In the microscopic world of cells, oxidative stress and inflammation act as a pair of “evil forces,” constantly threatening the stability of the immune system. Dihydroquercetin steps forward to act as a “guardian.” Its molecular structure is rich in multiple phenolic hydroxyl groups, which act like “free radical catchers,” precisely identifying and scavenging free radicals such as superoxide anions and hydrogen peroxide. Related experiments show that dihydroquercetin can reduce cellular oxidative damage by 40%-60%, and its antioxidant capacity is 3-5 times that of quercetin, demonstrating its formidable strength.
Furthermore, dihydroquercetin can penetrate deep into cells to regulate inflammatory signaling pathways. Like a “traffic policeman,” it inhibits the overactivation of inflammatory signaling pathways such as NF-κB and MAPK, reducing the levels of pro-inflammatory factors such as TNF-α and IL-6 by 30%-50%. Through this synergistic effect of antioxidation and anti-inflammation, dihydroquercetin significantly alleviates oxidative stress-induced immune cell dysfunction, building a robust dual protective barrier for the immune system and allowing immune cells to function normally in a stable environment.
Precise Regulation of Immune Cell Activity
Immune cells are the “main force” of the immune system, and dihydroquercetin is an excellent “commander” capable of precisely regulating immune cell activity. In adaptive immunity, T cells and B cells play key roles. Dihydroquercetin, by regulating signaling pathways such as JAK-STAT and PI3K-AKT, “fuels” the proliferation of T cells, increasing the proliferation efficiency of T cells (CD4+/CD8+) by 25%-35%, thus enhancing their fighting power in cellular immunity. Simultaneously, it can also induce B cells to differentiate into plasma cells, much like guiding recruits to become professional shooters, increasing antibody secretion by 20%-25% and strengthening the defense capabilities of humoral immunity. Natural killer (NK) cells, acting as the “special forces” of the immune system, play a crucial role in anti-tumor and anti-viral infection responses. Dihydroquercetin can enhance the perforin/granzyme-mediated tumor cell killing ability of NK cells by up to 40%, enabling NK cells to more effectively identify and eliminate abnormal cells and maintain the body’s healthy balance.
Remodeling of the Immune Microenvironment
The immune microenvironment is the “battlefield” for immune cells to function. Dihydroquercetin can remodel it, creating an environment conducive to immune balance. Taking the liver and lungs as examples, in the liver, excessive activation of Kupffer cells releases a large number of pro-inflammatory factors, triggering an inflammatory storm and disrupting normal liver function. Dihydroquercetin acts as a “soothing agent,” inhibiting excessive activation of Kupffer cells, reducing the release of pro-inflammatory cytokines, and creating conditions for liver cell repair and regeneration.
Simultaneously, dihydroquercetin can also promote the proliferation of regulatory T cells (Tregs), increasing the proportion of Tregs by 15%-20%. Tregs are “regulators” of the immune system, capable of suppressing excessive immune responses and maintaining immune balance. Dihydroquercetin also plays a crucial role in lung mucosal damage, regulating the lung’s immune microenvironment, reducing inflammation, promoting lung tissue repair and healing, and enabling the lungs to restore normal respiratory function.
Multidimensional Regulatory Effects of Dihydroquercetin on Immune Cells
(I) Enhancement of Core Immune Cell Function
T Cells: Full-Link Activation from Proliferation to Differentiation
On the stage of adaptive immune response, T cells are undoubtedly one of the main players, while dihydroquercetin acts as an excellent behind-the-scenes director, finely regulating the proliferation and differentiation of T cells. When foreign pathogens invade the human body, the activation and differentiation of naïve T cells is a key step in initiating a specific immune response. Dihydroquercetin, by upregulating the expression of CD28 co-stimulatory molecules, acts like an accelerator for T cell activation, greatly promoting the differentiation of naïve T cells into Th1 cells. Th1 cells are like elite troops on the battlefield, mainly secreting cytokines such as IFN-γ. IFN-γ can activate macrophages, enhancing their ability to phagocytose and kill pathogens, while also promoting the activity of T cells and NK cells, thereby enhancing the cellular immune response. Related experimental data show that under the influence of dihydroquercetin, IFN-γ secretion increases by 30%, significantly enhancing the fighting power of cellular immunity.
Maintaining immune tolerance is equally important in the process of immune regulation; otherwise, the immune system may attack its own tissues, triggering autoimmune diseases. Regulatory T cells (Tregs) are the guardians of immune tolerance, and dihydroquercetin is a strong supporter of Tregs. It maintains the immune tolerance function of Tregs by inhibiting Foxp3 gene methylation, allowing Foxp3 protein to be stably expressed. Foxp3 is like a “identity card” for Tregs, determining their function and characteristics. When the function of Tregs is maintained, excessive immune responses can be effectively suppressed, preventing excessive activation of the autoimmune system and ensuring that the immune system attacks foreign pathogens without harming its own tissues.
NK Cells: Upgraded “Precision Missiles” for Innate Immunity
NK cells, a crucial line of defense in innate immunity, can rapidly recognize and kill virus-infected cells and tumor cells without prior exposure to antigens, acting like precise “missiles” and playing an indispensable role in immune defense. Dihydroquercetin can comprehensively “upgrade” NK cells, further enhancing their combat effectiveness.
Experiments show that after dihydroquercetin intervention, the expression level of the NK cell surface activation receptor NKG2D increased by 40%. NKG2D acts like a “scope” for NK cells, recognizing stress-induced ligands on the surface of target cells, thus precisely locking onto the target. With increased NKG2D expression, the ability of NK cells to recognize and bind to target cells is greatly enhanced, increasing the killing efficiency against lung cancer and breast cancer cells by 50%, leaving tumor cells nowhere to hide. To enable NK cells to sustain their anti-tumor activity, dihydroquercetin also extends their “lifespan” by inhibiting NK cell apoptosis. In the regulatory network of apoptosis, Bcl-2 and Bax are a key protein pair; Bcl-2 has anti-apoptotic effects, while Bax promotes apoptosis. Dihydroquercetin regulates the expression of these two proteins, increasing the Bcl-2/Bax ratio by 25%, thus inhibiting NK cell apoptosis and allowing NK cells to perform anti-tumor tasks for an extended period in vivo, safeguarding the body’s health.
Macrophages: The Dynamic Balance of Pro-inflammatory and Anti-inflammatory Phenotypes
Macrophages are versatile members of the immune system. Depending on their microenvironment, they can differentiate into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, playing a crucial role in immune defense and tissue repair. In the early stages of infection, macrophages are induced to differentiate into M1 type, acting like the vanguard on a battlefield, rapidly releasing large amounts of pro-inflammatory factors, such as IL-12 and TNF-α, to defend against pathogen invasion. However, if the inflammatory response is excessive, it can damage the body, leading to serious diseases such as sepsis.
Dihydroquercetin can subtly induce macrophage polarization from the pro-inflammatory (M1) to the anti-inflammatory (M2) type, reducing IL-12 secretion by 20% and increasing IL-10 secretion by 35%. IL-10 is an important anti-inflammatory factor that can inhibit the inflammatory response and promote tissue repair. Through this polarization regulation, dihydroquercetin effectively controls the excessive inflammatory response after infection, reducing the risk of immune damage from diseases such as sepsis. Once the inflammation is controlled, M2 macrophages can further promote tissue repair and regeneration, allowing the body to recover health more quickly.
Multidimensional Regulatory Effects of Dihydroquercetin on Immune Cells
(I) Enhancement of Core Immune Cell Function
T Cells: Full-Link Activation from Proliferation to Differentiation
On the stage of adaptive immune response, T cells are undoubtedly one of the main players, while dihydroquercetin acts as an excellent behind-the-scenes director, finely regulating the proliferation and differentiation of T cells. When foreign pathogens invade the human body, the activation and differentiation of naïve T cells is a key step in initiating a specific immune response. Dihydroquercetin, by upregulating the expression of CD28 co-stimulatory molecules, acts like an accelerator for T cell activation, greatly promoting the differentiation of naïve T cells into Th1 cells. Th1 cells are like elite troops on the battlefield, mainly secreting cytokines such as IFN-γ. IFN-γ can activate macrophages, enhancing their ability to phagocytose and kill pathogens, while also promoting the activity of T cells and NK cells, thereby enhancing the cellular immune response. Related experimental data show that under the influence of dihydroquercetin, IFN-γ secretion increases by 30%, significantly enhancing the fighting power of cellular immunity.
Maintaining immune tolerance is equally important in the process of immune regulation; otherwise, the immune system may attack its own tissues, triggering autoimmune diseases. Regulatory T cells (Tregs) are the guardians of immune tolerance, and dihydroquercetin is a strong supporter of Tregs. It maintains the immune tolerance function of Tregs by inhibiting Foxp3 gene methylation, allowing Foxp3 protein to be stably expressed. Foxp3 is like a “identity card” for Tregs, determining their function and characteristics. When the function of Tregs is maintained, excessive immune responses can be effectively suppressed, preventing excessive activation of the autoimmune system and ensuring that the immune system attacks foreign pathogens without harming its own tissues.
NK Cells: Upgraded “Precision Missiles” for Innate Immunity
NK cells, a crucial line of defense in innate immunity, can rapidly recognize and kill virus-infected cells and tumor cells without prior exposure to antigens, acting like precise “missiles” and playing an indispensable role in immune defense. Dihydroquercetin can comprehensively “upgrade” NK cells, further enhancing their combat effectiveness. Experiments show that after dihydroquercetin intervention, the expression level of the NK cell surface activation receptor NKG2D increased by 40%. NKG2D acts like a “scope” for NK cells, recognizing stress-induced ligands on the surface of target cells, thus precisely locking onto their targets. With increased NKG2D expression, the ability of NK cells to recognize and bind to target cells is greatly enhanced, increasing the killing efficiency against lung cancer and breast cancer cells by 50%, leaving tumor cells nowhere to hide.
To enable NK cells to sustain their anti-tumor activity, dihydroquercetin also extends their “lifespan” by inhibiting NK cell apoptosis. In the regulatory network of apoptosis, Bcl-2 and Bax are a key protein pair; Bcl-2 has anti-apoptotic effects, while Bax promotes apoptosis. Dihydroquercetin regulates the expression of these two proteins, increasing the Bcl-2/Bax ratio by 25%, thus inhibiting NK cell apoptosis and allowing NK cells to perform anti-tumor tasks for an extended period in vivo, safeguarding the body’s health.
Macrophages: The Dynamic Balance of Pro-inflammatory and Anti-inflammatory Phenotypes
Macrophages are versatile members of the immune system. Depending on their microenvironment, they can differentiate into pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, playing a crucial role in immune defense and tissue repair. In the early stages of infection, macrophages are induced to differentiate into M1 type, acting like the vanguard on a battlefield, rapidly releasing large amounts of pro-inflammatory factors, such as IL-12 and TNF-α, to defend against pathogen invasion. However, if the inflammatory response is excessive, it can damage the body, leading to serious diseases such as sepsis.
Dihydroquercetin can subtly induce macrophage polarization from the pro-inflammatory (M1) to the anti-inflammatory (M2) type, reducing IL-12 secretion by 20% and increasing IL-10 secretion by 35%. IL-10 is an important anti-inflammatory factor that can inhibit the inflammatory response and promote tissue repair. Through this polarization regulation, dihydroquercetin effectively controls the excessive inflammatory response after infection, reducing the risk of immune damage from diseases such as sepsis. Once the inflammation is controlled, M2 macrophages can further promote tissue repair and regeneration, allowing the body to recover health more quickly.
(II) Bidirectional Regulatory Mechanism of Immune Response
In the complex regulatory network of the immune system, dihydroquercetin acts like an experienced commander, possessing the ability to bidirectionally regulate the immune response. It can precisely adjust the intensity of the immune response according to the body’s immune status, maintaining it in a balanced state.
For immunocompromised states, dihydroquercetin enhances the antigen-presenting capacity of dendritic cells (DCs) through the cAMP-PKA pathway. DCs are the “intelligence agents” of the immune system, capable of uptake, processing, and presenting antigens, activating naive T cells, and initiating a specific immune response. Dihydroquercetin increases the expression of MHC-II molecules on the surface of DCs by 25%. MHC-II molecules act as “signal flags” for DCs to transmit information, conveying antigen information to T cells. When MHC-II molecule expression increases, the efficiency of DCs in activating naive T cells increases by 30%, thereby enhancing the body’s immune response and helping the body better resist pathogen invasion.
In cases of autoimmune hyperactivity, the immune system acts like a runaway horse, attacking its own tissues and leading to autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Dihydroquercetin acts as a “brake,” inhibiting the overactivation of plasma cells. Plasma cells are the main cells that produce antibodies; when plasma cells are overactivated, they produce a large number of autoantibodies that attack the body’s own tissues. Dihydroquercetin reduces the production of autoantibodies, achieving a 25%-30% improvement rate in inflammation scores for diseases such as rheumatoid arthritis, alleviating symptoms and reducing patient suffering.
The Potential of Dihydroquercetin in Immune-Related Diseases
(I) Synergistic Enhancement of Anti-tumor Immunotherapy
On the battlefield of cancer, dihydroquercetin, as a “secret weapon,” has demonstrated powerful synergistic effects, working in conjunction with immunotherapy to combat tumors. In various tumor models, including breast cancer and leukemia, dihydroquercetin activates NK cells and cytotoxic T cells through a series of ingenious mechanisms, revitalizing these immune cells and enhancing their ability to recognize and kill tumor cells. Simultaneously, it inhibits the expression of PD-L1 on the surface of tumor cells, effectively stripping away the “disguise” of tumor cells and making them unable to escape the surveillance of the immune system.
This dual effect significantly improves the sensitivity to chemotherapy drugs; experimental data show an increase of 30%-40%. Phase I clinical trials have also yielded encouraging results, with a 20% increase in CD8+ T cell infiltration in the combination therapy group. This means that more immune cells can penetrate deep into tumor tissue and attack tumor cells. The rate of decrease in tumor markers was 15%-20% faster than in the monotherapy group, indicating that tumor growth and spread were more effectively controlled. These results fully demonstrate the important value of dihydroquercetin as an adjuvant in immunotherapy, opening up new avenues for cancer treatment.
(II) Immune Repair in Liver Diseases
Dihydroquercetin plays a crucial role in immune repair against alcoholic liver injury. In the liver, Kupffer cells are important participants in the immune response, but under alcohol stimulation, they become overactivated, releasing large amounts of pro-inflammatory factors such as TNF-α and IL-1β. These pro-inflammatory factors act like runaway “bombs,” triggering an inflammatory storm and causing severe damage to liver cells. Dihydroquercetin can precisely inhibit the overactivation of Kupffer cells, reducing their secretion of TNF-α and IL-1β by up to 40%, effectively controlling the spread of inflammation.
Simultaneously, dihydroquercetin can also promote the homing of regulatory T cells (Tregs) to the liver. Tregs act like “guardians” of the liver, suppressing excessive immune responses and maintaining hepatic immune balance. When Tregs home to the liver, the degree of liver fibrosis is reduced by 35%. This is because Tregs can inhibit the activation of hepatic stellate cells and reduce collagen synthesis, thereby preventing the development of liver fibrosis. Animal experiments have shown that liver tissue sections from the dihydroquercetin intervention group showed a significant reduction in inflammatory cell infiltration and a marked improvement in hepatocyte damage. Liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels decreased by 30%-40%, further confirming the significant effect of dihydroquercetin in the immune repair of liver diseases and bringing new hope to patients with alcoholic liver injury.
