A Review of the Ethnopharmacology, Phytochemistry, Pharmacology, Application, Quality Control, Processing, Toxicology, and Pharmacokinetics of the Dried Rhizome of Atractylodes macrocephala.

The product investigated herein is the dried rhizome of Atractylodes macrocephala Koidz. [Asteraceae] (Baizhu), which is also known as Dongbaizhu, Wuzhu, Yuzhu, Zhezhu, and Zhongzhu, among others. It invigorates the spleen, replenishes qi, and removes dampness, diuresis, and hidroschesis, and impacts fetal safety. It is often used for the treatment of diseases such as spleen function deficiency, abdominal distension, diarrhea, sputum, vertigo, edema, fever, and sweating and also aids cessation of minimal vaginal bleeding during pregnancy. In this study, research pertaining to the ethnopharmacology, application, phytochemistry, analytical methods, quality control, processing, pharmacology, toxicology, and pharmacokinetics of Baizhu has been reviewed. Relevant information and data reported for Baizhu were collected from CNKI, VIP, PubMed, Web of Science, scientific databases, Chinese Medicinal Material Encyclopedia, Chinese herbal medicine classics, Chinese medicine dictionary, doctoral and master's theses, and so on. Baizhu demonstrates diuretic, antidiuretic, anti-inflammatory effects and antitumor function and aids regulation of gastrointestinal function, hypoglycemic effect, analgesic action, protection on the liver ischemia-reperfusion injury (IRI) in rats, inhibition of aromatase, treatment of bone disease, strengthening myocardial contraction ability, detoxification and cholagogic effect, fall hematic fat action, such as the treatment of acute renal injury, and so on. It also can be an anticoagulant, improve the nervous system disease, affect the immune system, and regulate uterine smooth muscle, antioxidation, antiaging, and antibacterial effect. Sesquiterpenoids, triterpenoids, polyacetylenes, phenylpropanoids, coumarins, flavonoids, flavonoid glycosides, steroids, benzoquinones, polysaccharides, and other compounds were isolated from Baizhu. Among them, sesquiterpenoids, polysaccharides, and polyacetylenes are the main components of Baizhu. Baizhu exhibits a wide range of pharmacological effects and constitutes a considerable proportion of the composition of many proprietary crude drugs. It mainly affects the endocrine, nervous, and urinary systems. The presented information suggests that we should focus on the development of new drugs related to Baizhu, including specific components, to achieve a greater therapeutic potential that can be considered to further explore the information related to Baizhu.

A review of the botany, traditional uses, phytochemistry, and pharmacology of the Flos Inulae.

ETHNOPHARMACOLOGICAL RELEVANCE: Plants of the genus Inula have long been used as an ethnomedicine in Asia, Europe, and North America for its high medicinal value and health benefits. Inula japonica Thunb. (I. japonica) and Inula britanica L. (I. britanica) are included in Chinese Pharmacopoeia (2020 edition) as the traditional Chinese medicine Flos inulae (FI). In TCM, FI tastes bitter, pungent, and salt, with warm nature and has the functions of water removal, reduction in nausea, and prevention of vomiting and is often used for cold-related coughs, sputum, wheezing coughs, vomiting, belching and other related diseases. In addition, Inula japonica Thunb is used as a botanical medicine in Korea and Inula britannica L. is also used as a traditional plant medicine in Iran. AIM OF THE STUDY: This paper collects the relevant research literature (1970-2021) and provides a systematic summary of the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods and quality control of FI to explore its potential and expand its scope for better clinical application. MATERIALS AND METHODS: Information on Inula japonica Thunb. and Inula britanica L. was collected from scientific databases (1970-2021), including Google Scholar, Baidu Scholar, Springer, PubMed, CNKI and Wan Fang DATA. Information was also collected from classic books of Chinese herbal medicine and Ph.D. and M.Sc. theses. RESULTS: More than 200 chemical compounds have been isolated from Inula japonica Thunb. and Inula britanica L., including sesquiterpenes, flavonoids, volatile oils, triterpenoids, diterpenoid glycosides, monoterpenoids, polysaccharides, steroid and small molecule acids. Based on a wide variety of chemically active ingredients, FI has a wide range of pharmacological effects. Modern pharmacological research has proven that the pharmacological effects of FI include anti-inflammatory, antitumor, antioxidant, antiallergy, antidiabetic, blood lipid reduction, skin whitening, liver protection, anticonstipation, and antinociceptive effects. CONCLUSIONS: FI is a very important traditional Chinese herbal medicine with anti-inflammatory antitumor, antioxidant, antiallergy, antidiabetic and other pharmacological effects that can treat a variety of related diseases. This paper summarizes the botany, ethnopharmacology, processing, phytochemistry, pharmacology, toxicity, analytical methods, and quality control of FI. However, the research on the processing, toxicity and quality control of FI is currently too shallow, especially concerning the relationship between the changes in active components before and after processing and the changes in its pharmacological action, which remains unclear. There are few toxicity experiments conducted with FI, so it is impossible to evaluate the safety of FI objectively and impartially. There are also few studies on the material basis and doses of FI causing toxicity and side effects, and more in-depth and concrete researches should be carried out in the future regarding these aspects. Furthermore, to ensure effective and safe clinical medication, we should also pay attention to the mixed use of FI in various regions of China to control the quality of the FI plant.

A review: the botany, ethnopharmacology, phytochemistry, pharmacology of Cinnamomi cortex.

Cinnamomi Cortex (CC) is the dried bark of Cinnamomum cassia (L.) J. Presl. Modern pharmacological research shows that CC can be used to treat diabetes, breast cancer, leukemia and other diseases. It has been used for more than 2000 years in China, mainly distributed in Guangxi, Guangdong, Yunnan and Fujian. In this paper, the botany, ethnopharmacology, phytochemistry, pharmacology, pharmacokinetics and other aspects of CC are summarized. We hope to provide convenience for the further exploration and development of CC. There are more than 300 components isolated from CC including essential oils, polyphenols, diterpenes and sesquiterpenes, flavonoids, polysaccharides and others. Pharmacological studies show that CC has a wide range of pharmacological activities such as anti-inflammatory, antibacterial, antioxidant, antitumor, improving glucose and lipid metabolism, neuroprotection and so on. It shows that CC has great potential to develop into a cheap, low-toxicity and highly-efficient natural therapeutic drug. However, there is still a long way to go for research of CC, although great progress has been made. For instance, clinical practices for CC recorded in traditional medicine books need to be paid more attention. Present achievements are still not enough to clearly explain the mechanism for some diseases. New skeletons and new drugs will be required to be discovered, so that the potential of CC can be brought into full play.

Panacis Quinquefolii Radix: A Review of the Botany, Phytochemistry, Quality Control, Pharmacology, Toxicology and Industrial Applications Research Progress.

On January 2, 2020, The National Health Commission and the State Administration for Market Regulation listed Panacis Quinquefolii Radix (PQR) as a medicinal and food homologous product. PQR is the dry root of Panax quinquefolium L., which has the functions of replenishing qi and nourishing Yin, clearing heat and producing body fluid. It is often used for qi deficiency and Yin deficiency, heat exhaustion, asthma and phlegm, dry mouth and pharynx. PQR is sweet, slightly bitter and cool in nature, and enter the heart, lung and kidney meridian exerts the remedial and hygienical effect. At present, active components such as saponins, flavonoids, fatty acids, polyalkynes, volatile oils and other nutrients such as amino acids, carbohydrates, vitamins and trace elements have been isolated from PQR. Modern pharmacological studies have shown that PQR has the effects of hypoglycemic, antihypertensive, anti fatigue, anti-oxidation, anti-tumor, immunomodulatory, neuroprotective and so on. In addition, PQR is recognized as a health care product to strengthen the body and dispel diseases. It is not only the raw material of Traditional Chinese medicine preparations, but also the treasure of dietary therapy and herbal cuisine. This study not only reviewed the botany, phytochemistry and pharmacology of PQR, but also summarized its quality control, toxicity and industrial applications for the first time. This paper not only summarizes the development status of PQR, but also analyzes the shortcomings of the current research on PQR, and puts forward the corresponding solutions, in order to provide reference for future scholars to study PQR.

Botany, traditional uses, phytochemistry, analytical methods, processing, pharmacology and pharmacokinetics of Bupleuri Radix: A systematic review.

Bupleuri Radix (BR) is the dry root of Bupleurum chinense DC. and Bupleurum scorzonerifolium Willd. It has the functions of evacuation and antipyretic, soothing liver and relieving depression and often used to treat cold fever, chest and rib swelling pain, irregular menstruation, uterine prolapse, rectocele and other diseases. In this paper, the botany, traditional application, phytochemistry, pharmacology and toxicity of BR were reviewed. On the basis of limited literature, the analytical method, quality control, processing method, processing effect and pharmacokinetics of BR were summarized and analyzed for the first time. This review makes an in-depth discussion on the shortcomings of the current research on BR, and puts forward its own views and solutions. This has never been summarized in the previous review of BR. It is of great practical significance for future scholars to find a breakthrough point in the study of BR. So far, its mechanism has not been satisfactorily explained. Moreover, the comprehensive quality evaluation and multi-target network pharmacology of BR need to be further studied. In the future, more in vitro and in vivo experiments are needed to give full play to the therapeutic potential of BR.

A Review of the Botany, Traditional Use, Phytochemistry, Analytical Methods, Pharmacological Effects, and Toxicity of Angelicae Pubescentis Radix.

Angelicae Pubescentis Radix (AP), as a traditional Chinese medicine (TCM), has been used for thousands of years in China. In this paper, the botany, traditional use, phytochemistry, analytical methods, quality control, pharmacological effects, and toxicity of AP were reviewed. It can provide a reference for the further research and lay a foundation for the rational clinical application of AP. The relevant information on AP was collected from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The components which have been isolated and identified in AP include coumarins, volatile oils, organic acids, terpenes, polysaccharides, flavonoids, sterols, and trace elements. Most of them were analyzed by HPLC and GC. A pharmacological study shows that the AP has extensive pharmacological effects, including anti-inflammatory, antirheumatism, sedative and hypnotic, neuroprotection, antioxidation, antitumor, and allergy, and it is widely used in the treatment of the rheumatoid arthritis, knee osteoarthritis, lumbar disc, ankylosing spondylitis, headaches, stroke hemiplegia, Alzheimer's, and arrhythmia. AP is a valuable natural medicinal plant. So far, significant advances have been made in phytochemistry and pharmacology. Some traditional uses have been demonstrated by modern pharmacology. However, the chemical components and pharmacological effects of AP are complex and varied, and there are different standards for the evaluation of its quality and efficacy. The mechanism of action, the structure-activity relationship among the components, and the potential synergistic and antagonistic effects remain to be studied. At the same time, there are few studies on the specific compounds related to its pharmacodynamics. In order to better develop and utilize AP, we should establish a more reasonable, reliable, and accurate quality control standard and focus on the study of bioactive constituents and the demonstration of their mechanism of action.

Pharmacokinetic Comparisons of Eight Active Components from Raw Farfarae Flos and Honey-Processed Farfarae Flos after Oral Administration in Rats by UHPLC-MS/MS Approaches.

Farfarae flos (FF) is widely used for cough over thousands of years in China, but little is known about their pharmacokinetics properties. This study was aimed to establish a rapid and accurate ultraperformance liquid chromatography with triple-quadrupole tandem mass spectrometry method for compare pharmacokinetics studies of eight active compounds after oral administration between raw and honey-processed farfarae flos extracts. Optimum separation was performed on a Thermo Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 µm particles size) with a gradient elution of acetonitrile as mobile phase A and 0.3% formic acid aqueous solution as mobile phase B. The flow rate was set as 0.3 mL/min and separated for 34.0 minutes. Electrospray ionization in the negative ion mode and selected reaction monitoring were used to identify and separate active components. The results met the acceptance criteria and showed that this method exhibited good linear, precision, accuracy, and stability. The extraction recoveries ranged from 81.54% to 104.48%, and the matrix effects ranged from 81.94% to 103.02%. These results show that the validated method could be successfully applied to evaluate the pharmacokinetic study in rats after oral administration of raw farfarae flos (R-FF) and honey-processed farfarae flos (H-FF).

A strategy for qualitative and quantitative profiling of Angelicae Pubescentis Radix and detection of its analgesic and anti-inflammatory components by spectrum-effect relationship and multivariate statistical analysis.

This study established a spectrum-effect relationship method for screening and quantifying the analgesic and anti-inflammatory active ingredients in Angelicae Pubescentis Radix (AP) by ultra-high-performance liquid chromatography-quadrupole mass spectrometry detector analysis (UPLC-QDA). First, the fingerprint of AP was established to determine the common peaks. Next, six batches of AP samples, with significant differences, were selected for evaluation of pharmacological activity. Subsequently, the spectrum-effect relationship was used to screen the active ingredients. Finally, the screened ingredients were quantified using UPLC-QDA. In total, 21 common peaks were identified and four effective compounds (bergapten, columbianetin acetate, osthole and isoimperatorin) were selected using the gray relational analysis and partial least squares regression analysis. Quantitative analysis showed that the content of the four effective compounds was the highest in a randomly selected batch, S7 (Hubei). To our knowledge, this is the first attempt that evaluated the quality and spectrum-effect relationship of AP by quantitative analysis and chemometrics. This study identified the key pharmacologically active components of AP and thereby improved the quality evaluation system of AP. This method has broad application prospects for screening effective components and will be helpful in establishing more reliable, scientific and reasonable quality standards for AP and other traditional Chinese medicines.

Screening and quantification of TNF-α ligand from Angelicae Pubescentis Radix by biosensor and UPLC-MS/MS.

The aim of this study is to establish a method for rapid screening of active ingredients targeting TNF-α from Chinese herbal medicines. Take Angelicae Pubescentis Radix (APR) as an example, surface plasma resonance technique was used to establish for screening small molecule inhibitors of TNF-α from APR extract. Then UPLC-MS/MS coupled with chemometric was used for quantitative and evaluate the differences of the candidate compounds bound to TNF-α in APR from different sources. In the experiment, TNF-α protein was fixed on the CM5 chip surface of biacore T200 biosensor by amino coupling. A series of small molecular compounds in APR were screened and six phenolic acid compounds had a strong affinity for TNF-α protein and could be used as TNF-α antagonists. In summary, the targeted drug screening method for TNF-α protein based on SPR technology established in this study can be used to screen anti-TNF-α small molecule inhibitors. UPLC-MS/MS can accurately quantify 15 active ingredients, which provides reliable experimental data and new research ideas for targeted drug research on TNF-α protein.

Discovering the Major Antitussive, Expectorant, and Anti-Inflammatory Bioactive Constituents in Tussilago Farfara L. Based on the Spectrum-Effect Relationship Combined with Chemometrics.

Farfarae Flos (FF) is the dried flower bud of Tussilago farfara L, which has antitussive, expectorant, and anti-inflammatory effects. However, little research on the main active composition of FF has been reported. The purpose of this study is to find the main active compounds responsible for the three pharmacological effects (i.e., antitussive, expectorant, and anti-inflammatory effects) of Farfarae Flos, based on the spectrum-effect relationship combined with chemometrics. First, this study uses the UPLC-QDA method to establish the chromatography fingerprint of Farfarae Flos, which is combined with chemometrics to analyze 18 batches of samples. Then, we study the antitussive, expectorant, and anti-inflammatory effects of Farfarae Flos. Finally, the spectrum-effect relationship between the fingerprint and the three pharmacological effects are studied by grey correlation analysis and partial least squares regression. The results show that four, four, and three main active constituents were found for the antitussive, expectorant, and anti-inflammatory pharmacological effects, respectively. In conclusion, we found the main active compounds corresponding to the main pharmacodynamic effects of Farfarae Flos. To our knowledge, this is the first time that spectrum-effect relationships in FF have been established using both raw and processed samples, which provides an experimental basis for further studies on the pharmacodynamic material basis of Farfarae Flos, as well as providing reference for the comprehensive evaluation of Farfarae Flos quality and the development of substitute resources.

The chemical constituents from the active fractions of Eleutherine bulbosa with their antimicrobial activity.

Six compounds including three new polyketide ones named eleubosas A-C (1-3) were isolated from the active frations of Eleutherine bulbosa. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS and IR spectroscopic analyses data. All the isolates were evaluated against three pathogenic bacteria, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and the results showed that compounds 1 and 2 displayed moderate inhibitory activities against E. coli with MIC values both 12.5 µg/mL, which are consistent with the clinical applications and need further studies.

Ursane-type triterpenoids from the roots of Rosa multiflora with their anti-inflammatory activity.

Nine ursane-type triterpenoids including three new ones 2α, 19α-dihydroxyurs-3-O-acetyltormentic acid (1), 1α, 2α, 3α, 20ß-tetrahydroxyurs -13(18)-en-28-oic acid (2), and 2α, 3α, 20ß, 24-tetrahydroxyurs-13(18)-en-28-oic acid (3) were isolated from the roots of Rosa multiflora. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS, and IR spectroscopic analyses data. All the isolates were evaluated for their anti-inflammatory activity in vitro and the results showed that compounds 1-9 displayed moderate inhibitory activity with IC50 values ranging from 24.7 to 86.2 µM compared with the postitive control Amino guanidine (IC50 4.3 µM).[Formula: see text].

Comparison of pharmacokinetics of phytoecdysones and triterpenoid saponins of monomer, crude and processed Radix Achyranthis Bidentatae by UHPLC-MS/MS.

1. The aim of this study was to develop a selective, rapid, accurate and sensitive ultrahigh performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for pharmacokinetic (PK) studies of phytoecdysones and triterpenoid saponins after oral administration of five monomers, crude, wine-processed and salt-processed Radix Achyranthis bidentatae (RAB).2. A Thermo Hypersil GOLD C18 column (100 mm × 2.1 mm, 1.9 µm) coupled with a mobile phase of (A) acetonitrile and (B) water (both containing 0.3% acetic acid) was used for sample separation. The mass analysis was performed in a triple quadruple mass spectrometer using selected reaction monitoring (SRM) with negative scan mode.3. The results showed that this method exhibited desirable sensitivity, precision, stability and repeatability. The extraction recoveries of the compounds ranged from 94.2 to 99.8% and the matrix effects ranged from 93.3 to 100.5%. Comparing the Cmax and AUC of five analytes in those groups showed this tendency: salt-processed RAB > wine-processed RAB > crude RAB > monomer group. The results confirmed the feasibility of TCM theory to enhance the efficacy of processed RAB.

A simple liquid chromatography coupled with tandem mass spectrometry approach for the simultaneous quantification of thirteen compounds in rats following oral administration of raw and processed Fructus Xanthii: Application in a comparative pharmacokinetic study.

A simple and sensitive analysis using ultra high performance liquid chromatography with a tandem mass spectrometric system operated in selected reaction monitoring mode was developed for the determination of 11 phenolic acids, atractyloside, and carboxyatractyloside in rat plasma. The two classes of analytes were then separated on a Waters ACQUITY™ UPLC HSS T3 column (50 mm × 2.1 mm, 1.8 µm) using gradient elution with a mobile phase of 0.2% formic acid in water containing 10 mM ammonium acetate and methanol. Detection was accomplished by selected reaction monitoring scanning via an electrospray source operating in negative ionization mode. The calibration curve was linear (R2  = 0.990) over a concentration range of 1.20-3500 ng/mL, while the validated lower limit of quantification was 1.20 ng/mL. The precision varied from 0.84 to 4.62%, and the accuracy varied within ±5%. The method proved robust with sample freezing and thawing and with short- and long-term sample storage. The established method was used for simultaneous quantification and was successfully used for the first time for the pharmacokinetic evaluation of 13 compounds after the intragastric administration of raw and processed Fructus Xanthii in rats. The results indicated that processing affects the absorption and metabolism of Fructus Xanthii extract. Importantly, the results also indicated the importance of processing for the clinical application of traditional Chinese medicine.

A Biosensor-Based Quantitative Analysis System of Major Active Ingredients in Lonicera japonica Thunb. Using UPLC-QDa and Chemometric Analysis.

In the study, a surface plasmon resonance-based (SPR-based) competitive assay was performed to analyze different compounds' inhibitory activity to TNF-, an important pro-inflammatory cytokine in the pathogenesis of chronic inflammatory diseases. Moreover, the single mass spectrometry (MS) detection method was coupled with an ultra-high-performance liquid chromatography (UPLC) system for the routine quality control (QC) of a traditional Chinese medicine (TCM). The above quality control strategy was evaluated with Lonicera japonica Thunb. Analytes were firstly separated on a Waters ACQUITYTM UPLC HSS T3 column (2.1 × 50 mm; particle size = 1.8 µm) using a 0.1% formic acid gradient elution, then detected by negative ESI mass spectrometry. The limits of quantification (LOQ) for analytes reached 0.005-0.56 µg/mL. The LOD of the QDa detector was lower than that of the PDA detector, indicating its wider detection range. The QDa detector was also more suitable for the analysis of the complex matrix of TCM. The method showed excellent linearity, with regression coefficients higher than 0.9991. The average recoveries of the investigated analytes were in the range of 98.78-105.13%, with an RSD below 3.91%. The inter-day precision range (n = 3 days) was 2.51-4.54%. Compared to other detectors, this strategy could be widely applied in the quantitative analysis of TCM. In addition, the chemically latent data could be revealed using chemometric analysis. Importantly, this study provides an efficient screening method for small-molecule inhibitors targeting the TNF-α pathway.

Simultaneous Determination of Thirteen Q-Markers in Raw and Processed Tussilago farfara L. by UPLC-QQQ-MS/MS Coupled with Chemometrics.

The purpose of this study was to establish a rapid, reliable, and sensitive ultra-performance liquid chromatography with triple-quadrupole tandem mass spectrometry coupled with chemometric method to measure and evaluate the differences between thirteen compounds in raw and processed Tussilago farfara L. from different sources. This assay method was validated, and the results indicated that the calibration curves for the thirteen compounds had good linearity (R² > 0.9990). The limits of detection and limits of quantification of the thirteen compounds ranged from 0.0012 to 0.0095 µg/mL and from 0.0038 to 0.0316 µg/mL, respectively. The relative standard deviations (RSD) of the intra- and inter-day precisions and stability ranged from 1.06 to 2.00%, 0.26 to 1.99%, and 0.75 to 1.97%, respectively. The sample recovery rates of the thirteen compounds with different concentrations were 94.47⁻104.06%. The chemometric results, including principal component analysis, hierarchical clustering analysis, three-dimensional analysis, and box plot analysis, indicated that there are significance differences in raw and processed Tussilago farfara L. The results of this study confirm that the proposed method is the first reported method that has been successfully applied for simultaneous determination and discovery of the difference between thirteen compounds of raw and processed Tussilago farfara L. Thus, this method could be a helpful tool for the detection and confirmation of the quality of traditional Chinese medicines and provide a basis for future pharmacological studies.

Quantitative analysis of different batches of raw, wine-processed, and vinegar-processed Paeoniae Alba Radix using ultra-performance convergence chromatography coupled with photo diode array detection.

Supercritical fluid chromatography is a safe and ecofriendly analytical technique that has not been fully applied to the analysis of traditional Chinese medicine. This is the first study on the separation of six quality markers-paeoniflorin, albiflorin, benzoyl paeoniflorin, oxypaeoniflorin, gallic acid and benzoic acid-from raw, wine-baked and vinegar-baked Paeoniae Alba Radix (PAR) by Supercritical fluid chromatography. Optimum separation was achieved on an HSS C18 SB column (100 × 3.0 mm, 1.8 µm particles) with a gradient elution of high-purity carbon dioxide as mobile phase A and methanol-acetonitrile (70:30, v/v) with 0.10% phosphoric acid as mobile phase B. The flow rate was set at 0.7 mL/min for 15.0 min. The method was validated in terms of the overall intraday and interday precision, with relative standard deviations (RSDs) of 0.87-2.87 and 1.47-3.63%, respectively. The recoveries were 98.10-103.60% with an RSD of 1.00-3.40%. The stability of the RSD values was in the range 1.10-3.78%. The developed approach was successfully applied and provides a valuable reference for the quality assessment of PAR and processed PAR. The results also revealed that the standardization of processing technology is of great significance to the fluctuations in quality before and after the processing of traditional Chinese medicine.

A UPLC-MS/MS application for comparisons of the hepatotoxicity of raw and processed Xanthii Fructus by energy metabolites.

The ripe fruit of Xanthium strumarium L. (Xanthii Fructus) cannot be widely used as a Chinese herbal medicine (CHM) owing to its hepatotoxicity. However, Xanthii Fructus (XF) can be used effectively and safely after correct processing based on traditional experience, although a high hepatotoxicity risk remains owing to improper usage. Therefore, the processing methods used must be clarified to ensure safety. The adenosine-5'-triphosphate (ATP) level in tissues is an important indicator reflecting the functional status of liver cells. Therefore, this study aims to evaluate the hepatotoxicity of XF using UPLC-MS/MS. The hepatotoxicity of raw XF (RXF) and XF processed by intermediary energy metabolites (PXF) is compared. The method is evaluated for its analytical performance and successfully applied to the quantification of ATP, adenosine-5'-diphosphate (ADP), adenosine-5'-monophosphate (AMP), atractyloside, and carboxyatractyloside in mouse liver. The hepatotoxicity results also indicate that the toxicity of XF is decreased after processing, perhaps due to the decrease in atractyloside and carboxyatractyloside contents. Importantly, the experimental evidence provides a rationale for the reduction in toxicity. These data show that mouse livers are damaged between the days 20 and 30 of RXF oral administration, and that the ATP level is decreased. Importantly, no significant difference is observed between the PXF treatment group and control group, while the RXF treatment group is significantly different. Therefore, processing can reduce the toxicity of XF.