Some Skeletons in the Mature Silkworm Larvae: Not only Spinning Silk Threads but also Preventing Parkinson's Disease

¹Department of Agricultural Biology, National Academy of Agricultural Science, Rural Development Administration, Wanju-gun, Jeollabuk-do, Republic of Korea

²Department of Biomedical Gerontology, Graduate School of Hallym University, Chuncheon, Gangwon-do, Republic of Korea

³Ilsong Institute of Life Science, Hallym University, Anyang, Gyeonggi-do, Republic of Korea

*Corresponding Author:

Young Ho Koh
Professor, Department of Biomedical Gerontology
Graduate School, Ilsong Institute of Life Science
Hallym University, Anyang, Gyenggi-do
Republic of Korea
Tel: 821099793703
E-mail: kohyh@hallym.ac.kr

Received date: November 03, 2016; Accepted date: November 30, 2016; Published date: December 07, 2016

Citation: Ji SD, Son JG, Koh YH (2016) Some Skeletons in the Mature Silkworm Larvae: Not only Spinning Silk Threads but also Preventing Parkinson’s Disease. J Alzheimers Dis Parkinsonism 6:289. doi:10.4172/2161-0460.1000289

Copyright: © 2016 Ji SD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Visit for more related articles at Journal of Alzheimers Disease & Parkinsonism

Keywords

Steamed and freeze-dried mature silkworm larval powder (SMSP); Parkinson’s disease (PD); Healthspan; Rotenone; Olfaction.

Overview

Innovations in medicine and improvement in hygiene in developed countries significantly increased the life expectancies of humans (http:// gamapserver.who.int/gho/interactive_charts/mbd/life_expectancy/atlas. html). However, increased life expectancies do not guarantee extension of survival duration without suffering from various chronic diseases (a.k.a. healthspan) [1,2]. Although the life expectancies in most developed countries are now more than 80 years, healthspans in those countries are still around 70 years [2,3]. Thus, most of peoples have suffered from various chronic diseases including neurodegenerative disorders, cancers, metabolic syndromes and cardiovascular diseases at least for their last 10 years. Therefore, health costs for treating elderly peoples are enormously increased and caused severe economic crisis in healthcare systems in most of developed countries [4]. There are several simple but difficult and tedious ways to extend healthspan in humans. It has been shown that calorie restriction and moderate exercise regimen while healthy could extend healthspan in humans and animal models [5,6].

One of most important goals in nutrient and health improvement supplement researches is to find calorie restriction mimetics which induce the similar physiological effects which were accomplished by calorie restriction or moderate exercise. Even though many calories restriction mimetic candidates were suggested, most of them were not proven to be effectives in humans or animal models [2,5,6].

Health Benefits from Mulberry Silkworm Products

Mulberry silkworms have been used to weave silk fabrics and provided pupae which are valuable protein and lipid sources for many years [7]. Since 1980’s, unknown health improvement effects of mulberry silkworm products have been investigated. The most well-known health improvement effect of silkworm products is hyperglycemic effects induced by uptake of freeze-dried 3^rd day of 5^th instar silkworm larval powder (FDSP) [8,9]. In addition, peptides derived from silk proteins have been shown to improve cognitive functions in animal models [10]. These two products are sold as human health supplementary materials in several countries including Korea.

Previous researches in mulberry silkworms suggested that mature silkworm larvae might have several unknown health improvement effects since they have enlarged silk glands enriched with silk proteins and other functional materials. However, it was not possible to eat mature silkworm larvae because their silk glands became too hard to chew if not processed properly. Recently, we developed and patented the protocol make silk glands in mature silkworm larvae chewable [7]. If mature silkworm larvae were steamed 130 min at 100oC, their silk glands were became crunchy and edible. Steamed mature silkworm larvae were immediately freeze-dried at –50oC and then grinded to make powders for easy intake [7].

The most significant health benefits from steamed and freeze-dried mature silkworm larval powder (SMSP, a.k.a. boiled and freeze-dried mature silkworm larval powder) was increased life expectancy and extension of healthspan [11]. More flies raised with SMSP food (SMSPf) retained their locomotor ability significantly longer than normal food (Nf) raised flies.

SMSP Increased Resistance to Rotenone, a PD Causative Chemical

PD is a movement disorder caused by loss of dopaminergic neurons in Substantia nigra pas compact in human central nervous system [12]. PD could be divided into familial or sporadic forms based on their causes. Familial PDs are known to be caused by mutations in certain specific genes. Sporadic PDs are known to be caused by combinations of genetic and/or environmental risk factors. One of known environmental risk factors in PD is chronic exposure to pesticides [13]. Drosophila has been extensively used to investigate molecular and cellular mechanisms underlying familial and sporadic PDs [14]. Exposure to rotenone was known to faithfully replicate PD’s symptoms in Drosophila [15]. We followed the rotenone treatment protocol published by Coulom and Birman [15]. We found that SMSPf flies showed significantly enhanced motor control and life expectancy compared with Nf flies when they were treated with various concentration of rotenone. We used 100 flies for each treatment and used Kaplan-Meier survival analyses for performing statistical analyses. We also found that integrity of mitochondria that was measured by mitochondrial citrate synthase activities was increased in SMSPf flies compared with Nf flies [11]. In addition, SMSP increased PD resistance in flies by enhancing expression of olfactory genes and olfaction. The loss of olfaction is one of common symptoms observed from PD patients [16] and other neurodegenerative disorders. These results suggested that SMSP could prevent onset of PD in Drosophila by maintaining integrity of mitochondria and enhancing olfaction.

Nutrient Composition of SMSP Suggested Various Health Improvement Effects in Humans

To elucidate unknown nutritional basis of SMSP in health improvement effects, we investigate the nutrient compositions of SMSP [17]. Proximate analysis showed that crude proteins were most abundant components followed by crude lipids. The amino acid composition analysis showed that ASP, SER, GLY, ALA and TYR contents in SMSP were significantly higher compared with those of FDSP. Those amino acids are known to have unique health improvement effects such as enhancing secretion of ammonia (ASP), immune system (SER, GLY), and metabolisms (ALA) and production of dopamine in brains (TYR) [18]. In addition the contents of Ω-3 (n-3) fatty acids, which are one of the most popular health improvement supplements, were ~4 times more than those of Ω-6 (n-6) fatty acids. Recent studies suggested that the very low ratio of n-3 fatty acids to n-6 fatty acids in the Western diet (1/15~1/16) might cause various cardiovascular diseases in humans [19]. Indeed, mulberry silkworm chrysalis oil which has similar n-3 fatty acid to n-6 fatty acid ratio to SMSP has shown to improve hyeprlipidaemia and hyperglycaemia [20]. Furthermore, it contained very high amounts of essential minerals with a very high ratio of K/ Na (71.4). It has been shown that ingesting high K/Na ratio food could make blood pressure lower in humans [21]. Because SMSP might contain other chemicals known to give health benefits in humans, such as flavonoids, polyphenols, carotenoids, etc., we are now investigating what kinds of mulberry originated chemicals are present in SMSP and their contribution to health benefits.

Another interesting finding we obtained was that SMSPf flies had reduced expression of carbohydrate and amino acid metabolism related genes [11]. Decreased expression of metabolism related genes suggested that SMSP could mimic several benefits from calorie restriction and moderate exercises at gene levels.

Conclusion

Is SMSP not only preventing PD, but also being a good candidate for calorie restriction mimetics?

Since the SMSP production protocol was recently developed [7], there was only few reports [11,17]. However, previous studies investigating various health benefits from mulberry silkworm larvae [8,9], pupae [20], and silk proteins [10] provided strong evidences supporting their positive effects in hyperglycemia [8,9,20], hyperlipidaemia [20], mild cognition defects [10] in animal models. Since SMSP shared ingredients with 3rd day of 5th instar larvae, pupae and silk proteins, the synergistic health improvement effects of its ingredients could extended healthspans and prevent onset of PD in fly models.

Taken together, SMSP could be a good candidate for a calorie restriction mimetic food and preventing onset of PD in humans. Performing further researches confirming those benefits in humans are utmost important.

Acknowledgement

This work was carried out with the support of the “Cooperative Research Program for Agriculture Science and Technology Development (Project title: Elucidation the health improvement effects of boiled silk worm larvae, project no: PJ010828012016) Rural Development Administration.

References

1. Bansal A, Zhu LJ, Yen K, Tissenbaum HA (2015) Uncoupling lifespan and healthspan in Caenorhabditis elegans longevity mutants. Proc Natl Acad Sci 112: E277-E286.
2. Hansen M, Kennedy BK (2016) Does longer lifespan mean longer healthspan? Trends Cell Biol 26: 565-568.
3. Crimmins EM (2015) Lifespan and healthspan: Past, present and promise. Gerontologist 55: 901-911.
4. Knickman JR, Snell EK (2002) The 2030 problem: Caring for aging baby boomers. Health Serv Res 37: 849-884.
5. Testa G, Biasi F, Poli G, Chiarpotto E (2014) Calorie restriction and dietary restriction mimetics: A strategy for improving healthy aging and longevity. Curr Pharm Design 20: 2950-2977.
6. Handschin C (2016) Caloric restriction and exercise "mimetics": Ready for prime time? Pharmacol Res 103: 158-166.
7. Ji SD, Kim NS, Lee JY, Kim MJ, Kweon H, et al. (2015) Development of processing technology for edible mature silkworm. J Sericult Entomol Sci 53: 38-43.
8. Ryu KS, Lee HS, Kim IS (2002) Effects and mechanisms of silkworm powder as a blood glucose-lowering agent. Int J Indust Entomol 4: 93-100.
9. Ryu KS, Lee HS, Kim KY, Kim MJ, Kang PD, et al. (2012) Anti-diabetic effects of the silkworm (Bombyx mori.) extracts in the db/db mice. Planta Med 78: PI458.
10. Kim DK, Kang YK, Lee MY, Lee KG, Yeo JH, et al. (2005) Neuroprotection and enhancement of learning and memory by BF-7. J Health Sci 5: 317-324.
11. Nguyen P, Kim KY, Kim AY, Kim NS, Kweon HY, et al. (2016) Increased healthspan and resistance to Parkinson's disease in Drosophila by boiled and freeze-dried mature silk worm larval powder. J Asia-Pacific Entomol 19: 551-561.
12. Pringsheim T, Jette N, Frolkis A, Steeves TDL (2014) The prevalence of ParkinsonâÂ?Â?s disease: A systematic review and meta-analysis. Movement Disord 29: 1583-1590.
13. Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, et al. (2011) Rotenone, paraquat and ParkinsonâÂ?Â?s disease. Environ Heath Persp 119: 866-872.
14. Friedmann T, Dunlap JC, Stephen FG (2011) Drosophila models of Parkinson's disease. Adv Genet 73: 1-50.
15. Coulom H, Birman, S (2004) Chronic exposure to rotenone models sporadic ParkinsonâÂ?Â?s disease in Drosophila melanogaster. J Neurosci 24: 10993-10998.
16. Casjens S, Eckert A, Woitalla D, Ellrichmann G, Turewicz M, et al. (2013) Diagnostic value of the Impairment of olfaction in ParkinsonâÂ?Â?s disease. PLoS ONE 8: e64735.
17. Ji SD, Kim NS, Kweon H, Choi BH, Yoon SM, et al. (2016) Nutrient compositions of Bombyx mori mature silkworm larval powders suggest their possible health improvement effects in humans. J Asia-Pacific Entomol 19: 1027-1033.
18. Belitz HD, Grosch W, Schieberle P (2009) Amino acids, peptides, proteins. In: Food Chemistry. Berlin, Heidelberg: Springer Berlin Heidelberg.
19. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Phamacoth 56: 365-379.
20. Mentang F, Maita M, Ushio H, Ohshima T (2011) Efficacy of silkworm (Bombyx mori L.) chrysalis oil as a lipid source in adult Wistar rat. Food Chemistry 127: 899-904.
21. Aburto NJ, Hanson S, Gutierrez H, Hooper L, Elliott P, et al. (2013) Effect of increased potassium intake on cardiovascular risk factors and disease: Systematic review and meta-analyses. BMJ 346: 1-19.