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Rg1 attenuates inflammation response in LPS-induced A549 cell. (a–c) Secreted level of TNF-α, IL-1β, and IL-6 in cultured A549 cells. (d) Representative images for the expression of p-p65 and iNOS proteins in cultured cells after Rg1 treatment. (e, f) Quantification of relative expression level of iNOS and p-p65. ∗P<0.05; ∗∗P<0.01; ∗∗∗P<0.01, compared to the control or LPS group. Data were shown as mean + SD based on three independent experiments.
Source publication
Objectives:
To investigate the protective effect of ginsenoside Rg1 on relieving sepsis-induced lung inflammation and injury in vivo and in vitro.
Methods:
Cultured human pulmonary epithelial cell line A549 was challenged with LPS to induce cell injury, and CLP mouse model was generated to mimic clinical condition of systemic sepsis. Rg1 was app...
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Introduction
Depression is one of the most common neuropsychiatric illnesses which leads to a huge social and economic burden on modern society. So, it is necessary to develop an effective and safe pharmacological intervention for depression. Accumulating evidence has shown that adenosine monophosphate-activated protein kinase/sirtuin 1 (AMPK/SIRT1...
Citations
... It notably reduced apoptosis in LPS-induced A549 cells and lessened oxidative stress damage. Rg1 significantly decreased pro-inflammatory cytokines (TNF-a, IL-6) in A549 cells and mouse lung tissues and reduced ER stress by upregulating SIRT1 and lowering marker protein expressions (178). Additional compounds that modulate sepsisinduced multi-organ damage through the Sirtuin family are exemplified in Table 3. ...
Sepsis is a life-threatening organ dysfunction caused by the host’s dysfunctional response to infection. Abnormal activation of the immune system and disturbance of energy metabolism play a key role in the development of sepsis. In recent years, the Sirtuins (SIRTs) family has been found to play an important role in the pathogenesis of sepsis. SIRTs, as a class of histone deacetylases (HDACs), are widely involved in cellular inflammation regulation, energy metabolism and oxidative stress. The effects of SIRTs on immune cells are mainly reflected in the regulation of inflammatory pathways. This regulation helps balance the inflammatory response and may lessen cell damage and organ dysfunction in sepsis. In terms of energy metabolism, SIRTs can play a role in immunophenotypic transformation by regulating cell metabolism, improve mitochondrial function, increase energy production, and maintain cell energy balance. SIRTs also regulate the production of reactive oxygen species (ROS), protecting cells from oxidative stress damage by activating antioxidant defense pathways and maintaining a balance between oxidants and reducing agents. Current studies have shown that several potential drugs, such as Resveratrol and melatonin, can enhance the activity of SIRT. It can help to reduce inflammatory response, improve energy metabolism and reduce oxidative stress, showing potential clinical application prospects for the treatment of sepsis. This review focuses on the regulation of SIRT on inflammatory response, energy metabolism and oxidative stress of immune cells, as well as its important influence on multiple organ dysfunction in sepsis, and discusses and summarizes the effects of related drugs and compounds on reducing multiple organ damage in sepsis through the pathway involving SIRTs. SIRTs may become a new target for the treatment of sepsis and its resulting organ dysfunction, providing new ideas and possibilities for the treatment of this life-threatening disease.
... Rg1 employs a multiple approach to mitigate the effects of sepsis-induced ALI. Specifically, Ginsenoside Rg1 alleviates sepsis-induced ALI through various mechanisms, including reducing apoptosis, inhibiting the inflammatory response, and lessening lung tissue injury [104]. ...
Sepsis-induced acute lung injury (ALI), characterized by widespread lung dysfunction, is associated with significant morbidity and mortality due to the lack of effective pharmacological treatments available clinically. Small-molecule compounds derived from natural products represent an innovative source and have demonstrated therapeutic potential against sepsis-induced ALI. These natural small molecules may provide a promising alternative treatment option for sepsis-induced ALI. This review aims to summarize the pathogenesis of sepsis and potential therapeutic targets. It assembles critical updates (from 2014 to 2024) on natural small molecules with therapeutic potential against sepsis-induced ALI, detailing their sources, structures, effects, and mechanisms of action.
... Previously, Lu et al. noted that quercetin nanoparticles mitigate renal dysfunction, renal inflammation, and apoptosis in LPS-induced S-AKI experimental models by regulating SIRT1/NF-κB signaling [22]. Wang et al. reported that Rg1 prevents lung injury induced by sepsis by relieving pulmonary inflammation and endoplasmic reticulum stress through the regulation of SIRT1 [23]. However, whether Rg1 can regulate SIRT1/NF-κB signaling pathways in S-AKI remains unclear. ...
Introduction:
During sepsis, the kidney is one of the most vulnerable organs. Sepsis-associated acute kidney injury (S-AKI) is hallmarked by renal inflammation, apoptosis, and oxidative injury. Ginsenoside Rg1 (Rg1) is a natural product that possesses abundant pharmacological actions and protects against many sepsis-related diseases. Nevertheless, its role and related mechanism in S-AKI remain to be determined.
Materials and methods:
S-AKI was induced using lipopolysaccharide (LPS, 10 mg/kg) via a single intraperitoneal injection. Rg1 (200 mg/kg) was intraperitoneally administered for 3 consecutive days before LPS treatment. For histopathological examination, murine kidney tissues were stained with hematoxylin and eosin. Tubular injury score was calculated to evaluate kidney injury. Serum creatinine and BUN levels were measured for assessing renal dysfunction. The levels and activities of oxidative stress markers (MDA, 4-HNE, PC, GSH, SOD, and CAT) in renal tissue were measured by corresponding kits. Renal cell apoptosis was detected by TUNEL staining. The protein levels of apoptosis-related markers (Bcl-2, Bax, and Cleaved caspase-3), proinflammatory factors, SIRT1, IκBα, p-NF-κB p65, and NF-κB p65 in kidneys were determined using western blotting. Immunofluorescence staining was employed to assess p-NF-κB p65 expression in renal tissues.
Results:
LPS-induced injury of kidneys and renal dysfunction in mice were ameliorated by Rg1. Rg1 also impeded LPS-evoked renal cell apoptosis in kidneys. Moreover, Rg1 attenuated LPS-triggered inflammation and oxidative stress in kidneys by inhibiting proinflammatory cytokine release, enhancing antioxidant levels and activities, and reducing lipid peroxidation. However, all these protective effects of Rg1 in LPS-induced AKI mice were reversed by EX527, an inhibitor of sirtuin 1 (SIRT1). Mechanistically, Rg1 upregulated SIRT1 protein expression, increased SIRT1 activity, and inactivated NF-κB signaling in the kidney of LPS-induced AKI mice, which was also reversed by EX527.
Conclusions:
Rg1 ameliorates LPS-induced kidney injury and suppresses renal inflammation, apoptosis, and oxidative stress in mice via regulating the SIRT1/NF-κB signaling.
... A549 cell is a human alveolar epithelial type II cell line. For various studies associated with respiratory diseases including pneumonia, A549 cells treated with LPS have been used as a cellular model (35)(36)(37). To investigate the role of Slfn5 in LPS-induced injury, sh-Slfn5 was transfected into A549 cells to construct low-expressed cells ( Figure 4A). ...
Background
In recent years, the incidence of pneumonia has been increasing, which is the main cause of death and morbidity of children and the elderly in the world. Slfn5 is implicated in multiple cancers, and Slfn5 promotes epithelial-mesenchymal transition and metastasis in lung cancer. However, the influences of Slfn5 in pneumonia have not yet been completely cleared. Herein, we aimed to explore the underlying effects and regulatory mechanisms of Slfn5 in lipopolysaccharide (LPS)-induced pneumonia in mice and A549 cells.
Methods
Mice were intratracheally administered 5 mg/kg LPS to construct pneumonia model. In vitro, A549 cells were treated with 10 µg/mL LPS to construct cellular pneumonia model. Slfn5 expression was detected using immunohistochemistry and western blotting. Haematoxylin and eosin staining, TUNEL (terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate‑biotin nick end‑labelling), and western blotting were performed to assess pathological injury and inflammation. MTT [3(4,5‑dimethyl‑2‑thiazolyl)‑2,5‑diphenyl‑2‑H‑tetrazolium bromide], flow cytometry, and enzyme-linked immunosorbent assay analysis were performed to analyze cell viability, apoptosis, and inflammation. Gene set enrichment analysis was performed to explore the mechanism of Slfn5 in pneumonia.
Results
Slfn5 expression was upregulated in LPS-induced pneumonia in mice and A549 cells. In mice, knockdown of Slfn5 weakened LPS-induced lung injury and inflammation and decreased the expression of p-JAK2, p-JAK3, and p-STAT3. In LPS-stimulated A549 cells, downregulation of Slfn5 expression increased and Slfn5 overexpression decreased cell viability. Downregulation of Slfn5 expression decreased and Slfn5 overexpression increased cell apoptosis, inflammation and the expression of p-JAK2, p-JAK3, and p-STAT3. AG490, an inhibitor of the JAK/STAT pathway, reversed the damaging effects of Slfn5 overexpression.
Conclusions
In the LPS-induced pneumonia model, Slfn5 knockdown alleviated LPS-induced lung injury by regulating the JAK/STAT pathway.
... Inhibition of ERS-mediated apoptosis has been reported to reduce susceptibility to Streptococcus pneumoniae co-infection after influenza infection (32). Furthermore, ginsenoside Rg1 regulates sirtuin 1 and improves lung inflammation and injury caused by sepsis by inhibiting ERS and inflammation (33). In addition, caspase12 is a pro-apoptotic molecule specific to the outer membrane of the ER and activation of caspase12 is one of the core links in the development of ERS phase decay (34). ...
Pneumonia is a disease caused by inflammation and has high morbidity and mortality rates. Stromal interaction molecule 1 (STIM1) is involved in the regulation of inflammatory processes. However, to the best of the authors' knowledge, the role of STIM1 in pneumonia has not yet been reported. In the present study, lipopolysaccharide (LPS) was administered to A549 cells to construct a cell damage model. The expression of STIM1 in the model cells was detected by western blotting and reverse transcription-quantitative PCR. Then, STIM1 expression was inhibited and cell survival was detected by Cell Counting Kit-8 and flow cytometry. The expression of inflammatory factors was detected by enzyme-linked immunosorbent assay and endoplasmic reticulum stress (ERS)-related proteins were detected by immunofluorescence and western blotting. Subsequently, the relationship between insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and STIM1 was verified by RNA-binding protein immunoprecipitation assay and actinomycin D treatment. Finally, the regulatory mechanism of IGF2BP2 and STIM1 in LPS-induced A549 cells was further investigated. The results of the present study demonstrated that STIM1 expression was increased in LPS-induced A549 cells and that STIM1 knockdown inhibited LPS-induced A549 cell apoptosis and alleviated LPS-induced A549 cell inflammation and ERS. In addition, IGF2BP2 enhanced the stability of STIM1 mRNA and knockdown of IGF2BP2-regulated STIM1 expression alleviated LPS-induced ERS and inflammatory responses in A549 cells. In conclusion, knockdown of IGF2BP2-regulated STIM1 improved cell damage in the LPS-induced pneumonia cell model by alleviating ERS and the inflammatory response.
... It has been reported that honey contain nigerose (a sugar derivative) acts as immune stimulator (Peixoto et al., 2016). Different types of honey such as Manuka, Royal jelly, pasture, and Nigerian Jungle honey has ability to enhance the moderators of immune reaction including TNF-α, IL-1β, IL-6, and albumin 1 production (Wang et al., 2019). It has been studied that consumption of increases the levels of ascorbic acid, glutathione reductase, minerals, and immune cells such as eosinophils, monocytes, and lymphocytes in human body. ...
... TNF-α and COX-2, by inhibiting NF-κB and its translocation into the nucleus. Act ivation of NF-κB plays very important role in the inflammation (Hadagali & Chua, 2014;Peixoto et al., 2016;Ayazi et al., 2017;Ghazali et al., 2017;Samarghandian et al., 2017;Wang et al., 2019;Conti et al., 2020) (Table 3). ...
This article sums up the possible impact of honey in the amelioration of COVID-19 induced recognized pathogenesis. The pandemic due to the current outbreak of COVID-19 infected thousands of individuals round the globe. The indicator of COVID-19 infection suggests that increased inflammation, oxidation, and an overstressed immune reaction are key contributor of COVID-19 pathogenesis. This overstressed immune response leads to numerous cytokine production and consequently and led to the development of severe injury in lungs (ALI)/acute respiratory distress disorder and in some conditions becomes reason of death. Honey is formed when honey bees collect nectar from various, and then process it to form the honey. It is a natural remedy to reduce the incidence of various diseases, due to its potential anti-inflammatory, anti-oxidative, immune booster, antiviral, anti-diabetic, antimicrobial, anti-proliferative, cardiovascular, neurological and gastrointestinal diseases and anti-metastatic properties. Honey has been used for the curing of bronchial asthma, throat infections, tuberculosis, thirst, hiccups, fatigue, and hepatitis and also for the ALI/ARDS treatment caused by virus or any other pathogen. Doctors recommend honey as a nutritional supplement to boost the immunity of patients under critical conditions, reducing oxidative stress, inflammation, viral infections that confirm that honey may be used to combat the infection and other complications caused by COVID-19 pandemic. There are many reports which reveal that honey may be used in bacterial and viral infections such as COVID-19, however, further experimental studies are required to validate these speculations.
... 8 In addition, a number of studies have reported that SIRT1 has a protective effect on various types of lung injury, LPSinduced lung injury is also included. [9][10][11][12] However, whether SIRT6 can play a role in LPS-induced ALI is unknown. ...
Background:
Acute lung injury (ALI) is a severe and fatal respiratory disease. SIRT6 exerts pivotal activities in the process of lung diseases, but whether SIRT6 impacts ALI has not been covered.
Methods:
Lentivirus recombinant expressing vector SIRT6 gene (Lent-SIRT6) was constructed in mice, and there were control, lipopolysaccharide (LPS), LPS + Vehicle, and LPS + Lent SIRT6 groups. RT-qPCR and western blot detected SIRT6 expression in lung tissues. HE staining observed pathological alternations in lung tissues. Wet-to-dry ratio of the lungs was then measured. The cell count of bronchoalveolar lavage fluid (BALF) was evaluated. Serum inflammation was examined with enzyme-linked immunosorbent assay, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and western blot were to measure apoptosis. Western blot tested the expression of ACE2/STAT3/PIM1 signaling-associated factors. At the cellular level, LPS was used to induce lung epithelial cells BEAS-2B to establish cell injury models. SIRT6 was overexpressed and ACE2 expression was inhibited by cell transfection, and the mechanism of SIRT6 in LPS-induced lung injury model was further explored by Cell Counting Kit-8 (CCK-8), western blot, quantitative reverse-transcription polymerase chain reaction, TUNEL, and other techniques.
Results:
The results of animal experiments showed that SIRT6 overexpression could reduce LPS-induced lung pathological injury, pulmonary edema, and BALF cell ratio and attenuate LPS-induced inflammatory response and cell apoptosis. In the above process, ACE2, STAT3, p-STAT3, and PIM1 expression were affected. In cell experiments, SIRT6 expression was reduced in LPS-induced BEAS-2B cells. Inhibition of ACE2 expression could reverse the inhibitory effect of SIRT6 overexpression on ACE2/STAT3/PIM1 pathway, and cellular inflammatory response and apoptosis.
Conclusion:
SIRT6 eased LPS-evoked inflammation and apoptosis of lung epithelial cells in ALI through ACE2/STAT3/PIM1 signaling.
... This has been achieved either by reducing oxidative stress via increasing the content of reduced glutathione (GSH) and by modulating the activity of superoxide dismutase (SOD), catalase (CAT), and myeloperoxidase (MPO) in treatments with Ginsenoside Rg3 [75]. It can also be achieved by decreasing the oxidative stress via increasing the expression of sirtuin 1 (SIRT1) in the endoplasmic reticulum in treatment with Ginsenoside Rg1 [76]. It could also be achieved by decreasing oxidative stress by inhibiting proinflammatory signaling pathways, including nuclear factor-kappa B(NF-kB) and mitogen-activated protein kinase (MAPK) pathways mediated by Toll-like receptor (TLR)-2 in Ginsenoside treatment Rb1 [77] and Ginsenoside Rg1 [78]. ...
In the post-COVID-19 pandemic era, the new global situation and the limited therapeutic management of the disease make it necessary to take urgent measures in more effective therapies and drug development in order to counteract the negative global impacts caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its new infectious variants. In this context , plant-derived saponins-glycoside-type compounds constituted from a triterpene or steroidal aglycone and one or more sugar residues-may offer fewer side effects and promising beneficial pharmacological activities. This can then be used for the development of potential therapeutic agents against COVID-19, either as a therapy or as a complement to conventional pharmacological strategies for the treatment of the disease and its prevention. The main objective of this review was to examine the primary and current evidence in regard to the therapeutic potential of plant-derived saponins against the COVID-19 disease. Further, the aim was to also focus on those studies that highlight the potential use of saponins as a treatment against SARS-CoV-2. Saponins are antiviral agents that inhibit different pharmacological targets of the virus, as well as exhibit anti-inflammatory and antithrombotic activity in relieving symptoms and clinical complications related to the disease. In addition, saponins also possess immunostimulatory effects, which improve the efficacy and safety of vaccines for prolonging immunogenicity against SARS-CoV-2 and its infectious variants.
... The study was completed by manufacturer's procedure. The samples of blood were taken via retro-orbital plexus and then centrifuged at 1000 rpm for 15 min for serum collection (Wang et al. 2019;Zhuang et al. 2017). By assessing cytokines level in serum samples, the influence of pretreatment with LPS and TAK-242 on the participation of inflammation in ovalbumin-induced inflammatory features was determined. ...
Air pollution and environmental issues significantly impact life, resulting in the emergence and exacerbation of allergic asthma and other chronic respiratory infections. The main objective of this study is to suppress allergic asthma by TAK-242 from lipopolysaccharide-induced airway inflammation primarily stimulating toll-like receptor-4, and also to determine the potential mechanism of asthma eradication. The TAK-242 anti-allergic action was assured through the ovalbumin murine model of asthma via bronchial hyperresponsiveness and inflammation of the respiration tract in a pre-existing allergic inflammation paradigm. Swiss albino mice were sensitized and then challenged by ovalbumin and lipopolysaccharide for 5 days straight. TAK-242 reaction was assessed by inflammatory cytokines, and inflammatory cell count was determined from blood serum and bronchoalveolar lavage fluid, as well as group-wise regular weight assessments. After ovalbumin, lipopolysaccharide infusion, toll-like receptor-4 agonists caused a substantial increase in airway hyperresponsiveness, specific cellular inflammation, histological alterations, and immune mediator synthesis, as well as dose-related body-weight variations. A decrease in lipopolysaccharide-induced leukocyte count and Th1/Th17 related cytokines, TNF-α, and IL-6 expression through the ELISA study was particularly noticeable. Finally in treated groups, TAK-242, a TLR4/MD2 complex inhibitor, reduced airway inflammation and histopathological changes, cytokine expression, and body-weight management. TAK-242 has been found in an ovalbumin allergic asthma model to be a potential inhibitor of lipopolysaccharide-induced respiratory infection.
... Rg1 inhibited the activation of platelet as well as arterial thrombosis [30]. Rg1 reduced lung inflammation and damage by inhibiting endoplasmic reticulum stress and inflammation [31]. Additionally, Rg1 plays an increasingly important role in the treatment of atherosclerosis [32]. ...
... The results suggest that the protective effect of Rg1 on lidocaine-induced apoptosis is mediated by downreg- ulating caspase-3 expression [58]. In addition, it has been confirmed that Rg1 inhibits apoptosis induced by amyloid-beta peptide fragment [25][26][27][28][29][30][31][32][33][34][35] through Akt and extracellular-regulated protein kinases (ERK) signaling [59]. Rg1 reduced the production of dopamine-induced ROS and the release of mitochondrial cytochrome-C into the cytoplasm, and subsequently inhibited the activation of caspase-3. ...
... Rg1 reduced hepatic insulin resistance induced by high fat and high glucose by inhibiting inflammation [28]. Rg1 reduced sepsis-induced lung inflammation and damage by inhibiting endoplasmic reticulum stress and inflammation [31]. Rg1 improved liver fibrosis by inhibiting epithelial and mesenchymal transition (EMT) and production of ROS in vivo and in vitro [32]. ...
Neurological diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), stroke, cerebral infarction, ischemia-reperfusion injury, depression and, stress, have high incidence and morbidity and often lead to disability. However, there is no particularly effective medication against them. Therefore, finding drugs with a suitable efficacy, low toxicity and manageable effects to improve the quality of life of patients is an urgent problem. Ginsenoside Rg1 (Rg1) is the main active component of ginseng and has a variety of pharmacological effects. In this review, we focused on the therapeutic potential of Rg1 for improving neurological diseases. We introduce the mechanisms of Ginsenoside Rg1 in neurological diseases, including apoptosis, neuroinflammation, the microRNA (miRNA) family, the mitogen-activated protein kinase (MAPK) family, oxidative stress, nuclear factor-κB (NF-κB), and learning and memory of Rg1 in neurological diseases. In addition, Rg1 can also improve neurological diseases through the interaction of different signal pathways. The purpose of this review is to explore more in-depth ideas for the clinical treatment of neurological diseases (including PD, AD, HD, stroke, cerebral infarction, ischemia–reperfusion injury, depression, and stress). Therefore, Rg1 is expected to become a new therapeutic method for the clinical treatment of neurological diseases.
