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14 pages, 4410 KiB

Open AccessArticle

Paeoniflorin Alleviates Cisplatin-Induced Diminished Ovarian Reserve by Restoring the Function of Ovarian Granulosa Cells via Activating FSHR/cAMP/PKA/CREB Signaling Pathway

by Qingchang Wu, Miao Chen, Yao Li, Xiangyun Zhao, Cailian Fan and Yi Dai

Molecules 2023, 28(24), 8123; https://doi.org/10.3390/molecules28248123 - 15 Dec 2023

Cited by 3 | Viewed by 1837

Abstract

Paeoniflorin (PAE) is the main active compound of Radix Paeoniae Rubra (a valuable traditional Chinese medicine and a dietary supplement) and exerts beneficial effects on female reproductive function. However, the actions of PAE on diminished ovarian reserve (DOR, a very common ovarian function [...] Read more.

Paeoniflorin (PAE) is the main active compound of Radix Paeoniae Rubra (a valuable traditional Chinese medicine and a dietary supplement) and exerts beneficial effects on female reproductive function. However, the actions of PAE on diminished ovarian reserve (DOR, a very common ovarian function disorder) are still unclear. Herein, our study investigated the effect and potential mechanism of PAE on DOR by using cisplatin-induced DOR mice and functional impairment of estradiol (E₂) synthesis of ovarian granulosa-like KGN cells. Our data show that PAE improved the estrous cycle, ovarian index, and serum hormones levels, including E₂, and the number of antral follicles and corpora lutea in DOR mice. Further mechanism results reveal that PAE promoted aromatase expression (the key rate-limiting enzyme for E₂ synthesis) and upregulated the FSHR/cAMP/PKA/CREB signaling pathway in the ovaries. Subsequently, PAE improved the levels of E₂ and aromatase and activated the FSHR/cAMP/PKA/CREB signaling pathway in KGN cells, while these improving actions were inhibited by the siRNA-FSHR and FSHR antagonist treatments. In sum, PAE restored the function of E₂ synthesis in ovarian granulosa cells to improve DOR by activating the FSHR/cAMP/PKA/CREB signaling pathway, which exhibited a new clue for the development of effective therapeutic agents for the treatment of DOR. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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19 pages, 4749 KiB

Open AccessArticle

Analyzing the Material Basis of Anti-RSV Efficacy of Lonicerae japonicae Flos Based on the PK-PD Model

by Yuting Liang, Mingjun Liu, Yanghai Wang, Lu Liu and Yan Gao

Molecules 2023, 28(18), 6437; https://doi.org/10.3390/molecules28186437 - 5 Sep 2023

Cited by 3 | Viewed by 1466

Abstract

Lonicerae japonicae Flos (LJF) possesses a good anti-respiratory syncytial virus (RSV) effect. However, the material basis of LJF in treating RSV is still unclear. In this study, a sensitive and accurate quantitative method based on UHPLC-QQQ MS was established and validated for the [...] Read more.

Lonicerae japonicae Flos (LJF) possesses a good anti-respiratory syncytial virus (RSV) effect. However, the material basis of LJF in treating RSV is still unclear. In this study, a sensitive and accurate quantitative method based on UHPLC-QQQ MS was established and validated for the simultaneous determination of the 15 ingredients from LJF in RSV-infected mice plasma. Multiple reaction monitoring was performed for quantification of the standards and of the internal standard in plasma. All the calibration curves show good linear regression within the linear range (r² > 0.9918). The method validation results, including specificity, linearity, accuracy, precision, extraction recovery, matrix effect, and stability of 15 ingredients, are all within the current acceptance criteria. This established method was successfully applied to the pharmacokinetic study of 15 compounds from LJF. Furthermore, the repair rate of lung index and the improvement rate of IFN-γ and IL-6 improved after administration of the LJF, indicating that LJF possessed a positive effect on the treatment of RSV infection. Finally, by combining Spearman and Grey relation analysis, isochlorogenic acid B, isochlorogenic acid C, secoxyloganin, chlorogenic acid, and loganic acid are speculated to be the main effective ingredients of LJF in treating RSV. This study lays the foundation for attempts to reveal the mechanisms of the anti-RSV effect of LJF. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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15 pages, 4620 KiB

Open AccessArticle

Platycodonis Radix Alleviates LPS-Induced Lung Inflammation through Modulation of TRPA1 Channels

by Tan Yang, Shuang Zhao, Yu Yuan, Xiaotong Zhao, Fanjie Bu, Zhiyuan Zhang, Qianqian Li, Yaxin Li, Zilu Wei, Xiuyan Sun, Yanqing Zhang and Junbo Xie

Molecules 2023, 28(13), 5213; https://doi.org/10.3390/molecules28135213 - 5 Jul 2023

Cited by 3 | Viewed by 1898

Abstract

Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the [...] Read more.

Platycodonis Radix (PR), a widely consumed herbal food, and its bioactive constituents, platycodins, have therapeutic potential for lung inflammation. Transient Receptor Potential Ankyrin 1 (TRPA1), which is essential for the control of inflammation, may be involved in the development of inflammation in the lungs. The aim of this study was to determine the TRPA1-targeted effects of PR against pulmonary inflammation and to investigate the affinity of PR constituents for TRPA1 and their potential mechanisms of action. Using a C57BL/6J mouse lipopolysaccharides (LPS) intratracheal instillation pneumonia model and advanced analytical techniques (UPLC-Q-TOF-MS/MS, molecular docking, immuno-fluorescence), five platycodins were isolated from PR, and the interaction between these platycodins and hTRPA1 was verified. Additionally, we analyzed the impact of platycodins on LPS-induced TRPA1 expression and calcium influx in BEAS-2B cells. The results indicated that PR treatment significantly reduced the severity of LPS-triggered inflammation in the mouse model. Interestingly, there was a mild increase in the expression of TRPA1 caused by PR in healthy mice. Among five isolated platycodins identified in the PR extract, Platycodin D₃ (PD₃) showed the highest affinity for hTRPA1. The interaction between platycodins and TRPA1 was verified through molecular docking methods, highlighting the significance of the S5–S6 pore-forming loop in TRPA1 and the unique structural attributes of platycodins. Furthermore, PD₃ significantly reduced LPS-induced TRPA1 expression and calcium ion influx in BEAS-2B cells, substantiating its own role as an effective TRPA1 modulator. In conclusion, PR and platycodins, especially PD₃, show promise as potential lung inflammation therapeutics. Further research should explore the precise mechanisms by which platycodins modulate TRPA1 and their broader therapeutic potential. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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12 pages, 3124 KiB

Open AccessFeature PaperArticle

Discrepancy Study of the Chemical Constituents of Panax Ginseng from Different Growth Environments with UPLC-MS-Based Metabolomics Strategy

by Yizheng Sun, Xiaoyan Liu, Xiaojie Fu, Wei Xu, Qingmei Guo and Youbo Zhang

Molecules 2023, 28(7), 2928; https://doi.org/10.3390/molecules28072928 - 24 Mar 2023

Cited by 10 | Viewed by 2324

Abstract

Panax ginseng (P. ginseng), the dried root and rhizome of P. ginseng C. A. Meyer, is widely used in many fields as dietary supplements and medicine. To characterize the chemical constituents in P. ginseng cultivated in different growth environments, a UPLC-TOF-MS [...] Read more.

Panax ginseng (P. ginseng), the dried root and rhizome of P. ginseng C. A. Meyer, is widely used in many fields as dietary supplements and medicine. To characterize the chemical constituents in P. ginseng cultivated in different growth environments, a UPLC-TOF-MS method was established for qualitative analysis. Four hundred and eight ginsenosides, including 81 new compounds, were characterized in P. ginseng from different regions. Among the detected compounds, 361 ginsenosides were recognized in P. ginseng cultivated in the region of Monsoon Climate of Medium Latitudes, possessing the largest amount of ginsenosides in all samples. Furthermore, 41 ginsenosides in 12 batches of P. ginsengs were quantified with a UPLC-MRM-MS method, and P. ginsengs from different regions were distinguished via chemometric analysis. This study showed that the different environments have a greater influence on P. ginseng, which laid a foundation for further quality control of the herb. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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19 pages, 3742 KiB

Open AccessArticle

The Metabolites and Mechanism Analysis of Genistin against Hyperlipidemia via the UHPLC-Q-Exactive Orbitrap Mass Spectrometer and Metabolomics

by Zhe Li, Weichao Dong, Yanan Li, Xin Liu, Hong Wang, Long Dai, Jiayu Zhang and Shaoping Wang

Molecules 2023, 28(5), 2242; https://doi.org/10.3390/molecules28052242 - 28 Feb 2023

Cited by 2 | Viewed by 2094

Abstract

Genistin, an isoflavone, has been reported to have multiple activities. However, its improvement of hyperlipidemia is still unclear, and the same is true with regard to its mechanism. In this study, a high-fat diet (HFD) was used to induce a hyperlipidemic rat model. [...] Read more.

Genistin, an isoflavone, has been reported to have multiple activities. However, its improvement of hyperlipidemia is still unclear, and the same is true with regard to its mechanism. In this study, a high-fat diet (HFD) was used to induce a hyperlipidemic rat model. The metabolites of genistin in normal and hyperlipidemic rats were first identified to cause metabolic differences with Ultra-High-Performance Liquid Chromatography Quadrupole Exactive Orbitrap Mass Spectrometry (UHPLC-Q-Exactive Orbitrap MS). The relevant factors were determined via ELISA, and the pathological changes of liver tissue were examined via H&E staining and Oil red O staining, which evaluated the functions of genistin. The related mechanism was elucidated through metabolomics and Spearman correlation analysis. The results showed that 13 metabolites of genistin were identified in plasma from normal and hyperlipidemic rats. Of those metabolites, seven were found in normal rat, and three existed in two models, with those metabolites being involved in the reactions of decarbonylation, arabinosylation, hydroxylation, and methylation. Three metabolites, including the product of dehydroxymethylation, decarbonylation, and carbonyl hydrogenation, were identified in hyperlipidemic rats for the first time. Accordingly, the pharmacodynamic results first revealed that genistin could significantly reduce the level of lipid factors (p < 0.05), inhibited lipid accumulation in the liver, and reversed the liver function abnormalities caused by lipid peroxidation. For metabolomics results, HFD could significantly alter the levels of 15 endogenous metabolites, and genistin could reverse them. Creatine might be a beneficial biomarker for the activity of genistin against hyperlipidemia, as revealed via multivariate correlation analysis. These results, which have not been reported in the previous literature, may provide the foundation for genistin as a new lipid-lowering agent. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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13 pages, 2551 KiB

Open AccessArticle

Polygonati Rhizoma Polysaccharide Prolongs Lifespan and Healthspan in Caenorhabditis elegans

by Yage Luan, Yu Jiang, Rong Huang, Xuan Wang, Xiujuan He, Yonggang Liu and Peng Tan

Molecules 2023, 28(5), 2235; https://doi.org/10.3390/molecules28052235 - 27 Feb 2023

Cited by 11 | Viewed by 2541

Abstract

Polygonati Rhizoma is the dried rhizome of Polygonatum kingianum coll.et hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua, and has a long history of medication. Raw Polygonati Rhizoma (RPR) numbs the tongue and stings the throat, while prepared Polygonati Rhizoma (PPR) can remove [...] Read more.

Polygonati Rhizoma is the dried rhizome of Polygonatum kingianum coll.et hemsl., Polygonatum sibiricum Red. or Polygonatum cyrtonema Hua, and has a long history of medication. Raw Polygonati Rhizoma (RPR) numbs the tongue and stings the throat, while prepared Polygonati Rhizoma (PPR) can remove the numbness of the tongue, and at the same time enhance its functions of invigorating the spleen, moistening the lungs and tonifying the kidneys. There are many active ingredients in Polygonati Rhizoma (PR), among which polysaccharide is one of the most important active ingredients. Therefore, we studied the effect of Polygonati Rhizoma polysaccharide (PRP) on the lifespan of Caenorhabditis elegans (C. elegans) and found that polysaccharide in PPR (PPRP) was more effective than Polysaccharide in RPR (RPRP) in prolonging the lifespan of C. elegans, reducing the accumulation of lipofuscin, and increasing the frequency of pharyngeal pumping and movement. The further mechanism study found that PRP can improve the anti-oxidative stress ability of C. elegans, reduce the accumulation of reactive oxygen species (ROS) in C. elegans, and improve the activity of antioxidant enzymes. The results of quantitative real-time PCR(q-PCR) experiments suggested that PRP may prolong the lifespan of C. elegans by down-regulating daf-2 and activating daf-16 and sod-3, and the transgenic nematode experiments were consistent with its results, so it was hypothesized that the mechanism of age delaying effect of PRP was related to daf-2, daf-16 and sod-3 of the insulin signaling pathway. In short, our research results provide a new idea for the application and development of PRP. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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14 pages, 1541 KiB

Open AccessArticle

Screening of Potential α-Glucosidase Inhibitors from the Roots and Rhizomes of Panax Ginseng by Affinity Ultrafiltration Screening Coupled with UPLC-ESI-Orbitrap-MS Method

by Hong-Ping Wang, Chun-Lan Fan, Zhao-Zhou Lin, Qiong Yin, Chen Zhao, Ping Peng, Run Zhang, Zi-Jian Wang, Jing Du and Zhi-Bin Wang

Molecules 2023, 28(5), 2069; https://doi.org/10.3390/molecules28052069 - 22 Feb 2023

Cited by 7 | Viewed by 2350

Abstract

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests [...] Read more.

Panax ginseng was a traditional Chinese medicine with various pharmacological activities and one of its important activities was hypoglycemic activity; therefore, panax ginseng has been used in China as an adjuvant in the treatment of diabetes mellitus. In vivo and in vitro tests have revealed that ginsenosides, which are derived from the roots and rhizomes of panax ginseng have anti-diabetic effects and produce different hypoglycemic mechanisms by acting on some specific molecular targets, such as SGLT1, GLP-1, GLUTs, AMPK, and FOXO1. α-Glucosidase is another important hypoglycemic molecular target, and its inhibitors can inhibit the activity of α-Glucosidase so as to delay the absorption of dietary carbohydrates and finally reduce postprandial blood sugar. However, whether ginsenosides have the hypoglycemic mechanism of inhibiting α-Glucosidase activity, and which ginsenosides exactly attribute to the inhibitory effect as well as the inhibition degree are not clear, which needs to be addressed and systematically studied. To solve this problem, affinity ultrafiltration screening coupled with UPLC-ESI-Orbitrap-MS technology was used to systematically select α-Glucosidase inhibitors from panax ginseng. The ligands were selected through our established effective data process workflow based on systematically analyzing all compounds in the sample and control specimens. As a result, a total of 24 α-Glucosidase inhibitors were selected from panax ginseng, and it was the first time that ginsenosides were systematically studied for the inhibition of α-Glucosidase. Meanwhile, our study revealed that inhibiting α-Glucosidase activity probably was another important mechanism for ginsenosides treating diabetes mellitus. In addition, our established data process workflow can be used to select the active ligands from other natural products using affinity ultrafiltration screening. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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12 pages, 8823 KiB

Open AccessArticle

Characterization of Ginsenosides from the Root of Panax ginseng by Integrating Untargeted Metabolites Using UPLC-Triple TOF-MS

by Yizheng Sun, Xiaojie Fu, Ying Qu, Lihua Chen, Xiaoyan Liu, Zichao He, Jing Xu, Jiao Yang, Wen Ma, Jun Li, Qingmei Guo and Youbo Zhang

Molecules 2023, 28(5), 2068; https://doi.org/10.3390/molecules28052068 - 22 Feb 2023

Cited by 5 | Viewed by 2228

Abstract

To compare the chemical distinctions of Panax ginseng Meyer in different growth environments and explore the effects of growth-environment factors on P. ginseng growth, an ultra-performance liquid chromatography–tandem triple quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS) was used to characterize the ginsenosides obtained by ultrasonic [...] Read more.

To compare the chemical distinctions of Panax ginseng Meyer in different growth environments and explore the effects of growth-environment factors on P. ginseng growth, an ultra-performance liquid chromatography–tandem triple quadrupole time-of-flight mass spectrometry (UPLC-Triple-TOF-MS/MS) was used to characterize the ginsenosides obtained by ultrasonic extraction from P. ginseng grown in different growing environments. Sixty-three ginsenosides were used as reference standards for accurate qualitative analysis. Cluster analysis was used to analyze the differences in main components and clarified the influence of growth environment factors on P. ginseng compounds. A total of 312 ginsenosides were identified in four types of P. ginseng, among which 75 were potential new ginsenosides. The number of ginsenosides in L15 was the highest, and the number of ginsenosides in the other three groups was similar, but it was a great difference in specie of ginsenosides. The study confirmed that different growing environments had a great influence on the constituents of P. ginseng, and provided a new breakthrough for the further study of the potential compounds in P. ginseng. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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16 pages, 4373 KiB

Open AccessArticle

Neuroprotective Effects of Savinin on LPS-Induced Neuroinflammation In Vivo via Regulating MAPK/NF-κB Pathway and NLRP3 Inflammasome Activation

by Siqi Tang, Chunying Li, Zongwu Suo, Yi Xu, Kaixin Wei, Lei Zhao, Hao Huang, Xiangqian Liu, Dongxu Liu and Xiaojun Li

Molecules 2023, 28(4), 1575; https://doi.org/10.3390/molecules28041575 - 7 Feb 2023

Cited by 7 | Viewed by 2466

Abstract

The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. [...] Read more.

The traditional herb Eleutherococcus henryi Oliv. is commonly used to treat inflammatory conditions including rheumatism, arthritis, and hepatitis, as well as mental fatigue and amnesia, according to traditional Chinese medicine (TCM) theory. Savinin is a natural lignan obtained from the roots of E. henryi. The present study was undertaken to determine whether savinin can relieve LPS-induced neuroinflammation and if so, what the mechanism is. Groups of male C57BL/6 mice were administered savinin (5, 10, 20 mg/kg) and DEX (10 mg/kg) by gavage once daily for a continuous 7 days. On the 5th day of continuous pre-administration, LPS (2.5 mg/kg) was injected into the lateral ventricles of the mice for modeling 48 h. We found that treatment with savinin decreased the levels of neuroinflammatory cytokines and histopathological alterations dramatically. Consequently, it improved the LPS-induced neuroinflammatory response in mice. Furthermore, savinin inhibited the up-regulated expression of related proteins in the activated MAPK/NF-κB and NLRP3 inflammasome signaling pathways caused by LPS. Docking studies demonstrated the binding of savinin to three receptors (MAPK, NF-κB and NLRP3) using a well-fitting mode. These findings suggest that savinin may suppress neuroinflammation induced by LPS in vivo via modulating MAPK/NF-κB and NLRP3 signaling pathways. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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18 pages, 12734 KiB

Open AccessArticle

Comprehensive Identification of Ginsenosides in the Roots and Rhizomes of Panax ginseng Based on Their Molecular Features-Oriented Precursor Ions Selection and Targeted MS/MS Analysis

by Hong-Ping Wang, Zi-Jian Wang, Jing Du, Zhao-Zhou Lin, Chen Zhao, Run Zhang, Qiong Yin, Chun-Lan Fan, Ping Peng and Zhi-Bin Wang

Molecules 2023, 28(3), 941; https://doi.org/10.3390/molecules28030941 - 17 Jan 2023

Cited by 7 | Viewed by 1947

Abstract

Panax ginseng is widely used in Asian countries and its active constituents—ginsenosides—need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack [...] Read more.

Panax ginseng is widely used in Asian countries and its active constituents—ginsenosides—need to be systematically studied. However, only a small part of ginsenosides have been characterized in the roots and rhizomes of panax ginseng (RRPG) up to date, mainly because of a lack of the fragmentation ions of many more ginsenosides. In order to comprehensively identify ginsenosides in RRPG, molecular features of ginsenosides orienting precursor ions selection and targeted tandem mass spectrometry (MS/MS) analysis strategy were proposed in our study, in which the precursor ions were selected according to the molecular features of ginsenosides irrespective of their peak abundances, and targeted MS/MS analysis was then performed to obtain their fragmentation ions for substance characterization. Using this strategy, a total of 620 ginsenosides were successfully characterized in RRPG, including 309 protopanaxadiol-type ginsenosides, 258 protopanaxatriol-type ginsenosides and 53 oleanane-type ginsenosides. It is worth noting that, except for the known aglycones mass-to-charge ratio (m/z) 459, 475 and 455, twelve other aglycones, including m/z 509, 507, 493, 491, 489, 487, 477, 473, 461, 457, 443 and 441, were first reported in our experiment and they were probably the derivatizations of the protopanaxatriol and protopanaxadiol. Our study will not only help people to improve the cognition of ginsenosides in RRPG, but will also play a guiding and reference role for the isolation and characterization of potentially new ginsenosides from RRPG. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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20 pages, 5401 KiB

Open AccessArticle

Antioxidant Effects of Roasted Licorice in a Zebrafish Model and Its Mechanisms

by Qian Zhou, Shanshan Zhang, Xue Geng, Haiqiang Jiang, Yanpeng Dai, Ping Wang, Min Hua, Qi Gao, Shiyue Lang, Lijing Hou, Dianhua Shi and Meng Zhou

Molecules 2022, 27(22), 7743; https://doi.org/10.3390/molecules27227743 - 10 Nov 2022

Cited by 8 | Viewed by 2599

Abstract

Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting [...] Read more.

Licorice (Gan-Cao, licorice) is a natural antioxidant and roasted licorice is the most common processing specification used in traditional Chinese medicine prescriptions. Traditional Chinese medicine theory deems that the honey-roasting process can promote the efficacy of licorice, including tonifying the spleen and augmenting “Qi” (energy). The antioxidant activity and mechanisms underlying roasted licorice have not yet been reported. In this study, we found that roasted licorice could relieve the oxidative stress injury induced by metronidazole (MTZ) and could restrain the production of excessive reactive oxygen species (ROS) induced by 2,2′-azobis (2-methylpropionamidine) dihydrochloride (AAPH) in a zebrafish model. It was further found that roasted licorice could exert its oxidative activity by upregulating the expression of key genes such as heme oxygenase 1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1), glutamate–cysteine ligase modifier subunit (GCLM), and glutamate–cysteine ligase catalytic subunit (GCLC) in the nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway both in vivo and in vitro. Furthermore, consistent results were obtained showing that rat serum containing roasted licorice was estimated to reduce cell apoptosis induced by H₂O₂. Then, the UHPLC-Q-Exactive Orbitrap MS analysis results elucidated the chemical composition of rat plasma containing roasted licorice extracts, including ten prototype chemical components and five metabolic components. Among them, six compounds were found to have binding activity with Kelch-like ECH-associated protein 1 (KEAP1), which plays a crucial role in the transcriptional activity of NRF2, using a molecular docking simulation. The results also showed that liquiritigenin had the strongest binding ability with KEAP1. Immunofluorescence further confirmed that liquiritigenin could induce the nuclear translocation of NRF2. In summary, this study provides a better understanding of the antioxidant effect and mechanisms of roasted licorice, and lays a theoretical foundation for the development of a potential antioxidant for use in clinical practice. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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23 pages, 1637 KiB

Open AccessArticle

The Analytical Strategy of “Ion Induction and Deduction Based on Net-Hubs” for the Comprehensive Characterization of Naringenin Metabolites In Vivo and In Vitro Using a UHPLC-Q-Exactive Orbitrap Mass Spectrometer

by Yi-Fang Cui, Wen-Wen Zhang, Ya-Nan Li, Jing Xu, Xian-Ming Lan, Shu-Yi Song, Yong-Qiang Lin, Long Dai and Jia-Yu Zhang

Molecules 2022, 27(21), 7282; https://doi.org/10.3390/molecules27217282 - 26 Oct 2022

Cited by 4 | Viewed by 1938

Abstract

Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic [...] Read more.

Naringenin (5,7,4′-trihydroxyflavanone), belonging to the flavanone subclass, is associated with beneficial effects such as anti-oxidation, anticancer, anti-inflammatory, and anti-diabetic effects. Drug metabolism plays an essential role in drug discovery and clinical safety. However, due to the interference of numerous endogenous substances in metabolic samples, the identification and efficient characterization of drug metabolites are difficult. Here, ultra-high-performance liquid chromatography (UHPLC) coupled with high-resolution mass spectrometry was used to obtain mass spectral information of plasma (processed by three methods), urine, feces, liver tissue, and liver microsome samples. Moreover, a novel analytical strategy named “ion induction and deduction” was proposed to systematically screen and identify naringenin metabolites in vivo and in vitro. The analysis strategy was accomplished by the establishment of multiple “net-hubs” and the induction and deduction of fragmentation behavior. Finally, 78 naringenin metabolites were detected and identified from samples of rat plasma, urine, feces, liver tissue, and liver microsomes, of which 67 were detected in vivo and 13 were detected in vitro. Naringenin primarily underwent glucuronidation, sulfation, oxidation, methylation, ring fission, and conversion into phenolic acid and their composite reactions. The current study provides significant help in extracting target information from complex samples and sets the foundation for other pharmacology and toxicology research. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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17 pages, 3173 KiB

Open AccessFeature PaperArticle

Structural Prediction and Characterization of Canavalia grandiflora (ConGF) Lectin Complexed with MMP1: Unveiling the Antiglioma Potential of Legume Lectins

by Rodrigo Bainy Leal, Josiane Mann, Vanir Reis Pinto-Junior, Messias Vital Oliveira, Vinicius Jose Silva Osterne, Ingrid Alessandra Victoria Wolin, Ana Paula Machado Nascimento, Priscilla Gomes Welter, Valeria Maria Sousa Ferreira, Alice Araujo Silva, Rodrigo Lopes Seeger, Kyria Santiago Nascimento and Benildo Sousa Cavada

Molecules 2022, 27(20), 7089; https://doi.org/10.3390/molecules27207089 - 20 Oct 2022

Cited by 5 | Viewed by 1884

Abstract

A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for [...] Read more.

A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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9 pages, 1475 KiB

Open AccessArticle

(±)-Cryptamides A–D, Four Pairs of Novel Dopamine Enantiomer Trimers from the Periostracum Cicadae

by Junjian Luo, Wenjun Wei, Pan Wang, Tao Guo, Suiqing Chen, Liping Zhang and Shuying Feng

Molecules 2022, 27(19), 6707; https://doi.org/10.3390/molecules27196707 - 9 Oct 2022

Cited by 5 | Viewed by 1694

Abstract

Four pairs of novel dopamine enantiomer trimers, (±)-cryptamides A–D (1–4), and 10 pairs of previously described dopamine enantiomer dimers (5–14) were isolated from the Periostracum cicadae, the cast-off shell of the insect Cryptotympana pustulata. [...] Read more.

Four pairs of novel dopamine enantiomer trimers, (±)-cryptamides A–D (1–4), and 10 pairs of previously described dopamine enantiomer dimers (5–14) were isolated from the Periostracum cicadae, the cast-off shell of the insect Cryptotympana pustulata. Aside from being pairs of enantiomers, the eight trimers were also elucidated to be regioisomers, most likely resulting from their mechanism of formation, [4 + 2] cycloaddition. The discovery of dopamine trimers is rarely reported when it comes to natural products derived from insects. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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34 pages, 9136 KiB

Open AccessArticle

Identification of Hair Growth Promoting Components in the Kernels of Prunus mira Koehne and Their Mechanism of Action

by You Zhou, Jingwen Zhang, Wanyue Chen, Xiaoli Li, Ke Fu, Weijun Sun, Yuan Liang, Min Xu, Jing Zhang, Gang Fan, Hongxiang Yin and Zhang Wang

Molecules 2022, 27(16), 5242; https://doi.org/10.3390/molecules27165242 - 17 Aug 2022

Cited by 6 | Viewed by 2949

Abstract

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic [...] Read more.

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic Medicine. This study aims to reveal the effective components and mechanism of hair growth promotion in the kernel of Prunus mira Koehne. Network pharmacology was used to predict the mechanism of action and effective components in the treatment of the kernel of Prunus mira Koehne. The contents of amygdalin in 12 batches of the kernel of Prunus mira Koehne were determined by HPLC. An animal model of the depilation of KM mice induced by sodium sulfide was created, and five effective components that promoted hair growth were initially screened. In the study of the effectiveness and mechanism of action, KM and C57BL/6 mice are selected as experimental objects, three screening tests for active components of the kernel of P. mira are performed, and three effective components are screened out from the eight components. HE staining was used to detect the number of hair follicles and the thickness of the dermis. RT-PCR and immunohistochemistry were used to evaluate the influence of the expression of indicators in the Wnt/β-catenin signaling pathway in skin, including β-catenin, GSK-3β, and mRNA and protein expression levels of Cyclin D 1 and LEF 1. The network pharmacology study showed 12 signaling pathways involving 25 targets in the treatment of alopecia by the kernel of Prunus mira Koehne. vitamin E (3.125 mg/cm²/d), β-sitosterol (0.061 mg/cm²/d), and linoleic acid (0.156 mg/cm²/d) in the kernel of Prunus mira Koehne can promote hair growth in mice, and the mechanism of action may be related to the Wnt/β-catenin pathway. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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12 pages, 3717 KiB

Open AccessArticle

Phenolic Acids from Fructus Chebulae Immaturus Alleviate Intestinal Ischemia-Reperfusion Injury in Mice through the PPARα/NF-κB Pathway

by Junjie Liu, Bin Li, Jing Liu, Feng Qiu, Yunpeng Diao, Yuxin Lei, Jianjun Liu and Wei Zhang

Molecules 2022, 27(16), 5227; https://doi.org/10.3390/molecules27165227 - 16 Aug 2022

Cited by 5 | Viewed by 2249

Abstract

Intestinal ischemia/reperfusion (II/R) injury is a common life-threatening complication with high morbidity and mortality. Chebulae Fructus Immaturus, the unripe fruit of Terminalia chebula Retz., also known as “Xiqingguo” or “Tibet Olive” in China, has been widely used in traditional Tibetan medicine [...] Read more.

Intestinal ischemia/reperfusion (II/R) injury is a common life-threatening complication with high morbidity and mortality. Chebulae Fructus Immaturus, the unripe fruit of Terminalia chebula Retz., also known as “Xiqingguo” or “Tibet Olive” in China, has been widely used in traditional Tibetan medicine throughout history. The phenolic acids’ extract of Chebulae Fructus Immaturus (XQG for short) has exhibited strong antioxidative, anti-inflammation, anti-apoptosis, and antibacterial activities. However, whether XQG can effectively ameliorate II/R injuries remains to be clarified. Our results showed that XQG could effectively alleviate II/R-induced intestinal morphological damage and intestinal barrier injury by decreasing the oxidative stress, inflammatory response, and cell death. Transcriptomic analysis further revealed that the main action mechanism of XQG protecting against II/R injury was involved in activating PPARα and inhibiting the NF-κB-signaling pathway. Our study suggests the potential usage of XQG as a new candidate to alleviate II/R injury. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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15 pages, 4512 KiB

Open AccessArticle

Kinetic Characteristics of Curcumin and Germacrone in Rat and Human Liver Microsomes: Involvement of CYP Enzymes

by Shaofeng Su, Hongxian Wu, Jingfan Zhou, Guangwei Yuan, Haibo Wang and Jie Feng

Molecules 2022, 27(14), 4482; https://doi.org/10.3390/molecules27144482 - 14 Jul 2022

Cited by 1 | Viewed by 2565

Abstract

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and [...] Read more.

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t_1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The V_max of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the V_max of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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15 pages, 1422 KiB

Open AccessArticle

A Rapid and Efficient Strategy for Quality Control of Clinopodii herba Encompassing Optimized Ultrasound-Assisted Extraction Coupled with Sensitive Variable Wavelength Detection

by Yao Liu, Xiaojun Song, Xuebin Shen, Yuangen Xiong, Li Liu, Yuexi Yang, Sihui Nian and Limin Liu

Molecules 2022, 27(14), 4418; https://doi.org/10.3390/molecules27144418 - 10 Jul 2022

Viewed by 1767

Abstract

Clinopodii herba is a folk herbal medicine for treatments of hemorrhagic disorders. However, there is not even a quantitative standard for clinopodii herba deposited in the Chinese Pharmacopoeia. The development of a strategy for rapid and efficient extraction and simultaneous detection of multiple [...] Read more.

Clinopodii herba is a folk herbal medicine for treatments of hemorrhagic disorders. However, there is not even a quantitative standard for clinopodii herba deposited in the Chinese Pharmacopoeia. The development of a strategy for rapid and efficient extraction and simultaneous detection of multiple components in clinopodii herba is therefore of great value for its quality evaluation. Here, a variable wavelength strategy was firstly applied to quantity multiple components by segmental monitoring by UHPLC with diode array detector following ultrasound-assisted extraction. The parameters of ultrasound-assisted extraction were optimized using single factor optimization experiments and response surface methodology by a Box–Behnken design combined with overall desirability. Subsequently, a rapid, efficient, and sensitive method was applied for simultaneous determination of eleven compounds, which represented the major and main types of components in clinopodii herba. Moreover, the performance of the validated method was successfully applied for the quality control of various batches of clinopodii herba and provided sufficient supporting data for the optimum harvest time. The Box-Behnken-optimized ultrasound-assisted extraction coupled with variable wavelength detection strategy established in this work not only improves the quality control of clinopodii herba, but also serves as a powerful approach that can be extended to quality evaluation of other traditional Chinese medicines. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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15 pages, 9984 KiB

Open AccessArticle

Protective Effects of Liquiritigenin against Cisplatin-Induced Nephrotoxicity via NRF2/SIRT3-Mediated Improvement of Mitochondrial Function

by Meng Zhou, Yanpeng Dai, Yong Ma, Yi Yan, Min Hua, Qi Gao, Xue Geng and Qian Zhou

Molecules 2022, 27(12), 3823; https://doi.org/10.3390/molecules27123823 - 14 Jun 2022

Cited by 17 | Viewed by 2992

Abstract

Acute kidney injury (AKI) induced by cisplatin (CP), a first-line anticancer drug for chemotherapy, is common. To date, there is an urgent need to find effective treatments to reduce the nephrotoxicity caused by CP. Meanwhile, the restoration of mitochondrial dysfunction shows potential to [...] Read more.

Acute kidney injury (AKI) induced by cisplatin (CP), a first-line anticancer drug for chemotherapy, is common. To date, there is an urgent need to find effective treatments to reduce the nephrotoxicity caused by CP. Meanwhile, the restoration of mitochondrial dysfunction shows potential to be used as an adjunct to conventional therapeutic strategies. This study found that liquiritigenin can ameliorate mitochondrial dysfunction and acute kidney injury induced by CP in mice. The intraperitoneal injection of 15 mg/kg body weight liquiritigenin for 2 days markedly protected against CP-induced mitochondrial dysfunction, restored renal tubule and mitochondrial morphology, decreased blood Scr and BUN levels, and decreased cell apoptosis. Furthermore, the elevated expression of SIRT3 induced by liquiritigenin, which can be upregulated by NRF2, was confirmed in vivo and in vitro. The underlying protective mechanisms of liquiritigenin in CP-induced nephrotoxicity were then investigated. Molecular docking results showed that liquiritigenin has potent binding activities to KEAP1, GSK-3β and HRD1. Further results showed that liquiritigenin induced the nuclear translocation of NRF2 and increased the levels of mitochondrial bioenergetics-related protein such as PGC-1α, and TFAM, which are related to NRF2 activity and mitochondrial biogenesis. In addition, liquiritigenin was found to possibly reverse the decrease in BCL2/BAX ratio induced by CP in live cultured renal tubule epithelial cells. Collectively, these results indicated that liquiritigenin could be used as a potential nephroprotective agent to protect against cisplatin-induced acute kidney injury in a NRF2-dependent manner by improving mitochondria function. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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21 pages, 5774 KiB

Open AccessReview

Chemical Composition, Functional and Anticancer Properties of Carrot

by Luigi Mandrich, Antonia Valeria Esposito, Silvio Costa and Emilia Caputo

Molecules 2023, 28(20), 7161; https://doi.org/10.3390/molecules28207161 - 19 Oct 2023

Cited by 9 | Viewed by 10437

Abstract

Plants are a valuable source of drugs for cancer treatment. Daucus carota has been investigated for its health properties. In particular, Daucus carota L. subsp. Sativus, the common edible carrot root, has been found to be rich in bioactive compounds such as [...] Read more.

Plants are a valuable source of drugs for cancer treatment. Daucus carota has been investigated for its health properties. In particular, Daucus carota L. subsp. Sativus, the common edible carrot root, has been found to be rich in bioactive compounds such as carotenoids and dietary fiber and contains many other functional components with significant health-promoting features, while Daucus carota L. subsp. Carrot (Apiacae), also known as wild carrot, has been usually used for gastric ulcer therapy, diabetes, and muscle pain in Lebanon. Here, we review the chemical composition of Daucus carota L. and the functional properties of both edible and wild carrot subspecies. Then, we focus on compounds with anticancer characteristics identified in both Daucus carota subspecies, and we discuss their potential use in the development of novel anticancer therapeutic strategies. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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18 pages, 1183 KiB

Open AccessReview

Protective Effects of Ferulic Acid on Metabolic Syndrome: A Comprehensive Review

by Lei Ye, Pan Hu, Li-Ping Feng, Li-Lu Huang, Yi Wang, Xin Yan, Jing Xiong and Hou-Lin Xia

Molecules 2023, 28(1), 281; https://doi.org/10.3390/molecules28010281 - 29 Dec 2022

Cited by 27 | Viewed by 4213

Abstract

Metabolic syndrome (MetS) is a complex disease in which protein, fat, carbohydrates and other substances are metabolized in a disorderly way. Ferulic acid (FA) is a phenolic acid found in many vegetables, fruits, cereals and Chinese herbs that has a strong effect on [...] Read more.

Metabolic syndrome (MetS) is a complex disease in which protein, fat, carbohydrates and other substances are metabolized in a disorderly way. Ferulic acid (FA) is a phenolic acid found in many vegetables, fruits, cereals and Chinese herbs that has a strong effect on ameliorating MetS. However, no review has summarized the mechanisms of FA in treating MetS. This review collected articles related to the effects of FA on ameliorating the common symptoms of MetS, such as diabetes, hyperlipidemia, hypertension and obesity, from different sources involving Web of Science, PubMed and Google Scholar, etc. This review summarizes the potential mechanisms of FA in improving various metabolic disorders according to the collected articles. FA ameliorates diabetes via the inhibition of the expressions of PEPCK, G6Pase and GP, the upregulation of the expressions of GK and GS, and the activation of the PI3K/Akt/GLUT4 signaling pathway. The decrease of blood pressure is related to the endothelial function of the aortas and RAAS. The improvement of the lipid spectrum is mediated via the suppression of the HMG-Co A reductase, by promoting the ACSL1 expression and by the regulation of the factors associated with lipid metabolism. Furthermore, FA inhibits obesity by upregulating the MEK/ERK pathway, the MAPK pathway and the AMPK signaling pathway and by inhibiting SREBP-1 expression. This review can be helpful for the development of FA as an appreciable agent for MetS treatment. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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23 pages, 3060 KiB

Open AccessReview

Origanum syriacum Phytochemistry and Pharmacological Properties: A Comprehensive Review

by Joelle Mesmar, Rola Abdallah, Adnan Badran, Marc Maresca and Elias Baydoun

Molecules 2022, 27(13), 4272; https://doi.org/10.3390/molecules27134272 - 2 Jul 2022

Cited by 13 | Viewed by 3422

Abstract

Herbal medicine has been gaining special interest as an alternative choice of treatment for several diseases, being generally accessible, cost-effective and safe, with fewer side-effects compared to chemically synthesized medicines. Over 25% of drugs worldwide are derived from plants, and surveys have shown [...] Read more.

Herbal medicine has been gaining special interest as an alternative choice of treatment for several diseases, being generally accessible, cost-effective and safe, with fewer side-effects compared to chemically synthesized medicines. Over 25% of drugs worldwide are derived from plants, and surveys have shown that, when available, herbal medicine is the preferred choice of treatment. Origanum syriacum (Lamiaceae) is a widely used medicinal plant in the Middle East, both as a home and a folk remedy, and in the food and beverage industry. Origanum syriacum contains numerous phytochemical compounds, including flavonoids, phenols, essential oils, and many others. Because of its bioactive compounds, O. syriacum possesses antioxidant, antimicrobial, and antiparasitic capacities. In addition, it can be beneficial in the treatment of various diseases such as cancer, neurodegenerative disorders, and peptic ulcers. In this review, the chemical compositions of different types of extracts and essential oils from this herb will first be specified. Then, the pharmacological uses of these extracts and essential oils in various contexts and diseases will be discussed, putting emphasis on their efficacy and safety. Finally, the cellular and molecular mechanisms of O. syriacum phytochemicals in disease treatment will be described as a basis for further investigation into the plant’s pharmacological role. Full article

(This article belongs to the Special Issue Natural Medicines: Chemical Constituents and Pharmacological Activities)

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