Delving into the Latest Updates on Kakonein with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

Puerarin

Target

BK channel x L-type calcium channel

Mechanism

BK channel agonists(Calcium-activated potassium channel alpha/beta 1 agonists), L-type calcium channel blockers(Voltage-gated L-type calcium channel blockers)

Therapeutic Areas

Cardiovascular DiseasesOther Diseases

Active Indication

Cardiovascular DiseasesAlcoholism

Inactive Indication-

Originator Organization

Natural Pharmacia International

Active Organization

Natural Pharmacia International

Yantai Luyin Pharmaceutical Co. Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1993),

Cardiovascular Diseases

Regulation-

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Structure

Molecular FormulaC21H20O9

InChIKeyHKEAFJYKMMKDOR-VPRICQMDSA-N

CAS Registry3681-99-0

Pyroptosis is a critical pathological mechanism implicated in myocardial damage following myocardial infarction (MI), and the crosstalk between macrophages and pyroptotic cardiomyocytes presents a formidable challenge for anti-pyroptosis therapies of MI. However, as single-target pyroptosis inhibitors frequently fail to address this crosstalk, the efficacy of anti-pyroptosis treatment post-MI remains inadequate. Therefore, the exploration of more potent anti-pyroptosis approaches is imperative for improving outcomes in MI treatment, particularly in addressing the crosstalk between macrophages and pyroptotic cardiomyocytes. Here, in response to this crosstalk, we engineered an anti-pyroptosis biomimetic nanoplatform (NM@PDA@PU), employing polydopamine (PDA) nanoparticles enveloped with neutrophil membrane (NM) for targeted delivery of puerarin (PU). Notably, network pharmacology is deployed to discern the most efficacious anti-pyroptosis drug (puerarin) among the 7 primary active monomers of TCM formulations widely applied in clinical practice and reveal the effect of puerarin on the crosstalk. Additionally, targeted delivery of puerarin could disrupt the malignant crosstalk between macrophages and pyroptotic cardiomyocytes, and enhance the effect of anti-pyroptosis by not only directly inhibiting cardiomyocytes pyroptosis through NLRP3-CASP1-IL-1β/IL-18 signal pathway, but reshaping the inflammatory microenvironment by reprogramming macrophages to anti-inflammatory M2 subtype. Overall, NM@PDA@PU could enhance anti-pyroptosis effect by disrupting the crosstalk between M1 macrophages and pyroptotic cardiomyocytes to protect cardiomyocytes, ameliorate cardiac function and improve ventricular remodeling, which providing new insights for the efficient treatment of MI.

01 Jan 2025·Journal of Ethnopharmacology

Ge-Zhi-Jie-Jiu decoction alleviates alcoholic liver disease through multiple signaling pathways

Article

Author: Liu, Sijing ; Guo, Jinlin ; Bai, Jing ; Chen, Yangyang ; Gao, Tinghui ; Li, Yaoguang ; Liu, Yixin ; Yu, Lilu ; Zhang, Wenjing ; Niu, Shuqi

ETHNOPHARMACOLOGICAL RELEVANCEAlcoholic liver disease (ALD) is a growing public health concern caused by excessive alcohol consumption, but effective treatments are limited. Ge-Zhi-Jie-Jiu decoction (JJY) is a modified traditional Chinese herbal remedy that aims to alleviate ALD. This formula contains various components such as Ge Hua, Ge Gen, Zhi Ju Zi, and other medicinal-food herbs. However, the specific pharmacotherapeutic compounds of JJY and its pharmacological mechanisms remain unclear.AIM OF THE STUDYThis study aimed to elucidate the molecular mechanism and pharmacodynamic basis of JJY in treating ALD.MATERIALS AND METHODSUPLC-Q-Orbitrap HRMS, HPLC fingerprinting, and LC-MS techniques were used for the composition identification and quality control of JJY. The pharmacological components and molecular mechanisms of JJY in anti-ALD were then predicted using network pharmacology and molecular docking approaches. Ultimately, an acute alcoholic liver injury mouse model was developed, and the potential mechanisms were verified by hematoxylin-eosin (H&E), Oil Red O, and TUNEL staining, real-time fluorescence quantitative PCR (RT-qPCR), Western blot (WB) and molecular docking analysis.RESULTSThe results showed that the main components of JJY are organic acids, flavonoids, and isoflavonoids, in which puerarin, daidzein, glycitein, ononin, quercetin, and tectorigenin can be used as the indicator components of JJY. In addition, JJY might ameliorate ALD through several pathways, including potentially promoting alcohol metabolism via alcohol-metabolizing enzymes, and possibly inhibiting oxidative stress, inflammation and apoptosis via the Nrf2/Keap1/HO-1 and MAPK signaling pathways. Furthermore, JJY may also alleviated hepatic lipid accumulation through the PPARα signaling pathway.CONCLUSIONSJJY has significant anti-ALD efficacy with multiple mechanisms. This study offers a solid experimental foundation for JJY's development as a medicine with anti-ALD characteristics and elucidates its probable active components.

01 Jan 2025·Journal of Ethnopharmacology

A novel framework for uncovering the coordinative spectrum-effect correlation of the effective components of Yangyin Tongnao Granules on cerebral ischemia-reperfusion injury in rats

Article

Author: Jin, Weifeng ; Chen, Qianqian ; Chen, Junjie ; Xiao, Peng ; Yu, Li

ETHNOPHARMACOLOGICAL RELEVANCEIschemic stroke is currently a major public health hazard.Yangyin Tongnao Granules (YYTN), a traditional Chinese medicinal prescription, exerts potential therapeutic effects on subsequent cerebral ischemia-reperfusion injury (CIRI) after ischemic stroke. However, further studies are required to comprehend the underlying mechanism of YYTN for treating CIRI and the associated spectrum-effect mechanisms.AIM OF THE STUDYTo investigate the coordinated correlation between the fingerprint and the pharmacodynamic indexes of the effective components (total flavonoids, total saponins, total alkaloids, and total phenolic acids) in YYTN for treating CIRI in rats.METHODSThe fingerprints of five specific components (ligustrazine, puerarin, ferulic acid, calycosin, and formononetin) of YYTN in rats with middle cerebral artery occlusion (MCAO) were established using high-performance liquid chromatography (HPLC), and their peak areas were quantified in plasma samples. The pharmacodynamic indexes of tumor necrosis factor-alpha (TNF-α), cytochrome c (Cyt-C), and total superoxide dismutase (T-SOD) were integrated using the Criteria Importance Through Intercriteria Correlation (CRITIC) method to create a comprehensive evaluation index. Spectrum-effect correlation was analyzed by performing gray relation analysis (GRA), correlation analysis (CA), and partial least squares regression (PLSR). The Borda method was then applied to integrate the obtained results.RESULTSIn MCAO rats, the effective components of YYTN reduced TNF-α and Cyt-C and increased T-SOD, which indicates their anti-inflammatory, antiapoptotic, and antioxidant effects. Spectrum-effect CA revealed certain associations between the chromatographic peaks of the five main components and the comprehensive pharmacodynamic evaluation index. Of these components, formononetin displayed the highest correlation, whereas ferulic acid exhibited the lowest correlation. All components showed a positive correlation. Using the Borda method, the components were ranked as follows based on correlation: formononetin > calycosin > ligustrazine > puerarin > ferulic acid.CONCLUSIONSThe effective components of YYTN exhibited synergistic effects in the treatment of MCAO rats, which could potentially be attributed to their multitarget and multipathway mechanisms. The Borda method-based spectrum-effect correlation analysis provides a coordinated approach to investigate the relationship between fingerprint and pharmacodynamics of traditional Chinese medicine (TCM).

100 Deals associated with Kakonein

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB12290

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Cardiovascular Diseases	CN	Yantai Luyin Pharmaceutical Co. Ltd.	01 Jan 1993

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Alcoholism	Phase 2	-	Natural Pharmacia International	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00854724 (PAD, CTgov)	Phase 2	Alcoholism	16	Placebo+Puerarin (Placebo, Then Puerarin)	mgssedfzby(ppxhvoohgt) = brmdojporv ntzwhyxctx (jdztqalwna, gfceunvxjs - kzyifpnisy) View more	-	12 Aug 2011
				Placebo+Puerarin (Puerarin, Then Placebo)	mgssedfzby(ppxhvoohgt) = qsstwmikbh ntzwhyxctx (jdztqalwna, cfmneptqfn - sdxhfoqqyn) View more
ARVO2009	Not Applicable	-	-	Microemulsion with ion-triggered in situ gelling system for puerarin (ME-G-PU)	(opneniggfd) = rcoksjecqb gemmaaxbbk (wgulgtefxe ) View more	-	01 Apr 2009
				Microemulsion containing 1% PU (ME-PU)	(opneniggfd) = dxcabfaxpv gemmaaxbbk (wgulgtefxe ) View more