Loganin Research Articles

Loganin Ameliorates Acute Kidney Injury and Restores Tofacitinib Metabolism in Rats: Implications for Renal Protection and Drug Interaction.

Tofacitinib, a Janus kinase (JAK) inhibitor used to treat rheumatoid arthritis, is metabolized through hepatic cytochrome P450 (CYP), specifically CYP3A1/2 and CYP2C11. Prolonged administration of rheumatoid arthritis medications is generally associated with an increased risk of renal toxicity. Loganin (LGN), an iridoid glycoside, has hepatorenal regenerative properties. This study investigates the potential of LGN to mitigate acute kidney injury (AKI) and its effects on the pharmacokinetics of tofacitinib in rats with cisplatin-induced AKI. Both intravenous and oral administration of tofacitinib to AKI rats significantly increased the area under the plasma concentration-time curve from time 0 to infinity (AUC) compared with control (CON) rats, an increase attributed to the decelerated non-renal clearance (CLNR) and renal clearance (CLR) of tofacitinib. Administration of LGN to AKI rats, however, protected kidneys from severe impairment, restoring the pharmacokinetic parameters (AUC, CLNR, and CLR) of tofacitinib to those observed in untreated CON rats, with partial recovery of kidney function, as evidenced by an increase in creatinine clearance (CLCR). Possible interactions between drugs and natural components should be considered, especially when co-administering both a drug and a natural extract containing LGN or iridoid glycosides to patients with kidney injury.

1Comprehensive multi-omics analysis reveals the mechanism of loganin from Corni Fructus in improving insulin resistance in mice

Corni Fructus (CF) has great potential as a food product in the treatment of T2DM (thirst-quenching). As the main active ingredient of CF, loganin (LOG) possesses multiple pharmacological propertiesincluding hypoglycemic, hypolipidemic, anti-inflammatory and antibacterial. In this study, we firstly verified the efficacy of LOG in improving the disordered glycolipid metabolism and liver damages in a murine insulin resistance (IR) model, and then determined the ameliorative effect of LOG on IR-HepG2 cell model. To clarify the mechanism of LOG on IR, a series of differentially expressed metabolites (DEM) and genes (DEG) were screened out through non-targeted metabolomics and transcriptomics techniques. In addition, integrative metabolomics and transcriptomics analyses revealed a few key pathways (foxO signaling pathway, glycine serine and threonine metabolism, glutamatergic synapse, cocaine addiction, amphetamine addiction, and valine leucine and isoleucine biosynthesis), important DEM (l-Glutamate), and DEGs (Sgk2, Grin3b, Acadsb, Grik1) were reversely regulated by LOG as compared with the IR model. It is hypothesized that LOG may exert the anti-IR effect via finely tuning amino acid metabolism. Taken together, our data may shine light on the screening of new intervention targets and developing of new LOG-related agents for IR treatment.

Analysis of Quality Differences in Radix Dipsaci before and after Processing with Salt Based on Quantitative Control of HPLC Multi-Indicator Components Combined with Chemometrics.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

Studies of the pharmacokinetics of morroniside and loganin in rat after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS


 
 
 
 Purpose: To study the pharmacokinetics of morroniside (MR) and loganin (LG) in rats after oral administration of raw and wine-processed Corni fructus by UPLC-QqQ-MS/MS.
 Methods: Arctiin (AT) was used as internal standard, and the plasma or tissue samples were extracted twice using ethyl acetate. Electrospray ionization (ESI) negative ion mode was used, and the multiple reaction monitoring mode (MRM) was set in acquisition mode. The extraction and detection method is supported by selectivity, sensitivity, precision, accuracy, stability, extraction, recovery and matrix effect. The non-atrioventricular model of das2.0 software was used to calculate the pharmacokinetic parameters.
 Results: The absorption rate of MR (PTmax=0.092) and LG (PTmax=0.092) in Corni Fructus after wine-processing was faster in rats. The mean residence time was longer, and distribution of MR (PMRT0~t = 0.294) and LG (PMRT0~t = 0.000) in wine-processed Corni Fructus group increased in liver and kidneys.
 Conclusion: The proposed method has been successfully validated and is suitable for studying the pharmacokinetics of the two analytes in rats.
 
 
 

Cornel Iridoid Glycoside Regulates Modification of Tau and Alleviates Synaptic Abnormalities in Aged P301S Mice

Alzheimer's disease (AD), also defined as a tauopathology, is a common neurodegenerative disease. Hyper-phosphorylation, cleavage or truncation, and aggregation of tau contribute to AD. Thus, targeting the post-translational modifications on tau may be a therapeutic strategy to treat AD. This study understood how cornel iridoid glycoside (CIG) affects tau post-translational modifications and synaptic abnormalities. The 10-month old P301S tau transgenic mice were given CIG at 100 and 200 mg/kg every day orally for 1 month. Hyperphosphorylated and truncated tau, synapse-associated proteins and glutamatergic receptors were all detected using Western blotting. The interactions between Morroniside (MOR) or Loganin (LOG) and tau were detected using Autodock and Surface Plasmon Resonance (SPR). The effects of CIG on the aggregation of tau were investigated using a cell-free system. CIG attenuated tau hyperphosphorylation at Thr205, Ser212, Ser262, Thr231 and Ser235 (AT180), but had no effect on tau truncation in the brains of 10-month old P301S mice. Binding free energies and interactions revealed that MOR and LOG bound with tau. We also found that CIG upregulated synapse-associated proteins such as PSD-95, syntaxin1A and synaptotagmin. In addition, CIG restored N-methyl-D-aspartic acid receptor and glutamate receptor levels. CIG improves post-translational modification of tau as well as synaptic abnormalities. The data presented here reveal that CIG may be used in the treatment of AD.

Impact and mechanism of Loganin on epithelial mesenchymal transformation of gastric cancer cells

Objective To explore impact and molecular mechanism of Loganin on epithelial mesenchymal transformation of gastric cancer cells. Methods Human gastric cancer cell lines AGS, BGC823 and SGC7901 were cultured routinely. The effect of Loganin on cells activity was tested by utilizing methyl thiazol tetrazolium (MTT) assay. Also Wound assay and Transwell assay were employed to detect the effect of Loganin on migration and invasion in BGC823 cells. Furthermore, real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) and Western blotting were used to examine the variations of associated genes and phosphatidylinositol 3 kinase (PI3K)-protein kinase B (Akt) signal pathway in BGC823 cells prior and post Loganin interventions. Results Results of MTT assay showed that the activity of BGC823 was lowest among AGS (0.748±0.051), BGC823 (0.581±0.042) and SGC7901 (0.412±0.037) (F=44.101, P<0.01); the expression level of PCNA mRNA and protein declined gradually with the increase dose of Loganin (F=36.298, 47.942, P<0.01). Compared with the control group, the ability of migration and invasion in BGC 823 cells decreased, and this changes were particularly distinct in high dose Loganin group (200 mg/L), which were more significant than in low dose group (50 mg/L) (migration: F=87.750, P<0.01; invasion: F=85.749, P<0.01). Results of qPCR and Western blotting showed that expressions of migration, invasion associated genes in BGC823 cells changes significantly compared with the control group, especially in high dose Loganin group (P<0.01). Results of qPCR and Western blotting illustrated that EMT related gene in BGC823 cells changes significantly compared with the control group, especially in high dose Loganin group (P<0.01). The activity of PI3K-Akt signal pathway declined significantly post Loganin intervention, and expression of p-PI3K, p-Akt decreased significantly, especially in high dose Loganin group (F=38.590, 63.563; P<0.01). Conclusion Loganin may inhibit EMT in gastric cancer cells via regulating PI3K-Akt signal pathway. Key words: Gastric cancer; Loganin; Invasion; Epithelial mesenchymal transformation; Phosphatidylinositol 3 kinase-protein kinase B signal pathways

LC/MS/MS determination and pharmacokinetic studies of six compounds in rat plasma following oral administration of the single and combined extracts of Eucommia ulmoides and Dipsacus asperoides

AimTo establish and apply a new LC/MS/MS method for the simultaneous, quantitative determination of six ingredients, aucubin (AU), geniposide (GP), geniposidic acid (GPA), pinoresinol diglucoside (PDG), secologanin (SLG), and loganin (LG) in single and combined extracts of Eucommia ulmoides and Dipsacus asperoides. MethodUsing the LC/MS/MS-ESI--MRM mode to detect the six compounds, chromatographic separation was achieved on an Agilent Eclipse plus C18 column, and the mobile phase consisted of solvent A (CH3CN) and solvent B (H2O containing 0.01% CH3COOH V/V). ResultsThis method was successfully applied to quantify the six compounds in rat plasma after oral administration, and showed good precision, accuracy, reproducibility, and linear regression (r2>0.99). ConclusionThe results showed that following the use of the two medicinal plants, for AU and GP, the values of tmax markedly increased, and the values of cmax markedly decreased. It was found that the compatibility of the medicinal plants might affect their pharmacokinetic properties of their constituents.

Loganin production in Palicourea rigida H.B.K. (Rubiaceae) from populations native to Brazilian Cerrado

Palicourea rigida HBK, known as “douradinha”, “bate-caixa” and “douradao” is endemic to Brazilian Cerrado and belongs to the Rubiaceae family. The aqueous and hydroalcoholic extracts of P. rigida have been traditionally used in the treatment of urinary tract disorders. The aim of this work was to study the chemical diversity of eight populations of P. rigidanative to Brazilian Cerrado regions in the states of Sao Paulo, Goias and Minas Gerais. The loganin quantification was performed by (High-performance liquid chromatography) HPLC and the correlation among iridoid contents and geographic (latitude, longitude and altitude), biotic (diameter and height) and abiotic (soil’s macro and micronutrient) factors was estimated using Pearson's correlation coefficient. The concentration of loganin varied (20.09 to 101.63 mg/ g d.w.) among and within populations. The main factors related to this divergence were latitude, longitude and nutrient-poor soils. Key words: Medicinal plant, iridoid, Cerrado, Rubiaceae.

Preparation of a prostanoid intermediate from loganin

Synthese d'acetoxy-4 [dimethyl-4,4' oxo-3' octene-1' yl]-2 methyl-3 cyclopentaneacetate de methyle

Structure, stereochemistry, and biosynthesis of loganin

Structure, stereochemistry, and biosynthesis of loganin

The structure of loganin

The structure of loganin

Loganin. I. Some observations on the structure

The glucoside, loganin, is shown to contain the groupings C-CH3, C=C-C=O, and CO2CH3, and several new derivatives are described. As a working hypothesis formula I is advanced.