ABSTRACT
To explore the mechanism of the active ingredients of Qishiwei Zhenzhu Pills in inhibiting the hepatorenal toxicity of the zogta component based on serum pharmacochemistry and network pharmacology, thereby providing references for the clinical safety application of Qishiwei Zhenzhu Pills. The small molecular compounds in the serum containing Qishiwei Zhenzhu Pills of mice were identified by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS). Then, by comprehensively using Traditional Chinese Medicines Systems Pharmacology(TCMSP), High-throughput Experiment-and Reference-guided Database(HERB), PubChem, GeneCards, SuperPred, and other databases, the active compounds in the serum containing Qishiwei Zhenzhu Pills were retrieved and their action targets were predicted. The predicted targets were compared with the targets of liver and kidney injury related to mercury toxicity retrieved from the database, and the action targets of Qishiwei Zhenzhu Pills to inhibit the potential mercury toxicity of zogta were screened out. Cytoscape was used to construct the active ingredient in Qishiwei Zhenzhu Pills-containing serum-action target network, and STRING database was used to construct the protein-protein interaction(PPI) network of intersection targets. The Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out on the target genes by the DAVID database. The active ingredient-target-pathway network was constructed, and the key ingredients and targets were screened out for molecular docking verification. The results showed that 44 active compounds were identified from the serum containing Qishiwei Zhenzhu Pills, including 13 possible prototype drug ingredients, and 70 potential targets for mercury toxicity in liver and kidney were identified. Through PPI network topology analysis, 12 key target genes(HSP90AA1, MAPK3, STAT3, EGFR, MAPK1, APP, MMP9, NOS3, PRKCA, TLR4, PTGS2, and PARP1) and 6 subnetworks were obtained. Through GO and KEGG analysis of 4 subnetworks containing key target genes, the interaction network diagram of active ingredient-action target-key pathway was constructed and verified by molecular docking. It was found that taurodeoxycholic acid, N-acetyl-L-leucine, D-pantothenic acid hemicalcium, and other active ingredients may regulate biological functions and pathways related to metabolism, immunity, inflammation, and oxidative stress by acting on major targets such as MAPK1, STAT3, and TLR4, so as to inhibit the potential mercury toxicity of zogta in Qishiwei Zhenzhu Pills. In conclusion, the active ingredients of Qishiwei Zhenzhu Pills may have a certain detoxification effect, thus inhibiting the potential mercury toxicity of zogta and playing a role of reducing toxicity and enhancing effect.
Subject(s)
Animals , Mice , Medicine, Tibetan Traditional , Network Pharmacology , Molecular Docking Simulation , Tandem Mass Spectrometry , Toll-Like Receptor 4 , Medicine, Chinese Traditional , Mercury , Drugs, Chinese Herbal/toxicityABSTRACT
Momordica charantia has been a traditional Chinese medicine （TCM） and food since ancient times. The discussions on its nature， taste and efficacy in ancient books of TCM are almost the same. With a high nutritional value， M. charantia is rich in a variety of vitamins and minerals， and has been widely used in the production of a wide range of dietary supplements and functional foods. At the same time， M. charantia is one of the most deeply studied natural medicines in traditional alternative medicine， with a wide range of pharmacological effects， especially in the treatment of metabolic diseases. Clinical trials have confirmed that M. charantia has a hypoglycemic effect， and could reduce blood lipids and weight loss， so as to improve metabolism in a comprehensive manner. According to the study on the mechanism of M. charantia in the treatment of diabetes， M. charantia could reduce blood sugar by improving islet β-cell function， improving insulin resistance， inhibiting intestinal glucose absorption and resisting inflammation and oxidative stress. However， at present， there is a lack of unified standards for the hypoglycemic effects and various mechanisms of action of M. charantia， and the safety has not been fully confirmed. Further studies shall be conducted to investigate the hypoglycemic effect and mechanisms of M. charantia， explore active components of M. charantia， define the pharmacodynamics material basis， extract monomer compounds with a clear structure and confirm its effectiveness and safety， which is helpful to develop and utilize the homologous value of medicine and food of M. charantia and further apply it in clinic. The application of the hypoglycemic effect of M. charantia in clinic has important economic benefits and a social significance.
ABSTRACT
Tibetan medicine Edgeworthia gardneri is the flower bud of Edgeworthia gardneri, mainly distributed in the eastern Tibet as well as the northwest and west parts of Yunnan. It is called one of the " Eighteen treasures of Qinghai-Tibet" and has been used in many Tibetan secret recipes for a long time. Nowadays, the local people often drink E. gardneri Meisn tea for blood glucose regulation and health care. In this study, the related papers were searched in CNKI, Wanfang, Weipu, PubMed and other databases by using the keywords " Lv luo hua" and " flower of E. gardneri Meisn" . Then the status quo of the flower of E. gardneri was summarized from three aspects: provenance, chemical compositions and extraction method, as well as efficacy and function. It is found that E. gardneri mainly contains coumarins, flavonoids, polysaccharides and polyphenols. The extraction methods of E. gardneri include ultrasonic extraction, microwave extraction, supercritical CO2 extraction, and bio-enzyme-assisted extraction method, et al. The extraction of flavonoids and polyphenols is more common. In terms of medicinal efficacy, it has many medicinal effects such as regulating blood sugar, lowering blood fat, anti-oxidation, enhancing immunity and anti-tumor. The flower of E. gardneri has broad pharmacological effect, attracting more and more scholars to research it. However, studies on its medicinal effectiveness both at home and abroad are mainly focusing on it' s crude extractions or extracts, with no in-depth studies on action mechanism. This review aims to summarize the provenance, main chemical compositions and extraction methods, efficacy and effect of the flower of E. gardneri, especially focusing on the research on the medicinal efficacy and mechanism of the flower of E. gardneri, and provide a reference for the further research of the flower of E. gardneri.
ABSTRACT
The active ingredients in some Tibetan medicinal herbs are toxic components as well,and we need to have a clear understanding of their mechanism and metabolic pathways in use. The endogenous toxic components of highly toxic Tibetan herbal medicines are mainly alkaloids, such as aconitum alkaloids, methyllycaconitine, tropane alkaloids, brucine, strychnine, papaverine and swainso-nine. The majority of endogenous toxic alkaloids in Tibetan medicine herbs exist in roots, fruits and seeds of plants, exerting neurotoxicity or cardiotoxicity as highly toxic inherent chemicals. Most alka-loids are metabolized in phaseⅠvia de-alkylation, hydroxylation, hydrolysis and other reactions, as well as in phaseⅡvia glucuronic acid and sulfonic acid conjugation. They form various metabolites with high polarities and reduced toxicities so as to be easily excreted. The closeness between the therapeutic dose and toxic dose of alkaloids components in Tibetan medicinal herbs leads to their attenuated prep-aration via frying, dairy, highland barley wine soaking, or in combination with Terminalia Chebula to decrease toxicity, as is cited classic books on in Tebitan medicine. Focused on twelve alkaloids of five classes including aconitine, tropane and brucine, we have reviewed the characteristics of their metabo-lism and transformation, as well as their toxicity attenuation and safety evaluation.