Project description:Rheumatoid arthritis (RA) is an autoimmune disease characterized by bone and joint degeneration. Existing anti-inflammatory chemotherapy drugs offer temporary relief but come with undesirable side effects. Herbal medications have shown positive effects on RA symptoms with minimal adverse reactions. In this study, we investigated the potential of Nyctanthes arbor-tristis (NAT) through in vitro and in silico research. Hydroethanolic extracts of harsingar were prepared using the reflux method, containing alkaloids, phenol, saponin, steroids, proteins, tannins, terpenoids, carbohydrates, glycosides, and flavonoids, which exhibited TPC (98.56 ± 0.46 mg GAE/g) and TFC (34.51 ± 0.45 mg CE/g). LC-MS/MS analyzes the active compounds in the extract. NAT exhibited the best scavenging capabilities at 1 mg/mL in anti-oxidant and anti-arthritic activity. Maximum splenocyte proliferation occurred at 250 µg/mL. In vitro cell splenocyte studies revealed the downregulation of TNF-α and the upregulation of IL-10. Additionally, an in silico study demonstrated that bioactive constituents and targets bind with favorable binding affinity. These findings demonstrate the potential of Nyctanthes arbor-tristis in exerting anti-arthritic effects, as supported by in vitro and in silico studies. Further mechanistic research is necessary to validate the therapeutic potential of all phytoconstituents in RA treatment.
Project description:BackgroundAn unceasing threat of drug resistance continuously poses demand for new antimalarial drugs. A scientific assessment of traditionally used antimalarial plants through reverse pharmacology is crucial for a fast track drug discovery. An Ayurvedic plant Nyctanthes arbor-tristis Linn. - (Parijat) is being used in clinical practice and had shown antimalarial activity, with a parasite clearance in 76.6% of 120 patients, in an earlier clinical study.ObjectiveTo further explore antimalarial potential of the plant through additional objective markers.Materials and methodsAn open-labelled observational study was conducted at M.A. Podar Hospital - Ayurveda (MAPH-A) after ethics committee approval. Administration of a paste of 5 fresh leaves, thrice a day for a week was a standard practice for management of malaria at MAPH-A. Clinical activity of N. arbor-tristis was evaluated by monitoring pyrexia, parasitemia and morbidity score (MS) in twenty patients. In addition, immune and biochemical markers and organ functions were monitored for objective markers of response. Student's paired-'t' test was applied to assess statistical significance.ResultsTen out of 20 patients showed both fever and parasite clearance, which was confirmed by polymerase chain reaction. Remaining ten patients had persistent but decreasing parasitemia. Four of them needed chloroquine as a fail-safe procedure. Irrespective of the degree of parasitemia all the patients showed decrease in MS. There was also an increase in platelet count and normalization of plasma lactic acid. There was a good clinical tolerability and an improvement in organ function. The inflammatory cytokines showed a reduction; particularly in TNF-α within a day.ConclusionsAt the given dosage, N. arbor-tristis showed disease-modifying activity; early clinical recovery with a decline of TNF-α and a gradual parasite clearance. Further studies with a standardised formulation for dose-searching and optimizing the treatment schedule are needed in a larger sample size.Clinical trial registration noThe process of trial registration had not begun when the study was conducted in 2000.
Project description:Background and aim Orange colored tubular calyx of the flowers of Nyctanthes arbor-tristis contains an apocarotenoid crocin as a major ingredient, which is originally detected to be major colouring principle of saffron stigma. Saffron stigma exhibits good wound healing activity owing to the presence of crocin. The present study is aimed at isolation of crocetin, from tubular calyx of N. arbortristis and improve stability through entrapping in vesicles followed by evaluation of wound healing activity of the topical formulation thereof. Experimental procedure Crocetin was isolated by treating ethanolic extract of tubular calyx of N. arbor-tristis with sodium bicarbonate followed by regeneration of crocetin using hydrochloric acid. The phytosomes were prepared by lipid film hydration technique. The gel containing phytosomes equivalent to crocetin 1% w/w, was then evaluated for wound healing activity through applications on incision and excision wounds inflicted in Wister albino rats. Results Stability of crocetin was found to be increased due to entrapment into phytosomes. The studies revealed that both types of wounds upon treatment with gel containing crocetin phytosomes, indicated good wound healing potential, as the epithelization period was significantly (P < 0.001)decreased as compared to the control group from 26 to 9 days, in excision wound model and significant (P < 0.001)increase in breaking strength of repaired skin, as compared to control from 328.8 to 857.0 gm in incision wound model. Conclusion Crocetin from tubular calyx of Nyctanthes arbor-tristis indicated to be potential wound healing phytoconstituent. Graphical abstract Image 1 Highlights • Significant (P < 0.01) increase in entrapment (71.4%) as compared to the crocin enriched extract (34.4%)• Improved stability with retention of crocetin content in the range of 97–98% w/w in accelerated stability studies• Significant (P < 0.001) reduction period of epithelization (18 days) of excision wound, as compared to control group (26 days).• Significant increase (P < 0.01) in hydroxyproline content in granulation tissue• Significant (P < 0.01) increase in the breaking load of the repaired skin, in case of incision wound• Accelerated healing of both the incision and excision wounds due to topical application of the gel
Project description:The leaves, flowers, seeds, and bark of the Nyctanthes arbor-tristis Linn plant have been pharmacologically evaluated to signify the medicinal importance traditionally described for various ailments. We evaluated the anti-inflammatory potentials of 26 natural compounds using AutoDock 4.2 and Molecular Dynamics (MDS) performed with the GROMACS tool. SwissADME evaluated ADME (adsorption, distribution, metabolism, and excretion) parameters. Arb_E and Beta-sito, natural compounds of the plant, showed significant levels of binding affinity against COX-1, COX-2, PDE4, PDE7, IL-17A, IL-17D, TNF-α, IL-1β, prostaglandin E2, and prostaglandin F synthase. The control drug celecoxib exhibited a binding energy of -9.29 kcal/mol, and among the tested compounds, Arb_E was the most significant (docking energy: -10.26 kcal/mol). Beta_sito was also observed with high and considerable docking energy of -8.86 kcal/mol with the COX-2 receptor. COX-2 simulation in the presence of Arb_E and control drug celecoxib, RMSD ranged from 0.15 to 0.25 nm, showing stability until the end of the simulation. Also, MM-PBSA analysis showed that Arb_E bound to COX-2 exhibited the lowest binding energy of -277.602 kJ/mol. Arb_E and Beta_sito showed interesting ADME physico-chemical and drug-like characteristics with significant drug-like effects. Therefore, the studied natural compounds could be potential anti-inflammatory molecules and need further in vitro/in vivo experimentation to develop novel anti-inflammatory drugs.
Project description:Arabidopsis FLOWERING LOCUS T (FT) is a pivotal component of florigen, a long-range mobile flowering signal. Here, we determined the 1.0 Å-resolution crystal structure of FT, a significantly higher-resolution crystal structure of FT than previously reported one (2.6 Å). The present crystallographic studies revealed 4 alternative configurations with the precise location of the surrounding water molecules. Using this structural data, computational docking simulation predicted the putative binding sites for phosphatidylcholine (PC), an endogenous ligand that interacts with FT to modulate flowering time. In vitro reconstitution of the lipid-protein interaction showed that mutations at two of the predicted sites significantly compromised the lipid binding ability of FT. In planta, one of the mutant FT proteins significantly affected FT function in flowering, emphasizing the involvement of PC binding in modulating FT function. Our structural, biochemical, and transgenic analyses reveal the molecular mechanism of PC binding in FT-mediated flowering time control.
Project description:Flowering Chinese cabbage is a type of leafy vegetable that belongs to the Brassica genus. Originally native to South China, it is now widely cultivated and consumed across the globe, particularly in Asian countries. The recent cultivation and regional expansion of flowering Chinese cabbage provides a valuable opportunity to elucidate the genomic basis underlying environmental adaptation and desired traits during a short-term artificial selection process. Here, we investigate the genetic variation, population structure, and diversity of a diverse germplasm collection of 403 flowering Chinese cabbage accessions. Our investigation seeks to elucidate the genomic basis that guides the selection of adaptability, yield, and pivotal agronomic traits. We further investigated breeding improvement associated with stem development by integrating transcriptome data. Genome-wide association analysis identified 642 loci and corresponding candidate genes associated with 11 essential agronomic traits, including plant architecture and yield. Furthermore, we uncovered a significant disparity in the allele frequency distribution of nonsynonymous mutations in these candidate genes throughout the improvement stages. Our results shed light on the genetic basis of improvement and crucial agronomic traits in flowering Chinese cabbage, offering invaluable resources for upcoming genomics-assisted breeding endeavors.