Polypeptides from traditional Chinese medicine: Comprehensive review of perspective towards cancer management.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polypeptides obtained from traditional Chinese medicine are good anti-cancer ingredients. The anticancer activity has been fully demonstrated in vivo and in vitro. However, most of the functional studies on traditional Chinese medicine polypeptides are at the stage of basic experimental research, and fewer of them have been applied to clinical trials. Hence, this review mainly discusses the chemical structure, extraction, separation and purification methods, the anti-cancer mechanism, and structure-activity relationships of traditional Chinese medicine polypeptides. It provides theoretical support for strengthening the rapid separation and purification and the overall efficacy and mechanism of action, as well as the industrialization and clinical application of traditional Chinese medicine polypeptides.

Uncovering quality markers of Yiqi-Tongluo capsule against myocardial ischemia and optimization of its extraction process.

Myocardial ischemia (MI), a condition in which the heart is unable to function due to insufficient blood and oxygen supply, is a major cause of death from coronary heart disease (CHD). Yiqi Tongluo capsule (YTC) is a Chinese patent drug which commonly used for treatment of MI in clinic. However, the related active components of YTC for treatment of MI were still uncovered. This paper is aimed to study the quality markers (Q-markers) of YTC and further optimize the extraction process of YTC based on Q-markers, providing research foundation for the further modern pharmaceutical preparations of YTC. We firstly used UPLC-QTOF-MS to analyze the constituents of YTC absorbed in blood, then isoprenaline (ISO) induced H9c2 cell model was used further screen the active constituents with protective effects on cardiomyocytes. After that, the orthogonal table (L9 (34)) was used to optimize the extraction process with three levels of 4 factors (water addition, immersion time, extraction time and decoction times). Finally, the HPLC fingerprint of 15 batches of optimized YTC was established. In our present study, a total of 33 components were identified in YTC, of which 10 components were absorbed in blood. Among the 10 components, 8 compounds had significant protective effects on ISO stimulated H9c2 cells, including Paeoniflorin, Ferulic acid, Calycosin, Senkyunolide A, N-butylphthalide, Z-ligustilide, LevistilideA, and Astragaloside IV, which were considered as the Q-markers of YTC. The optimized extraction process based on Q-marker as follows: soaking 1 h, then adding 8 times water to extract 3 times by decoction, each extraction lasts 1.5 h. The HPLC fingerprint of optimized YTC was established with 15 batches of YTC samples, and the optimized YTC samples has no significant toxicity to the heart, liver, spleen, lungs, and brain tissues of rats.

Fast Inspection of Quality of Indigo Naturalis by Multiple Light Scattering.

Quality control of Chinese herbal medicine is a crucial component of Chinese herbal medicine research and development. Faced with the challenges of modernization and internationalization of Chinese herbal medicine, it is urgent to establish thorough and effective procedures for quality identification of Chinese herbal medicine, and there is an urgent need for new analytical and testing techniques that are efficient, accurate, and environmentally friendly. Multiple light scattering is a cutting-edge and analytical method that can accurately and rapidly assess the quality of Chinese herbal medicine without altering the nature or state of the sample or using organic reagents. Indigo Naturalis is considered a good remedy for pediatric hyperthermia, psoriasis, leukemia, and ulcerative colitis. In this study, the process of addition of Indigo Naturalis powder in water was recorded precisely using a multiple light scattering instrument. The qualitative and quantitative measurements of the instrument can be used to accurately capture the overall trajectory and sinking behavior of Indigo Naturalis powder into water and to establish a rapid evaluation method for the quality of Indigo Naturalis with the transmission and backscattering spectrograms of the sample as qualitative indicators and stability index as a quantitative indicator. The analytical technique based on multiple light scattering provides a fast, accurate, green, and environmentally friendly method for the quality evaluation of Indigo Naturalis and supports the development and transformation of high-quality Indigo Naturalis.

Research progress on the treatment of epilepsy with traditional Chinese medicine.

BACKGROUND: Traditional Chinese Medicine (TCM) system is a medical system that has been expanding for thousands of years that was formed by the extensive clinical practice experience of many physicians and the accumulation of personal medication habits in China. In TCM, there is a history of long-term medication for epilepsy, the main treatment for epilepsy is TCM drugs and its prescription, supplemented by TCM modalities such as acupuncture therapy, moxibustion therapy, tuina, emotion adjustment therapy, etc. PURPOSE: With the modernization of TCM, the active ingredients and molecular mechanisms of TCM for epilepsy treatment have been gradually revealed. This review aimed to comprehensively summarize the TCM treatment of epilepsy, focusing on the current TCM drugs and some TCM formulae for the treatment of epilepsy, and to discuss the research progress of TCM for the treatment of epilepsy, and to provide a reference to develop future related studies in this field. MATERIALS AND METHODS: The mechanism of action of antiepileptic drugs (AEDs) was interpreted from different perspectives by searching online databases and querying various materials identify drugs used in both modern medicine and TCM systems for the treatment of epilepsy. We collected all relevant TCM for epilepsy literature published in the last 30 years up to December 2022 from electronic databases such as PubMed, CNKI and Web of Science, and statistically analyzed the literature for the following keyword information. The search terms comprise the keywords "TCM", "phytochemistry", "pharmacological activity", "epilepsy" and "traditional application" as a combination. Scientific plant names were provided by "The Plant List" (www.theplantlist.org). RESULTS: Epilepsy is a complex and serious disease of the brain and nervous system. At present, the treatment of epilepsy in modern medicine is mainly surgery and chemotherapy, but there are many serious side effects. By summarizing the treatment of epilepsy in TCM, it is found that there are various methods to treat epilepsy in TCM, mainly TCM drugs and its formulae. Many TCM drugs have antiepileptic effects. Now found that the main effective TCM drugs for the treatment of epilepsy are Curcumae Longae Rhizoma, Scorpio, Acori Tatarinowii Rhizoma, Uncariae Ramulus Cum Uncis and Ganoderma, etc. And the main compounds that play a role in the treatment of epilepsy are curcumin, gastrodin, ligustrazine, baicalin and rhynchophylline, etc. These TCM drugs have played an important role in the treatment of epilepsy in TCM clinic. However, the chemically active components of these TCM drugs are diverse and their mechanisms of action are complex, which are not fully understood and need to be further explored. CONCLUSIONS: TCM treats epilepsy in a variety of ways, and with the discovery of a variety of potential bioactive substances for treatment of epilepsy. With the new progress in the research of other TCM treatment methods for epilepsy, TCM will have greater potential in the clinical application of epilepsy.

[Effect of processing with vinegar on efficacy of Curcuma longa in treatment of dysmenorrhea in rats with syndrome of liver depression and Qi stagnation].

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P<0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P<0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E_2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P<0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(ß-EP) level(P<0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P<0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

[Material basis and mechanism of Curcuma longa tuberous roots with and without vinegar processing in treating primary dysmenorrhea].

Liquid chromatography-mass spectrometry was employed to analyze the chemical components in Curcuma longa tuberous roots(HSYJ), C. longa tuberous roots processed with vinegar(CHSYJ), and rat serum after the administration. The active components of HSYJ and CHSYJ absorbed in serum were identified based on the secondary spectrum of database and literature. The targets of primary dysmenorrhea was screened out from database. The protein-protein interaction network analysis, gene ontology(GO) functional annotation, and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed for the common targets shared by the drug active components in serum and primary dysmenorrhea, and the component-target-pathway network was constructed. AutoDock was used to conduct molecular docking between the core components and targets. A total of 44 chemical components were identified from HSYJ and CHSYJ, including 18 absorbed in serum. On the basis of network pharmacology, we identified 8 core components(including procurcumenol, isobutyl p-hydroxybenzoate, ferulic acid, and zedoarondiol) and 10 core targets \[including interleukin-6(IL-6), estrogen receptor 1(ESR1), and prostaglandin-endoperoxide synthase 2(PTGS2)\]. The core targets were mainly distributed in the heart, liver, uterus, and smooth muscle. The molecular docking results showed that the core components were well bound to the core targets, indicating that HSYJ and CHSYJ may exert therapeutic effect on primary dysmenorrhea via estrogen, ovarian steroidogenesis, tumor necrosis factor(TNF), hypoxia-inducible factor-1(HIF-1), IL-17 and other signaling pathways. This study clarifies the HSYJ and CHSYJ components absorbed in serum, as well as the corresponding mechanism, providing a reference for further elucidating the therapeutic material basis and clinical application of HSYJ and CHSYJ.

Combination Therapy with Indigo and Indirubin for Ulcerative Colitis via Reinforcing Intestinal Barrier Function.

Indigo and indirubin, the active molecules of traditional Chinese medicine indigo naturalis, exert therapeutic activity for ulcerative colitis (UC). Indigo and indirubin are isomers and have distinctive profiles in anti-inflammation, immune regulation, intestinal microbiota regulation, oxidative stress regulation, and intestinal mucosal repair for UC treatment. Thus, exploring its combined administration's integrated advantages for UC is critical. This study is aimed at clarifying the effect and mechanisms of the combined administration of indigo and indirubin on colitis mouse models. The results showed that all the treatment groups could improve the disease symptoms, and the combined administration showed the best effect. Additionally, compared with indigo and indirubin alone, the combination group could significantly reinforce intestinal barrier function by increasing the expression of E-cadherin, occludin, ZO-1, and MUC2 and improving intestinal permeability. The treatment groups significantly improved the expression of cytokines, including TNF-α, IFN-γ, IL-12, IL-23, and IL-17A, and indirubin presented the most potent anti-inflammatory effect. Furthermore, all the treatment groups reduced the infiltration of the immune cells in intestinal lamina propria and the production of ROS/RNS. Notably, indigo exhibited a more substantial capacity to regulate natural killer (NK) cells, ILC3, neutrophils, and dendritic cells, followed by the combination group and indirubin alone. Finally, all the treatment groups modulated intestinal microbiota composition, increased the proportion of beneficial microbiota, and decreased the proportion of microbiota. Our results indicated that indigo and indirubin synergistically reinforced the intestinal barrier function, which may be associated with integrating the indirubin anti-inflammatory and intestinal microbiota regulating strength and indigo immune and ROS/RNS regulation advantage.

Analysis of the pharmacodynamic difference between Xiaojin Pills taken with Chinese Baijiu and water based on serum pharmacochemistry and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs "taken orally after soaked with Chinese Baijiu" in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. AIM OF THE STUDY: To analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu". MATERIALS AND METHODS: Ultra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. RESULTS: The identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-ß-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-ß-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-ß-boswellic acid in XJP&B were relatively longer. CONCLUSION: This research proved that "taking XJPs orally after being soaked with Chinese Baijiu" can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu", which can provide a theoretical basis for the optimization of XJPs' clinical administration method.

[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.

Comparative and mechanistic study of pharmacodynamic difference in anti-breast cancer activity between water and liquor extracts of Xiaojin Pills.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills was first recorded during the Qing Dynasty and have a history of nearly 300 years. It is the first choice among Chinese patent medicines for the clinical treatment of diseases of the mammary glands in contemporary traditional Chinese medicine. It was also widely used in the treatment of breast cancer, lung cancer, thyroid cancer, and other malignant tumors. Its initial administration method was "taken orally after soaking with Chinese baijiu"; however, the method was changed to "taken orally with water" within the last 40 years. There is no scientific evidence for the difference in efficacy against breast cancer between the two methods of administration. AIM OF THE STUDY: In vitro and in vivo experiments were carried out to confirm the therapeutic advantages of the liquor extract of Xiaojin Pills to improve the efficacy against breast cancer, and the mechanism was explained in terms of metabolomics and molecular biology. MATERIALS AND METHODS: In vitro, a cell counting kit-8 cell activity assay and flow cytometry were used to detect the activity and apoptosis of MCF-7 breast cancer cells. In vivo, pharmacodynamic evaluation was performed by constructing a heterotopic transplantation model of breast cancer in BALB/c-nu mice. TUNEL staining was used to observe the apoptosis of cells in tumor tissues. The expression of proteins associated with the phosphoinositide 3-kinase (PI3K)/Akt pathway in BALB/c-nu mice tissue was investigated by metabolomics analysis, immunohistochemistry and western blotting. RESULTS: CCK-8 assay showed that the IC50 of XJP-L for the inhibition of the activity of MCF-7 cells was less than that of XJP-W at different times. Flow cytometry assay suggested that the apoptosis rate in the XJP-L group was higher than that in the normal control group (p < 0.01). Animal experiment results indicated that both XJP-W group and XJP-L group reduced the volume and quality of the tumor after administration, and the reduction was more significant in the XJP-L group (p < 0.01). Metabolomics analysis results demonstrated that there are about 26 different metabolites have been screened in the serum metabolites between the liquor and water extract, mainly involved in glycerophospholipid, glutamic acid, aspartic acid, nitrogen and pyrimidine metabolism. In addition, immunohistochemistry and WB results showed that compared with the model group, the protein expression of PTEN, AKT, BAX and in tumor tissues of XJP-L and XJP-W groups both exhibited an upward trend, while the expression of BCL-2, p-PI3K and p-AKT exhibited a downward trend, which was much more obvious in XJP-L group. CONCLUSIONS: This study demonstrates that the liquor extract of Xiaojin Pills had a stronger anti-breast cancer effect than that of the water extract. The PI3K/Akt signaling pathway might play an important role in the mechanism of the liquor extract of Xiaojin Pills and thus improve the efficacy against breast cancer.

Microwave technology: a novel approach to the transformation of natural metabolites.

Microwave technology is used throughout the world to generate heat using energy from the microwave range of the electromagnetic spectrum. It is characterized by uniform energy transfer, low energy consumption, and rapid heating which preserves much of the nutritional value in food products. Microwave technology is widely used to process food such as drying, because food and medicinal plants are the same organisms. Microwave technology is also used to process and extract parts of plants for medicinal purposes; however, the special principle of microwave radiation provide energy to reaction for transforming chemical components, creating a variety of compounds through oxidation, hydrolysis, rearrangement, esterification, condensation and other reactions that transform original components into new ones. In this paper, the principles, influencing factors of microwave technology, and the transformation of natural metabolites using microwave technology are reviewed, with an aim to provide a theoretical basis for the further study of microwave technology in the processing of medicinal materials.

[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.

From longevity grass to contemporary soft gold: Explore the chemical constituents, pharmacology, and toxicology of Artemisia argyi H.Lév. & vaniot essential oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia argyi H.Lév. & Vaniot is known as the longevity grass in eastern countries for its warm effect to cure many cold diseases. It has been widely used in medicine, food, bathing, moxibustion, and fumigation for more than two thousand years. Nowadays it even becomes the cultural symbol of the Dragon Boat Festival. In traditional application, A. argyi is considered to be an important hemostatic drug and a common drug for gynecological diseases. In modern application, the Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) is regarded as the important medicinal substance of A. argyi, and has been made into many health products, forming a large-scale A. argyi industry. AIM OF THE REVIEW: This review aims to summarize the research status of AAEO and evaluate its application value. The manuscript focuses on the reported extraction methods, chemical components and influencing factors, pharmacological action, and toxicity. MATERIALS AND METHODS: In the literature search, several databases, such as Google Scholar, Science Direct, PubMed, Elsevier, CNKI, and Wanfang, were searched for key words, including "Artemisia argyi H.Lév. & Vaniot essential oil," "Artemisia argyi H.Lév. & Vaniot," "cineole," "caryophyllene," "cyclamen," "borneol," and "camphor." RESULTS: At present, more than 200 kinds of chemical components have been detected in AAEO, including terpenes, ketones (aldehydes), alcohols (phenols), acids (esters), alkanes (olefins) hydrocarbons, and so on. It has great anti-disease-resistant microorganism, anti-inflammatory, analgesic, and anti-cancer effects in clinical treatment and has good development potential and application prospects. CONCLUSION: Present review provides an insight into chemical composition, extraction method, quality influencing factors, pharmacological action and toxicological action of AAEO. As an important traditional medicine herb, remarkable efficacy has been demonstrated in comprehensive literature reports, which has shown the great medicinal potential of this plant. However, the toxicity of AAEO cannot be ignored, the exact mechanism of action remains to be elucidated.

Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. AIM OF THE STUDY: To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). MATERIALS AND METHODS: COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200-220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. RESULTS: The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. CONCLUSION: In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.

Mechanisms exploration of Xiaojin Pills on lung cancer based on metabolomics and network pharmacology.

OBJECTIVES: This study was designed to evaluate the pharmacological activity and therapeutic mechanism of Xiaojin Pills (XJW) on lung cancer. METHODS: Mice were orally administered with Xiaojin Pills for 21 days. Tumour samples were collected to evaluate the antilung cancer effect, and blood samples were collected to identify differential metabolites with metabolomics. Through the analysis of network pharmacology, the active ingredients and targets related to XJW therapy for lung cancer were filtered. KEY FINDINGS: Different expression of seven metabolites related to seven pathways, including Arachidonic acid metabolism, Citrate cycle, tryptophan metabolism, glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, primary bile acid biosynthesis and nicotinate and nicotinamide metabolism, were demonstrated to explain the efficacy of XJW in the treatment of lung cancer. Furthermore, a total of 19 active ingredients (ursolic acid, α-thujone, pelargonidin, succinic acid, boswellic acid, muscone, daidzein, xanthorrhizol, isoeugenol, oleic acid, ß-caryophyllene, vanillin, ß-sitosterol, lupeol, palmitic acid, eugenol, methylbutenol, ß-elemene and quercetin) acted directly on 9 targets (CAT, PTGS2, PTGS1, CTH, ABTA, ALT1, ME2, AGXT and AGXT 2) and regulated 3 out of 7 metabolites (3-Hydroxyanthranilic acid, Pyruvate and Prostaglandin G2). CONCLUSIONS: Through metabolomics and network pharmacology analyses, this study demonstrated that the major metabolites of XJW in treating lung cancer were regulated by multitarget and multicomponent interaction network.

Fever and Antipyretic Supported by Traditional Chinese Medicine: A Multi-Pathway Regulation.

The coronavirus disease, 2019 (COVID-19), has spread rapidly around the world and become a major public health problem facing the world. Traditional Chinese medicine (TCM) has been fully committed to treat COVID-19 in China. It improved the clinical symptoms of patients and reduced the mortality rate. In light of the fever was identified as one of leading clinical features of COVID-19, this paper will first analyze the material basis of fever, including pyrogenic cytokines and a variety of the mediators of fever. Then the humoral and neural pathways of fever signal transmission will be described. The scattered evidences about fever recorded in recent years are connected in series. On this basis, the understanding of fever is further deepened from the aspects of pathology and physiology. Finally, combining with the chemical composition and pharmacological action of available TCM, we analyzed the mechanisms of TCMs to play the antipyretic effect through multiple ways. So as to further provide the basis for the research of antipyretic compound preparations of TCMs and explore the potential medicines for the prevention and treatment of COVID-19.

Potential effect of tropical fruits Phyllanthus emblica L. for the prevention and management of type 2 diabetic complications: a systematic review of recent advances.

Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting ß-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions.