Emodin-8-O-ß-D-glucopyranoside-induced hepatotoxicity and gender differences in zebrafish as revealed by integration of metabolomics and transcriptomics.

BACKGROUND: Emodin-8-O-ß-D-glucopyranoside (Em8G) is an active ingredient of traditional Chinese medicine Rhei Radix et Rhizoma and Polygonum multiflorum Thunb.. And it caused hepatotoxicity, while the underlying mechanism was not clear yet. PURPOSE: We aimed to explore the detrimental effects of Em8G on the zebrafish liver through the metabolome and transcriptome integrated analysis. STUDY DESIGN AND METHODS: In this study, zebrafish larvae were used in acute toxicity tests to reveal the hepatotoxicity of Em8G. Adult zebrafish were then used to evaluate the gender differences in hepatotoxicity induced by Em8G. Integration of transcriptomic and metabolomic analysis was used further to explore the molecular mechanisms underlying gender differences in hepatotoxicity. RESULTS: Our results showed that under non-lethal concentration exposure conditions, hepatotoxicity was observed in Em8G-treated zebrafish larvae, including changes in liver transmittance, liver area, hepatocyte apoptosis and hepatocyte vacuolation. Male adult zebrafish displayed a higher Em8G-induced hepatotoxicity than female zebrafish, as demonstrated by the higher mortality and histopathological alterations. The results of transcriptomics combined with metabolomics showed that Em8G mainly affected carbohydrate metabolism (such as TCA cycle) in male zebrafish and amino acid metabolism (such as arginine and proline metabolism) in females, suggesting that the difference of energy metabolism disorder may be the potential mechanism of male and female liver toxicity induced by Em8G. CONCLUSIONS: This study provided the direct evidence for the hepatotoxicity of Em8G to zebrafish models in vivo, and brought a new insight into the molecular mechanisms of Em8G hepatotoxicity, which can guide the rational application of this phytotoxin. In addition, our findings revealed gender differences in the hepatotoxicity of Em8G to zebrafish, which is related to energy metabolism and provided a methodological reference for evaluating hepatotoxic drugs with gender differences.

Multi-omics landscape to decrypt the distinct flavonoid biosynthesis of Scutellaria baicalensis across multiple tissues.

Scutellaria baicalensis Georgi, also known as huang-qin in traditional Chinese medicine, is a widely used herbal remedy due to its anticancer, antivirus, and hepatoprotective properties. The S. baicalensis genome was sequenced many years ago; by contrast, the proteome as the executer of most biological processes of S. baicalensis in the aerial parts, as well as the secondary structure of the roots (xylem, phloem, and periderm), is far less comprehensively characterized. Here we attempt to depict the molecular landscape of the non-model plant S. baicalensis through a multi-omics approach, with the goal of constructing a highly informative and valuable reference dataset. Furthermore, we provide an in-depth characterization dissection to explain the two distinct flavonoid biosynthesis pathways that exist in the aerial parts and root, at the protein and phosphorylated protein levels. Our study provides detailed spatial proteomic and phosphoproteomic information in the context of secondary structures, with implications for the molecular profiling of secondary metabolite biosynthesis in non-model medicinal plants.

The synergistic effect of full-spectrum light therapy and transient immunosuppressants prolonged allotransplant survival.

BACKGROUND: The lifelong administration of immunosuppressants remains its largest drawback in vascularized composite allotransplantation (VCA). Therefore, developing alternative strategies to minimize the long-term use of immunosuppressive agents is crucial. This study investigated whether full-spectrum bright light therapy (FBLT) combined with short-term immunosuppressant therapy could prolong VCA survival in a rodent hindlimb model. METHODS: Hindlimb allotransplantation was conducted from Brown-Norway to Lewis rats, and the rats were divided into 4 groups. Group 1 did not receive treatment as a rejection control. Group 2 received FBLT alone. Group 3 was treated with short-term anti-lymphocyte serum and cyclosporine-A. Group 4 was administered short-term ALS/CsA combined with FBLT for 8 weeks. Peripheral blood and transplanted tissues were collected for analysis. RESULTS: The results revealed median survival time of FBLT alone (group 2) did not increase allograft survival compared to the control (group 1). However, group 4 with FBLT combined with short-term ALS/CsA significantly prolonged median composite tissue allograft survival time (266 days) compared with groups 1 (11 days), 2 (10 days), and 3 (41 days) (p<0.01). Group 4 also showed a significant increase in Treg cells (p = 0.04) and TGF-ß1 levels (p = 0.02), and a trend toward a decrease in IL-1ß levels (p = 0.03) at 16 weeks after transplantation as compared to control Group 1. CONCLUSIONS: FBLT combined with short-term immunosuppressants prolonged allotransplant survival by modulating T-cell regulatory functions and anti-inflammatory cytokine expression. This approach could be a potential strategy to increase VCA survival.

Herbal medicines for insomnia through regulating 5-hydroxytryptamine receptors: a systematic review.

Insomnia is a common sleep disorder without effective therapy and can affect a person's life. The mechanism of the disease is not completely understood. Hence, there is a need to understand the targets related to insomnia, in order to develop innovative therapies and new compounds. Recently, increasing interest has been focused on complementary and alternative medicines for treating or preventing insomnia. Research into their molecular components has revealed that their sedative and sleep-promoting properties rely on the interactions with various neurotransmitter systems in the brain. In this review, the role of 5-hydroxytryptamine (5-HT) in insomnia development is summarized, while a systematic analysis of studies is conducted to assess the mechanisms of herbal medicines on different 5-HT receptors subtypes, in order to provide reference for subsequent research.

Mechanisms of Epichloë bromicola to Promote Plant Growth and Its Potential Application for Coix lacryma-jobi L. Cultivation.

Endophytic fungi play important roles in regulating plant growth and development and usually used as a promising strategy to enhance the biosynthesis of host valuable secondary metabolite, but the underlying growth-promoting mechanisms are only partly understood. In this study, the wild-type Arabidopsis thaliana seedlings co-cultured with fungal endophyte Epichloë bromicola showed auxin (IAA)-stimulated phenotypes, and the growth-promoting effects caused by E. bromicola were further verified by the experiments of spatially separated co-culture and fungal extract treatment. IAA was detected and identified in the extract of E. bromicola culture by LC-HRMS/MS, whereas 2,3-butanediol was confirmed to be the predominant volatile active compound in the diethyl ether and ethyl acetate extracts by GC-MS. Further study observed that IAA-related genes including synthesis key enzyme genes (CYP79B2, CYP79B3, NIT1, TAA1 and YUCCA1) and controlling polar transport genes (AUX1, BIG, EIR1, AXR3 and ARF1), were highly expressed at different periods after E. bromicola inoculation. More importantly, the introduction of fungal endophyte E. bromicola could effectively promote the growth and accumulation of coixol in Coix under soil conditions. Our study showed that endophytic fungus E. bromicola might be considered as a potential inoculant for improving medicinal plant growth.

"Trojan Horse" Phototheranostics: Fine-Engineering NIR-II AIEgen Camouflaged by Cancer Cell Membrane for Homologous-Targeting Multimodal Imaging-Guided Phototherapy.

Multimodal phototheranostics on the basis of a single molecule with one-for-all characteristics represents a convenient approach for effective cancer treatment. In this report, a versatile molecule featured by aggregation-induced emission, namely DHTDP, synchronously enabling second near-infrared (NIR-II) fluorescence emission and efficient photothermal conversion is developed by elaborate structural modulation. By camouflaging DHTDP nanoparticles with cancer cell membrane, the resultant biomimetic nanoparticles exhibit significantly both facilitated delivery efficiency and homologous targeting capability, and afford precise imaging guidance and maximize therapeutic outcomes in form of NIR-II fluorescence imaging (FLI)-photoacoustic imaging (PAI)-photothermal imaging (PTI) trimodal imaging-guided photothermal therapy (PTT). This study presents the first example of biomimetic multimodal phototheranostics loaded by homogeneity-targeting cell membrane, thus brings a new insight into the exploration of superior phototheranostics for practical cancer theranostics.

An endophytic fungus Schizophyllum commune isolated from Panax ginseng enhances hairy roots growth and ginsenoside biosynthesis.

Using endophytic fungal elicitors to increase the accumulation of valuable secondary metabolites in plant tissue culture is an effective biotechnology strategy. In this study, a collection of 56 strains of endophytic fungi were isolated from different organs of cultivated Panax ginseng, of which seven strains can be symbiotically co-cultured with the hairy roots of P. ginseng. Further experiments observed that strain 3R-2, identified as endophytic fungus Schizophyllum commune, can not only infect hairy roots but also promote the accumulation of specific ginsenosides. This was further verified because S. commune colonization significantly affected the overall metabolic profile of ginseng hairy roots. By comparing the effects of S. commune mycelia and its mycelia extract (EM) on ginsenoside production in P. ginseng hairy roots, the EM was confirmed to be a relatively better stimulus elicitor. Additionally, the introduction of EM elicitor can significantly enhance the expressions of key enzyme genes of pgHMGR, pgSS, pgSE, and pgSD involved in the biosynthetic pathway of ginsenosides, which was deemed the most relevant factor for promoting ginsenosides production during the elicitation period. In conclusion, this study is the first to show that the EM of endophytic fungus S. commune can be considered as an effective endophytic fungal elicitor for increasing the biosynthesis of ginsenosides in hairy root cultures of P. ginseng.

Effects of nano metal oxide particles on denitrifying phosphorus removal system: Potential stress mechanism and recovery strategy.

The accumulation of nano metal oxide particles (NMOPs) in municipal sewage treatment systems harms the microbial community and its metabolism in activated sludge system, resulting in the degradation of its pollutants removal performance. In this work, the stress effect of NMOPs on the denitrifying phosphorus removal system was systematically investigated in terms of pollutants removal performance, key enzyme activities, microbial community diversity and abundances, and intracellular metabolites. Among the ZnO NPs, TiO2 NPs, CeO2 NPs, and CuO NPs, the ZnO NPs showed the most significant impacts with the chemical oxygen demand, total phosphorus, and nitrate nitrogen removal ratio decreased from above 90 % to 66.50 %, 49.13 %, and 57.11 %, respectively. The addition of surfactants and chelating agents could relieve the toxic effect of NMOPs on the denitrifying phosphorus removal system, and the chelating agents were more effective than surfactants in performance recovery. After adding ethylene diamine tetra acetic acid, the removal ratio of chemical oxygen demand, total phosphorus, and nitrate nitrogen under ZnO NPs stress was restored to 87.31 %, 88.79 %, and 90.35 %, respectively. The study provides valuable knowledge to better understand the impacts and stress mechanism of NMOPs on activated sludge systems and provides a solution to recover the nutrients removal performance of denitrifying phosphorus removal system under NMOPs stress.

Jin-Zhen oral liquid for pediatric coronavirus disease (COVID-19): A randomly controlled, open-label, and non-inferiority trial at multiple clinical centers.

Background: As the coronavirus disease 2019 (COVID-19) pandemic progressed, especially with the emergence of the Omicron variant, the proportion of infected children and adolescents increased significantly. Some treatment such as Chinese herbal medicine has been administered for COVID-19 as a therapeutic option. Jin-Zhen Oral Liquid is widely used for pediatric acute bronchitis, while the efficacy and safety in the treatment of pediatric COVID-19 are unclear. Methods: We conducted a randomized controlled, open-label, multicenter, non-inferiority clinical study involving hospitalized children with mild to moderate COVID-19. Children eligible for enrollment were randomly assigned in a 1:1 ratio to Jin-Zhen Oral Liquid (the treatment group) and Jinhua Qinggan Granules (the positive control group) and received the respective agent for 14 days, followed by a 14-day follow-up after discontinuation of the treatment. The primary efficacy endpoint was the time to first negative viral testing. The secondary endpoints were the time and rate of major symptoms disappearance, duration of hospitalization, and the proportion of symptoms changed from asymptomatic or mild to moderate or severe/critical illness. In addition, the safety end points of any adverse events were observed. Results: A total of 240 child patients were assigned randomly into the Jin-Zhen Oral Liquid (117 patients) and Jinhua Qinggan Granules (123 patients) groups. There was no significant difference of the baselines in terms of the clinical characteristics and initial symptoms between the two groups. After 14-day administration, the time to first negative viral testing in the Jin-Zhen group (median 6.0 days, 95% CI 5.0-6.0) was significantly shorter compared with the positive control Jinhua Qinggan Granules group (median 7.0 days, 95% CI 7.0-8.0). The time and rate of major clinical symptoms disappearance were comparable to the positive control. The symptom disappearance time of pharyngalgia and hospitalization duration were significantly shortened in the Jin-zhen Oral Liquid group. No participants in either group experienced post-treatment exacerbation to severe or critical illness. No adverse events were observed in the Jin-Zhen Oral Liquid treatment group (0.0%) while 1 patient with adverse events occurred in the positive control Jinhua Qinggan granules group (0.8%). No serious adverse events were observed during the study period in both groups. Conclusion: Jin-Zhen Oral Liquid is safe and effective in the treatment of mild to medium COVID-19 in children. It is non-inferior to Jinhua Qinggan granules in shortening the time to first negative viral testing, the time and rate of major clinical symptoms disappearance, and the hospitalization duration. The results suggest that Jin-Zhen Oral Liquid can be a recommended drug for treatment of pediatric COVID-19 patients.

Humulus lupulus L. Extract Protects against Senior Osteoporosis through Inhibiting Amyloid ß Deposition and Oxidative Stress in APP/PS1 Mutated Transgenic Mice and Osteoblasts

As aging progresses, ß-amyloid (Aß) deposition and the resulting oxidative damage are key causes of aging diseases such as senior osteoporosis (SOP). Humulus lupulus L. (hops) is an important medicinal plant widely used in the food, beverage and pharmaceutical industries due to its strong antioxidant ability. In this study, APP/PS1 mutated transgenic mice and Aß-injured osteoblasts were used to evaluate the protective effects of hops extracts (HLE) on SOP. Mice learning and memory levels were assessed by the Morris water maze. Mice femurs were prepared for bone micro-structures and immunohistochemistry experiments. The deposition of Aß in the hippocampus, cortex and femurs were determined by Congo red staining. Moreover, protein expressions related to antioxidant pathways were evaluated by Western blotting. It was found that HLE markedly improved learning abilities and ameliorated memory impairment of APP/PS1 mice, as well as regulated antioxidant enzymes and bone metabolism proteins in mice serum. Micro-CT tests indicated that HLE enhanced BMD and improved micro-architectural parameters of mice femur. More importantly, it was discovered that HLE significantly reduced Aß deposition both in the brain and femur. Further in vitro results showed HLE increased the bone mineralization nodule and reduced the ROS level of Aß-injured osteoblasts. Additionally, HLE increased the expression of antioxidant related proteins Nrf2, HO-1, NQO1, FoxO1 and SOD-2. These results indicated that Humulus lupulus L. extract could protect against senior osteoporosis through inhibiting Aß deposition and oxidative stress, which provides a reference for the clinical application of hops in the prevention and treatment of SOP.

Influence of biocurrent self-generated by indigenous microorganisms on soil quality.

The redox process driven by anaerobic respiration is a link between matter conversion and energy exchange in soil biogeochemistry. Microbial extracellular electron transfer forming biocurrents is a force in element cycling and community living in soil. However, the effect of indigenous microorganisms generating biocurrents on soil quality is unclear. We found that soil biocurrent showed little adverse influence on soil pH, cation exchange capacity, and available nitrogen, phosphorus and potassium and deblocked sequestered organic matter (29%). In addition, the bioelectric field derived from biocurrent obviously forced the migration of mineral elements, which was a supplement to the theory of water-salt transport, providing a new perspective on element transport. Moreover, the soil biocurrent directly regulated the availability of Ca and Fe (increase of 7-fold), indicating that electron transfer plays an important role in weathering and mineralization and thus pedogenesis. From a microbial ecology point of view, the soil bacterial richness and diversity were perfectly restored to their original state when the biocurrent stopped; including bacterial functions; although a temporary enrichment of certain species was observed. The above results provide new insights into the interactions between electron transfer and soil quality and confirm the safety of soil bioelectrochemical technology.

Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies. OBJECTIVE: This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM. SEARCH STRATEGY: Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used. INCLUSION CRITERIA: Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included. DATA EXTRACTION AND ANALYSIS: A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently. RESULTS: There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay. CONCLUSION: Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Anisodamine potently inhibits SARS-CoV-2 infection in vitro and targets its main protease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) provoked a pandemic of acute respiratory disease, namely coronavirus disease 2019 (COVID-19). Currently, effective drugs for this disease are urgently warranted. Anisodamine is a traditional Chinese medicine that is predicted as a potential therapeutic drug for the treatment of COVID-19. Therefore, this study aimed to investigate its antiviral activity and crucial targets in SARS-CoV-2 infection. SARS-CoV-2 and anisodamine were co-cultured in Vero E6 cells, and the antiviral activity of anisodamine was assessed by immunofluorescence assay. The antiviral activity of anisodamine was further measured by pseudovirus entry assay in HEK293/hACE2 cells. Finally, the predictions of crucial targets of anisodamine on SARS-CoV-2 were analyzed by molecular docking studies. We discovered that anisodamine suppressed SARS-CoV-2 infection in Vero E6 cells, and reduced the SARS-CoV-2 pseudovirus entry to HEK293/hACE2 cells. Furthermore, molecular docking studies indicated that anisodamine may target SARS-CoV-2 main protease (Mpro) with the docking score of -6.63 kcal/mol and formed three H-bonds with Gly143, Cys145, and Cys44 amino acid residues at the predicted active site of Mpro. This study suggests that anisodamine is a potent antiviral agent for treating COVID-19.

Synergistic effects of two naturally occurring iridoids in eliciting a rapid antidepressant action by up-regulating hippocampal PACAP signalling.

BACKGROUND AND PURPOSE: Current mainstream antidepressants have limited efficacy with a delayed onset of action. Yueju, a herbal medicine, has a rapid antidepressant action. Identification of the active ingredients in Yueju and the mechanism/s involved was carried out. EXPERIMENTAL APPROACH: Key molecule/s and compounds involved in this antidepressant action was identified by transcriptomic and HPLC analysis, respectively. Antidepressant effects were evaluated using various behavioural experiments. The signalling involved was assessed using site-directed pharmacological intervention or optogenetic manipulation. KEY RESULTS: Transcriptomic analysis showed that Yueju up-regulated pituitary adenylate cyclase activating polypeptide (PACAP) expression in the hippocampus. Two iridoids, geniposide and shanzhiside methyl ester, were identified and quantified from Yueju. Only co-treatment with both, at an equivalent concentrations found in Yueju, increased PACAP expression and elicited a rapid antidepressant action, which were blocked by intra-dentate gyrus infusion of a PACAP antagonist or optogenetic inactivation of PACAP expressing neurons. Geniposide and shanzhiside methyl ester co-treatment rapidly inhibited CaMKII phosphorylation and enhanced mTOR/4EBP1/P70S6k/BDNF ignalling, while intra-dentate gyrus infusions of a CaMKII activator blunted the rapid antidepressant action and BDNF expression up-regulation induced by the co-treatment. A single co-treatment of them rapidly improved depression-like behaviours and up-regulated hippocampal PACAP signalling in the repeated corticosterone-induced depression model, further confirming the involvement of PACAP. CONCLUSION AND IMPLICATIONS: Geniposide and shanzhiside methyl ester co-treatment had a synergistic rapid onset antidepressant action by triggering hippocampal PACAP activity and associated CaMKII-BDNF signalling. This mechanism could be targeted for development of fast onset antidepressants.

Advances in Photodynamic Therapy Based on Nanotechnology and Its Application in Skin Cancer.

Comprehensive cancer treatments have been widely studied. Traditional treatment methods (e.g., radiotherapy, chemotherapy), despite ablating tumors, inevitably damage normal cells and cause serious complications. Photodynamic therapy (PDT), with its low rate of trauma, accurate targeting, synergism, repeatability, has displayed great advantages in the treatment of tumors. In recent years, nanotech-based PDT has provided a new modality for cancer treatment. Direct modification of PSs by nanotechnology or the delivery of PSs by nanocarriers can improve their targeting, specificity, and PDT efficacy for tumors. In this review, we strive to provide the reader with a comprehensive overview, on various aspects of the types, characteristics, and research progress of photosensitizers and nanomaterials used in PDT. And the application progress and relative limitations of nanotech-PDT in non-melanoma skin cancer and melanoma are also summarized.

Biochanin A alleviates cognitive impairment and hippocampal mitochondrial damage in ovariectomized APP/PS1 mice.

BACKGROUND: Estrogen deficiency leads to mitochondrial defects that precede Alzheimer's disease (AD)-associated pathological changes in a postmenopausal mouse model. Biochanin A (BCA) is a phytoestrogen isolated from Trifolium pratense L. used to relieve postmenopausal problems in women. In previous work, we observed that oral BCA treatment led to neuroprotection in an ovariectomized rat model. The objective of this study was to investigate whether and how BCA protects against hippocampal mitochondrial damage in a postmenopausal model of AD. METHOD: APP/PS1 mice underwent bilateral ovariectomy and then, seven days later, received oral BCA at 20 or 40 mg/kg, or oral estradiol at 0.5 mg/kg, daily for 90 days. Sham animals were not ovariectomized and received no additional treatments. Cognitive function was examined using the passive avoidance task, novel object recognition test, and Morris water maze test. The level of circulating estrogen in vivo was assessed indirectly by measuring the wet weight of the uterus. We detected Aß deposition and PGC-1α in brain by immunohistochemistry; p62, by immunofluorescence; and ERα, ERß, PGC-1α, NRF1, mtTFA, Drp1, OPA1, Mfn2, Beclin1, LC3B, Pink1, and Parkin by immunoblotting. RESULTS: BCA treatment rescued cognitive decline and reduced Aß deposition and BACE1 expression in the hippocampus of ovariectomized APP/PS1 mice. BCA reversed the imbalance of mitochondrial dynamics caused by ovariectomy by increasing the expression of phospho-Drp1 (ser637), OPA1, and Mfn2. BCA reversed abnormal mitophagy induced by ovariectomy by increasing the expression of Beclin1, LC3B, Pink1, and Parkin, as well as by reducing the expression of p62. CONCLUSIONS: BCA treatment enhances learning and memory abilities and alleviates AD symptoms in a postmenopausal model of AD. A possible mechanism is that BCA rescues the reduction of mitochondrial biogenesis, imbalance of mitochondrial dynamics, and abnormal mitophagy caused by ovariectomy. This study supports further research on BCA to develop treatments for postmenopausal women with AD.

Hops extract and xanthohumol ameliorate bone loss induced by iron overload via activating Akt/GSK3ß/Nrf2 pathway.

INTRODUCTION: Osteoporosis is closely related to iron metabolism. This study aimed to investigate whether hops extract (HLE) and its active component xanthohumol (XAN) could ameliorate bone loss caused by iron overload, and explored its potential mechanism. MATERIALS AND METHODS: Iron overload mice induced by iron dextran (ID) were used in vivo, and were treated with HLE and XAN for 3 months. Bone micro-structure and bone morphology parameters were determined by Micro-CT and TRAP staining. Bone metabolism markers and oxidation indexes in serum and bone tissue were evaluated. For in vitro experiment, bone formation indexes were determined. Moreover, the expression of key proteins in protein kinase B (Akt)/glycogen synthetase kinase 3ß (GSK3ß)/nuclear factor E2-related (Nrf2) pathway was evaluated by Western blotting. RESULTS: HLE and XAN effectively improved the bone micro-structure of the femur in mice, altered bone metabolism biomarkers, and regulated the expression of proteins related to bone metabolism. Additionally, they significantly promoted cell proliferation, runt-related gene 2 (Runx2) expression, and increased ALP activity in ID-induced osteoblasts. Moreover, HLE and XAN markedly inhibited the increase of oxidative stress caused by iron overload in vivo and in vitro. Further studies showed that they significantly up-regulated the expression of p-Akt, p-GSK3ß, nuclear-Nrf2, NAD(P)H: quinone oxidoreductase 1 (NQO1), and heme oxygenase-1 (HO-1) in ID-induced osteoblasts. CONCLUSION: These findings indicated hops and xanthohumol could ameliorate bone loss induced by iron overload via activating Akt/GSK3ß/Nrf2 pathway, which brought up a novel sight for senile osteoporosis therapy.

Natural products for the treatment of stress-induced depression: Pharmacology, mechanism and traditional use.

ETHNOPHARMACOLOGICAL RELEVANCE: Depression, one of the most common psychiatric disorders, is the fourth leading cause of long-term disability worldwide. A series of causes triggered depression, including psychological stress and conflict, as well as biological derangement, among which stress has a pivotal role in the development of depression. Traditional herbal medicine has been used for the treatment of various disorders including depression for a long history with multi-targets, multi-levels and multi-ways, attracting great attention from scholars. Recently, natural products have been commercialized as antidepressants which have become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated and updated vast amount of data associated with natural products in antidepressant-like activity. AIMS OF THE REVIEW: This review aims to briefly discuss the pathological mechanism, animal models of stress-induced depression, traditional use of herbal medicines and especially recapitulate the natural products with antidepressant activity and their pharmacological functions and mechanism of action, which may contribute to a better understanding of potential therapeutic effects of natural products and the development of promising drugs with high efficacy and low toxicity for the treatment of stress-induced depression. MATERIALS AND METHODS: The contents of this review were sourced from electronic databases including PubMed, Sci Finder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wan Fang, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM). Additional information was collected from Yao Zhi website (https://db.yaozh.com/). Data were obtained from April 1992 to June 2021. Only English language was applied to the search. The search terms were 'stress-induced depression', 'pathological mechanism' in the title and 'stress', 'depression', 'animal model' and 'natural products' in the whole text. RESULTS: Stress-induced depression is related to the monoaminergic system, hypothalamic-pituitary-adrenal (HPA) axis, neuronal plasticity and a series of inflammatory factors. Four main types of animal models of stress-induced depression were represented. Fifty-eight bioactive phytochemical compounds, fifty-six herb medicines and five formulas from traditional Chinese medicine were highlighted, which exert antidepressant effects by inhibiting monoamine oxidase (MAO) reaction, alleviating dysfunction of the HPA axis and nerve injury, and possessing anti-inflammatory activities. CONCLUSIONS: Natural products provide a large number of compounds with antidepressant-like effects, and their therapeutic impacts has been highlighted for a long time. This review summarized the pathological mechanism and animal models of stress-induced depression, and the natural products with antidepressant activity in particular, which will shed light on the action mechanism and clinical potential of these compounds. Natural products also have been a vital and promising source for future antidepressant drug discovery.

Traditional Chinese medicine treatment for COVID-19: An overview of systematic reviews and meta-analyses / 中西医结合学报

BACKGROUND@#Coronavirus disease 2019 (COVID-19) is a rapidly spreading disease that has caused an extensive burden to the world. Consequently, a large number of clinical trials have examined the efficacy of traditional Chinese medicine (TCM) for treating and preventing COVID-19, with coinciding proliferation of reviews summarizing these studies.@*OBJECTIVE@#This study aimed to evaluate the methodological quality and evidence quality of systematic reviews and meta-analyses on the efficacy of TCM.@*SEARCH STRATEGY@#Seven electronic databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chongqing VIP, Wanfang Data and SinoMed, were searched for systematic reviews and meta-analyses in October 2021. Search terms such as "Chinese medicine," "Lianhua Qingwen" and "COVID-19" were used.@*INCLUSION CRITERIA@#Systematic reviews and meta-analyses of randomized controlled trials that evaluated the efficacy of TCM treatment of COVID-19 were included.@*DATA EXTRACTION AND ANALYSIS@#A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2) was used to evaluate the methodological quality. The quality of evidence was graded using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Data extraction and analysis were performed by two reviewers independently.@*RESULTS@#There were 17 meta-analyses included in our overview. The intervention group was defined as TCM combined with Western medicine, while the control group was Western medicine alone. The methodological quality of all the included studies was moderate to poor. A total of 89 outcome indicators were evaluated, of which, 8 were rated as moderate quality, 39 as low quality, and 41 as very low quality. Only one outcome measure was graded as being of high quality. The moderate quality of evidence indicated that, for the treatment of COVID-19, the clinical efficacy of TCM in combination with Western medicine was better, in terms of lung recovery, rate of conversion to severe/critical cases, symptom scores, duration of symptoms, mortality, and length of hospital stay.@*CONCLUSION@#Evidence from the included studies shows that, compared with conventional Western medical therapy alone, the addition of TCM to COVID-19 treatment may improve clinical outcomes. Overall, the quality of evidence of TCM for COVID-19 was moderate to poor. Meta-analyses of the use of TCM in the treatment of COVID-19 can be used for clinical decision making by accounting for the experiences of clinical experts, medical policies, and other factors.

Study on the Mechanism of Reducing Hepatotoxicity of Water-Grinding Realgar by Metabolomics, Morphology, and Chemical Analysis.

BACKGROUND: Realgar was usually selected as a substitute for arsenic trioxide to treat acute promyelocytic leukemia due to its higher effect without high cardiotoxicity. In traditional Chinese medicine (TCM), realgar is usually processed by the water-grinding method clinically, but the mechanism of realgar processing detoxification is still unclear. However, it is necessary to take safety and efficacy into account while evaluating a drug. METHODS: Sixty male Wistar rats were divided into control group, realgar products-treated groups, and corresponding subgroups. Biochemistry analysis and histopathological examination were performed in the study, and plasma samples were collected from all the rats for metabolomics analysis. RESULTS: No significant toxicity was observed in rats treated with 0.64 g/kg/day grinding realgar (G-r) and water-grinding realgar (WG-r). When the dose increased to 1.92 g/kg/day, the liver weight coefficients of the rats treated with G-r (HG-r: 3.65 ± 0.26%) and WG-r (HWG-r: 3.67 ± 0.14%) increased significantly and severe hepatic injury occurred in comparison to the control group (Group C: 3.00 ± 0.21%). After one week's withdrawal, the liver injury caused by the high dose of WG-r significantly recovered, while the liver damage caused by G-r was more difficult to recover. In metabolomics analysis, 14 metabolites were identified as the potential biomarkers in realgar-treated rats. These metabolites indicated that there were perturbations of the primary bile acid biosynthesis, arachidonic acid metabolism, linoleic acid metabolism, and glycerophospholipid metabolism in the realgar-treated groups. CONCLUSIONS: These results illustrate that, as a TCM processing method, water grinding had the effect of reducing toxicity, and the metabolomics method may be a valuable tool for studying the toxicity induced by TCM and the mechanism of TCM processing.