Quercetin promotes the secretion of musk by regulating the hormone level and microbial structure of forest musk deer

Abstract

Musk is a scarce and precious medical resource secreted by male forest musk deer (FMD). Current research to promote musk secretion in FMD has used almost exclusively hormone injections, but this approach can be detrimental to the health of FMD. In order to conserve this endangered species as much as possible while increasing the production of musk, this study first used bioinformatics methods to predict the function of quercetin, a flavonoid that promotes testosterone (T) production and prevents late-onset male hypogonadism. On the basis of good prediction effect, different concentrations of quercetin were added to the diet of FMD. The results showed that quercetin could change the levels of T, luteinizing hormone releasing hormone, luteinizing hormone, and estradiol, and regulate the structure of intestinal microorganisms and musk microorganisms of FMD. Moreover, there is a correlation among musk components, hormones, intestinal microorganisms, and musk microorganisms, which indicates that the production of musk may be regulated by these three at the same time, and the addition of quercetin with 800 mg per kg diet could significantly increase the yield of muscone (P < 0.05), the most effective ingredient in musk. In addition, quercetin decreased the high level of cortisol during musk secretion, which may relieve the stress on FMD in this process. This may help to protect the health of FMD. Combined with the results of software prediction, we finally proposed a possible mechanism for the complex process of musk secretion in FMD with a view to providing ideas for further studies.

Keywords

forest musk deer / microorganism / musk / network pharmacology / quercetin

References

[1] AbdEWM,AliSS, AyuobNN (2018). The role of musk in relieving the neurodegenerative changes induced after exposure to chronic stress. American Journal of Alzheimers Disease and Other Dementias 33,221–231.

[2] AmevorFK,CuiZ, NingZ et al. (2022). Dietary quercetin and vitamin E supplementation modulates the reproductive performance and antioxidant capacity of aged male breeder chickens. Poultry Science 101,101851.

[3] BalakrishnanS,Mukherjee S,DasS et al. (2017). Gold nanoparticles-conjugated quercetin induces apoptosis via inhibition of EGFR/PI3K/Akt-mediated pathway in breast cancer cell lines (MCF-7 and MDA-MB-231). Cell Biochemistry and Function 35,217–231.

[4] BarkaEA,VatsaP, SanchezL et al. (2016). Taxonomy, physiology, and natural products of Actinobacteria. Microbiology and Molecular Biology Reviews 80,1–43.

[5] BehairyA,HashemMM, Abo-El-SooudK,El-MetwallyAE,HassanBA, Abd-ElhakimYM (2022). Quercetin abates aluminum trioxide nanoparticles and lead acetate induced altered sperm quality, testicular oxidative damage, and sexual hormones disruption in male rats. Antioxidants 11,2133.

[6] BhartiS,MisroMM, RaiU (2014). Quercetin supplementation restores testicular function and augments germ cell survival in the estrogenized rats. Molecular and Cellular Endocrinology 383,10–20.

[7] CaniPD,Depommier C,DerrienM et al. (2022). Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms. Nature Reviews Gastroenterology & Hepatology 19,625–637.

[8] ChenM,JieH, XuZ et al. (2018). Isolation, primary culture, and morphological characterization of gland epithelium from forest musk deer (Moschus berezovskii). In Vitro Cellular & Developmental Biology-Animal 54,545–548.

[9] DuY,GuX, MengH et al. (2018). Muscone improves cardiac function in mice after myocardial infarction by alleviating cardiac macrophage-mediated chronic inflammation through inhibition of NF-kappaB and NLRP3 inflammasome. American Journal of Translational Research 10,4235–4246.

[10] FanD-C,QiJ-Y, ZhangM-Z (2017). Insights of Chinese medicine on ventricular remodeling: Multiple-targets, individualized-treatment. Chinese Journal of Integrative Medicine 23,643–647.

[11] FanM,ZhangM, ShiM et al. (2018). Sex hormones play roles in determining musk composition during the early stages of musk secretion by musk deer (Moschus berezovskii). Endocrine Journal 65,1111–1120.

[12] GaillardT (2018). Evaluation of AutoDock and AutoDock Vina on the CASF-2013 benchmark. Journal of Chemical Information and Modeling 58,1697–1706.

[13] GoymannW (2012). On the use of non-invasive hormone research in uncontrolled, natural environments: The problem with sex, diet, metabolic rate and the individual. Methods in Ecology and Evolution 3,757–765.

[14] GuangZL (2020). Study on the expression of genes related to necroptosis and macroautophagy during the development and atrophy of scent gland in muskrat (Ondatra zibethicus) (Dissertation). Northeast Forestry University,Harbin, Heilongjiang. (In Chinese.)

[15] HawkinsTH (1950). Musk and the musk deer. Nature 166,262.

[16] HeL,WangW-X, LiL-H et al. (2014). Effects of crowding and sex on fecal cortisol levels of captive forest musk deer. Biological Research 47,48.

[17] HeY,WangJ, WangM,Zhang J (2018). Discrimination of wild and domestic deer musk using isotope ratio mass spectrometry. Journal of Mass Spectrometry 53,1078–1085.

[18] HosseiniA,RazaviBM, BanachM,Hosseinzadeh H (2021). Quercetin and metabolic syndrome: A review. Phytotherapy Research 35,5352–5364.

[19] HuberS,PalmeR, ArnoldW (2003). Effects of season, sex, and sample collection on concentrations of fecal cortisol metabolites in red deer (Cervus elaphus). General and Comparative Endocrinology 130,48–54.

[20] JenksBG (2009). Regulation of proopiomelanocortin gene expression: An overview of the signaling cascades, transcription factors, and responsive elements involved. Annals of the New York Academy of Sciences 1163,17–30.

[21] JieH,FengXL, ZhaoGJ et al. (2014). Research progress on musk secretion mechanism of forest musk deer. China Journal of Chinese Materia Medica 39,4522–4525.

[22] KalamS,BasuA, AhmadI et al. (2020). Recent understanding of soil Acidobacteria and their ecological significance: A critical review. Frontiers in Microbiology 11,580024.

[23] KellyGS (2011). Quercetin. Monograph. Alternative Medicine Review 16,172–194.

[24] KielakAM,Castellane TCL,CampanharoJC et al. (2017). Characterization of novel Acidobacteria exopolysaccharides with potential industrial and ecological applications. Scientific Reports 7,41193.

[25] LeeSH,MoonSJ, PaengJ et al. (2015). Podocyte hypertrophy precedes apoptosis under experimental diabetic conditions. Apoptosis 20,1056–1071.

[26] LiC,JiangZ, ZengY,You Z (2007). A note on environmental elements as essential prerequisites for behavioral expression: A case study of Pere Davids deer. Applied Animal Behaviour Science 103,174–180.

[27] LiY (2022). The bioactivities of phycocyanobilin from spirulina. Journal of Immunology Research 2022,4008991.

[28] LiY,ZhangT, QiL et al. (2018). Microbiota changes in the musk gland of male forest musk deer during musk maturation. Frontiers in Microbiology 9,3048.

[29] LiY,ZhangT, ZhouJ et al. (2017). Transcriptome analysis of muskrat scented glands degeneration mechanism. PLoS ONE 12,e0176935.

[30] LiuM-J,YangJ-Y, YanZ-H et al. (2022). Recent findings in Akkermansia muciniphila-regulated metabolism and its role in intestinal diseases. Clinical Nutrition 41,2333–2344.

[31] LiuY,LiY, XuL et al. (2021). Quercetin attenuates podocyte apoptosis of diabetic nephropathy through targeting EGFR signaling. Frontiers in Pharmacology 12,792777.

[32] LuL,LiuS, LiQ et al. (2014). Seasonal expression of androgen receptor in scented gland of muskrat (Ondatra zibethicus). General and Comparative Endocrinology 204,1–7.

[33] MartinLJ,Touaibia M (2020). Improvement of testicular steroidogenesis using flavonoids and isoflavonoids for prevention of late-onset male hypogonadism. Antioxidants 9,237.

[34] McewenBS (2004). Protection and damage from acute and chronic stress: Allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Annals of the New York Academy of Sciences 1032,1–7.

[35] NaudS,IbrahimA, VallesC et al. (2022). Candidate phyla radiation, an underappreciated division of the human microbiome, and its impact on health and disease. Clinical Microbiology Reviews 35,e0014021.

[36] NogalesC,MamdouhZM, ListM,Kiel C,CasasAI,SchmidtHHHW (2022). Network pharmacology: Curing causal mechanisms instead of treating symptoms. Trends in Pharmacological Sciences 43,136–150.

[37] PochiPE,StraussJS, DowningDT (1979). Age-related changes in sebaceous gland activity. Journal of Investigative Dermatology 73,108–111.

[38] QiW-H,LiJ, ZhangX-Y et al. (2011). The reproductive performance of female forest musk deer (Moschus berezovskii) in captivity. Theriogenology 76,874–881.

[39] RosignoliC,NicolasJC, JomardA,Michel S (2003). Involvement of the SREBP pathway in the mode of action of androgens in sebaceous glands in vivo. Experimental Dermatology 12,480–489.

[40] ShabbirU,RubabM, DaliriEB-M,Chelliah R,JavedA,OhD-H (2021). Curcumin, quercetin, catechins and metabolic diseases: The role of gut microbiota. Nutrients 13,206.

[41] SharmaP,AslamKI, SinghR (2018). Curcumin and quercetin ameliorated cypermethrin and deltamethrin-induced reproductive system impairment in male wistar rats by upregulating the activity of pituitary-gonadal hormones and steroidogenic enzymes. International Journal of Fertility & Sterility 12,72–80.

[42] SmithMI,Yatsunenko T,ManaryMJ et al. (2013). Gut microbiomes of Malawian twin pairs discordant for kwashiorkor. Science 339,548–554.

[43] SongY,ChuY, MaX et al. (2017). GC-MS/MS method for the determination and pharmacokinetic analysis of borneol and muscone in rat after the intravenous administration of Xingnaojing injection. Journal of Separation Science 40,4264–4271.

[44] StojilkovicSS (2012). Molecular mechanisms of pituitary endocrine cell calcium handling. Cell Calcium 51,212–221.

[45] SuYY,WeiGD (1991). A study on the secondary musk secretion of male musk deer induced physiologically by androgen within successive two years. Acta Theriologica Sinica 11,9–12.

[46] VertèsAA,InuiM, YukawaH (2012). Postgenomic approaches to using corynebacteria as biocatalysts. Annual Review of Microbiology 66,521–550.

[47] WangH,JiangW, HuY et al. (2021). Quercetin improves atrial fibrillation through inhibiting TGF-beta/Smads pathway via promoting MiR-135b expression. Phytomedicine 93,153774.

[48] WangL,DingJ, YangZ et al. (2019). Pere David’s deer gut microbiome changes across captive and translocated populations: Implications for conservation. Evolutionary Applications 12,622–635.

[49] WangYL,HaCY (2018). Research progress on musk and artificial propagation technique of forest musk deer. China Journal of Chinese Materia Medica 43,3806–3810.

[50] WuS-N,ChiangH-T, ShenA-Y,Lo Y-K (2003). Differential effects of quercetin, a natural polyphenolic flavonoid, on L-type calcium current in pituitary tumor (GH₃) cells and neuronal NG108-15 cells. Journal of Cellular Physiology 195,298–308.

[51] YangJ,PengG, ShuF et al. (2021). Characteristics of steroidogenesis-related factors in the musk gland of Chinese forest musk deer (Moschus berezovskii). Journal of Steroid Biochemistry and Molecular Biology 212,105916.

[52] YangQ,MengX, XiaL,FengZ (2003). Conservation status and causes of decline of musk deer (Moschus spp.) in China. Biological Conservation 109,333–342.

[53] ZhangT,PengD, QiL et al. (2017). Musk gland seasonal development and musk secretion are regulated by the testis in muskrat (Ondatra zibethicus). Biological Research 50,10.

[54] ZhouC,ZhangW, WenQ et al. (2019). Comparative genomics reveals the genetic mechanisms of musk secretion and adaptive immunity in Chinese forest musk deer. Genome Biology and Evolution 11,1019–1032.

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