Protective effect of ginsenoside Rb1 against aconitine cardiotoxicity studied by myocardial injury, action potential, and calcium signaling.

Aconitine is the main active component of Aconitum plants. Although aconitine has effects that include strengthening the heart, analgesia, anti-tumor, and immune-regulating effects, aconitine has both efficacy and toxicity, especially cardiotoxicity. Severe effects can include arrhythmia and cardiac arrest, which limits the clinical application of aconitine-containing traditional Chinese medicine. Ginsenoside Rb1(Rb1) is mainly found in plants, such as ginseng and Panax notoginseng, and has cardiovascular-protective and anti-arrhythmia effects. This study aimed to investigate the detoxifying effects of Rb1 on aconitine cardiotoxicity and the electrophysiological effect of Rb1 on aconitine-induced arrhythmia in rats. Pathological analysis, myocardial enzymatic indexes, and Western blotting were used to investigate the ameliorating effect of Rb1 on aconitine cardiotoxicity. Optical mapping was used to evaluate the effect of Rb1 on action potential and calcium signaling after aconitine-induced arrhythmia. Rb1 inhibited pathological damage caused by aconitine, decreased myocardial enzyme levels, and restored the balance of apoptotic protein expression by reducing the expression of Bax and cleaved caspase 3 and increasing the expression of Bcl-2, thereby reducing myocardial damage caused by aconitine. Rb1 also reduced the increase in heart rate caused by aconitine, accelerated action potential conduction and calcium signaling, and reduced the dispersion of action potential and calcium signal conduction. Rb1 reduced the cardiotoxicity of aconitine by attenuating aconitine-induced myocardial injury and inhibiting the aconitine-induced retardation of ventricular action potential and calcium signaling in rats.

Oxaliplatin-induced peripheral neurotoxicity in colorectal cancer patients: mechanisms, pharmacokinetics and strategies.

Oxaliplatin-based chemotherapy is a standard treatment approach for colorectal cancer (CRC). However, oxaliplatin-induced peripheral neurotoxicity (OIPN) is a severe dose-limiting clinical problem that might lead to treatment interruption. This neuropathy may be reversible after treatment discontinuation. Its complicated mechanisms are related to DNA damage, dysfunction of voltage-gated ion channels, neuroinflammation, transporters, oxidative stress, and mitochondrial dysfunction, etc. Several strategies have been proposed to diminish OIPN without compromising the efficacy of adjuvant therapy, namely, combination with chemoprotectants (such as glutathione, Ca/Mg, ibudilast, duloxetine, etc.), chronomodulated infusion, dose reduction, reintroduction of oxaliplatin and topical administration [hepatic arterial infusion chemotherapy (HAIC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), and hyperthermic intraperitoneal chemotherapy (HIPEC)]. This article provides recent updates related to the potential mechanisms, therapeutic strategies in treatment of OIPN, and pharmacokinetics of several methods of oxaliplatin administration in clinical trials.

Corrigendum: The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis.

[This corrects the article DOI: 10.3389/fphar2021.714287.].

The Therapeutic Principle of Combined Strengthening Qi and Eliminating Pathogens in Treating Middle-Advanced Primary Liver Cancer: A Systematic Review and Meta-Analysis.

Background: The combination of strengthening Qi and eliminating pathogens is an available therapeutic principle in traditional Chinese medicine (TCM) for primary liver cancer (PLC) at middle-advanced stage. However, there is a lack of reasonable evidence to support the proper application of this therapeutic principle. This meta-analysis aims to evaluate the efficacy and safety of Chinese medicinal formulas (CMFs), including two subgroup analyses of the principle of strengthening Qi and eliminating pathogens. Method: Clinical trials were obtained through searching of EMBASE, Web of Science, PubMed, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang Database, Chinese Scientific Journal Database, Chinese Biomedical Literature Database, and two clinical trial registries. The randomized controlled trials with the combination of CMFs and transcatheter arterial chemoembolization (TACE) in the experiment group were acceptable, in contrast to the TACE alone in the control group. The statistics analysis was performed on Review Manager 5.4. Results: A total of eligible 24 trials were accessed in this work. Overall, CMFs could improve the survival duration of 6 months, 1 year, and 2 years, Karnofsky Performance Status, tumor objective response rate (ORR), AFP, and symptom. In the subgroup analysis, trials complying with the principle of single strengthening Qi did not show any significant difference in increasing tumor ORR. Meanwhile, the principle of combined strengthening Qi and eliminating pathogens was uncertain in improving symptoms and 1-year and 2-year survival time. In addition, the outcome indexes of ALT and AST were heterogeneous. In last, the total occurrence of adverse events could not be reduced via using CMFs. Patients treated with CMFs exhibited liver injury, fever, and white blood cell decline, with mild events occurring more frequently and severe events occurring less. Conclusion: CMFs are an effective treatment method to cure PLC at the middle-advanced stage. Adopting the principle of single strengthening Qi presents better efficacy in the long term by prolonging the survival duration. Following the principle of combined strengthening Qi and eliminating pathogens could be more beneficial to patients in short term by lessening the tumor size. CMFs have the advantage of reducing certain serious adverse events.