Abstract
Erectile dysfunction (ED) is a common problem in diabetic men, which affects the quality of life. Zosima absinthifolia (Vent.) Link (syn. Zosima orientalis Hoffm.) is the only member of Zosima genus growing in Turkey. Its fruits and aerial parts have been used in folk medicine as a sedative and digestive problems. This study aimed to investigate the possible beneficial effect of intracavernosal injection of umbelliferone isolated from Z. absinthifolia Link roots on ED of streptozotocin-induced diabetic rats. Adult Sprague–Dawley (n = 20) rats were divided into control and streptozotocin-induced diabetic groups. In vivo erectile responses were also repeated after intracavernosal injection of umbelliferone (1 µM). Umbelliferone-induced relaxant responses in the presence of inhibitors of nitric oxide synthase (NOS) and cyclic guanosine monophosphate (cGMP) were assessed in corpus cavernosum (CC) strips from control rats. The relaxant responses of CC strips from both groups were evaluated in the presence or absence of umbelliferone (100 μM). In vivo erectile responses in diabetic rats were significantly lower than in controls, which were partially prevented by umbelliferone. Umbelliferone resulted in a relaxation of CC in a concentration-dependent manner. NOS and cGMP inhibitors antagonized the umbelliferone-induced relaxations in CC. Acetylcholine, sodium nitroprusside, a phosphodiesterase type 5 inhibitor, sildenafil and electrical field stimulation-induced relaxation responses in diabetic CC strips were potentialized after pre-incubation with umbelliferone. In conclusion, intracavernosal administration of umbelliferone may prevent ED in diabetic rats by recovering of NO/cGMP pathway. These results may be supported by further studies using combinations of umbelliferone and phosphodiesterase type 5 inhibitors for the treatment of diabetic ED.
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References
Al-Shamma A, Mitscher LA (1979) Comprehensive survey of indigenous Iraqi plants for potential economic value. 1. Screening results of 327 species for alkaloids and antimicrobial agents. J Nat Prod 42(6):633–642
Angulo J, González-Corrochano R, Cuevas P, Fernández A, La Fuente JM, Rolo F, Allona A, de Tejada IS (2010) Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries. J Sex Med 7(2):758–768
Bahadir O, Citoglu GS, Ozbek H, Dall’Acqua S, Hosek J, Smejkal K (2011) Hepatoprotective and TNF-alpha inhibitory activity of Zosima absinthifolia extracts and coumarins. Fitoterapia 82(3):454–459
Baser KHC, Ozek T, Demirci B, Kurkcuoglu M, Aytac Z, Duman H (2000) Composition of the essential oils of Zosima absinthifolia (Vent.) Link and Ferula elaeochytris Korovin from Turkey. Flavour Fragr J 15:371–372
Cengiz T, Kaya E, Oral DY, Ozakca I, Bayatli N, Karabay AZ, Ensari TA, Karahan T, Yilmaz E, Gur S (2017) Intracavernous injection of human umbilical cord blood mononuclear cells improves erectile dysfunction in streptozotocin-induced diabetic rats. J Sex Med 14(1):50–58
Chen J, Chiou WF, Chen CC, Chen CF (2000) Effect of the plant-extract osthole on the relaxation of rabbit corpus cavernosum tissue in vitro. J Urol 163(6):1975–1980
Evans JD, Pace K, Evans EW (2011) Natural therapies used by adult men for the treatment of erectile dysfunction, benign prostatic hyperplasia, and for augmenting exercise performance. J Pharm Pract 24(3):323–331
Gao D, Zhang YL, Xu P, Lin YX, Yang FQ, Liu JH, Zhu HW, Xia ZN (2015) In vitro evaluation of dual agonists for PPARgamma/beta from the flower of Edgeworthia gardneri (wall.) Meisn. J Ethnopharmacol 162:14–19
Garud MS, Kulkarni YA (2017) Attenuation of renal damage in type I diabetic rats by umbelliferone—a coumarin derivative. Pharmacol Rep 69(6):1263–1269
Iwase M, Yamamoto T, Nishimura K, Takahashi H, Mohri S, Li Y, Jheng HF, Nomura W, Takahashi N, Kim CS, Yu R, Taniguchi M, Baba K, Murakami S, Kawada T, Goto T (2017) Suksdorfin promotes adipocyte differentiation and improves abnormalities in glucose metabolism via PPARgamma activation. Lipids 52(7):657–664
Jang D-J, Lee MS, Shin B-C, Lee Y-C, Ernst E (2008) Red ginseng for treating erectile dysfunction: a systematic review. Br J Clin Pharmacol 66(4):444–450
Karakaya S, Koca M, Yılmaz SV, Yıldırım K, Pınar NM, Demirci B, Brestic M, Sytar O (2019) Molecular docking studies of coumarins isolated from extracts and essential oils of Zosima absinthifolia Link as potential inhibitors for Alzheimer’s disease. Molecules 24(4):E722
Kim JS, Kim JC, Shim SH, Lee EJ, Jin WY, Bae K, Son KH, Kim HP, Kang SS, Chang HW (2006) Chemical constituents of the root of Dystaenia takeshimana and their anti-inflammatory activity. Arch Pharm Res 29(8):617–623
Kong L-Y, Li Y, Min Z-D, Li X, Zhu T-R (1996) Coumarins from Peucedanum praeruptorum. Phytochemistry 41(5):1423–1426
MacKay D (2004) Nutrients and botanicals for erectile dysfunction: examining the evidence. Alternat Med Rev 9(1):4–16
Mazzilli R, Elia J, Delfino M, Benedetti F, Scordovillo G, Mazzilli F (2015) Prevalence of diabetes mellitus (DM) in a population of men affected by erectile dysfunction (ED). Clin Ter 166(5):e317–e320
Nunes KP, Teixeira CE, Priviero FBM, Toque HA, Webb RC (2015) Beneficial effect of the soluble guanylyl cyclase stimulator BAY 41-2272 on impaired penile erection in db/db-/- type II diabetic and obese mice. J Pharmacol Exp Therap 353(2):330–339
Onal E, Yilmaz D, Kaya E, Bastaskın T, Bayatlı N, Gur S (2016) Pomegranate juice causes a partial improvement through lowering oxidative stress for erectile dysfunction in streptozotocin-diabetic rat. Int J Impot Res 28(6):234–240
Ramesh B, Pugalendi KV (2006) Antioxidant role of Umbelliferone in STZ-diabetic rats. Life Sci 79(3):306–310
Ramesh B, Pugalendi KV (2005) Antihyperlipidemic and antidiabetic effects of umbelliferone in streptozotocin diabetic rats. Yale J Biol Med 78(4):189–196
Ramu R, Shirahatti PS, Nanjunda Swamy S, Zameer F, Dhananjaya BL, Nagendra Prasad MN (2016) Assessment of in vivo antidiabetic properties of umbelliferone and lupeol constituents of banana (Musa sp. var. Nanjangud Rasa Bale) flower in hyperglycaemic rodent model. PLoS One 11(3):e0151135
Rastrelli G, Corona G, Mannucci E, Maggi M (2015) Vascular and chronological age in subjects with erectile dysfunction: a cross-sectional study. J Sex Med 12(12):2303–2312
Razavi SM, Imanzadeh G, Jahed FS, Zarrini G (2013) Pyranocoumarins from Zosima absinthifolia (Vent) Link roots. Bioorg Khim 39(2):244–246
Roberts RE, Allen S, Chang AP, Henderson H, Hobson GC, Karania B, Morgan KN, Pek AS, Raghvani K, Shee CY, Shikotra J, Street E, Abbas Z, Ellis K, Heer JK, Alexander SP (2013) Distinct mechanisms of relaxation to bioactive components from chamomile species in porcine isolated blood vessels. Toxicol Appl Pharmacol 272(3):797–805
Ruan Y, Li M, Wang T, Yang J, Rao K, Wang S, Yang W, Liu J, Ye Z (2016) Taurine supplementation improves erectile function in rats with streptozotocin-induced type 1 diabetes via amelioration of penile fibrosis and endothelial dysfunction. J Sex Med 13(5):778–785
Yilmaz-Oral D, Bayatli N, Gur S (2017) The beneficial effect of fesoterodine, a competitive muscarinic receptor antagonist on erectile dysfunction in streptozotocin-induced diabetic rats. Urology 107:271.e1–271.e7
Yilmaz D, Bayatli N, Un O, Kadowitz PJ, Sikka SC, Gur S (2014) The effect of intracavernosal avanafil, a newer phosphodiesterase-5 inhibitor, on neonatal type 2 diabetic rats with erectile dysfunction. Urology 83(2):508 e507–e512
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Karakaya, S., Yilmaz-Oral, D., Kilic, C.S. et al. Umbelliferone isolated from Zosima absinthifolia roots partially restored erectile dysfunction in streptozotocin-induced diabetic rats. Med Chem Res 28, 1161–1167 (2019). https://doi.org/10.1007/s00044-019-02359-9
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DOI: https://doi.org/10.1007/s00044-019-02359-9