Trypanosuppressive effects of Kolaviron may be associated with down regulation of Trypanothione reductase in Trypanosoma congolense infection

@#Trypanothione reductase is a key enzyme that upholds the redox balance in hemoflagellate protozoan parasites such as T. congolense. This study aims at unraveling the potency of Kolaviron against trypanothione reductase in T. congolense infection using Chrysin as standard. The experiment was performed using three different approaches; in silico, in vitro and in vivo. Kolaviron and Chrysin were docked against trypanothione reductase, revealing binding energies (-9.3 and -9.0 kcal/mol) and Ki of 0.211μM and 0.151μM at the active site of trypanothione reductase as evident from the observed strong hydrophobic/hydrogen bond interactions. Parasitized blood was used for parasite isolation and trypanothione reductase activity assay using standard protocol. Real-time PCR (qPCR) assay was implored to monitor expression of trypanothione reductase using primers targeting the 177-bp repeat satellite DNA in T. congolense with SYBR Green to monitor product accumulation. Kolaviron showed IC50 values of 2.64μg/ml with % inhibition of 66.78 compared with Chrysin with IC50 values of 1.86μg/ml and % inhibition of 53.80. In vivo studies following the administration of these compounds orally after 7 days post inoculation resulted in % inhibition of Chrysin (57.67) and Kolaviron (46.90). Equally, Kolaviron relative to Chrysin down regulated the expression trypanothione reductase gene by 1.352 as compared to 3.530 of the infected group, in clear agreement with the earlier inhibition observed at the fine type level. Overall, the findings may have unraveled the Kolaviron potency against Trypanosoma congolense infection in rats.

Protective Roles of Kolaviron Extract from Garcinia kola Seeds against Isoniazid-induced Kidney Damage in Wistar Rats

Background: Garcinia kola seeds have been observed to be medically important and kolaviron, a bioflavonoid obtained from the seeds was studied for its biological activities. The study investigated the protective effect of kolaviron extract obtained from the seed of Garcinia kola against isoniazid-induced kidney damage. Methodology: Kolaviron was extracted from fresh seeds of Garcinia kola (2 kg) using soxhlet extractor and partitioned with chloroform. Nephrotoxicity was induced in wistar rats by oral administration of isoniazid (20 mg/kg bwt) while kolaviron was administered on wistar rats an hour before isoniazid administration and lasted for 30 days. Protective effect of kolaviron was measured in the plasma of wistar rats by estimating the levels of key metabolites used as kidney biomarkers which are total protein, creatinine, urea and uric acid concentration. Results: The isoniazid-treated group showed a significant (p < 0.05) decrease in total protein concentration of 3.57 ± 0.12 (mg/dl) while there was a significant (p < 0.05) increase in urea, uric acid and creatinine concentrations with values of 70.30 ± 4.77, 55.71 ± 11.15 and 18.04 ± 5.33 (mg/dl) respectively. However, kolaviron-treated group showed a remarkable increase (6.15 ± 0.96) in total protein concentration while urea, uric acid and creatinine concentrations significantly decreased to 45.25 ± 2.29, 35.60 ± 11.01 and 13.28 ± 4.41 (mg/dl) respectively. Conclusion: Kolaviron extract obtained from Garcinia kola seeds exhibited a remarkable protective effect against kidney damage caused by isoniazid by regulating renal biomarkers and preventing toxic affront of isoniazid. Thus, it may be relatively safe when used therapeutically at this dose in the treatment and management of diseases associated with kidney damage.

Comparison of antioxidant effects of kolaviron and vitamin C interventions on testicular structures following nevirapine administration in Sprague-Dawley rats / Comparación de los efectos antioxidantes en la intervención con kolaviron y vitamina C sobre las estructuras testiculares después de la administración de nevirapina en ratas Sprague-Dawley

Testicular toxicity has been implicated in highly active anti-retroviral therapy (HAART) treatment. Hence there is need to identify an effective antioxidant product that can alleviate testicular necrosis due to HAART administration. Forty eight adult male Sprague-Dawley rats were used in this study. The animals were divided into eight (8) groups: A-H (n= 6). Group A animals received normal saline as the control; Group B was given Nevirapine (Nv); Group C was given Kolaviron (Kv); Group D was given vitamin C; Group E was given Nv and Kv; Group F was given Nv and Vitamin C; Group G was given Nv for 56 d and Kv for 28 d serving as a withdrawal group; Group H was given corn oil. Nv, Kv and Vit. C were given at 1.54, 200 and 250 (mg·kg)/bw respectively while all administrations were through oral gavage. The body weights were taken every other day. Thereafter, they were anaesthetized with halothane. The testes were excised, weighed, fixed in Bouin's fluid and stained with H&E while the epididymes removed for semen fluid analyses. The results showed a significant (P<0.05) decrease in sperm motility in group E (Nevirapine + kolaviron) when compared with group F (Nevirapine + Vitamin C) while Sperm count was not significantly different (P>0.05) across the groups. The testicular histoarchitectural studies revealed indistinct spermatogonia, necrotic interstititial endocrine cells in the altered interstitial space, fragmented spermatids, atrophy of mature spermatocytes, degenerated germ cells, obliterated seminiferous tubules lumen, undifferentiated spermatogonia and cellular debris in the somniferous tubules lumen of nevirapine administered group but normal across the other groups. In the testis, there were no significant reduction in SOD, Catalase and GPx activities but a significant decrease in GST activity (P<0.001) when group E was compared with group F. In conclusion, vitamin C presents a better remediation in nevirapine induced spermiotoxicity compared to kolaviron in Sprague-Dawley rats.

La toxicidad testicular ha sido implicada en la terapia antirretroviral altamente activa (TARAA). Por lo tanto existe la necesidad de identificar un producto antioxidante eficaz que pueda aliviar la necrosis testicular en la administración de la TARAA. Cuarenta y ocho ratas macho Sprague-Dawley adultas fueron utilizadas. Los animales se dividieron en ocho (8) grupos: AH (n= 6). Grupo A, animales recibieron solución salina normal como el control; Grupo B, recibió Nevirapina (Nv); Grupo C, recibió Kolaviron (Kv); Grupo D, recibió vitamina C; Grupo E, recibió Nv y Kv; Grupo F, recibió Nv y vitamina C; Grupo G, recibió Nv durante 56 d y Kv por 28 d como un grupo de retirada; Grupo H, recibió aceite de maíz. Nv, Kv y Vit. C se administraron en dosis de 1, 54, 200 y 250 (mg · kg) de peso corporal respectivamente; todas las administraciones fueron por sonda oral. Los pesos corporales se tomaron cada dos días. A partir de ese momento los animales fueron anestesiados con halotano. Los testículos fueron extirpados, pesados y fijados en solución de Bouin y teñidos con H&E, mientras que el epidídimo se retiró para analizar el semen. Los resultados mostraron un descenso (p<0,05) en la motilidad de los espermatozoides en el grupo E (Nevirapina + Kolaviron) en comparación con el grupo F (Nevirapina + vitamina C), mientras que el recuento espermático no mostró diferencias significativas (P>0,05) entre los grupos. El estudio de la histoarquitectura testicular reveló espermatogonias indiferenciadas, con células intersticiales necróticas en el espacio intersticial y espermátidas fragmentadas. Además, en el grupo que recibió Nevirapina mostró espermatocitos maduros atrofiados, degeneración de células germinales, lumen de los túbulos seminíferos obliterados, espermatogonias indiferenciadas y restos celulares en el lumen de los tubulos seminíferos. En el resto de los grupos los resultados fueron normales. En el testículo hubo una reducción significativa en las actividades de la superóxido dismutasa, catalasa y glutatión peroxidasa, pero una disminución significativa en la actividad glutatión S-transferasa (P <0,001) al comparar los grupo E y F.

Antimalarial potential of kolaviron, a biflavonoid from Garcinia kola seeds, against Plasmodium berghei infection in Swiss albino mice

OBJECTIVE@#To investigate the antimalarial potential of kolaviron (KV), a biflavonoid fraction from Garcinia kola seeds, against Plasmodium berghei (P. berghei) infection in Swiss albino mice.@*METHODS@#The study consists of seven groups of ten mice each. Groups I, II and III were normal mice that received corn oil, KV1 and chloroquine (CQ), respectively. Groups IV, V, VI and VII were infected mice that received corn oil, CQ, KV1 and KV2, respectively. CQ, KV1 and KV2 were given at 10-, 100- and 200-mg/kg daily, respectively for three consecutive days.@*RESULTS@#Administration of KV1 and KV2 significantly (P<0.05) suppressed P. berghei-infection in the mice by 85% and 90%, respectively, while CQ produced 87% suppression relative to untreated infected group after the fifth day of treatment. Also, KV2 significantly (P<0.05) increased the mean survival time of the infected mice by 175%. The biflavonoid prevented a drastic reduction in PCV from day 4 of treatment, indicating its efficacy in ameliorating anaemia. Significant (P<0.05) oxidative stress assessed by the elevation of serum and hepatic malondialdehydewere observed in untreated P. berghei-infected mice. Specifically, serum and hepatic malondialdehyde levels increased by 93% and 78%, respectively in the untreated infected mice. Furthermore, antioxidant indices, viz; superoxide dismutase, catalase, glutathione-s-transferase, gluathione peroxidase and reduced gluathione decreased significantly (P<0.05) in the tissues of untreated P. berghei-infected mice. KV significantly (P<0.05) ameliorated the P. berghei-induced decrease in antioxidant status of the infected mice.@*CONCLUSIONS@#This study shows that kolaviron, especially at 200 mg/kg, has high antimalarial activities in P. berghei-infected mice, in addition to its known antioxidant properties.

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents.

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess  anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 g/ml compared with omeprazole with IC50 of 32.3 g/ml. KV showed both cyto-protective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound.