木犀草素: 來源、益處與用途

Luteolin (Luteolin) Luteolin belongs to a large class of substances called flavonoids , which are secondary metabolites characterized by a diphenylpropane structure (C6–C3–C6) and can be divided into many groups. Luteolin is a tetrahydroxyflavone with four hydroxyl groups located at the 3, 4, 5 and 7 positions.

It is a naturally occurring flavonoid compound found in a variety of plants, fruits and vegetables. It belongs to the flavonoid class of flavonoids, known for its antioxidant and anti-inflammatory properties.

  • CAS No. 491-70-3

History and background

It is a flavonoid (3',4',5,7-tetrahydroxyflavone) with a yellow crystalline appearance. Due to its color, the luteolin-containing plant Mignonette has been used as a source of dye since the first millennium BC. French chemist Michel Eugène Chevreul was the first to isolate luteolin in 1829, but the correct structure was proposed by British chemist Arthur George Perkin in 1896.

Luteolin is a substance found in a variety of plant species, including those used in traditional medicine to treat a variety of illnesses. It is widely distributed in the plant kingdom and has been extensively studied for its pharmacological properties such as anti-inflammatory, antioxidant, and neuroprotective properties. Luteolin glycosides have been found in fossils of species in the family Ulmaceae that date from 36 to 25 million years ago. More than 350 plant species have been found to contain luteolin and/or its various glycoside forms.

source

plant

Luteolin is found in a variety of plants, fruits, and vegetables commonly found in the human diet, including celery, parsley, thyme, chamomile, broccoli, carrots, peppers, and citrus fruits.

fruits and vegetables

It is also found in fruits such as oranges, lemons and olive oil, as well as vegetables such as broccoli, onions and spinach.

health benefits

antioxidant activity

Luteolin acts as an antioxidant and helps neutralize harmful free radicals in the body, protecting cells from oxidative stress.

Like most flavonoids, luteolin can act as an antioxidant or pro-oxidant. Studies have shown that it can induce ROS, and its accumulation plays a key role in inhibiting NF-κB and enhancing JNK. It does not involve mitochondrial electron transport and may be achieved by inhibiting superoxide dismutase activity. These effects sensitize cancer cells to undergo TNF-induced apoptosis.

anti-inflammatory properties

chronic inflammation

Acute inflammation is an acute form of inflammation caused by cell damage caused by the presence of pathogenic microorganisms or harmful stimuli. After a reasonable period of time, under normal circumstances, the irritation disappears, tissue healing ceases, and inflammation and associated symptoms, including pain, cease. Multiple factors, including environmental and genetic parameters, contribute to the maintenance of chronic inflammation activated by DAMPs. Chronic, unresolved inflammation leads to a progressive deterioration in the structure and function of tissues and organs. If the pathology is mild or chronic inflammation, pain may be one of the symptoms. Chronic diseases such as osteoarthritis, rheumatoid arthritis, and inflammatory bowel disease are characterized by pathological and chronic pain. This type of pain results from activation of nociceptors that stimulate inflammatory mediators at the inflamed site, causing a shift in activation threshold from a high to a low activation threshold. In the absence of a cure, anti-inflammation is the gold standard approach to treating chronic inflammation to achieve long-term relief and pain relief.

Anti-inflammatory properties of luteolin in chronic inflammatory pain

Research shows that luteolin may help reduce inflammation by inhibiting inflammatory pathways and cytokines, which may have benefits for conditions such as arthritis and inflammatory diseases.

Luteolin exhibits pleiotropic effects on various signaling pathways involved in chronic inflammation, and its safety profile makes it a promising option as an adjunctive treatment to suppress inflammation and associated pain. Its effects are mainly due to the inhibition of several biochemical pathways and inflammatory mediators associated with a variety of chronic diseases, of which persistent inflammation is a common feature of the pathogenesis.

The regulatory effect of luteolin on inflammatory mediators (such as cytokines IL-6, IL-1β and TNF-α, enzyme COX-2 and prostaglandin PGE). In addition, luteolin inhibits the increased expression of inducible nitric oxide synthase (iNOS) and metalloproteinases (MMPs) under chronic inflammatory conditions. However, in chronic inflammation, the synthase iNOS synthesizes an inducible form of nitric oxide, leading to overexpression of nitric oxide up to 1,000-fold the physiological production. In particular, increased expression of various types of MMPs is associated with tissue remodeling and destruction under chronic inflammatory conditions. Among them, three pilin domains include nuclear factor kappa B (NF-κB), Janus kinase signal transducer and activator of transcription (JAK-STAT), and inflammasome NOD-like receptors (NLR family). (NLRP3) plays an important role. Role in gene expression of inflammation. NF-κB is considered a key transcription factor in acute and chronic inflammation and is involved in the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, iNOS, and metalloproteinases (MMPs). JAK-STAT is another signaling pathway whose activation has been implicated in autoimmune and inflammatory diseases. It is used as a signaling pathway for cytokines that promote inflammatory responses and is associated with activation of the NF-κB signaling pathway. Research shows that luteolin can actively modulate these signaling pathways during inflammation.

Based on its multi-target anti-inflammatory effects, luteolin appears to be a very promising natural drug to inhibit abnormal inflammatory responses in chronic inflammatory conditions.

Oxidative stress is closely related to inflammation. In fact, there is evidence of a bidirectional relationship between free radical production and inflammation. Chronic inflammation is characterized by oxidative stress and vice versa. Excessive production of free radicals leads to chronic inflammation: they cause damage to major components of cells such as DNA, lipids and proteins, and stimulate inflammatory processes such as NF-κB. Luteolin exhibits powerful antioxidant properties through its ability to destroy free radicals and promote cellular antioxidant defenses (direct action).

Neuroprotective effect

Some studies suggest that luteolin may have neuroprotective properties, support brain health, and may reduce the risk of neurodegenerative diseases such as Alzheimer's disease.

neuropathic pain

Neuropathic pain is a type of pain caused by injury or disease of the somatosensory nervous system. Although the pathogenic mechanisms are not fully understood, increasing evidence suggests that nitrosative and oxidative stress, as well as nerve inflammation, play important roles in neuropathic pain. Oxidative stress and nitrosative stress represent the loss of intracellular redox balance due to high levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), respectively. Cells typically produce superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and heme oxygenase 1 (HO-1). Neurons have weaker antioxidant defense mechanisms and higher lipid content than other cell types, making them more susceptible to nitrooxidative damage. Therefore, nitro-oxidative stress in neurons is considered to be a major cause of neuropathic pain. Furthermore, ROS appear to contribute to the activation of the ion channel TRP, which is highly expressed in nociceptor neurons and plays an important role in pain transmission. In addition to damage directly caused by ROS and NOS, nerve inflammation appears to be an important process in the development and maintenance of neuropathic pain. Neuroinflammation is an inflammation caused by damage to nerve tissue in the peripheral or central nervous system. In addition, microglia and stellate cells in the dorsal horn of the spine are activated, contributing to the release of inflammatory mediators in the central nervous system and increasing excitability. Inflammation and nitrosative stress should not be considered separate processes in neuropathic pain. Rather, it's because they work together in a two-way relationship. For example, the transcription factor NF-κB is one of the most typical examples of inflammatory biochemical pathways. It can be activated by ROS/RNS to increase the expression of inflammatory mediators, thereby increasing the expression of various nitrosative substances. Medical options for treating neuropathic pain treat pain as a symptom rather than inhibiting its pathogenesis. First-line medications include tricyclic antidepressants, serotonin-norepinephrine reuptake inhibitors, gabapentin, and pregabalin. Effective treatment of neuropathic pain can be difficult due to the lack of efficacy of these drugs and the serious side effects associated with long-term use. Newer, safer methods can be adopted in a variety of ways to more effectively prevent nitrosative damage while inhibiting neuroinflammation.

Neuroprotective and analgesic effects of luteolin on neuropathic pain

Luteolin is very effective in combating neuropathic pain because of its effects on two cellular processes involved in neuropathy: oxidative stress and inflammation. Its powerful antioxidant properties, effects on nerve inflammation, and pain relief make luteolin an effective brain treatment. Additionally, studies have shown that luteolin can enhance endogenous antioxidant capacity. As we said before, direct antioxidants may not be as effective as expected, and recent research has shifted toward drugs that activate antioxidant processes rather than interfere with free radicals. Luteolin appears to do this by activating the key antioxidant transcription factor Nrf2. In various clinical studies, luteolin has been shown to have pleiotropic effects on diseases associated with neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In addition, the main symptoms of luteolin effects are anti-inflammatory and antioxidant symptoms, including inhibition of NF-κB and induction of Nrf2. Although the neuroprotective effects of luteolin on the central nervous system have been well established through in vitro and in vivo studies, its effects on peripheral nerve inflammation are unclear. Certainly, the few but important in vivo studies on the effects of luteolin on neuropathic pain are very encouraging.

Luteolin inhibits mechanical and cold hyperalgesia in an animal model of neuropathic pain in a dose-dependent manner. Daily intraperitoneal injection of luteolin (50 mg/kg, 100 mg/kg, 200 mg/kg) can activate Nrf2, increase the activities of antioxidant enzymes SOD, GST, GPx and CAT, and reduce the production of ROS. Luteolin treatment improves neurological function (measured by increases in movement and conduction velocity). Additionally, mechanical withdrawal threshold, cold, and sweating were increased, showing that luteolin can reduce hyperalgesia and allodynia. All results were dose-dependent, with 100 mg/kg and 200 mg/kg luteolin showing better results than the 50 mg/kg dose. Luteolin capsules (5 mg/kg and 10 mg/kg body weight) significantly reduce neuropathic pain in multiple animal models. Intraperitoneal injection of luteolin improved Lewis lung carcinoma (LLC)-induced bone pain in rats (50 mg/kg significantly improved pain behavior compared with 1 mg/kg and 10 mg/kg).

cardiovascular health

Luteolin may help promote cardiovascular health by improving blood flow, reducing inflammation of blood vessels, and lowering blood pressure.

Anti-cancer potential

Preliminary research suggests that luteolin may have anti-cancer properties, inhibiting the growth of cancer cells and inducing apoptosis in some types of cancer.

Luteolin sensitizes cancer cells to treatment-induced cytotoxicity by inhibiting cell survival pathways such as phosphatidylinositol 3'-kinase (PI3K)/Akt, NF-κB, and X-linked inhibitor of apoptosis protein (XIAP). It also stimulates the apoptotic pathway induced by the tumor suppressor protein p53. These properties suggest that luteolin may be an anticancer agent, but epidemiological studies also suggest that this compound has cancer-preventive properties, with significant inhibitory effects on tumor growth in squamous cell carcinoma of the head and neck (SCCHN).

Purpose and application

Dietary Supplements

Luteolin is available in supplement form, usually derived from plant sources such as celery seed extract or chamomile.

functional food

Certain foods, such as drinks, snacks and health bars, may have luteolin added to enhance their potential health benefits.

Topical skin care products

Luteolin is sometimes added to skin care products for its antioxidant and anti-inflammatory properties, which can benefit skin health and protect against environmental damage.

Precautions

bioavailability

The bioavailability of luteolin from dietary sources may vary, and more research is needed to understand its absorption and metabolism in the body.

Like many dietary compounds, luteolin shows low bioavailability due to poor water solubility, and to address this issue, luteolin nanoparticles are being developed.

interaction

Taking luteolin as a dietary supplement can be dangerous because it can interact with certain medications, such as blood thinners, and may cause side effects such as nausea, vomiting, and diarrhea. It may also cause allergic reactions in some people and may interact with other supplements or medications. It is important to consult a doctor before taking any dietary supplement, especially if you are taking any medications or have any underlying health conditions.

natural food sources

Including luteolin-rich foods (such as fruits, vegetables, and herbs) into your diet is generally considered safe and may provide additional nutritional benefits over and above those of luteolin alone.

How luteolin is regulated around the world

Regulation of luteolin varies around the world. In the United States, luteolin is classified as a dietary supplement and regulated by the Food and Drug Administration (FDA). In the EU, luteolin is classified as a food supplement and regulated by the European Food Safety Authority (EFSA). In Canada, luteolin is classified as a natural health product and regulated by Health Canada. In Australia, luteolin is classified as a complementary medicine and regulated by the Therapeutic Goods Administration (TGA).

in conclusion

While luteolin has shown promising health benefits in preclinical studies, further research, including human clinical trials, is needed to fully understand its potential therapeutic applications and optimal dosage. As with any dietary supplement, luteolin supplements must be used under the guidance of a healthcare provider for personalized advice and monitoring.

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