Antifungal alkaloids from the branch-leaves of Clausena lansium Lour. Skeels (Rutaceae).

BACKGROUND: The rational utilization of botanical secondary metabolites is one of the strategies to reduce the application of chemical fungicides. The extensive biological activities of Clausena lansium indicate that it has the potential to develop botanical fungicides. RESULTS: A systematic investigation on the antifungal alkaloids from C. lansium branch-leaves following bioassay-guided isolation was implemented. Sixteen alkaloids, including two new and nine known carbazole alkaloids, one known quinoline alkaloid and four known amides, were isolated. Compounds 4, 7, 12 and 14 showed strong antifungal activity on Phytophthora capsiciwith EC50 values ranging from 50.67 to 70.82 µg mL-1 . Compounds 1, 3, 8, 10, 11, 12 and 16 displayed different degrees of antifungal activity against Botryosphaeria dothidea with EC50 values ranging from 54.18 to 129.83 µg mL-1 . It was reported for the first time that these alkaloids had antifungal effects on P. capsici or B. dothidea, and their structure-activity relationships were further discussed systematically. Additionally, among all alkaloids, dictamine (12) had the strongest antifungal activities against P. capsici (EC50  = 50.67 µg mL-1 ) and B. dothidea (EC50  = 54.18 µg mL-1 ), and its physiological effects on P. capsici and B. dothidea also were further evaluated. CONCLUSION: Capsicum lansium is a potential source of antifungal alkaloids, and C. lansium alkaloids had the potential as lead compounds of botanical fungicides in the development of new fungicides with novel action mechanism. © 2023 Society of Chemical Industry.

The sesquiterpenes from the stem and leaf of Clausena lansium with their potential antibacterial activities.

Two new C13-norsesquiterpenes claulanterpene A (1) and B (2), together with two known sesquiterpenes (3-4), were isolated from methanol extract of the stem and leaf of Clausena lansium collected from Qingyuan county, Guangdong Province, China. Their structures were elucidated on the base of extensive spectroscopic analysis and comparison with data reported in the literature. Among them, compound 4 showed antibacterial activity against Bacillus cereus.

Performance of endoscopic ultrasound for diagnosis of agenesis of the dorsal pancreas: a case report.

Agenesis of the dorsal pancreas is a rare congenital pancreatic malformation. We herein describe a 67-year-old woman with a 5-day history of lower back pain who was eventually diagnosed with agenesis of the dorsal pancreas. Abdominal computed tomography showed an enlarged pancreatic head, but the pancreatic body and tail were invisible. The magnetic resonance imaging findings were similar to the computed tomography findings. Magnetic resonance cholangiopancreatography showed that the major pancreatic duct was mildly dilated but otherwise normal. Endoscopic ultrasound revealed absence of the pancreatic body and tail, an enlarged head of the pancreas, and mild pancreatic duct dilation. The final diagnosis was dorsal pancreatic agenesis.

Prehypertension exercise training attenuates hypertension and cardiac hypertrophy accompanied by temporal changes in the levels of angiotensin II and angiotensin (1-7).

Appropriate exercise training (ExT) has been shown to decrease high blood pressure. Accumulating data have indicated the beneficial effects of ExT on prehypertension. This study tested whether prehypertension ExT protects against hypertension and cardiac remodeling in spontaneously hypertensive rats (SHR) and explored the underlying mechanisms by examining the cardiac angiotensin-converting enzyme (ACE) and ACE2 signaling axes. Low-intensity ExT was started in male SHR and control Wistar-Kyoto rats prior to the onset of hypertension and maintained for 8 or 16 weeks. Blood pressure (BP) was measured biweekly by the tail-cuff method. Cardiac function and remodeling were assessed, and changes in the ACE and ACE2 axes were examined after the final ExT session. The results showed that prehypertension ExT slowed the onset and progression of hypertension in SHR. In parallel, hypertrophy in the hearts of hypertensive rats was attenuated, myocardial fibrosis was reduced, and impairment of left ventricular diastolic function was reduced. In the SHR myocardium, the levels of components involved in the ACE-Ang II-AT1 axis were homogeneously and progressively increased, whereas those involved in the ACE2-Ang(1-7)-MAS axis were heterogeneously decreased. Different temporal responses were observed for the key effectors Ang II and Ang(1-7). Myocardial Ang II levels were progressively increased in SHR and were consistently reduced by ExT. By contrast, Ang(1-7) decreased only after 16 weeks of sedentariness, and this decrease was abolished by ExT. In addition, 16 weeks of ExT increased the levels of Ang(1-7) in normotensive control rats. In summary, prehypertension ExT attenuates hypertension and cardiac remodeling. Downregulation of Ang II seems to serve as a protective mechanism during ExT, while upregulation of Ang(1-7) is induced after a relatively long period of ExT.

Carbazole alkaloids isolated from the branch and leaf extracts of Clausena lansium.

The present study carried out a phytochemical investigation of the methanol extract of the branches and leaves of Clausena lansium and afforded nine carbazole alkaloids (compounds 1-9) including two new carbazole alkaloids, claulansiums A and B (compounds 1 and 2). The new compounds were elucidated on the basis of extensive spectroscopic data (MS, NMR, IR, and UV) and the known compounds were identified by comparing spectroscopic data with those reported in literature. All the isolated compounds were tested for their cytotoxic activity against A549 and Hela cancer cell lines. Our results showed that compounds 2-6 exhibited varying degrees of cytotoxicity to cancer cells, with IC50 values ranging from 8.67 to 98.89 µmol·L-1.

[Monoterpenes and sesquiterpenes from Clausena excavata].

To investigate monoterpenes and sesquiterpenes of the stems and leaves of Clausena excavata, an AcOEt fraction of the methanol extract was subjected on column chromatographies including silica gel and RP-18, as well as preparative HPLC. The structures of compounds isolated were identified on the basis of spectroscopic data as excamonoterpene (1), (6R, 9S)-9, 10-dihydroxy-4-megastigmen-3-one (2), (3R, 6R, 7E) -3-hydroxy-4, 7-megastigmadien-9-one (3), (3S) -3-hydroxy-7, 8-dihydro-beta-ionone (4), (3S, 5R, 6S) -3-hydroxy-5,6-epoxy-beta-ionone (5), (6R, 9R) -9-hydroxy-4-megastigmen-3-one (6), (3S, SR) -dihydroxy-6, 7-megstigmadien-9-one(7), (-)-loliolide(8), caryolane-1, 9alpha-diol(9) and 2, 6-dihydroxyhumula-3 (12), 7 (13), 9(E)-triene (10), were isolated from the stems and leaves of C. excavata. Compound 1 is a new monoterpene, named as excamonoterpene. Compounds 2-10 were isolated from this plant for the first time.

Twelve benzene derivatives from Clausena excavata.

A new phenethanol, (2'R)-4-(2', 3'-dihydroxy-3'-methyl-butanoxy)-phenethanol (1), along with other eleven known benzene derivatives (2-12) were isolated from the roots, stems and leaves of Clausena excavata (Rutaceae). Compounds 3 and 4 are new natural products, and compounds 5-8, 10-12 were isolated from C. excavata for the first time. Their structures were elucidated on the basis of MS, 1D and 2D NMR spectroscopic analyses including HSQC, COSY and HMBC experiments. 1 was tested for its cytotoxicities against A549, HeLa and BGC-823 cancer cell lines, and antimicrobial activities against Candida albicans and Staphylococcus aureus. The results showed that 1 did not exhibit cytotoxic and antimicrobial activities.

A new cytotoxic carbazole alkaloid and two new other alkaloids from Clausena excavata.

One new carbazole alkaloid, excavatine A (1), and two additional new alkaloids, excavatine B (2) and excavatine C (3), were isolated from the stems and leaves of Clausena excavata Burm.f. (Rutaceae). Their structures were determined on the basis of detailed spectroscopic analyses, especially 2D-NMR and HR-EI-MS data. Compounds 1-3 were tested for their cytotoxic activities against A549, HeLa, and BGC-823 cancer cell lines, and for their antimicrobial activities against Candida albicans and Staphylococcus aureus. Only 1 exhibited cytotoxicity against A549 and HeLa cell lines with the IC50 values of 5.25 and 1.91 µg/ml, respectively.

Comparative pharmacokinetics of aloe-emodin, rhein and emodin determined by liquid chromatography-mass spectrometry after oral administration of a rhubarb peony decoction and rhubarb extract to rats.

This study aimed to clarify the rationality of herbaceous compatibility of a rhubarb peony decoction (DaHuang-Mu-Dan-Tang, RPD) by comparing the pharmacokinetics of aloe-emodin, rhein and emodin in rats' plasma after oral administration of RPD and rhubarb extract. A rapid, sensitive LC-MS method was developed and validated for the determination of the plasma concentrations of the three analytes after oral administration RPD and rhubarb extract. The developed method was successfully applied to a pharmacokinetic study of aloe-emodin, rhein and emodin in rats' plasma after oral administration. Compared with administration of single rhubarb, the C(max) of rhein in RPD was decreased significantly (p < 0.05). Meanwhile, the T1/2 of aloe-emodin and emodin were increased significantly (p < 0.05) after administration of RPD. In addition, the T(max) of rhein and emodin were also increased significantly (p < 0.05) in RPD. These results indicated that the absorption of rhein in rats was suppressed after oral administration RPD. Moreover, The time for rhein and emodin to reach the peak concentration was delayed and the elimination of aloe-emodin and emodin was also postponed in RPD. This study could provide a meaningful basis for evaluating the clinical application of traditional Chinese medicine in terms of pharmacokinetics.

The effects of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids in herb couple of Radix Aconiti Lateralis-Rhizoma Zingiberis.

ETHNOPHARMACOLOGICAL RELEVANCE: Radix Aconiti Lateralis (Fuzi in Chinese, derived from the lateral roots of Aconitum Carmichaeli Debx.) is widely used for the treatment of heart failure, internal cold, arthralgia, diarrhea and edema for thousands of years. It was usually prescribed in combination with Rhizoma Zingiberis (Ganjiang in Chinese, derived from the dry rhizome of Zingiber officinale Rosc.) to decrease toxicity and increase efficacy. AIM OF THE STUDY: In order to investigate the influence of Rhizoma Zingiberis on pharmacokinetics of six Aconitum alkaloids, i.e. aconitine (AC), hypaconitine (HA), mesaconitine (MA), benzoylaconine (BAC), benzoylhypaconine (BHA) and benzoylmesaconine (BMA), in Fuzi-Ganjiang herb couple, the comparative pharmacokinetics of six Aconitum alkaloids after oral administration of Fuzi and Fuzi-Ganjiang aqueous extract was carried out. MATERIALS AND METHODS: A sensitive, specific and rapid LC-MS/MS method was developed to determine the six analytes in plasma. Then the rats were randomly divided into two groups and orally administered with Fuzi and Fuzi-Ganjiang aqueous extract. At designated time points after oral administration, the concentrations of the six Aconitum alkaloids in rat plasma were determined, and main pharmacokinetic parameters were investigated using 3P97 (Practical Pharmacokinetics Program Version 1.0). RESULTS: Comparing with Fuzi group, both T1/2 and AUC0-t of AC and HA decreased (P<0.05), while T1/2, AUC0-t and Cmax of BAC, BHA increased (P<0.05) in Fuzi-Ganjiang group, which indicated that Ganjiang could promote the elimination of AC and HA and enhance the absorption of BAC, BHA and BMA. CONCLUSION: The differences of pharmacokinetics of Aconitum alkaloids in rat plasma could support those of pharmacologics and toxicity in previous reports between Fuzi and Fuzi-Ganjiang herb couple. The results might be helpful in explaining the mechanism of combination of Fuzi-Ganjiang to decrease toxicity and increase efficacy.

[One new chroman glycoside derivative from unmatured fruits of Citrus aurantium].

OBJECTIVE: To study the chemical constituents of the unmatured fruits of Citrus aurantium. METHOD: The AcOEt fraction of the methanol extracts of the unmatured fruits of C. aurantium were subjected on column chromatographies including silica gel, RP-18 and HPLC. Compound structures isolated were determined on the basis of spectroscopic data. RESULT: Three compounds were isolated from the unmatured fruits of C. aurantium, which were identified as citrauranoside (1), limonexin (2) and limonin (3). CONCLUSION: Compound 1 is a new chroman glycoside derivative, named as citrauranoside.

Coumarins from roots of Clausena excavata.

Two new coumarins, clauexcavatins A (1) and B (2), along with seven known ones (3-9), were isolated from the roots of Clausena excavata Burm. f. (Rutaceae). Their structures were elucidated on the basis of spectral data.