Volume 17,Issue 3,2025 Table of Contents

1 Epigenetics and traditional Chinese medicine: A noteworthy research area

Thomas Efferth

2025, 17(3):409-413. DOI: https://doi.org/10.1016/j.chmed.2025.05.004

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2 Unraveling bioactive potential and production in Ganoderma lucidum through omics and machine learning modeling

Sonali Khanal a , Anand Kumar b , Pankaj Kumar c , Pratibha Thakur d , Atul M. Chander e , Rachna Verma f , g , Ashwani Tapwal d , Vinay Chauhan c , Dinesh Kumar a , g , ? , Deepak Kumar b , ?

2025, 17(3):414-427. DOI: https://doi.org/10.1016/j.chmed.2025.05.003

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Ganoderma lucidum, a medicinal mushroom renowned for its production of a diverse array of compounds, accounts for the pharmacological effects including anti-inflammatory, antioxidant, immunomodulatory, and anticancer characteristics. Thus, it is recognized as a valuable species of interest in the pharmaceutical and nutraceutical industries due to its important medicinal properties. Recent advances in omics technologies such as genomes, transcriptomics, proteomics, and metabolomics have considerably increased our understanding of the bioactives in G. lucidum. This review explores the application of molecular breeding techniques to enhance both the yield and quality of G. lucidum across the food, pharmaceutical, and industrial sectors. The article discusses the current state of research on the use of contemporary omics technologies which studies and highlights future research directions that may increase the production of bioactive compounds for their therapeutic potential. Additionally, predictive methods with computational studies have recently emerged as effective tools for investigating bioactive constituents in G. lucidum, providing an organized and cost-effective strategy for understanding their bioactivity, interactions, and possible therapeutic uses. Omics and machine learning techniques can be applied to identify the candidates for pharmaceutical applications and to enhance the production of bioactive compounds in G. lucidum. The quantification and production of the bioactive compounds can be streamlined by the integrating computational study of bioactive compounds with non-destructive predictive machine learning models of the same. Synergistically, these techniques have the potential to be a promising approach for the future prediction of the bioactive constituents, without compromising the integrity of the fungal organism.

3 Curcumae Rhizoma: An anti-cancer traditional Chinese medicine

Yu Luo a , Lin Zhu a , Zhengyu Ren a , Jian Xiao b , Erwei Hao b , Jiahong Lu a , Jinmin Zhao c , Chun Yao b , ? , Yitao Wang a , d , Hua Luo a , c , ?

2025, 17(3):428-447. DOI: https://doi.org/10.1016/j.chmed.2025.04.006

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Curcumae Rhizoma, derived from the rhizome of Curcuma phaeocaulis, Curcuma kwangsiensis and Curcuma wenyujin, was called Ezhu in China. In the past, Curcumae Rhizoma extracts were obtained through water decoction or alternative methods, which showed significant anti-cancer effects. However, the mixed extracts contain various compound components of Curcumae Rhizoma, leading to an ambiguous mechanism of action for Curcumae Rhizoma extracts anti-cancer. Contemporary researchers have extracted the chemical components of Curcumae Rhizoma separately for experimental verification of its active ingredients in the anti-cancer field. Numerous studies demonstrated that curcumol, germacrone, b-elemene, and curcumin in Curcumae Rhizoma extracts have significant governing effects in anti-cancer activities. Pharmacological studies have shown that Curcumae Rhizoma suppresses cancer cell proliferation, invasion, and migration, triggering apoptosis and regulating cellular autophagy to achieve anticancer effects. Here, we summarized the research progress of Curcumae Rhizoma on anti-cancer effects from 2013 to 2022, aiming to explore the deeper molecular mechanisms of Curcumae Rhizoma’s active components in cancer treatment.

4 Mechanisms and benefits of phytochemicals as an alternative therapeutic strategy in female cancers

Yufan Zhao a , b , c , Shimenghui Deng a , b , c , Danli Cao a , b , c , Caiji Lin a , b , c , Mengzhi Xu a , b , c , Jiaxing Wang a , b , c , Lingjie Luo a , b , c , Shulin Liu a , b , c , e , f , ? , Huidi Liu a , b , c , d , f , ?

2025, 17(3):448-463. DOI: https://doi.org/10.1016/j.chmed.2025.04.002

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Cancer is a highly deadly disease, with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer being the most prevalent in women. However, traditional cancer treatments present challenges due to their strong toxic side effects and adverse reactions. Numerous studies have demonstrated that natural products derived from various plants possess therapeutic and preventive properties against cancer. These phytochemicals have been extensively investigated as a potential alternative to conventional chemotherapy drugs, owing to their safety and efficacy. This article provides a comprehensive review of the recent advances in the chemoprevention and mechanisms of phytochemicals against the four major female cancers. The focus will be on how these phytochemicals regulate cancer cell proliferation, apoptosis, invasion, and metastasis to impede cancer progression. Given their extensive clinical applications, phytochemicals hold great promise in the field of cancer treatment. It hopes that this review will inspire more researchers to explore the potential of these natural compounds in combating female cancers.

5 Research progress of regulating intestinal flora by traditional Chinese medicine in treating coronary heart disease

Qiwen Lu a , Sang Luo a , Chengyan Guan a , Hao Zhang a , Haoyue Jia a , Qiang Wan b , ?

2025, 17(3):464-472. DOI: https://doi.org/10.1016/j.chmed.2025.04.007

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Coronary atherosclerotic heart disease is a major cardiovascular condition driven by atherosclerosis, distinguished by chronic inflammation and dysregulated lipid metabolism. The gut microbiota plays an essential role in human health and disease, with research indicating a strong association between gut microbial metabolism and the development and progression of coronary heart disease. This article provides a review of the relationship between gut microbiota and coronary heart disease, as well as the mechanisms by which traditional Chinese medicine regulates digestive tract microbiota to treat coronary heart disease, which systematically explains how the gut microbiota, through metabolic products and immune regulation, contributes to the occurrence and progression of coronary heart disease, and summarizes recent advances in research on traditional Chinese medicine’s regulation of gut microbiota for treating coronary heart disease. It aims to provide further reference and insights for exploring the relationship between gut microbiota and coronary heart disease, as well as traditional Chinese medicine approaches for treating coronary heart disease.

6 Role of borneol as enhancer in drug formulation: A review

Manqun Tang a , b , Wenwei Zhong a , , Liwei Guo c , Haoran Zeng c , Yuxin Pang a , b , d ,

2025, 17(3):473-483. DOI: https://doi.org/10.1016/j.chmed.2024.04.003

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As a traditional Chinese medicine (TCM), borneol has shown superior ability for anti-inflammatory and analgesic activities when coupled with other active ingredients from ancient times. Furthermore, borneol is believed to improve blood concentration and bioavailability of drugs. Thus, it has been paired with various TCM formulas since ancient time. The physiological barriers in human can cause significant limitations in drug efficiency as the drug is primarily restricted from entering into blood and brain. Borneol has been proven to enhance the permeability of biological barriers such as the blood–brain, transdermal, corneal, and intestinal barriers. Moreover, growing interest has been shown in the drug delivery system design for trans-barrier transport involving borneol. Nano drug delivery system with increased surface area and improved active sites, has been applied to increase the bioactivity of water insoluble drugs. Nano-drug delivery system has been used to enhance drug efficacy by reducing the time of action as compared to conventional administration approach of TCM formulas. Given its ability to enhance crossbarrier permeation and drug efficacy, borneol has been integrated into TCM formulas of drug delivery system for precise and prolonged targeting at tumor sites. However, the design and preparation of a drug delivery system consisting of borneol still face great challenges. Current research fails to unravel the difference in mechanism of action between nano-drug delivery systems comprised of borneol and conventional drug systems coupled with borneol. Enhanced penetration of borneol in drug delivery system is rarely verified compared to conventional administration with identical drug formulation consisting of borneol regarding dosage and medical indications. This study outlines the current state of research on the properties, formulation and pharmacological effects of borneol, allowing cross-comparison of borneol coupled with single compound and classical TCM formulas for various medical indications. This study aims to provide insights into the design of borneol-based enhanced cross-barrier delivery drug formulation, and the potential development of nano-drug system for TCM formulas with borneol for enhanced bioavailability.

7 Unveiling secrets of traditional Chinese medicine: Cutting-edge techniques in component analysis

Tingting Zhou

2025, 17(3):484-487. DOI: https://doi.org/10.1016/j.chmed.2025.05.006

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Chemical component analysis is a critical challenge in Chinese herbal medicine research, involving the qualitative and quantitative identification of complex constituents in traditional Chinese medicine (TCM). However, traditional analytical methods are insufficient for efficient and comprehensive analysis of complex composition of TCM. Limitations exist in sample preparation, instrumental technology, data processing, and activity-related quality marker research. Recent advancements have significantly improved analytical precision, enabling more comprehensive profiling of TCM components. New pretreatment methods improve extraction efficiency and detection sensitivity, while novel instrumental technologies, such as mass spectrometry imaging, preserve spatial information lost in homogenization. AI enhances data interpretation, improving accuracy and efficiency. Online activity analysis links chemical composition with bioactivity, overcoming the limitations of purely chemical profiling and enabling a more comprehensive evaluation of TCM efficacy. This perspective provides an overview of the development trends in component analysis, aiming to advance the field and support TCM modernization.

8 Anthraquinones of Cassiae Semen alleviate lipid accumulation in obesity by regulating brown adipose tissue and liver function

Yijie Li a , Ruiyu Wu b , Xin Li b , Jianan Li a , Yinhao Zhang a , Yanbo Huang c , Guifang Fan b , Xiaojiaoyang Li a , ?

2025, 17(3):488-499. DOI: https://doi.org/10.1016/j.chmed.2025.02.003

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Objective: Cassiae Semen (CS, Juemingzi in Chinese) is a widely used traditional Chinese medicine with a variety of pharmacological effects. This study aimed to investigate the potential therapeutic effects and molecular mechanisms of anthraquinones of CS (AQS) for adiposity. Methods: The chemical components of the AQS were determined using high-performance liquid chromatography (HPLC). Network pharmacology analysis was used to predict potential anti-obesity targets of action for AQS. We constructed high fat with high sugar water diet-induced obese mice and observed their body weight and whole-body lipid metabolism to evaluate the efficacy of AQS in promoting lipid metabolism. Subsequently, the epidermal temperature at the brown adipose tissue (BAT) before and after cold stimulation was observed and the expression of lipid metabolism-related genes in the liver and BAT tissues was detected to clarify the mechanism of action of AQS. Results: Network pharmacology analysis showed that AQS was involved in the regulation of liver and adipose tissue function under obesity. Pathological and biochemical results showed that AQS reduced lipid accumulation in the liver and adipose tissue induced by an unhealthy diet. With the increase of cold tolerance, the volume and weight of BAT were increased by AQS, suggesting that it regulated the body heat production dominated by BAT. After AQS treatment, the levels of genes related to uncoupling protein1 (UCP1) mediated adaptive thermogenesis in BAT tissues and lipid metabolism in the liver were also increased, which further proved that AQS activated BAT function to promote lipid metabolism in the whole body. Conclusion: This study revealed the pharmacological effects of AQS, thereby providing a scientific basis for regulating BAT thermogenesis and liver lipid metabolism to alleviate obesity and providing clues for further exploring the application of natural active ingredients in the treatment of metabolismrelated diseases.

9 Qingjie Fuzheng Granule prevents colitis-associated colorectal cancer by inhibiting abnormal activation of NOD2/NF-κB signaling pathway mediated by gut microbiota disorder

Bin Huang a , b , Honglin An a , b , Mengxuan Gui a , b , Yiman Qiu a , b , Wen Xu d , Liming Chen a , c , Qiang Li c , Shaofeng Yao a , Shihan Lin d , Tatyana Aleksandrovna Khrustaleva e , Ruiguo Wang b , d , ? , Jiumao Lin a , b , ?

2025, 17(3):500-512. DOI: https://doi.org/10.1016/j.chmed.2025.04.001

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Objective: This study investigates the efficacy and mechanisms of Qingjie Fuzheng Granules (QFG) in inhibiting colitis-associated colorectal cancer (CAC) development via RNA sequencing (RNA-seq) and 16S ribosomal RNA (rRNA) correlation analysis. Methods: CAC was induced in BALB/c mice using azoxymethane (AOM) and dextran sulfate sodium (DSS), and QFG was administered orally to the treatment group. The effects of QFG on CAC were evaluated using disease index, histology, and serum T-cell ratios. RNA-seq and 16S rRNA analysis assessed the transcriptome and microbiome change. Key pharmacodynamic pathways were identified by integrating these data and confirmed via Western blotting and immunofluorescence. The link between microbiota and CACrelated markers was explored using linear discriminant analysis effect size and Spearman correlation analysis. Results: Long-term treatment with QFG prevented AOM/DSS-induced CAC formation, reduced levels of interleukin (IL)-1b, tumor necrosis factor-alpha (TNF-a), IL-6, and interferon c (IFN-c), and increased CD3+ and CD4+/CD8+ T cells ratio, without causing hepatic or renal toxicity. A 16S rRNA analysis revealed that QFG rebalanced the Firmicutes/Bacteroidetes ratio and mitigated AOM/DSS-induced microbiota disturbances. Transcriptomics and Western blotting analysis identified the nucleotide-binding oligomerization domain-containing protein 2 (NOD2)/nuclear factor kappa-B (NF-jB) pathway as key for QFG’s treatment against CAC. Furthermore, QFG decreased the abundance of Bacilli, Bacillales, Staphylococcaceae, Staphylococcus, Lactobacillales, Aerococcus, Alloprevotella, and Akkermansia, while increasing Clostridiales, Lachnospiraceae, Lachnospiraceae_NK4A136_group, Ruminococcaceae, and Muribaculaceae, which were highly correlated with CAC-related markers or NOD2/NF-jB pathway. Conclusion: By mapping the relationships between CAC, immune responses, microbiota, and key pathways, this study clarifies the mechanism of QFG in inhibiting CAC, highlighting its potential for clinical use as preventive therapy.

10 Riboflavin metabolism involved into comparison of therapeutic action of wild-simulated and transplanted Astragali Radix to treat chronic atrophic gastritis rats based on endogenous-xenobiotics metabolism

Kaidi Fan a , b , Xu Lian a , b , Weicong Zhang c , d , Xuemei Qin a , b , , Yuetao Liu a , b , ?

2025, 17(3):513-528. DOI: https://doi.org/10.1016/j.chmed.2025.03.006

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Objective: Astragali Radix (AR, Huangqi in Chinese) has been utilized generally as a bulk drug for the treatment of chronic atrophic gastritis (CAG) in China. The efficacy of wild-simulated AR (WAR) and transplanted AR (TAR) commercially available is unclear. This study aimed to further clarify the therapeutic action of WAR and TAR to treat CAG rats based on endogenous-xenobiotics metabolism. Methods: Ultra-high performance liquid chromatography coupled with quadrupole-time of flight mass spectrometer (UHPLC-Q-TOF/MS) based metabolomics had been used to analyze the cecal contents metabolic features and metabolic process differences of two ARs in the treatment of CAG. Results: Apparent pharmacodynamic indicator examination revealed that the WAR group had a more substantial curative effect. Metabolomics studies revealed that seven endogenous metabolites were significant differences in two ARs. Furthermore, following treatment, 77 and 65 xenobiotics metabolites were identified in the WAR and TAR groups, respectively. Finally, the most critical riboflavin metabolic route in the formation of CAG was chosen for molecular docking with the relevant exogenous components, and WAR scored higher than TAR. Conclusion: In this work, we analyzed the efficacy differences of AR from diverse cultivation forms by combining metabolomics and medicinal chemistry technologies, and it gave a fresh perspective for TCM efficacy evaluation and quality control research.

11 Coptis chinensis shows distinct effects on hyperlipidemia and gut microbiota in high-fat diet induced mice with cold or hot syndrome

Yanan Yang a , Jiaguo Zhan a , Jiale Cheng a , Ying Cao a , Chongming Wu a , b , ?

2025, 17(3):529-538. DOI: https://doi.org/10.1016/j.chmed.2025.04.009

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Objective: Coptis chinensis (Huanglian in Chinese, HL) is commonly utilized in clinical settings to counteract dyslipidemia in patients with hot syndrome. Its lipid-reducing efficacy has been consistently demonstrated in high-fat diet (HFD)-induced hyperlipidemic animal models. However, whether HL’s efficacy differs in HFD-fed animals with hot or cold syndromes remains unclear. This study aims to discern the variations in the anti-hyperlipidemic effects of HL in HFD-fed mice with hot or cold syndromes. Methods: HFD-induced C57BL/6 mice were subjected to cold or hot syndrome via two weeks of ice water (0 °C) and levothyroxine sodium (240 lg/kg) treatment, respectively. Then, an aqueous extract of HL was administered to the mice via oral gavage over the following four-week period. Lipid levels in the serum and liver were gauged to determine the lipid-reducing effects of HL. Furthermore, gut microbiota composition was elucidated using full-length 16S rRNA gene sequencing. Results: HL notably reduced lipid levels in HFD-induced hyperlipidemic mice. Its efficacy was amplified in hyperlipidemic mice with a hot syndrome but was markedly reduced in those with a cold syndrome. HL treatment led to a decline in alpha-diversity (characterized by ACE, Chao1, Shannon and Simpson index) of the gut microbiota in both sets of mice but affected specific microbial populations based on the syndrome. Specifically, while HL led to a notable increase in Eubacterium, Robinsoniella, and Lachnoclostridium genera, along with the enhancement of Clostridium innocuum and Bacteroides thetaiotaomicron species across all conditions, it syndrome-dependently stimulated Romboutsia ilealis and Parabaceroides_sp_HGS0025 species in mice with hot syndrome. Conclusion: HL shows stronger lipid-lowering effect on hyperlipidemic mice with hot syndrome, which is in accordance with its traditional usage in clinic. The therapeutic outcomes of HL are intrinsically tied, at least in part, to its modulatory effects on the gut microbiota, offering fresh insights into the foundational principles of traditional Chinese medicine.

12 Hyssopus cuspidatus extract inhibited OVA-sensitized allergic asthma through PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation

Yali Zhang a , Huiming Peng b , Jingjing Li c , Pan Lv d , Mengru Zhang a , Xu Wang a , Siyu Wang a , Siying Zhu a , Jiankang Lu a , Xuepeng Fan e , f , , Jinbo Fang a ,

2025, 17(3):539-547. DOI: https://doi.org/10.1016/j.chmed.2024.11.009

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Objective: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. Methods: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. Results: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCEtreated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. Conclusion: HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

13 Compound Danshen Tablets ameliorate myocardial ischemia/reperfusion injury-induced ventricular remodeling by regulating autophagy via AMPK/mTOR signaling pathway

Qiaoyu Li a , b , c , d , Yun Luo a , b , c , d , Haibiao Guo e , Wenxiu Liu a , b , c , d , Hui Yu e , Chuyuan Li e , Rongchang Chen a , b , c , d , , Xiaobo Sun a , b , c , d ,

2025, 17(3):548-554. DOI: https://doi.org/10.1016/j.chmed.2024.03.003

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Objective: Left ventricular remodeling induced by myocardial ischemia/reperfusion injury (MI/RI) is a common cardiac dysfunction. Accumulating evidence has demonstrated that autophagy plays a vital role in protecting against ventricular remodeling. This study aims to investigate the performance of Compound Danshen Tablets (CDT) in rescuing ventricular remodeling and whether autophagy as the potential mechanism. Methods: The left anterior descending arteries of rats were temporarily ligated for 30 min to construct the MI/RI model. Ventricular remodeling was induced by reperfusion for 28 d, during which the MI/RI rats were administered CDT (300 mg/kg and 600 mg/kg), atorvastatin (2 mg/kg), and diltiazem (16 mg/kg). Cardiac function and structure were examined by echocardiography. Immunohistochemistry, Masson’s trichrome staining, and hematoxylin-eosin (HE) staining were utilized to assess the fibrosis and histological alterations in the heart tissue. The expression of autophagy-related proteins was detected using Western blotting. Results: CDT attenuated the cardiac dysfunction, structural changes, histopathological changes and fibrosis induced by MI/RI. CDT significantly enhanced the level of Beclin1 and microtubule-associated protein 1 light chain 3 beta (LC3b), and reduced p62 levels in MI/RI rats. Moreover, CDT significantly increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and inhibited mammalian target of rapamycin (mTOR) phosphorylation. Conclusion: CDT ameliorated MI/RI-induced ventricular remodeling by activating autophagy and improving autophagic flux via the AMPK/mTOR signaling pathway.

14 Applications and challenges of DNA barcoding in rapid radiation groups: Rhodiola (Crassulaceae) as a case study

Jinxin Liu a , b , Erhuan Zang a , Yu Tian a , c , Xinyi Li a , c , Tianyi Xin a , Lingchao Zeng a , c , Lijia Xu a , , Peigen Xiao a ,

2025, 17(3):555-561. DOI: https://doi.org/10.1016/j.chmed.2024.08.001

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Objective: Rhodiolae Crenulatae Radix et Rhizoma (Hongjingtian in Chinese, RCRR), the roots and rhizomes of Rhodiola crenulata and its application in the medicinal market is very chaotic. In this study, DNA barcoding database and identification engine of Rhodiola species were established, decoction pieces from the medicinal market were identified, and the application and challenges of DNA barcoding in the rapid radiation of Rhodiola species were analyzed. This study provides reference for the protection, rational development, and utilization of endangered resources within Rhodiola species. Methods: A total of 50 original plant samples from 20 species of the genus Rhodiola from Hebei, Xinjiang, Tibet, Jilin, and other major production areas were collected. Theses samples cover the typical distribution area (Qinghai-Tibetan Platea) of Rhodiola species and other scattered alpine regions (Changbai Mountain, Taibai Mountain, Lushan Mountain, etc.), it encompasses all Rhodiola species with thick rhizomes in China. ITS2 and psbA-trnH barcode of Rhodiola database (BORD) were established and an identification engine named Rhodiola-IDE was developed. The stability and accuracy of the standard DNA barcoding database were evaluated using two datasets. Rhodiola-IDE identified 31 decoction pieces of RCRR from the medicinal material market. Results: The BORD containing 1 532 sequences of 88 Rhodiola species has been established, and the identification efficiency results showed good accuracy and stability. According to the Chinese Pharmacopoeia (2020 edition), 23 samples (74.2%) were identified as authentic R. crenulata, while the rest of the marketed varieties were R. kirilowii, R. dumulosa, and R. fastigiata. The product label ‘‘Larger flower, Hongjingtian” was identified as R. crenulata. Samples labeled as ‘‘Smaller flower, Hongjingtian” were identified as R. crenulata, R. kirilowii, and R. fastigiata. Conclusion: ITS2 and psbA-trnH barcodes can identify monophyletic groups represented by R. crenulata. However, for non-monophyletic species, it is necessary to collect as many samples as possible and combine them with multiple markers for joint identification. This study discussed the application and challenges of DNA barcodes in Rhodiola under rapid radiation conditions, providing a scientific basis for the rational development and utilization of Rhodiola varieties.

15 Ecological factors impacting genetic characteristics and metabolite accumulations of Gastrodia elata

Zhaoyu Zhang a , b , Xiaodong Li c , Yuchi Zhang c , Niegui Yin c , Guoying Wu c , Guangfei Wei b , Yuxin Zhou b , d , Shilin Chen b , d , , Linlin Dong b ,

2025, 17(3):562-574. DOI: https://doi.org/10.1016/j.chmed.2024.09.002

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Objective: The investigation of the correlation between ecological factors and the genetic characteristics or metabolites of plants offers valuable insights into the regional causes of genetic and metabolic diversity. Here, Gastrodia elata, a medicinal plant, is employed as a model to explore the environmental factors that influence its genetic characteristics and metabolic accumulations. Methods: A total of 23 G. elata populations from six cultispecies and 11 cultivated regions were selected based on the predictions of the global geographic information system. The genetic characteristics of these populations were evaluated using highly polymorphic simple sequence repeat markers. Additionally, the metabolic accumulations and antioxidant capacity of mature tubers were measured employing colorimetry and high performance liquid chromatography (HPLC). Ecological data of each region were obtained from the WorldClim-global climate database and harmonized world soil database. To assess the influence of ecological factors on the genetic characteristics and metabolic profiles of G. elata, Pearson’s correlation analysis was conducted. Results: Genetic variation among G. elata populations exceeded that within populations. Genetic diverisity, distance and structure manifested regional and species-specific patterns. Metabolic profiling and antioxidant capacity exhibited regional variations. Notably, the Lueyang region demonstrated that a content range of total polysaccharide, total protein, and phenolic glycosides was 9.34%-189.67% higher than the average. Similarly, in the Hubei region, total phenolic content, p-hydroxybenzyl alcohol content, and antioxidant indicators were observed to be higher than the average levels, by 106.57%, 136.47% and 12.50%-91.14%, respectively. Furthermore, ecological factors had a significant comprehensive impact on G. elata genetic characteristics (r > 0.256 and P < 0.05). Multivariate metabolite accumulations in G. elata were influenced by dominant ecological factors. Temperature notably impacted the accumulation of total protein (|r| > 0.528 and P < 0.05). Moisture, encompassing precipitation and soil content, significantly affected the production of phenolic glycosides (|r| > 0.503 and P < 0.05). Conclusion: The genetic characteristics of G. elata manifested regional and species-specific patterns, with the metabolic accumulations and antioxidant capacity of mature tubers exhibited regional variations. Specifically, multivariate ecological factors comprehensively influenced genetic characteristics. Temperature and moisture played pivotal roles in regulating the accumulations of proteins and phenolic glycosides, respectively. These findings underscore the significant impact of ecological factors on the shaping of G. elata, highlighting their crucial role in enhancing the quality of Chinese medicinal materials.

16 Research on comprehensive quality consistency evaluation strategy for TCM Granules: A case study with sugar-free Yangwei Granules produced by fluid-bed granulation

Jie Zhao , Geng Tian , Haibin Qu

2025, 17(3):575-583. DOI: https://doi.org/10.1016/j.chmed.2024.11.001

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Objective: To develop a quality consistency evaluation strategy for traditional Chinese medicine (TCM) granules using sugar free Yangwei Granules as a model drug, and demonstrate the effectiveness of the developed method. Methods: The strategy integrates several methods including, HPLC fingerprint and physical fingerprint methods analyze the similarity in chemical and physical properties of the TCM granule samples. Nearinfrared (NIR) spectroscopy with principal components cluster analysis method is used to monitor normal operating conditions (NOC) samples accurately and to identify different types of abnormal operating conditions (AOC) samples, particularly those that deviate from the normal range. Results: The combined use of HPLC fingerprint and physical fingerprint provides insights into the chemical and physical properties of the samples. NIR spectroscopy, combined with principal components cluster analysis, achieves high accuracy in monitoring NOC samples and identifying AOC samples without misjudgment. The approach proves useful as a complementary method in cases where HPLC fingerprint and physical fingerprint alone lack sufficient resolution. Conclusion: This study establishes the feasibility and utility of the integrated approach for assessing the quality consistency of TCM granules. The strategy shows a high degree of generalization and holds significant importance for enhancing the quality control processes of TCM granules.

17 Traditional Chinese medicine formulas alleviated acute pancreatitis via improvement of microcirculation: A systematic review and meta-analysis

Ji Gao a , Chenxia Han a , Ning Dai b , Wen Wang c , Tao Jin a , Dan Du d , , Qing Xia a ,

2025, 17(3):584-600. DOI: https://doi.org/10.1016/j.chmed.2024.12.002

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Objective: Microcirculatory disturbance is pathologically critical to acute pancreatitis (AP), which can be effectively alleviated by traditional Chinese medicine (TCM) formulas that activate blood flow. However, there has been no evidence-based research to date. Therefore, a well-designed systematic review and meta-analysis is necessary to elucidate the therapeutic transformative benefit of improving microcirculation during AP. This study aims to confirm the therapeutic efficacy of TCM formulas and explore the potential mechanisms underlying their effects on AP treatment. Methods: Studies from eight databases including Pubmed, Embase, Web of Science, Cochrane Library, CNKI, CBM, Wanfang, and Chinese VIP, were screened for the eligible randomized controlled trials (RCTs). The APACHE II score and effectiveness rate were set as primary outcomes, while mortality rate, complications, total hospital stays, serum amylase recovery time, the time until the disappearance of abdominal pain, microcirculation indicators, and inflammation indicators were chosen as secondary outcomes. A systematic review and meta-analysis were subsequently conducted. Network pharmacology analysis was performed to analyze potential bioactive components with relevant targets of the core herbs included in the TCM formulas for activating blood flow. Results: A total of 51 RCTs (n = 3 721) were included. Compared with conventional western medical treatments alone, TCM groups were associated with lower APACHE II score (SMD = 1.36, 95% CI: 2.01 to 0.71, P = 0.000) and higher effectiveness rate (RR: 1.22, 95% CI: 1.18 to 1.26, P = 0.000). Furthermore, the formulas for activating blood flow demonstrated significant efficacy in improving both microcirculation and inflammation indicators. Additionally, six core Chinese herbal medicines including Rhei Radix et Rhizoma with the highest frequency, Aurantii Fructus Immaturus, Paeoniae Radix Rubra, Bupleuri Radix, Salviae Miltiorrhizae Radix et Rhizoma, and Corydalis Rhizoma were filtered out from the adopted TCM formulas. Finally, 166 shared targets between the six herbs and AP were identified. KEGG analysis indicated that lipid and atherosclerosis pathway is highly related to microcirculation. Conclusion: TCM formulas for activating blood flow significantly improve microcirculation and alleviate AP. Further high-quality, well-designed RCTs and deep mechanism exploration are required.

18 Shufeng Jiedu Granule against mild COVID-19: Protocol of the randomized, double-blind, placebo-controlled, multi-center heal-COVID phase III study

Li Yang a , Thomas Friedemann c , Jun Pan a , Xiangyu Li a , Fuxiang Wang b , Yuanlong Lin b , Qiang Zhu a , Sven Schr?der c , Qingsong Liu d , ? , Hongzhou Lu b , ?

2025, 17(3):601-608. DOI: https://doi.org/10.1016/j.chmed.2025.04.005

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Abstract:
Objective: Since Omicron will likely persist, this trial evaluates the safety and efficacy of Shufeng Jiedu Granule (SFJDG) for mild Omicron infection, aims at finding new therapies especially for home-treated patients. Methods: This randomized, double-blind, placebo-controlled, multi-center phase III trial involves 844 patients, divided into a treatment group (422) and control group (422). Participants will receive SFJDG or placebo for 7 d (1.2 g/bag, 2 bags, 3 times/d). Hospital evaluations will be done on days 1 and 8, with telephone assessments on days 3 and 5. Follow-up continues on days 10 and 14. Diary cards will track symptom scores and safety data. The primary outcome is the time to sustained clinical recovery from corona virus disease 2019 (COVID-19) symptoms. An interim analysis will occur after 70 % of patients complete follow-up, with Type I error correction (a1 = 0.015) at interim analysis based on O’Brien-Flemingtype cumulative error spending function. Results: This phase III trial evaluates the efficacy and safety of SFJDG for mild COVID-19, focusing on realworld applicability for home-managed patients. The study’s randomized, double-blind, placebocontrolled design ensures methodological rigor, while its comprehensive outcome measures address both symptom recovery and treatment safety. By emphasizing symptom resolution and recovery time, the trial aligns with the clinical priorities for managing mild cases of COVID-19. The findings could offer valuable insights into SFJDG’s role in improving patient outcomes and addressing gaps left by existing antiviral therapies, particularly in symptom management. Conclusion: The global risk assessment remains high due to the ongoing virulence of SARS-CoV-2 Omicron sub-lineages. This Phase III study adopts a robust methodology to investigate SFJDG as a treatment for mild COVID-19 as well as it’s effectiveness and safety. Furthermore, this study aim to provide sufficient scientific evidence for the market registration of SFJDG especially for home-treated patients. If successful, SFJDG could be a meaningful addition to therapeutic options for mild infections, supporting public health strategies in managing the ongoing impact of SARS-CoV-2.

Volume 17,Issue 3,2025 Table of Contents

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