Synonym name: Eutannin
Catalogue No.: BP0339
Cas No.: 18942-26-2
Formula: C₄₁H₃₂O₂₇
Mol Weight: 956.68
Botanical Source: Tannin derived from divi-divi (fruit of Caesalpinia coriaria) and myrobalans (fruit of Terminalia chebula). Also obtainable from Geranium thunbergii and the seeds of sal (Shorea robusta)

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 Chebulinic acid 

HNMR of Chebulinic acid

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

Introduction/Overview

Chebulinic acid (CAS No.: 18942-26-2) is a natural polyphenolic compound derived from traditional medicinal plants, widely recognized for its unique chemical structure and significant biological activity. As a natural M. Tuberculosis DNA gyrase inhibitor and hesitate show potential drug development value in the fields of anti-tuberculosis and drug-resistant bacterial infections. Additionally, heprosic acid has been found to inhibit the phosphorylation of SMAD-3 and the activity of H+ K+-ATPase in gastric parietal cells, suggesting its potential in the treatment of antifibrosis and gastric acid-related diseases. This paper will systematically review the chemical structure, plant origin, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Heizic acid, aiming to provide a reference for the pharmacology of natural products and related drug development.

Chemical structure and physicochemical properties

Heproziic acid is a high molecular weight polyphenolic water-soluble compound with a molecular weight of 956.67, a complex molecular formula, and contains multiple phenolic hydroxyl groups and ester bond structures. Its LogP value is -2.5, indicating strong hydrophilicity, and its topological pole surface area (TPSA) reaches 500, indicating strong polarity. It has as many as 27 hydrogen bond acceptors, reflecting its abundant polar groups and potential hydrogen bonding capabilities. These physicochemical properties determine the absorption and distribution characteristics of hezinic acid in the body, especially limiting its ability to cross the blood-brain barrier (whether it is permeable or not). Additionally, there is currently no clear data on safety indicators such as hepatotoxicity, cardiotoxicity, hERG channel inhibition, and mutagenicity (Ames assay), and further systematic evaluation is needed.

Structurally, heprozinic acid is a hydrolyzed tannin containing multiple gallic acid and hexose residues, with a complex structure and good stability. Its abundant phenolic hydroxyl groups provide excellent antioxidant activity, while also influencing its interactions with biomacromolecules, especially binding to proteases and enzyme targets.

Plant Origins and Extraction Methods

Hezi acid is mainly found in plants such as Hezi (Terminalia chebula Retz.), which is an important medicinal herb in traditional Chinese medicine and Indian Ayurvedic medicine, widely used to treat digestive system diseases and infectious diseases. Besides Hezi, other Terminalia species such as Terminalia bellirica and Terminalia arjuna also contain certain amounts of Hezi acid.

Traditional extraction methods mostly use water extraction or ethanol extraction, combined with ultrasound-assisted extraction and microwave-assisted extraction to improve extraction efficiency and purity. Typical processes include:

1. Crush and dry plant material;
2. Use 70%-80% ethanol or water as solvent for reflux extraction;
3. Purification by liquid-liquid partitioning, column chromatography (such as silica gel, reversed-phase C18 column), and other methods;
4. Purity and structure are confirmed using high-performance liquid chromatography (HPLC) and mass spectrometry (MS).

In recent years, supercritical CO2 extraction and membrane separation technologies have also been attempted for the extraction and purification of hesogenic acid, aiming to achieve green and efficient industrial production.

Pharmacological activity research

Anti-tuberculosis and anti-drug-resistant bacteria

Heziic acid, as M. A natural inhibitor of tuberculosis DNA gyrase, it effectively inhibits the ATPase activity of this enzyme, blocking the formation of bacterial DNA supercoil structures, thereby inhibiting bacterial replication and transcription. DNA gyrase is an important target for Mycobacterium tuberculosis, especially in drug-resistant strains, where drug development targeting this target is of great significance.

In vitro experiments showed that prosizic acid had a significant inhibitory effect on various drug-resistant strains, especially showing a relatively low minimum inhibitory concentration (MIC) against multidrug-resistant tuberculosis strains. In addition, proscidioic acid also exhibits certain inhibitory activity against other related targets such as GYPB, DHFR, MECA, and PENA, indicating broad-spectrum antibacterial potential.

Anti-fibrotic effects

Heprosic acid can inhibit the phosphorylation of SMAD-3, blocking activation of the transforming growth factor β (TGF-β) signaling pathway, thereby slowing the fibrotic process. SMAD-3 is a key transcription factor for TGF-β signaling, and its abnormal activation forms the pathological basis for various fibrotic diseases. Both animal models and cell experiments have confirmed that heproziic acid can effectively inhibit fibrosis in organs such as the liver and lungs, offering potential value for anti-fibrotic drug development.

Inhibits gastric acid secretion

Heprozinic acid has also been found to inhibit the activity of H+ K+-ATPase in gastric parietal cells, reducing gastric acid secretion and helping to treat gastric acid-related conditions such as gastric ulcers and gastroesophageal reflux. Its mechanism of action is similar to proton pump inhibitors (PPIs), but as a natural product, probosic acid may have better safety and tolerability.

Other biological activities

In addition to the main activities mentioned above, heproziic acid also exhibits antioxidant, anti-inflammatory, anti-tumor, and other biological effects, with related research continuing to deepen.

Mechanism of action and molecular targets

DNA gyrase inhibition mechanism

DNA gyrase is a topoisomerase unique to bacteria, responsible for maintaining the supercoil state of DNA. Heproziic acid binds to the ATP binding site of DNA gyrase, blocking its ATPase activity and inhibiting the enzyme's supercoil introduction, leading to inhibition of DNA replication and transcription, and suppressed bacterial growth.

Molecular docking and kinetic simulations show that the polyphenolic hydroxyl group of Heproziic acid forms stable hydrogen bonds and hydrophobic interactions with key amino acid residues in DNA gyrase, enhancing binding affinity.

SMAD-3 phosphorylation is inhibited

The TGF-β signaling pathway activates receptor kinases, promoting SMAD-3 phosphorylation and translocation to the nucleus, thereby regulating the expression of fibrosis-related genes. Hesitic acid can interfere with this phosphorylation process, block signal transduction, and alleviate pathological changes in fibrosis. The specific mechanism may involve direct inhibition of receptor kinases or regulation of upstream signaling molecules.

H+ K+-ATPase inhibition

H+ K+-ATPase is the proton pump of gastric parietal cells, responsible for the secretion of gastric acid. Heprosic acid binds to the catalytic subunit of enzymes, inhibiting its ATP hydrolysis activity, reducing proton pump function, and decreasing gastric acid secretion. This mechanism differs from traditional PPIs and may offer new therapeutic strategies.

Other target effects

The inhibitory effects of heproziic acid on targets such as GYPB (erythrocyte membrane glycoprotein), DHFR (dihydrofolate reductase), MECA, and PENA suggest that it may exert antibacterial and other pharmacological effects through multi-target synergistic action.

Druggability evaluation and pharmacokinetics

The high molecular weight (956.67 Da) and high polarity (LogP-2.5, TPSA 500) of heproziic acid limit its oral bioavailability and cell membrane permeability, making it especially difficult to cross the blood-brain barrier and limiting its application in central nervous system diseases. Its abundant number of hydrogen bond receptors facilitates target binding but also increases metabolic and excretion complexity.

Currently, there is no systematic data on the hepatotoxicity, cardiotoxicity (including hERG channel inhibition), and mutagenicity of heproziic acid, requiring systematic toxicological studies to assess safety. Additionally, pharmacokinetic studies show that heprochetinic acid is metabolized rapidly in the body, mainly through hepatic enzyme systems, with strong intestinal metabolism and first-pass effects, which limit the maintenance of its plasma concentration.

To improve its druggability, researchers have attempted to enhance its stability, bioavailability, and targeting by using nanocarriers, liposomal encapsulation, and structural modification.

Prospects and outlooks for clinical applications

As a multi-target natural product, heprozinic acid exhibits significant antimicrobial activity, especially targeting M. The inhibitory effect of tuberculosis DNA gyrase provides new approaches for treating tuberculosis, especially multidrug-resistant tuberculosis. Combined with its anti-fibrotic and acid-inhibiting effects, heprosic acid demonstrates potential clinical value in various disease fields.

Future research focuses should include:

1. Optimize extraction and purification processes to improve product purity and yield;
2. In-depth analysis of its molecular mechanisms, especially multi-target synergistic effects;
3. Systematic pharmacokinetics and toxicology studies are conducted to clarify safety and dosage ranges;
4. Improving druggability through drug design and carrier technology;
5. Conduct preclinical animal models and clinical trials to verify efficacy and safety.

Moreover, the polyphenolic structure of prosicic acid provides a good platform for synthesizing analogs and derivatives, and future structural optimization can enhance its efficacy and pharmacokinetic properties.

Conclusion

As a natural polyphenolic compound with multiple biological activities, hesolic acid shows broad application prospects in the treatment of anti-drug-resistant bacterial infections, anti-fibrosis, and gastric acid-related diseases. Its unique mechanism of action and multi-target characteristics provide valuable resources for pharmacological research of natural products and new drug development. However, the high polarity and large molecular weight of hesolic acid limit its druggability, and it urgently needs to be improved through modern medicinal chemistry and pharmaceutics. In the future, combining systematic pharmacological research with clinical validation, hesolic acid is expected to become an important representative of the new generation of natural medicines, providing new solutions for clinical treatment of drug-resistant bacterial infections and related diseases.