Dirigent isoflavene-forming PsPTS2: 3D structure, stereochemical, and kinetic characterization comparison with pterocarpan-forming PsPTS1 homolog in pea.

Pea phytoalexins (-)-maackiain and (+)-pisatin have opposite C6a/C11a configurations, but biosynthetically how this occurs is unknown. Pea dirigent-protein (DP) PsPTS2 generates 7,2'-dihydroxy-4',5'-methylenedioxyisoflav-3-ene (DMDIF), and stereoselectivity toward four possible 7,2'-dihydroxy-4',5'-methylenedioxyisoflavan-4-ol (DMDI) stereoisomers was investigated. Stereoisomer configurations were determined using NMR spectroscopy, electronic circular dichroism, and molecular orbital analyses. PsPTS2 efficiently converted cis-(3R,4R)-DMDI into DMDIF 20-fold faster than the trans-(3R,4S)-isomer. The 4R-configured substrate's near ß-axial OH orientation significantly enhanced its leaving group abilities in generating A-ring mono-quinone methide (QM), whereas 4S-isomer's α-equatorial-OH was a poorer leaving group. Docking simulations indicated that the 4R-configured ß-axial OH was closest to Asp51, whereas 4S-isomer's α-equatorial OH was further away. Neither cis-(3S,4S)- nor trans-(3S,4R)-DMDIs were substrates, even with the former having C3/C4 stereochemistry as in (+)-pisatin. PsPTS2 used cis-(3R,4R)-7,2'-dihydroxy-4'-methoxyisoflavan-4-ol [cis-(3R,4R)-DMI] and C3/C4 stereoisomers to give 2',7-dihydroxy-4'-methoxyisoflav-3-ene (DMIF). DP homologs may exist in licorice (Glycyrrhiza pallidiflora) and tree legume Bolusanthus speciosus, as DMIF occurs in both species. PsPTS1 utilized cis-(3R,4R)-DMDI to give (-)-maackiain 2200-fold more efficiently than with cis-(3R,4R)-DMI to give (-)-medicarpin. PsPTS1 also slowly converted trans-(3S,4R)-DMDI into (+)-maackiain, reflecting the better 4R configured OH leaving group. PsPTS2 and PsPTS1 provisionally provide the means to enable differing C6a and C11a configurations in (+)-pisatin and (-)-maackiain, via identical DP-engendered mono-QM bound intermediate generation, which PsPTS2 either re-aromatizes to give DMDIF or PsPTS1 intramolecularly cyclizes to afford (-)-maackiain. Substrate docking simulations using PsPTS2 and PsPTS1 indicate cis-(3R,4R)-DMDI binds in the anti-configuration in PsPTS2 to afford DMDIF, and the syn-configuration in PsPTS1 to give maackiain.

Cytotoxic leuconoxine-type diazaspiroindole alkaloids isolated from Cryptolepis dubia.

Two leuconoxine-type diazaspiroindole alkaloids, the known compound, (+)-melodinine E (1), and its new analogue, (+)-11-chloromelodinine E (2), were isolated from the stems of Cryptolepis dubia (Burm.f.) M.R. Almeida (Apocynaceae), collected in Laos. The chemical structures of these compounds were determined by analysis of their spectroscopic data and by comparison of these data with literature values, of which the molecular structure of 1 has been determined previously by analysis of its single-crystal X-ray diffraction data. The absolute configurations of 1 and 2 have been defined by their experimental and simulated electronic circular dichroism (ECD) spectroscopic data and supported by 1H and 13C NMR-based DP4+ probability analysis and specific rotation calculations. When tested against a small panel of human cancer cell lines, these two compounds exhibited selective cytotoxicity toward OVCAR3 human ovarian cancer cells.

Revisiting the Cyclocephagenols via Astragalus condensatus: Structural Insights and Configurational Revision.

The phytochemical investigation of the MeOH extract of Astragalus condensatus roots led to the discovery of a new tetrahydropyran cycloartane-type triterpenoid, astracondensatol A (1), alongside six known cyclocephagenol derivatives (2, 3, 20, 32, 35, and 36). Elucidation of their structures involved 1D and 2D-NMR spectroscopy and mass data analysis. Upon comparing NMR spectroscopic data with prior literature, several carbon shift anomalies, particularly at C-24, prompted a reevaluation using quantum chemical calculations, resulting in the revision of the 24S to 24R absolute configuration for compound 2 and 38 other reported cyclocephagenol-type triterpenoids. X-ray crystallography data further supported the analysis in establishing the absolute configuration of compound 2. Ambiguous NOE correlations and publication bias could have played a significant role in miss-assigning the C-24 absolute configuration in tetrahydropyran cycloartane-type triterpenoids.

iso-Guttiferone J and Structure Revision of Guttiferone J from Garcinia gummi-gutta: A Combined Experimental and Integrated QM/NMR Approach.

Many polyprenylated acylphloroglucinols with fascinating chemical structures and intriguing biological activities have been identified as key to phytochemicals isolated from Garcinia, Hypericum, and related genera. In the present work, two chiral, tautomeric, highly-oxygenated polyprenylated acylphloroglucinols tethered with acyl and prenyl moieties on a bicyclo[3.3.1]nonanetrione core were isolated from the 95% ethanolic extract of Garcinia gummi-gutta fruit. The structures of both compounds were elucidated based on the NMR and MS data with ambiguity in the exact position of the enol and keto functions at C-1 and C-3 of the core structure. The structures of both polyprenylated acylphloroglucinols were established as a structurally revised guttiferone J and the new iso-guttiferone J with the aid of gauge-independent atomic orbital NMR calculations, CP3 probability analyses, specific rotation calculations, and electronic circular dichroism calculations in combination with the experimental data. The structures of both compounds resemble hyperforin, a potent activator of the human pregnane X receptor. As expected, both compounds showed strong pregnane X receptor activation at 10 µM [7.1-fold (guttiferone J) and 5.0-fold (iso-guttiferone J)], explained by a molecular docking study, necessitating further in-depth investigation to substantiate the herb-drug interaction potential of G. gummi-gutta upon co-administration with pharmaceutical drugs.

Chemistry of Isoeugenol and Its Oxidation Products: Mechanism and Kinetics of Isoeugenol as a Skin Sensitizer.

Structurally similar phytochemical compounds may elicit markedly different skin sensitization responses. Eugenol and isoeugenol are natural phenylpropanoids found in various essential oils are frequently used as fragrance ingredients in consumer products due to their pleasing aromatic properties. Both compounds are also skin sensitizers with isoeugenol being a stronger sensitizer than eugenol. The most commonly accepted mechanisms for haptenation by eugenol involve formation of a quinone methide or an ortho-quinone intermediate. The mechanism for the increased skin response to isoeugenol remains elusive, although quinone methide intermediates have been proposed. The recent identification of diastereomeric 7,4'-oxyneolignans as electrophilic, thiol-depleting isoeugenol derivatives has revived interest in the possible role of elusive reactive intermediates associated with the isoeugenol's haptenation process. In the present work, integrated non-animal skin sensitization methods were performed to determine the ability of syn-7,4'-oxyneolignan to promote haptenation and activation of further molecular pathways in keratinocytes and dendritic cells, confirming it as a candidate skin sensitizer. Kinetic NMR spectroscopic studies using dansyl cysteamine (DCYA) confirmed the first ordered nature of the nucleophilic addition for the syn-7,4'-oxyneolignan. Computational studies reaffirmed the "syn" stereochemistry of the isolated 7,4'-oxyneolignans along with that of their corresponding DCYA adducts and provided evidence for the preferential stereoselectivity. A plausible rationale for isoeugenol's strong skin sensitization is proposed based on the formation of a hydroxy quinone methide as a reactive intermediate rather than the previously assumed quinone methide.

Is Baikiain in Tara Flour a Causative Agent for the Adverse Events Associated with the Recalled Frozen French Lentil & Leek Crumbles Food Product? - A Working Hypothesis.

The French Lentil & Leek Crumbles frozen food product was recently recalled due to reports of gastrointestinal issues. So far, 393 adverse illness complaints and 133 hospitalizations have been reported from consumption of this food, and the tara (Tara spinosa) protein flour ingredient is hypothesized to be responsible. A multipronged approach resulted in identification of (S)-(-)-baikiain in tara as a compound of interest due to its abundance, possible metabolic fate, and close resemblance to irreversible inhibitors of L-pipecolate oxidase. Oral administration of baikiain in ND4 mice showed a statistically significant increase in blood ALT levels and a reduction in liver GSH.

Unprecedented Benzoquinone Motifs Reveal Post-Oligomerizational Modification of Proanthocyanidins.

Proanthocyanidins (PACs) are complex flavan-3-ol polymers with stunning chemical complexity due to oxygenation patterns, oxidative phenolic ring linkages, and intricate stereochemistry of their heterocycles and inter-flavan linkages. Being promising candidates for dental restorative biomaterials, trace analysis of dentin bioactive cinnamon PACs now yielded novel trimeric (1 and 2) and tetrameric (3) PACs with unprecedented o- and p-benzoquinone motifs (benzoquinonoid PACs). Challenges in structural characterization, especially their absolute configuration, prompted the development of a new synthetic-analytical approach involving comprehensive spectroscopy, including NMR with quantum mechanics-driven 1H iterative functionalized spin analysis (HifSA) plus experimental and computational electronic circular dichroism (ECD). Vital stereochemical information was garnered from synthesizing 4-(2,5-benzoquinone)flavan-3-ols and a truncated analogue of trimer 2 as ECD models. Discovery of the first natural benzoquinonoid PACs provides new evidence to the experimentally elusive PAC biosynthesis as their formation requires two oxidative post-oligomerizational modifications (POMs) that are distinct and occur downstream from both quinone-methide-driven oligomerization and A-type linkage formation. While Nature is known to achieve structural diversity of many major compound classes by POMs, this is the first indication of PACs also following this common theme.

Cannabinoid Receptor Type II Ligands from Sandalwood Oil and Synthetic α-Santalol Derivatives.

Bioassay-guided fractionation of the essential oil of Santalum album led to the identification of α-santalol (1) and ß-santalol (2) as new chemotypes of cannabinoid receptor type II (CB2) ligands with Ki values of 10.49 and 8.19 µM, respectively. Nine structurally new α-santalol derivatives (4a-4h and 5) were synthesized to identify more selective and potent CB2 ligands. Compound 4e with a piperazine structural moiety demonstrated a Ki value of 0.99 µM against CB2 receptor and did not show binding activity against cannabinoid receptor type I (CB1) at 10 µM. Compounds 1, 2, and 4e increased intracellular calcium influx in SH-SY5Y human neuroblastoma cells that were attenuated by CB2 antagonism or inverse agonism, supporting the results that these compounds are CB2 agonists. Molecular docking showed that 1 and 4e had similar binding poses, exhibiting a unique interaction with Thr114 within the CB2 receptor, and that the piperazine structural moiety is required for the binding affinity of 4e. A 200 ns molecular dynamics simulation of CB2 complexed with 4e confirmed the stability of the complex. This structural insight lays a foundation to further design and synthesize more potent and selective α-santalol-based CB2 ligands for drug discovery.

Identification of the Putative Binding Site of a Benzimidazole Opioid (Etazene) and Its Metabolites at µ-Opioid Receptor: A Human Liver Microsomal Assay and Systematic Computational Study.

The synthetic benzimidazole opioid etazene (which has a 70-times higher analgesic activity than morphine), a recreational drug, has gained popularity as a novel psychoactive substance (NPS) on the illegal/darknet market; however, no experimental information is available at the molecular level on the binding mechanism and putative binding site of etazene and its metabolites at the µ-opioid receptor (MOR). In the present study, we investigated the metabolism of etazene in human liver microsomes using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). We also explored the possibilities of MOR activation by etazene and its metabolites by studying their binding mechanisms and interaction profiles at an active-state MOR model via molecular docking, binding free energy calculations, and all-atom molecular dynamics (MD) simulations. The putative metabolites of etazene were also predicted using the ADMET Predictor 10.1. The molecular docking studies and free energy calculations showed that etazene and its metabolites (M1, M2, and M5-M7) exhibited strong predicted binding affinity at MOR and showed overlapped binding orientation with MOR-bound agonist BU72, which was co-crystallized in the MOR X-ray crystal structure (PDB ID: 5C1M). MD also confirmed the stability of the MOR-etazene and MOR-M6 complexes. These results suggest that etazene and its metabolites may act as strong MOR agonists, highlighting the necessity of experimental validation. The insights from this study, such as key interactions between etazene and its metabolites and the MOR, will allow authorities to predict potential analogs and clarify the target-protein interactions associated with this illicit substance, granting advanced or rapid reactions to confiscating or banning potential emerging drugs.

In Vitro and In Silico Studies of Neolignans from Magnolia grandiflora L. Seeds against Human Cannabinoids and Opioid Receptors.

Magnolia grandiflora L. (Magnoliaceae) is a plant of considerable medicinal significance; its flowers and seeds have been used in various traditional remedies. Radioligand binding assays of n-hexane seeds extract showed displacement of radioligand for cannabinoid (CB1 and CB2) and opioid δ (delta), κ (kappa), and µ (mu) receptors. Bioactivity-guided fractionation afforded 4-O-methylhonokiol (1), magnolol (2), and honokiol (3), which showed higher binding to cannabinoid rather than opioid receptors in radioligand binding assays. Compounds 1-3, together with the dihydro analog of 2 (4), displayed selective affinity towards CB2R (Ki values of 0.29, 1.4, 1.94, and 0.99 µM, respectively), compared to CB1R (Ki 3.85, 17.82, 14.55, and 19.08 µM, respectively). An equal mixture of 2 and 3 (1:1 ratio) showed additive displacement activity towards the tested receptors compared to either 2 or 3 alone, which in turn provides an explanation for the strong displacement activity of the n-hexane extract. Due to the unavailability of an NMR or X-ray crystal structure of bound neolignans with the CB1 and CB2 receptors, a docking study was performed to predict ligand-protein interactions at a molecular level and to delineate structure-activity relationships (SAR) of the neolignan analogs with the CB1 and CB2 receptors. The putative binding modes of neolignans 1-3 and previously reported related analogs (4, 4a, 5, 5a, 6, 6a, and 6b) into the active site of the CB1 and CB2 receptors were assessed for the first time via molecular docking and binding free-energy (∆G) calculations. The docking and ∆G results revealed the importance of a hydroxyl moiety in the molecules that forms strong H-bonding with Ser383 and Ser285 within CB1R and CB2R, respectively. The impact of a shift from a hydroxyl to the methoxy group on experimental binding affinity to CB1R versus CB2R was explained through ∆G data and the orientation of the alkyl chain within the CB1R. This comprehensive SAR, influenced by the computational study and the observed in vitro displacement binding affinities, has indicated the potential of magnolia neolignans for developing new CB agonists for potential use as analgesics, anti-inflammatory agents, or anxiolytics.

Benzoylcyclopropane Derivatives from Hypoxis hemerocallidea Corms.

Two monobenzoylcyclopropane (hypoxhemerol A (1: ) and hypoxhemeroloside G (2: )) and three dibenzoylcyclopropane (hypoxhemerol B (3: ), hypoxhemeroloside H (4: ), and hypoxhemeroloside I (5: )) derivatives were isolated from the hydro-alcoholic extract of Hypoxis hemerocallidea corms. This is the first instance where benzoylcyclopropane analogs were isolated from any natural source. Structure elucidation was mainly based on 1D- and 2D-NMR and HRESIMS data. The absolute configuration (2R, 4R) of 1: was determined via NOESY NMR and experimental and calculated ECD data analyses. Compounds 1: -5: and 11 recently reported metabolites (hypoxoside, obtuside A, interjectin, acuminoside, curcapicycloside, and hypoxhemerolosides A - F) were screened for in vitro antimicrobial activity against various bacterial and fungal strains. Curcapicycloside and acuminoside exhibited antibacterial activity against Escherichia coli with 78 and 79% inhibition at 20 µg/mL, respectively. Hypoxhemeroloside A showed mild antifungal activity against Cryptococcus neoformans with 63% inhibition at 20 µg/mL.

Glutamate binding triggers monomerization of unliganded mGluR2 dimers.

The Metabotropic glutamate receptor 2 (mGluR2) is involved in several neurological and psychiatric disorders and is an attractive drug target. It is believed to form a strict dimer and the dimeric assembly is necessary for glutamate induced activation. Although many studies have focused on glutamate induced conformational changes, the dimerization propensity of mGluR2 with and without glutamate has never been investigated. Also, the role of the unstructured loop in dimerization of mGluR2 is not clear. Here, using Forster Resonance Energy Transfer (FRET) based assay in live cells we show that mGluR2 does not form a "strict dimer" rather it exists in a dynamic monomer-dimer equilibrium. The unstructured loop moderately destabilizes the dimers. Furthermore, binding of glutamate to mGluR2 induces conformational change that promotes monomerization of mGluR2. In the absence of an unstructured loop, mGluR2 neither undergoes conformational change nor monomerizes upon binding to glutamate.

Forrestiacids†A and†B, Pentaterpene Inhibitors of ACL and Lipogenesis: Extending the Limits of Computational NMR Methods in the Structure Assignment of Complex Natural Products.

Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels-Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC50 s <5 µM) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.

Unstructured loop is essential for the activation of mGluR2.

Metabotropic Glutamate Receptors (mGluRs) are Class C G-protein coupled receptors (GPCRs) that are expressed throughout the central nervous system and are involved in several neurological and psychiatric disorders. Although, many studies focused on Glutamate induced activation of mGluR2, however, the role of unstructured loop (or "BC loop") in activation of metabotropic Glutamate receptors is currently unknown. Here, using Förster Resonance Energy Transfer (FRET) based assay in live cells we show that unstructured loop is required for Glutamate induced conformation and hence the activation of the receptor.

CRISPR/Cas9 directed editing of lycopene epsilon-cyclase modulates metabolic flux for ß-carotene biosynthesis in banana fruit.

Banana is one of the most economically important fruit crops worldwide. Genetic improvement in banana is a challenging task due to its parthenocarpic nature and triploid genome. Genetic modification of crops via the CRISPR/Cas9 module has emerged as a promising tool to develop important traits. In the present work, a CRISPR/Cas9-based approach was used to develop the ß-carotene-enriched Cavendish banana cultivar (cv.) Grand Naine (AAA genome). The fifth exon of the lycopene epsilon-cyclase (LCYε) gene was targeted. The targeting specificity of the designed guide-RNA was also tested by its ability to create indels in the LCYε gene at the A genome of cv. Rasthali (AAB genome). Sequence analysis revealed multiple types of indels in the genomic region of Grand Naine LCYε (GN-LCYε). Metabolic profiling of the fruit pulp of selected edited lines showed enhanced accumulation of ß-carotene content up to 6-fold (~24 µg/g) compared with the unedited plants. These lines also showed either an absence or a drastic reduction in the levels of lutein and α-carotene, suggesting metabolic reprogramming, without any significant effect on the agro-morphological parameters. In addition, differential expression of carotenoid pathway genes was observed in the edited lines in comparison to unedited plants. Overall, this is the first report in banana to improve nutritional trait by using a precise genome editing approach.

Potential Modulation of Human NAD[P]H-Quinone Oxidoreductase 1 (NQO1) by EGCG and Its Metabolites-A Systematic Computational Study.

At high doses, green tea extracts and green tea's major active constituent, (-)-epigallocatechin gallate (EGCG), despite their generally perceived health benefits, have been suspected to cause hepatotoxicity in certain human populations. It has been reported that o-quinone metabolites of gallic acid or EGCG are causative agents for this hepatotoxicity. However, no experimental information is available at the molecular level on the possible role of NQO1 in the detoxification of EGCG and its metabolites, including reactive intermediates. In the present study, we investigated the possibility of NQO1 inhibition by EGCG and its metabolites by studying their interaction profiles and binding mechanism at the active site of NQO1 using molecular docking, binding free energy calculations, and molecular dynamics (MD) simulations. The binding free energy calculations showed that some metabolites exhibited strong predicted binding affinity and found that the binding orientation of the EGCG metabolites overlapped with that of dicoumarol found in an NQO1 X-ray crystal structure. The results suggest that these metabolites may act as strong NQO1 inhibitors, highlighting the need for experimental validation of this with appropriate biological methods. The Prime MM-GBSA computed average binding free energies after MD simulations of compounds 1, 2, 24, 31, and 33 revealed that these compounds highly favored van der Waals (VdW) and Coulombic interactions with NQO1. In addition, the MD results revealed that selected EGCG metabolites formed a stable and strong complex with NQO1, with amino acids W105, Y126, Y128, H161, F178, H194, F232, and F236 being critical for potential NQO1 binding. The current results together with experimental data as well as studies of the polymorphisms of NQO1 (especially C609T) may explain the observed idiosyncratic hepatotoxicity caused by the consumption of green tea and its constituents.

Ubiquity of complex coacervation of DNA and proteins in aqueous solution.

We report complex coacervation between a primarily hydrophobic protein, elastin, and a strong polyanion DNA (2 kbp) in aqueous and salty solutions at room temperature, 25 °C. The associative interaction at fixed elastin and varying DNA concentration, thereby maintaining a mixing ratio of r = [DNA] : [elastin] = 0.0027 to 0.093, was probed. What distinguishes this study from protein-DNA coacervation reported earlier is that the protein used here was mostly a hydrophobic polyampholyte with low linear charge density, and its complementary polyelectrolyte, DNA, concentration was chosen to be extremely small (1-35 ppm). The interaction profile was found to be strongly hierarchical in the mixing ratio, defined by three distinct regions: (i) Region I (r < 0.02) was defined as the onset of primary binding leading to condensation of DNA; (ii) Region II (0.02 < r < 0.08) indicated secondary binding which led to the formation of fully charge neutralized complexes signaling the onset of coacervation; and (iii) Region III (0.08 < r < 0.12) revealed growth of insoluble complexes of large size facilitating liquid-solid phase separation. The degree of complex coacervation was suppressed in the presence of a monovalent salt implying that screened Coulomb interactions governed the binding. Small angle neutron scattering data attributed an amorphous structure to the coacervates. The elastin-DNA system belongs to a rare class of interacting biopolymers where very weak electrostatic interactions may drive coacervation, thereby implying that coacervation between DNA and proteins may be ubiquitous.

Hypervalent Iodine Mediated Oxidative Cyclization of Acrylamide N-Carbamates to 5,5-Disubstituted Oxazolidine-2,4-diones.

A metal-free oxidative cyclization of N-Boc-acrylamides with (diacetoxyiodo)benzene in acetic acid produced 5,5-disubstituted oxazolidine-2,4-diones with the formation of a C-O bond in moderate to excellent yields. In addition, the reaction was diastereospecific with N-Boc-2,3-dimethylacrylamides and proceeded with phenyl migration in the case of an N-Boc-2-phenylacrylamide to generate a 5-acetoxy-5-benzyloxazolidine-2,4-dione.

Tridiscorhabdin and Didiscorhabdin, the First Discorhabdin Oligomers Linked with a Direct C-N Bridge from the Sponge Latrunculia biformis Collected from the Deep Sea in Antarctica.

Guided by LC-MS/MS molecular networking-based metabolomics and cytotoxic activity, two new discorhabdin-type alkaloids, tridiscorhabdin (1) and didiscorhabdin (2), were isolated from the sponge Latrunculia biformis, collected from the Weddell Sea (Antarctica) at -291 m depth. Their structures were established by HRESIMS, NMR, [α]D, and ECD data coupled with DFT calculations. Both compounds bear a novel C-N bridge (C-1/N-13) between discorhabdin monomers, and 1 represents the first trimeric discorhabdin molecule isolated from Nature. Tridiscorhabdin (1) exhibited strong cytotoxic activity against the human colon cancer cell line HCT-116 (IC50 value 0.31 µM).

Olfaction in Juvenile Nasopharyngeal Angiofibroma: The first study.

BACKGROUND: To study the pattern of olfactory dysfunction/recovery in juvenile nasopharyngeal angiofibroma (JNA). METHODS: Olfactory assessment was undertaken in 30 patients (category1) both pre- & post-operatively and in another 18 (category 2) only postoperative. All patients underwent transpalatal excision and variables of interest included age, radiological stage/parameters & tumor size. RESULTS: Objective olfactory dysfunction was seen in 60% while involvement of olfactory strip was suggested in 50%. Despite some marginal trends only noted between size/age with change of olfaction, Pearson's correlation test did not reveal any significance amongst multiple variables. However a better recovery of olfaction following surgery was evident in Category-2 where Chi-Square test (p < 0.05) significantly revealed this to be a function of postoperative duration. This regenerative course in JNA suggests an optimum period of 4 years for full recovery after surgery. CONCLUSION: In this first study of olfaction in JNA many new trends have been appreciated. In general, deteriorations of olfaction were seen due to 'vascular-concussion' effect in early postoperative phase where post-surgical clearance of airway showed minimal effect in terms of improvement. The hypervascularity of olfactory epithelium with possible hormonal effects may be responsible for the unique pattern of olfactory function and recovery in JNA.