title: Oral treatment with the herbal formula B307 alleviates cardiac toxicity in doxorubicin-treated mice via suppressing oxidative stress, inflammation, and apoptosis.
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-2-associated 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Athletics, National Taiwan University, Taipei, Taiwan.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lien
authors.affiliation: Department of Athletics, National Taiwan University, Taipei, Taiwan.
authors.forename: Tai-Yuan
authors.initials: TY
authors.lastname: Chuang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chih-Hsiang
authors.initials: CH
authors.lastname: Hsu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Ching-Lung
authors.initials: CL
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Sheue-Er
authors.initials: SE
authors.lastname: Wang
authors.affiliation: Brion Research Institute of Taiwan, New Taipei City, Taiwan.
authors.forename: Shuenn-Jyi
authors.initials: SJ
authors.lastname: Sheu
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chiang-Ting
authors.initials: CT
authors.lastname: Chien
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chung-Hsin
authors.initials: CH
authors.lastname: Wu
keywords: Chinese herbal formula; apoptosis; cardiac protection; doxorubicin; inflammation; mouse model; oxidative stress