There are many chemical components in the volatile oil of Dictamni Cortex. The complex network relationship of "component-target-disease" can be revealed by using the network pharmacology method, and the mechanism of the efficacy of Dictamni Cortex can be revealed. In this study, we used Swiss Target Prediction database to predict the target of action, STRING database to build protein interaction network, and Cytoscape software to build "component-target-disease" network. The results showed that the antibacterial, anti-inflammatory and antiallergic effects of Dictamni Cortex were closely related to the components of thymol methyl ether, elemenol, anethole, and the related targets of each component were cross-linked to play a multi-target pharmacodynamic role. This study laid a foundation for the study of the effective substance basis and quality control evaluation of the Dictamni Cortex, and provided a scientific basis for further revealing its mechanism.
Dictamnus/chemistry* ; Drugs, Chinese Herbal/pharmacology* ; Oils, Volatile/pharmacology* ; Protein Interaction Maps ; Quality Control ; Software

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.
Chemical and Drug Induced Liver Injury ; epidemiology ; China ; Dictamnus ; chemistry ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Liver ; Retrospective Studies ; Risk Factors

Nineteen compounds, including kihadanin D (1), obacunone (2), kihadanin A (3), kihadanin B (4), kihadanin C (5), limonin (6), evodol (7), fraxinellone (8), furo[2,3-b]quinolin-4-ol (9), preskimmianine (10), ifflaiamine (11), dictamnol (12), naringenin (13), diosmetin (14), wogonin (15), scopoletin (16), cleomiscosin A (17), apocynin (18), and methyl pyroglutamate (19), were isolated from the methanol extract of the root barks of Dictamnus dasycarpus by using various column chromatographies. Their chemical structures were extensively determined on basis of UV, IR, NMR, MS, and CD spectroscopic data analyses. Among them, 1 is a new limonoid, 9 was isolated from plant kingdom for the first time, 11, 13-14 and 17-19 were obtained from the genus Dictamnnus for the first time. Cytotoxicities of compounds 1-18 were tested, and the results indicated that 1 exhibited cytotoxicities against three human cancer cell lines MDA-MB-231, A549 and HT29 with IC₅₈ values of 16.22, 21.72 and 31.06 μmol·L⁻¹, respectively.
Cell Line, Tumor ; Dictamnus ; Humans ; Molecular Structure ; Plant Bark ; Plant Extracts ; Plant Roots

The root bark of Dictamnus dasycarpus is one of common traditional Chinese medicines (TCMs). Quinoline alkaloids are one of the main active substances in this TCM and possess many biological activities including anti-titumor, anti-inflammation, anti-bacteria, anti-oxidation, and anti-platelet aggregation activities. In this study, eight quinoline alkaloids 1-8 were firstly separated from the root barks of D. dasycarpus. It was difficult to isolate more quinoline alkaloids from the remaining fraction 8 in D. dasycarpus by this conventional chemical separation, so the target analysis method combined LC-MS guided-separation of quinoline alkaloids from fraction 8 was established. MS/MS fragmentation patterns of eight quinoline alkaloids reference standard compounds 1-8 were studied by ultra-performance liquid chromatography-electrospary ionization-mass spectrometry (UPLC-ESI-MS/MS). Based on the feature fragment ion 200, the parent ion scan mode was established for the target analysis of quinoline alkaloids in fraction 8. Finally, 8-methoxyflindersine (9) and N-metilatanina (10) were discovered and isolated quickly from fraction 8 guided by LC-MS, and their structures were identified by NMR and MS. Among them, compound 10 was isolated from the genus Dictamnus for the first time. These results indicated that this method is not only quick and sensitive for analyzing the quinoline alkaloids, but also to effectively guided-separate this kind of alkaloids in the root barks of D. dasycarpus.
Alkaloids ; isolation & purification ; Chromatography, High Pressure Liquid ; Dictamnus ; chemistry ; Ions ; Phytochemicals ; isolation & purification ; Plant Roots ; chemistry ; Quinolines ; isolation & purification ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry

The present study carried out a phytochemical investigation on the root barks of Dictamnus dasycarpus Turcz, leading to the isolation and characterization of two new aromatic ring butyrolactone derivatives, dasycarpusphenol acid A (1) and dasycarpusphenol acid B (2). Their structures were elucidated by using spectroscopic techniques and HR-FAB-MS. Compounds 1 and 2 exhibited antioxidant activity, with their IC values being 28.95 and 41.76 mg·mL, respectively.
4-Butyrolactone ; chemistry ; isolation & purification ; Antioxidants ; chemistry ; isolation & purification ; Dictamnus ; chemistry ; Molecular Structure ; Plant Bark ; chemistry ; Plant Extracts ; chemistry ; isolation & purification

Toxoplasma gondii (T. gondii) causes a life-threatening opportunistic infection. Despite its clinical importance, very few therapeutic drugs against T. gondii are available. Furthermore, these therapeutic regimens are not always suitable for prolonged treatment due to adverse side effects as well as the potential of clinical failure by selecting drug-resistant parasite variants. Dictamnus dasycarpus is known to have many medicinal properties, including anti-inflammatory, anti-fever, and anti-rheumatic activities. In this study, 70% ethanol extract of Dictamnus dasycarpus showed anti-T. gondii effects. Ethanolic extracts of Dictamnus dasycarpus used to treat T. gondii were tested in vitro for their anti-T. gondii activity and cytotoxicity. The selectivity of Dictamnus dasycarpus extract was 7.52, which was higher than that of Sulfadiazine (2.08). We conducted an in vivo animal test to evaluate the anti-T. gondii activity of Dictamnus dasycarpus extract as compared with that of Sulfadiazine. In T. gondii-infected mice, the inhibition rate of Dictamnus dasycarpus extract was high, similar to that of Sulfadiazine. This indicates that Dictamnus dasycarpus extract may be a source of new anti-T. gondii compounds.
Animals ; Dictamnus* ; Ethanol ; Mice ; Opportunistic Infections ; Parasites ; Sulfadiazine ; Toxoplasma* ; Toxoplasmosis

Anticoccidial effects of the root bark of Dictamnus dasycarpus Turcz (Rutaceae) extract (DDE) were evaluated in chickens following oral infection with Eimeria (E.) tenella. Three-day-old chickens (n=30) were assigned to three groups (control, untreated, and DDE 0.1% treated). Chickens were fed a standard diet supplemented with or without DDE for 1 week prior to infection with E. tenella (10,000 sporulated oocysts per chicken). The effects of DDE on E. tenella infection were assessed by two parameters; fecal oocysts shedding and body weights gain. The DDE-fed chickens produced significantly reduced fecal oocysts (P<0.05) when compared to the E. tenella-infected group fed standard diet. Also, DDE-based diet, improved body weight loss caused by E. tenella infection. Our data demonstrated that DDE had remarkable anticoccidial activities against E. tenella. This finding might have implications for the development of anticoccidial drug. This study is the first to demonstrate anticoccidial effect of DDE on Eimeria parasites.
Body Weight ; Chickens ; Dichlorodiphenyl Dichloroethylene ; Dictamnus* ; Diet ; Eimeria ; Eimeria tenella* ; Oocysts ; Parasites ; Rutaceae

AIM: To investigate the quinoline alkaloids from the roots of Dictamnus angustifolius G.Don ex Sweet (Rutaceae). METHOD: The quinoline alkaloids were isolated by various column chromatographic methods and their structures were elucidated on the basis of spectral analysis. RESULTS: A new quinoline alkaloid, 5-methoxylrobustine (1), along with five known quinoline alkaloids were obtained, and their structures were identified as dictamnine (2), robustine (3), isopteleine (4), γ-fagarine (5), and skimmianine (6). Cytotoxicity testing of these alkaloids showed that all of them had weak cytotoxic activities against human breast cancer cells (MCF7). CONCLUSION Compound 1 is a new quinoline alkaloid. Alkaloid 3 showed stronger anti-proliferation effect than the other alkaloids.
Antineoplastic Agents, Phytogenic ; isolation & purification ; pharmacology ; therapeutic use ; Breast Neoplasms ; drug therapy ; Cell Line, Tumor ; Dictamnus ; chemistry ; Humans ; Hydroxyquinolines ; chemistry ; isolation & purification ; pharmacology ; therapeutic use ; Molecular Structure ; Phytotherapy ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Plant Roots ; chemistry ; Quinolines ; chemistry ; isolation & purification ; pharmacology ; therapeutic use

We report a case of fulminant hepatic failure related to ingesting Dictamnus dasycarpus. The patient had taken D. dasycarpus for 8 weeks after boiling down the root of D. dasycarpus in water, to promote health. The main symptoms and signs were general weakness and jaundice. Serology found no evidence of hepatitis A, B, or C infections. Imaging studies, including abdominal ultrasonography and abdominal computed tomography, did not reveal any bile duct structural abnormalities. Based on the RUCAM score (8 points), D. dasycarpus was the probable cause for the drug-induced liver injury. Despite meticulous monitoring and supportive care, the patient died by a progression to fulminant hepatic failure. This case indicates that D. dasycarpus can cause lethal outcomes by fulminant hepatic failure.
Bile Ducts ; Dictamnus ; Drug-Induced Liver Injury ; Hepatitis A ; Humans ; Jaundice ; Liver Failure, Acute ; Water

BACKGROUND/AIMS: The aim of this study was to investigate the clinical features of acutely toxic hepatitis associated with ingesting Dictamnus dasycarpus (D. dasycarpus). METHODS: Between January 2004 and July 2009, 28 patients were enrolled in this study. We reviewed the medical records retrospectively. Acutely toxic hepatitis associated with D. dasycarpus was diagnosed by a Roussel Uclaf Causality Assessment Method Values (RUCAM) score of 6 or above. All patients were tested for viral hepatitis A, B, C, cytomegalovirus, and Epstein-Barr virus. Other tests included anti-nuclear antibody, anti-mitochondrial antibody, and anti-smooth muscle antibody. Abdominal pelvic computed tomography was performed. RESULTS: The incidence was female predominant (64% vs. 36%). The mean patient age was 53.0+/-11 years. The symptoms were jaundice (68%), fatigue (57%), nausea (43%), anorexia (43%), and abdominal pain (24%). The mean RUCAM score was 7.0+/-0.8. The biochemical patterns of hepatotoxicity were hepatocellular (n=23, 82%) and mixed types (n=5, 18%). Radiologic findings were as follows: normal findings (29%), lymphadenopathy (50%), edema of the gall bladder wall (46%), periportal edema (43%), splenomegaly (11%), fatty liver (11%), and ascites (7%). The mean hospitalization period was 21.6+/-11.6 days. The mean duration of recovery from hepatitis was 56.6+/-30.4 days, and all patients recovered completely from the toxic hepatitis. One patient who had severe jaundice developed a complication of pure red cell aplasia during the hospitalization period. CONCLUSIONS: The biochemical pattern of liver injury was hepatocellular predominant. Although the initial manifestations and clinical course were variable, all patients completely recovered with supportive care or steroid treatment. Toxic hepatitis was accompanied by pure red cell aplasia in one patient.
Abdominal Pain ; Anorexia ; Ascites ; Cytomegalovirus ; Dictamnus ; Drug-Induced Liver Injury ; Edema ; Fatigue ; Fatty Liver ; Female ; Hepatitis ; Hepatitis A ; Herpesvirus 4, Human ; Hospitalization ; Humans ; Incidence ; Jaundice ; Liver ; Lymphatic Diseases ; Medical Records ; Muscles ; Nausea ; Red-Cell Aplasia, Pure ; Retrospective Studies ; Splenomegaly ; Urinary Bladder