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  • research-article
    Xuechun Chen, Lu Li, Mingxu Zhang, Jian Yang, ChunMing Lyu, Yizhou Xu, Yang Yang, Yi Wang
    Acupuncture and Herbal Medicine, 2024, 4(1): 1-15. https://doi.org/10.1097/HM9.0000000000000105

    High-content screening (HCS) technology combines automated high-speed imaging hardware and single-cell quantitative analysis. It can greatly accelerate data acquisition in cellular fluorescence imaging and is a powerful research technique in traditional Chinese medicine (TCM). An increasing number of laboratories and platforms, including TCM laboratories, have begun utilizing HCS systems. However, this technology is still in its infancy in TCM research and there is a lack of sufficient experience with the associated concepts, instrument configurations, and analysis methods. To improve the understanding of HCS among researchers in the field of TCM, this paper summarizes the concept of HCS, software and hardware configuration, the overall research process, as well as common problems and related solutions of HCS in TCM research based on our team's previous research experience, providing several research examples and an outlook on future perspectives, aiming to provide a technical guide for HCS in TCM research.

  • research-article
    Zihao Zhang, Raorao Li, Yu Chen, Hui Yang, Martin Fitzgerald, Qiaochu Wang, Ziwen Xu, Nanxi Huang, Dajun Lu, Lu Luo
    Acupuncture and Herbal Medicine, 2024, 4(1): 68-78. https://doi.org/10.1097/HM9.0000000000000089

    Traditional medicine has garnered significant global recognition, with an estimated 80% of the global population using it. Therefore, it is essential to fully understand the integration of traditional medicines into current healthcare systems. This review aims to provide a comprehensive overview of the standard process to modernize traditional medicine scientifically in the context of modern biomedicine, further termed here as “scientization”. Specifically, we aim to summarize the advancements made in understanding the efficacy, effectiveness, and underlying mechanisms of herbal medicine. We also examined the transition from experience- to evidence-based medicine during acupuncture. Furthermore, we explore the development of universal safety and quality control standards. Finally, we discuss international trade and export markets for Chinese medical products. The development and integration of traditional medicine have allowed it to further improve human health, resulting in a more comprehensive health solution for the global population.

  • research-article
    Huan Zhong, Zhi-Qing Tang, Yi-Fang Li, Mei Wang, Wan-Yang Sun, Rong-Rong He
    Acupuncture and Herbal Medicine, 2024, 4(1): 19-35. https://doi.org/10.1097/HM9.0000000000000104
  • research-article
    Li Liu, Yanqing Liu, Shujie Zhang, Junzhe Zhang, Yuqing Meng, Dandan Liu, Liwei Gu, Ying Zhang, Liting Xu, Ziyue Zhang, Minghong Zhao, Yinkwan Wong, Qixin Wang, Yongping Zhu, Jigang Wang
    Acupuncture and Herbal Medicine, 2024, 4(1): 92-101. https://doi.org/10.1097/HM9.0000000000000102

    Objective: Celastrol is a pentacyclic triterpenoid extracted from the traditional Chinese medicinal herb, Tripterygium wilfordii. This study aims to provide a scientific basis for the rational development and use of celastrol in breast cancer.
    Method: A quantitative chemical biology approach was used to investigate the protein targets and molecular mechanisms of celastrol in breast cancer cells.
    Results: Low-concentration celastrol exerted an anti-tumor effect by directly binding to hydroxysteroid dehydrogenase-like 2 (HSDL2) and inhibiting its expression. Moreover, the expression of the pro-apoptotic protein, Bcl-2-associated X (BaX), increased, the level of the anti-apoptotic protein, B-cell lymphoma-2 (Bcl-2), decreased, and the rate of apoptosis increased. After the transfection of cells with si-HSDL2, the apoptosis rate was similar to that observed after the administration of celastrol. However, apoptosis was reversed by the overexpression of HSDL2. Furthermore, our mass spectrometry (MS) data indicated a relationship between HSDL2 and the mitogen-activated protein kinase (MAPK) signaling pathway. We also found that the expression of HSDL2 was directly related to the degree of extracellular signal-regulated kinase (ERK) phosphorylation.
    Conclusion: Celastrol may promote apoptosis by suppressing the HSDL2/MAPK/ERK signaling pathway.

  • research-article
    Jing Zhang, Weiqiang Su, Nina Filipczak, Ying Luo, Anping Wan, Yao He, Shijuan Yan, Xiang Li, Ming Yang
    Acupuncture and Herbal Medicine, 2024, 4(1): 79-91. https://doi.org/10.1097/HM9.0000000000000090

    Volatile oil (VO) is the main chemical component of common plants in Chrysanthemum genus, and it possesses several beneficial pharmacological properties, including bacteriostatic, antioxidant, anti-tumor, anti-inflammatory, antipyretic, analgesic, anti-osteoporotic, antihypertensive, sedative, and hypnotic effects. To date, research on the effective components of Chrysanthemum extract has mainly focused on flavonoids, whereas limited data are available on the chemical constituents and underlying mechanisms of action of the VO components. In this review, the pharmacological activities and mechanisms of VO are comprehensively reviewed with the aim of providing a foundation for further development for medicinal, aromatherapy, and diet therapy applications.

  • research-article
    Ye Xiu, Zhixin Wu, Yichong Chen, Wenqing Mu, Xiaomei Zhao, Ming Dong, Yurong Li, Zhaofang Bai, Xiaohe Xiao
    Acupuncture and Herbal Medicine, 2024, 4(2): 209-221. https://doi.org/10.1097/HM9.0000000000000115

    Objective: Polygonum multiflorum Thunb. (PM) is a commonly used tonic herb known to cause idiosyncratic drug-induced liver injury (IDILI). This study explored the detoxification effects and potential mechanisms of action of Paeoniae Radix Alba (PRA) on PM-induced IDILI.
    Methods: Network pharmacology analysis was utilized to predict the related targets of “PRA-PM-innate immunity.” A non-hepatotoxic lipopolysaccharide (LPS) and PM-induced IDILI model was used to evaluate the detoxification effects of PRA by measuring liver function indicators, pathological examinations, and macrophage-related factors. Bone marrow-derived macrophages (BMDMs) were stimulated with IL-4 to differentiate into M2 macrophages, and the effects of PM and PRA on M2 macrophage polarization were explored.
    Results: Target screening of “PRA-PM-innate immunity” identified 21 intersecting targets, most of which were closely associated with macrophage polarization. In rat models of IDILI induced by PM, the combined use of PRA significantly reduced the extent of liver damage and the levels of inflammatory factors, while promoting the expression of M2 macrophage-related factors such as interleukin (IL)-4, IL-10, arginase 1 (Arg1), and CD206. In vitro, PM dose-dependently inhibited the expression of the Arg1 protein and M2 macrophage-related genes, whereas PRA exhibited the opposite effect. When used in combination, PRA ameliorated the inhibitory effect of PM on M2 macrophage polarization.
    Conclusions: Our results demonstrate that PRA has a therapeutic effect on PM-induced IDILI; its mechanism may involve alleviating liver injury by promoting M2 macrophage polarization, thus reducing the expression of inflammatory factors.

  • research-article
    Lingling Dang, Yajing Jin, Ye Yuan, Rui Shao, Wang Yu
    Acupuncture and Herbal Medicine, 2024, 4(1): 136-150. https://doi.org/10.1097/HM9.0000000000000103

    Licorice, a perennial herb of Leguminosa, is one of the oldest and most widely used herbal medicines worldwide. Its distinct sweet flavor and rich medicinal value make it an integral component of traditional Chinese medicine (TCM) formulations, which continue to be widely employed. The main chemical constituents of licorice include triterpenoid saponins, flavonoids, and polysaccharides. Experimental and clinical studies have demonstrated that various extracts and pure compounds derived from licorice exhibit a wide range of pharmacological properties including anti-inflammatory, antioxidant, antimicrobial, antiviral, antitumor, immune-regulatory, and neuroprotective activities. The bioactive constituents of licorice offer therapeutic benefits for cardiovascular and cerebrovascular diseases, diabetes mellitus, and liver disorders. This comprehensive review discusses the primary chemical constituents of licorice and their pharmacological activities, describes in vivo and in vitro models employed for studying licorice, and its potential targets and mechanisms of action. Furthermore, we discuss the toxicological profile, side effects, dosage recommendations, and clinical applications of licorice. This review aims to establish a foundation for further research on the safe and effective utilization of licorice while facilitating an in-depth exploration of its properties and fostering the development of novel therapeutic agents.

  • research-article
    Junrong Li, Xiaobing Zhai, Jixing Liu, Chi Kin Lam, Weiyu Meng, Yuefei Wang, Shu Li, Yapeng Wang, Kefeng Li
    Acupuncture and Herbal Medicine, 2024, 4(1): 122-133. https://doi.org/10.1097/HM9.0000000000000098

    Objective: Chronic fatigue syndrome (CFS) is a prevalent symptom of post-coronavirus disease 2019 (COVID-19) and is associated with unclear disease mechanisms. The herbal medicine Qingjin Yiqi granules (QJYQ) constitute a clinically approved formula for treating post-COVID-19; however, its potential as a drug target for treating CFS remains largely unknown. This study aimed to identify novel causal factors for CFS and elucidate the potential targets and pharmacological mechanisms of action of QJYQ in treating CFS.
    Methods: This prospective cohort analysis included 4,212 adults aged ≥65 years who were followed up for 7 years with 435 incident CFS cases. Causal modeling and multivariate logistic regression analysis were performed to identify the potential causal determinants of CFS. A proteome-wide, two-sample Mendelian randomization (MR) analysis was employed to explore the proteins associated with the identified causal factors of CFS, which may serve as potential drug targets. Furthermore, we performed a virtual screening analysis to assess the binding affinity between the bioactive compounds in QJYQ and CFS-associated proteins.
    Results: Among 4,212 participants (47.5% men) with a median age of 69 years (interquartile range: 69-70 years) enrolled in 2004, 435 developed CFS by 2011. Causal graph analysis with multivariate logistic regression identified frequent cough (odds ratio: 1.74, 95% confidence interval [CI]: 1.15-2.63) and insomnia (odds ratio: 2.59, 95% CI: 1.77-3.79) as novel causal factors of CFS. Proteome-wide MR analysis revealed that the upregulation of endothelial cell-selective adhesion molecule (ESAM) was causally linked to both chronic cough (odds ratio: 1.019, 95% CI: 1.012-1.026, Pβ=β2.75 e-05) and insomnia (odds ratio: 1.015, 95% CI: 1.008-1.022, Pβ=β4.40 e-08) in CFS. The major bioactive compounds of QJYQ, ginsenoside Rb2 (docking score: -6.03) and RG4 (docking score: -6.15), bound to ESAM with high affinity based on virtual screening.
    Conclusions: Our integrated analytical framework combining epidemiological, genetic, and in silico data provides a novel strategy for elucidating complex disease mechanisms, such as CFS, and informing models of action of traditional Chinese medicines, such as QJYQ. Further validation in animal models is warranted to confirm the potential pharmacological effects of QJYQ on ESAM and as a treatment for CFS.

  • research-article
    Xiaohe Xiao, Jiabo Wang, Haibo Song, Dongsheng Ouyang, Zhengsheng Zou, Ruilin Wang, Tingting He, Jing Jing, Yuming Guo, Zhaofang Bai, Xiaoyan Zhan, Ming Niu, Zhijie Ma, Chunyu Li, on Behalf of the Branch of Chinese Patent Medicine, China Association of Chinese Medicine, Branch of Hepatobiliary Diseases, China Association of Chinese Medicine, Committee of Clinical Chinese Pharmacy, Chinese Pharmaceutical Association, Subcommittee of Liver Diseases, Committee of Drug-Induced Diseases, Chinese Pharmacological Society, Committee of Clinical Toxicology, Chinese Society of Toxicology
    Acupuncture and Herbal Medicine, 2024, 4(2): 151-158. https://doi.org/10.1097/HM9.0000000000000113

    Polygoni Multiflori Radix (He Shou Wu) is a Chinese medicine widely used in clinical treatment and preventive healthcare. However, recently there have been frequent reports of liver injury caused by Polygoni Multiflori Radix and its related preparations, and some patients have serious adverse outcomes, attracting wide attention worldwide. The risk of liver damage caused by preparations containing Polygoni Multiflori Radix or Polygoni Multiflori Caulis has been repeatedly reported by the Chinese Food and Drug Administration. Fortunately, substantial progress has recently been made in revealing the basic properties, main causes, material basis, and molecular mechanism of Polygoni Multiflori Radix-related liver injury. The basic characteristics and biomarkers of susceptible people have been identified, indicating that Polygoni Multiflori Radix has the risk of inducing liver injury only in a few specific populations and is safe for most populations. This study provides a scientific basis for a correct and objective understanding of liver injury caused by Polygoni Multiflori Radix, and a reasonable formulation of safe medication measures for Polygoni Multiflori Radix and related preparations. The China Association of Chinese Medicine organized experts in relevant fields across the country to draft and formulate the “Guidelines for Safe Use of Polygoni Multiflori Radix” with the aim of helping the public and relevant institutions at home and abroad to scientifically understand, evaluate, and avoid the risk of liver injury; guide the rational use; protect the health rights and interests of consumers; and promote the healthy and sustainable development of Polygoni Multiflori Radix and related preparations. These guidelines were issued by the China Association of Chinese Medicine (No. T/CACM 1328-2019).

  • research-article
    Bo Cao, Yingying Li, Mengmeng Lin, Jing Xu, Taifeng Li, Xiaofei Fei, Xiaohe Xiao, Guohui Li, Chunyu Li
    Acupuncture and Herbal Medicine, 2024, 4(2): 222-233. https://doi.org/10.1097/HM9.0000000000000099

    Objective: Xianling gubao (XLGB), a widely used Chinese patent medicine for osteoporosis, has garnered significant attention due to its potential to cause liver injury. The constituents Psoraleae Fructus (PF, the dried ripe seeds of Psoralea corylifolia L.) and Epimedii Folium (EF, the dried leaves of various Epimedium species) present in XLGB have been implicated in causing idiosyncratic drug-induced liver injury (IDILI). However, the specific components and mechanisms underlying liver injury related to these tonics remain elusive. This study aims to establish that the combination of bavachin (the primary active compound in PF, and icariside II, the main active compound in EF) induces IDILI in a tumor necrosis factor-α (TNF-α)-mediated mouse model.
    Methods: To assess the impact of bavachin and icariside II on the liver in the presence of TNF-α immune stress, an animal model was developed. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics technology was employed to identify biomarkers associated with TNF-α-induced IDILI and the combination of bavachin and icariside II. Additionally, 16S rRNA high-throughput sequencing technology was utilized to explore changes in the species composition and relative abundance of gut microbiota. Spearman correlation analysis was conducted to unveil the relationship between gut microbiota and in vivo metabolites.
    Results: The study observed that the combined administration of bavachin and icariside II induced liver injury in the TNF-α mediated susceptibility mouse model of IDILI. Under TNF-α stimulation, there was an elevation in levels in mouse livers following bavachin and icariside II administration, while Gly-Tyr, Leu-Gly, and Trp-Ser levels decreased. These differentially expressed metabolites associated with liver injury were predominantly enriched in metabolic pathways such as sphingolipid metabolism, sphingolipid signaling pathway, and necroptosis. it is noteworthy that the gut of mice with liver injury induced by the bavachin and icariside II combination exhibited a significant increase in Bacteroides and Desulfovibrionaceae abundance. Correlation analysis revealed a positive association between Bacteroidaceae and Desulfovibrionaceae with methylcarbamoyl PAF and methyl Indole-3-acetate, while a negative correlation was observed with Gly-Tyr, Leu-Gly, and Trp-Ser.
    Conclusions: These findings demonstrated that the combination of bavachin and icariside II increased the risk of IDILI in vivo, providing a promising scientific basis for understanding the component basis of IDILI resulting from the compatibility of EF and PF.

  • research-article
    Xinran Liu, Tao Gong
    Acupuncture and Herbal Medicine, 2024, 4(1): 134-135. https://doi.org/10.1097/HM9.0000000000000100
  • research-article
    Dandan Huang, Zhongjie Tang, Xiao Pu, Tianqi Wang, Feiyan Gao, Chong Li
    Acupuncture and Herbal Medicine, 2024, 4(1): 113-121. https://doi.org/10.1097/HM9.0000000000000096

    Objective: In this study, we aim to enhance the anti-prostate cancer efficacy of cabazitaxel (CTX) and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1 (Rk1/CTX-Lip).
    Methods: Physical and chemical properties of Rk1/CTX-Lip were investigated. We evaluated the biological functions of Rk1/CTX-Lip, both in vitro and in vivo. A subcutaneous prostate cancer (RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors. Simultaneously, a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip. Finally, biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.
    Results: We successfully prepared Rk1/CTX-Lip, achieving high CTX encapsulation efficiency (97.24β±β0.75)% and physical stability. Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis, effective tumor tissue targeting, and a significant reduction (>50%) in average tumor volume compared with Chol/CTX-Lip. Moreover, it relieved the concurrent infection burden and effectively regulated immune organs and cells, demonstrating superior biocompatibility.
    Conclusion: Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.

  • research-article
    Weiming Zhu, Qingqing Jia, Alberto Cantidio Ferreira, Hailun Jiang, Jieying Zhang, Boxuan Li, Menglong Zhang, Bifang Zhuo, Yuanhao Lyu, Junjie Chen, Li Li, Guang Tian, Shizhe Deng, Zhihong Meng, Xuemin Shi
    Acupuncture and Herbal Medicine, 2024, 4(1): 36-55. https://doi.org/10.1097/HM9.0000000000000094

    Acupuncture is an effective treatment for ischemic stroke (IS) and plays a key role in neurological rehabilitation after IS. Acupuncture can improve the clinical symptoms of various complications after IS, including motor dysfunction, swallowing disorders, speech disorders, cognitive impairment, depression, insomnia, and fatigue. However, the mechanisms underlying the effects of acupuncture in IS remain unclear. Available evidence suggests that acupuncture may exert neuroprotective effects through neuroplasticity (neurogenesis and synaptogenesis), angiogenesis, cell proliferation and apoptosis, and regulation of oxidative stress, inflammation, and immunity. Further studies should be conducted to improve the high-quality evidence-based system of acupuncture intervention for IS, by focusing on the clinical and basic research design, increasing the sample size, standardizing and quantifying the standards of acupuncture operations, using multidisciplinary techniques and methods to systematically explore the key targets of acupuncture intervention for IS, and reveal the efficacy and mechanism of acupuncture in the treatment of IS.

  • research-article
    Huangan Wu, Luyi Wu
    Acupuncture and Herbal Medicine, 2024, 4(1): 16-18. https://doi.org/10.1097/HM9.0000000000000091
  • research-article
    Yu-Xin Zhu, Zi-Ling Tang, Lu Lu, Zuo-Cheng Qiu, Dabo Pan, Yang Yu, Hui-Hui Xiao, Man-Sau Wong
    Acupuncture and Herbal Medicine, 2024, 4(1): 102-112. https://doi.org/10.1097/HM9.0000000000000095

    Objective: Gut-derived serotonin strongly inhibits bone formation by inhibiting osteoblast proliferation. Our previous study demonstrated that the lignan-rich fraction prepared from Sambucus willimasii Hance, a folk herbal medicine used to treat bone fractures and joint diseases in China, exerted bone-protective effects, and its actions were modulated by suppressing the synthesis of gut-derived serotonin via the inhibition of intestinal tryptophan hydroxylase 1 (TPH-1). However, there is no direct evidence for the action of lignans on TPH-1. This study aimed to verify the direct action of lignans on the TPH-1 and its influence on serotonin synthesis and bone properties.
    Methods: Molecular docking and surface plasmon resonance were performed to determine the affinities of lignans to TPH-1. The cell viability and the protein activity and expression of TPH-1 were measured in RBL2H3 cells. The serum serotonin level and bone mineral density upon lignan treatment in ovariectomized mice were determined.
    Result: The lignans showed high binding scores and binding affinities to TPH-1, inhibited the activity and protein expression of TPH-1, suppressed the serum serotonin levels in ovariectomized mice as well as promoted bone mineral density.
    Conclusion: This is the first study to report that lignans are novel TPH-1 inhibitors and that these lignans could be potential agents for the management of serotonin-related diseases, including osteoporosis.

  • research-article
    Mengyue Fang, Yuye Lan, Man Li, Chennan Li, Bin Xu, Yan Ma, Sulukkana Noiprasert, Xianghong Jing, Lingling Yu
    Acupuncture and Herbal Medicine, 2024, 4(1): 56-67. https://doi.org/10.1097/HM9.0000000000000092

    Sepsis is a life-threatening inflammatory syndrome with high morbidity and mortality rates. However, options for sepsis are still limited to general treatment in intensive care units (ICUs), and effective therapies that improve sepsis survival are required. Immune disturbances play a vital role in the pathology of sepsis and are associated with protracted inflammation, susceptibility to infections, and death. Therefore, many investigators have focused on the potential benefits of immunomodulation therapy for sepsis. Electroacupuncture (EA) has been practiced in clinics for many years and has shown advantages in treating infectious diseases. Over the last few decades, our understanding of the efficacy and mechanisms of EA in sepsis has undergone considerable developments. We searched the literature regarding “CNKI, Wan Fang Data, VIP Database, PubMed, and Ingenta Connect” from 2010 to 2023, using the keywords “sepsis” “septic” and “electroacupuncture” and 336 sources were searched. Finally, we included 82 studies that targeted the immune system to determine EA's anti-inflammatory and immunomodulatory effects on sepsis. In this review, we found that EA has clinical benefits in relieving septic inflammation, improving immune function, and attenuating related multi-organ injury through several mechanisms, such as activation of the cholinergic anti-inflammatory pathway (CAP), vagal-adrenal axis, inhibition of the nuclear factor Kappa-B (NF-κB) signaling pathway, signal transducers and activators of transcription (STAT) signaling pathway, and improvement of immune cell function. Therefore, EA may be a promising complementary therapy for sepsis treatment. We also expect these data will contribute to further studies on EA in sepsis.

  • research-article
    Jianzhi Wu, Zhi Ma, Yinhao Zhang, Shuni Duan, Rong Sun, Runping Liu, Yijie Li, Xiaojiaoyang Li
    Acupuncture and Herbal Medicine, 2024, 4(2): 243-256. https://doi.org/10.1097/HM9.0000000000000107

    Objective: Drug-induced liver injury (DILI) is the leading cause of acute liver failure and poses a significant challenge to human health. Rhubarb (Rheum officinale Baill. DaHuang) has been clinically used for its heat-clearing and diuresis-promoting effects. However, its toxic effects on different organelles in the liver require further validation.
    Methods: We analyzed the potential targets affecting hepatotoxicity in rhubarb and the potential damage relationship with five major organelles, including microsomes, mitochondria, endoplasmic reticulum (ER), Golgi apparatus (GA), and lysosomes through Integrated Traditional Chinese Medicine (ITCM)/HERB databases and network pharmacology. We isolated and purified different organelles, incubated them with different fractions and monomers of rhubarb in an adenosine triphosphate (ATP) culture system and examined the structural and functional changes in the organelles using particle size analysis and molecular biological experiments to investigate whether rhubarb affects the damage and rupture of major organelles in the liver.
    Results: By combining virtual predictions and experimental verification, our research confirmed that emodin isolated from the anthraquinone of rhubarb, catechin in the tannins of rhubarb, and palmitic acid in the organic acids of rhubarb caused the most significant functional and structural damage to the representative organelles. Among all the monomeric compounds, emodin caused the most damage to the microsome, mitochondria, ER, and lysosome; catechin induced microsome and GA damage; and palmitic acid caused the most damage to microsomes and GA in the liver, suggesting that rhubarb components may exert hepatotoxicity through multi-organelle injury.
    Conclusions: Our findings revealed that rhubarb has varying degrees of damaging effects on different organelles, which in turn affects cellular life activities by impairing organelle morphology and function. This study provides a theoretical basis and technical support for a refined analysis of the toxic components and targets of rhubarb.

  • research-article
    Chunqi Yang, Chengcai Lai, Yi Ru, Baoying Shen, Xiangjun Wu, Jialu Cui, Fangyang Li, Cheng Zhang, Zhuo Shi, Qingyuan Qian, Chengrong Xiao, Yuguang Wang, Boli Zhang, Yue Gao
    Acupuncture and Herbal Medicine, 2024, 4(2): 257-270. https://doi.org/10.1097/HM9.0000000000000108

    Objective: Euodia rutaecarpa, (Wu Zhu Yu) a Chinese medicine clinically used to treat gastrointestinal disorders, has been widely employed. However, Euodia rutaecarpa is regarded as a small toxic traditional Chinese medicine in the Chinese Pharmacopoeia and other herbal works. Using toxicity predictions combined with in vitro and in vivo studies, this study aimed to identify the toxic components and toxic target organs of Euodia rutaecarpa, and explore its toxic mechanism from a metabolic perspective.
    Methods: The toxic target organs of Euodia rutaecarpa were identified through in vitro and in vivo studies. In vitro toxicity screening was performed by alkaloid enrichment and isolation. The potential toxicity of compounds was predicted by Absorption, Distribution, Metabolism, Excretion, and Toxicity Predictor (ADMET Predictor) based on Quantitative Structure-Activity Relationship (QSAR) construction. In addition, the study integrated the serum metabolomic analysis after the administration of potentially toxic components to clarify the effect of potentially toxic substances on metabolism in mice.
    Results: Comparing the acute toxicity in mice of different extraction methods and before and after processing, it was evident that Euodia rutaecarpa alcoholic extract had the highest toxicity, and the target organ of Euodia rutaecarpa toxicity was the liver. The alkaloid fraction of alcoholic extract of Euodia showed strong cytotoxicity. The potential toxicity of Euodia rutaecarpa was calculated and predicted by ADMET Predictor, and alkaloids are suspected to be responsible for the toxicity of Euodia rutaecarpa. Evodiamine significantly reduced the number of cells and increased the mitochondrial membrane potential in vitro. Different metabolites were significantly identified by serum metabolomics, of which bile acid metabolism and steroid hormone biosynthesis are the key pathways of hepatotoxicity.
    Conclusions: Clarify the scientific significance of clinical use of processed products by comparing the acute toxicity of different extraction methods before and after processing. Combining the toxicity prediction based on QSAR with the toxicity screening in vitro and in vivo, the potential toxic target organs and toxic components of Euodia rutaecarpa can be identified. Through metabolomics, we preliminarily revealed that the hepatotoxicity of Euodia rutaecarpa may be related to bile acid metabolism and steroid hormone biosynthesis. This study lays the foundation for elucidating the mechanism of Euodia rutaecarpa and evaluating its safety and quality.

  • research-article
    Yuyang Liu, Xu Wang, Minglu Liu, Xialing Hao, Ying Peng, Jiang Zheng
    Acupuncture and Herbal Medicine, 2024, 4(2): 184-196. https://doi.org/10.1097/HM9.0000000000000118

    Ensuring the safety of traditional Chinese medicines (TCM) has perennially presented a universal challenge in the healthcare realm. Meticulous investigations into the toxicological intricacies of natural products are of paramount significance, particularly regarding the metabolic transformation of these substances and the subsequent generation of reactive intermediates. This biochemical process underlies the genesis of diverse toxic manifestations, including hepatotoxicity, nephrotoxicity, pulmonary toxicity, and genotoxicity. Compounds sorted within TCM, including pyrrolizidine alkaloids, anthraquinones, furanoterpenoids, alkenylbenzenes, bisbenzylisoquinoline alkaloids, flavonoids, and methylenedioxyphenyl derivatives, evince a spectrum of deleterious mechanisms upon metabolic activation. This review provides a comprehensive delineation of the pathways through which these compounds induce toxicity via metabolic activation. This review emphasizes the chemical mechanisms involved in the metabolic activation of natural products that may trigger a toxic cascade, rather than a superficial phenomenon. Furthermore, this study enriches the extant literature by delving into advancements in elucidating the mechanisms of toxicity engendered by metabolic activation. In conclusion, this review highlights the importance of scrutinizing the mechanisms of toxicity and provides insights into the judicious and safe use of TCM.

  • research-article
    Xu Zhao, Zhaofang Bai, Xiaoyan Zhan, Jiabo Wang, Yungchi Cheng, Xiaohe Xiao
    Acupuncture and Herbal Medicine, 2024, 4(2): 171-175. https://doi.org/10.1097/HM9.0000000000000119

    Today, as the use of traditional Chinese medicine (TCM) becomes widespread globally, TCM is confronted with numerous new safety issues and challenges. In particular, the frequent emergence of safety issues/events such as liver and kidney injury associated with traditionally “non-toxic” TCM has overturned the conventional understanding of the toxicity and safety of TCM. This has also posed significant challenges to the development and internationalization of TCM. So, how should we understand the situation and problems of TCM safety? How can we scientifically solve the problems in evaluation and risk control of TCM? Our team proposes the following: First, we must keep pace with the times and view the issues of TCM safety in a dialectical manner, without exaggeration or underestimation. Second, we must break through the traditional perception that toxicity only came from the medicine itself, and innovate the theories of TCM toxicity. Third, we must establish precise prevention and control strategies for TCM with different types of toxicity, promoting a shift in the management of TCM safety risks from passive response to scientific and proactive control. On this basis, we have put forward the concept and methodological system of the “New Outlook on TCM safety”, hoping to provide new theories, strategies, methods, and successful examples for systematically solving the problems in the evaluation and risk control of TCM.

  • research-article
    Qianhui Tang, Qinwei Yu, Bin Ni, Zhenzhou Jiang, Luyong Zhang
    Acupuncture and Herbal Medicine, 2024, 4(2): 176-183. https://doi.org/10.1097/HM9.0000000000000117

    Psoraleae Fructus, the dried mature fruit of the leguminous plant Psoralea corylifolia L., contains flavonoids, coumarins, monoterpene phenols, and benzofurans. It exhibits various pharmacological activities, including immune regulation, antioxidant properties, photosensitivity, and estrogen-like effects, and finds extensive use in the clinical treatment of osteoporosis, vitiligo, and psoriasis. Extensive pharmacological research has demonstrated that Psoraleae Fructus and its components improve liver function and protect hepatocytes in animal and cellular models of liver diseases. Moreover, with the increasing clinical applications of Psoraleae Fructus and its derivatives, as well as the progression in adverse drug reaction surveillance, there is an increase in clinical cases involving these preparations and the enhancement of monitoring for any adverse reactions linked to Psoraleae Fructus and its related compounds. Here, we examined the hepatoprotective effects and hepatotoxicity of the monomer components, extracts, and related preparations of Psoraleae Fructus. We aim to contribute to safety evaluation, facilitate informed clinical application, and foster advancements in Psoraleae Fructus and its derivatives.

  • research-article
    Huanhua Xu, Wei Zhou, Jianfeng Yi, Boli Zhang, Yue Gao
    Acupuncture and Herbal Medicine, 2024, 4(2): 167-170. https://doi.org/10.1097/HM9.0000000000000101
  • research-article
    Xin Li, Ranyun Chen, Shuni Duan, Yijie Li, Huiping Zhou, Runping Liu, Rong Sun
    Acupuncture and Herbal Medicine, 2024, 4(2): 197-208. https://doi.org/10.1097/HM9.0000000000000114

    Asari Radix et Rhizoma (ARR), also known as Xixin, has been broadly used as a traditional herbal medicine in East Asia and is an important component of classic prescriptions, including Mahuang Fuzi Xixin decoction. It was initially classified as a “top grade” herb in ancient Chinese Pharmacopeia, Shennong’s Materia Medica. Volatile oils, lignans, fatty acids, flavonoids, and nitrogen-containing compounds are the main ARR components. Previous pharmacological studies have shown that ARR exerts beneficial effects in humans for treating headaches, toothaches, and several inflammatory diseases by dispelling wind and cold, alleviating pain, and eliminating phlegm. However, “the dosage of ARR should not exceed one coin (approximately 3.75 grams),” as stated in Shizhen Li’s Compendium of Materia, which emphasized the considerable ARR toxicity and significantly constrained its clinical application. This review aimed to consolidate recent advancements in the understanding of the toxic ARR components. Additionally, we provide an overview of the hepatotoxicity, genotoxicity, neurotoxicity, and pulmonary toxicity of ARR and discuss the underlying molecular mechanisms. This study reviews the limitations of current studies and enhances our understanding of the toxic effects of ARR from the perspective of its toxic components and mechanisms, thereby providing a theoretical basis for the rational clinical practice of ARR-based medications.

  • research-article
    Can Tu, Yuan Gao, Zhaofang Bai, Xiaohe Xiao, Jiabo Wang
    Acupuncture and Herbal Medicine, 2024, 4(2): 271-281. https://doi.org/10.1097/HM9.0000000000000116

    In recent years, adverse reactions and events associated with traditional Chinese medicines (TCM) and herbal medicines (HM) have frequently occurred. In particular, with regard to the safety of newly discovered TCM that have been deemed “toxic,” providing a scientifically based answer and developing effective solutions is challenging. Owing to the complexity of TCM/HM products and lack of systematic research, our understanding of the potential causes of TCM/HM-induced liver injury is limited. Therefore, significant advancements in understanding the toxicity of TCM and preventing and managing safety risks are urgently needed to address the safety concerns associated with TCM/HM. Using Polygoni Multiflori Radix (PMR) hepatotoxicity as a typical example, we evaluated the “integrated evidence chain” based on the causality evaluation of TCM-induced liver injury, and confirmed the objective authenticity of PMR hepatotoxicity. Furthermore, we first proposed and established a disease-syndrome-combined toxicology model that was applied to the material basis and analysis of the mechanism of PMR-induced hepatotoxicity. The mechanism hypothesis of “three-factor-induced toxicity” of idiosyncratic hepatotoxicity of TCM was proposed and confirmed. Based on this, the disease characteristics of the population susceptible to PMR idiosyncratic hepatotoxicity were elucidated, and various biomarkers were screened and identified, including the genetic marker HLA-B*35:01 and immunological and metabolomic markers. Finally, the study explored and established a safe medication strategy and method for “host-drug-use” three-dimensional risk prevention and control based on identifying susceptible individuals, controlling susceptible substances, and clinical precision medication. This study provides a foundation for comprehensively understanding the scientific implications of TCM/HM toxic side reactions and establishing scientific and effective risk prevention and control strategies.

  • research-article
    Willow JH Liu
    Acupuncture and Herbal Medicine, 2024, 4(2): 159-166. https://doi.org/10.1097/HM9.0000000000000110
  • research-article
    Zhuo Shi, Jin-Chao Pan, Cheng Zhang, Jia-Lu Cui, Xiang-Jun Wu, Fang-Yang Li, Mao-Xing Li, Cheng-Rong Xiao, Zeng-Chun Ma, Yu-Guang Wang, Yue Gao
    Acupuncture and Herbal Medicine, 2024, 4(2): 234-242. https://doi.org/10.1097/HM9.0000000000000112

    Objective: To compare the acute toxicity and chemical ingredients of Psoraleae Fructus (PF) with those of two classic prescriptions, Ershen Wan (ESW) and Sishen Wan (SSW).
    Methods: Based on classical toxicological methods, body weight, food and water consumption, lethal conditions, and toxic reactions were recorded after administering single oral doses of PF, ESW, and SSW. The 50% lethal dose (LD50) values of PF and ESW and the maximum tolerance dose (MTD) of SSW were determined. In addition, PF, ESW, and SSW constituents were detected using ultra-high-performance liquid chromatography/mass spectrometry (UPLC-MS), and the spectrum-toxicity correlation was analyzed.
    Results: The LD50 of PF and ESW were 53.9 g/kg/day (46.2-63.0 g/kg/day, 95% confidence limit [CL]) and 68.3 g/kg/day (59.0-78.9 g/kg/day, 95% CL), which were respectively about 40 and 50 times the human daily dosage. The MTD of SSW was 41.0 g/kg/day, indicating the highest safety. What can be inferred from the chemical ingredients and toxicity correlation analyses is that compatibility reduced the contents of 13 potential hepatotoxin compounds in PF.
    Conclusions: The classic compatibility of ESW and SSW effectively attenuated the hepatotoxicity of PF, which was related to the reduced content of potentially toxic substances, particularly coumarins. This study explored the principles of attenuating the toxicity of classic prescriptions to provide a reference for the rational clinical use of PF.