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Peloso M, Capriotti A, Accurso D, Butovskaya E, Fedrizzi G, Caprai E. UPLC-MS/MS Analysis of Hydroxyanthracene Derivatives in Botanical Food Products and Supplements: Surveillance of the Italian Market. Foods 2025; 14:1229. [PMID: 40238473 PMCID: PMC11988599 DOI: 10.3390/foods14071229] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 03/18/2025] [Accepted: 03/28/2025] [Indexed: 04/18/2025] Open
Abstract
Hydroxyanthracene derivatives (HADs) are natural compounds that occur in several botanical species belonging to the genera Aloe L., Cassia L., Rheum L., Frangula Mill., and Rhamnus L. While they are widely used for their laxative effects, concerns persist about their potential genotoxicity and carcinogenicity. This study presents the development, validation, and application of a sensitive and rapid LC-MS/MS method to detect HAD (aloins, aloe-emodin, emodin, and danthron) levels in botanical food products and supplements. The method was validated according to criteria established by the European Union Reference Laboratory for Mycotoxins and Plant Toxins, and Regulation (EU) No 2783/2023 and was demonstrated to be fit-for-purpose. It was applied to 43 samples collected from the Italian market, including beverages, liquid and solid food supplements, herbal infusions, and jam based on aloe, senna, cassia, rhubarb, and frangula. The results revealed that 33% of the analyzed samples contained detectable HAD concentrations above the limit of quantification (LOQ = 0.5 mg/kg). The highest concentrations, up to 1352.9 mg/kg for the sum of aloin A and B, were found in solid food supplements derived from senna, cascara, rhubarb, and frangula. Aloe-emodin reached 213.4 mg/kg in a solid food supplement sample containing the same plant species, while the maximum detected concentration of emodin was 259.7 mg/kg in a senna-based supplement. No sample contained danthron. Conversely, in the majority of aloe beverage samples, HAD levels were found to be below the LOQ. In order to ensure the safety of consumers, it is essential that a more rigorous market surveillance of botanical food products is implemented, along with further toxicological studies.
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Affiliation(s)
- Mariantonietta Peloso
- National Reference Laboratory for Plant Toxins in Food, Food Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via P. Fiorini 5, 40127 Bologna, Italy; (M.P.); (A.C.); (D.A.); (G.F.)
| | - Alessandro Capriotti
- National Reference Laboratory for Plant Toxins in Food, Food Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via P. Fiorini 5, 40127 Bologna, Italy; (M.P.); (A.C.); (D.A.); (G.F.)
| | - Damiano Accurso
- National Reference Laboratory for Plant Toxins in Food, Food Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via P. Fiorini 5, 40127 Bologna, Italy; (M.P.); (A.C.); (D.A.); (G.F.)
| | - Elena Butovskaya
- Food and Feed Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via A. Bianchi 9, 25124 Brescia, Italy;
| | - Giorgio Fedrizzi
- National Reference Laboratory for Plant Toxins in Food, Food Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via P. Fiorini 5, 40127 Bologna, Italy; (M.P.); (A.C.); (D.A.); (G.F.)
| | - Elisabetta Caprai
- National Reference Laboratory for Plant Toxins in Food, Food Chemistry Department, Istituto Zooprofilattico Sperimentale della Lombardia e dell’Emilia Romagna “Bruno Ubertini” (IZSLER), Via P. Fiorini 5, 40127 Bologna, Italy; (M.P.); (A.C.); (D.A.); (G.F.)
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Malysheva SV, Guillaume B, Vanhee C, Masquelier J. Determination of 16 Hydroxyanthracene Derivatives in Food Supplements Using LC-MS/MS: Method Development and Application. Toxins (Basel) 2024; 16:505. [PMID: 39728763 PMCID: PMC11728519 DOI: 10.3390/toxins16120505] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2024] [Revised: 11/13/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
Hydroxyanthracene derivatives (HADs) are plant substances produced by a variety of plant species, including different Aloe, Rheum, and Rhamnus species and Cassia senna. These plants are often used in food supplements to improve bowel function. However, recently, the European Commission prohibited a number of HADs due to toxicological concerns. These HADs included aloin (aloin A and aloin B), aloe-emodin, emodin, and danthron. Most of the currently available analytical methods are restricted to the analysis of only these compounds and do not include other HADs. In this view, a multi-analyte method could be useful for both regulatory analysis and dietary intake studies. To this end, such a method, employing liquid chromatography-tandem mass spectrometry and targeting 16 different HADs, was developed and validated in this study. Limits of quantification were in the range from 0.025 mg kg-1 to 1 mg kg-1. The recovery of the method was within the acceptable range of 80% to 120%, with the exception of physcion. Repeatability varied from 0.5% to 11.6%, and the range for within-laboratory reproducibility was from 3.4% to 16.3%. The expanded measurement uncertainty was below 50% for all HADs. Subsequently, 24 commercial samples of food supplements and herbal infusions sourced in Belgium were analyzed. The results indicated that although the industry put a great effort into minimizing the amount of aloin and danthron present in food supplements, more than half of the products still exceeded the maximum tolerated levels suggested for aloe-emodin and emodin.
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Affiliation(s)
- Svetlana V. Malysheva
- Toxins, Organic Contaminants and Additives, Physical and Chemical Health Risks, Sciensano, Leuvensesteenweg 17, 3080 Tervuren, Belgium; (B.G.); (J.M.)
| | - Benoît Guillaume
- Toxins, Organic Contaminants and Additives, Physical and Chemical Health Risks, Sciensano, Leuvensesteenweg 17, 3080 Tervuren, Belgium; (B.G.); (J.M.)
| | - Céline Vanhee
- Medicines and Health Products, Physical and Chemical Health Risks, Sciensano, Juliette Wytsmanstraat 14, 1050 Brussels, Belgium;
| | - Julien Masquelier
- Toxins, Organic Contaminants and Additives, Physical and Chemical Health Risks, Sciensano, Leuvensesteenweg 17, 3080 Tervuren, Belgium; (B.G.); (J.M.)
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Alqarni MH, Alam P, Shakeel F, Alam A, Salkini MA, Muharram MM. Simultaneous Estimation of Rhein and Aloe-Emodin in Traditional and Ultrasound-Based Extracts of Rheum palmatum L. (Rhubarb) Using Sustainable Reverse-Phase and Conventional Normal-Phase HPTLC Methods. AGRONOMY 2022; 12:1295. [DOI: 10.3390/agronomy12061295] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/22/2023]
Abstract
The greenness indices of literature analytical procedures for the simultaneous measurement of rhein and aloe-emodin have not been determined. As a consequence, the first goal of this study was to design and validate a sensitive and sustainable reverse-phase high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of rhein and aloe-emodin in a traditional extract (TE) and ultrasound-based extract (UBE) of commercial Rhubarb and Rhubarb plant extracts in comparison to the conventional normal-phase HPTLC method. The second goal was to determine the greenness indices for both methods using the AGREE approach. For the sustainable reverse-phase HPTLC approach, the method was linear in the 50–1000 ng/spot range for rhein and 25–1000 ng/spot range for aloe-emodin. However, for the conventional normal-phase HPTLC approach, the method was linear in the 50–600 ng/spot range for rhein and 100–600 ng/spot range for aloe-emodin. The limit of detection (LOD) for rhein and aloe-emodin was 16.81 ng/spot and 8.49 ng/spot, respectively, using the sustainable analytical method. However, the LOD for rhein and aloe-emodin was 18.53 ng/spot and 39.42 ng/spot, respectively, using the conventional analytical method. For the simultaneous determination of rhein and aloe-emodin, the sustainable analytical method was more sensitive, accurate, precise, and robust than the conventional analytical method. The amount of rhein and aloe-emodin was higher in the UBE of commercial Rhubarb and Rhubarb plant extract over their TE. For the simultaneous quantification of rhein and aloe-emodin in the TE and UBE of marketed Rhubarb and Rhubarb plant extract, the sustainable analytical method was superior to the conventional analytical method. The AGREE index for the sustainable reverse-phase and conventional normal-phase HPTLC methods was determined to be 0.78 and 0.49, respectively, indicating an excellent greenness profile of the sustainable reverse-phase HPTLC method over the conventional normal-phase HPTLC approach. The sustainable analytical method was found to be superior to the conventional analytical method based on these results.
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Affiliation(s)
- Mohammed H. Alqarni
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Prawez Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Faiyaz Shakeel
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Aftab Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Mohammad A. Salkini
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Magdy M. Muharram
- Department of Microbiology, College of Science, Al-Azhar University, Nasr City, Cairo 11884, Egypt
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Neural Network-Based Study about Correlation Model between TCM Constitution and Physical Examination Indexes Based on 950 Physical Examinees. JOURNAL OF HEALTHCARE ENGINEERING 2020; 2020:8812678. [PMID: 32952990 PMCID: PMC7481996 DOI: 10.1155/2020/8812678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/26/2020] [Accepted: 08/12/2020] [Indexed: 11/18/2022]
Abstract
Purpose To establish the correlation model between Traditional Chinese Medicine (TCM) constitution and physical examination indexes by backpropagation neural network (BPNN) technology. A new method for the identification of TCM constitution in clinics is proposed, which is trying to solve the problem like shortage of TCM doctor, complicated process, low efficiency, and unfavorable application in the current TCM constitution identification methods. Methods The corresponding effective samples were formed by sorting out and classifying the original data which were collected from physical examination indexes and TCM constitution types of 950 physical examinees, who were examined at the affiliated hospital of Chengdu University of TCM. The BPNN algorithm was implemented using the C# programming language and Google's AI library. Then, the training group and the test (validation) group of the effective samples were, respectively, input into the algorithm, to complete the construction and validation of the target model. Results For all the correlation models built in this paper, the accuracy of the training group and the test group of entire physical examination indexes-constitutional-type network model, respectively, was 88% and 53%, and the error was 0.001. For the other network models, the accuracy of the learning group and the test group and error, respectively, was as follows: liver function (31%, 42%, and 11.7), renal function (41%, 38%, and 6.7), blood routine (56%, 42%, and 2.4), and urine routine (60%, 40%, and 2.6). Conclusions The more the physical examination indexes are used in training, the more accurate the network model is established to predict TCM constitution. The sample data used in this paper showed that there was a relatively strong correlation between TCM constitution and physical examination indexes. Construction of the correlation model between physical examination indexes and TCM constitution is a kind of study for the integration of Chinese and Western medicine, which provides a new approach for the identification of TCM constitution, and it may be expected to avoid the existing problem of TCM constitution identification at present.
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Yao JQ, Zhu L, Miao YF, Zhu L, Chen H, Yuan L, Hu J, Yi XL, Wu QT, Yang XJ, Wan MH, Tang WF. Optimal dosing time of Dachengqi decoction for protection of extrapancreatic organs in rats with experimental acute pancreatitis. World J Gastroenterol 2020; 26:3056-3075. [PMID: 32587448 PMCID: PMC7304110 DOI: 10.3748/wjg.v26.i22.3056] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/26/2020] [Accepted: 05/12/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Acute pancreatitis (AP) is a pancreatic inflammatory disorder that is commonly complicated by extrapancreatic organ dysfunction. Dachengqi decoction (DCQD) has a potential role in protecting the extrapancreatic organs, but the optimal oral administration time remains unclear.
AIM To screen the appropriate oral administration time of DCQD for the protection of extrapancreatic organs based on the pharmacokinetics and pharmacodynamics of AP rats.
METHODS This study consisted of two parts. In the first part, 24 rats were divided into a sham-operated group and three model groups. The four groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 4 h, 12 h, and 24 h postoperatively, respectively. Tail vein blood was taken at nine time points after administration, and then the rats were euthanized and the extrapancreatic organ tissues were immediately collected. Finally, the concentrations of the major DCQD components in all samples were detected. In the second part, 84 rats were divided into a sham-operated group, as well as 4 h, 12 h, and 24 h treatment groups and corresponding control groups (4 h, 12 h, and 24 h control groups). Rats in the treatment groups were intragastrically administered with DCQD (10 g/kg) at 4 h, 12 h, and 24 h postoperatively, respectively, and rats in the control groups were administered with normal saline at the same time points. Then, six rats from each group were euthanized at 4 h and 24 h after administration. Serum amylase and inflammatory mediators, and pathological scores of extrapancreatic organ tissues were evaluated.
RESULTS For part one, the pharmacokinetic parameters (C max, T max, T 1/2, and AUC 0 → t) of the major DCQD components and the tissue distribution of most DCQD components were better when administering DCQD at the later (12 h and 24 h) time points. For part two, delayed administration of DCQD resulted in lower IL-6 and amylase levels and relatively higher IL-10 levels, and pathological injury of extrapancreatic organ tissues was slightly less at 4 h after administration, while the results were similar between the treatment and corresponding control groups at 24 h after administration.
CONCLUSION Delayed administration of DCQD might reduce pancreatic exocrine secretions and ameliorate pathological injury in the extrapancreatic organs of AP rats, demonstrating that the late time is the optimal dosing time.
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Affiliation(s)
- Jia-Qi Yao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lin Zhu
- Digestive System Department, Sichuan Integrative Medicine Hospital, Chengdu 610041, Sichuan Province, China
| | - Yi-Fan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jing Hu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xiao-Lin Yi
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Qiu-Ting Wu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Xi-Jing Yang
- Animal Experiment Center, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Yuan L, Zhu L, Zhang Y, Chen H, Kang H, Li J, Zhao X, Wan M, Miao Y, Tang W. Effect of Da-Cheng-Qi decoction for treatment of acute kidney injury in rats with severe acute pancreatitis. Chin Med 2018; 13:38. [PMID: 30013616 PMCID: PMC6045888 DOI: 10.1186/s13020-018-0195-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2018] [Accepted: 07/09/2018] [Indexed: 02/05/2023] Open
Abstract
Background The traditional Chinese formula Da-Cheng-Qi-decoction (DCQD) has been used to treat acute pancreatitis for decades. DCQD could ameliorate the disease severity and the complications of organ injuries, including those of the liver and lungs. However, the pharmacological effects in the kidney, a target organ, are still unclear. This study aimed to investigate the herbal tissue pharmacology of DCQD for acute kidney injury (AKI) in rats with severe acute pancreatitis (SAP). Methods Rats were randomly divided into the sham-operation group (SG), the model group (MG) and the low-, medium- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Sodium taurocholate (3.5%) was retrogradely perfused into the biliopancreatic duct to establish the model of SAP in rats. Different doses of DCQD were administered to the treatment groups 2 h after the induction of SAP. The major components of DCQD in kidney tissues were detected by HPLC–MS/MS. Inflammatory mediators in the kidney tissues, as well as serum creatinine (Scr), blood urea nitrogen (BUN) and pathologic scores, were also evaluated. Results Ten components of DCQD were detected in the kidneys of the treatment groups, and their concentrations increased dose-dependently. Compared with the SG, the levels of inflammatory mediators, Scr, BUN and pathological scores in the MG were obviously increased (p < 0.05). The high dose of DCQD showed a maximal effect in downregulating the pro-inflammatory mediators interleukin-6 (IL)-6 and tumour necrosis factor-α (TNF-α), upregulating anti-inflammatory mediators IL-4 and IL-10 in the kidney and alleviating the pathological damages. DCQD decreased the pancreas and kidney pathological scores of rats with SAP, especially in the HDG (p < 0.05). Compared with the MG, the level of Scr in the HDG was significantly decreased (p < 0.05). Conclusions DCQD ameliorated AKI in rats with SAP via regulating the inflammatory response, which might be closely related to the distribution of its components in the kidney. Electronic supplementary material The online version of this article (10.1186/s13020-018-0195-8) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ling Yuan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Yumei Zhang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Hongxin Kang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Juan Li
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Xianlin Zhao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Meihua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Yifan Miao
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
| | - Wenfu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu, 610041 Sichuan People's Republic of China
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Zhang YM, Zhu L, Zhao XL, Chen H, Kang HX, Zhao JL, Wan MH, Li J, Zhu L, Tang WF. Optimal timing for the oral administration of Da-Cheng-Qi decoction based on the pharmacokinetic and pharmacodynamic targeting of the pancreas in rats with acute pancreatitis. World J Gastroenterol 2017; 23:7098-7109. [PMID: 29093618 PMCID: PMC5656457 DOI: 10.3748/wjg.v23.i39.7098] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Revised: 08/27/2017] [Accepted: 09/13/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To identify the optimal oral dosing time of Da-Cheng-Qi decoction (DCQD) in rats with acute pancreatitis (AP) based on the pharmacokinetic and pharmacodynamic parameters.
METHODS First, 24 male Sprague-Dawley rats were divided into a sham-operated group [NG(a)] and three model groups [4hG(a), 12hG(a) and 24hG(a)]. The NG(a) and model groups were administered DCQD (10 g/kg.BW) intragastrically at 4 h, 4 h, 12 h and 24 h, respectively, after AP models induced by 3% sodium taurocholate. Plasma samples were collected from the tails at 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, 8 h, 12 h and 24 h after a single dosing with DCQD. Plasma and pancreatic tissue concentrations of the major components of DCQD were determined by high-performance liquid chromatography tandem mass spectroscopy. The pharmacokinetic parameters and serum amylase were detected and compared. Second, rats were divided into a sham-operated group [NG(b)] and three treatment groups [4hG(b), 12hG(b) and 24hG(b)] with three corresponding control groups [MG(b)s]. Blood and pancreatic tissues were collected 24 h after a single dosing with DCQD. Serum amylase, inflammatory cytokines and pathological scores of pancreatic tissues were detected and compared.
RESULTS The concentrations of emodin, naringin, honokiol, naringenin, aloe-emodin, chrysophanol and rheochrysidin in the 12hG(a) group were higher than those in the 4hG(a) group in the pancreatic tissues (P < 0.05). The area under the plasma concentration-time curve from time 0 to the time of the last measurable concentration values (AUC0→t) for rhein, chrysophanol, magnolol and naringin in the 12hG(a) group were larger than those in the 4hG(a) or 24hG(a) groups. The 12hG(a) group had a higher Cmax than the other two model groups. The IL-10 levels in the 12hG(b) and 24hG(b) groups were higher than in the MG(b)s (96.55 ± 7.84 vs 77.46 ± 7.42, 251.22 ± 16.15 vs 99.72 ± 4.7 respectively, P < 0.05), while in the 24hG(b) group, the IL-10 level was higher than in the other two treatment groups (251.22 ± 16.15 vs 154.41 ± 12.09/96.55 ± 7.84, P < 0.05). The IL-6 levels displayed a decrease in the 4hG(b) and 12hG(b) groups compared to the MG(b)s (89.99 ± 4.61 vs 147.91 ± 4.36, 90.82 ± 5.34 vs 171.44 ± 13.43, P < 0.05).
CONCLUSION Late-time dosing may have higher concentrations of the most major components of DCQD, with better pharmacokinetics and pharmacodynamics of anti-inflammation than early-time dosing, which showed the late time to be the optimal dosing time of DCQD for AP.
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Affiliation(s)
- Yu-Mei Zhang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lin Zhu
- Digestive System Department, Sichuan Integrative Medicine Hospital, Chengdu 610041, Sichuan Province, China
| | - Xian-Lin Zhao
- Department of Integrative Medicine, Chengdu Integrated TCM and Western Medicine Hospital, Chengdu 610016, Sichuan Province, China
| | - Huan Chen
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Hong-Xin Kang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Jian-Lei Zhao
- Department of Pharmacology, School of Preclinical and Forensic Medicine, West China Medical Center, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Mei-Hua Wan
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Juan Li
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Lv Zhu
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
| | - Wen-Fu Tang
- Department of Integrative Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Zhang YM, Ren HY, Zhao XL, Li J, Li JY, Wu FS, Su H, Tang WF. Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis. World J Gastroenterol 2017; 23:1367-1374. [PMID: 28293083 PMCID: PMC5330821 DOI: 10.3748/wjg.v23.i8.1367] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Revised: 11/06/2016] [Accepted: 01/11/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.
METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.
RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG.
CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.
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Formula Compatibility Identification of Dachengqi Decoction Based on the Effects of Absorbed Components in Cerulein-Injured Pancreatic AR42J Cells. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2016; 2016:3198549. [PMID: 27123032 PMCID: PMC4830714 DOI: 10.1155/2016/3198549] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2015] [Revised: 01/19/2016] [Accepted: 01/28/2016] [Indexed: 02/05/2023]
Abstract
Objective. To identify the herbal formula compatibility law based on the effects of the absorbed components from DCQD on the cerulein-injured AR42J cells. Methods. AR42J cells were pretreated for 30 min with or without the different concentrations of the absorbed components from DCQD individually or in combination or DCQD and coincubated with cerulein (10 nM) for a further 24 h. Cell viability, lactate dehydrogenase (LDH) release, and the levels of apoptosis and necrosis were measured. Results. Compared to DCQD, the individual or combination components partially protected cerulein-injured AR42J cells by increasing cell viability, reducing LDH release, and promoting apoptosis. Rhein, naringin, and honokiol were the main absorbed components from DCQD in cerulein-induced pancreatitis. Moreover, rhein in combination with naringin and honokiol had synergistic effects in protecting cerulein-injured AR42J cells and was better than the individual or the pairwise combination of the three components. Conclusions. The ten effective components from DCQD may elicit similar protective effects as DCQD on cerulein-induced pancreatitis. The principle of the formula compatibility of DCQD may be identified based on the effects of its absorbed components in cerulein-injured AR42J cells.
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Ren YY, Gong HL, Tang WF, Wan MF, Huang X. [Effects of ranitidine on pharmacokinetics of rhein from Dachengqi Decoction in rats after oral administration]. ACTA ACUST UNITED AC 2016; 7:868-72. [PMID: 19747444 DOI: 10.3736/jcim20090913] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
OBJECTIVE To explore the effects of ranitidine on pharmacokinetics of rhein in rats after oral administration of Dachengqi Decoction (DCQD), a compound traditional Chinese herbal medicine. METHODS Twelve male Sprague-Dawley rats were divided into DCQD group and DCQD plus ranitidine group, and were orally administered with DCQD at a dose of 10 g/kg or DCQD (10 g/kg) combined with ranitidine (150 mg/kg), respectively. Blood samples were gathered after a series of time intervals. Metabolism of rhein was determined with a reversed-phase high-performance liquid chromatography with internal standard of 1, 8-dihydroxyanthraquinone and the data were analyzed with DAS 2.1 program. The pharmacokinetic parameters were compared between the two groups. RESULTS The pharmacokinetic parameters of rhein in the DCQD group, including peak concentration (C(max)), area under the plasma concentration-time curve (AUC), distribution phase half-life (t(1/2alpha)), elimination rate constant (K(10)) and central to peripheral transfer rate constant (K(12)), were significantly different to those in the DCQD plus ranitidine group (P<0.05, P<0.01). There were no significant differences in the other parameters between the two groups. CONCLUSION Ranitidine can influence the pharmacokinetics of rhein in rats after oral administration of DCQD.
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Affiliation(s)
- Yan-yi Ren
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China
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Wang J, Chen G, Gong H, Huang W, Long D, Tang W. Amelioration of experimental acute pancreatitis with Dachengqi Decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell. PLoS One 2012; 7:e40160. [PMID: 22768339 PMCID: PMC3388070 DOI: 10.1371/journal.pone.0040160] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2012] [Accepted: 06/01/2012] [Indexed: 02/05/2023] Open
Abstract
Severity of acute pancreatitis contributes to the modality of cell death. Pervious studies have demonstrated that the herb medicine formula “Dachengqi Decoction” (DCQD) could ameliorate the severity of acute pancreatitis. However, the biological mechanisms governing its action of most remain unclear. The role of apoptosis/necrosis switch within acute pancreatitis has attracted much interest, because the induction of apoptosis within injured cells might suppress inflammation and ameliorate the disease. In this study, we used cerulein (10−8 M)-stimulated AR42J cells as an in vitro model of acute pancreatitis and retrograde perfusion into the biliopancreatic duct of 3.5% sodium taurocholate as an in vivo rat model. After the treatment of DCQD, cell viability, levels of apoptosis and necrosis, reactive oxygen species positive cells, serum amylase, concentration of nitric oxide and inducible nitric oxide syntheses, pancreatic tissue pathological score and inflammatory cell infiltration were tested. Pretreatment with DCQD increased cell viability, induced apoptosis, decreased necrosis and reduced the severity of pancreatitis tissue. Moreover, treatment with DCQD reduced the generation of reactive oxygen species in AR42J cells but increased the concentration of nitric oxide of pancreatitis tissues. Therefore, the regulation of apoptosis/necrosis switch by DCQD might contribute to ameliorating the pancreatic inflammation and pathological damage. Further, the different effect on reactive oxygen species and nitric oxide may play an important role in DCQD-regulated apoptosis/necrosis switch in acute pancreatitis.
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Affiliation(s)
- Jia Wang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Guangyuan Chen
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Hanlin Gong
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
| | - Wei Huang
- Physiological Laboratory, University of Liverpool, Liverpool, United Kingdom
| | - Dan Long
- Department of Laboratory of Transplant Engineering and Immunology, West China Hospital, Sichuan University, Chengdu, PR China
| | - Wenfu Tang
- Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, PR China
- * E-mail:
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Rokaya MB, Maršík P, Münzbergová Z. Active constituents in Rheum acuminatum and Rheum australe (Polygonaceae) roots: A variation between cultivated and naturally growing plants. BIOCHEM SYST ECOL 2012. [DOI: 10.1016/j.bse.2011.11.004] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
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13
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Simultaneous determination of six active components in traditional herbal medicine 'Oyaksungisan' by HPLC-DAD. J Nat Med 2012; 66:510-5. [PMID: 22359188 DOI: 10.1007/s11418-011-0617-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2011] [Accepted: 12/06/2011] [Indexed: 10/28/2022]
Abstract
In this study, an effective high performance liquid chromatography-diode array detector (HPLC-DAD) method was established for simultaneous determination of six marker compounds, ephedrine hydrochloride, 6-gingerol, glycyrrhizin, hesperidin, imperatorin and ferulic acid, in a Korean traditional prescription, Oyaksungisan, which is used for hemiplegia, arthralgia and paralysis. The six marker compounds of Oyaksungisan were separated on a LUNA C18 column (S-5 μm, 4.6 mm I.D. × 250 mm) at a column temperature of 35°C. The gradient elution was composed of water with 0.1% trifluoroacetic acid and methanol. The detection UV wavelengths were set at 207, 250, 280 and 320 nm. Calibration curves for the six compounds showed good linear regressions (R (2) > 0.9999). The limits of detection and limits of quantification were within the ranges 0.003-0.01 and 0.01-0.04 μg/ml, respectively. The relative standard deviation (RSD) values of intra- and inter-day testing were within the ranges 0.10-1.82 and 0.04-1.59%, respectively. The results of the recovery test were 95.05-104.27% with a RSD value of 0.11-1.85%. In conclusion, the simultaneous determination method developed was useful in the quality evaluation of Oyaksungisan.
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Higashi Y, Liu J, Fujii Y. HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED WITH FLUORESCENCE DETECTION FOR SIMULTANEOUS DETERMINATION OF HONOKIOL AND MAGNOLOL IN HANGE-KOBOKU-TO DRIED EXTRACT GRANULES. J LIQ CHROMATOGR R T 2012. [DOI: 10.1080/10826076.2011.601486] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Affiliation(s)
- Yasuhiko Higashi
- a Faculty of Pharmaceutical Sciences, Department of Analytical Chemistry , Hokuriku University , Kanazawa , Japan
| | - Jie Liu
- a Faculty of Pharmaceutical Sciences, Department of Analytical Chemistry , Hokuriku University , Kanazawa , Japan
| | - Youichi Fujii
- a Faculty of Pharmaceutical Sciences, Department of Analytical Chemistry , Hokuriku University , Kanazawa , Japan
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Lin JW, Chen JT, Hong CY, Lin YL, Wang KT, Yao CJ, Lai GM, Chen RM. Honokiol traverses the blood-brain barrier and induces apoptosis of neuroblastoma cells via an intrinsic bax-mitochondrion-cytochrome c-caspase protease pathway. Neuro Oncol 2012; 14:302-14. [PMID: 22259050 DOI: 10.1093/neuonc/nor217] [Citation(s) in RCA: 100] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Neuroblastomas, an embryonic cancer of the sympathetic nervous system, often occur in young children. Honokiol, a small-molecule polyphenol, has multiple therapeutic effects and pharmacological activities. This study was designed to evaluate whether honokiol could pass through the blood-brain barrier (BBB) and induce death of neuroblastoma cells and its possible mechanisms. Primary cerebral endothelial cells (CECs) prepared from mouse brain capillaries were cultured at a high density for 4 days, and these cells formed compact morphologies and expressed the ZO-1 tight-junction protein. A permeability assay showed that the CEC-constructed barrier obstructed the passing of FITC-dextran. Analyses by high-performance liquid chromatography and the UV spectrum revealed that honokiol could traverse the CEC-built junction barrier and the BBB of ICR mice. Exposure of neuroblastoma neuro-2a cells and NB41A3 cells to honokiolinduced cell shrinkage and decreased cell viability. In parallel, honokiol selectively induced DNA fragmentation and cell apoptosis rather than cell necrosis. Sequential treatment of neuro-2a cells with honokiol increased the expression of the proapoptotic Bax protein and its translocation from the cytoplasm to mitochondria. Honokiol successively decreased the mitochondrial membrane potential but increased the release of cytochrome c from mitochondria. Consequently, honokiol induced cascade activation of caspases-9, -3, and -6. In comparison, reducing caspase-6 activity by Z-VEID-FMK, an inhibitor of caspase-6, simultaneously attenuated honokiol-induced DNA fragmentation and cell apoptosis. Taken together, this study showed that honokiol can pass through the BBB and induce apoptotic insults to neuroblastoma cells through a Bax-mitochondrion-cytochrome c-caspase protease pathway. Therefore, honokiol may be a potential candidate drug for treating brain tumors.
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Affiliation(s)
- Jia-Wei Lin
- Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, 250 Wu-Hsing St, Taipei 110, Taiwan
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Cardile V, Frasca G, Rizza L, Rapisarda P, Bonina F. Antiinflammatory effects of a red orange extract in human keratinocytes treated with interferon-gamma and histamine. Phytother Res 2010; 24:414-418. [PMID: 19655299 DOI: 10.1002/ptr.2973] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Red oranges are an important component of the so-called Mediterranean diet and they have been used by traditional medicine for their health protective properties, particularly to heal sore throat and cough, suggesting an interesting antiinflammatory activity. The purpose of this study was to evaluate the antiinflammatory activity of a red orange (Citrus sinensis varieties: Moro, Tarocco, Sanguinello) complex (ROC), characterized by high levels of anthocyanins, flavanones, hydroxycinnamic acids and ascorbic acid, on the human keratinocyte line NCTC 2544 exposed to interferon-gamma (IFN-gamma) and histamine. The expression of immunomodulatory membrane molecules such as inter-cellular adhesion molecule-1 (ICAM-1) by Western blot analysis, and the release of chemokines such as monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) through ELISA kits, were determined. ICAM-1 modulates the permanence and activation of T lymphocytes in the epidermis. MCP-1 is a specific chemoattractant for monocytes and dendritic cells. IL-8 is important for the recruitment of both neutrophils and T lymphocytes. Addition of ROC at different concentrations together with IFN-gamma and histamine induced a dose-dependent inhibition of ICAM-1 expression and MCP-1 and IL-8 release. ROC shows interesting antiinflammatory properties in human keratinocyte cells NCTC 2544. This natural complex could have a topical employment and mitigate the consequences of some skin pathologies.
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Affiliation(s)
- Venera Cardile
- Department of Physiological Sciences, University of Catania, V. le A. Doria 6, 95125 Catania, Italy.
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Gong HL, Tang WF, Yu Q, Xiang J, Xia Q, Chen GY, Huang X, Liang MZ. Effect of severe acute pancreatitis on pharmacokinetics of Da-Cheng-Qi Decoction components. World J Gastroenterol 2009; 15:5992-9. [PMID: 20014465 PMCID: PMC2795188 DOI: 10.3748/wjg.15.5992] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats.
METHODS: Rats were divided into SAP group and sham-operation group as a control group (n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics.
RESULTS: Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The Cmax (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T1/2α of chrysophanol and rheochrysidin (P = 0.0467 and 0.0005, respectively) and Tmax of chrysophanol and rheochrysidin (P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group.
CONCLUSION: SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.
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Un C, Cheang L, Lei J, Leung SW, Yeung HW. Chinese Medicine (CM) matters. Chin Med 2008; 3:16. [PMID: 19040725 PMCID: PMC2607278 DOI: 10.1186/1749-8546-3-16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2008] [Accepted: 11/28/2008] [Indexed: 11/10/2022] Open
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