Targeting RhoA expression with formononetin and salvianolic acid B to mitigate pancreatic cancer-associated endothelial cells changes.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the theory of Qi and blood in Traditional Chinese Medicine (TCM), the combination of Qi-reinforcing herbs and blood-activating herbs has a synergistic effect in improving blood stasis syndrome, especially in tumor treatment. The classic "Radix Astragali - Salvia miltiorrhiza" duo exemplifies this principle, renowned for invigorating Qi and activating blood flow, employed widely in tumor therapies. Our prior research underscores the potent inhibition of pancreatic tumor xenografts by the combination of Formononetin (from Radix Astragali) and Salvianolic acid B (from Salvia miltiorrhiza) in vitro. However, it remains unclear whether this combination can inhibit the abnormal vascularization of pancreatic tumors to achieve its anti-cancer effect. AIM OF THE STUDY: Abnormal vasculature, known to facilitate tumor growth and metastasis. Strategies to normalize tumor-associated blood vessels provide a promising avenue for anti-tumor therapy. This study aimed to unravel the therapeutic potential of Formononetin combined with Salvianolic acid B (FcS) in modulating pancreatic cancer's impact on endothelial cells, illuminate the underlying mechanisms that govern this therapeutic interaction, thereby advancing strategies to normalize tumor vasculature and combat cancer progression. MATERIALS AND METHODS: A co-culture system involving Human Umbilical Vein Endothelial Cells (HUVECs) and PANC-1 cells was established to investigate the potential of targeting abnormal vasculature as a novel anti-tumor therapeutic strategy. We systematically compared HUVEC proliferation, migration, invasion, and lumenogenesis in both mono- and co-culture conditions with PANC-1 (H-P). Subsequently, FcS treatment of the H-P system was evaluated for its anti-angiogenic properties. Molecular docking was utilized to predict the interactions between Formononetin and Salvianolic acid B with RhoA, and the post-treatment expression of RhoA in HUVECs was assessed. Furthermore, we utilized shRhoA lentivirus to elucidate the role of RhoA in FcS-mediated effects on HUVECs. In vivo, a zebrafish xenograft tumor model was employed to assess FcS's anti-tumor potential, focusing on cancer cell proliferation, migration, apoptosis, and vascular development. RESULTS: FcS treatment demonstrated a significant, dose-dependent inhibition of PANC-1-induced alterations in HUVECs, including proliferation, migration, invasion, and tube formation capabilities. Molecular docking analyses indicated potential interactions between FcS and RhoA. Further, FcS treatment was found to downregulate RhoA expression and modulated the PI3K/AKT signaling pathway in PANC-1-induced HUVECs. Notably, the phenotypic inhibitory effects of FcS on HUVECs were attenuated by RhoA knockdown. In vivo zebrafish studies validated FcS's anti-tumor activity, inhibiting cancer cell proliferation, metastasis, and vascular sprouting, while promoting tumor cell apoptosis. CONCLUSIONS: This study underscores the promising potential of FcS in countering pancreatic cancer-induced endothelial alterations. FcS exhibits pronounced anti-abnormal vasculature effects, potentially achieved through downregulation of RhoA and inhibition of the PI3K/Akt signaling pathway, thereby presenting a novel therapeutic avenue for pancreatic cancer management.

Exploring the bioactive ingredients of three traditional Chinese medicine formulas against age-related hearing loss through network pharmacology and experimental validation.

Traditional Chinese medicine (TCM) formulas, including the Er-Long-Zuo-Ci pill, Tong-Qiao-Er-Long pill, and Er-Long pill, have long been utilized in China for managing age-related hearing loss (ARHL). However, the specific bioactive compounds, pharmacological targets, and underlying mechanisms remain elusive. This study aims to find the shared bioactive ingredients among these three formulas, uncover the molecular pathways they regulate, and identify potential therapeutic targets for ARHL. Furthermore, it seeks to validate the efficacy of these major components through both in vivo and in vitro experiments. Common bioactive ingredients were extracted from the TCMSP database, and their putative target proteins were predicted using the Swiss Target Prediction database. ARHL-related target proteins were collected from GeneCards and OMIM databases. Our approach involved constructing drug-target networks and drug-disease-specific protein-protein interaction networks and conducting clustering, topological property analyses, and functional annotation through GO and KEGG enrichment analysis. Molecular docking analysis was utilized to delineate interaction mechanisms between major bioactive ingredients and key target proteins. Finally, in vivo and in vitro experiments involving ABR recording, immunofluorescent staining, HE staining, and quantitative PCR were conducted to validate the treatment effects of flavonoids on the declining auditory function in DBA/2 J mice. We identified 11 common chemical compounds across the three formulas and their associated 276 putative targets. Additionally, 3350 ARHL-related targets were compiled. As an intersection of the putative targets of the common compounds and ARHL-related proteins, 145 shared targets were determined. Functional enrichment analysis indicated that these compounds may modulate various biological processes, including cell proliferation, apoptosis, inflammatory response, and synaptic connections. Notably, potential targets such as TNFα, MAPK1, SRC, AKT, EGFR, ESR1, and AR were implicated. Flavonoids emerged as major bioactive components against ARHL based on target numbers, with molecular docking demonstrating diverse interaction models between these flavonoids and protein targets. Furthermore, baicalin could mitigate the age-related cochlear damage and hearing loss of DBA/2 J mice through its multi-target and multi-pathway mechanism, involving anti-inflammation, modulation of sex hormone-related pathways, and activation of potassium channels. This study offers an integrated network pharmacology approach, validated by in vivo and in vitro experiments, shedding light on the potential mechanisms, major active components, and therapeutic targets of TCM formulas for treating ARHL.

Calming the Wind: A Traditional Chinese Medicine Practitioner's Approach to Wartime Acute Stress Disorder Symptoms.

In this narrative essay, a traditional Chinese medicine (TCM) practitioner describes the challenge of treating three survivors of a terror attack, all of whom were presenting various symptoms of acute stress disorder (ASD). Working in new and exceptionally demanding circumstances - with thousands of people injured in an extensive and direct terror attack, with relatives taken hostages and entire communities evacuated from their homes - the practitioner looked for an effective treatment strategy to alleviate symptoms of stress response. He found it in the interface between TCM and the function of the autonomic nervous system.

Effects and Safety of the Traditional Chinese Exercise Baduanjin on Depression and Anxiety in COVID-19 Patients: A Systematic Review and Meta-analysis.

AIM: This systematic review and meta-analysis aimed to assess the safety and efficacy of Baduanjin, a traditional Chinese exercise (TCM), for reducing depression and anxiety in individuals suffering from coronavirus disease 2019 (COVID-19). METHODS: Nineteen databases were searched from their inception through August 2024 to gather data for this study. The focus of this study was randomized controlled trials (RCTs) in which Baduanjin was administered for the treatment of COVID-19 patients with depression and anxiety. The study included various types of Baduanjin exercise, whether used alone or in conjunction with other treatment modalities, for the control group. The comparators included a waitlist control, usual care, health education and supportive counseling, psychosocial support therapy, pharmacotherapies, and other common exercises. The exclusion criteria for trials were trials comparing different treatment durations, different treatment frequencies, and different types of Baduanjin exercise. Moreover, other traditional Chinese medicine (TCM) therapeutic methods applied in either the intervention or control group were also excluded. Throughout the entire study, the selection process, data extraction and quantitative analysis were carried out in strict adherence to all relevant guidelines. The Cochrane criteria for risk of bias were used to assess the methodological quality of the trials. In our review, a meta-analysis was performed using the software STATA MP14. RESULTS: After conducting a meta-analysis, eight RCTs were found to have satisfied the inclusion criteria. The effects of Baduanjin exercise on self-rating anxiety scale (SAS) scores were investigated in five RCTs comprising a total of 228 patients. Analysis of the results revealed that the combination of Baduanjin exercises and conventional therapies led to a statistically significant reduction in SAS scores [MD=-3.21 (95% CI= -3.64, -2.79), P< 0.001] compared to conventional therapies alone. Moreover, this systematic review explored the effect of Baduanjin exercise on self-rating depression scale (SDS) scores (three RCTs involving 83 participants), Hamilton Anxiety Rating Scale (HAM-A) scores (one RCT involving 103 participants), Patient Health Questionnaire (PHQ-9) scores (one RCT involving 70 participants) and Generalized Anxiety Disorder-7 (GAD-7) scores (one RCT involving 59 participants) for patients with COVID-19. The results showed that, in addition to conventional therapies, Baduanjin exercise had a more favorable impact on reducing the SDS score [mean difference (MD) =-2.86 (95% CI=4.11, -1.61), P=0.025], PHQ-9 score [MD=-5.31, 95% CI=-8.73, -1.89), P=0.002] and HAM-A score [MD=-3.00, 95% CI=-5.33, -0.67], P=0.010] in patients with COVID-19 than did the use of conventional therapies alone. Furthermore, the combination of Baduanjin exercise and conventional therapies effectively decreased the number of patients who experienced severe or moderate anxiety according to the GAD-7 score compared to that of patients who experienced severe or moderate anxiety according to conventional therapies alone [Relative Risk (RR) =0.03, 95% CI=0.00, 0.51); P=0.020]. However, the included clinical trials lacked a detailed description of the randomization process, and only a small portion of the studies reported proper allocation concealment procedures, which may introduce selection bias. Moreover, owing to the nature of Baduanjin exercise, it is difficult to blind participants and practitioners, which may lead to performance bias. Furthermore, the lack of blinding may lead to subjective influences of assessors on the results, thereby causing detection bias. These methodological shortcomings and potential biases should be addressed in future studies. CONCLUSIONS: It is difficult to draw firm conclusions on whether Baduanjin exercise is an effective intervention for reducing depression and anxiety in COVID-19 patients because of the high risk of bias among the available RCTs. Further rigorous RCTs are warranted but need to overcome the methodological shortcomings of the existing evidence.

Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) infection posed a huge threat and burden to public healthcare in late 2022. Non-drug measures of traditional Chinese medicine (TCM), such as acupuncture, cupping and moxibustion, are commonly used as adjuncts in China to help in severe cases, but their effects remain unclear. OBJECTIVES: To observe the clinical effect of TCM non-drug measures in improving respiratory function and symptoms among patients with severe COVID-19. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This study was designed as a multicenter, assessor-blind, randomized controlled trial. Hospitalized patients with COVID-19 were randomly assigned to the treatment or control group. The treatment group received individualized TCM non-drug measures in combination with prone position ventilation, while the control group received prone position ventilation only for 5 consecutive days. MAIN OUTCOME MEASURES: The primary outcome measures were the percentage of patients with improved oxygen saturation (SpO2) at the end of the 5-day intervention, as well as changes of patients' respiratory rates. The secondary outcome measures included changes in SpO2 and total score on the self-made respiratory symptom scale. The improvement rate, defined as a 3-day consecutive increase in SpO2, the duration of prone positioning, and adverse events were recorded as well. RESULTS: Among the 198 patients included in the intention-to-treat analysis, 159 (80.3%) completed all assessments on day 5, and 39 (19.7%) patients withdrew from the study. At the end of the intervention, 71 (91%) patients in the treatment group had SpO2 above 93%, while 61 (75.3%) in the control group reached this level. The proportion of participant with improved SpO2 was significantly greater in the intervention group (mean difference [MD] = 15.7; 95% confidence interval [CI]: 4.4, 27.1; P = 0.008). Compared to the baseline, with daily treatment there were significant daily decreases in respiratory rates in both groups, but no statistical differences between groups were found (all P ≥ 0.05). Compared to the control group, the respiratory-related symptoms score was lower among patients in the treatment group (MD = -1.7; 95%CI: -2.8, -0.5; P = 0.008) after day 3 of treatment. A gradual decrease in the total scores of both groups was also observed. Thirty-one adverse events occurred during the intervention, and 2 patients were transferred to the intensive care unit due to deterioration of their illness. CONCLUSION: TCM non-drug measures combined with prone positioning can effectively treat patients with severe COVID-19. The combined therapy significantly increased SpO2 and improved symptom scores compared to prone positioning alone, thus improving the patients' respiratory function to help them recover. However, the improvement rate did not differ between the two groups. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2300068319). Please cite this article as: Yin X, Jin Z, Li F, Huang L, Hu YM, Zhu BC, Wang ZQ, Li XY, Li JP, Lao LX, Mi YQ, Xu SF. Effectiveness and safety of adjunctive non-drug measures in improving respiratory symptoms among patients with severe COVID-19: A multicenter randomized controlled trial. J Integr Med. 2024; Epub ahead of print.

The Mechanisms and Quality Markers of Anti-rheumatoid Arthritis of Traditional Chinese Medicine.

BACKGROUND: RA is a recurrent autoimmune disease that has significant adverse effects on the physical and mental health of patients. Traditional Chinese medicine has shown significant advantages in the prevention and treatment of RA. Numerous clinical and experimental studies have confirmed that traditional Chinese medicine components have clear therapeutic effects and minimal adverse reactions in treating RA. The research on traditional Chinese medicine for the prevention and treatment of RA has become a hot topic in the field of autoimmune diseases. METHODS: The related references about the mechanisms and Q-markers of anti-RA of traditional Chinese medicine in this review were collected from Willy, SpringLink, Web of Science, Elsevier, PubMed, SciFinder, Scopus, ACS publications, Baidu Scholar, Google Scholar, and CNKI. RESULTS: The traditional Chinese medicine components such as terpenoids, flavonoids, and alkaloids have significant anti-RA effects, and their mechanisms are mainly to inhibit NF-κB signaling pathway, inhibit the proliferation of RA fibroblasts like synovial cells, and regulate Th1/Th2 cell balance, and so on. Predicting and studying the Q-markers of traditional Chinese medicine anti-RA by plant phylogeny and chemical componentss, traditional medicinal properties, pharmacokinetics, component measurability, correlation between composition and efficacy, and gut microbiota will provide scientific foundations for the research and further development of anti-RA traditional Chinese medicine. CONCLUSIONS: The active components of traditional Chinese medicine exhibited the characteristic of multiple mechanisms in the treatment of RA, such as terpenoids had anti-angiogenesis effects, flavonoids had anti-inflammatory and cartilage protective effects, and alkaloids had antiinflammatory and analgesic effects. The proposal of Q-markers for anti-RA provided new research ideas for promoting the development of new drugs for anti-RA and ensuring the safety and effectiveness of clinical medications.

Traditional Chinese Medicine Herbs for Breast Cancer Prevention and Survival: A Narrative Review of Epidemiological Studies from Taiwan.

PURPOSE OF REVIEW: This review aims to describe the association of integrating traditional Chinese medicine (TCM) herbs into conventional medicine (CM) in preventing breast cancer and improving survival rates among breast cancer patients of Taiwan. RECENT FINDINGS: Of 7 relevant studies, spanning 2014-2023, 4 investigated breast cancer risk in women with menopausal symptoms and other comorbidities. All 4 reported that TCM herbal use was associated with lower risks of developing breast cancer. Three studies investigated survival in newly-diagnosed breast cancer patients receiving CM. All reported that adjunctive TCM users had lower mortality rates than CM-only patients. However, the heterogeneity of study designs, populations, and interventions may limit the generalizability and robustness of the findings. TCM herbs may promote breast cancer prevention and survival when used alongside CM. More rigorous observational research and clinical trials in specific patient populations are needed to guide clinical decision-making.

Correlation Analysis of Traditional Chinese Medicine Constitution and Metabolic Indexes in General Physical Examination People.

OBJECTIVE: Analysis of Traditional Chinese Medicine (TCM) constitution type general medical patients and the relationship between the metabolic index. METHODS: A cohort of 1,029 general individuals who underwent a physical examination at the Affiliated Hospital of Changchun University of Chinese Medicine for identification of their TCM constitution between January 2021 and April 2023 were included in this study. Their data were sorted and analyzed using Microsoft Excel and SPSS26.0 statistical software. RESULTS: Among the 1029 study participants, the balanced constitution (BC) type was the most prevalent (33.24%), and the blood stasis constitution (BSC) type was the least prevalent (2.62%). Compared with BC, phlegm-dampness constitution (PDC) (P=0.000), yang-deficiency constitution (YADC) (P=0.000) and BSC (P=0.008) had significant differences in body mass index (BMI) (P<α). The systolic blood pressure (SBP) of PDC was different (P=0.042, P<α). There was a significant difference in diastolic blood pressure (P=0.001, P<α). The diastolic blood pressure (DBP) of YADC was significantly different (P=0.001, P<α). Yin-deficiency constitution (YIDC) (P = 0.007) and YADC differences between fasting blood glucose (FBG) (P = 0.025) were significantly (P<α). There were significant differences in uric acid (UA) of YADC (P=0.000), BSC (P=0.004), PDC (P=0.007) and qi-stagnation constitution (QSC) (P=0.012, P<α). The triglyceride (TG) of YADC (P=0.000) and PDC (P=0.005) were significantly different (P<α). There was a difference in total cholesterol (TC) between PDC (P=0.046) and BC (P<α). BSC (P = 0.028) and PDC (P = 0.023) of low-density lipoprotein cholesterol (LDL-C) also had a significant difference (P<α). CONCLUSION: People with PDC, YADC and BSC had more abnormal metabolic indexes than people with BC, and the metabolic indexes of people with YIDC constitution were different from those with BC. Individuals with these four TCM constitution types should pay attention to making appropriate changes in lifestyles and dietary habits and take required measures to prevent the incidence and development of metabolic diseases.

Matching traditional Chinese medicine and western medicine-based research: Advanced nutraceutical development for proactive gastric cancer prevention.

Gastric cancer (GC), the third leading cause of cancer-related death globally, is complex and heterogeneous. This review explores multidisciplinary investigations of traditional Chinese medicine (TCM) combined with Western medical practices, emphasizing the development of nutraceuticals for cancer prevention. Using advanced analytical chemistry and food chemistry techniques, this study investigated how TCM components may be optimized for nutraceutical development. Focusing on molecular interactions with GC pathways, particularly the NF-κB, PI3K/Akt, and Wnt/ß-catenin pathways, we examined the effects of TCM polyherbal formulas, extracts, and isolated compounds. These agents modulate apoptosis and cellular proliferation, underscoring their potential in preventive strategies. The convergence of nutraceutical and medicine food homology studies highlights a significant shift towards integrating TCM-derived compounds in a preventive health framework. This approach aims not only to enhance efficacy and reduce side effects but also to champion a preventive paradigm using personalized medicine to advance proactive health maintenance and disease prevention. The combination of TCM and western medical practices offers promising avenues for future research and practical applications in GC prevention.

Modern technology-based exploration of mechanism of traditional Chinese medicine in prevention and treatment of gastric cancer.

This review comments on the article "To explore the mechanism of Yigong San anti-gastric cancer and immune regulation". We are interested that the article applied network pharmacology and bioinformatics techniques to elucidate the mechanism of action of Yigong Sang, a traditional Chinese medicine (TCM), in the treatment of gastric cancer (GC). The mechanism of action of Yigong Sang in the treatment of GC has not yet been elucidated because it is composed of multiple Chinese medicines with multiple components and multiple targets. The emergence of network pharmacology and bioinformatics analysis helps explain the mechanism of action of TCM in preventing and treating GC, and provides a possibility for TCM to transform from empirical to evidence-based medicine. This is of great significance for the application of TCM in oncology, new drug development, formula optimization, and the improvement of clinical efficacy.

From traditional Chinese medicine formulations to effective anticancer agents: Insights from Calculus bovis.

This editorial examines the therapeutic potential of traditional Chinese medicine (TCM) for aggressive cancers, particularly liver cancer. It highlights the study by Huang et al, which shows how Calculus bovis, a component of the TCM Pien Tze Huang, suppresses liver cancer by inhibiting M2 macrophage polarization via the Wnt/ß-catenin pathway. This research emphasizes the importance of transitioning from effective TCM formulations to isolating active components and understanding their mechanisms. While the study provides valuable insights, it primarily focuses on the Wnt/ß-catenin pathway and does not delve deeply into the mechanisms of individual components. Future research should aim to comprehensively study these components, explore their interactions, and validate findings through clinical trials. This approach will integrate traditional wisdom with modern scientific validation, advancing the development of innovative cancer treatments based on TCM formulations.

Synergistic Integration of Traditional Chinese Medicine and Western Medical Intervention in the Treatment of Brain Abscess: A Case Report.

Brain abscess is life-threatening and carries a high risk of mortality. Despite advances in sensitive imaging techniques, effective antimicrobial therapies, and sophisticated surgical procedures, diagnosing and treating brain abscesses remains challenging. Although empirical antimicrobial therapy and neurosurgery are considered primary treatments for brain abscesses, their efficacy is limited by potential side effects including neutropenia development, the need for repeat surgeries, and the risk of new-onset epilepsy. Here, we present a case of a 52-year-old male patient who experienced paroxysmal convulsions accompanied by left-sided limb weakness and numbness for over 2 months. Despite a brain MRI revealing a multilocular cystic lesion in the right frontal lobe, with about 28 mm × 19 mm × 21 mm in size, the patient declined neurosurgical interventions. After completing a 6-week course of antimicrobial therapy, the patient sought traditional Chinese medicine (TCM) treatment. As a result, the patient remained free of paroxysmal convulsions for about 60 days after a 4-month TCM treatment. A follow-up MRI imaging at 8 months showed a reduction in the size of the lesion in the right frontal lobe to 8 mm × 4 mm. To the best of our knowledge, this is the first well-documented case of a brain abscess that was successfully managed with a combination of antimicrobial therapy and TCM. This case report suggests that TCM may provide significant supplementary benefits in managing infections like brain abscesses. However, further evidence from prospective studies is necessary to substantiate the efficacy of Chinese herbal medicine for the treatment of brain abscesses.

Anti-inflammatory effects of Tao Hong Si Wu Tang in mice with lung cancer and chronic obstructive pulmonary disease.

BACKGROUND: Lung cancer (LC) combined with chronic obstructive pulmonary disease (COPD) is a common combination of comorbidities. Anti-inflammation and modulation of oxidative/antioxidative imbalance may prevent COPD-induced LC, and are also crucial to the treatment of LC combined with COPD. Modern studies have shown that Tao Hong Si Wu Tang (THSW) has vasodilatory, anti-inflammatory, anti-fatigue, anti-shock, immunoregulatory, lipid-reducing, micronutrient-supplementing, and anti-allergy effects. AIM: To observe the effects of THSW on COPD and LC in mice. METHODS: A total of 100 specific pathogen-free C57/BL6 mice were randomly divided into five groups: Blank control group (group A), model control group (group B), THSW group (group C), IL-6 group (group D), and THSW + IL-6 group (group E), with 20 mice in each group. A COPD mouse model was established using fumigation plus lipopolysaccharide intra-airway drip, and an LC model was replicated by in situ inoculation using the Lewis cell method. RESULTS: The blank control group exhibited a clear alveolar structure. The model control and IL-6 groups had thickened alveolar walls, with smaller alveolar lumens, interstitial edema, and several inflammatory infiltrating cells. Histopathological changes in the lungs of the THSW and THSW + IL-6 groups were less than those of the model control group. The serum IL-1ß, IL-6, and TNF-α levels and IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R expression levels in lung tissues of mice in the rest of the groups were significantly higher than those of the blank control group (P < 0.01). Compared with the model control group, the IL-6 group demonstrated significantly higher levels for the abovementioned proteins in the serum and lung tissues (P < 0.01), and the THSW group had significantly higher serum IL-1ß, IL-6, and TNF-α levels and IL-7R expression levels in lung tissues (P < 0.01) but significantly decreased IL-6R, JAK, p-JAK, STAT1/3, p-STAT1/3, FOXO, p-FOXO, and IL-7R levels (P < 0.01). CONCLUSION: THSW reduces the serum IL-1ß, IL-6, and TNF-α levels in the mouse model with anti-inflammatory effects. Its anti-inflammatory mechanism lies in inhibiting the overactivation of the JAK/STAT1/3 signaling pathway.

Simultaneous detection of multiple mycotoxins in Radix Dipsaci and estimation of exposure risk for consumers.

Like many traditional Chinese herbal medicines, preparations from Radix Dipsaci are at risk of contamination by harmful mycotoxins; however, there have been no reports of actual contamination. In this study, we developed an analytical method to simultaneously detect eight mycotoxins in Radix Dipsaci and estimate the exposure risk for consumers. We have developed an analytical method utilizing ultra-high performance liquid chromatography and tandem mass spectrometry to accurately determine the levels of AFB1, AFB2, AFG1, AFG2, OTA, ZEN, T-2 and ST mycotoxins in 45 batches of Radix Dipsaci sourced from major medicinal herb markets across five regions in China. We also analyzed migration of mycotoxins from the raw herbs into water decoction. Based on these results and data on human consumption of the herbal medicine, we estimated risk of exposure and acceptable exposure limits to mycotoxins in the Radix Dipsaci using the "margin of exposure (MOE)" method. Of the 45 batches of Radix Dipsaci, 48.89% contained at least one of the eight mycotoxins, 24.44% contained one, 17.78% contained two and 6.67% contained three. The most frequent mycotoxins were aflatoxin B1, present in 35.56% of batches (at 0.25-34.84 µg/kg); aflatoxin G1, 15.56% (1.99-44.05 µg/kg); and ochratoxin A, 22.22% (16.11-143.38 µg/kg). These three mycotoxins transferred from the raw herb into water decoction at respective rates of 20.20%, 29.14%, and 24.80%. The 95th percentile values of the MOE risk factors for health effects of AFB1 were below 10,000 at high doses but above 10,000 at low doses of Radix Dipsaci long-term treatment. With the reduction in duration of exposure years, the MOE values of AFB1 and AFG1 gradually reverted to within the acceptable range. The mean, 50th, and 95th percentile values of the MOE risk factors for health effects of OTA exceeded 10,000 regardless of whether consumers received a low or high dose of Radix Dipsaci treatment for durations ranging from 1 to lifetime. Based on this exposure and a typical human diet, we have estimated the respective 20-year exposure limits for Radix Dipsaci to be 5.821 µg/kg, 4.035 µg/kg, and 56.073 µg/kg for the three mycotoxins under consideration. Contamination with multiple mycotoxins is frequently observed in Radix Dipsaci, and the three most prevalent contaminants have been found to leach into water decoctions, thereby posing a potential health hazard for individuals consuming this herbal preparation. This work highlights the need to monitor herbal medicines for mycotoxin contamination in order to protect consumers.

Targeting the neurovascular unit: Therapeutic potential of traditional Chinese medicine for the treatment of stroke.

Stroke poses a significant global health challenge due to its elevated disability and mortality rates, particularly affecting developing nations like China. The neurovascular unit (NVU), a new concept encompassing neurons, brain microvascular endothelial cells, pericytes, astrocytes, microglia, and the extracellular matrix, has gained prominence in recent years. Traditional Chinese medicine (TCM), deeply rooted in Chinese history, employs a combination of acupuncture and herbal treatments, demonstrating significant efficacy across all stages of stroke, notably during recovery. The holistic approach of TCM aligns with the NVU's comprehensive view of treating stroke by addressing neurons, surrounding cells, and blood vessels collectively. This review examines the role of NVU in stroke and endeavors to elucidate the mechanisms through which traditional Chinese medicine exerts its anti-stroke effects within the NVU framework. The NVU contributes to neuroinflammation, immune infiltration, blood-brain barrier permeability, oxidative stress, and Ca2+ overload during stroke occurs. Additionally, TCM targeting the NVU facilitates nerve repair post-stroke through various pathways and approaches. Specific herbs, including panax notoginseng, ginseng, and borneol, alleviate brain injury by enhancing brain-derived neurotrophic factor expression and targeting astrocytes and microglia to yield anti-inflammatory and antioxidant effects. Acupuncture, another facet of TCM, promotes brain injury repair by augmenting cerebral blood flow and improving circulation. This exploration aims to assess the viability of stroke treatment by directing TCM interventions toward the NVU, thus paving the way for its broader clinical application.

Jiang Tang San Hao Formula exerts its anti-diabetic effect by affecting the gut-microbiota-brain axis.

BACKGROUND: Type 2 diabetes is a complex metabolic disorder characterized by insulin resistance and impaired insulin secretion, with growing evidence highlighting the critical role of the gut-microbiota-brain axis in modulating glucose and lipid metabolism. OBJECTIVE: To evaluate the effects of Jiang Tang San Hao Formula (JTSHF) on blood glucose control in type 2 diabetic mouse model and to explore its mechanism through the gut- microbiota-brain axis. METHODS: A type 2 diabetes model was established using six-week-old male C57BL6/J mice, induced by a high-fat diet combined with streptozotocin injection. The diabetic mice then randomly assigned to the model group, metformin (Glucophage) group and JTSHF group, receiving 11 weeks of treatment by gavage. Body weight and fasting blood glucose were monitored biweekly. The oral glucose tolerance test was performed during the fifth and 10th weeks of the intervention. The measurements of body composition were conducted pre- and post-treatment. After the intervention, serum insulin, lipid levels, glucagon like peptide-1 (GLP-1), peptide YY, ghrelin, and leptin were detected. The fresh feces of mice were collected before sacrifice for gut microbiota analysis and short chain fatty acids quantification. The colon tissues of mice in each group were collected to observe the morphological structure and to measure the expression levels of GPR41 and GPR43. The hypothalamus was collected to assess the expression of POMC, AgRP and NPY. RESULTS: JTSHF significantly boosted sugar and lipid metabolism and contributed to weight reduction in diabetic mice (p < 0.05). At the genus level, JTSHF increased the relative abundance of Bacteroides, Prevotella, and Parabacteroides, and decreased Clostridium, Lactobacillus, and Oscillibacter in the gut microbiota. JTSHF enhanced the content of short chain fatty acids, improved the expression level of GPR43/41 in colonic tissue (p < 0.05), and increased POMC expression while decreasing AgRP and NPY expression in the hypothalamus (p < 0.05). Serum GLP-1 was increased, and ghrelin was decreased significantly after JTSHF intervention (p < 0.05). CONCLUSION: By affecting the composition, relative abundance, and metabolites of gut microbiota, JTSHF regulates various gut brain peptides, affects the hypothalamic feeding center, improves glucose and lipid metabolism, and thus plays the anti-diabetic role. The study provides novel insights into how traditional Chinese medicine modulates the gut-brain connection to exert anti-diabetic effects, highlighting the innovative potential of JTSHF in metabolic disease management.

A comprehensive review on pharmacokinetic mechanism of herb-herb/drug interactions in Chinese herbal formula.

Oral administration of Chinese Herbal Medicine (CHM) faces various challenges in reaching the target organs including absorption and conversion in the gastrointestinal tract, hepatic metabolism via the portal vein, and eventual systemic circulation. During this process, factors such as gut microbes, physical or chemical barriers, metabolic enzymes, and transporters play crucial roles. Particularly, interactions between different herbs in CHM have been observed both in vitro and in vivo. In vitro, interactions typically manifest as detectable physical or chemical changes, such as facilitating solubilization or producing precipitates when decoctions of multiple herbs are administered. In vivo, such interactions cause alterations in the ADME (absorption, distribution, metabolism, and excretion) profile on metabolic enzymes or transporters in the body, leading to competition, antagonism, inhibition, or activation. These interactions ultimately contribute to differences in the therapeutic and pharmacological effects of multi-herb formulas in CHM. Over the past two thousand years, China has cultivated profound expertise and solid theoretical frameworks over the scientific use of herbs. The combination of multiple herbs in one decoction has been frequently employed to synergistically enhance therapeutic efficacy or mitigate toxic and side effects in clinical settings. Additionally combining herbs with increased toxicity or decreased effect is also regarded as a remedy, a practice that should be approached with caution according to Traditional Chinese Medicine (TCM) physicians. Such historical records and practices serve as a foundation for predicting favorable multi-herb combinations and their potential risks. However, systematic data that are available to support the clinical practice and the exploration of novel herbal formulas remain limited. Therefore, this review aims to summarize the pharmacokinetic interactions and mechanisms of herb-herb or herb-drug combinations from existing works, and to offer guidance as well as evidence for optimizing CHM and developing new medicines with CHM characteristics.

Treatment of acute pharyngitis in rats with season tea decoctions from traditional Chinese medicine through a synergistic and subtle regulation of ARNTL and BHLHE40.

ETHNOPHARMACOLOGICAL RELEVANCE: While the seasonal variations in the human immune function and many infectious diseases are well-known, to develop therapeutic strategies regarding such seasonality is quite challenging. However, some traditional medical practices have already taken the seasonality into account, such as the "Season Tea" (ST) decoctions investigated in the present study. AIM OF THE STUDY: We present a study of the ST decoctions from traditional Chinese medicine, which include four formulae designed for the four seasons, aiming to investigate their pharmacological commonality and distinction. MATERIALS AND METHODS: A rat model of acute pharyngitis was utilized for the pharmacological study, and the effects of the ST decoctions were evaluated through histology, biomedical assays, microarray analysis, real-time quantitative PCR and western blot. RESULTS: The experimental data show that all of the four ST formulae display good pharmaceutical effects on acute pharyngitis, and circadian rhythm appears to be a significant pathway for investigating their pharmacological commonality and distinction. Specifically, while all of the four ST decoctions can regulate the circadian-rhythm-related genes ARNTL and BHLHE40, the regulation is along different directions with the modification of the supplements and the substrates in each ST formula. CONCLUSION: These results indicate the correlation between the acute pharyngitis and circadian rhythm, and illustrate the possibility of synergistically and subtly regulating ARNTL and BHLHE40, which is significant for relevant drug development.

The impact of traditional Chinese medicine and dietary compounds on modulating gut microbiota in hepatic fibrosis: A review.

Traditional Chinese medicine (TCM) and dietary compounds have a profound influence on the regulation of gut microbiota (GM) in hepatic fibrosis (HF). Certain substances found in both food and herbs that are edible and medicinal, such as dietary fiber, polyphenols, and polysaccharides, can generate beneficial metabolites like short-chain fatty acids (SCFAs), bile acids (BAs), and tryptophan (Trp). These compounds contribute to regulate the GM, reduce levels of endotoxins in the liver, and alleviate fibrosis and inflammation in the liver. Furthermore, they enhance the composition and functionality of GM, promoting the growth of beneficial bacteria while inhibiting the proliferation of harmful bacteria. These mechanisms mitigate the inflammatory response in the intestines and maintain the integrity of the intestinal barrier. The purpose of this review is to analyze how the GM regulates the pathogenesis of HF, evaluate the regulatory effect of TCM and dietary compounds on the intestinal microflora, with a particular emphasis on modulating flora structure, enhancing gut barrier function, and addressing associated pathogenic factors, thereby provide new insights for the treatment of HF.

Corrigendum: Study on the effects of intestinal flora on gouty arthritis.

[This corrects the article DOI: 10.3389/fcimb.2024.1341953.].