Kolaviron, a flavonoid-rich extract ameliorates busulfan-induced chemo-brain and testicular damage in male rats through inhibition of oxidative stress, inflammatory, and apoptotic pathways.

Previous reports revealed that increased oxidative stress with up-regulated inflammatory proteins and apoptotic factors have serious implications in busulfan-induced chemo-brain and testicular damages. Hence, we investigated the potential reversal effects of kolaviron (KV), a neuro-active extract rich in flavonoids with proven anti-oxido-inflammatory and anti-apoptotic properties, on busulfan-induced oxidative damage, inflammatory proteins, and apoptosis in the brains and testes of male rats. In the treatment-regimen, animals in groups 1 and 2 had saline (10 ml/kg/p.o./day) and dimethyl sulfoxide (DMSO; 10 ml/kg/p.o./day), group 3 received KV extract (200 mg/kg/p.o./day), group 4 was given busulfan (50 mg/kg/p.o./day) and animals in group 5 were pretreated with busulfan (50 mg/kg/p.o./day) successively for 56 days in addition to KV extract (200 mg/kg/p.o./day) from days 29-56. Non-spatial memory function was valuated with a novel-object recognition memory test. Thereafter, testicular and brain oxidative/antioxidant status, proinflammatory- and apoptotic-related proteins, testicular enzymatic markers were evaluated respectively. Kolaviron extract improved cognitive function by increasing exploration of novel-object of busulfan-treated rats. Kolaviron extract reversed busulfan-mediated increased malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and decreased superoxide dismutase, catalase, glutathione, and glutathione-peroxidase in brains and testes as well as the testicular enzyme markers. Increased brain and testicular weights, and TNF-α, IL-1ß, and NF-κß productions due to busulfan administration were also reduced by the extract. The reduced testicular B-cell lymphoma-2, sperm mitochondrial cytochrome-C, and membrane potential, increased DNA fragmentation, caspases -3 and -9 levels were also profoundly reversed by KV. Additionally, KV extract ameliorated busulfan-induced testicular histopathological changes in rats. Conclusively, KV extract reverses busulfan-induced neuroendopathobiological derangements via oxidative stress inhibition, down-regulation of inflammatory and apoptotic mediators in rats' brains and testes. PRACTICAL APPLICATIONS: Busulfan is an orally effective chemotherapy drug widely used for cancer treatment. It has been reported that chronic usage of busulfan increases the tendency for carcinogenic and teratogenic activities with severe side effects on the functions of the gonads and other body organs such as brain, popularly regarded as chemo-brain. When taken over a prolonged period of time, busulfan causes sterility in animals and destroyed spermatogonial stem cells along with the seminiferous tubules and sperm morphology of animals as well as memory impairments. The findings from the study revealed that KV extract prevent busulfan-induced cognitive and testicular impairments following kolaviron supplementation. Thus, the findings from this scientific investigation suggest that KV extract could improve the quality of reproductive life and cognitive functions of male patients during busulfan chemotherapy, particularly during prolonged therapy.

Effect of ethanol and aqueous extracts of seed pod of Copaifera salikounda (Heckel) on complete Freund's adjuvant-induced rheumatoid arthritis in rats.

The antirheumatoid arthritis potential of ethanol and aqueous extracts of seed pod of Copaifera salikounda (SPCS) was evaluated using the chicken collagen/complete Freund's adjuvant-induced arthritic rats model. Adjuvat-induced rats were treated with varied doses of the extracts (400, 600, and 800 mg/kg body weight) and with reference drug, indomethacin for 21 days. Antiarthritic evaluation was done through measurement of body weight, paw size, inflammatory makers, hematological parameters, cytokines, antioxidant enzymes, reduced glutathione, lipid peroxidation as well as histopathological examinations. Treatment with the ethanol and aqueous extracts of SPCS markedly inhibited the paw size and caused weight gain. The extracts considerably modulated the hematological as well as the antioxidant parameters. Likewise, the extract restored the altered lipid peroxidation, pro-inflammatory mediators, and inflammatory factors which further accentuate the implication in adjuvant-induced arthritis. Thus, the ethanol and aqueous extracts of SPCS showed a significant antiarthritic activity that was statistically analogous to that of indomethacin. Practical applications Copaifera salikounda (Heckel) has been used in treatment of different ailments including rheumatoid arthritis in folklore medicine. This is the first reported proof of the antiarthritic potential of the seed pod. Oxidative stress has been implicated in rheumatoid arthritis. Ethanol extract of SPCS has been shown to be predominantly rich in phenols, terpenoids, alkaloids, and flavonoids which are natural antioxidant. The present study has demonstrated that ethanol and aqueous extracts of SPCS can exert antioxidative and antiinflammatory effects, thus strengthening its antiarthritic potentials.