Nauclea Officinalis: Chemical Components And Pharmacological Effects

Nauclea officinalis is a plant of the madder family and grows in subtropical areas including southern China. The plant has long been used as a medicinal herb in the traditional medicine of China and some other countries. Its stems and barks are used and they are believed to have anti-inflammatory and antibacterial effects. Plants of the nauclea genus are rich in alkaloids that are potentially responsible for the pharmacological effects. More than 40 alkaloids have been isolated from the plants and various bioactivities, such as antirheumatism, antimicrobial, and antimalarial activities, have been reported. Pharmaceutical preparations made from nauclea officinalis extracts have been available in southern provinces of China, such as Hainan, Guandong and Guangxi provinces, and used for the treatment of respiratory infections, bronchitis, and urinary infections. The preparations have shown a general effective rate of 90% and little side effect. However, these applications are mainly based on experiences or traditions. Information on the effective components and their pharmacological characteristics is lacking.Prompted by the effectiveness and safety of the medicinal use of the plant, we systematically investigated the chemical components of the plant and evaluated the pharmacological properties of the major components.To investigate the chemical components, the plant was extracted with various solvents and the extracts were subjected to silica absorption column chromatography, gel filtration column chromatography and preparative high performance liquid chromatography for the isolation of individual components. Eight (8) components were isolated and various spectral analyses (e.g.1H-NMR,13C-NMR, DEPT,1H-1HCOSY, HMBC, HMQC, IR, MS, and UV) were performed for the identification of the components. Based on these analyses,7 of the 8 components were identified as (1) biknauchuxoside(temporary), (2) strictosamide, (3) pumiloside, (4) 3,4-dihydroxybenzoic acid,(5) methyl 3,4-dihydroxybenzoate,(6)β-sitosterol and (7) daucosterol. It was the first time to obtain biknauchuxoside, strictosamide and pumiloside amide from this plant.To look at the inorganic element profile of the plant, the element contents in the plant was investigated with ICP-MS. Various conditions for the digestion of the plant material and for the ICP-MS measurement of the elements were tested and optimized, and a procedure for the measurement of Mg, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Cd, Sn, Ba, Hg and Pb in nauclea officinalis was established. The procedure showed a detection limit of about 1μg·mL-1, imprecision (coefficients of variation) of 2.4-8.9% and analytical recoveries of 70%-130%. With this produre elements in 6 batches of the plant were measured.The new alkaloid strictosamide might be one of the major effective component of the plant. Measurement of the component are needed for both the assessment of different medicinal materials of the plant and further investigation of the component. With the isolated strictosamide as an reference material, an HPLC method for the measurement of strictosamide was established and strictosamide contents in water extracts and the stem and bark materials were measured. It was found that the strictosamide contents in 3 water extracts were 5.455%,6.267% and 5.155% and in the bark and stem 0.162% and 0.440%, respectively.Quality control of medicinal herbs is an important issue in traditional medicine. Chromatographic profiling of the major components is often used to control the quality of the herbs. For this purpose, an HPLC procedure for the profiling of the major component was established. The extracts was chromatographed on a reversed phase column with a acetonitrile-water gradient elution. Nauciewsirine was used as an internal reference. Ten (10) batchs of water extracts were tested with the procedure and 9 typical chromatographic peaks were observed. The peak areas or heights and retention times relative to the internal reference were calculated and criteria for the "fingerprints" were constructed according to the national guidelines. Little information about the pharmacological, effects has been reported. The in vitro antibacterial activity of strictosamide was compared to that of pipercillin and ampicillin/sulbactam on clinical isolates and similar activities were observed on gram-negative bacteria and anaerobe. Strictosamide showed similar MIC and MBC onβ-lactamases producing bacteria, suggesting that strictosamide would be an effective antimicrobial agent for these bacteria.The pharmacokinetics of strictosamide in rats was also investigated. Wistar rats were used in the study and alkaloid was administered p.o. at dosage of 100 mg/kg body weight. A liquid chromatography tandem mass spectrometry (LC/MS/MS) method was established for the monitoring of blood drag levels. The drug was recovered with a solid-phase extraction and analyzed by LC/MS/MS with the MRM mode. Pharmacokinetic results showed that the drug concentration in plasma of eight male rats ranged from 0.51 to7.24μg·L-1. The average Cmax, Tmax, t1/2,AUC0-t ,AUC0-∞were (3.25±1.84)μg·L-1, (0.94±0.42) h, (3.44±1.98) h, (8.42±4.85)μg·L-1·h-1 and (11.31±5.27)μg·L-1·h-1, repectively.