ABSTRACT
O. gratissimum is one of the most common medicinal plants in every community in Nigeria. This plant has been presumed to be useful in the management of diseases including breast cancer, which is one the commonest cancers affecting women globally. Hence, this study aimed to computationally investigate the phytochemicals present in O. gratissimum by elucidate their binding dynamics against five selected molecular targets of breast cancer and predict their pharmacokinetics properties. Molecular docking, MMGBSA calculation and ADMET prediction were used. The results showed that isovitexin has the highest binding affinity of -9.11 kcal/mol and -9.80 kcal/mol for Human Epidermal Growth Factor Receptor 2 (HER2) and Epidermal Growth Factor Receptor (EGFR) respectively. Rosmarinic acid has the highest binding affinity of -12.15 kcal/mol for Phosphatidylinositol 3-kinase (PI3K), Nepetoidin A has the highest binding affinity of -9.14 kcal/mol for oestrogen receptor (ER), and Vitexin has the highest binding affinity of -12.90 kcal/mol for Progesterone receptor (PR). MMGBSA provided total binding energy that confirmed the stability of the complexes under physiological conditions. The ADMET profiles showed that O. gratissimum top phytochemicals identified would be safe for oral administration with no hepatoxicity. Overall, this study identified isovitexin, vitexin, rosmarinic acid, nepetoidin A and luteolin among others, as compounds that exhibit strong anti-cancer properties against breast cancer cells.
ABSTRACT
Plasmodium falciparum parasites are the primary cause of malaria across Africa. The problem of drug resistance to malaria is ever growing and novel therapeutic strategies need to be developed, particularly those targeting the parasite and also the host or host-pathogen interaction. Previous studies have shown that the development of cerebral malaria (CM) is related to dysregulation of the immune system in a murine malaria model of experimental cerebral malaria. It involves a complex interaction of events and interferon-gamma seems to be the unifying factor. Therefore, the antiplasmodial activity targeting the parasite and immunomodulatory strategies that reduce overall host inflammation, with IFN-γ in focus, could delay CM onset and prove beneficial in malaria infection therapy. Phyllanthus niruri is used to treat fever and other symptoms of malaria in Nigeria. Its modes of action as an anti-malarial remedy have not been exhaustively investigated. This study therefore examined the aqueous extract of P. niruri (PE) for its antiplasmodial activity in vitro using the Plasmodium falciparum HB3 strain. Furthermore, in vivo murine malaria model using the Plasmodium berghei ANKA strain was used to investigate its anti-malarial effects. We showed that PE has multiple anti-malarial effects, including anti-parasitic and host immunomodulatory activities. Co-culture of P. falciparum with PE and some of its phytoconstituents drastically reduced parasite number. PE also decreased parasitemia, and increased the survival of infected mice. We also observed that the integrity of the blood-brain barrier was maintained in the PE-treated mice. The results confirmed that PE showed moderate antiplasmodial activity. In vivo murine malaria model using P. berghei ANKA for experimental cerebral malaria revealed that PE suppressed parasite growth, and modulate the production of interferon-gamma. The findings demonstrate that PE affects malaria progression, targeting parasites and host cells.
