Salvianolic acid B protects hepatocytes from H<sub>2</sub>O<sub>2</sub>injury by stabilizing the lysosomal membrane

Yan, Xiaofeng; Zhao, Pei; Ma, Dongyan; Jiang, Yi-Lu; Luo, Jiaojiao; Liu, Liu; Wang, Xiaoling

doi:10.3748/wjg.v23.i29.5333

Cited by 23 publications

(24 citation statements)

References 47 publications

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“…ROS can also damage mitochondria and induce apoptosis by affecting lysosomal membrane permeability to release of hydrolase (Gao C. et al, 2014). In the H 2 O 2 -induced apoptosis of BNL CL.2, a mouse liver cell line, Sal B can stabilize lysosomal membranes by increasing the expression of lysosomal-associated membrane protein 1 and antagonizing cathepsin B/D leakage into the cytoplasm (Yan et al, 2017). These results indicate that both the death receptor pathway and the mitochondrial pathway are related to excess ROS overdose, and the inhibitory effect of Sal B on these two classical apoptotic pathways may be a continuation of its antioxidant effect.…”

Section: Classical Apoptotic Pathwaymentioning

confidence: 99%

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Xiao¹,

Liu²,

Mu³

et al. 2020

Front. Pharmacol.

103

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Salvianolic acid B (Sal B) is one of the main active ingredients of Salvia miltiorrhiza, with strong antioxidant effects. Recent findings have shown that Sal B has anti-inflammatory, anti-apoptotic, anti-fibrotic effects and can promote stem cell proliferation and differentiation, and has a beneficial effect on cardiovascular and cerebrovascular diseases, aging, and liver fibrosis. Reactive oxygen species (ROS) include oxygen free radicals and oxygen-containing non-free radicals. ROS can regulate cell proliferation, survival, death and differentiation to regulate inflammation, and immunity, while Sal B can scavenge oxygen free radicals by providing hydrogen atoms and reduce the production of oxygen free radicals and oxygen-containing non-radicals by regulating the expression of antioxidant enzymes. The many pharmacological effects of Sal B may be closely related to its elimination and inhibition of ROS generation, and Nuclear factor E2-related factor 2/Kelch-like ECH-related protein 1 may be the core link in its regulation of the expression of antioxidant enzyme to exert its antioxidant effect. What is confusing and interesting is that Sal B exhibits the opposite mechanisms in tumors. To clarify the specific target of Sal B and the correlation between its regulation of oxidative stress and energy metabolism homeostasis will help to further understand its role in different pathological conditions, and provide a scientific basis for its further clinical application and new drug development. Although Sal B has broad prospects in clinical application due to its extensive pharmacological effects, the low bioavailability is a serious obstacle to further improving its efficacy in vivo and promoting clinical application. Therefore, how to improve the availability of Sal B in vivo requires the joint efforts of many interdisciplinary subjects.

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Section: Classical Apoptotic Pathwaymentioning

confidence: 99%

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Xiao¹,

Liu²,

Mu³

et al. 2020

Front. Pharmacol.

103

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“…As previously reported, H 2 O 2 treatment induced lysosome destabilization. 34 We next investigated the effects of PTL on the lysosomes damage. It is known that lysosomotropic reagent LLME induces lysosomal membrane permeabilization, 35 but the PTL actions in LLMEinduced lysosomes damage has not been investigated.…”

Section: Ptl Prevents H 2 O 2 -Induced Lysosomes Damage In C2c12 Cellsmentioning

confidence: 99%

Parthenolide regulates oxidative stress‐induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts

Ren

et al. 2019

J of Cellular Biochemistry

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Muscle redox disturbances and oxidative stress have emerged as a common pathogenetic mechanism and potential therapeutic intervention in some muscle diseases. Parthenolide (PTL), a sesquiterpene lactone found in large amounts in the leaves of feverfew, possesses anti‐inflammatory, anti‐migraine, and anticancer properties. Although PTL was reported to alleviate cancer cachexia and improve skeletal muscle characteristics in a cancer cachexia model, its actions on oxidative stress‐induced damage in C2C12 myoblasts have not been reported and the regulatory mechanisms have not yet been defined. In our study, PTL attenuated H2O2‐induced growth inhibition and morphological changes. Furthermore, PTL exhibited scavenging activity against reactive oxygen species and protected C2C12 cells from apoptosis in response to H2O2. Meanwhile, PTL suppressed collapse of the mitochondrial membrane potential, thereby contributing to normalizing H2O2‐induced autophagy flux and mitophagy, correlating with inhibiting degradation of mitochondrial marker protein TIM23, the increase in LC3‐II expression and the reduction of mitochondria DNA. Besides its protective effect on mitochondria, PTL also prevented H2O2‐induced lysosomes damage in C2C12 cells. In addition, the phosphorylation of p53, cathepsin B, and Bax/Bcl‐2 protein levels, and the translocation of Bax from the cytosol to mitochondria induced by H2O2 in C2C12 cells was significantly reduced by PTL. In conclusion, PTL modulates oxidative stress‐induced mitophagy and protects C2C12 myoblasts against apoptosis, suggesting a potential protective effect against oxidative stress‐associated skeletal muscle diseases.

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“…Although Sal B has been reported a variety of bene cial metabolic effects including ameliorated the histopathological alterations of pancreas, increased muscle glycogen content, increased p-AMPK protein expression in skeletal muscle and liver; increased protein expressions of PPARαand p-ACC in liver. [17,18] Our study showed that Sal B reduced intracellular accumulation of LDs and TG level whereas stimulated autophagosome formation by increasing expression of autophagosome formation marker LC3 II and decreasing autophagy substrates marker p62 expression in hepatocytes. Meanwhile, Beclin-1, another aytophagy biomarker which mainly activated autophagy by formation of class III PI3-kinase complex to stimulate ATG proteins, was found signi cantly higher expression in Sal B treated hepatocytes.…”

Section: Discussionmentioning

confidence: 63%

“…[13][14][15][16] In hepatocytes, Sal B has been reported a strong ability to protect cells from injury induced by oxidative stress, in ammation and enhance hepatic differentiation. [17][18][19] However, the effect of Sal B on improving hepatic lipid disorder is rarely reported. In this study, we interestingly found that Sal B could stimulated hepatic autophagy while reduced lipid accumulation in hepatocyte, which indicated a possible mechanism for Sal B improved lipid disorder and contributed to metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

Salvianolic acid B ameliorates hepatocyte lipid droplet accumulation via stimulation of autophagy

Shi

Yuan

Yan

et al. 2020

Preprint

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Salvianolic acid B (Sal B) the most abundant bioactive member in Salvia miltiorrhiza and has been reported lots of benefits on the treatment of cardio-cerebral vascular diseases and metabolic diseases. Lipid droplets are dynamic organelles, excessive lipid droplets accumulation in liver caused fatty liver disease. In this study, we are interested in the effect of Sal B on hepatic lipid accumulation and its possible mechanism. We found Sal B treatment significantly decreased lipid accumulation and TG level in primary hepatocytes. Meanwhile, we discovered Sal B significantly stimulated hepatic autophagy. Then we used autophagy inhibitor 3-MA and reveled that Sal B showed little effect on improving hepatic lipid accumulation when autophagy was inhibited, which indicated Sal B reduced cellular lipid accumulation through activating autophagy. This study demonstrates Sal B ameliorate hepatic lipid accumulation through activation of autophagy. These findings contribute to its benefit on liver disease related to hepatic lipid accumulation and hepatic autophagy.

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Salvianolic acid B protects hepatocytes from H₂O₂injury by stabilizing the lysosomal membrane

Cited by 23 publications

References 47 publications

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Parthenolide regulates oxidative stress‐induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts

Salvianolic acid B ameliorates hepatocyte lipid droplet accumulation via stimulation of autophagy

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Salvianolic acid B protects hepatocytes from H2O2injury by stabilizing the lysosomal membrane

Cited by 23 publications

References 47 publications

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Pharmacological Effects of Salvianolic Acid B Against Oxidative Damage

Parthenolide regulates oxidative stress‐induced mitophagy and suppresses apoptosis through p53 signaling pathway in C2C12 myoblasts

Salvianolic acid B ameliorates hepatocyte lipid droplet accumulation via stimulation of autophagy

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Salvianolic acid B protects hepatocytes from H₂O₂injury by stabilizing the lysosomal membrane