Extract of Torreya nucifera Pericarps Exhibits a Parasiticidal Effect on the Nematode Parasite, Trichinella spiralis

Mi Jin Jeong,Shin Ae Kang,유선녕,Soon Cheol Ahn,Shin-Ichi Miyoshi,Hye Sook Kim,유학선 한국식품영양과학회 2023 Journal of medicinal food Vol.26 No.9

Benzimidazole derivatives can effectively treat nematode parasitic infections; however, some derivativesdemand distinct administrative strategies depending on plasma concentration and patient conditions. Numerous studies haveexamined the potential of natural extracts to exert parasiticidal activity with minimal side effects. Herein, we examined thepotential parasiticidal effects of Torreya nucifera extract. The pericarps of T. nucifera were extracted with methanol, dried,and the pellet was dissolved in hot water (Tn-Phw). We designed four individual mouse experiments to clarify the prophylacticand therapeutic effects of Tn-Phw on Trichinella spiralis infection. Also, 100 L1 larvae were isolated and treatedwith Tn-Phw (10 mg/mL) in vitro to confirm the killing effect. Furthermore, we microscopically examined the morphology ofL1 larvae to confirm the parasite-killing effect and analyzed the morphology using a scanning electron microscope (SEM). The expression of three molting-related genes was confirmed to determine whether Tn-Phw induced morphological changes inL1 larvae. Following treatment with Tn-Phw, L1 larvae death was observed after 16 h. Following SEM examination, thehealthy muscle larvae showed striated ridges and wrinkles; this was not observed in extract-treated muscle larvae. Expressionlevels of the three molting-related genes did not differ between the Tn-Phw-treated and control groups. T. spiralis-infectedmice pretreated with Tn-Phw showed significantly reduced muscle larva infection when compared with control mice. In allexperiments, treatment with Tn-Phw afforded preventive and therapeutic effects against T. spiralis infection and parasitism. Natural substances against nematode parasites could be developed as therapeutic agents with few side effects and enhancedparasiticidal efficacy.

Evaluating the activity of N-89 as an oral antimalarial drug

Nagwa S. M. Aly,Hiroaki Matsumori,Thi Quyen Dinh,Akira Sato,Shin-Ichi Miyoshi,장경수,유학선,Takaaki Kubota,Yuji Kurosaki,Duc Tuan Cao,Gehan A. Rashed,김혜숙 대한기생충학ㆍ열대의학회 2023 The Korean Journal of Parasitology Vol.61 No.3

Despite the recent progress in public health measures, malaria remains a troublesome disease that needs to be eradicated. It is essential to develop new antimalarial medications that are reliable and secure. This report evaluated the pharmacokinetics and antimalarial activity of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) using the rodent malaria parasite Plasmodium berghei in vivo. After a single oral dose (75 mg /kg) of N-89, its pharmacokinetic parameters were measured, and t1/2 was 0.97 h, Tmax was 0.75 h, and bioavailability was 7.01%. A plasma concentration of 8.1 ng/ml of N-89 was maintained for 8 h but could not be detected at 10 h. The dose inhibiting 50% of parasite growth (ED50) and ED90 values of oral N-89 obtained following a 4-day suppressive test were 20 and 40 mg/kg, respectively. Based on the plasma concentration of N-89, we evaluated the antimalarial activity and cure effects of oral N-89 at a dose of 75 mg/kg 3 times daily for 3 consecutive days in mice harboring more than 0.5% parasitemia. In all the N-89- treated groups, the parasites were eliminated on day 5 post-treatment, and all mice recovered without a parasite recurrence for 30 days. Additionally, administering oral N-89 at a low dose of 50 mg/kg was sufficient to cure mice from day 6 without parasite recurrence. This work was the first to investigate the pharmacokinetic char-acteristics and antimalarial activity of N-89 as an oral drug. In the future, the following steps should be focused on developing N-89 for malaria treatments; its administration schedule and metabolic pathways should be investigated.

Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice

Nagwa S. M. Aly,Hiroaki Matsumori,Thi Quyen Dinh,Akira Sato,Shin-Ichi Miyoshi,장경수,유학선,Fumie Kobayashi,김혜숙 대한기생충학ㆍ열대의학회 2023 The Korean Journal of Parasitology Vol.61 No.1

The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.

Evidence That Temporally Alternative Expression of the Vibrio vulnificus Elastase Prevents Proteolytic Inactivation of Hemolysin

RHEE, JEE EUN,LEE, JEONG HYUN,JEONG, HYE SOOK,PARK, URYUNG,LEE, DONG-HA,WOO, GUN-JO,MIYOSHI, SHIN-ICHI,CHOI, SANG-HO 한국미생물 · 생명공학회 2003 Journal of microbiology and biotechnology Vol.13 No.6

Numerous secreted and cell-associated virulence factors have been proposed to account for the fulminating and destructive nature of Vibrio vulnificus infections. Among the putative virulence factors are an elastase, elastolytic protease, and a cytolytic hemolysin. Effects of the elastase on the hemolysin were assessed by evaluating changes of hemolytic activities either in the presence or absence of the protease. Although hemolytic activity in the culture supernatant was lowered by the purified elastase added in Litro, the cellular level of hemolytic activity was unaffected by the mutation of vvpE encoding the elastase. Growth kinetic studies revealed that hemolysin reached its maximum level in the exponential phase of growth, and the elastase appeared at the onset of the stationary phase. These results have provided insight into the regulation of virulence factors: temporally coordinate regulation of virulence factors is essential for the overall success of the pathogen during pathogenesis.

Evaluation of schistosomula lung antigen preparation and soluble egg antigen vaccines on experimental schistosomiasis mansoni

Nagwa S. M. Aly,김혜숙,Maysa A. Eraky,Asmaa A. El Kholy,Basma T. Ali,Shin-Ichi Miyoshi,Rabab E. Omar 대한기생충학ㆍ열대의학회 2023 The Korean Journal of Parasitology Vol.61 No.3

Schistosomiasis causes significant morbidity and mortality worldwide. This study aimed to assess the effect of schistosomula lung antigen preparation (SLAP) and soluble egg antigen (SEA) on a murine schistosomiasis mansoni model. Ninety laboratory-bred male Swiss albino mice were divided into 6 groups. Two doses of the vaccine were given at 2-week intervals. All mice were subcutaneously infected with 80±10 Schistosoma mansoni cercariae 2 weeks after the last vaccination dose. They were sacrificed 7 weeks post-infection. Parasitological and histopathological studies were conducted to assess the effect of inoculated antigens (single or combined). The results showed that the combination of SLAP and SEA (combination group) led to a significant reduction in worm burden (65.56%), and liver and intestine egg count (59% and 60.59%, respectively). The oogram pattern revealed a reduction in immature and mature eggs (15±0.4 and 10±0.8, respectively) and an increased number of dead eggs in the combination group (P<0.001). In terms of histopathological changes, the combination group showed notably small compact fibrocellular egg granuloma and moderate fibrosis in the liver. A high percentage of destroyed ova was observed in the intestine of the combination group. This study demonstrates for the first time the prophylactic effect of combined SLAP and SEA vaccine. The vaccine induced a significant reduction in the parasitological and pathological impacts of schistosomiasis mansoni in hepatic and intestinal tissues, making it a promising vaccine candidate for controlling schistosomiasis.