RESUMEN
BACKGROUND: Non-alcoholic steatohepatitis (NASH) can develop into cirrhosis, liver failure, or hepatocellular carcinoma without effective treatment. However, there are currently no drugs for NASH treatment, and the development of new therapeutics has remained a major challenge in NASH research. Advances in traditional Chinese medicine to treat liver disease inspired us to search for new NASH candidates from Chi-Shao, a widely used traditional Chinese medicine. PURPOSE: In this research, we aimed to clarify the anti-NASH effect and the underlying mechanism of isopropylidenyl anemosapogenin (IA, 1), which was a new lead compound isolated from Chi-Shao. STUDY DESIGN AND METHODS: Isopropylidenyl anemosapogenin (IA, 1) was first discovered by collagen type I α 1 promoter luciferase bioassay-guided isolation and then characterized by single crystal X-ray diffraction analysis and enriched by semi-synthesis. Using various molecular biology techniques, the multiple anti-NASH efficacies and mechanisms of IA were clarified based on in vitro LX-2 and Huh7 cell models, along with the in vivo choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD)-induced mouse model and bile duct ligation (BDL)-induced rat model. The UPLC-MS/MS method was used to assess the plasma concentration of IA. RESULTS: A new lead compound IA was isolated from the traditional Chinese medicine Chi-Shao, which showed significant anti-liver fibrosis activity in TGF-ß1-treated LX-2 cells and anti-liver steatosis activity in oleic acid-treated Huh7 cells. Furthermore, IA could significantly ameliorate in vivo CDAHFD-induced liver injury by activating the farnesoid X receptor pathway, including its targets Nr0b2, Abcb11, and Slc10a2. Simultaneously, IA activated the autophagy pathway by activating the TFEB factor, thereby promoting lipid degradation. Its liver-protective and anti-fibrosis activities were verified by the BDL-induced rat model. Finally, with an oral administration of 100 mg/kg, IA achieved the maximum plasma concentration of 1.23 ± 0.18 µg/ml at 2.67 ± 0.58 h. CONCLUSION: IA, an unreported lupine-type triterpenoid isolated from Chi-shao, can significantly alleviate liver injury and fibrosis via farnesoid X receptor activation and TFEB-mediated autophagy, which indicates that IA could serve as a novel therapeutic candidate against NASH.
Asunto(s)
Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/metabolismo , Animales , Autofagia , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Cromatografía Liquida , Modelos Animales de Enfermedad , Fibrosis , Hígado , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Ratas , Espectrometría de Masas en TándemRESUMEN
An immunologically stressed rat model was used in a metabolomics study on the ability of Paeoniae Rubra Radix to reduce the liver toxicity of Psoraleae Fructus. Different groups of rats were given the extracts of Psoraleae Fructus and Psoraleae Fructus together with Paeoniae Rubra Radix or combined with a non-toxic dose of lipopolysaccharide (LPS). The biochemical indices of liver function and pathological changes in liver tissue were used to evaluate histopathological changes. UHPLC-QTOF/MS was used to analyze the metabolic profile of serum samples, combined with principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) methods. The HMDB database and Metabo Analyst online tool were used for biomarker identification and metabolic pathway-enrichment analysis. The results show that the co-treatment Psoraleae Fructus and LPS resulted in significant liver injury, indicated by the elevation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, as well as obvious pathological changes. Liver injury was significantly decreased by treatment with Paeoniae Rubra Radix. Metabolomic analysis showed that the addition of Paeoniae Rubra Radix ameliorated the abnormal serum metabolism in rats mainly through regulation of arachidonic acid metabolism and glycerophospholipid metabolism pathways.
RESUMEN
To analyze and compare the chemical compositions of Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix based on "component structure" theory. Thirteen batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix from different origins and 10 batches of Paeoniae Alba Radix from different origins were analyzed by HPLC-DAD method. Hierarchical cluster analysis and principal component analysis were used for analysis. The significant differences of principal component from Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix were investigated by using F test. HPLC fingerprints were established for 13 batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix and 10 batches of Paeoniae Alba Radix, and 7 glycosides and phenolic acids components were identified. Comparative study of Moutan Coetex, Paeoniae Rubra Radix and Paeoniae Alba Radix was conducted according to the results of hierarchical cluster analysis, principal component analysis and "component structure" theory. Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix have significant differences in mass fraction of major chemical components and their ratios, leading to different curative effects.
Asunto(s)
Medicamentos Herbarios Chinos/química , Paeonia/química , Cromatografía Líquida de Alta Presión , Análisis de Componente PrincipalRESUMEN
Objective: To investigate the effects of Moutan Cortex, Paeoniae Rubra Radix, and Paeoniae Alba Radix on the acute blood stasis model rats, and reveal their mechanism and differences in efficacy. Methods: The actue blood stasis model of rats was induced by sc injecting adrenaline hydrochloride and soaking in ice water. Salvia Injection was used as the positive control drug. The changes of viscosity of whole blood and plasma, thrombin activity, blood platelet system, and the contents of TXB2 and 6-keto-PGF1α were detected in the acute blood stasis model rats. Results: Compared with the model group, Moutan Cortex obviously extended PT, and TT (P < 0.05), inhibited platelet adhesion rate (P < 0.01), reduced TXB2 (P < 0.01), increased 6-keto-PGF1α in serum (P < 0.01), and regulated eNOS and p-eNOS expression (P < 0.01, 0.001). Paeoniae Rubra Radix significantly improved whole blood viscosity at different shear rates, extended APTT, TT, and PT (P < 0.05, 0.01), reduced platelet adhesion rate (P < 0.05), decreased TXB2, increased 6-keto-PGF1α in serum (P < 0.01), and increased eNOS and p-eNOS expression (P < 0.05). Paeoniae Alba Radix had no significant effect on hemorheology, but could significantly prolong APTT and TT (P < 0.05), reduce platelet adhesion rate (P < 0.05), increase the content of 6-keto-PGF1α in serum (P < 0.05) and increase the eNOS and p-eNOS expression in platelet. Conclusion: All Moutan Cortex, Paeoniae Rubra Radix, and Paeoniae Alba Radix have varying degrees on hemorheology, coagulation system, platelet system, but Moutan Cortex and Paeoniae Rubra Radix have the better role in promoting blood circulation compared with Paeoniae Alba Radix.
RESUMEN
To analyze and compare the chemical compositions of Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix based on "component structure" theory. Thirteen batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix from different origins and 10 batches of Paeoniae Alba Radix from different origins were analyzed by HPLC-DAD method. Hierarchical cluster analysis and principal component analysis were used for analysis. The significant differences of principal component from Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix were investigated by using F test. HPLC fingerprints were established for 13 batches of Moutan Cortex, 14 batches of Paeoniae Rubra Radix and 10 batches of Paeoniae Alba Radix, and 7 glycosides and phenolic acids components were identified. Comparative study of Moutan Coetex, Paeoniae Rubra Radix and Paeoniae Alba Radix was conducted according to the results of hierarchical cluster analysis, principal component analysis and "component structure" theory. Moutan Cortex, Paeoniae Rubra Radix and Paeoniae Alba Radix have significant differences in mass fraction of major chemical components and their ratios, leading to different curative effects.
RESUMEN
Paeoniae Rubra Radix (PRR) with the function of clearing heat and cooling blood, dissipationg blood stasis and relieving pain, has been widely used in clinics. PRR, containing total glucosides of paeony, tannins, flavones, and volatile oil, is the current research focus because its significant hepatoprotective, antitumor, neuroprotective, and cardio-protective effect thus far, as well as its antithrombosis and anti-oxidative activities. According to vast information from literatures in the last decade, we summarize the chemical compositions and pharmacological actions, in hopes of offering more clues for further research as well as clinical application of PRR. Meanwhile, despite of enormous progress has been made all over the international research on PRR, the development of relevant safe and effective agents is still needed. At present, the definition of the mechanism and the extension of the clinical application remain as the primary tasks of the exploration of PRR.
RESUMEN
Objective: To conduct computing network pharmacological studies on Paeoniae Rubra Radix (Chishao) and Phellodendri Cortex (Huangbai), and to explore their mechanism for intervening Alzheimer's disease (AD). Methods: The interactions among 199 compounds from the two kinds of Chinese Herbs (Chishao and Huangbai) and 23 approved drug targets related to AD were studied with molecular docking and network pharmacological analysis methods. Results: The most of the compounds in Chishao and Huangbai exhibit good drug-like properties. The mechanism of Chishao and Huangbai may be that they modulate the expression of GSK-3β, caspase-7, BchE, and mTOR to resist AD. Conclusion: The method of network pharmacological studies is helpful to explore the possible active molecules in Chishao and Huangbai and elucidate the mechanism of action.
RESUMEN
Objective: A high performance liquid chromatographic method was established to simultaneously quantify the gallic acid, methyl gallate, albiflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, benzoylpaeoniflorin of red peony root, and white peony root. Methods: The content of six components from 32 batches of samples collected from different product areas and markets was determined and compared by means of this established method. The mobile phase comprised of acetonitrile and water containing 0.1% phosphoric acid. Flow rate was 0.8 mL/min and column temperature was 30℃. Chromatography was monitored at 230 and 270 nm. Results: The correlation coefficients between concentration and chromatographic peak area of gallic acid, methyl gallate, albiflorin, paeoniflorin, 1,2,3,4,6-O-pentagalloylglucose, and benzoylpaeoniflorin, respectively were over 0.9999 in the ranges of 0.7830-50.10, 1.094-70.00, 2.367-151.5, 7.823-500.6, 3.125-200.0, and 0.3480-22.25 μg/mL. The average recoveries of the six compounds were 102.1%, 98.88%, 99.25%, 100.4%, 104.2%, and 100.6%, respectively. Conclusion: All the contents of albiflorin, 1,2,3,4,6-O-pentagalloylglucose, gallic acid, and methyl gallate show a remarkable difference between Paeoniae Rubra Radix and Paeoniae Alba Radix. And the latter usually contains more monoterpene glycosides than the former dose except paeoniflorin. On the other hand, Paeoniae Rubra Radix, especially originating from Paeoniae veitchii always contains more polyphenols than Paeoniae Alba Radix dose.
RESUMEN
Objective: To compare the chemical constituents of Paeoniae Alba Radix and Paeoniae Rubra Radix, and to provide a basis for quality evaluation. Methods: NMR-based metabolomic approach combined with multivariate statistical analysis was used to investigate the differential metabolites between Paeoniae Alba Radix and Paeoniae Rubra Radix. Results: Thirty-two metabolites were identified in the 1H-NMR spectra, and the multivariate statistical analysis showed that Paeoniae Alba Radix and Paeoniae Rubra Radix could be separated clearly. Paeoniae Alba Radix contained more arginine, threonine, acetic acid, aspartic acid, glutamine, GABA, citric acid, succinate, lactate, albiflorin, 6-O-galloyl albiflorin, 1, 2, 3, 4, 6-pentagalloyglucose, and gallic acid, while Paeoniae Rubra Radix contained more alanine, α-glucose, sucrose, paeoniflorin, catechin, β-sitosterol, fatty acid, and paeonol. In addition, the Pearson correlations between differential metabolites of Paeoniae Alba Radix and Paeoniae Rubra Radix also showed apparent differences. Conclusion: The results reveal the chemical differences between Paeoniae Alba Radix and Paeoniae Rubra Radix in a holistic way, and provide a scientific basis for assessing the quality of Paeoniae Alba Radix and Paeoniae Rubra Radix, as well as the correlations between the chemical constituents and pharmacological efficacy.
RESUMEN
Chinese Materia Medica (CMM) decoction dregs are the residues of medicinal materials after decoction. Accurate identification of CMM in decoction dregs will be helpful for exploring the causes of poisoning or other medical incidents arising after the ingestion of CMM decoctions. To determine how decoction affects the characteristics used to authenticate specific CMM, a systematic study was carried out. In this study, two pairs of Materia Medica that are commonly confused-namely, Baizhu (Atractylodis Macrocephalae Rhizoma) and Cangzhu (Atractylodis Rhizoma), Baishao (Paeoniae Alba Radix) and Chishao (Paeoniae Rubra Radix)-were chosen for investigation. Each pair of Materia Medica has similar morphology in appearance, but they have different functions in Chinese clinic. After decoction, with regard to gross morphological characters, the results showed that bark and wood could be easily distinguished. The striation of vessels and fibers became more prominent because of the contraction of parenchymatous cells, but the lignified cells did not. As for the microscopic characteristics, the cells with thickened walls, such as stone cells and fibers, were basically stable. Most of the parenchymatous cells were broken. Crystals of calcium oxalate showed no changes as they were insoluble in water. Starch granules were gelatinized and aggregated in parenchymatous cells. Inulins were substantially reduced in number as they dissolved in water during decoction. According to these changes in morphological and microscopic characteristics after decoction, the dregs of two pairs of Materia Medica could be distinguished.