Volume 17,Issue 2,2025 Table of Contents

1 Epigenetics and traditional Chinese medicine: A noteworthy research area

Chunfu Wu

2025, 17(2):201-202. DOI: https://doi.org/10.1016/j.chmed.2025.02.004

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2 Therapeutic potentials of natural products for post-traumatic stress disorder: A focus on epigenetics

Meijing Xu , Minghui Cui , Yu Wang , Boru Li , Lijin Feng , Hang Xing , Kuo Zhang

2025, 17(2):203-219. DOI: https://doi.org/10.1016/j.chmed.2024.07.004

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Post-traumatic stress disorder (PTSD) is a relatively common but complex mental illness with a range of diverse risk factors. Typical symptoms include the re-experience or avoidance of traumatic events, cognitive impairment, and hypervigilance. While the exact pathogenesis of PTSD is unclear, many studies indicate that epigenetic regulation plays a key role in its development. Specifically, numerous studies have indicated that the levels of histone acetylation and methylation, DNA methylation, and noncoding RNA are altered in PTSD patients. Further to this, natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes, long noncoding RNA (lncRNA), and miRNA, thereby playing a role in improving PTSD symptoms. To date, however, no epigenetic regulation related drugs have been used in the treatment of PTSD. Furthermore, while natural products that can epigenetically regulate PTSD have received increasing levels of attention, there have not yet been any systematic reports on the topic. Here, we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD, providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

3 Prevention and treatment of radiation injury by traditional Chinese medicine: A review

Lixue He a , Shixing Edi a , Jun Ma a , Zilin Kong a , Chunguang Dai a , Linfang Huang c , Rui Zeng a , b , Kaijun Gou b ,

2025, 17(2):220-234. DOI: https://doi.org/10.1016/j.chmed.2024.09.005

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Nuclear radiation exposure events and tumor radiotherapy are highly susceptible to a range of psychological, physiological and other health problems, which can seriously affect patients’ quality of life. It has been shown that 87.5 % of tumor patients are exposed to varying degrees of radiation injury during radiotherapy. The treatment of radiation injury (RI) in modern medicine is limited to drug therapy, cell therapy, etc. Among them, the most chemical drugs cause many adverse reactions including fatigue, nausea, vomiting, etc., and there are very few drugs dedicated to the treatment of RI. Traditional Chinese medicine (TCM) is a rich natural medicinal resource, which has a wide range of pharmacological activities, multiple targets of action and minimal toxic side effects. Many studies have demonstrated that TCM and its compound preparations have enormous potential in the treatment of radiation induced comprehensive diseases. However, TCM is limited in clinical application due to its slow onset of action, complex active ingredients, and low bioavailability. Therefore, the article reviews the application, molecular mechanisms, and new dosage forms of TCM in the prevention and treatment of RI. On this basis, we will focus on discussing the development advantages and application prospects of the combination of traditional Chinese and Western medicine to achieve highly efficient treatment of RI. This review aims to provide scientific and effective drug delivery strategies and basic theoretical support for the clinical effective treatment of RI with TCM, and further promote the innovative development of TCM.

4 Research advancements in molecular glues derived from natural product scaffolds: Chemistry, targets, and molecular mechanisms

Lina Yin a , Tingting Niu a , Ling Li b , Wei Yu a , Bo Han a , Asma Rehman c , Kewu Zeng a , b ,

2025, 17(2):235-245. DOI: https://doi.org/10.1016/j.chmed.2025.01.001

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The mechanism of action of traditional Chinese medicine (TCM) remains unclear. Historically, research on TCM has mainly focused on exploring the mechanisms of active components acting on single targets. However, it is insufficient to explain the complex mechanisms by which these active components in TCM treat diseases. In recent years, the emergence of molecular glues (MGs) theory has provided new strategies to address this issue. MGs are small molecules that can promote interactions between proteins at their interface. The characteristic of MGs is to establish connections between diverse protein structures, thereby enabling a chemically-mediated proximity effect that triggers a wide spectrum of biological functions. Natural products are the result of billions of years of evolutionary processes in the natural environment. Thus, the extensive structural diversity of natural products renders them a rich source of MGs, including polyketides, terpenoids, steroids, lignans, organic acids, alkaloids and other classes. Currently, several well-known natural MGs, including the immunosuppressants cyclosporin A (CsA) and tacrolimus (FK506), as well as the anticancer agent taxol, have been incorporated into clinical practice. Meanwhile, the advancement of new technologies is propelling the discovery of novel MGs from natural products. Thus, we primarily summarize a growing variety of MGs from natural origins reported in recent years and categorize them based on the chemical structural types. Moreover, the main sources of TCM are natural products. The discovery of natural MGs promises to provide a new perspective for the elucidation of the molecular mechanism behind the efficiency of TCM. In summary, this review aims to provide insights from the perspective of natural products that could potentially influence TCM and modern drug development.

5 A systematical review on traditional Chinese medicine treating chronic diseases via regulating ferroptosis from the perspective of experimental evidence and clinical application

Yuanyuan Zhang a , Fazhi Su a , Enlin Zhu c , Yanping Sun a , Haixue Kuang a , ? , Qiuhong Wang a , b , ?

2025, 17(2):246-260. DOI: https://doi.org/10.1016/j.chmed.2025.01.003

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Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and nonalcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.

6 Research and utilization status of Lophatherum gracile: A medicinal and food homologous plant

Bin Yao a , b , Meng Zhang a , b , Shaolei Zhao a , b , Hongjian Yu a , d , Jingze Zhang a , b , c , , Dailin Liu a , b , c ,

2025, 17(2):261-278. DOI: https://doi.org/10.1016/j.chmed.2024.07.006

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Lophatheri Herba (Danzhuye in Chinese) is derived from the dried stems and leaves of Lophatherum gracile and has a long history of use as a medicinal and food source. Flavonoids and phenolic acids are the main active ingredients in Lophatheri Herba, which produce diuretic, anti-inflammatory, and antipyretic effects. Flavonoid glycosides and hydroxybenzoic acids are respectively the main structure in 44 flavonoids and 16 phenolic acids obtained from Lophatheri Herba. Modern pharmacological studies have found that the main chemical constituents of Lophatheri Herba play important roles in anti-inflammatory, cardioprotective, hepatoprotective and hypoglycaemic effects. Studies have demonstrated that flavonoid monomers, for example, luteolin, isoorientin, luteolin-7-O-b-D-glucoside and apigenin are more effective in exerting the above pharmacological effects. In addition, Lophatheri Herba is used in different food products as the main ingredient or as an accessory. This review describes Lophatheri Herba in terms of its chemical composition, pharmacological effects and efficacy, food development and applications, and clinical utility, and discusses the problems facing its use. This study provides valuable ideas and a scientific basis for the future development and use of L. gracile.

7 Natural polyphenols as novel interventions for aging and age-related diseases: Exploring efficacy, mechanisms of action and implications for future research

Wenze Wu a , Yan Mi a , Qingqi Meng a , Ning Li b , Wei Li c , Pu Wang d , , Yue Hou a ,

2025, 17(2):279-291. DOI: https://doi.org/10.1016/j.chmed.2024.09.001

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Natural polyphenols are a group of components widely found in traditional Chinese medicines and have been demonstrated to delay or prevent the development of aging and age-related diseases in recent years. As far as we know, the studies of natural polyphenols in aging and aging-related diseases have never been extensively reviewed. In the present paper, we reviewed recent advances of natural polyphenols in aging and common age-related diseases and the current technological methods to improve the bioavailability of natural polyphenols. The results showed that natural polyphenols have the potential to prevent or treat aging and common age-related diseases through multiple mechanisms. Nanotechnology, structural modifications, and matrix processing could provide strong technical support for the development of natural polyphenols to prevent or treat aging and age-related diseases. In conclusion, natural polyphenols have important potential in the prevention and treatment of aging and agerelated diseases.

8 Modernization of charcoal drugs: Integrating research paradigms of carbon dots to gain new perspectives

Sichao Tian a , Zhanglu Hu a , Weidong Zhang a , b , ?

2025, 17(2):292-295. DOI: https://doi.org/10.1016/j.chmed.2025.01.004

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With the modernization drive of traditional Chinese medicine (TCM), this perspective innovatively proposes integrating carbon dot research paradigms to facilitate the modernization of charcoal drugs in TCM. The research focuses on five core areas: analyzing and validating charcoal drugs components pharmacologically, exploring modern preparation methods, establishing a quality evaluation system, fixing preparation process parameters, and probing into the material basis. These steps aim to deepen the scientific understanding of the material basis of charcoal drugs, optimize its preparation process, and establish a comprehensive quality control system. This work provides a theoretical foundation and experimental evidence for the scientific understanding of charcoal drugs, further promoting their modernization and internationalization.

9 MYB polymorphism molecular marker: A novel molecular marker for authenticity and geographical origin identification of Citri Reticulatae Pericarpium

Qiqing Cheng b , d , Ziyu Tang c , Yue Ouyang c , Chunsong Cheng d , Chichou Lao c , Hao Cui g , Hua Zhou e , f , ? , Yongshu Liang a , ?

2025, 17(2):296-306. DOI: https://doi.org/10.1016/j.chmed.2025.02.006

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Objective: Citri Reticulatae Pericarpium (Chenpi, CRP) is one of the most used traditional Chinese medicines with great medicinal, dietary and collection values, among which the Citrus reticulata cv. ‘Chachi’ (Citrus reticulata cv. Chachiensis) from Guangdong Xinhui is the geoherb of CRP. Xinhui CRP in the market was often counterfeited with other varieties or origins, molecular identification method can effectively distinguish different CRP varieties, but it’s still a difficult problem to identify the same CRP variety from different origin. It is necessary to discover a newmolecular marker to ensure the safe and effective application of Xinhui CRP. Methods: We selected one of the most studied transcription factor families in Citrus genus, MYB, to design the specific candidate primers on the conserved region. The primers with good band repeatability and high polymorphism were screened for PCR amplification of the test materials, and the genetic similarity coefficient among different families, genera, species, and origins were calculated. The cluster analysis was performed by unweighted pair group method using arithmetic average (UPGMA). Results: A total of ten MYB primers were screened out to identify Xinhui CRP from plants from different family (Panax ginseng and Morus alba), genus (Clausena lansium and Zanthoxylum schinifolium), and species (Citrus reticulata, C. sinensis and C. maxima). Furthermore, two from the ten primers, M1 and M10, were found to distinguish Xinhui CRP from other origins. There were 169, 113, 133 and 134 polymorphic bands in the identification of different families, genera, species, and origins respectively, and the accordingly polymorphism ration were 79.88%, 76.87%, 79.20% and 82.84%. Moreover, M1was discovered to be the best primer to identify Xinhui CRP from other seven origins, the cluster analysis results based on the genetic similarity coefficients were consistent with the geographical distribution. Conclusion: This study established a novel molecular identification method according toMYB transcription factor, which can analyze the potential parental relationship of CRP germplasm, as well as identify the quality and origins of Xinhui CPR.

10 Identification and functional characterization of a new flavonoid glycosyltransferase from Rheum palmatum

Shiwen Zhang a , Jianzhen Zou a , Zitong Hao a , Mengqi Gao a , Gang Zhang b , , Mengmeng Liu a ,

2025, 17(2):307-314. DOI: https://doi.org/10.1016/j.chmed.2024.08.003

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Objective: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. Methods: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. Results: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent sitedirected mutagenesis studies highlighted the crucial role of K307 in catalysis. Conclusion: These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

11 Analysis of fungal composition in different layers of Bantou agarwoodforming trunk of Aquilaria sinensis revealing presence of Aspergillusinhibiting substances in agarwood sites

Xuyu Chen a , Yun Yang a , Yangyang Liu a , Chun Sui b , ? , Jianhe Wei a , b , ?

2025, 17(2):315-321. DOI: https://doi.org/10.1016/j.chmed.2025.02.001

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Objective: The objective of this study was to analyse fungal composition and exploit application potential in the Bantou (BT) agarwood-forming trunk of Aquilaria sinensis. Methods: BT agarwood is a naturally formed agarwood that was collected after cutting. Total genomic DNA of the fungi in BT agarwood was extracted by the hexadecyltrimethy ammonium bromide (CTAB) method, followed by PCR amplification and library construction. The effective tags were obtained by the HiSeq2500 platform, and the data were subjected to bioinformatics and statistical analyses. Results: A total of 7 850 040 effective tags were obtained, Ascomycota was the most abundant fungus at the phylum level, with a relative abundance of 56.36%–61.44%, followed by Basidiomycota, with a relative abundance of 10.49%–20.39%. Dothideomycetes, Agaricomycetes and Sordariomycetes were dominant at the class level, accounting for 26.21%–33.88%, 8.40%–17.66%, and 18.41%–24.11%, respectively. Lignosphaeria, Phaeoacremonium and Hermatomyces were dominant at the genus level, with relative abundances of 6.25%–7.64%, 1.95%–9.05% and 1.5%–5.4%, respectively. Diversity and richness analysis showed that the fungal composition in the agarwood formation sites (agarwood layer, upper agarwood layer and lower agarwood layer) were significantly lower than those in the decomposing layer and the healthy layer. That is, the fungal diversity and richness were significantly reduced during agarwood formation by the action of open wounds. The fungal community structure in the decomposing layer and agarwood formation sites obviously differed from that in the healthy layer. The number of Aspergillus taxa in agarwood formation sites decreased significantly (healthy layer is 0.5%, decomposing layer is 0.022%, upper agarwood layer is 0.012%, agarwood layer is 0.01%, and lower agarwood layer is 0.013%), indicating that agarwood may contain potential substances to inhibit the growth of Aspergillus. Conclusion: Agarwood from agarwood formation sites contains potential substances that inhibit Aspergillus, which provides valuable information for the control of the genus of Aspergillus.

12 Enhancement of apoptosis in HCT116 and HepG2 cells by Coix lacryma-jobi var. lacryma-jobi seed extract in combination with sorafenib

Supawadee Parhira a , b , c , Guoyuan Zhu d , Apirat Wangteeraprasert e , Suphunwadee Sawong f , Pennapha Suknoppakit f , Julintorn Somran g , Naphat Kaewpaeng b , h , Khemmachat Pansooksan b , h , Dumrongsak Pekthong b , c , i , ? , Piyarat Srisawang b , f , j , ?

2025, 17(2):322-339. DOI: https://doi.org/10.1016/j.chmed.2025.02.005

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Objective: Coix lacryma-jobi, a highly regarded Asian herb widely used in traditional Chinese medicine, is recognized for its dual benefits in promoting overall health and treating various diseases. While it exhibits moderate anticancer efficacy when used alone, this study investigated the enhanced anticancer potential of raw and cooked Coix lacryma-jobi var. lacryma-jobi (CL) seed extracts in combination with sorafenib against HCT116 and HepG2 cancer cell lines. The combination of sorafenib with other anticancer agents, including natural extracts, has garnered significant attention as a promising strategy for developing more effective cancer therapies. Methods: Dry powders of raw (R) and cooked (C) CL seeds, obtained from a local commercial source in Thailand, were extracted and fractionated using ethanol (E), dichloromethane (D), ethyl acetate (A), and water (W) to produce eight fractions: CLRE, CLCE, CLRD, CLCD, CLRA, CLCA, CLRW, and CLCW. The coixol content in raw and cooked seed extracts was quantified and expressed as lg of coixol per gram of extract. The cytotoxic effects of these fractions were evaluated against HCT116 and HepG2 cells using the MTT assay. Fractions demonstrating the most significant cytotoxic responses were combined with sorafenib to evaluate their synergistic effects. Apoptosis induction and mitochondrial membrane potential (MMP) were assessed, and the underlying mechanism of apoptosis was explored by analyzing reactive oxygen species (ROS) generation and antioxidant protein expression levels. Additionally, the combination treatment’s effect on the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) pathway was investigated. Results: One gram of CLCE and CLCD extracts contained higher coixol levels (7.02 lg and 9.69 lg, respectively) compared to CLRE and CLRD (2.66 lg and 5.96 lg, respectively). Coixol content in CLRA, CLRW, and CLCW fractions was undetectable under the study conditions. All extract fractions exhibited IC50 values exceeding 1 mg/mL after 24- and 48-hour incubations with HCT116 and HepG2 cells, indicating limited cytotoxicity when used independently. CLRD and CLCD fractions were selected for combination studies at a concentration of 1 mg/mL, combined with sub-IC50 concentrations of sorafenib to minimize its side effects. This combination significantly increased cytotoxicity, inducing apoptosis in HCT116 and HepG2 cells by elevating ROS levels and reducing the expression of superoxide dismutase 2 and catalase. Furthermore, the combination treatment downregulated the PI3K/AKT/mTOR pathway, indicating a targeted anticancer mechanism. Conclusion: The combination of CLCD with sorafenib demonstrates significant potential as a strategy for future anticancer therapies. This CL seed extract, cultivated and commercially available in Thailand, shows promise as a natural supplement to enhance the efficacy of chemotherapy in upcoming clinical anticancer applications.

13 Ameliorating vascular endothelial injury for lipolysacharide-induced via mitochondrial targeting function of octaarginine-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres

Lingyan Li a , b , c , Zengqiu Yang a , b , c , Qiqi Li a , b , c , Qianqian Guo a , b , c , Xingjie Wu a , b , c , Yu’e Wang a , b , c , Xiangchun Shen a , b , c , Ying Chen a , b , c , , Ling Tao a , b , c ,

2025, 17(2):340-351. DOI: https://doi.org/10.1016/j.chmed.2024.11.004

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Objective: To investigate the therapeutic potential of octaarginine (R8)-modified essential oil from Fructus Alpiniae zerumbet (EOFAZ) lipid microspheres (EOFAZ@R8LM) for cardiovascular therapy. Methods: EOFAZ@R8LM was developed by leveraging the volatilization of EOFAZ and integrating it with the oil phase of LM, followed by surface modification with cell-penetrating peptide R8 to target the site of vascular endothelial injury. The therapeutic effects of this formulation in alleviating lipopolysaccharide-induced vascular endothelial inflammation were evaluated by assessing mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) levels, as well as inflammatory factors interleukin-6 (IL-6) and interleukin-1b (IL-1b) levels. Results: EOFAZ@R8LM effectively delivered EOFAZ to the site of injury and specifically targeted the mitochondria in vascular endothelial cells, thereby ameliorating mitochondrial dysfunction through regulation of MMP and reduction of intracellular ROS levels. Moreover, it attenuated the expression levels of IL-6 and IL-1b, exerting protective effects on the vascular endothelium. Conclusion: Our findings highlight the significant therapeutic potential of EOFAZ@R8LM in cardiovascular therapy, providing valuable insights for developing novel dosage forms utilizing EOFAZ for effective treatment against cardiovascular diseases.

14 Amelioration of atherosclerotic complications and dyslipidemia by verbascoside-enriched fraction of Clerodendrum glandulosum leaves targeting LDL-R and LXR-mediated reverse cholesterol transport

Puspanjali Khound a , b , Nonibala Gurumayum a , b , Rajlakshmi Devi a , b , ?

2025, 17(2):352-367. DOI: ttps://doi.org/10.1016/j.chmed.2025.02.007

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Objective: Clerodendrum glandulosum is widely used in traditional Chinese and Indian systems of medicine for conditions like hypertension and diabetes. While various pharmacological benefits have been reported, research on its anti-atherosclerotic properties remains limited. Atherosclerosis (AS) is a chronic cardiovascular disease linked to dyslipidemia (DLD) and inflammation. This study aims to identify the bioactive fraction from C. glandulosum extract, evaluate its potential against AS and DLD, and explore the molecular mechanisms of cholesterol metabolism. Methods: Bioactivity-guided fractionation was employed to investigate the bioactivity of C. glandulosum by screening biochemical enzyme inhibitory potential. The active fraction was subjected to in vitro testing to assess the anti-inflammatory and anti-adhesion properties. The fraction was administered at 50 and 100 mg/kg per os (p.o.) to cholesterol-cholic acid-thiouracil (CCT) diet-induced atherosclerotic Wistar rats. Changes in lipid and antioxidant profiles, inflammatory markers, and cholesterol metabolism pathways were assessed using Western blotting. Histopathological analyses of the aorta, liver, heart, and kidneys were also conducted. Molecular docking was conducted for the verbascoside (VER) and the standard statin, atorvastatin (ATS), for their binding capabilities with the molecular targets considered in this study. Results: Bioactivity-guided fractionation and screening revealed that ethyl acetate fraction (EAF) contained VER as the principal phytoconstituent. EAF exhibited potent enzyme inhibitory activity, with IC50 values of 1.059 mg/mL for pancreatic lipase and 22.48 lg/mL for a-glucosidase. In vitro analysis revealed that EAF significantly lowered cell-to-cell adhesion to 0.57 folds from 2.5 folds in the disease control and normalized the inflammatory cytokines. In CCT-diet-induced rats, elevated serum cholesterol and low-density lipoproteins (LDL) levels (92.1 mg/dL and 78.49 mg/dL, respectively) were reduced to 63.52 mg/dL and 58.51 mg/dL with EAF at 100 mg/kg. EAF at 100 mg/kg reduced oxidized LDL to 53.63 ng/mL compared to 157.1 ng/mL in CCT-diet-fed rats. EAF also restored antioxidant activity by increasing superoxide dismutase and catalase levels to 73.78 and 17.72 U/mg protein, respectively, compared to 42.22 and 9.62 U/mg protein in CCT-diet-fed rats. EAF restored inflammatory cytokines to normal levels. Histological analyses validated the protective benefits of EAF supplementation for the structural integrity of the aorta, liver, heart, and kidney tissues. Western blotting analysis of liver tissues revealed changes in the cholesterol metabolic pathway by upregulating peroxisome proliferatoractivated receptor gamma (PPARc)/liver X receptor alpha (LXRa)/adenosine triphosphate-binding cassette sub-family G member 1 (ABCG1) and low-density lipoprotein receptor (LDL-R) expression. Unlike ATS, molecular docking analyses indicated strong interactions between VER and molecular targets. Conclusion: EAF prevented DLD and AS by reverse cholesterol transport via the PPARc/LXRa/ABCG1 pathway, offering potential therapeutic benefits for cardiovascular health.

15 Osthole ameliorates chronic pruritus in 2,4-dichloronitrobenzeneinduced atopic dermatitis by inhibiting IL-31 production

Shuang He a , b , c , Xiaoling Liang a , b , c , Weixiong Chen d , e , Yangji Nima a , Yi Li a , Zihui Gu a , Siyue Lai a , Fei Zhong a , Caixiong Qiu a , b , c , Yuying Mo f , Jiajun Tang f , Guanyi Wu a , b , c ,

2025, 17(2):368-379. DOI: https://doi.org/10.1016/j.chmed.2024.01.003

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Objective: This study aims to elucidate the therapeutic potential of osthole for the treatment of atopic dermatitis (AD), focusing on its ability to alleviate chronic pruritus (CP) and the underlying molecular mechanisms. Methods: In this study, we investigated the anti-inflammatory effects of osthole in both a 2,4- dichloronitrobenzene (DNCB)-induced AD mouse model and tumor necrosis factor-a (TNF-a) and interferon-c (IFN-c) stimulated human immortalized epidermal (HaCaT) cells. The anti-itch effect of osthole was specifically assessed in the AD mouse model. Using methods such as hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), western blot (WB), quantitative real-time PCR (qRT-PCR), and immunofluorescence staining. Results: Osthole improved skin damage and clinical dermatitis scores, reduced scratching bouts, and decreased epidermal thickness AD-like mice. It also reduced the levels of interleukin (IL)-31 and IL-31 receptor A (IL-31 RA) in both skin tissues and HaCaT cells. Furthermore, Osthole suppressed the protein expression levels of phosphor-p65 (p-p65) and phosphor-inhibitor of nuclear factor kappa-Ba (p-IjBa). Meanwhile, it increased the protein expression levels of peroxisome proliferator-activated receptor a (PPARa) and PPARc in HaCaT cells. Conclusion: These findings indicated that osthole effectively inhibited CP in AD by activating PPARa, PPARc, repressing the NF-jB signaling pathway, as well as the expression of IL-31 and IL-31 RA.

16 Banxia Xiexin Decoction inhibits colitis-associated colorectal cancer development by modulating STAT3 signaling and gut microbiota

Yinzi Yue a , Lianlin Su b , Yahui Wang c , Xiaoman Li b , Xiaoyan Xiao b , Jin Xie a , Shuai Yan c ,

2025, 17(2):380-391. DOI: https://doi.org/10.1016/j.chmed.2024.02.004

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Objective: To investigate the therapeutic effects of Banxia Xiexin Decoction (BXD), a herbal medicine formula, on inflammation and the imbalance of the gut microbiota in a rat model of colorectal cancer (CRC) induced by azoxymethane (AOM) /dextran sulfate sodium (DSS). Methods: A total of 75 male C57BL/6 mice were randomly divided into five groups: normal control group (NC), model group (MODEL), low-dose BXD treatment group (L-BXD), high-dose BXD treatment (H-BXD) group and MS treatment group (MS). BXD and MS were used in CRC mice at the doses of 3.915 g/kg, 15.66 g/kg, 0.6 g/kg for 3 weeks consecutively. Histopathological changes in the colon were observed using hematoxylin-eosin (HE) staining. The content of inflammatory factors in serum was detected by an enzyme-linked immunosorbent assay (ELISA), and the expression of mRNA and protein of genes related to immunity, apoptosis, inflammation, and inflammatory factors was evaluated. Changes in the intestinal flora of mouse fecal were determined based on high throughput sequencing of the 16S rRNA microbial gene. Results: Compared to the model group, the low-dose BXD and high-dose BXD groups decreased the number of colon tumors, reversed weight loss, and shortened colon length of mice. The pathological examination showed that BXD alleviated the malignancy of intestinal tumors. It also suppressed signal transducer and activator of transcription 3 (STAT3), matrix metalloproteinase-9 (MMP-9), and transforming growth factor beta 1 (TGF-b1) expression, while increasing the expression of the tight junction protein ZO-1 in colon tissues. Additionally, the levels of key pathway proteins involved in inflammation (phosphorylated-STAT3, Bcl-2, COX-2) and cell cycle regulatory molecules (c-Myc and PCNA) were reduced. According to 16S rRNA sequence analysis, BXD enhanced the relative abundance of potentially beneficial bacteria, while that of cancer-related bacteria decreased. Conclusion: BXD plays a preventive role in developing colorectal cancer; its mechanisms are related to the inhibition of inflammation and tumor proliferation, as well as maintenance of intestinal homeostasis.

17 Overexpression of SULT1E1 alleviates salt-processed Psoraleae Fructus-induced cholestatic liver damage

Yu Wu a , b , Yan Xu b , Hao Cai b , Zhengying Hua b , Meimei Luo b , Letao Hu b , Nong Zhou b , c , Xinghong Wang a , , Weidong Li b ,

2025, 17(2):392-403. DOI: https://doi.org/10.1016/j.chmed.2024.11.002

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Objective: Salt-processed Psoraleae Fructus (SPF) is widely used as a phytoestrogen-like agent in the treatment of osteoporosis. However, due to improper clinical use or misuse, resulting in liver damage. In this study, network pharmacology was employed to analyze the mechanism of cholestatic liver damage. An adeno-associated virus overexpressing SULT1E1 (rAAV8-SULT1E1) was constructed and the hepatotoxicity of SPF, psoralen, and isopsoralen was determined. Methods: By utilizing three databases inclding TCMSP, TCMID, and BATMAN- TCM, the targets of the three databases were summarized, and a total of 45 psoralen compounds were included. Network pharmacology analysis was then performed. The adenoviral vectors were injected into the tail vein of C57BL6 mice to elucidate the role of SULT1E1 in SPF-induced cholestasis-mediated hepatotoxicity in vivo. SPF (10 g/kg), psoralen, and isopsoralen (50 mg/kg each) were intragastrically administered to mice for 30 d. B-ultrasound and samples were collected and examined for follow-up experiments. Results: A total of 854 targets were predicted for 45 active components, with 151 cholestasis-mediated hepatotoxicity-related disease targets obtained for SPF. A total of 126 pathways were enriched based on KEGG pathway analysis, with the ‘‘estrogen signaling pathway” identified as one of the top 20 pathways. In terms of pathological hepatic changes, treated mice had visually swollen hepatocytes, dilated bile ducts, and elevated serum biochemical markers, which were more prominent in mice treated with isopsoralen than in those treated with other compounds. Notably, the overexpression of SULT1E1 could reverse liver damage in each treatment group. B-ultrasound was used to observe the size of the gallbladder in vivo. The size of the gallbladder was found to significantly increase on day 30 after treatment in the SPF-, psoralen-, and isopsoralen-treated groups, especially the SPF group. Compared with the expression levels in the negative control group (rAAV8-empty + con), the expression levels of FXR, Mrp2, Bsep, SULT1E1, SULT2A1, Ntcp, and Nrf2 decreased, whereas those of CYP7a1 and IL-6 increased in the SPF-, psoralen-, and isopsoralen-treated groups. Conclusion: The overexpression of SULT1E1 could alleviate the decreased or increased expression of indicators, indicating that SULT1E1 is an important target gene for SPF-induced liver damage. The severity of liver damage was significantly lower in the rAAV8 SULT1E1 groups than in the rAAV8-empty groups.

18 Two new polyketides from Rhodiola tibetica endophytic fungus Penicillium sp. HJT-A-6

Dongliang Xiao a , Xiaobao Li a , Xuemei Zhang a , Nan Jiang a , Dunzhu Luosang b , Weixing Feng a , Xuan Lu a , , Baomin Feng a ,

2025, 17(2):404-408. DOI: https://doi.org/10.1016/j.chmed.2024.06.004

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Abstract:
Objective: To study bioactive compounds from the endophytic fungus Penicillium sp. HJT-A-6 isolated from stem of Rhodiola tibetica, and evaluate its allelopathic activity. Methods: The chemical constituents were isolated and purified by silica gel, Sephadex LH-20 column chromatography and semi-preparative HPLC. Their structures were elucidated by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. In addition, the allelopathic activity of compound 1 was evaluated by measuring the seed germination rate of R. tibetica. Results: Two new polyketides 4-hydroxy-3,6-dimethyl-2H-pyran-2-one (1) and penilactone E (2), together with six known compounds walterolactone A (3), 5-hydroxyhexan-4-olide (4), 3-methyl-2-penten-5-olide (5), chaetoquadrin F (6), (Z)-6-acetyl-3-(1,2 -dihydroxypropylidene)-5-hydroxy-8-methylchroman-2-one (7) and 4-hydroxy-3-(4-hydroxyhexanoyl)-5-methylfuran-2(5H)-one (8) were isolated from Penicillium sp. HJT-A-6. Compound 1 showed moderate seed-germination-promoting activity at a concentration of 0.001 mg/mL while inhibiting the seed germination at concentrations of 0.1 and 0.01 mg/mL. Compared with the positive drug 6-benzyladenine (6-BA), compound 1 could extend the seed-germination period of R. tibetica (up to 11 d). Conclusion: Two new compounds were isolated from R. tibetica endophytic fungus Penicillium sp. HJT-A-6. Compound 1 displayed plant hormone-like activity, which inhibited the seed germination of the host plant at high concentrations and promoted the seed germination of the host plant at low concentrations. The results not only enrich the chemical constituents of the endophytic fungi isolated from Rhodiola tibetica, but also provide a theoretical basis for understanding the interaction mechanism between Rhodiola tibetica endophytic fungi and the host plant.

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