13,14-seco withaphysalins from Physalis minima and their inhibitory effects on NLRP3 inflammasome activation.

Seven new 13,14-seco withaphysalins including two new skeletons (1 and 9) were isolated from the whole plants of Physalis minima, together with three known analogues (6-8). Among them, compound 1 was an extremely rare steroid with a 6, 8-cyclo ring. Their structures were established by extensive analysis of spectroscopic data, experimental electronic circular dichroism measurements, and single-crystal X-ray crystallographic analysis. In Raw264.7 cells, compounds 1-3, 5, 6, and 8 demonstrated potent ability to reduce the NLRP3-dependent caspase-1 activation. Among these compounds, 1 and 2 showed a superior potential, consistently concentration-dependent downregulating NLRP3-dependent proinflammatory cytokine IL-1ß production in macrophage. Mechanistically, compounds 1 and 2 reduced the cleavage of caspase-1 and GSDMD, and exhibited no obvious impact both on the NF-κB activation and the expression of NLRP3 and IL-1ß, suggesting that the compounds target the activation of the NLRP3 pathway mainly by inhibiting the NLRP3 inflammasome activation step rather than the priming step.

[Chemical constituents of Physalis minima].

Fifteen compounds(1-15) were isolated from the 95% EtOH extract of the whole herb of Physalis minima by various chromatography techniques including silica gel, Sephadex LH-20, middle chromatogram isolated gel(MCI), octadecyl silica(ODS), and semi-preparative high performance liquid chromatography(HPLC). Their structures were elucidated by infrared spectroscopy(IR), ultraviolet spectroscopy(UV), high-resolution electrospray ionization mass spectrometry(HR-ESI-MS), nuclear magnetic re-sonance(NMR), and circular dichroism(CD) as(5S)-5,11-dihydroxy-3-methyl-5-pentylfuran-2(5H)-one(1), withaphysalin R(2), withaphysalin Q(3), withaphysanolide A(4), phaseic acid(5), grasshopper ketone(6), 3S,5R-dihydroxy-6S,7-megastigmadien-9-one(7), vanillic acid(8), 2-trans,4-trans-abscisic acid(9), capillasterolide(10), 5,3'-dihydroxy-3,7,4'-trimethoxyflavone(11),(-)-loliolide(12), 4-hydroxyacetophenone(13), acetosyringone(14), and aurantiamide acetate(15). Compound 1 was a new butenolide, and compounds 5-7 and 10-12 were isolated from the Physalis for the first time. Compounds 4, 13, and 15 were isolated for the first time from P. minima. Moreover, their anti-inflammatory activity was evaluated in vitro. Compound 12 was found to possess an inhibitory effect on the transcription of an NF-κB-dependent reporter gene in LPS-induced 293 T/NF-κB-luc cells at 10 µmol·L~(-1), showing an inhibitory rate of 62.31%±4.8%.

13,14-seco-Withanolides from Physalis minima with Potential Anti-inflammatory Activity.

Four new 13,14-seco-withanolides, minisecolides A - D (1 - 4), together with three known analogues 5 - 7, were isolated from the whole plants of Physalis minima. The structures of new compounds were determined on the basis of spectroscopic analysis, including (1) H-, (13) C-NMR, 2D-NMR (HMBC, HSQC, ROESY), and HR-ESI-MS. Evaluation of all isolates for their inhibitory effects on nitric oxide (NO) production was conducted on lipopolysaccaride-activated RAW264.7 macrophages. Compounds 2, 3, 5, and 6 showed inhibitory activities, especially for compound 5 with IC50 value of 3.87 µm.

New steroids with anti-inflammatory activity from the whole plants of Physalis minima.

Two new steroids, phyminiolide J (1) and phyministerol A (2), along with three known compounds (3-5) were isolated from the whole plants of Physalis minima. The structures of the new compounds were elucidated by comprehensive spectroscopic analysis and the absolute configurations were determined by using computational ECD calculations. All isolates were evaluated for their anti-inflammatory activity via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells, and the results indicated that 1-3 exposed moderate inhibition with IC50 values ranging from 9.73 to 23.26 µM.

Two new withanolides from Physalis minima L.

Two new withanolides named physaminilides L (1) and M (2), together with four known ones (3-6) were isolated from the Physalis minima L. The structures were established by analysis of the HR ESIMS, IR and NMR spectroscopic data. The absolute configurations were determined through NOESY and ECD spectra. For compounds 1-5 assayed at 20 µM and compound 6 at 10 µM, inhibition rates of hepatic fibrosis were 22.19%, 15.29%, 37.07%, 9.27%, 12.45%, and 37.03%, respectively.

Cytotoxicity of Physalis minima Linn (Solanaceae) fruit against HCT116 and HT29 colorectal cancer cell lines.

The pantropical Physalis minima are traditionally used for the prevention and treatment of various illnesses, diseases, and cancers. While most earlier studies on the species have focused on the phytochemistry of the leaf and stem extracts, recent studies have indicated that its fruit may contain bioactive compounds of medical interest. In this study, we investigated the cytotoxicity of extracts from the fruit of P. minima against colorectal cancer cell lines and revealed its phytochemical profile via high-resolution tandem mass spectrometry analysis. Following a 24-h treatment with the fruit extract, cytoplasm shrinkage and nucleus condensation were observed in the colorectal cancer cell lines HCT116 and HT29, indicating the induction of programmed cell death. Phytochemically, 71 putative metabolites were identified. Some of these metabolites have been reported to inhibit cancers to varying degrees, further supporting the correlation of the putative metabolites with the cytotoxicity against colorectal cancer cells demonstrated in this study.

Begomovirus and DNA-satellites association with mosaic and leaf curl disease of Solanum nigrum and Physalis minima: the new hosts for chilli leaf curl virus.

The numerous plants of Solanum nigrum L, and Physalis minima L, well-known weeds with medicinal properties in agriculture and horticulture crops exhibiting severe mosaic, enation and leaf curl symptoms, were collected from the Varanasi and Mirzapur districts of Uttar Pradesh, India. The begomovirus infection in S. nigrum and P. minima was validated by PCR using virus-specific primers. The whole genome of the represented isolate of S. nigrum (SN1), P. minima (PM1), and beta satellite was amplified, cloned and sequenced. The SDT analysis showed that the DNA-A of PM1 and SN1 isolate showed the highest nt identity of 87.4 to 99.1%, with several chilli leaf curl virus (ChiLCuV) isolates from India and Oman, respectively. The betasatellite sequence (PM1ß) obtained from the PM1 isolate showed a very low identity of 83.1-84.5%. A demarcation threshold of 91% for betasatellite species delineation has led to identifying a new betasatellite in the PM1 sample. This unique betasatellite has been named "physalis minima leaf curl betasatellite," indicating its novelty with the plant. Whereas, betasatellite sequence (SN1ß) obtained from the SN1 sample showed 86.8-91.2% nucleotide identity with ChiLCB isolates infecting several crops in Indian subcontinents. The RDP analysis of the viral genome and betasatellite of SN1 and PM1 isolates revealed recombination in substantial portions of their genetic makeup, which appeared to have originated from pre-existing begomoviruses known to infect diverse host species. The present research also highlights the potential role of these plants as significant reservoir hosts for ChiLCuV in chili plants. Supplementary Information: The online version contains supplementary material available at 10.1007/s13337-023-00850-x.

Nephroprotective effect of PHYMIN-22 on ethylene glycol induced urolithiasis rat model.

The present study was designed to evaluate the antiurolithiatic effect of PHYMIN-22 against ethylene glycol-induced urolithiasis in rats. Healthy Albino male rats with 200-230 g body weight were randomly divided into five groups, each with 5 animals, control group, EG group (0.75%), PHYMIN-22 treatment group (0.75% EG 14 days and 100 mg/kg PHYMIN-22 next 14 days), PHYMIN-22 drug control group (100 mg/kg) and cystone treatment group (0.75% EG 14 days and 750 mg/kg cystone next 14 days). Biochemical testing was adopted for measuring the blood and urine parameters, as well as the level of antioxidants including superoxide dismutase (SOD), Catalase (Cat), Glutathione peroxidase (GPx) and glutathione (GSH) in kidney tissues. Hematoxylin and eosin (HE) staining was utilized to observe the histopathological changes in the kidney tissue. End of the experiment the PHYMIN-22 treatment reduced the urine and serum calcium (p < 0.01; p < 0.01), oxalate (p < 0.01; p < 0.01), phosphate (p < 0.01; p < 0.01), uric acid (p < 0.001; p < 0.001), protein (p < 0.001; p < 0.001), and creatinine (p < 0.001; p < 0.001) respectively, serum indicators ALT (p < 0.001) and AST (p < 0.001) level and non-enzymic antioxidant GSH (p < 0.001) compared to EG induced urolithiasis animals (Diseased control group). PHYMIN-22 treatment significantly increased urine volume, pH, and body weight, and antioxidants include CAT (p < 0.001; p < 0.001), SOD (p ˃ 0.05; p < 0.05), and GPX (p < 0.01; p < 0.001) compared to Diseased control group animals. The effect of PHYMIN-22 on EG-induced urolithiasis animals could be by improving kidney function, normalizing the urine and serum parameters, maintaining the kidney antioxidants, eliminating crystal deposition, and excretion of unwanted ions from the kidney and urinary tract.

A new 1,2-diketone physalin isolated from Physalis minima and TRAIL-resistance overcoming activity of physalins.

A new 1,2-diketone physalin, physalin XII (1), and 13 known compounds were isolated from the methanol extract of Physalis minima whole plant collected in Thailand. Among them, five physalins (2-6) had tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistance overcoming activity, and physalin F (3) was the most active with an IC50 value of 0.39 µM against human gastric adenocarcinoma cell line AGS in the presence of TRAIL (100 ng/mL). An investigation of the TRAIL-resistance overcoming activity of physalins using western blot analysis showed that 3 promoted TRAIL-induced apoptosis by suppressing anti-apoptotic proteins c-FLIP and Bcl-2.

Withanolides, the hidden gem in Physalis minima: A mini review on their anti-inflammatory, anti-neuroinflammatory and anti-cancer effects.

The Southeast Asian rainforests, notably in East Malaysia, are home to a diverse range of medicinal plant species with limitless therapeutic potential. Physalis minima (family Solanaceae) is a native East Malaysia plant which is closely linked to P. angulata, are recognized for their various pharmacology properties are abundance in Withanolides, a C28-steroidal lactones based on an ergostane skeleton. This review focuses on the bioactive compounds of this herb, as it is frequently used to treat inflammation, neurodegenerative disease and cancer among East Malaysian ethnic groups. In this review, a total of 103 Withanolides were reported, with 59 of them being newly characterized. Previous scientific data revealed that Withanolides were intriguing principal compounds for inflammatory, neuroinflammatory and cancer treatment due to unique steroidal structure and strong bioactivities. Despite their excellent pharmacological characteristics, only a few Withanolides have been extensively studied, and the majority of them, particularly the newly discovered Withanolides, remained unknown for their therapeutic properties. This indicates that P. minima compounds are worth to be investigate for its pharmacological effects.

Anti-inflammatory withanolides from the aerial parts of Physalis minima.

Eight undescribed and two known withanolides were obtained from the aerial parts of Physalis minima. The structures of these compounds were defined by spectroscopic methods including 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) data analysis. Physminin E was elucidated to be a rare 13,14-seco-withanolide. Inhibitory effects of these compounds on nitric oxide (NO) production were evaluated by using LPS-activated RAW264.7 macrophages, and physminin C was shown to be the most active with an IC50 value of 3.5 µM. The further mechanistic analysis of NO inhibition was performed by molecular docking and Western blotting.

Withaphysalins from Medicinal and Edible Physalis minima and Their Anti-inflammatory Activities.

Physalis minima is a medicinal and edible plant in China. In this study, 22 new withaphysalins, including a novel 1(10 → 6)abeo-14ß-hydroxy one (1) and other 15 unusual 14ß-hydroxy ones (3-4, 6-17, 19), were isolated from the whole herbs of P. minima together with two known analogues (23-24). Their structures were established by extensive analysis of high-resolution electrospray ionization mass spectrometry, IR, and 1D and 2D NMR spectroscopic data. Their absolute configurations were determined by electronic circular dichroism (ECD) spectra and single-crystal X-ray crystallographic analyses, together with DFT NMR calculations. All isolated compounds were evaluated for their anti-inflammatory activity via measuring the colorimetric reporter of the secreted embryonic alkaline phosphatase gene driven by an IFN-ß minimal promoter fused to five copies of the NF-κB consensus transcriptional response element and three copies of the c-Rel binding site in LPS-stimulated human THP1-Dual cells. Compounds 2, 5, 6, 9, 10, 11, and 20 showed significant anti-inflammatory effects with IC50 values in the range of 3.01-13.39 µM. Among them, compounds 2 and 10 showed better anti-inflammatory effects to inhibit the secretion of IL-6, IL-1ß, and TNF-α in LPS-stimulated THP1-Dual cells.

Identification Of Potential Cytotoxic Inhibitors From Physalis Minima.

A phytochemical investigation of Physalis minima led to the isolation of six withanolides, including withanolide E (1), withaperuvin C (2), 4ß-hydroxywithanolide E (3), 28-hydroxywithaperuvin C (4), physaperuvin G (5), and 4-deoxywithaperuvin (6). Their chemical structures were elucidated by 1 D-NMR and 2 D-NMR data, as well as comparison with the data reported in the literature. All isolated compounds were evaluated for their cytotoxic activity against HepG2, SK-LU-1, and MCF7 cancer cell lines. As the obtained results, compounds 1 and 3 displayed the strongest cytotoxicity against HepG2, SK-LU-1, and MCF7 cell lines with IC50 value ranging from 0.051 ± 0.004 to 0.86 ± 0.09 µg/mL.

New cytotoxic withanolides from Physalis minima.

Phytochemical investigation of Physalis minima led to the isolation of six new withanolides, including physaminilides HK (1-4), two artificial withanolides (5-6), and 19 known ones (7-25). Their structures were elucidated on the basis of spectroscopic analysis, including NMR and electronic circular dichroism (ECD) data. The isolates were evaluated for their cytotoxic activities against A375 human melanoma cells. Compounds 1, 8-9, 12-13, 15-17 and 19 exhibited significant cytotoxic activities with IC50 values in the range of 1.2-7.5 µM.

Five new 5,6-ß-epoxywithanolides from Physalis minima.

Five new 5,6-ß-epoxywithanolides (1-5) were isolated from the whole plants of Physalis minima L. Their structural elucidations were achieved by the extensive spectroscopic analysis (IR, UV, HR-ESI-MS, 1D-NMR, and 2D-NMR). The isolates were evaluated for their anti-inflammatory activities on lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells and cytotoxic activities against three cancer cell lines, viz. A549 lung adenocarcinoma cells, SMMC-7721 hepatic carcinoma cells and MCF-7 breast cancer cells by using the MTT-based assay. All of them possessed moderate inhibition to the production of nitric oxide with IC50 values from 42.18 to 73.26 µM, and the IC50 values of the cytotoxic activities were in the range of 31.25 to 80.14 µM.

Withaminimas A-F, six withanolides with potential anti-inflammatory activity from Physalis minima.

Withaminimas A-F (1-6), six new withaphysalin-type withanolides were isolated from the aerial parts of Physalis minima L.. The structures of these compounds were elucidated through a variety of spectroscopic techniques including HR-MS, NMR, and ECD. Compound 1 belongs to rare 18-norwithanolides, and 2-3 were 13/14-secowithanolides. According to the traditional usage of P. minima, inhibitory effects on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages were evaluated, and compounds 1-4 exhibited significant inhibitory effects with IC50 values among 3.91-18.46 µmol·L-1.

Anti-inflammatory and cytotoxic withanolides from Physalis minima.

Six undescribed withanolides were isolated and characterized during the investigation of anti-inflammatory and cytotoxic constituents from the whole plants of Physalis minima L. Their structures were elucidated by extensive spectroscopic analyses (IR, UV, HR-ESI-MS, 1D-NMR, and 2D-NMR), and their anti-inflammatory and cytotoxic activities were evaluated in vitro. All the compounds exhibited anti-inflammatory ability via inhibiting the production of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated murine macrophage RAW 264.7 cells. Moderate cytotoxic activities against A549 lung adenocarcinoma cells, SMMC-7721 hepatic carcinoma cells and MCF-7 breast cancer cells with IC50 values in the range of 40.01-82.17 µM were observed for these withanolides.

Host Infection beyond the Traditional Range of Sclerotium (Athelia) rolfsii with Physalis minima.

Physalis minima is an herbaceous plant and inhabitant of the porous and organic matter containing soil of bunds in crop fields, wastelands, around the houses, and on the roadsides. S. rolfsii is soil borne and it can infect over 500 plant species of different families. It is of interest to study the pathogenesis of S. rolfsii on P. minima. The S. rolfsii isolated from P. minima (physr1) was characterized by morphology and sequence of Internal Transcribed Spacer (ITS) region. The population structure determination and phylogenetic analysis showed the isolate physr1 significantly differs from other isolates. The null hypothesis of equal evolutionary rate was rejected throughout the Maximum likelihood (ML) tree topology of different S. rolfsii ITS sequences. The site-specific mean (relative) evolutionary rate analysis showed that most of the sites (80.59 % sites) evolved at a slower rate than average. Finally, the result of Tajima's neutrality test indicated that the population of S. rolfsii has recently begun to expand and that's why the pathogen was infecting the new host P. minima and pose a serious threat of infecting several other cropped and non-cropped hosts.

Identity of Tankari (Physalis Minima Linn.) in Ayurvedic Classics: A Literature Review.

Proper identification of drugs and their use in proper doses are important for successful treatment. Physalis minima Linn commonly known as country gooseberry has anti-cancerous, anti-diabetic, analgesic, antipyretic and anti-inflammatory potentials. The present paper is aimed to ascertain the proper identity of Tankari (Physalis minima Linn.) in Ayurvedic classics by a meticulous search and hence a review of the drug Tankari (Physalis minima Linn) was carried out in the texts of Ayurveda, modern literature, journals and online publications. The result of the search showed that the name "Tankari" is not found in Vedic lore. In Samhitas, it is mentioned in Bhavaprakasa. Reference of the drug "Sarngestha" is found in Brhattrayi, Bhela, Kasyapa, Cakradatta and Vangasena. It is variously named as Cirapotika, Kakatikta, and Vayasi by dalhana and he describes it as gaura (pale), vartula (round), and as having avagunthita/vesthita (covered) fruit which matches the description of Tankari (P. minima Linn). A search for terms Kakatikta and Vayasi showed Kakatikta to be synonymous to Sarngestha and Vayasi to be synonymous to both Kakatikta and Kakamaci (Solanum nigrum). Madanapala and Saligrama Nighantus have mentioned the name Cirapotika to be synonymous with Tankari. Sodhala has used the term Parpoti as a synonym of Tankari, which is the Gujarati name of P. minima Linn. Recent authors have considered Sarngestha as either P. minima or Cardiospermum helicabum. The regional names of P. minima are Cirpoti (Hindi), Cirboli (Marathi), also the folklore uses and pharmacological activities of P. minima are in accordance with the indications of Sarngestha in classics. Thus with a complete review of both Ayurveda and modern literatures, it can be concluded that the drug mentioned as Tankari in Bhavaprakasa is the same as Sarngestha mentioned in the classics. Cirapotika and Kakatikta are its synonyms. Cardiospermum helicabum is Karnaspotha, and hence Sarngestha of classics is P. minima which is supported by the regional names, pharmacological activity and folklore claims.

Chemopreventive Agents from Physalis minima Function as Michael Reaction Acceptors.

BACKGROUND: The fruits of some varieties of genus Physalis have been used as delicious fruits and functional food in the Northeast of China. MATERIALS AND METHODS: To reveal the functional material basis, we performed bioactivity-guided phytochemical research and chemopreventive effect assay of the constituents from Physalis minima. RESULTS: It was demonstrated that the ethyl acetate extract of P. minima L. (EEPM) had potential quinone reductase (QR) inducing activity with induction ratio (IR, QR induction activity) value of 1.47 ± 0.24, and glutathione binding property as potential Michael reaction acceptors (with an α, ß-unsaturated ketone moiety). Furthermore, bioactivity-guided phytochemical research led eight compounds (1-8), which were elucidated as 3-isopropyl-5-acetoxycyclohexene-2-one-1 (1), isophysalin B (2), physalin G (3), physalin D (4), physalin I (5), physordinose B (6), stigmasterol-3-O-ß-D-glucopyranoside (7) and 5α-6ß-dihydroxyphysalin R (8) on the basis of nuclear magnetic resonance spectroscopy analyses and HRESIMS. Then, isophysalin B (2) and physordinose B (6) showed significant QR inducing activity with IR value of 2.80 ± 0.19 and 2.38 ± 0.46, respectively. SUMMARY: An ultra-performance liquid chromatographic method with glutathione as the substrate was used to detect the Michael reaction acceptors in extracts of Physalis minima (EPM)We investigated the chemical constituents of EPM guided by biological activity methodIsophysalin B (1) and physordinose B (6) showed strong quinone reductase inducing activity with induction ratio values of 2.80 ± 0.19 and 2.38 ± 0.46This study generated useful information for consumers and many encourage researchers to utilize edible fruits from Physalis as a source of phytochemicals Abbreviations used: EPM: Extracts of Physalis minima, EEPM: Ethyl acetate extract of Physalis minima L., GSH: Glutathione, MRAs: Michael reaction acceptors, QR: Quinone reductase.