Chemical Constituents From Two Plants Of Apiaceae And Their Biological Activities

Plants of Apiaceae are rich in chemicals including coumarins, essential oils, flavonoids, phenols, alkaloids. They have a variety of applications such as medicine, vegetables, spices, chemicals, etc. Various chemical constituents with strong pharmacological activities have been found and the antibacterial active ingredients are drawing our attention. Plant Ferula ferulaeoides belongs to the genus Ferula (Apiaceae). As a traditional herb, several species of Ferula have a reputation in the treatment of various diseases such as neurological disorders, inflammations, digestive disorders, rheumatism and arthritis. In pharmacological research, Ferula were found to possess biological effects including anti-virus, anti-inflammatory, cytotoxicity, insecticide and antibacterial activities. So far, there have been about 55 compounds isolated from this herb, most of which are sesquiterpenes and their derivatives.In the first section, chemical compositions of F. ferulaeoides were studied by the direction of antibacterial activity against drug-resistant S. aureus. The inhibit and sinergestic effect of the natural compounds against drug-resistant S. aureus, structure-activity relationship and mechanism of active compounds were studied. Biological activities of the compounds including anti-tumor, anti-virus and insecticidal activity were also evaluated.In phytochemical research, dichloromethane fraction of F. ferulaeoides was analysed by GC-MS and thirty-four compounds were identified. The main component of the fraction was guaiol (37.01%). Forty compounds have been isolated from this fraction of F. ferulaeoides. Thirty-four compounds were identified. Twelve of them are new compounds (9-10,12-16, 24-28), another known ten (1-4,24,29-31,33-34) are first reported from this plant. Biosynthetic pathways leading to these compounds were proposed. Fifteen derivatives were obtained according to structural modifications of the natural products.In pharmaceutical research, attentions have been focus on activity of natural products from F. ferulaeoides against drug-resistant S. aureus. A rapid screening method, TLC-bioautography, was introduced and improved. Two compounds (5 and 11) with activity against drug-resistant S. aureus were obtained from F. ferulaeoides using this method. The minimal inhibitory concentrations (MICs) for natural compounds were determined using the standard broth micro-dilution method. Results showed that sesquiterpenoids and most of the coumarins had no antibacterial activity. Only individual coumarins (17,18,21,22,27 and 28) showed unique inhibitory activity against tetracycline resistant strains Xu212 which possessed the TetK tetracycline efflux protein with MIC values at 2 μg/mL. Compounds of acetophenone (5-13) derivatives showed widespread activity against S. aureus. Compound (10) showed the best activity against strain XU212 and EMRSA-16 with MIC value at 0.5 μg/mL。 The mechanism of active compounds against drug-resistant S. aureus was studied and two new natural compounds (9 and 12) were found to possess effect of efflux pump inhibition. In the presence of compounds 9 and 12, the fluorescent absorption of intracellular EtBr decreased slowly within the experimental duration, and the absorption was at a higher level than that in the absence of compounds 9 and 12.Sixteen derivatives were obtained by structural modifications of the natural products. Structure-active relationships study showed that 2’,4’-dihydroxy-phenyl, the length of side chain, hydroxyl of benzene ring, the double bonds, ketone group and its alpha bits played important roles in their activity against drug-resistant S. aureus.Synergistic effects of compounds that had no inhibit activity against drug-resistant S. aureus were studied. Five coumarins (17,18,21,22 and 25) were screened to have synergistic effect. The combination of antibiotics with these compounds can greatly reverse bacteria resistance to antibiotics. Compound 17 and 22 can improve effect of the antibiotics whose MIC can be changed from 64 μg/mL to 1 μg/mL.The anti-tumor, antiviral and insecticidal activities of natural products from F. ferulaeoides were studied. Compounds of phenyl ethyl ketone and terpene had no inhibition on SMMC-7721 and SGC-7901 while coumarins showed certain inhibitory activity with IC50 from 22.5 to 69.0 μM. Compounds of coumarin (17-19) showed inhibitory activity to both HBsAg and HBeAg under the condition of non-toxic. Compounds 17 and 18 also showed inhibitory activity to the DNA of HBV. Sesquiterpenoids compound (31) showed good killing activity against common plant insects.In the second section, the activity against phytopathogenic fungi of celery seed and its chemical compositions were studied. Celery seed belonging to Apiaceae is the seed of celery. Its functional components were reported to have good antioxidant, anticancer, antibacterial, insecticidal bioactivity and so on. In pharmaceutical research, the low polarity of celery seed, QCZ-P, showed the best inhibitory activity to test strains Rhizoctonia solani, Alternaria fasciculate and Fusarium oxysporium. Bioactive directed separation offered a more active fraction QCZ-P-4, with the best activity of 64.6%,54.7% and 88.4% against R. solani, A. fasciculate and F. oxysporium, respectively. QCZ-P-4 was shown to contain 5 compounds by GC-MS. This indicated that it might be developed to be a natural non-toxicity pesticide. The activity against drug-resistant S. aureus of QCZ-P and QCZ-P-4 showed they had no inhibition activity in low concentrations.