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This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. These compounds exhibit diverse biological activities, such as anti-inflammatory, anti-cancer, and anti-diabetic effects, which are attributed to the combination of different flavonoid scaffolds and alkaloid groups. Flavonoid alkaloids have attracted researchers' attention due to their diverse structures and important bio-activities. Therefore, this review summarizes recent advances in the extraction, purification, structural characterization, synthesis pathways and biological activities of flavonoid alkaloids from natural sources. Finally, the potential prospects and challenges associated with this class of compounds in pharmacological research are discussed along with details of a mechanistic investigation and future clinical applications in this research field. This paper explores the potential of flavonoid alkaloids, a unique class of compounds that contain both flavonoid and alkaloid structures, as emerging targets for drug discovery. [Display omitted] [ABSTRACT FROM AUTHOR]

In recent decades, numerous herbal products have been shown to have antihyperglycemic and beta cell-regenerative effects in animal studies. However, there is no clinical evidence that those products completely cure patients with type-1 diabetes (T1D). Therefore, it seems that most of the phytochemicals do not have a significant impact on human beta cells, and the results of experimental studies conducted on them may not be generalizable to the clinic. The present work aims to review extensively the methods and results of preclinical studies on phytotherapy of T1D published in the last 10 years. This paper critically analyzes the designs of studies, treatment protocols, methods of diabetes induction, characteristics of the studied animals, clinical relevance, reproducibility of research, and other aspects related to conducting preclinical studies on T1D. We discussed limitations that make many of the results of these studies not generalizable to the clinic. Finally, some recommendations were given to improve studies on the phytotherapy of T1D to avoid misleading interpretations about the antidiabetic effect of herbal compounds. This paper can be considered a practical guide for researchers interested in the field of phytotherapy of T1D to increase the reliability, reproducibility, and validity of their preclinical studies. [Display omitted] [ABSTRACT FROM AUTHOR]

The global incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been steadily increasing, making it a leading chronic liver disease. MAFLD refers to a metabolic syndrome linked with type 2 diabetes mellitus, obesity. However, its pathophysiology is complex, there are currently no effective and approved medicines for therapy. Rutin, a naturally occurring polyphenolic flavonoid, is widely distributed in fruits, vegetables, and other plants. It exhibits a plethora of bioactive properties, such as antioxidant, anticancer, and anti-inflammatory and neuroprotective activities, making it an extremely promising phytochemical. Rutin has shown great potential in the treatment of a wide variety of metabolic diseases and received considerable attention in recent years. Fortuitously, various research studies have validated rutin's extensive biological functions in treating metabolic disorders. Despite the fact that the exact pathophysiological mechanisms through which rutin has a hepatoprotective effect on MAFLD are still not fully elucidated. This review comprehensively outlines rutin's multifaceted preventive and therapeutic effects in MAFLD, including the modulation of lipid metabolism, reduction of insulin resistance, diminution of inflammation and oxidative stress, combatting of obesity, and influence on intestinal flora. This paper details the known molecular targets and pathways of rutin in MAFLD pathogenesis. It endeavored to provide new ideas for treating MAFLD and accelerating its translation from bench to bedside. [Display omitted] • A comprehensive summary of rutin's effect in treating MAFLD. • To review the multifaced mechanisms of rutin on MAFLD. • To elucidate rutin's safety and the therapeutic potential for treating MAFLD. [ABSTRACT FROM AUTHOR]

The essential oil (EO) obtained from hemp (Cannabis sativa L.) biomass is rich of bioactive constituents and its oral administration can be valuable. In this paper two different hemp EOs were orally administered to CD1 mice. One EO, obtained from the fresh plant material, resulted rich in monoterpenes (monoterpene rich oil, MRO) and the other, obtained from the dried biomass, contained mainly sesquiterpenes and CBD (sesquiterpene rich oil, SRO). The blood levels of the most abundant constituents were evaluated in the animals 30 and 90 min after oral administration of hemp EOs. Furthermore, compounds were also measured in brain, liver, kidney, spleen, and cecum content to evaluate their tissue distribution at the same times. Results showed the easy absorption and the ability of the major hemp EOs constituents to reach brain, liver, and kidney. Oral administration of MRO resulted in blood levels of monoterpenes in the range 45–115 ng/g at 30 min and significant tissue distribution with the detection of monoterpenes in brain, liver, and kidney. Oral administration of SRO resulted in blood levels, at 30 min, in the range 70–80 ng/g of sesquiterpenes and 139 ng/g of CBD. The compounds are still detectable in blood and brain 90 min after oral administration and significant concentrations of terpenoids are observed in liver and kidney. MRO and SRO can be considered as valuable sources of these bioactive compounds and further investigations are needed to evaluate the potential uses of hemp EO as constituent of innovative drug formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Pandan (Pandanus amaryllifolius Roxb.), a member of the Pandanaceae family, has been consumed as food and medicine since ancient times. The current paper provides an overview of the botanical profile, phytochemistry, pharmacology, and applications of P. amaryllifolius. Information regarding P. amaryllifolius was collected from online sources (using PubMed, Science Direct, Google Scholar, Web of Science, ACS, and CNKI) as well as traditional textbooks. Over 100 compounds have been identified, including its characteristic components 2-Acetyl-1-pyrroline and Pandanus alkaloids. Several therapeutic uses of P. amaryllifolius , such as antioxidant, hypoglycemic, antimicrobial, and antitumor activities, have been demonstrated in modern pharmacological studies. Additionally, it could be applied in various fields, including food, energy, material, and the environment. Continued research on P. amaryllifolius can contribute to the development of new drugs and therapies for various diseases. And further studies are needed to improve its utilization. [Display omitted] [ABSTRACT FROM AUTHOR]

Daphne genkwa , as a traditional medicine, is widely distributed in China, Korea and Vietnam. In China, the dried flower buds of this plant are named "Yuanhua". It has the ability to effectively promote urination, eliminate phlegm and alleviate cough, eliminate parasites and cure of scabies, with a broad spectrum of pharmacological effects and considerable clinical efficacy. This paper provides a summary and classification of the main chemical constituents of D. genkwa based on a review of relevant domestic and foreign literature. It also outlines the current research status of traditional clinical usage, pharmacological effects, and toxicity of D. genkwa. The aim is to provide a theoretical basis for further study of D. genkwa and its potential new clinical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is a widely studied plant that shows potential in treating urinary diseases. Previous studies have focused on its chemical composition, pharmacological effects, and clinical applications. This review aims to provide a comprehensive summary and evaluation of the existing literature on CS. It also suggests future research directions to increase our understanding of its medicinal value. 129 pieces of literature were selected from several databases, including PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), Wan-fang Database, and Google Scholar, and were analyzed. Forty-five active compounds of CS have pharmacological effects such as lowering uric acid, anti-inflammation, anti-oxidation, and kidney protection. The potential mechanisms of these effects may be related to inhibiting transforming growth factor β1 (TGF-β1) activation, reducing inflammatory factors such as IL-8, IL-1β, TNF-α, PGE2, IFN-γ, and IL-6 levels, suppressing the activation of NF-κB, JAK/STAT pathway, enhancing the clearance of ROS, MDA DPPH·, and O 2 ̇ −, and regulating the expression of apoptosis-related pathways and proteins. This paper also discusses the quality control of CS and its efficacy and safety in treating urinary diseases. The study concludes that CS has a high potential for treating urinary diseases. Future studies should focus on observing the metabolic changes of CS active compounds in vivo and investigating the effects of CS on key signaling pathways. Additionally, more standardized and reasonable clinical studies and safety evaluation experiments should be conducted to obtain more clinical data. [Display omitted] • The mechanism of CS treatment in urinary disease was summarized. • Summarized the role of active constituents or sites of CS in underlying mechanisms. • It presents conclusions about the cytokine changes observed in patients after applying CS. • The assistant therapy action and side effect evaluation of CS were discussed in detail. [ABSTRACT FROM AUTHOR]

Major polyphenols in Rosmarinus officinalis L. primarily consist of phenolic acids, phenolic diterpenes, and flavonoids, all of which have pharmacological properties including anti-inflammatory and antibacterial characteristics. Numerous in vitro and animal studies have found that rosemary polyphenols have the potential to decrease the severity of intestinal inflammation. The beneficial effects of rosemary polyphenols were associated with anti-inflammatory properties, including improved gut barrier (increased mucus secretion and tight junction), increased antioxidant enzymes, inhibiting inflammatory pathways and cytokines (downregulation of NF-κB, NLRP3 inflammasomes, STAT3 and activation of Nrf2), and modulating gut microbiota community (increased core probiotics and SCFA-producing bacteria, and decreased potential pathogens) and metabolism (changes in SCFA and bile acid metabolites). This paper provides a better understanding of the anti-inflammatory properties of rosemary polyphenols and suggests that rosemary polyphenols might be employed as strong anti-inflammatory agents to prevent intestinal inflammation and lower the risk of inflammatory bowel disease and related diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

The genus Antidesma L. (Phyllanthaceae) consists of 102 species and is distributed throughout the subtropical, temperate, and subpolar regions. Numerous species in this genus are employed in ethnomedical practices to treat a range of ailments including anaemia, diabetes, herpes, skin infections, typhoid, throat and lung diseases, gastrointestinal, jaundice, rheumatic, and many more diseases. This review aimed to highlight the ethnopharmacological uses, phytochemical components, biological activities, and future research opportunities of the genus. A total number of 112 research papers published between the period 1977 and 2023 were considered and reviewed were retrieved from scientific databases such as Scopus, Web of Science, Elsevier Scient Direct, Google Scholar, and PubMed. The literature study revealed that both plant extracts and phytochemicals exhibited a wide range of biological activities including antidiabetes, anticancer, antimicrobial, anti-inflammation, and many other activities. Overall, a total number of 236 compounds have been encountered from the different species of Antidesma. These compounds belong to different chemical groups such as alkaloids, flavonoids, fatty acids, lignans, sterols, terpenoids, coumarins, and others. Three compounds such as antidesmone, amentoflavone, and β-sitosterol were found to be possible chemotaxonomic markers for the genus Antisema. Furthermore, only 16 species have been investigated in the context of phytochemistry and pharmacological activities of the genus so far. This review could serve as a comprehensive resource for future research in drug discovery and also lay the groundwork for the exploration of additional species within this genus for pharmaceutical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

A total of 12 abietane diterpenoids were isolated and identified from Rosmarinus officinalis in which 6 ones were undescribed compounds. Their structures were illuminated by the HRESIMS, NMR, and ECD methods and named as rosmarinusin Q-V (1 – 6). It worthy mentioned that rosmarinusin Q was a novel abietane diterpenoid with 6/6/5 skeleton whose C ring was an α , β -unsaturated five-element ketone. All the compounds and four compounds (13 – 16) reported in our previous paper were evaluated their anti-neuroinflammatory activities on the LPS-induced BV2 cells. Compounds 5 , 8 , 9 , 11 , and 15 displayed significant anti-neuroinflammatory activity at the concentration of 10, 20, and 40 μM respectively. These results confirmed that R. officinalis contained abundant abietane diterpenoids and these compounds showed potential values of anti-neuroinflammation which could be developed as neuroprotective agents for the treatment of nerve damage caused by inflammation. [Display omitted] [ABSTRACT FROM AUTHOR]

A systematic mechanistic review was performed to determine mechanistic evidence for curcumin on pro-inflammatory matrix metalloproteinases and Osteoarthritis to understand the underlying pathophysiology, and to evaluate available human intervention evidence to inform clinical decision making. The systematic literature search was performed in 3 tranches (reviews, mechanistic, intervention studies) using PubMed, with no date limitations and using specific search terms. 65 out of 393 screened papers were accepted based on detailed inclusion and exclusion criteria. The mechanistic search was divided into three searches and the intervention searches were subdivided into four searches. Curcumin demonstrated significant inhibition of matrix metalloproteinases linked to cartilage degradation in Osteoarthritis through reduced activation of the nuclear factor kappa-B signaling pathway via suppressing phosphorylation of Iκβa and p65 nuclear translocation. Mechanistic evidence implicated matrix metalloproteinases in Osteoarthritis by decreasing Type II collagen, leading to cartilage damage. As a potential nutritional intervention for Osteoarthritis, curcumin could reduce inflammatory markers and improve pain and function scores. The evidence indicates most formulations of turmeric extract and curcumin extract, bio-enhanced and non-bio-enhanced, are effective at improving inflammatory markers and pain and function to a greater or lesser extent. Due to the high heterogeneity of the formulations, dosage, and duration of the studies, further research is needed to fully understand curcumin's potential as a promising non-pharmaceutical intervention for Osteoarthritis. This mechanism review identifies a gap in current research for the mechanism by which Type II collagen is mediated. [Display omitted] • NFkB is a key inflammatory mediator in the development and progression of Osteoarthritis. • MMPs interact with type II collagen and proteoglycans leading to cartilage damage. • Curcumin inhibits matrix metalloproteinases linked to cartilage degradation by modulating NFkB. • Curcumin demonstrates significant improvements in inflammation, pain and function scores. • All formulations of turmeric extract and curcumin extract demonstrated similar improvements. [ABSTRACT FROM AUTHOR]

A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X -ray diffraction analysis. The test results of EC 50 values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC 50 values of 236.8, 206.0 μg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 μg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (K d) value of 0.045 μM, which was superior to the ningnanmycin (0.700 μM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents. [Display omitted] • In this paper, 20 myricetin derivatives containing benzoxazinone were designed and synthesized. • Compound Y8 exhibited excellent antiviral against tobacco mosaic virus in vivo. • The binding ability of Y8 to TMV-CP were explored by microscale thermophoresis and molecular docking technology. • Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA and increasing SOD content. [ABSTRACT FROM AUTHOR]

The chemical structure of sinoacutine is formed by a phenanthrene nucleus and an ethylamine bridge. Because it has a similar parent structure to morphine, it is subdivided into morphinane. At present, all reports have pointed out that the basic skeleton of morphine alkaloids is salutaridine (the isomer of sinoacutine), which is generated by the phenol coupling reaction of (R)-reticuline. This study shows that the biosynthetic precursors of sinoacutine and salutaridine are different. In this paper, the sinoacutine synthetase (SinSyn) gene was cloned from Sinomenium acutum and expressed SinSyn protein. Sinoacutine was produced by SinSyn catalyzed (S)-reticuline, according to the results of enzyme-catalyzed experiments. The optical activity, nuclear magnetic resonance, and mass spectrum of sinoacutine and salutaridine were analyzed. The classification and pharmacological action of isoquinoline alkaloids were discussed. It was suggested that sinoacutine should be separated from morphinane and classified as sinomenine alkaloids. [Display omitted] [ABSTRACT FROM AUTHOR]

The husks of Xanthoceras sorbifolia Bunge have gradually attracted widespread attention in recent years due to the abundant resources and ideal pharmacological activities, with barrigenol-like triterpenoid saponins being its biological constituents. In this study, a feature-based molecular networking (FBMN) was utilized to perform the targeted isolation of triterpenoids. As a result, six undescribed barrigenol-type saponins (1-6) along with fourteen known analogues (7-22) were isolated from the extract of X. sorbifolia husk. Their structures were determined through a comprehensive analysis of NMR and HRMS spectroscopic data. Among them, compounds 1-3 are a specific type of saponin featuring a fucose moiety attached at C-21. The antitumor activities of isolated compounds were evaluated and compounds 7, 9 and 10 showed significant inhibitory activities against A549 and HepG2 cell lines in a dose-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Artemisia plants are well-known for their abundant sesquiterpene compounds, which encompass various structural types and exhibit a range of biological activities. In this study, a systematic investigation of Artemisia atrovirens revealed the presence of germacrane-type sesquiterpenes for the first time. This included the discovery of 10 new compounds and three known analogues, among which were two rare dimeric germacrane-type compounds. Their structures were fully characterized through a comprehensive analysis involving MS, IR, 1D- and 2D-NMR spectroscopic data, single crystal X-ray diffraction, density functional theory (DFT) NMR calculations, and time-dependent DFT electronic circular dichroism (TDDFT ECD) calculations. Furthermore, all isolated compounds were evaluated for their anti-inflammatory activity in LPS-stimulated RAW 264.7 murine macrophages. Compound 10 demonstrated a potent inhibitory effect on NO production, with an IC 50 value of 4.01 ± 0.09 μM. This study highlights the diverse chemical repertoire of Artemisia species and underscores their potential in drug discovery and development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This review investigates the therapeutic effects of Ulmus species extracts, traditionally used as tea ingredients in East Asia, on bone health and inflammatory conditions. Through the analysis of 9757 studies, narrowing down to 56 pertinent ones, we evaluated the safety and efficacy of Ulmus extracts. The focus was on catechin glycosides (CG) and flavonoid glycosides (FG), key compounds identified for their potential benefits. The research highlights the extracts' role in enhancing bone mineral density (BMD) by stimulating osteoblast activity and suppressing osteoclast differentiation, suggesting a protective effect against osteoporosis. Furthermore, the extracts demonstrated significant anti-inflammatory properties by modulating inflammatory markers and pathways. The findings confirm the historical use of Ulmus extracts in East Asia for health benefits and recommend further exploration into functional foods and nutraceuticals. The review calls for more rigorous research, including clinical trials, to establish optimal use and integration into modern health solutions. It underscores the potential of Ulmus extracts in promoting bone health and managing inflammation, advocating for a bridge between traditional practices and contemporary scientific validation. In conclusion, Ulmus extracts, a material long consumed as tea ingredients in East Asia, exhibit significant potential for improving bone health and reducing inflammation. This review calls for additional research to explore their full therapeutic capabilities, emphasizing the need for optimized extraction methods and clinical trials. It reinforces the importance of bridging traditional knowledge with contemporary scientific approaches to health and dietary solutions, promoting overall wellness., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins PU (1-6). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p-AKT, GLUT4 and p-GSK3β proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. Ilex hainanensis Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of I. hainanensis extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The present study is focused on the isolation and identification of new therapeutic candidates from Chrysanthellum americanum Vatke., and their efficacy against pteridine reductase-1 (PTR1), a valid chemotherapeutic target in the Leishmania parasite. Henceforth, a new compound, chrysanamerine (1), along with 7 known compounds, polyacetylene 2, and flavonoids 3-8, were isolated from C. americanum. Their structures were determined by chemical and spectroscopic analyses and compared with the reported spectroscopic data. All compounds were evaluated for their anti-leishmanial activity against PTR1 via biochemical mechanism-based assay. The in vitro results showed five potential hits including a new compound, chrysanamerine (1), and four known compounds against the PTR1 enzyme. Among them, compound 1 showed a potent enzyme inhibition with an IC 50 of 31.02 ± 2.36 μM, whereas a moderate inhibition was observed in cases of compounds 5 and 6 (IC 50  = 59.86 ± 3.32, and 45.32 ± 3.5 μM, respectively). Whereas, compounds 3 and 8 showed mild inhibition (IC 50  = 72.12 ± 1.12, and 97.18 ± 1.23 μM, respectively) against PTR1, compared with trimethoprim (positive control) (IC 50  = 21.07 ± 1.6 μM). Moreover, the results were further validated via molecular docking and molecular dynamics (MD) simulations. Compound 1 showed a strong affinity to the binding site with a docking score of -11.83, along with the formation of a stable protein-ligand complex over the trajectory of 100 ns. Besides, compounds 1-8 were found to be non-cytotoxic on BJ (human fibroblast) cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Three new sesquiterpenes, 4S-1-(3-hydroxybutyl)-7-(11-hydroxypropyl)-10-methyl- cyclohepta-7,5,10-trien-8-one (1), 8R-hydroxy-7-(4S-4,10-dimethyl-5-oxooct-1-en-7-yl)-11- methylfuran-12-one (2), (1S,5R,7S,10R)-1-hydroxy-7-(11-hydroxypropyl)-10-methyl-4- methyleneoctahydronaphthalen-8-one (3), along with 30 known terpenoids (4-33) were obtained from the rhizomes of Curcuma kwangsiensis S.G. Lee et C.F. Ling. Through comprehensive analysis of chemical evidence and spectral data including UV, ECD, IR, 1D and 2D NMR and HR-ESI-MS, as well as quantum chemical calculation, the structures of these novel compounds were successfully determined. Additionally, the inhibitory effects of compounds 1-2, 4-33 on NO production were evaluated in lipopolysaccharide (LPS)-induced RAW264.7 cells. Notably, compound 33 exhibited the most significant inhibitory effect with an IC 50 value of 3.55 ± 0.55 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Hydroxytyrosol-typed phenylpropanoid glycosides (HPGs), composed of phenylethanol and various complex oligosaccharides, are widespread and abundant in different plant, and have a diverse range of biological activities. All HPGs reported previously have been isolated from natural sources, and most of them showed significant bioactivities, such as anti-inflamatory, anti-cancer, cytoprotection, neuro-protective effects, enzyme-inhibitory, anti-microbial effects, and cardiovascular activity. The goal of this review is to summarize the structures of HPGs reported over the past few decades, as well as to introduce their pharmacological effects. We also introduce the possible relationship between the structures of HPGs and their source plants, as well as the structure-activity relationships of some important activities. This review will serve as a resource for future research into this class of compounds, and demonstrate their potential value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The traditional Chinese medicine Tetrastigma Hemsleyanum (TH) is employed in treating respiratory diseases; however, the aerial parts by which its total flavonoids alleviate acute lung injury (ALI) are still unknown. This study investigated the protective effect and mechanism of Tetrastigma Hemsleyanum flavonoids (THF) in lipopolysaccharide (LPS)-induced ALI in mice., Methods: Firstly, the total flavonoids from the above-ground part of TH were extracted. Subsequently, the composition of THF was analyzed using LC-MS. In vivo, the impact of THF on ALI mice was assessed through lung histopathology and the evaluation of various inflammatory factors' expression in mice. After treating RAW264.7 cells with THF in vitro, changes in inflammatory markers were examined upon LPS stimulation, and mRNA expression levels of inflammatory factors were detected using RT-qPCR. Finally, Western blot analysis was performed to determine TLR4/NF-κB pathway-associated proteins expression., Results: In summary, a total of 24 flavonoids have been identified in THF. In vivo and vitro results show that THF effectively reduces the damage caused by LPS inflammation by blocking the expression and release of inflammatory factors. THF alleviates inflammatory injury by modulating the TLR4/NF-KB pathway., Conclusion: The results suggest that flavonoids exhibit a potent anti-inflammatory effect and effectively mitigate LPS-induced injury both in vivo and in vitro. We suggested that these flavonoids exert their therapeutic effects by modulating the TLR4/NF-KB pathway. In conclusion, the development of THF is anticipated to represent a promising new pharmaceutical for treatingALI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The author is an Editorial Board Member/Editor-in-Chief/Associate Editor/Guest Editor for [Journal name] and was not involved in the editorial review or the decision to publish this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Marine algal toxins are usually produced by some toxic algae during toxic algal blooms which can be accumulated in marine organisms through food chains, leading to contamination of aquatic products. Consumption of the contaminated seafood often results in poisoning in human being. Although algal toxins are harmful for human health, their unique structures and broad spectrum of biological activities have attracted widespread attention of chemists and pharmacologists. Marine algal toxins are not only a reservoir of biological active compound discovery, but also powerful tools for exploring life science. This review first provides a comprehensive overview of the chemistry and biological activities of marine algal toxins, with the aim of providing references for biological active compound discovery. Additionally, typical shellfish poisoning incidents occurred in China in the past 15 years and the geographical distribution of the marine algal toxins in China Sea are discussed, for the purpose of enhancing public awareness of the possible dangers of algal toxins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ammi majus L. is a rich source of coumarins in addition to various flavonoids, alkaloids, and terpenoids. Medicinal products of Ammi majus seed, with sunlight exposure, are worldwide used for the treatment of vitiligo (pale-white patches on the skin). To increase the content of seed-coumarins and to investigate the physiological reasons in this respect, two net-house experiments were conducted using foliar-spray treatments (0, 25, 50, 100 and 200 mg L -1 ) of salicylic acid (SA) (Experiment 1) and putrescine (PUT) (Experiment 2). All studied parameters were improved due to the foliar application of both growth elicitors (SA and PUT). The best outcomes for SA and PUT were obtained at 50 mg L -1 which maximally increased the growth characteristics, physiological and biochemical attributes, and seed quality parameters. In comparison to the control, 50 mg L -1 of SA and PUT increased the chlorophyll content by 26.3% and 25.5%, carotenoid content by 31.4% and 18.5%. In addition 50 mg L -1 of both SA and PUT gives the best results of FTIR (Fourier Transform Infrared Spectrophotometer) & XRD (X-ray Diffraction) analysis. In GC-MS analysis, 50 mg L -1 of SA and PUT increases the Methoxsalen content (17.44 and 16.81%) and 7H-Furo[3,2-g]. Bown (1995) [1] Benzopyran-7-one, 4,9-dimethoxy content(14.92 and 13.93%) and p-camphorene content (13.11 and 12.27%) in contrast to the control. Other important constituents were Pimpinellin (6.31 and 4.08%), Bergapten (8.72 and 6.220, Isospathulenol (7.80 and 2.47), Octadecenoic acid (5.78 and 3.59) and Vitamin E (1.48 and 0.16)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Breast and gynecological cancers are major health concerns due to their increasing incidence rates, and in some cases, their low survival probability. In recent years, multiple compounds of natural origin have been analyzed as alternative treatments for this disease. For instance, Acetogenins are plant secondary metabolites from the Annonaceae family, and its potential anticancer activity has been reported against a wide range of cancer cells both in vitro and in vivo. Several studies have demonstrated promising results of Acetogenins' antitumor capacity, given their selective activity of cellular inhibition at low concentrations. This review outlines the origin, structure, and antineoplastic activities in vitro and in vivo of Acetogenins from Annonaceae against breast cancer and gynecological cancers reported to date. Here, we also provide a systematic summary of the activity and possible mechanisms of action of Acetogenins against these types of cancer and provide references for developing future therapies based on Acetogenins and nanotechnologies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Morus plants played a pivotal role in ancient Chinese sericulture and silk production, which served as critical components of economy and culture. Besides, many parts of mulberry trees, including roots, leaves, stems, and fruits, hold various medicinal value, and have been utilized in traditional medicine for thousands of years. The chemical composition of mulberry has been reported in many literatures, while the characteristic compounds have not been systematically summarized. In this review, we focused on the polyphenolic compounds in mulberry, including flavonoids, 2-arylbenzofurans, and Diels-Alder (D-A) adducts, and summarized their structural features, structure-activity relationships, and potential biosynthetic pathways. The results revealed a characteristic class of 2'-hydroxylated flavonoids and stilbenes which played an important role in the biosynthesis of downstream 2-arylbenzofurans and D-A adducts in mulberry but had been overlooked by most studies. The prenylated modifications of different compounds were also discussed and their function as precursors of D-A adducts was emphasized. We also describe the effects of different modifications on biological activities. Besides, the chemical composition of Morus was most similar to that of Artocarpus in the Moraceae family in that they had almost identical characteristic compounds. Finally, a putative total biosynthetic pathway of D-A adducts in mulberry was proposed based on structure derivation and combination of verified reactions. This review contributes to the understanding of the biological activity and biosynthesis of the characteristic components of Morus plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Agarwood is resin-containing wood produced by plants that have been injured. It is widely used in herbal medicine, incense, decorative items, and so on. In this study, we conducted resin area statistical analysis, determined starch particle and reducing sugar contents, and performed multivariate statistical analysis of chemical composition by GC-MS and UPLC-Q-TOF-MS to explore the different components in sections cut from an agarwood column, designated as A1-A4. The results showed that after stimulation by Agar-Bit inducer, the internal phloem parenchyma cells of the column started to form agarwood, and then starch granules were converted into soluble reducing sugars and agarwood resin. Section A1 showed rapid loss of starch granules, resulting in higher contents of reducing sugars and resin. The resin areas of agarwood in the respective sections were different, gradually decreasing on going from A1 to A4. Total numbers of metabolites of 87 and 63 were identified by GC-MS and UPLC-Q-TOF-MS, respectively. Of these, 10 and 16 metabolites with significant differences (variable importance projection >1) were selected through multivariate statistical analysis. These metabolites included chromones, sesquiterpenes, alkanes, and fatty acids. Among them, 6-methoxy-2-(2-phenylethyl)chromone and 6,7-dimethoxy-2-(2-phenylethyl)chromone were significant markers detected by both GC-MS and UPLC-Q-TOF-MS, which may be essential substances responsible for differences in the agarwood-forming capacities of the cut sections. In conclusion, there has been limited research on the different agarwood-forming capacities of agarwood columns. Here, we explored the differences in various sections of agarwood through chemical analysis to provide a more comprehensive and in-depth understanding of its constitution., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Ganweikang tablet (GWK) is a traditional Chinese prescription and has been clinically used in treating liver diseases for decades. Although GWK has been shown to exert potential therapeutic effect for hepatotoxicity protection, the underlying biological mechanisms are still not well clarified. In the present study, the compositional analysis of GWK was performed by HPLC analysis, and the hepato-protective effects of GWK were assessed in H 2 O 2 -stimulated acute oxidative injured HL-7702 hepatocytes in vitro. As a result, 7 components in GWK were quantified to be 0.06 ± 0.01% (calycosin), 0.46 ± 0.02% (calycosin-7-glucoside), 0.13 ± 0.01% (liquiritin), 0.17 ± 0.02% (glycyrrhizic acid), 0.45 ± 0.02% (forsythoside A), 0.07 ± 0.01% (5-O-methylvisammioside) and 0.45 ± 0.02% (forsythin), respectively. Furthermore, GWK (100, 200 and 400 μg/mL, 24 h) dose-dependently alleviated HL-7702 hepatocytes from H 2 O 2 (200 μM, 2 h)-induced cell apoptosis by decreasing the intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) level, as well as the cellular aminotransferases (ALT and AST) activities. GWK increased the expressions of HO-1, NQO1 and Nrf2, while suppressing the expression of KEAP1 in H 2 O 2 - stimulated HL-7702 cells. A specific Nrf2 inhibitor, ML385, was further employed to investigate the regulation of Nrf2 in HL-7702 cells stimulated by H 2 O 2 . In addition, the activation of MAPKs (JUN, ERK and p38) was simultaneously detected in H 2 O 2 - stimulated HL-7702 cells. In conclusion, GWK exerted potential therapeutic effect to protect hepatocytes from acute oxidative injury through activating the Nrf2/HO-1 and MAPKs pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Three new neo-5,10-seco-clerodane diterpenoids (1-3), four previously undescribed ethoxy/methoxy acetal analogues (4-7), one new etherified labdane diterpenoid (8), and seven known diterpenoids (9-15) were isolated from the whole plant of Schnabelia terniflora. Their structures were established on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction data, calculated electronic circular dichroism (ECD), and Mo 2 (OAc) 4 -induced circular dichroism. Compounds 2 and 3 represent the first examples of neo-5,10-seco-clerodane diterpenoids containing a 1H-pyrrole-2,5-dione and a pyrrolidine-2,5-dione moiety, respectively. A plausible biosynthetic pathway for 1-3 is proposed. All diterpenoids were evaluated for their cytotoxic activity against non-small-cell lung cancer lines (A549 and H460) and gastric cancer lines (HGC27 and AGS). Among them, 2 and 14 showed moderate cytotoxicity against four cell lines., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Metabolites produced by the genus Streptomyces are the most important resource for discovering bioactive compounds. In this study, chemical investigation on the metabolites produced by the marine-derived Streptomyces sp. ZZ735 in rice solid medium led to the isolation of eighteen compounds (1-18). Chemical structures of the isolated compounds were determined based on their HRESIMS data and the extensive NMR spectral analyses. Streptonaphthothiazines A (1), B (2), 2-(2-hydroxy-2-methylpropanoylamino)-benzoic acid (7), and streptomycinoic acids A (17), B (18) are characterized as five previously undescribed compounds. The structural backbones of streptonaphthothiazines A (1), B (2) and streptomycinoic acids A (17), B (18) are found from a natural resource for the first time. It is also the first report of 2-(2-methylpropanoylamino)-benzoic acid (3), 2-(2-methylpropanoylamino)-benzamide (4), methyl 2-(3-hydroxypropanoylamino)-benzoate (5), 2-propionylaminobenzamide (6), and (2E)-3-(3-hydroxy-4,5-dimethoxyphenyl)-2-propenoic acid (15) as natural products. Streptonaphthothiazines A (1), B (2) and streptomycinoic acids A (17), B (18) have antiproliferative activity against human glioma U87MG or U251 cells with IC 50 values ranging from 31.8 to 37.9 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1-5), together with eighteen known triterpenoid saponins (6-23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-β-d-glucose moiety from Panax species. Compounds 1-4, 7, 10, 12, 21-22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two new heptapeptides, [1-7-NαC]-crocaorbs A1 (1) and A2 (2), were isolated from the latex of Croton campanulatus. Their structures were determined using NMR spectroscopic techniques, ESI-HRMS data, Marfey's method, and further refined using molecular dynamics with simulated annealing (MD/SA). Molecular dynamics calculations of peptides 1 and 2 demonstrated greater stability in simulations using a biological solvent compared to those using DMSO. Compound 1, the most abundant peptide in latex, was assessed for NO production, antiplasmodial and cytotoxicity activities. The peptide significantly increased nitric oxide (NO) production at concentrations of 40, 20 or 10 μM (17.932 ± 1.1, 18.270 ± 0.9, 18.499 ± 0.7, respectively). Its antiplasmodial activity exhibited limited efficacy, with only 5% inhibition of Plasmodium falciparum 3D7 growth at a concentration of 50 μM. Also, it exhibited no cytotoxic effects in the J774A.1 murine macrophages cell line. This study represents the first report of a phytochemical investigation of the species C. campanulatus, which showed orbitides with distinctive sequences in contrast to other peptides described for the genus Croton and contributes to the study of structural diversity within this particular class of compounds., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carbon‑carbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid β (Aβ)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aβ-induced neuronal damage., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The phytochemical investigations on the fruits of Kadsura coccinea led to the isolation of six undescribed dibenzocyclooctadiene lignans named kadcolignans B-G, together with eleven previously described analogues. The structures of these compounds were established by spectroscopic methods including NMR, HRESIMS, and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity by measuring the levels of triglyceride (TG), total cholesterol (TC), and reactive oxygen species (ROS) in FFA-induced HepG2 cells. As a result, compounds 4, 5, 9, 13, and 15 showed potent inhibitory effects on hepatocyte lipid accumulation at a concentration of 100 μM. Our research not only broadens the understanding on the chemical composition of K. coccinea but also provides experimental and theoretical evidences supporting the fruit's active ingredients in alleviating nonalcoholic fatty liver disease (NAFLD)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four undescribed butanolides, linderangolides A-D (1-4), along with four known congeners, lincomolide A (5), (-)-epilitsenolide C2 (6), (-)-epilitsenolide C1 (7) and litseakolide H (8), were isolated from the roots of Lindera angustifolia. The planar structures of 1-4 were elucidated based on extensive spectroscopic analyses, the relative and absolute configurations of 1-4 were determined by the NOESY spectra and the comparison of calculated and experimental ECD. The cytotoxic activities of all isolated compounds were tested, 4 showed inhibitory activity against SGC-7 cells with IC 50 value of 6.62 μM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In present study, seventeen α-nitrile substituted guaiazulene-based chalcone derivatives including twelve new were designed, synthesized, and assayed for antiviral, cytotoxicity and signal pathway activities. All derivatives showed potential antiviral activity towards influenza virus or herpes simplex virus (HSV), 7 g with the substitution of nitro group showed strong effects towards H1N1 virus at 30 μM with inhibitory rate of 66.0%, 7o with thiophene exhibited potent anti HSV-1 activities with inhibitory rate of 65.8%. Moreover, several compounds exhibited inhibitory effects on tumor cells and hypoxia-inducible factor-1 (HIF1) signaling pathways. These results showed that α-nitrile substituted guaiazulene-based chalcones offered a promising framework for the further development of new highly efficient drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lanxangia tsaoko (L. tsaoko) is a natural medicine which could be used to treat type 2 diabetes mellitus (T2DM). However, there is no systematic and comprehensive research on the its active compounds and mechanism. This study aimed to investigate the active ingredients and potential mechanism of L. tsaoko for the treatment of T2DM. The chemical constituents of L. tsaoko were identified by UPLC-Q-Exactive Orbitrap/MS. The active compounds and mechanism of L. tsaoko were predicted by network pharmacology. Then the docking modes of key components and core targets were analyzed by molecular docking. Finally, animal experiments were conducted to verify the efficacy and targets of L. tsaoko in T2DM treatment. 70 compounds from L. tsaoko were identified. We obtained 37 active components, including quercetin, genistein and kaempferol, 5 core targets were AKT1, INS, TP53, TNF and IL-6. Mainly involved in PI3K/Akt, MAPK, RAGE/AGE, HIF-1, FoxO signaling pathways. Molecular docking results showed that the L. tsaoko had good binding potential to TNF. Therefore, we took the inflammatory mechanism as the prediction target for experimental verification. Animal experiments showed that L. tsaoko could alleviated colon injury of T2DM mice, improve glucose metabolism and decrease inflammatory levels. L. tsaoko exerted therapeutic effects on T2DM through multi-component, multi-target and multi-pathway regulation. Its action mechanisms were related to PI3K/Akt, MAPK, RAGE/AGE, HIF-1 and FoxO signaling pathways. This study provided new insights for the clinical treatment of T2DM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The biological activities of plant products are extremely correlated to the constituents present in each derivate. The present research aims to obtain by gas chromatography, the chemical profile of Prunus armeniaca L. kernel volatile fractions. The evaluation of the in vitro antifungal activities of the sterilized powder and volatile fractions of the plant P. armeniaca L. kernels was performed. Diffusion in a solid medium and broth microdilution methods were applied on fungi with medical importance (dermatophytes, yeasts and Aspergillus spp.). P. armeniaca L. powder based antidermatphyte cream has been formulated. Hydro-distillation generated two volatile fractions (VF1 and VF2) and chromatographic analysis showed the presence of three compounds for VF1 (98.7 % benzaldehyde, 1.0 % benzyl alcohol and 0.3 % 1,8-cineole) and two compounds for VF2 (90.3 % benzaldehyde and 9.3 % benzyl alcohol). The 2.5 % to 5 % concentrations in powder showed antifungal activities against dermatophytic strains. 1.25 to 2 mg/mL concentrations in volatile fractions were efficient against yeast strains, with a better efficiency for the VF1. The creams formulated were stable, cosmetically attractive with satisfactory pH, viscosity and spread ability. Prunus armeniaca L. kernel powders and the cream derived from them exhibit potent antifungal activities. This work presents a simple, ecological and economical means of formulating antifungal active substances and valorizing natural products., Competing Interests: Declaration of competing interest The contributing authors declared there were no conflicts of interest in this paper. This work was completely funded by the Tunisian ministry of higher education and scientific research., (Copyright © 2024. Published by Elsevier B.V.)

Background: Apigenin, a naturally occurring compound with a flavone core structure, is known for its diverse bioactivities, including anti-inflammation, anti-toxicant, anti-cancer and so on. There has been significant interest in the medicinal chemistry community. To address these challenges, researchers have developed various derivatives of apigenin to address challenges such as poor water-solubility and low intestinal absorption, aiming to enhance the pharmacological activities and pharmacokinetic properties of this compound., Objective: In recent years, there has been a proliferation of apigenin derivatives with enhanced bioactivity. However, there is a lack of comprehensive reviews on the function-based modification of these derivatives. In this paper, we provide an overview of the apigenin derivatives with varying bioactivities and explored their structure activity relationships. And the functions of different groups of apigenin derivatives were also analyzed., Conclusion: This review summarized the current achievements that could provide some clues for further study of apigenin-based drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Three previously undescribed sesquiterpenes, along with three known ones were isolated from the seeds of Cichorium glandulosum. The structures of them were elucidated by the analysis of spectroscopic data. The isolated compounds were tested for their neuroprotective effects against LPS-induced neuroinflammation in BV-2 cells. Santamarine (5) exhibited inhibitory activity on LPS-induced NO production in BV-2 cells with IC 50 of 0.89 ± 0.12 μM. The mechanism of the compound 5 was related to activating the NF-κB, MAPK and cGAS/STING pathways., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The biotransformation of natural compounds by fungal microorganisms is a complex biochemical process. Tandem whole-cell biotransformation offers a promising, alternative, and cost-effective method for modifying of bioactive novel compounds. This approach is particularly beneficial for structurally complex natural products that are difficult to be synthesized through traditional synthetic methods. Biotransformation also provides significant regio- and stereoselectivity, making it a valuable tool for the chemical modification of natural compounds. By utilizing microbial conversion reactions, the biological activity and structural diversity of natural products can be enhanced. In this review, we have summarized 282 novel metabolites resulting from microbial transformation by various microorganisms. We discussed the chemical structures and pharmacological properties of these novel biotransformation products. The review would assist scientists working in the fields of biotechnology, organic chemistry, medicinal chemistry, and pharmacology., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Four new spirobenzylisoquinoline mucroniferanines N - Q (1-4) and a rare chlorinated isoquinoline mucroniferanine R (5) were isolated from Corydalis mucronifera Maxim. Their structures were elucidated based on extensive spectroscopic data analysis of HRESIMS, 1D and 2D NMR, and their absolute configurations were confirmed by ECD data. The isolated compounds were evaluated for acetylcholinesterase (AChE) inhibitory activities. Mucroniferanine R showed significant activities with IC 50 values of 0.78 μM compared to galanthamine (1.34 μM). The AChE inhibitory activity was further supported by the molecular docking analysis that exhibited the accommodation of mucroniferanine R in the active site of human AChE., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Polygala japonica Houtt. (P. japonica), a member of the Polygala genus in the Polygalaceae family, has been historically utilized in traditional folk medicine as an expectorant, anti-inflammatory, anti-bacterial, and anti-depressant agent. This paper systematically reviews the latest research in botany, traditional uses, phytochemistry, pharmacology, and pharmacokinetics, aiming to provide a scientific foundation for the future development and application of P. japonica and to explore its potential value comprehensively. Approximately 86 compounds have been isolated from P. japonica, with triterpenoid saponins being the most prevalent and bioactive components. Extensive pharmacological activities of P. japonica extracts or compounds have been confirmed in vivo and in vitro, including anti-inflammatory, anti-depressant, neuroprotective, anti-obesity, anti-apoptotic, and skin-protective effects. Additionally, P. japonica has demonstrated significant curative effects and relatively clear pharmacological mechanisms in treating inflammatory and nervous system diseases. Specific components of its primary triterpenoid saponins are rapidly absorbed in the body. This review advocates for deeper scientific research on P. japonica, noting that most current research remains in its early stages and many reported biological activities require further clinical validation. Despite this, the traditional medical use of P. japonica across various cultures attests to its broad application value. Presently, the pharmacological activities of P. japonica extracts and compounds provide a scientific basis for its traditional uses. Future research must ensure the safety and effectiveness of P. japonica through in-depth pharmacokinetic studies, and the establishment of a refined and standardized quality evaluation system is essential for its clinical development and application., Competing Interests: Declaration of competing interest The authors have no conflict of interest regarding the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Leading by the antiviral activities against HSV-2 virus, bioactivity-guided the fraction of crude alkaloids from seeds of Peganum harmala led to the isolation of nine structurally novel indole alkaloids, pegaharolines A - I (1-9), and 11 known ones (10-20). Compound 3 was an unusual 6/5/5/5 spirotetracyclic indole-derived alkaloids featuring a classic bicyclic indole unit fused with an additional pyrrolizine ring via a spiral atom (C-3). Compound 4 was determined as a novel indole alkaloid, characterized with a rare hexacyclic 6/5/6/5-6/6 ring system, by a single-crystal X-ray diffraction. Compounds 5 and 6 were peculiar indole dimers featuring with the rare carbon skeleton of an octacyclic scaffold. Compounds 1-6 were six racemates. Most compounds exhibited different levels of antiviral activities against HSV-2. Especially, the anti-HSV-2 activity of compound 1 (IC 50  = 0.90 ± 0.10 μM) was much better than that of the positive control (acyclovir, IC 50  = 1.12 ± 0.15 μM). In this study, the discovery of anti-HSV-2 components from the seeds of P. harmala, could benefit development and utilization of this plant in antiviral medicinal products., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Decoctions of Ferula orientalis L. (Apiaceae), have been traditionally used to lower blood glucose levels (BGLs). After in vitro enzyme inhibition tests on the dichloromethane extracts of the roots (FOD) and the methanol extract of the roots (FOM), isolation studies were carried out on the FOD extract. The anti-hyperglycemic effects of the FOD extract and the pure compounds were studied in mice using the Oral Glucose Tolerance Test (OGTT) and streptozotocin (STZ)-induced diabetes mellitus (DM) models. Molecular docking studies were performed on potent compounds in the binding pockets of enzymes α-glucosidase and α-amylase. The isolations of 11 compounds were isolated from the FOD extract, which comprised teferidine (1), ferutinin (FT) (2), teferin (3), epoxy-jaeschkeanadiol-p-hydroxybenzoate (4), epoxy-jaeschkeanadiol-6-vanillate (5), tovarol-8-angelate (6), leucoferin (7), tovarol-8-p-hydroxybenzoate (8), tovarol-8-vanillate (9), 6-β-p-hydroxybenzoyloxy-germacra-1(10),4-diene (10), and chimgin (11). Compounds 2 and 8-11 exhibited a higher inhibitory activity on α-glucosidase. In the OGTT, pretreatment with the FOD extract or compound 2 did not alter the BGLs after administration of the glucose solution compared to the control. In the STZ-induced diabetic mice model, no significant difference in the BGLs was observed with the FOD extract (200 mg/kg) or compound 2 (100 mg/kg)-treated diabetic mice compared to the diabetic control mice. The experimental studies all showed that the F. orientalis extract had significant effects on the enzyme systems involved in DM, and it would be appropriate to plan further studies on possible problems of bioavailability of the compound FT and the FOD extract, inadequate dose, and duration of administration., Competing Interests: Declaration of competing interest A part of this study was presented as an oral presentation at the 9th International Mediterranean Symposium on Medicinal and Aromatic Plants (MESMAP-9). The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The members of the genus Centaurea have a great interest in pharmaceutical and nutraceutical fields due to their biological potential. Based on this information, we aimed to evaluate the biological properties (antioxidant, enzyme inhibition and cytotoxicity) and chemical profile of the extract of Centaurea stapfiana, an unstudied species. The highest total phenolic content was found in the ethanol/water extract with 32.17 mg GAE/g. A total of 102 of them were identified by HPLC-ESI-QTOF-MS analysis. These compounds were mainly hydroxybenzoic acid and hydroxycinnamic acid as well as flavonoids. In the antioxidant tests, the ethanol/water extract had the best free radical scavenging and reducing ability. However, in the enzyme inhibition test, the ethanol extract was the most active. The extracts were also tested on two tumour cell lines (RAW 264.7 and HepG2) and one non-tumour cell line (S17). The ethanol extract showed the promising effect on HepG2 (cell viability: 28.6 % at 50 g/ml). Furthermore, we examined the interactions between the compounds and enzymatic and cellular targets. A good interaction was found between quercetin-3-xylosyl-(1- > 6)-glucoside and iNOS. In summary, our results suggest that C. stapfiana can be considered as a versatile raw material for the development of health-promoting applications in the pharmaceutical and cosmeceutical fields., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As insufficient sleep has become a widespread concern in modern society, potential sleep-improving effect of mulberry (Morus alba L.) leaf ethanol extract (MLE) and the related mechanism were investigated in the present study. According to the results, MLE could significantly shorten sleep latency by 33 %, extend sleep duration by 56 % and increase sleep ratio of mice through increasing 5-HT and GABA release in serum, hypothalamus and hippocampus. Metabonomic analysis showed that phenylalanine metabolism, arginine and proline metabolism might be the potential pathways of MLE to improve sleep. Network pharmacological and LC-MS analysis suggested that the key sleep-improving active ingredients in MLE might be luteolin, kaempferol, naringenin, morin, stigmasterol and β-sitosterol. Further molecular docking and qRT-PCR results demonstrated that the key targets for MLE to improve sleep might be MAOA, GABRA1 and GABRA2. In conclusion, MLE showed outstanding sleep-improving effect and great potential for the application as novel sleep-improving functional food., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD). Currently, there is no cure for PD, and medications can only control the progression of the disease. Various experimental studies have shown the significant efficacy of TCM in treating PD, and combination with western medicine can enhance the effects and reduce toxicity. Thus, exploring effective anti-PD compounds from TCM has become a popular research fields. This review summarizes commonly used TCM extracts and natural products for the treatment of PD, both domestically and internationally. Furthermore, it delves into various mechanisms of TCM in treating PD, such as anti-oxidative stress, anti-inflammatory, anti-apoptotic, improve mitochondrial dysfunction, inhibits α-synuclein (α-Syn) misfolding and aggregation, regulating neurotransmitters, regulates intestinal flora, enhances immunity, and so on. The results reveal that most TCMs exert their neuroprotective effects through anti-inflammatory and anti-oxidative stress actions, thereby slowing down the progression of the disease. These TCM may hold the key to improving PD therapy and have tremendous potential to be developed as novel anti-PD drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-β-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

The late-stage difunctionalization of diterpene oridonin by light-promoted direct oxyamination with various O-benzoylhydroxylamines was carried out to afford C16α-N-C17-OBz-oridonin derivatives (1-25) for the first time. Though as a radical reaction, it features high stereoselectivity to only produce C16α-N-C17-OBz-oridonins. The in vitro antiproliferative activity of these C16α-N-C17-OBz-oridonins against the human breast cancer cell lines (MCF-7) was evaluated by MTT assay, showing that most of the synthesized compounds possessed moderate anticancer activity against MCF-7 cell lines superior or similar to the parent compound oridonin. The derivative 25 with a N-methyl-N-(naphthalen-1-ylmethyl) substitution showed better cytotoxicity against MCF-7 cells (IC 50 value of 11.75 μM) than oridonin (IC 50 value of 17.95 μM)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)