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Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs

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Abstract

Objective

To explore the underlying mechanism of inhibition by Jinkui Shenqi Pills (JKSQP) on glucocorticoid-enhanced axial length elongation in experimental lens-induced myopia (LIM) guinea pigs.

Methods

Sixty 2-week old male guinea pigs were randomly divided into 4 groups with 15 guinea pigs in each group, according to the random numbers generated by SPSS software: control, LIM, saline and JKSQP groups. The control group includes animals with no treatment, while the guinea pigs in the other 3 groups received lens-induced myopization on the right eyes throughout the experiment (for 8 weeks). The saline and JKSQP groups were given daily intraperitoneal injections of 10 mg/kg hydrocortisone for 2 consecutive weeks at the same time, and then orally administered either saline or JKSQP [13.5 g/(kg•d) for 6 consecutive weeks. Body weight, anal temperature and animal appearance were observed and recorded to evaluate the GC-associated symptoms. The ocular parameters, including refraction and axial length, were measured by streak retinoscopy and A-scan ultrasonography, respectively. The levels of plasma hormones associated with the hypothalamic-pituitary-adrenal axis (HPAA), including free triiodothyronine, free thyroxine, estradiol and testosterone, were measured by radioimmunoassay, and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate were measured by enzyme-linked immunosorbent assay. In addition, the mRNA and protein expressions of retinal amphiregulin (AREG) was measured by quantitative real-time polymerase chain reaction and Western blotting, respectively.

Results

JKSQP effectively increased body weight and anal temperature, improved animal appearance and suppressed axial length elongation in glucocorticoid-enhanced myopic guinea pigs with normalization of 4 HPAA-associated plasma hormones (all P<0.05). The plasma level of cAMP was significantly increased, whereas the plasma level of cGMP and the mRNA and protein expressions of retinal AREG were decreased after treatment with JKSQP (all P<0.05).

Conclusion

JKSQP exhibited a significant inhibitory effect on axial length elongation with decreased expression of AREG in the retina, and normalized 4 HPAA-associated plasma hormones and the expression of cAMP and cGMP in GC-enhanced myopic guinea pigs.

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Data Availability

The datasets used during in current study can be obtained from the corresponding author upon reasonable request.

References

  1. Baird PN, Saw SM, Lanca C, Guggenheim JA, Smith III EL, Zhou X, et al. Myopia. Nat Rev Dis Primers 2020;6:99.

    Article  PubMed  Google Scholar 

  2. Zeng Y, Li T, Zhang X, Ren Y, Huang Q, Wang J, et al. Effects of Haima Duobian Pill in a rat model of Kidney yang deficiency syndrome. Evid Based Complement Alternat Med 2021;2021:6696234.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ge W, Zhou BG, Zhong YB, Liu SQ, Huang JQ, Yuan WY, et al. Sishen Pill ameliorates dextran sulfate sodium (DSS)-induced colitis with Spleen-Kidney yang deficiency syndromes: role of gut microbiota, fecal metabolites, inflammatory dendritic cells, and TLR4/NF-kappaB pathway. Evid Based Complement Alternat Med 2022;2022:6132289.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ji B, Li YY, Yang WJ, Zhang LZ, Fang MS, Fu HY, et al. Jinkui Shenqi Pills ameliorate asthma with “Kidney yang deficiency” by enhancing the function of the hypothalamic-pituitary-adrenal axis to regulate T helper 1/2 imbalance. Evid Based Complement Alternat Med 2018;2018:7253240.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cai XY, Zhang ZJ, Xiong JL, Yang M, Wang ZT. Experimental and molecular docking studies of estrogenlike and anti-osteoporosis activity of compounds in Fructus Psoraleae. J Ethnopharmacol 2021;276:114044.

    Article  CAS  PubMed  Google Scholar 

  6. Ding M, Guo D, Wu J, Ye X, Zhang Y, Sha F, et al. Effects of glucocorticoid on the eye development in guinea pigs. Steroids 2018;139:1–9.

    Article  CAS  PubMed  Google Scholar 

  7. Zhang T, Jiang Q, Xu F, Zhang R, Liu D, Guo D, et al. Alternation of resting-state functional connectivity between visual cortex and hypothalamus in guinea pigs with experimental glucocorticoid enhanced myopia after the treatment of electroacupuncture. Front Neuroinform 2020;14:579769.

    Article  PubMed  Google Scholar 

  8. Zhao L, Zhao A, Chen T, Chen W, Liu J, Wei R, et al. Global and targeted metabolomics evidence of the protective effect of Chinese patent medicine Jinkui Shenqi Pill on adrenal insufficiency after acute glucocorticoid withdrawal in rats. J Proteome Res 2016;15:2327–2336.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Xiong X, Wang P, Li X, Zhang Y. Shenqi Pill, a traditional Chinese herbal formula, for the treatment of hypertension: a systematic review. Complement Ther Med 2015;23:484–493.

    Article  PubMed  Google Scholar 

  10. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 2001;25:402–408.

    Article  CAS  PubMed  Google Scholar 

  11. Costello RE, Yimer BB, Roads P, Jani M, Dixon WG. Glucocorticoid use is associated with an increased risk of hypertension. Rheumatology (Oxford) 2021;60:132–139.

    Article  CAS  PubMed  Google Scholar 

  12. Du K, Gao XX, Feng Y, Li J, Wang H, Lv SL, et al. Integrated adrenal and testicular metabolomics revealed the protective effects of Guilingji on the Kidney-yang deficiency syndrome rats. J Ethnopharmacol 2020;255:112734.

    Article  CAS  PubMed  Google Scholar 

  13. Zhang L, Lang J, Jin L, Jin L, Cao B, Shao X, et al. Effect of Hirsutella sinensis Fungus on the hypothalamic-pituitary-adrenal axis in Lewis rats with Kidney-yang deficiency syndrome. Evid Based Complement Alternat Med 2020;2020:5952612.

    PubMed  PubMed Central  Google Scholar 

  14. Shang Q, Zhao W, Shen G, Yu X, Zhang Z, Huang X, et al. Jingui Shenqi Pills regulate bone-fat balance in murine ovariectomy-induced osteoporosis with Kidney yang deficiency. Evid Based Complement Alternat Med 2020;2020:1517596.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Wang J, Cheng T, Zhang B, Xiong S, Zhao H, Li Q, et al. Puberty could regulate the effects of outdoor time on refractive development in Chinese children and adolescents. Br J Ophthalmol 2021;105:191–197.

    Article  PubMed  Google Scholar 

  16. Chen ZT, Wang IJ, Liao YT, Shih YF, Lin LL. Polymorphisms in steroidogenesis genes, sex steroid levels, and high myopia in the Taiwanese population. Mol Vis 2011;17:2297–2310.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Yu T, Xie X, Wei H, Wu Q, Zhang X, Tian Q, et al. Electroacupuncture improves choroidal blood flow to inhibit the development of lens-induced myopia in guinea pigs. Evid Based Complement Alternat Med 2022;2022:3286583.

    PubMed  PubMed Central  Google Scholar 

  18. Mocking RJ, Ruhe HG, Assies J, Lok A, Koeter MW, Visser I, et al. Relationship between the hypothalamic-pituitary-adrenal-axis and fatty acid metabolism in recurrent depression. Psychoneuroendocrinology 2013;38:1607–1617.

    Article  CAS  PubMed  Google Scholar 

  19. Richard D, Baraboi D. Circuitries involved in the control of energy homeostasis and the hypothalamic-pituitary-adrenal axis activity. Treat Endocrinol 2004;3:269–277.

    Article  PubMed  Google Scholar 

  20. Zhao F, Zhou H, Chen W, Zhao C, Zheng Y, Tao Y, et al. Declines in PDE4B activity promote myopia progression through downregulation of scleral collagen expression. Exp Eye Res 2021;212:108758.

    Article  CAS  PubMed  Google Scholar 

  21. Srinivasalu N, Lu C, Pan M, Reinach PS, Wen Y, Hu Y, et al. Role of cyclic adenosine monophosphate in myopic scleral remodeling in guinea pigs: a microarray analysis. Invest Ophthalmol Vis Sci 2018;59:4318–4325.

    Article  CAS  PubMed  Google Scholar 

  22. Chun RK, Shan SW, Lam TC, Wong CL, Li KK, Do CW, et al. Cyclic adenosine monophosphate activates retinal apolipoprotein a1 expression and inhibits myopic eye growth. Invest Ophthalmol Vis Sci 2015;56:8151–8157.

    Article  CAS  PubMed  Google Scholar 

  23. Wu S, Guo D, Wei H, Yin X, Zhang L, Guo B, et al. Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in guinea pigs. Arch Biochem Biophys 2020;688:108403.

    Article  CAS  PubMed  Google Scholar 

  24. Wang B, Liu Y, Chen S, Wu Y, Lin S, Duan Y, et al. A novel potentially causative variant of NDUFAF7 revealed by mutation screening in a Chinese family with pathologic myopia. Invest Ophthalmol Vis Sci 2017;58:4182–4192.

    Article  CAS  PubMed  Google Scholar 

  25. Feliciello A, Gottesman ME, Avvedimento EV. cAMP-PKA signaling to the mitochondria: protein scaffolds, mRNA and phosphatases. Cell Signal 2005;17:279–287.

    Article  CAS  PubMed  Google Scholar 

  26. Signorile A, Ferretta A, Ruggieri M, Paolicelli D, Lattanzio P, Trojano M, et al. Mitochondria, oxidative stress, cAMP signalling and apoptosis: a crossroads in lymphocytes of multiple sclerosis, a possible role of nutraceutics. Antioxidants (Basel) 2020;10:21.

    Article  PubMed  Google Scholar 

  27. Ravnskjaer K, Madiraju A, Montminy M. Role of the cAMP pathway in glucose and lipid metabolism. Handb Exp Pharmacol 2016;233:29–49.

    Article  CAS  PubMed  Google Scholar 

  28. Tan Y, Liu X, Lu C, He X, Li J, Xiao C, et al. Metabolic profiling reveals therapeutic biomarkers of processed Aconitum carmichaeli Debx in treating hydrocortisone induced Kidney-yang deficiency syndrome rats. J Ethnopharmacol 2014;152:585–593.

    Article  CAS  PubMed  Google Scholar 

  29. Feng L, Lin L, Wang S, Zhao X, Dai Q, Wang L, et al. Clinical practice guidelines for the treatment of allergic rhinitis in children with traditional Chinese medicine. Anat Rec (Hoboken) 2021;304:2592–2604.

    Article  PubMed  Google Scholar 

  30. Zhang Y, Xu SY, Liu MN, Jia TY, Qu WJ, Han T, et al. Comparative studies on chemical contents and effect in Kidney-yang deficiency rats of salt-processed product and wine-processed product of Cuscutae Semen. Evid Based Complement Alternat Med 2019;2019:2049497.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Nan Y, Zhou X, Liu Q, Zhang A, Guan Y, Lin S, et al. Serum metabolomics strategy for understanding pharmacological effects of Shenqi pill acting on Kidney yang deficiency syndrome. J Chromatogr B Analyt Technol Biomed Life Sci 2016;1026:217–226.

    Article  CAS  PubMed  Google Scholar 

  32. Che WJ, He XZ, Jiang JP, Cai WY, Xie SJ. Preliminary study on treatment of partial androgen deficiency in aging males with Jingui Shenqi Pill. Chin J Integr Med 2005;11:300–302.

    Article  PubMed  Google Scholar 

  33. Singh SS, Chauhan SB, Kumar A, Kumar S, Engwerda CR, Sundar S, et al. Amphiregulin in cellular physiology, health, and disease: potential use as a biomarker and therapeutic target. J Cell Physiol 2022;237:1143–1156.

    Article  CAS  PubMed  Google Scholar 

  34. Jiang WJ, Song HX, Li SY, Guo B, Wu JF, Li GP, et al. Amphiregulin antibody and reduction of axial elongation in experimental myopia. EBio Med 2017;17:134–144.

    Google Scholar 

  35. Dong L, Shi XH, Kang YK, Wei WB, Wang YX, Xu XL, et al. Amphiregulin and ocular axial length. Acta Ophthalmol 2019;97:e460–e470.

    Article  CAS  PubMed  Google Scholar 

  36. Ciarloni L, Mallepell S, Brisken C. Amphiregulin is an essential mediator of estrogen receptor alpha function in mammary gland development. Proc Natl Acad Sci U S A 2007;104:5455–5460.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

Authors

Contributions

Jiang Q and Jiang WJ contributed equally to this study. Jiang WJ and Bi HS conceived and formulated the experiments. Jiang Q, Jiang WJ, Yang CX, Zhang RX, Sun W, Guo DD, Wu JF and Guo B performed the experiments. Jiang Q, Jiang WJ, Wu JF, and Wang XR collected and analyzed the data. Jiang WJ and Bi HS contributed reagents/materials/analysis tools. Jiang Q and Jiang WJ wrote the paper. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hong-sheng Bi.

Ethics declarations

The authors declare that there are no conflicts of interest regarding the publication of this paper.

Additional information

Supported by the National Key Research and Development Program (Nos. 2021YFC2702103 and 2019YFC1710204), the Key Research and Development Program of Shandong Province (No. 2019GSF108252) and the Natural Science Foundation of Shandong Province (No. ZR2020MH393)

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Jiang, Q., Jiang, Wj., Yang, Cx. et al. Inhibitory Effect of Jinkui Shenqi Pills on Glucocorticoid-Enhanced Axial Length Elongation in Experimentally Myopic Guinea Pigs. Chin. J. Integr. Med. 29, 989–997 (2023). https://doi.org/10.1007/s11655-023-3738-x

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