A Fungal Cu/Zn-Containing Superoxide Dismutase Enhances the Therapeutic Efficacy of a Plant Polyphenol Extract in Experimental Influenza Virus Infection

Abstract

The combined protective effect of a polyphenol-rich extract, isolated from Geranium sanguineum L. (PC), and a novel naturally glycosylated Cu/Zn-containing superoxide dismutase, produced from the fungal strain Humicula lutea 103 (HL-SOD), in the experimental infl uenza A virus infection (EIVI) in mice, induced with the virus A/Aichi/2/68 (H3N2), was investigated.The combined application of HL-SOD and PC in doses, which by themselves do not defend signifi cantly mice in EIVI, resulted in a synergistically increased protection, determined on the basis of protective indices and amelioration of lung injury. Lung weights and consolidation as well as infectious lung virus titers were all decreased signifi cantly parallel to the reduction of the mortality rates; lung indices were raised. The excessive production of reactive oxygen species (ROS) by alveolar macrophages (aMØ) as well as the elevated levels of the lung antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), induced by EIVI, were brought to normal. For comparative reasons the combined protective effect of PC and vitamin C was investigated. The obtained results support the combined use of antioxidants for the treatment of infl uenza virus infection and in general indicate the benefi cial protective role of combinations of viral inhibitors of natural origin with diverse modes of action.

Intracellular Redox State as Target for Anti-Influenza Therapy: Are Antioxidants Always Effective?

“…While the single treatment did not significantly protect mice against the infection, HL-SOD and rimantadine combination decreased lung viral titers, lung weights and mortality rates, and prolonged survival times. Interestingly, similar results were obtained with the combined application of HL-SOD with a polyphenol-rich extract, isolated from Geranium sanguineum L. [ 143 ]. An inhibitory effect on influenza virus infection has been demonstrated by the treatment of infected mice with MnSOD an enzyme with a longer plasma clearance time (half-life [t1/2], about 6 h in mice), in combination with ribavirin each administered with small-particle aerosol [ 144 ].…”

Emerging Therapeutic Potential of Polyphenols from Geranium sanguineum L. in Viral Infections, Including SARS-CoV-2

“…In alveolar macrophages, the combined treatment decreased superoxide and hydrogen peroxide levels and restored the activity of SOD and CAT enzymes [53]. The extract alone was also effective in restoring their enzymatic activity [46].…”

“…Both the PPC and the fraction extracted with EtOAc exhibited strong superoxide scavenging capabilities, synergizing with the presence of SOD in the test environment [40]. When employed to support an exogenous SOD from Humicula lutea, the G. sanguineum extract displayed a synergistic response, even at doses that are typically considered too low (up to 8 times less) to have a significant effect on their own [53].…”

Bioactivity of the Geranium Genus: A Comprehensive Review

“…The combined dosage of the polyphenolic complex and ε-aminocaproic acid to the infected mice was shown to revert the levels of lung protease and protease-inhibitory activity, which were increased due to the infection, back to normal. Serkedjieva et al also investigated the combined protective effect of the G. sanguineum polyphenolic complex and a glycosylated Cu/Zn-containing superoxide dismutase produced by the fungus Humicula lutea 103 in experimental influenza A/Aichi/2/68 (H3N2) virus infection in ICR mice [214]. The result was a synergistically increased protection demonstrated by the significant reduction of infectious parameters, such as lung consolidation, lung virus titers, lung weights and mortality rates of infected animals, and the increase of survival times.…”