23 October 2025, Volume 15 Issue 5

    

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REVIEW
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  Review on NMR spectroscopic data and recent analytical methods of aristolochic acids and derivatives in Aristolochia herbs

  Phan Minh Giang, Nguyen Nghia Vu, Vu Thanh Loc, Dong Ngoc Phuc, Ngiem Duc Trong, To Phuong Linh, Tran Thi Thu Thuy

  Natural Products and Bioprospecting. 2025, 15(5): 41-41. https://doi.org/10.1007/s13659-025-00506-x

  Abstract ( 24) Download PDF ( 29 ) HTML   Knowledge map   Save

  Aristolochic acids (AAs) are an important group of secondary metabolites in the genus Aristolochia. The presence of aristolochic acids infers the potency of many Aristolochia herbs used for ages in traditional medicine of China, Europe, Central America, India, and some other countries. Although being moderately cytotoxic, intake of AAs is associated with serious health problems, such as nephrotoxicity and carcinogenicity. Analyzing AAs in Aristolochia herbs is crucial for regulating their efficacy and toxicity because phytochemistry works have shown the occurrence of AAs in almost all Aristolochia herbs studied. Using two-dimensional parameters, chemical shifts and coupling constants, NMR spectroscopy is a modern, accurate, and reliable method in the analysis of secondary metabolites. Comparing experimental spectroscopic data with those of known and related compounds helps simplify the structural identification of secondary metabolites. The compilation of an NMR database of AAs from scattered sources would also be useful in NMR-based metabolomics. The present review provides updated information on sources and NMR spectroscopic data of 54 aristolochic acid derivatives, including AAs and their methyl esters, denitroaristolochic acids and their derivatives, and sesqui- and diterpene esters of AAs. The report also covers the newest development of analytical and preparative methods used in separation, identification, and quantification of AAs in Aristolochia herbal samples.
ORIGINAL ARTICLE
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  Bioprospecting cultivable bacteria associated with deep sea (mesopelagic) fish of the North Atlantic Ocean

  Ernest Oppong-Danquah, Jana Heumann, Hannah Moosbauer, Martina Blümel, Arlette Wenzel-Storjohann, Deniz Tasdemir

  Natural Products and Bioprospecting. 2025, 15(5): 42-42. https://doi.org/10.1007/s13659-025-00527-6

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  The microbiota associated with fish is increasingly recognized as a valuable source of bioactive metabolites for pharmaceutical application. The mesopelagic zone, a deep and unique ecosystem with a diverse biological community, is among the least studied marine environments. This study explored the potential of cultivable microbiota associated mainly with mesopelagic fish for pharmaceutical and agricultural applications. We isolated and identified 643 cultivable bacteria predominantly from various organs of fish collected from the mesopelagic zone of the North Atlantic Ocean, with additional samples from jellyfish, squid and krill. The bacterial community was dominated by the Gram-negative phylum Pseudomonadota, particularly the genera Psychrobacter, Pseudoalteromonas and Vibrio. A total of 394 bacterial isolates were selected and cultured in two growth media. Microbial extracts (590) were assessed for their anticancer and antimicrobial activities against human and fish pathogens. Over 60% of extracts exhibited activity against two ESKAPE pathogens methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium, as well as the fish pathogen Lactococcus garvieae, highlighting their antimicrobial potential. We used an LC-MS/MS-based computational untargeted metabolomics and cutting-edge cheminformatics tools as well as manual dereplication strategies to chemically profile 26 most active extracts, and annotated compound classes such as bile acids, diketopiperazines, indole alkaloids and lipids. Many peak ions remained unannotated, suggesting the presence of new bioactive molecular families. These findings highlight the bioprospecting potential of cultivable bacteria associated with mesopelagic fauna.
REVIEWS
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  Exploring the antineoplastic potential of α-mangostin in breast cancer

  Daniela Amador-Martínez, Mizraim Flores, Rafael Vargas-Castro, Rocío García-Becerra, Euclides Avila, Lorenza Díaz, Janice García-Quiroz

  Natural Products and Bioprospecting. 2025, 15(5): 43-43. https://doi.org/10.1007/s13659-025-00528-5

  Abstract ( 24) Download PDF ( 17 ) HTML   Knowledge map   Save

  Among women, breast cancer is the most frequently diagnosed cancer and the leading cause of cancer-related mortality globally. Despite improvements in early detection and diagnosis, some risk factors have been on the rise, including the decline in birth rate, the use of oral contraceptives, and the escalation in alcohol consumption and obesity. Thus, there is an imperative urgent need to expand accessible prevention and treatment options for breast cancer. Regarding these tumors, several natural compounds have shown efficacy in slowing or preventing their progression, offering a promising therapeutic alternative. Among these, α-mangostin, a xanthone derived from mangosteen, has demonstrated promising antitumor effects against different malignancies, particularly breast cancer. The mechanisms involved in α-mangostin′s therapeutic effects include downregulation of oncogenic ion channels, modulation of cell cycle progression, suppression of oncogene expression, and interference with steroid and growth factor receptors signaling. This review thoroughly explores these mechanisms, as well as updates information on α-mangostin chemical structure and its potential as a coadjuvant to conventional breast cancer therapies. Furthermore, we provide scientifically supported insights for the development of clinically applicable α-mangostin-based treatments, highlighting the robust body of evidence supporting its cancer-fighting properties, despite the absence of clinical studies to date.
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  Unlocking potent anti-tuberculosis natural products through structure–activity relationship analysis

  Delfly Booby Abdjul, Fitri Budiyanto, Joko Tri Wibowo, Tutik Murniasih, Siti Irma Rahmawati, Dwi Wahyu Indriani, Masteria Yunovilsa Putra, Asep Bayu

  Natural Products and Bioprospecting. 2025, 15(5): 44-44. https://doi.org/10.1007/s13659-025-00529-4

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  Tuberculosis (TB) remains a world health problem due to the high number of affected individuals, high mortality rates, prolonged treatment durations, and the increasing prevalence of resistance to commercial TB drugs. The emergence of resistance to anti-TB drugs has necessitated urgent research into drug discovery and development, focusing on novel mechanisms of action against Mycobacterium tuberculosis resistant strains. Natural products, with their remarkable structural diversity and bioactivity, are promising sources for the development of new TB drugs or the identification of potential chemical scaffolds exhibiting potent and novel biological activity with minimal or no cytotoxicity to host cells. This review focuses on potent anti-TB natural products with minimum inhibitory concentration (MIC) values below 5 μg mL^-1 and examines their structure-activity relationship (SAR). Significant characteristics and relevant biological properties of each compound were analysed using a Random Forest, machine learning algorithm, to explore SAR. Using molecular docking, AutoDock Vina was utilised to assess molecular interactions with protein targets, and predictive accuracy was enhanced using the XGBoost machine learning model. These analyses provide insights into the mode of action of these compounds and help identify key structural features contributing to their anti-TB activity. In addition, this review examines the correlation between the potency of selected anti-TB compounds and their cytotoxicity, offering valuable insights for the identification of promising scaffolds in TB drug discovery.
ORIGINAL ARTICLES
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  Chemoprofiling of Himantoglossum robertianum (Loisel.) P. Delforge leaves reveals predominance of gastrodigenin and structurally related compounds

  Ilaria Chiocchio, Antonio De Agostini, Manuela Mandrone, Pierluigi Cortis, Clarissa Tarozzi, Ferruccio Poli, Cinzia Sanna

  Natural Products and Bioprospecting. 2025, 15(5): 45-45. https://doi.org/10.1007/s13659-025-00526-7

  Abstract ( 22) Download PDF ( 13 ) HTML   Knowledge map   Save

  PurposeThe purpose of this study was to phytochemically profile Himantoglossum robertianum leaves. In fact, despite its wide distribution and its use in traditional medicine, this orchid is still understudied and little is known about its phytochemicals.MethodsThe analyses were performed by ¹H NMR fingerprinting, elucidated by further 2D NMR and UHPLC-MS experiments. Both primary and secondary metabolites were qualified and quantified. The study was carried out comparing six natural populations by metabolomics approach, allowing further considerations on the influence of the environment on the concentration of metabolites.ResultsThis work brings to light a surprising phytochemical parallel between H. robertianum and the medicinal orchid Gastrodia elata. In fact, the most abundant specialized metabolites resulted: gastrodigenin, gastrodin, bis(4-hydroxybenzyl)ether, parishin A, parishin C, and parishin E. Interestingly, these metabolites are all known for their potential in the treatment of neurological disorders and are, indeed, the active principles of Gastrodia elata, an important orchid used in Traditional Chinese Medicine. The active metabolites were present in all the natural populations, where only slight variations in their concentration were revealed.ConclusionMapping the metabolome of H. robertianum leaves has provided new insights into the study of orchids, including diagnostic signals for rapid identification of gastrodigenin-like compounds directly from the ¹H NMR profile of a crude extract. From a bioprospecting perspective, finding active metabolites in leaves makes the plant source more valuable than the perennial hypogeal organs that are usually the herbal drug of orchids (i.e. G. elata).
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  Novel polycyclic meroterpenoids with protein tyrosine phosphatase 1B inhibitory activity isolated from desert-derived fungi Talaromyces sp. HMT-8

  Xin-yi Zhai, Jin-jie Liu, Cui-duan Wang, Yi-fan Dou, Jian-hua Lv, Li-an Wang, Jin-xiu Zhang, Zhuang Li

  Natural Products and Bioprospecting. 2025, 15(5): 46-46. https://doi.org/10.1007/s13659-025-00530-x

  Abstract ( 21) Download PDF ( 18 ) HTML   Knowledge map   Save

  Seven previously undescribed polycyclic meroterpenoids talarines K-Q (1-7), along with five known ones (8-12), were isolated from desert-derived fungi Talaromyces sp. HMT-8. The structure of the novel compounds were elucidated using spectroscopic methods, including electronic circular dichroism (ECD), HRESIMS and nuclear magnetic resonance (NMR) spectroscopy. Among the isolated meroterpenoids, compounds 3, 5, and 7 exhibited rare chlorine substitution patterns. Halogenation, particularly chlorination, is uncommon in natural meroterpenoids and implies the involvement of halogenase enzymes during biosynthesis. Compounds 1-12 were evaluated for their inhibitory activity against protein tyrosine phosphatase 1B (PTP1B). Compounds 1-4 and 12 exhibited inhibitory activity against PTP1B with IC₅₀ values ranging from 1.74 to 17.60 μM. Among them, compounds 2 and 12 displayed significant inhibitory effects with an IC₅₀ value of 1.74 and 3.03 μM, respectively. Furthermore, Molecular docking analysis revealed that compounds 2 and 12 bind tightly to the catalytic site of PTP1B, forming key hydrogen bonding and hydrophobic interactions. Enzyme kinetics studies further demonstrated that both compounds act as competitive inhibitor.
REVIEW
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  Nitrogen-containing secondary metabolites from Meliaceae Family and their biological activity: a review

  Ni Wayan Martiningsih, Siska Elisahbet Sinaga, Wahyu Safriansyah, Unang Supratman, Desi Harneti

  Natural Products and Bioprospecting. 2025, 15(5): 47-47. https://doi.org/10.1007/s13659-025-00531-w

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  The Meliaceae family, widely distributed in tropical and subtropical regions, has been traditionally used for medicinal purposes, particularly in treating infections and inflammatory diseases. The objective of this study is to provide a comprehensive account of the nitrogen-containing secondary metabolites and their biological activities that have been isolated from the Meliaceae family between the years 1979 and 2024. Studies on nitrogen-containing compounds of the Meliaceae family were collected and analyzed using data from SciFinder, PubMed, Google Scholar, Scopus and World Flora Online. Over the course of more than four decades, numerous studies have been conducted on a variety of plant parts, including twigs, stems, barks, roots, fruits, seeds, and leaves. These studies have identified approximately 326 compounds belonging to diverse chemical groups, such as alkaloids, limonoids, triterpenoids, and nitrogen-containing flavaglines being the largest group of natural products, comprising 118 compounds (36.2%). Several compounds have been evaluated for insecticidal, anti-inflammatory, molluscicide, antibacterial, antimalarial, tyrosinase inhibition, osteoclast differentiation inhibition, and α-glucosidase inhibition activity. The systematic classification and analysis of these compounds provide insights into their biosynthesis and bioactivities, paving the way for future drug development.
ORIGINAL ARTICLES
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  Novel peptaibiotics identified from Trichoderma clade Viride

  Tamás Marik, Bonaya Gufu, Anusha Vishwanathula, Dóra Balázs, Ákos Rozsnyói, Gergő Terna, Fanni Kovács, Sándor Kocsubé, Mónika Varga, András Szekeres, Irina S. Druzhinina, Csaba Vágvölgyi, Tamás Papp, Chetna Tyagi, László Kredics

  Natural Products and Bioprospecting. 2025, 15(5): 48-48. https://doi.org/10.1007/s13659-025-00524-9

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  This study focuses on the peptaibiome produced by different species of Trichoderma belonging to clade Viride: T. koningii SZMC 28387 (CBS 979.70), T. cf. strigosellum SZMC 28007 (TUCIM 4886/IQ 191), T. cf. dorothopsis SZMC 28390 (TUCIM 416/TUB F-597), T. cf. strigosellum SZMC 28391 (TUCIM 423/DAOM 230018), T. atroviride SZMC 28748 (IMI 206040), T. hamatum SZMC 28747 (TUCIM 2730) and T. cf. dorothopsis SZMC 28005 (TUCIM 4882/IQ 11). We were able to identify new compounds with similarity to already known groups of peptaibiotics, as well as completely newly discovered compounds using high-performance liquid chromatography (HPLC) -mass spectrometry (MS). From the 367 peptaibiotics identified, 216 are peptaibols and 111 are lipopeptaibols. Out of all peptaibols, 55 are previously known, while 161 are newly discovered. The new peptaibol subgroups Strigosellin A, B and Dorothopsin A, B are introduced. Furthermore, besides 38 previously known lipopeptaibols, 73 new lipopeptaibol sequences, named Lipostrigosellins and Lipohamatins are also reported. In addition, 41 peptaibol-like compounds with unusual C-terminus were also found. Out of the 7 strains examined, 5 produced both peptaibols and lipopeptaibols, while 2 only peptaibols. The well-known compound, Trikoningin KA V (TRK-V) also produced by T. koningii SZMC 28387 (CBS 979.70), was studied for its folding dynamics using accelerated molecular dynamics simulations (aMD) for understanding the plausible three-dimensional structures adopted by these peptaibols of clade Viride. We observed a propensity to form kinked, right-handed helical structures when simulated in an aqueous environment.
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  Initial shoot regeneration in the selenium hyperaccumulator Neptunia amplexicaulis and in vitro test system for selenium tolerance and accumulation

  Bennet Buhmann, Jeroen van der Woude, Traud Winkelmann, Antony van der Ent

  Natural Products and Bioprospecting. 2025, 15(5): 49-49. https://doi.org/10.1007/s13659-025-00532-9

  Abstract ( 14) Download PDF ( 15 ) HTML   Knowledge map   Save

  The trace element selenium is essential for human nutrition but is distributed unevenly in soils worldwide with extensive selenium-deficient regions and selenium-enriched (seleniferous) areas. Neptunia amplexicaulis is one of the strongest selenium hyperaccumulator plants known and native to Australian seleniferous soils. Research in the genetic background of the selenium accumulation and tolerance mechanisms of this species lacks biotechnological and molecular tools for functional genetics. Therefore, this study aimed to develop a de novo shoot regeneration protocol for N. amplexicaulis and validate an selenium accumulation test system. Callus was induced on root and hypocotyl explants excised from 5-day old seedlings and cultured on an adjusted MS medium (SIM9) containing 4.5 μM Thidiazuron (TDZ) for two weeks in darkness. After this period, the TDZ concentration was reduced to 0.45 μM, and the explants were transferred to light conditions. In addition, seedlings of N. amplexicaulis, N. heliophila and Medicago truncatula were placed on vertical MS agar plates containing 1.5 mM (standard) or 0.1 mM (low) magnesium sulphate with 0, 30, 90 μM sodium selenate. Initial shoot differentiation was observed 6 weeks after culture initiation. This regeneration response was successfully repeated in a second experiment. The outgrow of the shoot buds into complete shoots was not yet achieved but requires additional media optimization. Additionally, spontaneous shoot regeneration from a root was observed, highlighting potential for further studies. In vitro grown seedlings demonstrated efficient, selective selenium uptake in N. amplexicaulis and identified M. truncatula as a secondary selenium accumulator with selenium concentrations of > 300 μg Se g^-1 DM. This project presents the first protocol for inducing early stages of development of indirect shoot organogenesis in N. amplexicaulis from hypocotyl and root explants as prerequisite for genetic transformation, though completing the regeneration cycle remains challenging. Neptunia amplexicaulis hyperaccumulates selenium also under in vitro conditions.
REVIEW
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  Ginkgetin from Ginkgo biloba: mechanistic insights into anticancer efficacy

  Bei Xiong, Jin-Jian Lu, Hongwei Guo, Mingqing Huang, Ting Li

  Natural Products and Bioprospecting. 2025, 15(5): 50-50. https://doi.org/10.1007/s13659-025-00535-6

  Abstract ( 23) Download PDF ( 12 ) HTML   Knowledge map   Save

  The extraction of anticancer agents from medicinal plants represents a highly promising research frontier. Ginkgetin, a natural biflavone, is one of the effective pharmacological components of Ginkgo biloba leaves (GBLs). This natural product exhibits significant anti-cancer efficacy against a variety of cancer cells in vitro and demonstrates a potent inhibitory impact on tumor growth in vivo without severe toxicity. Additionally, ginkgetin synergizes with chemotherapy drugs or adjuvant therapies to potentiate antitumor effects and reduce side effects. These compelling findings underscore Ginkgetin's potential as a promising candidate for novel anti-cancer therapeutics. Therefore, this review systematically summarizes the remarkable anticancer effects of ginkgetin and elucidates its multifaceted anticancer mechanisms, including inducing cell cycle arrest, triggering programmed cell death, and preventing invasion and angiogenesis. From a molecular mechanism perspective, ginkgetin exerts anti-cancer activity by modulating critical signaling pathways (e.g. JAK/STAT, Wnt/β-catenin, AKT/GSK-3β, MAPKs, and estrogen receptor pathways) and regulating microRNA expression levels. Furthermore, target identification, research limitations, future directions, and application prospects are comprehensively outlined, aiming to facilitate the clinical translation of ginkgetin.
ORIGINAL ARTICLE
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  Synthesis and biological activity study of tanshinone I-pyridinium salt derivatives

  Huimin Zhao, Yuyang Wang, Zining Liu, Lin Lin, Jiasi Xiang, Zihao Zhu, Xiongli Yang, Yongsheng Fang, Lingmei Kong, Yan Li

  Natural Products and Bioprospecting. 2025, 15(5): 51-51. https://doi.org/10.1007/s13659-025-00534-7

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  Natural product tanshinone I exhibits weak potency and poor drug-like properties, which have restricted its clinical development as an anticancer agent. Herein, twenty novel tanshinone I-pyridinium salt derivatives and a pyridinium salt precursor were designed and synthesized, and their antitumor activities were evaluated. Among these tanshinone I-pyridinium salts, compound a4, bearing a 4-bromobenzoylmethyl substituent at the N-1 position of the pyridine ring, showed the most potent cytotoxicity against breast cancer (MDA-MB-231), hepatocellular carcinoma (HepG2), and prostate cancer (22RV1) cell lines, with IC₅₀ values of 1.40-1.63 μM. Preliminary mechanistic studies suggest that a4 targets PI3Kα with the IC₅₀ of 9.24 ± 0.20 μM and exerts effective inhibition of the phosphorylation of key PI3K/Akt/mTOR signaling proteins. Besides, a4 significantly downregulates the expression of the immune checkpoint protein PD-L1, indicating its potential to activate tumor immunity. These findings demonstrate that tanshinone I-pyridinium salt derivative a4 is a novel PI3Kα inhibitor, providing a solid foundation for further development of antitumor agents.