Rosmarinic acid interferes with influenza virus A entry and replication by decreasing GSK3β and phosphorylated AKT expression levels

Jheng, Jia-Rong; Hsieh, Chung-Fan; Chang, Yu‐Hsin; Ho, Jin‐Yuan; Tang, Wen-Fang; Chen, Ziyi; Liu, Chien-Jou; Lin, Ta-Jen; Huang, Luqi; Chern, Jyh-Haur; Horng, Jim-Tong

doi:10.1016/j.jmii.2022.04.012

Cited by 12 publications

(9 citation statements)

References 58 publications

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“…According to Hu et al, in the serum and lung tissue, RA significantly increased the levels of IFN‐γ and IL‐10 and decreased the levels of interleukin‐6 (IL‐6) and tumor necrosis factor‐α (TNF‐α) 42 . RA inhibits influenza virus A infection in its early stages, suppresses viral RNA replication but not RNA‐dependent RNA polymerase complex activity, downregulates the Akt signaling pathway, and may prevent influenza A virus entry into host cells by reducing glycogen synthase kinase‐3β (GSK‐3β) and phospho‐AKT expressions 57 …”

Section: Resultsmentioning

confidence: 99%

“…In reported publications, R. officinalis was used as an EO, [43][44][45][46] chloroform extract, 47 aqueous and ethanolic extracts, [48][49][50][51] as well as two main constituents including CaA 52 and RA. 42,[53][54][55][56][57] The reported research was focused on the antiviral (hRSV, SARS-CoV-2, influenza virus-induced pneumonia such as H1N1 and H5N1) and anti-bacterial (Escherichia coli, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus, Klebsiella pneumoniae) activities of rosemary and its derivatives against lung infections.…”

Section: Pulmonary Fibrosismentioning

confidence: 99%

“…42 RA inhibits influenza virus A infection in its early stages, suppresses viral RNA replication but not RNAdependent RNA polymerase complex activity, downregulates the Akt signaling pathway, and may prevent influenza A virus entry into host cells by reducing glycogen synthase kinase-3β (GSK-3β) and phospho-AKT expressions. 57 Because of the presence of many groups of chemicals, the mechanism of action of the rosemary plant has not been well investigated. However, it is believed that a number of processes, including cell wall destruction or degradation, may be responsible for the activity, 58 for instance, changes in the cytoplasmic membrane, cell leakage, harm to the proteins that make up the membrane, or active transport and coagulation of the contents of the cell.…”

Section: Pulmonary Fibrosismentioning

confidence: 99%

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Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

et al. 2022

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This review aimed to identify preclinical and clinical studies examining the effects of rosmarinic acid (RA), carnosic acid (CaA), rosmanol (RO), carnosol (CA), and ursolic acid (UA) against allergic and immunologic disorders. Various online databases, including PubMed, Science Direct, EMBASE, Web of Sciences, Cochrane trials, and Scopus, were searched from inception until October 2022. Due to the suppression of the nuclear factor-κB (NF-κB) pathway, the main factor in allergic asthma, RA may be a promising candidate for the treatment of asthma. The other ingredients comprising CA and UA reduce the expression of interleukin (IL)-4, IL-5, and IL-13 and improve airway inflammation. Rosemary's anti-cancer effect is mediated by several mechanisms, including DNA fragmentation, apoptosis induction, inhibition of astrocyte-upregulated gene-1 expression, and obstruction of cell cycle progression in the G1 phase. The compounds, essentially found in Rosemary essential oil, prevent smooth muscle contraction through its calcium antagonistic effects, inhibiting acetylcholine (ACH), histamine, and norepinephrine stimulation. Additionally, CA exhibits a substantially greater interaction with the nicotinic ACH receptor than a family of medications that relax the smooth muscles, making it a potent antispasmodic treatment. The components have

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Section: Resultsmentioning

confidence: 99%

Section: Pulmonary Fibrosismentioning

confidence: 99%

Section: Pulmonary Fibrosismentioning

confidence: 99%

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Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

et al. 2022

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“…The influenza A virus A/WSN/33 (H1N1) was amplified in MDCK cells. Details on the origin and propagation of other influenza viruses, enteroviruses, herpes simplex virus (HSV), dengue virus, Japanese encephalitis virus, human coronavirus 229E, and adenovirus have been previously reported [ 28 , 29 , 30 , 31 ].…”

Section: Methodsmentioning

confidence: 99%

Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus

Chen,

Chao,

Hsieh

et al. 2024

Viruses

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Gu-Sui-Bu, the dried rhizome of Davallia mariesii, is a traditional Chinese herbal remedy with a significant history of treating osteoporosis and inflammatory conditions. However, its potential as an anti-influenza agent and its underlying mechanisms of action remain unexplored. To obtain a more potent extract from D. mariesii and gain insights into its mechanism of action against influenza A virus (IAV), we utilized a partitioning process involving organic solvents and water, resulting in the isolation of butanolic subfractions of the D. mariesii extract (DMBE). DMBE exhibited a broad anti-viral spectrum, effectively inhibiting IAV, with an EC50 of 24.32 ± 6.19 µg/mL and a selectivity index of 6.05. We subsequently conducted a series of in vitro assays to evaluate the antiviral effects of DMBE and to uncover its mechanisms of action. DMBE was found to inhibit IAV during the early stages of infection by hindering the attachment of the virus onto and its penetration into host cells. Importantly, DMBE was observed to hinder IAV-mediated cell–cell fusion. It also inhibited neuraminidase activity, plaque size, and the expression levels of phospho-AKT. In summary, this study provides evidence for the effectiveness of D. mariesii as a complementary and alternative herbal remedy against IAV. Specifically, our data highlight DMBE’s capabilities in inhibiting viral entry and the release of virions.

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“…Rosmarinic acid (RA), an ester of caffeic acid and 3,4-dihydroxy phenyl lactic acid, is commonly found in the Nepetoideae subfamily of the Lamiaceae and Boraginaceae family [ 20 ]. This natural compound and its derivatives have been reported to exert protective effects against some viral infections, including hepatitis B virus, influenza, and SARS-CoV-2, but the precise mechanisms remain unknown [ 21 – 23 ]. In the present study, we utilized stress/CORT-established HSV-1 susceptible in vivo and in vitro models and revealed that stress provokes phospholipid peroxidation, thereby rewiring STING-mediated antiviral innate immunity and augmenting HSV-1 infection.…”

Section: Introductionmentioning

confidence: 99%

Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1

et al. 2023

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Psychological stress increases the susceptibility to herpes simplex virus type 1 (HSV-1) infection. There is no effective intervention due to the unknown pathogenesis mechanisms. In this study we explored the molecular mechanisms underlying stress-induced HSV-1 susceptibility and the antiviral effect of a natural compound rosmarinic acid (RA) in vivo and in vitro. Mice were administered RA (11.7, 23.4 mg·kg −1 ·d −1 , i.g.) or acyclovir (ACV, 206 mg·kg −1 ·d −1 , i.g.) for 23 days. The mice were subjected to restraint stress for 7 days followed by intranasal infection with HSV-1 on D7. At the end of RA or ACV treatment, mouse plasma samples and brain tissues were collected for analysis. We showed that both RA and ACV treatment significantly decreased stress-augmented mortality and alleviated eye swelling and neurological symptoms in HSV-1-infected mice. In SH-SY5Y cells and PC12 cells exposed to the stress hormone corticosterone (CORT) plus HSV-1, RA (100 μM) significantly increased the cell viability, and inhibited CORT-induced elevation in the expression of viral proteins and genes. We demonstrated that CORT (50 μM) triggered lipoxygenase 15 (ALOX15)-mediated redox imbalance in the neuronal cells, increasing the level of 4-HNE-conjugated STING, which impaired STING translocation from the endoplasmic reticulum to Golgi; the abnormality of STING-mediated innate immunity led to HSV-1 susceptibility. We revealed that RA was an inhibitor of lipid peroxidation by directly targeting ALOX15, thus RA could rescue stress-weakened neuronal innate immune response, thereby reducing HSV-1 susceptibility in vivo and in vitro. This study illustrates the critical role of lipid peroxidation in stress-induced HSV-1 susceptibility and reveals the potential for developing RA as an effective intervention in anti-HSV-1 therapy.

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Rosmarinic acid interferes with influenza virus A entry and replication by decreasing GSK3β and phosphorylated AKT expression levels

Cited by 12 publications

References 58 publications

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

Effects of rosmarinic acid, carnosic acid, rosmanol, carnosol, and ursolic acid on the pathogenesis of respiratory diseases

Novel Anti-Viral Properties of the Herbal Extract of Davallia mariesii against Influenza A Virus

Reducing lipid peroxidation attenuates stress-induced susceptibility to herpes simplex virus type 1

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