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Ethnopharmacological Relevance: Justicia adhatoda L. is used as traditional medicine in Nepal to treat cough, asthma, and inflammatory disorders, and is indicated as "Asuro". Leaves are used worldwide as herbal medicine due to cardiotonic, expectorant, anti-asthmatic, and bronchodilatory properties. The aim of this work was to study the phytochemical composition of leaves of Nepalese J. adhatoda and assess their anti-inflammatory and antioxidant properties in vitro., Materials and Methods: Secondary metabolites were extracted from dried leaves using methanol (JAME: J. adhatoda methanol extract). They were analysed by means of liquid chromatography coupled with multiple-stage mass spectrometry (LC-MS n ). Anti-inflammatory potential was determined by the NF-κB and AP-1 inhibition assay, and DPPH, ABTS, and β-carotene bleaching assays were performed to assess its antioxidant properties., Results: JAME is a rich source of secondary metabolites, especially quinazoline alkaloids such as vasicine, vasicinone, vasicoline, and adhatodine. 7-Hydroxy derivatives of peganidine, vasicolinone, and adhatodine were also identified by means of MS n data and are here reported in J. adhatoda for the first time. JAME inhibited NF-κB and AP-1 expression in THP-1 cells to a greater extent than the positive control prednisolone. A moderate radical-quenching property was observed in DPPH and ABTS assays, but the anti-carotene bleaching activity was significantly higher than the reference BHT., Conclusions: To the best of our knowledge, this is the first insight into the phytochemical composition of Asuro leaves from Nepal and their bioactivity. Our results will contribute to the valorisation of this medicinal species still widely used in the traditional and complementary medicine., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

In total, 16 undescribed steroidal alkaloids (1-16), along with nine known ones (17-25), were isolated from the bulbs of Fritillaria ussuriensis Maxim. Among the undescribed compounds mentioned, compounds 1-6, 8 bearing an 16β-hydroxy substituent, as well as compounds 13 and 14 exhibited an unusual seven-membered skeleton. Their structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR (1D and 2D), and comparison with the data reported in the literature. Furthermore, all the compounds were evaluated for their anti-inflammatory effect on the NO production of LPS-stimulated RAW264.7 cells. Compounds 1, 4, 11, 15, 22 and 24 could significantly inhibit NO production with IC 50 values below 10 μM., Competing Interests: Declaration of competing interest All authors have read and approved this version of the article, and due care has been taken to ensure the integrity of the work. This article or anyone with similar content has not been submitted to any other journal. No conflict of interest exists in the submission of this manuscript., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

(±)-Hypernumqulins A-H (1-8), eight pairs of enantiomeric quinoline alkaloids fused with an isopentenyl and a germacrane-type sesquiterpenoid, featuring an unprecedented skeleton with 6/6/6/4/10 ring system, were isolated from Hypericum monogynum L. under the guidance of molecular networking strategy. Their structures including absolute configuration were elucidated by NMR spectroscopy analysis, X-ray crystallography and quantum chemical calculation. The proposed [2+2] cycloaddition may play a key biogenic step in building the unexpected skeleton. Most of the isolates exhibited cytotoxicity with IC 50 values ranging from 2.82 ± 0.03 to 45.25 ± 1.26 μM against MCF-7, A549 or SGC7901 cells. Furthermore, compounds (±)-1 and (-)-1 could induce apoptosis by upregulating the protein expression level of Bax and downregulating of Bcl-2 in MCF-7 cells. These findings provided the first example of germacrane sesquiterpene quinoline alkaloids, and supported the possibilities for the development of new anti-tumor 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. Published by Elsevier Inc.)

Eleven alkaloids including four previously undescribed oxoisoaporphine alkaloids, menisoxoisoaporphines A-D (1-4), four known analogues (5-8), and three aporphine alkaloids (9-11), were isolated and identified from the rhizomes of Menispermum dauricum. Their structures were elucidated by extensive spectroscopic data and single-crystal X-ray diffraction analyses. Among them, compounds 1 and 4 were the first samples of oxoisoaporphine with C-6 isopentylamino moiety, and 2 was a rare C-4 methylation product of oxoisoaporphine alkaloid. The in vitro anti-inflammatory activity of compounds 1-11 was performed by evaluating the inhibition of NO level in LPS-induced RAW264.7 macrophages. Among them, compound 4 exhibited the most potent NO inhibition activity with an IC 50 value of 1.95 ± 0.33 μM. The key structure-activity relationships of those oxoisoaporphine alkaloids for anti-inflammatory effects have been summarized., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Two new glucosidated indole-containing quinazoline alkaloids designated fumigatosides G (1) and H (2) were isolated from mangrove-derived fungus Aspergillus fumigatus SAl12, together with the known analogues fumigatoside B (3) and fumiquinazoline J (4). The planar structures of the new compounds were elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configurations were determined by comparison of electronic circular dichroic (ECD) spectra with that of the known compound fumigatoside B and with the calculated ECD spectrum. All these indole-quinazoline compounds were tested for anti-bacterial and cytotoxic activities.

A new alkaloid named aspergilalkaloid A ( 1 ) with pyridoindole hydroxymethyl piperazine dione structure along with six known compounds 2-7 were isolated from deep-sea derived fungus Aspergillus sp. HDN20-1401. The structure including absolute configuration was elucidated by extensive NMR analyses, HRESIMS, ECD calculation, and theoretical NMR calculation with DP4+ analysis. All isolated compounds were tested for antimicrobial and anticancer activity. Aspergilalkaloid A ( 1 ) showed inhibitive activity against Bacillus cereus with MIC value of 12.5  μ M and weak activity against MRCNS.

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC 50 value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model., Competing Interests: Declaration of competing interest The authors declare no competing financial interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A pair of atropisomers secofumitremorgins C ( 1a ) and D ( 1b ), together with fifteen known alkaloids ( 2-16 ), were isolated from a saltern-derived fungus Aspergillus fumigatus GXIMD00544. The structures of atropisomers 1a and 1b were elucidated by the detailed spectroscopic data, chemical reaction and quantum chemical calculations. Compounds 1 and 8 displayed antifungal spore germination effects against plant pathogenic fungus associated with sugarcane Fusarium sp. with inhibitory rates of 53% and 77% at the concentration of 100 µM, repectively. Atropisomers 1 also exhibited antifouling potential against Balanus amphitrite larval settlement with an inhibitory rate of 96% at the concentration of 100 µM.

A pair of epimers of flavonoid alkaloids, with a pyrrolidone moiety, 2 S ,5'' R -eupodoratin A ( 1 ), 2 S ,5'' S -eupodoratin A ( 2 ), together with two known analogues, drahebephin A ( 3 ), drahebephin B ( 4 ), were isolated from the flowers of Chromolaena odorata (L.) R.M.King & H.Rob. Their structures were elucidated on the basis of HR-ESI-MS, 1D/2D NMR spectral analyses. The absolute configuration of compounds ( 1 ) and ( 2 ) was determined by its experimental and calculated electronic circular dichroism (ECD) spectra. All compounds were isolated from the Asteraceae family for the first time. The ABTS · + scavenging activity of compound ( 4 ) reached 93.56% at a concentration of 0.5 mM, while the scavenging capacity of positive control Trolox was 55.94%. In addition, all compounds show moderate antimicrobial activity against Escherichia coli (ATCC, 337304), Staphylococcus aureus (ATCC, 337371) and Candida albicans (ATCC, 186382) with a MIC value of more than 50 µg/mL.

Two unprecedented aconitine-type C19-diterpenoid alkaloids, refractines A-B ( 1 - 2 ), along with 12 known compounds ( 3 - 14 ) were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand. -Mazz. Their structures were elucidated based on extensive spectroscopic analyses, including 1D and 2D NMR, IR, and HR-ESI-MS data. All compounds were tested for inhibitory activities against NO production in LPS induced RAW 264.7 macrophages, compounds 10 and 14 had slight inhibited NO production with rate of 29.4% and 22.1% at the concentration of 30 μM, respectively.

Chemical investigation of the Penicillium sp. SCSIO 41038 led to the isolation and characterization of one new cyclopiazonic acid-type alkaloid, speradine I ( 1 ), and one new phloroglucinol derivative, speradine J ( 8 ), along with 13 known compounds. Their structures were determined on the basis of extensive spectroscopic analysis, and by a comparison with data from the literature. All the compounds were evaluated for their antitumor (22Rv1 and PC-3) and enzyme inhibitory activity against acetylcholinesterase (AChE) in vitro .

A chemical investigation of the aerial parts of Piper sarmentosum resulted in the isolation and identification of 14 amide alkaloids, including three new amide alkaloids, pipersarmenoids A - C (1-3), three new natural amide alkaloids, pipersarmenoids D - F (4-6), and 8 known analogues, N-p-coumaroyltyramine (7), piperlotine C (8), piperlotine D (9), pellitorine (10), sarmentine (11), aurantiamide acetate (12), 1-cinnamoyl pyrrolidine (13) and sarmentamide B (14). Their structures were determined by spectroscopic analysis including HRESIMS and 1D and 2D NMR. The cytotoxicity, neuroinflammation-inhibiting and acetylcholinesterase (AChE) inhibitory activities of those compounds were tested. Compounds 1, 2 and 12 inhibited NO production induced by LPS in BV2 cells with IC 50 values of 9.36, 12.53 and 10.77 μM, respectively. Moreover, 1, 2, 7 and 11 showed moderate inhibitory activity on AChE with IC 50 values ranging from 37.56 to 48.84 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. Published by Elsevier B.V.)

The ethanol extract of the whole plant of Delphinium trichophorum Franch was subjected to a phytochemical study, leading to the isolation of ten unprecedented diterpenoid alkaloids, including nine delnudine-type C 20 -diterpenoid alkaloids named trichophodines A-I and one kusnezoline-type C 20 -diterpenoid alkaloid named trichophozine A. Additionally, seven known compounds were also identified. Their structures were elucidated on the basis of extensive spectroscopic analysis, including HSQC, HMBC, 1 H- 1 H COSY, NOESY and X-ray crystallographic analysis. Most isolated compounds were screened for inhibitory activities against LPS-induced NO production in RAW 264.7 macrophage cells and acetylcholinesterase inhibitory effects. Guan-fu base V exhibited potent inhibitory activity against acetylcholinesterase, demonstrating an inhibitory rate of 53.81% at a concentration of 40 μM., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Ltd.)

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., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Seven previously undescribed compounds, including four diketomorpholine alkaloids (1‒4), one indole diketopiperazine alkaloid (9), one chromone (10), and one benzoic acid derivative (13), and nine known compounds (5-8, 11, 12, and 14-16) were isolated from two different fungal sources. Nine of these metabolites (1-9) were obtained from a seagrass-derived Aspergillus alabamensis SYSU-6778, while the others were obtained from a mixed culture of A. alabamensis SYSU-6778 and a co-isolated fungus A. fumigatiaffinis SYSU-6786. The chemical structures of the compounds were deduced via spectroscopic techniques (including HRESIMS, 1D and 2D NMR), chemical reactions, and ECD calculations. It is worth noting that compound 10 was identified as a defensive secondary metabolite of strain SYSU-6786, produced through the induction of compound 8 under co-culture conditions. Compounds 3 and 4 possessed a naturally rare isotryptophan core. Moreover, compounds 1 and 2 exhibited potent inhibitory activities against fish pathogenic bacterium Edwardsiella ictalurid, with minimum inhibitory concentration values of 10.0 μg/mL for both 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. none., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A high throughput screen performed to identify catalytic inhibitors of the oncogenic fusion form of cAMP-dependent protein kinase A catalytic subunit alpha (J-PKAcα) found an individual fraction from an organic extract of the marine soft coral Acrozoanthus australiae as active. Bioassay-guided isolation led to the identification of a 2-amino adenine alkaloid acroamine A ( 1 ), the first secondary metabolite discovered from this genus and previously reported as a synthetic product. As a naturally occurring protein kinase inhibitor, to unambiguously assign its chemical structure using modern spectroscopic and spectrometric techniques, five N -methylated derivatives acroamines A 1 -A 5 ( 2 - 6 ) were semisynthesized. Three additional brominated congeners A 6 -A 8 ( 7 - 9 ) were also semisynthesized to investigate the structure-activity relationship of the nine compounds as J-PKAcα inhibitors. Compounds 1 - 9 were tested for J-PKAcα and wild-type PKA inhibitory activities, which were observed exclusively in acroamine A ( 1 ) and its brominated analogs ( 7 - 9 ) achieving moderate potency (IC 50 2-50 μM) while none of the N -methylated analogs exhibited kinase inhibition.

Guatteria olivacea R.E. Fries is an Amazonian species known as 'envira-bobó' and 'envira-fofa' and is common in the states of Amazonas, Acre, and Pará. Recently, the essential oil from the leaves of this species has shown promising antitumor activity both in vitro and in vivo. The presence of isoquinoline-derived alkaloids, including aporphinoids and tetrahydroprotoberberine alkaloids, has also been previously reported. In our ongoing search for bioactive compounds from Annonaceae Amazonian plants, the bark of G. olivacea was investigated via classical chromatography techniques, which revealed nine compounds, eight isoquinoline-derived alkaloids, a rare alkaloid with a α -gem-dimethyltetradehydrocularine structure known as gouregine, seven known aporphinoid alkaloids: isopiline, O -methylisopiline, melosmine, 9-hydroxyiguattescine, dihydromelosmine, lysicamine, and guattouregidine, and one known pimaradiene diterpene: acanthoic acid. All the isolated compounds were described for the first time in the bark of G. olivacea, and their structures were elucidated by extensive analyses of their 1D and 2D NMR spectra in combination with MS data. The NMR data of the alkaloids isopiline, O -methylisopiline, melosmine, dihydromelosmine, and guattouregidine were revised due to incomplete data in the literature and some ambiguities. The in vitro cytotoxic activities of the isolated compounds were evaluated against human cancer (HepG2, KG-1a, and HCT116) and noncancerous (MRC-5) cell lines via the Alamar blue assay after 72 h of incubation. Among the compounds evaluated against human cancer cell lines, the most active was the oxoaporphine alkaloid lysicamine, which has strong activity against HCT116 cells, with an IC 50 value of 6.64 µg/mL (22.79 µmol/L). Melosmine had a moderate effect on HCT116 cells, with an IC 50 value of 16.77 µg/mL (49.70 µmol/L), whereas acanthoic acid had moderate effects on HepG2 and HCT116 cells, with IC 50 values of 14.63 µg/mL (48.37 µmol/L) and 21.25 µg/mL (70.25 µmol/L), respectively.

Ethnopharmacology Relevance: Zanthoxylum bungeanum Maxim. (Z. bungeanum), a member of the Rutaceae family, has a rich history of traditional use in Asia for treating arthritis and toothache conditions. As characteristic chemical components, numerous kinds of alkaloids have been extracted from plants and their diverse biological activities have been reported. However, research on the isoquinoline alkaloid, a specific type of alkaloids, in Z. bungeanum was scarce., Aim of the Study: The study aimed to isolate a novel isoquinoline alkaloid from Z. bungeanum and explore its pharmacological activity in vitro and analgesic activity in vivo., Materials and Methods: Isoquinoline alkaloid isolation and identification from Z. bungeanum were conducted using chromatographic and spectroscopic methods. The whole-cell patch-clamp technique was applied to assess its impact on neuronal excitability, and endogenous voltage-gated potassium (Kv) and sodium (Nav) currents in acutely isolated mouse small-diameter dorsal root ganglion (DRG) neurons. Its inhibitory impacts on channels were further validated with HEK293 cells stably expressing Nav1.7 and Nav1.8, and Chinese hamster ovary (CHO) cells transiently expressing Kv2.1. The formalin inflammatory pain model was utilized to evaluate the potential analgesic activity in vivo., Results: A novel isoquinoline alkaloid named HJ-69 (N-13-(3-methoxyprop-1-yl)rutaecarpine) was isolated and identified from Z. bungeanum for the first time. HJ-69 significantly suppressed the firing frequency and amplitudes of action potentials in DRG neurons. Consistently, it state-dependently inhibited endogenous Nav currents of DRG neurons, with half maximal inhibitory concentration (IC 50 ) values of 13.06 ± 2.06 μM and 30.19 ± 2.07 μM for the inactivated and resting states, respectively. HJ-69 significantly suppressed potassium currents in DRG neurons, which notably inhibited the delayed rectifier potassium (I K ) currents (IC 50  = 6.95 ± 1.29 μM) and slightly affected the transient outward potassium (I A ) currents (IC 50  = 523.50 ± 39.16 μM). Furtherly, HJ-69 exhibited similar potencies on heterologously expressed Nav1.7, Nav1.8, and Kv2.1 channels, which correspondingly represent the main components in neurons. Notably, intraperitoneal administration of 30 mg/kg and 100 mg/kg HJ-69 significantly alleviated pain behaviors in the mouse inflammatory pain model induced by formalin., Conclusion: The study concluded that HJ-69 is a novel and active isoquinoline alkaloid, and the inhibition of Nav and Kv channels contributes to its analgesic activity. HJ-69 may be a promising prototype for future analgesic drug discovery based on the isoquinoline alkaloid., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhaobing Gao, Junli Yang, Xianhua Meng, Yueming Zheng, Tian Chai and Yin Zhang are inventors on patents pending for the use of HJ-69 to treat pain conditions (CN 202110666488.1, PCT/CN2022/098816). All other authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Dendrobium nobile Lindl. (DNL) is a well-known traditional Chinese medicine that has been recorded in the Chinese Pharmacopoeia (2020 edition). The previous data showed that Dendrobium nobile Lindl. alkaloids (DNLA) protect against CCl 4 -induced liver damage via oxidative stress reduction and mitochondrial function improvement, yet the exact regulatory signaling pathways remain undefined., Aim of the Study: The aim of the present study was to investigate the role of necroptosis in the mode of CCl 4 -induced liver injury and determine whether DNLA protects against CCl 4 -induced acute liver injury (ALI) by inhibiting mitochondrial ROS (mtROS)-mediated necroptosis., Materials and Methods: DNLA was extracted from DNL, and the content was determined using liquid chromatograph mass spectrometer (LC-MS). In vivo experiments were conducted in C57BL/6J mice. Animals were administrated with DNLA (20 mg/kg/day, ig) for 7 days, and then challenged with CCl 4 (20 μL/kg, ip). CCl 4 -induced liver injury in mice was evaluated through the assessment of biochemical indicators in mouse serum and histopathological examination of hepatic tissue using hematoxylin and eosin (H&E) staining. The protein and gene expressions were determined with western blotting and quantitative real-time PCR (RT-qPCR). Reactive oxygen species (ROS) production was detected using the fluorescent probe DCFH-DA, and mitochondrial membrane potential was evaluated using a fluorescent probe JC-1. The mtROS level was assessed using a fluorescence probe MitoSOX., Results: DNLA lessened CCl 4 -induced liver injury, evident by reduced AST and ALT levels and improved liver pathology. DNLA suppressed necroptosis by decreasing RIPK1, RIPK3, and MLKL phosphorylation, concurrently enhancing mitochondrial function. It also broke the positive feedback loop between mtROS and RIPK1/RIPK3/MLKL activation. Similar findings were observed with resveratrol and mitochondrial SOD2 overexpression, both mitigating mtROS and necroptosis. Further mechanistic studies found that DNLA inhibited the oxidation of RIPK1 and reduced its phosphorylation level, whereby lowering the phosphorylation of RIPK3 and MLKL, blocking necroptosis, and alleviating liver injury., Conclusions: This study demonstrates that DNLA inhibits the necroptosis signaling pathway by reducing mtROS mediated oxidation of RIPK1, thereby reducing the phosphorylation of RIPK1, RIPK3, and MLKL, and protecting against liver injury., 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.)

Waltheria indica (Malvaceae) is a plant popularly used in folk medicine by traditional African and indigenous communities, and in various countries worldwide, to treat general inflammation. Several biological activities of this plant have been reported, including acetylcholinesterase inhibition and potential anti-human immunodeficiency virus (HIV), antinociceptive, analgesic, antifungal, anticancer, anti-inflammatory, leishmanicidal, trypanocidal, antioxidant, and antibacterial activities. The chemical profile of Waltheria indica was assessed by dereplication analysis using UPLC-MS/MS, and data acquisition was performed using chemoinformatics tools, such as Mass Spectrometry-Data Independent AnaLysis (MS-DIAL) and MS-FINDER softwares. The preprocessed data were sent to the GNPS to build a feature-based molecular network (FBMN). Thirty-three 4-quinolone alkaloids were annotated in the extracts and fractions of stems and roots, whereas 12 were annotated in the extracts and fractions of flowers and leaves. This represents an inaugural chemical investigation study employing UPLC-Q-TOF-MS/MS analysis, along with a molecular network approach, within this species and genus., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Eight previously undescribed cevanine-type steroidal alkaloids, cirrhosinones I-N and cirrhosinols A-B, along with five known analogs, were isolated from the bulbs of Fritillaria cirrhosa D. Don. Their structures were elucidated on the basis of comprehensive analysis of HRESIMS, 1D and 2D NMR spectroscopic data, and single-crystal X-ray diffraction analyses. All compounds revealed weak NO inhibitory activities in the LPS-stimulated NR8383 cells at the concentration of 20 μM, with inhibition ratios ranging from 5.1% to 14.3%., 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 Ltd. All rights reserved.)

Lycopodiales, an order comprising 388 distinct species, is the source of Lycopodium alkaloids (LAs), a group of naturally occurring alkaloids that share a common biosynthesis and structural attributes. These remarkable organisms are considered vestiges of ancient ferns, with fossil evidence dating their existence back to an impressive 300 million years. LAs usually are tricyclic or tetracyclic compounds with C 16 N or C 16 N 2 skeleton. But then there are also have a few C 11 N, C 15 N, C 15 N 2 , C 22 N 2 , and C 27 N 3 skeleton. LAs have attracted much scientific attention because of their important biological activities related to acetylcholinesterase and unique structural characteristics. From 1881 to December 2023, there are 593 LAs from 49 species of Lycopodiales have been reported. Because the total amount of LAs is nearly five times that of 1994, the classification and group allocation of some newly isolated LAs is often challenging and not unambiguous by Ayer's simple classification. This review makes a more systematic and detailed classification for it and provides extensive coverage of naturally occurring LAs discovered from 1881 to December 2023. Until now, there is no comprehensively summary of biological activity of the LAs. This review is the first time covered the biological activity of the all LAs., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Trace natural products (TNPs) are still the vital source of drug development. However, the mining of novel TNPs is becoming increasingly challenging due to their low abundance and complex interference. A comprehensive strategy was proposed in which the functionalized magnetic particles integrated with LC-MS for TNPs discovery. Under the guidance of the approach, fifteen trace Nuphar alkaloids including seven new ones, cyanopumiline A sulfoxide (1), cyanopumiline C sulfoxide (8) and cyanopumilines A-E (4-5, 10, 12-13) featuring an undescribed nitrile-containing 6/6/5/6/6 pentacyclic ring system were isolated from the rhizomes of Nuphar pumila. Their structures and absolute configurations were determined on the basis of detailed spectroscopic data analysis and single-crystal X-ray diffraction analysis. Notably, a concise method based on 13 C NMR spectroscopy was established to determine the relative configurations of spiroatoms. Biologically, compounds 1-12 exhibited potent immunosuppressive activities with IC 50 values ranging from 0.1-12.1 μM against anti-CD3/CD28 induced human peripheral T cell proliferation. Mechanistic studies revealed that 4 could dose-dependently decrease pro-inflammatory cytokines and the expression levels of CD25 and CD71., 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 Inc. All rights reserved.)

Two previously uncharacterized compounds, an aconitine-type C 19 -diterpenoid alkaloid (1) and a napelline-type diterpenoid alkaloid C 20 -diterpenoid alkaloid (2), as well as ten known compounds (3-12), were isolated from Aconitum pendulum. Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR, IR, HR-ESI-MS, and single-crystal X-ray diffraction analysis. The anti-insecticidal activities of these compounds were evaluated by contact toxicity tests against two-spotted spider mites, and compounds 1, 2, and 9 showed moderate contact toxicity, with LC 50 values of 0.86±0.09, 0.95±0.23, and 0.89±0.19 mg/mL, respectively. This study highlights the potential use of diterpenoid alkaloids as natural plant-derived pesticides for the management of plant pests., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

To explore the phytochemistry of the African ethnomedicinal plant Cryptolepis sanguinolenta (Lindl.) Schltr. (Apocynaceae) for rare indoloquinoline alkaloids, two novel indoloquinoline alkaloid glycosides, namely Cryptospirosanguine A ( 1 ) and B ( 2 ), were isolated from an ethanolic extract of the root. Their structures were elucidated based on spectral evidence. Furthermore, two known terpenoids were isolated from this plant for the first time.

Four new γ-lactam alkaloids, suberitolactams A-D (1-4), two new pyridine alkaloids, suberitopyridines A-B (7-8), and two known compounds (5-6) were isolated from the South China Sea sponge Pseudospongosorites suberitoides. The structures were elucidated by detailed 1D and 2D NMR experiments along with HRESIMS analysis and single crystal X-ray diffraction. Compounds 1 and 8 showed moderate to weak antiviral activity against H1 N1 virus with IC 50 values of 27.6 and 13.3 μM, respectively., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sinica resulted in the identification of forty-one Buxus alkaloids, including twenty undescribed ones, namely cyclobuxusinines A-I (1-7, 16 and 20), as well as secobuxusinines A-K (8-15 and 17-19). Their structures were delineated by detailed analysis using various spectroscopic techniques. cyclobuxusinines B (2) was the first Buxus alkaloid, whose CH 3 -18 was oxidized, implying the presence of special oxidative enzymes in this plant. Secobuxusinines C (10), D (11), and E (12), whose C-12 or C-19 have an OH group substitution, enriched the substituent pattern in Buxus alkaloid and suggested more structurally diverse alkaloids in the Buxus spp. In the assessment of their bioactivities, some of them exhibited significant cytotoxic effects on two human tumor ovarian cancer cell lines. Notably, compound 36 displayed more potent cytotoxic effect against ES2 and A2780 cell lines with the IC 50 value of 1.33 μM and 0.48 μM, respectively., 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 Ltd.)

This study carried out to investigate the anti-inflammatory and antinociceptive effect of tropane alkaloid (EB7) isolated from E. bezerrae. It evaluated the toxicity and possible involvement of ion channels in the antinociceptive effect of EB7, as well as its anti-inflammatory effect in adult zebrafish (Zfa). Docking studies with EB7 and COX-1 and 2 were also performed. The tested doses of EB7 (4, 20 and 40 mg/kg) did not show any toxic effect on Zfa during the 96h of analysis (LD50>40 mg/kg). They did not produce any alteration in the locomotor behavior of the animals. Furthermore, EB7 showed promising pharmacological effects as it prevented the nociceptive behavior induced by hypertonic saline, capsaicin, formalin and acid saline. EB7 had its analgesic effect blocked by amiloride involving the neuromodulation of ASICs in Zfa. In evaluating the anti-inflammatory activity, the edema induced by κ-carrageenan 3.5 % was reduced by the dose of 40 mg/kg of EB7 observed after the fourth hour of analysis, indicating an effect similar to that of ibuprofen. Molecular docking results indicated that EB7 exhibited better affinity energy when compared to ibuprofen control against the two evaluated targets binding at different sites in the cocrystallized COX-1 and 2 inhibitors., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Djulis ( Chenopodium formosanum Koidz ), is rich in nutrients and contains various bioactive components such as polyphenols and alkaloids. The new compound has a broad application prospect, including food additives, health products, drugs, etc. The purpose of this study was to find out new compounds from Djulis. It was found that 24 compounds including 7 phenols, 11 flavonoids, 4 plant alkaloids, 2 sterols. Among those, TCI-CF-22-S (Methyl 3,6-dihydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-23-S (Methyl 6-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-24-S (Kaempferol-3-O-b-D-apifuranosyl-(1→2)-a-L-arabinopyranoside) were isolated from djulis sources for the first time, and the structures of compounds were assigned by 1D, 2D NMR spectroscopy. TCI-CF-01(Caffeic acid), TCI-CF-02 (20-Hydroxyecdysone), TCI-CF-03 (Japonicone), TCI-CF-04 (3,4-Dihydroxyphenylacetiate), TCI-CF-05 (Quercetin-3-O-rutinoside-7-O-rhamnopyranoside), TCI-CF-06 (Guanosine), TCI-CF-07(Adenine), TCI-CF-08 (Coumaric acid) increased collagen production, and TCI-CF-03 (Japonicone), TCI-CF-04 (3,4-Dihydroxyphenylacetiate), TCI-CF-06 (Guanosine), TCI-CF-17 (Rutin), TCI-CF-20 (Protocatechuic acid) decreased advanced glycation end products (AGEs). In addition, TCI-CF-22-S (Methyl 6-hydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate), TCI-CF-23-S (Methyl 3,6-dihydroxy-2-oxo-1,2,3,4-tetrahydroquinoline-3-carboxylate) inhibited the formation of fatty oil droplets. Djulis has 24 compounds that may have various applications, including increasing collagen production and reducing advanced glycation end products and fatty oil droplets.

Research studies on plant secondary metabolites have increased over the last decades as a consequence of the growing consumer demand for natural products in pharmaceutics and therapeutics, as well as in perfumery and cosmetics. In this perspective, many Mediterranean plant species could be an appreciated source of bioactive compounds with pharmacological and health-promoting properties, including antioxidant, antimicrobial, antiviral, anti-inflammatory, and antitumor ones. Calendula officinalis and Foeniculum vulgare are commercially important plants of the Mediterranean flora, with great therapeutic use in the treatment of many disorders since ancient times, and are now listed in several world pharmacopoeias and drug agencies. The present review offers an overview of the main phytochemicals, phenols, terpenes, and alkaloids, biosynthesized in C. officinalis and F. vulgare , both species endemic to the Mediterranean region. Further, all current knowledge and scientific data on taxonomic classification, botanical description, traditional uses, pharmacological studies, and potential toxicity of both species were reported. The principal aim of this review is to point out the prospective use of C. officinalis and F. vulgare as valuable reservoirs of beneficial plant-derived products with interesting biological properties, also providing suggestions and future challenges for the full exploitation of these two Mediterranean species for human life improvement.

Co-cultivation is a powerful emerging tool for awakening biosynthetic gene clusters (BGCs) that remain transcriptionally silent under artificial culture conditions. It has recently been used increasingly extensively to study natural interactions and discover new bioactive metabolites. As a part of our project aiming at the discovery of structurally novel and biologically active natural products from mangrove endophytic fungi, an established co-culture of a strain of Phomopsis asparagi DHS-48 with another Phomopsis genus fungus DHS-11, both endophytes in mangrove Rhizophora mangle , proved to be very efficient to induce the production of new metabolites as well as to increase the yields of respective target metabolites. A detailed chemical investigation of the minor metabolites produced by the co-culture of these two titled fungal strains led to the isolation of six alkaloids ( 1 - 6 ), two sterols ( 7 , 8 ), and six polyketides ( 9 - 14 ). In addition, all the compounds except 8 and 10 , as well as three new metabolites phomopyrazine ( 1 ), phomosterol C ( 7 ), and phomopyrone E ( 9 ), were not present in discrete fungal cultures and only detected in the co-cultures. The structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations were assumed by electronic circular dichroism (ECD) calculations. Subsequently, the cytotoxic, immunosuppressive, and acetylcholinesterase inhibitory properties of all the isolated metabolites were determined in vitro. Compound 8 exhibited moderate inhibitory activity against ConA-induced T and LPS-induced B murine splenic lymphocytes, with IC 50 values of 35.75 ± 1.09 and 47.65 ± 1.21 µM, respectively.

Three Stemona alkaloids named stemotuberines A-C (1-3) with unique C 17 N frameworks, presumably formed by elimination of the C-11-C-15 lactone ring of the stichoneurine skeleton, were isolated from the roots of Stemona tuberosa. Their structures were elucidated by spectroscopic analysis, X-ray diffraction, and computational methods. Compounds 2 and 3 showed inhibition (IC 50 values of 37.1 and 23.2 μM, respectively) against LPS-induced nitric oxide production in RAW 264.7 cells. In addition, concern was expressed about the reported plant origin (S. sessilifolia) of the recently described alkaloids tuberostemonols O-R (4-7), which should be S. tuberosa. NMR calculations indicated structural misassignment of these compounds except for 6. Isolation of tuberostemonol P (5) from our material of S. tuberosa allowed for a close examination of the spectroscopic data leading to the revised structure 5a. Tuberostemonol R (7) was found to have identical 1 H and 13 C NMR data to the well-known alkaloid croomine, and therefore its structure including relative stereochemistry must be revised as 7a., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Eleven undescribed isoquinoline alkaloids (1-8, 14, 15, and 24), along with 19 analogues (9-13, 16-23, and 25-30) were isolated from the barks of Alangium salviifolium. The structures of the undescribed compounds were elucidated through the analysis of their HR-ESI-MS, 1D and 2D NMR, IR, UV, and X-ray diffraction. The absolute configuration of 8 was established via the ECD calculation. Notably, compounds 1/2 and 3/4 were two pairs of C-14 epimers. The isolated alkaloids were evaluated for their cytotoxicity against various cancer cell lines, including SGC-7901, HeLa, K562, A549, BEL-7402, HepG2, and B16, β-carboline-benzoquinolizidine (14-22) and cepheline-type (24-28) alkaloids exhibited remarkable cytotoxicity, with IC 50 values ranging from 0.01 to 48.12 μM. Remarkably, compounds 17 and 21 demonstrated greater cytotoxicity than the positive control doxorubicin hydrochloride. Furthermore, a significant proportion of these bioactive alkaloids possess a C-1' epimer configuration. The exploration of their structure-activity relationship holds promise for directing future investigations into alkaloids derived from Alangium, potentially leading to novel insights and therapeutic advancements., 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 Ltd. All rights reserved.)

Six previously undescribed prenylated indole diketopiperazine alkaloids, talaromyines A-F (1-6), were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures including absolute configurations were elucidated on the basis of comprehensive spectroscopic data including NMR, HR-ESI-MS, and electronic circular dichroism calculations, together with chemical analysis of hydrolysates. Compounds 1-5 represent the first example of spirocyclic indole diketopiperazines biosynthesized from the condensation of L-tryptophan and L-alanine. Compounds 2 and 4-5 showed selective inhibitory activities against phosphatases TCPTP and MEG2 with IC 50 value of 17.9-29.7 μM, respectively. Compounds 4-5 exhibited mild cytotoxic activities against two human cancer cell lines H1975 and HepG-2., 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 Ltd. All rights reserved.)

Huperzia serrata, belonging to the Lycopodiaceae family, has been traditionally utilized for the management of treating rheumatic numbness, arthritic pain, dysmenorrhea, and contusions. This plant is a rich source of lycopodium alkaloids, some of which have demonstrated notable cholinesterase inhibitory activity. The objective of this study was to identify lycopodium alkaloids with cholinesterase inhibitory properties from H. serrata. The structures of these alkaloids were elucidated by HRESIMS, NMR (including a 1 H- 15 N HMBC experiment), ECD methods and single-crystal X-ray diffraction. The inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were assessed using a modified Ellman's method. Consequently, sixteen lycopodium alkaloids (1-16), including ten previously undescribed ones named huperradines A-G and huperradines I-K (1-7 and 9-11), along with one previously undescribed naturally occurring compound, huperradine H (8), were isolated from H. serrata. Among these, compounds 7 and 1 exhibited potent and moderate AChE inhibition, with IC 50 values of 0.876 ± 0.039 μM and 13.125 ± 0.521 μM, respectively. Our results suggest that huperradine G (7) may be a promising lead compound for the development of new AChE inhibitors for Alzheimer's disease., 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 Ltd. All rights reserved.)

The utilization of deep eutectic solvents (DES) in sustainable extracting and separating of phytochemicals shows promising prospect. An exceptionally fast, eco-friendly, and sustainable approach was proposed for extracting bioactive compounds from Coptidis Rhizoma based on deep eutectic solvent-based ultrasound-assisted matrix solid phase dispersion (DES-UA-MSPD). Single-factor experiments and Box-Behnken design were utilized to explore the optimal extraction conditions. The analysis indicated that the acidic DES, especially betaine-acrylic acid (Bet-Aa 1:4 mol/mol) with 50% water content, was proved to be the most effective medium for the extraction of alkaloids (magnoflorine, groenlandicine, coptisine, epiberberine, berberine and palmatine) and organic acid (chlorogenic acid). With the parameters optimized, the total maximum extraction yield of alkaloids and organic acids reached 128.83 mg g -1 applying the optimal DES, which was 1.33-5.33 folds higher than conventional extraction solvents. Additionally, through microstructure analysis using scanning electron microscopy, density functional theory , and frontier molecular orbitals theory, a deeper understanding of the extraction principle was gained, and the molecular mechanism of DES synthesis and the interactions between target compounds were systematically elucidated. The sustainable and green potential of the DES-UA-MSPD method was demonstrated through Green Analytical Procedure Indexanalysis. The overall results of this investigation revealed that the proposed technology was a highly promising and sustainable alternative for effective extraction and quantification of natural 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.)

Daphmacrimines A-K (1-11) were isolated from the leaves and stems of Daphniphyllum macropodum Miq. Their structures and stereochemistries were determined by extensive techniques, including HRESIMS, NMR, ECD, IR, and single-crystal X-ray crystallography. Daphmacrimines A-D (1-4) are unprecedented Daphniphyllum alkaloids with a 2-oxazolidinone ring. Daphmacrimine I (9) contains a nitrile group, which is relatively rare in naturally occurring alkaloids. The abilities of daphmacrimines A-D and daphmacrimines G-K to enhance lysosomal biogenesis were evaluated through LysoTracker Red staining. Daphmacrimine K (11) can induce lysosomal biogenesis and promote autophagic flux., 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 Ltd.)

Herein, we describe the synthesis of the proposed structure of the caffeamide alkaloid bassiamide A. The amide moiety of bassiamide A was readily formed via an amide coupling reaction between caffeic acid and the known N-(3-aminopropyl)-3-methylbutanamide. However, the spectral data of the synthesized bassiamide A did not agree with that of a previous study. The structure of the synthesized bassiamide A was confirmed using combined two-dimensional NMR analysis. Extended analyses of the bioactivity of the synthesized bassiamide A revealed its efficacy in protecting dopaminergic neurons from MPP + -induced neurotoxicity in Caenorhabditis elegans. Additionally, treatment with bassiamide A notably ameliorated the impaired food-sensing ability and locomotion of Caenorhabditis elegans, suggesting a protective effect on the functionality of dopaminergic neurons., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

A total of twenty-two diterpenoid alkaloids, including ten unprecedented ones, namely refractines C-L, were isolated from the roots of Aconitum refractum (Finet et Gagnep.) Hand.-Mazz. Refractine C was the first example of a natural diterpenoid alkaloid wherein C-19 is linked to N position by an oxaziridine ring. Refractine L was a rare glycosidic diterpenoid alkaloid with fructofuranoside. Most of the isolated compounds obtained from a previous study were screened for their anti-inflammatory and myocardial protective activities. The autophagy-inducing effects of some of these compounds on RAW 264.7 cells were evaluated by assessing the expression of microtubule-associated protein 1 light chain 3 (LC3-II/LC3-I). Results revealed that some compounds exerted varying levels of inhibitory effects on the proliferative activity of RAW 264.7 cells., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Ltd.)

The current standard treatment for ovarian cancer consists of surgery to reduce the size of the tumor, followed by treatment with chemotherapeutic drugs, which have major side effects. Therefore, finding a new natural product drug with fewer side effects is a strategy. Delphinium brunonianum (D. brunonianum) is a traditional Tibetan medicine, mainly from southern Tibet, China, whereas the chemical constituents in this plant remain elusive. The major metabolites in the dichloromethane fraction of D. brunonianum were analyzed and purified by HPLC and various column chromatography techniques. Nine diterpenoid alkaloids (1-9) and one amide alkaloid (10) were isolated from D. brunonianum, including three novel C19-type diterpenoid alkaloids (Brunonianines D-F) (1-3). Their structures were elucidated by 1D/2D NMR, HR-ESI-MS and single-crystal X-ray diffraction analyses. All compounds were evaluated for toxicity in four tumor cell lines. Most of the compounds exhibited potent inhibitory effects on Skov-3 cell lines, with IC 50 values ranging from 2.57 to 8.05 μM. The western blotting experiment was used to further analyze the expression levels of molecules in the Bax/Bcl-2/Caspase-3 signaling pathway for compound 1. Molecular docking was performed to predict the binding modes of Brunonianine D with target proteins. In vivo experiments were also performed and evaluated in real time by monitoring the size of the Skov-3 tumor. Additionally, tumor H&E staining and the TUNEL assay used to evaluate anti-tumor effects., 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 Inc.)

Endophytic fungi is an important source for the discovery of bioactive natural compounds. A chemical investigation of the ethyl acetate extract of the endophytic fungus Schizophyllum sp. HM230 derived from stems of the herb Vincetoxicum mongolicum Maxim led to isolation of five alkaloids, including two new compounds, schizophyllins M ( 1 ) and N ( 2 ), along with three known ones ( 3 - 5 ). The planar structures of two new compounds were elucidated by extensive spectroscopic methods including MS, 1D and 2D NMR. Their absolute configurations were determined by Mosher's method and comparison of the ECD data. All the isolates were evaluated for their cytotoxicity and antioxidant activities. Compounds 1 - 4 showed middle cytotoxicity against MCF-7 cells with IC 50 values range of 68.1 ∼ 87.32 μM. Compounds 1 - 5 displayed obvious antioxidant activity with the IC 50 values range of 0.86 ∼ 5.78 mg/mL.

Sixteen alkaloid compounds were isolated from the dried rhizomes of P. zanlanscianense , including a pair of new enantiomers ( R / S )-7'-ethoxy- trans -p-couma-royltyramine ( 1a / 1b ) and 14 known compounds (2-14) isolated from this plant for the first time. The structures of new compounds were identified by IR, NMR and MS spectroscopic analysis, and their absolute configurations were determined by comparison of the experimental and calculated ECD data.

Ethnopharmacology Relevance: Lepidium meyenii Walp. (maca) has been traditionally used for centuries in the Central Andes region both as food and as medicine. In the last decades, its fertility enhancer properties have gained importance, with the majority of the scientific literature related to this topic. However, other traditional uses are less known as metabolic or infectious diseases., Aim of the Study: The main purpose of this study is to investigate the anti-infectious activity of L. meyenii, specifically in HIV-1 infection. There are previous reports of the transcriptional related activity of L. meyenii extracts in human T lymphocytes via transcription factors as NF-κB. Since T lymphocytes are the main target of HIV-1 infection and NF-κB is strongly involved in HIV-1 transcription, L. meyenii could display antiviral activity., Material and Methods: Chromatography and spectroscopy techniques were used to isolate and identify the compounds in the active extracts. An antiviral assay system based on recombinant viruses was used to evaluate the anti-HIV activity. Cell toxicity was tested for all the extracts and compounds. Viral entry was studied using VSV-HIV chimera viruses and reverse transcription and viral integration were studied by qPCR of viral DNA in infected cells. Finally, viral transcription was studied in primary lymphocytes transfected with HIV-1 or NF-κB luciferase reporter plasmids., Results: n-Hexane extracts of purple maca displayed anti-HIV activity in an in vitro assay. A bioassay-guided fractionation led to the identification of three thiadiazole alkaloids with antiviral activity. All the compounds were able to inhibit HIV infection of MT-2 cell lines and primary lymphocytes (PBMCs) with IC 50 values in the low micromolar range. The mechanism of action differs between the three compounds: one of them showed activity on viral entry, and all the three compounds inhibited viral integration at low concentrations. Remarkably, none of the compounds inhibited reverse transcription or viral transcription., Conclusions: n-Hexane extracts of the purple ecotype of L. meyenii inhibit HIV-1 infection in vitro and three active thiadiazole alkaloids were isolated acting mainly on viral integration and viral entry., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:L.A.T., J.A.G., J.A. P.B and L.M.B. participate as inventors in a patent application involving the antiviral activity of maca and thiadiazole compounds., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.7 macrophages., 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 Ltd. All rights reserved.)

Ethnopharmacological Relevance: Dendrobium crepidatum Lindl. ex Paxton is a perennial epiphyte of Dendrobium genus, distributed in southern China, and utilized as the traditional Chinese medicine "Shihu" in Yunnan Province. Due to its heat-clearing and detoxicating properties, it is formulated as the "XiaoCuoWan" as recorded in the China Pharmacopoeia, and specially used to treat chronic skin inflammatory diseases, such as acne., Aim of the Study: This research aimed to estimate impact of the octahydroindoline alkaloid Homocrepidine A (HCA), isolated from D. crepidatum, on acne inflammation using both human THP-1 cells and mouse models. Furthermore, the potential anti-inflammatory mechanism of HCA has been analyzed through molecular biology methods and computer simulation., Materials and Methods: THP-1 cells and mouse models induced by live Propionibacterium acnes (P. acnes) were employed to evaluate the anti-inflammatory properties of crude extract of D. crepidatum (DCE) and HCA. ELISA was utilized to detect the release of inflammatory cytokines in both cellular and murine ear tissues. RNAseq was used to screen the pathways associated with HCA-mediated inflammatory inhibition, while Western blot, RT-qPCR, and immunofluorescence were utilized to detect the expression of relevant proteins. Additionally, molecular docking simulations and cellular thermal shift assays were employed to confirm the target of HCA., Results: Our research shows that DCE and HCA can effectively alleviate acne inflammation. HCA inhibits TLR2 expression by interacting with amino acid residues in the TIR domain of hTLR2, including Pro-681, Asn-688, Trp-684, and Ile-685. Moreover, HCA disrupts inflammatory signal transduction mediated by MAPK and NF-κB pathways through MyD88-dependent pathway. Additionally, HCA treatment facilitates Nrf2 nuclear translocation and upregulates HO-1 expression, thereby inhibiting NLRP3 inflammasomes activation. In vivo experiments further revealed that HCA markedly attenuated erythema and swelling caused by P. acnes in mice ears, while also decreasing the expression of pro-inflammatory cytokines IL-1β and IL-8., Conclusions: Our research highlights the protective effects of D. crepidatum and its bioactive compound HCA against acne inflammation, marking the first exploration of its potential in this context. The discoveries indicate that HCA treatment may represent a promising functional approach for acne therapy., 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.)

Ethnopharmacological Relevance: Parkinson's disease (PD) is the second most common neurodegenerative disorder with limited therapeutic options available. Neuroinflammation plays an important role in the occurrence and development of PD. Alkaloids extracted from Uncaria rhynchophylla (URA), have emerged as a potential neuroprotective agent because of its anti-inflammatory and anti-oxidant properties. Nevertheless, the underlying mechanism by which URA exerts neuroprotective effects in PD remains obscure., Aim of the Study: The main aim of this study was to investigate the neuroprotective effects and underlying mechanism of URA in the treatment of PD through in vivo and in vitro models, focusing on the neuroinflammation and oxidative stress pathways., Materials and Methods: The protective effects of URA against PD were evaluated by neurobehavioral tests, immunohistochemistry, serum biochemical assays, and real-time quantitative polymerase chain reaction in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mice. The role of the TLR4/NF-κB/NLRP3 pathway and the Nrf2/HO-1 pathway in URA-mediated effects was examined in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells and a microglia-neuron coculture system., Results: URA significantly alleviated motor deficits and dopaminergic neurotoxicity, and reversed the abnormal secretion of inflammatory and oxidative stress factors in the serum of MPTP-induced mice. URA suppressed the gene expression of Toll-like receptor 4 (TLR4), NOD-like receptor protein 3, and cyclooxygenase 2 (COX2) in the striatum of PD mice. Further studies indicated that URA inhibited activation of the TLR4/NF-κB/NLRP3 pathway and enhanced activation of the Nrf2/HO-1 pathway, reduced reactive oxygen species (ROS) production, and reversed the secretion of inflammatory mediators in LPS-stimulated BV-2 microglial cells, thereby alleviating neuroinflammatory damage to SH-SY5Y neuronal cells., Conclusion: URA exerted neuroprotective effects against PD mainly by the inhibition of the TLR4/NF-κB/NLRP3 pathway and activation of the Nrf2/HO-1 antioxidant pathway, highlighting URA as a promising candidate for PD treatment., 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.)

Ethnopharmacological Relevance: Snakebite envenomation (SBE) is the world's most lethal neglected tropical disease. Bothrops jararaca is the species that causes the greatest number of SBEs in the South and Southeastern of Brazil. The main symptoms are local (inflammation, edema, hemorrhage, and myonecrosis) and systemic (hemorrhage, hemostatic alterations with consumptive coagulopathy, and death) effects. Species of the genus Siparuna, Siparunaceae, are used in folk and traditional medicine to treat SBE. However, limited information is available concerning Brazilian Siparuna species against SBE., Aim of the Study: To investigate the correlation between the compounds present in the extracts of five Siparuna species as potential agents against proteolytic activity, plasma coagulation, and phospholipase A 2 (PLA 2 ) activity caused by B. jararaca venom, using data obtained by UHPLC-MS/MS, biological activity, and multivariate statistics., Materials and Methods: The ethanol extracts from leaves of S. ficoides, S. decipiens, S. glycycarpa, S. reginae, and S. cymosa were fractionated by liquid-liquid extraction using different solvents of increasing polarity (hexane, dichloromethane, ethyl acetate, and n-butanol), affording their respective extracts, totaling 25 samples that were assayed through in vitro plasma coagulation and proteolytic activity assays. Moreover, the extracts were analyzed by UHPLC-MS/MS, using electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI) in negative and positive ionization modes. The data was processed in MZmine v. 2.53 and evaluated by multivariate statistical tests (PLS) using the software UnscramblerX v. 10.4. These data were also used to build molecular networks (GNPS), and some ions of interest could be annotated using the library of molecules on the GNPS platform., Results: A total of 19 extracts inhibited B. jararaca-induced plasma coagulation, with emphasis on S. cymosa and S. reginae (800 s). The inhibition of the proteolytic activity was also promising, ranging from 16% (S. glycycarpa) to 99% (S. cymosa, S. decipiens, and S. reginae). In addition, most extracts from S. cymosa and S. reginae inhibited 70-90% of PLA 2 activity. Based on data from positive mode APCI analyses, it was possible to obtain a statistic model with reliable predictive capacity which exhibited an average R 2 of 0.95 and a Q 2 of 0.88, indicating a robust fit. This process revealed five ions, identified as the alkaloids: coclaurine (1), stepholidine (2) O-methylisopiline (3), nornantenine (4) and laurolitsine (5). This is the first study to evidence the potential antivenom of alkaloids from Siparuna species., Conclusions: Altogether, our results give support to the popular use of Siparuna extracts in SBE accidents, suggesting their potential as an alternative or complementary strategy against envenoming by B. jararaca venom. The predicted ions in the chemometric analysis for the assayed activities can also be correlated with the blocking activity and encourage the continuation of this study for possible isolation and testing of individual compounds on the used models., 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.)

Cephalostatins and ritterazines represent fascinating classes of dimeric marine derived steroidal alkaloids with unique chemical structures and promising biological activities. Originally isolated from marine tube worms and the tunicate Ritterella tokioka collected off the coast of Japan, cephalostatins and ritterazines display potent anticancer effects by inducing apoptosis, disrupting cell cycle progression, and targeting multiple molecular pathways. This review covers the chemistry and bioactivities of 45 cephalostatins and ritterazines from 1988 to 2024, highlighting their complex structures and medicinal contributions. With insights into their structure activity relationships (SAR). Key structural elements, such as the pyrazine ring and 5/6 spiroketal moieties, are found crucial for their biological effects, suggesting interactions with lipid membranes or hydrophobic protein domains. Additionally, the formation of oxocarbenium ions from spiroketal cleavage may enhance their potency by covalently modifying DNA. The pharmacokinetics, ADMET and Drug likeness properties of these steroidal alkaloids are thoroughly addressed. Drug likeness analysis shows that these compounds fit well with the Rule of 4 (Ro4) for Protein-Protein Interaction Drugs (PPIDs), underscoring their potential in this area. Ten compounds (20, 27, 33, 34, 39, 40, 41, 42, 43, and 45) have demonstrated favourable pharmacokinetic and ADMET profiles, making them promising candidates for further research. Future efforts should focus on alternative administration routes, structural modifications, and innovative delivery systems, such as prodrugs and nanoparticles, to improve bioavailability and therapeutic effects. Advances in synthetic chemistry, mechanistic insights, and interdisciplinary collaborations will be essential for translating cephalostatins and ritterazines into effective anticancer therapies., 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 Inc. All rights reserved.)

Tuberculosis remains a significant global health pandemic. There is an urgent need for new anti-tubercular agents to combat the rising incidence of drug resistance and to offer effective and additive therapeutic options. High-throughput screening of a subset of the NatureBank marine fraction library ( n = 2000) identified a sample derived from an Australian marine sponge belonging to the order Haplosclerida that displayed promising anti-mycobacterial activity. Bioassay-guided fractionation of the organic extract from this Haplosclerida sponge led to the purification of previously identified antimicrobial pyrrole alkaloids, axinellamines A ( 1 ) and B ( 2 ). The axinellamine compounds were found to have a 90% minimum inhibitory concentration (MIC 90 ) of 18 µM and 15 µM, respectively. The removal of protein and complex carbon sources reduced the MIC 90 of 1 and 2 to 0.6 and 0.8 µM, respectively. The axinellamines were not toxic to mammalian cells at 25 µM and significantly reduced the intracellular bacterial load by >5-fold. These data demonstrate that axinellamines A and B are effective anti-tubercular agents and promising targets for future medicinal chemistry efforts.