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Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach.

ABSTRACT: There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional "glucose/galactose" assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assessed the mitochondrial toxicity of TCM injections. Four of the 35 TCM injections, including Xiyanping, Dengzhanhuasu, Shuanghuanglian, and Yinzhihuang, significantly reduced cellular ATP production in galactose medium in the first assay, and presented less cytotoxic in the respiration deficient cells in the second assay, indicating that they have mitochondrial toxicity. Furthermore, we identified scutellarin, rutin, phillyrin, and baicalin could be the potential mitochondrial toxic ingredients in the 4 TCM injections by combining molecular docking analysis with experimental validation. Collectively, the dual in vitro approach is worth applying to the safety evaluation of more TCM products, and mitochondrial toxic TCM injections and ingredients found in this study deserve more attention.

SUBMITTER: Shen Y

PROVIDER: S-EPMC9667049 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach.

Shen Yunfu Y Guo Kaiqiang K Ma Aijun A Huang Zhe Z Du Jingjing J Chen Junhe J Lin Qianyu Q Wei Chengming C Wang Zi Z Zhang Fuming F Zhang Juan J Lin Wanjun W Feng Na N Ma Wenzhe W

Frontiers in pharmacology 20221102

There are technical obstacles in the safety evaluation of traditional Chinese medicine (TCM) injections due to their complex chemical nature and the lack of rapid and accurate in vitro methods. Here, we established a dual in vitro mitochondrial toxicity approach combing the conventional "glucose/galactose" assay in HepG2 cells with the cytotoxic assay in mitochondrial respiration deficient cells. Using this dual in vitro approach, for the first time, we systematically assess ...[more]

PMID: 36408232

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Project description:Background: Hypertension, a risk factor for cardiovascular events, is often associated with chronic kidney disease. This is called hypertensive nephropathy (HN), which negatively affects physical fitness and body mass, leading to economic burden. Traditional Chinese medicine injections (TCMIs) are common traditional Chinese-patent medicine preparations in China. There was a lack of evidence to prove which TCMIs combine with ADs (TCMIs+ADs) may be a therapeutic option for HN. Thus, we systematically reviewed the efficacy and safety of various TCMIs + ADs in patients with HN. Methods: We conducted a comprehensive search of PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP information resource integration service platform databases for relevant Chinese- and English-language randomized controlled trials (RCTs) published from database inception until May 2021. Literature screening, data extraction, and quality assessment was performed by two reviewers independently but using the same criteria. We performed the effect modeling to analyze the data for all outcomes and ranked each intervention using the P-score. Furthermore, sensitivity analysis, meta-regression, and funnel plots were used to test the stability, heterogeneity, and publication bias, respectively. Results: We included 69 RCTs with 6373 patients and including six TCMIs + ADs. Network analysis indicated that the ginkgo leaf extract and dipyridamole combined with ADs (GLED + ADs) was the most efficacious in terms of 24-h urinary protein excretion [mean difference (MD) = -0.70, 95% confidence interval (CI): -0.82 to -0.58; P-score = 1] and systolic blood pressure (MD = -12.95, 95% CI: -21.03 to -4.88; P-score = 0.88), whereas the salvianolate combined with ADs (SA + ADs) showed the highest effectiveness for diastolic blood pressure (MD = -6.88, 95% CI: -10.55 to -3.21; P-score = 0.9). Based on the combined P-score of network meta-analysis results (88% and 85.26%) and sensitivity analysis results (72% and 71.54%), the biplots showed that the GLED + ADs was the most efficacious intervention in all TCMIs + ADs for primary outcomes, followed by the SA + ADs and sodium tanshinone IIA sulfonate combined with ADs (STS + ADs). There was no significant difference in terms of safety between TCMIs + ADs and ADs alone. Conclusion: Of all the TCMIs + ADs, GLED + ADs, SA + ADs, and STS + ADs may demonstrate a higher efficacy than ADs alone for HN. Weighing with the potential benefits and limitations in methodology, potential heterogeneity and outcomes, we should use various TCMIs with caution in clinical practice. Nevertheless, additional high-quality RCTs are warranted and future research should focus on the clinical value of core outcomes to confirm the effectiveness and safety of TCMIs for HN. Systematic Review Registration: clinicaltrials.gov, identifier CRD42020205358.

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF), acutely or slowly progressing into irreversible pulmonary disease, causes severe damage to patients' lung functions, as well as death. In China, Chinese medicine injections (CMIs) have been generally combined with Western medicine (WM) to treat IPF, which are safe and effective. This study aimed to systematically compare the efficacy of 14 CMIs combined with WM in the treatment of IPF based on a systematic review and network meta-analysis (NMA).Material and methodsPubMed, Web of Science, Embase, Cochrane Library, MEDLINE, and Chinese databases, including the China National Knowledge Infrastructure, Wanfang Database, Scientific Journal Database, and China Biology Medicine Database were searched from inception to October 31, 2021. The inclusion criterion was randomized controlled trials (RCTs) on CMIs with WM for treating IPF. Reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.4 software and Stata software (version 16.0) were used for the data analysis. NMA were carried out for calculating the odd ratios (ORs) with 95% confidence intervals (CI), the surface under cumulative ranking curve (SUCRA) and the probabilities of being the best.ResultsA total of 63 eligible RCTs involving 14 CMIs were included in this NMA. More CMIs can significantly improve the clinical effectiveness rate (CER); Shuxuening injection (SXN)+WM (OR 8.91, 95% CI 3.81-20.83), Shuxuetong injection (SXT)+WM (OR 7.36, 95% CI 3.30-16.00), Shenxiong injection (SX)+WM (OR 5.42, 95% CI 2.90-10.13), Danhong injection (DH)+WM (OR 4.06, 95% CI 2.62-6.29), and Huangqi injection (HQ)+WM (OR 3.47, 95% CI 1.55-7.77) were the top five treatment strategies. Furthermore, DH +WM ranked relatively high in the SUCRA value of the nine outcome indicators, oxygen partial pressure (PaO2) (OR -13.39; 95% CI -14.90,-11.89; SUCRA 83.7%), carbon dioxide partial pressure (PaCO2) (OR -4.77; 95% CI -5.55,-3.99; SUCRA 83.3), orced vital capacity (FVC) (OR -1.42; 95% CI -2.47,-0.36; SUCRA 73.5%), total lung capacity (TLC) (OR 0.93; 95% CI 0.51,1.36; SUCRA 89.0%), forced expiratory volume 1/ forced vital capacity (FEV1/FVC%) (OR -10.30; 95% CI -12.98,-7.62; SUCRA 72.7%), type III collagen (IIIC) (OR 13.08; 95% CI 5.11,21.05; SUCRA 54.9%), and transforming growth factor (TGF) (OR -4.22; 95% CI -6.06,-2.37; SUCRA 85.7%) respectively, which seems to indicate that DH+WM had the highest likelihood of being the best treatment.ConclusionsThis review specified several CMIs combined with WM in the treatment of IPF in China. In contrast to glucocorticoids or antioxidants, CMIs combined with WM delayed the decline in lung function, maintained oxygenation and quality of life in patients with IPF. The combined use of DH, SXN, SX, and safflower yellow sodium chloride injection (HHS) with WM exerted a more positive effect in treating IPF than WM alone. However, there were limitations to the conclusions of this study due to quality control differences in the included trials.

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Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual in vitro approach.

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Mitochondrial toxicity evaluation of traditional Chinese medicine injections with a dual <i>in vitro</i> approach.

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