scholarly journals Efficiently Capturing Mitochondria-Targeted Constituents with Hepatoprotective Activity from Medicinal Herbs

2019 ◽  
Vol 2019 ◽  
pp. 1-18 ◽  
Author(s):  
Xing-Xin Yang ◽  
Li Liang ◽  
Xin Liu ◽  
Feng-Jiao Li ◽  
Jin-Cai Dong ◽  
...  

Targeting mitochondria as a hepatic-protective strategy has gained attention, because of their important roles in energy production, adjustment of apoptosis, and generation of reactive oxygen species. To promote the discovery of natural mitochondria-targeted hepatic-protectants, we established a hepatocellular mitochondria-based capturing method by coupling affinity ultrafiltration with liquid chromatography/mass spectrometry (LC/MS), which is suitable for identifying mitochondrial ligands from medicinal herbs (MHs). After evaluating the feasibility of the method, it was applied for capturing mitochondria-targeting constituents from Peucedani Radix extract. A total of 10 active compounds were identified by LC/MS, all of which were newly identified mitochondrial ligands. The mitochondria-remedying activity of 4 of the 10 hits was confirmed by pharmacological tests in vitro. Additionally, the hepatic-protective abilities of 4 hits were verified in both carbon tetrachloride-damaged liver L02 cells and mice. These results indicated that the method could be used for identifying hepatic mitochondria-targeting constituents in MHs, which might be beneficial for hepatic-protective development.

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Li Liang ◽  
Feng-Jiao Li ◽  
Xin Liu ◽  
Jian-Kang Mu ◽  
Xi Wang ◽  
...  

In recent years, the incidence of diseases associated with hepatic injury has increased in prevalence. Targeting the mitochondria to protect liver function has gained momentum due to their central role in energy production, apoptotic cell death, oxidative stress, calcium homeostasis, and lipid metabolism. In this study, we employed a hepatic mitochondria-based centrifugal ultrafiltration/liquid chromatography/mass spectrometry method (CM-HMC) to identify hepatic mitochondria ligands from medicinal herbs (MHs) including Notopterygii Rhizoma et Radix (NRR) that possess hepatic-protective effects. A total of 4 newly identified mitochondrial ligands were successfully identified by CM-HMC. The mitochondria-regulating activities of 3 of the 4 hits were confirmed using isolated mitochondria. The hepatic-protective effects of one of these hits were validated in carbon tetrachloride-damaged human liver L02 cell models. We have thus identified new natural hepatic-protectants that enhance our understanding of the hepatic-protective mechanisms of MHs. CM-HMC was proven to efficiently screen for mitochondrial ligands from MHs.


2010 ◽  
Vol 7 (2) ◽  
pp. 203-212 ◽  
Author(s):  
Nadejda Rozanova (Torshina) ◽  
Jin Z. Zhang ◽  
Diane E. Heck

Catalytic therapy (CT) is a cancer treatment modality based on the generation of reactive oxygen species (ROS) using a combination of substrate molecules and a catalyst. The most frequently used substrate/catalyst pair is ascorbate/Co phthalocyanine (PcCo). In the present work, herb extracts containing pigments have been studied as a catalyst in place of PcCo. Extracts from herbs are expected to have efficiency comparable with that of phthalocyanines but as natural products, to exhibit fewer side effects. The present studies demonstrate that a combined use of ascorbate and herbal extracts results in ROS production and a significant decrease in the number of cancer cells after a singlein vitrotreatment. Treatment with ascorbate in conjunction with extracts prepared from several medicinal herbs stimulated apoptosis and disrupted the cell cycle. The number of cells accumulating in the sub-G0/G1 stage of the cell cycle was increased 2- to 7-fold, and cells in G2/M increased 1.5- to 20-fold, indicating that the treatment protocol was highly effective in suppressing DNA synthesis and potentially reflecting DNA damage in the tumor cells. In addition, 20–40% of the cells underwent apoptosis within 24 h of completing treatment. Our results suggest that herbal extracts can function as CT catalysts in the treatment of cancer.


Author(s):  
Phung N. Thai ◽  
Lu Ren ◽  
Wilson Xu ◽  
James Overton ◽  
Valeriy Timofeyev ◽  
...  

Abstract Purpose Nonsteroidal anti-inflammatory drugs (NSAIDs) are among one of the most commonly prescribed medications for pain and inflammation. Diclofenac (DIC) is a commonly prescribed NSAID that is known to increase the risk of cardiovascular diseases. However, the mechanisms underlying its cardiotoxic effects remain largely unknown. In this study, we tested the hypothesis that chronic exposure to DIC increases oxidative stress, which ultimately impairs cardiovascular function. Methods and Results Mice were treated with DIC for 4 weeks and subsequently subjected to in vivo and in vitro functional assessments. Chronic DIC exposure resulted in not only systolic but also diastolic dysfunction. DIC treatment, however, did not alter blood pressure or electrocardiographic recordings. Importantly, treatment with DIC significantly increased inflammatory cytokines and chemokines as well as cardiac fibroblast activation and proliferation. There was increased reactive oxygen species (ROS) production in cardiomyocytes from DIC-treated mice, which may contribute to the more depolarized mitochondrial membrane potential and reduced energy production, leading to a significant decrease in sarcoplasmic reticulum (SR) Ca2+ load, Ca2+ transients, and sarcomere shortening. Using unbiased metabolomic analyses, we demonstrated significant alterations in oxylipin profiles towards inflammatory features in chronic DIC treatment. Conclusions Together, chronic treatment with DIC resulted in severe cardiotoxicity, which was mediated, in part, by an increase in mitochondrial oxidative stress.


Planta Medica ◽  
2015 ◽  
Vol 81 (16) ◽  
Author(s):  
Z Kokanova-Nedialkova ◽  
M Kondeva-Burdina ◽  
V Tzankova ◽  
S Nikolov ◽  
J Heilmann ◽  
...  

2019 ◽  
Vol 18 (4) ◽  
pp. 297-302
Author(s):  
Sriset Yollada ◽  
Chatuphonprasert Waranya ◽  
Jarukamjorn Kanokwan

Bergenin is a C-glucoside derivative of gallic acid but its antioxidant and hepatoprotective effects have not previously been compared with gallic acid. Male ICR mice were administered bergenin (10, 50, and 250 mg/kg/day) or gallic acid (100 mg/kg/day) for 7 consecutive days before a single administration of ethanol (5 g/kg). Liver sections were histopathologically examined. Aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels were determined in plasma. Total glutathione, reduced glutathione, and oxidized glutathione levels were determined in liver homogenates. Ethanol induced hepatic injury with prominent histopathological markers including nuclear pyknosis and necrotic areas and this accorded with increases in the plasma levels of aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde. Moreover, ethanol disturbed hepatic glutathione homeostasis by reducing glutathione stores. Hepatic injury in the ethanol-induced mice was prevented with bergenin and gallic acid by significant decreases in plasma aspartate aminotransferase, alanine aminotransferase, reactive oxygen species, and malondialdehyde levels and restoration of the hepatic glutathione profile through an increase in the reduced glutathione/oxidized glutathione ratio. Bergenin at 10 mg/kg/day showed comparable hepatoprotective activity to gallic acid in an ethanol-induced mouse model of oxidative stress. Therefore, bergenin might be a promising candidate for further development as a novel hepatoprotective product.


Author(s):  
Anatolii Onishchenko ◽  
Valeriy Myasoedov ◽  
Svetlana Yefimova ◽  
Oksana Nakonechna ◽  
Volodymyr Prokopyuk ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2529
Author(s):  
Haeyeop Kim ◽  
Woo Seok Yang ◽  
Khin Myo Htwe ◽  
Mi-Nam Lee ◽  
Young-Dong Kim ◽  
...  

Dipterocarpus tuberculatus Roxb. has been used traditionally as a remedy for many diseases, especially inflammation. Therefore, we analyzed and explored the mechanism of the anti-inflammatory effect of a Dipterocarpus tuberculatus Roxb. ethanol extract (Dt-EE). Dt-EE clearly and dose-dependently inhibited the expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β in lipopolysaccharide (LPS)-treated RAW264.7 cells. Also, Dt-EE suppressed the activation of the MyD88/TRIF-mediated AP-1 pathway and the AP-1 pathway related proteins JNK2, MKK4/7, and TAK1, which occurred as a result of inhibiting the kinase activity of IRAK1 and IRAK4, the most upstream factors of the AP-1 pathway. Finally, Dt-EE displayed hepatoprotective activity in a mouse model of hepatitis induced with LPS/D-galactosamine (D-GalN) through decreasing the serum levels of alanine aminotransferase and suppressing the activation of JNK and IRAK1. Therefore, our results strongly suggest that Dt-EE could be a candidate anti-inflammatory herbal medicine with IRAK1/AP-1 inhibitory and hepatoprotective properties.


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