Multidrug‐resistant Staphylococcus aureus infections place a huge burden on the healthcare sector and the wider community. An increasing rate of infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) has necessitated the development of alternative agents. We previously reported that usnic acid (UA) has activity against MRSA; here, we report the effect of UA in combination with norfloxacin on the drug resistance of MRSA clinical isolates. We observed that the combination of UA–norfloxacin significantly reduces the bacterial burden in mouse models infected with S. aureus, without causing any detectable associated toxicity. Proteomic analysis indicated that UA–norfloxacin induces oxidative stress within cells, which leads to membrane damage and inhibits metabolic activity and biosynthesis of peptidoglycan and fatty acids. Collectively, this study provides evidence that UA in combination with norfloxacin may be a potential candidate for development into a resistance‐modifying agent for the treatment of invasive MRSA infections.

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Rutin (3,3',4' 5,7-pentahydroxy avone-3-rhamnoglucoside) is a avonoid glycoside, found in many edible plants such as buckwheat and berries. Rutin as a food supplement is recommended for the treatment of various diseases, which directed us to investigate its valuable effects in malaria induced pathogenesis. In the present study, Rutin was tested for its anti-plasmodial activity against chloroquine sensitive and resistant strains (NF-54 and K1) of Plasmodium falciparum and studied for its anti-oxidative and antiin ammatory potential against LPS stimulated macrophage cells. In vitro observations were further validated using an in-vivo physiological rodent model of Plasmodium berghei-induced malaria pathogenesis. Rutin was also tested for its effect in combination with chloroquine.Rutin was found to have potent anti-plasmodial activity against both chloroquine sensitive and resistant strains of P. falciparum (NF-54 and K1). It was able to reduce the oxidative stress induced by LPS in macrophage cells with decreased production of pro-in ammatory cytokines (IL-6, TNF-α and IL-1β). Rutin was found to signi cantly suppress the parasitaemia, increase the mean survival time and restored the haemoglobin and glucose level in in vivo assays. This was corroborated by reduced production of malondialdehyde (MDA) and pro-in ammatory mediators in rutin treated mice in P.berghei-induced malaria pathogenesis. Interestingly, the combination of rutin with chloroquine had shown synergy in both in vitro and in vivo experiments. The ndings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria, alone or in combination with other compounds.

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Rutin (3,3’,4’ 5,7-pentahydroxyflavone-3-rhamnoglucoside) is a flavonoid glycoside, found in many edible plants such as buckwheat and berries. Rutin as a food supplement is recommended for the treatment of various diseases, which directed us to investigate its valuable effects in malaria induced pathogenesis. In the present study, Rutin was tested for its anti-plasmodial activity against chloroquine sensitive and resistant strains (NF-54 and K1) of Plasmodium falciparum and studied for its anti-oxidative and anti-inflammatory potential against LPS stimulated macrophage cells. In vitro observations were further validated using an in-vivo physiological rodent model of Plasmodium berghei-induced malaria pathogenesis. Rutin was also tested for its effect in combination with chloroquine.Rutin was found to have potent anti-plasmodial activity against both chloroquine sensitive and resistant strains of P. falciparum (NF-54 and K1). It was able to reduce the oxidative stress induced by LPS in macrophage cells with decreased production of pro-inflammatory cytokines (IL-6, TNF-α and IL-1β). Rutin was found to significantly suppress the parasitaemia, increase the mean survival time and restored the haemoglobin and glucose level in in vivo assays. This was corroborated by reduced production of malondialdehyde (MDA) and pro-inflammatory mediators in rutin treated mice in P.berghei-induced malaria pathogenesis. Interestingly, the combination of rutin with chloroquine had shown synergy in both in vitro and in vivo experiments. The findings of the present study thus highlighted the suitability of rutin for further study in the management of drug resistant malaria, alone or in combination with other compounds.