Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway
Background: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but th...
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| Format: | Article |
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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1197433/full |
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| author | Maryam Mazhar Maryam Mazhar Guoqiang Yang Guoqiang Yang Houping Xu Yulin Liu Yulin Liu Pan Liang Pan Liang Luyin Yang Luyin Yang Roman Spáčil Hongping Shen Hongping Shen Dechou Zhang Dechou Zhang Wei Ren Wei Ren Sijin Yang Sijin Yang |
| author_facet | Maryam Mazhar Maryam Mazhar Guoqiang Yang Guoqiang Yang Houping Xu Yulin Liu Yulin Liu Pan Liang Pan Liang Luyin Yang Luyin Yang Roman Spáčil Hongping Shen Hongping Shen Dechou Zhang Dechou Zhang Wei Ren Wei Ren Sijin Yang Sijin Yang |
| author_sort | Maryam Mazhar |
| collection | DOAJ |
| description | Background: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. Purpose: To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway.Methods: Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage.Results: ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. Conclusion: ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets. |
| first_indexed | 2024-03-13T07:00:30Z |
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| spelling | doaj.art-cb769d670d7648b59a492e01c6cde31a2023-06-07T04:34:37ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-06-011410.3389/fphar.2023.11974331197433Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathwayMaryam Mazhar0Maryam Mazhar1Guoqiang Yang2Guoqiang Yang3Houping Xu4Yulin Liu5Yulin Liu6Pan Liang7Pan Liang8Luyin Yang9Luyin Yang10Roman Spáčil11Hongping Shen12Hongping Shen13Dechou Zhang14Dechou Zhang15Wei Ren16Wei Ren17Sijin Yang18Sijin Yang19National Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaResearch Center for Integrated Chinese and Western Medicine, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, Sichuan, ChinaMolecular Imaging and Therapy Research Unit, Center of Radiation Research and Medical Imaging, Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, ThailandPreventive Treatment Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaChengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, ChinaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaThe Czech Center for Traditional Chinese Medicine, Olomouc, CzechiaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaNational Traditional Chinese Medicine Clinical Research Base and Drug Research Center, the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University, Luzhou, ChinaInstitute of Integrated Chinese and Western Medicine of Southwest Medical University, Luzhou, ChinaBackground: One of the severely debilitating and fatal subtypes of hemorrhagic stroke is intracerebral hemorrhage (ICH), which lacks an adequate cure at present. The Zhilong Huoxue Tongyu (ZLHXTY) capsule has been utilized effectively since last decade to treat ICH, in some provinces of China but the scientific basis for its mechanism is lacking. Purpose: To investigate the neuroprotective role of ZLHXTY capsules for ICH-induced oxidative injury through the regulation of redox imbalance with the Nrf2 signaling pathway.Methods: Autologous blood injection model of ICH in C57BL/6J mice was employed. Three treatment groups received ZLHXTY once daily through oral gavage at doses 0.35 g/kg, 0.7 g/kg, and 1.4 g/kg, started after 2 h and continued for 72 h of ICH induction. The neurological outcome was measured using a balance beam test. Serum was tested for inflammatory markers IL-1β, IL-6, and TNF-α through ELISA, oxidative stress through hydrogen peroxide content assay, and antioxidant status by total antioxidant capacity (T-AOC) assay. Nuclear extract from brain tissue was assayed for Nrf2 transcriptional factor activity. RT-qPCR was performed for Nfe2l2, Sod1, Hmox1, Nqo1, and Mgst1; and Western blotting for determination of protein expression of Nrf2, p62, Pp62, Keap, HO1, and NQO1. Fluoro-jade C staining was also used to examine neuronal damage.Results: ZLHXTY capsule treatment following ICH demonstrated a protective effect against oxidative brain injury. Neurological scoring showed improvement in behavioral outcomes. ELISA-based identification demonstrated a significant decline in the expression of serum inflammatory markers. Hydrogen peroxide content in serum was found to be reduced. The total antioxidant capacity was also reduced in serum, but the ZLHXTY extract showed a concentration-dependent increase in T-AOC speculating at its intrinsic antioxidant potential. Nrf2 transcriptional factor activity, mRNA and protein expression analyses revealed normalization of Nrf2 and its downstream targets, which were previously elevated as a result of oxidative stress induced by ICH. Neuronal damage was also reduced markedly after ZLHXTY treatment as revealed by Fluoro-jade C staining. Conclusion: ZLHXTY capsules possess an intrinsic antioxidant potential that can modulate the ICH-induced redox imbalance in the brain as revealed by the normalization of Nrf2 and its downstream antioxidant targets.https://www.frontiersin.org/articles/10.3389/fphar.2023.1197433/fullintracerebal haemorrhagetraditional Chinese medicineNrf2 signallingredox imbalanceantioxidants |
| spellingShingle | Maryam Mazhar Maryam Mazhar Guoqiang Yang Guoqiang Yang Houping Xu Yulin Liu Yulin Liu Pan Liang Pan Liang Luyin Yang Luyin Yang Roman Spáčil Hongping Shen Hongping Shen Dechou Zhang Dechou Zhang Wei Ren Wei Ren Sijin Yang Sijin Yang Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway Frontiers in Pharmacology intracerebal haemorrhage traditional Chinese medicine Nrf2 signalling redox imbalance antioxidants |
| title | Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway |
| title_full | Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway |
| title_fullStr | Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway |
| title_full_unstemmed | Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway |
| title_short | Zhilong Huoxue Tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of Nrf2 signaling pathway |
| title_sort | zhilong huoxue tongyu capsule attenuates intracerebral hemorrhage induced redox imbalance by modulation of nrf2 signaling pathway |
| topic | intracerebal haemorrhage traditional Chinese medicine Nrf2 signalling redox imbalance antioxidants |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1197433/full |
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