Honokiol Suppresses Cell Proliferation and Tumor Migration through ROS in Human Anaplastic Thyroid Cancer Cells.

BACKGROUND: Honokiol is a natural polyphenolic compound extracted from Magnolia officinali, which is commonly used material in Chinese herbal medicine, has a variety of biological functions, including anti-tumor, anti-oxidant, anti-inflammation, anti-microbial and anti-allergy. Although honokiol has numerous beneficial effects on human diseases, the underlying mechanisms of tumor metastasis are still unclear. Previously, we reported that honokiol suppresses thyroid cancer cell proliferation with cytotoxicity through cell cycle arrest, apoptosis, and dysregulation of intracellular hemostasis. Herein, we hypothesized that the antioxidant effect of honokiol might play a critical role in thyroid cancer cell proliferation and migration. METHODS: The cell viability assays, cellular reactive oxygen species (ROS) activity, cell migration, and immunoblotting were performed after cells were treated with honokiol. RESULTS: Based on this hypothesis, we first demonstrated that honokiol suppresses cell proliferation in two human anaplastic thyroid carcinoma (ATC) cell lines, KMH-2 and ASH-3, within a dosage- and time-dependent manner by cell counting kit-8 (CCK-8) assay. Next, we examined that honokiol induced ROS activation and could be suppressed by pre-treated with an antioxidant agent, N-acetyl-l-cysteine (NAC). Furthermore, the honokiol suppressed cell proliferation can be rescued by pre-treated with NAC. Finally, we demonstrated that honokiol inhibited ATC cell migration by modulating epithelial-mesenchymal transition (EMT)-related markers by Western blotting. CONCLUSION: Taken together, we provided the potential mechanism for treating ATC cells with honokiol, which significantly suppresses tumor proliferation and inhibits tumor metastasis in vitro through reactive oxygen species (ROS) induction.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

Use of the improved tug-of-war acupuncture for promoting cartilage repair by inducing macrophage polarization in knee osteoarthritis.

Introduction: Knee osteoarthritis (KOA) is a type of joint disease causing degenerative changes that are challenging to treat. The improved tug-of-war acupuncture (BHZF) can improve joint pain in KOA. However, the associated mechanism has not been validated. Methods: The KOA rabbit model was established. After the surgery, the improved BHZF was provided as an intervention, and the animals were euthanized after 2 weeks. Histopathological changes in the synovium and cartilage were observed on hematoxylin & eosin staining and Safranin O-Fast Green staining. Synovial fluid and serum samples were collected to assess the presence of cytokines using the enzyme-linked immunosorbent assay. The expression of M1 macrophage (CD86) and M2 macrophage (ARG1) markers in the cartilage and synovium was detected via immunohistochemistry and immunofluorescence assays. Results: The improved BHZF could reduce KOA-related pain and inhibit joint swelling. Further, it significantly maintained the morphology of articular chondrocytes in KOA and reduced the decomposition of the cartilage matrix. Then, it significantly reduced the expression of CD86-positive cells (P < 0.05), and increased the expression of ARG1-positive cells in the cartilage and synovium (P < 0.05). Moreover, it significantly decreased the expression of inflammatory factors interleukin (IL)-1 beta and tumor necrosis factor-alpha in the serum and synovial fluid (P < 0.05), and significantly increased the expression levels of anti-inflammatory cytokines IL-4 and IL-10 (P < 0.05). Conclusions: The improved BHZF can relieve pain and improve cartilage damage by regulating macrophage polarization in KOA.

Proteomics analysis of lung tissue reveals protein makers for the lung injury of adjuvant arthritis rats.

Lung injury is one of the common extra­articular lesions in rheumatoid arthritis (RA). Due to its insidious onset and no obvious clinical symptoms, it can be easily dismissed in the early stage of diagnosis, which is one of the reasons that leads to a decline of the quality of life and subsequent death of patients with RA. However, its pathogenesis is still unclear and there is a lack of effective therapeutic targets. In the present study, tandem mass tag­labeled proteomics was used to research the lung tissue proteins in RA model (adjuvant arthritis, AA) rats that had secondary lung injury. The aim of the present study was to identify the differentially expressed proteins related to RA­lung injury, determine their potential role in the pathogenesis of RA­lung injury and provide potential targets for clinical treatment. Lung tissue samples were collected from AA­lung injury and normal rats. The differentially expressed proteins (DEPs) were identified by tandem mass spectrometry. Bioinformatic analysis was used to assess the biological processes and signaling pathways associated with these DEPs. A total of 310 DEPs were found, of which 244 were upregulated and 66 were downregulated. KEGG anlysis showed that 'fatty acid degradation', 'fatty acid metabolism', 'fatty acid elongation', 'complement and coagulation cascades', 'peroxisome proliferator­activated receptor signaling pathway' and 'hypoxia­inducible factor signaling pathway' were significantly upregulated in the lung tissues of AA­lung injury. Immunofluorescence staining confirmed the increased expression of clusterin, serine protease inhibitors and complement 1qc in lung tissue of rats with AA lung injury. In the present study, the results revealed the significance of certain DEPs (for example, C9, C1qc and Clu) in the occurrence and development of RA­lung injury and provided support through experiments to identify potential biomarkers for the early diagnosis and prevention of RA­lung injury.

Comparative Activities of Novel Therapeutic Agents against Molecularly Characterized Clinical Carbapenem-Resistant Enterobacterales Isolates.

Limited treatment options exist for the treatment of carbapenem-resistant Enterobacterales (CRE) bacteria. Fortunately, there are several recently approved antibiotics indicated for CRE infections. Here, we examine the in vitro activity of various novel agents (eravacycline, plazomicin, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam) and comparators (tigecycline, amikacin, levofloxacin, fosfomycin, polymyxin B) against 365 well-characterized CRE clinical isolates with various genotypes. Nonduplicate isolates collected from the largest public health hospital in Singapore between 2007 and 2020 were subjected to antimicrobial susceptibility testing (broth microdilution or antibiotic gradient test strips). Susceptibilities were defined using Clinical and Laboratory Standards Institute (CLSI) or Food and Drug Administration (FDA) interpretative criteria. Sequence types and resistance mechanisms were characterized using short-read whole-genome sequencing. Overall, tigecycline and plazomicin exhibited the highest susceptibility rates (89.6% and 80.8%, respectively). However, the tigecycline susceptibility breakpoint utilized here may be outdated in view of prevailing pharmacokinetic-pharmacodynamic (PK/PD) data. Susceptibility varied by carbapenemase genotype; the ß-lactam/ß-lactamase inhibitor combinations were equally active (92.3 to 99.2% susceptible) against KPC producers, but only ceftazidime-avibactam retained high susceptibility (98.7%) against OXA-48-like producers. Against metallo-ß-lactamase producers, only plazomicin exhibited moderate activity (77.0% susceptible). Aminoglycoside activity was also influenced by carbapenemase genotypes. This work provides an insight into the comparative activity and presumptive utility of novel agents in this geographic region. IMPORTANCE This study determined the susceptibilities of carbapenem-resistant Enterobacterales isolates to various novel antimicrobial agents (ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, eravacycline, and plazomicin). Whole-genome sequencing was performed for all strains. Our study findings provide insights into the comparative activities of novel agents in this geographic region. Plazomicin and ceftazidime-avibactam exhibited the lowest nonsusceptibility rates and may be considered promising agents in the management of carbapenem-resistant Enterobacterales infections. We note also that antibiotic activity is influenced by genotypes and that understanding the geographic region's molecular epidemiology could aid in the definition of the presumptive utility of novel agents and contribute to antibiotic decision-making.

[Effect of acupuncture combined with infantile tuina on intestinal flora in children with tic disorders].

OBJECTIVE: To observe the effect of acupuncture combined with infantile tuina on intestinal flora and its efficacy in children with tic disorders (TD), and to explore its mechanism. METHODS: A total of 15 children with TD were recruited as an observation group and 10 healthy children as a healthy control group. Regulating spleen and stomach acupuncture combined with infantile tuina were received in the observation group. First, acupuncture was applied to Zhongwan (CV 12), Tianshu (ST 25), Guanyuan (CV 4), Hegu (LI 4), Zusanli (ST 36), etc., and then abdominal massage and other tuina techniques were applied, once a day, 6 times a week, 2 weeks as a course of treatment, a total of 2 courses of treatment were required. No intervention was given in the healthy control group. In the observation group, Yale global tic severity scale (YGTSS) score and TCM syndrome score were compared before treatment and after 1 and 2 courses of treatment. 16S rRNA sequencing technology was used to detect the intestinal flora in the healthy control group and before and after treatment in the observation group. RESULTS: After 1 and 2 courses of treatment, the scores of YGTSS and TCM syndrome in the observation group were lower than those before treatment (P<0.01, P<0.05). Compared with the healthy control group, the number of operational taxonomic units (OTU) and indexes of Chao1, Sobs, Ace and Shannon were decreased in the observation group before treatment (P<0.05, P<0.01). Compared with before treatment, the number of OTU and indexes of Chao1, Sobs, Ace and Shannon were increased in the observation group after treatment (P<0.01, P<0.05). Compared with the healthy control group, the relative abundance of Firmicutes in the observation group before treatment was decreased (P<0.001), while the relative abundance of Bacteroidetes, Bacteroides and Erysipelatoclostridium was increased (P<0.001, P<0.05). Compared with before treatment, the relative abundance of Bacteroidetes in the observation group was decreased (P<0.001) after treatment, while the relative abundance of Actinobacteria, Bifidobacterium and Atopobium was increased (P<0.05, P<0.01). CONCLUSION: Acupuncture combined with infantile tuina based on the principle of regulating spleen and stomach could effectively improve TD symptoms in children, which may be related to regulating the diversity of intestinal flora, increasing beneficial bacteria, maintaining intestinal microecological balance, and playing a role in improving neurological disorders.

Network pharmacology and bioinformatics study on the treatment of renal fibrosis with persicae semen-carthami flos drug pair.

To use network pharmacology and bioinformatics technology to reveal the mechanism of persicae semen-carthami flos drug pair in the treatment of renal fibrosis (RF). Compounds in traditional Chinese medicine were obtained through the Herb database. Appropriate compounds and corresponding drug targets were screened out based on the 5 rules of Lipinski and pharmacokinetics. Screening of suitable disease miRNAs by microarray chips in the GEO database. Find differentially expressed genes by analyzing miRNAs. Protein-protein interaction analysis and enrichment analysis of therapeutic targets were performed using String database and Omicshare platform. Molecular docking via the DockThor platform. A total of 28 drug compounds and 228 drug targets were screened in this study. A total of 9 miRNAs and 6649 disease targets were obtained by GEO2R software analysis. Finally, 97 therapeutic targets were obtained. A total of 1124 Gene Ontology enrichment analysis results were obtained. Therapeutic targets play multiple roles in biological processes, molecular functions, and cellular organization. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the persicae semen-carthami flos drug pair played a role in the treatment of RF mainly through calcium signaling pathway, pathways in cancer, cAMP signaling pathway, and other pathways. Molecular docking showed that the traditional Chinese medicine compounds had good binding ability to the target. Persicae semen and carthami flos play a role in the treatment of RF through multiple targets and multiple pathways. It provides ideas and references for follow-up research and new drug development.

Reverse predictive analysis of Rhizoma Pinelliae and Rhizoma Coptidis on differential miRNA target genes in lung adenocarcinoma.

To use bioinformatics and network analysis to reveal the mechanism of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma. The target and pathway of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma were explored by online databases and network analysis tools, and the potential biomarkers of "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair in the treatment of lung adenocarcinoma were predicted in reverse. A total of 59 traditional Chinese medicine compounds and 510 drug targets were screened in this study. A total of 25 micro-RNAs and 15,323 disease targets were obtained through GEO2R software analysis. In the end, 294 therapeutic targets and 47 core targets were obtained. A total of 186 gene ontology enrichment assays were obtained, and core therapeutic targets play multiple roles in biological processes, molecular functions, and cellular composition. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that the core targets were mainly enriched in cancer-related pathways, immune-related pathways, endocrine-related pathways, etc, among which the non-small cell lung cancer pathway was the most significant core pathway. Molecular docking shows that the compound and the target have good binding ability. "Rhizoma Pinelliae-Rhizoma Coptidis" herb pair plays a mechanism of action in the treatment of lung adenocarcinoma through multiple targets and pathways. miR-5703, miR-3125, miR-652-5P, and miR-513c-5p may be new biomarkers for the treatment of lung adenocarcinoma.

The mechanism of Qingwen Gupi decoction on pulmonary fibrosis based on metabolomics and intestinal flora.

AIMS: To evaluate the effects of the Qingwen Gupi decoction (QGT) in a rat model of bleomycin-induced pulmonary fibrosis (PF), and explore the underlying mechanisms by integrating UPLC-Q-TOF/MS metabolomics and 16S rDNA sequencing of gut microbiota. METHODS AND RESULTS: The animals were randomly divided into the control, PF model, pirfenidone-treated, and low-, medium-, and high-dose QGT groups. The lung tissues were examined and the expression of TGF-ß, SMAD-3, and SMAD-7 mRNAs in the lung tissues were analyzed. Metabolomic profiles were analyzed by UPLC-QTOF/MS, and the intestinal flora were examined by prokaryotic 16 rDNA sequencing. Pathological examination and biochemical indices revealed that QGT treatment improved the symptoms of PF by varying degrees. Furthermore, QGT significantly downregulated TGF-ß1 and Smad-3 mRNAs and increased the expression levels of Smad-7. QGT-L in particular increased the levels of 18 key metabolic biomarkers that were associated with nine gut microbial species and may exert antifibrosis effects through arachidonic acid metabolism, glycerophospholipid metabolism, and phenylalanine metabolism. CONCLUSIONS: QGT alleviated PF in a rat model through its anti-inflammatory, antioxidant, and anti-fibrotic effects, and by reversing bleomycin-induced gut dysbiosis.This study lays the foundation for further research on the pathological mechanisms of PF and the development of new drug candidates.

Natural products of traditional Chinese medicine treat atherosclerosis by regulating inflammatory and oxidative stress pathways.

Atherosclerosis (AS) is a prevalent arteriosclerotic vascular disease that forms a pathological basis for coronary heart disease, stroke, and other diseases. Inflammatory and oxidative stress responses occur throughout the development of AS. Treatment for AS over the past few decades has focused on administering high-intensity statins to reduce blood lipid levels, but these inevitably damage liver and kidney function over the long term. Natural medicines are widely used to prevent and treat AS in China because of their wide range of beneficial effects, low toxicity, and minimal side effects. We searched for relevant literature over the past 5 years in databases such as PubMed using the keywords, "atherosclerosis," "traditional Chinese medicine," "natural medicines," "inflammation," and "oxidative stress." We found that the PI3K/AKT, TLR4, JAK/STAT, Nrf2, MAPK, and NF-κB are the most relevant inflammatory and oxidative stress pathways in AS. This review summarizes studies of the natural alkaloid, flavonoid, polyphenol, saponin, and quinone pathways through which natural medicines used to treat AS. This study aimed to update and summarize progress in understanding how natural medicines treat AS via inflammatory and oxidative stress-related signaling pathways. We also planned to create an information base for the development of novel drugs for future AS treatment.

Limosilactobacillus reuteri FN041 prevents atopic dermatitis in pup mice by remodeling the ileal microbiota and regulating gene expression in Peyer's patches after vertical transmission.

Objectives: Limosilactobacillus reuteri FN041 is a potential probiotic bacterium isolated from breast milk in traditional farming and pastoral areas of China. The purpose of this study was to investigate the optimal intervention mode and potential mechanism of FN041 to prevent atopic dermatitis (AD) in mice. Methods: In intervention mode I, FN041 was supplemented to dams during the late trimester and lactation and pups after weaning; in intervention mode II, FN041 was supplemented after pups were weaned. AD was induced in pups with MC903 plus ovalbumin on the ear after weaning. Results: The effect of intervention mode I in preventing AD was significantly better than that of intervention mode II. Compared with the model group, the inflammatory response of the pup's ears, the proportion of spleen regulatory T cells and the plasma IgE were significantly decreased in mice in intervention mode I. Furthermore, the intestinal mucosal barrier was enhanced, and the Shannon index of the ileal microbiota was significantly increased. The microbiota structure deviated from the AD controls and shifted toward the healthy controls according to the PCoA of unweighted UniFrac. The relative abundances of Limosilactobacillus, Faecalibacterium, Bifidobacterium, and Akkermansia in the ileum were significantly increased compared to the AD group. Based on RNA-seq analysis of pups' Peyer's patches (PPs), FN041 inhibits autoimmune pathways such as asthma and systemic lupus erythematosus and activates retinol metabolism and PPAR signaling pathways to reduce inflammatory responses. Intervention mode II also significantly reduced AD severity score, but the reduction was approximately 67% of that of intervention mode I. This may be related to its ineffective remodeling of the ileal microbiota. Conclusion: Prenatal and postnatal administration of FN041 is an effective way to prevent AD in offspring, and its mechanism is related to remodeling of ileal microbiota and PPs immune response.

Pumpkin Skin Polysaccharide-Zn(II) Complex: Preparation, Characterization, and Suppression of Inflammation in Zebrafish.

In this study, pumpkin (Cucurbita moschata) skin polysaccharide-zinc(II) (PSP-Zn) complex was successfully prepared. The structure and physicochemical properties of PSP and PSP-Zn were analyzed. The anti-inflammatory activity of PSP and PSP-Zn was investigated in zebrafish larvae induced by copper sulphate. PSP and PSP-Zn consisted of rhamnose, arabinose, galactose, glucose, and galacturonic acid. The molecular weight (Mw) of PSP and PSP-Zn were 3.034 × 106 and 3.222 × 106 Da, respectively. Fourier transform infrared spectrum (FT-IR) and circular dichroism (CD) analysis results suggested that the chemical modification of zinc might occur through hydroxyl groups of PSP. The PSP-Zn complex had lamellar texture, smooth surface morphology, and larger particle size. X-ray Diffraction (XRD) analysis revealed that both PSP and PSP-Zn were semi-crystalline substances. PSP-Zn solution showed superior stability in a weak acid and alkaline environment, especially at pH = 6.0. Moreover, PSP and PSP-Zn showed a good inhibitory effect on inflammation cells in zebrafish. Real-time quantitative polymerase chain reaction (RT-PCR) result suggested that the anti-inflammatory mechanism of PSP and PSP-Zn were through downregulation of the expression of nitric oxide synthase 2b (nos2b), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), and nuclear factor-kappa B2 (NF-κB2). The present study indicated that PSP-Zn is expected to be a safe and efficient novel zinc supplement with anti-inflammatory activity.

eEF-2K knockdown synergizes with STS treatment to inhibit cell proliferation, migration, and invasion via the TG2/ERK pathway in A549 cells.

Emerging research has suggested the anticancer potential of tanshinone IIA, the bioactive ingredient isolated from the traditional Chinese herb Salvia miltiorrhiza. However, the molecular mechanism of sodium tanshinone IIA sulfonate (STS) antilung cancer effect is not very clear. In this study, our purpose is to investigate the roles of STS and elongation factor-2 kinase (eEF-2K) in regulating the proliferation, migration, and invasion of A549 cells and explore the implicated pathways. We found that STS suppressed A549 cell survival and proliferation in a time- and xdose-dependent manner. Knockdown of eEF-2K and treatment with STS synergistically exerted antiproliferative, -migratory, and -invasive effects on A549 cells. These effects were caused by attenuation of the extracellular signal-regulated kinase (ERK) pathway via inhibition of tissue transglutaminase (TG2). In summary, the inhibition of eEF-2K synergizes with STS treatment, exerting anticancer effects on lung adenocarcinoma cells through the TG2/ERK signaling pathway, which provides a potential therapeutic target for treating lung adenocarcinoma.

Exploring the Anti-inflammatory Effects of Protopine Total Alkaloids of Macleaya Cordata (Willd.) R. Br.

Macleaya cordata (Willd). R. Br. is a Chinese medicinal plant commonly used externally to treat inflammatory-related diseases such as arthritis, sores, and carbuncles. This study aimed to evaluate the anti-inflammatory activity of protopine total alkaloids (MPTAs) in Macleaya cordata (Willd.) R. Br. in vivo tests in rats with acute inflammation showed that MPTA (2.54 and 5.08 mg/kg) showed significant anti-inflammatory activity 6 h after carrageenan injection. Similarly, MPTA (3.67 and 7.33 mg/kg) showed significant anti-inflammatory activity in the mouse ear swelling test. In addition, the potential mechanisms of the anti-inflammatory effects of MPTA were explored based on network pharmacology and molecular docking. The two main active components of MPTA, protopine and allocryptopine, were identified, and the potential targets and signaling pathways of MPTA's anti-inflammatory effects were initially revealed using tools and databases (such as SwissTargetPrediction, GeneCards, and STRING) combined with molecular docking results. This study provides the basis for the application of MPTA as an anti-inflammatory agent.

Sanghuang Tongxie Formula Ameliorates Insulin Resistance in Drosophila Through Regulating PI3K/Akt Signaling.

Insulin resistance (IR) is a pivotal pathological characteristic that affects the occurrence and development of type 2 diabetes mellitus (T2DM). Thus, the effective control of IR is of great significance for diabetes prevention and treatment. Traditional Chinese medicine (TCM) represents a valuable tool handed down to the world by the Chinese nation and has a long history of use for diabetes clinical therapy. In this study, we focused on a self-drafted TCM-patented formula, Sanghuang Tongxie Formula (SHTXF), which exhibits clinical efficacy in the treatment of diabetes. To explore the effect and molecular mechanism of SHTXF on IR in vivo, Drosophila melanogaster was used and a (Collagen) Cg > InRK1409A diabetic IR fly model was established. SHTXF water extract was found to contribute toward carbohydrate clearance from the circulating system by converting it into triglycerides (TAG), not glycogen, for nutrient storage. In addition, SHTXF activated phosphatidylinositol-3-kinase (PI3K) activity and improved protein kinase B (PKB, also termed Akt) phosphorylation. Finally, SHTXF promoted Drosophila Forkhead Box O (dFoxO) cytoplasmic localization and inhibited its transcriptional activity. Taken together, these findings not only highlight the positive role of SHTXF in ameliorating IR via the PI3K/Akt pathway but also provide potential drug targets and key insights for use in T2DM clinical treatment strategies.

Safety assessment of MPTA: An oral acute and 90-day sub-chronic toxicity study in Sprague-Dawley rats.

MPTA is a novel extract product derived from Macleaya cordata (Willd.) R. Br., which has good anti-inflammatory and antioxidant activity. The aim of this study was to investigate the acute oral toxicity and 90-day sub-chronic oral toxicity of MPTA. In the acute toxicity study, 50 SD rats of both sexes were randomly divided into 5 groups and dosed in a gradient from 197.53 mg/kg to 1000.00 mg/kg bw. Toxic effects were observed up to 14 days and LD50 was calculated. In a subchronic toxicity test, male and female SD rats were orally dosed repeatedly with 96.40, 19.28, 3.86 mg/kg bw of MPTA for 90 days. In addition, a control group was set up in the subchronic study. The acute toxicity test showed that the oral LD50 of MPTA was 481.99 mg/kg with a 95% confidence interval of 404.24-574.70 mg/kg. MPTA did not appear to induce toxic effects in the longer term in terms of food and water consumption, weight gain, haematological and clinical biochemical parameters and pathological examination. The first data on the potential toxicity of MPTA was provided to highlight the safety of short-term to longer-term oral administration of MPTA, and the experimental results yield and establish a NOEAL of 96.40 mg/kg/d for MPTA.

Heme peroxidases are responsible for the dehydrogenation and oxidation metabolism of harmaline into harmine.

Harmaline and harmine are ß-carboline alkaloids with effective pharmacological effects. Harmaline can be transformed into harmine after oral administration. However, enzymes involved in the metabolic pathway remain unclear. In this study, harmaline was incubated with rat liver microsomes (RLM), rat brain microsomes (RBM), blood, plasma, broken blood cells, and heme peroxidases including horseradish peroxidase (HRP), lactoperoxidase (LPO), and myeloperoxidase (MPO). The production of harmine was determined by a validated UPLC-ESI-MS/MS method. Results showed that heme peroxidases catalyzed the oxidative dehydrogenation of harmaline. All the reactions were in accordance with the Hill equation. The reaction was inhibited by ascorbic acid and excess H2O2. The transformation of harmaline to harmine was confirmed after incubation with blood, plasma, and broken blood cells, rather than RLM and RBM. Harmaline was incubated with blood, plasma, and broken cells liquid for 3 h, and the formation of harmine became stable. Results indicated an integrated metabolic pathway of harmaline, which will lay foundation for the oxidation reaction of dihydro-ß-carboline. Moreover, the metabolic stability of harmaline in blood should not be ignored when the pharmacokinetics study of harmaline is carried out.

Complementary and Alternative Medicine for Premature Ovarian Insufficiency: A Review of Utilization and Mechanisms.

Premature ovarian insufficiency (POI) is defined as a decline in ovarian function before the age of 40 and is one of the leading causes of infertility in women. The etiology is complex, and the pathogenesis is not clear. The main treatment is hormone replacement therapy, but a growing body of data confirms that such treatment can increase the risk of endometrial disease and cardiovascular disease. Complementary and alternative medicine (CAM) has been widely used in patients with POI due to its limited adverse reactions and high efficiency. According to literature reports, CAM therapy for POI mainly includes traditional Chinese medicine, acupuncture, psychotherapy, dietary supplements, and exercise therapy. This article reviews the application of CAM in the treatment of POI and attempts to determine the therapeutic effects and the mechanisms behind these effects based on existing clinical and experimental studies in order to provide theoretical support for the treatment of POI.

Green tea consumption and risk of depressive symptoms: Results from the TCLSIH Cohort Study.

BACKGROUND: The prospective studies on the effect of particular type of tea consumption, especially green tea, on depressive symptoms are limited. OBJECTIVE: The aim of this study is to investigate the prospective association between green tea consumption and depressive symptoms in a large general adult population. METHODS: This prospective cohort study investigated 7524 participants aged 25 to 90 years from May 2013 to December 2018 and they were free of cardiovascular disease, cancer, and depressive symptoms at baseline. Green tea consumption was obtained through a validated food frequency questionnaire. Depressive symptoms were assessed by using the Self-Rating Depressive Scale (SDS). The association between green tea consumption and depressive symptoms was analyzed by Cox proportional hazards regression models. RESULTS: A total of 1064 first incident cases of depressive symptoms (SDS ≥45) occurred during 14,661 person-years of follow-up (median follow-up of 2.0 years). In the crude model, the hazard ratios (95% confidence intervals) were 1.00 (reference), 0.95 (0.81, 1.12), 0.97 (0.83, 1.14) and 0.95 (0.79, 1.14), respectively. After adjusting for demographic characteristics, lifestyle factors, and dietary intake, the multivariable adjusted hazard ratios (95% confidence intervals) were 1.00 (reference), 0.88 (0.74, 1.05), 0.84 (0.69, 1.02) and 0.78 (0.63, 0.97), respectively. CONCLUSIONS: The prospective study suggests that frequent green tea consumption is associated with a decreased risk of depressive symptoms in the general Chinese population.

Prevention, treatment and potential mechanism of herbal medicine for Corona viruses: A review.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.