Delving into the Latest Updates on Tetrahydropalmatine sulfate with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

DRDs

Action

antagonists

Mechanism

DRDs antagonists(Dopamine receptors antagonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication

Pain

Inactive Indication-

Originator Organization-

Active Organization-

Inactive Organization-

License Organization-

Drug Highest PhaseApproved

First Approval Date-

Regulation-

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Structure/Sequence

Molecular FormulaC21H26ClNO4

InChIKeyMGSZZQQRTPWMEI-UHFFFAOYSA-N

CAS Registry6024-85-7

As a traditional Chinese medicine, Corydalis Decumbentis Rhizoma (Xiatianwu, XTW) is known for its beneficial effects in dispelling wind-dampness, promoting blood circulation, and alleviating pain. Conducting detailed pharmacokinetic studies on the bioavailable components of XTW will contribute to its scientific and rational development.

AIM OF THE STUDY:

To explore and explain the pharmacokinetic characteristics of different types of isoquinoline alkaloids and the differences in their pharmacokinetic parameters between normal and middle cerebral artery occlusion (MCAO) model groups following oral administration of aqueous extract of XTW.

MATERIALS AND METHODS:

This study established a quantitative method for the simultaneous determination of 18 alkaloids in rat plasma via ultra-performance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-TQ-MS/MS). The 18 alkaloids were then quantified in the plasma of normal and MCAO rats following a single oral gavage of aqueous extract of XTW.

RESULTS:

The quantitative method developed via UPLC-TQ-MS/MS demonstrated excellent selectivity, specificity, linearity, precision, accuracy, matrix effects, recoveries, stability, dilution reliability and carry-over. Following the administration of three doses of XTW, the AUC_0-t values of 5 compounds, hydrohydrastinine, corypalmine, tetrahydropalmatine, allocryptopine, and muramine, showed strong linear correlations with the administered doses. At the low dose, 16 out of 18 compounds in the normal group were rapidly absorbed (T_max < 2 h) and the C_max of oxyhydrastinine and tetrahydropalmatine both exceeded 100 ng/mL. Compared with those of normal rats, the AUC_0-t values of 16 compounds tended to increase in MCAO rats, with a significant increase observed for 8 compounds.

CONCLUSION:

After an oral administration of aqueous extract of XTW to rats, the compounds generally exhibited rapid absorption and elimination. Moreover, slight structural differences could lead to significant variations in pharmacokinetic properties, which may be closely related to the selectivity of intestinal bacteria, transporters, and metabolic enzymes involved in in vivo processes. Pathological damage in MCAO rats could significantly alter pharmacokinetic behaviors after oral administration of XTW aqueous extract, primarily manifesting as increased absorption and in vivo exposure. The results of pharmacokinetics of three single doses in normal rats and comparative pharmacokinetics in normal and MCAO rats provide valuable insights for elucidating the pharmacological substances in XTW and identifying more suitable lead compounds.

01 May 2025·SENSORS AND ACTUATORS B-CHEMICAL

Nanopore characterization of DNA–COR–DNA duplex and the sensitive detection of coralyne

Author: Song, Shaojiao ; Cao, Yu ; Lu, Wei ; Li, Ting ; Zhao, Qiuyue ; Zheng, Xin ; Wang, Hailong

Owing to the high selectivity and binding affinity of coralyne (COR) with DNA (DNA)/RNA, COR has been confirmed as an effective anticancer drug.However, a direct and sensitive detection assay for a DNA-COR-DNA structure with a portable instrument has not been reported because of the lack of a high-resolution sensor that can identify DNA-COR interaction at a single-mol. level.Here, specific Types I and II signals generated by a DNA-COR-DNA duplex were observed using a versatile α-hemolysin nanopore sensor.The Type I signal featuring a unique current pattern was preferentially selected via DNA sequence design and voltage control.Subsequently, the rapid and sensitive detection of COR was established with a detection limit of 0.1 nM.The pH environment, observed to influence the binding of the DNA-COR-DNA duplex, was significant for drug release controlling during targeted delivery process.Similar alkaloids were tested, and the nanopore sensor exhibited a high selectivity for COR.The results demonstrate a potential platform for investigating DNA-COR interaction and could be applied in the drug therapy and pharmacodynamic studies of COR.

01 May 2025·HISTOLOGY AND HISTOPATHOLOGY

Tetrahydropalmatine promotes macrophage autophagy by inhibiting the AMPK/mTOR pathway to attenuate atherosclerosis.

Article

Author: Ding, Ke ; He, Jiaqi ; Wang, Jiahong ; Wang, Hui

BACKGROUND:

Atherosclerosis (AS) is a chronic progressive arterial disease that is associated with macrophage autophagy and AMP-activated protein kinase (AMPK)/mechanistic target of the rapamycin (mTOR) pathway. Tetrahydropalmatine (THP) can activate AMPK-dependent autophagy. We aim to study the mechanism of macrophage autophagy mediated by THP in the treatment of AS via the AMPK/mTOR pathway.

METHODS:

High-fat diet apolipoprotein E-deficient mice and ox-LDL-induced RAW264.7 cells were used to mimic the AS model, then THP was administered. Cell viability was detected by MTT. Pathological aorta lesions were detected using Hematoxylin and Eosin, Masson, and oil red staining. Lipid metabolism indices and inflammatory factors were measured using ELISA. A transmission electron microscope was used to observe autophagosomes. Autophagy and AMPK/mTOR pathway protein expression was detected by immunofluorescence and Western blot. The AMPK inhibitor 9-β-d-Arabinofuranosyl Adenine (Ara-A) was used to validate the effect of THP. The mRNA expression of Beclin-1 and MCP-1 was detected by q-PCR.

RESULTS:

THP administration regulated lipid metabolism by lowering total cholesterol, triacylglycerol, low-density lipoprotein, and high-density lipoprotein levels, and suppressed aortic damage. THP suppressed aortic damage and regulated lipid metabolism by altering serum lipid levels. THP reduced inflammation and macrophage CD68 expression. Twenty μg/mL THP reduced cell viability. THP decreased cholesterol uptake and increased efflux, promoting autophagy. THP increased autophagosome number, LC3B expression, and autophagy markers p-AMPK/AMPK and LC3-II/LC3-I. THP also decreased p-mTOR/mTOR and P62. THP increased Beclin-1 mRNA expression and decreased MCP-1 mRNA expression. Ara-A reversed THP's effects.

CONCLUSION:

THP promotes macrophage autophagy by inhibiting the AMPK/mTOR pathway to attenuate AS.

100 Deals associated with Tetrahydropalmatine sulfate

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