Effect of Astragalus polysaccharide combined with cisplatin on exhaled volatile organic compounds as biomarkers for lung cancer and its anticancer mechanism

Article

作者: Shi, Wenmin ; Feng, Weisheng ; Zhang, Zhijuan ; Zhang, Huanqing ; Tang, Hanxiao

Cisplatin (DDP) is widely used to fight lung cancer, but there is a risk of immune damage. Astragalus polysaccharides (APS) is the main active component of Astragalus membranaceus Bunge. It has demonstrated anticancer properties across a range of cancer types as well as to be effective against cisplatin induced immune damage. However, its therapeutic mechanism has not been fully explored. This study aimed to explore the antitumor mechanisms of APS and elucidate the relationship between APS and volatile organic compounds (VOCs) in exhaled breath of Lewis lung cancer (LLC) mice. Gas chromatography-mass spectrometry (GC-MS) was utilized to analyze the exhaled VOCs in LLC mice. A specific group of VOCs was identified as potential biomarkers for monitoring tumor progression. Furthermore, the effects of combined treatment with APS and DDP on the concentration of exhaled VOCs in LLC mice was evaluated. Stoichiometric analysis revealed that the levels of 12 VOCs exhibited substantial recovery following APS treatment. And a high concentration of APS (400 mg/kg), when combined with DDP, exhibited enhanced antitumor efficacy. The metabolic pathways involved in the action of APS include 12 pathways. Our methodology elucidated both the effects and mechanisms of APS on lung cancer, as well as the pharmacological enhancement of cisplatin by APS. These findings facilitate real-time monitoring of lung cancer treatments and contribute to the future development of anticancer therapies.

2025-05-01·INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES

Acanthopanax senticosus polysaccharide alleviates LPS-induced intestinal inflammation in piglets by gut microbiota and hyodeoxycholic acid regulation

Article

作者: Han, Rui ; Dong, Yangyunyi ; Tao, Dapeng ; Che, Dongsheng ; Wang, Zhongshen ; Jiang, Hailong ; Zheng, Yingying

The purpose of this study is to investigate the effects and mechanisms of Acanthopanax senticosus polysaccharides (ASPS) on lipopolysaccharide (LPS)-induced intestinal injury and growth performance in piglets. Our results indicated that ASPS improved the growth performance in LPS-challenged piglets, including the increase in average daily gain (ADG), average daily feed intake (ADFI), and the feed to gain ratio (F/G). ASPS alleviated LPS-induced intestinal inflammation in piglets, accompanied by the increase in the villus height to crypt depth ratio (VCR) and the decreased in the expression levels of IL-1β, IL-6, and TNF-α. 16S rRNA sequencing results showed that ASPS improved gut microbiota dysbiosis and increased Lactobacillus_sp._L_YJ abundance. The combined analysis of untargeted metabolomics of intestinal contents and serum showed that ASPS significantly increased the levels of hyodeoxycholic acid (HDCA), DHA ethyl ester, and alanylalanine, and the level of HDCA is the highest among all metabolites, suggesting that ASPS regulated the metabolites of intestinal contents and serum to alleviate LPS-induced intestinal inflammation in piglets, and HDCA might play a significant role during this process. Furthermore, we investigated the effects of HDCA on growth performance and intestinal inflammation in LPS-challenged piglets. The results indicated that HDCA alleviated LPS-induced intestinal inflammation and improved the growth performance in piglets. In conclusion, ASPS could alleviate LPS-induced intestinal inflammation in piglets by gut microbiota and hyodeoxycholic acid regulation. These findings might provide strong evidence for ASPS as a feed additive to improve piglet diarrhea, and reveal the therapeutic potential of hyodeoxycholic acid in preventing intestinal inflammation in piglets.

2025-04-01·CURRENT PHARMACEUTICAL BIOTECHNOLOGY

The Protective Effect of Astragalus Polysaccharide on Experimental Autoimmune Encephalomyelitis in Mice by Activating the AMPK/JAK/ STAT3/Arginase-1 Signaling Pathway

Article

作者: He, Xue-Xin ; Wang, Jin-Li ; Wang, Jue-Qiong ; Li, Bin ; Guo, Ruo-Yi ; Gao, Chang-Yu ; Fan, Jing-Yi ; Xie, Tao ; Song, Shuang ; Zhang, Ya-Nan ; Quan, Mo-Yuan

Objective::

This study aimed to investigate the protective effect and mechanism of Astragalus polysaccharide (APS) on autoimmune encephalomyelitis.

Methods::

C57BL/6 mice were randomly divided into the blank control group, EAE group, and APS intervention group (n=15/group). The Experimental Autoimmune Encephalomyelitis (EAE) mouse model was established by active immunization. The pathological changes in the spinal cord were evaluated by Hematoxylin-eosin (HE) and Luxol Fast Blue (LFB) staining. The number of CD11b+ Gr-1+ myeloid-derived suppressor cells (MDSCs) in the spleen tissues of mice in each group was determined by immunofluorescence staining. The expression of Arginase-1 in the spinal cord and spleen of each group was detected by immunofluorescence double staining. The TNF-α, IL-6, and Arginase-1 levels in the spleen were detected by ELISA assay. A western blot was used to detect the protein expression of the AMPK/JAK/STAT3/Arginase-1 signaling pathway.

Results::

After the intervention of APS, the incidence of autoimmune encephalomyelitis in mice of the APS group was significantly lower than that in the EAE group, and the intervention of APS could significantly delay the onset time in the EAE mice, and the score of neurological function deficit in mice was significantly lower than that in EAE group (P < 0.05). APS intervention could reduce myelin loss and improve the inflammatory response of EAE mice. Moreover, it could induce the expression of CD11b+ GR-1 + bone MDSCs in the spleen and increase the expression of Arginase-1 in the spinal cord and spleen. This study further demonstrated that APS can protect EAE mice by activating the AMPK/JAK/STAT3/Arginase-1 signaling pathway.

Conclusion::

After the intervention of APS, myelin loss and inflammatory response of EAE mice were effectively controlled. APS promoted the secretion of Arginase-1 by activating MDSCs and inhibited CD4+T cells by activating AMPK/JAK/STAT3/Arginase-1 signaling pathway, thus improving the clinical symptoms and disease progression of EAE mice.

项与黄芪多糖相关的新闻（医药）

2024-09-16

·PRNewswire

PhytoHealth Corporation announced a new clinical study results published at 2024 ESMO Congress: PG2 plus preoperative chemoradiotherapy improves survival in patients with locally advanced esophageal cancer

TAIPEI and BARCELONA, Spain, Sept. 16, 2024 /PRNewswire/ -- A groundbreaking study conducted by PhytoHealth Corporation, a leading provider of botanical medicine, has revealed that combining Astragalus Polysaccharides (PG2®Lyo. Injection) with standard concurrent chemoradiotherapy (CCRT) significantly improves survival rates for patients with advanced esophageal cancer. The study enrolled 38 patients with stage IIb to IIIb esophageal cancer. Participants were randomly assigned to receive either CCRT alone or CCRT combined with PG2, a proprietary extract of Astragalus membranaceus roots developed by PhytoHealth Corporation. Results showed that patients who received PG2 in addition to CCRT experienced significantly longer overall survival compared to those who received CCRT alone. Furthermore, the combination therapy resulted in a higher tumor objective response rate. The study also found that PG2 helped strengthen the immune system by modulating the tumor immune microenvironment (TIME) and enhancing the suppression of tumor growth. 'These findings offer a new hope for patients with esophageal cancer,'' said Dr. Wen-Chieh Huang, Chief of Division of Thoracic Surgery at Mackay Memorial Hospital, Taiwan and the Principal Investigator of the clinical trial for PG2, a drug for cancer-related fatigue (CRF) relief developed by PhytoHealth Corporation, Taiwan. "PG2 has the potential to become a valuable addition to the standard treatment regimen, and can achieve improved patient outcomes.'' The data will be presented as a poster at the prestigious 2024 ESMO Congress. [ESMO abstract link]. Dr. Huang noted that treatment options for esophageal cancer patients are relatively limited compared to those for other cancers. However, this study has shown that PG2 combination therapy can reduce inflammation markers in the blood, decrease the differentiation of macrophages towards the M2 type, and even help shrink tumors while improving survival rates. This represents a significant breakthrough in the treatment of esophageal cancer. Dr. Huang further added that esophageal cancer patients often face tremendous challenges during treatment, with many unable to complete their therapy. However, by incorporating CRF medication, most patients were able to regain their strength, complete the full courses of cancer treatment, and achieve the expected therapeutic effects. Esophageal cancer is a challenging disease with high recurrence rates and poor survival outcomes. PG2, previously established as a treatment for cancer-related fatigue (already approved by Taiwan Food and Drug Administration) has shown promise as a potential treatment enhancer. This latest discovery marks a significant advancement in the ongoing battle against this challenging cancer. About PhytoHealth Corporation PhytoHealth Corporation is a leader in the development and manufacturing of botanical medicine and natural health products based in Taiwan. With a focus on scientific research and innovation, PhytoHealth is committed to providing safe, effective, and high-quality products that support overall health and well-being. Contact: Alison [email protected] Logo - WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果

2023-07-20

·CPHI制药在线

免疫 | 植物多糖免疫调节作用机制研究进展（上）

关注并星标CPHI制药在线植物多聚糖简称植物多糖，是由许多相同或不同的单糖以α-或 β-糖苷键构成的化合物，包括淀粉、纤维素、果胶和多聚糖等重要的生物大分子，是生物体维持生命活动的主要能源物质。研究表明，植物多糖有抗病毒、抑菌、抗肿瘤、降血糖血脂和抗血栓等多种生理功能。此外，近年来国内外学者研究发现蛹虫草多糖、黄芪多糖和人参多糖等多种植物多糖都具有显著的免疫活性，可以提高机体巨噬细胞及淋巴细胞等免疫活性。随着研究的不断深入，植物多糖免疫活性机理、功效因子也愈加明确和清晰，主要包括激活巨噬细胞、激活补体系统、促进机体免疫器官的生长、刺激产生相关的细胞因子以活化淋巴T细胞和淋巴B细胞，调节红细胞免疫影响蛋白质的合成和抗体的生成从而达到影响机体免疫信息，包括促进白细胞介素及干扰素的生成，参与神经-内分泌-免疫系统调节，提高免疫系统对抗原的识别能力和机体免疫系统损伤造成的免疫耐受能力等。植物多糖对固有免疫的影响固有免疫又称先天性免疫和非特异性免疫，具有广泛性强、免疫速度快和种群差异性小等特点，是个体自出生时就具备的一种免疫机制，对非特异性病菌感染具有免疫作用，包括巨噬细胞和自然杀伤细胞 (natural killer cell，NK)。 01对巨噬细胞的影响巨噬细胞是一种位于组织内的白血球，源自单核细胞，可以以固定细胞或游离细胞的形式对病原体进行吞噬及消化并激活淋巴球或其他免疫细胞。巨噬细胞不仅具有引起先天性免疫反应且对感染和炎症均有抵抗效果，当多糖与巨噬细胞特异性膜受体结合时，免疫应答反应将被正式激活发挥作用，且随着剂量的增加对直接杀死病原体具有显著的调节作用。植物多糖多也通过改变巨噬细胞形态、促进巨噬细胞产生一氧化氮（NO）、提高巨噬细胞分泌细胞因子、影响细胞内酶活性以及降低巨噬细胞迁移因子分泌的方式来增强巨噬细胞的吞噬作用。研究发现，一定浓度的猪苓多糖可以增大巨噬细胞体积，改变细胞形态，从而增强巨噬细胞的免疫。均质海带多糖可降低高脂喂养小鼠模型的动脉粥样硬化病变比例，减轻氧化型低密度脂蛋白（Ox-LDL）造成的巨噬细胞的脂质沉积，降低M1巨噬细胞标志物的表达，增加M2巨噬细胞标志物的表达，从而降低了M1/M2巨噬细胞表型比，影响细胞的巨噬功能。从桔梗中分离得到一种新型多糖组分（PGP Ⅳ），能显著刺激小鼠单核巨噬细胞白血病细胞（RAW264.7）增殖，并以剂量依赖性方式增强其吞噬能力。而更高剂量的PGP Ⅳ处理能诱导NO、肿瘤坏死因子（TNF）和白介素（IL）的分泌。黄芪多糖通过降低巨噬细胞迁移抑制因子分泌，从而抑制肺癌细胞的侵袭性。使用灵芝孢子多糖（GLSP）进行体外细胞培养小鼠中提取的原代巨噬细胞，研究证实GLSP能促进原代巨噬细胞M1型极化，上调TNF-α、IL-1β、IL-6、TGF-β1等细胞因子。 02对自然杀伤细胞的影响自然杀伤细胞(NK细胞)是机体极为重要的免疫细胞，是一种天然存在于生物体内的非特异性免疫杀伤细胞，在机体胞内对寄生菌感染、抗肿瘤和抗病毒免疫过程有着至关重要的作用，具有免疫调节和细胞毒性双重功能。研究显示，明参多糖能有效激活机体 NK细胞和促进 T细胞增殖分化，对体内细胞因子数目有明显的增加效果。多糖通过增强 NK细胞活性，从而使靶细胞YAC-1失去贴壁功能而释放胞内乳酸脱氢酶(LDH)、乳酸锂脱氢和烟酰胺腺嘌呤二核苷酸(NADH)还原，继而经递氢体吩嗪二甲酯硫酸盐还原碘硝基氯化四氮唑还原为甲瓒类化合物以实现通过细胞毒性作用介导杀伤肿瘤细胞和病毒感染细胞，从而提高机体非特异性免疫能力。研究发现，使用水提法得到的岩藻多糖可以刺激RAW264.7鼠巨噬细胞分泌NO、TNF-α、IL-1β和IL-6，且可通过NF-κB和丝裂原活化蛋白激酶（MAPK）信号通路激活NK细胞，促进释放TNF-α、TNF-γ、颗粒酶-B、穿孔素，提高NK细胞的杀伤活力。香菇多糖对免疫抑制性小鼠进行治疗性给药后，在一定浓度内可提升小鼠NK细胞的杀伤活性以及免疫球蛋白M（IgM）的分泌。同时，当香菇多糖以多糖-藻酸盐微胶囊的形式可激活NK，产生协同作用，增加对结肠癌细胞的杀伤力。金银花多糖（LJP）可以显著增加水溶性葡聚糖硫酸钠(DSS)处理的小鼠体重、器官指数和IL、TNF和IFN-γ细胞因子的分泌，提高分泌性免疫球蛋白A（SigA）水平以及提升NK细胞和细胞毒性淋巴细胞（CTL）的活性。植物多糖对适应性免疫应答的影响适应性免疫应答也称获得性免疫应答，是生物体在长期种系发育和进化过程中逐渐形成的防御机制。适应性免疫应答可以通过识别"自身"和"非己"达到有效排除体内抗原性异物，以保持机体内环境的相对稳定。根据参与免疫应答细胞的种类和机制将适应性免疫应答分为 T淋巴细胞介导的细胞免疫应答和 T、B 淋巴细胞共同介导的体液免疫应答。 01对细胞免疫的影响T细胞是参与细胞免疫的淋巴细胞，受到抗原刺激后，转化为致敏淋巴细胞，并表现出特异性免疫应答，免疫应答只能通过致敏淋巴细胞传递，故称细胞免疫。研究发现，使用当归多糖（ASP）治疗再生障碍性贫血小鼠，可通过改变P-p38/ p38 和Treg/Th17比率，增加调节性T细胞（Treg）的活力。灰树花多糖可通过增加CD4+T细胞和CD8+T细胞的免疫功能，促进IL-2、TNF-α细胞因子的分泌，从而抑制肿瘤的生长。使用黄芪多糖对B16黑色素瘤小鼠进行给药后，CD4+和CD4+/CD8+T细胞比率均有所升高，减少黑色素瘤小鼠的髓源性抑制细胞数量，增强免疫功能。同时，使用黄芪多糖与PD-L1抗体联合治疗Lewis肺癌小鼠时发现可增加脾脏和胸腺指数、CD4+T细胞比例和CD4+/CD8+T 细胞比例，改善T细胞相关细胞因子水平，提升脾淋巴细胞肿瘤杀伤能力。秋葵粗多糖提取物（ORPE）对二乙基亚硝胺（DEN）诱导的肝癌小鼠施用后，直接抑制了Treg细胞的积累，抑制巨噬细胞的活化，平衡了效应T细胞的数量。它在低剂量下促进CD8+T细胞活化，并在所有剂量下增加IL-2水平。这些结果表明，ORPE具有独特的免疫抑制剂和免疫刺激剂双重功能。 02对体液免疫的影响体液免疫，即以浆细胞产生抗体来达到保护目的的免疫机制。负责体液免疫的细胞是B细胞，在抗原刺激下转化为浆细胞，合成免疫球蛋白，能与靶抗原结合的免疫球蛋白即为抗体。抗体是由B细胞经抗原刺激后，经一系列增殖分化为浆细胞后分泌的一种糖蛋白，主要存在于血清等体液中以参与相应抗原抗体特异性表达，而抗体生成水平是机体非特异性免疫功能主要指标之一。多糖本身不仅可通过调节小鼠巨噬细胞的吞噬能力和血清溶血素水平来提高小鼠血清抗体水平，同时增强体外脾淋巴细胞分泌 IL-2 浓度水平以增加参与抗体反应水平，继而提高机体体液免疫功能，增强机体的免疫活性。此外，多糖还可提高免疫功能低下大鼠血清中具有抗体活性的免疫球蛋白分泌水平和 C3、C4 补体水平，当二者协同作用时对杀死病原微生物效果显著。研究表明，沙棘多糖（HRP）具有抗氧化和免疫调节作用，对猪空肠上皮细胞（IPEC-J2）进行处理时，在一定水平范围内可使超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、IL-1β、IL-2、IL-6、IL-8、TNF-α升高，以及IPEC-J2细胞中的相对mRNA水平升高。同时IgM、IgA和IgG的水平均随着HRP水平升高而升高。茯苓多糖（PCP）可显著上调C57BL/6小鼠血液中组织相容性复合体II（MHC-II）、CD40、CD80、CD86的表面表达，并促进IL-6和IL-12p40的产生。使用PCP+卵清蛋白（OVA）皮下免疫时，PCP显著提高血清中OVA 特异性IgG、IgG2a和IgG1抗体水平，增加了分泌OVA 特异性IFN-γ的CD8+、CD4+T细胞，促进CD8+T 细胞增殖，并上调辅助性T细胞1型（Th-1）产生IFN-γ、IL-2细胞因子。参考资料 [1]林智敏，肖健.植物多糖免疫调节作用研究进展[J].标记免疫分析与临床，2022，29(07):1252-1255. [2]杨许花，赵梦潇，陈红等.植物多糖免疫调节作用机制研究进展[J].食品安全质量检测学报，2021，12(13):5349-5355. 作者简介：小泥沙，食品科技工作者，现就职于国内某大型药物研发公司，从事营养食品及功能性食品的开发与研究。智药研习社近期课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~

免疫疗法细胞疗法

100 项与黄芪多糖相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
脑脊髓炎	临床前	中国	上海中医药大学	2024-12-01
黑色素瘤	临床前	中国	上海中医药大学	2024-08-21
血栓形成	临床前	中国	中山大学	2019-07-08