Current Issue

2025 Vol. 15, No. 2

News
Holistic integrative medicine declaration
Daiming Fan
2025, 15(2): 101230. doi: 10.1016/j.jpha.2025.101230
Abstract:
Commentary
Comment on “Integration of deep neural network modeling and LC-MS-based pseudo-targeted metabolomics as a practical strategy to differentiate ginseng species”
Li Ping
2025, 15(2): 101231. doi: 10.1016/j.jpha.2025.101231
Abstract:
Review paper
Application of spectroscopic technology with machine learning in Chinese herbs from seeds to medicinal materials: The case of genus Paris
Yangna Feng, Xinyan Zhu, Yuanzhong Wang
2025, 15(2): 101103. doi: 10.1016/j.jpha.2024.101103
Abstract:

To ensure the safety and efficacy of Chinese herbs, it is of great significance to conduct rapid quality detection of Chinese herbs at every link of their supply chain. Spectroscopic technology can reflect the overall chemical composition and structural characteristics of Chinese herbs, with the multi-component and multitarget characteristics of Chinese herbs. This review took the genus Paris as an example, and applications of spectroscopic technology with machine learning (ML) in supply chain of the genus Paris from seeds to medicinal materials were introduced. The specific contents included the confirmation of germplasm resources, identification of growth years, cultivar, geographical origin, and original processing and processing methods. The potential application of spectroscopic technology in genus Paris was pointed out, and the prospects of combining spectroscopic technology with blockchain were proposed. The summary and prospects presented in this paper will be beneficial to the quality control of the genus Paris in all links of its supply chain, so as to rationally use the genus Paris resources and ensure the safety and efficacy of medication.

Application of lipidomics in the study of traditional Chinese medicine
Yang Yang, Guangyi Yang, Wenpeng Zhang, Lingyi Xin, Jing Zhu, Hangtian Wang, Baodong Feng, Renyan Liu, Shuya Zhang, Yuanwu Cui, Qinhua Chen, Dean Guo
2025, 15(2): 101083. doi: 10.1016/j.jpha.2024.101083
Abstract:

Lipidomics is an emerging discipline that systematically studies the various types, functions, and metabolic pathways of lipids within living organisms. This field compares changes in diseases or drug impact, identifying biomarkers and molecular mechanisms present in lipid metabolic networks across different physiological or pathological states. Through employing analytical chemistry within the realm of lipidomics, researchers analyze traditional Chinese medicine (TCM). This analysis aids in uncovering potential mechanisms for treating diverse physiopathological conditions, assessing drug efficacy, understanding mechanisms of action and toxicity, and generating innovative ideas for disease prevention and treatment. This manuscript assesses recent literature, summarizing existing lipidomics technologies and their applications in TCM research. It delineates the efficacy, mechanisms, and toxicity research related to lipidomics in Chinese medicine. Additionally, it explores the utilization of lipidomics in quality control research for Chinese medicine, aiming to expand the application of lipidomics within this field. Ultimately, this initiative seeks to foster the integration of traditional medicine theory with modern science and technology, promoting an organic fusion between the two domains.

Exploring the potential protective role of anthocyanins in mitigating micro/nanoplastic-induced reproductive toxicity: A steroid receptor perspective
Jiaojiao Zhang, Wenyi Liu, Fuqiang Cui, Marjukka Kolehmainen, Jing Chen, Lei Zhang, Iman Zarei
2025, 15(2): 101148. doi: 10.1016/j.jpha.2024.101148
Abstract:

Microplastics and nanoplastics (MPs/NPs) are ubiquitous environmental pollutants that act as endocrine-disrupting chemicals (EDCs), raising significant concerns about their impact on human health. Research highlights the hazardous effects of MPs/NPs on both male and female reproductive systems, influencing germ cells, embryo development, and progeny. Additionally, studies show that MPs/NPs affect the gene expression of anabolic steroid hormones in vitro and in vivo, inducing reproductive toxicity through mechanisms such as oxidative stress and inflammation. Considering these adverse effects, identifying natural compounds that can mitigate the toxicity of MPs/NPs is increasingly important. Plants offer a wealth of antioxidants and anti-inflammatory compounds that can counteract these harmful effects. Among these, anthocyanins, natural colorants responsible for the vibrant hues of fruits and flowers, exhibit a wide range of biological activities, including antioxidant, anti-inflammatory, and anti-neoplastic properties. Moreover, anthocyanins can modulate sex hormone levels and alleviate reproductive toxicity. Cyanidin-3-glucoside (C3G), one of the most extensively studied anthocyanins, shows promise in reducing reproductive toxicity, particularly in females, and in protecting male reproductive organs, including the testis and epididymis. This protective effect is believed to result from its interaction with steroid receptors, specifically the androgen and estrogen receptors (ERs). These findings highlight the need to explore the mechanisms by which anthocyanins mitigate the reproductive toxicity caused by MPs/NPs. This review provides novel insights into how natural compounds can be leveraged to lessen the impact of environmental contaminants on human health, especially concerning reproductive health.

Natural products based on Correa's cascade for the treatment of gastric cancer trilogy: Current status and future perspective
Wenhao Liao, Jing Wang, Yuchen Li
2025, 15(2): 101075. doi: 10.1016/j.jpha.2024.101075
Abstract:

Gastric carcinoma (GC) is a malignancy with multifactorial involvement, multicellular regulation, and multistage evolution. The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa, in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis (Phase I) to gastric precancerous lesions (Phase II) and finally to GC (Phase III). Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa. Intervening in early gastric mucosal lesions, i.e., Phases I and II, will be the key strategy to prevent and treat GC. Natural products (NPs) have been an important source for drug development due to abundant sources, tremendous safety, and multiple pharmacodynamic mechanisms. This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis. In Phase I, NPs modulate Helicobacter pylori urease activity, motility, adhesion, virulence factors, and drug resistance, thereby inhibiting H. pylori-induced gastric mucosal inflammation and oxidative stress, and facilitating ulcer healing. In Phase II, NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle, apoptosis, autophagy, and angiogenesis to reverse gastric precancerous lesions. In Phase III, NPs suppress cell proliferation, migration, invasion, angiogenesis, and cancer stem cells, induce apoptosis and autophagy, and enhance chemotherapeutic drug sensitivity for the treatment of GC. In contrast to existing work, we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development, providing new ideas for gastric cancer prevention, treatment, and drug development.

Exosomal circRNAs: Deciphering the novel drug resistance roles in cancer therapy
Xi Li, Hanzhe Liu, Peiyu Xing, Tian Li, Yi Fang, Shuang Chen, Siyuan Dong
2025, 15(2): 101067. doi: 10.1016/j.jpha.2024.101067
Abstract:

Exosomal circular RNA (circRNAs) are pivotal in cancer biology, and tumor pathophysiology. These stable, non-coding RNAs encapsulated in exosomes participated in cancer progression, tumor growth, metastasis, drug sensitivity and the tumor microenvironment (TME). Their presence in bodily fluids positions them as potential non-invasive biomarkers, revealing the molecular dynamics of cancers. Research in exosomal circRNAs is reshaping our understanding of neoplastic intercellular communication. Exploiting the natural properties of exosomes for targeted drug delivery and disrupting circRNA-mediated pro-tumorigenic signaling can develop new treatment modalities. Therefore, ongoing exploration of exosomal circRNAs in cancer research is poised to revolutionize clinical management of cancer. This emerging field offers hope for significant breakthroughs in cancer care. This review underscores the critical role of exosomal circRNAs in cancer biology and drug resistance, highlighting their potential as non-invasive biomarkers and therapeutic targets that could transform the clinical management of cancer.

Mitochondria and myocardial ischemia/reperfusion injury: Effects of Chinese herbal medicine and the underlying mechanisms
Chuxin Zhang, Xing Chang, Dandan Zhao, Yu He, Guangtong Dong, Lin Gao
2025, 15(2): 101051. doi: 10.1016/j.jpha.2024.101051
Abstract:

Ischemic heart disease (IHD) is associated with high morbidity and mortality rates. Reperfusion therapy is the best treatment option for this condition. However, reperfusion can aggravate myocardial damage through a phenomenon known as myocardial ischemia/reperfusion (I/R) injury, which has recently gained the attention of researchers. Several studies have shown that Chinese herbal medicines and their natural monomeric components exert therapeutic effects against I/R injury. This review outlines the current knowledge on the pathological mechanisms through which mitochondria participate in I/R injury, focusing on the issues related to energy metabolism, mitochondrial quality control disorders, oxidative stress, and calcium. The mechanisms by which mitochondria mediate cell death have also been discussed. To develop a resource for the prevention and management of clinical myocardial I/R damage, we compiled the most recent research on the effects of Chinese herbal remedies and their monomer components.

Advances and mechanisms of traditional Chinese medicine and its active ingredients against antibiotic-resistant Escherichia coli infections
Shuo Yang, Ping Su, Lu Li, Shuang Liu, Yi Wang
2025, 15(2): 101117. doi: 10.1016/j.jpha.2024.101117
Abstract:

In clinical practice, antibiotics have historically been utilized for the treatment of pathogenic bacteria. However, the gradual emergence of antibiotic resistance among bacterial strains has posed a significant challenge to this approach. In 2022, Escherichia coli, a Gram-negative bacterium renowned for its widespread pathogenicity and high virulence, emerged as the predominant pathogenic bacterium in China. The rapid emergence of antibiotic-resistant E. coli strains has rendered antibiotics insufficient to fight E. coli infections. Traditional Chinese medicine (TCM) has made remarkable contributions to the health of Chinese people for thousands of years, and its significant therapeutic effects have been proven in clinical practice. In this paper, we provide a comprehensive review of the advances and mechanisms of TCM and its active ingredients against antibiotic-resistant E. coli infections. First of all, this review introduces the classification, antibiotic resistance characteristics and mechanisms of E. coli. Then, the TCM formulas and extracts are listed along with their active ingredients against E. coli, including extraction solution, minimum inhibitory concentration (MIC), and the antibacterial mechanisms. In addition, there is growing evidence supporting the synergistic therapeutic strategy of combining TCM with antibiotics for the treatment of antibiotic-resistant E. coli infections, and we provide a summary of this evidence and its underlying mechanisms. In conclusion, we present a comprehensive review of TCM and highlight its potential and advantages in the prevention and treatment of E. coli infections. We hold the opinion that TCM will play an important role in global health, pharmaceutical development, and livestock farming in the future.

Original article
Coupling of an Au@AgPt nanozyme array with an micrococcal nuclease-specific responsiveness strategy for colorimetric/SERS sensing of Staphylococcus aureus in patients with sepsis
Xueqin Huang, Yingqi Yang, Hanlin Zhou, Liping Hu, Annan Yang, Hua Jin, Biying Zheng, Jiang Pi, Jun Xu, Pinghua Sun, Huai-Hong Cai, Xujing Liang, Bin Pan, Junxia Zheng, Haibo Zhou
2025, 15(2): 101085. doi: 10.1016/j.jpha.2024.101085
Abstract:

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3’,5,5’-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this “on-to-off” triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense “hot spot” substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database
Xuan Li, Minwen Huang, Yue-Mei Zhao, Wenxin Liu, Nan Hu, Jie Zhou, Zi-Yi Wang, Sheng Tang, Jian-Bin Pan, Hian Kee Lee, Yao-zuo Yuan, Taijun Hang, Hai-Wei Shi, Hongyuan Chen
2025, 15(2): 101072. doi: 10.1016/j.jpha.2024.101072
Abstract:

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometry (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS). A high concentration of phosphate buffer mobile phase was used in the first-dimensional LC system to get the components well separated. For efficient and high-accuracy screening of CMS, a targeted method based on a self-constructed high resolution (HR) mass spectrum database of CMS components was established. The database was built based on the commercial MassHunter Personal Compound Database and Library (PCDL) software and its accuracy of the compound matching result was verified with six known components before being applied to genuine sample screening. On this basis, the unknown peaks in the CMS chromatograms were deduced and assigned. The molecular formula, group composition, and origins of a total of 99 compounds, of which the combined area percentage accounted for more than 95% of CMS components, were deduced by this 2D-LC-MS method combined with the MassHunter PCDL. This profiling method was highly efficient and could distinguish hundreds of components within 3 h, providing reliable results for quality control of this kind of complex drugs.

Supramolecular prodrug inspiried by the Rhizoma Coptidis-Fructus Mume herbal pair alleviated inflammatory diseases by inhibiting pyroptosis
Wenhui Qian, Bei Zhang, Ming Gao, Yuting Wang, Jiachen Shen, Dongbing Liang, Chao Wang, Wei Wei, Xing Pan, Qiuying Yan, Dongdong Sun, Dong Zhu, Haibo Cheng
2025, 15(2): 101056. doi: 10.1016/j.jpha.2024.101056
Abstract:

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

Natural product virtual-interact-phenotypic target characterization: A novel approach demonstrated with Salvia miltiorrhiza extract
Rui Xu, Hengyuan Yu, Yichen Wang, Boyu Li, Yong Chen, Xuesong Liu, Tengfei Xu
2025, 15(2): 101101. doi: 10.1016/j.jpha.2024.101101
Abstract:

Natural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.

Ginger protects against vein graft remodeling by precisely modulating ferroptotic stress in vascular smooth muscle cell dedifferentiation
Xiaoyu Yu, Weiwei Wu, Jingjun Hao, Yuxin Zhou, Deyang Yu, Wei Ding, Xuejuan Zhang, Gaoli Liu, Jianxun Wang
2025, 15(2): 101053. doi: 10.1016/j.jpha.2024.101053
Abstract:

Vein graft (VG) failure (VGF) is associated with VG intimal hyperplasia, which is characterized by abnormal accumulation of vascular smooth muscle cells (VSMCs). Most neointimal VSMCs are derived from pre-existing VSMCs via a process of VSMC phenotypic transition, also known as dedifferentiation. There is increasing evidence to suggest that ginger or its bioactive ingredients may block VSMC dedifferentiation, exerting vasoprotective functions; however, the precise mechanisms have not been fully characterized. Therefore, we investigated the effect of ginger on VSMC phenotypic transition in VG remodeling after transplantation. Ginger significantly inhibited neointimal hyperplasia and promoted lumen (L) opening in a 3-month VG, which was primarily achieved by reducing ferroptotic stress. Ferroptotic stress is a pro-ferroptotic state. Contractile VSMCs did not die but instead gained a proliferative capacity and switched to the secretory type, forming neointima (NI) after vein transplantation. Ginger and its two main vasoprotective ingredients (6-gingerol and 6-shogaol) inhibit VSMC dedifferentiation by reducing ferroptotic stress. Network pharmacology analysis revealed that 6-gingerol inhibits ferroptotic stress by targeting P53, while 6-shogaol inhibits ferroptotic stress by targeting 5-lipoxygenase (Alox5), both promoting ferroptosis. Furthermore, both ingredients co-target peroxisome proliferator-activated receptor gamma (PPARγ), decreasing PPARγ-mediated nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1) expression. Nox1 promotes intracellular reactive oxygen species (ROS) production and directly induces VSMC dedifferentiation. In addition, Nox1 is a ferroptosis-promoting gene that encourages ferroptotic stress production, indirectly leading to VSMC dedifferentiation. Ginger, a natural multi-targeted ferroptotic stress inhibitor, finely and effectively prevents VSMC phenotypic transition and protects against venous injury remodeling.

Hemodynamic disturbance and mTORC1 activation: Unveiling the biomechanical pathogenesis of thoracic aortic aneurysms in Marfan syndrome
Ming-Yuan Liu, Meili Wang, Junjun Liu, An-Qiang Sun, Chang-Shun He, Xin Cong, Wei Kong, Wei Li
2025, 15(2): 101120. doi: 10.1016/j.jpha.2024.101120
Abstract:

Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity—collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

Short communication
An economical and flexible chip using surface-enhanced infrared absorption spectroscopy for pharmaceutical detection: Combining qualitative analysis and quantitative detection
Jikai Wang, Pengfei Zeng, Haitao Xie, Suisui He, Xilin Xiao, Cuiyun Yu
2025, 15(2): 101076. doi: 10.1016/j.jpha.2024.101076
Abstract:
Permeable polydimethylsiloxane microneedles for the delivery of traditional Chinese medicine elemene
Qingchang Tian, Mengmeng Liu, Yiqiu Wang, Zhaoming Li, Daizhou Zhang, Tian Xie, Shuling Wang
2025, 15(2): 101094. doi: 10.1016/j.jpha.2024.101094
Abstract:
Identification of the fruit of Brucea javanica as an anti-liver fibrosis agent working via SMAD2/SMAD3 and JAK1/STAT3 signaling pathways
Di Yan, Liansheng Qiao, Wenting Huang, Xiaoling Zhang, Chengmei Ma, Quansheng Feng, Jing Cheng, Lan Xie
2025, 15(2): 101047. doi: 10.1016/j.jpha.2024.101047
Abstract:
Radiosynthesis and preclinical evaluation of [18F]AlF-labeled HBED-CC-FAPI derivatives for imaging of cancer-associated fibroblasts
Haiyan Hong, Yan Zhang, Jinping Qiao, Wensheng Zhang, Lin Zhu, Jiehua Xu
2025, 15(2): 101107. doi: 10.1016/j.jpha.2024.101107
Abstract: