Product name: Dihydrowithaferin A
Synonym name: 2,3-Dihydrowithaferin-A
Catalogue No.: BP4187
Cas No.: 5589-41-3
Formula: C₂₈H₄₀O₆
Mol Weight: 472.622
Botanical Source: Ashwagandha
Physical Description:
Type of Compound: Terpenoids

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.

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

Introduction/Overview

Dihydrowithaferin A (CAS No.: 5589-41-3) is a lactone natural product isolated from the traditional medicinal plant Withania somnifera. As an important medicinal ingredient in India's traditional Ayurvedic medicine, Nightshade has been widely studied for its many bioactive components. Dihydroisoledone A, as one of its key active ingredients, has attracted significant attention in pharmacology in recent years due to its significant acetylcholinesterase inhibitory activity and multi-target anti-inflammatory effects. Its unique chemical structure and favorable druggability parameters make it highly valuable for the treatment of neurodegenerative diseases, chronic inflammation, and related pathological conditions.

This paper will systematically review the chemical structure and physicochemical properties of dihydrosucolysidin A, plant origin and extraction methods, pharmacological activity, and its mechanism of action. It focuses on its molecular targets and signaling pathway regulation in the anti-inflammatory field, and, combined with druggability evaluation and pharmacokinetic characteristics, anticipates its clinical translation prospects and provides theoretical support for subsequent basic and applied research.

Chemical structure and physicochemical properties

Dihydrosizandsidium A is a typical lysolalactone compound, with the chemical formula C28H38O6 and a molecular weight of 472.6220. Its structural basis is a steroid backbone, containing a characteristic lactone ring, and hydrogenated modifications exist at positions 2 and 3, hence it is called 2,3-dihydrodracysolin A. This structure imparts high lipid solubility (LogP about 3.23), which facilitates penetration of cell membranes and the blood-brain barrier.

In terms of physicochemical properties, the polar surface area (TPSA) of dihydrotozotonin A is 96.36 Ų, indicating moderate polarity that facilitates binding to protein targets. Low water solubility (0.0214 mg/mL) suggests that in vivo it may require improved bioavailability via liposomes or other carrier systems. Importantly, dihydrodrunolin A does not exhibit hERG channel inhibitory activity, reducing the risk of cardiotoxicity; The Ames test result was 0, indicating no significant mutagenicity and good safety.

The steroid framework and lactone ring in its structure play a decisive role in its bioactivity, and by modifying different sites in this structure, its pharmacodynamics and pharmacokinetic characteristics may be further optimized.

Plant Origins and Extraction Methods

Dihydronidutisolin A is mainly isolated from the Indian medicinal plant Withania somnifera (also known as Cordyceps). Nightshade belongs to the Solanaceae family, widely distributed across the Indian subcontinent and parts of Asia. Its roots, leaves, and fruits all contain various bioactive steroid esters, with dihydroisolysidin A being particularly abundant.

Traditional extraction methods mostly use organic solvent extraction combined with column chromatography for separation. The general process is as follows:
1. Collect dried nightshade roots or leaves and crush them into powder.
2. Use moderately polar solvents such as methanol, ethanol, or ethyl acetate for reflux extraction.
3. After concentration, the extract is separated and purified using silica gel column chromatography or high-performance liquid chromatography (HPLC).
4. Pure products are identified by nuclear magnetic resonance (NMR), mass spectrometry (MS), and other methods.

In recent years, to improve extraction efficiency and purity, green technologies such as ultrasound-assisted extraction and supercritical fluid extraction have gradually been applied to the extraction of dihydrotolysidin A, balancing environmental protection and economic efficiency.

Pharmacological activity research

The pharmacological activity of dihydrosusol A mainly focuses on neuroprotection, anti-inflammation, and inhibition of acetylcholinesterase (AChE). Its inhibitory effect on AChE lays the foundation for its potential application in the treatment of neurodegenerative diseases such as Alzheimer's disease (AD). Relevant in vitro enzymatic experiments indicate that dihydrotalysol A can effectively reduce AChE activity, delay the breakdown of acetylcholine, and improve neurotransmitter function.

Anti-inflammatory activity is another important pharmacological property of dihydrotoxicin A. Multiple cell and animal model studies have confirmed that it can significantly inhibit the expression of inflammatory factors such as tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6), thereby reducing inflammatory responses. Its efficacy in chronic inflammatory diseases, neuroinflammation, and pain models is gradually gaining recognition.

In addition, dihydrotozotonin A has shown multiple effects in modulating oxidative stress, inhibiting apoptosis, and providing neuroprotection, suggesting broad pharmacological potential.

Mechanism of action and molecular targets

The pharmacological mechanism of dihydrosusol A involves multiple molecular targets and signaling pathways, with particularly outstanding performance in the anti-inflammatory field. Its main targets include:

• IL-6 (interleukin 6): Dihydrosusolin A can downregulate IL-6 expression, inhibit inflammatory cascades, and alleviate cytokine storms.
• STAT3 (Signal Transduction and Transcription Activator 3): As a key transcription factor in the IL-6 signaling pathway, STAT3 inhibition blocks the transmission of inflammatory signals.
• CASP1 (caspase-1): regulates the activation of inflammatory bodies. Dihydrolysidrolin A reduces the release of inflammatory mediators by inhibiting CASP1 activity.
• TRPV1 and TRPA1 (transient receptor potential channels): involved in the transmission of pain and inflammatory signals, the regulatory effect of dihydroduplysidium A helps alleviate inflammation-related pain.
• PTGS1 and PTGS2 (cyclooxygenases 1 and 2): Dihydroduperosol A inhibits the activity of these two enzymes, reduces prostaglandin synthesis, and exerts anti-inflammatory and analgesic effects.
• TNF (tumor necrosis factor): As the core mediator of inflammatory responses, inhibition of TNF expression is a crucial link in the anti-inflammatory mechanism of dihydrolysidrolin A.
• NOS2 (induced nitric oxide synthase): By inhibiting NOS2, it reduces excess nitric oxide production, alleviating oxidative stress and inflammatory damage.
• NFKB1 (nuclear factor κB): As a key transcription factor for inflammatory signals, dihydroduplysidin A blocks inflammatory gene expression by inhibiting NF-κB activation.

In summary, dihydroduplysidium A inhibits the generation and signaling of inflammatory factors through multi-target synergistic regulation, reducing inflammatory responses and related pathological processes. Additionally, its inhibitory effect on acetylcholinesterase provides a mechanistic basis for neuroprotection.

Druggability evaluation and pharmacokinetics

Druggability is a key step in the clinical transformation of natural products. Dihydrodrunisolin A performs excellently in druggability parameters:

• The molecular weight (472.62) complies with the Lipinski rule, facilitating oral absorption.
• LogP (3.23) showed moderate lipid solubility, which facilitates cell membrane penetration and blood-brain barrier permeability.
• TPSA (96.36 Ų) is moderate, supporting good bioavailability.
• Water solubility is relatively low (0.0214 mg/mL), suggesting the need for pharmacological improvement of solubility.
• The high permeability of the blood-brain barrier provides a foundation for its application in central nervous system diseases.
• hERG inhibitors are negative, reducing the risk of cardiotoxicity.
• Ames test was negative, indicating no mutagenicity and relatively high safety.

In terms of pharmacokinetics, although there is currently limited research on metabolic kinetics in vivo, preliminary data already indicate that dihydrodunitolium A has good stability and half-life in vivo. Its lipophilic solubility and blood-brain barrier permeability support its potential as a central nervous system drug. Future studies on in vivo absorption, distribution, metabolism, and excretion (ADME) are needed to clarify its pharmacokinetic characteristics and metabolic pathways.

Prospects and outlooks for clinical applications

Based on the multi-target anti-inflammatory effects and acetylcholinesterase inhibitory activity of dihydrotolysidrolin A, it has broad application prospects in the treatment of various diseases:

1. Neurodegenerative diseases: such as Alzheimer's disease and Parkinson's disease, dihydrolythiolin A may slow disease progression and improve cognitive function by improving cholinergic function and suppressing neuroinflammation.
2. Chronic inflammatory diseases: including rheumatoid arthritis and inflammatory bowel disease, dihydroduplysidin A can regulate inflammatory signaling pathways through multiple targets, reducing tissue damage.
3. Pain management: Its regulatory effect on the TRPV1/TRPA1 channel offers new ideas for relieving inflammatory pain.
4. Immune regulation: By regulating CASP1 and NFKB1, dihydrolysidrolin A may play a regulatory role in immune-related diseases.

Future research should focus on:
- Optimize its pharmaceutical formulations to improve bioavailability and targeting.
- In-depth analysis of its molecular mechanisms and signaling networks.
- Conduct systematic in vivo pharmacokinetic and toxicological assessments.
- Design preclinical and clinical trials to verify their safety and efficacy.

In addition, structural modification and derivative development will also offer opportunities to enhance its efficacy and reduce potential side effects.

Conclusion

Dihydrosizandazurin A, as an important steroidal ester natural product in nightshade, demonstrates significant acetylcholinesterase inhibition and anti-inflammatory potential due to its unique chemical structure and multi-target bioactivity. Its excellent druggability parameters and safety evaluation have laid a solid foundation for clinical translation. With further analysis of its mechanism of action and advances in pharmacokinetic research, dihydrodunitazole A is expected to become a novel candidate for the treatment of neurodegenerative and chronic inflammatory diseases. In the future, multidisciplinary collaborative research will further promote its transition from the laboratory to clinical applications, benefiting a wide range of patients.