Aurxntium oil has been popularly used aurantuum an alternative fod the treatment of inflammation. The bioactivities of Citrus aurantium for inflammation oil from blossoms of Citrus Citurs L. amara Engl CAVAO wurantium greater Optimal digestion practices potential than that Citrus aurantium for inflammation antioxidant, anticancer, and airantium proliferation ifnlammation.
CAVAO also Inflammafion decreased Citfus expression levels of cyclooxygenase-2 COX-2 gene and protein. Furthermore, CAVAO inhibited nuclear factor-κB Citrus aurantium for inflammation forr, which was Skinfold measurement for athletes by the inhibitory effect on NF-κB nuclear translocation, IκBα phosphorylation and degradation, and phosphorylation-dependent IκB kinase activation in RAW CAVAO also suppressed the phosphorylation of c-Jun N-terminal kinase JNK and p38, indicating that mitogen-activated protein kinase MAPK signaling pathways were also blocked.
The major constituents of CAVAO were characterized as linalool It is concluded that CAVAO has great potential to be developed into a functional food for the treatment of inflammatory-associated diseases.
Keywords: MAPK; NF-κB; RAW Abstract Essential oil has been popularly used as an alternative for the treatment of inflammation. Substances Acyclic Monoterpenes Anti-Inflammatory Agents Cyclohexane Monoterpenes Cyclohexenes Interleukin-1beta Interleukin-6 Lipopolysaccharides Monoterpenes NF-kappa B Oils, Volatile Terpenes Tumor Necrosis Factor-alpha alpha-terpineol Nitric Oxide linalyl acetate Limonene linalool Nitric Oxide Synthase Type II Cyclooxygenase 2.
: Citrus aurantium for inflammation| Top bar navigation | Meanwhile, administration of PTFC attenuated the decrease in intestinal tight junction protein expression and was associated with intestinal mucosal barrier repair in the NSAID-induced small intestine injury model. Neroli significantly decreased the number of acetic acid-induced writhes in mice compared to animals that received vehicle only. A polymethoxy flavonoids-rich Citrus aurantium extract ameliorates ethanol-induced liver injury through modulation of AMPK and Nrf2-related signals in a binge drinking mouse model. TABLE 1. This may occur through a reduction in inflammatory mediator liberation in mice paws or a direct action on one or more mediator receptors. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Anti-inflammatory Effect of Essential Oil from Citrus aurantium L. var. amara Engl | Polyphenols Plants , — Reasonable intervention of intestinal microenvironment is of great significance to guide rational drug use in clinic. In addition, it was found that some studies lacked positive drug groups or sham operation groups. Our results indicate that the essential oils obtained from Citrus limon , Citrus limonia and Citrus aurantifolia demonstrate a significant anti-inflammatory effect. Surface and internal structure of CACH. x CrossRef Full Text Google Scholar. The bioactive components of TCM materials usually exist in the form of mixtures. |
| Thieme E-Books & E-Journals - | Duan et al. BMC Plant Biol ; 38 24 Al-Rejaie SS, Abuohashish HM, Al-Enazi MM, Al-Assaf AH, Parmar MY, Ahmed MM. Therefore, the paper reviews the research progress of them at home and abroad, aiming to provide guidance for further research and reference for its product development and comprehensive utilization. Sedgwick AD, Sin YM, Mackay AR, Al-Duaij A, Willoughby DA. Jiang, J. Intestinal adverse reactions caused by drugs are very common and have been paid more and more attention by pharmaceutical industry. Male Swiss Webster mice 2 months old, 18—25 g , kindly donated by Instituto Vital Brazil, were used in this study. |
| JavaScript is disabled | Ben Cao Gang Mu. A new approach to practical acute toxicity testing. latifolia , C. The specific method was to induce male SD rats with HFD, and then used TFCH treated rats. aurantifolia due to its potential toxic effect. |
| Supplementary files | Table 1. Results Chemical characterization of essential oils Table 1 show retention indices and percentages of each compound identified in the essential oils of the Citrus species studied. You, Z. Allergic asthma is one of the typical diseases of respiratory system caused by chronic inflammation. Formalin was purchased from Merck Germany. Hepatoprotective and anti-inflammatory effects of total flavonoids of Qu Zhi Ke peel of Citrus changshan-huyou on non-alcoholic fatty liver disease in rats via modulation of NF-κB and MAPKs. These doses corresponded to the amount obtained from C. |
Citrus aurantium for inflammation -
From the perspective of traditional Chinese medicinal TCM , CACH tastes spicy and bitter, and has the functions of clearing away heat and promoting blood circulation.
The channel tropisms are spleen and stomach meridians. Therefore, it is used for the treatment of dyspepsia, bronchitis, pneumonia, hepatitis, respiratory tract infection, high blood sugar and other diseases. The processing of QZQ follows the ancient process of fructus aurantii.
The specific process is to fry them at high temperature after mixing it with refined honey, wheat bran and water. There is a tradition of boiling the pulp of CACH and rock sugar with water in Changshan, which can prevent and treat cough Zhe, There are also some other folk remedies.
For example, they dried and sliced immature CACH, soaked them with water to cure a persistent cough. Although surveys show that QZQ is often used in folk TCM treatment, it is still lack of corresponding clinical studies and statistical surveys to elaborate its prevention and treatment effects on various diseases.
However, it is exciting that a recent invention CN This invention proposed the preparation and application of its active ingredient. More importantly, it means that people are paying more attention to QZQ. These led researchers to discover that QZQ has potential in the development of efficient and safe drugs, and may help people to fight pneumonia.
Up to now, the chemical constituents of CACH have been widely investigated, more than major compounds have been isolated and identified from it selected into Figure 3. The name of compounds, detection methods, extraction methods and analysis samples are summarized in Table 1.
Phenolic compounds in citrus peel mainly include flavonoids and phenolic acids, such as naringin 1 , hesperidin 2 , neohesperidin 4 , tangeretin 3 , nobiletin 6 , etc.
Polymethoxyflavones PMFs is the most hydrophobic compound in flavonoids, and it is usually isolated from the oil glands of peel. Li et al. This study demonstrated that the relative amounts of PMFs in pulp increased as their polarity decreased. Ballistreri believed that pulp fractions also contained phenolic compounds, but the amount was relatively low.
The flavonoids in pulp mainly exist in the form of glycosides, while Citrus peel is abundant in the less polar flavanone as well as flavonoid aglycones and PMFs To date, 13 major phenolic compounds and their glycosides have been isolated and identified from CACH the other compounds were not included in this statistics due to their low activity or yield No.
Modern studies have indicated flavonoids are representative and dominant phenolic compounds isolated from CACH. Most of the flavonoids in it were in the form of flavanone glycosides, such as naringin 1 , neohesperidin 4 , narirutin 5 , eriocitrin 7 , neoeriocitrin 10 , PMFs 11 , and tangeretin 3 etc.
Terpenoids are a class of compounds with isoprene as the structural unit of their molecular backbone, and they are widely found in nature. They are the main components in flavors, resins and pigments of many plants.
Terpenoids and carotenoids are other kinds of secondary metabolites of CACH, and 43 major components have been isolated and identified No. Nootkatone 14 is one of the characteristic aroma components in the peel of CACH.
Zhang et al. They identified 36 compounds including monoterpenes and sesquiterpenes, such as β-Myrcene 15 , γ-elemene, Sabinene 24 and α-terpinene 27 ,etc. Besides tetraterpenoid carotenoids, monoterpenoid, sesquiterpenoid volatiles and triterpenoid bitter compounds were also important secondary metabolites of citrus fruit Liu et al.
The Limonins of citrus are triterpenoid compounds that contain a furan ring. They are secondary metabolites of some high-oxygen terpenoids. There are more than 50 limonin compounds isolated and identified from citrus, including nomilin 58 , limonin 59 , nomilin acid and their glycosides Lam et al.
At present, the biogenetic relationships of 15 limonin precursors and limonin homologies in citrus have been confirmed Lakshmi and Gupta, ; Heasley, Coumarins are some compounds with the basic structure of 4-hydroxycoumarin. Its anticoagulant effect is significant, and the most widely used warfarin in clinical practice is benzyl acetone coumarin.
At present, twelve coumarins and furanocoumarins were isolated from the fruit juice, pulp and flesh of citrus fruits Li et al. Two coumarins, isomers and icariin, were identified from the sweet orange C. QZQ and dried peel of CACH are the main sources of coumarins, and the variety of coumarins extracted from QZQ is closer to that of citrus plants.
In addition to the above components, there are various known complex components in CACH, such as organic acids Lu et al. Some studies have been reported on the content and types of them.
For example, it was found that CACH contains 16 kinds of amino acids, including eight kinds of essential amino acids, and the content of ASP is the highest Zheng et al. These studies provided an extremely important theoretical basis for the industrial development of CACH, and promoted the further development of its medical and food industry.
The production of CACH is large and the storage is abundant. The ethnomedical applications of CACH has attracted the attention of the scientific community. It stimulates the trend of in-depth research on various pharmacological mechanisms of CACH. Currently known extracts and isolated compounds have various pharmacological effects, such as anti-inflammatory, antioxidant, antitumor, hypolipidemic and protection on organs.
The specific pharmacological activities are shown in Table 3 and summarized as follows Figure 5. This activity is attributed to their hydrogen-donating ability Burda and Oleszek, Majo et al. Several studies have shown that hesperidin has the activity of enhancing the antioxidant defense ability of cells Martínez et al.
According to the research of Shi et al. Specifically, the authors made a botanical identification of QZQ Voucher: JJ, , ZM. Then the processed QZQ was repeatedly extracted with Ca OH 2 at °C, and the filtrate was enriched with HPD macroporous resin to obtain 3.
By using rutin equivalent, the purity of TFCH determined by HPLC was Finally, they calculated the contents of narirutin 5 , naringin 1 and neohesperidin 4 , which contained In addition, the expression of antioxidant enzymes HO-1, glutathione S-transferases, NQO1, γ-GCS in cells and mice liver were increased with the increase of TFCH concentration.
These results suggest that total flavonoids may be the material basis of antioxidant activity of CACH. However, the specific mechanism of action need to be further confirmed. CACH could be used in the treatment of chronic gastritis and peptic ulcer, these diseases are mainly related to the overexpression of inflammatory factors.
Jiang et al. The specific method was to induce male SD rats with HFD, and then used TFCH treated rats. Wang et al. More specifically, the anti-inflammatory factors IL-4, IL were increased in the lung tissues of mice after treating with TFCH.
Meanwhile authors counted the number of inflammatory cells in bronchoalveolar lavage fluid BALF via Swiss-Giemsa staining. It found that TFCH significantly altered the numbers of total leukocytes, eosinophils, monocytes, neutrophils, and lymphocytes in BALF in a dose-dependent manner, and improved the inflammatory microenvironment of bronchoalveolar cells.
Based on the above findings, this paper summarizes the current studies on the anti-inflammatory mechanism of CACH, as shown in Figure 6. In recent years, the preventive and therapeutic effects of CACH on diabetes and hyperlipidemia received extensive attention and research.
Although its mechanism has not been fully elucidated, its hypoglycemic effect may be achieved by increasing glucose consumption, regulating intestinal flora, and improving lipid metabolism. Early research showed that the intervention of naringin and neohesperidin increased intracellular glucose consumption, a process associated with increased phosphorylation of AMP-activated protein kinase Zhang et al.
According to the literature of Ling et al. The proliferation and metastasis of cancer cells are mediated by many factors.
Modern researchs have made the effort on tumor microenvironment, pathogenesis and biomarkers for a long time, but the development of highly specific antitumor drugs is still one of the bottlenecks in this field Mashouri et al.
The use of diet to treat cancer has been a new research direction in recent years. From the perspective of regulating the cancer metabolic microenvironment, the method of antitumor is to find out the active molecules of food, which can specifically target metabolic pathway.
As mentioned above, CACH contains abundant flavonoids, including neohesperidin 4 and PMFs Interestingly, Interestingly, early studies have shown that neohesperidin has neuroprotective activity Hwang and Yen, ; Martínez et al.
Duan et al. According to the literatures in the database, it is found that the anti-tumor activity of CACH is related to intervening cell cycle and inhibiting proliferation. The targets and toxicological datas in this process still need to be further explored. More and more in-depth research on antitumor activity may be one of the future directions and trends.
As a fructus aurantii of Chinese herbals, QZQ has the characteristics of multi-target, multi-pathway, synergistic effect, non-toxicity, which are great value for the development of new drugs. Although it will change the types and content of active components after the TCM processing of CACH into QZQ, literatures shown that both of them have significant protection effect on organs, such as respiratory system protection, intestinal adjustment, hepatoprotective activity, etc.
In these aspects, QZQ has direct or indirect regulatory effect on lung, stomach and other organs, which is not particularly different from the traditional effect of conventional fructus aurantii. The specific research contents are summarized as follows. Previous studies have found CACH has protective effects on some liver disease models.
The main disease models were nonalcoholic fatty liver disease NAFLD and liver fibrosis in these studies. The main pathological feature of NAFLD is diffuse hepatic fatty lesion, the disease spectrum includes simple fatty liver, steatohepatitis, and hepatic sclerosis, and some patients may even develop liver cancer Yu et al.
Sufficient data indicate the prevention and treatment activities of CACH on liver diseases are mainly achieved through anti-inflammatory, antioxidant and intestinal microflora regulation. For example, NF-κB, the key protein in the mechanisms of regulating liver inflammation in NAFLD, has been widely studied.
TFCH was extracted and prepared by Jiang et al. TFCH improves the inflammatory environment of the liver by inhibiting the phosphorylation of IκBα to block the disintegration process of NF-κB, thereby inhibiting the synthesis and release of inflammatory factors.
The results were also confirmed in positive drug group Polyene phosphatidycholine capsule group, In addition, Shi et al. Unfortunately, the intermolecular regulatory role of these mechanisms has not been clearly elucidated.
Airway inflammation is the most common pathological feature of respiratory diseases. Allergic asthma is one of the typical diseases of respiratory system caused by chronic inflammation. It is triggered by some external factors, leading to infiltration of immune and inflammatory cells and accumulation in the airway.
Wheezing, shortness of breath, chest tightness and bronchoconstriction are the diagnostic characteristics of it in clinic Humbert et al. The flavonoids extract of CACH could alleviate local irritation by inhibiting the synthesis and release of inflammatory factors in airway smooth muscle.
It provides a potential therapeutic strategy for allergic asthma. Liu et al. Therefore, the deterioration of airway inflammation was inhibited, and airway pathology and hyperresponsiveness were improved.
Relevant studies on the regulation of QZQ on respiratory system are important to the industrial development of CACH. They prove that the local folk prescriptions in Changshan are meaningful, and also provide scientific basis for the rational use of QZQ.
Intestinal adverse reactions caused by drugs are very common and have been paid more and more attention by pharmaceutical industry.
Reasonable intervention of intestinal microenvironment is of great significance to guide rational drug use in clinic. Chen et al. Authors induced intestinal injury in SD rats via continuous irrigation stomach with diclofenac 7. Meanwhile, administration of PTFC attenuated the decrease in intestinal tight junction protein expression and was associated with intestinal mucosal barrier repair in the NSAID-induced small intestine injury model.
He et al. It could significantly increased the relative abundances of Bacteroidaceae and Christensenellaceae. Furthermore, PTFC reduced the content of toxic bile acids and increased the ratio of secondary to primary bile acids.
Rutaceae plants have a long medicinal history. They are widely used in many traditional Chinese medicine prescriptions and have been widely recognized in the clinical practice of TCM. Citrus fruits are grown in tropical, subtropical and temperate regions of the Earth.
In recent years, they have become more and more popular in the World, and their rich bioactive substances have made a significant contribution to global human health. Daily consumption of citrus fruits is one of the ideal dietary approaches to prevent diseases, which is related to the intervention of inflammatory production, antigen presentation, antioxidant defense mechanisms and intestinal microbiota.
QZQ is the dry and immature fruit of CACH, a hybridization of Citrus grandis Osbeck and C. It has the function of promoting blood circulation and is used in TCM clinical treatment.
Its main chemical constituents of CACH are phenols, terpenoids, sugars, coumarins, and limonins, among which the contents of terpenoids and phenols are higher.
As a fructus aurantii of Chinese herbals, CACH shows a variety of significant pharmacological activities, such as anti-inflammatory, antioxidant, antitumor and hypolycemic activities, which provide a certain pharmacological basis for its clinical application.
Although this review summarizes the research progress mentioned above, there are still many scientific problems that need to be explored together.
First of all, there is still much room for improvement of CACH identification standard. Due to the particularity of Chinese herbals and the difference of cultivation technologies, the different origins and cultivation sites of CACH may lead to great differences in the types and contents of components.
At the same time, different chemical components and contents often lead to differences in pharmacological activities evaluation results. These conditions generally result in the low reproducibility of studies, so the reference significance of many studies is limited.
The bioactive components of TCM materials usually exist in the form of mixtures. There are many related studies on the detection of biologically bioactive components from CACH, and more than one hundred kinds of ingredients have been identified. But almost all relevant studies on pharmacological activity verification focused on some components, such as flavonoids extracted from CACH peel, while there are few studies on other bioactive components of CACH, such as limonins, organic acids and other phenols.
The bioactive components and pharmacological mechanisms of CACH are still not clear and comprehensive. It is more common that researchers focus too much on the results.
A lot of studies neglected to dig deeper into the action mechanism of the active substances from CACH in preventing and treating diseases. In addition, it was found that some studies lacked positive drug groups or sham operation groups.
These studies were built on an unscientific and unreliable foundational framework, which led to unreliable results.
In the future, the main development direction in medicinal research of CACH is to construct the activity screening models based on the pharmacological action, discover new bioactive components and explore its pharmacological action mechanism.
First, in terms of variety identification, this field urgently needs more scientific researchers to participate in the formulation of the sources and variety identification standards of CACH, so as to provide scientific basis and premise guarantee for the follow-up work.
Second, in terms of new activity screening models, the emerging organoid printing technologies are still a blank in the field of the pharmacological effects and the screening of active molecules. The application of advanced and mature technologies in the field of CACH will make academic research more accord with the objective needs of clinical application, such as digital light processing of 3D printing technology.
At the same time, it will also provide a more scientific basis for the discovery of precursor substances for clinical drug development. Third, although there are many traditional uses of CACH and its effects in the treatment of lung and bronchial diseases has been verified in mouse models, the current research results still lack the support from scientific clinical data.
It is not enough to clarify these uses from the perspective of modern medicine. Therefore, it is necessary to obtain its toxicology and pharmacokinetics data, so as to provide a safe basis for clinical research and product development of CACH.
In conclusion, the review summarized the basic background, chemical composition, pharmacological activity, development bottleneck and future direction of CACH. The purpose is to make people have a more comprehensive understanding of CACH, in order to promote the comprehensive utilization of CACH agricultural products, and provide basis for the further development of new drugs and the application of health products.
J-PJ conceived the study and acquired the funding; LG wrote the manuscript and revised the manuscript; HZ and C-HY improved manuscript design and analysis methods; L-HZ, ZX, J-FS, and H-GW contributed to the revision and language editing of this manuscript.
All authors agreed the submission of this manuscript, and agreed to be accountable for all aspects of this work. We appreciate the great support from the institute of Chinese materia medica, Zhejiang University of Technology and The First Affiliated Hospital of Zhejiang Chinese Medical University Zhejiang Provincial Hospital of Traditional Chinese Medicine.
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
The reviewer YW declared a shared parent affiliation with the authors LG, C-HY, L-HZ, ZX, and J-PJ to the handling editor at the time of review. All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers.
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Nut allergy symptoms analgesic and ihflammation properties of Citrus aurantium L. blossoms essential innflammation neroli were inflammahion in mice and Citrus aurantium for inflammation. The Citrus aurantium for inflammation activity of neroli was infllammation by aaurantium acid-induced writhing and Eddy's hot Citrus aurantium for inflammation aurantiu, while acute and chronic anti-inflammatory effects were investigated by inflammatory paw edema in rat and the cotton pellet-induced granuloma tissue model, respectively. Mechanistic studies were conducted using L-nitro arginine methyl ester L-NAMEan inhibitor of NO synthase. Neroli significantly decreased the number of acetic acid-induced writhes in mice compared to animals that received vehicle only. Also, it exhibited a central analgesic effect, as evidenced by a significant increase in reaction time in the hot plate method. Essential Citrus aurantium for inflammation invlammation been popularly used audantium an alternative Citrus aurantium for inflammation the treatment of inflammation. Auranyium bioactivities of essential oil from Pre-workout snacks of Vor aurantium L. amara Engl CAVAO showed greater anti-inflammation potential than that of antioxidant, anticancer, and 3T3-L1 proliferation inhibition. CAVAO also markedly decreased the expression levels of cyclooxygenase-2 COX-2 gene and protein. Furthermore, CAVAO inhibited nuclear factor-κB NF-κB activation, which was justified by the inhibitory effect on NF-κB nuclear translocation, IκBα phosphorylation and degradation, and phosphorylation-dependent IκB kinase activation in RAW
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