Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish
The treatment for tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), has a prolonged cycle which can last up to a year. This is partially due to the lack of effective therapies. The development of novel anti-TB drugs from the perspective of host immune regulation can provide an important...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-08-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.936295/full |
| _version_ | 1797999656943222784 |
|---|---|
| author | Shumei He Hongyan Fan Hongyan Fan Bin Sun Meipan Yang Hongxu Liu Hongxu Liu Jianwei Yang Jianwei Yang Jianxin Liu Jianxin Liu Sizhu Luo Sizhu Luo Zihan Chen Zihan Chen Jing Zhou Jing Zhou Lu Xia Shulin Zhang Shulin Zhang Bo Yan |
| author_facet | Shumei He Hongyan Fan Hongyan Fan Bin Sun Meipan Yang Hongxu Liu Hongxu Liu Jianwei Yang Jianwei Yang Jianxin Liu Jianxin Liu Sizhu Luo Sizhu Luo Zihan Chen Zihan Chen Jing Zhou Jing Zhou Lu Xia Shulin Zhang Shulin Zhang Bo Yan |
| author_sort | Shumei He |
| collection | DOAJ |
| description | The treatment for tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), has a prolonged cycle which can last up to a year. This is partially due to the lack of effective therapies. The development of novel anti-TB drugs from the perspective of host immune regulation can provide an important supplement for conventional treatment strategies. Salidroside (SAL), a bioactive component from the Tibetan medicine Rhodiola rosea, has been used in the treatment of TB, although its mechanism remains unclear. Here, the bacteriostatic effect of SAL in vivo was first demonstrated using a zebrafish–M. marinum infection model. To further investigate the underlying mechanism, we then examined the impact of SAL on immune cell recruitment during wound and infection. Increased macrophage and neutrophil infiltrations were found both in the vicinity of the wound and infection sites after SAL treatment compared with control, which might be due to the elevated chemokine expression levels after SAL treatment. SAL treatment alone was also demonstrated to improve the survival of infected zebrafish larvae, an effect that was amplified when combining SAL treatment with isoniazid or rifampicin. Interestingly, the reduced bacterial burden and improved survival rate under SAL treatment were compromised in tnfα-deficient embryos which suggests a requirement of Tnfα signaling on the anti-mycobacterial effects of SAL. In summary, this study provides not only the cellular and molecular mechanisms for the host anti-mycobacterial effects of the Tibetan medicine SAL but also proof of concept that combined application of SAL with traditional first-line anti-TB drugs could be a novel strategy to improve treatment efficacy. |
| first_indexed | 2024-04-11T11:08:09Z |
| format | Article |
| id | doaj.art-0dfd491006824713a92ca6dad4318f30 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T11:08:09Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-0dfd491006824713a92ca6dad4318f302022-12-22T04:28:13ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.936295936295Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafishShumei He0Hongyan Fan1Hongyan Fan2Bin Sun3Meipan Yang4Hongxu Liu5Hongxu Liu6Jianwei Yang7Jianwei Yang8Jianxin Liu9Jianxin Liu10Sizhu Luo11Sizhu Luo12Zihan Chen13Zihan Chen14Jing Zhou15Jing Zhou16Lu Xia17Shulin Zhang18Shulin Zhang19Bo Yan20Key Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaDepartment of Stomatology, The First Affiliated Hospital of Shihezi University Medical College, Shihezi, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaKey Laboratory of Molecular Mechanistic and Interventional Research of Plateau Diseases in Tibet Autonomous Region, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Central Laboratory for Active Components and Pharmacological Mechanism of Tibetan Medicine, School of Medicine, Xizang Minzu University, Xianyang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaMedical College, China Three Gorges University, Yichang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaMedical College, China Three Gorges University, Yichang, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaDepartment of Immunology and Microbiology, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaThe treatment for tuberculosis (TB), especially multidrug-resistant TB (MDR-TB), has a prolonged cycle which can last up to a year. This is partially due to the lack of effective therapies. The development of novel anti-TB drugs from the perspective of host immune regulation can provide an important supplement for conventional treatment strategies. Salidroside (SAL), a bioactive component from the Tibetan medicine Rhodiola rosea, has been used in the treatment of TB, although its mechanism remains unclear. Here, the bacteriostatic effect of SAL in vivo was first demonstrated using a zebrafish–M. marinum infection model. To further investigate the underlying mechanism, we then examined the impact of SAL on immune cell recruitment during wound and infection. Increased macrophage and neutrophil infiltrations were found both in the vicinity of the wound and infection sites after SAL treatment compared with control, which might be due to the elevated chemokine expression levels after SAL treatment. SAL treatment alone was also demonstrated to improve the survival of infected zebrafish larvae, an effect that was amplified when combining SAL treatment with isoniazid or rifampicin. Interestingly, the reduced bacterial burden and improved survival rate under SAL treatment were compromised in tnfα-deficient embryos which suggests a requirement of Tnfα signaling on the anti-mycobacterial effects of SAL. In summary, this study provides not only the cellular and molecular mechanisms for the host anti-mycobacterial effects of the Tibetan medicine SAL but also proof of concept that combined application of SAL with traditional first-line anti-TB drugs could be a novel strategy to improve treatment efficacy.https://www.frontiersin.org/articles/10.3389/fphar.2022.936295/fullmycobacteriumsalidrosidezebrafishinnate immunityneutrophilmacrophage |
| spellingShingle | Shumei He Hongyan Fan Hongyan Fan Bin Sun Meipan Yang Hongxu Liu Hongxu Liu Jianwei Yang Jianwei Yang Jianxin Liu Jianxin Liu Sizhu Luo Sizhu Luo Zihan Chen Zihan Chen Jing Zhou Jing Zhou Lu Xia Shulin Zhang Shulin Zhang Bo Yan Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish Frontiers in Pharmacology mycobacterium salidroside zebrafish innate immunity neutrophil macrophage |
| title | Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| title_full | Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| title_fullStr | Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| title_full_unstemmed | Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| title_short | Tibetan medicine salidroside improves host anti-mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| title_sort | tibetan medicine salidroside improves host anti mycobacterial response by boosting inflammatory cytokine production in zebrafish |
| topic | mycobacterium salidroside zebrafish innate immunity neutrophil macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.936295/full |
| work_keys_str_mv | AT shumeihe tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT hongyanfan tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT hongyanfan tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT binsun tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT meipanyang tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT hongxuliu tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT hongxuliu tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jianweiyang tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jianweiyang tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jianxinliu tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jianxinliu tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT sizhuluo tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT sizhuluo tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT zihanchen tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT zihanchen tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jingzhou tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT jingzhou tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT luxia tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT shulinzhang tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT shulinzhang tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish AT boyan tibetanmedicinesalidrosideimproveshostantimycobacterialresponsebyboostinginflammatorycytokineproductioninzebrafish |