Product name: Sanggenol L
Synonym name:
Catalogue No.: BPF2787
Cas No.: 329319-20-2
Formula: C₂₅H₂₈O₆
Mol Weight: 424.493
Botanical Source:
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.

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

Introduction/Overview

Natural products, as an important source of drug discovery, play an irreplaceable role in the long history of human struggle against diseases. Flavonoids, as one of the most widely distributed and structurally diverse secondary metabolites in nature, have attracted much attention due to their rich and diverse biological activities. From basic antioxidant and anti-inflammatory properties to complex anti-tumor and neuroprotective effects, flavonoids have shown tremendous therapeutic potential. Among the numerous members of flavonoids, a more complex and unique class of "Extended Flavonoids" has gradually become a research hotspot. Sanggenol L is an outstanding representative of this type of compound.

Mulberry root alcohol L, CAS number 329319-20-2, is derived from the mulberry family plants（Morus A unique isoprenyl substituted extended flavonoid compound isolated from the root bark of spp. The "Sanggenol" series of compounds in its name specifically refers to a class of polyphenolic substances derived from the genus Morus, structurally based on flavonoid mother nuclei and connected with side chains such as isopentenyl and geranyl groups, or forming complex cyclic systems. Compared with simple flavonoids such as quercetin and kaempferol, extended flavonoids such as mulberry root alcohol L have a more complex molecular structure and significantly enhanced lipid solubility due to the introduction of hydrophobic isopentenyl side chains. This often endows them with stronger interaction ability with biological membranes and protein targets, thereby exhibiting unique pharmacological activities beyond traditional flavonoids.

In recent years, with the gradual deepening of research on mulberry root alcohol L, its potential application value in multiple fields such as antioxidant, anti-inflammatory, anti-tumor, neuroprotective, and skin protection has been continuously revealed. Especially its role in regulating oxidative stress-related signaling pathways and key targets has aroused widespread interest among pharmacologists. Oxidative stress is considered to be one of the core pathological mechanisms for the occurrence and development of aging, cardiovascular diseases, neurodegenerative diseases, diabetes, cancer and other major diseases. The strong antioxidant capacity of Sanggenol L, as well as its regulatory effects on a series of antioxidant enzymes and transcription factors such as NFE2L2 (NRF2), SOD1, CAT, GPX1, HMOX1, make it an ideal candidate molecule for developing new antioxidant drugs or functional food/cosmetic additives.

This article aims to provide a systematic review of the current research status of mulberry root alcohol L. We will start from its unique chemical structure, explore its physicochemical properties, plant sources, and extraction processes, focusing on its pharmacological activities such as antioxidant and anti-inflammatory effects, as well as the underlying molecular mechanisms. We will evaluate its potential as a lead compound based on its pharmacological parameters, and finally look forward to its future application prospects in the pharmaceutical and health industries. Through this review, it is expected to provide a comprehensive and in-depth professional reference on mulberry root alcohol L for researchers engaged in natural product chemistry, pharmacology, and drug development.

Chemical structure and physicochemical properties

Chemical structural characteristics

Mulberry root alcohol L is a typical extended flavonoid compound. Its core skeleton is the classic flavonoid structure (2-phenylchromenone), but unlike simple flavonoids, mulberry root alcohol L has prenyl side chains attached to the A and/or B rings. According to existing literature reports, the molecular formula of mulberry root alcohol L is C ₂₅ H ₂₈ O ₆, and its precise structure is usually described as containing an isopentenyl group at a specific position (such as C-8 or C-6) in the flavonoid mother nucleus, and may have an ortho dihydroxy group structure on the B ring. This structural feature combines the planarity of the flavonoid core with the flexibility of the isopentenyl side chain, which facilitates its insertion into the lipid bilayer of biological membranes or interaction with the hydrophobic pockets of proteins.

Physical and chemical property parameters

Based on the provided pharmacological parameters, we can conduct a comprehensive analysis of the physicochemical properties of Sanggenol L

1. Molecular weight (MW): 424.4930 Da The molecular weight falls within the range of drug like rules (such as Lipinski's Five Rules) (MW<500), indicating its fundamental potential as an oral medication. However, for natural products, this molecular weight is moderate to high, indicating that they may face certain absorption challenges.

2. Lipid water partition coefficient (LogP): 5.2993 LogP is an important indicator for measuring the lipophilicity of compounds. The LogP value of Sanggenol L is 5.30, significantly higher than most traditional flavonoids (usually between 1-3), and also exceeds the limit of LogP<5 in Lipinski's rule. This is mainly attributed to the isopentenyl side chain in its molecule, which greatly enhances the lipophilicity of the molecule. A high LogP value means that mulberry root alcohol L is highly soluble in organic solvents, but its solubility in water will be very low. This is both an advantage (advantageous for penetrating cell membranes and binding to membrane proteins) and a challenge (which may lead to poor water solubility and low oral bioavailability).

3. Polar surface area (TPSA): 96.22 Å ²TPSA reflects the ability of compounds to form hydrogen bonds. The TPSA of Sangen alcohol L is 96.22 Å ², mainly due to multiple phenolic hydroxyl and carbonyl groups in its molecule. It is generally believed that the TPSA of oral medications should be less than 140 Å ², and molecules below 60-70 Å ² are more likely to penetrate the blood-brain barrier. The TPSA value of Sanggenol L indicates a moderate degree of polarity and a certain potential for oral absorption, but its ability to penetrate the blood-brain barrier may be limited.

4. Water solubility: 0.0447 mg/mL The extremely low value confirms the problem of poor water solubility caused by its high LogP. Low water solubility is one of the main reasons for the failure of the development of many natural products and candidate drugs. The poor solubility of Sanggenol L means that its dissolution rate in the gastrointestinal tract may be slow, which seriously affects its oral absorption.

5. Blood-brain barrier (BBB) permeability: low Combined with its high TPSA and molecular weight, sangol L is predicted to have low blood-brain barrier permeability. This suggests that it may be difficult to enter the central nervous system, so its pharmacological effects may mainly be concentrated in peripheral tissues. This may be a favorable factor for developing drugs targeting peripheral diseases such as skin aging, inflammation, and metabolic disorders, which can avoid side effects on the central nervous system.

6. HERG inhibition: No The hERG (human Ether - à - go Related Gene) potassium ion channel is closely associated with prolonged QT interval and the risk of fatal arrhythmias in the heart. Sanggenol L is predicted to have no hERG inhibitory activity, which is a very positive signal indicating its low risk of cardiac toxicity and good safety.

7. Ames test: 0.0 The Ames test is used to evaluate the mutagenicity of compounds. The Ames test result of Sanggenol L is 0.0, indicating that it has no mutagenicity and low genetic toxicity risk in this prediction model, further supporting its safety as a lead compound.

Summary The chemical structure of Sanggenol L determines its unique physicochemical properties. Its high LogP and low water solubility are the core features, which are both the structural basis for its potent biological activity and the main bottleneck for its drug development. However, its low hERG inhibition risk and negative Ames test results provide preliminary assurance for its safety. Future pharmaceutical chemistry research needs to focus on addressing the issue of poor water solubility, such as through prodrug design, nano formulations, or structural modifications.

Plant sources and extraction methods

Plant-based

Mulberry root alcohol L mainly comes from the Moraceae genus in the Moraceae family（Morus）The root bark of plants. Mulberry trees have a long cultivation history in East Asian countries such as China, Japan, and South Korea. Their root bark (mulberry bark) is a commonly used medicinal herb in traditional Chinese medicine, which has the effects of clearing the lungs, relieving asthma, promoting diuresis, and reducing swelling. Modern research has shown that mulberry bark is rich in various active ingredients, including Diels Alder type adducts, flavonoids, stilbenes (such as resveratrol and oxidized resveratrol), and benzofuran derivatives. Mulberry root alcohol L was discovered in a systematic study of the chemical composition of mulberry bark.

Except for mulberry trees（Morus alba L. In addition, other mulberry plants such as chicken mulberry（Morus australis）Meng Sang（Morus mongolica）It may also contain mulberry root alcohol L or its structural analogues. Plant chemistry studies have shown that the content of mulberry root alcohol L in mulberry plants is usually low and belongs to trace active ingredients, which poses challenges for its large-scale extraction and purification.

Extraction and Separation Methods

Given the high lipid solubility of Sanggenol L, its extraction and separation processes typically follow the principle of "similar phase solubility" and are refined using modern chromatographic techniques. The typical process flow is as follows:

1. Raw material pretreatment Collect mulberry bark, wash, dry in the shade or at low temperature, and grind it to an appropriate particle size (such as 20-40 mesh) to increase the extraction contact area.

2. Extract：

   • Solvent selection Due to the high L LogP value and low polarity of mulberry root alcohol, organic solvents with medium to low polarity are often used for extraction. The most commonly used solvents are aqueous solutions of ethanol (EtOH) or methanol (MeOH) (such as 70% -95%), and sometimes ethyl acetate (EtOAc) or acetone may also be used. Heating reflux extraction or room temperature cold soaking/percolation are commonly used methods. In order to improve extraction efficiency, modern technologies such as ultrasound assisted extraction (UAE) and microwave-assisted extraction (MAE) have also been widely used, which can destroy cell walls and accelerate the dissolution of target components.
   • Extraction liquid treatment After filtration, the extract is concentrated under reduced pressure to recover the solvent and obtain the total extract.

3. Preliminary separation and enrichment：

   • Liquid-liquid extraction Disperse the total extract in water, and then extract it sequentially with solvents of different polarities such as petroleum ether, ethyl acetate, n-butanol, etc. Due to its high lipophilicity, Sanggenol L is mainly enriched in the ethyl acetate extraction layer or petroleum ether extraction layer. This step can remove a large amount of water-soluble impurities (such as sugars, tannins) and strongly polar components.
   • Column chromatography Separate the target extraction layer (such as ethyl acetate layer) by silica gel column chromatography. Gradient elution is usually performed using mixed solvent systems such as chloroform methanol or petroleum ether acetone. Collect the fraction containing mulberry root alcohol L through thin-layer chromatography (TLC) monitoring.

4. Fine purification：

   • Reverse phase column chromatography After preliminary separation, the crude product usually needs to be further purified using reverse phase silica gel (such as ODS-C18) column chromatography. The use of methanol water or acetonitrile water systems for gradient elution can more effectively separate structurally similar flavonoids.
   • Gel column chromatography Sephadex LH-20 gel column chromatography is a classical method for purifying flavonoids. It can be separated based on molecular size and adsorption, and has significant effects on removing pigments and separating compounds with similar molecular weights.
   • Preparation type high performance liquid chromatography (Prep HPLC)For high-purity (>98%) samples of mulberry root alcohol L, it is usually necessary to refine them using preparative HPLC. Choosing a suitable reverse phase C18 chromatography column and mobile phase (such as acetonitrile water or methanol water, with a small amount of formic acid or acetic acid added) can achieve baseline separation of the target compound.

5. Structural Identification The purified compounds were structurally confirmed using modern spectroscopic techniques, including nuclear magnetic resonance spectroscopy (¹ H-NMR, ¹ ³ C-NMR, 2D-NMR) and high-resolution mass spectrometry (HR-ESI-MS). By comparing with the L-spectral data of mulberry root alcohol reported in literature, its chemical structure was finally determined.

Summary The extraction and separation of mulberry root alcohol L is a typical natural product chemistry research process, which relies on its high lipid solubility to gradually enrich and purify target components from complex plant matrices through a combination of organic solvent extraction, liquid-liquid extraction, and various column chromatography techniques. Due to its low content in plants, the development of efficient and green extraction processes (such as enzyme assisted extraction, supercritical fluid extraction) and large-scale preparation technologies is the key to promoting its research and application in the future.

Pharmacological activity research

As a characteristic component of mulberry plants, the pharmacological activity research of mulberry root alcohol L mainly focuses on its antioxidant, anti-inflammatory, anti-tumor, and skin protection aspects, among which antioxidant activity is its most core and fundamental function.

antioxidant activity

Oxidative stress is a state in which the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the body is imbalanced with the antioxidant defense system. The molecular structure of Sangen alcohol L contains multiple phenolic hydroxyl groups, which can directly scavenge free radicals and are the chemical basis for its antioxidant activity.

• Direct free radical scavenging ability In vitro chemical experiments (such as DPPH, ABTS, FRAP, etc.) have confirmed that Sanggenol L has significant direct free radical scavenging ability. Its clearance efficiency is usually superior to or equivalent to classical antioxidants such as vitamin C or vitamin E. The ortho dihydroxy structure in its molecule (if present) can interrupt the free radical chain reaction by providing hydrogen atoms or electrons to convert unstable free radicals into stable quinone structures.
• Cellular level antioxidant In cell models, sangentol L can effectively reduce intracellular ROS levels induced by hydrogen peroxide (H ₂ O ₂), tert butyl hydroperoxide (t-BHP), or ultraviolet (UV) radiation. For example, in human keratinocytes (HaCaT) or fibroblasts, mulberry root alcohol L pretreatment can significantly reduce oxidative damage and improve cell survival rate.
• Regulating the endogenous antioxidant enzyme system The antioxidant effect of Sanggenol L is not limited to direct clearance, but more importantly, it can activate the endogenous antioxidant defense system of cells. Research has shown that mulberry root alcohol L can promote the expression of a series of downstream antioxidant enzyme genes by activating the NFE2L2 (NRF2) signaling pathway, including:
  • SOD1 (Cu/Zn SOD) and SOD2 (Mn SOD)Superoxide dismutase is responsible for dismutation of superoxide anions (O ₂⁻) into H ₂ O ₂ and O ₂.
  • CAT (Catalase)Catalase breaks down H ₂ O ₂ into water and oxygen.
  • GPX1 (Glutathione Peroxidase 1)Glutathione peroxidase uses glutathione (GSH) to reduce H ₂ O ₂ and organic peroxides.
  • HMOX1 (Heme Oxygenase 1)Heme oxygenase-1 catalyzes the degradation of heme, producing biliverdin, carbon monoxide, and ferrous ions with antioxidant and anti-inflammatory properties.
    By upregulating the expression of these key enzymes, mulberry root alcohol L can significantly enhance the overall ability of cells to resist oxidative stress, which is a more persistent and efficient antioxidant mechanism.

anti-inflammatory activity

Inflammation is the body's defense response to harmful stimuli, but chronic inflammation is a common pathological basis for various diseases. Sanggenol L has shown significant anti-inflammatory activity in various inflammatory models.

• Inhibit inflammatory mediators In the lipopolysaccharide (LPS) - stimulated macrophage model (such as RAW264.7 cells), sangentol L can significantly inhibit the production of nitric oxide (NO), mainly by suppressing the expression of inducible nitric oxide synthase (iNOS). At the same time, it can also reduce the level of prostaglandin E2 (PGE2), which is related to the inhibition of cyclooxygenase-2 (COX-2) expression.
• Inhibit pro-inflammatory cytokines Sanggenol L can effectively reduce the secretion and mRNA expression of pro-inflammatory cytokines such as tumor necrosis factor - α (TNF - α), interleukin-1 β (IL-1 β), and interleukin-6 (IL-6) induced by LPS.
• Regulating signal pathways Its anti-inflammatory mechanism is closely related to the inhibition of key inflammatory signaling pathways, especially the nuclear factor kappa B (NF - κ B) and mitogen activated protein kinase (MAPK) pathways. Sanggenol L can inhibit the phosphorylation and degradation of I κ B α, thereby preventing the nuclear translocation of NF - κ B p65 subunit, reducing its binding to DNA, and ultimately inhibiting the transcription of inflammation related genes.

Antitumor activity

Sanggenol L exhibits inhibitory effects on proliferation and induces apoptosis in various cancer cell lines.

• cytotoxicity: Research shows that mulberry root alcohol L has different degrees of cytotoxicity to human leukemia cells (such as HL-60), liver cancer cells (such as HepG2), breast cancer cells (such as MCF-7), lung cancer cells (such as A549), and its IC ₀ value is usually in the micromolar level.
• Inducing apoptosis Its anti-tumor mechanism involves inducing cell apoptosis. Sanggenol L can activate the mitochondrial apoptosis pathway, manifested by a decrease in mitochondrial membrane potential (Δ PSI m), release of cytochrome c into the cytoplasm, and activation of Caspase-9 and Caspase-3, ultimately leading to cell apoptosis. In addition, it may also promote apoptosis by upregulating the expression of pro apoptotic protein Bax and downregulating the expression of anti apoptotic protein Bcl-2.
• cell cycle arrest Sanggenol L can also block cancer cells at specific cell cycle stages (such as G0/G1 phase or G2/M phase), thereby inhibiting cancer cell proliferation. This may be related to the regulation of the expression of cyclins and cyclin dependent kinases (CDKs).

Skin protective activity

Due to its strong antioxidant and anti-inflammatory activities, Sanggenol L has shown great potential in skin protection, especially in anti photoaging and whitening.

• Anti photoaging Ultraviolet radiation (especially UVA and UVB) is the main exogenous factor causing skin photoaging. Mulberry root alcohol L can effectively protect skin cells from UV damage. Its mechanism of action includes:
  • Eliminate UV induced ROS Reduce oxidative damage.
  • Inhibiting the expression of matrix metalloproteinases (MMPs)UV irradiation induces overexpression of MMP-1 (collagenase) and MMP-3 (matrix metalloproteinase) in skin fibroblasts, leading to degradation of collagen and elastin, which is a key cause of skin sagging and wrinkle formation. Sanggenol L can significantly inhibit UV induced expression of MMP-1 and MMP-3, thereby protecting the skin matrix. This is related to the regulation of MAPK and AP-1 signaling pathways.
  • Promote collagen synthesis Partial studies have shown that sangentol L may promote the synthesis of type I procollagen by activating the TGF - β/Smad signaling pathway.
• Whitening activity Mulberry root alcohol L has an inhibitory effect on tyrosinase (TYR). Tyrosinase is a key rate limiting enzyme in melanin synthesis. Mulberry root alcohol L can inhibit the activity of tyrosinase, thereby reducing the production of melanin. In B16 melanoma cells or zebrafish models, Sanggenol L showed good whitening effects and low cytotoxicity.

Mechanism of action and molecular targets

The pharmacological activity of Sanggenol L is the result of multi-target and multi pathway synergistic effects. Its core mechanism of action can be summarized as regulating the redox balance and intervening in key signaling pathways.

Core mechanism: Activation of NRF2/ARE antioxidant pathway

NRF2 (Nuclear factor erythroid 2-related factor 2) is composed of genes NFE2L2 Coding is the core transcription factor that cells use to respond to oxidative stress and electrophilic substances. Under normal physiological conditions, NRF2 binds to the inhibitory protein KEAP1 (Kelch like ECH associated protein 1) in the cytoplasm and is degraded by ubiquitination. When stimulated by oxidants or electrophilic substances (such as the phenolic hydroxyl oxidation product of Sanggenol L), the conformation of KEAP1 changes, leading to the release and stabilization of NRF2. Subsequently, NRF2 translocates into the nucleus and binds to antioxidant response elements (ARE), initiating the expression of a series of downstream protective genes.

Sanggenol L is an effective activator of NRF2. By activating NRF2, it upregulated including SOD1, SOD2, CAT, GPX1, HMOX1 Multiple antioxidant enzyme genes are included. This mechanism is the core of its antioxidant, anti-inflammatory, and cell protective effects. For example, the products of HMOX1, biliverdin and carbon monoxide, have strong anti-inflammatory and anti apoptotic effects. Therefore, Sanggenol L constructs a powerful cellular defense network through the NRF2 pathway.

Regulation of skin related targets

1. Inhibition of Tyrosinase (TYR)Mulberry root alcohol L can directly bind with tyrosinase, inhibiting its catalytic activity. Tyrosinase catalyzes the hydroxylation of L-tyrosine to L-dopa and further oxidizes it to dopa quinone, which is the starting and limiting step in melanin synthesis. The inhibitory effect of Sanggenol L may be achieved by chelating copper ions from the active center of tyrosinase or competing with substrates for binding sites. This is the direct molecular basis of its whitening activity.

2. Inhibition of matrix metalloproteinases (MMP-1, MMP-3)MMPs are key enzymes involved in the degradation of extracellular matrix (ECM). During the process of skin photoaging, UV irradiation activates epidermal growth factor receptor (EGFR) and cytokine receptor, thereby activating the MAPK pathway (such as ERK, JNK, p38). Activated MAPK phosphorylates and activates transcription factor AP-1 (c-Fos/c-Jun dimer), which enters the nucleus and binds to the MMP-1 and MMP-3 gene promoters, promoting their transcription. Sanggenol L can inhibit the phosphorylation of the MAPK pathway, thereby blocking the activation of AP-1 and ultimately downregulating the expression of MMP-1 and MMP-3, protecting skin collagen and elastin from degradation.

Regulation of anti-inflammatory signaling pathway

1. Inhibition of NF - κ B pathway NF - κ B is the core regulatory factor of inflammatory response. In the resting state, NF - κ B binds to I κ B and exists in an inactive form in the cytoplasm. Inflammatory stimuli such as LPS and TNF - α activate I κ B kinase (IKK), leading to phosphorylation and ubiquitination degradation of I κ B α, releasing NF - κ B into the nucleus and activating pro-inflammatory genes (such as iNOS, COX-2, TNF-α, IL-1β, IL-6）The transcription. Mulberry root alcohol L can inhibit the activity of IKK or the phosphorylation of I κ B α, thereby blocking the nuclear translocation of NF - κ B and exerting anti-inflammatory effects.

2. Inhibition of MAPK pathway As mentioned earlier, the MAPK pathway (ERK, JNK, p38) not only participates in the regulation of MMP, but also in the production of inflammatory factors. The inhibition of MAPK pathway by Sanggenol L is a common mechanism for its anti-inflammatory and anti-aging activities.

Summary The mechanism of action of mulberry root alcohol L exhibits a network like feature. It focuses on activating the NRF2 antioxidant pathway as its core, while simultaneously inhibiting key pro-inflammatory and pro degradation signaling pathways such as MAPK and NF - κ B, achieving multiple regulation of oxidative stress, inflammation, and ECM degradation. This multi-target mode of action is the fundamental reason for its broad pharmacological activity, and also makes it a potential pleiotropic drug for treating complex diseases related to oxidative stress, such as metabolic syndrome, neurodegenerative diseases, and skin aging.

Evaluation of drug properties and pharmacokinetics

Based on the aforementioned physicochemical properties and pharmacological activity, it is crucial to objectively evaluate the pharmacological properties of Sanggenol L.

Advantage

1. Clear pharmacological activity and novel mechanism of action Sanggenol L has potent antioxidant, anti-inflammatory, anti-tumor, and skin protective activities, especially its multi-target mode of action as an NRF2 agonist and MMP/TYR inhibitor, which gives it unique advantages in the treatment of oxidative stress-related diseases.
2. Preliminary prediction of good security HERG inhibition negative and Ames test negative indicate a low risk of cardiac and genetic toxicity, which is an important addition factor for it as a lead compound.
3. Potential advantages brought by high fat solubility A high LogP value makes it easy to penetrate the cell membrane, which is beneficial for binding to intracellular targets such as NRF2 and NF - κ B. For topical applications (such as skin) or indications that require high tissue permeability (such as anti-tumor), this may be a favorable factor.

Challenges and bottlenecks

1. Extremely poor water solubility The water solubility is only 0.0447 mg/mL, which is the biggest challenge facing its drug development. Low water solubility directly leads to poor oral absorption and low bioavailability, making it difficult to achieve effective blood drug concentrations. This is the main reason why many highly active natural products cannot enter clinical development.
2. Potential issues brought by high LogP LogP>5 exceeds the drug like rule and may cause the following issues:
   • High metabolic clearance rate Highly lipophilic compounds are easily metabolized by cytochrome P450 enzymes (CYP450) in the liver, resulting in a short half-life and low systemic exposure.
   • Non-specific binding Easy to highly bind with plasma proteins (such as albumin), reducing the concentration of free drugs and affecting drug efficacy.
   • Organizational accumulation toxicity May accumulate in adipose tissue or liver, causing long-term toxicity.
3. Pharmacokinetic properties unknown At present, there is a lack of research data on the in vivo pharmacokinetics (ADME) of sangentol L. Its absorption, distribution, metabolism, and excretion (ADME) processes in animal bodies are not yet clear. Whether its metabolites are active or toxic is also a question that needs to be studied.

Improvement strategy

In response to the above challenges, future research in medicinal chemistry and pharmacy can start from the following aspects:

1. Prodrug design Phosphorylation, amino acid esterification, or glycosylation modification of the phenolic hydroxyl group of Sanggenol L to prepare a prodrug. The prodrug is released from the body through enzymatic hydrolysis or hydrolysis, which can significantly improve water solubility and oral absorption.
2. Structural modification Introducing polar groups (such as carboxyl, amino, sulfonic acid) or reducing the overall lipophilicity of the molecule while retaining key pharmacophore groups (such as phenolic hydroxyl, isopentenyl) to balance LogP and water solubility.
3. New drug delivery system：
   • Liposomes/Nanoparticles Encapsulating mulberry root alcohol L in liposomes or polymer nanoparticles can significantly improve its water dispersibility, stability, and bioavailability.
   • Cyclodextrin inclusion complex Using β - cyclodextrin or its derivatives to encapsulate sangol L can increase its apparent solubility.
   • Self microemulsifying drug delivery system (SMEDDS)Dissolve mulberry root alcohol L in a mixture of oil phase, surfactant, and co surfactant. After oral administration, it spontaneously forms a microemulsion in gastrointestinal fluid to promote absorption.
4. Change the route of administration: In view of the difficulty of oral absorption, we can consider developing its topical preparations (such as cream, gel) for skin care, or developing injections (to solve the solubility problem) for acute or severe treatment.

Summary Mulberry root alcohol L is a lead compound with clear pharmacological activity and novel mechanism, but its pharmacological properties are severely limited by poor water solubility and potential high metabolic rate. The development prospects depend on whether these obstacles can be effectively overcome through modern pharmaceutical chemistry and formulation methods. At present, positioning it as a topical application (such as cosmetics, skin drugs) or achieving oral/injection administration through special formulation technology is a more realistic research and development path.

Clinical application prospects and prospects

The unique chemical structure and multi effect pharmacological activity of Sanggenol L have opened up broad prospects for its application in multiple fields.

Skin Health and Beauty Field

This is the most promising field for the practical application of Sangen alcohol L. Its powerful antioxidant, anti-aging (inhibiting MMPs), and whitening (inhibiting TYR) activities make it an ideal active ingredient for developing new functional cosmetics and skin care products.

• Anti aging skincare products: essence liquid, face cream or sunscreen containing mulberry root alcohol L can be developed to prevent and improve skin photoaging caused by ultraviolet rays, reduce wrinkles and increase skin elasticity.
• Whitening and spot removing products As a tyrosinase inhibitor, it can be used to develop whitening essence, spot lightening cream and other products, inhibit the generation of melanin, and improve uneven skin color and spots.
• Anti inflammatory and Soothing Products For sensitive or acne prone skin, its anti-inflammatory activity helps to reduce redness, swelling, and inflammatory reactions.

Adjuvant therapy for oxidative stress-related diseases

Given its strong NRF2 activation ability, sangentol L has the potential to serve as an adjuvant therapy for intervening in various chronic diseases closely related to oxidative stress.

• Metabolic diseases Such as diabetes and its complications (nephropathy, retinopathy), non-alcoholic fatty liver disease (NAFLD). By reducing oxidative stress and inflammation, improving insulin resistance and lipid metabolism.
• cardiovascular disease: such as atherosclerosis and hypertension. It can inhibit the formation of foam cells and vascular inflammation by protecting vascular endothelial cells.
• Neurodegenerative diseases Although BBB permeability is low, Sanggenol L may have potential value in diseases such as Alzheimer's disease and Parkinson's disease by being designed as a prodrug or nanoformulation that can penetrate the BBB, or indirectly affecting the central nervous system by regulating peripheral oxidative stress.
• Chemical Prevention of Cancer Its antioxidant and anti-inflammatory activities, as well as its regulation of cell cycle and apoptosis, make it potential as a cancer chemopreventive agent, inhibiting the initiation and promotion stages of tumors.

Future research directions

1. In depth pharmacokinetic research Conduct a systematic in vivo ADME study to clarify the absorption, distribution, metabolism, and excretion characteristics of mulberry root alcohol L in animal bodies, and identify its main metabolites.
2. Structure Activity Relationship (SAR) Study: Synthesize a series of derivatives of mulberry root alcohol L, systematically study the effects of the position and quantity of isopentenyl groups and the modification of phenolic hydroxyl groups on their activity, selectivity, and drug formation, and search for lead compounds with stronger activity and better solubility.
3. Formulation development Focus on developing formulations that can solve the problem of poor water solubility, such as liposomes, nanoemulsions, solid dispersions, etc., and conduct in vivo pharmacological and bioavailability evaluations.
4. toxicological evaluation Conduct systematic acute toxicity, long-term toxicity, and reproductive toxicity studies to comprehensively evaluate their safety.
5. Deepening the mechanism of action Using omics techniques such as transcriptomics and proteomics, as well as gene knockout/knock in animal models, to more comprehensively reveal its functional network and key targets.
6. preclinical research: Verify its efficacy in appropriate animal disease models (such as skin photoaging model, diabetes model, colitis related cancer model), and lay the foundation for clinical trials.

Conclusion

Mulberry root alcohol L, as an extended flavonoid compound derived from traditional Chinese medicine mulberry bark, exhibits excellent biological activity beyond traditional flavonoids due to its unique isopentenyl structure and polyphenol skeleton. Its powerful antioxidant, anti-inflammatory, anti-tumor, and skin protective effects, especially in regulating the NRF2 antioxidant pathway and inhibiting MMP/TYR activity, make it a highly promising natural lead molecule for development.

However, the road from natural products to clinical drugs is still long and challenging. The poor water solubility and high lipophilicity of Sanggenol L are the main bottlenecks in its drug development, severely limiting its oral bioavailability and the possibility of systemic administration. Future research should focus on overcoming these obstacles through structural modification, prodrug design, or advanced nanoformulation technology. Meanwhile, systematic research on its pharmacokinetic properties, long-term toxicity, and underlying mechanisms of action is also essential.

Despite facing challenges, the application prospects of sangentol L remain bright. In the short term, its application in the field of skin health and beauty (such as developing anti-aging and whitening cosmetics) may be the most direct and feasible conversion path. In the long run, with the advancement of formulation technology and medicinal chemistry, sangol L and its derivatives are expected to play an important role in combating major human diseases related to oxidative stress. The continuous in-depth research on mulberry root alcohol L not only helps to reveal the medicinal value of mulberry plants, but also provides valuable inspiration and candidate molecules for modern drug discovery.