Category: Phytochemicals

A Review of Nervonic Acid Production in Plants: Prospects for the Genetic Engineering of High Nervonic Acid Cultivars Plants

Nervonic acid (NA) is a very-long-chain monounsaturated fatty acid that plays crucial roles in brain development and has attracted widespread research interest. The markets encouraged the development of a refined, NA-enriched plant oil as feedstocks for the needed further studies of NA biological functions to the end commercial application. Plant seed oils offer a renewable and environmentally friendly source of NA, but their industrial production is presently hindered by various factors. This review focuses on the NA biosynthesis and assembly, NA resources from plants, and the genetic engineering of NA biosynthesis in oil crops, discusses the factors that affect NA production in genetically engineered oil crops, and provides prospects for the application of NA and prospective trends in the engineering of NA. This review emphasizes the progress made toward various NA-related topics and explores the limitations and trends, thereby providing integrated and comprehensive insight into the nature of NA production mechanisms during genetic engineering. Furthermore, this report supports further work involving the manipulation of NA production through transgenic technologies and molecular breeding for the enhancement of crop nutritional quality or creation of plant biochemical factories to produce NA for use in nutraceutical, pharmaceutical, and chemical industries.

Nervonic acid (NA; 24:1 Δ15, 24:1 ω-9; cis-tetracos-15-enoic acid) is a very-long-chain monounsaturated fatty acid (VLCMFA, 22–26 carbons) (Merrill et al., 1997; Figure 1) that was first isolated in shark brain and molecular structure was determined more than 100 years ago; it is also known as shark oil acid or selacholeic Acid (Tsujimoto and Kimura, 1926). It was found that the shark brain could repair itself in a short time after being severely damaged, suggesting the exceptional effect of NA in promoting the repair and regeneration of nerve fibers in damaged brain tissues (Sinclair and Crawford, 1972). NA combines with sphingosines via amide bonds to form nervonyl sphingolipids, which are chiefly found in nervous and brain tissues, comprising the white matter and myelin sheath of nerve fibers (Poulos, 1995; Merrill et al., 1997; Martínez and Mougan, 1998). NA plays a vital role in developing and maintaining the brain and biosynthesizing and improving nerve cells. NA is a natural component of maternal milk and can promote infant growth by assisting nervous system development (Farquharson et al., 1996; Ntoumani et al., 2013; Yu et al., 2019). Decreased NA levels are closely associated with a high risk of developing psychotic disorders in individuals (Coupland and Raoul, 2001; Amminger et al., 2012; Vozella et al., 2017), and supplementation with NA is an established effective treatment for symptoms of several neurological diseases, such as demyelinating disorders (Sargent et al., 1994; Vozella et al., 2017; Lewkowicz et al., 2019). NA can also function as a non-competitive inhibitor of human immunodeficiency virus type-1 reverse transcriptase (HIV-1 RT) in a dose-dependent manner (Kasai et al., 2002). Increasing dietary NA improves energy metabolism in mice and may be an effective strategy for the treatment of obesity and obesity-related complications (Keppley et al., 2020). (Front. Plant Sci., 05 March 2021)

Capsaicin consumption reduces brain amyloid-beta generation and attenuates Alzheimer’s disease-type pathology and cognitive deficits in APP/PS1 mice

Alzheimer’s disease (AD) is the most common cause of age-related dementia and is currently incurable. The failures of current clinical trials and the establishment of modifiable risk factors have shifted the AD intervention from treatment to prevention in the at-risk population. Previous studies suggest that there is a geographic overlap between AD incidence and spicy food consumption. We previously reported that capsaicin-rich diet consumption was associated with better cognition and lower serum Amyloid-beta (Aβ) levels in people aged 40 years and over. In the present study, we found that intake of capsaicin, the pungent ingredient in chili peppers, reduced brain Aβ burden and rescued cognitive decline in APP/PS1 mice. Our in vivo and in vitro studies revealed that capsaicin shifted Amyloid precursor protein (APP) processing towards α-cleavage and precluded Aβ generation by promoting the maturation of a disintegrin and metalloproteinase 10 (ADAM10). We also found that capsaicin alleviated other AD-type pathologies, such as tau hyperphosphorylation, neuroinflammation and neurodegeneration. The present study suggests that capsaicin is a potential therapeutic candidate for AD and warrants clinical trials on chili peppers or capsaicin as dietary supplementation for the prevention and treatment of AD.

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Overproduction of Aβ plays a key role in the pathogenesis of AD. Aβ is derived from sequential cleavage of APP by β-secretase and γ-secretase within neurons, and then secreted to extracellular space.  ADAM10 is the major α-secretase that catalyses α-cleavage and promotes non-amyloidogenic processing of APP. ADAM10 is first generated as an inactive proenzyme (proADAM10) and matures into an active protease after the removal of its prodomain. We found that capsaicin treatment significantly increased brain levels of matADAM10 relative to APP/PS1 controls but did not affect proADAM10 protein or mRNA expression, suggesting that capsaicin increases the level of ADAM10 by promoting its maturation or activation. 

Capsaicin, as a natural component of spicy food, has potential advantages as an AD intervention strategy. Considering that chili peppers have been a vital part of culinary cultures worldwide and have a long history of application for flavouring, they are feasible to utilized for AD prevention. In addition, capsaicin is a potential therapeutic molecule for various human diseases, such as obesity, cardiovascular diseases, hypertension, and atherosclerosis, which are established risk factors for AD. Taken together, the current and previous findings suggest capsaicin may prevent AD by targeting multiple pathways that drive the pathogenesis of AD. (Translational Psychiatry volume 10, Article number: 230 (2020))

Vanillin: a review on the therapeutic prospects of a popular flavouring molecule

Vanilla is the world’s most popular flavour extracted from the pods of Vanilla planifolia orchid. It is a mixture of ~ 200 compounds but its characteristic flavour and fragrance primarily come from vanillin. While the importance of its wide usage in flavour and fragrance is well established, there have been limited investigations to evaluate its bioactive potential. However, a few studies have reported a promising array of bioactivities that could be exploited for multiple therapeutic applications. Recently, bioactive properties of vanillin, such as neuroprotection, anticarcinogenic, and antioxidant are gaining attention. Besides this, vanillin and its synthetic analogues are found to regulate gene expression and exhibit biological activities. Therefore, here we summarize the potential bioactivates of vanillin and its derivative with an aim to change the perspective from being a popular flavour to a new age therapeutics molecule.

Typically, there are three sources of vanillin, i.e. natural, chemical/synthetic and biotechnological. Depending on the source and the synthesis procedure, the vanillin is categorized as either natural or artificial flavour. Of these, the natural and biotechnologically produced vanillin (from ferulic acid as a substrate) is considered as food-grade additives by most food control authorities across the world. (Advances in Traditional Medicine volume 21, pages1–17 (2021))

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