Latest ArticlesFour previously undescribed lanostane tetracyclic triterpenoids baoslingzhines T-W (1-4) were isolated from Ganoderma lucidum. Their structures including relative and absolute configurations were assigned by spectroscopic methods and ECD calculations.
In recent years, a large number of peptide compounds have been obtained from natural sources or synthesized chemically, which have attracted significant interest due to their high biological activity and low side effects. However, linear peptides encounter many challenges in the field of drug development because they are easily broken down by enzymes and do not pass through cell membranes well. Cyclic peptides, on the other hand, have a stable structure, strong binding to targets, and lower toxicity. They combine the advantages of natural peptides and small molecule drugs in terms of biological activity and drug metabolism, addressing the shortcomings of linear peptides and becoming increasingly important in drug research. This article focuses on the development history of cyclic peptides, discusses the sources, acquisition methods, and specific applications in the field of pharmacology in recent years, and prospects for their future development potential, aiming to provide a theoretical and practical basis for the clinical application of cyclic peptides.
Polygonatum Mill. (Asparagaceae) is a pharmaceutically important genus with many species are of significant medicinal value. Taxonomy and interspecific identification of Polygonatum species have long been controversial due to their considerable morphological variation, wide geographic distribution, complex speciation processes, and lacking of high-resolution molecular markers. To evaluate species discrimination power of 14 plastid divergence hotspot regions (candidate sequences) and their combinations in Polygonatum, a total of 166 individuals from 32 populations representing 15 medicinal Polygonatum species distributed in China were sampled for study. The interspecific and intraspecific genetic variation of each sequence and sequence combination were estimated, and tree-based and pairwise genetic distance (PWG-distance) methods were applied. The results indicated that except for trnT-trnL, the designed primers for all the other 13 candidate sequences showed good universality. Varying degrees of overlaps were detected between intraspecific and interspecific genetic distances in each of the 14 single candidate sequences and their combinations. Nonetheless, overlaps in the combined sequences were significantly lower than those in single sequences. Species resolution of the 14 single sequences were 6.67%-40% and 20%-60% based on tree-based and PWG-distance methods, separately. The combined sequences possessed higher species-resolving power with 40%-73.33% by tree-based method and 46.67%-73.33% by PWG-distance method, accordingly. Among them, the combined sequences C0 and C1 (in both tree-based and PWG-distance methods), C2 and C3 (in tree-based method), and C25 (in PWG-distance method) all showed the best resolution degree of 73.33%, indicating that combination of sequences could effectively improve species discrimination power. In addition, sequences psaJ-rpl33, rps16-trnQ, trnF-ndhJ, trnT-trnL, trnK-matK and atpF all exhibited relatively higher species-resolving degree, which could be used as specific molecular markers for the identification of medicinal Polygonatum species, and we propose the combination of psaJ-rpl33+rps16-trnQ+trnF-ndhJ+trnK-matK+atpF as the most ideal high-resolution molecular marker for discriminating the medicinal Polygonatum. This study will provide a basis for conservation and utilization of germplasm resources and accurate identification of medicinal Polygonatum, as well as standardizing the market for Polygonati Rhizoma.
The genus Gynostemma, with abundant plant resources, is widely distributed in China. Gynostemma plants have gathered widespread attention both domestically and internationally due to their abundant contents of diverse dammarane triterpenoid saponins and various promising pharmacological activities. At present, the studies on the chemical constituents and pharmacological activities of Gynostemma plants mainly focus on G. pentaphyllum (Thunb.) Makino and G. longipes C. Y. Wu ex C. Y. Wu & S. K. Chen, with less attention given to other species within genus. In this study, the chemical constituents of G. burmanicum King ex Chakrav were systematically identified by ultra-high performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UHPLC-Q-TOF-MS). Firstly, the LC-MS analysis of G. burmanicum from different sources was carried out to evaluate the consistency. According to the mass spectrometry fragmentation pattern of dammarane triterpenoid saponins from Gynostemma, the fragmentation characteristics of malonylated and acetylated saponins, combined with the self-built database and online database such as ChemSipder, SciFinder, PubChem, the chemical components of G. burmanicum were identified. The similarities and differences in the components between G. burmanicum and G. longipes were further assessed by comparing their base peak chromatogram. The experimental results indicated a good consistency in the composition of G. burmanicum samples from different sources. A total of 47 chemical components were identified from G. burmanicum, including 12 flavonoids and 35 triterpenoid saponins, among which 6 were new compounds. Saponins in G. burmanicum generally exhibited malonylation and acetylation, appearing after the corresponding prototypical saponins on a reversed phase chromatography. The base peak ion (BPI) chromatograms showed that the saponins of G. burmanicum were highly consistent with those of G. longipes, with comparable contents of the main components gypenoside XLIX and gypenoside A and their malonylated derivatives. In summary, this study comprehensively clarified the chemical composition and characteristics of G. burmanicum, which provided an experimental basis for the development and utilization of G. burmanicum.
Liver fibrosis is a chronic liver injury caused by various pathogenic factors, leading to excessive accumulation of extracellular matrix such as collagen. It represents a common pathological hallmark during the progression of most chronic liver diseases. However, there is currently no universally recognized specific and effective drug for the clinical treatment of liver fibrosis. Therefore, this study investigates the effects of Alisma Rhizoma on bile duct ligation (BDL)-induced liver fibrosis and explores the potential pharmacological mechanisms. The animal experimental protocol was reviewed and approved by the Animal Welfare and Ethics Committee of Shanghai University of Traditional Chinese Medicine (registration No. PZSHUTCM2303280007), in compliance with relevant animal welfare and ethical standards. Mice were subjected to BDL to induce liver fibrosis. Mice were divided into five groups: sham operation group (Sham), model group (BDL), ethanol extract protection group (BDL+EE, 1.6 g·kg-1), water extract protection group (BDL+WE, 4.0 g·kg-1), obeticholic acid protection group (BDL+OCA, 10 mg·kg-1). The results showed that both of EE and WE could attenuate BDL-induced liver fibrosis as evident by reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT) activities, total bile acids (TBA) levels, and improved pathological conditions such as cholestasis, collagen deposition, inflammatory cell infiltration, and liver tissue necrosis. Notably, EE showed better efficacy than WE. Further studies showed that EE improved liver fibrosis dose dependently. EE treatment impaired the bile acids homeostasis in serum and liver, and recovered the hepatic mRNA expression of farnesoid X receptor (FXR) as well as the downstream genes including small heterodimer partner (SHP), cholesterol 7-alpha hydroxylase (CYP7A1) and bile salt export pump (BSEP). Further study also proved that the four major triterpenes in EE increased the transcriptional activities of FXR in vitro. This study provides a theoretical basis for the clinical application of Alisma Rhizoma in the prevention and treatment of liver fibrosis.
Pulmonary fibrosis (PF) is a lung disease with a very poor prognosis that seriously affects the quality of life of patients and is characterized by scarring and thickening of the tissue surrounding the alveolar walls, ultimately leading to respiratory failure. Currently, the Food and Drug Administration (FDA) approved drugs for the treatment of PF include pirfenidone and nidazanib, however, these two drugs can only delay the progression of the disease but cannot achieve the reversal of PF, and their clinical application is limited due to high price and multiple adverse effects. The pathogenesis of PF has not been fully elucidated, and studies have demonstrated that aberrant immune cell activation and regulation play an important role in PF. This review aims to discuss the role of immune cell activation and regulation in PF in recent years. The aim of this review is to discuss recent advances in the study of the role of immune cells in the process of PF, with the aim of providing theoretical guidance for the development of novel immunotherapies.
The 95% ethanol extract of Curcuma longa was isolated and purified by silica gel column chromatography, polyamide column chromatography, preparative thin layer chromatography and semi-preparative HPLC. Then, the structures of the obtained compounds were identified by HR-MS, IR, and NMR. Absolute configuration of the new compound was determined by calculating ECD. Finally, two bisabolane-type sesquiterpenoids were obtained from C. longa and identified as (7S)-1,3,5,10-bisabolatetraen-3-nitro-9-one (1) and turmeronol A (2). Compound 1 was a novel nitro-substituted bisabolane-type sesquiterpenoid.
Oral probiotics are susceptible to the gastrointestinal environment, so the number of probiotics reaching the intestine is small and difficult to colonize, limiting the application of probiotic therapy. In this study, Lactobacillus rhamnosus (LGG), a common probiotic, was chosen as a model, and layer-by-layer encapsulated LGG-loaded porous microspheres with glycol chitosan (GCS) and sodium alginate (SA) were prepared to investigate it's in vitro properties. Poly-L-lactic acid porous microspheres (PLPM) were prepared by the complex milk-solvent evaporation method, with rounded morphology, uniform size, open and connected porous structure, and the average particle size of 138.5 μm. The PLPM were co-incubated with LGG for 8 h at 37 ℃ to obtain the LGG-loaded porous microspheres (LPM) with high bacterial loadings. The surface of the LPM were wrapped with GCS and SA layer by layer by electrostatic action to obtain the layer-by-layer encapsulated LGG-loaded porous microspheres with GCS and SA (AGLPM). In vitro experiments demonstrated that AGLPM could tolerate simulated gastric fluid at pH 1.2 and simulated intestinal fluid at pH 7.4 for 2 h, and its stability was significantly better than that of bare LGG. AGLPM was a better probiotic dosage form.
Neurodegenerative diseases are one of the leading causes of death and disability worldwide, with complex pathogenesis and lacking effective therapeutic drugs. Increasing researches have shown that most neurodegenerative diseases involve abnormalities in iron homeostasis and activation of immune cells in the brain. Iron accumulation in microglia promotes ferroptosis, leading to cellular dysfunction and death. In contrast, inhibiting ferroptosis can alleviate neuroinflammation, protect neurons, and slow disease progression, highlighting the pivotal roles of ferroptosis and neuroinflammation in neurodegenerative diseases. This review summarizes the roles of ferroptosis and neuroinflammation in neurodegenerative diseases, further discusses the related targets regulating these processes, and reviews the therapeutic potential of drugs targeting ferroptosis and neuroinflammation in neurodegenerative diseases. This review aims to provide novel targets and therapeutic drugs for the treatment of neurodegenerative disease, offering new strategies for clinical management and improving the symptoms and prognosis of neurodegenerative disease.
Based on mass spectrometry imaging method, we investigated the effects of Panax notoginseng in improving diabetic retinopathy (DR) and interfering with corneal, vitreous and retinal metabolites, to reveal the mechanism of Panax notoginseng's action in improving DR. All animal experiments were approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (Approval No.: BUCM-2023052204-2117). Streptozotocin (STZ)-induced diabetes mellitus (DM) rat model was used, and fasting blood glucose (FBG) and glucosylated serum protein (GSP) levels were measured in each group of rats. Occludin and zonula occludens-1 (ZO-1) were detected by immunofluorescence staining; air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to detect endogenous metabolites in the cornea, vitreous, and retinal microregions of the eyes of rats in the DM group and Panax notoginseng group. Endogenous metabolites were detected in the cornea, vitreous, and retinal microregions of the DM and Panax notoginseng groups, and the DM and Panax notoginseng groups were screened for different metabolites by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Differential metabolites were screened in the DM and Panax notoginseng groups, the in situ spatial information of differential metabolites in each microregion was analyzed, and the related metabolic pathways were analyzed by the Kyoto encyclopedia of genes and genomes (KEGG) database. The results showed that compared with the DM group, diabetic rats in the Panax notoginseng group showed a decreasing trend in both FBG and GSP, and an increase in the expression of ZO-1 and occludin in the retina (P < 0.001); AFADESI-MSI analysis showed that there were a total of 34 differential metabolites in the cornea, vitreous body, and retinal microregion in the Panax notoginseng group, of which Panax notoginseng called back 13 differential metabolites. In the retinal microregion, Panax notoginseng significantly regulated lysophosphatidylserine (18∶0), phosphatidylethanolamine (34∶2) and phosphatidylserine (40∶7/42∶7). The metabolic pathway enrichment results indicated that Panax notoginseng mainly regulated glycerophospholipid metabolism, glycosylphosphatidylinositol synthesis, niacin and nicotinamide metabolism as well as glycerol ester metabolic pathways. In conclusion, Panax notoginseng improves the blood-retinal barrier (BRB) in diabetic rats, and its mechanism of action may be closely related to glycerophospholipid metabolism. This study provides scientific evidence for the mechanism of action of Panax notoginseng in improving DR, and demonstrates the potential of mass spectrometry imaging technology applied to the study of pharmacological mechanisms.