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Psidium guajava (L.) belongs to the Myrtaceae family and it is an important fruit in tropical areas like India, Indonesia, Pakistan, Bangladesh, and South America. The leaves of the guava plant have been studied for their health benefits which are attributed to their plethora of phytochemicals, such as quercetin, avicularin, apigenin, guaijaverin, kaempferol, hyperin, myricetin, gallic acid, catechin, epicatechin, chlorogenic acid, epigallocatechin gallate, and caffeic acid. Extracts from guava leaves (GLs) have been studied for their biological activities, including anticancer, antidiabetic, antioxidant, antidiarrheal, antimicrobial, lipid-lowering, and hepatoprotection activities. In the present review, we comprehensively present the nutritional profile and phytochemical profile of GLs. Further, various bioactivities of the GL extracts are also discussed critically. Considering the phytochemical profile and beneficial effects of GLs, they can potentially be used as an ingredient in the development of functional foods and pharmaceuticals. More detailed clinical trials need to be conducted to establish the efficacy of the GL extracts.

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Background Hyperactivation of the RAS-RAF-MEK-ERK signaling pathway is exploited by glioma cells to promote their growth and evade apoptosis. MEK activation in tumor cells can increase replication of ICP34.5-deleted herpes simplex virus type 1 (HSV-1), but paradoxically its activation in tumor-associated macrophages promotes a pro-inflammatory signaling that can inhibit virus replication and propagation. Here we investigated the effect of blocking MEK signaling in conjunction with oncolytic HSV-1 (oHSV) for brain tumors. Methods Infected glioma cells co-cultured with microglia or macrophages treated with or without trametinib were used to test trametinib effect on macrophages/microglia. Enzyme-linked immunosorbent assay, western blotting, and flow cytometry were utilized to evaluate the effect of the combination therapy. Pharmacokinetic (PK) analysis of mouse plasma and brain tissue was used to evaluate trametinib delivery to the CNS. Intracranial human and mouse glioma-bearing immune deficient and immune competent mice were used to evaluate the antitumor efficacy. Result Oncolytic HSV treatment rescued trametinib-mediated feedback reactivation of the mitogen-activated protein kinase signaling pathway in glioma. In vivo, PK analysis revealed enhanced blood–brain barrier penetration of trametinib after oHSV treatment. Treatment by trametinib, a MEK kinase inhibitor, led to a significant reduction in microglia- and macrophage-derived tumor necrosis factor alpha (TNFα) secretion in response to oHSV treatment and increased survival of glioma-bearing mice. Despite the reduced TNFα production observed in vivo, the combination treatment activated CD8+ T-cell mediated immunity and increased survival in a glioma-bearing immune-competent mouse model. Conclusion This study provides a rationale for combining oHSV with trametinib for the treatment of brain tumors.