Halloween Hope: Quercetin: Inhibiting PD-L1 (Uncloaking Cancer) and Inhibiting Amyloid Fibrillation Once again, Quercetin shines brightly with a new study showing that it definitively inhibits the formation of amyloid fibrils. WALTER M CHESNUT OCT 31
We have discussed the benefits of Quercetin in combating SARS-CoV-2 and its Spike Protein several times. Now there is additional evidence supporting how Quercetin is highly instrumental in combating diseases of aging – diseases which the Spike Protein has been shown to induce and/or accelerate. Today we will discuss how it is beneficial in combating two of those diseases – cancer and neurodegenerative disease.
You may not realize it, but Quercetin is King when it comes to the daily flavonoid intake of humans – 65% - 75%! And it is actually safe!
Quercetin is an essential flavonoid derived from plants, accounting for 60 % to 75 % of the daily dietary flavonoids intake in humans [[1], [2], [3]]. In recent years, it has gained significant attention due to its diverse physiological activities, including antioxidant, free radical scavenging, anti-inflammatory, antibacterial, and anticancer properties [4]. Additionally, Quercetin is non-toxic and safe for long-term consumption, making it an ideal natural therapeutic agent. In China, the extraction and preparation process of Quercetin has become well-established, providing both cost advantages and convenient conditions for large-scale application. These factors, combined with Quercetin’s excellent physicochemical properties, form a solid foundation for its development in drug therapy and therapeutic intervention [5,6].
Earlier this week, we discussed how the Spike Protein enhances the expression of a protein called PD-L1. This is a protein expressed by cancer cells allowing them to hide from the immune system, which would otherwise destroy them. Please see Monday’s post for a detailed explanation.
Here Quercetin comes to the rescue as it inhibits the expression and interaction of PD-L1, allowing the immune system to “see” “cloaked” cancer cells and resume destroying them.
As a safe dietary supplement, quercetin (Que) is one of the richest dietary flavonoids found in a wide range of vegetables and fruits. Que has various health benefits and exerts antioxidant, antibacterial, immunomodulatory,anti-inflammatory, and anti-allergic effects that enhance resistance to disease. Recent studies investigating the anti-tumor effects of Que have suggested that Que can play a role in cancer treatment through autophagy, apoptosis, EMT, and oxidation [204], [205], [206].
Jing et al. found that Que dihydrate had a high affinity for PD-L1 and blocked the PD-1/PD-L1 interaction. Immunohistochemical analysis revealed that Que dihydrate induced significantly elevated protein levels of CD8 + , GZMB, and IFN-γ, further demonstrating that Que dihydrate reactivated T cell-mediated tumor cell killing [157]. Another study reported that Que increased the phosphorylation of JAK2 in the JAK/STAT1 pathway and increased nuclear localization of p-STAT1 by activating IFNγ-R on tumor cells, thereby decreasing PD-L1 expression on breast cancer cells. Notably, Que promoted the proliferation of Vδ2 T subsets of γδ T cells, thus enhancing the killing effect on breast cancer cells [96]. In addition, pentamethylquercetin, obtained by methylation modification of quercetin, inhibited the progression of hepatocellular carcinoma caused by high expression of PD-L1 in obese mice and demonstrated that it downregulated adipocyte-induced PD-L1 expression at least partially through IFN-γ signaling, the relevant mechanisms are under further investigation [158]. A series of studies has expanded the understanding of the immunomodulatory activity of quercetin and demonstrated the exciting potential of this natural compound as a cancer chemopreventive agent.
Fantastically, a just-published paper (currently available online, in print in March) shows that Quercetin also DEFINTIVELY inhibits the formation of amyloid fibrils. This is a panoptical benefit as it applies to many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Of course, readers of this Substack will know that the Spike Protein is itself amyloidogenic in addition to being oncogenic.
This study elucidates the anti-fibrillation mechanisms of Quercetin through its interaction with BSA. By integrating ThT-ANS-CR multi-spectral analysis with molecular simulations, we established a multi-dimensional framework to decipher protein fibrillation suppression. ThT fluorescence quantified β-sheet formation kinetics, ANS probes monitored hydrophobic exposure dynamics, and CR absorption spectroscopy validated mature fibril β-sheet stacking, collectively corroborating Quercetin’s inhibitory efficacy. UV–vis and variable-temperature fluorescence spectroscopy revealed a hydrophobic burial-driven static quenching mechanism at Sudlow site I, stabilized by hydrogen bonding and π-π stacking. Molecular docking and SEM confirmed a 1:1 binding stoichiometry and Quercetin’s capacity to reduce fibril density and length, underscoring the critical roles of Trp-214 and polar residues (e.g. SER-192, HIS-145) in complex stabilization. This work constructs a complete evidence chain spanning macroscopic phenotypes to molecular interactions, demonstrating that the multi-technique approach outperforms single-method analyses by mitigating technical bias. These findings highlight Quercetin’s potential as a biocompatible, low-toxicity inhibitor for treating neurodegenerative diseases linked to protein fibrillation, while the integrated methodology offers a universal paradigm for studying biomolecular interactions in amyloid-related pathologies.
Bearing in mind all the previously discussed benefits of Quercetin, it is a tremendous comfort to learn that Quercetin is also a significant orchestrator in the prevention and treatment of two of the greatest scourges of the aging human. By addressing cancer and neurodegenerative disease, Quercetin, once again, shows its worth, along with Vitamin D, as one of the greatest stars in the therapy firmaments of Spike Protein disease/injury, cancer and neurodegenerative disease. As I posted recently on X, Quercetin may be my favorite molecule.
The pioneers of our great nation were certainly onto something when they created a unique (to say the least) recipe – that happens to be a Quercetin supernova! I will conclude today’s post with this recipe, as it is also apt for Autumn, and will make Halloween less scary for all of us. Please have a blessed weekend.
Sautéed apples and onions was once a pioneer favorite. Yes, it sounds weird, but it’s delicious. You’ll want to have something to go with this that has some protein, like a garden burger or a brown rice packet, both of which you can microwave. Sautéed apples and onions only takes about 10 minutes, a few dollars and it’s delicious as a topping for rice or even by itself for a light snack.…
Halloween Hope: Quercetin: Inhibiting PD-L1 (Uncloaking Cancer) and Inhibiting Amyloid Fibrillation
Once again, Quercetin shines brightly with a new study showing that it definitively inhibits the formation of amyloid fibrils.
WALTER M CHESNUT
OCT 31
万圣节希望：槲皮素：抑制 PD-L1（揭露癌症）和抑制淀粉样纤维颤动
一项新研究表明，槲皮素能明确抑制淀粉样原纤维的形成，再次大放异彩。
沃尔特·M·切斯纳特
10 月 31 日
https://open.substack.com/pub/wmcresearch/p/halloween-hope-quercetin-inhibiting
We have discussed the benefits of Quercetin in combating SARS-CoV-2 and its Spike Protein several times. Now there is additional evidence supporting how Quercetin is highly instrumental in combating diseases of aging – diseases which the Spike Protein has been shown to induce and/or accelerate. Today we will discuss how it is beneficial in combating two of those diseases – cancer and neurodegenerative disease.
You may not realize it, but Quercetin is King when it comes to the daily flavonoid intake of humans – 65% - 75%! And it is actually safe!
Quercetin is an essential flavonoid derived from plants, accounting for 60 % to 75 % of the daily dietary flavonoids intake in humans [[1], [2], [3]]. In recent years, it has gained significant attention due to its diverse physiological activities, including antioxidant, free radical scavenging, anti-inflammatory, antibacterial, and anticancer properties [4]. Additionally, Quercetin is non-toxic and safe for long-term consumption, making it an ideal natural therapeutic agent. In China, the extraction and preparation process of Quercetin has become well-established, providing both cost advantages and convenient conditions for large-scale application. These factors, combined with Quercetin’s excellent physicochemical properties, form a solid foundation for its development in drug therapy and therapeutic intervention [5,6].
Dual binding modes of Quercetin to BSA: Insights from spectroscopy and molecular simulations in amyloid suppression
https://www.sciencedirect.com/science/article/abs/pii/S1386142525014003
Earlier this week, we discussed how the Spike Protein enhances the expression of a protein called PD-L1. This is a protein expressed by cancer cells allowing them to hide from the immune system, which would otherwise destroy them. Please see Monday’s post for a detailed explanation.
Here Quercetin comes to the rescue as it inhibits the expression and interaction of PD-L1, allowing the immune system to “see” “cloaked” cancer cells and resume destroying them.
As a safe dietary supplement, quercetin (Que) is one of the richest dietary flavonoids found in a wide range of vegetables and fruits. Que has various health benefits and exerts antioxidant, antibacterial, immunomodulatory,anti-inflammatory, and anti-allergic effects that enhance resistance to disease. Recent studies investigating the anti-tumor effects of Que have suggested that Que can play a role in cancer treatment through autophagy, apoptosis, EMT, and oxidation [204], [205], [206].
Jing et al. found that Que dihydrate had a high affinity for PD-L1 and blocked the PD-1/PD-L1 interaction. Immunohistochemical analysis revealed that Que dihydrate induced significantly elevated protein levels of CD8 + , GZMB, and IFN-γ, further demonstrating that Que dihydrate reactivated T cell-mediated tumor cell killing [157]. Another study reported that Que increased the phosphorylation of JAK2 in the JAK/STAT1 pathway and increased nuclear localization of p-STAT1 by activating IFNγ-R on tumor cells, thereby decreasing PD-L1 expression on breast cancer cells. Notably, Que promoted the proliferation of Vδ2 T subsets of γδ T cells, thus enhancing the killing effect on breast cancer cells [96]. In addition, pentamethylquercetin, obtained by methylation modification of quercetin, inhibited the progression of hepatocellular carcinoma caused by high expression of PD-L1 in obese mice and demonstrated that it downregulated adipocyte-induced PD-L1 expression at least partially through IFN-γ signaling, the relevant mechanisms are under further investigation [158]. A series of studies has expanded the understanding of the immunomodulatory activity of quercetin and demonstrated the exciting potential of this natural compound as a cancer chemopreventive agent.
Focus on immune checkpoint PD-1/PD-L1 pathway: New advances of polyphenol phytochemicals in tumor immunotherapy
https://www.sciencedirect.com/science/article/pii/S0753332222010071
Fantastically, a just-published paper (currently available online, in print in March) shows that Quercetin also DEFINTIVELY inhibits the formation of amyloid fibrils. This is a panoptical benefit as it applies to many neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease. Of course, readers of this Substack will know that the Spike Protein is itself amyloidogenic in addition to being oncogenic.
This study elucidates the anti-fibrillation mechanisms of Quercetin through its interaction with BSA. By integrating ThT-ANS-CR multi-spectral analysis with molecular simulations, we established a multi-dimensional framework to decipher protein fibrillation suppression. ThT fluorescence quantified β-sheet formation kinetics, ANS probes monitored hydrophobic exposure dynamics, and CR absorption spectroscopy validated mature fibril β-sheet stacking, collectively corroborating Quercetin’s inhibitory efficacy. UV–vis and variable-temperature fluorescence spectroscopy revealed a hydrophobic burial-driven static quenching mechanism at Sudlow site I, stabilized by hydrogen bonding and π-π stacking. Molecular docking and SEM confirmed a 1:1 binding stoichiometry and Quercetin’s capacity to reduce fibril density and length, underscoring the critical roles of Trp-214 and polar residues (e.g. SER-192, HIS-145) in complex stabilization. This work constructs a complete evidence chain spanning macroscopic phenotypes to molecular interactions, demonstrating that the multi-technique approach outperforms single-method analyses by mitigating technical bias. These findings highlight Quercetin’s potential as a biocompatible, low-toxicity inhibitor for treating neurodegenerative diseases linked to protein fibrillation, while the integrated methodology offers a universal paradigm for studying biomolecular interactions in amyloid-related pathologies.
Dual binding modes of Quercetin to BSA: Insights from spectroscopy and molecular simulations in amyloid suppression
https://www.sciencedirect.com/science/article/abs/pii/S1386142525014003
Bearing in mind all the previously discussed benefits of Quercetin, it is a tremendous comfort to learn that Quercetin is also a significant orchestrator in the prevention and treatment of two of the greatest scourges of the aging human. By addressing cancer and neurodegenerative disease, Quercetin, once again, shows its worth, along with Vitamin D, as one of the greatest stars in the therapy firmaments of Spike Protein disease/injury, cancer and neurodegenerative disease. As I posted recently on X, Quercetin may be my favorite molecule.
The pioneers of our great nation were certainly onto something when they created a unique (to say the least) recipe – that happens to be a Quercetin supernova! I will conclude today’s post with this recipe, as it is also apt for Autumn, and will make Halloween less scary for all of us. Please have a blessed weekend.
Sautéed apples and onions was once a pioneer favorite. Yes, it sounds weird, but it’s delicious. You’ll want to have something to go with this that has some protein, like a garden burger or a brown rice packet, both of which you can microwave. Sautéed apples and onions only takes about 10 minutes, a few dollars and it’s delicious as a topping for rice or even by itself for a light snack.…
我们讨论了槲皮素在对抗SARS-COV-2及其穗蛋白的份量几次的益处。 现在存在额外的证据，支持槲皮素如何在对抗尖刺蛋白已被证明诱导和/或加速的衰老疾病方面的高度乐曲。 今天，我们将讨论如何有利于对抗两种疾病和神经变性疾病。 你可能没有意识到这一点，但槲皮素是王者的日常黄酮类动物摄入量 - 65％ - 75％！ 它实际上是安全的！ 槲皮素是衍生自植物的必需品，占人人类每日膳食黄酮类化合物的60％至75％[[1]，[2]，[3]]。 近年来，由于其不同的生理活动，包括抗氧化剂，自由基清除，抗炎，抗菌和抗癌性能（包括抗氧化，抗菌和抗癌性能，它效率显着 此外，槲皮素对长期消费无毒和安全，使其成为理想的天然治疗剂。 在中国，槲皮素的提取和制备过程已经确定，为大型应用提供了成本优势和方便的条件。 这些因素与槲皮素的优异物理化学性质相结合，形成了其在药物治疗和治疗干预中的发展的坚实基础[5,6]。 槲皮素对BSA的双重结合模式：淀粉样抑制中光谱和分子模拟的见解Https://www.scienceRect.com/science/article/abs/pii/s138614252 这是癌细胞表达的蛋白质，允许它们隐藏免疫系统，否则会破坏它们。 请参阅星期一的帖子以获得详细的解释。 这里槲皮素抑制PD-L1的表达和相互作用，允许免疫系统“看到”“含有”癌细胞并恢复摧毁它们。 作为一种安全的膳食补充剂，槲皮素（QUE）是在各种蔬菜和水果中发现的最富有的膳食类黄酮之一。 Que具有各种健康益处，并施加抗氧化剂，抗菌，免疫调节，抗炎和增强疾病抗性的抗过敏作用。 近期研究调查QUE的抗肿瘤作用表明，阙可以通过自噬，细胞凋亡，EMT和氧化在癌症治疗中发挥作用[204]，[205]，[206]。 景等。 发现QUE二水合物对PD-L1具有高亲和力并阻断PD-1 / PD-L1相互作用。 免疫组织化学分析显示，QUE二水合物诱导CD8 +，GZMB和IFN-γ的显着升高的蛋白质水平，进一步证明QUE二水合物再激活T细胞介导的肿瘤细胞杀灭[157]。 另一项研究报告说，Que通过在肿瘤细胞上激活IFNγ-r，增加了JAK / Stat1途径中JAK2的磷酸化并增加了P-STAT1的核定位，从而降低了乳腺癌细胞的PD-L1表达。 值得注意的是，que促进了γδt细胞的Vδ2t子集的增殖，从而提高了对乳腺癌细胞的杀伤作用[96]。 此外，通过槲皮素的甲基化改性获得的五甲基Qcercetin抑制了肥胖小鼠PD-L1高表达引起的肝细胞癌的进展，并证明其下调脂肪细胞 一系列研究扩大了对槲皮素免疫调节活性的理解，并证明了这种天然化合物作为癌症化学预防剂的激动潜力。 专注于免疫检查点PD-1 / PD-L1路径：肿瘤免疫治疗中多酚植物化学症的新进展https://www.scienceirect.com/science/article/pii/s075 这是一个令人痛苦的益处，因为它适用于许多神经变性疾病，包括阿尔茨海默病，帕金森病和亨廷顿疾病。 当然，这种词形的读者仍然知道，除了致癌性外，尖峰蛋白也是淀粉样蛋白化。 本研究通过其与BSA的相互作用阐明了槲皮素的抗原纤化机制。 通过将THT-ANS-CR多光谱分析与分子模拟相结合，我们建立了一种多维框架来破译蛋白质颤动抑制。 THT荧光定量β-片状形成动力学，ANS探针监测疏水暴露动力学，CR吸收光谱验证成熟纤维β-片堆叠，共同证实槲皮素的抑制效果。 UV-Vis和可变温度荧光光谱揭示了Sudlow位点I的疏水性埋地静电猝灭机制，通过氢键和π-π堆叠稳定。 分子对接和SEM证实了1：1结合化学计量和槲皮素的减少纤维密度和长度的能力，强调TRP-214和极性残留物的关键作用（例如Ser-192，His-145） 这项工作构建了一个完整的证据链，跨越宏观表型对分子相互作用，证明了通过减轻技术偏压来实现单方法分析。 这些发现突出了槲皮素作为一种生物相容性的低毒性抑制剂，用于治疗与蛋白质颤动相关的神经变性疾病，而综合方法提供了用于研究上午的生物分子相互作用的普遍范式 槲皮素对BSA的双重结合模式：淀粉样抑制中光谱和分子模拟的见解Https://www.scienceRect.com/science/article/abs/pii/s138614252 通过解决癌症和神经退行性疾病，槲皮素再次表现出其价值，以及维生素D，作为穗蛋白疾病，癌症和神经变性疾病的治疗型恒生症中最伟大的恒星之一。 当我最近发布的x时，槲皮素可能是我最喜欢的分子。 我们伟大的国家的先驱肯定是在他们创造一个独特的（最重要的）食谱时的东西 - 恰好是槲皮素超新星！ 我将结束今天的帖子用这个配方，因为它也适用于秋天，并将为我们所有人提供万圣节吓人。 请有一个幸福的周末。