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Screening, Characterization and Evaluation of Mangiferin Polymorphs
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Shiying Yang, Qi Zhou, Baoxi Zhang, Li Zhang, Dezhi Yang, Haiguang Yang, Guanhua Du, Yang Lu
Natural Products and Bioprospecting. 2020, 10 (4): 187-200.
DOI: 10.1007/s13659-020-00247-z
Mangiferin is a compound with many pharmacological activities and exists in many natural products. Anhydrous and hydrate of mangiferin have been reported separately in two literatures, but the polymorphism of this compound has not been realized until this paper. In this study, polymorph screening of mangiferin has been carried out and five forms have been obtained including three new forms never reported. Several solid state characterization methods, such as powder X-ray diffraction, differential scanning calorimetry and thermogravimetry, are used to identify and characterize all of mangiferin forms. The comparison of the crystallographic data and hirshfeld surface analysis were first reported for mangiferin anhydrous and hydrate. Furthermore, the studies on stability, transformation and solubility have been undertaken, the results prompt that form V can be used as the dominant polymorph for the development of innovative pharmaceuticals.
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Arthrinins E-G, Three Botryane Sesquiterpenoids from the Plant Endophytic Fungus Arthrinium sp. HS66
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Xiao-Zheng Su, Jian-Wei Tang, Kun Hu, Xiao-Nian Li, Han-Dong Sun, Pema-Tenzin Puno
Natural Products and Bioprospecting. 2020, 10 (4): 201-207.
DOI: 10.1007/s13659-020-00248-y
Arthrinins E-G (1-3), three new sesquiterpenoids possessing non-isoprenoid botryane skeleton, were isolated from the fermentation of an endophytic fungus named Arthrinium sp. HS66 which colonized in the stems of Isodon xerophilus. Their structures were determined by extensive spectroscopic methods. Furthermore, the structure of 1 was unambiguously confirmed by X-ray diffraction, while those of 2 and 3 were verified through quantum chemical calculation of NMR data and ECD spectra.
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Acute and Sub-chronic Toxicity of Indole Alkaloids Extract from Leaves of Alstonia scholaris (L.) R. Br. in Beagle Dogs
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Yun-Li Zhao, Min Su, Jian-Hua Shang, Xia Wang, Guang-Lei Bao, Jia Ma, Qing-Di Sun, Fang Yuan, Jing-Kun Wang, Xiao-Dong Luo
Natural Products and Bioprospecting. 2020, 10 (4): 209-220.
DOI: 10.1007/s13659-020-00246-0
Alstonia scholaris (L.) R. Br., an evergreen tropical plant rich in indole alkaloids with significant physiological activity, is traditionally used to treat respiratory diseases in China. This study was conducted to establish the toxicity profile of the alkaloid extract (TA) of A. scholaris leaves in non-rodents. After oral administration of a single dose (4 g/kg.bw), a number of transient symptoms, such as unsteady gait, drooling, emesis, and reddening of peri-oral mucosa, were observed, but no treatment-related mortality. A sub-chronic toxicity study with a range of doses of TA (20, 60 and 120 mg/kg.bw) was conducted for a 13-week treatment period, followed by 4-week recovery observation. Except for emesis and drooling in majority of animals in 120 mg/kg.bw treatment group, no clinical changes were observed in TA-treated animals. Data from electrocardiography, bone marrow, urine, fecal, hematology and clinical chemistry analyses were comparable between TAtreated and control animals. No significant differences in the relative organ weights and histopathological characteristics were evident between the TA-treated and control groups. Accordingly, the non-observed-adverse-effect-level (NOAEL) of TA was established as 120 mg/kg.bw. Our results add further knowledge to the safety database for indole alkaloid extracts from A. scholaris with potential utility as novel drug candidates.
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Artificial Triterpenoid Fatty Acid Ester Isolated From the Leaves of Phytolacca icosandra L
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Elier Galarraga, Andersson Mavares, Neudo Urdaneta, Rafael E. Rodríguez-Lugo, Juan Manuel Amaro-Luis
Natural Products and Bioprospecting. 2020, 10 (4): 221-225.
DOI: 10.1007/s13659-020-00249-x
The methanol extract form the leaves of Phytolacca icosandra L., afforded the unprecedented artificial triterpenoid fatty acid ester 1 derived from the new natural triterpenoid phytolaccagenic acid 3-O-myristate (1a), along with the three known triterpenoids serjanic, acinosolic and phytolaccagenic acid (2-4). Their structures were stablished by HR-EI-MS, 1D and 2D NMR techniques. The possible mechanistic formation of 1 is proposed, and the in vitro toxicity of all compounds was assessed using the brine shrimp lethality assay (BSLA).
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Acute and Sub-Acute Toxicological Evaluations of Bioactive Alkaloidal Extract from Melodinus henryi and Their Main Chemical Constituents
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Meilian Yang, Yudan Wang, Zhifeng Fan, Qingwang Xue, Guy Sedar Singor Njateng, Yaping Liu, Jianxin Cao, Tianrui Zhao, Guiguang Cheng
Natural Products and Bioprospecting. 2020, 10 (4): 227-241.
DOI: 10.1007/s13659-020-00252-2
Melodinus henryi is a good source of terpenoid indole alkaloids, and traditionally used as a folk medicine in the treatment of meningitis and fracture. In order to further exploit their potential uses, its anti-inflammatory and immunosuppressive activities, safety evaluations and chemical profiles have been illustrated. Compared to the crude methanol extract from M. henryi and its non-alkaloidal fraction, the total alkaloidal fraction (MHTA) had the strongest anti-inflammatory and immunosup-pressive activities. In the acute oral toxicity assay, the half lethal dose (LD50) of MHTA was more than 2000 mg/kg. The sub-acute toxicity assay for consecutive 28 days exhibited MHTA at a lower concentrations of less than 500 mg/kg might be regarded as safe, and might damage spleen, liver, kidney, and heart when the dose is higher than 1000 mg/kg. In addition, a phytochemical investigation on MHTA led to the isolation of 15 monoterpenoid indole alkaloids. Thus, in regard with the potent side effects of MHTA, it should be used with caution in the development of phytomedicine.
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Artemlavanins A and B from Artemisia lavandulaefolia and Their Cytotoxicity Against Hepatic Stellate Cell Line LX2
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Cheng Shen, Xiao-Yan Huang, Chang-An Geng, Tian-Ze Li, Shuang Tang, Li-Hua Su, Zhen Gao, Xue-Mei Zhang, Jing Hu, Ji-Jun Chen
Natural Products and Bioprospecting. 2020, 10 (4): 243-250.
DOI: 10.1007/s13659-020-00254-0
Two new sesquiterpenoids, artemlavanins A (1) and B (3), together with fifteen known compounds (2 and 4-17) were isolated from the EtOH extract of Artemisia lavandulaefolia. The structures of new compounds were elucidated by extensive spectroscopic analyses (HRESIMS, 1D and 2D NMR) and ECD calculations. Compound 1 was a sesquiterpenoid lactone possessing a rearranged eudesmane skeleton; compounds 2-5, 6-8, 9 and 10-12 belonged to the eudesmane, guaiane, oppositane and farnesane sesquiterpenoids, respectively; compounds 13-17 were the phenyl derivatives with a 4-hydroxy-acetophenone moiety. Twelve compounds (1-3, 5-7, 10-12, 14, 15 and 17) displayed cytotoxicity against hepatic stellate cell line LX2 (HSC-LX2) with IC50 values ranging from 35.1 to 370.3 μM. Compounds 2, 7, 10-12 and 17 exhibited the stronger cytotoxicity than silybin (IC50, 169.6 μM) with IC50 values of 82.1, 35.1, 95.0, 83.8, 81.6 and 90.1 μM. Compound 7 as the most active one showed significant inhibition on the deposition of human collagen type I (Col I), human hyaluronic acid (HA) and human laminin (HL) with IC50 values of 10.7, 24.5 and 13.3 μM.
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Artemyrianins A-G from Artemisia myriantha and Their Cytotoxicity Against HepG2 Cells
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Shuang Tang, Yun-Bao Ma, Chang-An Geng, Cheng Shen, Tian-Ze Li, Xue-Mei Zhang, Li-Hua Su, Zhen Gao, Jing Hu, Ji-Jun Chen
Natural Products and Bioprospecting. 2020, 10 (4): 251-260.
DOI: 10.1007/s13659-020-00255-z
Four new sesquiterpenoids, artemyrianins A-D (1-4), and three new norlignans, artemyrianins E-G (5-7), together with five known compounds (8-12), were isolated from the aerial parts of Artemisia myriantha (Asteraceae). The new compounds were established by spectroscopic data analyses (HRMS, IR, 1D and 2D NMR), and their absolute configurations were confirmed by the single-crystal X-ray diffraction or ECD calculations. The isolates showed cytotoxicity against HepG2 cells with IC50 values ranging from 33.3 to 145.2 μM.
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Crystal Structures, Stability, and Solubility Evaluation of a 2: 1 Diosgenin-Piperazine Cocrystal
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Ningbo Gong, Hongmei Yu, Ying Wang, Cheng Xing, Kun Hu, Guanhua Du, Yang Lu
Natural Products and Bioprospecting. 2020, 10 (4): 261-267.
DOI: 10.1007/s13659-020-00256-y
A cocrystal of diosgenin with piperazine in 2:1 stoichiometry was successfully synthesized. The solid form was prepared by liquid assisted grinding, slurry and crystallization methods. The cocrystal was characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, Fourier transform infrared spectroscopy, and structure determined by single crystal X-ray diffraction, the hydrogen bonds formed into fish bone structure along the[010] direction and all the molecules packed into 3D layer structure along a axis. After formation of cocrystal, the solubility of diosgenin was improved, and the solubility value in 0.2% SDS solution was approximately 1.5 times as large as that of the parent material.
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