Chinese Herbal MedicinesPub Date : 2026-04-01Epub Date: 2024-12-27DOI: 10.1016/j.chmed.2024.12.004
Ruihong Ma , Xiaogang Li , Xiaolei An , Juntao Li , Jianguo Zhu , Temuqile , Liping Zhan , Peiyang Zhou , Baolong Ren , Baoai Wang , Yuanyuan Sun , Wei Xiao , Meng Xu
{"title":"Shuxuening injection for acute ischemic stroke: Efficacy and safety − a randomized, double-blind, placebo controlled, multi-center clinical trial","authors":"Ruihong Ma , Xiaogang Li , Xiaolei An , Juntao Li , Jianguo Zhu , Temuqile , Liping Zhan , Peiyang Zhou , Baolong Ren , Baoai Wang , Yuanyuan Sun , Wei Xiao , Meng Xu","doi":"10.1016/j.chmed.2024.12.004","DOIUrl":"10.1016/j.chmed.2024.12.004","url":null,"abstract":"<div><h3>Objective</h3><div>To evaluate the efficacy and safety of Shuxuening injection, a Chinese remedy from <em>Ginkgo biloba</em>, in treating patients with acute ischemic stroke (AIS).</div></div><div><h3>Methods</h3><div>A randomized, double-blind, placebo-controlled, multi-center clinical trial was conducted from 21 November 2018 to 20 January 2022 in 31 participating research centers involving 446 patients with AIS. Patients received either a Shuxuening injection (experimental group) or a placebo (control group) alongside basic treatment (aspirin enteric-coated tablets). The primary efficacy endpoint was the percentage of patients with a modified Rankin scale (mRS) score ≤ 2 at 90-day post-stroke. The secondary efficacy endpoints were the changes in mRS, National Institute of Health stroke scale (NIHSS), and Barthel index (BI) scores, and the incidence of adverse events.</div></div><div><h3>Results</h3><div>The percentage of patients with mRS scores ≤ 2 at 90-day post-stroke was significantly higher in the experimental than in the control (<em>P</em> < 0.05) group. The percentage of patients with scores ≤ 1 at 90-day post-stroke was higher in the experimental group (<em>P</em> < 0.05). The change value of NIHSS scores in the experimental group was higher at 10-day post-treatment and 90-day post-stroke (<em>P</em> < 0.05). The percentage of NIHSS score reduction ≥ 50% was higher in the experimental group at 90-day post-stroke (<em>P</em> < 0.05). The change value of BI score and percentage of BI score ≥ 75 were higher in the experimental group at 90-day post-stroke (<em>P</em> < 0.05). Safety profiles did not differ between the groups.</div></div><div><h3>Conclusion</h3><div>Shuxuening injection effectively improves the functional outcome of patients, reduces disability rates, improves neurological deficits, enhances activities of daily living, and demonstrates good safety profiles.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 2","pages":"Pages 461-469"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617743","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-04-01Epub Date: 2026-02-04DOI: 10.1016/j.chmed.2026.02.001
Rubing Wang , Yanan Zhang , Huanyu Zhang , Wenqi Yang , Yaowu Su , Hongyan Jing , Juan Wang , Wenyuan Gao
{"title":"Biosynthetic pathway analysis of ginsenoiside Rh1 to notoginsenoside R2","authors":"Rubing Wang , Yanan Zhang , Huanyu Zhang , Wenqi Yang , Yaowu Su , Hongyan Jing , Juan Wang , Wenyuan Gao","doi":"10.1016/j.chmed.2026.02.001","DOIUrl":"10.1016/j.chmed.2026.02.001","url":null,"abstract":"","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 2","pages":"Pages 484-486"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-04-01Epub Date: 2025-04-17DOI: 10.1016/j.chmed.2025.04.004
Hualing Li , Wenlei Wang , Zhihui Zheng , Yuqian Zhang , Danting Li , Qin Su , Hailin Wei , Zehua Wang , Rui Min , Xinyue Zhang , Zihan Chen , Xiaoquan Wang , Pinghu Zhang
{"title":"Combined network pharmacology and biological verification to investigate anti-influenza A virus effect and potential mechanism of Pudilan Xiaoyan Oral Liquid","authors":"Hualing Li , Wenlei Wang , Zhihui Zheng , Yuqian Zhang , Danting Li , Qin Su , Hailin Wei , Zehua Wang , Rui Min , Xinyue Zhang , Zihan Chen , Xiaoquan Wang , Pinghu Zhang","doi":"10.1016/j.chmed.2025.04.004","DOIUrl":"10.1016/j.chmed.2025.04.004","url":null,"abstract":"<div><h3>Objective</h3><div>Influenza is a common respiratory disease affecting human health and life. Pudilan Xiaoyan Oral Liquid (PDL) has frequently been used to treat respiratory infections such as COVID-19, pharyngitis, and tonsillitis. However, its efficacy against influenza A virus (IAV) infection remains unclear. This study investigates the anti-IAV activity and potential mechanism of action of PDL.</div></div><div><h3>Methods</h3><div>The <em>in vitro</em> anti-IAV activity was investigated in a virus-infected MDCK (Madin-Darby canine kidney) cell model. The <em>in vivo</em> protective effect on AIV infection was evaluated in a virus-infected mice model. qRT-PCR was performed to examine the anti-inflammatory effects of the PDL. A network pharmacology method was used to investigate the underlying mechanism of PDL against IAV. Western blotting was performed to confirm the antiviral mechanism of PDL against IAV.</div></div><div><h3>Results</h3><div>Our findings indicated that PDL had a broad-spectrum anti-IAV effect <em>in vitro</em> and exhibited an excellent protective effect against IAV infection by significantly increasing the survival rate, extending the survival time, and reducing pathological lung tissue damage. Moreover, PDL effectively inhibited the mRNA expression of inflammatory factors in lung tissue. GO analysis revealed that the potential targets were primarily associated with defense response regulation, positive regulation of cytokine production, and positive regulation of responses to external stimulation. PPI analysis indicated that Sarcoma (SRC), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase1 (MAPK1), phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1), and epidermal growth factor receptor (EGFR) might be potential PDL targets against IAV infection. Mechanistically, inhibition of the Toll-like receptor 3 (TLR3)/myeloid differentiation primary response gene (88) (MyD88) signaling pathway to attenuate an excessive inflammatory response might be one of the primary mechanisms of PDL against IAV.</div></div><div><h3>Conclusion</h3><div>PDL efficiently suppressed <em>in vitro</em> IAV replication and provided protection against lethal influenza virus infection <em>in vivo</em>. Network pharmacology analysis revealed that the key PDL targets against influenza might be highly associated with biological processes, such as regulation of defense responses, cytokine production, and the Toll-like receptor signaling pathway. Mechanistically, regulating the TLR3/MyD88 signaling pathway may be one of the primary mechanisms of PDL against influenza virus infection. These findings indicate that PDL could be a potential therapeutic option for the clinical treatment of influenza viral infections.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 2","pages":"Pages 262-271"},"PeriodicalIF":8.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147617896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-05-23DOI: 10.1016/j.chmed.2025.05.005
Jun Li , Xuewen Zhu , Yupeng Du , Wenxiao Chen , Jing Xu , Ying Wang , Shasha Zhou , Zhichao Xu , Shuangcheng Ma , Zhenhao Li , Wei Sun , Yaolei Mi
{"title":"Comprehensive genomic identification and functional analysis of bHLH transcription factors in Ganoderma lucidum","authors":"Jun Li , Xuewen Zhu , Yupeng Du , Wenxiao Chen , Jing Xu , Ying Wang , Shasha Zhou , Zhichao Xu , Shuangcheng Ma , Zhenhao Li , Wei Sun , Yaolei Mi","doi":"10.1016/j.chmed.2025.05.005","DOIUrl":"10.1016/j.chmed.2025.05.005","url":null,"abstract":"<div><h3>Objective</h3><div>The basic helix-loop-helix (<em>bHLH</em>) transcription factors (TFs) are pivotal in regulating fungal growth, development, and secondary metabolism. However, the knowledge about the <em>Ganoderma lucidum bHLHs</em> (<em>GlbHLHs</em>) in ganoderic acid (GA) biosynthesis of <em>G</em>. <em>lucidum</em> was limited. This study aimed to explore the functions of <em>bHLH</em> genes in ganoderic acid biosynthesis during <em>G. lucidum</em> growth development.</div></div><div><h3>Methods</h3><div>First, the genome-wide identification of <em>GlbHLHs</em> was performed through Hidden Markov model searches and Two-way blast. Furthermore, through physicochemical properties, gene structure, and phylogenetic analysis, as well as combining the transcriptome and metabolome data from different developmental stages of <em>G. lucidum</em>, candidate <em>GlbHLHs</em> were screened. Subsequently, their regulatory roles in ganoderic acid biosynthesis were explored using yeast one-hybrid and dual-luciferase reporter assays.</div></div><div><h3>Results</h3><div>A total of 11 <em>GlbHLH</em> members were characterized in <em>G. lucidum</em>. The upstream promoter regions of these genes enriched hormones and abiotic stress responsive elements. Although individual ganoderic acid monomers demonstrated marked differences in accumulation patterns across specific growth phases and tissue types, overall, the total GA content was consistently higher in caps than in stipes throughout development. In addition, all <em>GlbHLH</em>s exhibited high expression in whole <em>G. lucidum</em> from the primordium to maturation stages. Among them, <em>GlbHLH5</em> and <em>GlbHLH7</em> showed the highest expression in any stage and highly correlated with key genes associated with GA pathway. Functional validation through dual-luciferase assays and yeast one-hybrid experiments had demonstrated that <em>GlbHLH5</em> activated the P2 region of the lanosterol synthase promoter, while <em>GlbHLH7</em> activated the promoters of squalene epoxidase and squalene synthase.</div></div><div><h3>Conclusion</h3><div>Compared to plants, <em>G. lucidum</em> harbored a small number of <em>bHLH</em> members but all high expression in any stages. Additionally, <em>GlbHLH5</em> and <em>GlbHLH7</em> with the highest expression among <em>GlbHLHs</em> showed activation in regulating the biosynthesis of GA. These results provide a theoretical reference for further research on ganoderic acid regulation in <em>G. lucidum</em>, and thereby providing a molecular foundation for enhancing ganoderic acid yield to optimize the medicinal value of <em>G. lucidum.</em></div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 200-211"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.chmed.2025.11.007
Yuwei Ma , Yaning Fu , Ge Bai , Shancen Zhao , Ya Tian , Ziyuan Zhao , Yan Wang , Zhichao Xu , Yong Chen , Zhoujie An , Ranran Gao
{"title":"Genome-wide identification and characterization of methyltransferase involved in benzylisoquinoline alkaloids biosynthesis from Menispermum dauricum","authors":"Yuwei Ma , Yaning Fu , Ge Bai , Shancen Zhao , Ya Tian , Ziyuan Zhao , Yan Wang , Zhichao Xu , Yong Chen , Zhoujie An , Ranran Gao","doi":"10.1016/j.chmed.2025.11.007","DOIUrl":"10.1016/j.chmed.2025.11.007","url":null,"abstract":"<div><h3>Objective</h3><div>Benzylisoquinoline alkaloids (BIAs) are valuable plant metabolites whose structural diversity largely depends on <em>O</em>-/<em>N</em>-methyltransferases (OMTs/NMTs). Although the CYP450-mediated backbone formation of BIAs was previously elucidated in <em>Menispermum dauricum</em> DC., the specific OMTs/NMTs responsible for their functional methylation remain unknown. This study aims to systematically identify and characterize these methyltransferases to define their roles in BIA biosynthesis.</div></div><div><h3>Methods</h3><div>Combining genomic and biochemical approaches, a genome-wide identification of methyltransferase (MT) genes was conducted using the published<!--> <em>M. dauricum</em> <!-->genome. The candidate MTs were functionally evaluated through <em>in vitro</em> enzymatic assays employing diverse BIA substrates to determine their methylation specificities. The substrate-binding modes of MdOMT1 and MdOMT11 were predicted and compared by protein modeling and molecular docking.</div></div><div><h3>Results</h3><div>Functional characterization of the 75 methyltransferases identified in the <em>M. dauricum</em> genome revealed four key enzymes (three OMTs and one NMT) that contribute to the diversification of BIA scaffolds through their distinct substrate specificities and positional preferences. Specifically, MdOMT1 preferentially catalyzed <em>O</em>-methylation at C7 position of 1-benzylisoquinolines (1-BIAs) and C2 position of tetrahydroprotoberberines. In contrast, MdOMT11 exhibited superior affinity and a strong preference for <em>O</em>-methylation at the C9 position of (<em>S</em>)-scoulerine. Meanwhile, MdNMT3 demonstrated effective <em>N</em>-methylation activity toward both 1-BIAs and tetrahydroprotoberberines.</div></div><div><h3>Conclusion</h3><div>This research elucidates the functional landscape of OMTs/NMTs in <em>M. dauricum</em>, revealing their crucial roles in BIA structural diversification. The newly identified enzymes provide valuable biocatalytic tools for synthetic biology approaches aimed at the sustainable and optimized production of high-value BIAs.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 97-109"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-03-19DOI: 10.1016/j.chmed.2025.03.004
Wen Liu , Biqiong Zhang , Zhengxi Hu , Si Yao , Yunpeng Zhao , Fengqing Wang , Yuanyuan Wang , Xinxin Yang , Jie Yin , Weiguang Sun , Qingyi Tong , Lianghu Gu , Yonghui Zhang
{"title":"Design and synthesis of butyrolactone V derivatives and its anti-inflammatory activity analysis","authors":"Wen Liu , Biqiong Zhang , Zhengxi Hu , Si Yao , Yunpeng Zhao , Fengqing Wang , Yuanyuan Wang , Xinxin Yang , Jie Yin , Weiguang Sun , Qingyi Tong , Lianghu Gu , Yonghui Zhang","doi":"10.1016/j.chmed.2025.03.004","DOIUrl":"10.1016/j.chmed.2025.03.004","url":null,"abstract":"<div><h3>Objective</h3><div>To design and synthesize an amount of butyrolactone V derivatives, evaluate the anti-inflammatory effects of all the derivatives, look for potential drugs that inhibit inflammatory bowel disease (IBD), and determine the structure-activity relationship (SAR).</div></div><div><h3>Methods</h3><div>The butyrolactone V derivatives were synthesized with high yield by oxidation reaction, substitution reaction, and esterification reaction in sequence, and the production of nitric oxide was assessed in RAW264.7 cells treated with the lipopolysaccharide and the compounds. Then, the target compounds were studied for their activity in dextran sodium sulfate (DSS)-induced ulcerative colitis.</div></div><div><h3>Results</h3><div>A total of three series of compounds encompassing 60 derivatives of the natural product butyrolactone V were designed and synthesized. The results showed that compounds <strong>5p</strong> and <strong>7e</strong> could alleviate the symptoms of DSS-induced colitis in mice, including alleviating diarrhea, inhibiting the reduction of colon length, and reducing tissue damage. The preliminary mechanism exploration indicated that compounds <strong>5p</strong> and <strong>7e</strong> could improve the symptoms of IBD in mice mainly by reducing the expression of chemokines and exerting anti-inflammatory effects.</div></div><div><h3>Conclusion</h3><div>This study reports the synthesis and the derivatization of butyrolactone V and analysis on anti-inflammatory activity. The most effective compounds <strong>5p</strong> and <strong>7e</strong> have the potential to be further developed as drugs to treat IBD.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 142-152"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-11-14DOI: 10.1016/j.chmed.2025.11.004
Keqian Li , Fangyu Xiang , Xin Yang , Mengqi Liu , Rui Long , Li Han , Ming Yang , Dingkun Zhang , Yanan He
{"title":"Advances in microbial biosynthesis of indirubin","authors":"Keqian Li , Fangyu Xiang , Xin Yang , Mengqi Liu , Rui Long , Li Han , Ming Yang , Dingkun Zhang , Yanan He","doi":"10.1016/j.chmed.2025.11.004","DOIUrl":"10.1016/j.chmed.2025.11.004","url":null,"abstract":"<div><div>Indirubin (IND), a bisindole alkaloid with remarkable pharmacological activities, has attracted significant attention in the pharmaceutical field due to its antileukemic, anti-inflammatory, and immunomodulatory properties. Currently, indirubin primarily relies on plant extraction and chemical synthesis, which are hindered by complex processes, low yields, and poor environmental compatibility. These challenges pose serious obstacles to clinical supply and sustainable industrial development. In recent years, microbial synthesis technology, which is based on synthetic biology and metabolic engineering, has provided a novel approach for the efficient production of indirubin. This method offers several advantages, including high efficiency, environmental sustainability, and eco-friendliness. Hence, this manuscript systematically summarizes the biosynthesis mechanisms of indirubin, the catalytic characteristics of key enzymes, the construction strategies of engineered bacteria, and the progress in fermentation condition. To address challenges such as the difficult separation of indirubin isomers, by-product inhibition, and industrialization bottlenecks, potential solutions are proposed, aiming to promote the green biomanufacturing of indirubin.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 45-58"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-11-12DOI: 10.1016/j.chmed.2025.11.002
Mengyue Wang , Haotian Wu , Li Xiang , Ranran Gao , Qinggang Yin , Yang Chu , Lan Wu , Yanyan Su , Gangqiang Dong , Yuhua Shi
{"title":"Natural novel vitamin C derivative, 2-O-β-D-glucopyranosyl-L-ascorbic acid: Resources, biosynthesis, and applications","authors":"Mengyue Wang , Haotian Wu , Li Xiang , Ranran Gao , Qinggang Yin , Yang Chu , Lan Wu , Yanyan Su , Gangqiang Dong , Yuhua Shi","doi":"10.1016/j.chmed.2025.11.002","DOIUrl":"10.1016/j.chmed.2025.11.002","url":null,"abstract":"<div><div>As the only naturally occurring stable derivative of <em>L-</em>ascorbic acid (AA; vitamin C), 2-<em>O</em>-<em>β</em>-<em>D</em>-glucopyranosyl-<em>L</em>-ascorbic acid (AA-2<em>β</em>G) is hydrolyzed <em>in vivo</em> to release active AA. AA-2<em>β</em>G exhibits strong antioxidant and antiphotoaging effects comparable to those of AA, and it plays a key role in maintaining organismal health. Owing to its superior stability and bioavailability, AA-2<em>β</em>G is considered as a promising, longer-lasting natural alternative to conventional vitamin C. It was first identified and is particularly abundant in <em>Lycii Fructus</em> (Gouqizi in Chinese) but has been detected in several crop plants. This review offers a comprehensive overview of recent advances in AA-2<em>β</em>G research, covering key aspects including discovery, structure, natural sources, extraction and detection methods, chemical and <em>in vitro</em> enzymatic synthesis, biosynthetic pathways, as well as applications in health care, skin care, and functional foods. Additionally, we highlight strategies for leveraging plant resources and enhancing AA-2<em>β</em>G biosynthesis, which are expected to accelerate future research and support the sustainable development and utilization of AA-2<em>β</em>G and other high-value natural products.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 77-88"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2025-11-12DOI: 10.1016/j.chmed.2025.11.003
Chenhao Jia , Junying Ma , Lingli Fang , Huanzi Guo , Meiling Ding , Yishuang Wang , Renxiang Tan
{"title":"Enhancement of levopimaradiene production in Escherichia coli via engineering isopentenol utilization pathway","authors":"Chenhao Jia , Junying Ma , Lingli Fang , Huanzi Guo , Meiling Ding , Yishuang Wang , Renxiang Tan","doi":"10.1016/j.chmed.2025.11.003","DOIUrl":"10.1016/j.chmed.2025.11.003","url":null,"abstract":"<div><h3>Objective</h3><div>Plant-derived terpenoid ginkgolides exhibit significant pharmacological efficacy, however, their extraction remains costly. Given that levopimaradiene is a key biosynthetic precursor to ginkgolides, its high-yield production via heterologous gene expression therefore establishes a critical foundation for scaling up their manufacture. This study primarily aims to enhance the yield of levopimaradiene in <em>Escherichia coli</em> (LB medium) by remodeling the unnatural isopentenol utilization pathway (IUP).</div></div><div><h3>Methods</h3><div>Plasmid construction was driven by the mechanism of homologous recombination, which utilizes recombinase to facilitate the ligation process. The expression of kinase was carried out using type 7 (T7) promoter and isopropyl <em>β</em>-<em>D</em>-1-thiogalactopyranoside (IPTG) as the inducer. The quantification of levopimaradiene produced by E. coli was determined by comparison with a standard curve that we constructed.</div></div><div><h3>Results</h3><div>Combining the selection of kinases, ribosome-binding site (RBS) screening, protein directed evolution and optimization of fermentation parameters, the production of levopimaradiene in <em>E. coli</em> was ultimately enhanced to 2691.3 mg/L, surpassing the highest reported titers of levopimaradiene with 6-fold in <em>E. coli</em> to date. Additionally, the engineered <em>E. coli</em> was designed to collaborate with farnesyl pyrophosphate (FPP) synthase and geranylfarnesyl pyrophosphate (GFPP) synthase to efficiently produce FPP and GFPP for sesquiterpene and sesterterpene synthesis.</div></div><div><h3>Conclusion</h3><div>Our work showcases a combinatorial engineering strategy that employs an IUP-enhanced <em>E. coli</em> chassis for the microbial production of levopimaradiene, as well as other natural terpenoids.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 89-96"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chinese Herbal MedicinesPub Date : 2026-01-01Epub Date: 2024-06-20DOI: 10.1016/j.chmed.2024.06.003
Wenjing Li , Yuan Gao , Jingjing Yan, Min Cai, Chenchen Zang, Zhuangzhuang Liu, Ximeng Li, Runlan Cai, Yun Qi
{"title":"Safflower yellow in Carthami Flos is responsible for Xuebijing Injection-induced immediate hypersensitivity reaction through activating complement C3","authors":"Wenjing Li , Yuan Gao , Jingjing Yan, Min Cai, Chenchen Zang, Zhuangzhuang Liu, Ximeng Li, Runlan Cai, Yun Qi","doi":"10.1016/j.chmed.2024.06.003","DOIUrl":"10.1016/j.chmed.2024.06.003","url":null,"abstract":"<div><h3>Objective</h3><div>Xuebijing Injection (XBJI) is mainly used for treating sepsis in China, and even COVID-19 recently. This study aimed to clarify the molecular mechanism(s) and identify the potential “common culprit(s)” for XBJI-caused immediate hypersensitivity reaction (IHR) which is the main type of its adverse reactions.</div></div><div><h3>Methods</h3><div>Antiserum against XBJI was prepared by intraperitoneal immunization in combination with aluminum adjuvant for five weeks. Antagonistic experiments were performed by using several antagonists against different mediators in Evans Blue leakage model. Propranolol-pretreated mice were used to determine the capacity of XBJI to trigger systemic IHR. Serum total IgE (tIgE) and mouse mast cell protease 1 (MCPT-1) levels, complement activation, and the levels of supernatant inflammatory mediators were determined by ELISAs. Lipopolysaccharide (LPS)-activated RAW264.7 macrophages were used for evaluating the anti-inflammatory activity of XBJI, while human mast cells (LAD2) were used for assessing the effect of XBJI on mast cell degranulation.</div></div><div><h3>Results</h3><div>Continuous treatment (<em>i.p.</em>) with XBJI along with aluminum adjuvant did not elevate the levels of serum tIgE and MCPT-1. <em>In vitro</em>, XBJI could not directly cause the degranulation of LAD2 cells. It induced a robust Evans Blue leakage after the first injection in mouse paw. Mechanism study demonstrated that antagonists for histamine H1/H2 receptors and complement C3a receptor counteracted XBJI-induced IHR. XBJI also directly activated complement C3 in human serum. Through screening five herbs of XBJI and the constituents, only safflower yellow (SY) in <em>Carthami Flos</em> was able to induce IHR. The discolored-XBJI not only did not induce IHR locally and systemically, but also could suppressing the production of proinflammatory mediators in LPS-activated RAW264.7 macrophages.</div></div><div><h3>Conclusion</h3><div>XBJI failed to induce immune IHR, but potently triggered non-immune IHR through direct activating complement C3 to provoke histamine release. SY in <em>Carthami Flos</em> was the underlying “common culprit” responsible for XBJI-caused IHR. The anti-inflammatory action of XBJI can be retained after decolorization. Our study provides a scientific basis for not only preventing and treating XBJI-caused IHR clinically, but also improving its production process.</div></div>","PeriodicalId":9916,"journal":{"name":"Chinese Herbal Medicines","volume":"18 1","pages":"Pages 188-199"},"PeriodicalIF":8.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}