The structures of the identified compounds of C. dahurica, C. foetida and C. heracleifolia. (1) 2-Feruloyl fukinolic acid-1-metyl ester; (2) 2-feruloyl piscidic acid; (3) 7,8-didehydro cimigenol-24-O-cimicifuga alcohol-3-O-β-D-xyl; (4) cimicifugoside H-2; (5) 12β-hydroxy cohosh alcohol-3-O-β-D-gal; (6) 7,8-deoxy cohosh alcohol-24-O-acetyl alcohol-ara; (7) 27-deoxy Arcot hormone; (8) acimicifugic acid D. 

The structures of the identified compounds of C. dahurica, C. foetida and C. heracleifolia. (1) 2-Feruloyl fukinolic acid-1-metyl ester; (2) 2-feruloyl piscidic acid; (3) 7,8-didehydro cimigenol-24-O-cimicifuga alcohol-3-O-β-D-xyl; (4) cimicifugoside H-2; (5) 12β-hydroxy cohosh alcohol-3-O-β-D-gal; (6) 7,8-deoxy cohosh alcohol-24-O-acetyl alcohol-ara; (7) 27-deoxy Arcot hormone; (8) acimicifugic acid D. 

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Rhizoma Cimicifugae (Sheng ma) is a Ranunculaceae herb belonging to a composite family and well known in China. has been widely used in traditional Chinese medicine. The Pharmacopoeia of the People׳s Republic of China contains three varieties (Cimicifuga dahurica (Turcz.), Cimicifuga foetida L. and Cimicifuga heracleifolia Kom.) which have been use...

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... to Fig. 2A, SM ion markers can be seen to be located in the left area of the PCA axis, whereas the DSM and XSM ion markers are located in the right area of the PCA axis. The DSM ion compounds are mainly located in the upper half of the axis and the XSM ion compounds located in lower part. The structures of the 8 marker compounds are shown in Fig. ...

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... The ethanol extract of Cimicifugae Rhizoma can effectively alleviate OVA ovalbumin-induced inflammatory and oxidative stress injury by up-regulating Nrf2/HO-1/NQO1 signaling and down-regulating NF-κB phosphorylation [18]. The previous studies focused on the quality markers and components of Cimicifugae Rhizoma from original plants [19,20]. But our study aimed to comprehensively identify the components absorbed into the plasma after administration of Cimicifugae Rhizoma and screen out the component with the best antioxidant effect on podocytes impaired by oxidative stress, so as to provide the potential evidence of the renal protection of Cimicifugae Rhizoma. ...
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Background and Objectives: Cimicifugae Rhizoma, also known as ‘Sheng ma’ in Madeiran, is a widely used Chinese herbal medicine that has several pharmacological qualities, one of which is its antioxidant activity. Isoferulic acid, a prominent phenolic compound found in Cimicifugae Rhizoma, has potent antioxidant properties. This study was aimed to comprehensively analyze the components in Cimicifugae Rhizoma and rat plasma to evaluate the in vitro antioxidant and anti-inflammatory properties of Cimicifugae Rhizoma extract and Isoferulic acid as potential candidates for developing herbal formulations targeting podocyte injury in diabetic nephropathy for further clinical utilization. Materials and Methods: UPLC/Q-TOF-MS and HPLC were utilized as analytical tools to identify components of Cimicifugae Rhizoma extract or rat plasma after administrating it. MPC5 cells were cultured with H2O2 and high glucose and subjected to oxidative stress injury. The CXCL12/CXCR4 system plays a crucial role at certain stages of multiple kidney diseases’ injury. Apoptosis-related and target CXCL12/CXCR4/mTOR/Caspase-3 and Cask protein levels were assessed, and the levels of inflammatory-related factors, motility, morphology, ROS level, and apoptosis in podocytes were tested. Results: A total of 82 and 39 components were identified in the Cimicifugae Rhizoma extract and plasma, and Isoferulic acid content was determined as 6.52 mg/g in the Cimicifugae Rhizoma extract. The Cimicifugae Rhizoma extract (1 μg/mL) and Isoferulic acid (10, 25, 50 μM) considerably decreased high glucose and oxidative-stress-mediated toxicity, impaired mobility and adhesion and apoptotic changes in MPC5 cells, and reversed inflammation response. Moreover, the Cimicifugae Rhizoma extract and Isoferulic acid down-regulated Cask, mTOR, and Caspase-3, while significantly blocking the overactivation of CXCL12/CXCR4 in podocytes stimulated by oxidative stress and high glucose. Conclusions: These results indicate that the renal protective mechanism of the Cimicifugae Rhizoma extract and Isoferulic acid on simulating H2O2-induced podocyte injury involves mainly the of CXCL12/CXCR4 pathways and the inactivation of oxidative-stress-mediated apoptotic pathways after comprehensive qualitative and quantitative research by UPLC/Q-TOF-MS and HPLC. These findings provide an important efficacy and ingredient basis for further study on the clinical utilities of Cimicifugae Rhizoma and Isoferulic acid on podocyte and kidney impairment.
... Compounds 27-deoxy arcot hormone and cimicifugic acid D were identified as the markers of A. dahurica. On the other hand, the compounds 2-feruloyl piscidic acid, 2-feruloyl fukinolic acid-1-methyl ester, 7,8-didehydrocimigenol-24-O-cimicifugaalcohol-3-O-β-D-xyl, and cimicifugoside H-2 were identified as the markers of A. cimicifuga; while 12β-hydroxy cohosh alcohol-3-O-β-D-gal and 7,8-deoxy cohosh alcohol-24-O-acetyl alcohol were markers of A. heracleifolia (Fan et al., 2017). ...
Article
Introduction: The genus Actaea L., comprising of 32 species, has recently emerged as a source of potential phytochemicals with promising pharmacological properties. However, there is no review available integrating the scattered scientific studies on this genus. To fill this knowledge gap, an extensive review of the genus Actaea is presented with focus on its ethnomedical uses, phytochemistry, and pharmacology. Methods: For this review, 162 publications including 152 research papers, 7 books, 2 dictionaries and one glossary published from 1896 to April, 2020 A.D. were critically reviewed and relevant data extracted. The chemical structures and formulae of compounds have been sourced and validated using PubChem database; and drawn using Chem Draw Ultra 6.0. The scientific nomenclature follows The Plant List. Results & Discussion: For over more than a century, the ethnomedical uses of 8 species of this genus in treating 29 types of human diseases under different traditional medical systems have been reported. Over the last two decades, the phytochemical studies so far conducted on 16 species of Actaea have led to the isolation of more than 400 different compounds, notably cycloartane triterpenoids, flavonoids, phenylpropanoids, and nitrogenous compounds. Based on these phytochemical studies on Actaea species, the recent resurgence on pharmacological research conducted on 16 species has led to novel leads with potential applications. Conclusions: We highlight the current knowledge gaps and discuss future research prospects on genus Actaea, which can guide its bio-prospection and sustainable use in near future.
... UPLC-MS/MS technology is a combination of high-resolution UPLC and highly sensitive and selective MS. The use of this technology does not require the measured samples to be subjected to purification or derivatization with complicated separation and enrichment processes prior to analysis (32). A large amount of reliable qualitative and quantitative information can be quickly obtained following a simple pre-treatment with UPLC-MS/MS technology (32). ...
... The use of this technology does not require the measured samples to be subjected to purification or derivatization with complicated separation and enrichment processes prior to analysis (32). A large amount of reliable qualitative and quantitative information can be quickly obtained following a simple pre-treatment with UPLC-MS/MS technology (32). The present study described a novel, rapid and effective UPLC-MS/MS method for the discovery and identification of ellagic acid in the cassia seed decoction. ...
... Compared with traditional methods such as HPLC or UPLC, UPLC-MS/MS can identify a number of metabolites in a short time, reduce the use of animals and facilitate the metabolite identification process (23). The environmental factors influencing the metabolic process are easy to control in the UPLC-MS/MS system (28,32,35). Moreover, certain active metabolites in the biological samples were likely to be generated at relatively low levels and UPLC-MS/MS is able to detect low levels of metabolites. ...
... However, molecular components of DSO remain undetermined. UPLC-Q-TOF-MS, regarded as a cogent hyphenated technique for the determination of constituent structures, has been widely applied to analyse the chemical components of traditional Chinese herbs [35,36]. In the present study, we conducted a UPLC-Q-TOF-MS-based analysis of DSO, which revealed the presence of 14 constituents, including flavonoids, tanshinones, salvianolic acids, glycosides, and phthalides, as well as 74 constituents, including tanshinone II b, hydroxysafflor yellow A, stachydrine, senkyunolide, leonurine, kaempferol, miltirone, quercetin, amarogentin, and lithospermic acid B, among others. ...
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Hypertrophic scarring (HS), caused by excessive fibrosis of injured skin, imposes a psychological burden and creates a source of distress that impairs the quality of life of affected individuals. However, the gold standard for HS treatment has not yet been determined due to the complicated and difficult nature of the routines and procedures involved. Previous studies have indicated that the topical application of certain active components found in traditional Chinese medicines shows potential as a therapeutic alternative for scars. Here, single-cell RNA-sequencing was performed to determine cellular heterogeneity and identify marker genes and mechanisms associated with HS. It was found that fibroblasts comprise the largest proportion of HS cell types. The marker genes that were highly expressed in fibroblasts were extracellular matrix (ECM)-related, whereas ECM-receptor interactions and the transforming growth factor (TGF)-β signalling pathway were also found to be active. Ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, which was applied to identify the molecular compounds of Dispel-Scar Ointment (DSO), revealed 74 effective chemical components belonging to 14 types of constituents, such as flavonoids, tanshinones, salvianolic acids, glycosides, and phthalides. Furthermore, in vivo studies using rat scar models showed that the topical application of Salvia miltiorrhiza, Ligusticum chuanxiong, peach kernel, safflower, and motherwort exerted beneficial effects on fibroblasts. DSO promoted scar maturation and reduced scar areas, its efficacy being similar to that of topically applied silicone. Functional studies using immunofluorescence staining, western blotting, and quantitative real-time polymerase chain reaction demonstrated that DSO may target the TGF-β/Smad pathway to inhibit collagen synthesis and promote ECM remodelling. However, further in vitro mechanistic research and single-drug prescription studies may be required to identify the specific effective compound or active ingredient of DSO, which would provide more substantial evidence regarding the potential therapeutic value of traditional herbs in HS.
... With the development of biometric techniques, the identification of medicinal plants based on their signature components is becoming increasingly popular. Ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) offers higher resolution and sensitivity; thus, UPLC-Q-TOF-MS/MSbased metabolomics has been used to determinate the raw materials of various plants, including Salvia officinalis (Sarrou et al., 2017), Cimicifugae Rhizoma (Fan et al., 2017), Carthamus tinctorius (Yao et al., 2017), and Plantago (Yao et al., 2017). ...
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Rhizomes of the Polygonatum species are well-known in traditional Chinese medicine. The 2020 edition of Chinese Pharmacopoeia includes three different species that possess different pharmacological effects. Due to the lack of standardized discriminant compounds there has often been inadvertently incorrect prescriptions given for these medicines, resulting in serious consequences. Therefore, it is critical to accurately distinguish these herbal Polygonatum species. For this study, UPLC-Q-TOF-MS/MS based metabolomics was employed for the first time to discriminate between three Polygonatum species. Partial least squares discriminant analysis (PLS-DA) models were utilized to select the potential candidate discriminant compounds, after which MS/MS fragmentation patterns were used to identify them. Meanwhile, metabolic correlations were identified using the R language package corrplot, and the distribution of various metabolites was analyzed by box plot and the Z-score graph. As a result, we found that adenosine, sucrose, and pyroglutamic acid were suitable for the identification of different Polygonatum species. In conclusion, this study articulates how various herbal Polygonatum species might be more accurately and efficiently distinguished.
... foetida). This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. ...
... This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. ...
... This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. C. foetida has wideranging biological activities comprising like as antitumor, anti-inflammatory, antiviral, antimenopause, analgesic, antiosteoporosis, and antipyretic [88,89]. ...
Article
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Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.
... foetida). This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. ...
... This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. ...
... This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. C. foetida has wideranging biological activities comprising like as antitumor, anti-inflammatory, antiviral, antimenopause, analgesic, antiosteoporosis, and antipyretic [88,89]. ...
Article
Full-text available
Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.
... foetida). This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. ...
... This medicinal plant is a member of Ranunculaceae family and originally was found in Asian region such as China, India, and Tibet [88]. This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. ...
... This medicinal plant has been used a traditional Chinese herbal medicine globally since old times and commonly known as Shengma [88]. C. foetida is mostly used in the treatment/cure of headache, sore throat, aphtha, uterine, prolapse, archoptosis, spot poison, and nonerupting measles and many other related diseases [88,89]. C. foetida has wideranging biological activities comprising like as antitumor, anti-inflammatory, antiviral, antimenopause, analgesic, antiosteoporosis, and antipyretic [88,89]. ...
Article
Full-text available
Cancer is one of the primary causes of mortality globally, and the discovery of new anticancer drugs is the most important need in recent times. Natural products have been recognized as effective in fight against various diseases including cancer for over 50 years. Plants and microbes are the primary and potential sources of natural compounds to fight against cancer. Moreover, researches in the field of plant-based natural compounds have moved towards advanced and molecular level understandings from the last few decades, leading to the development of potent anticancer agents. Also, plants have been accepted as abundant and prosperous sources for the development of novel therapeutic agents for the management and prevention of different cancer types. The high toxicity of some cancer chemotherapy drugs, as well as their unfavorable side effects and drugs resistance, drives up the demand for natural compounds as new anticancer drugs. In this detailed evidence-based mechanistic review, facts and information about various medicinal plants, their bioactive compounds with their potent anticancer activities against different cancers have been gathered, with further approach to represent the molecular mechanism behind the anticancer activity of these plants. This review will be beneficial for investigators/scientists globally involved in the development of natural, safe, effective, and economical therapeutic agents/drugs against various cancers. This might be an important contribution in the field of drug discovery, where drugs can be used alone or in combination to increase the efficacy of newly synthesized drugs.
... Then, by comparing the retention time and the accurate relative molecular mass, the structure of the detected chemical composition is determined. In addition, we combined our laboratory's previous experience in the isolation and identification of cimicifuga and summarized the fragmentation regularities of these compounds by mass spectrometry [10,17,18]; some compounds were determined by comparison with the mass spectrometry data of the reference substance. Figure 1 shows the UHPLC-Q-TOF-MS base peak intensity chromatograms of the rhizomes and fibrous roots of C. dahurica in positive and negative electrospray (ESI) modes. ...
Article
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The cause of liver damage by using black cohosh preparation has been concerned but remains unclear. After a preliminary investigation, the black cohosh medicinal materials sold in the market were adulterated with Asian cohosh (Cimicifuga) without removing the fibrous roots. The safety of Cimicifuga rhizome and fibrous roots is unknown and has not been reported. Therefore, in this paper, the rhizome and fibrous roots of Cimicifuga dahurica (Turcz.) Maxim (C. dahurica) were completely separated, extracted with 70% ethanol, and freeze-dried to obtain crude rhizome extract (RC) and fibrous roots extract (FRC). UHPLC-Q-TOF-MS was used to identify 39 compounds in the rhizome and fibrous roots of Cimicifuga, mainly saponins and phenolic acids. In the L-02 cytotoxicity experiment, the IC50 of fibrous roots (1.26 mg/mL) was slightly lower than that of rhizomes (1.417 mg/mL). In the 90-day sub-chronic toxicity study, the FRC group significantly increased the level of white blood cells, ALP, ALT, AST, BILI and CHOL (p < 0.05); large area of granular degeneration and balloon degeneration occurred in liver tissue; and the expression of p-NF-kB in the nucleus increased in a dose-dependent manner. Overall, Fibrous roots of Cimicifuga are at risk of hepatotoxicity and should be strictly controlled and removed during the processing.
... To comprehensively investigate the chemical information, it is necessary to determine the constituents of CSF and SCSF. Nowadays, UPLC-Q-TOF-MS has been widely used to characterize the structural constituents of TCM owing to its high resolution, excellent sensitivity, reproducibility, accuracy, and capability of generating abundant fragment information [5][6][7]. us, this technology was employed to identify the constituents of CSF and SCSF. ...
Article
Full-text available
Background. Citri Sarcodactylis Fructus (CSF) is widely used as folk medicine in traditional Chinese medicine (TCM). The dried and steam-processed CSF (SCSF) has been employed for harmonizing the stomach over thousands of years under the guidelines of TCM theory. However, little is known about the differences in chemical compositions between CSF and SCSF. Moreover, the gastroprotective effects of CSF and SCSF on ethanol-induced gastric mucosal injuries in rats have yet to be investigated. Consequently, the present study aimed to investigate the chemical differences and gastroprotective effects of CSF and SCSF, providing some experimental framework for the development of CSF and SCSF. Methods. The chemical compositions of CSF and SCSF extracts were determined using an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometer (UPLC-Q-TOF-MS), and their gastroprotective effects of different doses were assessed in rats with ethanol-induced gastric injuries on the levels of oxidative stress and inflammatory cytokines. Results. A total of 42 components were identified in CSF and SCSF, and most of them were flavonoids, limonoids, coumarins, and glycosides. There were no differences in the compositions between CSF and SCSF, but the relative contents of the components were different. Among them, nine screened compounds were considered as potential discriminating markers responsible for the differences between CSF and SCSF. Besides, pretreatments with CSF and SCSF markedly improved the gastric mucosal injuries in rats for their antioxidant and anti-inflammatory properties. And SCSF exhibited a better gastroprotective effect than CSF. Conclusion. The compositions of CSF were unchanged after steam-processing, while the relative contents of their components were changed. These changes may be the major reasons for the differentiation of their efficacies. In addition, CSF and SCSF could alleviate ethanol-induced gastric mucosal injury through the enhancement of antioxidant and anti-inflammatory activities. SCSF exhibited a better gastroprotective effect than CSF, which emphasized the necessity of steam processing. 1. Introduction Citri Sarcodactylis Fructus is a qi-regulating TCM derived from the dried ripe fruit Citrus medica L. var. sarcodactylis Swingle. It is officially named as Fo Shou in China. It has been used in traditional and folk medicines for thousands of years to treat liver-qi stagnation, chest pain, stomach irritation, loss of appetite, vomiting, frequent cough, and excessive phlegm, by harmonizing stomach, relieving the depressed liver, and reducing dampness and phlegm (Chinese Pharmacopoeia, 2015). However, it has been reported that the crude CSF possesses the property of dryness, which is prone to deplete qi and injure yin as a result of long-term administration. Processing is capable of altering the chemical constituents of the Chinese medicinal material, which can change its TCM property for treating different syndromes [1]. Yet, the processing method of CSF has not been documented in the Chinese Pharmacopoeia, 2015. Lingnan region, the southernmost part of China, has formed its own unique processing technologies to characterize a wide variety of TCM decoction pieces. Steam processing is often applied on CSF to reduce its dryness in this region. According to the Specification for Processing Traditional Chinese Medicine Pieces of Guangdong Province 1984, the Lingnan characteristic processing procedure of CSF was recorded as follows: remove impurities, steam for 2-3 hours, and then dry. To inherit the tradition of the local processing technique, we selected this method to process CSF. In modern clinical practice, SCSF has been applied for the treatment of chronic superficial gastritis, gastric cancer, gastric ulcer, and gastric neurosis. Phytochemical studies have shown that flavonoids, coumarins, and limonoids are the major bioactive compounds of CSF [2]. For example, limonin (limonoid) exerted a protective effect on hepatic toxicity by attenuating inflammation and reducing oxidative stress [3]. The flavonoid hesperidin exhibited gastric healing activity in the ulcerated mucosa by alleviating oxidative damage at sites of ulceration [4]. To comprehensively investigate the chemical information, it is necessary to determine the constituents of CSF and SCSF. Nowadays, UPLC-Q-TOF-MS has been widely used to characterize the structural constituents of TCM owing to its high resolution, excellent sensitivity, reproducibility, accuracy, and capability of generating abundant fragment information [5–7]. Thus, this technology was employed to identify the constituents of CSF and SCSF. In present, little is known about the chemical differences between CSF and SCSF and their gastroprotective effects on ethanol-induced gastric mucosal injuries in rats. Therefore, the aims of this study were to distinguish the chemical variations between CSF and SCSF by UPLC-Q-TOF-MS coupled with multivariate statistical analysis. Besides, the gastroprotective efficacies of CSF and SCSF in rats with ethanol-induced gastric mucosal injury were investigated by assessing the levels of oxidative stress and inflammatory cytokines. And these will provide some experimental references for the development of CSF and SCSF. 2. Materials and Methods 2.1. Chemicals and Reagents Reference standards, hesperidin, diosmin, and bergapten with purities greater than 98%, were obtained from National Institute for Food and Drug Control (Beijing, China). Ethanol was supplied by Damao Chemical Reagent Factory (Tianjin, China). High-performance liquid chromatography (HPLC) grade methanol was obtained from Merck (Darmstadt, Germany). HPLC grade formic acid was purchased from Sigma (St. Louis, USA). Ultrapure water was purified by a Milli-Q water purification system (Millipore, MA, USA). Lansoprazole (LSZ) tablets and Sanjiu Weitai granules (SWG) were purchased from Hunan Warrant Pharmaceutical Co., Ltd. (Hunan, China) and China Resources Sanjiu Medical and Pharmaceutical Co., Ltd. (Guangzhou, China), respectively. Glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were supplied by Nanjing Jiancheng Bioengineering Co., Ltd. (Nanjing, China). Tumor necrosis factor-α (TNF-α), interleukin-2 (IL-2), interleukin-6 (IL-6), and interleukin-10 (IL-10) enzyme-linked immunosorbent assay (ELISA) kits were obtained from MultiSciences (Lianke) Biotech Co., Ltd. (Hangzhou, China). Pierce™ BCA protein assay kit was purchased from Thermo Fisher Scientific Inc. (MA, USA). All other chemicals and reagents were of analytical grade. 2.2. Plant Materials and Steam Processing The details of samples are shown in Table 1. The decoction pieces of CSFs and SCSFs were obtained from Zisun Chinese Pharmaceutical Co., Ltd. (Guangzhou, China) and Lingnan Traditional Chinese Medicine Tablets Co., Ltd. (Foshan, China), which were authenticated as Citrus medica L. var. sarcodactylis Swingle by Prof. Kang Chen (College of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, China) and deposited in our group’s laboratory. For comparative analysis, 1 kg of each CSF except for No.2 was immersed in 200 mL ddH2O in a closed container until softness, and then steamed in a perforated stainless steel steam boiler for 2.5 h at normal atmosphere. After drying overnight in an oven at 60°C, SCSF was obtained. The quality controls of CSFs and SCSFs are shown in Supplementary Materials (available here). No. Origin Batch number Type 1 Zisun Chinese Pharmaceutical Co., Ltd. 171101 CSF 2 Zisun Chinese Pharmaceutical Co., Ltd. 171101 CSF and SCSF 3 Lingnan Traditional Chinese Medicine Tablets Co., Ltd. 1808001 CSF