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(searched for: doi:10.1016/j.jep.2017.08.022)
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Published: 7 November 2022
Abstract:
The full text of this preprint has been withdrawn by the authors while they make corrections to the work. Therefore, the authors do not wish this work to be cited as a reference. Questions should be directed to the corresponding author.
Yutong Li, Linlin Zhang, Wang Wang, Yang Liu, Dejuan Sun, Hua Li, Lixia Chen
Published: 1 November 2022
Bioorganic Chemistry, Volume 128; https://doi.org/10.1016/j.bioorg.2022.106106

Liyuan Qu, Chunli Gan, Xiaoling Cheng, Congcong Lin, Yanli Wang, Libo Wang, ,
Published: 10 October 2022
Frontiers in Plant Science, Volume 13; https://doi.org/10.3389/fpls.2022.956083

Abstract:
Physalins, active ingredients from the Physalis alkekengi L. var. franchetii (P. alkekengi) plant, have shown anti-inflammatory, antioxidant and anticancer activities. Whereas the bioactivity of physalins have been confirmed, their biosynthetic pathways, and those of quite a few derivatives, remain unknown. In this paper, biosynthesis and structure modification-related genes of physalins were mined through transcriptomic and metabolomic profiling. Firstly, we rapidly and conveniently analyzed physalins by UPLC-Q-TOF-MS/MS utilizing mass accuracy, diagnostic fragment ions, and common neutral losses. In all, 58 different physalin metabolites were isolated from P. alkekengi calyxes and berries. In an analysis of the physalin biosynthesis pathway, we determined that withanolides and withaphysalins may represent a crucial intermediate between lanosterol and physalins. and those steps were decanted according to previous reports. Our results provide valuable information on the physalin metabolites and the candidate enzymes involved in the physalins biosynthesis pathways of P. alkekengi. In addition, we further analyzed differential metabolites collected from calyxes in the Jilin (Daodi of P. alkekengi) and others. Among them, 20 physalin metabolites may represent herb quality biomarkers for Daodi P. alkekengi, providing an essential role in directing the quality control index of P. alkekengi.
Meiqi Liu, Guoqiang Liu, Zicheng Ma, Jie Gao, Yi Liu, Lili Sun, Xiaoliang Ren
Published: 6 October 2022
Abstract:
Physalis Calyx seu Fructus (PCF) is one herb with the function of clearing heat and detoxify, benefiting pharynx and reducing phlegm, widely used in health care and tea drinking in China. However, the storage period of fruit and calyx was short and the quality was uneven. It is very important to further develop other parts with long storage period and obvious effect of medicine in PCF. Firstly, the fingerprint of differernt parts of PCF was developed by High-performance Liquid Chromatography (HPLC). The chemical markers were screened out by a variety of chemometric analyses. It was found that the calyxes of PCF could self-cluster among fruits, roots, stems, and leaves. It was found that the significant active components of PCF were mainly in persistent calyxes, and flavonoids were mainly in persistent calyxes and leaves. Moreover, the extraction of persistent calyxes had the strongest scavenging ability of DPPH and ABTS. Finally, the important chemical markers were verified by network pharmacological analysis and molecular docking. It provides a reference for clinical application of PCF, and the obtained chemical markers also provide a scientific reference for quality evaluation.
Qiu Zhong, Yaogui Sun, Ajab Khan, Jianhua Guo, Zhirui Wang, Na Sun,
Published: 12 September 2022
Oxidative Medicine and Cellular Longevity, Volume 2022, pp 1-12; https://doi.org/10.1155/2022/4189083

Abstract:
The administration of 4,7-didehydro-neophysalin B is expected to be a promising strategy for mitigating oxidative stress in respiratory diseases. This study was aimed at investigating the efficacy of 4,7-didehydro-neophysalin B for apoptosis resistance of rat lung epithelial cells (RLE-6TN) to oxidative stress and evaluating its underlying mechanism of action. The RLE-6TN cells treated with hydrogen peroxide (H2O2) were divided into five groups, and 4,7-didehydro-neophysalin B was administered into it. To evaluate its mechanism of action, the expression of oxidative stress and apoptotic proteins was investigated. 4,7-Didehydro-neophysalin B significantly inhibited H2O2-induced RLE-6TN cell damage. It also activated the Nrf2 signaling pathway which was evident from the increased transcription of antioxidant responsive of KLF9, NQO1, Keap-1, and HO-1. Nrf2 was found to be a potential target of 4,7-didehydro-neophysalin B. The protein levels of Bcl-2 and Bcl-xL were increased while Bax and p53 were decreased significantly. Flow cytometry showed that 4,7-didehydro-neophysalin B protected RLE-6TN cells from apoptosis and has improved the oxidative damage. This study provided a promising evidence that 4,7-didehydro-neophysalin B can be a therapeutic option for oxidative stress in respiratory diseases.
Jiang-Ping Wu, Ling-Yu Li, Jing-Rong Li, Meng Yu, Jianping Zhao, , , Tao Zhang,
Journal of Natural Products, Volume 85, pp 1522-1539; https://doi.org/10.1021/acs.jnatprod.2c00101

Published: 25 April 2022
by MDPI
Journal: Horticulturae
Abstract:
Physalis alkekengi L. is the only representative of the genus Physalis (Solanaceae) that is native to Bulgaria, found in wild habitats under different climatic and soil conditions. The plant is poisonous, but produces edible fruit, which are a source of functional nutrients—vitamins, phenolic antioxidants, minerals, etc. Therefore, the objective of this work was to determine the presence of certain nutrient and bioactive substances in two phenotypes of P. alkekengi fruit from Bulgaria, in order to better reveal the prospects of fruit use in nutrition. Different macro and micronutrients were determined in the fruit—protein, ash, lipids, fiber, natural pigments, sugars, amino acids, minerals—and the results showed differences between the phenotypes. Fruit energy values were low and identical in the samples, 43 kcal/100 g. The fruits were rich in extractable phenolics (TPC, 17.74–20.25 mg GAE/100 g FW; flavonoids, 15.84–18.03 mg QE/100 g FW) and demonstrated good antioxidant activity (DPPH, 171.55–221.26 mM TE/g; FRAP, 193.18–256.35 mM TE/g). P. alkekengi fruits were processed to obtain a dry extract with ethanol (yield 47.92–58.6%), and its individual composition was identified (GC-MS). The results in this study supported the presumed phytonutritive potential of P. alkekengi fruit, thus, opening doors for further research.
Cássio Santana Meira, José Waldson Capinan Soares, Bruna Padilha Zurita Claro dos Reis, Luciano Vasconcellos Pacheco, Ivanilson Pimenta Santos, Dahara Keyse Carvalho Silva, Julia Costa de Lacerda, Sérgio Ricardo Teixeira Daltro, Elisalva Teixeira Guimarães, Milena Botelho Pereira Soares
Published: 5 April 2022
Frontiers in Pharmacology, Volume 13; https://doi.org/10.3389/fphar.2022.864714

Abstract:
Physalins, or 16,24-cyclo-13,14-seco steroids, are compounds belonging to the class of withanolides that can be found in plants of Solanaceae family, mainly in species belonging to the genus Physalis spp., which are annual herbaceous plants widely distributed in tropical and subtropical regions of the world. Physalins are versatile molecules that act in several cell signaling pathways and activate different mechanisms of cell death or immunomodulation. A number of studies have shown a variety of actions of these compounds, including anticancer, anti-inflammatory, antiparasitic, antimicrobial, antinociceptive, and antiviral activities. Here we reviewed the main findings related to the anticancer, immunomodulatory, and antiparasitic activities of physalins and its mechanisms of action, highlighting the \challenges and future directions in the pharmacological application of physalins.
Published: 21 March 2022
by MDPI
Current Issues in Molecular Biology, Volume 44, pp 1407-1416; https://doi.org/10.3390/cimb44030094

Abstract:
(1) Background: Three isolated compounds from Physalis alkekengi var. franchetii (PAF) have been investigated to possess a variety of biological activities. Their structures were elucidated by spectroscopic analysis (Ultraviolet (UV), High-resolution electrospray mass spectrometry (HR-ESI-Ms), and their anti-inflammatory effects were evaluated in vitro; (2) Methods: To investigate the mechanisms of action of PAF extracts and their isolated compounds, their anti-inflammatory effects were assessed in RAW 264.7 macrophages stimulated by lipopolysaccharide (LPS). RAW 264.7 cells were treated with different concentrations of Physalis alkekengi var. franchetii three isolated compounds of PAF for 30 min prior to stimulation with or without LPS for the indicated times. The inflammatory cytokines, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were determined using reverse transcription-polymerase chain (RT-PCR); (3) Results Treatment of RAW 264.7 cells with LPS alone resulted in significant increases in inflammatory cytokine production as compared to the control group (p < 0.001). However, with the treatment of isophysalin B 100 μg/mL, there was a significant decrease in the mRNA expression levels of TNF-α in LPS-stimulated raw 264.7 cells (p < 0.001). With treatment of physalin 1–100 μg/mL, there was a markedly decrease in the mRNA expression levels of TNF-α in LPS stimulated raw 264.7 (p < 0.05). Moreover, TNF-α mRNA (p < 0.05) and IL-1β mRNA (p < 0.001) mRNA levels were significantly suppressed after treatment with 3′,7-dimethylquercetin in LPS stimulated Raw 264.7 cells; (4) Conclusions: These findings suggest that three isolated compounds from can suppress inflammatory responses in LPS stimulated macrophage.
Xue‐Yi Wu, Tian Wang, Hui‐Xin Hu, Kan Zhang, Yu Zhao, Bao‐Bing Zhao, Hong‐Xiang Lou, Xiao‐Ning Wang,
Published: 7 February 2022
Phytotherapy Research, Volume 36, pp 1692-1707; https://doi.org/10.1002/ptr.7403

The publisher has not yet granted permission to display this abstract.
Published: 28 January 2022
by MDPI
Journal: Molecules
Abstract:
Natural products are a major source of biologically active compounds that make promising lead molecules for developing efficacious drug-like molecules. Natural withanolides are found in many flora and fauna, including plants, algae, and corals, that traditionally have shown multiple health benefits and are known for their anti-cancer, anti-inflammatory, anti-bacterial, anti-leishmaniasis, and many other medicinal properties. Structures of these withanolides possess a few reactive sites that can be exploited to design and synthesize more potent and safe analogs. In this review, we discuss the literature evidence related to the medicinal implications, particularly anticancer properties of natural withanolides and their synthetic analogs, and provide perspectives on the translational potential of these promising compounds.
Published: 21 January 2022
by MDPI
Journal: Molecules
Abstract:
The calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino (P. alkekengi), a medicinal and edible plant, are frequently used as heat-clearing and detoxifying agents in thousands of Chinese medicine prescriptions. For thousands of years in China, they have been widely used in clinical practice to treat throat disease, hepatitis, and bacillary dysentery. This systematic review summarizes their structural analysis, quality control, pharmacology, and pharmacokinetics. Furthermore, the possible development trends and perspectives for future research studies on this medicinal plant are discussed. Relevant information on the calyxes and fruits of P. alkekengi was collected from electronic databases, Chinese herbal classics, and Chinese Pharmacopoeia. Moreover, information was collected from ancient documents in China. The components isolated and identified in P. alkekengi include steroids, flavonoids, phenylpropanoids, alkaloids, nucleosides, terpenoids, megastigmane, aliphatic derivatives, organic acids, coumarins, and sucrose esters. Steroids, particularly physalins and flavonoids, are the major characteristic and bioactive ingredients in P. alkekengi. According to the literature, physalins are synthesized by the mevalonate and 2-C-methyl-d-erythritol-4-phosphate pathways, and flavonoids are synthesized by the phenylpropanoid pathway. Since the chemical components and pharmacological effects of P. alkekengi are complex and varied, there are different standards for the evaluation of its quality and efficacy. In most cases, the analysis was performed using high-performance liquid chromatography coupled with ultraviolet detection. A pharmacological study showed that the crude extracts and isolated compounds from P. alkekengi had extensive in vitro and in vivo biological activities (e.g., anti-inflammatory, anti-tumor, immunosuppressive, antibacterial, anti-leishmanial, anti-asthmatic, anti-diabetic, anti-oxidative, anti-malarial, anti-Alzheimer’s disease, and vasodilatory). Moreover, the relevant anti-inflammatory and anti-tumor mechanisms were elucidated. The reported activities indicate the great pharmacological potential of P. alkekengi. Similarly, studies on the pharmacokinetics of specific compounds will also contribute to the progress of clinical research in this setting.
Yu Hu, Jianxin Li, Alan K. Chang, Zhina Wang, Weiping Su, Yanan Li, Wenbao Liu, Jiao Ai, Xia Tao, Pingyi Zheng, et al.
Published: 5 January 2022
Journal: Food & Function
Food & Function, Volume 13, pp 3308-3317; https://doi.org/10.1039/d1fo03712a

Abstract:
In Asia, the flower of Hosta plantaginea (Lam.) Aschers (hosta flower) is both an edible food and medicine.
Venelina Popova, Tanya Ivanova, Magdalena Stoyanova, Nadezhda Mazova, Ivanka Dimitrova-Dyulgerova, Albena Stoyanova, Sezai Ercisli, , Mohammed Kara, Hayat Topcu, et al.
Published: 1 January 2022
Journal: Open Chemistry
Open Chemistry, Volume 20, pp 1292-1303; https://doi.org/10.1515/chem-2022-0226

Abstract:
Physalis alkekengi L. (Solanaceae) is encountered in different regions of Bulgaria as a wild growing or ornamental plant. The objective of this work was to characterize the phytochemical composition (macro and micro components) of the leaves and stems of two local phenotypes (PA-SB and PA-NB), with the view of revealing their use potential. The dry leaves contained (DW) protein (16.25 and 19.27%), cellulose (25.16 and 25.31%), and ash (18.28 and 16.16%) and the stems contained protein (6.83 and 7.35%), cellulose (39.34 and 38.25%), and ash (15.01 and 7.48%) for PA-SB and PA-NB, respectively. The dominant amino acids (by HPLC) in the leaves of both phenotypes were arginine (21.3–22.3 mg/g) and aspartic acid (8.8–18.4 mg/g), and those in the stems were proline and aspartic acid for PA-SB (8.8, 7.7 mg/g); isoleucine and tyrosine for PA-NB (12.8, 6.6 mg/g). Mineral elements, determined by AAS (K, Ca, Mg, Na, Cu, Fe, Zn, Mn, Pb, Cr), also varied between phenotypes and plant parts. The leaves alone were further processed by extraction with n-hexane, for the identification of leaf volatiles (by gas chromatography-mass spectrometry). The analysis identified 28 components (97.99%) in the leaf extract of PA-SB and 32 components (97.50%) in that of PA-NB. The volatile profile of PA-SB leaves was dominated by diterpenes (49.96%) and oxygenated sesquiterpenes (35.61%), while that of PA-NB was dominated by oxygenated aliphatics (40.01%) and diterpenes (35.19%). To the best of our knowledge, the study provides the first data about the phytochemical composition of the leaves and stems of P. alkekengi from Bulgaria, in a direct comparison of phenotypes from two distinct wild populations, which could be of further scientific interest.
Meiqi Liu, Ziying Qiu, Xiaoran Zhao, , , , Yanru Deng
Published: 22 December 2021
Journal of Chemistry, Volume 2021, pp 1-11; https://doi.org/10.1155/2021/8502929

Abstract:
Physalis alkekengi L. var. franchetii (PALF) is a traditional Chinese medicine, which is well known for its antimicrobial, anti-inflammatory, antipyretic, and expectorant properties. Its fruits and fruiting calyxes are used as dietary supplements and traditional herbs in China. However, the quality of calyxes is uneven, and it is prone to getting moldy or moth-eaten during storage. High-performance liquid chromatography (HPLC) fingerprints and multivariate chemometric methods were combined to evaluate quality, and three representative compounds were chosen as the quality markers (Q-markers). Hierarchical cluster analysis (HCA) and principal component analysis (PCA) provided a clear discrimination of PALF samples. Through further verification by partial least squares discriminant analysis (PLS-DA), backpropagation artificial neural network (BP-ANN), machine learning, and combination with the determination of the content, biology, and pharmacology effect judgment, galuteolin, rutin, and physalin O could be used as Q-markers that their contents affect the quality of PALF grade evaluation. A simple method was established to rapidly assess the quality of PALF that is important for its clinical application and storage and provide a reference for evaluating the quality of materials used in Chinese medicine.
Wei Zhang, Shan-Shan Bai, Qi Zhang, Ru-Ling Shi, He-Cheng Wang, You-Cai Liu, Tian-Jun NI, Ying Wu, Zhao-Yang Yao, , et al.
Published: 20 October 2021
Chinese Journal of Natural Medicines, Volume 19, pp 732-740; https://doi.org/10.1016/s1875-5364(21)60090-0

The publisher has not yet granted permission to display this abstract.
Liqiang Qiu, Lingli Hu, Xiaoxiong Liu, Wenjing Li, Xutao Zhang, Hao Xia, Changjiang Zhang
Published: 20 September 2021
Journal: Food & Function
Food & Function, Volume 12, pp 10950-10966; https://doi.org/10.1039/d1fo01926k

Abstract:
Vascular intimal hyperplasia is a hallmark event in vascular restenosis. The excessive proliferation, migration and phenotypic transformation of vascular smooth muscle cells (VSMCs) play important roles in the pathological mechanism of vascular intimal hyperplasia. Physalin B is an alcoholate isolated from Physalis (Solanaceae) that has a wide range of biological activities. However, the effect of physalin B on VSMCs is currently unclear. In this study, we demonstrated that physalin B significantly inhibited the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. Physalin B also reduced inflammation and oxidative stress in VSMCs induced by PDGF-BB. Mechanistic studies showed that physalin B plays a role mainly by activating Nrf2. After Nrf2 activation, physalin B mitigates oxidative stress by enhancing the expression of the antioxidant gene HO-1; on the other hand, physalin B inhibits the NF-κB pathway to alleviate the inflammatory response. These two effects ultimately reduce the proliferation, migration and phenotypic transformation of VSMCs induced by PDGF-BB. In addition, in the mouse carotid artery ligation model, physalin B prevented intimal hyperplasia and inhibited the proliferation, migration and phenotypic transformation of cells in the hyperplastic intima. In conclusion, we provided significant evidence that physalin B abrogates PDGF-BB-induced VSMC proliferation, migration, phenotypic transformation and intimal hyperplasia by activating Nrf2-mediated signal transduction. Therefore, physalin B may be a potential therapeutic agent for preventing or treating restenosis.
Jiangping Wu, Jianping Zhao, Tao Zhang, , Ikhlas A. Khan, ,
Published: 3 September 2021
Journal: Phytochemistry
The publisher has not yet granted permission to display this abstract.
, Priyank Tandel, Jyoti Wadekar
Published: 6 March 2021
Phytomedicine Plus, Volume 1; https://doi.org/10.1016/j.phyplu.2021.100052

The publisher has not yet granted permission to display this abstract.
Wei Wu, Zixiang Geng, Haoran Bai, Te Liu, Bimeng Zhang
International Journal of Medical Sciences, Volume 18, pp 1899-1909; https://doi.org/10.7150/ijms.54860

Abstract:
The morbidity and mortality rates associated with non-small-cell lung carcinoma (NSCLC) are increasing every year, placing new demands on existing therapies and drugs. Ammonium ferric citrate (AFC) is often used as a food additive for iron supplementation; however, to our knowledge, no studies have investigated whether AFC can induce ferroptosis in NSCLC. In this study, we demonstrated that specific concentrations of AFC effectively inhibit the proliferation and invasion of lung cancer cell lines in vitro using a cell proliferation inhibition test, a transwell assay, and flow cytometry analysis of cell cycle and apoptosis. In addition, AFC significantly induced oxidative stress injury in lung cancer cell lines. A quantitative polymerase chain reaction assay showed that AFC markedly reduced the expression levels of cell growth factors, negative regulators of ferroptosis, and autophagy regulators. Lastly, a protein-protein interaction analysis revealed that glutathione peroxidase 4 (GPX4) exerted its biological role through the regulation of the GSS/GSR complex and downstream GGT family proteins. When the expression of GPX4 changes, its biological activities, such as the glutathione metabolic process, cellular biosynthetic process, cellular response to chemical stimulus, and antioxidant activity, change accordingly, thereby affecting the survival quality and physiological and biochemical activities of cells. Overall, this study verifies that AFC has the biological activity of activating oxidative stress injury in NSCLC cell lines, leading to a decrease in their autophagy and inducing ferroptosis. We also confirmed that the GPX4-GSS/GSR-GGT axis is a crucial target of AFC-induced ferroptosis.
T A Ivanova, V T Popova, S T Tasheva, N N Mazova, A S Stoyanova
Iop Conference Series: Materials Science and Engineering, Volume 1031; https://doi.org/10.1088/1757-899x/1031/1/012092

Abstract:
The aim of the study was the provision of a technological background for obtaining ethanol extracts with prospective cosmetic application from the leaves of P. alkekengi L. Extraction was carried out in laboratory conditions, as a batch static mode process, with four solvents, 95%, 70%, 50%, and 30% ethanol, respectively. The influence of the main technological factors, temperature (20°C, 40°C, and 60°C) and duration (1 h, 3 h, 5 h and 7 h), upon the content of tannins in the extracts was studied by mathematical modelling of the experiment. The equations of extraction, based on the concentration of extracted tannins were derived. The optimal conditions for the extraction procedure of P. alkekengi leaves were determined (70% ethanol, 5 h, 60°C). The results from the study, i.e. the dynamics of tannin extraction, the equations of extraction and the technological factors’ combination, could be applied in the obtaining of P. alkekengi leaf extraction products intended for use in different personal care products; of course, additional investigations on the subject are necessary, especially in terms of extracts’ individual composition and biological activities.
, S T Tasheva, T A Ivanova, A S Stoyanova
Iop Conference Series: Materials Science and Engineering, Volume 1031; https://doi.org/10.1088/1757-899x/1031/1/012093

Abstract:
Physalis alkekengi L. (Solanaceae) is a wild growing plant, native to Bulgaria. The plant produces edible fruit rich in phytonutrients; the fruit and the leaves have been used in Bulgarian and other folk medicines for centuries. The leaves of P. alkekengi can be considered as a promising resource for obtaining extracts rich in bioactive ls is performed by molecular diffusion; a generalized indicator of the diffusive properties is the coefficient of diffusion (D). It takes individual values for different plant matrices and depends on various factors in the mass transfer process. To the best of our knowledge, there are no data about the diffusion coefficients of tannins in P. alkekengi leaf extracts, which was set as the objective of the study. Extraction was carried out in a batch static mode, under the following conditions: raw material to solvent ratio of 1:33 (w/v); size of leaf particles – 0.0125 m χ 0.002 m; duration of extraction – 1 h, with the solvent being replaced and analyzed for extracted tannins after each 600 s; solvents – 95%, 70%, 50%, and 30% ethanol; temperature – 20°C, 40°C and 60°C. The values of the coefficient showed variation over time and temperature, for each of the solvents. The highest D value obtained was 0.1690.10-9 m2.s-1 (70% ethanol, 60°C). These are the first data about the coefficient of diffusion of tannins in ethanol extracts from Physalis alkekengi L. leaves.
Published: 17 August 2020
by MDPI
Journal: Molecules
Abstract:
To find new natural remedies in diabetes, this study investigated the biological activity of two extracts obtained from the fruits (PhyF) and herba (PhyH) of Physalis alkekengi var. franchetii L. on human umbilical vein endothelial cells (HUVECs) exposed to normo- and hyperglycemic conditions. The biological effect was quantified by malondialdehyde, IL-31 and IL-33 levels in correlation with physico-chemical characterization and antioxidant activity. Additionally, from PhyP extract, the caspase-3, IL-6, IL-10, tumor necrosis factor (TNF)-α and nuclear transcription factor NFkB expressions were evaluated. HPLC analysis revealed a significant number of phenolic compounds, especially in PhyF extract, with a good antioxidant activity as highlighted by TEAC, CUPRAC or DPPH methods. On HUVECS cells, the extracts were not toxic even at high concentrations. Particularly PhyF extract, diminished lipid peroxidation and inhibited the IL-31 and IL-33 secretions induced by hyperglycemia. The inhibitory effect on proinflammatory cytokines was noticed after both doses of PhyF extract in parallel with the upregulation of anti-inflammatory cytokine IL-10. Moreover, PhyF, especially in a low dose, reduced caspase-3 active form. These experimental findings suggest that Physalis fruits extract exerted beneficial effects in hyperglycemia by inhibition of oxidative stress, inflammation and apoptosis being a good adjuvant option in diabetes.
Guihua Wang, Li Xu, Wei Liu, Wen Xu, Yu Mu, Zhanyou Wang, ,
Published: 25 July 2020
Journal: Fitoterapia
The publisher has not yet granted permission to display this abstract.
Hui-Xin Hu, Lin-Tao Xu, Hui Gao, Hui Lv, Min Huang, Kai-Li Fang, Shu-Qi Wang, Bao-Bing Zhao, , Xiao-Ning Wang, et al.
Published: 15 July 2020
Journal: Planta Medica
Planta Medica, Volume 86, pp 1191-1203; https://doi.org/10.1055/a-1197-7019

Abstract:
Physalis Calyx seu Fructus, a traditional Chinese medicine consisting of the calyxes and fruits of Physalis alkekengi var. franchetii, has been used as therapy for inflammation-related respiratory diseases such as excessive phlegm, cough, sore throat, and pharyngitis for a long history in China. The aim of the present study was to investigate the chemical constituents of Physalis Calyx seu Fructus and identify the bioactive constituents responsible for its traditional application as therapy for inflammation-related diseases. In the present study, one new phenylpropanoid (1), two new steroids (17 and 18), together with 55 known constituents have been purified from the EtOH extract of Physalis Calyx seu Fructus. Among them, seven and twelve known constituents were isolated for the first time from Physalis Calyx seu Fructus and the genus Physalis, respectively. Fourteen constituents, including steroids [physalins (5 – 9, 12 – 14, and 15) and ergostane (21)], a sesquiterpenoid (35), alkaloids (36 and 37), and a flavonoid (44), showed inhibitory effects against oxidative stress. Ten constituents, including steroids (5, 6, 8, 13, and 15), sesquiterpenoids (34 and 35), alkaloids (37 and 41), and a flavonoid (43), were found be potential anti-inflammatory constituents of this medicinal plant. The inhibition of oxidative stress and inflammatory response may be related to the regulation of Nrf2 and nuclear factor-κB pathways. The ethnomedical use of Physalis Calyx seu Fructus as a treatment for respiratory diseases might be attributed to the combined inhibitory effects of steroids, alkaloids, sesquiterpenoids, and flavonoids against oxidative stress and inflammatory response.
XiaoRi Zhan, Xiujun Luo, Jinyu He, Chengchao Zhang, Xinyue Liao, Xinyun Xu, Shangguo Feng, Chunna Yu, Zhifang Jiang, Yijun Meng, et al.
Published: 29 March 2020
Plant Molecular Biology, Volume 103, pp 341-354; https://doi.org/10.1007/s11103-020-00996-y

Abstract:
We employed both metabolomic and transcriptomic approaches to explore the accumulation patterns of physalins, flavonoids and chlorogenic acid in Physalis angulata and revealed the genes associated with the biosynthesis of bioactive compounds under methyl-jasmonate (MeJA) treatment.
Yanni Yang, Zihe Ding, Yi Wang, RenXing Zhong, Yanlin Feng, Tianyi Xia, Yuanyuan Xie, Bingyou Yang, Xiaobo Sun,
Published: 27 March 2020
Journal of Cellular and Molecular Medicine, Volume 24, pp 5039-5056; https://doi.org/10.1111/jcmm.15126

Abstract:
Acute lung injury (ALI) is an important cause of mortality of patients with sepsis, shock, trauma, pneumonia, multiple transfusions and pancreatitis. Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF) has been extensively used in Chinese folk medicine because of a good therapeutic effect in respiratory diseases. Here, an integrated approach combining network pharmacology, proton nuclear magnetic resonance‐based metabolomics, histopathological analysis and biochemical assays was used to elucidate the mechanism of PAF against ALI induced by lipopolysaccharide (LPS) in a mouse model. We found that the compounds present in PAF interact with 32 targets to effectively improve the damage in the lung undergoing ALI. We predicted the putative signalling pathway involved by using the network pharmacology and then used the orthogonal signal correction partial least‐squares discriminant analysis to analyse the disturbances in the serum metabolome in mouse. We also used ELISA, RT‐qPCR, Western blotting, immunohistochemistry and TUNEL assay to confirm the potential signalling pathways involved. We found that PAF reduced the release of cytokines, such as TNF‐α, and the accumulation of oxidation products; decreased the levels of NF‐κB, p‐p38, ERK, JNK, p53, caspase‐3 and COX‐2; and enhanced the translocation of Nrf2 from the cytoplasm to the nucleus. Collectively, PAF significantly reduced oxidative stress injury and inflammation, at the same time correcting the energy metabolism imbalance caused by ALI, increasing the amount of antioxidant‐related metabolites and reducing the apoptosis of lung cells. These observations suggest that PAF may be an effective candidate preparation alleviating ALI.
Wen-Jing Yang, Xue-Mei Chen, Shu-Qi Wang, Hui-Xin Hu, Xin-Ping Cheng, Lin-Tao Xu, , , Bao-Bing Zhao, , et al.
Published: 11 March 2020
Journal of Natural Products, Volume 83, pp 1217-1228; https://doi.org/10.1021/acs.jnatprod.9b01265

Abstract:
Environmental toxicant- and oxidant-induced [e.g., cigarette smoke (CS)] respiratory oxidative stress and inflammatory response play a vital role in the onset and progression of COPD. The nuclear factor erythroid 2-related factor 2 (Nrf2) represents an important mechanism for regulating intracellular oxidative stress and inflammatory response and is a promising target for developing agents against COPD. Herein, a bioactivity-guided purification of goldenberry (whole fruits of Physalis peruviana L.) led to the isolation of a novel and potent Nrf2 activator 4β-hydroxywithanolide E (4β-HWE). Our study indicated that (i) 4β-HWE activated the Nrf2-mediated defensive response through interrupting Nrf2-Keap1 protein–protein interaction (PPI) via modification of Cys151 and Cys288 cysteine residues in Keap1 and accordingly suppressing the ubiquitination of Nrf2. (ii) 4β-HWE enhanced intracellular antioxidant capacity and inhibited oxidative stress in normal human lung epithelial Beas-2B cells and wild-type AB zebrafish. (iii) 4β-HWE blocked LPS-stimulated inflammatory response and inhibited LPS-stimulated NF-κB activation in RAW 264.7 murine macrophages. (iv) 4β-HWE effectively suppressed oxidative stress and inflammatory response in a CS-induced mice model of pulmonary injury. Collectively, these results display the feasibility of using 4β-HWE to prevent or alleviate the pathological progression of COPD and suggest that 4β-HWE is a candidate or a leading molecule against COPD.
Published: 6 March 2020
by MDPI
International Journal of Molecular Sciences, Volume 21; https://doi.org/10.3390/ijms21051836

Abstract:
We aimed to study the effects of an ethyl acetate fraction of Physalis alkekengi (PAE) on d-galactose (d-gal)-induced senescence and the underlying mechanism. Firstly, analysis of the phytochemical composition revealed total flavonoids, total phenolics, total saponins, rutin, and luteolin contents of 71.72 ± 2.99 mg rutin equivalents/g, 40.19 ± 0.47 mg gallic acid equivalents/g, 128.13 ± 1.04 mg oleanolic acid equivalents/g, 1.67 ± 0.07 mg/g and 1.61 ± 0.01 mg/g, respectively. The mice were treated with d-gal for six weeks, and from the fifth week, the mice were administered with PAE by gavage once a day for five weeks. We found significant d-gal-induced ageing-related changes, such as learning and memory impairment in novel object recognition and Y-maze, fatigue in weight-loaded forced swimming, reduced thymus coefficient, and histopathological injury of the liver, spleen, and hippocampus. The PAE effectively protected from such changes. Further evaluation showed that PAE decreased the senescence-associated β-galactosidase of the liver, spleen, and hippocampus, as well as the oxidative stress of the liver, plasma, and brain. The abundance of flavonoids, phenols, and saponins in PAE may have contributed to the above results. Overall, this study showed the potential application of PAE for the prevention or treatment of ageing-associated disorders.
Yuan Yee Lee, Minki Kim, Muhammad Irfan, Seung-Hyung Kim, ,
Published: 1 March 2020
Journal of Medicinal Food, Volume 23, pp 312-318; https://doi.org/10.1089/jmf.2019.4625

Abstract:
The aim of this study was to investigate the efficacy of an ethanol extract of Physalis alkekengi (PA) and its mechanistic pathway of action at the molecular level for its antiobesity properties. Four-week old male Institute of Cancer Research (ICR) mice were acclimatized for a week before starting the high-fat diet (HFD) for 2 weeks to induce obesity, followed by 8 more weeks of oral administration of 10 mg/kg orlistat and 300 mg/kg of PA extract, along with HFD. Body weights of the mice and feed and water intake were recorded weekly. After a total of 12 weeks, mice were euthanized, and blood, liver, and adipose tissues were harvested for further analysis. Administration of PA extract inhibited the progression of obesity by reducing weight gain, weight of adipose tissue, and normalizing serum triglyceride, glucose, total cholesterol, high-density lipoprotein, low-density lipoprotein, alanine aminotransferase, and aspartate aminotransferase. PA extract prevented the progression of nonalcoholic steatohepatitis induced by HFD and prevented the enlargement of liver. Phosphorylation of adenosine monophosphate-activated protein kinase α increased while phosphorylation of acetyl-CoA carboxylase was reduced. The browning gene uncoupling protein 1 expression was also increased by PA extract treatment. Our findings revealed that the antiobesity properties of PA extract may be mediated by browning of white adipose tissue.
Published: 5 February 2020
by MDPI
Journal: Biomedicines
Abstract:
As part of the search for new bioactive plants from the Colombian Caribbean, the dichloromethane fraction of the calyces of Physalis angulata L. (PADF) was selected for its anti-inflammatory activity. In this work, we investigated the immunomodulatory effect of PADF in activated macrophages and during dextran sulfate sodium (DSS)-induced colitis. PADF displayed a low content of withanolides or phenolic compounds, and a higher content of sucrose esters, representative anti-inflammatory metabolites of the Physalis genus. The PADF fraction at 12.5 μg/mL prevented the induction of interleukin (IL)-1β, tumor necrosis factor (TNF-α), IL-6, IL-12, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) by lipopolysaccharide (LPS), while increased the levels of arginase (ARG1), IL-10, and mannose receptor C (MRC1). The polarization towards an anti-inflammatory profile was also observed in resting macrophages, without promoting the typical gene profile induced by IL-4, suggesting that PADF promotes a shift to a regulatory status rather than to an alternative one. In vivo, the administration of PADF to mice with chronic DSS-colitis reduced disease signs (i.e., body weight loss and colon shortening), and improved the histology score by diminishing the levels of pro-inflammatory cytokines and increasing the production of IL-10. Overall, results suggest that the regulatory effect on PADF towards macrophages might contribute to the therapeutic activity observed in the murine model of inflammatory bowel disease.
Arefeh Rahimi Shokooh, Hassanali Naghdi Badi, Vahid Abdossi, , مرکز تحقیقات گیاهان دارویی، پژوهشکده گیاهان دارویی جهاددانشگاهی، کرج، ایران
Published: 1 February 2020
Journal of Medicinal Plants, Volume 4, pp 1-13; https://doi.org/10.29252/jmp.4.72.s12.1

, Tao Guo, Fang-Bo Zhang, Ya-Nan Wang, Zhiguo Liu, Shanshan Guo,
Published: 25 January 2020
Bioorganic Chemistry, Volume 96; https://doi.org/10.1016/j.bioorg.2020.103614

The publisher has not yet granted permission to display this abstract.
Min Huang, Ji-Xiang He, Hui-Xin Hu, Kan Zhang, Xiao-Ning Wang, Bao-Bing Zhao, Hong-Xiang Lou, Dong-Mei Ren,
Journal of Pharmacy and Pharmacology, Volume 72, pp 649-669; https://doi.org/10.1111/jphp.13209

Abstract:
Objectives Withanolides are a group of modified C28 ergostane‐type steroids with a C‐22, C‐26 δ‐lactone side chain or a C‐23, C‐26 γ‐lactone side chain. They enjoy a limited distribution in the plant kingdom and predominantly occur in several genera of Solanaceae. Of which, the genus Physalis is an important resource for this type of natural molecules. The present review aims to comprehensively illustrate the structural characteristics and classification of withanolides, and particularly focus on the progression on phytochemical and pharmacological aspects of withanolides from Physalis ranging from January 2015 to June 2019. Key findings Approximately 351 natural withanolides with novel and unique structures have so far been identified from genus Physalis, mainly isolated from the species of P. angulata and P. peruviana. Withanolides demonstrated diverse biological activity, such as anticancer, anti‐inflammatory, antimicrobial, immunoregulatory, trypanocidal and leishmanicidal activity. Their observed pharmacological functions supported the uses of Physalis species in traditional or folk medicines. Summary Due to their unique structure skeleton and potent bioactivities, withanolides are regarded to be promising drug candidates, particularly for developing anticancer and anti‐inflammatory agents. Further investigations for discovering novel withanolides of genus Physalis, exploiting their pharmacological values and evaluating their potency as therapeutic agents are significant work.
, Yun Tang, Yanni Yang, Zihe Ding, RenXing Zhong, Tianyi Xia, Xinjia Li, Cuiying Zheng, Zhixiong Wen, , et al.
Published: 25 July 2019
Natural Product Research, Volume 35, pp 1274-1280; https://doi.org/10.1080/14786419.2019.1645657

Abstract:
Two new hexenol glycosides, (Z)-hex-3-en-1-ol O-β-d-xylcopyranosyl-(1-6)-β -d-glucopyranosyl-(1-2)-β-d-glucopyranoside (1) and (E)-hex-3-en-1-ol O-β-d-xylcopyranosyl-(1-6)-β-d-glucopyranosyl-(1-2)-β-d-glucopyranoside (2), were isolated from the 50% ethanol elution of macroporous resin of Physalis alkekengi var. franchetii. Their structures were established by detailed spectroscopic analysis, including extensive 2D-NMR data. This is the first time to report the (Z) and (E) 3-hexenol glycosides from Physalis alkekengi var. franchetii.
Weixiao An, Honglin Lai, Yangyang Zhang, Minghua Liu, ,
Published: 12 July 2019
Frontiers in Pharmacology, Volume 10; https://doi.org/10.3389/fphar.2019.00758

Abstract:
Cancer is a leading cause of morbidity and mortality worldwide. Apoptosis is a process of programmed cell death and it plays a vital role in human development and tissue homeostasis. Mounting evidence indicates that apoptosis is closely related to the survival of cancer and it has emerged as a key target for the discovery and development of novel anticancer drugs. Various studies indicate that targeting the apoptotic signaling pathway by anticancer drugs is an important mechanism in cancer therapy. Therefore, numerous novel anticancer agents have been discovered and developed from traditional Chinese medicines (TCMs) by targeting the cellular apoptotic pathway of cancer cells and shown clinically beneficial effects in cancer therapy. This review aims to provide a comprehensive discussion for the role, pharmacology, related biology, and possible mechanism(s) of a number of important anticancer TCMs and their derivatives mainly targeting the cellular apoptotic pathway. It may have important clinical implications in cancer therapy.
Wenjie Gao, Feng Chen, Hongquan Li, Xiaowen Wang,
Journal of Food Measurement and Characterization, Volume 13, pp 2921-2934; https://doi.org/10.1007/s11694-019-00213-5

The publisher has not yet granted permission to display this abstract.
Zhiming Shan, Song Cai, Jie Yu, Zhongjun Zhang, Tissiana Gabriela Menna Vallecillo, Maria Jin Serafini, Ann Mary Thomas, Nancy Yen Ngan Pham, Shreya Sai Bellampalli, Aubin Moutal, et al.
Published: 4 April 2019
ACS Chemical Neuroscience, Volume 10, pp 2939-2955; https://doi.org/10.1021/acschemneuro.9b00166

The publisher has not yet granted permission to display this abstract.
, , Mo Li, Kunli Wang, , Ralf Martin Schweiggert, , Reinhold Carle
Published: 4 March 2019
Food Research International, Volume 120, pp 389-398; https://doi.org/10.1016/j.foodres.2019.03.002

Abstract:
Physicochemical characteristics and phytochemical profiles of red (Physalis alkekengi L., RP) and yellow (P. pubescens L., YP) Physalis fruits cultivated in three provinces of China were characterized. YP fruits showed significantly lower levels of total organic acids and elevated total sugars than those of RP. A total of 18 compounds was tentatively identified in hydromethanolic extracts of Physalis fruits applying HPLC-DAD-ESI-MSn and HR-ESI-MS. Cinnamoyl and hydroxycinnamoyl conjugates prevailed in both fruits. Diverse mono- and dihexosides of cinnamic, coumaric, caffeic, ferulic, and sinapic acid were found in YP, while RP merely contained feruloyl and sinapoyl hexosides. N,N´-dicaffeoylspermidine isomers were found in YP fruits, whereas N,N´-bis(dihydrocaffeoyl)spermine was exclusively detected in two of the RP samples. Additionally, two HDMF (4-hydroxy-2,5-dimethyl-3(2H)-furanone) hexosides were tentatively identified for the first time in YP. Both RP and YP fruits collected from three different provinces in China showed a significant intraspecific variability regarding their phytochemical profiles, despite their similar morphological fruit traits.
Xuegui Liu, Jun Bian, Danqi Li, Changfeng Liu, Shuangshuang Xu, Gongling Zhang, Lixin Zhang,
Published: 1 March 2019
Industrial Crops and Products, Volume 129, pp 654-661; https://doi.org/10.1016/j.indcrop.2018.12.047

Published: 5 July 2018
Journal of Ethnopharmacology, Volume 225, pp 202-210; https://doi.org/10.1016/j.jep.2018.07.007

Abstract:
The edible plant Physalis alkekengi (PA) is used in traditional medicine to treat diabetes. However, the anti-diabetic effects and constituents of the fruit and aerial parts of this plant have not been studied extensively.
Hui Lv, Chun-Sheng Fu, Hui-Xin Hu, Xiao-Ning Wang, Dong-Mei Ren, , Tao Shen
Published: 1 June 2018
Biochemical Systematics and Ecology, Volume 78, pp 63-65; https://doi.org/10.1016/j.bse.2018.04.003

Xiao-Fang Hu, Qiang Zhang, Pan-Pan Zhang, , Ji-Chao Liang, Susan L. Morris-Natschke, Yong Chen,
Published: 1 June 2018
Journal: Fitoterapia
Fitoterapia, Volume 127, pp 129-137; https://doi.org/10.1016/j.fitote.2018.02.015

Abstract:
The aims of the present study were to assess the anti-diabetic effects of Physalis alkekengi L. (PA) in 3T3-L1 pre-adipocyte cells and HepG2-GFP-CYP2E1 (E47) cells and in a pre-diabetic rat model, as well as to identify the active chemical constituents. The in vitro results showed that PA has a strong anti-diabetic capacity to relieve oxidative stress and inhibit α-glucosidase activity. Mechanistic analysis also showed that ethyl acetate extracts of aerial parts and fruit of PA (PAG-EA and PAF-EA) enhanced glucose transporter 4 expression and function as well as enhanced insulin sensitivity by inhibiting the expression of cytochrome P450-2E1 (CYP2E1) mRNA and protein. In vivo, PAG-EA and PAF-EA significantly decreased the levels of fasting blood glucose and fasting insulin, as well as total cholesterol and triglyceride, in the pre-diabetic rats. The results from insulin sensitivity index and homeostasis model assessment-insulin resistance index along with an oral glucose tolerance test also showed that PAG-EA and PAF-EA could significantly enhance the insulin sensitivity, which confirmed the in vitro findings. Moreover, HPLC-ESI-QTOF-MS analysis identified flavonoids, physalins and phenolic acids as the main plant constituents. Our findings support the ethnopharmacological use of PA fruit, along with its aerial parts, as a strong anti-diabetic agent. The EA fraction, especially the constituent polyphenols and flavonoids, may have a good potential to treat diabetes.
Published: 15 March 2018
Cell Stress and Chaperones, Volume 23, pp 763-772; https://doi.org/10.1007/s12192-018-0887-0

Abstract:
Physalis alkekengi var. francheti is an indigenous herb well known for its anti-inflammatory, sedative, antipyretic, and expectorant properties. However, the information regarding the impacts of P. alkekengi fruits (PAF) in modulation of oxidative stress and learning memory are still unknown. This study therefore evaluated the antioxidant properties of ethyl acetate (EA) fraction of PAF and its impacts on learning and memory. The antioxidant activities of PAF were evaluated in LPS-induced BV2 microglial cells. The potent EA fraction then investigated and confirmed for its involvement of HO-1 pathway using hemin (HO-1 inducer) and ZnPP (HO-1 inhibitor) through Western blotting, DCFH-DA, and/or Griess assay. The involvements of PI3K/Akt, MEK, and p38 MAPK also investigated. Furthermore, we applied EA fraction to the animals at 100 and 200 mg/kg doses to check if the extract could improve scopolamine-induced memory deficits in passive avoidance and elevated plus maze tests. Our results demonstrated that the fractions from PAF significantly inhibited the generation of intracellular reactive oxygen species (ROS) induced by LPS in concentration-dependent manners. In comparison to other fractions, the EA fraction exhibited potent effect in suppressing intracellular ROS generation. Besides, EA fraction also induced the expression of HO-1 in time- and concentration-dependent manners. ZnPP significantly reversed the suppressive effect of EA fraction on LPS-induced ROS generation and NO production, which confirm the involvement of HO-1 signaling in EA-fraction-mediated antioxidant activities. Consistently, blocking of PI3K/Akt, MEK, and p38 MAPK pathways by PAF-EA suppressed the production of intracellular ROS, indicating their potential participation. In addition, one of the major constituents of EA fraction, luteolin-7-O-β-D-glucoside, also demonstrated HO-1-dependent antioxidant effects in BV2 cells. Further, the EA fraction significantly (p < 0.05) improves scopolamine-induced memory deficits in mice. Taken together, our findings highlight the antioxidant effects of EA fraction of PAF which may be beneficial in treatment of different neurodegenerative diseases associated with free radicals.
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