Clinical study on the safety and preliminary efficacy of biosynthetic cordycepin in the treatment of patients with pancarcinogenic advanced solid tumors treated with capecitabine monotherapy or combination chemotherapy due to fatigue

开始日期2024-08-26

申办/合作机构

Shanghai Sixth People's Hospital

ChiCTR2400080990 / Suspended早期临床1期IIT

An exploratory study of food grade cordycepin on the rapid treatment of anxiety disorder

开始日期2024-03-01

申办/合作机构-

ChiCTR2300075042 / Recruiting临床1期IIT

Safety evaluation and effective dose of PD-1 antibody combined with cordycepin in the treatment of advanced non-small cell lung cance

开始日期2022-07-30

申办/合作机构-

100 项与虫草素相关的临床结果

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100 项与虫草素相关的转化医学

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100 项与虫草素相关的专利（医药）

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1,444

项与虫草素相关的文献（医药）

2025-01-01·JOURNAL OF ETHNOPHARMACOLOGY

Evidence to support cultivated fruiting body of Ophiocordyceps sinensis (Ascomycota)'s role in relaxing airway smooth muscle

Article

ETHNOPHARMACOLOGICAL RELEVANCE:

Ophiocordyceps sinensis (O. sinensis) is a genus of Ascomycete fungus that is endemic to the alpine meadows of the Tibetan Plateau and adjoining Himalayas. It has been used traditionally as a tonic to improve respiratory health in ancient China as well as to promote vitality and longevity. Bioactive components found in O. sinensis such as adenosine, cordycepin, 3-deoxyadenosine, L-arginine and polysaccharides have gained increasing interest in recent years due to their antioxidative and other properties, which include anti-asthmatic, antiviral, immunomodulation and improvement of general health.

AIM OF THE STUDY:

This study's primary aim was to investigate the effect of a cultivated fruiting body of O. sinensis strain (OCS02®) on airways patency and the secondary focus was to investigate its effect on the lifespan of Caenorhabditis elegans.

MATERIALS AND METHODS:

A cultivated strain, OCS02®, was employed and the metabolic profile of its cold-water extract (CWE) was analysed through liquid chromatography-mass spectrometry (LC-MS). Organ bath approach was used to investigate the pharmacological properties of OCS02® CWE when applied on airway tissues obtained from adult male Sprague-Dawley rats. The airway relaxation mechanisms of OCS02® CWE were explored using pharmacological tools, where the key regulators in airway relaxation and constriction were investigated. For the longevity study, age-synchronised, pos-1 RNAi-treated wild-type type Caenorhabditis elegans at the L4 stage were utilised for a lifespan assay.

RESULTS:

Various glycopeptides and amino acids, particularly a high concentration of L-arginine, were identified from the LC-MS analysis. In airway tissues, OCS02® CWE induced a significantly greater concentration-dependent relaxation when compared to salbutamol. The relaxation response was significantly attenuated in the presence of NG-Nitro-L-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) and several K⁺ channel blockers. The longevity effect induced by OCS02® CWE (5 mg/mL and above) was observed in C. elegans by at least 17%.

CONCLUSIONS:

These findings suggest that the airway relaxation mechanisms of OCS02® CWE involved cGMP-dependent and cGMP-independent nitric oxide signalling pathways. This study provides evidence that the cultivated strain of OCS02® exhibits airway relaxation effects which supports the traditional use of its wild O. sinensis in strengthening respiratory health.

2024-12-01·BIORESOURCE TECHNOLOGY

Low-carbon and overproduction of cordycepin from methanol using engineered Pichia pastoris cell factory

Article

作者: Zhao, Bingjie ; Zhao, Guishen ; Li, Yu ; Pan, Meixi ; Guo, Yanbin ; Zhang, Yong

Cordycepin, a nucleoside analog, is widely used in medicine and health products. However, the production of cordycepin from Cordyceps militaris faces the challenges of low productivity and high rate of greenhouse gas emissions. In this study, by optimizing the cordycepin biosynthesis pathway through promoter combination, Kozak sequence, and enzyme fusion, enhancing the methanol assimilation capacity in peroxisomes, adjusting the synthesis of NADPH and ATP, and combining the enhanced supply of adenosine and 3'-AMP, the cordycepin high-yield strain Pp29 was constructed, which produced 1551.44 mg/L cordycepin by shake-flask fermentation. In fed-batch fermentation, Pp29 achieved the highest yield (8.11 g/L, 67.64 mg/g DCW, and 1.35 g/L/d) to date in 10 L fermenter, and the CO_2-eq emissions were 1.9-17.3 times lower than C. militaris and other yeast systems. This study provide basis for Pichia pastoris to be used as chassis cell for synthesizing cordycepin and other nucleoside analogs by methanol as carbon source.

2024-12-01·BIOORGANIC CHEMISTRY

Cordycepin alleviates diabetes mellitus-associated hepatic fibrosis by inhibiting SOX9-mediated Wnt/β-catenin signal axis

Article

作者: Wang, Yu ; Yan, Bingrong ; Chen, Shuang ; Suo, Jialiang ; Hou, Yuyang ; Shen, Tao ; Tang, Chenglun ; Ma, Bo ; Zhang, Qi ; Li, Jiaqi ; Ma, Beiting

Diabetes mellitus can induce liver injury and easily progress to liver fibrosis. However, there is still a lack of effective treatments for diabetes-induced hepatic fibrosis. Cordycepin (COR), a natural nucleoside derived from Cordyceps militaris, has demonstrated remarkable efficacy in treating metabolic diseases and providing hepatoprotective effects. However, its protective effect and underlying mechanism in diabetes-induced liver injury remain unclear. This study utilized a high-fat diet/streptozotocin-induced diabetic mouse model, as well as LX-2 and AML-12 cell models exposed to high glucose and TGF-β1, to explore the protective effects and mechanisms of Cordycepin in liver fibrosis associated with diabetes. The results showed that COR lowered blood glucose levels, enhanced liver function, mitigated fibrosis, and suppressed HSC activation in diabetic mice. Mechanistically, COR attenuated the activation of the Wnt/β-catenin pathway by inhibiting β-catenin nuclear translocation, and β-catenin knockdown further intensified this effect. Meanwhile, COR significantly inhibited SOX9 expression in vivo and in vitro. Knockdown of SOX9 downregulated Wnt3a and β-catenin expression at the protein and gene levels to exacerbate the inhibitory action of COR on HG&TGF-β1-induced HSCs activations. These results indicate SOX9 is involved in the mechanism by which COR deactivates the Wnt/β-catenin pathway in hepatic fibrosis induced by diabetes. Moreover, prolonged half-life time, slower metabolism and higher exposure of COR were observed in diabetes-induced liver injury animal model via pharmacokinetics studies. Altogether, COR holds potential as a therapeutic agent for ameliorating hepatic injury and fibrosis in diabetes by suppressing the activation of the SOX9-mediated Wnt/β-catenin pathway.

项与虫草素相关的新闻（医药）

2024-08-30

·Firstwordpharma

NuCana halts mid-stage colorectal study of chemotherapy derivative

NuCana said Thursday that a pre-planned initial analysis of the Phase II NuTide:323 trial revealed that NUC-3373 is unlikely to meet the primary endpoint of superior progression-free survival (PFS) versus a standard-of-care drug cocktail, prompting the company to shut down the study.NUC-3373 is a derivative of the nucleoside analogue 5-fluorouracil, a commonly used chemotherapy agent. NuCana was testing its candidate in combination with leucovorin, irinotecan and Avastin (bevacizumab). The experimental regimen was being compared against a standard treatment that combines those same three drugs with5-fluorouracil. According to NuCana, there were "prognostic imbalances favouring the control arm," though the company didn't elaborate on the specific imbalances. "We gained valuable knowledge from the NuTide:323 study which will inform our ongoing development programmes," CEO Hugh Griffith said. "These results highlight the challenges associated with developing new medicines for patients with complex and heterogeneous cancers such as metastatic colorectal cancer." The firm is also testing NUC-3373 in the Phase I/II NuTide:303 trial, which is exploring a combination of the candidate with either Merck & Co.'s Keytruda (pembrolizumab) or the chemotherapy docetaxel in patients with lung cancer.NuCana's pipeline also includes NUC-7738, a derivative of cordycepin designed to have long-lasting cytotoxic activity. At the annual European Society for Medical Oncology (ESMO) meeting next month, the company plans to share data from the Phase II NuTide:701 study of the asset in combination with Keytruda in patients with melanoma.

临床2期

2022-09-28

·生物探索

糖尿病损害男性生育！男性不育记得筛查是否存在这一疾病

摘要：糖尿病是一组由多病因引起的以慢性高血糖为特征的终身性代谢性疾病。根据相关数据统计，糖尿病并发症高达100多种，是目前已知并发症最多的一种慢性疾病。而既往研究表明，糖尿病不仅会通过导致性激素分泌障碍和降低睾丸的生精能力来影响男性生育力，而且糖尿病还可能会引起男性勃起功能障碍，进而降低男性生育能力。当下生育率的急转直下与各种原因导致的不孕不育也是息息相关，而在这其中，男性不育症又是其中一个大难题。国家统计局数据显示，我国育龄夫妇不孕不育率攀升至12%-18%，男性因素造成的不育占其中50%。因此，有必要探讨一下糖尿病与男性生育力之间的关系。目前，糖尿病引起的性功能障碍已经成为全球男性面临的一个主要生殖健康威胁，也是导致男性不育的一个主要原因。对于准备生育的夫妻来说，一定要注意糖尿病引起的勃起功能障碍。研究发现，在男性糖尿病患者中，约有75%的患者会出现勃起功能障碍这一并发症，其发病率是非糖尿病群体的2-5倍，且发病时间可提前至10-15年。并且随着糖尿病病程的延长，很可能会发展成为完全性阳痿，严重影响男性的生育能力。糖尿病影响男性生殖健康，严重或致不育由于高血糖和胰岛素缺乏的影响，1型糖尿病可能会影响男性的生育能力、性腺轴、精液参数和精子发生。并且动物和体外研究表明，胰岛素对性腺功能和精子发生很重要，而胰岛素缺乏是1型糖尿病患者的标志，因此可能会影响男性性腺功能。研究人员对1980年1月至2020年12月期间发表的文献进行回顾性分析，以期捋清1型糖尿病与男性生育能力的关系。他们发现，1型糖尿病患者尤其是患病时间比较长的患者，其自然生育率低于对照组。相关研究成果以“The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis”为题，发表在Andrology上。图1 研究成果（图源：[1]）在这项研究中，研究人员通过“1型糖尿病”、“胰岛素依赖性糖尿病”、“年轻糖尿病患者与男性生育能力”、“男性不育症”、“精液参数”等关键词，对1980年1月至2020年12月期间的相关文献进行搜集并分析，对比研究了患有1型糖尿病男性与健康男性的生育能力。其中四项研究评估了1型糖尿病对男性自然生育率的影响，Schiavi等人发现糖尿病组的平均自然生育率为2.5（范围0-4），Holstein等人发现患有1型糖尿病的男性中超过50%没有孩子，Sjöberg等人发现患有糖尿病男性的活产率低于对照组，Wiebe等人发现与对照组相比，较早被诊断出患有糖尿病的男性生育孩子的比例显著较低，也即在儿童期发病的男性，其生育率显著较低。九项研究分析了1型糖尿病男性患者的精液参数，这些研究表明，1型糖尿病患者的精液量、总精子数量和活力低于对照组；1型糖尿病患者的精子形态较差；1型糖尿病患者的精子活力差且存在缺陷的精子数量多；1型糖尿病患者的精子存在精子核DNA碎片和线粒体DNA缺失较多的情况；在患病超过10年的患者中，线粒体功能异常的精子比例增加。综合以上研究分析，有证据表明1型糖尿病可能在不同层面影响男性生殖健康，包括最终导致患者生育力降低的功能性精子改变。但是，关于1型糖尿病损害男性生育能力的机制仍尚未明确，需要进一步研究。虫草素可通过Sirt1/Foxo3a 通路改善糖尿病引起的睾丸损伤上个部分提到糖尿病会对男性生殖健康造成负面影响，那如何改善这种负面影响呢？有研究表明，虫草的提取物虫草素可以保护血睾丸屏障的完整性，抑制细胞凋亡，抵抗氧化应激，在糖尿病引起的男性睾丸损伤中或可发挥有效治疗作用。来自部分中国高校的研究学者试图通过研究，发现虫草素对高血糖引起的睾丸损伤的保护机制，相关研究成果以“Cordycepin, a major bioactive component of Cordyceps militaris, ameliorates diabetes-induced testicular damage through the Sirt1/Foxo3a pathway”为题发表在Andrologia上。他们发现，虫草素可以通过 SIRT1/Foxo3a信号通路调节下游抗氧化酶活性来改善高血糖引起的睾丸损伤，恢复血睾丸屏障，并改善生精功能[2]。图2 研究成果（图源：[2]）Sirtuin 1（SIRT1）是发现的第一个Sirtuin蛋白家族，是哺乳动物中一种关键的NAD+依赖性脱乙酰酶。研究表明，SIRT1可以通过脱乙酰作用直接或间接调节Foxo转录因子的活性。特别是，SIRT1可以使Foxo3a脱乙酰，以增强抵抗氧化应激的能力，这可能是糖尿病并发症最重要的潜在目标。此外，一些研究表明SIRT1与睾丸细胞活性之间存在广泛的关联。因此，寻找一种天然安全有效的SIRT1激活剂对预防糖尿病引起的睾丸损伤至关重要。在这项研究中，通过喂食C57BL/6雄性小鼠高脂饮食4周建立糖尿病模型，并连续5天腹腔注射50mg/kg链脲佐菌素，检查小鼠血糖水平，并使用血糖含量大于16.7 mmol/L的小鼠进行研究。正常组小鼠接受标准饮食和腹腔注射生理盐水，持续5天。糖尿病小鼠被分成三组，分别服用生理盐水、10mg/kg虫草素、20mg/kg虫草素，治疗8周后，对这些小鼠进行分析。研究发现：■ 虫草素减轻了糖尿病引起的小鼠睾丸损伤，虫草素显著逆转了小鼠睾丸体积和睾丸指数的下降，且虫草素治疗组显著提高了精子浓度，抑制精子头尾畸形率；■ 虫草素恢复了高血糖引起的血睾屏障破坏；■ 虫草素抑制了糖尿病诱导的睾丸细胞凋亡；■ 虫草素可预防糖尿病引起的睾丸氧化应激，所有虫草素治疗组小鼠睾丸组织中的MDA水平均显著低于未治疗糖尿病组；■ 虫草素主要是通过SIRT1/Foxo3a途径刺激睾丸中的抗氧化酶发挥保护作用。根据国际糖尿病联合会发布的数据，2019年全国20至79岁的成年人中，每11人就有1人患有糖尿病，预计到2045年，这一数字将增至7亿。随着糖尿病发病率的增加和治疗策略的限制，糖尿病引起的睾丸损伤已成为全球男性生殖健康的主要威胁。在本文中，我们有提到虫草素或许可以改善糖尿病引起的睾丸损伤，进而保护男性生育能力不受损害。但是其作用大小还无法验证，再加上每个人病情的特殊性，虫草素对于每位患者的保护性还有待商榷。撰文|木子久排版|风立宵End参考资料：[1]Facondo P, Di Lodovico E, Delbarba A, et al. The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis. Andrology. 2022 Mar;10(3):426-440. doi: 10.1111/andr.13140. Epub 2021 Dec 22. PMID: 34904793.[2]Huang T, Zhou Y, Lu X, et al. Cordycepin, a major bioactive component of Cordyceps militaris, ameliorates diabetes-induced testicular damage through the Sirt1/Foxo3a pathway. Andrologia. 2022 Feb;54(1):e14294. doi: 10.1111/and.14294. Epub 2021 Nov 22. Erratum in: Andrologia. 2022 Jul;54(6):e14430. PMID: 34811786. 本文系生物探索原创，欢迎个人转发分享。其他任何媒体、网站如需转载，须在正文前注明来源生物探索。往期精选围观突破！CAR-T再升级：iPSC可大规模生产通用型CAR-T，治愈多种癌症！热文有多少人是看了《亲爱的生命》，才意识到婚前基因检测对后代罕见病的重要性？热文造血干细胞实现人工制造，或可满足血液疾病对造血干细胞捐献的需求热文近90位专家呼吁：统一精液‍检查标准！热文发现罕见癌症特异性T细胞，TCR-T新锐完成1400万美元融资点击“阅读原文”，了解更多~

细胞疗法免疫疗法基因疗法

100 项与虫草素相关的药物交易

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外链

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-	虫草素	-	DB12156

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
淋巴细胞白血病	临床2期	-	Danisco Holdings (UK) Ltd.	-
淋巴细胞白血病	临床2期	-	National Cancer Institute	-
淋巴细胞白血病	临床2期	-	OncoVista Innovative Therapies, Inc.	-
TDT阳性急性淋巴细胞白血病	临床1期	美国	National Cancer Institute	1997-12-01
结直肠癌	临床前	中国	成都道博勤医药科技有限公司	2022-04-08
胃癌	临床前	中国	成都道博勤医药科技有限公司	2022-04-08