Delving into the Latest Updates on Isoliquiritigenin with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

Mechanism

ALOX12 inhibitors(12-lipoxygenase inhibitors), Aldehydes inhibitors(Aldehydes inhibitors), COX inhibitors(Cyclooxygenases inhibitors)

Therapeutic Areas

NeoplasmsSkin and Musculoskeletal DiseasesUrogenital Diseases

Active Indication

Breast CancerProstatic Cancer

Inactive Indication

Diabetes Complications

Originator Organization

Tsumura & Co.

Active Organization

Hallym University

Yonsei University

Inactive Organization

Tsumura & Co.

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Structure

Molecular FormulaC15H12O4

InChIKeyDXDRHHKMWQZJHT-FPYGCLRLSA-N

CAS Registry961-29-5

Isoliquiritigenin (ISL), a flavonoid derived from licorice root, has diverse biological and pharmacological properties. This study aimed to investigate the hepatoprotective effects and mechanism of action of ISL on the pathogenesis of metabolic dysfunction-associated steatohepatitis (MASH). C57BL/6 mice fed a chow diet or choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) received ISL (10 mg/kg) or vehicle daily via oral administration. To further explore the mechanism of ISL in MASH pathogenesis, AML12 cells were exposed to palmitic acid (PA) as an in vitro model of lipid toxicity. The results showed that, compared with vehicle-treated mice, ISL treatment alleviated liver injury, steatosis, inflammation, and fibrosis in MASH mice. Moreover, ISL treatment reduced the recruitment of CD68⁺ macrophages and activated hepatic stellate cells (HSCs) in MASH livers. In vitro experiments showed that ISL reduced lipid accumulation and mitigated inflammatory responses in PA-induced AML12 cells. Notably, RNA-sequencing analyses revealed that the anti-MASH effect of ISL enhanced autophagy via the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway. This was further validated by assessing autophagy markers in both MASH liver tissues and PA-stimulated AML12 cells in vitro. Additionally, molecular docking analysis demonstrated that the target proteins of ISL exhibited strong binding affinity to PIK3 isoforms. In conclusion, our findings highlight that ISL mitigates MASH and fibrosis in mice by promoting autophagy through the PI3K/Akt/mTOR signaling pathway, providing reliable evidence to support further studies on MASH in humans.

01 Feb 2025·JOURNAL OF ETHNOPHARMACOLOGY

Comprehensive profiling of traditional herbomineral formulation Manasamitra vatakam in rat brain following oral administration and in-silico screening of the identified compound for anti-Alzheimer's activity

Article

Author: Lakshmi, P.K. ; Aneesh, T P ; Lakshmi, P K ; Nair, Anju C. ; Sudheesh, M S ; Benny, Sonu ; Nair, Anju C ; Sudheesh, M.S. ; TP, Aneesh

ETHNOPHARMACOLOGICAL RELEVANCE:

Multi-targeted drug therapy has received substantial attention for the treatment of diseases of multifactorial origin, such as neurodegenerative diseases. Manasamitra vatakam (MMV) is a traditional Ayurvedic formulation used to improve cognitive impairment and mental illness. Here we have used a unique method for leveraging the barrier properties of the intestinal and blood-brain barrier (BBB) to screen and identify the bioactive molecules against Alzheimer's disease (AD). The current method exemplifies a facile method to expedite drug discovery from traditional formulations.

AIM OF THE STUDY:

The present study aimed to identify the phytoconstituents of MMV that reach the brain tissue and to predict major bioactive constituents by computational docking studies.

MATERIALS AND METHODS:

After oral administration of the formulation, brain samples from male Sprague Dawley rats were collected at different time intervals and analyzed by liquid chromatography-mass spectrometry (LC-MS) to identify the phytoconstituents. In silico molecular docking studies were carried out to analyze the binding affinity of the compounds to the target proteins of AD using Schrodinger Maestro. The molecular dynamic studies were carried out for all the docked complexes having higher docking scores.

RESULTS:

34 phytoconstituents were identified by LC-MS analysis of brain homogenates. In the in silico docking study, the phytoconstituents chrysin, convolvin, rutin, galangin, palmatoside G, isoliquiritigenin, quercetin, and naringenin showed higher docking score against the target proteins of AD. These compounds may serve as the primary bioactive compounds responsible for the neuroprotective activity of the herbal formulation. Furthermore, molecular dynamic studies indicated that the galangin-acetylcholinesterase enzyme complex has the highest stability among these eight compounds.

CONCLUSION:

The study, together with previous in vivo and in vitro efficacy results, suggests that BBB-permeable compounds with high binding affinities for the target proteins of AD might be responsible for the effectiveness of MMV against AD.

01 Feb 2025·JOURNAL OF ETHNOPHARMACOLOGY

Combining virus-based affinity ultrafiltration method with serum pharmacochemistry to identify the antiviral pharmacodynamic substances in licorice

Article

Author: Jiang, Jiayu ; Dong, Meiyue ; Li, Zhongyuan ; Cui, Qinghua ; Liu, Miaomiao ; Chen, Zinuo ; Zhang, Chengcheng

ETHNOPHARMACOLOGICAL RELEVANCE:

Liorice (Glycyrrhiza uralensis Fisch.), a widely used Chinese herbal medicine, is frequently employed in clinical practice to treat viral pneumonia. However, the pharmacodynamic substances and mechanisms of action responsible for its antiviral effects against H1N1 and RSV remain unclear.

AIM OF THE STUDY:

To investigate the antiviral effects of licorice against H1N1 and RSV. Building on this, we aimed to more comprehensively and accurately identify the pharmacodynamic substances in licorice responsible for its antiviral activity and mechanisms of action against these two viruses.

MATERIALS AND METHODS:

Firstly, the antiviral effects of licorice against H1N1 and RSV were confirmed through in vivo and in vitro experiments. Then, a combination of virus-based affinity ultrafiltration method (VAUM) and serum pharmacochemistry were used to screen for pharmacological substances in licorice and identify their molecular targets against H1N1 and RSV.

RESULTS:

The in vivo experiments showed that licorice effectively alleviates H1N1 and RSV induced weight loss and lung tissue damage in mice, while also reducing viral loads of H1N1 and RSV in the lungs. Subsequent in vitro experiments confirmed the presence of original compounds in licorice that directly inhibit H1N1 and RSV. By combining both methods, glycyrrhizic acid, glycyrrhetinic acid (GA), isoliquiritigenin (ISL), and glyasperin A (targeting the M2 ion channel) were ultimately identified as the pharmacodynamic substances in licorice responsible for anti-H1N1 activity. Additionally, licochalcone A (LCA) and glyasperin A, which target RSV surface proteins, were identified as the pharmacodynamic substances responsible for anti-RSV activity.

CONCLUSIONS:

Traditional Chinese medicine (TCM) exerts its antiviral effects through a 'multi-component, multi-target' mechanism, which poses challenges for single active compound screening methods to adequately address. By integrating VAUM and serum pharmacochemistry for the first time, one approach focused on identifying compounds in TCM that directly bind to viral surface proteins, while the other targeted compounds that enter the bloodstream in their original form and exhibit antiviral activity. This provides a novel approach for studying the pharmacodynamic substances of antiviral effects in TCM.

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R&D Status

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Indication	Highest Phase	Country/Location	Organization	Date
Breast Cancer	Preclinical	KR	Yonsei University	15 Apr 2006
Prostatic Cancer	Preclinical	KR	Hallym University	01 May 2005
Diabetes Complications	Preclinical	JP	Tsumura & Co.	-
Neoplasms	Preclinical	JP	Tsumura & Co.	-