Product name: Isotheaflavin
Synonym name:
Catalogue No.: BP2112
Cas No.: 31701-93-6
Formula: C₂₉H₂₄O₁₂
Mol Weight: 564.499
Botanical Source: Black Tea
Type of Compound:

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 Isotheaflavin

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

Introduction/Overview

Isotheaflavins are a class of natural polyphenolic compounds found in black tea and are important members of the theaflavin family. As a widely consumed beverage worldwide, black tea's unique fermentation process causes tea polyphenols to oxidize and polymerize, forming various theaflavin compounds, among which isotheaflavins are among the most biologically active components. In recent years, with the deepening development of natural product pharmacology, isotheaflavins have become a research hotspot due to their excellent antioxidant properties and potential anti-aging effects. This paper aims to systematically review the chemical structure and physicochemical properties of isotheaflavins, plant origins and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and clinical application prospects, aiming to provide scientific evidence for the in-depth development and application of this natural product.

Chemical structure and physicochemical properties

The chemical formula of isotheaflavin is C_30H_24O_12, with a molecular weight of 564.4990 and CAS number 31701-93-6. Its structure is based on the diphenol framework of theaflavins, featuring polyphenolic hydroxyl groups and phenolic structures, which give it strong antioxidant capacity. The LogP value of isotheaflavins is 1.4223, indicating moderate lipid solubility that aids membrane penetration, but low water solubility (0.1715), limiting their solubility in aqueous environments. Its topological polar surface area (TPSA) is relatively large, at 217.6 Ų, indicating strong polarity that may affect biofilm permeability.

Structurally, isotheaflavins contain multiple phenolic hydroxyl groups, which are not only key sites for their antioxidant activity but also affect their ability to bind to biological macromolecules such as proteins and enzymes. Additionally, isotheaflavins did not show hERG channel inhibitory activity, indicating a low cardiotoxicity risk. The Ames test value was 0.6, indicating low genotoxicity risk and meeting safety requirements.

Plant Origins and Extraction Methods

Isotheaflavins are mainly found in black tea (Camellia sinensis), especially during the fermentation of black tea, where catechin compounds in tea leaves are catalyzed by polyphenol oxidase catalytic oxidative polymerization. The fermentation process of black tea is a key step in the production of isotheaflavins, with fermentation time and temperature directly affecting its content and composition.

Traditional methods for extracting isotheaflavins include water extraction, ethanol extraction, and their combined extraction, combined with modern technologies such as ultrasound-assisted extraction and microwave-assisted extraction, which can improve extraction efficiency and purity. The crude extract after extraction is usually separated, purified, and qualitatively analyzed using techniques such as liquid chromatography (HPLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and other methods. In recent years, supercritical fluid extraction technology has also been explored for the extraction of isotheaflavins, offering advantages of being green, environmentally friendly, and highly efficient.

Pharmacological activity research

As an important polyphenolic antioxidant in black tea, isotheaflavins exhibit various pharmacological activities, especially attracting attention for their potential in antioxidant, anti-inflammatory, anti-aging, and neuroprotective aspects.

1. Antioxidant activity
   Isoflavins can eliminate free radicals, inhibit lipid peroxidation, and protect cells from oxidative stress damage. Its polyphenolic hydroxyl structure allows it to directly capture reactive oxygen species (ROS) and nitrogen radicals, reducing cell damage caused by oxidative stress.

2. Anti-aging effects
   The aging process is closely related to oxidative stress. Isoflavins activate intracellular antioxidant enzyme systems (such as SOD1, CAT, GPX1) and regulate the NFE2L2 signaling pathway, enhancing cellular antioxidant defenses and delaying cellular aging. In addition, isotheaflavins regulate lipid metabolism-related enzymes (SMPD1, ASAH1, UGCG, CERK, SGMS1), maintain lipid homeostasis in cell membranes, and protect cell function.

3. Anti-inflammatory effects
   Isoflavins can inhibit the expression of pro-inflammatory factors and reduce chronic inflammatory responses, providing protection against various age-related diseases.

4. Neuroprotective effects
   Although the istheaflavin blood-brain barrier has relatively low permeability, it indirectly exerts neuroprotective effects by regulating peripheral antioxidant and anti-inflammatory mechanisms, thereby reducing the risk of neurodegenerative diseases.

Mechanism of action and molecular targets

The mechanism of action of isotheaflavins mainly regulates various age-related molecular targets:

• NFE2L2 (nuclear factor red cell 2, related factor 2)
  NFE2L2 is a key transcription factor for cellular antioxidant stress. Isoflavins can activate NFE2L2, promote its nuclear translocation, induce the expression of downstream antioxidant enzymes (SOD1, CAT, GPX1, HMOX1), and enhance cellular antioxidant capacity.

• Antioxidant enzyme systems (SOD1, CAT, GPX1, HMOX1)
  These enzymes play a central role in eliminating superoxide anions, hydrogen peroxide, and harmful free radicals. Istheaflavins reduce oxidative damage by upregulating the activity of these enzymes.

• Lipid metabolism-related enzymes (SMPD1, ASAH1, UGCG, CERK, SGMS1)
  These enzymes participate in lipid metabolism and signal transduction in cell membranes, maintaining the integrity and function of the membrane. Isoflavins regulate these targets, helping lipid homeostasis in cell membranes and preventing cellular dysfunction caused by lipid metabolism disorders.

In summary, isotheaflavins exert their anti-aging and cell-protective pharmacological effects through multi-target and multi-pathway synergistic effects.

Druggability evaluation and pharmacokinetics

Druggability evaluation of isotheaflavins shows that they have certain development potential:

• Molecular weight and physicochemical properties
  The molecular weight of 564.5 is slightly higher than the 500 recommended by Lipinski's rules, but its LogP value of 1.42 is moderate, which facilitates cell membrane penetration. Higher TPSA (217.6) and lower water solubility (0.1715) may limit oral absorption and bioavailability.

• Blood-brain barrier permeability
  Isoflavin has relatively low permeability of the blood-brain barrier, limiting its direct effect on central nervous system diseases, but its protective effect on peripheral tissues remains valuable.

• Security
  No hERG inhibitory activity, indicating a low risk of cardiotoxicity. Ames test results showed that the genotoxicity risk was low and met safety requirements.

• Pharmacokinetics
  Currently, data on the absorption, distribution, metabolism, and excretion (ADME) of isotheaflavins in vivo are relatively limited. Its larger molecular weight and polar structure may lead to lower oral bioavailability. In the future, drug carrier systems or structural modifications will be needed to improve in vivo stability and bioavailability.

Prospects and outlooks for clinical applications

Isotheaflavins, as natural antioxidant polyphenols in black tea, have good safety and multi-target anti-aging effects, and have broad clinical application potential:

1. Anti-aging health supplements
   Based on their antioxidant and cellular function regulation abilities, isotheaflavins can serve as active ingredients in anti-aging health supplements to help slow down the aging process.

2. Supports treatment for chronic diseases
   By regulating oxidative stress and inflammatory responses, isotheaflavins are expected to assist in the treatment of chronic diseases related to aging, such as cardiovascular disease, metabolic syndrome, and neurodegenerative disorders.

3. Functional foods and beverages
   As a natural ingredient, isotheaflavins can be widely used in functional foods and beverages to enhance the health value of products.

Future research should focus on optimizing the pharmacokinetics, developing formulations, and verifying the efficacy and safety of isotheaflavins through clinical trials. In addition, by integrating modern drug design technologies, developing isotheaflavin derivatives or compound formulations to enhance their bioavailability and targeting will further drive their clinical translation.

Conclusion

As an important natural polyphenolic antioxidant in black tea, isotheaflavins demonstrate remarkable pharmacological activity and good safety thanks to their unique chemical structure and multi-target anti-aging mechanisms. Although its water solubility and blood-brain barrier permeability are limited, through modern extraction techniques and optimization of drug carrier systems, isotheaflavins have broad application prospects in anti-aging, chronic disease prevention and treatment, and functional food applications. In the future, pharmacokinetic research and clinical validation should be strengthened to promote the transformation of isotheaflavins from natural products into clinical drugs, benefiting human health.