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Product name: 7-Ketocholesterol
Synonym name: 7-Oxocholesterol
Catalogue No.: BP4652
Cas No.: 566-28-9
Formula: C27H44O2
Mol Weight: 400.647
Botanical Source:
Type of Compound: Steroids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
For Reference Standard and R&D, Not for Human Use Directly.
HPLC of 7-Ketocholesterol
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
37.3000
6.6655
6.6655
.0005
7.1656
10.5270
High
92.2640
4.3201
No
No
No
No
No
No
0.0
No
No
No
No
7-Ketocholesterol (7-Ketocholesterol, abbreviated as 7-KC, CAS No.: 566-28-9) is an oxidation product of cholesterol and is an important member of the group of oxidized cholesterol (oxysterols). It plays a complex and crucial role in both internal and external physiological and pathological processes, especially in the pathogenesis of cardiovascular diseases such as atherosclerosis. 7-KC is not only a marker of cholesterol oxidation but is also considered one of the key pathogenic factors in the formation and development of atherosclerotic plaques due to its stronger pro-inflammatory and pro-apoptotic effects than cholesterol. In recent years, with in-depth research into the biological functions of oxidized cholesterol, the pharmacological properties, molecular mechanisms of action, and potential clinical applications of 7-KC have gradually attracted attention.
This paper will systematically review the chemical structure and physicochemical properties of 7-keto cholesterol, plant origin and extraction methods, pharmacological activity, mechanism of action and molecular targets, druggability evaluation, and pharmacokinetic characteristics. Finally, it explores its prospects and challenges in clinical application, aiming to provide a theoretical foundation and reference for research on natural product pharmacology and cardiovascular diseases.
7-Keto cholesterol is a type of oxidized cholesterol with the chemical formula C27H44O2 and a molecular weight of 400.6470. Its structural feature is the introduction of a ketone group (C=O) at the 7-position carbon atom of cholesterol, significantly altering its molecular polarity and biological activity. The chemical structure of 7-KC determines its high lipid solubility, with a LogP value as high as 6.6655, demonstrating strong hydrophobicity. Its polar surface area (TPSA) is 37.3 Ų, with extremely low water solubility (0.0005 mg/mL), which gives 7-KC strong penetration into biofilms and makes it easy to accumulate in lipid environments.
Additionally, 7-KC has a high blood-brain barrier penetration capability, a characteristic that suggests its potential impact in central nervous system diseases. Toxicological evaluation showed that 7-KC does not have hERG channel inhibitory activity, and Ames mutagenicity test results are negative, indicating low risk in terms of cardiotoxicity and genotoxicity.
7-Ketone cholesterol is mainly found in animal tissues as a cholesterol oxidation product, especially abundant in atherosclerotic plaques and oxidized low-density lipoprotein (oxLDL). Although 7-KC is present in low amounts in plants, trace amounts can also be detected in some plant oils and oxidized plant extracts.
Currently, 7-KC is mostly extracted and purified by isolating animal tissues or oxidized LDL. Common methods include organic solvent extraction (such as chloroform-methanol mixed solvent), silica gel column chromatography, and high-performance liquid chromatography (HPLC) purification. Due to its extremely low water solubility, care must be taken to avoid excessive oxidation and degradation during extraction. In recent years, supercritical CO2 extraction technology and solid-phase extraction technology have demonstrated advantages in efficient separation of 7-KC, improving purity and yield.
The pharmacological activity of 7-ketocholesterol mainly centers on its role in atherosclerosis and related cardiovascular diseases. Numerous in vivo and in vitro studies have shown that 7-KC exhibits significant pro-inflammatory, apoptotic, and cytotoxic effects.
Pro-inflammatory effects: 7-KC can activate various inflammatory signaling pathways, inducing macrophages and endothelial cells to secrete inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1). By activating nuclear factor κB (NF-κB) and NLRP3 inflammasomes, it promotes inflammatory cascade reactions and drives the formation and instability of atherosclerotic plaques.
Apoptotic effect: 7-KC can induce programmed cell death in various cell types, including vascular endothelial cells, smooth muscle cells, and macrophages. Its mechanism involves mitochondrial dysfunction, increased reactive oxygen species (ROS) production, and endoplasmic reticulum stress responses, ultimately activating the caspase family and triggering the apoptosis pathway.
Inhibition of cholesterol-metabolizing enzyme activity: 7-KC can inhibit key rate-limiting enzymes in cholesterol metabolism, such as cholesterol 7α-hydroxylase (CYP7A1) and HMG-CoA reductase, affecting bile acid synthesis and endogenous cholesterol synthesis, thereby regulating cholesterol homeostasis.
Oxidative stress and cellular dysfunction: Oxidative stress damage induced by 7-KC is at the core of its toxic effects, leading to lipid peroxidation of cell membranes, abnormal protein function, and DNA damage, further exacerbating vascular lesions.
7-Keto cholesterol mediates its biological effects through multiple signaling pathways and targets, involving cellular metabolic regulation, inflammatory responses, and cell survival regulation.
AMPK (PRKAA1): As a key regulator of cellular energy metabolism, AMPK is involved in regulating 7-KC-induced metabolic stress responses. 7-KC can influence AMPK activity, thereby regulating cellular autophagy and metabolic homeostasis.
EHMT2 (G9a): EHMT2 is a histone methyltransferase involved in epigenetic regulation. 7-KC may influence the transcription of inflammation- and apoptosis-related genes by regulating EHMT2-mediated gene expression.
MCL1 and BCL2: These two anti-apoptotic proteins are important regulators of cell survival. During apoptosis induced by 7-KC, the expression of MCL1 and BCL2 is downregulated, promoting the activation of apoptosis signals.
RECQ1: As a DNA helicase, RECQ1 participates in DNA repair. Oxidative stress induced by 7-KC may damage DNA, and dysfunction of RECQ1 further exacerbates cellular damage.
LOX-1 (oxidized low-density lipoprotein receptor 1): LOX-1 is a receptor that recognizes oxidized LDL. 7-KC, as an important component of oxLDL, promotes endothelial cell dysfunction and inflammatory responses through LOX-1-mediated signaling pathways.
ABCA1: As a key transporter for cholesterol excretion, ABCA1 regulates intracellular cholesterol levels. 7-KC regulation of ABCA1 affects cholesterol metabolism and plaque stability.
IDO1 (indole amine 2,3-dioxygenase 1): IDO1 participates in immune regulation, and 7-KC may modulate the local immune environment by affecting IDO1 activity, promoting inflammatory responses.
The interactions of these targets form a complex network of 7-KC mechanisms, revealing its multidimensional regulatory mechanisms in atherosclerosis and related diseases.
The druggability evaluation of 7-keto cholesterol shows that it poses certain challenges. Its high LogP value (6.6655) and extremely low water solubility limit its oral bioavailability and uniformity in vivo. However, 7-KC has a high blood-brain barrier penetration capability, suggesting it may affect the central nervous system and requires attention to potential neurotoxicity risks.
Toxicological data indicate that 7-KC does not inhibit hERG channels, reducing the risk of cardiotoxicity; A negative Ames test indicates low genotoxicity, which is beneficial for drug safety evaluation. Pharmacokinetics, 7-KC is mainly metabolized in the liver in the body; the metabolites and their clearance pathways still require further research.
Due to the inherent toxic characteristics of 7-KC being pro-inflammatory and pro-apoptotic, its direct use as a drug has limitations; however, its structure and mechanism of action provide important clues for designing derivatives or antagonists.
As a key pathogenic factor in atherosclerosis, 7-ketocholesterol has potential value for its detection and regulation in clinical diagnosis and treatment. 7-KC can serve as a biomarker for atherosclerosis and related cardiovascular diseases, helping to assess disease risk and progression.
Future research can focus on the following directions:
Drug development targeting 7-KC: Designing molecules that can specifically clear or neutralize 7-KC molecules, or developing small-molecule drugs that block their interactions with key targets (such as LOX-1, AMPK, etc.) to slow the progression of atherosclerosis.
Antioxidant and anti-inflammatory strategies: Combining the pro-inflammatory and apoptotic properties of 7-KC to develop combined antioxidant and anti-inflammatory drugs to enhance therapeutic outcomes.
Metabolic regulation research: In-depth analysis of the regulatory mechanisms of 7-KC on cholesterol-metabolizing enzymes, exploring new strategies to regulate cholesterol homeostasis.
Neurological Effects: Given the blood-brain barrier penetration of 7-KC, its role and potential risks in neurodegenerative diseases were studied.
Bioanalytical and detection technology: Establish highly sensitive 7-KC detection methods to promote their application in clinical and basic research.
In summary, 7-keto cholesterol, as an important oxidized cholesterol in natural products, offers new perspectives and targets for cardiovascular disease prevention and treatment due to its multidimensional biological functions and complex mechanisms.
7-Ketocholesterol, as a cholesterol oxidation product, plays a key role in the pathology of atherosclerosis. Its unique chemical structure gives it strong pro-inflammatory and pro-apoptotic activities, affecting cholesterol metabolism and cellular function. Although its drug-like properties are limited, in-depth research on 7-KC not only helps reveal the pathogenesis of atherosclerosis, but also provides important evidence for the diagnosis and treatment of related diseases. In the future, combining precise regulation of molecular targets with novel drug design is expected to enable effective interventions in 7-KC-related pathological processes, promoting the development of natural product pharmacology and cardiovascular disease treatment.
Shenshuai
Wenjing
Hedandan
