral infarction, ischemia-reperfusion injury, depression and, stress, have high incidence and morbidity and often lead to disability. However, there is no particularly effective medication against them. Therefore, finding drugs with a suitable efficacy, low toxicity and manageable effects to improve the quality of life of patients is an urgent problem. Ginsenoside Rg1 (Rg1) is the main active component of ginseng and has a variety of pharmacological effects. In this review, we focused on the therapeutic potential of Rg1 for improving neurological diseases. We introduce the mechanisms of Ginsenoside Rg1 in neurological diseases, including apoptosis, neuroinflammation, the microRNA (miRNA) family, the mitogen-activated protein kinase (MAPK) family, oxidative stress, nuclear factor-κB (NF-κB), and learning and memory of Rg1 in neurological diseases. In addition, Rg1 can also improve neurological diseases through the interaction of different signal pathways. The purpose of this review is to explore more in-depth ideas for the clinical treatment of neurological diseases (including PD, AD, HD, stroke, cerebral infarction, ischemia-reperfusion injury, depression, and stress). Therefore, Rg1 is expected to become a new therapeutic method for the clinical treatment of neurological diseases.

The Anti-Neuroinflammatory Effect of Fuzi and Ganjiang Extraction on LPS-Induced BV2 Microglia and Its Intervention Function on Depression-Like Behavior of Cancer-Related Fatigue Model Mice.

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to Yang deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies in vitro and in vivo. According to the UPLC-Q-TOF/MSE results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE2 and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.

Novel antidepressant mechanism of ginsenoside Rg1: Regulating biosynthesis and degradation of connexin43.

ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng C. A. Meyer is a valuable medicinal herb and "alternative" remedy for the prevention and treatment of depression. Dysfunction of connexin43 (Cx43)-gap junction in astrocytes is predisposed to the precipitation of depression. Ginsenoside Rg1 (Rg1), the main bioactive constituent extracted from ginseng, is efficacious in the management of depression by upregulating the content of Cx43. Our previous results indicated that pretreatment with Rg1 significantly improved Cx43-gap junction in corticosterone (CORT)-treated astrocytes. However, the antidepressant mechanism underlying how Rg1 upregulates Cx43-gap junction in astrocytes hasn't been proposed. AIM OF THE STUDY: To dissect the mechanisms of Rg1 controlling Cx43 levels in primary astrocytes. METHODS: We examined the changes of the level of Cx43 mRNA, the degradation of Cx43, as well as the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43 followed by Rg1 prior to CORT in rat primary astrocytes isolated from prefrontal cortex and hippocampus. Furthermore, the recognized method of scrape loading/dye transfer was performed to detect Cx43-gap junctional function, an essencial indicator of the antidepressant effect. RESULTS: Pretreatment with Rg1 could reverse CORT-induced downregulation of Cx43 biosynthesis, acceleration of Cx43 degradation, and upregulation of two Cx43 degradation pathways in primary astrocytes. CONCLUSION: The findings in the present study provide the first evidence highlighting that Rg1 increases Cx43 protein levels through the upregulation of Cx43 mRNA and downregulation of Cx43 degradation, which may be attributed to the effect of Rg1 on the ubiquitin-proteasomal and autophagy-lysosomal degradation pathways of Cx43.

Administration of a mixture of triterpenoids from yeyachun and phenolic acids from danshen ameliorates carbon tetrachloride-induced liver fibrosis in mice by the regulation of intestinal flora.

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.

Combination of high-resolution accurate mass spectrometry and network pharmacology provides a new method for the chemical constituents' study and target prediction in vivo of Garcinia multiflora.

Garcinia multiflora is a kind of evergreen tree which is widely distributed in the south of China. However, few researches focused on the constituents in different parts of G. multiflora as well as their potential targets and pathways in vivo. To clarify the chemical constituents of G. multiflora rapidly and predict the potential targets as well as pathways in vivo that this plant may have effects on, a feasible and accurate strategy was developed to identify the chemical constituents in fruits, leaves, and branches of G. multiflora by ultra-high performance liquid chromatography with Q-Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry. Network pharmacology was then employed and a "compounds-targets-diseases" network was established. Sixty-one compounds including polycyclic polyprenylated acylphloroglucinols, xanthones, and flavonoids were finally identified in different parts of G. multiflora, and the contents of seven constituents were quantified, respectively. On the basis of the network pharmacology analysis results, compounds in this plant were speculated to have potential pharmacodynamic effect on cancer, inflammatory, respiratory diseases, cardiovascular diseases, and metabolic diseases. This research will provide a new method for the advanced study on the pharmacodynamic materials basis of G. multiflora, and offer valuable evidences for medicinal purpose of this plant.

[Research status of common processing technology of traditional Chinese medicine "maintaining medicinal properties after carbonisatus" and supramolecular "imprinting template" characterization technology].

Based on the characteristics of biological supramolecules and the law of " imprinting template",the research status and common problems in " maintaining medicinal properties after carbonisatus" in traditional Chinese medicine( TCM) were analyzed,and the further countermeasures were put forward. According to the historical evolution of " maintaining medicinal properties after carbonisatus" in TCM processing,the origin of its common problems was clarified by using the theory of biosupramolecular chemistry. TCM is a megacomplex biological supramolecular system,so TCM processing is just the processing of megacomplex biological supramolecular system,and its essence is a TCM pharmaceutical technology with chemical changes in host and guest of biological supramolecular system with or without adjuvant material under high temperature and humidity. In this study on pharmaceutical technology,host molecule was destructed in the process of carbonizing,but guest molecule was retained. The changing law of the host and guest molecule was controlled by the " imprinting template",which was reflected in the degree of change in the drug properties and efficacy of the decoction pieces. Supramolecular chemistry ran through the whole process,and the " imprinting template" of charcoal medicine was characterized by the supramolecular topological structure characteristics and imprinting behavior. After being combined with the quantitative mathematical model of heating degree in processing,it can realize the accurate processing of " maintaining medicinal properties after carbonisatus" from the source,quantitatively control the quality of carbonic herbs,and formulate stable and controllable quality standards.

[Dynamic chromatopharmacokinetics model for components in Chinese medicine and validation in Buyang Huanwu Decoction].

The Chinese medicine is mostly derived from plants or animals, highly polymorphic, with dynamic components which are reflected by the characteristic peaks and fingerprint peaks in chromatographic fingerprints. The chromatopharmacokinetics method for determined components is not applicable due to dynamic changes of chromatopharmacokinetics. Based on the preliminary study, dynamic pharmacokinetics mathematical model for multiple components in Chinese medicine was set up and verified by Buyang Huanwu Decoction as the model drug, applying the principle of the total quantum statistical moment(TQSM), superimposing or subtracting the relevant statistical parameters in blood samples and blank samples. This provided a new method for the chromatopharmacokinetic study of Chinese medicine. HPLC was used to determine the TQSM parameters in blood and blank sample fingerprints of Buyang Huanwu Decoction at each point, and the overall TQSM parameters of drug-containing blood sample and blank samples were obtained with addition calculation of TQSM; while the initial TQSM of the pure drug can be obtained with subtraction calculation. The metabolic and absorption equilibrium constants were calculated iteratively to a steady state using the estimated metabolic equilibrium constants, then the metabolic chromatopharmacokinetic parameters in rats were obtained: VUC_T 1.262×10~8 mAu·s, MRT_T 37.48 h, VRT_T 9.016×10~2 h~2, CL_T 25.79 mL·h~(-1)·kg~(-1), Vs 1.586×10~2 mL·kg~(-1), t_(T,0.5) 6.15 h, respectively. This suggested that 95% of the compounds in whole recipe were metabolized and secreted from the body after 0-96.33 h. The experiment verified that the established mathematical model and the total quantum moment statistics parameters can represent the dose-time relationship of Buyang Huanwu Decoction, which can be used to study on in vivo metabolism dynamics for Chinese medicine.

Novel mathematic models for quantitative transitivity of quality-markers in extraction process of the Buyanghuanwu decoction.

BACKGROUND: Nowadays, to research and formulate an efficiency extraction system for Chinese herbal medicine, scientists have always been facing a great challenge for quality management, so that the transitivity of Q-markers in quantitative analysis of TCM was proposed by Prof. Liu recently. In order to improve the quality of extraction from raw medicinal materials for clinical preparations, a series of integrated mathematic models for transitivity of Q-markers in quantitative analysis of TCM were established. Buyanghuanwu decoction (BYHWD) was a commonly TCMs prescription, which was used to prevent and treat the ischemic heart and brain diseases. In this paper, we selected BYHWD as an extraction experimental subject to study the quantitative transitivity of TCM. STUDY DESIGN: Based on theory of Fick's Rule and Noyes-Whitney equation, novel kinetic models were established for extraction of active components. Meanwhile, fitting out kinetic equations of extracted models and then calculating the inherent parameters in material piece and Q-marker quantitative transfer coefficients, which were considered as indexes to evaluate transitivity of Q-markers in quantitative analysis of the extraction process of BYHWD. METHODS: HPLC was applied to screen and analyze the potential Q-markers in the extraction process. Fick's Rule and Noyes-Whitney equation were adopted for mathematically modeling extraction process. Kinetic parameters were fitted and calculated by the Statistical Program for Social Sciences 20.0 software. The transferable efficiency was described and evaluated by potential Q-markers transfer trajectory via transitivity availability AUC, extraction ratio P, and decomposition ratio D respectively. The Q-marker was identified with AUC, P, D. RESULTS: Astragaloside IV, laetrile, paeoniflorin, and ferulic acid were studied as potential Q-markers from BYHWD. The relative technologic parameters were presented by mathematic models, which could adequately illustrate the inherent properties of raw materials preparation and affection of Q-markers transitivity in equilibrium processing. AUC, P, D for potential Q-markers of AST-IV, laetrile, paeoniflorin, and FA were obtained, with the results of 289.9 mAu s, 46.24%, 22.35%; 1730 mAu s, 84.48%, 1.963%; 5600 mAu s, 70.22%, 0.4752%; 7810 mAu s, 24.29%, 4.235%, respectively. CONCLUSION: The results showed that the suitable Q-markers were laetrile and paeoniflorin in our study, which exhibited acceptable traceability and transitivity in the extraction process of TCMs. Therefore, these novel mathematic models might be developed as a new standard to control TCMs quality process from raw medicinal materials to product manufacturing.

Application of TQSM polypharmacokinetics and its similarity approach to ascertain Q-marker by analyses of transitivity in vivo of five candidates in Buyanghuanwu injection.

BACKGROUND: It is well-known that the public still have been facing on a severe issue about the inconsistency of quality and therapeutic efficacy of traditional medicines. Recently, Professor Chang-Xiao Liu has created a new promising concept for identifying relevant quality-markers (Q-marker) from herbs, their formulas and manufacturing products. Therefore, building up a new approach is necessary for us to bridge over quality to efficacy of pharmaceutical products. STUDY DESIGN: In this paper, five candidate Q-markers, astragaloside IV, paeonflorin, amygdalin, tetramethylpyrazine, ferulic acid in Buyanghuanwu injection (BYHWI) had been designed to carry out in rat by using single and polypharmacokinetic models for total quanta to ascertain adequate Q-marker. METHODS: The Q-marker transitivity in vivo was studied with polypharmacokinetic model and its similarity approach, which were modeled with TQSM principle. The Q-marker was ascertained with transitive similarity and bioavailability in polypharmacokinetics. Their concentrations in plasma sample of white rat were determined by RP-HPLC. Data analyses were used by the DAS software for singles and myself-written-program with EXCEL for multiples. RESULTS: In BYHWI, five candidate Q-marker pharmacokinetic profiles were singly fixed to two compartmental models in rat using classical compartmental analysis, but there were tremendous differences among which the candidate parameters were fluctuated from nearly 3552 folds to equivalency. The theoretical value of TQSM polypharmacokinetic parameters such as AUCT, MRTT, VRTT, CLT, VT over the mixure of five drugs were 110.8 ±â€¯51.91 mg min ml-1, 176.0 ±â€¯36.5 min, 39,921 ±â€¯4311 min2, 0.3116 ±â€¯0.02347 ml min-1 kg-1, 54.83 ±â€¯7.683 ml kg-1 respectively. The TQSM polypharmacokinetic parameters in astragaloside Ⅳ ordered by AUCT, MRTT, VRTT, CLT, VT were 110.8 ±â€¯51.91 mg min ml-1, 176.0 ±â€¯36.5 min, 39,921 ±â€¯4311 min2, 0.3116 ±â€¯0.02347 ml min-1 kg-1, 54.83 ±â€¯7.683 ml kg-1, respectively, which were closed to the theoretical values. TQSM similarity versus astragaloside Ⅳ was 0.9661. CONCLUSION: The results represented that the optimum Q-marker in BYHWI is astragaloside Ⅳ, whose transitivity in vivo similarity was close to the behavior of polypharmacokinetics with maximum bioavailability to the total quanta. It is feasible for Q-marker in CMMs to screen on the comparison of single pharmacokinetic behavior and bioavailability to the total quanta.

[Analysis on property of meridian supramolecules by biological evolution path].

With human placed in the whole nature, by following the biologic evolution path, the property of channel structure for "imprinting template" in meridian and zang-fu was explored with supramolecular chemistry. In the history of biologic evolution, each molecule in "molecule society" gradually developed into various highly-ordered supramolecular bodies based on self-identification, self-assembly, self-organization, self-replicating of"imprinting template", and thereby the original biochemical system was established, and finally evolved into human. In the forming process of supramolecular bodies, the channel structure of"imprinting template" in guest supramolecular bodies would be kept by host supramolecular bodies, and communicate with the outside to exchange materials, energy, information, otherwise life phenomenon could not continue, for which it was the chemical nature of biolo-gical supramolecular bodies for body to develop meridian. Therefore, the human was a gigantic and complicated supramolecules body in biological nature, and possessed the supramolecules "imprinting template" at each stage of evolution, for which the meridians were formed. When meridians converged, acupoints appeared; when acupointsconverged, zang-fu appeared. With the promotion of the blood from heart, according to"imprinting template", the guest supramolecular bodies and host meridian produced qi-analysis, which was the qi-phenomenon of guest in meridian. It presented as zang-fu image of physiology and pathology as well as action regularities of medication and acupuncture tolerance, by which current various meridian viewpoints could be explained and propose the hypothesis of meridian supramolecular bodies. The meridian and its phenomenon was decide by its "imprinting template" of supramolecular bodies and self-reaction regularities, which abided through the living nature. This was the substance for meridian biology.

[Q-marker of Chinese medicine and metabolic regularity of co-network compatibility and rainbow potential].

The effect of Chinese medicine (CM) compound prescription is the combined action results of single herbs based on the basic theory of Chinese medicine, and its function embodies the characteristics of multi components, multi targets and comprehensive effects. It is difficult to study the therapeutic material, establish quality standards or determine Q-marker, so we can't strictly monitor the quality of the whole process of CM. The identification of Q-marker has a profound influence on the whole process of the pharmaceutical engineering of CM. The scattered effect of CM multi-components is regarded as the integral action of the parent nucleus group by the metabolic rule of co-network compatibility and rainbow potential (CCRP). The rule can be used to communicate the individual components and macro components, to reveal the metabolism of CM in organism body and basic law of information exchange, thus revealing the action law of CM on human body. Through the systematic analysis of the Q-marker's guidance to the development of CM and its relationship with the metabolic rule of CCRP, we try to provide some ideas for the identification of Q-marker.

[Investigation of supramolecular chemical mechanism of traditional Chinese medicine processing].

To analyze the research status of traditional Chinese medicine (TCM) processing and key scientific issues to be resolved by using characteristic of TCM biological supramolecules and reaction theories of 'Qi chromatography' to human being, and then put forward the solution countermeasures. Based on the previous explications of theories of the Chinese medicine with supramolecular chemistry as 'Qi chromatograpy', biological supramolecular chemistry theory was used to explain the root of the problem in TCM processing and form the countermeasures for supramolecular chemistry research in the processing of TCM decoction pieces. TCM is a huge complex biological supramolecular body, so the processing of TCM is in view of the processing of huge complex biological supramolecular body. In nature, it is a TCM pharmaceutical technology with chemical changes of the subject and object of biological supramolecular body with or without auxiliary materials, under the condition of high temperature and high humidity. Supramolecular chemistry was throughout the processing of TCM, so the use of supramolecular technology was appropriate in research. TCM decoction pieces were the product of subject and object molecular changes after supramolecular chemistry reaction, with changes in physical and chemical properties of the subject and object molecules, such as bound water overflow, chemical bond rupture, dehydration, carbonization, and reaction with auxiliary materials. Changes in drug property and drug efficacy after processing depended on the degree of subject and object "imprinting template" change, which can be measured by 'Qi chromatography' function of supermolecular imprinting template in human body. In this paper, the research ideas, methods, variety attribution, processing principle, quality standard and clinical application were analyzed to find out the sticking point of the problems, and form the countermeasures with supramolecular chemistry as the core. The processing of TCM is a chemical technology of biological supramolecular body based on the function of supermolecular 'imprinting template' (medical element) of human meridian-viscera, and its reaction products (decoction pieces) showed determinacy when used alone and compatibility when used together, which may constitute a compatible drug delivery system of TCM in clinical application.

[Investigation on supramolecular mechanism of multi-component overall control in Chinese medicine controlled sustained-release preparation].

Controlled sustained-release preparation (CSRP) is a definitely important source of innovative medicines, however, its further researches and development are limited due to the complexity of Chinese medicine (CM) compositions, and a series of unclear key problems like the apparent properties from physical and chemical aspects. Combined with the CM characteristics of the multiple components and synergistic effect, a series of bottleneck problems in the preparation of CSRP were analyzed. Then the mechanism and influences of supermolecular chemical theory in the CSRP about the multiple-components overall-control were explored under the guideline of "overall control, synchronous dissolution" in CSRP, based on the previous explications about supramolecular chemistry theories and with the application of single component precision controlling technologies. The supermolecular mechanism of multi-component overall control and synchronous release of the CSRP was investigated, providing an useful academic reference for the research and development of the CSRP and laying the theoretical and technical foundation for the manufacturing process of CSRP.

[Impact of ″imprinting templates″ characteristics of traditional Chinese medicine injection supramolecules on (anaphylactoid) hypersensibility].

The (anaphylactoid) hypersensibility mechanism of ″imprinting templates″ characteristics of traditional Chinese medicine (TCM) injection supramolecules was clarified to lay the foundation to build safety evaluation method. Based on the previous publication on special impact of Chinese medicine theories on supramolcular chemistry, combined with the natural origination of (anaphylactoid) hypersensitized special rules as well as the sensitization phenomenon of cordate houttuynia injection, the impact of the structure characteristics of ″imprinting templates″ in TCM injection supramolecules on its (anaphylactoid) hypersensibility was clarified. In Chinese medicine injections, the supramolecular structures can independently be generated, showing overall apparent (anaphylactoid) hypersensibility nature, and their structure characteristics were dependent on the strength. In addition, (anaphylactoid) hypersensitive critical supramolecular structure was present. When it was administrated by ″injection″, it's structure was not easy to be destroyed, often showing apparent immunogenicity, whereas if it was administrated by ″oral″, the structure would be destroyed by the gastrointestinal tract, showing weaker or no apparent immunogenicity. Therefore, there are differences in (anaphylactoid) hypersensibility between ″injection″ and ″oral″ administration of TCM. TCM injections would produce the supramolecules between ″molecular society″ by independent reaction of supramolecular ″imprinting template″ (chemical determinants), showing apparent immune process of recognition, copying, and storage. Single molecule is a special example for this. The screening of anaphylactoid (sensitinogen) includes the single ingredients and their forming supramolecules for TCM injection. This is the unique feature for safety evaluation of Chinese medicine injection.

[Chinese medicine preparation supramolecular imprinting templates based on in vitro release characteristics of BYHW sustained-release tablet].

The study focused on the in vitro release of Buyanghuanwu (BYHW) elementary osmotic pump sustained release tablets. Its band similarity was calculated by the total quantum statistical moment. Meanwhile, in vitro release characteristics were analyzed to discuss the existence of supramolecular imprinting templates. The results show that the same imprint templates may exist in different structures of traditional Chinese medicine(TCM)'s multi-components. The BYHW sustained release tablets prepared by elementary osmotic pump can meet the objectives of "overall control, synchronous release". However, the supramolecular imprinting templates in TCM compound prescriptions should be further explored, the overall and synchronous release of different components was controlled through imprinting templates, so as to seek the more suitable sustained release preparation technology for multiple components of TCM, and make it in line with the characteristics of TCM.