Immunoglobulin A nephropathy (IgAN) is the most common form of chronic glomerulonephritis and a major cause of end-stage renal disease worldwide, currently lacks safe, effective therapies. Ophiocordyceps sinensis, a well-known traditional medicinal fungus and used for treating kidney-related disorders. In this study, we report for the first time the nephroprotective potential of Ophiocordyceps indica Gireesh Nadda & Aakriti Sharma 2023, a newly described entomopathogenic fungus isolated from the Indian Himalayas, against IgAN. UPLC-based metabolomic profiling of O. indica confirmed the presence of key nucleosides, including adenosine and cordycepin, exhibiting a profile comparable to O. sinensis. In vitro, O. indica extract significantly reduced oxidative stress and inflammatory markers in SV40-MES13 mesangial cells without inducing cytotoxicity. In vivo, oral administration of the extract to IgAN-induced mice improved renal function by reducing serum creatinine, urea, and urine microalbumin levels, while restoring body and kidney weights. The extract also significantly reduced pro-inflammatory cytokines (TNFα, IL6, IL18) and galactose-deficient IgA1 levels. Histological and molecular analyses revealed amelioration of glomerular hypertrophy and tubular degeneration, along with downregulation of fibrotic and kidney injury markers (TGFβ, αSMA, Nephrin, WT1, VEGF, Desmin). The nephroprotective and anti-inflammatory effects of O. indica were comparable to those of O. sinensis and dexamethasone. Our findings highlight the potent anti-inflammatory and nephroprotective properties of O. indica, supporting its potential as a novel therapeutic agent for managing IgAN.
INTRODUCTION:Lipids are a fundamental class of biomolecules essential for membrane structure, energy storage, and cellular signaling, whereas lipidomics is an advanced dedicated way to understand the lipids, including biological lipids. OBJECTIVE:Keeping in mind the importance of lipid makeup, the current study was focused to understand the lipid diversity present within Picrorhiza kurroa (leaves, rhizomes, and roots) at three different localities of Himachal Pradesh, India: Bhatori (Pangi), Bharmaur (Chamba), and Gumna (Shimla). METHOD:UHPLC-QTOF-IMS was used for lipid profiling of P. kurroa locational samples. The data were analyzed for each extraction parameter. Moreover, targeted specialized metabolites were also analyzed using UPLC-PDA. Further, multivariate analysis including supervised orthogonal projections to latent structures discriminant analysis and unsupervised principal component analysis were employed to understand the lipid makeup, its dissemination, and similarity traits among the samples. RESULTS:Q-TOF/MS revealed the comprehensive lipidome of P. kurroa that includes the important presence of Cer, FA, (L) PE, TG, PA, PI, PS, MGDG, and DGDG. Leaves of P. kurroa collected from the Pangi region showed higher lipid content than other targeted parts and localities, whereas targeted metabolites including picrosides were present higher in the rhizomes of the Pangi region. Further, statistical analysis showed clear dissemination and similarity traits among the samples. The current study suggested variability among the chemo-profile of different locational samples. CONCLUSION:We concluded that leaves of P. kurroa collected from the Pangi region constitute higher lipid content than other parts and P. kurroa plants collected from another area. Also, the findings revealed that the plant P. kurroa contains Cer, FA, (L)PE, TG, DG, PG, PA, PI, PS, MGDG, and DGDG. The variation in picroside contents was also observed through UPLC-DAD analysis; rhizomes collected from the Bhatori (Pangi) region exhibited the highest picroside content.
Malnutrition of protein and essential nutrients in children can lead to serious health problems. It significantly alters hepatic physiology and leads to impaired liver function. The present study investigated the underlying mechanism of malnutrition-induced steatohepatitis in a rat model. Weanling rats were divided into two groups. The control rats received a standard protein diet, while the other group was fed a low protein diet (LPD) for eight weeks. LPD significantly reduced the body and liver weights and altered the blood parameters. LPD resulted in elevated serum liver injury markers and lowered glucose, albumin, and total protein levels. The reduced levels of TIBC and TSI and upregulated expression of Hamp gene were observed in the LPD group. Histopathology revealed the severe fat accumulation in the hepatocytes, leading to inflammation and fibrognesis. LPD upregulated the de novo lipogenesis (Srebp1c, Fas, Acc, and Scd1) markers and oxidative stress in the hepatic tissue. The downregulation of Pgc1α, Tim23, and Tfam indicated mitochondrial dysfunction in the LPD group. Transcriptomic analysis revealed the upregulation of 7,545 genes in the LPD group mainly associated with metabolic dysfunction-associated steatotic liver disease (MASLD), beta-oxidation, AMPK signalling and oxidative phosphorylation. Hepatic lipidome revealed the elevated levels of various lipid species in the LPD group. Further, LPD altered the gut microbiome of rats and reduced the relative abundance of beneficial bacteria. The present study revealed that malnutrition induces hepatic steatoheptitis by altering the hepatic lipid metabolism and disrupting mitochondrial function and gut-liver axis.
The present study investigated the impact of different photoperiods and temperatures as growing conditions (GCs) on the metabolomic profile of Brassica microgreens. The research delves into the intricate chlorophyll content, macroelement composition and metabolomic profiles of Brassica species cultivated under varied GC by utilizing targeted and non-targeted compound analysis. Under the G3 (a prolonged photoperiod of 22 h with temperatures of 26 °C/20 °C:: light/dark), Brassica microgreens demonstrated a rise in chlorophyll content by about 32 %, while microgreen height increased by approximately 20 %. The macroelement composition also varied significantly with GC, notably potassium content increased from 42.93 to 66.18 mg/g under G3. The phenolic composition analysis revealed a prominent presence of gallic and ferulic acid in the microgreens, significantly influenced by the GCs. Additionally, sugar profile indicated elevated levels of glucose and sucrose in response to G3. The UHPLC-QToF-IMS metabolomic profile highlighted the variation in expression levels of different classes of compounds, specifically (2R)-2-Hydroxy-3-butenyl, and 3-Indolylmethyl, which were upregulated under the G3.
Understanding how plant-associated yeasts mediate plant fitness under environmental stress remains mostly elusive. Here, the role of auxin and salicylic acid (SA)-producing psychrophilic yeast endophyte Naganishia liquefaciens strain ARY7, isolated from the roots of cold-desert plant Arnebia euchroma, was investigated for low temperature (LT; 10°C) tolerance in Arabidopsis thaliana. ARY7-inoculated plants had higher biomass, exhibited higher photosynthetic efficiency, starch accumulation, and reduced stress-responsive parameters at 10°C than their non-inoculated controls. ARY7-inoculation in the Arabidopsis enhanced auxin signaling in the roots, leading to more lateral roots and root hair development at 10°C. Increased exopolysaccharide (EPS) accumulation around roots and root colonization by ARY7 at 10°C also suggested its role in cold tolerance. The SA-production ability of ARY7 was supported by the elevated SA levels and upregulation of key SA biosynthesis genes (SID2 and PBS3) in ARY7-inoculated plants at 10°C. In addition, an improved seedling phenotype in ARY7-inoculated sid2 (SA-deficient) mutants of Arabidopsis further confirmed the role of ARY7-produced SA-mediated plant fitness. The downregulated expression of key cold-responsive genes (CBF, COR, RD29A, and P5CS1) in the leaves of ARY7-inoculated plants indicated reduced sensitivity to LT. This study established that the ARY7-mediated plant cold tolerance is due to the increased ARY7-root colonization through EPS production and involves auxin and SA signaling. This study provides valuable insights to explore plant-associated psychrophilic yeasts for protecting plants from various abiotic stresses, including cold temperature.
Ferula assa-foetida L., a herbaceous perennial plant usually found in temperate regions, exhibits persistent dormancy when grown under ambient conditions. To address this, the present study investigated the role of endogenous and exogenous hormones in the germination of F. assa-foetida L. and its wild relative F. jaeschkeana Vatke. Comparative endogenous hormonal changes were analyzed at different periods of seed germination in both species using ultra-high performance quadrupole time of flight mass spectrometry/ mass spectrometry (UHPLC-MS). For exogenous treatments, seeds of both species were treated with three hormones viz, gibberellic acid (GA3), 6-benzylaminopurine (BAP) and kinetin (KIN) at three different concentrations (50, 100, and 150 ppm) and two temperatures conditions (4 degrees C and 25 degrees C) to break seed dormancy. Results showed that there was a significant abrupt change in the content of the hormones during germination. The concentration of GA3, indole-3-acetic acid (IAA), and jasmonic acid (JA) reduced successively in both species from the dry seed stage till seedling emergence while abscisic acid (ABA) content increased significantly in imbibed seeds up to seedling emergence in F. assa-foetida L. Besides, treatment of seeds with exogenous GA3, BAP, and KIN in both species exhibited a significant increase in germination percentage at 4 degrees C than 25 degrees C. Chilling treatment along with 50 ppm GA3 hormone treatment increased the seed germination up to 94% and 78% in F. assa-foetida L. and F. jaeschkeana Vatke, respectively. Hence, this study suggests that GA3 can be used to boost overall seed germination, accelerate seedling development, and overcome seed dormancy in both Ferula species. Future investigations should focus on elucidating the molecular mechanisms underlying hormonal regulation during seed dormancy and germination in both species while optimizing synergistic hormonal treatments to accelerate germination and support its large-scale cultivation worldwide. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
Systemic acquired resistance (SAR) is a vital long-distance defense mechanism in plants, orchestrated by salicylic acid (SA) and its mobile signaling derivatives, methyl salicylate (MeSA) and azelaic acid (AzA). While SAR-disabling viral suppressors have been extensively studied in monopartite begomoviruses, their role in bipartite viruses remains largely unexplored. This study provides the first experimental evidence that the AC4 protein encoded by Tomato leaf curl Palampur virus (ToLCPalV), a bipartite begomovirus, contributes to suppression of SAR responses. Using quantitative gene expression profiling and targeted metabolite assays, we observed a reduction in the transcription of SAR marker genes ICS1 and PR1, as well as significant reduction in SA, MeSA, and AzA levels at progressive infection stages. These alterations were substantially alleviated in plants infected with an AC4-deficient mutant virus, confirming that AC4 plays a functional role in diminishing SAR activation. Complementary in silico analyses predicted that both AC4 and another ToLCPalV-encoded suppressor AV2 may interact with key enzymes associated with SA biosynthesis and metabolism, and may bind SAR-related mobile signals, including MeSA, AzA, pipecolic acid, and glycerol-3-phosphate. Together, the experimental results supported by computational modeling indicate that AC4 likely interferes with specific steps of SA production and movement of SAR signals during systemic immunity. Our study suggests that the viral proteins AC4 and AV2 may suppress SAR in a bipartite begomovirus and provides a clear starting point for future experiments, including interaction studies, targeted mutations, or resistant plants, to test and confirm their roles in plant immunity.
Summary In the present study, rice bran protein (RBP) from the PB1121 variety was hydrolysed using trypsin and subjected to non‐targeted IMS profiling to identify antioxidant and antihypertensive amino acids in the resulting RBP hydrolysates. The hydrolysate was then separated into three fractions using ultrafiltration, and each fraction was tested for antioxidant and ACE inhibitory activities. The ACE activity was assessed using the tripeptide hippuryl‐histidyl‐leucine (HHL) as a model peptide via HPLC‐DAD. The fraction with the molecular weight (>3000 Da) displayed the strongest antioxidant and ACE inhibitory activity. This fraction was further divided into five fractions using gel Sephadex G‐25, and the greatest levels of antioxidant and ACE inhibitory activity were found in fraction F3B. Fraction F3B was then fractionated using HPLC, and the fraction with ACE inhibitory activity (IC 50 of 43 mg mL −1 ) was analysed using MALDI‐TOF‐TOF mass spectrometry to determine its exact molecular mass and amino acid sequence. The amino acid sequence FMKSK (phe‐met‐lys‐ser‐lys) with a Mw of 655.376 Da was detected, and the molecular docking investigation revealed that FMKSK suppresses ACE by forming strong hydrogen bonds with the active pockets of human ACE. These findings suggest that rice bran contains bioactive peptides with antioxidant and ACE inhibitory effects, making it a promising raw material for the production of beneficial products.
Ocimum Sanctum L. (Basil) is a perennial herb belonging to the Lamiaceae family. The composition of microgreens is influenced by environmental conditions. Consequently, Ocimum microgreens were cultivated under varying growing conditions, assessing average height, total chlorophyll content, targeted compounds, and nontargeted UHPLC-QToF-IMS-based metabolomic profile. Under T3 growing condition (longer photoperiod of 22 h with 26 degrees C in light and 20 degrees C in the dark), Ocimum microgreens exhibited approximately 43% and 26% increases in average height and chlorophyll content, respectively. The targeted phenolic profile analysis identified gallic acid, caffeic acid, and resveratrol in microgreens. The growing conditions significantly influenced the phenolic profile. Also, sugar profiling indicated elevated levels of myo -inositol, glucose, fructose, sucrose, and D -raffinose under longer photoperiods with T3 conditions. Furthermore, microgreens exhibited a high abundance of amino acids such as aspartic acid, glutamic acid, proline, arginine, and phenylalanine. Notably, proline concentration increased from 13.40 mg/g to 25.15 mg/g in response to T3 growth condition. The comprehensive non-targeted UHPLC-QToF-IMS analysis revealed various metabolite classes, including organic compounds, phenolic and flavonoid derivatives, alkaloids, terpenoids, amino acids, sugars, polyalcohol and a few nucleic acid derivatives. Also, some organic acids, specifically rosmarinic acid, salvianolic acid D, and chicoric acid, showed highest expression level under T3 condition.
SummaryThe use of cutting‐edge omics technology to edible fruits has transformed the disciplines of fruit biology, pre‐ and post‐harvest investigations, metabolite biosynthesis and the identification of novel therapeutic fruit bioactives for health by leveraging varied omics data. Combining modern analytical chromatography tools (LC, GC) with mass spectrometry has significantly improved our ability to examine complex fruit tissues or extracted components, advancing our understanding of the fruit metabolome. Studies aiming at understanding the full metabolome and future quality characteristics have concentrated on quantifying the number of metabolites in edible fruit species and cultivars from diverse geographical locations. These studies have also helped to develop new databases for precise and comprehensive qualitative analysis of metabolites, allowing for the analysis of metabolite biosynthesis pathways to identify differences in metabolites among developed hybrids, metabolite origins and potential derivatives. Bioactive metabolite information is currently being utilised to manage illnesses, provide nutrition and creation of novel food products. Furthermore, this research has helped us better understand fruit quality and how metabolites interact with biological systems. In conclusion, this review emphasises the importance of metabolomics approaches in studying fruit metabolomes in the context of current research perspectives.
Cold stratification is known to affect the speed of seed germination; however, its regulation at the molecular level in Ferula assa-foetida remains ambiguous. Here, we used cold stratification (4 degrees C in the dark) to induce germination in F. assa-foetida and adopted a proteomic and metabolomic approach to understand the molecular mechanism of germination. Compared to the control, we identified 209 non-redundant proteins and 96 metabolites in germinated F. assa-foetida seed. Results highlight the common and unique regulatory mechanisms like signaling cascade, reactivation of energy metabolism, activation of ROS scavenging system, DNA repair, gene expression cascade, cytoskeleton, and cell wall modulation in F. assa-foetida germination. A protein-protein interaction network identifies 18 hub protein species central to the interactome and could be a key player in F. assa-foetida germination. Further, the predominant metabolic pathways like glucosinolate biosynthesis, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, and carotenoid biosynthesis in germinating seed may indicate the regulation of carbon and nitrogen metabolism is prime essential to maintain the physiology of germinating seedlings. The findings of this study provide a better understanding of cold stratification-induced seed germination, which might be utilized for genetic modification and traditional breeding of Ferula assa-foetida. Significance: Seed germination is the fundamental checkpoint for plant growth and development, which has ecological significance. Ferula assa-foetida L., commonly known as "asafoetida," is a medicinal and food crop with huge therapeutic potential. To date, our understanding of F. assa-foetida seed germination is rudimentary. Therefore, studying the molecular mechanism that governs dormancy decay and the onset of germination in F. assa-foetida is essential for understanding the basic principle of seed germination, which could offer to improve genetic modification and traditional breeding.
Summary Rice bran protein isolates and seven legume protein isolates (moong bean, green pea, white pea, black chickpea and white chickpea, soya bean and lentil) were evaluated for functional, structural and metabolomic properties. Rice bran protein isolates (RBI) had higher solubility, foaming, oil absorption capacity and water absorption capacity but lower denaturing temperature compared to legume proteins. The functionality of proteins isolates impacted significantly with structural characteristics. The β ‐sheet, α ‐helix, β ‐turn and anti‐parallel β ‐sheets proportions were evaluated by FTIR. RBI revealed lower molecular weight, less rigid conformational structure and lower proportion of β ‐sheet. The evaluation of untargeted metabolomics compounds was determined by ultraperformance liquid chromatography quadruple time‐of‐flight ion mobility mass spectrometry (UHPLC‐QTOF‐IMS), evaluated using PCA and presented as a heatmap. Analysis revealed 46 metabolites including sugars, amino acids, lipids, terpenoid, phenolics, saponins and their derivatives. Significant differences in selected compounds from 126 identified metabolites among protein isolates were observed. This work provides new insights into metabolite distribution among protein isolates and also presents future implementations for applications in food and nutraceuticals.
Summary Fruit is a crucial component of our diet, and breeding to produce nutrient‐rich cultivars necessitates a thorough examination of their metabolite composition. Fruit contains hundreds of different chemicals, including both primary and secondary (or specialised) metabolites. The structural diversity of health promoting and sensory attributes imparting metabolites and their complex interactions during fruit growth and developments were uncovered by high‐throughput metabolomics. Both targeted and non‐targeted metabolomics approach are used for the comprehensive analysis of small molecules from various complex matrices, addressing genetic, environment effect, metabolic programming, etc. With advances of mass spectrometer (MS), targeted metabolomics with non‐targeted metabolomics, MS‐based fingerprinting, profiling or imaging strategies and pseudo‐targeted are being employed to elucidate novel bioactive compounds. The exemplary reports cover a wide range of fruit metabolic implications, addressing the impact of processing on fruit flavour quality, the identification of sensory and nutraceutical biomarkers in fruits, metabolic alterations in fruits during post‐harvesting and future prospects. The examination of metabolomics profiles of multiple fruit species is anticipated to be benefitted for the expansion of fruits in terms of nutritional and health benefits aspects in the upcoming years.
Ethnopharmacological relevanceGentiana kurroo Royle is a medicinal plant mentioned as Traymana in Ayurveda. In the folklore, it is used to cure fever, stomach ache, skin diseases and liver disorders. However, limited reports are available on the therapeutic potential of Gentiana kurroo Royle against alcohol-induced liver damage.Aim of the studyTo assess the effectiveness of the hydroethanolic extract of Gentiana kurroo Royle rhizome (GKRE) against alcohol-induced liver injury and explore the mechanism of action.Materials and methodsGKRE was characterized using UHPLC-QTOF-MS/MS. The binding affinity of the identified compound was studied in silico. In vitro studies were performed in the Huh-7 cell line. An acute oral toxicity study (2 g/kg BW) of GKRE was done in rats following OECD 420 guidelines. In the efficacy study, rats were treated with 50% ethanol (5 mL/kg BW, orally) for 4 weeks, followed by a single intraperitoneal dose of CCl4 (30%; 1 mL/kg BW) to induce liver injury. After 4th week, the rats were treated with GKRE at 100, 200 and 400 mg/kg BW doses for the next fifteen days. The biochemical and antioxidant parameters were analyzed using commercial kits and a biochemistry analyzer. Histopathology, gene and protein expressions were studied using qRT PCR and western blotting.ResultsThirteen compounds were detected in GKRE. Few compounds showed a strong interaction with the fibrotic and inflammatory proteins in silico. GKRE reduced (p < 0.05) the ethanol-induced ROS production and inflammation in Huh-7 cells. The acute oral toxicity study revealed no adverse effect of GKRE in rats at 2 g/kg BW. GKRE improved (p < 0.05) the body and liver weights in ethanol-treated rats. GKRE improved (p < 0.05) the mRNA levels of ADH, SREBP1c and mitochondrial biogenesis genes in the liver tissues. GKRE also improved (p < 0.05) the liver damage markers, lipid peroxidation and levels of antioxidant enzymes in the liver. A reduced severity (p < 0.05) of pathological changes, fibrotic tissue deposition and caspase 3/7 activity were observed in the liver tissues of GKRE-treated rats. Further, GKRE downregulated (p < 0.05) the expression of fibrotic (TGFβ, αSMA and SMADs) and inflammatory markers (TNFα, IL6, IL1β and NFκB) in the liver.ConclusionGKRE showed efficacy against alcohol-induced liver damage by inhibiting oxidative stress, apoptosis, inflammation and fibrogenesis in the liver.
Wild edible plants (WEPs) from the Western Himalayas consisting of three green leafy vegetables (GLVs), viz., Amaranthus spinosus, Urtica dioica, and Zanthoxylum armatum, and three fruits, namely, Ficus auriculata, Cordia obliqua, and Momordica dioica were characterized for their nutritional and phytochemical composition. We identified 107 compounds consisting of polyphenols, terpenoids, amino acids, and fatty acid derivatives through UHPLC-QTOF-IMS-based metabolomics. GLVs (A. spinosus and U. dioica) scored best in terms of proteins, micronutrients, carotenoids, and total polyphenols when compared to fruits. Polyunsaturated fatty acids, particularly alpha-linolenic acid, are abundant among WEPs. U. dioica possessed the highest radical scavenging activity, while A. spinosus and M. dioica exhibited strong reducing power activity. Strong alpha-glucosidase inhibition activity was observed with A. spinosus, Z. armatum, and M. dioica. Polyphenols, particularly flavonoids, from fruits were relatively more bioaccessible compared to GLVs. Potential applications of GLVs for combating protein and iron deficiency as well as wild fruits for functional food development should be explored further.
Background and ObjectivesTo optimize the utilization of rice by-products, the rice bran protein hydrolysate (RBPH) was subjected to a process of separation and purification using ultrafiltration and reversed-phase high-performance liquid chromatography (RP-HPLC). Subsequently, the identification of peptide sequences was carried out using mass spectrometer hybrid quadrupole-time-of-flight and nontargeted metabolomic profiling done using UHPLC-QTOF-IMS profiling to identify antioxidant and antihypertensive amino acids.FindingsThree novel bioactive peptides, namely, STCCK, FMKSK, and KICILVFTLTTC, were identified within RBPH through enzymatic digestion using alcalase, pepsin, and trypsin. These peptides showed significant antioxidant activity and angiotensin-converting enzyme (ACE) inhibitory activity. Molecular docking analyses elucidated various interaction mechanisms between these peptides and the ACE receptor protein, including hydrogen bonding and hydrophobic interactions. This suggested that the peptides effectively suppress ACE by forming hydrogen bonds with the active pockets of human ACE with a high affinity.ConclusionIn summary, peptides derived from rice bran protein exhibited distinguished antihypertensive and antioxidant properties, underscoring their potential for valuable utilization in addressing utilization of rice by-products.Significance and NoveltyThe study advances scientific knowledge and offers practical solutions for health improvement and sustainable agriculture.