Co-catalpol alleviates fluoxetine-induced main toxicity: Involvement of ATF3/FSP1 signaling-mediated inhibition of ferroptosis.

BACKGROUND: Fluoxetine is often used as a well-known first-line antidepressant. However, it is accompanied with hepatogenic injury as its main organ toxicity, thereby limiting its application despite its superior efficacy. Fluoxetine is commonly traditionally used combined with some Chinese antidepressant prescriptions containing Rehmannia glutinosa (Dihuang) for depression therapy and hepatoprotection. Our previous experiments showed that co-Dihuang can alleviate fluoxetine-induced liver injury while efficiencies, and catalpol may be the key ingredient to characterize the toxicity-reducing and synergistic effects. However, whether co-catalpol can alleviate fluoxetine-induced liver injury and its toxicity-reducing mechanism remain unclear. PURPOSE: On the basis of the first recognition of the dose and duration at which pre-fluoxetine caused hepatic injury, co-catalpol's alleviation of fluoxetine-induced hepatic injury and its pathway was comprehensively elucidated. METHOD AND RESULTS: The hepatoprotection of co-catalpol was evaluated by serum biochemical indexes sensitive to hepatic injury and multiple staining techniques for hepatic pathologic analysis. Subsequently, the pathway by which catalpol alleviated fluoxetine-induced hepatic injury was predicted by network pharmacology to be predominantly the inhibition of ferroptosis. These were validated and confirmed in subsequent experiments with key technologies and diagnostic reagents related to ferroptosis. Further molecular docking showed that activating transcription factor 3 (ATF3) and ferroptosis suppressor protein 1 (FSP1) were the the most prospective molecules for catalpol and fluoxetine among many ferroptosis-related molecules. The critical role of ATF3/FSP1 signaling was further observed by surface plasmon resonance, diagnostic reagents, transmission electron microscopy, Western blot, real-time PCR, immunofluorescence, and immunohistochemistry. Results showed that fluoxetine directly bound to ATF3 and FSP1; agonisting ATF3 or blocking FSP1 abolished the alleviation of catalpol on fluoxetine-induced liver injury, and both exacerbated ferroptosis. Moreover, co-catalpol significantly enhanced the antidepressant efficacy of fluoxetine against depressive behaviours in mice. CONCLUSION: The hepatic impairment properties of fluoxetine were largely dependent on ATF3/FSP1 target-mediated ferroptosis. Co-catalpol alleviated fluoxetine-induced hepatic injury while enhancing its antidepressant efficacy, and that ATF3/FSP1 signaling-mediated inhibition of ferroptosis was involved in its co-administration detoxification mechanism. This study was the first to reveal the hepatotoxicity characteristics, targets, and mechanisms of fluoxetine; provide a detoxification and efficiency regimen by co-catalpol; and elucidate the detoxification mechanism.

Investigation of the principle of concoction by using the processing excipient Glycyrrhiza uralensis Fisch. juice to reduce the main toxicity of Dioscorea bulbifera L. and enhance its main efficacy as expectorant and cough suppressant.

ETHNOPHARMACOLOGICAL RELEVANCE: Dioscorea bulbifera L. (Rhizoma Dioscoreae Bulbiferae; RDB) is commonly used as an expectorant and cough suppressant herb but is accompanied by severe hepatotoxicity. Using the juice of auxiliary herbs (such as Glycyrrhiza uralensis Fisch. (Glycyrrhizae Radix et Rhizoma; GRR) juice) in concocting poisonous Chinese medicine is a conventional method to reduce toxicity or increase effects. Our previous study found that concoction with GRR juice provided a detoxifying effect against the major toxic hepatotoxicity induced by RDB, but the principle for the detoxification of the concoction is unknown to date. AIM OF THE STUDY: The principle of concoction was investigated by using the processing excipient GRR juice to reduce the major toxic hepatotoxicity of RDB, and the efficacy of RDB as an expectorant and cough suppressant was enhanced. MATERIALS AND METHODS: In this study, common factors (RDB:GRR ratio, concocted temperature, and concocted time) in the concoction process were used for the preparation of each RDB concocted with GRR juice by using an orthogonal experimental design. We measured the content of the main toxic compound diosbulbin B (DB) and serum biochemical indicators and performed pathological analysis in liver tissues of mice to determine the best detoxification process of RDB concocted with GRR juice. On this basis, the biological mechanisms of target organs were detected by Western blot and enzyme-linked immunosorbent assay at the inflammation and apoptosis levels. Further, the effects of RDB on expectorant and cough suppressant with GRR juice were evaluated by the conventional tests of phenol red expectorant and concentrated ammonia-induced cough. Lastly, the major compounds in the GRR juice introduced to RDB concoction were determined. RESULTS: RDB concocted with GRR juice significantly alleviated DB content, serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase levels, and improved liver pathological damages. The best detoxification process was achieved by using an RDB:GRR ratio of 100:20 at 120 °C for 20 min. Further, RDB concocted with GRR juice down-regulated the protein levels of nuclear factor kappa B (NF-κB), cyclooxygenase 2 (COX-2), and Bcl-2 related X protein (Bax) in the liver and enhanced the expectorant and cough suppressant effects of RDB. Finally, liquiritin (LQ) and glycyrrhizic acid (GA) in the GRR juice were introduced to the RDB concoction. CONCLUSION: Concoction with GRR juice not only effectively reduced the major toxic hepatotoxicity of RDB but also enhanced its main efficacy as an expectorant and cough suppressant, and that the rationale for the detoxification and/or potentiation of RDB was related to the reduction in the content of the main hepatotoxic compound, DB, the introduction of the hepatoprotective active compounds, LQ and GA, in the auxiliary GRR juice, as well as the inhibition of NF-κB/COX-2/Bax signaling-mediated inflammation and apoptosis.

[Gender differences in antidepressant effect of raw Rehmanniae Radix].

For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.

Antidepressant effects of 70% ethanolic extract of Lonicerae japonicae flos and it contained chlorogenic acid via upregulation of BDNF-TrkB pathway in the hippocampus of mice.

Lonicera japonica flos (LJF) is a common clinical herb with outstanding medicinal and nutritional value. This study aimed to evaluate the antidepressant effects of LJF's active extract and compound chlorogenic acid (CGA) around brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B (TrkB) pathway. The results showed that LJF's extracts and CGA had significant antidepressant effects, and the antidepressant effects of different extracts of LJF were highly positively correlated with the content of CGA (forced swimming test, r = 0.998; tail suspension test, r = 0.934). Moreover, LJF-70% ethanolic extract and CGA improved chronic unpredictable mild stress-induced depressive behavior, upregulated protein expression levels of BDNF and p-TrkB in the hippocampus, restored the damage of hippocampal neurons, and protected liver from damage. In summary, this study demonstrated for the first time that LJF-70% ethanolic extract was the active extract of LJF in antidepressant and CGA was its active compound, and the antidepressant mechanisms mainly involved the upregulation of BDNF-TrkB signaling pathway in the hippocampus of mice.

Massage therapy can effectively relieve cancer pain: A meta-analysis.

BACKGROUND: To critically evaluate the effects of massage therapy on cancer pain. METHODS: Nine Chinese and English databases (PubMed, Cochrane Library, Embase, SCOPUS, Web of Science core, China Biomedical Literature Database, China National Knowledge Infrastructure, Wanfang, and VIP) were systematically searched from the inception of databases to November 2022 for randomized controlled trials. According to Cochrane Collaboration, 2 reviewers independently assessed the risk of bias and extracted data from the included studies. All analyses were performed with Review Manager 5.4. RESULTS: Thirteen randomized controlled trials were included in the meta-analysis, containing 1000 patients (498 in the massage therapy group and 502 in the control group). Massage therapy could significantly relieve cancer pain in patients (standardized mean difference = -1.16, 95% confidence interval [-1.39, -0.93], P < .00001), especially those in the perioperative period and those with hematological malignancies. Foot reflexology and hand acupressure had a moderate effect on cancer pain relief, with hand acupressure being more effective. Massage duration of 10 to 30 minutes and a program length of ≥1 week had a better effect and could significantly relieve pain. The occurrence of adverse events was reported in 4 of the 13 studies, all of which were no adverse events. CONCLUSIONS: Massage therapy can be used as a complementary alternative therapy to relieve cancer pain in patients with hematological malignancies, breast cancer, and cancers of the digestive system. It is suggested that chemotherapy patients use foot reflexology, and perioperative period patients use hand acupressure. A massage duration of 10 to 30 minutes and a program length of ≥1 week is recommended to achieve better effects.

Which Exercise Approaches Work for Relieving Cancer-Related Fatigue? A Network Meta-analysis.

OBJECTIVE: To determine the most effective exercise modalities for managing cancer-related fatigue during and after cancer treatment. DESIGN: Network meta-analysis (NMA) of randomized controlled trials. LITERATURE SEARCH: Seven electronic databases were systematically searched from inception to January 2022. STUDY SELECTION CRITERIA: Randomized controlled trials testing the effects of exercise on relieving cancer-related fatigue in adult patients with cancer. DATA SYNTHESIS: An NMA of 56 studies was conducted, and the PRISMA-NMA guidelines were followed when reporting results. To determine the most effective interventions, the surface under the cumulative ranking curve (SUCRA) value was calculated for each exercise modality. RESULTS: Combined aerobic and resistance exercise (standardized mean difference [SMD], 1.57; credible interval [CrI], 1.03-2.10), yoga (SMD, 1.02; CrI: 0.44, 1.60), and regular physical activity (SMD, 1.07; CrI: 0.21, 1.92) could significantly alleviate cancer-related fatigue compared to control groups (usual care, wait-list, and regular physical activity). Combined aerobic and resistance exercise (SUCRA, 97.2%) had the highest probability of efficacy, followed by yoga (SUCRA, 75.5%) and regular physical activity (SUCRA, 74.1%). During cancer treatment, combined aerobic and resistance exercise (SUCRA, 94.5%) ranked first in efficacy, followed by regular physical activity (SUCRA, 82.1%) and yoga (SUCRA, 73.8%). After cancer treatment, only combined aerobic and resistance exercise (SMD, 0.99; CrI: 0.13, 1.84) had a significant effect on cancer-related fatigue. CONCLUSION: Combined aerobic and resistance exercise, yoga, and regular physical activity were the most effective exercise modalities for alleviating cancer-related fatigue. Combined aerobic and resistance exercise is recommended during and after cancer treatment. J Orthop Sports Phys Ther 2023;53(6):1-10. Epub: 23 March 2023. doi:10.2519/jospt.2023.11251.

Aromatherapy with single essential oils can significantly improve the sleep quality of cancer patients: a meta-analysis.

OBJECTIVE: To investigate the effect of aromatherapy on sleep quality in cancer patients. METHODS: Published literature on the effect of aromatherapy in cancer patients with sleep disorders in the form of randomized controlled trials (RCTs) were systematically retrieved and screened from PubMed, Cochrane Library, Embase, CBM, CNKI, VIP, and Wanfang databases from inception to November 2021. The methodological quality of the included studies was critically and independently evaluated by two reviewers using the Cochrane Risk of Bias Assessment Tool for RCTs. The correlated data were extracted using the pre-designed form, and all analyses were performed using Reviewer Manager version 5.4. Due to the difference in sleep quality instruments, the data extracted in this study were in the form of standard mean difference (SMD). RESULTS: Ten RCTs included 933 patients (experimental group: 474, control group: 459), and the risk of bias in the included studies was moderate. Aromatherapy could significantly improve the sleep quality of cancer patients [SMD = - 0.79, 95% CI (- 0.93, - 0.66), p < 0.01], especially those with breast cancer [SMD = - 0.98, 95% CI (- 1.57, - 0.40), p < 0.01]. Aromatherapy with single essential oil had a better effect on sleep quality [SMD = -0.94, 95%CI (- 1.25, - 0.62), p < 0.01], of which lavender essential oil had the best effect [SMD = -1.06,95%CI (- 1.49, - 0.63), p < 0.01] while compound essential oils had no effect on sleep quality improvement in cancer patients [SMD = -0.21, 95%CI (- 0.57, 0.14), p = 0.23]. Four of the ten RCTs reported the occurrence of adverse events, of which only one RCT indicated that patients had headache and sneezing while the remaining six did not. CONCLUSIONS: This meta-analysis of 10 RCTs reveals that aromatherapy with single essential oil had a substantial effect on the sleep quality of cancer patients and should be recommended as a beneficial complementary therapy to promote sleep quality in cancer patients.

Aromatherapy with inhalation can effectively improve the anxiety and depression of cancer patients: A meta-analysis.

PURPOSE: This meta-analysis was to critically evaluate the effects of aromatherapy on the symptoms of anxiety and depression in cancer patients. METHODS: Eight Chinese and English databases (CNKI, Wanfang, VIP, CBM, Cochrane Library, PubMed, Embase, and PsycINFO) were systematically searched from the inception of databases to October 2021 for randomized controlled trials (RCTs). According to Cochrane Collaboration criteria, two reviewers independently assessed the risk of bias and extract data from included studies. All analyses were performed with Review Manager 5.4. RESULTS: Eleven qualified studies were included in the meta-analysis, ten of which reported the effect of aromatherapy on anxiety in cancer patients, including 1724 patients; five of the studies reported the effect on depression, including 1039 patients. The quality of the included studies was low, and most studies compared aromatherapy to usual care. This meta-analysis indicated that aromatherapy appeared to be effective for anxiety [SMD = -0.51, 95%CI (-0.83, -0.19), P = 0.002] and depression [SMD = -0.44, 95%CI (-0.76, -0.12), P = 0.008] symptoms in cancer patients. Inhalation aromatherapy may be more effective than massage. Aromatherapy seemed to improve the anxiety symptoms in cancer patients in a short time, especially in perioperative patients, but had no effect for patients treated with radiation, chemotherapy or palliative therapy. Placebo also appeared to be effective in some studies. CONCLUSIONS: Aromatherapy, especially inhalation aromatherapy, may help relieve symptoms of anxiety and depression in cancer patients, but more and higher-quality studies are needed. The literature does not yet support clinical implementation.

Mulberry Leaf Extract Alleviates Staphylococcus aureus-Induced Conjunctivitis in Rabbits via Downregulation of NLRP3 Inflammasome and Upregulation of the Nrf2 System and Suppression of Pro-Inflammatory Cytokines.

INTRODUCTION: Mulberry (Morus alba L.) leaves are widely used in traditional Chinese medicine for their antioxidant, anti-inflammatory, antibacterial, anti-obesity, antidiabetic, antiatherosclerotic, and anticancer properties. The current study aimed to investigate the effect of mulberry leaf extract (MLE) on Staphylococcus aureus (S. aureus)-induced conjunctivitis (5 × 109 colony-forming units, 0.5 mL/eye) in a rabbit model. METHODS: Rabbits were treated with MLE (5 mL/kg·d-1 and 10 mL/kg·d-1), 0.9% saline, pearl bright eye (PBE) drops, or erythromycin eye ointment (EEO) group for 5 days. The ocular infection symptoms, bacterial negative conversion rate, and conjunctival histopathological changes of rabbits in each group were observed. The expression of caspase-1, apoptosis-associated speck-like protein containing a caspase recruitment domain, NOD-like receptor leucine-rich pyrin domain-containing protein 3 (NLRP3), interleukin (IL)-18, IL-6, IL-1ß, TNFα, Keap1, and nuclear factor erythroid 2-related factor 2 (Nrf2) in conjunctival tissue of rabbits were detected by quantitative real-time reverse transcription PCR and/or Western blot analysis. RESULTS: The results showed that MLE treatment significantly reduced the clinical sign scores of conjunctivitis, alleviated clinical signs, and decreased bacterial load, and histological damage in a time- and dose-dependent manner was compared to that in the control group. The antibacterial and anti-inflammatory activities of MLE (10 mL/kg·d-1) were similar to those of the positive control drug PBE and EEO. In addition, MLE significantly decreased the levels of pro-inflammatory cytokines, downregulated the NLRP3 inflammasome, and upregulated the Nrf2 system. CONCLUSIONS: MLE is effective in alleviating S. aureus-induced conjunctivitis in rabbits, and this mechanism is associated with the inhibition of the NLRP3 inflammasome and activation of the Nrf2 system to regulate pro-inflammatory signaling.

Catalpol Weakens Depressive-like Behavior in Mice with Streptozotocin-induced Hyperglycemia via PI3K/AKT/Nrf2/HO-1 Signaling Pathway.

Depression has huge social risks of high incidence, disability, and suicide. Its prevalence and harm in people with hyperglycemia are 2-3 times higher than in normal people. However, antidepressants with precise curative effects and clear mechanisms for patients with hyperglycemia are currently lacking. Prescriptions containing Radix Rehmannia glutinosa Libosch., a traditional medicinal herb with a wide range of nutritional and medicinal values, are often used as antidepressants in Chinese clinical medicine. Catalpol is one of the main effective compounds of Radix R. glutinosa, with multiple biological activities such as hypoglycemia. Here, the antidepressant effect of catalpol on the pathological state of streptozotocin (STZ)-induced hyperglycemia and the underlying molecular mechanisms were analyzed. Results showed that administering catalpol orally to hyperglycemic mice for 21 consecutive days significantly reversed the abnormalities in tail suspension, forced swimming, and open field tests. Catalpol also reversed the abnormal phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the abnormal levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein, heme oxygenase-1 (HO-1), and antioxidants, including superoxide dismutase, glutathione peroxidase, glutathione-s transferase, reduced glutathione, and malondialdehyde in the hippocampus and frontal cortex of STZ-induced hyperglycemic mice. Thus, catalpol attenuates depressive-like behavior in pathological hyperglycemic state, and the antidepressant mechanism could at least be partly attributed to the upregulation of the PI3K/AKT/Nrf2/HO-1 signaling pathway in both brain regions, thus restoring the balance between oxidative and antioxidant damage. These data expanded the scientific understanding of catalpol and provided preclinical experimental evidence for its application.

Antidepressant mechanism of catalpol: Involvement of the PI3K/Akt/Nrf2/HO-1 signaling pathway in rat hippocampus.

Catalpol is a major compound in Rehmanniae Radix with outstanding medicinal and nutritional values. Our previous studies have demonstrated catalpol's antidepressant effect, but its mechanisms remain unclear. This study aimed to explore the antidepressant mechanisms of catalpol via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor E2-related factor 2(Nrf2)/heme oxygenase-1 (HO-1) pathway. Results demonstrated that chronic unpredictable mild stress (CUMS) for 5 consecutive weeks caused significant decreases in the sucrose preference and the horizontal and vertical scores of open-field test, as well as a significant increase in the swimming-immobility time of rats; catalpol administration significantly reversed the abnormality of these indicators. Further real-time fluorescent quantitative polymerase chain reaction and Western blotting results together showed that CUMS significantly downregulated the expression levels of hippocampal genes and proteins, including PI3K, Akt, Nrf2, HO-1, tropomyosin-related kinase B (TrkB), and brain-derived neurotrophic factor; catalpol administration significantly reversed the abnormal expression of these genes and proteins. CUMS also caused a significant decrease in the hippocampal superoxide dismutase, catalase, glutathione peroxidase, glutathione-s transferase, and reduced glutathione levels, as well as a significant increase in thiobarbituric acid reactive substances level in rats; catalpol administration significantly reversed the abnormality of these indicators. Taken together, this study confirmed for the first time that the antidepressant effect of catalpol on CUMS-induced depression involved the upregulation of the PI3K/Akt/Nrf2/HO-1 signaling pathway, thereby improving the hippocampal neurotrophic, neuroprotective, and antioxidant levels. The PI3K/Akt/Nrf2/HO-1 pathway-related molecules may serve as potential new biomarkers and candidate molecular targets for catalpol's antidepressant effects.

[Epidemiological characteristics of acupuncturists who are sensitive to stimulation of moxa smoke: a face-to-face sectional survey based on 733 participants].

OBJECTIVE: To explore the epidemiologic characteristics of acupuncturists who are sensitive to stimulation of moxa smoke, which could provide further direction for safety protection of exerting moxibustion and to further verify the feasibility of internet survey. METHODS: A self-made questionnaire regarding body response to moxa smoke was established, which was used to conduct a face-to-face survey among acupuncturists who had performed long-term moxibustion. The Logistic regression model was used to analyze the factors affecting the stimulation response of acupuncturists and the epidemiological characteristics of acupuncturists was obtained. RESULTS: A total of 733 valid data was obtained. The multivariate Logistic regression analysis showed that the history of chronic respiratory disease was the main risk factor of stimulus response including cough, phlegm in the throat, asthma, dyspnea, shortness of breath and nasal dryness after exposure to moxa smoke (P<0.05, P<0.01). The risk of stimulus response such as cough, tearing and nasal dryness was higher in women than in men (P<0.05, P<0.01). The risk of dry eyes and eyes pain in smokers was higher than those in non-smokers (P<0.05). The risk of shortness of breath in those who were exposed to second-hand smoke was higher than those who were not exposed to second-hand smoke (P<0.05). The analysis of index trend line showed that the results of internet survey were similar to those of face-to-face survey. CONCLUSION: The stimulus response of acupuncturist after long-term exposure to moxa smoke is related to the history of chronic respiratory disease, being female, smoking or exposure of second-hand smoke, therefore more attention should be paid to those populations. In addition, the internet survey can be used for the epidemiological investigation of safety of moxa smoke.

Does Moxa Smoke Have Significant Effect on the Acupuncturist's Respiratory System? A Population-Based Study.

OBJECTIVES: To evaluate the safety of moxa smoke, especially to provide quantitative information and details for the occupational prevention of acupuncturists. METHODS: We combined the questionnaire-based cross-sectional survey and lung function testing-based historical retrospective cohort research to investigate the safety of moxa smoke exposure (MSE) among acupuncturists. A mathematical regression model was established to quantitatively evaluate the relationship between moxa smoke exposure and the respiratory health of the acupuncturist. The smoke exposure time of the acupuncturist and the prevalence of abnormal respiratory symptoms or diseases were also evaluated. RESULTS: (1) The cross-sectional research showed that the incidence of expectoration (18.7%) and rhinitis (22.7%) was the most common respiratory symptom and disease after MSE. No statistical difference was found between smoke exposure time of the acupuncturist and the prevalence of abnormal respiratory symptoms or diseases, except the prevalence of rhinitis and shortness of breath (P < 0.01). Regression model for the incidence of first three symptoms (expectoration, shortness of breath, and wheezing) from the cross-sectional survey indicated that the weight coefficients of factors associated with moxa smoke were lower than those of factors unrelated to moxa smoke, such as gender and personal history of respiratory diseases. (2) Historical retrospective cohort research showed that there was no significant difference in the % predicted PEF. No statistic difference was found between the exposed and nonexposed group in large airway function indexes (% predicted FEV1, % predicted FVC, and % predicted FEV1/FVC) and small airway function indexes (% predicted FEF25, % predicted FEF50, % predicted FEF75, and % predicted MMEF), either. Especially, the % predicted MVV among males (106.23 ± 2.92 vs. 95.56 ± 1.92, P < 0.01 and % predicted VC among females (100.70 ± 1.59 vs. 95.91 ± 1.61, P < 0.05) between the two groups had statistical significance, but did not cause pulmonary ventilation dysfunction. CONCLUSIONS: MSE has no significant effect on the respiratory health of acupuncturists.

Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 µg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 µg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 µg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 µg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

Leigongteng (Radix et Rhizoma Tripterygii) via compatibility with Jinqiancao (Herba Lysimachiae): its toxicity-reduced efficacy in H22-bearing mice.

OBJECTIVE: To observe toxicity-reduced effects of Leigongteng (Radix et Rhizoma Tripterygii) (LGT) via compatibility with Jinqiancao (Herba Lysimachiae) (JQC) in H22-bearing mice and investigate the possible underlying mechanism, and further explore whether JQC can enhance LGT-evoked anti-tumor effect. METHODS: H22-bearing mice were orally administered with LGT alone and its compatibility with JQC, and tumors, serum, livers and kidneys were collected to evaluate the toxicity-reduced efficacy and the possible mechanism. RESULTS: LGT evoked significantly elevated biochemical indicators including serum alanine / aspartate transaminase (ALT/AST), creatinine (Cr) and urea nitrogen (BUN) as well as pathological damage in mice, which were all obviously reversed by JQC via compatibility at the ratios from 4/1 to 1/4. Further analysis indicated that pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), and malondialdehyde (MDA) levels significantly decreased, while anti-inflammatory cytokine interleukin (IL)-10, and glutathione (GSH), GSH-s transferase (GST), GSH peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) levels all increased in livers and kidneys of mice. Besides, after compatibility with JQC at the ratios of 4/1, 2/1, 1/1, 1/2 and 1/4, LGT-decreased tumor weight was further decreased by 48.4%, 57.3%, 54.0%, 49.3% and 52.9%, respectively (all P < 0.01). CONCLUSION: JQC could reduce LGT-induced hepatotoxicity and nephrotoxicity, and enhance the antitumor efficacy via compatibility with JQC, and the toxicity-reduced mechanism could involve inhibiting hepatic and kidney oxidative stress and inflammation.

Detoxication mechanisms of Radix Tripterygium wilfordii via compatibility with Herba Lysimachia christinae in S180-bearing mice by involving Nrf2.

The combined administration between Radix Tripterygium wilfordii Hook F (LGT) and Herba Lysimachia christinae Hance (JQC) belongs to mutual detoxication compatibility of seven emotions in traditional Chinese medicine (TCM) theory. However, until now, the compatibility detoxication mechanisms remain unknown. The present study was undertaken to observe detoxication mechanisms of LGT through compatibility with JQC in tumor-bearing mice by involving NF-E2-related factor 2 (Nrf2)-mediated antioxidant defenses. In addition, influence of compatibility on antitumor activity was also investigated here. Our results demonstrated that compatibility with JQC administration significantly reversed LGT-elevated serum alanine/aspartate transaminase (ALT/AST) levels and alleviated hepatocytes' swelling or degeneration damage, and at the ratio 2/1 (LGT/JQC) produced the strongest detoxication effect. Besides, compatibility with JQC administration reversed not only LGT-elevated hepatic malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) but also the LGT lowered GSH, glutathione-s transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and interleukin (IL)-10 levels. Furthermore, compatibility with JQC administration significantly up-regulated protein expression of Nrf2 and mRNA expression of it regulated downstream antioxidant genes such as heme oxygenase-1 (HO-1), NAD(P)H: quinone oxidoreductase-1 (NQO1), and glutamate cysteine ligase catalytic subunit (GCLC). In addition, compatibility with JQC further decreased LGT-decreased tumor weight and at the ratio 2/1 (LGT/JQC) also exerted the strongest synergistic effect. Collectively, through compatibility with JQC exerted detoxication effect on LGT-induced hepatotoxicity and the mechanisms could be at least partly attributed to up-regulation of Nrf2 and its downstream signals, thereby enhancing antioxidant defenses, and inhibiting lipid peroxidation, oxidative stress, and inflammation. Additionally, at the ratio 2/1 (LGT/JQC) exerted the strongest effects on both detoxication and synergism.

Synergistic effect of phytochemicals on cholesterol metabolism and lipid accumulation in HepG2 cells.

BACKGROUND: Crocin (CRO), chlorogenic acid (CGA), geniposide (GEN), and quercetin (QUE) are all natural compounds with anti-obesity properties, in particular, hypolipidemic effects, which have been widely used for the treatment of obesity-related metabolic diseases. However, it is not yet known whether these compounds interact synergistically. Here, we investigated the effects and molecular mechanisms of CRO, CGA, GEN, QUE, and a combination of all four compounds (CCGQ), on lipid accumulation in human hepatoma (HepG2 cells). METHODS: The optimal concentration of CRO, CGA, GEN, QUE to stimulate HepG2 cells proliferation was determined using MTT assay. HepG2 cells were pretreated with 10 µmol/L simvastatin, 1 µmol/L CRO, 30 µmol/L CGA, 10 µmol/L GEN, 10 µmol/L QUE, and CCGQ (a combination of 1 µmol/L CRO, 30 µmol/L CGA, 10 µmol/L GEN, and 10 µmol/L QUE) for 24 or 48 h. Oil red O staining and extracellular TC and TG levels were detected. The RT-PCR was used to observe on cholesterol metabolism-related gene expression. Immunocytochemistry and western-blot assayed the 3-hydroxy-3-methylglutaryl-coenzyme (HMGCR) protein expression in HepG2 cells. RESULTS: Compared to those of control, we demonstrated that treating HepG2 cells for 48 h with CCGQ resulted in a strong synergistic effect, causing a marked decrease in lipid deposition in comparison to individual treatments, in both triglyceride and total cholesterol (CRO, 5.74- and 1.49-folds; CGA, 3.38- and 1.12-folds; GEN, 4.04- and 1.44-folds; QUE, 3.36- and 1.24-folds; simvastatin, 5.49- and 1.83-folds; and CCGQ, 7.75- and 2.20-folds), and Oil red O staining assays. In addition, CCGQ treatment increased ATP-binding cassette transporter (ABCA1), cholesterol 7α-hydroxylase (CYP7A1), and AMP-activated protein kinase 2α (AMPKα2) mRNA expression, while decreasing sterol regulatory element binding protein 2 (SREBP2), and liver X receptor alpha (LXRα) mRNA expression. Notably, CCGQ was more effective in decreasing HMGCR expression than the individual treatments. CONCLUSION: The CCGQ combination has potential, both as a complementary therapy for hyperlipemia, and in preventing further obesity-related complications.

Ethanol extract of Rehmannia glutinosa exerts antidepressant-like effects on a rat chronic unpredictable mild stress model by involving monoamines and BDNF.

The dried roots of Rehmannia glutinosa Libosch. (Scrophulariaceae) are of both medicinal and nutritional importance. Our previous study has found that the 80% ethanol extract of R. glutinosa (RGEE) produced antidepressant-like activities in mouse behavioral despair depression models. However, its mechanisms are still unclear. The present study aimed to observe the antidepressant-like mechanisms of RGEE on a rat chronic unpredictable mild stress (CUMS) model by involving monoaminergic neurotransmitters and brain-derived neurotrophic factor (BDNF). CUMS-stressed rats were orally given RGEE daily (150, 300, and 600 mg/kg) or fluoxetine hydrochloride (FH) for 3 weeks after starting the CUMS procedure. Sucrose preference test was carried out to observe depression-like behavior, and serum and brain tissues were used for neurochemical and fluorescent quantitative reverse transcription PCR analysis. Results demonstrated that CUMS induced depression-like behavior, whereas RGEE and FH administration inhibited this symptom. Furthermore, CUMS caused excessively elevated levels of serum corticosterone (CORT), an index of hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, in a manner attenuated by RGEE and FH administration. RGEE administration also further elevated monoamine neurotransmitters and BDNF levels, up-regulated the mRNA expression of BDNF and tropomyosin-related kinase B (TrkB) in hippocampus of rats suffering CUMS. Together, our findings suggest that RGEE can improve CUMS-evoked depression-like behavior, and indicate its mechanisms may partially be associated with restoring HPA axis dysfunctions, enhancing monoamineergic nervous systems, and up-regulating BDNF and TrkB expression.

Symptoms of long-term exposure to moxa smoke in acupuncturists: a correlation analysis.

OBJECTIVE: To investigate the effects of long-term exposure to moxa smoke on acupuncturists and to consider the association between physical symptoms and gender, age, secondhand smoke (SHS) exposure, and the duration of exposure. METHODS: A self-report, web-based questionnaire was used to evaluate the effects of moxa smoke on acupuncturists. Logistic regression was used to analyze the relationship between physical symptoms and possible correlative factors. RESULTS: A total of 858 questionnaires were analyzed. The data showed that 42.42% of acupuncturists had been exposed to moxa smoke for 5-10 years. The most frequent symptom was tearing (32.98%) and the least frequent symptom was asthma (5.24%). Logistic regression analysis showed that female acupuncturists were slightly more susceptible to cough and tearing than males (cough: OR: 1.583, 95% CI: 1.079, 2.321, P = 0.019; tearing: OR: 1.519, 95% CI: 1.094, 2.108, P = 0.013). Acupuncturists aged over 25 years reported a slightly lower incidence of eye itchiness than those aged under 25 years (26-40 years: OR: 0.604, 95% CI: 0.379, 0.965, P = 0.035; over 40 years: OR: 0.330, 95% CI: 0.114, 0.958, P = 0.042). Ophthalmodynia occurred less in acupuncturists aged 26-40 years (OR: 0.591, 95% CI: 0.359, 0.970, P = 0.038) than in those younger than 25 years. The only association between prevalence of symptoms and tobacco use and SHS exposure was that smokers had a lower occurrence of phlegm in the throat (OR: 0.579, 95% CI: 0.392, 0.856, P = 0.006). Shortness of breath was less frequent in participants exposed to moxa smoke for more than 5 years (5-10 years: OR: 0.400, 95% CI: 0.204, 0.785, P = 0.008; 11-20 years: OR: 0.392, 95% CI: 0.178, 0.864, P = 0.02), but a slightly higher incidence of eye itchiness was found in those with over 20 years of moxa exposure (OR: 4.200, 95% CI: 1.344, 3.128, P = 0.014). CONCLUSION: The most frequent symptom of moxa smoke exposure in acupuncturists was tearing. The association of symptoms with age and duration of exposure to moxa smoke were rather complicated; hence, care should be taken in drawing conclusions about the safety of moxa smoke based solely on its potentially harmful ingredients.

Effect of Yupingfeng granules on the skin barrier in atopic dermatitis mice models.

OBJECTIVE: To investigate effect of Yupingfeng granules, prepared with Chinese Medicines, on the wound healing and on the expression of aquaporin 3 (AQP3) and the skin barrier in the animal models of atopic dermatitis (AD). METHODS: Acute skin lesions of AD models were prepared using 2,4-dinitrochlorobenzo (DNCB) in mice and animals were treated with either Yupingfeng granules or placebo for two weeks. Skin wound healing outcome was assessed by measuring skin thickness, weight (quality) of the skin, and trans-epidermal water loss (TEWL). Expression of AQP3 mRNA and protein was assessed by reverse transcriotion polymerase chain reaction (RT-PCR) and immunoblotting, respectively. RESULTS: Yupingfeng granule treatment resulted in significant acceleration of wound healing with 63.64% efficiency, which was significantly higher than that of placebo granule treatment (31.82%, P < 0.01 by Wilcoxon Rank-sum test). Skin thickness, weight of the wounded skin, and TEWL were significantly higher in the AD models compared to that of normal animals. Treatment with Yupingfeng granules resulted in significant decrease in skin thickness [(937 ± 31) vs (360 ± 21) urn, P < 0.01], weight of the wounded skin [(42 ± 4) vs (24 ± 5) mg, P < 0.01], and TEWL [(30 ± 4) vs (13 ± 4) g•h-1•m-2, P < 0.01]. Yupingfeng granules also significantly down-regulated mRNA and protein expression of AQP3 in the animal models. CONCLUSION: Our findings suggested that Yupingfeng granules could be used in AD treatment.