High-Throughput Electrophysiology Screen Revealed Cardiotoxicity of Strychnine by Selectively Targeting hERG Channel

2018 ◽  
Vol 46 (08) ◽  
pp. 1825-1840 ◽  
Author(s):  
Taiyi Wang ◽  
Xiaonan Chen ◽  
Jiahui Yu ◽  
Qunqun Du ◽  
Jie Zhu ◽  
...  

Although the efficacy and the health care advantages of Chinese herbal medicine (CHM) have become increasingly recognized worldwide, the potential side effects and toxicity still restrict its broader application. This study established and applied an integrated platform anchored on automatic patch clamp system to screen and evaluate a collection of CHM extracts, compositions and monomeric compounds for in vitro cardiac toxicity. Of 1036 CHM samples screened, 2.79% significantly inhibited hERG channel activity. Among them, Strychnine was identified for the first time as a potent hERG inhibitor with an IC[Formula: see text] of [Formula: see text]M in comparison to that of Dofetilide at [Formula: see text]M and Quinidine at [Formula: see text]M. Langendorff-perfusion experiments confirmed that strychnine increased QT interphase from [Formula: see text][Formula: see text]ms to [Formula: see text][Formula: see text]ms and decreased heart rates from [Formula: see text][Formula: see text]bmp to [Formula: see text][Formula: see text]bmp in isolated rat hearts. The cardiac toxicity effect of strychnine appears to be specific to hERG channel since an in vitro multiplex imaging analysis showed that it did not affect cellular phenotypes such as cell vitality, nucleus area, mitochondria mass and function, nor intracellular calcium in rat primary myocytes. This integrated high-throughput hERG patch clamp and high-content multi-parameter imaging cardiac toxicity screen approach should be useful for large-scale preclinical evaluation of complex Chinese herbal medicine.

2019 ◽  
Vol 20 (2) ◽  
pp. 138-146 ◽  
Author(s):  
Zhi Liu ◽  
Xin He ◽  
Lili Wang ◽  
Yunhua Zhang ◽  
Yue Hai ◽  
...  

Background:Due to the special nature of Chinese Herbal medicine and the complexity of its clinical use, it is difficult to identify and evaluate its toxicity and resulting herb induced liver injury (HILI).Methods:First, the database would provide full profile of HILI from the basic ingredients to clinical outcomes by the most advanced algorithms of artificial intelligence, and it is also possible that we can predict possibilities of HILI after patients taking Chinese herbs by individual patient evaluation and prediction. Second, the database would solve the chaos and lack of the relevant data faced by the current basic research and clinical practice of Chinese Herbal Medicine. Third, we can also screen the susceptible patients from the database and thus prevent the accidents of HILI from the very beginning.Results:The Roussel Uclaf Causality Assessment Method (RUCAM) is the most accepted method to evaluate DILI, but at present before using the RUCAM evaluation method, data resource collection and analysis are yet to be perfected. Based on existing research on drug-metabolizing enzymes mediating reactive metabolites (RMs), the aim of this study is to explore the possibilities and methods of building multidimensional hierarchical database composing of RMs evidence library, Chinese herbal evidence library, and individualized reports evidence library of herb induced liver injury HILI.Conclusion:The potential benefits lie in its ability to organize, use vast amounts of evidence and use big data mining techniques at the center for Chinese herbal medicine liver toxicity research, which is the most difficult key point of scientific research to be investigated in the next few years.


1986 ◽  
Vol 14 (03n04) ◽  
pp. 157-160 ◽  
Author(s):  
Akira Miyake ◽  
Jin-Woo Lee ◽  
Keiichi Tasaka ◽  
Shirou Ohtsuka ◽  
Toshihiro Aono

For examination of the effect on luteinizing hormone (LH) release of Wen-Jing-Tang, a traditional Chinese herbal medicine, the pituitary from normal female rats in diestrus was perifused alone or in sequence with the mediobasal hypothalamus (MBH) in a sequential double-chamber perifusion system. Wen-Jing-Tang at 5 or 500 μg/ml induced significant LH release (60-95 % increase) from the pituitary in series with the MBH, but had no effect on LH release from the pituitary perifused alone. These data suggest that Wen-Jing-Tang induces LH release from the pituitary through hypothalamic LH-RH.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mu-Lin Chiu ◽  
Yu-Lung Hsu ◽  
Chao-Jung Chen ◽  
Te-Mao Li ◽  
Jian-Shiun Chiou ◽  
...  

Aplastic Anemia (AA) is a rare but fatal hematologic disease that may occur at any age and especially higher in Asia. We investigated whether Chinese herbal medicine (CHM) is beneficial to AA patients as a complementary therapy using a nationwide population-based database in Taiwan between 2000–2016. Patient survival was estimated by Kaplan‒Meier survival analyses and Cox proportional-hazard model. CHM-users presented lower risks of overall and anemia-related mortalities when compared to non-users. The risk of overall mortality for CHM-users in AA patients was 0.70-fold [adjusted hazard ratio (aHR): 0.70, 95% confidence interval (CI): 0.66-0.74, p < 0.001). The risk of anemia-related mortality was lower in CHM-users when compared to non-users (aHR: 0.46, 95% CI: 0.32-0.67, p < 0.001). The association rule analysis revealed that CHM pairs were Ban-Zhi-Lian (BZL; Scutellaria barbata D. Don)→Bai-Hua-She-She-Cao (BHSSC; Oldenlandia diffusa (Willd.) Roxb.), followed by Dang-Gui (DG; Angelica sinensis (Oliv.) Diels)→Huang-Qi (HQi; Astragalus membranaceus (Fisch.) Bunge), and Xian-He-Cao (XHC; Agrimonia pilosa f. borealis (Kitag.) Chu)→Gui-Pi-Tang (GPT). Network analysis showed that BZL, BHSSC, DG, HQi, XHC, GPT, and Dan-Shen (DanS; Salvia miltiorrhiza var. charbonnelii (H.Lév.) C.Y.Wu) were commonly used CHMs for AA patients. Therefore, further studies for these commonly prescribed herbs are needed in functional investigations in hematopoiesis-stimulating effect and large-scale randomized controlled trials (RCT) in bone marrow failure related diseases.


Phytomedicine ◽  
2021 ◽  
pp. 153876
Author(s):  
Shu-Chun Liu ◽  
Meei-Ling Sheu ◽  
Yi-Ching Tsai ◽  
Yu-Chin Lin ◽  
Ching-Wen Chang ◽  
...  

1989 ◽  
Vol 17 (03n04) ◽  
pp. 171-175
Author(s):  
Ting-Xin Zhang ◽  
David K. Pomerantz

San Zhuang Wan (SZW) is a traditional Chinese herbal medicine used to treat male impotence. The mechanism of its therapeutic effect is not known nor have any of its potential physiologic actions been investigated. We examined the effect of SZW adminstered by gavage, on the reproductive system of the prepubertal male rat. After 10 days treatment of 21-day-old rats the concentration of testosterone in serum and testicular weight and decrease whereas the serum concentration of luteinizing hormone (LH) had significantly increased. When administered to gonadectomized rats SZW partially restored the weight of the accessory sex organs and concentration of LH toward normal, but serum androgen concentration was not changed. In vitro assessment of fragments of testicular tissue or purified Leydig cells for responsiveness to maximal doses of LH or cyclic AMP showed that SWZ significantly reduced testosterone secretion in response to either stimulant. The data demonstrate that SWZ has potent effects on the reproductive axis of the pubertal male rat. At least one locus for such action is on the Leydig cell at a point distal to the formation of cyclic AMP. Further study is necessary to determine whether these effects could be involved with or independent of the mechanism of the therapeutic action of SZW.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tsung-Jung Ho ◽  
Shinn-Jong Jiang ◽  
Guang-Huey Lin ◽  
Tzong Shiun Li ◽  
Lih-Ming Yiin ◽  
...  

“Jinchuang ointment” is a traditional Chinese herbal medicine complex for treatment of incised wounds. For more than ten years, it has been used at China Medical University Hospital (Taichung, Taiwan) for the treatment of diabetic foot infections and decubitus ulcers. Three different cases are presented in this study. “Jinchuang” ointment is a mixture of natural product complexes from nine different components, making it difficult to analyze its exact chemical compositions. To further characterize the herbal ingredients used in this study, the contents of reference standards present in a subset of the ointment ingredients (dragon’s blood, catechu, frankincense, and myrrh) were determined by HPLC. Twoin vitrocell based assay platforms, wound healing and tube formation, were used to examine the biological activity of this medicine. Our results show that this herbal medicine possesses strong activities including stimulation of angiogenesis, cell proliferation, and cell migration, which provide the scientific basis for its clinically observed curative effects on nonhealing diabetic wounds.


Sign in / Sign up

Export Citation Format

Share Document