Effects of Ferulic Sesquiterpene Compounds on Schistosoma

Yingqiong CHEN Hongmei ZHAO

japonicum at Different Developmental Stages in Infected Juvenile Rabbits

Abstract ［Objectives］ This study was conducted to explore the effects of ferulic sesquiterpene compounds on juvenile worms and adults of Schistosoma japonicum at different developmental stages in infected juvenile rabbits.

［Methods］Juvenile rabbits were infected with S. japonicum quantitatively, and administered with 500 mg/kg ferulic sesquiterpene compounds at 2 h, 1, 2, 6, 11, 13, 15, 24, 36, and 41 d after infection by gavage, 1 time/d, and a control group was administrated with normal saline. After 4 weeks of administration, the juvenile rabbits were dissected, and the worms were collected by portal vein perfusion for the calculation of worm reduction rate.

［Results］ The reduction rates of ferulic sesquiterpene compounds on 1, 2, 6, 11, 13, 15, 24, 36, and 41-day-old juveniles or adults were 15.8%, 17.0%, 60.2%, 50.2%, 36.9%, 31.3%, 45.3%, 57.0%, and 25.2%, respectively, and it was found that worms at the age of 6-36 d were most sensitive to the drug.

［Conclusions］Ferulic sesquiterpene compounds had a killing effect on S. japonicum at different developmental stages in juvenile rabbits, and the killing effect on 6-36-day-old worms was more significant.

Key words Ferulic sesquiterpene compounds; Schistosoma japonicum; Susceptibility

Received: May 21, 2021  Accepted: July 25, 2021

Supported by the Effects of Ferulic Sesquiterpene Esters on Active Enzymes of Schistosoma japonicum (No. KLPCAAB-2019-04).

Yingqiong CHEN (1996-), female, P. R. China, devoted to research about veterinary pharmacology.

*Corresponding author. E-mail: 269643126@qq.com.

Studies have shown that ferulic sesquiterpene compounds can kill worms, sterilize and kill Oncomelania, and can significantly inhibit the activity of energy metabolism enzymes in worms［1-3］. Studying the susceptibility of schistosomes at various developmental stages to ferulic sesquiterpene compounds is of great significance for optimizing medication regimens, developing and applying Ferula sinkiangensis K. M. Shen and preventing schistosomes from developing resistance to chemical pesticides［4-7］. In this study, ferulic sesquiterpene compounds were administrated to juvenile rabbits infected with Schistosoma japonicum cercariae at different times to observe their effects on S. japonicum bodies at different developmental stages, so as to explore the effects of ferulic sesquiterpene compounds in killing S. japonicum at different developmental stages.

Materials and Methods

Materials

Experimental animals

The experimental animals, Chinese white rabbits, were purchased from the experimental rabbit farm of Jingzhou Institute of Technology. They were bred and provided by College of Animal Science of Yangtze University. The body weight was (0.5±0.1) kg, which was not limited to males or females.

Experimental drugs

The extraction of the active ingredients of F. sinkiangensis and the preparation of different dosage forms were carried out according to the method of literature［7］. Then, 1% sodium carboxymethyl cellulose (CMC) solution was mixed with ferulic sesquiterpene powder into a 3% ferulic sesquiterpene suspension, which was administrated to rabbits.

Experimental worm species

The cercariae of S. japonicum for infecting juvenile rabbits were escaped from infected Oncomelania in the laboratory of College of Animal Science of Yangtze University.

Methods

Experimental grouping and treatments

The experimental rabbits were divided into 11 groups, 10 in each group, including 10 experimental groups and 1 control group. In the experimental groups, the animals were administrated intragastrically with 500 mg/kg of ferulic sesquiterpene suspension at 1, 2, 6, 11, 13, 15, 24, 36, and 41 d after infection with S. japonicum, 1 time/d. After 4 weeks, the juvenile rabbits were dissected to collect the worms by portal vein perfusion, and the reduction rate was calculated. The control group was infected with S. japonicum cercariae, but not administrated with the drug.

Infection of juvenile rabbits with S. japonicum cercariae

The abdominal wall infection method was adopted. The juvenile rabbits were fixed, and the abdominal fur was cut off by about 2 cm×2 cm. The skin was moistened with dechlorinated water at room temperature, and coverslips with counted cercariae were placed on the depilated skin. Each rabbit was infected with (45±1) cercariae of S. japonicum. The coverslips were removed after 20 min.

Collection and counting of worms

The juvenile rabbits of various groups were dissected after 4 weeks of infusion to collect and count the worms, and the rate of worm reduction was calculated.

Data processing

SPSS 11.0 statistical software was used for statistical processing of the data, and the differences between groups were evaluated by t test.

Results and Analysis

Effects of ferulic sesquiterpene compounds on different developmental stages of S. japonicum in infected juvenile rabbits

The average numbers of S. japonicum seized in rabbits of various infection experimental groups were 38.8, 37.4, 36.9, 12.9, 22.4, 28.4, 30.9, 24.6, 18.9, and 33.1 after intragastric administration of ferulic sesquiterpene compounds. Among them, the average numbers of the worms seized in the 6, 11, 13, 15, 24, and 36 d groups were extremely significantly different from that of the control group (P<0.01), and the average numbers of the worms seized in the 1, 2, and 41 d groups were significantly different from that of the control group (P<0.05), as shown in Table 1.

Effects of ferulic sesquiterpene compounds on the reduction rate of S. japonicum in infected juvenile rabbits

It can be seen from Table 1 that the reduction rates of S. japonicum in the infected juvenile rabbits in the 1, 2, 6, 11, 13, 15, 24, 36, and 41 d groups were 15.8%, 17.0%, 60.2%, 50.2%, 36.9%, 31.3%, 45.3%, 57.0%, and 25.2%, respectively, indicating that the ferulic sesquiterpene compounds had a killing effect on S. japonicum at different developmental stages in infected juvenile rabbits to different degrees, and juveniles or adults at the age of 6-36 d were most sensitive to the drug. The drug had the best killing effect on 6-day-old juvenile worms, with a reduction rate of 60.2% for S. japonicum, followed by 36-day-old adults, with a reduction rate of 57.0%.

Conclusions and Discussion

The results of this study indicated that ferulic sesquiterpene compounds had no obvious effect on the cercariae that had just entered the skin, and they had the greatest impact on  6-day-old juvenile S. japonicum worms, which is consistent with the results of Li et al.［2］. The results of this study also showed that ferulic sesquiterpene compounds could kill worms at the age of 6-36 d. Praziquantel only has obvious killing effect on Schistosoma mansoni at the age of 13-20 d, which may be related to the development time of S. mansoni later than S. japonicum by 1 week［3］. It indicates that the killing effect of ferulic sesquiterpene compounds on S. japonicum has the characteristic of being related to its developmental stage, and there are differences among different species of Schistosoma, which need to be confirmed by further research.

References

［1］ BAO F, ZHAO HM, LU H. Effect of ferulic sesquiterpene compounds against Schistosoma japonicum［J］. Journal of Traditional Chinese Veterinary Medicine, 2012, 31(2): 40-42. (in Chinese)

［2］ LI S, WU L LIU Z, et al. Studies on prophylactic effect of artesunate on Schistosomiasis japonica［J］. Chin Med J(Engl), 1996, 109(11): 848-852.

［3］ ISMAIL M, METWALLY A, FARGHALY A, et al. Characterization of isolates of Schistosoma mansonifrom Egyptian villagers that tolerate high doses of praziquantel［J］. Am J TropMed Hyg, 2006, 55(2): 214-218.

［4］ WU LJ, XUAN YX, YANG MJ, et al. Study on the interaction between artesunate and praziquantel in the prevention and treatment of schistosomiasis［J］. Chinese Journal of Schistosomiasis Control, 1998, 10(2): 65-68. (in Chinese)

［5］ QIAN W, ZHAO HM. Obervation on the effects of Ferula sinkiangensis K. M. Shen against Oncomelania by different treatment［J］. Journal of Traditional Chinese Veterinary Medicine, 2009, 28(6): 47-48. (in Chinese)

［6］ HE S, TAN DY. Advances in studies of Ferula L.［J］. Journal of Xinjiang Agricultural University, 2002, 25(2): 1-7.

［7］ YANG JR, LI GQ, LI ZH, et al. Chemical constituents from Ferula teterrima［J］. Natural Product Research and Development, 2006(2): 246-248. (in Chinese)