Exocarpium Citri Grandis Research Articles

CgLS mediates limonene synthesis of main essential oil component in secretory cavity cells of Citrus grandis ‘Tomentosa’ fruits

d-Limonene is the predominant component of essential oil from Exocarpium Citri Grandis, known for its antibacterial, antioxidant, insecticidal, and anti-inflammatory properties. The synthesis, transport, and accumulation of d-limonene in Citrus grandis ‘Tomentosa’ fruits are regulated by limonene synthase (LS) and its associated regulatory genes. This study addresses the gap in understanding the spatiotemporal cytological changes of LS and its regulatory genes. Through cytochemical techniques, we investigated the distribution of essential oil in the plastids, endoplasmic reticulum, and vacuoles of secretory cavity cells. We identified the LS-encoding gene CgLS via transcriptomics and demonstrated in vitro that CgLS catalyzes the formation of d-limonene from geranyl diphosphate (GPP). Transient overexpression of CgLS increased monoterpene limonene accumulation, while TRV virus-induced gene silencing reduced it. CgLS expression levels and d-limonene content showed spatiotemporal consistency with fruit development, with in situ hybridization revealing predominant expression in secretory cavity cells. Immunocytochemical localization indicated that CgLS is primarily located in the endoplasmic reticulum, plastids, and vacuoles. Our findings suggest that CgLS is translated in the endoplasmic reticulum and transported to plastids and vacuoles where d-limonene synthesis occurs. This study provides comprehensive insights into the characteristics of CgLS and its role in d-limonene synthesis at the tissue, cellular, and molecular levels in C. grandis ‘Tomentosa’.

Transcriptomic and targeted metabolome analyses revealed the regulatory mechanisms of the synthesis of bioactive compounds in Citrus grandis 'tomentosa'.

Exocarpium Citri Grandis is a popular Chinese herbal medicine prepared from Citrus grandis 'tomentosa', and it is rich in several bioactive compounds, including flavonoids, coumarins, and volatile oils. However, studies are yet to elucidate the mechanisms of synthesis and regulation of these active components. Therefore, the present study examined the profiles of flavonoids and volatile oil bioactive compounds in plant petals, fruits, and tender leaves, and then performed RNA sequencing on different tissues to identify putative genes involved in the synthesis of bioactive compounds. The results show that the naringin, naringenin, and coumarin contents of the fruitlets were significantly higher than those of the tender leaves and petals, whereas the tender leaves had significantly higher levels of rhoifolin and apigenin. A total of 49 volatile oils, of which 10 were mainly found in flowers, 15 were mainly found in fruits, and 18 were mainly found in leaves, were identified. RNA sequencing identified 9,942 genes that were differentially expressed in different tissues. Further analysis showed that 20, 15, and 74 differentially expressed genes were involved in regulating flavonoid synthesis, regulating coumarin synthesis, and synthesis and regulation of terpenoids, respectively. CHI1 (Cg7g005600) and 1,2Rhat gene (Cg1g023820) may be involved in the regulation of naringin synthesis in C. grandis fruits. The HDR (Cg8g006150) gene, HMGS gene (Cg5g009630) and GGPS (Cg1g003650) may be involved in the regulation and synthesis of volatile oils in C. grandis petals. Overall, the findings of the present study enhance our understanding of the regulatory mechanisms of secondary metabolites in C. grandis, which could promote the breeding of C. grandis with desired characteristics.

Selection and evaluation of quality markers for the regulation of PXR-CYP3A4/FXR-LXRα by Exocarpium Citri Grandis for the treatment of hyperlipidaemia with dispelling blood stasis and removing phlegm

Hyperlipidaemia is described as "excessive phlegm" and "blood stasis" in the classic theory of traditional Chinese medicine. Exocarpium Citri Grandis has the effect of dispelling blood stasis and removing phlegm, which can better meet the treatment needs of this disease. However, there is still a lack of focus and depth in the study of the chemical composition of this medicine, and the correlation between the study of relevant medicinal substances and the efficacy of dispelling stasis and removing phlegm is insufficient. To address this issue, this study was carried out to validate the overall efficacy and identify and determine the chemical composition of Exocarpium Citri Grandis. The regulatory mechanism of the PXR-CYP3A4/FXR-LXRα pathway and its active ingredients were screened, and a pharmacokinetic study of active ingredients was performed. The obtained multidimensional data were statistically analysed and comprehensively evaluated. The quality marker of Exocarpium Citri Grandis in the treatment of hyperlipidaemia based on the PXR-CYP3A4/FXR-LXRα mechanism to exert the efficacy of dispelling blood stasis and removing phlegm was finally determined. Based on the above experiments, we identified 27 compounds from the ethanol extract of Exocarpium Citri Grandis. Among them, naringenin, meranzin hydrate, apigenin, caffeic acid phenethyl ester, anacardiin, hesperidin and naringin can significantly regulate all or part of the targets in the PXR-CYP3A4/FXR-LXRα pathway. It also has suitable content and pharmacokinetic characteristics in vivo. In conclusion, this study established quality markers to characterize the efficacy of Exocarpium Citri Grandis in dispelling blood stasis and removing phlegm, which provides a scientific basis for the targeted evaluation of the hypolipidaemic activity of this medicinal plant.

Systems pharmacology-based dissection of potential mechanisms of Exocarpium Citri Grandis for the treatment of chronic bronchitis

Exocarpium Citri Grandis (ECG), a precious traditional Chinese medicine (TCM), has been widely utilized to improve the symptoms of chronic bronchitis (CB) such as cough or sputum. However, its underlying pharmacological mechanisms remain unclear. To investigate the potential mechanisms of ECG for the treatment of CB, a comprehensive systems pharmacology strategy combining network pharmacology, molecular docking, molecular dynamics simulations, and molecular biology experiments in vitro was carried out. In this study, 46 potential targets of CB screened for 10 active ingredients of ECG were strongly linked to inflammatory responses, immune processes, and apoptosis. Molecular docking revealed that the active ingredients of ECG have high binding activity for MyD88, NF-κB p65, Caspase9, and Caspase3, respectively. Meanwhile, MD simulations confirmed that neohesperidin and naringenin have high stability and low binding free energy with NF-κB p65 and Caspase3 in the binding pocket. In the LPS-induced RAW264.7 cell inflammatory model, ECG markedly reduced the secretion of IL1β, IL6, TNF-α, and NO. Transcriptomics showed a total of 337 differential expression genes (DEGs) were screened after ECG treatment, of which 233 down-regulated DEGs were closely associated with the NF-κ B signaling pathway, the Toll-like receptor signaling pathway, the IL-17 signaling pathway, and the TNF signaling pathway. Further analysis results revealed that ECG significantly down-regulated the expression of TLR4, MyD88, NF-κB p65, NF-κB p-p65 (S536), p-IκBα (S36), COX2, ICAM1, and iNOS, and up-regulated the expression of IκBα, inhibited NF-κB p65 entry into the nucleus, thereby suppressing NF-κB signaling transduction. Furthermore, ECG also significantly up-regulated the expression of Bcl-2 and down-regulated the expression of Bax, Caspase3, Caspase8, and Caspase9, inhibiting apoptosis in a dose-dependent manner. Our study reveals the potential pharmacological mechanisms of ECG for the treatment of CB and provides a scientific basis for its clinical application.

Research progress on the anti-tumor effect of Naringin.

Naringin is a kind of natural dihydro flavone, which mainly exists in citrus fruits of the Rutaceae family, as well as traditional Chinese medicines such as trifoliate orange, fingered citron, exocarpium citri grandis, and rhizoma dynamite. Modern pharmacological studies have shown that Naringin has excellent anti-tumor activity. Through reviewing the relevant literature at home and abroad in recent years, we summarized the pharmacological mechanism of Naringin to play an anti-cancer role in blocking tumor cell cycle, inhibiting tumor cell proliferation, inducing tumor cell apoptosis, inhibiting tumor cell invasion and metastasis, inducing tumor cell autophagy, reversing tumor cell drug resistance and enhancing chemotherapeutic drug sensitivity, as well as anti-inflammatory to prevent canceration, alleviate Adverse drug reaction of chemotherapy, activate and strengthen immunity, It provides theoretical basis and reference basis for further exploring the anticancer potential of Naringin and its further development and utilization.

Exocarpium Citri Grandis alleviates the aggravation of NAFLD by mitigating lipid accumulation and iron metabolism disorders

Ethnopharmacological relevanceExocarpium Citri grandis (ECG, Huajuhong in Chinese), the epicarp of C. grandis ‘Tomentosa’, has been used for hundreds of years as an anti-inflammatory, expectorant, hypoglycemic, and lipid-lowering medication in China. Nevertheless, there have been few papers that have explored the mechanism behind ECG's hypolipidemic characteristics from the perspective of treating nonalcoholic fatty liver disease (NAFLD). Aim of studyThe purpose of our study was to confirm the therapeutic and preventative effects of ECG in NAFLD by regulating lipid accumulation and iron metabolism, and to explore the specific mechanism of ECG in enhancing hepatic iron transport and excretion capabilities. Study designWe constructed a NAFLD model by feeding male C57BL/6 J mice with a high-fat diet for 12 weeks. Mice were gavaged with ECG beginning in the seventh week of modeling, and three dosage gradients were established: low dose group (2.5 g/kg/d), medium dose group (5 g/kg/d) y, and high dose group (10 g/kg/d) until the end of model construction in week 12. Materials and methodsWe used network pharmacology to analyze the relationship between ECG and NAFLD. In addition, we constructed a nonalcoholic fatty liver disease model by feeding male C57BL/6 J mice a high-fat diet for 12 weeks. Finally, lipid accumulation, iron accumulation, inflammation and oxidative stress were evaluated by serological index detection, histological detection, immunofluorescent and immunohistochemical staining, and western blotting. ResultsNetwork pharmacology confirmed the treatment effect of ECG in NAFLD. Three active components of ECG, including Naringenin, Naringin and Neohesperidin, were detected by UHPLC-HRMS analysis. The results of serum TC, TG, LDL concentration, HE staining, Oil red staining and Nile red staining demonstrated that ECG could improve lipid metabolism disorders. The results of serum iron concentration, liver tissue iron concentration, iron metabolism-related proteins Ferritin light chain, Ferroportin1, Transferrin receptor, and Transferrin demonstrated that ECG improved the iron transport and storage capacities of hepatic cells. ConclusionsOur results demonstrated that ECG relieved liver injury by inhibiting lipid accumulation and iron accumulation in NAFLD.

Research Progress on Chemical Composition and Pharmacological Action of Exocarpium Citri Grandis

Exocarpium Citri Grandis is a famous genuine regional drug in Guangdong province, which contains flavonoids, volatile oils, polysaccharides, curmarins and other effective components. In vivo and in vitro experiments have proved that it has many pharmacological actions, such as expelling phlegm and relieving cough, anti-inflammation, anti-oxidation, lowering blood glucose and lipids, protecting myocardium and so on. In order to better control the quality of tangerine and explore its potential pharmacological action, this paper reviews the research progress of Exocarpium Citri Grandis from two aspects of chemical composition and pharmacological action at home and abroad in recent years, and its applications in clinic and food industry are prospected.

Sequential grade evaluation method exploration of Exocarpium Citri Grandis (Huajuhong) decoction pieces based on “network prediction → grading quantization → efficacy validation"

Ethnopharmacological relevanceExocarpium Citri Grandis (Huajuhong) is an authentic Chinese materia medica with excellent curative effects on relieving cough and reducing phlegm, which has been reputed as “Southern Ginseng” in China for a long history.Aim of the study: To establish a sequential grade evaluation method with strong operability and controllable quality for Huajuhong decoction pieces. Materials and methods(1) Indicators of ingredients and bio-effects were predicted by network pharmacology, and the potential pharmacodynamic ingredients and key targets were analyzed integrating screening results and literatures. (2) 45 batches of Huajuhong decoction pieces from different producing areas were collected and graded by original plant, planting place, and harvesting time. The chemical indicators determination of Huajuhong decoction pieces was conducted by Ultra Performance Liquid Chromatography (UPLC). (3) 112 rats with idiopathic pulmonary fibrosis (IPF) model were used to evaluated the efficacy within graded groups. Results(1) There are 22 key targets corresponding to 20 potential ingredients related to immunity and inflammation pathways for Huajuhong. Naringin and rhoifolin were chosen as the chemical indicators, and IL-6, IL-8, MCP-1, MIP-1α, TNF-α, TGF-β1 were selected as bio-indicators for different grades of Huajuhong decoction pieces. (2) The contents of the naringin and rhoifolin can reflect the quality of different grades of Huajuhong decoction pieces. (3) The efficacy of different grades of Huajuhong decoction pieces can delay the progression of IPF in varying degrees via the selected bio-indicators’ pathways. ConclusionsThis sequential grading evaluation method is an attempt to apply systems pharmacology which integrates network pharmacology, quantitative chemical and experiments on animals to the classification of TCM decoction pieces. Combining the concepts of traditional theory and modern technology to explain the complex grading mechanism of TCM decoction pieces is worth popularizing and applying.

Sequential Grade Evaluation Method Exploration of Exocarpium Citri Grandis (Huajuhong) Decoction Pieces Based on "Network Prediction → Grading Quantization → Efficacy Validation"

Sequential Grade Evaluation Method Exploration of Exocarpium Citri Grandis (Huajuhong) Decoction Pieces Based on "Network Prediction → Grading Quantization → Efficacy Validation"

The effects of Exocarpium Citri Grandis on the volatile components of Green teabased on HS-SPME-GC-MS

Aroma is an important factor in the quality of green tea. In order to explore the effect of Exocarpium Citri Grandis(ECG) on the aroma formation of green tea, the aroma components of green tea were extracted and identified by HS-SPME-GC-MS. The results showed that the main aroma components of green tea were D-Limonene (58.69%), γ-Terpinene (14.51%), Myrcene (9.82%), 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (3.98%) and caffeine (2.67%).After co-fermentation with ECG, the main aroma components of green tea were changed to D-Limonene (33.64%), 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (11.7%), γ-Terpinene (9.38%), 2-pentadecanone (8.93%) and caffeine (6.04%).The content of terpenessuch as D-Limonene decreased, while the content of aromatic components such as linalool increased, and the types of volatile components increased in green tea. Among the newly added volatile components, the higher ones were2-pentadecanone (8.93%), β-ionone (2.76%) and dihydroactinidiolide (2.17%), which can give green tea fruity, violet and coumarin aroma. This study indicated that ECG contributes to the enrichment of greentea aroma, which provides theoretical support for the development of mixed tea with unique aroma.

Optimized preparation process for naringenin and evaluation of its antioxidant and α‐glucosidase inhibitory activities

Naringenin have attracted growing attention in food and medicine fields due to significant bioactivities. This study utilized response surface methodology to identify the optimal conditions for preparing naringenin via acid hydrolysis; Antioxidant and α-glucosidase inhibitory activities of naringenin were evaluated. A 33 Box–Behnken design, with extraction time, liquid–solid ratio, and acid concentration as independent variables, was employed for optimization. Naringenin was characterized with ultra-performance liquid chromatography–mass spectrometry and nuclear magnetic resonance spectroscopy. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) scavenging activities and α-glucosidase inhibitory activity of naringenin were considered. The conversion rate of naringin reached 97.2 ± 0.28% under optimized conditions (acid concentration: 3.0% (vol/vol); liquid–solid ratio: 50 ml/g; reaction time: 5 hr). Naringenin showed good antioxidant activity against ABTS and DPPH free radicals with half-maximal effective concentration values of 0.566 ± 0.098 and 18.406 ± 0.24 mg/ml. Naringenin showed better α-glucosidase inhibitory activity than naringin and acarbose. Practical applications Exocarpium Citri Grandis is rich in naringin, and naringenin can prepared from naringin by an acid hydrolysis method. However, the research in this field is not very thorough or comprehensive. The optimization of preparation process and antioxidant and α-glucosidase inhibitory activities of naringenin were investigated in this study, providing a theoretical basis for the application of naringin in functional foods, medicines or health products.

Optimization of extraction flavonoids from Exocarpium Citri Grandis and evaluation its hypoglycemic and hypolipidemic activities

Ethnopharmacological relevanceExocarpium Citri Grandis (ECG; Huajuhong in Chinese) is a precious traditional Chinese medicine with a history of hundreds of years in China. It has been demonstrated to possess numerous pharmacological properties, including antitussive, expectorant, anti-inflammatory, hypoglycemic, and hypolipidemic. However, no in-depth report exists on the hypoglycemic and hypolipidemic properties of ECG. Aim of the studyThis study aimed to evaluate the hypoglycemic and hypolipidemic properties of ECG flavonoids extract in vitro and in vivo so as to lay the foundation for further researches in this field. Materials and methodsTotal flavonoids (TF) and naringin were separately extracted from ECG, and the components of TF were identified by HPLC-MS. The antioxidant capacities of TF and naringin were determined by 2,2,1-diphenyl-1-picrylhydrazyl (DPPH)-free radical scavenging tests, and digestive enzymes activity inhibition assays in vitro in order to evaluate their hypoglycemic properties. Furthermore, diabetic mice experiments were performed to assess the hypoglycemic and hypolipidemic properties of TF and naringin in vivo. ResultsFive compounds were identified from TF, including naringin, rhoifolin, poncirin, bergaptol, and naringenin. The half maximal inhibitory concentration (IC50) of TF and naringin to DPPH-free radicals were 0.269 and 1.946 mg/mL, respectively. TF and naringin demonstrated a certain inhibitory effect on α-glucosidase and a weaker inhibitory effect on α-amylase. The results of animal experiments showed that TF and naringin had no significant effect on the blood glucose levels, but they could lead to significant (p < 0.05 or p < 0.01) increase in the serum insulin level and high-density lipoprotein cholesterol (HDL-C) levels with concomitant reduction in the total cholesterol (TC), total triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) levels in diabetic mice. In addition, TF and naringin could reduce the liver index of diabetic mice (p < 0.01) and reduce the kidney index at low doses (p < 0.05). ConclusionsOur study revealed that the hypoglycemic and hypolipidemic activities of TF is mainly derived from naringin, and other active ingredients in TF also have the effects of alleviating oxidative stress, inhibiting digestive enzyme activity and reducing blood lipids. Our results thus provide a scientific basis for the application of ECG in antidiabetic treatment.

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Huajuhong (Exocarpium Citri grandis, ECG) is a traditional Chinese herbal medicine and has been used for the treatment of respiratory diseases for hundreds of years. Recently, ECG has been listed in a traditional Chinese medicine formula in the Guidelines for the Diagnosis and Treatment of Coronavirus Disease 2019 (sixth edition) in China. To date, the effect and mechanism of ECG against respiratory diseases have not been systematically reviewed. In this paper, the researchers summarized the effects of ECG and its pharmacologically active compound naringin in functioning as an antitussive and expectorant, improving lung function, alleviating acute lung injury, attenuating pulmonary fibrosis, and enhancing antiviral immune response, so as to provide a reference for its clinical application in the prevention and treatment of multiple respiratory diseases, including coronavirus disease 2019.

A Review on the Pharmacokinetic Properties of Naringin and Its Therapeutic Efficacies in Respiratory Diseases.

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials.

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

The potential application of the traditional Chinese herb Exocarpium Citri grandis in the prevention and treatment of COVID-19

Effects of Total Flavonoids from Exocarpium Citri Grandis on Air Pollution Particle-Induced Pulmonary Inflammation and Oxidative Stress in Mice.

Exocarpium Citri Grandis (ECG) is a famous traditional Chinese medicine, which has been commonly used to alleviate cough and phlegm for more than several hundred years, and total flavonoids are the main effective components of this medicine. This study investigated the effects of total flavonoids from ECG (TFECG) on pulmonary inflammation and oxidative stress induced by PM2.5 in mice. Model mice received an intratracheal instillation of PM2.5 (10mg/mL) once at day 0. Bronchoalveolar lavage fluid (BALF) was collected after 72 hr to measure the total number of white blood cell (WBC), neutrophils (NEUT), lymphocytes (LYMPH), and monocytes (MONO). The levels of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), interleukin-6 (IL-6), and interleukin-18 (IL-18) in BALF were quantified by using enzyme-linked immunosorbent assay kits. Lung tissues were used to determine the contents of total protein (TP), malondialdehyde (MDA), nitric oxide (NO), reduced glutathione (GSH), oxidized glutathione (GSSG) and the activities of superoxide dismutase (SOD), lactate dehydrogenase (LDH), Glutathione Peroxidase (GSH-Px), and inducible nitric oxide synthase (iNOS). We found that TFECG significantly inhibited PM2.5 -stimulated overproduction of TNF-α, IL-1β, IL-6, and IL-18 and increased the numbers of WBC, NEUT, LYMPH, and MONO in BALF. TFECG observably relieved the PM2.5 -induced increases in the contents of TP, MDA, and NO, and the activities of LDH and iNOS. TFECG also alleviated PM2.5 -induced decreases in the activities of iNOS and GSH-Px as well as GSH/GSSG ratio. The results indicate that TFECG has anti-inflammatory and antioxidant activities, which may potentially contribute to the treatment of PM2.5 -induced lung injury. PRACTICAL APPLICATION: Exocarpium Citri Grandis (ECG) is rich in flavonoids, which are beneficial to improve anti-inflammation and antioxidant capacity. We proved that total flavonoids of ECG had a positive therapeutic effect on PM2.5 -induced lung injury, which expands the potential applications of ECG in the dietary supplement industries.

Inclusion Complex of Exocarpium Citri Grandis Essential Oil with β‐Cyclodextrin: Characterization, Stability, and Antioxidant Activity

The purpose of this study was to produce and characterize an inclusion complex between β-cyclodextrin (β-CD) and Exocarpium Citri Grandis essential oil (EEO), and to evaluate its antioxidant properties. The volatile compounds of EEO were characterized by gas chromatography-mass spectrometer. A comparison of the β-CD, EEO, and the physical mixture with the inclusion complex revealed differences in their thermal stabilities and morphologies, which confirmed the formation of the β-CD-EEO inclusion complex. Complexed with β-CD, the β-CD-EEO inclusion complex showed a higher stability and antioxidant activity when compared with physical mixture and EEO. Therefore, β-CD can be used to form inclusion complexes with EEO to expand its potential applications in the food and drug industries. PRACTICAL APPLICATION: Exocarpium Citri Grandis is rich in essential oil and other ingredients. The optimized extraction, constituent composition, and encapsulation of EEO in β-CD were investigated in this study. The results showed that the encapsulation process increased the antioxidant activity and stability of EEO, which provides both fundamental and practical knowledge for the application of EEO in the food and drug industries.

UFLC-Q-TOF-MS/MS-Based Screening and Identification of Flavonoids and Derived Metabolites in Human Urine after Oral Administration of Exocarpium Citri Grandis Extract.

Exocarpium Citri grandis (ECG) is an important Traditional Chinese Medicine (TCM) for the treatment of cough and phlegm, and the flavonoids contained were considered the main effective components. To date, the systematic chemical profiling of these flavonoids and derived in vivo metabolites in human have not been well investigated. ECG was extracted using boiling water and then provided to volunteers for oral administration. Following the ingestion, urine samples were collected from volunteers over 48 h. The extract and urine samples were analyzed using ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS) system to screen and identify flavonoids and derived in vivo metabolites. A total of 18 flavonoids were identified in the ECG extract, and 20 metabolites, mainly glucuronide and sulfate conjugates, were screened in urine samples collected post consumption. The overall excretion of naringenin metabolites corresponded to 5.45% of intake and occurred mainly within 4–12 h after the ingestion. Meanwhile, another 29 phenolic catabolites were detected in urine. Obtained data revealed that flavonoids were abundant in the ECG extract, and these components underwent extensive phase II metabolism in humans. These results provided valuable information for further study of the pharmacology and mechanism of action of ECG.

Therapeutic effects of naringin in a guinea pig model of ovalbumin-induced cough-variant asthma

Naringin, a well known component isolated from Exocarpium Citri Grandis, has significant antitussive effects. Recently, Naringin exhibited novel anti-inflammatory effect in chronic inflammatory diseases. In this work, we firstly evaluated the effects of naringin on enhanced cough, airway hyper-responsiveness (AHR), and airway inflammation in an ovalbumin-induced experimental cough-variant asthma (CVA) model in guinea pigs. We investigated the effect of naringin (18.4 mg/kg, per os, single dose or consecutively) on cough to inhaled capsaicin after challenge with an aerosolized antigen in actively sensitized guinea pigs. The effect of naringin on AHR to inhaled methacholine was evaluated 24 h after cough determination. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cytology and lung histopathology. Naringin, given consecutively, significantly reduced ovalbumin-induced enhanced cough and AHR, inhibited the increases in the leukocytes, interleukin-4 (IL-4), IL-5, and IL-13 in BALF compared with the model group. Moreover, the pathologic changes in lung tissues were clearly ameliorated by naringin treatment. These results suggest that naringin may be a beneficial agent for CVA treatment.

Chromatographic Fingerprint Analysis of Exocarpium Citri Grandis by High-Performance Liquid Chromatography Coupled with Diode-Array Detector

A newly validated HPLC fingerprint method has been developed for the identification and quality assessment of Exocarpium Citri Grandis. Twenty-three batches of Exocarpium Citri Grandis collected or purchased from different localities in China were investigated. The analyses were conducted on a Diamonsil C18 column (250 mm × 4.6 mm, 5-μm particle) preceded by a Diamonsil C18 guard column (10 mm × 4.6 mm, 5-μm particle). Mobile phases were composed of 0.5 % acetic acid (A) and methanol (B), with a flow rate of 1 mL/min under a gradient elution. The wavelength was set at 254 nm. The common fingerprint profile was established with professional analytical software. Common peaks were further identified using LC-DAD-MS/MS. Chemometric methods including similarity calculation and hierarchical clustering analysis were performed to differentiate the 23 batches of Exocarpium Citri Grandis samples. Fifteen batches of samples had a high similarity (more than 0.9) and the overall 23 batches of samples were divided into two clusters. This method presented good precision, repeatability, and stability; therefore, it would be a reliable and useful approach for the quality control of Exocarpium Citri Grandis.