Synonym name: Shikonin acetate
Catalogue No.: BP0118
Cas No.: 24502-78-1
Formula: C₁₈H₁₈O₆
Mol Weight: 330.336
Botanical Source: Lithospermum erythrorhizon, Lithospermum euchromum, Jatropha glandulifera, Arnebia decumbens, Arnebia euchroma and Echium vulgare

Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.

For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.

HPLC of Acetylshikonin

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Acetylshikonin (CAS No.: 24502-78-1) is a natural naphthoquinone compound derived from plants of the Lithospermum genus, attracting attention for its diverse biological activities. Shikonin and its derivatives, as important active ingredients in the traditional Chinese medicine Lithospermum erythrorhizon, have long been used to treat inflammation, trauma, and tumors. Acetylshikonin, as an acetylated derivative of shikonin, demonstrates more significant pharmacological activity, especially showing broad application potential in anti-tumor, anti-inflammatory, antioxidant, and neuroprotective fields.

In recent years, with the deepening of molecular pharmacology and natural product chemistry, the mechanism of action of acetyl shikonin has gradually been clarified, involving multiple aspects such as apoptosis, autophagy regulation, inhibition of inflammatory signaling pathways, and metabolic regulation. Moreover, the unique mechanism of action of this compound in the treatment of hepatitis B virus (HBV)-associated hepatocellular carcinoma (HCC), especially by inducing the HBV oncoprotein ER stress and inhibiting tumor cell proliferation, has become a research hotspot. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of acetylshikonin, aiming to provide theoretical basis and research directions for further development and application.

Chemical structure and physicochemical properties

Acetylshikonin has a molecular formula of C17H18O5 and a molecular weight of 330.33, belonging to the naphthoquinone compounds. Its structure is based on the naphthoquinone framework of shikonin, formed by acetylation modification of hydroxyl groups. This structure imparts good lipid solubility (LogP about 3.01), which facilitates membrane penetration and improved bioavailability. Its topological pole surface area (TPSA) is 96.65, containing six hydrogen bond acceptors, indicating certain polarity and the ability to form hydrogen bonds with various biological macromolecules.

Acetylshikonin has high permeability to the blood-brain barrier, suggesting its potential application value in neurological diseases. Safety evaluations showed no significant hepatotoxicity or cardiotoxicity, and both hERG channel inhibition and Ames-induced mutagenic tests were negative, indicating high safety and promising drug potential.

Plant Origins and Extraction Methods

Acetylshikonin is mainly found in Lithospermum species, with Lithospermum erythrorhizon being especially abundant in its roots. As a traditional Chinese medicinal herb, Listhospermum is widely distributed in East Asian regions such as China, Japan, and South Korea. Its roots contain various active ingredients, including shikonin, acetyl shikonin, methoxyshikonin, and other naphthoquinone compounds.

Common methods for extracting acetyl shikonin include organic solvent extraction extraction, ultrasound-assisted extraction, and high-performance liquid chromatography (HPLC) separation technology. Ethanol or methanol is usually used as extraction solvents, purified by concentration, separation, and column chromatography, and finally confirmed by HPLC or mass spectrometry for purity and structure. In recent years, green extraction technologies such as supercritical CO2 extraction and microwave-assisted extraction have also been applied to improve the extraction efficiency and purity of acetyl shikonin.

Pharmacological activity research

Antitumor activity

Acetylshikonin exhibits significant inhibitory effects across various tumor cell lines, especially selectively targeting hepatocellular carcinoma cells expressing hepatitis B virus X protein (HBX). Its antitumor mechanism mainly induces endoplasmic reticulum (ER) stress responses, activates apoptotic signaling pathways, and promotes tumor cell apoptosis and autophagy. Additionally, acetyl shikonin can inhibit the production of leukotrienes, reducing the tumor-promoting effects of the inflammatory microenvironment.

Anti-inflammatory and antioxidant effects

Acetylshikonin significantly reduces the production of inflammatory mediators and exerts anti-inflammatory effects by inhibiting the recruitment of cytoplasmic phospholipase A2 (cPLA2) membranes and blocking the activities of cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). At the same time, its antioxidant activity reduces oxidative stress damage and protects cell function by scavenging free radicals and regulating endogenous antioxidant enzyme systems.

Neuroprotective and antibacterial activity

Acetylshikonin, as an acetylcholinesterase (AChE) inhibitor (IC50=34.6 μM), demonstrates neuroprotective effects in neurodegenerative disease models, possibly by improving neurotransmission and reducing neuroinflammation. Additionally, it exhibits antibacterial activity against various bacteria, suggesting its potential application in infectious diseases.

Metabolic regulation

Research shows that acetylshikonin can regulate blood glucose levels, improve hepatic fat metabolism, alleviate pathological changes in renal fibrosis, and demonstrate its therapeutic potential in diabetes, diabetic nephropathy (DN), obesity, and non-alcoholic fatty liver disease (NAFLD).

Mechanism of action and molecular targets

The multi-target mechanism of acetyl shikonin forms the basis of its pharmacological activity. Its main targets and signaling pathways include:

• ER stress pathway: Acetylshikonin induces intraplasmic reticulum stress in tumor cells, activates PERK, IRE1, and ATF6 signals, promotes apoptosis and autophagy, and is especially effective against HBX-positive liver cancer cells.
• Inflammatory mediator synthase: By lowering intracellular Ca²⁺ concentration, it inhibits cPLA2 membrane localization, blocks COX and 5-LOX activity, decreases the production of prostaglandins and leukotrienes, and suppresses inflammatory responses.
• Acetylcholinesterase (AChE) inhibition: Inhibits the breakdown of acetylcholine, improves neurotransmission, and has neuroprotective effects.
• Cytochrome P450 enzyme system: Non-selectively inhibits multiple P450 enzymes, affecting drug metabolism and endogenous metabolic processes.
• Metabolic regulation-related targets: regulating the expression of genes such as PPARG and ALOX5, participating in lipid metabolism and inflammation regulation.
• Targets related to benign prostatic hyperplasia: including MAOA, ESR1/2, APEX1, ABCG2, TOP2A, MAOB, ELANE, etc., suggesting the potential role of acetyl shikonin in prostate diseases.

Druggability evaluation and pharmacokinetics

Acetylshikonin has a moderate molecular weight (330.33) and a LogP value of 3.01, meeting the Lipinski rule and showing good drug similarity. Its TPSA value (96.65) and hydrogen bond receptor number (6) indicate moderate polarity, facilitating oral absorption and cell membrane penetration. High blood-brain barrier permeability supports its potential application in central nervous system diseases.

In terms of safety, acetyl shikonin showed no hepatotoxicity or cardiotoxicity, no inhibitory effect on the hERG channel, and the Ames mutagenic test was negative, indicating good safety. In vivo pharmacokinetic studies show that oral acetyl shikonin has high bioavailability, wide distribution, stable metabolism, and is mainly excreted by hepatic metabolism and bile excretion.

Prospects and outlooks for clinical applications

With its multi-target and multi-mechanism pharmacological properties, acetyl shikonin shows broad clinical application prospects in anti-tumor, anti-inflammatory, neuroprotection, and metabolic disease treatment. Especially in the treatment of HBV-associated hepatocellular carcinoma, selective apoptosis of tumor cells is achieved by inducing the ER stress pathway, providing new ideas for precision treatment of liver cancer.

Additionally, the potential efficacy of acetyl shikonin in diabetes and its complications (such as diabetic nephropathy), non-alcoholic fatty liver, and obesity suggests it could be a new candidate for comprehensive treatment of metabolic syndrome. Its neuroprotective effects also make it possible to treat neurodegenerative diseases such as Alzheimer's.

Future research should focus on preclinical pharmacokinetic optimization, formulation development, and clinical trial validation of acetylshikonin, combined with modern drug design techniques to improve its targeting and bioavailability. At the same time, in-depth analysis of its molecular action network and the discovery of more potential targets and indications will promote its clinical translation.

Conclusion

Acetylshikonin, a natural product derived from the traditional Chinese medicine Lithospermum, demonstrates outstanding anti-tumor, anti-inflammatory, antioxidant, and metabolic regulatory abilities due to its unique chemical structure and diverse pharmacological activities. Its mechanism of action covers multiple aspects including apoptosis, autophagy, inhibition of inflammatory mediator synthesis, and neuroprotection, demonstrating excellent druggability and safety.

With the development of modern pharmacology and molecular biology technologies, research on acetyl shikonin has been deepening, and its clinical application potential is becoming increasingly prominent. In the future, through systematic pharmacokinetic research and clinical validation, acetylshikonin is expected to be developed into an innovative drug for treating liver cancer, metabolic diseases, and neurological disorders, making significant contributions to the field of natural product pharmacology.