Dihydroquercetin is primarily found in the Pinaceae family, with the highest concentrations (2%-3%) found in the roots of Siberian alpine larch (over 100 years old) and the bark and needles of Douglas fir. Other sources include Rosaceae fruits and legume seeds, but at lower concentrations. Its annual global production is less than 20 tons. Due to its scarcity and difficulty in extraction, it is known as the “luxury of plant flavonoids.”
Multidimensional Biological Activities: From Cell Repair to System Regulation
Antioxidant: A “Molecular Shield” for Scavenging Free Radicals
During human metabolism, various free radicals, such as superoxide anions and hydroxyl radicals, are inevitably produced as reactive oxygen species (ROS). These free radicals are extremely active, constantly seeking to steal electrons from surrounding molecules. Once successful, they trigger a series of oxidative chain reactions, wreaking havoc on cells. Dihydroquercetin, with its unique molecular structure, stands out as a “molecular shield” for scavenging free radicals. It can directly bind to reactive oxygen species such as superoxide anions and hydroxyl radicals, converting these highly destructive free radicals into relatively stable species, thereby successfully blocking the oxidative chain reaction.
Dihydroquercetin also activates endogenous antioxidant enzymes, such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Once activated, these antioxidant enzymes, like soldiers on the charge, actively engage in the battle to eliminate free radicals, significantly boosting the cell’s own antioxidant defenses. The five phenolic hydroxyl groups in the dihydroquercetin molecule work together to form a unique electron-conjugated system. This system endows dihydroquercetin with remarkable antioxidant capacity, making it an exceptionally effective free radical fighter, far exceeding the efficacy of a single antioxidant.
At the cellular level, DNA, proteins, and lipids are crucial for maintaining normal cellular function, yet they are highly vulnerable to free radical attack. Dihydroquercetin, with its potent antioxidant capacity, effectively protects these biomolecules from oxidative damage. To put it in a metaphor, it’s like putting a strong layer of armor on cells, protecting them from free radical damage and thus slowing the aging process. Numerous studies have shown that in an environment rich in dihydroquercetin, intracellular oxidative stress levels are significantly reduced, and cell vitality and lifespan are significantly improved.
Anti-Inflammation and Immune Regulation: Inhibiting the Inflammatory Cascade
When the body is invaded by pathogens, physical damage, or other adverse stimuli, an inflammatory response is triggered. During this process, inflammatory signaling pathways such as NF-κB and MAPK act like a lit fuse, rapidly activating and triggering the release of large amounts of pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). These pro-inflammatory cytokines help the body defend against external aggressors in the early stages of inflammation, but if the inflammatory response persists out of control, they can cause severe damage to tissues and organs. Dihydroquercetin acts like a calm commander, precisely inhibiting the overactivation of inflammatory signaling pathways like NF-κB and MAPK, thereby reducing the release of pro-inflammatory cytokines like TNF-α and IL-6. Simultaneously, it actively promotes the expression of anti-inflammatory factors like interleukin-10 (IL-10). IL-10 acts like a gentle mediator, effectively moderating the inflammatory response and alleviating the damage it causes.
The anti-inflammatory effects of dihydroquercetin have been fully demonstrated in animal studies. For example, in rheumatoid arthritis models, dihydroquercetin treatment significantly reduced joint inflammation, reduced swelling, and effectively alleviated pain. In ulcerative colitis models, intestinal inflammation was effectively controlled, and intestinal mucosal damage was significantly repaired.
The immune system is a crucial line of defense for the human body against disease, and dihydroquercetin plays a key role in immune regulation. It subtly regulates the activity of immune cells, such as macrophages and T cells. Macrophages are like the “scouts” and “cleaners” of the immune system. Dihydroquercetin enhances their phagocytic ability, enabling them to more efficiently identify and eliminate invading pathogens. T cells, on the other hand, play a central role in cellular immunity. Dihydroquercetin promotes T cell proliferation and differentiation, enhancing cellular immune function and helping the body better identify and eliminate abnormal cells, such as tumor cells. By regulating immune cell activity, dihydroquercetin can comprehensively enhance the body’s disease resistance, allowing the body to more effectively defend against various diseases.
Anti-tumor and Antibacterial Effects: Potential Benefits Validated in the Laboratory
The rampant proliferation and metastasis of tumor cells has always been a major challenge in the medical field. In in vitro studies, dihydroquercetin has demonstrated remarkable anti-tumor potential. Like a precise “killer,” it can specifically inhibit the proliferation of various tumor cells, including leukemia P388 cells and squamous cell carcinoma. Further research has revealed that dihydroquercetin achieves this effect primarily by inducing apoptosis in tumor cells. It cleverly regulates cell cycle proteins, causing tumor cells to arrest at specific cell cycle stages, preventing them from dividing and proliferating normally. Furthermore, dihydroquercetin inhibits tumor angiogenesis, depriving them of nutrients, effectively inhibiting tumor growth and spread.
Dihydroquercetin also demonstrates remarkable antibacterial activity against a variety of pathogens, including Staphylococcus aureus, Escherichia coli, and Salmonella typhi. Compared to traditional antibiotics, dihydroquercetin not only exhibits potent antibacterial effects but also possesses the unique advantage of being less susceptible to developing drug resistance. This property gives dihydroquercetin significant potential for addressing the growing problem of antibiotic resistance. In some experiments, dihydroquercetin has demonstrated significant inhibitory activity against certain drug-resistant strains, providing new insights and approaches for addressing clinical infection challenges.
Organ Protection: Targeted Systemic Care for the Heart, Brain, Liver, and Kidneys
Cardiovascular: Cardiovascular and cerebrovascular diseases pose a serious threat to human health, and dihydroquercetin plays a vital role in preventing and improving them. Like a caring “blood vessel guardian,” dilating blood vessels, making them more patency, reduces resistance to blood flow, and thus effectively lowers blood pressure. Dihydroquercetin also regulates blood lipids by inhibiting cholesterol synthesis, lowering total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C) levels, while increasing high-density lipoprotein (HDL-C) levels. HDL-C acts as a “scavenger” in the blood vessels, transporting cholesterol from the vessel walls to the liver for metabolism, reducing cholesterol deposition in the vessel walls and thus reducing the risk of atherosclerosis. Furthermore, dihydroquercetin improves endothelial function and promotes the release of nitric oxide (NO), a powerful vasodilator that relaxes vascular smooth muscle, further maintaining normal vascular function. It has a significant preventive effect on cardiovascular and cerebrovascular diseases such as hypertension and myocardial infarction.
Liver: The liver is a crucial metabolic and detoxification organ in the human body, and dihydroquercetin has comprehensive protective effects on the liver. When the liver is damaged by factors such as alcohol, drugs, or viruses, dihydroquercetin quickly takes effect, repairing damaged liver cells and promoting their regeneration. Like a liver “repair master,” dihydroquercetin activates cell cycle proteins and cyclin-dependent kinases, accelerating the transition of hepatocytes from the G1 phase to the S phase and promoting their proliferation. Simultaneously, it downregulates pro-apoptotic proteins and upregulates anti-apoptotic proteins, reducing programmed cell death and creating favorable conditions for regeneration. Furthermore, dihydroquercetin can inhibit the progression of liver fibrosis by inhibiting the activation of hepatic stellate cells, reducing collagen deposition, and preventing the hardening and brittleness of liver tissue caused by fibrosis. It has a significant effect on liver diseases such as alcoholic liver disease and hepatitis.
Nervous system: A healthy nervous system is crucial for normal physiological function. Due to its small molecular structure, dihydroquercetin can easily cross the blood-brain barrier and enter the brain. In the brain, it acts like a diligent “cleaner,” actively removing excess free radicals and protecting neurons from oxidative stress. Oxidative stress and neuroinflammation are key pathological mechanisms in neurodegenerative diseases such as Alzheimer’s and Parkinson’s. Dihydroquercetin can inhibit the release of neuroinflammatory mediators, alleviating neuronal damage caused by oxidative stress and inflammation. This potentially offers new hope for the prevention and treatment of these neurodegenerative diseases.
Cross-disciplinary Applications: Diverse Values from Medicine to Industry
Healthcare: From Clinical Practice to Functional Foods
Clinical Research: Dihydroquercetin has been extensively studied in the medical field, particularly in the areas of oncology, cardiovascular and cerebrovascular diseases, and metabolic syndrome. While it cannot be used solely as a first-line anticancer drug in cancer treatment, it holds great promise in adjuvant chemotherapy and radiotherapy. Studies have shown that dihydroquercetin can reduce the side effects of chemotherapy and radiotherapy and enhance the sensitivity of tumor cells to them. Clinical trials conducted by the Russian Academy of Sciences have shown that lung cancer patients who took dihydroquercetin supplements concurrently with chemotherapy and radiotherapy experienced significantly reduced adverse reactions such as nausea and vomiting, and significantly improved their quality of life. In cell-based experiments, dihydroquercetin modulated signaling pathways within tumor cells, inhibiting cancer cell migration and invasion, providing a theoretical basis for combination therapy.
For cardiovascular and cerebrovascular diseases, dihydroquercetin exerts protective effects through multiple pathways, including lowering blood lipids, inhibiting platelet aggregation, and improving endothelial function. A clinical study of patients with hypertension found that after three months of taking dihydroquercetin, patients’ blood pressure was significantly lowered and endothelial vasodilation significantly improved. For metabolic syndrome, dihydroquercetin can regulate glucose and lipid metabolism and improve insulin resistance. The Russian Pharmacopoeia (2006 edition) records its liver-protecting and immunomodulatory properties. Traditional Chinese medicines containing dihydroquercetin as a primary ingredient (such as Schisandra chinensis and White Peony Root) have been used clinically to treat liver disease, effectively improving liver function and alleviating liver inflammation.
Functional Foods: Due to its excellent antioxidant and health benefits, dihydroquercetin is widely used as a natural antioxidant in health products and dietary supplements. Numerous products on the market claiming to enhance immunity, combat fatigue, and delay aging contain dihydroquercetin. Its inclusion in sports nutrition supplements can help athletes quickly eliminate fatigue, improve exercise endurance, and promote muscle recovery. In the food industry, dihydroquercetin can effectively extend the shelf life of foods such as oils and meats. Studies have shown that oils and fats containing dihydroquercetin significantly slow the rate of oxidation and rancidity when stored at high temperatures, outperforming common synthetic antioxidants like BHT and BHA. Furthermore, it is safer and poses no potential health risks, meeting consumer demand for natural, healthy food additives.
Cosmetics: Natural Formulas for Anti-Aging and Whitening
In the cosmetics sector, dihydroquercetin is highly sought after for its antioxidant, anti-inflammatory, and collagen-boosting properties, making it a key natural active ingredient in high-end skincare products. Free radicals are a major factor in skin aging, and dihydroquercetin’s potent antioxidant capacity effectively scavenges free radicals in the skin, preventing and reducing signs of aging such as wrinkles and sagging. It inhibits the activity of matrix metalloproteinases (MMPs), reduces the degradation of collagen and elastin fibers, promotes collagen synthesis by fibroblasts, and enhances skin elasticity. A human trial showed that after eight weeks of continuous use of a skincare product containing dihydroquercetin, subjects experienced a 27% increase in skin elasticity and a 33% reduction in wrinkle depth. For pigmentation, dihydroquercetin inhibits tyrosinase activity, reducing melanin production and achieving a whitening and blemish-lightening effect. Its whitening properties have been demonstrated in some whitening serums and anti-freckle creams, effectively fading melasma and freckles, resulting in a more even and fairer skin tone. Dihydroquercetin also improves skin microcirculation, strengthens the skin barrier function, and significantly alleviates inflammation in sensitive skin. Adding dihydroquercetin to skincare products specifically for sensitive skin can reduce the release of inflammatory factors, alleviate symptoms such as redness, swelling, and itching, enhance skin tolerance, and repair damaged skin barriers.
Industry and Agriculture: Antioxidant Solutions for Specialized Applications
Industry: In the industrial sector, dihydroquercetin’s unique antioxidant properties make it an ideal additive for a variety of materials. In the aerospace sector, it is used as a stabilizer in rocket fuel and engine anti-vibration agents, effectively resisting damage to fuel and materials caused by high temperatures, high pressures, and highly oxidizing environments, ensuring stable engine operation and improving flight safety and reliability. In the coatings industry, adding dihydroquercetin to pigments and paints significantly enhances their antioxidant properties, slowing aging, fading, and chalking caused by factors like light, oxygen, and humidity. This extends the coating’s lifespan and maintains the surface’s aesthetic appeal and protective properties. Adding dihydroquercetin to automotive paint helps maintain its gloss after prolonged outdoor exposure, preventing discoloration and peeling.
Agriculture: In agricultural production, waste from dihydroquercetin extraction can be used to prepare plant growth regulators, which play an important role. These regulators enhance crop resistance and improve their adaptability to harsh environments like cold and drought. Studies have shown that treatment with plant growth regulators containing dihydroquercetin increases the survival rate of crops like wheat and corn in low-temperature environments, resulting in more developed root systems, thicker leaves, and enhanced photosynthesis. Dihydroquercetin also inhibits various fungal diseases, such as wheat scab and cucumber powdery mildew, reducing the use of chemical pesticides, lowering pesticide residues in agricultural products, and ensuring food safety. In seedling cultivation, the use of this regulator can increase the survival rate of seedlings, promote root growth, cultivate stronger seedlings, and improve afforestation quality and greening effects.
Safety and Application Limits: Scientific Use is Key
Potential Side Effects and Contraindications
Although dihydroquercetin has demonstrated promising biological activity and application prospects in numerous studies, its safety profile cannot be ignored. Based on currently available clinical data, dihydroquercetin is relatively safe. However, improper use may still cause adverse reactions.
The most common side effects of dihydroquercetin overdose are gastrointestinal, potentially causing nausea, vomiting, and other discomfort. This is because excessive dihydroquercetin can irritate the gastrointestinal mucosa, disrupting normal digestion and motility, leading to digestive disorders. It’s like a train running smoothly on track, suddenly interrupted by external interference and experiencing a malfunction. Allergic reactions are also a concern. Some people with allergies may experience a rash, small red bumps, and itching after exposure to dihydroquercetin. In severe cases, breathing difficulties may occur. This is because the allergic reaction causes swelling and congestion in the throat, which impairs normal gas exchange and poses a threat to life and health.
Extra caution is advised when using dihydroquercetin in certain populations, such as pregnant and breastfeeding women, and those with liver and kidney dysfunction. Pregnant women are in a unique physiological state, and the fetus requires a stable internal environment for growth and development. While dihydroquercetin has certain health benefits, its potential effects on the fetus are currently unknown. To avoid potential risks, pregnant women should avoid its use. Breastfeeding women’s breast milk can be passed to their babies. Similarly, due to the unknown safety of dihydroquercetin for infants, its use is not recommended for breastfeeding women. Individuals with hepatic and renal insufficiency have weaker metabolic and detoxification functions in their livers and kidneys. The metabolism and excretion of dihydroquercetin may increase the burden on the liver and kidneys, further impairing their function.
Regarding drug interactions, special caution is required when using dihydroquercetin with anticoagulants. Dihydroquercetin itself inhibits platelet aggregation, a property that is beneficial in preventing thrombosis. However, when used concurrently with anticoagulants, it can significantly increase the risk of bleeding. This is like two people simultaneously applying the brakes on a car, causing it to over-brake. Therefore, patients taking anticoagulants who require dihydroquercetin should only do so under the guidance of a physician. The physician will weigh the pros and cons of the individual patient and develop an appropriate dosing regimen to ensure safe use.
Research Status and Challenges
Although dihydroquercetin has demonstrated multiple biological activities, including antioxidant, anti-inflammatory, and anti-tumor effects, in basic research, providing a theoretical basis for its application in medicine, food, and cosmetics, current research still faces limitations and numerous challenges.
In terms of mechanism of action, while it has been established that dihydroquercetin can exert its biological activity through multiple pathways, its specific targets remain largely unidentified. For example, in its antioxidant activity, the specific molecular mechanisms of its binding to reactive oxygen species such as superoxide anions and hydroxyl radicals, as well as the detailed signaling pathways that activate endogenous antioxidant enzymes, require further investigation. Furthermore, in its anti-inflammatory activity, sufficient experimental evidence is currently lacking regarding the specific enzymes or receptors directly involved in the inhibition of inflammatory signaling pathways such as NF-κB and MAPK. Accurately identifying dihydroquercetin’s targets is like finding the precise key to unlocking a treasure trove, crucial for a deeper understanding of its mechanisms of action and the development of more effective applications.
Long-term toxicity studies are also currently a weak link. Currently, research on dihydroquercetin has mostly focused on short-term experiments and observations, leaving little understanding of the potential toxicity of long-term dihydroquercetin use. Does long-term dihydroquercetin consumption adversely affect the human immune system, reproductive system, and other organs? Does it accumulate in the body, leading to chronic toxicity? These questions urgently require answers through long-term, large-scale animal studies and clinical trials. Only by fully understanding the long-term toxicity of dihydroquercetin can we reliably guarantee its long-term safety in health supplements, pharmaceuticals, and other fields.
In terms of production technology, large-scale industrial extraction of dihydroquercetin currently relies primarily on chemical synthesis. While chemical synthesis can meet market demand for dihydroquercetin to a certain extent, it also has numerous drawbacks. Chemical synthesis typically requires large amounts of chemical reagents, which not only increase production costs but also may leave residues in the product, potentially posing a threat to human health and the environment. Furthermore, chemical synthesis is complex, requires demanding reaction conditions, and consumes significant amounts of energy, contributing to the high production costs of dihydroquercetin. The high cost of dihydroquercetin has limited its large-scale application and promotion, making it relatively expensive in the market and difficult to popularize to a wider consumer group. Therefore, the development of green, efficient, and low-cost extraction and synthesis technologies has become the key to promoting the development of the dihydroquercetin industry.
Future Outlook: From “Natural Treasure” to Precision Development
Technological Breakthroughs
Extraction Process: Currently, dihydroquercetin extraction technology still has significant room for improvement. While supercritical extraction technology has been applied, process details can be optimized. For example, by precisely controlling the temperature, pressure, and time parameters during the extraction process, the extraction yield of dihydroquercetin can be further increased by 10%-20% from the current level. In supercritical extraction of larch, controlling the temperature at 40-45°C, maintaining the pressure at 25-30 MPa, and extending the extraction time to 3-4 hours is expected to yield dihydroquercetin with higher purity and yield.
Enzyme-assisted extraction technology is also an important future development direction. By screening and cultivating highly efficient cellulases and hemicellulases, the efficiency of plant cell wall degradation can be improved, thereby promoting the release of dihydroquercetin. Furthermore, by combining genetic engineering techniques, enzyme-producing microorganisms can be modified to produce highly active enzymes under milder conditions, reducing production costs. During the enzyme-assisted extraction process, the enzyme dosage, reaction time, and reaction pH were optimized to achieve efficient extraction of dihydroquercetin. Using Larix olgensis as the raw material, cellulase-assisted flash extraction achieved a high extraction yield of dihydroquercetin under optimal conditions (ethanol volume fraction 60.93%, enzyme dosage 3.48 mg/g, liquid-to-solid ratio 103.64:1 (mL/g), and extraction time 120 s). With the continuous improvement of these technologies, the yield of natural sources of dihydroquercetin is expected to increase significantly, and costs will also decrease, laying a solid foundation for its large-scale application.
Formulation Innovation: Nanodelivery systems have great potential to improve the aqueous solubility and bioavailability of dihydroquercetin. Liposomes, as a common nanocarrier, can encapsulate dihydroquercetin to form stable nanoparticles. By adjusting the composition and structure of liposomes, such as selecting the appropriate phospholipid type and cholesterol content, the stability and targeting of liposomes can be improved. Encapsulating dihydroquercetin in liposomes composed of soy lecithin and cholesterol significantly improves its solubility in water, allowing it to be more evenly dispersed in aqueous solutions. Furthermore, the surface of the liposomes can be modified with specific ligands, such as antibodies or peptides, to target specific tissues or cells, enhancing the therapeutic efficacy of dihydroquercetin.
Microencapsulation technology is also an effective formulation innovation. By encapsulating dihydroquercetin in microcapsules, it can be protected from environmental influences and its shelf life can be extended. Natural polymer materials, such as chitosan and gelatin, can be used as microcapsule wall materials, which have excellent biocompatibility and biodegradability. During microcapsule preparation, spray drying and freeze-drying techniques are used to control the particle size and morphology of the microcapsules, allowing them to better meet different application requirements. The prepared dihydroquercetin microcapsules can be used in functional foods, not only improving the stability of dihydroquercetin but also enhancing its taste and consumption experience.
Collaboration between Research and Industry
Research institutions and enterprises should work closely together to focus on mechanistic research in areas such as targeted tumor therapy and neuroprotection. In the area of targeted tumor therapy, in-depth research should be conducted on the interaction between dihydroquercetin and tumor cell surface receptors, and dihydroquercetin formulations that can specifically target tumor cells should be developed. Combination therapy with chemotherapy drugs can enhance the efficacy of chemotherapy drugs and reduce their toxic side effects, providing more effective treatment options for cancer patients. In the area of neuroprotection, further research should be conducted on the protective mechanisms of dihydroquercetin on nerve cells, and drugs should be developed for the treatment of neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.
At the same time, dihydroquercetin should be expanded to include functional foods and high-end cosmetics. In the functional food sector, dihydroquercetin-rich beverages and health supplements should be developed to meet consumer demand for healthy foods. In the high-end cosmetics sector, dihydroquercetin-infused skincare and makeup products should be developed to enhance product efficacy and quality. Establish standards for the entire industry chain, from plant resources to end products, to ensure the quality and safety of dihydroquercetin products. During the plant cultivation process, standardized cultivation techniques are implemented to ensure the quality and stability of raw materials. During the extraction and processing stages, stringent quality control standards are established to ensure product purity and activity. During the product sales process, market supervision is strengthened to combat counterfeit and substandard products.
The research and application of dihydroquercetin not only scientifically decodes nature’s gifts but also epitomizes humanity’s pursuit of health and sustainable development. With technological advancements and deepening understanding, this natural ingredient is expected to unleash its potential in even more fields, becoming a vital bridge connecting phytochemistry and life sciences.
