Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis

Chia Ying Lien, Tai Yuan Chuang, Chih Hsiang Hsu, Ching Lung Lin, Sheue Er Wang, Shuenn Jyi Sheu, Chiang Ting Chien, Chung Hsin Wu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Objective: This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods: Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results: In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with the herbal formula B307. Conclusion: Our results revealed that oral treatment with the herbal formula B307 may provide cardioprotection in DOX-treated mice via suppressing oxidative stress, inflammation, and apoptosis in heart tissue. We believe that the herbal formula B307 may be developed as a potential alternative treatment for cancer patients under DOX treatment.

Original languageEnglish
Pages (from-to)1193-1210
Number of pages18
JournalOncoTargets and Therapy
Volume8
DOIs
Publication statusPublished - 2015 Jan 1

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Doxorubicin
Oxidative Stress
Apoptosis
Inflammation
Therapeutics
Neoplasms
bcl-X Protein
Cardiotoxicity
B307 herbal formula
Caspase 12
Placebos
Body Weight
Neurotrophin 3
Calpain
Mortality
Caspase 9
Nitric Oxide Synthase Type III
B-Cell Lymphoma
Caspase 3
Echocardiography

Keywords

  • Apoptosis
  • Cardiac protection
  • Chinese herbal formula
  • Doxorubicin
  • Inflammation
  • Mouse model
  • Oxidative stress

ASJC Scopus subject areas

  • Oncology
  • Pharmacology (medical)

Cite this

Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis. / Lien, Chia Ying; Chuang, Tai Yuan; Hsu, Chih Hsiang; Lin, Ching Lung; Wang, Sheue Er; Sheu, Shuenn Jyi; Chien, Chiang Ting; Wu, Chung Hsin.

In: OncoTargets and Therapy, Vol. 8, 01.01.2015, p. 1193-1210.

Research output: Contribution to journalArticle

Lien, Chia Ying ; Chuang, Tai Yuan ; Hsu, Chih Hsiang ; Lin, Ching Lung ; Wang, Sheue Er ; Sheu, Shuenn Jyi ; Chien, Chiang Ting ; Wu, Chung Hsin. / Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis. In: OncoTargets and Therapy. 2015 ; Vol. 8. pp. 1193-1210.
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abstract = "Objective: This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods: Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results: In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with the herbal formula B307. Conclusion: Our results revealed that oral treatment with the herbal formula B307 may provide cardioprotection in DOX-treated mice via suppressing oxidative stress, inflammation, and apoptosis in heart tissue. We believe that the herbal formula B307 may be developed as a potential alternative treatment for cancer patients under DOX treatment.",
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AU - Lin, Ching Lung

AU - Wang, Sheue Er

AU - Sheu, Shuenn Jyi

AU - Chien, Chiang Ting

AU - Wu, Chung Hsin

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N2 - Objective: This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods: Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results: In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with the herbal formula B307. Conclusion: Our results revealed that oral treatment with the herbal formula B307 may provide cardioprotection in DOX-treated mice via suppressing oxidative stress, inflammation, and apoptosis in heart tissue. We believe that the herbal formula B307 may be developed as a potential alternative treatment for cancer patients under DOX treatment.

AB - Objective: This study aimed to investigate whether the herbal formula B307 could alleviate doxorubicin (DOX)-induced acute cardiotoxicity. If so, we further unraveled possible molecular mechanisms of cardiac protection under treatment with the herbal formula B307. Methods: Before the animal experiment, we examined relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307. To test whether oral treatment with the herbal formula B307 could alleviate cardiotoxicity, equal volumes of B307 (50 mg/kg) or saline (sham treatment) were administered to 20-week-old male mice once daily for 14 consecutive days. Then, DOX (10 mg/kg; ip) was administered to male mice under B307 and sham treatments at 22–23 weeks of age. Cardiac functions in these mice were assessed via echocardiography at 23–24 weeks of age. Then, expressions of oxidative stress, inflammation, and apoptosis-related proteins were examined in the heart tissue by immunohistochemistry and Western blotting at 24–25 weeks of age. Apart from this, mortality rate and body weight were measured during the experiment. Results: In vitro, the relative viabilities of Huh7 cancer cells under treatment with the herbal formula B307 had shown no obvious change at doses of 10–160 ng/mL. Furthermore, the relative viabilities of Huh7 cancer cells were significantly reduced under DOX treatment but showed no significant change under DOX only and DOX plus B307 treatment. In vivo, the mortality rate, body weight, and cardiac function of DOX-treated mice were obviously improved under oral treatment with the herbal formula B307. Furthermore, cardiac expressions of endothelial nitric oxide synthase, superoxide dismutase 2, and B-cell lymphoma 2 were significantly enhanced, but tumor necrosis factor alpha, NFKB1 (p50 and its precursor, p105), neurotrophin-3, Bcl-2associated X protein, calpain, caspase 12, caspase 9, and caspase 3 were significantly suppressed in DOX-treated mice under oral treatment with the herbal formula B307. Conclusion: Our results revealed that oral treatment with the herbal formula B307 may provide cardioprotection in DOX-treated mice via suppressing oxidative stress, inflammation, and apoptosis in heart tissue. We believe that the herbal formula B307 may be developed as a potential alternative treatment for cancer patients under DOX treatment.

KW - Apoptosis

KW - Cardiac protection

KW - Chinese herbal formula

KW - Doxorubicin

KW - Inflammation

KW - Mouse model

KW - Oxidative stress

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