Latest ArticlesSesquiterpenoids are a class of terpenoids composed of 15 carbon atoms, with a basic framework formed by three C5 isoprene units. They exhibit diverse skeletal structures and an exceptionally rich variety of types. These compounds are widely distributed in plants and serve as bioactive metabolites in diverse medicinal species, demonstrating various pharmacological activities such as anti-tumor, antibacterial, and anti-inflammatory. The elucidation of biosynthetic pathways, their heterologous reconstruction, and the sustainable production of bioactive sesquiterpenoids have emerged as research focal points. In recent years, substantial advancements have been made in the field of sesquiterpenoid biosynthesis. Based on an overview of their biosynthetic pathways, this review provides a comprehensive progress in synthetic biology research on sesquiterpenoids derived from medicinal plants. This review summarizes the status of the heterologous biosynthesis of representative plant-derived sesquiterpenoids, and discusses the major bottlenecks along with their corresponding optimization strategies and future perspectives.
Toxic Chinese medicines constitute a significant component of the traditional Chinese medicine system. Taking aristolochic acid-containing herbs as an example, their clinical application and industrial development face severe challenges due to safety incidents caused by aristolochic acid-containing components. The Pharmacopoeia of the People's Republic of China has deleted relevant varieties based on drug safety considerations, which, while mitigating medication risks, also results in the waste of medicinal resources. Existing methods such as processing and combination therapy also have limitations in reducing the toxicity of these herbs, including limited efficacy and difficulties in standardizing processes, making it challenging to balance toxicity control with the preservation of pharmacological effects. Based on this, this paper systematically reviews the deletion of herbal materials and proprietary Chinese medicine formulations from the last five editions of the Chinese Pharmacopoeia, summarizing the medicinal value and controversies surrounding herbs derived from the Aristolochia genus, the toxic mechanisms of aristolochic acid, and existing detoxification methods along with their limitations. Addressing these limitations, this paper proposes application strategies for gene editing, enzyme engineering, and fermentation engineering in reducing the toxicity of Aristolochia and other Chinese medicinal herbs, from the perspective of modern biotechnology, and explores new pathways for the precise regulation of the synthesis and degradation of toxic components. Compared with traditional detoxification methods, the use of modern biotechnology holds promise for precisely regulating the synthesis or degradation of toxic components, thereby reducing toxicity while preserving the overall therapeutic efficacy of the herbal materials, with the aim of achieving "detoxification while preserving efficacy". Future efforts should be intensified to verify the botanical sources of toxic Chinese herbal medicines, elucidate the biosynthetic pathways of toxic components, and investigate their toxic mechanisms. Additionally, the development and utilization of toxic Chinese herbal resources should be advanced to promote the high-quality development of traditional Chinese medicine through inheritance, innovation, modernization, and internationalization.
Pharmacokinetic studies of traditional Chinese medicine polysaccharides (TCMPs) are essential for elucidating the material basis of their pharmacological effects. A central challenge in this field lies in the paradox between their low oral bioavailability and significant systemic efficacy. Research has demonstrated that TCMPs exhibit low plasma concentrations following oral administration, and their therapeutic effects are largely independent of direct prototype absorption, instead being mediated through indirect mechanisms such as gut microbiota-derived metabolites and immunomodulation. In terms of distribution, TCMPs selectively target organs rich in mononuclear phagocytes, such as the liver and spleen, where they engage pattern recognition receptors to initiate immune regulation. Their metabolism involves a synergistic action between host enzymes and gut microbiota, with fecal excretion serving as the primary elimination route. A groundbreaking study by Ding et al. has recently provided direct evidence that specific structural types of TCMPs, such as 1, 3- and 1, 4-linked glucans, can be absorbed as intact macromolecules via a clathrin/dynamin-1/Rab5-mediated endocytic pathway, offering a mechanistic explanation for their systemic efficacy. Current research continues to face challenges, including insufficient sensitivity of analytical methods and the complexity of metabolic networks. Future integration of highly sensitive analytical techniques, multi-omics approaches, and artificial intelligence will drive the field toward more precise and systematic investigation, facilitating the clinical translation of TCMPs.
In recent years, conjugated drugs have become a hotspot in drug research and development due to their precise target binding. Radionuclide drug conjugates (RDC) are an emerging class of targeted conjugated drugs that combine diagnostic and therapeutic functions, representing a new drug type with immense development potential. Due to structural differences, RDC drugs exhibit distinct in vivo processes — absorption, distribution, metabolism, excretion, and toxicity (ADMET) — as well as unique bioanalytical methods compared to small molecule drugs. Starting from the analysis of the physicochemical properties of RDC, this article analyzed the pharmacokinetic characteristics and its application in the PK model selection of RDC and summarized the bioanalysis methods of such drugs, aiming to promote further development of RDC.
Metastasis is the leading cause of cancer deaths. It involves intricate interactions between circulating tumour cell (CTC) and blood components such as platelets, neutrophils and macrophages. This review first summarizes how CTC interact with these cells to promote their survival, immune evasion and seeding in distant organs. We then focus on recent advances in nanodelivery systems designed to counteract these processes — including the targeted elimination of single CTC, disruption of CTC homotypic clusters, blocking of CTC-platelet/neutrophil aggregates, and inhibition of neutrophil extracellular traps (NETs). Various strategies, such as ligand-mediated targeting, biomimetic cell membrane coating, and stimuli-responsive release, are critically discussed. Finally, we highlight key challenges and future directions for translating these systems into clinical anti-metastatic therapies.
Natural plant essential oils, as secondary metabolites of plants, possess hydrophobicity and volatility, and exhibit a wide range of biological activities, including antibacterial, antioxidant, anti-inflammatory, anti-aging, and antitumor effects. They are considered potential alternatives to chemically synthesized drugs. However, their poor stability and low water solubility limit clinical applications. Nanotechnology, through the construction of delivery systems such as liposomes, nanoemulsions, nanogels, and polymeric nanoparticles, significantly improves the stability, bioavailability, and targeting ability of essential oils, thereby enhancing their pharmacological activity and reducing toxic side effects. This review systematically summarizes the chemical composition, biological activity mechanisms, and recent advances in nanoformulations of natural plant essential oils, with a particular focus on the application strategies and effects of nanodelivery systems in improving essential oil performance. Furthermore, it highlights their translational potential and future development directions in modern medicine.
Ginsenoside Rg3 possesses a variety of pharmacological activities. However, ginsenoside Rg3 has poor water solubility, which limits its full exertion of pharmacological effects. Existing delivery systems can not only improve the solubility of ginsenoside Rg3 but also leverage the unique advantages of each delivery system, enabling ginsenoside Rg3 to exert its pharmacological effects more effectively. This review focuses on the impact of ginsenoside Rg3 delivery systems, summarizes and compares the pharmacodynamics and pharmacokinetics of ginsenoside Rg3, and highlights the advantages of various delivery systems, provides a basis for the selection of ginsenoside Rg3 delivery systems, and serves as a cornerstone for the full development of ginsenoside Rg3.
Coxsackievirus B3 is a major pathogen responsible for viral myocarditis and is associated with various severe diseases, including dilated cardiomyopathy and pancreatitis. However, no vaccines or specific drugs have been approved for CVB3 infection to date. High content screening technology, which integrates confocal microscopy with multidimensional intelligent image analysis, offers significant advantages for drug screening. In this study, utilizing an EGFP-CVB3 reporter virus, we successfully established a stable and reliable quantitative high-content imaging system for screening anti-CVB3 drugs. This system enables the simultaneous acquisition of multi-parametric data at the single-cell level, including infection rate, cell morphology, and organelle status. The assay was validated using known positive compounds. In conclusion, this system facilitates high-throughput screening of candidate compounds against CVB3 within a single viral life cycle, providing a rapid and sensitive technological tool to accelerate the discovery of anti-CVB3 drugs.
Tumor necrosis factor receptor-associated factor 2 (TRAF2) is a central signaling adaptor that integrates multiple oncogenic pathways and represents potential target for cancer therapy. In this study, leveraging the extensive protein-protein interaction network of TRAF2, 100 "undruggable" key tumor-associated proteins were selected to screen for TRAF2 interactors. It was found that cytokine receptor-like factor 2 (CRLF2) is a novel interacting protein of TRAF2, and the liquidambaric acid (LDA), which can directly target TRAF2, can inhibit the TRAF2/CRLF2 interaction. Binding site studies revealed that CRLF2 binds to the TRAF domain of TRAF2 and can be blocked by LDA. Functional studies of CRLF2 indicated that TRAF2 is a key protein in the CRLF2-STAT3 (signal transducer and activator of transcription 3) signaling pathway, and LDA can regulate CRLF2-related STAT3 phosphorylation. In summary, this study reveals the TRAF2-mediated tumor protein interaction network and elucidates a new mechanism by which LDA exerts antitumor effects by inhibiting TRAF2/CRLF2 interaction to regulate the STAT3 signaling pathway. It also provides new theoretical guidance and potential strategies for the development of anti-tumor drugs targeting undruggable targets.
Salidroside (SAL), a principal active constituent of the medicinal plant Rhodiola crenulata, exerts diverse pharmacological activities including antioxidation, anti-inflammation, and anti-aging. However, its protective efficacy against liver injury and the underlying molecular mechanisms remain incompletely elucidated. The low oral bioavailability of SAL implies potential interactions with the gut microbiota. Therefore, this study focused on the metabolic transformation of SAL mediated by the gut microbiota. The results demonstrated that SAL is metabolized to tyrosol (TYR) in the gut microbiota. Virtual molecular docking and pure enzyme metabolic experiments further validated the critical role of β-glucosidase (β-G) in this transformation process. In vitro cellular experiments have demonstrated that SAL and its primary metabolite TYR exert a synergistic hepatoprotective effect. Based on network pharmacology screening, hub targets including NF-κB1, ESR1, BCL2, MMP9, and TLR4 were revealed. Furthermore, SAL intervention significantly increased the levels of short-chain fatty acids (SCFAs) by the gut microbiota in an in vitro culture system. Untargeted metabolomics analysis suggested that SAL may reshape the metabolic profile of the gut microbiota by modulating pathways including the urea cycle and tryptophan metabolism. This study provides a novel perspective for a deeper understanding of the hepatoprotective mechanism of SAL and offers valuable scientific evidence for future clinical translational research on natural medicines. The experimental protocol was approved by the Laboratory's Institutional Animal Care and Use Committee of the Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00009927).
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