Adrogenic effects of crude aqueous leaf extracts of citropsis articulata and mystroxylon aethiopicum and their safety profile in male albino rats.
Gakunga, Ndukui James
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Background: Erectile dysfunction is the inability of the male to attain or maintain an erection sufficient for satisfactory sexual intercourse. Many plants extracts are traditionally used to improve sexual performance in the world and Uganda in particular. Citropsis articulata (Rutaceae) locally known as Omuboro/Akatimbolo is prepared as an infusion for men in management of erectile dysfunction in western part of Uganda. M. aethiopicum (Celastraceae) commonly known as spike thorn and locally as Esasi is used for the management of helminthosis, erectile dysfunction, Black water in sheep and magic portion to keep communities together. Despite the wide use of C. articulata and M. aethiopicum by communities around the world, there is inadequate scientific information available on the actual pharmacological effects of aqueous leaves extracts on sex hormones, their safety profile and phytochemical composition. Study Objectives: The aim of this study was to determine the androgenic effects of crude aqueous leaf extracts of Citropsis articulata and Mystroxylon aethiopicum, their safety profile and phytochemical composition. Methodology: This was an experimental design whereby disease free adult male rats were randomly divided into eight groups (n=6) and kept in separate cages. The rats from group i-vii were orally dosed daily with 5mg/kg of flutamide to induce erectile dysfunction one hour prior to the administration of the extracts at doses of 150, 300 and 450 mg/kg body weight respectively of each extract. Group 7 rats received 100µg/kg bodyweight of testosterone intraperitoneally while those in group 8 were administered with 10mg/kg of normal saline (normal control). On days 0, 7, 14 and 21 the males from different groups were subjected to estrus induced females in separate cages. The sexual behavior of the rats i.e. mounting and intromission frequencies and body weights were recorded. Serum levels of sex hormones, biochemical and hematological parameters, organ weights and the histopathology were determined on day 22 with 18 hrs post last treatment. Acute toxicity used 8 weeks old Swiss mice (18-24g) that were divided into 4 groups (n=4) doses ranging from 7,500-12000mg/kg and 15,000-22,500mg/kg for both aqueous extracts respectively. Results: The phytochemical screening revealed strong presence of catechol tannins in both aqueous extracts of study plants. Rats treated with 450mg/kg of C. articulata and M. aethiopicum had a significant increase in serum testosterone levels (p<0.01 and P<0.001) respectively when compared to both normal and positive control. There was also a significant increase (p<0.01) in luteinizing hormone levels in rats treated with 450mg/kg of M. aethiopicum. Furthermore, a dose dependent increase in mounting and intromission frequencies, body weight, testis, liver, lungs and heart weight of animals treated with both aqueous extracts in all treatment groups. The LD50 value of C. articulata and M. aethiopicum were 18,985 and 9,708 mg/kg bodyweight respectively. Both aqueous extracts caused a significant dose dependent reduction (p<0.001) in Monocytes in al treatment groups. In serum biochemical parameters both aqueous extracts caused a significant reduction (p<0.05) in levels of Serum Alanine transferase enzyme. Histological examination of testis leydig cells revealed increased series of spermatogenesis and leydig cells proliferation at high doses of both extracts. Lastly, the Histopathological examination revealed no significant patho- physiological changes in the kidney and intestines in all treatment groups. However, the higher dose (450mg/kg) of M.aethiopicum caused pneumonitis and edema of lungs, focal areas of hepatic and perivascular degenerations with lymphocytes infiltration of the liver tissues. Conclusion: The study demonstrated the androgenic effects of both aqueous leaf extracts, which probably can be explained by the increase levels of serum testosterone and luteinizing hormone in all treated group. These results of the study may explain the use of these plants in the management of erectile dysfunction attributed to hypogonadism in local communities of Uganda. In addition, the extracts were found to be of less limited toxicity exonerated by the high LD50 values which is classified to be experimentally safe under OECD guidelines. However, prolonged use of higher doses of both extracts could result to Heamatological, biochemical and Histopathological changes in the living system, this implies the extracts potential to cause chronic toxicity.