Research Progress and Prospect Analysis of the Application of Flax Lignans

ABSTRACT

Lignan is one of the important components in flaxseed and has been paid increasing attention owing to its special therapeutic effects on many diseases. Herein, we retrieved the recently published studies on flaxseed lignan through the Web of Science to give a comprehensive understanding of the research advances of flaxseed lignan. Results showed that flaxseed lignan has been extensively applied to many industries, such as food, medicine, and cosmetics. Flaxseed lignan has great potential in the pharmaceuticals industry, many studies have proven its performance on antioxidant, anti-tumor, anti-cardiovascular disease, prevention of osteoporosis and diabetes. However, the depths of the research need to be enhanced and the mechanisms of lignan in curing each disease should be further clarified. Flaxseed lignan presents good performance in anti-skin sagging, maintains skin elasticity and radiance, and significantly delays the aging process. In addition, flaxseed lignan has been used in functional foods and dietary supplements in the food industry. Therefore, as a multiuse material, flaxseed lignan will play important roles in the product and development and utilization of food, medicine, and cosmetic and, accordingly, its source plant——flax, will also receive more attention in the future.

摘要

木脂素是亚麻籽中的重要成分之一, 由于其对许多疾病的特殊治疗作用而受到越来越多的关注。本文通过 Web of Science 检索了近期发表的关于亚麻籽木脂素的研究, 以期全面了解亚麻籽木脂素的研究进展。结果表明, 亚麻籽木脂素已广泛应用于食品、医药、化妆品等多个行业。亚麻籽木脂素在制药工业中具有巨大的潜力, 许多研究证明了其在抗氧化、抗肿瘤、抗心血管疾病、预防骨质疏松症和糖尿病方面的性能。然而, 研究的深度有待加强, 木脂素治疗各种疾病的机制有待进一步阐明。亚麻籽木脂素在抗皮肤松弛方面表现出良好的性能, 保持皮肤弹性和光泽, 并显著延缓衰老过程。此外, 亚麻籽木脂素已被用于食品工业中的功能性食品和膳食补充剂。因此, 作为一种多用途材料, 亚麻籽木脂素将在食品、医药和化妆品行业发挥重要作用, 其来源植物亚麻也将在未来受到更多关注。

KEYWORDS:

• Medical
• lignans
• cancer
• food
• cosmetics

关键词:

• 医学的
• 木脂素
• 癌症
• 食物
• 化妆品

Introduction

Flax (Linum usitatissimum L) is an annual herb and a significant bast fiber crop, categorized into three types based on its purpose: fiber flax, oil-fiber flax, and oil flax (Dudarev 2022). It thrives in shaded areas and is extensively cultivated in temperate regions due to its high yield and superior quality of flaxseeds (Zhao et al. 2020). The medicinal value of various biological components found in flaxseed, including lignans, flaxseed oil, and flax gum, has gained considerable attention (Tang et al. 2020; Ye et al. 2022). Lignans are crucial bioactive compounds present in several plants like sesame, barley, and carrots (Soleymani et al. 2020), but their content is significantly higher (about 1%~4%) in the coats of flaxseeds compared to other plants (Yi et al. 2020).

Numerous studies have highlighted the diverse medicinal effects of flaxseed lignan (Hu et al. 2022). Lignans possess potent antioxidant properties capable of effectively scavenging superoxide anion radicals (Gao et al. 2020). Therefore, comprehending the antioxidant mechanisms can be advantageous for utilizing them in cosmetics to address skin concerns. Cancer remains a global challenge characterized by uncontrolled cell proliferation. Research indicates that flaxseed lignans exhibit weak estrogenic activity which partially inhibits cell proliferation while also exerting certain suppressive effects on malignant tumors such as breast, colon and lung cancer (Tannous et al. 2020). Consequently, lignans hold great potential as anti-cancer agents. Cardiovascular disease is another prevalent ailment among middle-aged and elderly individuals often associated with chronic inflammation. Flaxseed lignans not only possess notable anti-inflammatory properties but may also serve as preventive measures against cardiovascular diseases in the future (Velalopoulou et al. 2016). Furthermore, they have shown promising results in preventing osteoporosis (Li et al. 2022) and diabetes (Kaur et al. 2023) as well.

To facilitate the advancement of flaxseed lignans product development and expedite their application in the fields of food, medicine, and cosmetics, this review provides a comprehensive analysis of the extraction and detection methods for flaxseed lignans, highlighting their advantages and disadvantages. Furthermore, it delves into the molecular mechanisms through which flaxseed lignans exert medicinal effects to enhance our understanding of these compounds. This knowledge will contribute to promoting product development and catering to the expanding domestic market.

Flaxseed lignan structure, toxicological profile, extraction and detection

Flaxseed lignan structure

Lignans are phytoestrogens that exhibit physiological activity similar to human estrogens. They are diphenolic compounds formed by coupling two coniferol residues commonly found in plant cell walls, often in dimer form (Chhillar, Chopra, and Ashfaq 2021). Various crops contain lignans with varying content levels depending on crop type (Hu et al. 2022). Lignans can be derived from cereals, oilseeds, nuts, berries, fruits and vegetables, and berries are also relatively abundant (Hu et al. 2022), but flaxseeds stand out as being exceptionally rich in lignans, with concentrations higher than these crops (Rodriguez-Garcia et al. 2019). Amongst the diverse range of lignans present in flaxseeds, secoisolariciresinol (SECO) and secoisolariciresinol diglucoside (SDG) are most abundant (Wu et al. 2021) (Figure 1). In addition, flax lignans also exist in monomeric forms, including matairesinol (MATA), lariciresinol (LARI), isolariciresinol (ISO), and so on (Shim et al. 2016).

Figure 1. Structures of SDG (A) and SECO (B).

Flaxseed lignan biosynthesis

Phenylalanine was synthesized into two molecules of phenylpropanoid monomer – coniferyl alcohol (CA) through the phenylpropanoid synthesis pathway, which provided a C6-C3 skeleton for flax lignans. Two molecules of CA are catalyzed by dirigent protein to produce pinoresinol, which is then catalyzed by pinoresinol-lariciresinol reductase enzyme to form SECO in two steps. SECO is the precursor of MATA and SDG. SECO forms MATA through dehydrogenase and SDG through glycosylation (Kezimana et al. 2018; Razna, Harencar, and Kucka 2022; Wang et al. 2020) (Figure 2).

Figure 2. The biosynthesis pathway of lignin in flax.

Flaxseed toxicological profile

Flaxseed contains a variety of toxic substances, such as linamarin, disaccharide linustatin, and neolinustatin, and its content is related to the variety, planting method, climate, and environment (Mueed et al. 2022). As an important substance for plant defense against herbivores, cyanogenic glycosides are not toxic in themselves, but the plant will produce hydrocyanic acid through the action of hydrolase enzymes during animal or human feeding or chewing, which can cause animal or human poisoning by inhibiting respiration (Zuk et al. 2020), and studies have shown that oral administration of linolenicin weighing 0.4‰ will produce a toxic reaction (Vil’chinskaya 1955), and excessive doses can cause death.

These toxic substances are present in flaxseed and flax coats and vary with flaxseed varieties, maturity, oil content, and external environmental conditions. In particular, the increase in cyanogenic glycosides during the sensitive period of flax growth may be an important way to protect the plant itself from persecution (Niedzwiedz-Siegien 1998). In addition, an interesting finding is that cyanogenic glycosides may be used as a source of nitrogen under transient nitrogen deficiency conditions, which may lead to the development of new utilization pathways (Siegien et al. 2021). The presence of these toxic substances limits the amount of flaxseed consumed. Rapid detoxification can be carried out by heating or flushing with running water.

Flaxseed lignan extraction

Owing to its hydroxyl groups’ presence. Several extraction methods for obtaining flaxseed lignan exist including traditional organic solvent extraction, microwave-assisted extraction, ultrasonic-assisted extraction, and supercritical carbon dioxide fluid extraction; each method possesses distinct advantages and disadvantages (Table 1). When selecting an appropriate method during experimentation considerations should be given to specific conditions and characteristics required for successful extractions.

Table 1. Extraction methods of flaxseed lignans.

Method	Process conditions	Features	References
Solvent extraction	Solvent: ethanol, Time: over 8 h	Operation: simple, Time: long, Solvent consumption: large	(Wang et al. 2019)
Microwave-assisted extraction.	Ethanol concentration: 60%, Microwave time: 1.5 min, Microwave power: 300W Material: liquid = 1: 20, Lignan yield: 14.74 mg/g	Yield: improved Time: short Energy: save Risk: leakage	(Gao et al. 2020)
Ultrasound-assisted extraction	Sodium hydroxide(w/w): 9% Isopropanol(w/w): 30% Time: 39 min Temperature: 40°C,	Power: large, Vibration: strong Impurities: more	(Zhang et al. 2022)
Supercritical CO2 fluid extraction	Temperature: 31.1°C, pressure (7.3 MPa)	Stability: strong Cost: high Operation: complex	(Sharma et al. 2019)
Pressurized liquid extraction	Ethanol concentration: 85% Temperature: 185°C,	Yield:high, Operation: complex	(Tripodo et al. 2018)

Due to the molecular structural characteristics of SDG, polar organic solvents are commonly employed for extraction based on their similar compatibility principles. However, this method is time-consuming and inefficient, leading to potential impurities and compromised product quality (Wang et al. 2019). The assisted extraction method incorporates microwave or ultrasonic assistance into the traditional polar solvent extraction process. Compared to conventional methods, this approach significantly reduces extraction time and enhances efficiency (Wu et al. 2022). Although the aforementioned methods are widely used for extraction purposes, they all rely on organic solvents which may introduce toxicity concerns during subsequent processing steps aimed at ensuring product quality (Patyra et al. 2022). Supercritical CO₂ refers to maintaining CO₂ above its critical temperature and pressure, exhibiting both gaseous and liquid properties that enable rapid dissolution of organic substances. Furthermore, supercritical CO₂ fluid exhibits exceptional stability, non-toxicity, and environmental friendliness – making it highly suitable for diverse applications in food processing industries and beyond (Razgonova et al. 2020). In comparison with alternative techniques, this approach ensures product safety while optimizing extraction yield and reducing processing costs; however, operational complexity arises due to the requirement for expensive specialized high-pressure equipment necessary to achieve the critical state of CO₂ (Zhang et al. 2014). Subsequent equipment maintenance and repair also contribute significantly to overall expenses. Polar pressurized liquid extraction is to heat water above the boiling point and change the polarity to make it suitable for the extraction of lignans (Tripodo et al. 2018). This method has a high yield, but the procedure is more cumbersome, and it is not suitable for large-scale applications at present.

Flaxseed lignan detection

Furthermore, there are several methods available for flax lignan detection as summarized in Table 2 regarding their principles and characteristics. High-performance liquid chromatography (HPLC) offers numerous advantages such as simplicity in operation and cost-effectiveness along with high efficiency and repeatability; hence it is frequently employed for lignan detection purposes (Brandao et al. 2017). Nevertheless, co-elution issues may arise when compounds with similar structures or polarities coexist within samples leading to reduced accuracy. Flax lignans exhibit maximum absorption at a wavelength of 260 nm under ultraviolet irradiation; thus visible photometry can be utilized for determining flaxseed lignan content (Schmidt et al. 2006). However, UV spectrophotometry may overestimate flaxseed lignan content since other physiologically active substances might also absorb at the same wavelength resulting in experimental errors that could impact subsequent product development quality. Thin-layer chromatography represents another inexpensive yet rapid detection method commonly used for qualitative analysis due to its lack of specific selectivity toward lignans during subsequent experiments (Wang et al. 2019). In addition, phosphomolybdic acid encounters flax lignans after heating to also produce a color reaction, so it can be used to detect lignans. Unfortunately, it shares similar limitations with thin-layer chromatography. Isotope dilution gas chromatographic-mass spectrometry is a rapid and highly precise method (Mazur et al. 1996). Experimental errors are minimized by utilizing isotope labeling; however, this approach increases the cost of analysis in experiments. Additionally, the operation of this method is complex.

Table 2. Detection methods of flaxseed lignans.

Method	Principle	Features	Reference
High performance liquid chromatography	Using liquid as the mobile phase, a single solvent of different polarities or a mobile phase of mixed solvents and buffers with different proportions are loaded into a column with a stationary phase through a high-pressure system for separation detection	Operation: simple Time: short Repeatability: good	(Brandao et al. 2017)
Ultraviolet spectrophotometric	the maximum characteristic absorption peak of lignan was determined at 276 nm.Ploting the standard curve can obtain the relationship between concentration and absorbance	Stability: strong, Repeatability: good Operation: simple Precision: low	(Zhang et al. 2023)
Thin-layer chromatography	Taking advantage of differences in the polarity of compounds separates detections	Time: short Qualitative analysis	(Willfor, Smeds, and Holmbom 2006)
Phosphomolybdic acid colorimetric	When phosphomolybdic acid is present, heating lignans to 120°C produces an observable color	Time: short Qualitative analysis	(Aid, Kaljurand, and Vaher 2015)
Isotope dilution gas chromatographic mass spectrometry	Isotope labeling is used for qualitative and quantitative analysis with chromatography and mass spectrometry	Accuracy: high Sensitivity: high Operation: complex Internal standards need to be added to compensate for losses	(Mazur et al. 1996)

There are several issues associated with these methods, including challenging operation, low precision, and difficulty in achieving both quantitative and qualitative measurements simultaneously. Accurately detecting the content becomes even more challenging when dealing with unstable and low concentrations of lignans. Therefore, different detection methods should be selected based on the required accuracy and efficiency of measurement.

Lignan application

Application in medicine

Effects of lignans on oxidation

The accumulation of free radicals can impair the body’s protective mechanisms, leading to gradual skin aging (Michalak 2022). Lignans interact with physiological and chemical reactions within the body, influencing protein synthesis and various metabolic processes that occur in humans. Particularly noteworthy is their ability to scavenge radicals and prevent skin oxidation to delay aging effects (Liu 2014).

In the 1990s, researchers began investigating SDG’s antioxidant activity and discovered its effectiveness at low concentrations (100 µM) (Kitts et al. 1999). The structure of lignans plays a crucial role in their capacity to scavenge free radicals; specifically, those containing catechol moieties exhibit superior radical scavenging abilities according to Eklund’s study involving 15 different lignans (Eklund et al. 2005).

Flax lignans demonstrate antioxidant properties both in vivo and in vitro (Hong et al. 2018). Upon metabolism, SDG is converted into enterodiol (ENL) and enterolactone (END) within the body (Mullens et al. 2022). The antioxidant effects of ENL and END do not cause DNA damage or exhibit any cytotoxicity, ensuring the high safety of lignan products that can meet consumer demands and expand foreign markets. Within a specific concentration range, flax lignans effectively prevent lipid peroxidation (Prasad 1997), with SDG demonstrating greater efficacy than END and ENL in terms of DNA damage and lipid peroxidation induced by AAPH-induced liposomes (Hu, Yuan, and Kitts 2007). This supports Eklund’s perspective that the bisphenol structure of SDG produces a stronger antioxidant effect compared to the monophenol structures of END and ENL (Eklund et al. 2005). To explore the antioxidant activity and mechanism of lignans, Wang et al. found that flaxseed lignans could reduce the content of malondialdehyde (MDA) produced in AAPH-induced injury, and increasing the content of SOD and CAT, thereby protecting the activity of antioxidant enzymes in erythrocytes and liver tissues, and this process was concentration-dependent (Wang et al. 2019). Given their concentration-dependent nature, it is crucial to extract and enrich flaxseed lignans effectively to enhance oxidative stability further (Yu et al. 2019).

It can be confirmed that flaxseed lignans possess certain antioxidant effects through scavenging free radicals, potentially influencing specific antioxidant enzymes and nonenzymatic molecules; however, maintaining stable physiological activity within the human body remains a significant challenge.

Effects of lignans on cancer

In recent years, cancer has emerged as one of the leading causes of mortality worldwide (Wang et al. 2023). Numerous studies have demonstrated anti-cancer effects associated with phytochemicals such as plant polyphenols – highlighting an important research direction (De Silva and Alcorn 2019) for investigating anti-prostate cancer (Saarinen et al. 2010) and anti-breast cancer (Flower et al. 2014) properties specifically related to flaxseed lignans. A limited number of studies have been conducted on various types of cancer, including lung (Pietrofesa et al. 2018), colonic (Ayella et al. 2010), endometrial (Aarestrup et al. 2013), and gastric cancer (Yang et al. 2012). One study discovered that the incidence of prostate cancer in China is significantly lower compared to Europe, which may be attributed to the consumption of soybeans by Asian men (Morton et al. 1997). Soybeans contain phytoestrogens such as lignans and enterolactone which are associated with reduced rates of cancer (Morton et al. 1999). Additionally, research has found that flaxseed lignans can decrease adhesion, invasion, and migration in breast cancer cells (Chen and Thompson 2003). The expression of C-erbB2 (HER2) is linked to the aggressiveness and metastasis of breast cancer cells; however, consuming 25 grams of flaxseed per day can significantly reduce tumor cell proliferation in breast cancer patients. Moreover, the reduction in expression proportion is closely related to the total intake of flaxseed (Thompson et al. 2005). For estrogen-dependent breast cancer cells MCF-7 treatment purposes, there isn’t a clear dose-effect relationship for SDG, but it may induce apoptosis by regulating cell growth; nevertheless, further investigation into its specific molecular biological mechanism is required (Hu et al. 2019). Increasing the dose does not lead to a more pronounced anti-cancer effect due to an unclear dose relationship. Abnormal cell cycles result in rapid proliferation of cancer cells; however, some studies have confirmed that flaxseed lignans inhibit cancers by regulating substances like Cyclin-dependent kinases. Studies have shown that flax lignans can up-regulate p53 and p21 and down-regulate cyclin D1 by activating the GPER/ERK pathway, affecting the G0/G1 phase of cancer cells, and similarly regulating substances to block the S phase of cancer cells, and ultimately achieve the purpose of inhibiting cancer (Ren et al. 2016). Inflammation commonly occurs later during cancer development; nonetheless, one study demonstrated that SDG might hinder tumor growth by inhibiting Nuclear factor-kappa B activity thereby reducing local inflammation levels (Bowers et al. 2019).

Numerous studies on anticancer effects from flaxseed lignans have shown their ability to achieve these effects through various pathways such as influencing the cell cycle and inhibiting inflammatory cytokines to achieve the aim of anti-cancer, but also affecting cell kinase activity, and activating transcription factors to achieve anti-cancer effects (Mueed et al. 2023). Flaxseed lignans exhibit activity against various cell kinases, including IGF-IR. SDG can directly bind to the kinase, inhibiting its activity and thereby impeding the signaling pathway of growth factors and reducing cancer cell expression (Saggar et al. 2010). STAT3 is renowned for its anticancer properties, and JAK2/STAT3 serves as a crucial pathway for cardioprotection (Boengler et al. 2008). SDG can be targeted as a molecular entity for STAT3 activation, which at a specific concentration impedes apoptosis in normal cells (Mueed et al. 2023).

Flaxseed lignans and their metabolites exhibit promising anticancer effects; however, further clinical trials are warranted to validate their efficacy, determine optimal dosage, and assess potential safety risks. Therefore, investigating these aspects should be considered as a future research direction.

Effects of lignans on cardiovascular disease

In terms of cardiovascular disease with high mortality rates primarily attributed to atherosclerosis pathology, studies on dietary habits in northern Italy have revealed a negative correlation between lignan intake and vascular inflammation incidence (Pellegrini et al. 2010). Inflammation represents a defensive response to infection or injury factors while atherosclerosis (AS) denotes chronic inflammatory arterial disease occurrence (Tian, Ma, and Xu 2017). This suggests that lignan consumption may be associated with AS development. Research has confirmed that administering flaxseed effectively inhibits AS progression in mice deficient in low-density lipoprotein (LDL) receptors by harnessing the antiproliferative and anti-inflammatory effects of flaxseed lignans (Dupasquier et al. 2007); however, inhibition does not equate regression of the disease itself. Subsequent investigations have demonstrated that SDG alone possesses the ability to regress or delay disease progression by inhibiting oxidative stress compared to the complex formed by flax lignans (Prasad and Jadhav 2016). It is possible that achieving an effective outcome requires reaching certain concentrations or content levels. Further studies have demonstrated that flaxseed lignans inhibit atherosclerosis by suppressing TXNIP and activating NLRP3 inflammasomes to mitigate inflammatory damage, which may be associated with the reduction of oxidative stress in the aorta, consistent with previous findings (Liu et al. 2020). Additionally, flaxseed consumption has been shown to lower blood cholesterol levels, reduce blood pressure, and decrease the risk of hepatic disease. However, it is important to note that the effect of SDG on blood pressure is dose-dependent and long-lasting (Prasad 2019). Nevertheless, caution should be exercised as flaxseed contains linoleside, a toxic substance; therefore blindly increasing dosage is not recommended. The stable efficacy of flaxseed lignans suggests that the frequency of consumption can be reduced without compromising its benefits. This stability in physiological activity facilitates quality control and standardization for large-scale production and market entry.

Flaxseed lignans can play a role in the fight against cardiovascular diseases by increasing cardiac neovascularization and also upregulating anti-apoptotic proteins to improve heart cell survival (Parikh, Netticadan, and Pierce 2018), particularly atherosclerosis. They can serve as a viable alternative medicine for alleviating and regressing this disease; however, further clinical experimental data involving human subjects is required to establish safety, stability, and optimal dosage (Prasad and Jadhav 2016). Therefore, additional research and exploration are necessary to validate these aspects.

Effects of lignans on osteoporosis disease

Since 1998, numerous scholars have conducted extensive research on the correlation between phytoestrogens and osteoporosis; however, no significant association was identified at that time (Kardinaal et al. 1998). Subsequent studies exposed female mouse offspring to purified SDG during different growth phases, revealing that the bones of female mice are more susceptible to SDG during early development, with limited long-term effects in adulthood; nevertheless, overall exposure did not adversely impact bone strength (Ward et al. 2001). Further investigations demonstrated a biphasic effect of SDG decomposition on osteoblast-like MG63 cells – low concentrations enhanced osteoblast activity while high content inhibited it, indicating a dual regulatory role (Gaoshun, Zhaoming, and Disheng 2011). This finding holds implications for product manufacturing as optimal results can only be achieved within an appropriate concentration range. However, randomized double-blind studies failed to demonstrate significant therapeutic effects of flaxseed lignan complex on osteoporosis in middle-aged and elderly men or menopausal women (Cornish et al. 2009). The decline in estrogen levels postmenopause increases the risk of developing osteoporosis in women (Snyman 2014). Conversely, another study found that SDG effectively increased bone mass and serum calcium levels while promoting new bone matrix formation among middle-aged and older women. Consequently, it exhibited potential preventive properties against bone loss and osteoporosis (Zhang 2013). These inconsistent findings may be attributed to variations in experimental concentration settings since SDG’s impact on bone health is dose-dependent (Dang and Lowik 2005). To determine the optimal content of flaxseed lignans, a comparative analysis was conducted to assess their inhibitory effects on apoptosis at different concentrations. The results revealed that chondrocyte apoptosis induced by IL-1β could be effectively inhibited at a concentration of 20 μM, thereby prolonging bone growth and potentially addressing height issues in adolescent children (Liang et al. 2022). This research may also have significant implications for addressing height issues in adolescent children by extending the duration of bone growth.

Flaxseed lignans have demonstrated potential as a preventive measure against osteoporosis; however, the molecular mechanisms underlying their protective effects remain unexplored. Additionally, the use of single animal models in previous studies necessitates expanding the scope of experimentation to gather more comprehensive data that can substantiate these effects and advance medical technology.

Effects of lignans on diabetes

Diabetes is a prevalent chronic metabolic disorder characterized by an increasing patient population encompassing individuals from progressively younger age groups while being associated with significant morbidity and mortality outcomes (Yaribeygi et al. 2020). Experimental findings in rats indicate that insulin-dependent diabetes mellitus (IDDM) is mediated by oxidative stress, while flaxseed lignans exhibit antioxidant efficacy and thus may be associated with the prevention of diabetes (Prasad 2000). In order to investigate the association between flaxseed lignans and diabetes, a large-scale survey was conducted in Europe in 2013, involving over 340 thousand individuals from eight European countries. However, no significant correlation was found between lignan intake and diabetes (Zamora-Ros et al. 2013). The variations in findings could potentially be attributed to differences in the population sources surveyed. Notably, an indirect relationship has been established between C-reactive protein (CRP) and diabetes. Epidemiological studies have demonstrated that administering flaxseed lignans to post-menopausal women in China may regulate CRP levels associated with insulin resistance and type 2 diabetes (Pan et al. 2009). Furthermore, a randomized cross-over study revealed that flaxseed consumption can reduce glucose levels and enhance insulin sensitivity (Zhou et al. 2020). These findings suggest that lignans possess potential inhibitory effects on diabetes at the protein and molecular level.

Indeed, the regulation of glycolipid metabolism in flaxseed is a highly intricate process, as evidenced by recent studies. Among them, inhibition of antioxidant activity caused by the phosphoenolpyruvate carboxykinase gene and lowering of blood glucose levels are two important mechanisms of anti-diabetes (Ebrahimi et al. 2021). Specifically, it has been discovered that SDG exerts control over glucose metabolism through the inhibition of pancreatic α-amylase activity. Furthermore, flaxseed lignans play a crucial role in improving blood sugar levels by regulating intestinal hormone secretion and enhancing insulin signaling transduction pathways (Shi and Sun 2020). The antioxidant properties of flaxseed lignans have been extensively studied in diabetes mellitus mediated by oxidative stress; however, further investigation is necessary to determine their potential anti-stress effects (Pilar et al. 2017). Moreover, considering the complexity of the regulatory pathway involved in utilizing flax lignans for diabetes treatment and mitigating potential complications, additional clinical trials are imperative to establish their safety and stability.

Application of lignans in food

As human living standards continue to improve, diets are becoming more refined, leading to an increasing prevalence of diet-related diseases. Consequently, there is a growing demand for functional foods that can enhance the body’s defense mechanisms and prevent certain illnesses (Terao 2015). Flaxseed lignans not only have the potential to be developed as functional foods with health benefits but also serve as dietary supplements (Goyal et al. 2014). Moreover, SDG exhibits ingredient stability at higher baking temperatures and has a prolonged shelf life, making it highly suitable for the baking industry (Imran et al. 2015). However, it is crucial to address how to maintain the texture and taste of baked goods after incorporating lignans. Additionally, flax lignan can act as an auxiliary additive in dairy products by significantly improving their heat resistance and light-induced oxidation while enhancing product stability and quality (Matumoto-Pintro et al. 2011). Since food has a limited shelf life that affects its taste, flaxseed lignans can be employed for food preservation purposes (Gao et al. 2014).

The diverse medicinal properties of flaxseed lignans make them valuable assets in the food industry, offering new strategies to tackle nutritional challenges with promising market prospects.

Application of lignans in cosmetics

Lignan is a natural antioxidant that exhibits remarkable properties in neutralizing free radicals without causing harm to the body. Incorporating flaxseed lignans into cosmetics can effectively prevent skin sagging, maintain skin elasticity and radiance, and significantly delay the aging process. Research has demonstrated that cosmetic products containing flaxseed lignans or extracts thereof are capable of preventing and treating dry, rough, and lackluster skin (Renault and Catroux 2004). Moreover, cosmetic lotions and essences enriched with lignans possess potent anti-aging functions (Wang et al. 2020). Flax lignans represent a naturally occurring physiologically active substance that not only demonstrates compatibility with human skin but also influences the physical and chemical properties of cosmetics themselves. It is worth noting that high-end cosmetics have limited shelf lives; therefore, exceeding their expiration date may result in compromised efficacy or even adverse effects on the skin. By influencing ingredient properties within cosmetics formulations, flax lignans serve as an effective alternative stabilizer for certain expensive emulsions while extending their shelf life unexpectedly (Hano et al. 2017). Given individual variations in skin types along with potential sensitivities to cosmetic ingredients among consumers, it becomes imperative during product development to conduct repeated testing of cosmetic ingredients to ensure safety and stability. The inclusion of flax lignans necessitates meticulous control over product stimulation levels to cater to a wider audience effectively. However, as a naturally active substance, flaxseed lignans alleviate excessive concerns regarding subsequent allergic reactions associated with product usage.

Conclusion and prospects

The present study provides a concise overview of the structural characteristics of flaxseed lignans, compares various extraction and detection methods employed for their analysis, and discusses their multifaceted functionalities. Flaxseed lignans exhibit potent antioxidant properties by scavenging free radicals, while also exerting inhibitory effects on abnormal cell proliferation through diverse molecular mechanisms to impede malignant tumor growth. Furthermore, these lignans hold promising potential as preventive agents against cardiovascular disease, osteoporosis, and diabetes in future therapeutic interventions. Additionally, they demonstrate remarkable utility in maintaining product composition stability and enhancing heat resistance. Consequently, the application prospects of flaxseed lignans within the pharmaceuticals, food products, and cosmetics industries are immense; thus warranting further investigation from researchers to maximize economic and societal benefits.

With the exploration of lignans’ application value in medicine, food, and chemical industries, the demand for flaxseed lignans has gradually expanded. Despite significant progress in studying flaxseed lignans, the precise molecular mechanism underlying their medicinal effects remains unclear. Therefore, gaining a comprehensive understanding of the medicinal molecular mechanism of flaxseed lignans, ensuring their stable physiological activities, and confirming their safety and stability are crucial steps before product development and future research directions. Additionally, it is imperative to develop more convenient, rapid, safe, and environmentally friendly methods for extracting and detecting lignans to reduce financial and human resources investment. Simultaneously, selecting and breeding superior flax varieties to enhance both flaxseed yield and grain lignan content is also essential.

Author contribution

Qiu Caisheng and Zhao Xinlin conceived and designed the article. Li Yazhi and Zhao Xinlin wrote the first draft, and Qiu Caisheng, Zhao Xinlin, Li Yazhi and Wang Yufu edited and revised the manuscript.

Highlights

• Flax lignans are effective for various incurable diseases such as diabetes.

• The therapeutic mechanism of flax lignans still needs to be further studied.

• The medicinal value of lignans can be used as a basis for the development of food and health products.

• The addition of flax lignans, a natural active substance, makes the cosmetic effect mild.

Acknowledgments

This research was supported by the Institute of Bast Crops, Chinese Academy of Agricultural Sciences, the National Modern Agricultural Industrial Technology System (CARS-16), and the Agricultural Science and Technology Innovation Program (ASTIP-IBFC).

Disclosure statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Additional information

Funding

This work was supported by the Supported by the earmarked fund for CARS [CARS-16].