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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Recently, immunotherapy has redefined cancer treatment by promoting the rapid killing of tumor cells through the immune system. Herbal medicines have been increasingly used as adjunct therapies to complement cancer treatment along with chemotherapy and radiotherapy to delay tumor development, reduce pain, and prolong patient survival. However, the potential immunotherapeutic effects of these herbal derivatives are limited by their structural instability, poor membrane permeability, and low bioavailability. To address this issue, nanotechnology has been used to enhance the activity of active compounds. Therefore, this review focuses on the effectiveness of the active ingredients of herbal medicines in suppressing tumor progression by modulating both the innate and adaptive immune systems, challenges in their delivery, and the application of nanocarriers for the effective delivery of these herbal components.

Objective: Bone is a tissue that is constantly remodeled to adjust the microarchitecture and maintain the mechanical needs of bone through the balance of bone resorption and formation processes. Alterations in these processes can lead to the development of different diseases, such as osteoarthritis and osteoporosis. In recent years, it has been shown that acupuncture is an effective treatment for pain, physical dysfunctions, and the immune system, so the stimulation of acupuncture points could affect genes associated with inflammatory processes and, therefore, osteoarthritis and osteoporosis. To analyze changes in gene expression post-acupuncture in data from a group of individuals with osteoarthritis that also manifests in osteoporosis.
Methods: Through using microarray technology and bioinformatics analysis, potential genes associated with osteoarthritis after acupuncture treatment are identified and compared with genes implicated in osteoporosis. The genes identified in each disease were evaluated through a Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis, where the results allowed the generation of an in-silico model that shows interaction networks between signaling pathways and genes involved in both diseases.
Results: In this interaction, 37 differentially expressed genes were identified in patients with osteoarthritis before and after acupuncture treatment, and 665 differentially expressed genes were involved in osteoporosis. In the osteoarthritis group, 15 signaling pathways involved in this disease were obtained, and for osteoporosis, 13 signaling pathways associated with immunological processes that participate in bone metabolism were obtained osteoarthritis and osteoporosis are two age-associated diseases that are characterized by alterations in the bone remodeling mechanism induced by changes in gene expression profiles.
Conclusions: Treatment with acupuncture can modify various cytokines involved in diseases related to the immune system so that it can have beneficial effects on osteoarthritis and osteoporosis. In addition, bioinformatics analysis allows us to know those signaling pathways through which they could have acupuncture effects.

Objective: Camellia nitidissima Chi, a Chinese medicine commonly used by ethnic minorities in Guangxi, China, is beneficial for clearing heat, detoxifying, inducing diuresis, and suppressing swelling. It has various pharmacological properties, including antitumor, anti-inflammatory, and antioxidant. However, its potential application in radioprotection remains unclear. In this study, we aimed to determine whether Camellia nitidissima Chi has radioprotective effects against radiation-induced gastrointestinal and hematopoietic damage.
Methods: The 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical and 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) techniques were used to assess the ability of Camellia nitidissima Chi to scavenge free radicals. We conducted a 30-day survival rate experiment to evaluate the radioprotective capabilities of Camellia nitidissima Chi. Additionally, we developed models of radiation-induced intestinal and hematopoietic damage. Alterations in the white blood cell (WBC) count, total superoxide dismutase (T-SOD), glutathione (GSH), and protein expression linked to apoptosis were observed.
Results: Camellia nitidissima Chi scavenged 84.72% and 93.47% of DPPH and ABTS, had a certain radiation protection potential, and increased the survival rate of mice to over 90%. Moreover, following exposure, Camellia nitidissima Chi enhanced WBC, T-SOD, and GSH levels. Camellia nitidissima Chi increased B-cell lymphoma-extra large (BCL-XL) expression and suppressed Bcl-2 associated X protein (BAX) expression, providing radioprotection to cells.
Conclusions: Camellia nitidissima Chi has a strong antioxidant ability; it can improve the survival rate of mice after lethal dose irradiation and protect against radiation-induced hematopoietic and gastrointestinal damage. These findings can serve as a guide for using Chinese medicines for radioprotection.

The meridian theory is an important component of traditional Chinese medicine, playing a crucial role in disease diagnosis, treatment, and health preservation. Serving as the media for the effects of acupuncture, moxibustion, herbal medicine, and acupressure massage, meridians exert undeniable impact on the human body. However, the essence of meridians remains a topic of debate. Recent research has primarily focused on their anatomical structures, leading to numerous hypotheses. Simultaneously, other researchers have approached this subject from an energetic perspective, discovering information interactions within the meridian system. These findings suggest that meridians possess both physical and information dimensions, indicating that a singular approach to their study is insufficient. To bridge this gap, a shift from purely structural research toward an exploration of the information aspects of meridians is necessary. By integrating this information approach with traditional meridian theory, it may be possible to develop a new, modernized meridian theory that is aligned with contemporary concepts, making it more accessible and applicable in clinical settings.

Objective: Patients with colon adenocarcinoma (COAD) who undergo radiation therapy develop radiation enteritis (RE). The predictive value of RE in COAD is yet to be established. Berberine, an active compound derived from the traditional Chinese medicinal plant, Coptis chinensis, has notable anti-inflammatory properties and offers protection to the intestinal mucosa. This study aimed to evaluate the possible therapeutic effect and mechanism of berberine as a treatment for COAD complicated with RE (COAD&RE).
Methods: Relevant genetic features of diverse COAD&RE populations were analyzed using bioinformatics and the Cox proportional hazards regression model. The therapeutic targets of berberine were predicted using network pharmacology and molecular docking. In vivo and in vitro experiments were conducted to validate the core genes identified using molecular docking.
Results: RE has a certain impact on the prognosis of COAD and berberine may play an important role in the treatment of COAD&RE. In addition, we identified five core therapeutic targets of berberine by network pharmacology and molecular docking: CCND1, MYC, AR, LEP, and CYP19A1. In vivo experiments showed that berberine increased short-term survival rate, body weight, and intestinal epithelial cell recovery in mice after radiation. In an in vitro study, berberine promoted the proliferation of human intestinal epithelial cells and enhanced the radiosensitivity of HT29 cells after radiation, and the relative mRNA expression levels of CCND1 and MYC closely correlated with these effects.
Conclusions: This study predicted the potential therapeutic effects of berberine on COAD&RE and verified the relevant mechanisms, which may provide insights and suggestions for the clinical treatment of COAD&RE.

People turn nervous when mention is made of radiation injuries, which cause multiple organ morbidities and are difficult to manage. However, the discovery of antiradiation drugs remains challenging. Traditional Chinese medicine (TCM) may be an effective treatment strategy because of its overall regulation. Herein, we systematically review TCM formulae, herbs, and natural products as potential antiradiation candidates. At the same time, we categorize them by their effective characteristics and target organs. In addition, TCM formulae, herbs, and ingredients used to block the absorption and accelerate the excretion of radionuclides are considered in this review. To better manage radiation injuries, the scientific basis of TCM for radioprotection requires further in-depth research.

Objective: Injury can lead to long-term changes that increase the sensitivity of afferent nerve endings to subsequent stimulation and pain can transition from acute to chronic. This phenomenon is known as hyperalgesic priming (HP). This study aimed to understand the mechanisms underlying the effect of electroacupuncture (EA) on HP and optimize acupoint selection for EA to prevent pain transition.
Methods: A rat HP model was established using sequential intraplantar injections of carrageenan (Cg) and prostaglandin E2 (PGE2). The pain thresholds were measured using von Frey filaments. EA on bilateral Zusanli (ST36) and Kunlun (BL60) was used to prevent pain transition. The number of mast cells in the ipsilateral hindpaw skin was determined using toluidine blue or fluorescence-labeled avidin staining. The protein expression levels of protein kinase C epsilon (PKCε) in the lumbar dorsal root ganglions (DRGs) were detected by western blotting 24 h after PGE2 injection. Serial pharmacological experiments were conducted to evaluate the relationship between mast cells and pain transition. Finally, EA on the bilateral ST36 and Chongyang (ST42) or a novel combination (ST36 and ST42 on the ipsilateral side, and ST36 and BL60 on the contralateral side) was used to prevent pain transition.
Results: Although EA applied to ST36 and BL60 alleviated acute pain induced by Cg injection, it failed to prevent the pain transition caused by PGE2 injection. Mast cell accumulation in the ipsilateral hind paw was observed 7 days after Cg injection. Furthermore, mast cell degranulation may be responsible for PKCε activation in the DRG, a marker of pain transition. EA significantly decreased the number of mast cells in the skin of the ipsilateral hind paw when applied at ST36 and ST42, but not when applied at ST36 and BL60. Furthermore, EA employed to ST36 and ST42 significantly reversed long-term hyperalgesia induced by PGE2 injection, even when administered before injection. However, EA did not alleviate acute pain caused by Cg injection. By using a novel acupoint combination, EA simultaneously alleviated acute pain and prevented pain transition.
Conclusions: Our study suggests that mast cells play a critical role in both HP and the transition from acute to chronic pain, whereas EA can prevent pain transition by decreasing the number of mast cells in the local tissue.

Objective: The paper is to comprehensively summarize and analyze the basic situation and methodological quality of clinical randomized controlled trials (RCTs) of traditional Chinese patent medicines and traditional Chinese classic famous prescriptions published in 2022, to provide evidence and reasonable suggestions for the advancement of clinical research and the formulation of policies and guidelines.
Methods: The Evidence Database System of clinical evidence-based evaluation of traditional Chinese medicine was searched, and data from China National Knowledge Infrastructure (CNKI), PubMed, and other databases were supplemented. The search duration was from January 1, 2022, to December 31, 2022. RCTs of traditional Chinese patent medicines and traditional Chinese classic famous prescriptions were included as the source of clinical evidence, and published information, sample size, intervention, control measures, treatment course, methodological quality, and key link report were analyzed and evaluated.
Results: A total of 1,464 RCTs of traditional Chinese patent medicines were included, which comprised 667 types of traditional Chinese patent medicines; “traditional Chinese patent medicinesβ+βWestern medicine vs. Western medicine” was the most widely used intervention and control setting, involving 417 RCTs (28.48%). A total of 245 RCTs of traditional Chinese classic famous prescriptions were included, comprising 55 types of traditional Chinese classic famous prescriptions. “Decoctionβ+βconventional treatment vs. conventional treatment” was the most widely used intervention and control setting, with 87 RCTs (35.51%). Published RCTs on traditional Chinese patent medicines and traditional Chinese classic famous prescriptions were limited by the study design and implementation. Most “allocation concealment” and “blinding of patients and personnel” were rated as medium to high risk. There are insufficient reports on key research links such as experimental registration and ethical approval.
Conclusions: The number of RCTs on traditional Chinese patent medicines has decreased in 2022, but there has been a slight improvement in the research quality and impact. There are relatively few studies on traditional Chinese classic famous prescriptions. Measures must be taken to improve clinical trial design, implementation, and reporting. Methodological experts should be invited to provide professional technical guidance on the trial design. In the research implementation process, attention should be paid to quality control, particularly the standardization of the randomized execution.

Star anise (Illicium verum Hook. f., SA) is a well-known culinary seasoning in China and Vietnam. Actually, SA also has been widely used as a traditional Chinese medicine in China with a long history. Phytochemical analysis has revealed that SA contains a high concentration of essential oils, phenols, flavonoids, and other bioactive compounds that contribute to its diverse pharmacological properties. These properties include antibacterial, anti-inflammatory and analgesic, anti-oxidation, antiviral, anti-cancer, anti-diabetes, antidiarrheal, and promoting hair growth. Various preclinical studies have shown that SA extracts and their active constituents may have potential therapeutic applications in preventing and treating various diseases. However, a comprehensive report on the relationship between the active ingredient, biological activity, and food characteristics of SA is rare. The medicinal value of SA has not been well valued and developed. This review provides an overview of the botanical chemistry and pharmacological properties of SA, as well as its potential innovative applications in food and personal care products, aiming to provide theoretical support for its further development and utilization.

Objective: A model of inflammatory damage was induced by radiation to investigate whether ferulic acid (FA) can reduce the inflammatory response through the Sirt1-NLRP3 inflammatory pathway. This will help discover radiation-protective drugs and elucidate the molecular mechanisms related to radiation-induced inflammatory damage.
Methods: A mouse model of radiation-induced immunoinflammatory injury was established to verify the anti-inflammatory effects of FA in vivo. C57BL/6J mice were randomly divided into six groups, and 5 Gy whole-body irradiation was used for modeling. Mice were administered a gastric solvent, amifostine, or 25, 50, or 100 mg/kg FA daily for 12 days, consecutively, before irradiation. The serum of mice was collected 24 hour after irradiation to observe the content of inflammatory factors interleukin (IL)-1β, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The spleen and thymus tissues of mice were weighed and the organ index was calculated for pathological testing and immunofluorescence detection.
Results: FA reduced the radiation-induced decrease in the spleen and thymus indices. FA significantly reduced the secretion of inflammatory factors in the serum and reversed the radiation-induced reduction in lymphocytes in the spleen and thymus of mice. FA activated Sirt1 and inhibited the expression of the NLRP3 inflammasome to alleviate the inflammatory response.
Conclusions: FA reduced radiation-induced inflammation in animals, possibly by activating Sirt1 and reducing nucleotide oligomerization domain (NOD)-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome expression, thereby reducing the secretion of inflammatory factors.

Objective: Radiotherapy is used to treat patients with tumors; however, radiation (IR)-induced testicular injury, which has no effective treatment approved in clinical practice, significantly influences their prognosis and quality of life. The protective effects and underlying mechanisms of action of isofraxidin (IF) against IR-induced testicular injury were investigated.
Methods: A mouse testis injury model was established using 5 Gy irradiation. Hematoxylin and eosin (H&E) staining, immunofluorescence staining, and enzyme-linked immunosorbent assay were used to measure DNA damage, apoptosis, inflammatory reactions, and oxidative stress in the testes of mice after irradiation. The effectiveness of IF irradiation on testicular injury was evaluated, and the mechanisms of the related oxidative stress and inflammatory response pathways were discussed.
Results: IF can improve IR-induced testicular injury by inhibiting the increased levels of DNA damage, apoptosis rate, oxidative stress, and inflammatory factors. The radioprotective effects of IF on testicular injury are mediated by the stimulation of nuclear factor E2-related factor 2 (Nrf2)/heme oxidase-1 (HO-1) or suppression of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome signaling pathways. In addition, crosstalk between the Nrf2/HO-1 and NLRP3 inflammasome signaling pathways was elucidated, in which the inhibition of the NLRP3 inflammasome was mediated by the activation of Nrf2 signaling with IF upon IR exposure.
Conclusion: IF can be a potent radioprotective agent to mitigate testicular damage, and may provide a new therapeutic option to alleviate the side effects of radiotherapy in male patients with tumors.

Acute myocardial infarction (MI) is associated with high morbidity and mortality and poses a significant challenge to human health. Despite advances in medicine, effective treatment options for MI are still associated with adverse outcomes, such as heart failure. Consequently, identifying the pathogenesis of MI is a promising avenue for developing practical treatments. The inflammatory response plays a critical role in the pathogenesis of MI. Gasdermin D (GSDMD)-mediated pyroptosis regulates the inflammatory response, which is a pathogenic and potential therapeutic target for MI. Therefore, anti-pyroptosis treatment is emerging as a promising therapeutic approach for MI. Overall, this article reviews the mechanism and treatment strategies for GSDMD-mediated pyroptosis in MI, with the hope of providing insights into pathogenic interventions.