Selection and evaluation of quality markers (Q-markers) of vladimiriae radix extract for cholestatic liver injury based on spectrum-effect relationship, pharmacokinetics, and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: As a representative local medicinal herb produced in China, Vladimiriae Radix (VR) has been proven to exert hepatoprotective and choleretic effects, with particular therapeutic efficacy in cholestatic liver injury (CLI), as demonstrated by the VR extract (VRE). However, the quality markers (Q-markers) of VRE for the treatment of CLI remain unclear. AIM OF THE STUDY: A new strategy based on the core element of "efficacy" was proposed, using a combination of spectrum-effect relationship, pharmacokinetics, and molecular docking methods to select and confirm Q-markers of VRE. MATERIAL AND METHODS: First, the HPLC fingerprinting of 10 batches of VRE was studied, and the in vivo pharmacological index of anti-CLI in rats was determined. The spectrum-effect relationship was utilized as a screening method to identify the Q-markers of VRE. Secondly, Q-markers were used as VRE pharmacokinetic markers to measure their concentrations in normal and CLI rat plasma, and to analyze their disposition. Finally, molecular docking was utilized to predict the potential interaction between the identified Q-markers and crucial targets of CLI. RESULTS: The fingerprints of 10 batches of VRE was established. The in vivo pharmacological evaluation of rats showed that VRE had a significant therapeutic effect on CLI. The spectrum-effect correlation analysis showed that costunolide (COS) and dehydrocostus lactone (DEH) were the Q-markers of VRE anti-CLI. The pharmacokinetic results showed that AUC(0-t), Cmax, CLZ/F, and VZ/F of COS and DEH in CLI rats had significant differences (P < 0.01). They were effectively absorbed into the blood plasma of CLI rats, ensuring ideal bioavailability, and confirming their role as Q-markers. Molecular docking results showed that COS, DEH had good affinity with key targets (FXR, CAR, PXR, MAPK, TGR5, NRF2) for CLI treatment (Binding energy < -4.52 kcal mol-1), further verifying the correctness of Q-marker selection. CONCLUSIONS: In this study, through the combination of experimental and theoretical approaches from the aspects of pharmacodynamic expression, in vivo process rules, and interaction force prediction, the therapeutic effect of VRE and Q-markers (COS、DEH) were elucidated. Furthermore, a new idea based on the principle of "efficacy" was successfully proposed for screening and evaluating Q-markers.

Research trends and hotspots of polyphyllin in high-incidence cancers: A bibliometric analysis.

Background: Polyphyllin, a natural compound derived primarily from the Paris genus, manifests its anticancer properties. Extensive research on its therapeutic potential in cancers has been reported. However, there is no systematical analysis of the general aspects of research on polyphyllin by bibliometric analysis. The aim of this study is to visualize emerging trends and hotspots and predict potential research directions in this field. Methods: In this study, we collected relevant research articles from the Web of Science Core Collection Bibliometrics. Using R-bibliometrix, we analyzed the research status, hotspots, frontiers, and development trends of polyphyllin in high-incidence cancers. To conduct a comprehensive visual analysis, CiteSpace and VOSviewer were used for visual analysis of authors, countries, institutions, keywords, and co-cited references within the published articles. Results: A total of 257 articles focusing on the research of polyphyllin in high-incidence cancers were retrieved from the WOSCC database, covering the period from 2005 to 2023. The analysis revealed a consistent increasing trend in annual publications during this timeframe. Notably, China emerged as the most productive country, with Tianjin University leading the institutions. The Journal of Ethnopharmacology stood out as the most prominent journal in this field, while Gao WY emerged as the most prolific author. Polyphyllin VI, polyphyllin II, and polyphyllin VII have emerged as the latest research hotspots. Additionally, the investigation of autophagy and its associated mechanisms has gained significant attention as a novel research direction. Conclusion: This study presents a novel visualization of the research on polyphyllin saponins in the field of highly prevalent cancers using bibliometric analysis. The investigation of polyphyllin D has emerged as a primary focus in this field, with lung cancer, breast cancer, and liver cancer being the key areas of current research. Lastly, polyphyllin saponins show potential application in the field of cancer.

Synergistic effect of berberine hydrochloride and dehydrocostus lactone in the treatment of ulcerative colitis: Take gut microbiota as the target.

Ulcerative colitis (UC) is a difficult-to-cure and recurrent inflammatory bowel disease, and it is difficult to maintain long-term results with a single drug. Inspired by clinical medication in traditional Chinese medicine, we used berberine hydrochloride (BBH) and dehydrocostus lactone (DEH) in combination for the first time and focused on studying their mechanism of treating UC based on gut microbiota. Therefore, we evaluated the therapeutic effects of BBH and DEH on DSS-induced UC mice using ELISA, HE and AB-PAS staining, 16s rDNA amplicon sequencing technology, and fecal transplantation experiments (FMT). In this study, the combination of BBH and DEH significantly relieved symptoms, colonic inflammation, and intestinal barrier damage of DSS-induced UC mice, and they did not show antagonism. In addition, the co-administration of BBH and DEH altered the composition and function of gut microbiota, with BBH increasing the abundance of key beneficial bacterial genus Akkermansia and DEH aiming to enhance species diversity and supplying intestinal proteins to prevent overconsumption. Furthermore, our data showed that BBH and DEH improve the levels of short-chain fatty acids, which also proved the positive regulation of gut microbiota by BBH and DEH. Finally, the FMT confirmed the strong correlation between BBH, DEH, and the gut microbiota. In conclusion, the co-administration of BBH and DEH protected the intestinal barrier and reduced inflammatory damage by regulating gut microbiota, targeting the key beneficial bacterial genus Akkermansia, and maintaining a normal supply of intestinal proteins.

Microglia Sirt6 modulates the transcriptional activity of NRF2 to ameliorate high-fat diet-induced obesity.

BACKGROUND: Microglia play a pivotal role in neuroinflammation, while obesity triggers hypothalamic microglia activation and inflammation. Sirt6 is an important regulator of energy metabolism in many peripheral tissues and hypothalamic anorexic neurons. However, the exact mechanism for microglia Sirt6 in controlling high-fat diet-induced obesity remain unknown. METHODS: Microglia Sirt6 expression levels under various nutritional conditions were measured in the hypothalamus of mice. Also, microglia Sirt6-deficient mice were provided various diets to monitor metabolic changes and hypothalamic inflammatory response. Besides, RNA-seq and Co-IP of microglia with Sirt6 alterations were conducted to further investigate the detailed mechanism by which Sirt6 modulated microglia activity. RESULTS: We found that Sirt6 was downregulated in hypothalamic microglia in mice given a high-fat diet (HFD). Additionally, knockout of microglia Sirt6 exacerbated high-fat diet-induced hypothalamic microglial activation and inflammation. As a result, mice were more prone to obesity, exhibiting a decrease in energy expenditure, impaired glucose tolerance, insulin and leptin resistance, and increased food intake. In vitro, Sirt6 overexpression in BV2 cells displayed protective effects against oleic acid and palmitic acid treatment-derived inflammatory response. Mechanically, Sirt6 deacetylated and stabilised NRF2 to increase the expression of anti-oxidative genes and defend against reactive oxygen species overload. Pharmacological inhibition of NRF2 eliminated the beneficial modulating effects of Sirt6 on microglial activity. CONCLUSION: Collectively, our results revealed that microglial Sirt6 was a primary contributor of microglial activation in the central regulation of obesity. Thus, microglial Sirt6 may be an important therapeutic target for obesity.

Comprehensive quality evaluation of two different geography originated Angelica sinensis Radix based on potential production area development and resource protection.

Angelica sinensis Radix (ASR) is mainly produced in the southern region of Gansu, China, and is a famous edible and medicinal herb. Noticeably, Aba region in Sichuan, China has similar geographical and climatic conditions to the southern region of Gansu, China, and has the potential to further develop the ASR planting industry chain. This study was the first to use an innovative method that combines GC-MS, HPLC-DAD fingerprints, and stoichiometric analysis to compare and explore the feasibility of using the Aba region as a source of high-quality ASR supplements. GC-MS analysis showed that the composition of ASR essential oil(AEO) in these two regions was highly similar (>99%). The HPLC data showed that the main sources of differences in ASR components between the two regions were coniferyl ferulate, E-ligustilide, Z-ligustilide, and Butylidenephthalide, which have great potential in anti-depression, regulating gut microbiota, and other aspects. The ASR in Aba region was rich in these components, and its biological activity might be higher to some extent than that in southern Gansu. This study confirmed the potential of the Aba region in Sichuan to become a high-quality production area for ASR, which was conducive to the expansion of ASR resources and the development of related industrial chains.

The effectiveness of postoperative rehabilitation interventions that include breathing exercises to prevent pulmonary atelectasis in lung cancer resection patients: a systematic review and meta-analysis.

BACKGROUND: The main aim of this systematic review was to determine the effectiveness of postoperative rehabilitation interventions that include breathing exercises as a component to prevent atelectasis in lung cancer resection patients. METHODS: In this review, we systematically and comprehensively searched the Cochrane Library, PubMed, EMBASE, and Web of Science in English and CNKI and Wanfang in Chinese from 2012 to 2022. The review included any randomized controlled trials focusing on the effectiveness of postoperative rehabilitation interventions that include breathing exercises to prevent pulmonary atelectasis in lung cancer patients. Participants who underwent anatomic pulmonary resection and received postoperative rehabilitation interventions that included breathing exercises as a component were included in this review. The study quality and risks of bias were measured with the GRADE and Cochrane Collaboration tools, and statistical analysis was performed utilizing RevMan 5.3 software. RESULTS: The incidence of atelectasis was significantly lower in the postoperative rehabilitation intervention group (OR = 0.35; 95% CI, 0.18 to 0.67; I2 = 0%; P = 0.67) than in the control group. The patients who underwent the postoperative rehabilitation program that included breathing exercises (intervention group) had higher forced vital capacity (FVC) scores (MD = 0.24; 95% CI, 0.07 to 0.41; I2 = 73%; P = 0.02), forced expiratory volume in one second (FEV1) scores (MD = 0.31; 95% CI, 0.03 to 0.60; I2 = 98%; P < 0.01) and FEV1/FVC ratios (MD = 9.09; 95% CI, 1.50 to 16.67; I2 = 94%; P < 0.01). CONCLUSION: Postoperative rehabilitation interventions that included breathing exercises decreased the incidence rate of atelectasis and improved lung function by increasing the FVC, FEV1, and FEV1/FVC ratio.

Polygonati Rhizoma with the homology of medicine and food: A review of ethnopharmacology, botany, phytochemistry, pharmacology and applications.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygonati Rhizoma (PR), which contains rich national cultural connotations, is a traditional Chinese medicine with homology of medicine and food. It has been used for a long time as a tonic in China's multi-ethnic medical system, and is also used to treat diseases such as premature graying hair, deficiency of blood and essence, diabetes, hypertension, etc. Meanwhile, PR is often used as food in China, India, South Korea and other Asian countries, which can satisfy hunger and provide many health benefits. AIM OF THE REVIEW: This paper systematically reviewed the ethnopharmacology, botany, phytochemistry, pharmacology and related applications research of PR, and provided a reference for the comprehensive applications of PR, including basic research, product development and clinical applications. This paper also refined the national application characteristics of PR, such as rich plant resources, special chemical components and anti-hidden hungry, which laid a foundation for its high value and high connotation development in the future. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine. RESULTS: A comprehensive analysis of the above literature confirmed that PR has been used in the ethnic medicine system of Asian countries such as China for thousands of years. In this paper, 12 species including official species that can be used as PR are summarized, which provide rich plant resources for PR. The chemical components in PR are divided into nutritional components and active components. The former not only contains non-starch polysaccharides and fructo-oligosaccharides, which account for about 50% in PR and are recognized as high-quality diet in the world, but also contains inorganic elements and mineral elements. And a total of 199 kinds active ingredients, including saponins, flavonoids, alkaloids, etc., were sorted out by us. The above ingredients make PR have a special property of anti-hidden hunger. Studies have shown that PR has a wide range of pharmacological activities, such as immune regulation, blood glucose regulation, lipid-lowering, antioxidant, anti-tumor, antibacterial, etc. It has been widely used in medicine, food, cosmetics, gardens and other fields. CONCLUSIONS: PR, as a classic medicinal material of the same origin, is widely used in the traditional ethnic medicine system. It contains abundant potential plant resources, chemical components and pharmacological activities. This paper also suggests that PR with high application value in food industry, has the potential to become a high-quality coarse grain. Exploring the way of grain and industrialization of PR is beneficial to fully develop the economic value of PR.

Detoxification mechanisms of ginseng to aconite: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Aconite (Fuzi, FZ), the processed root tuber of Aconitum carmichaelii Debx., is utilized as a classic medicine to treat diseases of the cardiovascular system and immune system. Resulting from the narrow margin of safety between a therapeutic dose and a toxic dose, FZ often causes cardiotoxicity including hypotension, palpitation, and bradycardia. Contributing to the detoxification effects of the other famous herbal medicine ginseng (Renshen, RS), which is the dried root and rhizome of Panax ginseng C. A. Meyer, people broadly combine FZ and RS as compatibility more than 1800 years to attenuate the toxicity of FZ. However, the systematic detoxification mechanisms of RS to FZ have not been fully revealed. AIM OF THE REVIEW: Aiming to provide a comprehensive interpretation of the attenuation processes of FZ via RS, this review summarizes the up-to-date information about regulatory mechanisms of RS to FZ to shed the light on the essence of detoxification. MATERIALS AND METHODS: Literature was searched in electronic databases, including PubMed, Web of Science ScienceDirect, Google Scholar, CNKI and WanFang Data. Relevant studies on detoxification mechanisms were included while irrelevant and duplicate studies were excluded. According to the study design, subject, intervention regime, outcome, first author and year of publication of included data, detoxification mechanisms of RS to FZ were summarized and visualized. RESULTS: A total of 144 studies were identified through databases from their inception up to Oct. 2022. Included information indicated that diester-diterpenoid alkaloids (DDAs) were the main toxic substances of FZ. The main mechanisms that RS attenuates the toxicity of FZ were transforming toxic compounds of FZ, affecting the absorption and metabolism of FZ as well as the FZ-induced cell toxicity alleviation. CONCLUSION: FZ, as a famous traditional Chinese medicine, has good prospects for utilization. The narrow margin of safety between a therapeutic dose and a toxic dose of FZ limits its clinical effect and safety while RS is always combined with FZ to alleviate its toxicity. However, mechanisms responsible for the detoxification process have not been well identified. Therefore, detoxification mechanisms of RS to FZ are reviewed to ensure the safety and effectiveness of FZ.

To join the rebuild or not? An exploration of the factors influencing the public's intention to participate in urban renewal.

Due to the lack of trust in the builder and indeterminate benefits, it is a struggle for people in Taiwan to make up their minds to participate in urban renewal. This leads to the completion rate of urban renewal of fewer than one ten-thousandth of the new construction needed. This study investigated the perspective on the research variables for people in Taiwan and how those influence their intention to participate in urban renewal. Using the Theory of Planned Behavior, the research framework is designed with the trust of urban renewal project builders and the perceived benefits of public participation as the independent variables. Attitudes, subjective norms, and perceived behavioral control are the mediating variables, and the general public's intention to participate in urban renewal is the dependent variable. A total of 545 valid questionnaires were collected through the survey. The results showed that the respondents' trust in the builder of the urban renewal project positively and significantly influenced their perceived benefits of the project, and the respondents' trust in the builder significantly influenced their subjective norms. The perceived benefits positively and significantly affected their attitudes and subjective norms, and people's attitudes, subjective norms, and perceived behavioral control positively and significantly affected their intention to participate in urban renewal. People's perceived benefits in urban renewal projects affected their participation intention through attitudes and subjective norms. The variable perceived benefits most strongly influenced people's intention to participate in urban renewal in this study. This study provides practical suggestions for the government and builders to increase people's intention to participate in urban renewal. This study modeled two independent variables, trust in the builder and perceived benefits, under the urban renewal context in Taiwan. In future works, other factors could be included, such as tax incentives, floor area rewards, and fair appraisal.

Mushroom-brush transitional conformation of mucus-inert PEG coating improves co-delivery of oral liposome for intestinal metaplasia therapy.

The blocking of gastric mucosal intestinal metaplasia (IM) has been considered to be the pivotal method to control the occurrence of gastric cancer. However, there is still a lack of effective therapeutic agent. Here, we developed mucus-penetrating liposome system by covering surface with polyethylene glycol (PEG) chains (hydrophilic and electroneutral mucus-inert material) to co-delivery candidate drugs combination. Then studied the impact on the transmucus performance of different conformations, which were constructed by controlling the density of PEG chains on the surface. The results showed that the particle size of 5%PEG-Lip was less than 120 nm, the polydispersity index was less than 0.3, and the surface potential tended to be neutral. The D value (long chain spacing) of 5% PEG-Lip was 3.25 nm, which was close to the RF value (diameter of spherical PEG long chain group without external force interference) of 3.44 nm, and the L value (extended length) was slightly larger than 3.44 nm. In this case, PEG showed mushroom-brush transitional conformation on the surface of liposomes. This conformation was not only promoted stable delivery, but also shielded the capture of mucus more favorably, leading to a more unrestricted transportation in mucus. The further in vivo experimental results demonstrated the rapid distribution of liposomes, which gradually appeared both in the superficial and deep glandular of mucosa and gland cells at 1 h and absorbed into the cell cytoplasm at 6 h. The 5% PEG-Lip with the mushroom-brush transitional configuration recalled abnormal organ index and improved inflammation and intestinal metaplasia. The modified PEG conformation assay presented here was more suitable for liposomes. This PEG-modified liposome system has potential of mucus-penetrating and provides a strategy for local treatment of gastric mucosal intestinal metaplasia.

Traditional Chinese Exercise for Neurodegenerative Diseases: A Bibliometric and Visualized Analysis With Future Directions.

Background: Traditional Chinese Exercise (TCE) has expanded out of China into the world and is frequently used in the prevention and treatment of many diseases. Although many studies have explored the ability of TCE as an intervention for neurodegenerative diseases, there are limited articles summarizing the research. The aim of this study was to investigate current research trends around TCE for neurodegenerative diseases and predict future directions for such research. Materials and Methods: Data was collected from the Web of Science Core Collection (WoSCC). All articles and reviews on TCE in relation to neurodegenerative diseases were retrieved. The data analysis was performed using the CiteSpace (5.8R3) software, and the results were displayed in network maps. Results: The search identified 220 publications between 1999 and 2021. The United States was the most productive country (n = 89), followed by China (n = 68). The United States had the greatest centrality, indicating its tremendous global influence and close collaborations with other countries. Fuzhong Li from the Oregon Research Institute, United States, was not only the most prolific author (n = 5), but also the most co-cited author (n = 120). The Shanghai University of Sport contributed to the most publications (n = 12). PLOS ONE was the most published journal, while Movement Disorders was the most cited journal. Tai Chi, Parkinson's disease, quality of life, balance, and older adult were the most high-frequency keywords, while Alzheimer's disease had the highest centrality. Conclusion: The number of publications on TCE related to neurodegenerative diseases has shown major growth in the past decade. However, there is a need for research institutions to strengthen cooperation between countries and institutions. Tai Chi, Parkinson's disease (PD), Alzheimer's disease, older adults and falls reduction have been the recent research focus. It is anticipated that in the future, PD will continue to be a central focus with the effects of Baduanjin, Wuqinxi, and Yijinjing requiring further research.

Promising traditional Chinese medicine for the treatment of cholestatic liver disease process (cholestasis, hepatitis, liver fibrosis, liver cirrhosis).

ETHNOPHARMACOLOGICAL RELEVANCE: Cholestatic liver disease (CLD) is mainly characterized by cholestasis. If not treated, it will deteriorate to cholestatic hepatitis, liver fibrosis, liver cirrhosis, and even liver failure. CLD has a high clinical incidence, and limited treatment with single therapy. In the long-term clinical exploration, traditional Chinese medicine (TCM) has been corroborated with unique therapeutic effects on the CLD process. AIM OF THIS REVIEW: This paper summarizes the effective single and compound TCMs for the treatment of CLD. According to 4 important clinical stages of CLD: cholestasis, hepatitis, liver fibrosis, liver cirrhosis, pharmacological effects and mechanisms of 5 typical TCM examples are reviewed, aims to provide basis for clinical drug selection in different processes of CLD. MATERIALS AND METHODS: Relevant scientific articles regarding therapeutic effects of TCM for the CLD were collected from different databases. We collated three single herbs including Artemisia scoparia Waldst. et Kit. or Artemisia capillaris Thunb. (Artemisiae Scopariae Herba, Yin Chen in Chinese), Paeonia lactiflora Pall. or Paeonia veitchii Lynch. (Paeoniae radix rubra, Chi Shao in Chinese), Poria cocos (Schw.) Wolf (Poria, Fu Ling in Chinese), and two compound herbs of Huang Qi Decoction (HQD) and Yin Chen Hao Decoction (YCHD) to studied and analyzed. RESULTS: We proposed five promising TCMs treatments for the important developmental stages of CLD. Among them, Yin Chen is an essential medicine for protecting liver and gallbladder, and its TCM prescription is also a promising strategy for cholestasis. Based on clinical evidence, high-dose application of Chi Shao is a clinical special treatment of cholestasis hepatitis. Fu Ling can regulate immune cells and increase antibody levels in serum, which is expected to be an emerging therapy to prevent cholestatic liver fibrosis to cirrhosis. HQD can be used as routine clinical medicine for liver fibrosis. In addition, YCHD can exert better comprehensive advantages with multiple components, can treat the whole course of CLD and prevent it from developing to the end-stage. CONCLUSION: Yin Chen, Chi Shao, Fu Ling, HQD and YCHD have shown good clinical efficacy in controlling the development of CLD. Clinically, it is easier to curb the development of CLD by adopting graded diagnosis and treatment measures. We suggest that CLD should be risk stratified in clinical treatment to ensure personalized treatment for patients, so as to slow down the development of the disease.

The Invasive Species Reynoutria japonica Houtt. as a Promising Natural Agent for Cardiovascular and Digestive System Illness.

Polygoni Cuspidati Rhizoma et Radix, the dry roots and stems of Reynoutria japonica Houtt (called Huzhang, HZ in Chinese), is a traditional and popular chinese medicinal herb for thousands of years. As a widely used ethnomedicine in Asia including China, Japan, and Korea, HZ can invigorate the blood, cool heat, and resolve toxicity, which is commonly used in the treatment of favus, jaundice, scald, and constipation. However, HZ is now considered an invasive plant in the United States and many European countries. Therefore, in order to take advantage of HZ and solve the problem of biological invasion, scholars around the world have carried out abundant research studies on HZ. Until now, about 110 compounds have been isolated and identified from HZ, in which anthraquinones, stilbenes, and flavonoids would be the main bioactive ingredients for its pharmacological properties, such as microcirculation improvement, myocardial protective effects, endocrine regulation, anti-atherosclerotic activity, anti-oxidant activity, anti-tumor activity, anti-viral activity, and treatment of skin inflammation, burns, and scalds. HZ has a variety of active ingredients and broad pharmacological activities. It is widely used in health products, cosmetics, and even animal husbandry feed and has no obvious toxicity. Efforts should be made to develop more products such as effective drugs, health care products, cosmetics, and agricultural and animal husbandry products to benefit mankind.

An effective method for preventing cholestatic liver injury of Aucklandiae Radix and Vladimiriae Radix: Inflammation suppression and regulate the expression of bile acid receptors.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR) were used to treat gastrointestinal, liver and gallbladder diseases at practice. In most conditions, VR was used to be a substitute of AR or a local habit may attribute to the same main active ingredients Costunolide and Dehydrocostus lactone, which presented many similar pharmacological activities. However, other different lactone compounds in AR and VR also play a role in disease treatment, so the difference in therapeutic effects of AR and VR in related diseases needs to be further studied. AIMS OF THE STUDY: Revealing the differences between the chemical compounds of the total lactone extracts of AR and VR (TLE of AR and VR) and the differences in the protective effects of cholestatic liver injury to ensure rational use of AR and VR. STUDY DESIGN AND METHODS: The macroporous adsorption resin was used to purify and enrich the lactone compounds to obtain the total lactone extracts of AR and VR. HPLC-PDA was used to obtain the data to establish chemical fingerprint and chemometric analysis to compare similarities and differences between TLE of AR and VR. The pharmacodynamic experiment revealed how TLE of AR and VR to show protect effects on cholestatic liver injury. RESULTS: Similarity analysis results showed TLE of AR and VR had a high similarity (>0.9). Nevertheless, difference analysis results showed 4 compounds, Costunolide, Dehydrocostus lactone, 3ß-acetoxy-11ß-guaia-4 (15), 10 (14)-diene-12,6α-olide and vladinol F may contribute to the differences between them. The pharmacodynamics experiments results showed the TLE of AR and VR affected the different liver cholate-associated transporters mRNA expression (TLE of AR up-regulated CYP7A1, TLE of VR down-regulated FXR and BSEP), the TLE of AR and VR had an effect to regulate biochemical indicators (AST, ALT, ALP, TBA) of liver function, and TLE of VR was better than TLE of AR in reducing the expression of inflammatory factors (IL-6 and IL-1ß). CONCLUSION: The liver protection of AR and VR have been confirmed, but the differences of material basis and mechanism of drug efficacy needed further study to guarantee formulation research and provide theoretical references for clinical rational applications of AR and VR.

A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, and pharmacokinetics of Schisandra chinensis (Turcz.) Baill. and Schisandra sphenanthera Rehd. et Wils.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis (called bei-wuweizi in Chinese, S. chinensis) and Schisandra sphenanthera (called nan-wuweizi in Chinese, S. sphenanthera) are two highly similar plants in the Magnoliaceae family. Their dried ripe fruits are commonly used as traditional Chinese medicine in the treatment of coughs, palpitation, spermatorrhea, and insomnia. They also are traditionally used as tonics in Russia, Japan, and Korea. AIM OF THE REVIEW: S. chinensis and S. sphenanthera are similar in appearance, traditional applications, ingredient compositions, and therapeutic effects. This review, therefore, aims to provide a systematic insight into the botanical background, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics, quality control, and toxicology of S. chinensis and S. sphenanthera, and to explore and present the similarities and differences between S. chinensis and S. sphenanthera. MATERIALS AND METHODS: A comprehensive literature search regarding S. chinensis and S. sphenanthera was collected by using electronic databases including PubMed, SciFinder, Science Direct, Web of Science, CNKI, and the online ethnobotanical database. RESULTS: In the 2020 Edition of Chinese Pharmacopoeia (ChP), there were 100 prescriptions containing S. chinensis, while only 11 contained S. sphenanthera. Totally, 306 and 238 compounds have been isolated and identified from S. chinensis and S. sphenanthera, respectively. Among these compounds, lignans, triterpenoids, essential oils, phenolic acid, flavonoids, phytosterols are the major composition. Through investigation of pharmacological activities, S. chinensis and S. sphenanthera have similar therapeutic effects including hepatoprotection, neuroprotection, cardioprotection, anticancer, antioxidation, anti-inflammation, and hypoglycemic effect. Besides, S. chinensis turns out to have more effects including reproductive regulation and immunomodulatory, antimicrobial, antitussive and antiasthmatic, anti-fatigue, antiarthritic, and bone remodeling effects. Both S. chinensis and S. sphenanthera have inhibitory effects on CYP3A and P-gp, which can mediate metabolism or efflux of substrates, and therefore interact with many drugs. CONCLUSIONS: S. chinensis and S. sphenanthera have great similarities. Dibenzocyclooctadiene lignans are regarded to contribute to most of the bioactivities. Schisandrin A-C, schisandrol A-B, and schisantherin A, existing in both S. chinensis and S. sphenanthera but differing in the amount, are the main active components, which may contribute to the similarities and differences. Study corresponding to the traditional use is needed to reveal the deep connotation of the use of S. chinensis and S. sphenanthera as traditional Chinese medicine. In addition, a joint study of S. chinensis and S. sphenanthera can better show the difference between them, which can provide a reference for clinical application. It is worth mentioning that the inhibition of S. chinensis and S. sphenanthera on CYP3A and P-gp may lead to undesirable drug-drug interactions.

[Q-marker prediction of Magnoliae Officinalis Cortex before and after "sweating"].

Magnoliae Officinalis Cortex, a common Chinese medicinal in clinic, should undergo "sweating" process in producing area according to Chinese Pharmacopoeia, which affects its genuineness and quality. In light of the concept and research mode of quality marker(Q-marker) for decoction pieces, the active components of Magnoliae Officinalis Cortex pieces which altered significantly before and after "sweating" were identified in this study. The main pharmacodynamic material basis was clarified by pharmacodynamic, pharmacokinetic and drug property research, followed by the prediction of Q-markers of Magnoliae Officinalis Cortex before and after "sweating", for better improving its quality standard.

Aucklandiae Radix and Vladimiriae Radix: A systematic review in ethnopharmacology, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandiae Radix (AR) and Vladimiriae Radix (VR), as commonly used traditional Chinese herbal medicine, were widely used in the treatment of gastrointestinal diseases. The two herbal medicines were warm, pungent and bitter. They entered the spleen, stomach, large intestine and gallbladder meridians, and had the effect of promoting qi circulation to relieve pain. It is usually used for chest and hypochondrium, abdominal fullness and pain, tenesmus, indigestion, and warming the middle to harmonize the stomach in clinically. AIM OF THIS REVIEW: To provide a reference for the identification of traditional use, the material basis of efficacy and preclinical research between AR and VR, this review systematically summarized the similarities and differences in ethnopharmacology, phytochemistry and modern pharmacology. MATERIALS AND METHODS: The literature information was collected systematically from the electronic scientific databases, including PubMed, Science Direct, Google Scholar, Web of Science, Geen Medical, China National Knowledge Infrastructure, as well as other literature sources, such as classic books of herbal medicine, master's thesis, doctoral thesis. RESULTS: In the plateau areas of Sichuan Province, VR used to be regarded as substitute or local habit for AR, which is regularly used for chest, abdominal fullness and pain, diarrhea, and other related diseases. In Chinese Pharmacopoeia (ChP) 2020 edition, 145 prescription preparations with AR were collected, such as Xianglian Wan, Muxiang Shunqi Wan, Liuwei Muxiang San. However, only one prescription preparation (Jiuxiang Zhitong Wan) contained VR. Additionally, 237 and 254 chemical components were separately isolated and identified from AR and VR, 69 kinds of compounds were common among them, and the significant differences were presented in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids. Moreover, Costunolide (COS) and Dehydrocostus lactone (DEH), two main research objects of modern pharmacology, showed multiple pharmacological activities. Not only could they inhibit the activity of some cancer cells (such as breast cancer and leukemia cells), but they regulated the levels of various inflammatory factors (including TNF-α, NF-κB, IL-1ß, IL-6) and repressed the growth and reproduction of various microorganisms (like Helicobacter pylori, Staphylococcus aureus). CONCLUSION: COS and DEH as the common active components, provide a certain basis for local medicine about the substitution of VR for AR in Sichuan province of China in the past. In addition, the sesquiterpenoids are the main common compounds in AR and VR by collecting and collating a large number of literature and various data websites. Furthermore, AR and VR have significant differences in ethnopharmacology and phytochemistry, especially in sesquiterpene lactones, monoterpenoids, triterpenoids and phenylpropanoids, and are probably viewed as reference of a separate list of AR and VR in Chinese Pharmacopoeia.

Study of the therapeutic effect of raw and processed Vladimiriae Radix on ulcerative colitis based on intestinal flora, metabolomics and tissue distribution analysis.

BACKGROUND: The intestinal flora imbalance and metabolic disorders are closely related to the pathogenesis of ulcerative colitis (UC). As a commonly used herb for the treatment of gastrointestinal diseases, Vladimiriae Radix (VR) has been used for hundreds of years, and its main active ingredients are costunolide (COS) and dehydrocostus lactone (DEH). Clinical usage habits and previous studies have shown that the processed Vladimiriae Radix (pVR) seems to be more suitable for treating bowel disease than the raw Vladimiriae Radix (rVR), but there is still no relevant comparative study. PURPOSE: To investigate the therapeutic effect of rVR and pVR on UC by analyzing the intestinal flora, metabolomics and tissue distribution. METHODS: UC rat models were established to investigate the anti-inflammatory activities of rVR and pVR by enzyme-linked immunosorbent assay (ELISA), and to study their regulation of intestinal flora and metabolism by 16s rRNA gene analysis and Ultra Performance Liquid Chromatography Tandem Mass Spectrometry (UPLC-MS/MS). Moreover, the distribution of COS and DEH in UC mouse tissues were also observed by High Performance Liquid Chromatography Mass Spectrometry (HPLC-MS). RESULTS: rVR and pVR reduced tissue damage and the levels of TNF-α, IL-6, IL-1ß, IL-10, TGF-ß and MPO, especially pVR. 16s rRNA gene analysis showed that rVR superior in ameliorating species evenness and restoring the abundance of Lachnospiraceae and Ruminococcaceae, while pVR is better at increasing the richness and the abundance of Prevotellaceae. Metabolomics analysis suggested that rVR regulates the ß-alanine, pantothenic acid and coenzyme A biosynthesis, but pVR regulates more abundant metabolic pathways. The tissue distribution data indicated the accumulation of COS and DEH in the gastrointestinal tract. CONCLUSION: rVR and pVR had obvious therapeutic effect on UC. The potential mechanisms might be regulating abnormal metabolism, affecting the diversity and structure of intestinal flora, and accumulation of COS and DEH in colon.

Shengmai Yin formula modulates the gut microbiota of spleen-deficiency rats.

BACKGROUND: Spleen-deficiency syndrome, an important pathological change in traditional Chinese medicine, has been proven to attribute to intestinal dysbacteriosis. Shengmai Yin (SMY), a classic formula for replenishing qi and restoring pulse, is a common medicine for critical emergencies in traditional Chinese Medicine. Interestingly, our previous study established a spleen-deficiency rat model and verified the potency of SMY formula in curing spleen-deficiency rats. Our goal herein was to explore whether SMY can modulate the composition of intestinal flora and alleviate spleen-deficiency in rats. METHODS: This experiment was randomly divided into three groups, namely the normal control group (NC), model control group (MC), and the Shengmai Yin group (SMY). After the treatment, the weight and symptom indexes of the rats were recorded, histological changes in the colon were observed, levels of serum D-xylose, gastrin (GAS), and vasoactive intestinal peptide (VIP) were measured, and gut microbiota profiling was conducted by 16S rRNA sequencing. RESULTS: The body mass of the spleen-deficiency model rats significantly decreased compared with that of the NC group, and SMY treatment significantly increased body mass compared with the MC group (P < 0.01). Colon histopathology revealed that SMY treatment alleviated colonic mucosal damage in spleen-deficiency rats. The serum levels of D-xylose and gastrin (GAS) were significant increased by SMY (P < 0.05, P < 0.01), and vasoactive intestinal peptide (VIP) was reduced by SMY (P < 0.01) compared with MC. Furthermore, alpha diversity was significantly decreased in the model rats compared to the normal rats (P < 0.05) and increased with SMY treatment (P < 0.01). The most abundant phyla were Firmicutes and Bacteroidetes, followed by Proteobacteria, Verrucomicrobia, and Actinobacteria. At the genus level, there was a lower relative abundance of Lactobacillus, Bacteroides, Akkermasia, and Allobaculum, and a higher relative abundance of Lachnospiraceae NK4A 136 group, Ruminococcaceae UCG-014, and Sphingomonas in the MC group. The relative abundance of Actinobacteria, Alistipes, Bifidobacterium, Bifidobacterium, Bifidobacteriaceae, Lachnospiraceae NK4A136group, Lactobacillus, Lactobacillaceae, Bacilli, Verrucomicrobiae, and Akkermansia were significantly abundant in the treatment groups, and thus may be singled out as potential biomarkers for SMY in the treatment of spleen deficiency. In addition, analysis on the correlation between species and physicochemical indexes showed that the abundance of Parasutterella was negatively correlated with the change in GAS, and positively correlated with the change in VIP (P < 0.01). CONCLUSION: Our findings have provided preliminary evidence that modulating the gut microbiota may play a role in the treatment of spleen deficiency with SMY. However, further studies are needed to clarify the mechanism by which SMY regulation of related gut microbiota occurs.

Comparative study of raw and processed Vladimiriae Radix on pharmacokinetic and anti-acute gastritis effect through anti-oxidation and anti-inflammation.

BACKGROUND: Vladimiriae Radix (VR) is the dry root of Vladimiria souliei (Franch.) Ling or Vladimiria souliei (Franch.) Ling var. cinerea Ling. Costunolide (CO) and dehydrocostus lactone (DE) are the two most effective active ingredients of VR. Raw Vladimiriae radix (rVR) and processed Vladimiriae radix (pVR) are the two most common forms. They have been used for hundreds of years to treat gastritis, gastric ulcer and gastrointestinal pain, but their protective effects on gastric mucosa have been widely considered to be different, and the mechanism is not clear. PURPOSE: A comparative study of in vivo process and efficacy difference of raw and processed Vladimiriae Radix was carried out to explore the treatment mechanism and to provide reference for the rationality of clinical usage. METHODS: In this study, multi-batch rVR and pVR were used to establish the characteristic chromatograms through high performance liquid chromatography (HPLC) to control the qualities of their extracts. A rapid and accurate ultra-high performance liquid chromatography - mass spectrometry (UPLC-MS) method was established and verified, and the concentrations of CO and DE in plasma of rats after oral administration were determined to analyze the pharmacokinetics. The anti-inflammatory and antioxidant activities of ethanol-induced acute gastric mucosa injury (AGMI) in rats were quantitatively analyzed by ELISA and Westernblot methods. RESULTS: Characteristic chromatograms study showed that there were 9 common characteristic peaks between the chromatograms of rVR and pVR, and there was a high level (> 0.90) of the similarity between batches (only one batch less than 0.90). The increased levels of Tmax, T1/2 and MRT were found in rats treated with the pVR. Animal model studies indicated that both the two forms of VR could relieve AGMI, but pVR could more effectively reduce the content of ethanol in blood and lower the levels of TNF-α, IL-6, IL-1ß, NO, iNOS and MDA, and increase the level of SOD. Results of Westernblot proved that pVR also could inhibit the expression of NF-κB p65, IκBα and up-regulate the expression of HO-1 and NRF2 more operatively to protect gastric mucosa through anti-inflammatory and antioxidant stress mechanisms. CONCLUSION: Compared with rVR, pVR has an accelerated absorption in vivo and its effect time was prolonged, and the observed improvement of anti-AGMI effect was achieved through anti-oxidation and anti-inflammation regulation.