Reducing oxidative stress may be important for treating pirarubicin‑induced cardiotoxicity with schisandrin B

Objective: Pirarubicin (THP), one of the anthracycline anticancer drugs, is widely used in the treatment of various cancers, but its cardiotoxicity cannot be ignored. Schisandrin B (SchB) has the ability to upregulate cellular antioxidant defense mechanism and promote mitochondrial function and antioxidant status. However, it has not been reported whether it can resist THP-induced cardiotoxicity. The aim of this study was to investigate the effect of SchB on THP cardiotoxicity and its mechanism.Methods: The rat model of cardiotoxicity induced by THP was established, and SchB treatment was performed at the same time. The changes of ECG, cardiac coefficient, and echocardiogram were observed. The changes of myocardial tissue morphology were observed by H&E staining. Apoptosis was detected by TUNEL. The levels of LDH, BNP, CK-MB, cTnT, SOD, and MDA in serum were measured to observe the heart damage and oxidative stress state of rats. The expression of cleaved-caspase 9, pro/cleaved-caspase 3, Bcl-2/Bax, and cytosol and mitochondrial Cyt C and Bax was evaluated by western blot. H9c2 cardiomyocytes were cocultured with THP, SchB, and mPTP inhibitor CsA to detect the production of ROS and verify the above signaling pathways. The opening of mPTP and mitochondrial swelling were detected by mPTP kit and purified mitochondrial swelling kit.Results: After 8 weeks, a series of cardiotoxicity manifestations were observed in THP rats. These adverse effects can be effectively alleviated by SchB treatment. Further studies showed that SchB had strong antioxidant and antiapoptotic abilities in THP cardiotoxicity.Conclusion: SchB has an obvious protective effect on THP-induced cardiotoxicity. The mechanism may be closely related to the protection of mitochondrial function, inhibition of mPTP opening, and alleviation of oxidative stress and apoptosis of cardiomyocytes.

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Schisandrin B Prevents Hind Limb from Ischemia-Reperfusion-Induced Oxidative Stress and Inflammation via MAPK/NF-κB Pathways in Rats

BioMed Research International ◽

10.1155/2017/4237973 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Ning Zhu ◽

Changhong Cai ◽

Aiming Zhou ◽

Xuyong Zhao ◽

Yijia Xiang ◽

...

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Hind Limb ◽

Ischemia Reperfusion ◽

Limb Ischemia ◽

Schisandrin B ◽

Sod Activity ◽

Neuroprotective Effects ◽

Beneficial Effects ◽

Injury Model

Schisandrin B (ScB), isolated from Schisandra chinensis (S. chinensis), is a traditional Chinese medicine with proven cardioprotective and neuroprotective effects. However, it is unclear whether ScB also has beneficial effects on rat hind limb ischemia/reperfusion (I/R) injury model. In this study, ScB (20 mg/kg, 40 mg/kg, and 80 mg/kg) was administered via oral gavage once daily for 5 days before the surgery. After 6 h ischemia and 24 h reperfusion of left hind limb, ScB reduced I/R induced histological changes and edema. ScB also suppressed the oxidative stress through decreasing MDA level and increasing SOD activity. Moreover, above changes were associated with downregulated TNF-α mRNA expression and reduced level of IL-1β in plasma. Meanwhile, ScB treatment downregulated activation of p38MAPK, ERK1/2, and NF-κB in ischemic skeletal muscle. These results demonstrate that ScB treatment could prevent hind limb I/R skeletal muscle injury possibly by attenuating oxidative stress and inflammation via p38MAPK, ERK1/2, and NF-κB pathways.

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Schisandrin B attenuates the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury via inhibition of p53 signaling in adult rats

Molecular Medicine Reports ◽

10.3892/mmr.2017.6622 ◽

2017 ◽

Vol 16 (1) ◽

pp. 533-538 ◽

Cited By ~ 11

Author(s):

D.Q. Xin ◽

Z.M. Hu ◽

H.J. Huo ◽

X.J. Yang ◽

D. Han ◽

...

Keyword(s):

Oxidative Stress ◽

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Response ◽

Traumatic Spinal Cord Injury ◽

Schisandrin B ◽

Adult Rats ◽

P53 Signaling ◽

Cord Injury

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Schisandrin B Prevents Doxorubicin Induced Cardiac Dysfunction by Modulation of DNA Damage, Oxidative Stress and Inflammation Through Inhibition of MAPK/p53 Signaling

Free Radical Biology and Medicine ◽

10.1016/j.freeradbiomed.2011.10.133 ◽

2011 ◽

Vol 51 ◽

pp. S52

Author(s):

Tetsuya Konishi ◽

Rajarajan a Thandavarayan ◽

Vijayasree V. Giridharan ◽

Somasundaram Arumugam ◽

Kenichi Watanabe

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Cardiac Dysfunction ◽

Schisandrin B ◽

P53 Signaling

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Schisandrin B: A Double-Edged Sword in Nonalcoholic Fatty Liver Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2016/6171658 ◽

2016 ◽

Vol 2016 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Pou Kuan Leong ◽

Kam Ming Ko

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Er Stress ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

Chinese Herb ◽

High Dose ◽

Schisandrin B ◽

Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit ofSchisandra chinensis(a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytesin vitroand in rodent liversin vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

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