Withanolides from Physalis angulata var. villosa and the Relative Configurational Revision of Some Known Analogs.

Physalis angulata var. villosa is a plant possessing abundant withanolides, but in-depth research is lacking. In our ongoing study of P. angulata var. villosa, 15 previously undescribed withanolides (1-15), along with 21 known analogs (16-36), were isolated from the whole plant. The structures of the withanolides (1-15) were elucidated based on analysis of their 1D and 2D NMR, HRESIMS, and ECD data. Additionally, the application of γ-gauche effects with the help of ROESY correlations led to the formulation of empirical rules for withanolides with 14-OH/15-OAc to rapidly determine the 14-OH orientations, making it possible to propose configurational revisions of 19 previously reported analogs (1'-19'). Withanolides 1, 4-6, and 10 showed potent cytotoxic activities against three human cancer cell lines (HCT-116, MDA-MB-231, and A549).

Target Separation and Potential Anticancer Activity of Withanolide-Based Glucose Transporter Protein 1 Inhibitors from Physalis angulata var. villosa.

The glucose transporter 1 (GLUT1) protein is involved in the basal-level absorption of glucose in tumor cells. Inhibiting GLUT1 decreases tumor cell proliferation and induces tumor cell damage. Natural GLUT1 inhibitors have been studied only to a small extent, and the structures of known natural GLUT1 inhibitors are limited to a few classes of natural products. Therefore, discovering and researching other natural GLUT1 inhibitors with novel scaffolds are essential. Physalis angulata L. var. villosa is a plant known as Mao-Ku-Zhi (MKZ). Withanolides are the main phytochemical components of MKZ. MKZ extracts and the components of MKZ exhibited antitumor activity in recent pharmacological studies. However, the antitumor-active components of MKZ and their molecular mechanisms remain unknown. A cell membrane-biomimetic nanoplatform (CM@Fe3O4/MIL-101) was used for target separation of potential GLUT1 inhibitors from MKZ. A new withanolide, physagulide Y (2), together with six known withanolides (1, 3-7), was identified as a potential GLUT1 inhibitor. Physagulide Y was the most potent GLUT1 inhibitor, and its antitumor activity and possible mechanism of action were explored in MCF-7 human cancer cells. These findings advance the development of technologies for the targeted separation of natural products and identify a new molecular framework for the investigation of natural GLUT1 inhibitors.

Two new sesquiterpenoid glycoside compounds from the calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-ß-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3-12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 µM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 µM, respectively.

Cape Gooseberry (Physalis peruviana L.) Volatile Compounds Determination by Vacuum-Assisted Sorbent Extraction (VASE)-Selected Aspects.

Vacuum-Assisted Sorbent Extraction (VASE) is a novel extraction technique that uses vacuum to facilitate the transfer of volatile compounds from the matrix to the sorbent. This technique was explored for extraction of volatiles from cape gooseberry fruit, for both qualitative and quantitative analyses. Selected extraction parameters were tested: sample size, extraction temperature and time, influence of tissue disintegration on release of volatiles, and also addition of Ag+1 ions in the form of AgNO3 to stop enzymatic formation of volatile compounds. For selected conditions (10 g sample, extraction for 30 min. at 40 °C of volatiles from blended fruit) quantitative aspects were explored. Twenty-two compounds of cape gooseberry were tested. The method was characterized with a very good linearity in a range of 10-5000 µg/kg and good reproducibility. The experiments proved the usefulness of VASE in both volatile profiling and quantitative analyses of cape gooseberry and in prospective other fruit.

Golden berry leaf extract containing withanolides suppresses TNF-α and IL-17 induced IL-6 expression in HeLa Cells.

Inflammation, characterized by the overexpression of IL-6 in various tissues, has been reported as a symptom of coronavirus disease 2019. In this study, we established an experimental system for overexpression of IL-6 in HeLa cells stimulated by TNF-α and IL-17, along with identification of anti-inflammatory materials and components from local agricultural, forestry, and fishery resources. We constructed a library of extracts from natural sources, of which 111 samples were evaluated for their anti-inflammatory activities. The MeOH extract of Golden Berry (Physalis peruviana L) leaf was found to exhibit strong anti-inflammatory properties (IC50 = 4.97 µg/mL). Preparative chromatography identified two active constituents, 4ß-hydroxywithanolide E (4ß-HWE) (IC50 = 183 nM) and withanolide E (WE) (IC50 = 65.1 nM). Withanolides are known anti-inflammatory ingredients of Withania somnifera, an Ayurvedic herbal medicine. P. peruviana leaves containing 4ß-HWE and WE should be considered as useful natural resources for anti-inflammatory products.

A comprehensive quality evaluation method of different medicinal parts of Physalis Calyx seu Fructus by fingerprints, chemometrics, antioxidant activity, network pharmacology and molecular docking.

Physalis Calyx seu Fructus (PCF) is a herb widely used in China for its function of clearing heat and detoxifying, benefitting the pharynx and reducing phlegm, both in health care and in tea drinking. However, the quality of its fruit and calyx is uneven and the storage period is short. Therefore, it is crucial to develop other parts of PCF with longer storage periods and obvious medicinal effects. Firstly, high-performance liquid chromatography was used to develop the fingerprint of different parts of PCF, and various chemometric analyses were conducted to screen out chemical markers. The calyxes of PCF were found to cluster together, distinct from the fruits, roots, stems and leaves. The active components of PCF were concentrated in the persistent calyxes, and flavonoids were mainly found in the persistent calyxes and leaves. Secondly, the extraction of persistent calyxes showed 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 the clinical application of PCF, and the obtained chemical markers offer a scientific basis for quality evaluation.

Withanolides from Physalin angulata and Their Inhibitory Effects on Nitric Oxide Production.

Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogs (7-18) were isolated from the whole plants of Physalis angulata. Their structures were elucidated by analysis of 1D and 2D NMR, ECD and IR spectra, HR-ESI-MS data, and ECD calculation. Compounds 1 and 6 were rare 1-10 seco withanolides. Compounds 2-4, 7-9, and 15 exhibited significant inhibitory activity on the production of nitric oxide in the LPS-activated RAW 264.7 mouse macrophage cell lines with IC50 values ranging from 0.23 to 9.06 µM.

Research on the Chemical Constituents against Alzheimer's Disease of the Fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino.

Physalis alkekengi L. var. franchetii (Mast.) Makino (PA) is a natural plant which is utilised as a traditional herbal medicine. It has properties that make it effective against inflammation and free radical damage. In the present study, the major constituents of four extraction parts of the fruits of PA (PAF) were investigated by combining ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The mice model of Alzheimer's disease (AD) induced by aluminum chloride (AlCl3 ) combined with D-galactose (D-gal) was established to comprehend the mechanism behind PAF's anti-AD activity from both behavioural and pathological perspectives. The results showed that four extraction parts of PAF (PAFE) had favorable anti-AD effects and the ethyl acetate (EA) group showed the best activity. UPLC-Q-TOF-MS analysis identified Physalin B, Nobiletin and Caffeic acid as the main anti-AD active constituents in EA extract. This study reveals that PAF can reduce neuroinflammatory damage by inhibiting p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway, which is the theoretical basis for clinical development and utilization of PAF in AD therapy.

Two new withanolides from the whole plants of Physalis peruviana.

Two new withaphysalin-type withanolides (18-O-ethylwithaphysalin R and 5-O-ethylphysaminimin C, 1 and 2), along with twelve known withanolides (3-14), were purified and identified from Physalis peruviana L. The chemical structures of these new isolates were elucidated through analyzing spectroscopic and HRESIMS data. All the obtained metabolites were appraised for their potential antiproliferative activity against the human breast cancer cell line MCF-7. Compound 7 was discovered to exhibit potent activity with an IC50 value of 3.51 µM and compounds 2, 6 and 14 showed weak cytotoxic effect.

Nutritional and antioxidant profile of the Physalis fruit grown in three Andean regions of Peru.

Background: Physalis peruviana L. fruit contains nutritional and bioactive compounds of immense importance to public health and represents a potential ingredient for the development of functional foods and beverages. Objective: This study aimed to determine the chemical and nutritional composition as well as the antioxidant capacity of the P. peruviana L. fruit grown in Peru in three areas of the Central Andean region. Material and methods: Proximal and physicochemical analyses and estimation of mineral content, vitamin C, total carotenoids, total polyphenols, and antioxidant capacity (2, 2-diphenyl-1-picrylhydrazyl [DPPH] and 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) [ABTS] assays) were performed using standardized methods. Results: The fruits were collected from three regions of the Peruvian Andes (Ancash, Cajamarca, and Cusco). The results showed that the content of potassium (306.54-327.60 mg/100 g) and iron (12.93-14.47 mg/kg) was prominent. The Physalis fruit had high levels of vitamin C (47.20-52.20 mg/100 g), total polyphenols (68.17-83.40 mg equivalents of gallic acid/100 g), and carotenoids (1.12-1.73 mg ß-carotene/100 g). Higher values for antioxidant capacity were obtained with the ABTS method (896-1003.33 µmol Trolox/100 g) than with the DPPH method (290-309 µmol Trolox/100 g). Conclusions: This study confirms that the P. peruviana fruit has properties that could provide important health benefits and that it could be used for the development of functional foods and food supplement.

Silencing Tautomerization to Isolate Unstable Physalins from Physalis minima.

The inherent structural instability of some physalins has hampered the isolation and identification of these compounds for approximately 50 years, and an effective method to overcome these challenges remains unavailable. In the present study, the unprecedented tautomerization mechanism of unstable physalins was elucidated by performing isotopic labeling experiments and DFT calculations, which led to the successful separation of tautomers and isolation of highly pure products for the first time. As a result, 15 new physalins, physaminins A-O (1-15), as well as 17 known analogues (16-32), were isolated from the whole plants of Physalis minima L. The chemical structures of the new compounds were established by performing a comprehensive analysis of spectroscopic data, and their absolute configurations were confirmed by using computational ECD calculations and/or single-crystal X-ray diffraction analyses. All obtained isolates were evaluated for their antiproliferative effects against four human cancer cell lines (A549, HepG2, MCF-7, and SCG-7901) and two noncancerous cell lines (RAW 264.7 and human normal hepatocytes L02), as well as their anti-inflammatory activities by measuring their abilities to inhibit NO production in LPS-stimulated murine RAW 264.7 cells in vitro. Compounds 1-5, 13, 16, 18, 19, 23, and 30 exerted significant antiproliferative effects on the four human cancer lines, with IC50 values ranging from 0.2(0) to 24.7(2) µM, and these compounds were not toxic to the two noncancerous cell lines at a concentration of 10 µM. Moreover, compounds 7, 10, 11, 12, 14, 17, 22, and 27 significantly inhibited NO production, with IC50 values ranging from 2.9(1) to 9.5(2) µM.

The alleviative effect of flavonol-type Nrf2 activator rhamnazin from Physalis alkekengi L. var. franchetii (Mast.) Makino on pulmonary disorders.

Rhamnazin (RN) is a flavonol isolated from the calyxes and fruits of Physalis alkekengi L. var. franchetii (Mast.) Makino, which has been used for treating pulmonary diseases in traditional Chinese medicine. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a therapeutic target for pulmonary diseases. In the present study, the underlying mechanism and pharmacological effect of RN against pulmonary disorders are investigated. Human lung epithelial Beas-2B cell and RAW 264.7 murine macrophage-based cell models, and a cigarette smoke (CS)-induced pulmonary impairment mice model are adopted for investigation in vitro and in vivo. RN is identified to be an Nrf2 activator, which promotes Nrf2 dissociation from Keap1 via reacting with the Cys151 cysteine residue of Keap1, and suppresses Nrf2 ubiquitination. In addition, RN is able to attenuate toxicant-stimulated oxidative stress and inflammatory response in vitro. Importantly, RN significantly relieves CS-induced oxidative insult and inflammation, and RN-induced inhibition of inflammation is related to inhibition of nuclear transcription factor-κB (NF-κB) and induction of cell autophagy. In conclusion, our data indicate that RN is an activator of the Nrf2 pathway and evidently alleviates pulmonary disorders via restricting NF-κB activation and promoting autophagy. RN is a promising candidate for the therapy of pulmonary disorders.

QTOF-ESI MS Characterization and Antioxidant Activity of Physalis peruviana L. (Cape Gooseberry) Husks and Fruits from Costa Rica.

There is increasing interest in research of secondary metabolites from Physalis peruviana (Cape gooseberry) because of their potential bioactivities. In this study, the profile of compounds found in fruits and husks from Costa Rica was determined through ultra-performance liquid chromatography coupled with high-resolution mass spectrometry using a quadrupole time-of-flight analyzer (UPLC-ESI-QTOF MS) on extracts (n = 10) obtained through pressurized liquid extraction (PLE) conditions. In total, 66 different compounds were identified, comprising 34 withanolides, 23 sucrose ester derivatives and 9 flavonoids. UPLC-DAD analysis was performed to determine the ß-carotene in fruits and to quantify the flavonoids in all 10 samples, with the results showing higher contents in samples from the Dota region (58.6−60.1 µg/g of dry material versus 1.6−2.8 mg/g of dry material). The Folin−Ciocalteau total polyphenolic content (FC) and antioxidant activity using the DPPH method showed better results for the husk extracts, with the ones from the Dota region holding the best values (4.3−5.1 mg GAE/g of dry material versus IC50 = 1.6−2.3 mg of dry material/mL). In addition, a significant negative correlation was found between the RU, FC and DPPH values (r = −0.902, p < 0.05), aligning with previous reports on the role of polyphenols in antioxidant activity. Principal correlation analysis (PCoA) and hierarchical clustering (HC) analysis were performed on HRMS results, and they indicated that the D1 and D2 fruit samples from the Dota region were clustered with husks related to a higher presence of the analyzed metabolites. In turn, principal component analysis (PCA) performed on the flavonoid content and antioxidant activity yielded results indicating that the D1 and D2 husks and fruit samples from the Dota region stood out significantly, showing the highest antioxidant activity. In summation, our findings suggest that P. peruviana husks and fruits from Costa Rica constitute a substrate of interest for further studies on their potential health benefits.

Production and Structural Diversification of Withanolides by Aeroponic Cultivation of Plants of Solanaceae: Cytotoxic and Other Withanolides from Aeroponically Grown Physalis coztomatl.

Withanolides constitute one of the most interesting classes of natural products due to their diversity of structures and biological activities. Our recent studies on withanolides obtained from plants of Solanaceae including Withania somnifera and a number of Physalis species grown under environmentally controlled aeroponic conditions suggested that this technique is a convenient, reproducible, and superior method for their production and structural diversification. Investigation of aeroponically grown Physalis coztomatl afforded 29 withanolides compared to a total of 13 obtained previously from the wild-crafted plant and included 12 new withanolides, physacoztolides I-M (9-13), 15α-acetoxy-28-hydroxyphysachenolide C (14), 28-oxophysachenolide C (15), and 28-hydroxyphysachenolide C (16), 5α-chloro-6ß-hydroxy-5,6-dihydrophysachenolide D (17), 15α-acetoxy-5α-chloro-6ß-hydroxy-5,6-dihydrophysachenolide D (18), 28-hydroxy-5α-chloro-6ß-hydroxy-5,6-dihydrophysachenolide D (19), physachenolide A-5-methyl ether (20), and 17 known withanolides 3-5, 8, and 21-33. The structures of 9-20 were elucidated by the analysis of their spectroscopic data and the known withanolides 3-5, 8, and 21-33 were identified by comparison of their spectroscopic data with those reported. Evaluation against a panel of prostate cancer (LNCaP, VCaP, DU-145, and PC-3) and renal carcinoma (ACHN) cell lines, and normal human foreskin fibroblast (WI-38) cells revealed that 8, 13, 15, and 17-19 had potent and selective activity for prostate cancer cell lines. Facile conversion of the 5,6-chlorohydrin 17 to its 5,6-epoxide 8 in cell culture medium used for the bioassay suggested that the cytotoxic activities observed for 17-19 may be due to in situ formation of their corresponding 5ß,6ß-epoxides, 8, 27, and 28.

Chemical Composition Assessment of Structural Parts (Seeds, Peel, Pulp) of Physalis alkekengi L. Fruits.

In recent years there has been an extensive search for nature-based products with functional potential. All structural parts of Physalis alkekengi (bladder cherry), including fruits, pulp, and less-explored parts, such as seeds and peel, can be considered sources of functional macro- and micronutrients, bioactive compounds, such as vitamins, minerals, polyphenols, and polyunsaturated fatty acids, and dietetic fiber. The chemical composition of all fruit structural parts (seeds, peel, and pulp) of two phenotypes of P. alkekengi were studied. The seeds were found to be a rich source of oil, yielding 14-17%, with abundant amounts of unsaturated fatty acids (over 88%) and tocopherols, or vitamin E (up to 5378 mg/kg dw; dry weight). The predominant fatty acid in the seed oils was linoleic acid, followed by oleic acid. The seeds contained most of the fruit's protein (16-19% dw) and fiber (6-8% dw). The peel oil differed significantly from the seed oil in fatty acid and tocopherol composition. Seed cakes, the waste after oil extraction, contained arginine and aspartic acid as the main amino acids; valine, phenylalanine, threonine, and isoleucine were present in slightly higher amounts than the other essential amino acids. They were also rich in key minerals, such as K, Mg, Fe, and Zn. From the peel and pulp fractions were extracted fruit concretes, aromatic products with specific fragrance profiles, of which volatile compositions (GC-MS) were identified. The major volatiles in peel and pulp concretes were ß-linalool, α-pinene, and γ-terpinene. The results from the investigation substantiated the potential of all the studied fruit structures as new sources of bioactive compounds that could be used as prospective sources in human and animal nutrition, while the aroma-active compounds in the concretes supported the plant's potential in perfumery and cosmetics.

Natural Products from Physalis alkekengi L. var. franchetii (Mast.) Makino: A Review on Their Structural Analysis, Quality Control, Pharmacology, and Pharmacokinetics.

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.

Withanolides from dietary tomatillo suppress HT1080 cancer cell growth by targeting mutant IDH1.

Isocitrate dehydrogenase (IDH) is one key rate-limiting enzyme in the tricarboxylic acid cycle, which is related to various cancers. Tomatillo (Physalis ixocarpa), a special tomato, is widely consumed as nutritious vegetable in Mexico, USA, etc. As a rich source for withanolides, the fruits of P. ixocarpa were investigated, leading to the isolation of 11 type-A withanolides including 4 new ones (1 is an artificial withanolide). All these withanolides were evaluated for their inhibition on mutant IDH1 enzyme activity. Among them, physalin F (11) exhibited potent enzyme inhibitory activity and binding affinity with mutant IDH1. It inhibits the proliferation of HT1080 cells by selectively inhibiting the activity of mutant IDH1. Since Ixocarpalactone A, another major type-B withanolide in this plant, could act on another energy metabolism target PHGDH, the presence of different types of withanolides in tomatillo and their synergistic effect could make it a potential antitumor functional food or drug.

Withanolide-Type Steroids from Physalis nicandroides Inhibit HIV Transcription.

The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (1-4), together with nine related known compounds (5-13) isolated from the aerial parts of Physalis nicandroides. Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs. Their biological evaluation as inhibitors of human immunodeficiency virus type 1 replication revealed that two compounds from this series, 7 and 13, displayed strong inhibition of HIV-1 replication with IC50 values lower than 2 µM. Moreover, cellular mechanism experiments showed that the main target of these compounds in the HIV replication cycle is viral transcription. This study is the first report of withanolide-type steroids as HIV inhibitors and provides insight into their potential as candidates for further preclinical studies.

Cytotoxic Physalins from Aeroponically Grown Physalis acutifolia.

Aeroponically grown Physalis acutifolia afforded five new and six known withanolides including 10 physalins. The structures of the new withanolides, acutifolactone (1), 5ß,6ß-epoxyphysalin C (2), 5α-chloro-6ß-hydroxyphysalin C (3), and an inseparable mixture of 5ß,6ß-epoxy-2,3-dihydrophysalin F-3ß-O-sulfate (4) and 5ß,6ß-epoxy-2,3-dihydrophysalin C-3ß-O-sulfate (5), were elucidated by analysis of their spectroscopic data and chemical interconversions. The known withanolides were identified as physalins B (6), D (7), F (8), H (9), I (10), and U (11) by comparison of their spectroscopic data with those reported. Evaluation of 1-11 and the derivatives, 13 and 13a, obtained from 4 and 5 against a panel of four human cancer cell lines [NCI-H460 (non-small-cell lung), SF-268 (CNS glioma), PC-3 (prostate adenocarcinoma), and MCF-7 (breast adenocarcinoma)] and normal human lung fibroblast (WI-38) cells revealed that physalins 2, 3, 8, and 9 exhibited selective cytotoxic activity to at least one of the cancer cell lines tested compared to the normal cells and that 7, 10, and 11 were inactive up to a concentration of 10.0 µM. These data provided some preliminary structure-activity relationships and suggested that the mechanism of cytotoxic activity of physalins may differ from other classes of withanolides.

Physalin A attenuates inflammation through down-regulating c-Jun NH2 kinase phosphorylation/Activator Protein 1 activation and up-regulating the antioxidant activity.

Physalin A (PA), a withanolide, was isolated from Physalis angulata L. In this study, it is shown that PA can inhibit the production of inflammatory cytokines such as PGE2, NO, IL-1ß, IL-6, and TNF-α in LPS-induced RAW 264.7 cells. Furthermore, the results indicated that PA suppressed the IκB/NF-κB and JNK/ AP-1 inflammatory signaling pathways and inhibited the levels of pro-inflammatory factors iNOS and COX-2 in LPS-stimulated RAW 264.7 cells. In the carrageenan-induced mouse hind paw edema study, PA was shown to inhibit the production of inflammatory mediators such as NO, MDA, and TNF-α production. Conversely, the antioxidant factor levels of SOD, CAT, and GPx were all increased by the treated PA. According to the data, we are suggesting that the anti-inflammatory effects of PA may be through the suppressions of the JNK/AP-1 and IκB/NF-κB signaling pathways and up-regulation of the anti-oxidative activity.