摘要
Ferroptosis, a new form of programmed cell death different from apoptosis, necrosis, and autophagy, is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis, the mechanism of which is related to intracellular lipid metabolism, iron metabolism, and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth, metastasis, and multi-drug resistance of tumors. Therefore, the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances, a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly, the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine, oleanolic acid, dihydroartemisinin, pseudolaric acid B, and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism, iron metabolism, system Xc-, and GPX4/GSH to regulate the development of tumors, demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis, this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors, providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.
摘要
Paridis Rhizoma possesses the functions of clearing heat and detoxifying, alleviating swelling and relieving pain, cooling the liver and calming the convulsion. Saponins are the main active components of Paridis Rhizoma. Studies have shown that total saponins in Paridis Rhizoma have obvious inhibitory effect on solid tumors such as breast cancer, lung cancer, gastric cancer, and liver cancer and non-solid tumors such as leukemia. The saponins may exert the anti-tumor effects by inhibiting the proliferation, migration, and invasion of tumor cells, regulating cell cycle, inducing apoptotic and non-apoptotic death pathways, and regulating metabolism and tumor microenvironment. Furthermore, total saponins in Paridis Rhizoma showed anti-inflammatory, antioxidant, antimicrobial, hemostatic, and uterus-contracting activities. At the same time, they may induce apoptosis of normal cells, inflammation and oxidative stress, and metabolic disorders. In recent years, the reports of liver injury, reproductive injury, gastrointestinal injury, hemolysis, and other adverse reactions caused by total saponins in Paridis Rhizoma have been increasing. Pharmacokinetic studies have shown that there are significant differences in the metabolism of total saponins in Paridis Rhizoma administrated in different ways. Injection has a fast clearance rate, while oral administration may have hepatoenteric circulation. Meanwhile, due to the low solubility and activation of P-glycoprotein (P-gp) molecular pump, the prototype absorption, intestinal permeability, and recovery rate of total saponins in Paridis Rhizoma are poor, which affects the bioavailability. The bioavailability can be improved to some extent by preparing new dosage forms or new drug delivery systems with advanced technology. This paper reviews the pharmacological effect, pharmacokinetics, and adverse reactions of Rhizoma Paridis total saponins by searching the China National Knowledge Infrastructure (CNKI), VIP, and Web of Science with ''Rhizoma Paridis total saponins'' as the keywords, hoping to provide references for the research, development, and clinical application of such components.
摘要
As a rare Chinese medicinal material, Paridis Rhizoma is mainly distributed in Yunnan, Guangxi, and Guizhou in southwestern China, with the effect of clearing heat and detoxifying, alleviating edema and relieving pain, cooling liver and tranquilizing mind. It is particularly effective for injuries from falls, fractures, contusions and strains, snake bites, cold wind-induced convulsion, and other diseases, which has been used for more than 2 000 years. According to modern research, polyphyllin Ⅱ, one of the main active components of Paridis Rhizoma, belongs to diosgenin in structure. It has the anti-tumor, anti-inflammatory, antiviral, antibacterial, immune-regulating, antioxidant, and multidrug resistance-reversing activities, showing good application prospect. Especially, the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention, and the mechanism is inhibiting proliferation, migration, and invasion of tumor cells, inducing cell cycle arrest, apoptosis, and autophagy, suppressing angiogenesis, and modulating tumor microenvironment. However, the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility, poor absorption, unsatisfactory distribution, and slow metabolism, which limit the clinical application. In recent years, there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ, such as the strong hemolytic activity and obvious cytotoxicity to liver, kidney, myocardium and cardiovascular cells. Thus, papers were retrieved from "CNKI", "VIP", "Wanfang Data", "PubMed", "Web of Science", and "Elsevier SD" with "Paris saponin Ⅱ", "Polyphyllin Ⅱ" as the main keywords, and the pharmacological activities and mechanisms, pharmacokinetics, and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research, development, and utilization of polyphyllin Ⅱ.
摘要
Isopropylidene shikimic acid [ISA], a new drug derviatived from Shikimic Acid, had been proved to be effective in the cerebral protection after cerebral ischemia and reperfusion. But there was little research on the physical pharmacy and biopharmaceutical properties about the drug. In order to provide some useful data for the pharmaceutical development of ISA, the solubility, stability and Oil/Water partition coefficient [LogP] were determined by the classic preformulation study method, and the transmembrane performance of ISA was studied by Franz -diffusion cell method in vitro. The results showed that ISA was water-soluble with a solubility 32.52mg/ml, which could be improved to 44.32 mg/ml by 1% [w/v] sodium dodecyl sulfate; the LogP was -0.63; ISA was less stable in water but it was stable when pH greater than 6.0 and unstable when pH less than 6.0; the accumulated permeation rates at 1h were about 50% and more than 80% at 6h. Data obtained by the study indicated that the medium selection and pH control were important for liquid preparation of ISA, and avoiding dissolution and absorption in stomach was critical for the oral solid dosage forms. Mucosal drug delivery systems would be considered, according to the certain hydrophilic-lipophilic characters and good transmembrane capability
摘要
OBJECTIVE:To investigate the effects of non-ionic polyacrylamide(model:NPAM 1400)alone or combined with nanoscale silica gel (nSiO2) on the stability of Glycyrrhetinic acid lipo-emulsion. METHODS:UV-spectrophotometer was used to determine absorbance of diluent at 500 nm before and after lipo-emulsion centrifugation. Using the preparation without stable excipient as blank,stability coefficient (KE) and it ratio (KE/KE blank) were calculated. Effects of different concentrations (200-600 mg/L) of non-ionic polyacrylamide on the stability of Glycyrrhetinic acid lipo-emulsion were evaluated. The optimal concentration of non-ionic polyacrylamide alone was determined primarily,and then the effects of it combined with different concentrations of hydrophilic nSiO2 (0.2%, 0.3%, 0.4%) or hydrophobic (0.2%, 0.3%, 0.5%) on the stability of Glycyrrhetinic acid lipo-emulsion were investigated. RESULTS:When adding non-ionic polyacrylamide alone,KE of Glycyrrhetinic acid lipo-emulsion mixed with 300 mg/L non-ionic polyacrylamide was the lowest,KE/KE blank was 0.22;when combined,KE of Glycyrrhetinic acid lipo-emulsion mixed with 300 mg/L non-ionic polyacrylamide and 0.2% hydrophobic nSiO2 was the lowest,KE/KE blank was 0.27. CONCLUSIONS:Non-ionic polyacrylamide alone or combined with nSiO2 all can promote the stability of Glycyrrhetinic acid lipo-emulsion,among which 300 mg/L non-ionic polyacrylamide alone is the best.
摘要
Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and gamma-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-alpha-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, gamma-amino-n-butyric acid and L-alpha-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant.