International Journal of Molecular Sciences

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14 pages, 5266 KiB

Open AccessArticle

New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit β-Amyloid42 Production and Phospho-Tau (Thr217)

by Sheng Li, Ling-Ling Han, Ke-Pu Huang, Ye-Han Ma, Ling-Li Guo, Yarong Guo, Xiaoqian Ran, Yong-Gang Yao, Xiao-Jiang Hao, Rongcan Luo and Yu Zhang

Int. J. Mol. Sci. 2023, 24(2), 1487; https://doi.org/10.3390/ijms24021487 - 12 Jan 2023

Cited by 4 | Viewed by 2343

Abstract

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A–C (1–3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan–ibogan-type bisindole alkaloid which is formed by the polymerization of two classic [...] Read more.

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A–C (1–3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan–ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1–3 all reduce Aβ42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer’s disease [AD] associated with BACE1-, NCSTN-, GSK3β-, and CDK5-mediated pathways, suggesting these alkaloids’ potential against AD. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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21 pages, 11344 KiB

Open AccessArticle

Jatrophane Diterpenoids from Euphorbia peplus Linn. as Activators of Autophagy and Inhibitors of Tau Pathology

by Ying Yan, Qi Zhou, Xiaoqian Ran, Qingyun Lu, Cuishan Zhang, Mingyou Peng, Lei Tang, Rongcan Luo, Yingtong Di and Xiaojiang Hao

Int. J. Mol. Sci. 2023, 24(2), 1088; https://doi.org/10.3390/ijms24021088 - 6 Jan 2023

Cited by 3 | Viewed by 2194

Abstract

Ten jatrophane diterpenoids were isolated from the whole plant Euphorbia peplus Linn. including seven new ones, named euphjatrophanes A-G (labeled compounds 1, 2, 4–8). Their structures were elucidated with a combination of spectroscopic and single-crystal X-ray crystallography, enabling [...] Read more.

Ten jatrophane diterpenoids were isolated from the whole plant Euphorbia peplus Linn. including seven new ones, named euphjatrophanes A-G (labeled compounds 1, 2, 4–8). Their structures were elucidated with a combination of spectroscopic and single-crystal X-ray crystallography, enabling the identification of compounds 3, 9, and 10 as the previously published euphpepluones G, K, and L, respectively. All compounds were evaluated for their bioactivity with flow cytometry in assays of autophagic flux in HM Cherry-GFP-LC3 (human microglia cells stably expressing the tandem monomeric mCherry-GFP-tagged LC3) cells. Euphpepluone K (9) significantly activated autophagic flux, an effect that was verified with confocal analysis. Moreover, cellular assays showed that euphpepluone K (9) induced autophagy and inhibited Tau pathology. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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16 pages, 8038 KiB

Open AccessArticle

Neuroprotection of Kaji-Ichigoside F1 via the BDNF/Akt/mTOR Signaling Pathways against NMDA-Induced Neurotoxicity

by Faju Chen, Li Wang, Fengli Jin, Liangqun Li, Tao Wang, Ming Gao, Lilang Li, Yu Wang, Zhongsheng Lou, Juan Yang, Qiji Li and Xiaosheng Yang

Int. J. Mol. Sci. 2022, 23(24), 16150; https://doi.org/10.3390/ijms232416150 - 18 Dec 2022

Cited by 3 | Viewed by 2375

Abstract

Kaji-ichigoside F1 (KF1), a natural oleanane-type triterpenoid saponin, is the main active constituent from Rosa roxburghii. In the southwest regions of China, particularly in Guizhou Province, this plant was used as a Miao ethnic medicine to prevent and treat dyspepsia, dysentery, hypoimmunity, [...] Read more.

Kaji-ichigoside F1 (KF1), a natural oleanane-type triterpenoid saponin, is the main active constituent from Rosa roxburghii. In the southwest regions of China, particularly in Guizhou Province, this plant was used as a Miao ethnic medicine to prevent and treat dyspepsia, dysentery, hypoimmunity, and neurasthenia. In the present study, the neuroprotective effect of KF1 was evaluated against N-methyl-D-aspartate (NMDA)-induced neurotoxicity in vivo and in vitro. An NMDA-induced PC12 cell neurotoxicity assay showed that KF1 effectively improved cellular viability, inhibited the release of lactate dehydrogenase (LDH), and reduced cell apoptosis. Furthermore, KF1-treated NMDA-induced excitotoxicity mice displayed a remarkable capacity for improving spatial learning memory in the Y-maze and Morris water maze tests. In addition, KF1 increased the levels of the neurotransmitters 5-hydroxytryptamine, dopamine, and monoamine oxidase and reduced the calcium ion concentration in the hippocampus of mice. Hematoxylin and eosin and Nissl staining indicated that KF1 effectively reduced the impairment of neurons. Furthermore, Western blot assays showed that KF1 decreased NMDAR1 expression. In contrast, the NMDAR2B (NR2B), glutamate receptor (AMPA), TrkB, protein kinase B (AKT), mammalian target of rapamycin (mTOR), PSD95, and synapsin 1 were upregulated in NMDA-induced PC12 cells and an animal model. These results suggest that KF1 has a remarkable protective effect against NMDA-induced neurotoxicity, which is directly related to the regulation of the NMDA receptor and the activation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and BDNF/AKT/mTOR signaling pathways. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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22 pages, 7979 KiB

Open AccessArticle

Phellinus baumii Polyphenol: A Potential Therapeutic Candidate against Lung Cancer Cells

by Xue Liu, Shiyao Cui, Caiyun Dan, Wenle Li, Hongqing Xie, Conghui Li and Liangen Shi

Int. J. Mol. Sci. 2022, 23(24), 16141; https://doi.org/10.3390/ijms232416141 - 17 Dec 2022

Cited by 3 | Viewed by 3076

Abstract

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition [...] Read more.

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition of Phellinus baumii polyphenol (PBP) and characterized its 17 chemical components by UPLC–ESI–QTOF–MS. Furthermore, to clarify the potential mechanism of PBP against Lung Cancer Cells, network pharmacology and experimental verification were combined. Molecular docking elucidated the binding conformation and mechanism of the primary active components (Osmundacetone and hispidin) to the core targets CASP3, PARP1 and TP53. In addition, potential molecular mechanisms of PBP predicted by network pharmacology analysis were validated in vitro. PBP significantly inhibited the human lung cancer A549 cells and showed typical apoptotic characteristics, without significant cytotoxicity to normal human embryonic kidney (HEK293) cells. Analysis using flow cytometry and western blot indicated that PBP caused apoptosis, cell cycle arrest, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) depression in A549 cells to exercise its antitumor effects. These results reveal that PBP has great potential for use as an active ingredient for antitumor therapy. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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15 pages, 5575 KiB

Open AccessArticle

Modulating Activity Evaluation of Gut Microbiota with Versatile Toluquinol

by Long-Long Zhang, Ya-Jun Liu, Yong-Hong Chen, Zhuang Wu, Bo-Ran Liu, Qian-Yi Cheng, Ke-Qin Zhang and Xue-Mei Niu

Int. J. Mol. Sci. 2022, 23(18), 10700; https://doi.org/10.3390/ijms231810700 - 14 Sep 2022

Cited by 2 | Viewed by 1717

Abstract

Gut microbiota have important implications for health by affecting the metabolism of diet and drugs. However, the specific microbial mediators and their mechanisms in modulating specific key intermediate metabolites from fungal origins still remain largely unclear. Toluquinol, as a key versatile precursor metabolite, [...] Read more.

Gut microbiota have important implications for health by affecting the metabolism of diet and drugs. However, the specific microbial mediators and their mechanisms in modulating specific key intermediate metabolites from fungal origins still remain largely unclear. Toluquinol, as a key versatile precursor metabolite, is commonly distributed in many fungi, including Penicillium species and their strains for food production. The common 17 gut microbes were cultivated and fed with and without toluquinol. Metabolic analysis revealed that four strains, including the predominant Enterococcus species, could metabolize toluquinol and produce different metabolites. Chemical investigation on large-scale cultures led to isolation of four targeted metabolites and their structures were characterized with NMR, MS, and X-ray diffraction analysis, as four toluquinol derivatives (1–4) through O1/O4-acetyl and C5/C6-methylsulfonyl substitutions, respectively. The four metabolites were first synthesized in living organisms. Further experiments suggested that the rare methylsulfonyl groups in 3–4 were donated from solvent DMSO through Fenton’s reaction. Metabolite 1 displayed the strongest inhibitory effect on cancer cells A549, A2780, and G401 with IC₅₀ values at 0.224, 0.204, and 0.597 μM, respectively, while metabolite 3 displayed no effect. Our results suggest that the dominant Enterococcus species could modulate potential precursors of fungal origin and change their biological activity. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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13 pages, 2069 KiB

Open AccessArticle

Tin Carboxylate Complexes of Natural Bacteriochlorin for Combined Photodynamic and Chemotherapy of Cancer è

by Sergey Tikhonov, Petr Ostroverkhov, Nikita Suvorov, Andrey Mironov, Yulia Efimova, Anna Plutinskaya, Andrei Pankratov, Anastasia Ignatova, Alexey Feofanov, Ekaterina Diachkova, Yuriy Vasil’ev and Mikhail Grin

Int. J. Mol. Sci. 2021, 22(24), 13563; https://doi.org/10.3390/ijms222413563 - 17 Dec 2021

Cited by 5 | Viewed by 3057

Abstract

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can [...] Read more.

Photodynamic therapy (PDT) is currently one of the most promising methods of cancer treatment. However, this method has some limitations, including a small depth of penetration into biological tissues, the low selectivity of accumulation, and hypoxia of the tumor tissues. These disadvantages can be overcome by combining PDT with other methods of treatment, such as radiation therapy, neutron capture therapy, chemotherapy, etc. In this work, potential drugs were obtained for the first time, the molecules of which contain both photodynamic and chemotherapeutic pharmacophores. A derivative of natural bacteriochlorophyll a with a tin IV complex, which has chemotherapeutic activity, acts as an agent for PDT. This work presents an original method for obtaining agents of combined action, the structure of which is confirmed by various physicochemical methods of analysis. The method of molecular modeling was used to investigate the binding of the proposed drugs to DNA. In vitro biological tests were carried out on several lines of tumor cells: Hela, A549, S37, MCF7, and PC-3. It was shown that the proposed conjugates of binary action for some cell lines had a dark cytotoxicity that was significantly higher (8–10 times) than the corresponding metal complexes of amino acids, which was explained by the targeted chemotherapeutic action of the tin (IV) complex due to chlorin. The greatest increase in efficiency relative to the initial dipropoxy-BPI was found for the conjugate with lysine as a chelator of the tin cation relative to cell lines, with the following results: S-37 increased 3-fold, MCF-7 3-fold, and Hela 2.4-fold. The intracellular distribution of the obtained agents was also studied by confocal microscopy and showed a diffuse granular distribution with predominant accumulation in the near nuclear region. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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Review

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22 pages, 46261 KiB

Open AccessReview

Toxic Potential of Cerrado Plants on Different Organisms

by Jamira Dias Rocha, Fernanda Melo Carneiro, Amanda Silva Fernandes, Jéssyca Moreira Morais, Leonardo Luiz Borges, Lee Chen-Chen, Luciane Madureira de Almeida and Elisa Flávia Luiz Cardoso Bailão

Int. J. Mol. Sci. 2022, 23(7), 3413; https://doi.org/10.3390/ijms23073413 - 22 Mar 2022

Cited by 8 | Viewed by 4136

Abstract

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science [...] Read more.

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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19 pages, 3332 KiB

Open AccessReview

Therapeutic Potential of Jasmonic Acid and Its Derivatives

by Iwona Jarocka-Karpowicz and Agnieszka Markowska

Int. J. Mol. Sci. 2021, 22(16), 8437; https://doi.org/10.3390/ijms22168437 - 5 Aug 2021

Cited by 28 | Viewed by 6179

Abstract

A modern method of therapeutic use of natural compounds that would protect the body are jasmonates. The main representatives of jasmonate compounds include jasmonic acid and its derivatives, mainly methyl jasmonate. Extracts from plants rich in jasmonic compounds show a broad spectrum of [...] Read more.

A modern method of therapeutic use of natural compounds that would protect the body are jasmonates. The main representatives of jasmonate compounds include jasmonic acid and its derivatives, mainly methyl jasmonate. Extracts from plants rich in jasmonic compounds show a broad spectrum of activity, i.e., anti-cancer, anti-inflammatory and cosmetic. Studies of the biological activity of jasmonic acid and its derivatives in mammals are based on their structural similarity to prostaglandins and the compounds can be used as natural therapeutics for inflammation. Jasmonates also constitute a potential group of anti-cancer drugs that can be used alone or in combination with other known chemotherapeutic agents. Moreover, due to their ability to stimulate exfoliation of the epidermis, remove discoloration, regulate the function of the sebaceous glands and reduce the visible signs of aging, they are considered for possible use in cosmetics and dermatology. The paper presents a review of literature data on the biological activity of jasmonates that may be helpful in treatment and prevention. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds for Human Health)

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