Tripterygium hypoglaucum (Lévl.) Hutch and Its Main Bioactive Components: Recent Advances in Pharmacological Activity, Pharmacokinetics and Potential Toxicity

Tripterygium hypoglaucum (Lévl.) Hutch (THH) is believed to play an important role in health care and disease treatment according to traditional Chinese medicine. Moreover, it is also the representative of medicine with both significant efficacy and potential toxicity. This characteristic causes THH hard for embracing and fearing. In order to verify its prospect for clinic, a wide variety of studies were carried out in the most recent years. However, there has not been any review about THH yet. Therefore, this review summarized its characteristic of components, pharmacological effect, pharmacokinetics and toxicity to comprehensively shed light on the potential clinical application. More than 120 secondary metabolites including terpenoids, alkaloids, glycosides, sugars, organic acids, oleanolic acid, polysaccharides and other components were found in THH based on phytochemical research. All these components might be the pharmacological bases for immunosuppression, anti-inflammatory and anti-tumour effect. In addition, recent studies found that THH and its bioactive compounds also demonstrated remarkable effect on obesity, insulin resistance, fertility and infection of virus. The main mechanism seemed to be closely related to regulation the balance of immune, inflammation, apoptosis and so on in various disease. Furthermore, the study of pharmacokinetics revealed quick elimination of the main component triptolide. The feature of celastrol was also investigated by several models. Finally, the side effect of THH was thought to be the key for its limitation in clinical application. A series of reports indicated that multiple organs or systems including liver, kidney and genital system were involved in the toxicity. Its potential serious problem in liver was paid specific attention in recent years. In summary, considering the significant effect and potential toxicity of THH as well as its components, the combined medication to inhibit the toxicity, maintain effect might be a promising method for clinical conversion. Modern advanced technology such as structure optimization might be another way to reach the efficacy and safety. Thus, THH is still a crucial plant which remains for further investigation.

STUDIES OF MAGNESIUM AND PHOSPHORUS COMBINED MEDICATION BASED ON CASEIN

Aim. The Department of Biochemistry and Physiology of Animals, named after Academician Guly NUBIP of Ukraine, developed magnesium and phosphorus combined medication based on casein. Our aim was to test its bioavailability based on the ability to be hydrolyzed by a mixture of pancreatic digestive enzymes trypsin and chymotrypsin, also check the absence of cytotoxic effects on cell cultures. Methods. To assess bioavailability, we used hydrolysis of the medication with a mixture of trypsin and chymotrypsin, followed by detection of hydrolysis products by polyacrylamide gel electrophoresis. A standard MTT-test performed on both MT-4 and Namalva cell lines was used to assess cytotoxic effects. Results. Based on electrophoresis data, it was found that despite chemical modifications of the natural casein, the medication based on it is characterized by a high ability to hydrolyze by digestive enzymes under the same conditions as casein. Also, an MTT-test demonstrates that the medication has no cytotoxic properties against cell lines MT-4 and Namalva. Conclusions. Since the negative effects of the drug associated with its digestibility and toxicity have not been observed, it is recommended to continue the study of its effects on living organisms.

A combined medication safety assessment of rivaroxaban with Tyrosine Kinase Inhibitors for cancer patients: focusing on CYP2J2 and CYP3A4

Background and purpose: Cancer patients are always complicated with vein thromboembolism, thus the combination of anticoagulants with anti-cancer drugs has profound foundations. This study aimed to assess the safety of rivaroxaban comminating with three tyrosine kinase inhibitors (TKIs) in cancer patients. Experimental Approach: The inhibition of three TKIs on CYP2J2- and CYP3A4-mediated rivaroxaban metabolism was first screened and then reversible and mechanism-dependent inhibitory kinetic constants were determined. Molecular docking was conducted to reveal the interactions between TKIs and CYP2J2 and CYP3A4. Finally, pharmacokinetic parameters of cancer patients were used to assess the safety. Key Results: Imatinib and gefitinib significantly reversibly inhibited CYP2J2- and CYP3A4-mediated rivaroxaban metabolism, while sunitinib only showed reversible inhibition of CYP3A4, not CYP2J2. Three TKIs also showed time-dependent inactivation of CYP3A4. Notably, sunitinib had the strongest inactivation effect on CYP3A4 than the other TKIs with a 4.00-fold IC50 shift, however, a slight effect on CYP2J2. Docking simulations revealed the relation of inhibitory activity to ChemScore. Additionally, drug-drug interaction risks of combinations were assessed using pharmacokinetic data of cancer patients. Imatinib, which showed the strongest inhibition, was predicted to cause a 114–244% increase in rivaroxaban exposure. Conclusion and Implications: Imatinib was predicted to have a moderate DDI risk when was combined with rivaroxaban. These results provide evidence for medication guidance when combining rivaroxaban with TKIs for cancer patients, and also give new insight for the DDI assessment involving rivaroxaban.

Therapeutic Efficacy and Safety of Safflower Injection in the Treatment of Acute Coronary Syndrome

Background. Safflower injection (SFI), a popular Chinese patent drug, is commonly used to treat acute coronary syndromes (ACSs) in China. The research seeks to scientifically estimate the clinical efficacy of SFI for ACS patients. Methods. Eight electronic databases were retrieved for eligible research from the founding date to September 8, 2020. Odds ratio (OR) was adopted to assess the total effective rate, ECG improvement, and adverse reaction, and mean difference (MD) was used for assessing the hemorheology indexes as well as the LVEF. Results. Sixteen randomized controlled trials involving 1620 sufferers with ACS were incorporated. The outcomes showed that, in comparison to conventional medication alone, SFI combined with conventional treatment remarkably enhanced the total effective rate (OR = 3.66, 95% CI [2.73, 4.90], P < 0.00001 ), ECG improvement (OR = 2.85, 95% CI [2.04, 3.99], P < 0.00001 ), and LVEF (MD = 5.13, 95% CI [3.73, 6.53], P < 0.00001 ). Moreover, SFI combined with conventional treatment significantly decreased hemorheology indexes including BV (MD = −0.95, 95% CI [−1.76, −0.13], P = 0.02 ), HCT (MD = −2.37, 95% CI [−3.25, −1.50], P < 0.00001 ), FIB (MD = −0.44, 95% CI [−0.60, −0.29], P < 0.00001 ), and PAR (OR = −7.65, 95% CI [−10.16, −5.14], P < 0.00001 ). However, no notable contrast was observed to link the experimental and the control team for PV (MD = −0.42, 95% CI [−0.83, 0.00], P = 0.05 ) and adverse reactions (OR = 0.59, 95% CI [0.13, 2.74], P = 0.50 ). Conclusion. Despite the limitations that existed in this meta-analysis, the outcomes demonstrated that SFI and conventional combined medication is an effective and relatively safe therapy for ACS sufferers.

Associations between individual antipsychotics and the risk of arrests and convictions of violent and other crime: a nationwide within-individual study of 74 925 persons

Background Individuals diagnosed with psychiatric disorders who are prescribed antipsychotics have lower rates of violence and crime but the differential effects of specific antipsychotics are not known. We investigated associations between 10 specific antipsychotic medications and subsequent risks for a range of criminal outcomes. Methods We identified 74 925 individuals who were ever prescribed antipsychotics between 2006 and 2013 using nationwide Swedish registries. We tested for five specific first-generation antipsychotics (levomepromazine, perphenazine, haloperidol, flupentixol, and zuclopenthixol) and five second-generation antipsychotics (clozapine, olanzapine, quetiapine, risperidone, and aripiprazole). The outcomes included violent, drug-related, and any criminal arrests and convictions. We conducted within-individual analyses using fixed-effects Poisson regression models that compared rates of outcomes between periods when each individual was either on or off medication to account for time-stable unmeasured confounders. All models were adjusted for age and concurrent mood stabilizer medications. Results The relative risks of all crime outcomes were substantially reduced [range of adjusted rate ratios (aRRs): 0.50–0.67] during periods when the patients were prescribed antipsychotics v. periods when they were not. We found that clozapine (aRRs: 0.28–0.44), olanzapine (aRRs: 0.46–0.72), and risperidone (aRRs: 0.53–0.64) were associated with lower arrest and conviction risks than other antipsychotics, including quetiapine (aRRs: 0.68–0.84) and haloperidol (aRRs: 0.67–0.77). Long-acting injectables as a combined medication class were associated with lower risks of the outcomes but only risperidone was associated with lower risks of all six outcomes (aRRs: 0.33–0.69). Conclusions There is heterogeneity in the associations between specific antipsychotics and subsequent arrests and convictions for any drug-related and violent crimes.

Cetylpyridinium chloride as a part of a combined medication for adults and children during the COVID-19 pandemic: established and perspective use

Despite the measures taken, SARS-CoV-2 continues to spread. However, an increase in acute respiratory infections (ARIs) in autumn 2021 is accounted for by the circulation of seasonal respiratory viruses, i.e., rhinovirus, respiratory syncytial virus, adenovirus, etc. The development of novel agents and study of the antiviral activity of well-established agents that inhibit the binding of SARS-CoV-2 and other respiratory viruses with nasopharyngeal and oropharyngeal receptors significantly reduces viral load. Cetylpyridinium chloride is an antiseptic without searing or damaging oropharyngeal epithelium that provides local effects without systemic immunomodulatory action. This agent is approved in Russian Federation for topical use in children over three years and adults as a part of a combined medication for infectious inflammatory throat diseases. This paper reviews current published data illustrating the antiviral activity of cetylpyridinium and its potential application as an antiseptic for preventive and therapeutic use in the COVID-19 pandemic. KEYWORDS: cetylpyridinium chloride, SARS-CoV-2, antiseptic, coronavirus infection, COVID-19, direct antiviral effect. FOR CITATION: Melekhina E.V., Muzyka A.D., Ponezheva Zh.B., Gorelov A.V. Cetylpyridinium chloride as a part of a combined medication for adults and children during the COVID-19 pandemic: established and perspective use. Russian Medical Inquiry. 2021;5(11):728–736 (in Russ.). DOI: 10.32364/2587-6821-2021-5-11-728-736.

Quick simultaneous analysis of bambuterol and montelukast based on synchronous spectrofluorimetric technique

Sensitive, simple and green analytical methodology for simultaneous estimation of bambuterol and montelukast as a combined medication based on their native fluorescence character was developed. The method relies on synchronous spectrofluorimetry to solve the problem of the overlapping emission spectra of the studied drugs. Using second derivative synchronous spectra enabled the simultaneous quantitation of bambuterol and montelukast without interference. The peak amplitudes of the aqueous solutions at Δ λ = 20 nm were estimated at 284 and 304 nm for bambuterol and at 374 and 384 nm for montelukast. A linear relationship was achieved over the concentration range of 0.2–1.00 µg ml –1 for bambuterol and 0.4–2.00 µg ml −1 for montelukast. All factors and parameters were carefully studied to obtain the highest sensitivity and good precision of the proposed method. Additionally, the validation criteria were assessed in accordance with International Council of Harmonization (ICH) guidelines. The method was used for the estimation of both drugs in their raw materials, synthetic mixtures as well their combined tablets with good agreement between its results and those from the comparison method.