Quality Evaluation of Polygonatum cyrtonema Hua Based on UPLC-Q-Exactive Orbitrap MS and Electronic Sensory Techniques with Different Numbers of Steaming Cycles.

In this study, electronic sensory techniques were employed to comprehensively evaluate the organoleptic quality, chemical composition and content change rules for Polygonatum cyrtonema Hua (PCH) during the steaming process. The results were subjected to hierarchical cluster analysis (HCA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). These analyses revealed, from a sensory product perspective, overall differences in colour, odour and taste among the samples of PCH with different numbers of steaming cycles. Using the UPLC-Q-Exactive Orbitrap MS technique, 64 chemical components, including polysaccharides, organic acids, saponins and amino acids were detected in PCH before and after steaming. The sensory traits were then correlated with the chemical composition. From the perspectives of sensory traits, chemical composition, and multi-component index content, it was preliminarily deduced that carrying out five cycles of steaming and sun-drying was optimal, providing evidence for the quality evaluation of PCH during the steaming process.

Full-length transcriptome profiling of Acanthopanax gracilistylus provides new insight into the kaurenoic acid biosynthesis pathway.

Acanthopanax gracilistylus is a deciduous plant in the family Araliaceae, which is commonly used in Chinese herbal medicine, as the root bark has functions of nourishing the liver and kidneys, removing dampness and expelling wind, and strengthening the bones and tendons. Kaurenoic acid (KA) is the main effective substance in the root bark of A. gracilistylus with strong anti-inflammatory effects. To elucidate the KA biosynthesis pathway, second-generation (DNA nanoball) and third-generation (Pacific Biosciences) sequencing were performed to analyze the transcriptomes of the A. gracilistylus leaves, roots, and stems. Among the total 505,880 isoforms, 408,954 were annotated by seven major databases. Sixty isoforms with complete open reading frames encoding 11 key enzymes involved in the KA biosynthesis pathway were identified. Correlation analysis between isoform expression and KA content identified a total of eight key genes. Six key enzyme genes involved in KA biosynthesis were validated by real-time quantitative polymerase chain reaction. Based on the sequence analysis, the spatial structure of ent-kaurene oxidase was modeled, which plays roles in the three continuous oxidations steps of KA biosynthesis. This study greatly enriches the transcriptome data of A. gracilistylus and facilitates further analysis of the function and regulation mechanism of key enzymes in the KA biosynthesis pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01436-7.

Efficacy of Forsythia suspensa (Thunb.) Vahl on mouse and rat models of inflammation-related diseases: a meta-analysis.

Objective: To evaluate the efficacy of the fruits of the medicinal plant Forsythia suspensa (Thunb.) Vahl (FS), in treating inflammation-associated diseases through a meta-analysis of animal models, and also probe deeply into the signaling pathways underlying the progression of inflammation. Materials and methods: All data analyses were performed using Review Manager 5.3 and the results are presented as flow diagrams, risk-of-bias summaries, forest plots, and funnel plots. Summary estimates were calculated using a random- or fixed-effect model, depending on the value of I2. Results: Of the 710 records identified in the initial search, 11 were selected for the final meta-analysis. Each study extracted data from the model and treatment groups for analysis, and the results showed that FS alleviated the inflammatory cytokine levels in serum; oxidant indicator: reactive oxygen species; enzymes of liver function; endotoxin and regulatory cells in blood; and improved the antioxidant enzyme superoxide dismutase. Conclusion: FS effectively reversed the change in acute or chronic inflammation indicators in animal models, and the regulation of multiple channel proteins in inflammatory signaling pathways suggests that FS is a good potential drug for inflammatory disease drug therapy.

Phillyrin: an adipose triglyceride lipase inhibitor supported by molecular docking, dynamics simulation, and pharmacological validation.

CONTEXT: Adipose triglyceride lipase (ATGL), a key enzyme responsible for lipolysis, catalyzes the first step of lipolysis and converts triglycerides to diacylglycerols and free fatty acids (FFA). Our previous work suggested that phillyrin treatment improves insulin resistance in HFD-fed mice, which was associated with ATGL inhibition. In this study, using docking simulation, we explored the binding pose of phillyrin and atglistatin (a mouse ATGL inhibitor) to ATGL in mouse. From the docking results, the interactions with Ser47 and Asp166 were speculated to have caused phillyrin to inhibit ATGL in mice. Further, molecular dynamics simulation of 100 ns and MM-GBSA were conducted for the protein-ligand complex, which indicated that the system was stable and that phillyrin displayed a better affinity to ATGL than did atglistatin throughout the simulation period. Moreover, the results of pharmacological validation were consistent with those of the in silico simulations. In summary, our study illustrates the potential of molecular docking to accurately predict the binding protein produced by AlphaFold and suggests that phillyrin is a potential small molecule that targets and inhibits ATGL enzymatic activity. METHODS: The ATGL-predicted protein structure, verified by PROCHECK, was determined using AlphaFold. Molecular docking, molecular dynamics simulation, and prime molecular mechanic-generalized born surface area were performed using LigPrep, Desmond, and prime MM-GBSA modules of Schrödinger software release 2021-2, respectively. For pharmacological validation, immunoblotting was performed to assess ATGL protein expression. The fluorescence intensity and glycerol concentration were quantified to evaluate the efficiency of phillyrin in inhibiting ATGL.

An insight review on the neuropharmacological effects, mechanisms of action, pharmacokinetics and toxicity of mitragynine.

Mitragynine is one of the main psychoactive alkaloids in Mitragyna speciosa Korth. (kratom). It has opium-like effects by acting on µ-, δ-, and κ-opioid receptors in the brain. The compound also interacts with other receptors, such as adrenergic and serotonergic receptors and neuronal Ca2+ channels in the central nervous system to have its neuropharmacological effects. Mitragynine has the potential to treat diseases related to neurodegeneration such as Alzheimer's disease and Parkinson's disease, as its modulation on the opioid receptors has been reported extensively. This review aimed to provide an up-to-date and critical overview on the neuropharmacological effects, mechanisms of action, pharmacokinetics and safety of mitragynine as a prospective psychotropic agent. Its multiple neuropharmacological effects on the brain include antinociceptive, anti-inflammatory, antidepressant, sedative, stimulant, cognitive, and anxiolytic activities. The potential of mitragynine to manage opioid withdrawal symptoms related to opioid dependence, its pharmacokinetics and toxic effects were also discussed. The interaction of mitragynine with various receptors in the brain produce diverse neuropharmacological effects, which have beneficial properties in neurological disorders. However, further studies need to be carried out on mitragynine to uncover its complex mechanisms of action, pharmacokinetics, pharmacodynamic profiles, addictive potential, and safe dosage to prevent harmful side effects.

Protective effects of Pudilan Tablets against osteoarthritis in mice induced by monosodium iodoacetate.

Osteoarthritis (OA) is a complicated disorder that is the most prevalent chronic degenerative joint disease nowadays. Pudilan Tablets (PDL) is a prominent traditional Chinese medicine formula used in clinical settings to treat chronic inflammatory illnesses. However, there is currently minimal fundamental research on PDL in the therapy of joint diseases. As a result, this study looked at the anti-inflammatory and anti-OA properties of PDL in vitro and in vivo, as well as the mechanism of PDL in the treatment of OA. We investigated the anti-OA properties of PDL in OA mice that were generated by monosodium iodoacetate (MIA). All animals were administered PDL (2 g/kg or 4 g/kg) or the positive control drug, indomethacin (150 mg/kg), once daily for a total of 28 days starting on the day of MIA injection. The CCK-8 assay was used to test the vitality of PDL-treated RAW264.7 cells in vitro. RAW264.7 cells that had been activated with lipopolysaccharide (LPS) were used to assess the anti-inflammatory properties of PDL. In the MIA-induced OA model mice, PDL reduced pain, decreased OA-induced cartilage damages and degradation, decreased production of pro-inflammatory cytokines in serum, and suppressed IL-1ß, IL-6, and TNF-α mRNA expression levels in tibiofemoral joint. In RAW264.7 cells, PDL treatment prevented LPS-induced activation of the ERK/Akt signaling pathway and significantly decreased the levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α. In conclusion, these results suggest that PDL is involved in combating the development and progression of OA, exerts a powerful anti-inflammatory effect on the knee joint, and may be a promising candidate for the treatment of OA.

Effective separation of protein from Polygonatum cyrtonema crude polysaccharide utilizing ionic liquid tetrabutylammonium bromide.

Extraction of plant polysaccharides often results in a large amount of proteins, which is hard to eliminate from the crude extract, and conventional approaches for deproteinization are time-consuming and often involve hazardous organic solvents. In this study, ionic liquid tetrabutylammonium bromide (TBABr) was used to create an ionic liquid aqueous two-phase system (ILATPS) for the separation of the polysaccharide (PcP) and protein extracted from the rhizome of Polygonatum cyrtonema. Bovine serum albumin (BSA) was first applied to assess the feasibility of the ILATPS, and MgSO4 was determined to be the most suitable inorganic salt. By adopting the Taguchi experiment with an L9 (3^4) orthogonal array, it was found that the best condition for the efficient separation of crude PcP was at 25°C, with 1.5 g of TBABr, 15 mg of PcP, and 2.0 g of MgSO4, with the extraction efficiency for the protein and polysaccharide as 98.6% and 93.5%, respectively. The purified PcP was homogeneous, and its weight average molecular weight (Mw) was 7,554 Da. Monosaccharide composition analysis indicated the PcP comprised mannose, galactose, glucose, galacturonic acid, arabinose, and rhamnose at a molar ratio of 33:13:8:3.5:2:1. This approach offers a practical tactic to purify polysaccharides of plant origin.

Phillyrin restores metabolic disorders in mice fed with high-fat diet through inhibition of interleukin-6-mediated basal lipolysis.

The function of white adipose tissue as an energy reservoir is impaired in obesity, leading to lipid spillover and ectopic lipid deposition. Adipose tissue inflammation can reduce the efficacy of lipid storage in adipocytes by augmenting basal lipolysis through producing interleukin-6 (IL-6). Therefore, pharmacological compounds targeting adipose tissue inflammation or IL-6 signaling might have the potential to combat obesity. This study aims to investigate the impact of Phillyrin, which is frequently used for treating respiratory infections in clinics in China, on obesity-related metabolic dysfunctions. Firstly, a mouse model of diet-induced obesity is used to assess the pharmacological applications of Phillyrin on obesity in vivo. Secondly, ex vivo culture of adipose tissue explants is utilized to investigate actions of Phillyrin on IL-6-linked basal lipolysis. Thirdly, a mouse model of IL-6 injection into visceral adipose tissue is explored to confirm the anti-basal lipolytic effect of Phillyrin against IL-6 in vivo. The results show that Phillyrin treatment reduces circulating level of glycerol, decreases hepatic steatosis and improves insulin sensitivity in obese mice. Meanwhile, Phillyrin attenuates obesity-related inflammation and IL-6 production in adipose tissue in obese mice. Furthermore, Phillyrin treatment results in resistance to IL-6-induced basal lipolysis in adipose tissue through suppressing expression of adipose triglyceride lipase (ATGL) both in vivo and in vitro. Collectively, these findings suggest that Phillyrin can restrain lipid efflux from inflamed adipose tissue in obesity by inhibiting IL-6-initiated basal lipolysis and ATGL expression, and thus is a potential candidate in the treatment of obesity-associated complications.

Comparison of the Antioxidant Activities and Polysaccharide Characterization of Fresh and Dry Dendrobium officinale Kimura et Migo.

It is generally believed that fresh Dendrobium officinale (FDO) has more significant pharmacological activity than dried Dendrobium officinale (DDO); however, the difference has not been clearly shown. Our study compared their antioxidant properties both in vitro and in vivo, and the molecular weight arrangement and monosaccharide composition of the fresh Dendrobium officinale polysaccharides (FDOPs) and the dried Dendrobium officinale polysaccharides (DDOPs) were analyzed by HPLC-GPC and GC-MS. The results showed that the FDO and its polysaccharides had more significant effects on scavenging DPPH, ABTS, and hydroxyl radicals than the DDO. In addition, both the FDO and DDO significantly reduced lipid peroxidation levels and increased the SOD, T-AOC, CAT, and GSH levels in mice with acute liver damage caused by CCl4, while the FDO and its polysaccharides were more effective. Histopathological analysis further verified the protective effect of the Dendrobium polysaccharides on CCl4-induced liver injury. The determination of the polysaccharides revealed that the polysaccharide and mannose contents of the FDO were significantly higher than their dried counterparts, and the homogeneous arrangement of the polysaccharides in the FDO was degraded into three polysaccharide fragments of different molecular weights in the DDO. Overall, our data identified differences in the antioxidant activities of the FDO and DDO, as well as the reasons for these differences.

A Comprehensive Review with Updated Future Perspectives on the Ethnomedicinal and Pharmacological Aspects of Moringa oleifera.

Moringa oleifera is an ancient remedy plant, known as the miraculous plant due to its many prominent uses and significant health benefits. It is a nutrient-rich plant, with exceptional bioactive compounds, such as polyphenols that possess several medicinal properties. Many significant studies have been carried out to evaluate the ethnomedicinal and pharmacological properties of M. oleifera in various applications. Therefore, this comprehensive review compiles and summarizes important findings from recent studies on the potential properties of different parts of M. oleifera. The pharmacological properties of M. oleifera have been studied for various potential biological properties, such as cardio-protective, anti-oxidative, antiviral, antibacterial, anti-diabetic and anti-carcinogenic effects. Therefore, the potential of this plant is even more anticipated. This review also highlights the safety and toxicity effects of M. oleifera treatment at various doses, including in vitro, in vivo and clinical trials from human studies.

Efficient Separation of Proteins and Polysaccharides from Dendrobium huoshanense Using Aqueous Two-Phase System with Ionic Liquids.

By applying the hydrophilic ionic liquid, 1-butyl-3-methylimidazolium chloride ([C4mim]Cl), and inorganic salts (K3PO4), an ionic liquid aqueous two-phase system (ILATPS) was established for the separation of Dendrobium huoshanense polysaccharides (DhPs) and proteins. The effects of inorganic salt concentration, IL quantity, crude DhPs concentration, pH value and temperature were studied to achieve the optimal condition. With the best combination of ILATPS (1.75 g K3PO4, 1.25 g [C4mim]Cl, 10 mg crude DhPs and 5.0 mL ddH2O at pH 7.0 under 25 °C), the extraction efficiency rates for DhPs and proteins were 93.4% and 90.2%, respectively. The processed DhPs retrieved from the lower salt-rich phase comprised mannose, glucose, galactose, arabinose, and galacturonic acid with a molar ratio of 185:71:1.5:1:1 and the molecular weight was 2.14 × 105 Da. This approach is fast, simple and environmentally friendly. It provides a new insight into purifying functional polysaccharides of plant origin.

Review on the Pharmacological Properties of Phillyrin.

Phillyrin is an effective lignan glycoside extracted from a traditional Chinese medicine Forsythia suspensa (Thunb.) Vahl (Oleaceae). It mainly exists in the roots, stems, leaves and fruits of the plant, with the highest content in the leaves. In terms of its medicinal application, there are a large number of experimental data proving its pharmacological effects in vitro and in animal models, such as anti-inflammatory, anti-obesity, anti-tumor, etc. Furthermore, pharmacokinetic experiments have also shown phillyrin's high effectiveness and low toxicity. Despite more than one thousand studies in the literature on phillyrin retrievable from Web of Science, PubMed, and CNKI, few reviews on its pharmacological activities have been presented conclusively. In this paper, we aimed to summarize the pharmacological and pharmacokinetic characteristics of phillyrin from the current literature, focusing on its anti-inflammatory, anti-aging, antiviral, antibacterial, hepatoprotective and anti-cancer effects, hoping to come up with new insights for its application as well as future studies.

Comparative Transcriptomic Analysis on White and Blue Flowers of Platycodon grandiflorus to Elucidate Genes Involved in the Biosynthesis of Anthocyanins.

BACKGROUND: Platycodon grandiflorus has long been used in Northeast Asia as a food and folk medicine to treat various diseases. The intense blue color of P. grandiflorus corolla is its characteristic feature. OBJECTIVES: By comparing deep transcriptomic data of P. grandiflorus and its white cultivar, we intended to elucidate the molecular mechanisms concerning the biosynthesis of anthocyanins in this plant. MATERIAL AND METHODS: We sampled blue mature flowers (PgB) and yellow young buds (PgY) of P. grandiflorus. Meanwhile, mature flowers (PgW) of P. grandiflorus white cultivar were also collected for RNA extraction and next-generation sequencing. After high-throughput sequencing, Trinity software was applied for de novo assembly and the resultant 49934 unigenes were subjected for expression analysis and annotation against NR, KEGG, UniProt, and Pfam databases. RESULTS: In all, 32.77 Gb raw data were generated and the gene expression profile for the flowers of P. grandiflorus was constructed. Pathway enrichment analysis demonstrated that genes involved in flavone and flavonol biosynthesis were differently expressed. CONCLUSIONS: The extremely low expression of flavonoid-3',5'-hydroxylase in PgY and PgW was regarded as the reason for the formation of its white cultivar. Our findings provided useful information for further studies into the biosynthetic mechanism of anthocyanins.

Remodeling of Macrophages in White Adipose Tissue under the Conditions of Obesity as well as Lipolysis.

Adipose tissue macrophages (ATM) are a major source of low-grade inflammation in obesity, and yet reasons driving ATM accumulation in white adipose tissue (WAT) are not fully understood. Emerging evidence suggested that ATM underwent extensive remodeling in obesity. In addition to abundance, ATM in obesity were lipid-laden and metabolically reprogrammed, which in turn was tightly related to their functional alterations and persistence in obesity. Herein, we aimed to discuss that activation of lipid sensing signaling associated with metabolic reprogramming in ATM was indispensible for their migration, retention, or proliferation in obesity. Likewise, lipolysis also induced similar but transient ATM remodeling. Therefore, we assumed that obesity might share overlapping mechanisms with lipolysis in remodeling ATM. Formation of crown-like structures (CLS) in WAT was presumably a common event initiating ATM remodeling, with a spectrum of lipid metabolites released from adipocytes being potential signaling molecules. Moreover, adipose interlerkin-6 (IL-6) exhibited homologous alterations by obesity and lipolysis. Thus, we postulated a positive feedback loop between ATM and adipocytes via IL-6 signaling backing ATM persistence by comparison of ATM remodeling under obesity and lipolysis. An elucidation of ATM persistence could help to provide novel therapeutic targets for obesity-associated inflammation.

Characterization of the chloroplast genome of Verbena officinalis Linn. (Verbenaceae) and its phylogenetic analysis.

Verbena officinalis has a long history as a source plant in traditional Chinese medicine. This study adopted next-generation sequencing technology in order to determine complete chloroplast genome of V. officinalis. The results of this investigation showed the chloroplast genome of V. officinalis was 153,286 bp in length, including a pair of inverted repeat (IR) regions (each 25,825 bp), separated by a large single-copy region (LSC) of 84,316 bp and a small single-copy region (SSC) of 17,320 bp, and the overall GC contents of the chloroplast genome was 39.04%. Additionally, we annotated 83 genes, including 48 protein-coding genes, 31 tRNA genes, and 4 rRNA genes. By creating the phylogenetic tree, relationship between V. officinalis and relevant species was discussed, and the result proved that V. officinalis was closely related to Avicennia marina. The findings of the study will serve as a stepping stone for follow-up researches regarding its chloroplast genome.

Characterization and phylogenetic analysis of the complete chloroplast genome of Juncus effusus L.

Juncus effusus L., a perennial herbaceous species of family Juncaceae, is distributed mainly in warm areas worldwide. We studied the complete chloroplast (cp) genome of J. effusus through next-generation sequencing technology. The whole cp genome contained 170,612 base pairs, with the GC ratio as 35.99%. The 70 genes annotated from the cp genome include 32 protein coding genes, eight rRNA genes and 30 tRNA genes. The genome's large single-copy region (LSC) was 80,640 bp, with the small single-copy region (SSC) 64,718 bp, and inverted repeat (IR) 12,627 bp. Furthermore, a phylogenetic tree was generated to evaluate evolutionary relationship between J. effusus and relevant species. This study will be beneficial for the further understanding and application of J. effusus.

Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose.

Dendrobium huoshanense has been used for centuries in China and its polysaccharides are the main active components in treating loss of body fluids resulting from fever and asthenic symptoms. However, the biosynthetic pathway of polysaccharides in D. huoshanense remains to be elucidated. In this study, we obtained a guanosine diphosphate (GDP)-mannose pyrophosphorylase (DhGMPP) from D. huoshanense and characterized its function to catalyze the conversion of α-D-mannose-phosphate to GDP-D-mannose involved in the production of polysaccharides. DhGMPP, with the open reading frame of 1,245 bp, was isolated from RNA-Seq data of D. huoshanense. Phylogenetic analysis as well as sequence characterization suggested its involvement in the biosynthesis of GDP-D-mannose. In vitro enzyme assay demonstrated that GMPP encoded a pyrophosphorylase that converted α-D-mannose-phosphate and GTP into GDP-D-mannose. Identification of DhGMPP could provide more insights into the mechanism concerning polysaccharide biosynthesis in D. huoshanense and be utilized for enhancing polysaccharide accumulation through metabolic engineering.

The complete chloroplast genome of Abutilon theophrasti medic (Malvaceae).

Abutilon theophrasti Medic is a traditional Chinese medicine, which can be seen nearly everywhere in China. In order to study its complete chloroplast genome, we collected leaves and obtained chloroplast genome information through next-generation sequencing. It showed that the genome whole length is 160,331 bp, resulted from 24,578,194 raw reads with 3,669,530,829 bases in total, and the GC contents ratio is 36.90%. Besides, the large single-copy region (LSC) is 89,006 bp, the small single-copy region (SSC) 20,149 bp, and inverted repeat (IR) 25,588 bp. The chloroplast genome encodes 76 genes, which contains 38 protein genes, five rRNA genes, and 33 tRNA. By conducting phylogenetic analysis for A.theophrasti, plants from genus Gossypium demonstrated close relationship with it.

The complete chloroplast genome of Viola philippica (Violaceae).

Viola philippica, as a traditional Chinese medicine, has great value in treating various diseases. Here, we report the chloroplast genome of V. philippica and its phylogenetic feature. The complete chloroplast genome is 156,744 bp in length, assembled from 22,346,570 reads, and its GC contents ratio is 36.26%. Its long single-copy (LSC) region is 85,892 bp. The small single-copy (SSC) region covers 18,006 bp and inverted repeat (IR) is 26,423 bp. It encodes 77 genes, including 43 protein genes, 4 rRNA genes, and 30 tRNA genes. Moreover, according to the phylogenetic analysis for a total of 12 chloroplast sequences, V. philippica demonstrated close relationship within genus Viola.

Function of Dicer with regard to Energy Homeostasis Regulation, Structural Modification, and Cellular Distribution.

As a type III ribonuclease (RNase III) specifically cleaving double-stranded RNA substrates into short fragments, Dicer is indispensable in a range of physi/pathologic processes, e.g., nutrient deprivation, hypoxia, or DNA damage. Therefore, much interest has been paid to the research of this protein as well as its products like microRNAs (miRNAs). The close relationship between Dicer levels and fluctuations of nutrient availability suggests that the protein participates in the regulation of systemic energy homeostasis. Through miRNAs, Dicer regulates the hypothalamic melanocortin-4 system and central autophagy promoting energy expenditure. Moreover, by influencing canonical energy sensors like adenosine monophosphate-activated protein kinase (AMPK) or mammalian target of rapamycin (mTOR), Dicer favors catabolism in the periphery. Taken together, Dicer might be targeted in the control of energy dysregulation. However, factors affecting its RNase activity should be noted. Firstly, modulation of structural integrity affects its role as a ribonuclease. Secondly, although previously known as a cytosolic endoribonuclease, evidence suggests Dicer can relocalize into the nucleus where it could also produce small RNAs. In this review, we probe into involvement of Dicer in energy homeostasis as well as its structural integrity or cellular distribution which affects its ability to produce miRNAs, in the hope of providing novel insights into its mechanism of action for future application.