Top

BMC Complementary Medicine and Therapies

Published in:

Open Access 01-12-2022 | Testosterone | Research

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration

Authors: Amirabbas Rostami, Sina Vakili, Farhad Koohpeyma, Bahia Namavar Jahromi, Ziba Afshari Aghajari, Fatemeh Mahmoudikohani, Forough Saki, Marzieh Mahmoodi, Khojaste Rahimi Jaberi, Ahmad Movahedpour, Majid Jafari Khorchani, Saam Noroozi

Published in: BMC Complementary Medicine and Therapies | Issue 1/2022

Abstract

Background

Busulfan is an antineoplastic medication that is broadly utilized for cancer treatment. It affects the testicular function and leads to sterility. The present study aimed to evaluate the effects of ellagic acid on testicular tissue changes, sexual hormones, antioxidant defense system, and caspase-9 and Bcl2 gene expression in the busulfan-induced relative sterile rat model.

Methods

This is an interventional-experimental animal study that was performed on 65 Adult male rats; they were randomly divided into five groups including control (1 ml of 0.9% normal saline), ellagic acid (50 mg/kg); busulfan (10 mg/kg); and busulfan plus ellagic acid (10 mg/kg and 50 mg/kg). At the end of the experiment, blood samples were collected, and plasma levels of sex hormones, antioxidant system, apoptosis-related genes, and testis histology were assessed.

Results

Busulfan reduced the levels of serum testosterone, total antioxidant capacity, gene expression of Bcl2, testicular volume, seminiferous tubule, germinal epithelium, interstitial tissue volume, and the number of spermatogonia, spermatocyte, round spermatid, elongated spermatid, Sertoli cells and Leydig cells (p < 0.05). Busulfan administration resulted in a significant increase (p < 0.05) in the level of LH, FSH, malondialdehyde, and caspase 9. Busulfan + ellagic acid (50 mg/kg) showed higher serum levels of testosterone, gene expression of Bcl-2 and antioxidant markers, and lower LH, FSH levels, and gene expression of caspase 9 compared to the Busulfan-treated rats (p < 0.05). Stereological parameters were also ameliorated in the group treated with Busulfan+ 50 mg/kg ellagic acid (p < 0.05).

Conclusion

In conclusion, the consumption of ellagic acid may have beneficial effects on the antioxidant defense system, sexual hormone abnormality, and testicular tissue damage induced by busulfan.

Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. JNCi Monographs. 2005;2005(34):12–7.CrossRef

Parsanezhad M, Jahromi B, Zare N, Keramati P, Khalili A, Parsa-Nezhad M. Epidemiology and etiology of infertility in Iran, systematic review and meta-analysis. J Womens Health, Issues Care. 2013;2(6):2.CrossRef

Schrader M, Müller M, Straub B, Miller K. The impact of chemotherapy on male fertility: a survey of the biologic basis and clinical aspects. Reprod Toxicol. 2001;15(6):611–7.PubMedCrossRef

De Sanctis V, Galimberti M, Lucarelli G, Polchi P, Ruggiero L, Vullo C. Gonadal function after allogenic bone marrow transplantation for thalassaemia. Arch Dis Child. 1991;66(4):517–20.PubMedPubMedCentralCrossRef

Afify Z, Shaw P, Clavano-Harding A, Cowell C. Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide. Bone Marrow Transplant. 2000;25(10):1087.PubMedCrossRef

Anderson PO, Knoben JE, Troutman WG. Handbook of clinical drug data: McGraw-Hill; 2002.

Trevor AJ, Katzung BG, Masters SB, Kruidering-Hall M. Pharmacology examination & board review: McGraw-Hill Medical New York; 2010.

Molenaar R, de Rooij DG, Rommerts FF, Reuvers PJ, van der Molen HJ. Specific destruction of Leydig cells in mature rats after in vivo administration of ethane dimethyl sulfonate. Biol Reprod. 1985;33(5):1213–22.PubMedCrossRef

Boujrad N, MHd R, Kamtchouing P, Perreau C, Carreau S. Evolution of somatic and germ cell populations after busulfan treatment in utero or neonatal cryptorchidism in the rat. Andrologia. 1995;27(4):223–8.PubMedCrossRef

10.

Jansz GF, Pomerantz DK. The effect of prenatal treatment with busulfan on in vitro androgen production by testes from rats of various ages. Can J Physiol Pharmacol. 1985;63(9):1155–8.PubMedCrossRef

11.

Bahmanpour S, Namavar Jahromi B, Koohpeyma F, Keshavarz M, Bakhtari A. Effects of different doses and time-dependency of busulfan on testes parameters and spermatogenesis in a rat model: a quantitative stereological study. J Adv Med Sci Applied Technol. 2017;3(3):155–62.

12.

Nasimi P, Tabandeh MR, Roohi S. Busulfan-mediated oxidative stress and genotoxicity decrease in sperm of Satureja Khuzestanica essential oil-administered mice. Syst Biol Reprod Med. 2018;64(5):348–57.PubMedCrossRef

13.

Fang F, Ni K, Cai Y, Zhao Q, Shang J, Zhang X, et al. Busulfan administration produces toxic effects on epididymal morphology and inhibits the expression of ZO-1 and vimentin in the mouse epididymis. Biosci Rep. 2017;37(6).

14.

Nasimi P, Tabandeh MR, Vahdati A, Khatamsaz S. Busulfan induces oxidative stress-and Bcl-2 family gene-related apoptosis in epididymal sperm and testis of adult male mice. Physiol Pharmacol. 2015;19(3):208–15.

15.

Brinster RL, Avarbock MR. Germline transmission of donor haplotype following spermatogonial transplantation. Proc Natl Acad Sci. 1994;91(24):11303–7.PubMedPubMedCentralCrossRef

16.

Honaramooz A, Behboodi E, Hausler CL, Blash S, Ayres S, Azuma C, et al. Depletion of endogenous germ cells in male pigs and goats in preparation for germ cell transplantation. J Androl. 2005;26(6):698–705.PubMedPubMedCentralCrossRef

17.

Frias MA, Somers S, Gerber-Wicht C, Opie LH, Lecour S, Lang U. The PGE2-Stat3 interaction in doxorubicin-induced myocardial apoptosis. Cardiovasc Res. 2008;80(1):69–77.PubMedCrossRef

18.

Shokoohi M, Khaki A, Abadi A RR, BoukaniL MZ, Hassanpour Khodaie S, Kalarestaghi H, et al. Minocycline can reduce testicular apoptosis related to varicocele in male rats. Andrologia. 2022;54(4):e14375.PubMedCrossRef

19.

Dolatshahi M, Farbood Y, Sarkaki A, Mansouri SMT, Khodadadi A. Ellagic acid improves hyperalgesia and cognitive deficiency in 6-hydroxidopamine induced rat model of Parkinson’s disease. Iranian J Basic Med Sci. 2015;18(1):38.

20.

Shokoohi M, Khaki A, Shoorei H, Khaki A, Moghimian M, Abtahi-Eivary SH. Hesperidin attenuated apoptotic-related genes in testicle of a male rat model of varicocoele. Andrology. 2020;8(1):249–58.PubMedCrossRef

21.

Dolatkhah MA, Shokoohi M, Charvandeh S, Tvrda E, Shoorei H, Moghimian M, et al. Fumaria parviflora regulates oxidative stress and apoptosis gene expression in the rat model of varicocele induction. Andrologia. 2020;52(11):e13826.PubMedCrossRef

22.

Czabotar PE, Lessene G, Strasser A, Adams JM. Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy. Nat Rev Mol Cell Biol. 2014;15(1):49–63.PubMedCrossRef

23.

Sankararamakrishnan R. Plasticity of hydrophobic grooves in anti-apoptotic Bcl-2 proteins. J Natural Sci, Biol Med. 2011;2(3).

24.

Bratton SB, MacFarlane M, Cain K, Cohen GM. Protein complexes activate distinct caspase cascades in death receptor and stress-induced apoptosis. Exp Cell Res. 2000;256(1):27–33.PubMedCrossRef

25.

Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999;15(1):269–90.PubMedCrossRef

26.

Gondo HK. The effect of Spirulina on apoptosis through the Caspase-3 pathway in a Preeclamptic Wistar rat model. J Nat Sci, Biol Med. 2021;12(3).

27.

Vakili S, Zal F, Mostafavi-pour Z, Savardashtaki A, Koohpeyma F. Quercetin and vitamin E alleviate ovariectomy-induced osteoporosis by modulating autophagy and apoptosis in rat bone cells. J Cell Physiol. 2021;236(5):3495–509.PubMedCrossRef

28.

Premkumar DR, Jane EP, Agostino NR, Scialabba JL, Pollack IF. Dasatinib synergizes with JSI-124 to inhibit growth and migration and induce apoptosis of malignant human glioma cells. J Carcinogenesis. 2010;9.

29.

Fossa S, Magelssen H. Fertility and reproduction after chemotherapy of adult cancer patients: malignant lymphoma and testicular cancer. Ann Oncol. 2004;15(Suppl 4):259–65.CrossRef

30.

Das UB, Mallick M, Debnath JM, Ghosh D. Protective effect of ascorbic acid on cyclophosphamide-induced testicular gametogenic and androgenic disorders in male rats. Asian J Androl. 2002;4(3):201–8.PubMed

31.

Ghosh D, Das UB, Misro M. Protective role of α-tocopherol-succinate (provitamin-E) in cyclophosphamide induced testicular gametogenic and steroidogenic disorders: a correlative approach to oxidative stress. Free Radic Res. 2002;36(11):1209–18.PubMedCrossRef

32.

Lear L, Nation R, Stupans I. Effects of cyclophosphamide and adriamycin on rat hepatic microsomal glucuronidation and lipid peroxidation. Biochem Pharmacol. 1992;44(4):747–53.PubMedCrossRef

33.

Kumar BA, Reddy AG, Kumar PR, Reddy YR, Rao TM, Haritha C. Protective role of N-acetyl L-cysteine against reproductive toxicity due to interaction of lead and cadmium in male Wistar rats. J Nat Sci, Biol, Med. 2013;4(2):414.CrossRef

34.

Sepúlveda L, Ascacio A, Rodríguez-Herrera R, Aguilera-Carbó A, Aguilar CN. Ellagic acid: biological properties and biotechnological development for production processes. Afr J Biotechnol. 2011;10(22):4518–23.

35.

Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem. 2005;16(6):360–7.PubMedCrossRef

36.

Letchoumy PV, Mohan KVPC, Prathiba D, Hara Y, Nagini S. Comparative evaluation of antiproliferative, antiangiogenic and apoptosis inducing potential of black tea polyphenols in the hamster buccal pouch carcinogenesis model. J Carcinog. 2007;6:19.PubMedPubMedCentralCrossRef

37.

Özten-Kandaş N, Bosland MC. Chemoprevention of prostate cancer: natural compounds, antiandrogens, and antioxidants–in vivo evidence. J Carcinog. 2011;10.

38.

Coates EM, Popa G, Gill CI, McCann MJ, McDougall GJ, Stewart D, et al. Colon-available raspberry polyphenols exhibit anti-cancer effects on in vitro models of colon cancer. Journal of Carcinog. 2007;6:4.CrossRef

39.

Uzar E, Alp H, Cevik MU, Fırat U, Evliyaoglu O, Tufek A, et al. Ellagic acid attenuates oxidative stress on brain and sciatic nerve and improves histopathology of brain in streptozotocin-induced diabetic rats. Neurol Sci. 2012;33(3):567–74.PubMedCrossRef

40.

Moskaug JØ, Carlsen H, Myhrstad MC, Blomhoff R. Polyphenols and glutathione synthesis regulation. Am J Clin Nutr. 2005;81(1):277S–83S.PubMedCrossRef

41.

Mansouri MT, Farbood Y, Naghizadeh B, Shabani S, Mirshekar MA, Sarkaki A. Beneficial effects of ellagic acid against animal models of scopolamine-and diazepam-induced cognitive impairments. Pharm Biol. 2016;54(10):1947–53.PubMedCrossRef

42.

Dalvi LT, Moreira DC, Andrade R Jr, Ginani J, Alonso A, Hermes-Lima M. Ellagic acid inhibits iron-mediated free radical formation. Spectrochim Acta A Mol Biomol Spectrosc. 2017;173:910–7.PubMedCrossRef

43.

Kaya N, Ozan G, Dabak DO, Gur S, Ozan IE. Antioxidant effects of ellagic acid on testicular tissue of rats exposed to tobacco smoke. J Turgut Ozal Med Cent. 2017;24(4):381–6.

44.

Hamza RZ, Al-Baqami NM. Testicular protective effects of ellagic acid on monosodium glutamate-induced testicular structural alterations in male rats. Ultrastruct Pathol. 2019;43(4-5):170–83.PubMedCrossRef

45.

Mehrzadi S, Bahrami N, Mehrabani M, Motevalian M, Mansouri E, Goudarzi M. Ellagic acid: a promising protective remedy against testicular toxicity induced by arsenic. Biomed Pharmacother. 2018;103:1464–72.PubMedCrossRef

46.

Türk G, Ateşşahin A, Sönmez M, Çeribaşi AO, Yüce A. Improvement of cisplatin-induced injuries to sperm quality, the oxidant-antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril. 2008;89(5):1474–81.PubMedCrossRef

47.

Zamani A, Saki F, Hatami N, Koohpeyma F. Stereological assessment of the effects of vitamin D deficiency on the rat testis. BMC Endocr Disord. 2020;20(1):1–8.CrossRef

48.

Khalifi S, Rahimipour A, Jeddi S, Ghanbari M, Kazerouni F, Ghasemi A. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia. Nitric Oxide. 2015;44:24–30.PubMedCrossRef

49.

Kalaivanam K, Dharmalingam M, Marcus SR. Lipid peroxidation in type 2 diabetes mellitus. Int J Diab Develop Countries. 2006;26(1).

50.

Koohpeyma F, Siri M, Allahyari S, Mahmoodi M, Saki F, Dastghaib S. The effects of L-carnitine on renal function and gene expression of caspase-9 and Bcl-2 in monosodium glutamate-induced rats. BMC Nephrol. 2021;22(1):1–11.CrossRef

51.

Zare S, Hossein Dabbaghmanesh M, Noorafshan A, Koohpeyma F, Bakhshayeshkaram M, Montazeri-Najafabady N. Protective effect of vitamin E and vitamin C alone and in combination on testicular damage induced by sodium metabisulphite in rats: a stereological study. Andrologia. 2019;51(2):e13193.PubMedCrossRef

52.

Noorafshan A. Stereology as a valuable tool in the toolbox of testicular research. Ann Anatomy-Anatomischer Anzeiger. 2014;196(1):57–66.CrossRef

53.

Bayat M, Dabbaghmanesh MH, Koohpeyma F, Mahmoodi M, Montazeri-Najafabady N, Bakhshayeshkaram M. The effects of soy Milk enriched with lactobacillus casei and Omega-3 on the tibia and L5 vertebra in diabetic rats: a stereological study. Probiotics and antimicrobial proteins. 2019;11(4):1172–81.PubMedCrossRef

54.

Ameli M, Moghimian M, Saeb F, Bashtani E, Shokoohi M, Salimnejad R, et al. The effect of clomiphene citrate and human chorionic gonadotropin on the expression of CatSper1, CatSper2, LHCGR, and SF1 genes, as well as the structural changes in testicular tissue of adult rats. Mol Reprod Dev. 2019;86(6):738–48.PubMedCrossRef

55.

Chen X, Liang M, Wang D. Progress on the study of the mechanism of busulfan cytotoxicity. Cytotechnology. 2018;70(2):497–502.PubMedPubMedCentralCrossRef

56.

Furukawa S, Usuda K, Abe M, Hayashi S, Ogawa I. Busulfan-induced apoptosis in rat placenta. Exp Toxicol Pathol. 2007;59(2):97–103.PubMedCrossRef

57.

Zhivotovsky B, Kroemer G. Apoptosis and genomic instability. Nat Rev Mol Cell Biol. 2004;5(9):752–62.PubMedCrossRef

58.

Lindsten T, Ross AJ, King A, Zong W-X, Rathmell JC, Shiels HA, et al. The combined functions of proapoptotic Bcl-2 family members bak and bax are essential for normal development of multiple tissues. Mol Cell. 2000;6(6):1389–99.PubMedPubMedCentralCrossRef

59.

Choi Y-J, Ok D-W, Kwon D-N, J-i C, Kim H-C, Yeo S-M, et al. Murine male germ cell apoptosis induced by busulfan treatment correlates with loss of c-kit-expression in a Fas/FasL-and p53-independent manner. FEBS Lett. 2004;575(1-3):41–51.PubMedCrossRef

60.

Dehghani F, Hassanpour A, Poost-Pasand A, Noorafshan A, Karbalay-Doust S. Protective effects of L-carnitine and homogenized testis tissue on the testis and sperm parameters of busulfan-induced infertile male rats. Iranian J Reproduct Med. 2013;11(9):693.

61.

Hakemi SG, Sharififar F, Haghpanah T, Babaee A, Eftekhar-Vaghefi SH. The effects of olive leaf extract on the testis, sperm quality and testicular germ cell apoptosis in male rats exposed to busulfan. Int J Fertil Steril. 2019;13(1):57.

62.

Olfati A, Moghaddam G, Baradaran B. FSH and estradiol benzoate administration recover spermatogenesis and sexual hormone levels in a busulfan-injured rat model. Comp Clin Pathol. 2020;29(1):53–9.CrossRef

63.

Chi H, Chun K, Son H, Kim J, Kim G, Roh S. Effect of genistein administration on the recovery of spermatogenesis in the busulfan-treated rat testis. Clin Exp Reproduct Med. 2013;40(2):60.CrossRef

64.

Wang D-Z, Zhou X-H, Yuan Y-L, Zheng X-M. Optimal dose of busulfan for depleting testicular germ cells of recipient mice before spermatogonial transplantation. Asian J Androl. 2010;12(2):263.PubMedCrossRef

65.

Ahar NH, Khaki A, Akbari G, Novin MG. The effect of busulfan on body weight, testis weight and MDA enzymes in male rats. Intern J Women’s Heal Reprod Sc. 2014;2:316–9.CrossRef

66.

Girish C, Shweta O, Raj V, Balakrishnan S, RGb V. Ellagic acid modulates sodium valproate induced reproductive toxicity in male Wistar rats. Indian J Physiol Pharmacol. 2014;58(4):416–22.PubMed

67.

Abarikwu S, Mgbudom-Okah C, Onuah C, Ogunlaja A. Fluted pumpkin seeds protect against busulfan-induced oxidative stress and testicular injuries in adult mice. Drug Chem Toxicol. 2019:1–11.

68.

Karashima T, Zalatnai A, Schally AV. Protective effects of analogs of luteinizing hormone-releasing hormone against chemotherapy-induced testicular damage in rats. Proc Natl Acad Sci. 1988;85(7):2329–33.PubMedPubMedCentralCrossRef

69.

Reznikov A. Feedback control of gonadotropin secretion in mammalian and human males: effects of gonadotropin receptor blockers. Endocrinol Exp. 1990;24(1-2):267–73.PubMed

70.

Shokoohi M, Soltani M, Abtahi-Eivary S-H, Niazi V, Poor MJR, Ravaei H, et al. Effect of hydro–alcoholic extract of Olea europaea on apoptosis–related genes and oxidative stress in a rat model of torsion/detorsion–induced ovarian damage. Asian Pacific J Reprod. 2019;8(4):148.CrossRef

71.

Bucak MN, Bodu M, Başpınar N, Güngör Ş, İli P, Acibaeva B, et al. Influence of Ellagic acid and Ebselen on sperm and oxidative stress parameters during liquid preservation of ram semen. Cell J (Yakhteh). 2019;12(1).

72.

Han DH, Lee MJ, Kim JH. Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Res. 2006;26(5A):3601–6.PubMed

73.

NASIMI P, VAHDATI A, TABANDEH M, KHATAMSAZ S. Study of side effects of busulfan on testis tissue and epididymal sperm of adult mice following treatment with clinical dose; 2016.

74.

Chen P, Chen F, Zhou B. Antioxidative, anti-inflammatory and anti-apoptotic effects of ellagic acid in liver and brain of rats treated by D-galactose. Sci Rep. 2018;8(1):1–10.

75.

Wu LL, Chiou C-C, Chang P-Y, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta. 2004;339(1-2):1–9.PubMedCrossRef

76.

Martinet W, Knaapen MW, De Meyer GR, Herman AG, Kockx MM. Oxidative DNA damage and repair in experimental atherosclerosis are reversed by dietary lipid lowering. Circ Res. 2001;88(7):733–9.PubMedCrossRef

77.

Yu Y-M, Chang W-C, Wu C-H, Chiang S-Y. Reduction of oxidative stress and apoptosis in hyperlipidemic rabbits by ellagic acid. J Nutr Biochem. 2005;16(11):675–81.PubMedCrossRef

78.

HOSHMAND MK, JAFARI BM, DEHGHAN MA, Vahdati A, Zargar H, Mahmoudi R: Protective effects of lycopene and Ellagic acid on gonadal tissue, Matern Newborn Rats Induced by Cadmiumchloride 2015.

79.

Utomo B, Daningtia NR, Yuliani GA, Yuniarti WM. Effects of a standardized 40% ellagic acid pomegranate (Punica granatum L.) extract on seminiferous tubule histopathology, diameter, and epithelium thickness in albino Wistar rats after heat exposure. Veterinary world. 2019;12(8):1261.PubMedPubMedCentralCrossRef

80.

Shoorei H, Khaki A, Shokoohi M, Khaki A, Alihemmati A, Moghimian M, et al. Evaluation of carvacrol on pituitary and sexual hormones and their receptors in the testicle of male diabetic rats. Hum Exp Toxicol. 2020;39(8):1019–30.PubMedCrossRef

81.

Coyne D, Acharya M, Qiu P, Abboud H, Batlle D, Rosansky S, et al. Paricalcitol capsule for the treatment of secondary hyperparathyroidism in stages 3 and 4 CKD. Am J Kidney Dis. 2006;47(2):263–76.PubMedCrossRef

Title: Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration
Authors: Amirabbas Rostami
Sina Vakili
Farhad Koohpeyma
Bahia Namavar Jahromi
Ziba Afshari Aghajari
Fatemeh Mahmoudikohani
Forough Saki
Marzieh Mahmoodi
Khojaste Rahimi Jaberi
Ahmad Movahedpour
Majid Jafari Khorchani
Saam Noroozi
Publication date: 01-12-2022
Publisher: BioMed Central
Keyword: Testosterone
Published in: BMC Complementary Medicine and Therapies / Issue 1/2022
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-022-03650-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Ellagic acid effects on testis, sex hormones, oxidative stress, and apoptosis in the relative sterility rat model following busulfan administration

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 1/2022

Formulation of Neem oil-loaded solid lipid nanoparticles and evaluation of its anti-Toxoplasma activity

Oridonin attenuates low shear stress-induced endothelial cell dysfunction and oxidative stress by activating the nuclear factor erythroid 2-related factor 2 pathway

Effectiveness of maturity of Rubus occidentalis on hyperalgesia induced by acidic saline injection in rats

Antimalarial activity of solvent fractions of a leaf of Eucalyptus globulus labill against Plasmodium berghei infected mice

The process of learning the autogenic training relaxation technique and its benefits on the wellness of people living with HIV

Network pharmacology and in vivo experiments reveal the pharmacological effects and molecular mechanisms of Simiao Powder in prevention and treatment for gout