Traditional Chinese medicine formulae: A complementary method for the treatment of polycystic ovary syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine condition that significantly affects women of all age groups and is characterized by metabolic dysfunction. The efficacy of existing pharmaceutical interventions for the treatment of PCOS remains inadequate. With a rich history and cultural significance spanning thousands of years, Traditional Chinese Medicine (TCM) is extensively employed for treating a variety of ailments and can serve as a supplementary therapy for managing PCOS. Multiple clinical observations and laboratory tests have unequivocally demonstrated the substantial effectiveness and safety of TCM formulae in treating PCOS, and further investigations are currently in progress. AIM OF THE STUDY: To summarize the TCM formulae commonly employed in the clinical management of PCOS, examine their therapeutic benefits, investigate their mechanism of action, active constituents, and establish the correlation between efficacy, mechanism of action, and active constituents. MATERIALS AND METHODS: We conducted a comprehensive search on PubMed, Web of Science, and China national knowledge infrastructure (CNKI) using the following keywords: "Polycystic Ovary Syndrome", "Traditional Chinese Medicine Decoctions", "Traditional Chinese Medicine formulae", "Traditional Chinese Medicine", "Clinical Observation", "Mechanism", "Treatment", "Pharmacology", and various combinations of these terms. From January 1, 2006 until October 7, 2023, (inclusive). RESULTS: This paper summarized the clinical effectiveness, mechanism of action, and active components of 8 TCM formulae for the treatment of PCOS. Our research indicates that TCM formulae can potentially treat PCOS by enhancing the levels of hyperandrogenism and other endocrine hormones, decreasing insulin resistance and hyperinsulinemia, and controlling chronic low-grade inflammation, among other modes of action. In addition, we found an association between epigenetics and TCM formulae for the treatment of PCOS. CONCLUSION: TCM formulae have specific advantages in the treatment of Polycystic Ovary Syndrome (PCOS). They achieve therapeutic benefits by targeting several pathways and connections, attracting considerable interest and playing a vital role in the treatment of PCOS. TCM formulae can be used as an adjunctive therapy for the treatment of PCOS.

Effect of an Asian-adapted Mediterranean diet and pentadecanoic acid on fatty liver disease: the TANGO randomized controlled trial.

BACKGROUND: Weight loss is the most effective treatment for nonalcoholic fatty liver disease (NAFLD). There is evidence that the Mediterranean diets rich in unsaturated fatty acids and fiber have beneficial effects on weight homeostasis and metabolic risk factors in individuals with NAFLD. Studies have also shown that higher circulating concentrations of pentadecanoic acid (C15:0) are associated with a lower risk for NAFLD. OBJECTIVES: To examine the effects of a Mediterranean-like, culturally contextualized Asian diet rich in fiber and unsaturated fatty acids, with or without C15:0 supplementation, in Chinese females with NAFLD. METHODS: In a double-blinded, parallel-design, randomized controlled trial, 88 Chinese females with NAFLD were randomly assigned to 1 of the 3 groups for 12 wk: diet with C15:0 supplementation (n = 31), diet without C15:0 supplementation (n = 28), or control (habitual diet and no C15:0 supplementation, n = 29). At baseline and after the intervention, body fat percentage, intrahepatic lipid content, muscle and abdominal fat, liver enzymes, cardiometabolic risk factors, and gut microbiome were assessed. RESULTS: In the intention-to-treat analysis, weight reductions of 4.0 ± 0.5 kg (5.3%), 3.4 ± 0.5 kg (4.5%), and 1.5 ± 0.5 kg (2.1%) were achieved in the diet-with-C15:0, diet without-C15:0, and the control groups, respectively. The proton density fat fraction (PDFF) of the liver decreased by 33%, 30%, and 10%, respectively. Both diet groups achieved significantly greater reductions in body weight, liver PDFF, total cholesterol, gamma-glutamyl transferase, and triglyceride concentrations compared with the control group. C15:0 supplementation reduced LDL-cholesterol further, and increased the abundance of Bifidobacterium adolescentis. Fat mass, visceral adipose tissue, subcutaneous abdominal adipose tissue (deep and superficial), insulin, glycated hemoglobin, and blood pressure decreased significantly in all groups, in parallel with weight loss. CONCLUSION: Mild weight loss induced by a Mediterranean-like diet adapted for Asians has multiple beneficial health effects in females with NAFLD. C15:0 supplementation lowers LDL-cholesterol and may cause beneficial shifts in the gut microbiome. TRIAL REGISTRATION NUMBER: This trial was registered at the clinicaltrials.gov as NCT05259475.

Targeted metabolomics reveals PFKFB3 as a key target for elemene-mediated inhibition of glycolysis in prostate cancer cells.

BACKGROUND: Elemene, an active anticancer extract derived from Curcuma wenyujin, has well-documented anticarcinogenic properties. Nevertheless, the role of elemene in prostate cancer (PCa) and its underlying molecular mechanism remain elusive. PURPOSE: This study focuses on investigating the anti-PCa effects of elemene and its underlying mechanisms. METHODS: Cell-based assays, including CCK-8, scratch, colony formation, cell cycle, and apoptosis experiments, to comprehensively assess the impact of elemene on PCa cells (LNCaP and PC3) in vitro. Additionally, we used a xenograft model with PC3 cells in nude mice to evaluate elemene in vivo efficacy. Targeted metabolomics analysis via HILIC-MS/MS was performed to investigate elemene potential target pathways, validated through molecular biology experiments, including western blotting and gene manipulation studies. RESULTS: In this study, we discovered that elemene has remarkable anti-PCa activity in both in vitro and in vivo settings, comparable to clinical chemotherapeutic drugs but with fewer side effects. Using our established targeted metabolomics approach, we demonstrated that ß-elemene, elemene's primary component, effectively inhibits glycolysis in PCa cells by downregulating 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3) expression. Furthermore, we found that ß-elemene accomplishes this downregulation by upregulating p53 and FZR1. Knockdown and overexpression experiments conclusively confirmed the pivotal role of PFKFB3 in mediating ß-elemene's anti-PCa activity. CONCLUSION: This finding presents compelling evidence that elemene exerts its anti-PCa effect by suppressing glycolysis through the downregulation of PFKFB3. This study not only improves our understanding of elemene in PCa treatment but also provides valuable insights for developing more effective and safer therapies for PCa.

Recycling of phosphate tailings for an efficient hydroxyapatite-based adsorbent to immobilize heavy metal cations.

Hydroxyapatite (HAP) is a promising adsorbent for immobilizing heavy metals in soil and water. However, the preparation and modification of HAP from pure chemicals increases its cost and limits its large-scale practical application. In this study, a hydroxyapatite-based adsorbent (HAPPT) was prepared from phosphate tailing produced in the phosphorus industry to sequester Pb, Cd and Zn from solution. The results showed that HAPPT was composed of HAP and MgO, with a surface area of 27.74 m2/g. The kinetics studies showed that most Pb and Cd were removed from the initial solution in 4 h and the adsorption of Zn increased with increasing contact time. Metals presented higher adsorption capacities at 35 °C than that at 25 °C. The adsorption isotherms showed that HAPPT presented high adsorption capacities for Pb, Cd and Zn in mono-metal solutions. The adsorption capacity of Cd at pH 6 was higher than that at pH 3, but the adsorption for Pb and Zn was similar at both pHs. HAPPT has selectivity for Pb in Pb-Cd-Zn multi-metals solution, and competitive adsorption reduced the adsorption quantity by 53%, 93% and 79% for Pb, Cd and Zn, respectively. The combined results of TEM-EDS, XRD and XPS showed that Pb was immobilized by forming phosphates due to the dissolution of HAP, whereas Cd and Zn were immobilized by forming hydroxide precipitates resulting from the function of MgO in HAPPT. The results of this study provided an efficient adsorbent for the removal of heavy metals in solution and provided a new perspective on the recycling of phosphate tailings in the phosphorus industry.

Elemene induces cell apoptosis via inhibiting glutathione synthesis in lung adenocarcinoma.

ETHNOPHARMACOLOGICAL RELEVANCE: The rhizome of Curcuma wenyujin Y.H. Chen & C. Ling, also known as Wen-E-Zhu, has been used for cancer treatment since ancient times, with roots dating back to the Song Dynasty. Elemene (EE), a sesquiterpene extract with potent anticancer properties, is extracted from Wen-E-Zhu, with ß-elemene (BE) being its main active compound, along with trace amounts of ß-caryophyllene (BC), γ-elemene and δ-elemene isomers. EE has demonstrated broad-spectrum anti-cancer effects and is commonly used in clinical treatments for various types of malignant cancers, including lung cancer. Studies have shown that EE can arrest the cell cycle, inhibit cancer cell proliferation, and induce apoptosis and autophagy. However, the exact mechanism of its anti-lung cancer activity remains unclear and requires further research and investigation. AIM OF THE STUDY: In this study, the possible mechanism of EE and its main active components, BE and BC, against lung adenocarcinoma was investigated by using A549 and PC9 cell lines. MATERIALS AND METHODS: The subcutaneous tumor model of nude mice was constructed to evaluate the efficacy of EE in vivo, then the in vitro half-inhibitory concentration (IC50) of EE and its main active components, BE and BC, on A549 and PC9 cells at different concentrations were determined by CCK-8. Flow cytometry was used to detect the apoptosis and cycle of A549 and PC9 cells treated with different concentrations of BE and BC for 24 h. Non-targeted metabolomics analysis was performed on A549 cells to explore potential target pathways, which were subsequently verified through kit detection and western blot analysis. RESULTS: Injection of EE in A549 tumor-bearing mice effectively suppressed cancer growth in vivo. The IC50 of EE and its main active components, BE and BC, was around 60 µg/mL. Flow cytometry analysis showed that BE and BC blocked the G2/M and S phases of lung adenocarcinoma cells and induced apoptosis, leading to a significant reduction in mitochondrial membrane potential (MMP). Results from non-targeted metabolomics analysis indicated that the glutathione metabolism pathway in A549 cells was altered after treatment with the active components. Kit detection revealed a decrease in glutathione (GSH) levels and an increase in the levels of oxidized glutathione (GSSG) and reactive oxygen (ROS). Supplementation of GSH reduced the inhibitory activity of the active components on lung cancer and also decreased the ROS content of cells. Analysis of glutathione synthesis-related proteins showed a decrease in the expression of glutaminase, cystine/glutamate reverse transporter (SLC7A11), and glutathione synthase (GS), while the expression of glutamate cysteine ligase modified subunit (GCLM) was increased. In the apoptosis-related pathway, Bax protein and cleaved caspase-9/caspase-9 ratio were up-regulated and Bcl-2 protein was down-regulated. CONCLUSIONS: EE, BE, and BC showed significant inhibitory effects on the growth of lung adenocarcinoma cells, and the mechanism of action was linked to the glutathione system. By down-regulating the expression of proteins related to GSH synthesis, EE and its main active components BE and BC disrupted the cellular redox system and thereby promoted cell apoptosis.

[Effect of Erjing Pills on alleviating neuroinflammation of AD rats based on TLR4/NF-κB/NLRP3 pathway and its mechanism].

This paper aimed to study the effect of Erjing Pills on the improvement of neuroinflammation of rats with Alzheimer's di-sease(AD) induced by the combination of D-galactose and Aß_(25-35) and its mechanism. SD rats were randomly divided into a sham group, a model control group, a positive drug group(donepezil, 1 mg·kg~(-1)), an Erjing Pills high-dose group(9.0 g·kg~(-1)), and an Erjing Pills low-dose group(4.5 g·kg~(-1)), with 14 rats each group. To establish the rat model of AD, Erjing Pills were intragastrically administrated to rats for 5 weeks after 2 weeks of D-galactose injection. D-galactose was intraperitoneally injected into rats for 3 weeks, and then Aß_(25-35) was injected into the bilateral hippocampus. The new object recognition test was used to evaluate the learning and memory ability of rats after 4 weeks of intragastric administration. Tissues were acquired 24 h after the last administration. The immunofluorescence method was used to detect the activation of microglia in the brain tissue of rats. The positive expressions of Aß_(1-42) and phosphory protein Tau~(404)(p-Tau~(404)) in the CA1 area of the hippocampus were detected by immunohistochemistry. The levels of inflammatory factors interleukin-1ß(IL-1ß), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6) in the brain tissue were determined by enzyme-linked immunosorbent assay(ELISA). Toll-like receptor 4(TLR4)/nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptors 3(NLRP3) pathway-associated proteins in the brain tissue were determined by Western blot. The results showed that as compared with the sham group, the new object recognition index of rats in the model control group decreased significantly, the deposition of Aß_(1-42) and p-Tau~(404) positive protein in the hippocampus increased significantly, and the levels of microglia activation increased significantly in the dentate gyrus. The levels of IL-1ß, TNF-α, and IL-6 in the hippocampus of the model control group increased significantly, and the expression levels of TLR4, p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus increased significantly. Compared with the model control group, the Erjing Pill groups enhanced the new object recognition index of rats, decreased the deposition of Aß_(1-42) and the expression of p-Tau~(404) positive protein in the hippocampus, inhibited the activation of microglia in the dentate gyrus, reduced the levels of inflammatory factors IL-1ß, TNF-α, and IL-6 in the hippocampus, and down-regulated the expression levels of TLR4, p-NF-κB P65/NF-κB P65, p-IκBα/IκBα, and NLRP3 proteins in the hippocampus. In conclusion, Erjing Pills can improve the learning and memory ability of the rat model of AD presumably by improving the activation of microglia, reducing the expression levels of neuroinflammatory factors IL-1ß, TNF-α, and IL-6, inhibiting the TLR4/NF-κB/NLRP3 neuroinflammation pathway, and decreasing hippocampal deposition of Aß and expression of p-Tau, thereby restoring the hippocampal morphological structure.

Advances in the Role and Mechanisms of Essential Oils and Plant Extracts as Natural Preservatives to Extend the Postharvest Shelf Life of Edible Mushrooms.

China has a large variety of edible mushrooms and ranks first in the world in terms of production and variety. Nevertheless, due to their high moisture content and rapid respiration rate, they experience constant quality deterioration, browning of color, loss of moisture, changes in texture, increases in microbial populations, and loss of nutrition and flavor during postharvest storage. Therefore, this paper reviews the effects of essential oils and plant extracts on the preservation of edible mushrooms and summarizes their mechanisms of action to better understand their effects during the storage of mushrooms. The quality degradation process of edible mushrooms is complex and influenced by internal and external factors. Essential oils and plant extracts are considered environmentally friendly preservation methods for better postharvest quality. This review aims to provide a reference for the development of new green and safe preservation and provides research directions for the postharvest processing and product development of edible mushrooms.

Diterpene promptly executes a non-canonical autophagic cell death in doxorubicin-resistant lung cancer.

16-hydroxycleroda-3,13-dien-15,16-olide (HCD) has antitumor activity reported in numerous types of cancers. However, the efficacy of HCD treatment in non-small-cell lung cancer (NSCLC) cells and doxorubicin-resistant (Dox-R)-NSCLC cells remains to be unraveled. The underlying anti-cancer mechanism of HCD on Dox-R and Dox-sensitive (Dox-S) of A549 cells was also investigated. Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot. A further examination of its anti-cancer efficacy was performed in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation, which showed that HCD could arrest both Dox-S and Dox-R cells at G2/M phase without altering the sub-G1 cycle along with increasing of cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI3K-ClassIII/Beclin-1 signals and upregulated p62/LC3-I/II expressions to further confirm that the cell autophagy of NSCLC cells after being HCD-induced. Morphological observations of mouse lung sections illustrated that fewer cancer cells accumulated close to the trachea while less neoplastic activities were found in HCD orthotopic treated mice without liver, kidney, and spleen toxicity. Lastly, Dox, HCD, and target therapy medicines of EGFR and ALK were nicely docked with EGFR, ALK, and mTOR. Conclusively, HCD was demonstrated the chemotherapeutic potential regardless of Dox-R and Dox-S cells, suggesting natural autophagic inducer HCD provides a promising lead compound for new drug discovery and development of lung cancer therapies.

Optimized dual therapy for treatment-naive patients of Helicobacter pylori infection: A large-scale prospective, multicenter, open-label, randomized controlled study.

BACKGROUND: The efficacy and safety of high-dose amoxicillin (AMX) and proton pump inhibitors (PPI) dual therapy raises much more attention in recent years. Comparative studies among the dual therapies are required to explore more suitable regimens. This study compared the efficacy, adverse events, and patient compliance of three different high-dose dual regimens in treatment-naive patients of Helicobacter pylori (H. pylori) infection. MATERIALS AND METHODS: The study was a prospective, multicenter, open-label, randomized controlled trial, including H. pylori-infected treatment-naive patients at 12 tertiary hospitals in China. The eligible subjects received high-dose AMX and esomeprazole (ESO) dual therapy of different regimens. They were randomly assigned to group A (ESO 20 mg plus AMX 750 mg, Qid for 14 days), group B (ESO 40 mg Bid plus AMX 1 g Tid for 14 days), or group C (ESO 20 mg plus AMX 1 g, Tid for 14 days). The eradication rates, adverse events, and patient compliance of the three groups were compared. RESULTS: Between April 2021 and January 2022, a total of 1080 subjects were screened and 945 were randomized. The eradication rates in groups A, B, and C were 88.6% (95% CI 84.5%-91.9%), 84.4% (95% CI 80.0%-88.3%), and 86.7% (95% CI 82.4%-90.2%; p = .315), respectively, based on intention-to-treat analysis; 90.3% (95% CI 86.4%-93.3%), 85.5% (95% CI 81.1%-89.2%), and 87.8% (95% CI 83.6%-91.2%; p = .197), respectively, according to modified intention-to-treat analysis; and 90.4% (95% CI 86.5%-93.5%), 85.8% (95% CI 81.4%-89.5%), and 88.3% (95% CI 84.1%-91.7%; p = .202) in per-protocol analysis. History of antibiotics use in 2 years reduced eradication effect in group B (ESO 40 mg Bid, AMX 1 g Tid). The modified intention-to-treat eradication rates were 81.4% vs 90.0% among those with or without a history of antibiotics use in group B (p = .031). The adverse event rates were 13.7%, 12.7%, and 12.1% in groups A, B, and C, respectively (p = .834). Patient compliance of the three groups was similar. CONCLUSIONS: Two optimized AMX and PPI dual regimens (ESO 40 mg Bid or 20 mg Tid plus AMX 1 g Tid for 14 days) had similar efficacy, safety and compliance as compared with classical dual regimen (ESO 20 mg plus AMX 750 mg Qid for 14 days) in H. pylori-infected treatment-naive patients.

Factors Associated with the Magnitude Of acUpuncture treatment effectS (FAMOUS): a meta-epidemiological study of acupuncture randomised controlled trials.

OBJECTIVE: To identify factors and assess to what extent they impact the magnitude of the treatment effect of acupuncture therapies across therapeutic areas. DATA SOURCE: Medline, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc, between 2015 and 2019. STUDY SELECTION: The inclusion criteria were trials with a total number of randomised patients larger than 100, at least one patient-important outcome and one of two sets of comparisons. DATA ANALYSIS: The potential independent variables were identified by reviewing relevant literature and consulting with experts. We conducted meta-regression analyses with standardised mean difference (SMD) as effect estimate for the dependent variable. The analyses included univariable meta-regression and multivariable meta-regression using a three-level robust mixed model. RESULTS: 1304 effect estimates from 584 acupuncture randomised controlled trials (RCTs) were analysed. The multivariable analyses contained 15 independent variables . In the multivariable analysis, the following produced larger treatment effects of large magnitude (>0.4): quality of life (difference of adjusted SMDs 0.51, 95% CI 0.24 to 0.77), or pain (0.48, 95% CI 0.27 to 0.69), or function (0.41, 95% CI 0.21 to 0.61) vs major events. The following produced larger treatment effects of moderate magnitude (0.2-0.4): single-centred vs multicentred RCTs (0.38, 95% CI 0.10 to 0.66); penetration acupuncture vs non-penetration types of acupuncture (0.34, 95% CI 0.15 to 0.53); non-pain symptoms vs major events (0.32, 95% CI 0.12 to 0.52). The following produced larger treatment effects of small magnitude (<0.2): high vs low frequency treatment sessions (0.19, 95% CI 0.03 to 0.35); pain vs non-pain symptoms (0.16, 95% CI 0.04 to 0.27); unreported vs reported funding (0.12, 95% CI 0 to 0.25). CONCLUSION: Patients, clinicians and policy-makers should consider penetrating over non-penetrating acupuncture and more frequent treatment sessions when feasible and acceptable. When designing future acupuncture RCTs, trialists should consider factors that impact acupuncture treatment effects.

[Current status and development strategy of ISO/TC 249 standards for Chinese materia medica].

The internationalization of traditional Chinese medicine(TCM) is one of the strategic development objectives in China, which has been incorporated into the national strategy as an important part of the Belt and Road Initiative development strategy. As the basis and prerequisite of TCM development, Chinese materia medica(CMM) has a direct impact on the internationalization of TCM. The International Organization for Standardization(ISO) is a global organization composed of national standardization bodies, and the ISO standards impact the world's economy, trade, communication and cooperation. Based on a brief introduction to ISO/Traditional Chinese Medicine Technical Committee(ISO/TC 249), this study elaborates the necessity of establishing ISO standards for CMM and analyzes the current status and challenges faced by the formulation of international standards for CMM. Finally, this study puts forward the development strategy of international standards for CMM. Specifically, efforts should be made to develop top-level design with international market demands as the guidance and improve the quality of standards to accelerate the transformation of domestic high-quality standards into international standards. Moreover, measures should be taken to give full play to the positive role of enterprises in the formulation of standards, vigorously cultivate compound talents for international standardization of TCM, and constantly strengthen international cooperation. The experience and thinking are of guiding significance for the scientific, efficient and reasonable formulation of high-quality ISO standards for CMM in the future.

[Significance of herbal/botanical monograph in international registration of Chinese medicine].

Herbal/botanical monograph, first emerging abroad, includes the scientific conclusions on safety and effectiveness of herbal medicine/botanical medicine, as it is often compiled by drug regulatory authorities. It is designed to unify the related technologies in this field and evaluation standards for review. Thus, herbal/botanical monograph is vital for the internationalization of Chinese medicine and being inscribed into the herbal/botanical monograph of target country is the first step for drug registration there. At the moment, there are few domestic studies on international herbal/botanical monographs, let alone the importance of the monographs in international registration of Chinese medicine preparations. This study first described international monographs on herbal/botanical medicine, then discussed the similarities and differences between international monographs and Chinese Pharmacopoeia, and finally analyzed the significance and value of the monographs in the international registration of Chinese medicine. On this basis, this study underscored the research on herbal/botanical monographs of key candidate countries for Chinese medicine registration, with a view to enhancing international recognition and laying the foundation for international registration and related policy formulation.

Gut microbiome responses to dietary intervention with hypocholesterolemic vegetable oils.

Hypercholesterolemia is becoming a problem with increasing significance. Dietary vegetable oils may help to improve this condition due to presence of phytonutrients with potentially synergistic cholesterol-lowering effects. The objective of this 8-week double-blinded randomized clinical trial was to investigate the effects of consuming 30 g of two different blended cooking oils, rich in omega-3 alpha-linolenic acid and phytonutrients, or refined olive oil on the intestinal microbiota in 126 volunteers with borderline hypercholesterolemia. Multi-factor analysis of relationships between the gut microbiota composition at various taxonomic ranks and the clinical trial parameters revealed the association between beneficial effects of the dietary intervention on the blood lipid profile with abundance of Clostridia class of the gut microbiota. This microbiota feature was upregulated in the course of the dietary intervention and associated with various plasma markers of metabolic health status, such as Triglycerides, Apolipoprotein B and Total Cholesterol to HDL ratio in a beneficial way. The relative abundance of a single species-Clostridium leptum-highly increased during the dietary intervention in all the three study groups. The oil blend with the highest concentration of omega-3 PUFA is associated with faster and more robust responses of the intestinal microbiota, including elevation of alpha-diversity. Butyrate production is being discussed as a plausible process mediating the observed beneficial influence on the plasma lipid profile. Causal mediation analysis suggested that Clostridium genus rather than the higher rank of the phylogeny-Clostridia class-may be involved in the diet-induced improvements of the blood lipid profile.

Comparison of high-dose dual therapy with bismuth-containing quadruple therapy in Helicobacter pylori-infected treatment-naive patients: An open-label, multicenter, randomized controlled trial.

OBJECTIVE: Bismuth-containing quadruple therapy for Helicobacter pylori (H. pylori) eradication has a relatively high rate of side effects and high cost, thus the option of a high-dose dual therapy with a high eradication rate and fewer adverse events is a consideration. However, studies of dual therapy are still scarce and are mostly single-center studies with limited generalizability. Large-scale, multicenter studies are required. Our study investigated and compared the effectiveness, adverse events, patient compliance, and costs of high-dose dual therapy with those of bismuth-containing quadruple therapy in H. pylori-infected treatment-naive patients in a prospective, multicenter, open-label, randomized controlled trial. METHOD: Treatment-naive patients infected with H. pylori were randomly assigned to receive high-dose dual therapy (esomeprazole 20 mg 4 times daily and amoxicillin 1000 mg 3 times daily, for 14 days) or bismuth-containing quadruple therapy (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, all twice daily for 14 days). The effectiveness, adverse events, patient compliance, and costs of both groups were compared. RESULTS: A total of 700 patients were enrolled. The high-dose dual therapy group (N = 350) achieved eradication rates of 89.4% (intention-to-treat), 90.4% (modified intention-to-treat), and 90.6% (per-protocol), which were similar to rates in the bismuth-containing quadruple therapy group (N = 350), 84.6%, 88.0%, and 88.2%, respectively (p > 0.05). The high-dose dual therapy group had a lower rate of adverse events (12.9% vs. 28.1%, p < 0.001) and lower costs (¥590.2 vs. ¥723.22) compared with the quadruple therapy group, respectively. The compliance of both groups was satisfactory (97.7% high-dose dual vs. 96.8% quadruple, p > 0.05). CONCLUSION: High-dose dual therapy for H. pylori eradication had similar efficacy and compliance, fewer adverse events, and lower costs than bismuth-containing quadruple therapy for treatment-naive patients.

neo-Clerodane Diterpenoids from the Aerial Parts of Scutellaria barbata with Anti-Inflammatory Activity.

The bioactivity-guided isolation on the Scutellaria barbata extract resulted in the purification of four undescribed neo-clerodane diterpenoids, scuttenlines A-D (1-4), alone with 20 known diterpenoids (5-24). The chemical structures of them were elaborated by extensive spectroscopic means, including 1D, 2D-NMR and HR-MS. The anti-inflammatory potential ability of 1-24 was screened in lipopolysaccharide-stimulated mouse RAW 264.7 cells. Scuttenline C (IC50 =1.9 µM) and 18 (IC50 =3.7 µM) exhibited potent activity to inhibit NO production.

PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease.

Alzheimer's disease (AD) and Parkinson's disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3ß (GSK-3ß), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

Bioactivity-guided discovery of quality control markers in rhizomes of Curcuma wenyujin based on spectrum-effect relationship against human lung cancer cells.

BACKGROUND: Due to the diversity of the ingredients, the complexity of the mechanism of action, the uncertainty of the effective ingredients, coupled with the multiple species and multiple growing areas, the quality control (QC) of Traditional Chinese Medicines (TCMs) is challenging. Discovering and identifying effective compounds from the complex extracts of TCMs and then establishing a scientific QC method is the key to the holistic QC of TCMs. PURPOSE: To develop an anti-lung-cancer-guided spectrum-effect relationship approach for the discovery of QC markers of the rhizome of Curcuma wenyujin (WEZ) and establish a bioactive compounds-based holistic QC method. METHODS: The chemical profiling of the volatile oil (WVO) from 42 batches of WEZ collected from different growing areas was performed by GC-MS. The anti-lung cancer activity of different WVO samples was determined by CCK-8 assay against human lung cancer cells (A549). The apoptosis and cell cycle analysis under different concentrations of WVO were detected by flow cytometry. SIMCA-P software was used to perform multivariate statistical analysis on the chemical composition of different WVO samples and to find the different components. Active compounds were screened using a PLSR model of the spectrum-effect relationship. Bioactive compounds-based fingerprint and quantification of the leading bioactive compounds were developed by GC-MS and GC-FID, respectively. RESULTS: Seventy-eight compounds were detected in WVO and 54 were successfully identified. The multivariate statistical analysis uncovered that WVO components and the anti-A549 activity of WVO at the concentration of 60 nl/ml differ greatly according to the origin of the plant. The WVO at the concentration of 60 nl/ml (IC50) increased A549 cells apoptosis significantly with late and early apoptosis of 15.61% and 7.80%, and the number of cells in the G2/M phase were also increased significantly under this concentration. The spectrum-effect relationship analysis revealed that 44 compounds were positively correlated with their activities, and the result was verified by A549 cell viability assay. Sixteen positively correlated compounds were further selected as QC markers according to their relative amount > 0.5% and anticancer activity. Finally, the 16 QC markers-based GC-MS fingerprint was established to holistically control the quality of WEZ, and a GC-FID method was developed for the quantification of leading bioactive compounds, ß-elemene and ß-caryophyllene. CONCLUSION: Based on an anti-lung-cancer-guided spectrum-effect relationship approach, the bioactive compounds-based holistic QC method was successfully developed for WEZ, which could provide a valuable reference for the QC of TCMs.

Anti-nociceptive effect of Portulaca oleracea L. ethanol extracts attenuated zymosan-induced mouse joint inflammation via inhibition of Nrf2 expression.

The aim of this study was to explore the effects of ethanol extracts from Portulaca oleracea L. (ePO) on joint inflammation and to explain the underlying mechanisms. A joint inflammation mouse model was constructed by injecting zymosan, and the Von Frey method was employed and the joint thickness measured. The numbers of leukocytes, neutrophils, and monocytes were counted in the joint cavity and the infiltration of inflammatory cells was assessed by joint histopathological analysis. The mRNA levels of inflammatory cytokines were determined by quantitative RT-PCR and their secretion levels were determined by specific ELISAs. Pre-treatment with ePO inhibited articular mechanical hyperalgesia and edema and ameliorated the recruitment of mononuclear neutrophils and leukocytes. In addition, pre-treatment with ePO improved pathological alternations in the joint tissues by reducing the number of inflammatory cells. Pre-treatment with ePO regulated the nuclear factor erythroid 2-related factor 2 (Nrf2)-related proteins and thereby inhibited oxidative stress. In addition, ePO inhibited NLR family pyrin domain containing 3 (NLRP3) inflammasome-related genes (NLRP3, ASC, pro-caspase-1 and pro-IL-1ß), modulated inflammatory cytokines and the activation of NF-κB. ePO attenuated zymosan-induced joint inflammation by regulating oxidative stress, NLRP3 inflammasome, and NF-κB.

Two Blends of Refined Rice Bran, Flaxseed, and Sesame Seed Oils Affect the Blood Lipid Profile of Chinese Adults with Borderline Hypercholesterolemia to a Similar Extent as Refined Olive Oil.

BACKGROUND: Individual vegetable oils have a characteristic fatty acids (FA) composition and unique phytonutrient profiles, enabling formulation of oil blends that may have health-promoting effects. OBJECTIVE: The primary objective of this study was to investigate effects of 2 oil blends made with refined rice bran, flaxseed, and sesame oils, with distinct monounsaturated to saturated FA, polyunsaturated to saturated FA, and omega-3 (n-3) to omega-6 FA ratios and different phytonutrient concentrations on blood lipid profile, compared with refined olive oil as a control. The secondary outcomes were other markers of cardiometabolic health. METHODS: A parallel-design, randomized controlled trial compared consumption of 30 g of allocated intervention oil per day for a period of 8 wk. The study recruited 143 borderline hypercholesterolemic (LDL cholesterol: 3.06-4.51 mmol/L) Chinese volunteers between 50 and 70 y old and with a BMI (kg/m2) ≤27.5. All outcomes were measured every 2 wk, and the time × treatment interactions and the main effects of treatment and time were analyzed using an intention-to-treat approach. RESULTS: Compared with baseline (week 0), there were significant reductions during the post-intervention time points in serum total cholesterol (-3.47%; P < 0.0001), LDL cholesterol (-4.16%; P < 0.0001), triglycerides (-10.3%; P < 0.0001), apoB (-3.93%; P < 0.0001), total to HDL-cholesterol (-3.44%; P < 0.0001) and apoB to apoA1 (-3.99%; P < 0.0001) ratios, systolic and diastolic blood pressures (-3.32% and -3.16%, respectively; both P < 0.0001), and serum glucose (-1.51%; P < 0.05) and a small but significant increase in body weight (+0.7%; P < 0.001) for all 3 intervention oils but no effects of intervention on HDL-cholesterol or apoA1 concentration. No significant effects of treatment or time × treatment interactions were found. CONCLUSIONS: Using blended vegetable oils that are extensively consumed in Asia, this study found that specific oil blends can improve blood lipid profile and other cardiometabolic parameters, to a similar extent as refined olive oil, in Chinese adults with borderline hypercholesterolemia. This trial is registered at www.clinicaltrials.gov as NCT03964857.

Enantioselective total syntheses of (+)-stemofoline and three congeners based on a biogenetic hypothesis.

The powerful insecticidal and multi-drug-resistance-reversing activities displayed by the stemofoline group of alkaloids render them promising lead structures for further development as commercial agents in agriculture and medicine. However, concise, enantioselective total syntheses of stemofoline alkaloids remain a formidable challenge due to their structural complexity. We disclose herein the enantioselective total syntheses of four stemofoline alkaloids, including (+)-stemofoline, (+)-isostemofoline, (+)-stemoburkilline, and (+)-(11S,12R)-dihydrostemofoline, in just 19 steps. Our strategy relies on a biogenetic hypothesis, which postulates that stemoburkilline and dihydrostemofolines are biogenetic precursors of stemofoline and isostemofoline. Other highlights of our approach are the use of Horner-Wadsworth-Emmons reaction to connect the two segments of the molecule, an improved protocol allowing gram-scale access to the tetracyclic cage-type core, and a Cu-catalyzed direct and versatile nucleophilic alkylation reaction on an anti-Bredt iminium ion. The synthetic techniques that we developed could also be extended to the preparation of other Stemona alkaloids.