Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice

Lin, Tsai-Jung; Wu, Chung-Yao; Tsai, Pei-Yi; Hsu, Wan-Han; Hua, Kuo-Feng; Chu, Chih‐Liang; Lee, Yu-Chieh; Chen, Ann; Lee, Sheau-Long; Lin, Yijin; Hsieh, Chih-Yu; Yang, Shin-Ruen; Liu, Feng‐Cheng; Ka, Shuk‐Man

doi:10.3389/fimmu.2019.01951

Cited by 25 publications

(28 citation statements)

References 61 publications

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“…The positive outcomes were showcased by inhibiting NF-κB-associated priming, and by modulating STAT3 signaling and NLRP3 inflammasome activation ( Table 4 ) [ 112 ]. Likewise, another study showed the protecting effects of CK on accelerated and severe lupus nephritis by hindering activation of NLRP3 inflammasome [ 113 ]. Ren and coworkers evaluated the protecting effects of CK and its analogues against asthma.…”

Section: Health-promoting Activitiesmentioning

confidence: 99%

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

2020

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Ginseng (Panax ginseng) is an herb popular for its medicinal and health properties. Compound K (CK) is a secondary ginsenoside biotransformed from major ginsenosides. Compound K is more bioavailable and soluble than its parent ginsenosides and hence of immense importance. The review summarizes health-promoting in vitro and in vivo studies of CK between 2015 and 2020, including hepatoprotective, anti-inflammatory, anti-atherosclerosis, anti-diabetic, anti-cancer, neuroprotective, anti-aging/skin protective, and others. Clinical trial data are minimal and are primarily based on CK-rich fermented ginseng. Besides, numerous preclinical and clinical studies indicating the pharmacokinetic behavior of CK, its parent compound (Rb1), and processed ginseng extracts are also summarized. With the limited evidence available from animal and clinical studies, it can be stated that CK is safe and well-tolerated. However, lower water solubility, membrane permeability, and efflux significantly diminish the efficacy of CK and restrict its clinical application. We found that the use of nanocarriers and cyclodextrin for CK delivery could overcome these limitations as well as improve the health benefits associated with them. However, these derivatives have not been clinically evaluated, thus requiring a safety assessment for human therapy application. Future studies should be aimed at investigating clinical evidence of CK.

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Section: Health-promoting Activitiesmentioning

confidence: 99%

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

2020

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“…CK inhibited the IgE/antigen-complex-induced cell degranulation in RBL-2H3 cells and oxazolone-induced chronic dermatitis in mice [36]. Lin et al reported that CK improved the accelerated and severe lupus nephritis in mice by blunting NLRP3 inflammasome activation and regulating T cell functions [85]. CK and its derivatives inhibited IgE production in mice with ovalbumin-sensitized asthma [86].…”

Section: Anti-allergic Effects Of Ginseng Constituentsmentioning

confidence: 99%

Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders

Han

Kim

2020

Biomolecules

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Both white ginseng (WG, dried root of Panax sp.) and red ginseng (RG, steamed and dried root of Panax sp.) are reported to exhibit a variety of pharmacological effects such as anticancer, antidiabetic, and neuroprotective activities. These ginsengs contain hydrophilic sugar-conjugated ginsenosides and polysaccharides as the bioactive constituents. When taken orally, their hydrophilic constituents are metabolized into hydrophobic ginsenosides compound K, Rh1, and Rh2 that are absorbable into the blood. These metabolites exhibit the pharmacological effects more strongly than hydrophilic parental constituents. To enforce these metabolites, fermented WG and RG are developed. Moreover, natural products including ginseng are frequently used for the treatment of allergic disorders. Therefore, this review introduces the current knowledge related to the effectiveness of ginseng on allergic disorders including asthma, allergic rhinitis, atopic dermatitis, and pruritus. We discuss how ginseng, its constituents, and its metabolites regulate allergy-related immune responses. We also describe how ginseng controls allergic disorders.

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“…The NLRP3 in ammasome has been proven to participate in immune rejection post-transplantation in graftversus-host disease (GVHD), as well as heart, kidney, and skin transplantations [11,12]. Studies have shown that the NLRP3 in ammasome is associated with the M1 polarization of macrophages [13].…”

Section: Introductionmentioning

confidence: 99%

Kaempferol alleviates corneal transplantation rejection by inhibiting NLRP3 inflammasome activation and macrophage M1 polarization via promoting autophagy

Tian

Lin

et al. 2021

Experimental Eye Research

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Corneal transplantation rejection remains a major threat to the success rate in high-risk patients. Given the many side effects presented by traditional immunosuppressants, there is an urgency to clarify the mechanism of corneal transplantation rejection and to identify new therapeutic targets. Kaempferol is a natural avonoid that has been proven in various studies to possess anti-in ammatory, antioxidant, anticancer, and neuroprotective properties. However, the relationship between kaempferol and corneal transplantation remains largely unexplored. To address this, both in vivo and in vitro, we established a model of corneal allograft transplantation in Wistar rats and an LPS-induced in ammatory model in THP-1 derived human macrophages. In the transplantation experiments, we observed an enhancement in the NLRP3 / IL-1 β axis and in M1 macrophage polarization post-operation. In groups to which kaempferol intraperitoneal injections were administered, this response was effectively reduced. However, the effect of kaempferol was reversed after the application of autophagy inhibitors. Similarly, in the in ammatory model, we found that different concentrations of kaempferol can reduce the LPS-induced M1 polarization and NLRP3 in ammasome activation. Moreover, we con rmed that kaempferol induced autophagy and that autophagy inhibitors reversed the effect in macrophages. In conclusion, we found that kaempferol can inhibit the activation of the NLRP3 in ammasomes by inducing autophagy, thus inhibiting macrophage polarization, and ultimately alleviating corneal transplantation rejection. Thus, our study suggests that kaempferol could be used as a potential therapeutic agent in the treatment of allograft rejection.

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Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice

Cited by 25 publications

References 61 publications

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities

Effects of Red and Fermented Ginseng and Ginsenosides on Allergic Disorders

Kaempferol alleviates corneal transplantation rejection by inhibiting NLRP3 inflammasome activation and macrophage M1 polarization via promoting autophagy

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