Inula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium

Gierlikowska, Barbara; Gierlikowski, Wojciech; Bekier, Katarzyna; Skalicka-Woźniak, Krystyna; Czerwińska, Monika E.; Kiss, Anna K.

doi:10.1016/j.jep.2019.112311

Cited by 32 publications

(30 citation statements)

References 55 publications

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“…Extract of Inulae radix in LPS-activated RAW264.7 cells not only inhibited NF-κB luciferase activity, phosphorylation of IκBα, and iNOS/NO, COX-2/PGE2, HMGB1 release, but also significantly suppressed expression of intracellular and vascular adhesion molecules in TNF-α activated human umbilical vein endothelial cells [129]. The main active compound in Inula helenium is alantolactone, showing significant suppression of IL-8, TNF-α, and IL-1β release [130].…”

Section: Perilla Frutescens (L) Brittonmentioning

confidence: 94%

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

Wyganowska‐Świątkowska¹,

Nohawica²,

Grocholewicz

et al. 2020

IJMS

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By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures.

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Section: Perilla Frutescens (L) Brittonmentioning

confidence: 94%

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

Wyganowska‐Świątkowska¹,

Nohawica²,

Grocholewicz

et al. 2020

IJMS

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“…Inula helenium possessed anti-inflammatory activity in cultured human respiratory epithelium and human neutrophils [10]. The natural sesquiterpene lactone alantolactone (ALT) was isolated from Inula helenium L. and Inula japonica, and there has been ample evidence to suggest that the compound possesses a wide range of biological activities, including anti-allergic, anti-bacterial, antimicrobial, anti-fungal, anti-oncogenic, anti-helminthic, hepatoprotective and neuroprotective activities [11,12].…”

Section: Introductionmentioning

confidence: 99%

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways

et al. 2020

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Background: It is well established that airway remodeling and inflammation are characteristics for chronic obstructive pulmonary disease (COPD). Moreover, cigarette smoke extract (CSE) promots inflammation, apoptosis and oxidative stress in COPD. And, there is evidence suggested that alantolactone (ALT), a sesquiterpene lactone isolated from Inula helenium, plays an adverse role in inflammation, apoptosis and oxidative stress. However, few studies have investigated the function and mechanism of ALT treatment on the COPD pathological process. Methods: The levels of IL-1 β, TNF-α, IL-6 and IFN-γ were examined by ELISA. Cells' apoptosis and caspase-3 activity were detected by Cell Death Detection PLUS enzyme-linked immunosorbent assay and caspase-Glo 3/7 Assay, respectively. The content of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using MDA and SOD assay kits. Reactive oxygen species (ROS) generation was measured by DCFH-DA assay. Protein expression was assayed by Western blot. Results: In the present study, we aimed to observe the protective effects of ALT against inflammation, apoptosis and oxidative stress in human bronchial epithelial Beas-2B and NHBE cells. Our results showed that different doses of CSE exposure induced Beas-2B and NHBE cell inflammatory cytokines IL-1 β, TNF-α, IL-6 and IFN-γ expression, cell apoptosis, caspase-3 activity and mediated oxidative stress markers MDA, ROS and SOD levels, while ALT treatment counteracted the effects of CSE. Further studies suggested that ALT attenuated NF-κB pathway activation. ALT also activated the Nrf2/HO-1 signal pathway through promoting Nrf2 nuclear aggregation and downstream HO-1 protein expression. HO-1 inhibitor tin protoporphyrin IX (SnPP IX) reversed the effects of ALT on Beas-2B and NHBE cell inflammation, apoptosis and oxidative stress.

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“…An example of plant with documented anti- S. aureus activity is Inula helenium L. (Asteraceae) ( O’Shea et al., 2009 ). Root of I. helenium was used in the traditional medicine to treat bacteria-induced respiratory tract infections ( Gierlikowska et al., 2020 ). I. helenium extract relieves symptoms of bronchial and throat infection, bronchitis, catarrh and colds ( Ivancheva and Stantcheva, 2000 ; Leporatti and Ivancheva, 2003 ; Jarić et al., 2015 ).…”

Section: Discussionmentioning

confidence: 99%

“…The aim of our study was to evaluate the biological activity of alantolactone, being the dominant compound occurring in Inula species, in context of S. aureus infection (Kim et al, 2017;Gierlikowska et al, 2020). We have evaluated influence of alantolactone on phagocytosis and cytokines release by macrophages.…”

Section: Introductionmentioning

confidence: 99%

Alantolactone Enhances the Phagocytic Properties of Human Macrophages and Modulates Their Proinflammatory Functions

2020

Self Cite

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Aim of the Study: Phagocytosis is a crucial element of innate immune defense involved in bacterial killing. The aim of our study was to evaluate the influence of alantolactone on phagocytosis and cytokines release by THP1-derived macrophages. We assessed whether antimicrobial compound alantolactone (a sesquiterpene lactone present in Inula helenium L.) is able to stimulate immune functions of macrophages by increase of S. aureus uptake, phagosome acidification and further stimulation of phago-lysosomes formation. Simultaneously, we tested influence of alantolactone on cytokines/chemokines production and p65 NF-kB concentration. The activity of alantolactone was compared with clarithromycin at concentration 20 µM. Methods: The cytotoxicity of alantolactone as well as S. aureus uptake, pH of phagosomes and phago-lysosomes fusion were analysed with flow cytometry. Reactive oxygen species and superoxide production were evaluated spectrophotometrically. The efficiency of phagocytosis was evaluated via quantifying viable bacteria (CFU). The effect on p65 protein concentration and cytokine production by macrophages were measured by enzyme-linked immunosorbent assay (ELISA). Results: Alantolactone enhanced phagocytosis via increase of S. aureus uptake, acidification of phagosomes, and later stimulation of phago-lysosomes fusion. Alantolactone treatment resulted in ROS and superoxide production decrease. Furthermore, alantolactone inhibited production of pro-inflammatory cytokines TNF-a, IL-1b, IL-6, and IL-8 as well as decreased p65 concentration, the subunit responsible for NF-kB activation and cytokine production and simultaneously stimulated release of antiinflammatory mediators (IL-10 and TGF-b). Conclusion: Results of our study indicate that alantolactone enhances clearance of S. aureus, and simultaneously modulates immune response, preventing collateral damage of the surrounding tissues. Considering the importance of phagocytosis in the pathogen killing, alantolactone may have a great potential as the supportive treatment of S. aureus infections. Further in vivo studies are warranted to confirm this hypothesis.

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Inula helenium and Grindelia squarrosa as a source of compounds with anti-inflammatory activity in human neutrophils and cultured human respiratory epithelium

Cited by 32 publications

References 55 publications

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review

Alantolactone suppresses inflammation, apoptosis and oxidative stress in cigarette smoke-induced human bronchial epithelial cells through activation of Nrf2/HO-1 and inhibition of the NF-κB pathways

Alantolactone Enhances the Phagocytic Properties of Human Macrophages and Modulates Their Proinflammatory Functions

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