Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo
Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with se...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1008274/full |
| _version_ | 1811230935052451840 |
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| author | Haijun Gao Haijun Gao Haijun Gao Lele Huo Xiaojin Mo Bin Jiang Yanping Luo Bin Xu Jingzhong Li Xingming Ma Tao Jing Zheng Feng Ting Zhang Ting Zhang Wei Hu Wei Hu |
| author_facet | Haijun Gao Haijun Gao Haijun Gao Lele Huo Xiaojin Mo Bin Jiang Yanping Luo Bin Xu Jingzhong Li Xingming Ma Tao Jing Zheng Feng Ting Zhang Ting Zhang Wei Hu Wei Hu |
| author_sort | Haijun Gao |
| collection | DOAJ |
| description | Echinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling. |
| first_indexed | 2024-04-12T10:37:43Z |
| format | Article |
| id | doaj.art-f4995523addc45b48f5a468af9127efc |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-12T10:37:43Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-f4995523addc45b48f5a468af9127efc2022-12-22T03:36:41ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2022-11-011310.3389/fmicb.2022.10082741008274Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivoHaijun Gao0Haijun Gao1Haijun Gao2Lele Huo3Xiaojin Mo4Bin Jiang5Yanping Luo6Bin Xu7Jingzhong Li8Xingming Ma9Tao Jing10Zheng Feng11Ting Zhang12Ting Zhang13Wei Hu14Wei Hu15National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, ChinaGanzr Tibetan Autonomous Prefecture Center for Disease Control and Prevention, Kangding, Sichuan, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaNational Health Commission Key Laboratory of Echinococcosis Prevention and Control, Tibet Autonomous Region Center for Disease Control and Prevention, Lhasa, Tibet, ChinaSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, ChinaSchool of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaNational Health Commission Key Laboratory of Echinococcosis Prevention and Control, Tibet Autonomous Region Center for Disease Control and Prevention, Lhasa, Tibet, ChinaNational Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research), NHC Key Laboratory of Parasite and Vector Biology, WHO Collaborating Center for Tropical Diseases, National Center for International Research on Tropical Diseases, Shanghai, ChinaDepartment of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, ChinaEchinococcus multilocularis, the causative agent of alveolar echinococcosis (AE), severely threats human health and livestock farming. The first line of chemotherapeutic drug for AE is albendazole, which limits rapid extension of E. multilocularis metacestodes, but is rarely curative for AE, with severe side effects in long-term use, thus development of new anti-echinococcal drugs is mandated. Pseudolaric acid B (PAB) has long been used to treat fungal-infected dermatosis, and exerted anti-tumor, -fertility, -angiogenesis, -tubulin and antiparasitic activity. However, the effect of PAB against Echinococcus spp. remains unclear. The present study is to understand the effect of PAB against E. multilocularis in vitro and in vivo, and identify potential anti-echinococcal mechanism, as well as its toxicity. After exposure to PAB at 20 μg/ml, significant reduction of the survival rate and substantial ultrastructural destructions in E. multilocularis protoscoleces were observed in vitro. Furthermore, the wet weight of E. multilocularis cysts in the infected mice was significantly decreased after treatment with PAB (40, 20 or 10 mg/kg) for 12 weeks. Meanwhile, significant increase of both protein and mRNA expression of transforming growth factor beta 1 (TGF-β1) was detected in the serum and liver of the infected mice, whereas PAB administration lowered its expression significantly. The toxicity tests demonstrated that PAB displayed lower cytotoxicity to human liver and kidney cells (HL-7702 and HK-2 cell) with IC50 = 25.29 and 42.94 μg/ml than albendazole with IC50 = 3.71 and 21.22 μg/ml in vitro, and caused lower hepatoxicity and nephrotoxicity in mice than ABZ. Our findings indicated that PAB possesses potent anti-echinococcal effect, with lower toxicity than albendazole, implying a potential chemotherapeutic agent for AE. Additionally, the present study demonstrated that the suppressive effect of PAB on the parasite may involve down-regulation of TGF-β1 signaling.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1008274/fullalveolar echinococcosispseudolaric acid BEchinococcus multilocularisprotoscolecesTGF-β1 |
| spellingShingle | Haijun Gao Haijun Gao Haijun Gao Lele Huo Xiaojin Mo Bin Jiang Yanping Luo Bin Xu Jingzhong Li Xingming Ma Tao Jing Zheng Feng Ting Zhang Ting Zhang Wei Hu Wei Hu Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo Frontiers in Microbiology alveolar echinococcosis pseudolaric acid B Echinococcus multilocularis protoscoleces TGF-β1 |
| title | Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo |
| title_full | Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo |
| title_fullStr | Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo |
| title_full_unstemmed | Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo |
| title_short | Suppressive effect of pseudolaric acid B on Echinococcus multilocularis involving regulation of TGF-β1 signaling in vitro and in vivo |
| title_sort | suppressive effect of pseudolaric acid b on echinococcus multilocularis involving regulation of tgf β1 signaling in vitro and in vivo |
| topic | alveolar echinococcosis pseudolaric acid B Echinococcus multilocularis protoscoleces TGF-β1 |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1008274/full |
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