[Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(â ¢): classification of granule dissolving behaviors].

Solubility is an important sensory quality attribute of traditional Chinese medicine(TCM) granules. In this paper, 90 batches of granules(30 batches of TCM formula granules, 30 batches of Chinese patent medicine granules and 30 batches of Japanese Kampo granules) were used as the research objects. The turbidity sensor was used to characterize the turbidity curve of the granule dissolution process. The classification system of granule dissolution behaviors was constructed from three dimensions: dissolution degree, equilibrium time, and dissolution mechanism. According to the equilibrium time, the granule dissolution rates were divided into three categories : faster(<100 s), general(101-300 s) and slow(>301 s). According to the turbidity curve profile, the granule dissolution mechanisms were classified into dissolution-controlled type(α-type), dispersion-controlled type(ß-type), and dispersion-controlled type followed by dissolution-controlled type(γ-type). The proportion of TCM formula granules, Chinese patent medicine granules and Japanese Kampo granules with complete dissolution or slight turbidity at the end of dissolution was 46.7%, 96.7%, and 10.0%. The proportion of TCM formula granules, Chinese patent medicine granules, and Japanese Kampo granules with faster dissolution rates(<100 s) was 23.3%, 26.7%, and 40.0%. The average dissolution rate of Japanese Kampo granules was faster than that of TCM formula granules, and it was slightly faster than the average dissolution rate of Chinese patent medicine granules. The dissolution mechanism of Chinese patent medicine granules was mainly α-type, while that of Japanese Kampo granules was mainly ß-type, and the three types of dissolution mechanisms of TCM formula granules accounted for a relatively average. The purpose of improving the solubility and dispersion of granules can be achieved by combining the comprehensive application of various functional excipients with the small dosage of Japanese Kampo granules and the wide addition scope of excipients. In the process of transforming TCM compound prescriptions into formulas, there is still much room for innovation in formula excipients and process optimization.

Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study.

Background: Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR). Methods: A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy. Results: The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP). Conclusion: The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

Synergistic adsorption and photocatalysis reduction of uranium by UiO-66 (Ce)-CdS/PEI-modified chitosan composite sponge.

Uranium is a critical element of the nuclear industry, and while extracting it from seawater is considered the most promising way to meet the growing demand for uranium, there are still some problems that still need to be solved. This work designed a UiO-66(Ce)-CdS/PEI-modified chitosan composite sponge (USPS) with an adsorption-photocatalytic synergistic effect to extract uranium efficiently. On the one hand, the drawback that the powder material is difficult to be recycled is solved. On the other hand, the uranium extraction capacity of the substrate sponge is improved. Compared with the unmodified PCS sponge, the uranium extraction capacity of the USPS-4 composite sponge is 1.63 fold higher than that of the PCS sponge. In addition, the USPS-4 composite sponge exhibits excellent selectivity and regenerability. The mechanism of uranium extraction can be summarized as the coordination chelation of uranium with active functional groups in the adsorption process and the reduction of hexavalent uranium by photogenerated electrons in the photocatalytic process. This study provides a new strategy for designing and preparing a novel material with high uranium extraction performance, easy separation, and recovery.

A new benzofuran compound from the resinous exudates of Commiphora myrrha.

A new benzofuran derivative, identified as myrrhain A (1), was isolated from the resinous exudates of Commiphora myrrha, together with the four known compounds: commipharane (2), myrrhterpeniod (3), myrrhone (4), and 9-methoxymyrrhone (5). All structures were elucidated by NMR and MS analyses. DPPH assay of compounds 1-5 revealed for the first time that all of them possess moderate antioxidative activity.

A New 1,3-Benzodioxole Compound from Hypecoum erectum and Its Antioxidant Activity.

The purpose of this study was to identify the chemical components in aerial parts of Hypecoum erectum. A new 1,3-benzodioxole derivative, identified as Hypecoumic acid (1), was isolated, together with the three known compounds: protopine (2), coptisine (3), and cryptopine (4). Their structures were identified based on extensive spectroscopic experiments, including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectra (HR-ESI-MS), as well as comparison with those reported in the literature. Meanwhile, the in vitro antioxidative activity of all compounds was determined using a DPPH-scavenging assay, and compound 1 (IC50 = 86.3 ± 0.2 µM) was shown to have moderate antioxidative activity.

Lactate Dehydrogenase-Inhibitors Isolated from Ethyl Acetate Extract of Selaginella doederleinii by Using a Rapid Screening Method with Enzyme-Immobilized Magnetic Nanoparticles.

BACKGROUND: Lactate dehydrogenase (LDH) is one of the important enzyme systems for glycolysis and gluconeogenesis. It can catalyze the reduction and oxidation reaction between propionic acid and L-lactic acid, which is usually overexpressed in cancer cells. Therefore, inhibiting the activity of LDH is a promising way for the treatment of cancer. In this study, an effective method based on ligand fishing and ultra performance liquid chromatography-mass spectrum (UPLC-MS) was established to screen and identify active ingredients from Selaginella doederleinii with potential inhibitory activity for LDH. METHODS: Firstly, LDH was immobilized on the magnetic nanoparticles (MNPs), three immobilization parameters including LDH concentration, immobilization time and pH were optimized by single factor and response surface methodology for maximum (max) immobilization yield. Then, a mixed model of galloflavin and chlorogenic acid (inhibitors and non-inhibitors of LDH) was used to verify the specificity of immobilized LDH ligand fishing, and the conditions of ligand fishing were further optimized. Finally, combined with UPLC-MS, immobilized LDH was used to simultaneously screen and identify potential LDH inhibitors from the ethyl acetate extract of Selaginella doederleinii. RESULTS: The prepared fishing material was comprehensively characterized by scanning electron microscopy (SEM), transmission electron microscope (TEM), X-ray diffraction (XRD) and fourier transform infrared spectrometer (FT-IR). The optimal immobilization conditions were obtained as LDH concentration of 0.7 mg/mL, pH value of 4.5, and immobilization time of 3.5 h. Under these conditions, the max immobilization yield was (3.79 ± 0.08) × 103 U/g. The specificity analysis showed that immobilized LDH could recognize and capture ligands, and the optimal ligand fishing conditions included that the incubation time was 30 min, the elution time was 20 min, and the concentration of methanol as eluent was 80%. Finally, two LDH inhibitors, amentoflavone and robustaflavone, were screened by immobilized LDH from the ethyl acetate extract of Selaginella doederleinii. CONCLUSIONS: The study provided a meaningful evidence for discovering the bioactive constituents in ethyl acetate extract of Selaginella doederleinii related to cancer treatment, and this ligand fishing method was feasible for screening enzyme inhibitors from similar complex mixtures.

A high-flux antibacterial poly(amidoxime)-polyacrylonitrile blend membrane for highly efficient uranium extraction from seawater.

Uranium is an important fuel for nuclear power, with 4.5 billion tons of it stored in the oceans, 1,000 times more than on land. Polymer membrane materials are widely used in the marine resources fields, due to their convenient collection, good separation and can work continuously. Herein, a poly(amidoxime)-polyacrylonitrile blend membrane (PCP) with high flux, excellent antibacterial properties and uranium adsorption performance has been prepared by using the phase inversion method, and the prepared membrane was used for highly efficient uranium extraction from seawater. In static adsorption experiments, the PCP membrane reached adsorption equilibrium after 48 h, and the adsorption capacity was 303.89 mg/g (C0 =50 mg/L). In dynamic adsorption experiments, it was found that the lower flow rate and higher number of membrane layers were favorable for dynamic adsorption. In addition, the water flux of the PCP membrane was 7.4 times higher than that of the PAN membrane. The adsorption mechanism can be attributed to the chelation between amino and hydroxyl groups in CS, amidoxime group in poly(amidoxime) and uranyl ions. The simple preparation process coupled with the excellent adsorption performance indicated that the PCP membrane would be a promising material for the uranium extraction from seawater.

The anti-diabetic activity of polyphenols-rich vinegar extract in mice via regulating gut microbiota and liver inflammation.

Polyphenols in vinegar are benefit to human health. The purpose of this research was to identify the polyphenols-rich vinegar extract (VE) and evaluate the anti-diabetic mechanisms in vivo. The results showed that 29 polyphenols were identified by UPLC-Q/Trap-MS/MS analysis. 4-Hydroxybenzoic acid, ferulic acid, and ethyl ferulate were the main polyphenols. In addition, VE relieved the symptoms of type 2 diabetes mellitus (T2DM) by down-regulating blood glucose and lipemia. VE reduced inflammation by inhibiting TLR4/NF-κB signaling pathway. Furthermore, VE treatment restored gut microbiota dysbiosis (upregulating Bacteroidetes, Lactobacillus, Bifidobacterium, and Bacteroides and downregulating Firmicutes, Proteobacteria, and Enterorhabdus abundances), and increased short chain fatty acids contents in diabetic mice, which participated in anti-diabetic effect of VE by correlation analysis. These findings suggest that VE may be a candidate for T2DM intervention by regulating gut microbiota and inflammation.

Traditional Chinese medicines differentially modulate the gut microbiota based on their nature (Yao-Xing).

BACKGROUND: Property theory is a unique principle guiding traditional Chinese medicine (TCM) that classifies various TCMs into four natures (hot, warm, cool, and cold) to reflect their medical actions on the human body. Despite successful application for thousands of years, characterizing the nature of medical TCMs by modern physiological indicators remains a challenge. PURPOSE: In this study, we investigated the potential relationship between the nature of TCMs and their modulation of the gut microbiota. STUDY DESIGN: We selected twelve TCMs with hot, warm, cool, or cold natures that possess antidiarrheal effects. Their aqueous extracts were orally administered to C57BL/6 mice at a clinical dose for 4 weeks. The gut microbiota was measured by 16S rRNA-based metagenomics, and the correlation between microbial composition/function and TCM nature was analyzed. RESULTS: Antidiarrheal TCMs with different natures showed distinct impacts on the gut microbiota. Hot-natured TCMs had no influence on the gut microbiota, warm-natured TCMs had a moderate influence, cool-natured TCMs had a strong influence, and cold-natured TCMs substantially changed the structure of the gut microbial community. The abundance of Anaerotruncus, Tyzzerella and Ruminiclostridium steadily increased, while that of Ruminococcaceae_UCG-010, Parasutterella and Bifidobacterium continuously decreased as the herbal nature turned from cold to hot. Microbiome functional prediction for Cluster of Orthologous Groups (COG) of proteins and Kyoto Encyclopedia of Genes and Genomes (KEGG) categories showed that colder TCMs imposed a stronger influence on microbial functional repertoires. Specifically, the abundance of ABC transporters, key bacterial proteins involved in nutrient absorption and drug resistance, was gradually decreased by colder TCMs. CONCLUSION: Our results demonstrated that the nature of TCMs could be reflected by their modulation of gut microbes. Cold TCMs may exert their antidiarrheal effects, at least partially, by modulating the gut microbiota, while hot TCMs may alleviate dysentery in other ways.

A dry powder inhalable formulation of salvianolic acids for the treatment of pulmonary fibrosis: safety, lung deposition, and pharmacokinetic study.

Salvianolic acids (SAL), the main bioactive component extracted from Salvia miltiorrhiza, is a natural product with a reported anti-pulmonary fibrosis (PF) effect. SAL is commonly administrated orally; however, it has a low oral bioavailability (less than 5%). The objective of this work was to develop a new dry powder inhalable formulation intended to facilitate the access of SAL to the target place. We prepared the new SAL powder formulation containing L-arginine and 2% of lecithin using the ball milling technique. L-arginine was used to regulate the strong acidity of the SAL solution, and lecithin was added to disperse the powder and improve the flowability. The resulting powder had a content in salvianolic acid B (SALB, the main active principle of SAL) of 66.67%, a particle size of less than 5 µm and a good flowability. In vivo fluorescence imaging showed that the powder could be successfully aerosolized and delivered to the lung. The acute lung irritation study proved that the presence of L-arginine improved the biocompatibility of the powder. Finally, according to the pharmacokinetic study, the new SAL powder formulation was found to significantly increase drug concentration in the lung and the bioavailability. In conclusion, the new dry powder inhalable formulation of SAL developed in this study could be a strategy to enhance the performance of SAL at the lung level. Graphical abstract.

The gut microbiota confers the lipid-lowering effect of bitter melon (Momordica charantia L.) In high-fat diet (HFD)-Induced hyperlipidemic mice.

The bitter melon (Momordica charantia) is a medical food with well-documented hypoglycemic and anti-hyperlipidemic activities. Previous studies showed that the M. charantia fruit (MC) could modulate the gut microbiota, but whether this modulation is essential for MC's pharmacological effects is largely unknown. Here, we assessed the causality of gut microbes in MC-elicited anti-hyperlipidemic effects for the first time. Oral administration of MC significantly prevented hyperlipidemia, but this amelioration substantially diminished when co-treated with antibiotics. Transplantation of gut flora from MC-treated donor mice also significantly decreased serum lipids. The microbiological analysis revealed that MC moderately increased diversity and shifted the overall structure of gut microbiota. It selectively enhanced the relative abundance of short-chain fatty acid (SCFAs)-producing genera and increased fecal SCFAs content. These results demonstrate that M. charantia fruit (MC) may exert an anti-hyperlipidemic effect through modulating gut microbes and increasing SCFAs production.

[Evaluation and classification of dissolution behavior and capability of Chinese medicine granules based on an inline turbidity sensor].

In this paper, the inline turbidity sensor technology was used to quantify the turbidity of the solution during the dissolution of Chinese medicine granules. The probe measurement position and the magnetic stirring speed were optimized. As a result, the stirring speed was 400 r·min~(-1), and the probe position was at 1/4 of the diameter of the beaker. The measurement results were accurate and reliable. Totally 105 batches of commercially available Chinese medicine granules were collected and dissolved according to the requirements of the Chinese Pharmacopoeia. At the time point of 5 min, 57 batches of granules were completely dissolved, and the corresponding turbidity values ranged between 0-70 FTU; 32 batches of granules showed a slight turbidity, and the corresponding turbidity values ranged between 70-350 FTU; 14 batches of granule solution were turbid, and the corresponding turbidity values ranged between 350-2 000 FTU; two batches of granule solution were heavily turbid, and the corresponding turbidity values were >2 000 FTU. Among the above results, the number of batches in line with the pharmacopoeia dissolution requirement was 84.76%, and the dissolution of some granules still needed to be improved. The turbidity sensor recorded the change curve of turbidity value over time(solubility behavior curve). The degree of important of disintegration and dissolution during the dissolution process showed disintegration > dissolution, disintegration≈dissolution, disintegration < dissolution. The dissolution behavior of the granules can be classified into three categories. The analysis of the mechanism in the process of granule solubility provides a basis for product process improvement.

The pandanus tectorius fruit extract (PTF) modulates the gut microbiota and exerts anti-hyperlipidaemic effects.

BACKGROUND: The gut microbiota plays a key role in the maintenance of human health and mediates the beneficial effects of natural products including polyphenols. Previous studies have demonstrated that the polyphenol-rich Pandanus tectorius fruit extract (PTF) was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia, and polyphenols can significantly change the structure of the gut microbiota. PURPOSE: In this study, we assessed whether the modulation of the gut microbiota plays a key role in the PTF-induced anti-hyperlipidaemic effects. METHODS: Male C57BL/6 J mice were induced with hyperlipidaemia by consuming a high-fat diet (HFD) for 4 weeks. Then, the mice were orally administered PTF, antibiotics (ampicillin+ norfloxacin), PTF+antibiotics or vehicle for another 6 weeks. Body weights and 24-h food intake were assessed weekly. At the end of the experiment, fresh stools were collected for 16S RNA pyrosequencing, and blood and liver and fat tissue were collected for pharmacological analysis. RESULTS: PTF was effective in ameliorating high-fat diet (HFD)-induced hyperlipidaemia and significantly changed the structure of the gut microbiota. However, the anti-hyperlipidaemic effect of PTF was not influenced by the co-treatment with antibiotics (ampicillin+norfloxacin). A microbiological analysis of the gut microbiotas revealed that PTF selectively enhanced the relative abundance of Lactobacillus and decreased the relative abundance of Bacteroides and Alistipes. A correlation analysis between biochemical indexes and individual taxon showed that Lactobacillus was negatively associated with serum lipids and glucose while Bacteroides and Alistipes were positively associated with serum lipids and glucose. The modulatory effect of PTF on Lactobacillus, Bacteroides and Alistipes was not disturbed by the administration of antibiotics. CONCLUSION: These results demonstrated that the polyphenol-rich PTF as a unique gut microbiota modulating agent and highlighted the richness of Lactobacillus and the decreased abundance of Bacteroides and Alistipes as an effective indicator of the therapeutic effect of medicinal foods on hyperlipidaemia.

Clinical practice of Chinese medicine navel therapy for chronic diarrhea: A literature review.

Chronic diarrhea is one of the most common complaints in clinical practice for both adults and children. The purpose of this study was to assess the commonly used Chinese herbal medicine navel therapy for the treatment of chronic diarrhea (traditional Chinese medicine syndrome of spleen deficiency). The literature search was up to June 2018. Four types of studies (clinical trials, case series, case reports, and experts' experience) researched on Chinese medicine navel therapy used alone or combined with other therapies for the treatment of chronic diarrhea all included. Information on prescriptions, effectiveness, and safety of intervention was collected. Traditional Chinese Medicine Inheritance Support System V2.5 was used to do data analysis. We included 416 studies. All these studies carried out in 194 cities of China. We obtained the most commonly used single herbs, herbal medicine combination, and Chinese patent medicine for both adults and children. The top 3 single herbs were Caryophylli Flos (Dingxiang), Cinnamomi Cortex (Rougui), and Euodiae Fructus (Wuzhuyu). The most frequently used Chinese patent medicines were Ding Gui Infantile Navel Paste and Huoxiang Zhengqi Liquid. The effectiveness assessment was based on clinical trials, but we did not perform a meta-analysis because of different study design and unsatisfactory methodological quality. No serious adverse reaction happened in original studies. The application of Chinese medicine navel therapy could be one of the ideal treatments for chronic diarrhea in the future, especially for children. However, high-quality studies are very needed to provide clear evidence.

The aqueous extract of Phellinus igniarius (SH) ameliorates dextran sodium sulfate-induced colitis in C57BL/6 mice.

Phellinus igniarius, which is called Sanghuang in Chinese, is a fungal herb widely used in Traditional Chinese Medicine to treat stomachache, inflammation and tumors. Recent studies have demonstrated the antitumor, anti-diabetic, anti-inflammatory and immunity-modulating activities of P. igniarius. In the present study, we investigated that ameliorating effect of the aqueous extract of P. igniarius fruiting body (SH) on dextran sodium sulfate (DSS)-induced colitis in C57BL/6 mice. Treatment with SH (250 and 400 mg/kg) for 8 weeks effectively alleviated the pathological indicators of colitis such as bodyweight reduction, disease activity index score, shortening of colon length and abnormal colon histology. The plasma levels of lipopolysaccharide (LPS) and inflammatory factors such as interleukin-6 (IL-6), IL-1ß and tumor necrosis factor (TNF)-α were all significantly reduced. Supplementation of SH (10 mg/L) also inhibited LPS-elicited IL-1ß production by RAW264.7 macrophages. Real-time PCR and western blot showed that treatment with SH significantly inhibited the phosphorylation of nuclear factor kappa B inhibitor alpha (IκBα) and decreased the expression of IL-6/IL-1ß-maturation genes such as apoptosis-associated speck-like protein (ASC3) and caspase-1 in the colon of DSS-induced colitis mice. These results suggest that SH is adequate for the treatment of colitis. Inhibiting the expression and release of inflammatory factors may participate in the colitis-ameliorating effect of SH.