A quantitative chemomics strategy for the comprehensive comparison of Murraya paniculata and M. exotica using liquid chromatography coupled with mass spectrometry.

Murrayae Folium et Cacumen (MFC) is a traditional Chinese medicine (TCM) derived from two plant species, Murraya exotica L. and Murraya paniculata (L.) Jack, as recorded in the Chinese Pharmacopoeia. However, there is no research available on the comprehensive analysis and comparison of the chemical constituents of these two species. In the present study, an integrated LC-MS-based quantitative metabolome strategy was proposed to conduct a comprehensive and in-depth qualitative and quantitative analysis and comparison of the chemome of M. exotica and M. paniculata. Firstly, the universal chemical information of two plants was obtained by quadrupole-time-of-flight mass spectrometry (Q-TOF-MS) combined with hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS). Subsequently, a UNIFI in house database, the proposed fragmentation patterns, and a quantitative structure chromatographic retention relationship (QSRR) model were integrated for the rapid, comprehensive, and accurate structural elucidation of the chemical constituents of these two species. Thirdly, a large-scale quantitation method was established using scheduled multiple reaction monitoring mode (sMRM) and 76 primary components were selected as quantitative markers for the method validation. The obtained dataset was then subjected for multivariate statistical analysis to comprehensive comparison of these two plants. As a result, a total of 209 and 212 compounds were identified from M. exotica and M. paniculata, respectively. Among them, 103 common constituents were disclosed in both plants. The multivariate statistical analysis and absolute quantitative analysis revealed noticeable differences in the contents of specific chemical constituents between these two plants. The higher quantity constituents in M. exotica are 7-methoxycoumarins, while polymethoxylated flavonoids are the major constituents in M. paniculata. The common compounds accounted for approximately 80 % of the quantitative components in both plants, which provides a theoretical basis for their common use as the official source of MFC. In sum, the established quantitative chemomics strategy supplies an effective means for comprehensive chemical comparison of multi-source TCMs.

Elastogenic potential and antisagging properties of a novel Murraya koenigii extract.

BACKGROUND: The process by which functional elastic fibers are produced, namely elastogenesis, is complex and difficult to assess in vitro. Identifying efficient elasticity-boosting ingredients thus represents a challenge. AIMS: The elasticity-boosting properties of a novel extract of Murraya koenigii leafy stems were assessed in vitro in 3D culture models before being evaluated in human female volunteers. METHODS: Synthesis of elastic fiber related proteins was evaluated in a skin-equivalent model. Using multiphoton microscopy, the structural organization of elastin deposits was studied within a scaffold-free dermal microtissue. Biomechanical properties of the 3D microtissue were also measured by atomic force microscopy. In vivo, fringe-projection and image analysis were used to evaluate nasogenian fold severity in a panel of Caucasian female volunteers. The impact of gravity on visible signs of facial aging was assessed by clinical scoring carried out alternatively in the supine and sitting positions. RESULTS: We showed the Murraya koenigii extract increased protein expressions of elastin and fibrillin-1 in a 3D skin equivalent model. Using scaffold-free dermal microtissue, we confirmed that Murraya koenigii extract allowed a proper and ordered network of elastin deposits and consequently improved tissue elasticity. Clinical data showed that a twice-daily application for 98 days of the extract formulated at 1% allowed to visibly reduce nasogenian fold severity, jowl severity and to mitigate the impact of gravity on the facial signs of aging. CONCLUSION: The newly discovered extract of Murraya koenigii leafy stems represents an innovative antiaging ingredient suited for elasticity-boosting and antisagging claims.

Green synthesis of copper oxide nanoparticles from Murraya koenigii and its corrosion resistivity on Ti-6Al-4V dental alloy.

The present work describes green-mediated copper oxide nanoparticles as a potential corrosion inhibitor for the dental alloy Ti-6Al-4V. The salt of copper was reduced to metal nanoparticles using Murraya koenigii leaves, which helps with the agglomeration and nanocluster formation through a reduction mechanism. The current synthesis is a single-step process and is cost-effective. The synthesized nanoparticle was characterized using UV, FTIR, XRD, Zeta potential and Particle size analyzer, SEM, and EDX. The particles were then electrodeposited on Ti-6Al-4V alloy, and the corrosion resistivity in the dental medium was analyzed using Electrochemical parameters such as Corrosion current, Corrosion potential, and anodic and cathodic intercepts through the Tafel and Nyquist plots. The synthesized nanoparticles showed characteristic absorbance at 359 nm. FTIR peaks confirm the phytochemical constituents present in the Murraya koenigii that accounts for the formation of nanoparticles. The XRD predicts the crystalline nature, which is further studied using SEM and EDX. The Zeta potential and Particle size analyzer confirms the negative-negative interactive nature of the synthesized CuO NPs. The NPs showed explicit corrosion inhibition properties with an overall inhibition efficiency of 58.15% and 25.6%, respectively. The study confirms the advantage of using Copper Oxide nanoparticles as a potential coating agent in dental implant alloys in increasing its corrosion efficiency.

Phytochemistry and Biological Activities of Murraya Species.

Murraya is a plant genus within the Rutaceae family comprising over 17 species, which are widely distributed in Asia, Australia, and the Pacific Islands. Furthermore, these species have been used in traditional medicine to treat fever, pain, and dysentery. Several reports have also extensively studied the leaves, seeds, stembark, and bark of Murraya from 1965 to 2023 to explore their natural product composition. Various phytochemical studies have revealed the isolation of 413 compounds recorded, comprising coumarins, terpenoids, flavonoids, and aromatics, as well as alkaloids, which constitute the largest proportion (46.9%). These isolated compounds have long been known to exhibit different bioactivities, such as cytotoxic and anti-inflammatory properties. Cytotoxic activity has been observed against HCT 116, HeLa, HepG2, and other cell lines. Previous studies have also reported the presence of antifungal, hepatoprotective, antihyperlipidemic, antidiarrheal, and antioxidant effects. Therefore, this review provides a comprehensive overview of Murraya species, highlighting their phytochemistry, biological activities, and potential as a source of active natural compounds.

Investigating the therapeutic potential of aqueous extraction of curry plant (Murraya koenigi) leaves supplementation for the regulation of blood glucose level in type 2 diabetes mellitus in female human subjects.

Type 2 diabetes mellitus is characterized by hyperglycemia and insulin resistance. It is spreading around the globe like a pandemic. Major factors behind the development of diabetes can be genetics, environmental factors, dietary choices and obesity. Many medicinal plants have anti-diabetic potential. This study has investigated the anti-diabetic effect of curry leaves extract. This study also investigated the chemical characterization of curry leaves. Phytochemicals including saponins, tannins, alkaloids, flavonoids, phenols and glycosides were also investigated. Encapsulated 5mg per kg of the body weight and 10mg per kg of the body weight were given to treatment groups I and II. Random blood sugar, fasting blood sugar and HbA1c of 45 diabetic female adults were measured on the 0-day and 45th days. All results were analyzed using the two-sample t-test in IBM SPSS Statistics 20. Curry leaves contained moisture (24.1±1.78)%, ash (17.82±2.13)%, nitrogen free extract (36.12±3.52)%, crude protein (8.32±0.83)%, crude fiber (6.98±2.31)% and crude fat (6.87±0.21)%. Mineral analysis showed that magnesium and calcium were major minerals present in curry leaves. Curry leaves extract contained saponins 2.71±0.23, flavonoids 7.84±0.42, tannins 0.91±0.09, glycosides 0.17±0.01, phenols 3.89±0.12, alkaloids 2.01±0.87. These phytochemicals were expressed in mg/100 g of the sample. Curry leaf extract showed a significant (p<0.05) reduction in fasting blood sugar, random blood sugar and glycated hemoglobin in both treatment groups.

The comparison of gut gene expression and bacterial community in Diaphorina citri (Hemiptera: Liviidae) adults fed on Murraya exotica and 'Shatangju' mandarin (Citrus reticulate cv. Shatangju).

BACKGROUND: Diaphorina citri Kuwayama is an important citrus pest. It serves as the vector for the transmission of Candidatus Liberibacter asiaticus (CLas), which induced a destructive disease, Huanglongbing, and caused huge economic losses. During the interaction between insects and plants, insects have evolved a series of mechanisms to adapt to various host plants. Murraya exotica and 'Shatangju' mandarin (Citrus reticulate cv. Shatangju) are the Rutaceae species from different genera that have been discovered as suitable hosts for D. citri adults. While the adaptation mechanism of this pest to these two host plants is unclear. RESULTS: In this study, RNA-seq and 16 S rDNA amplification sequencing were performed on the gut of D. citri adults reared on M. exotica and 'Shatangju' mandarin. RNA-seq results showed that a total of 964 differentially expressed genes were found in different gut groups with two host plant treatments. The impacted genes include those that encode ribosomal proteins, cathepsins, and mitochondrial respiratory chain complexes. According to 16 S rDNA sequencing, the compositions of the gut bacterial communities were altered by different treatments. The α and ß diversity analyses confirmed that the host plant changes influenced the gut microbial diversity. The functional classification analysis by Tax4Fun revealed that 27 KEGG pathways, mostly those related to metabolism, including those for nucleotide metabolism, energy metabolism, metabolism of cofactors and vitamins, amino acid metabolism, carbohydrate metabolism, xenbiotics biodegradation and metabolism, lipid metabolism, and biosynthesis of other secondary metabolites, were significantly altered. CONCLUSION: Our preliminary findings shed light on the connection between D. citri and host plants by showing that host plants alter the gene expression profiles and bacterial community composition of D. citri adults.

Phyto-Pharmacological Review on Murraya koenigii (L.) Spreng: As an Indigenous Plant of India with High Medicinal Potential.

The medicinal aspects of Murraya koenigii (L.) Spreng. It also provides the latest updated information on pharmacological and plant patents on phytoconstituents. The information was collected from various sources, including literature surveys, textbooks, databases, and internet sources like Scopus, Science Direct, Pubmed, Springer, Google Scholar, Taylor and Francis. The plant, Murraya koenigii (L.) Spreng is an extensive valuable, and important medicinal plant in the Indian System of Medicine. The plant proved to show various ethnomedicinal uses mentioned in the literature and even possessed various pharmacological activities. Different bioactive metabolites exhibit several biological activities. However, the biological efficacies of various other chemical constituents are yet to be clarified and proved concerning the molecular mechanisms.

Chromosome-level genome assembly of Murraya paniculata sheds light on biosynthesis of floral volatiles.

BACKGROUND: Murraya paniculata (L.) Jack, commonly called orange jessamine in the family Rutaceae, is an important ornamental plant in tropical and subtropical regions which is famous for its strong fragrance. Although genome assemblies have been reported for many Rutaceae species, mainly in the genus Citrus, full genomic information has not been reported for M. paniculata, which is a prerequisite for in-depth genetic studies on Murraya and manipulation using genetic engineering techniques. Here, we report a high-quality chromosome-level genome assembly of M. paniculata and aim to provide insights on the molecular mechanisms of flower volatile biosynthesis. RESULTS: The genome assembly with a contig N50 of 18.25 Mb consists of 9 pseudomolecules and has a total length of 216.86 Mb. Phylogenetic analysis revealed that M. paniculata diverged from the common ancestor approximately 25 million years ago and has not undergone any species-specific whole genome duplication events. Genome structural annotation and comparative genomics analysis revealed that there are obvious differences in transposon contents among the genomes of M. paniculata and Citrus species, especially in the upstream regions of genes. Research on the flower volatiles of M. paniculata and C. maxima at three flowering stages revealed significant differences in volatile composition with the flowers of C. maxima lacking benzaldehyde and phenylacetaldehyde. Notably, there are transposons inserted in the upstream region of the phenylacetaldehyde synthase (PAAS) genes Cg1g029630 and Cg1g029640 in C. maxima, but not in the upstream region of three PAAS genes Me2G_2379, Me2G_2381, and Me2G_2382 in M. paniculata. Our results indicated that compared to the low expression levels of PAAS genes in C. maxima, the higher expression levels of the three PAAS genes in M. paniculata are the main factor affecting the phenylacetaldehyde biosynthesis and causing the content difference of phenylacetaldehyde. The phenylacetaldehyde synthetic activities of the enzymes encoded by M. paniculata PAAS genes were validated by in vitro analyses. CONCLUSIONS: Our study provides useful genomic resources of M. paniculata for further research on Rutaceae plants, identifies new PAAS genes, and provides insights into how transposons contribute to variations in flower volatiles among Murraya and Citrus plants.

Influence of Murraya koenigii extract on diabetes induced rat brain aging.

Food supplements are used to improve cognitive functions in age-related dementia. This study was designed to determine the Murraya koenigii leaves' effect on Alloxan-induced cognitive impairment in diabetic rats and the contents of oxidative stress biomarkers, catalase, reduced glutathione, and glutathione reductase in brain tissue homogenates. Wistar rats were divided into seven groups (six rats per group). Group I received saline water (1 ml, p.o.), Diabetes was induced in Groups II-VII with Alloxan (120 mg/kg/p.o). Group III was provided with Donepezil HCl (2.5 mg/kg/p.o.), Group IV, V, VI, and VII with Murraya koenigii ethanol extract (200 and 400 mg/kg/p.o.) and aqueous extract (200 and 400 mg/kg/p.o.), respectively, for 30 days. Behavior, acetylcholinesterase (AChE) activity, oxidative stress status, and histopathological features were determined in the hippocampus and cerebral cortex. Administration of Murraya koenigii ethanolic and aqueous extracts significantly (P<0.05, P<0.001) increased the number of holes crossed by rats from one chamber to another. There was an increase in the (1) latency to reach the solid platform, (2) number of squares traveled by rats on the 30th day, and (3) percentage of spontaneous alternation behavior compared to the control group. Administration for successive days markedly decreased AChE activity (P<0.05), decreased TBARS level, and increased catalase, GSH, and GR levels. Murayya koenigii could be a promising food supplement for people with dementia. However, more research into sub-chronic toxicity and pharmacokinetic and pharmacodynamics interactions is essential.

Biomonitoring of polycyclic aromatic hydrocarbons (PAHs) by Murraya paniculata (L.) Jack in South Kolkata, West Bengal, India: spatial and temporal variations.

Attempts have been made in the present study for ascertaining the concentrations of atmospheric polycyclic aromatic hydrocarbons (PAHs) using passive biosamplers in preference to conventional air sampling methods. Mechanical stirring, sonication, Soxhlet technique and microwave-assisted Soxhlet extraction (MASE) were employed to extract PAHs from an evergreen plant (Murraya paniculata) leaves (having long life-span) sampled from polluted places of South Kolkata, India, with dense population and heavy traffic. Effects of extraction methods and operational parameters (solvent and time) on the recovery levels of PAHs were also investigated. Purified extracts, acquired through adsorption chromatography, were subjected to GC-MS and HPLC-UV analyses for qualitative and quantitative assessment of PAHs. Spatio-temporal distribution of accumulated PAHs across the sampling sites was monitored over premonsoon, postmonsoon and winter supported by pollutant source characterization. The results displayed that the extraction yields of Soxhlet (272.07 ± 26.15 µg g-1) and MASE (280.17 ± 15.46 µg g-1) were the highest among the four techniques. Conditions of extraction with toluene for 6 h were found to be most favorable for PAHs. In spatio-temporal analysis, total concentrations of PAHs in the foliar samples varied from 200.98 ± 2.72 to 550.79 ± 10.11 µg g-1 dry weight, and the highest values being recorded in the samples of Exide More because of daylong inexorable traffic flow/crowding increasing the burden of ambient PAHs. Widespread changes in meteorology exerted influence on seasonal concentrations of PAHs in plant leaves, and extent of leaf contamination by PAHs was observed extreme in winter followed by postmonsoon and then, premonsoon. Foliar accretion of PAHs differed in the study sites with diverse sources of emission from motor vehicles, fossil fuel and biomass burning along with other human interferences.

In vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity of Murraya koenigii leaf extract intercedes ZnO nanoparticles.

Nanotechnology is an emerging field with tremendous potential and usage of medicinal plants and green preparation of nanoparticles (NPs) is one of the widely explored areas. These have been shown to be effective against different biological activities such as diabetes mellitus, cancer, antioxidant, antimicrobial, etc. The current studies focus on the green synthesis of zinc NPs (ZnO NPs) from aqueous leaf extract of Murraya koenigii (MK). The synthesized Murraya koeingii zinc oxide NPs (MK ZnO NPs) were characterized using UV-visible spectroscopy, dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, field emission scanning electron microscopy (FESEM), energy-dispersive spectrum (EDS) and cyclic voltammetry (CV). The synthesized MK ZnO NPs were evaluated for their in vitro antidiabetic, antioxidant, antimicrobial, and cytotoxic activity. They demonstrated significant antidiabetic and cytotoxic activity, as well as moderate free-radical scavenging and antibacterial activity.

A Computational Study of Carbazole Alkaloids from Murraya koenigii as Potential SARS-CoV-2 Main Protease Inhibitors.

Despite COVID-19 vaccination, immune escape of new SARS-CoV-2 variants has created an urgent priority to identify additional antiviral drugs. Targeting main protease (Mpro) expressed by SARS-CoV-2 is a therapeutic strategy for drug development due to its prominent role in viral replication cycle. Leaves of Murraya koenigii are used in various traditional medicinal applications and this plant is known as a rich source of carbazole alkaloids. Thus, this computational study was designed to investigate the inhibitory potential of carbazole alkaloids from Murraya koenigii against Mpro. Molecular docking was initially used to determine the binding affinity and molecular interactions of carbazole alkaloids and the reference inhibitor (3WL) in the active site of SARS-CoV-2 Mpro (PDB ID: 6M2N).The top scoring compounds were further assessed for protein structure flexibility, physicochemical properties and drug-likeness, pharmacokinetic and toxicity (ADME/T) properties, antiviral activity, and pharmacophore modeling. Five carbazole alkaloids (koenigicine, mukonicine, o-methylmurrayamine A, koenine, and girinimbine) displayed a unique binding mechanism that shielded the catalytic dyad of Mpro with stronger binding affinities and molecular interactions than 3WL. Furthermore, the compounds with high affinity displayed favorable physicochemical and ADME/T properties that satisfied the criteria for oral bioavailability and druggability. The pharmacophore modeling study shows shared pharmacophoric features of those compounds for their biological interaction with Mpro. During the molecular dynamics simulation, the top docking complexes demonstrated precise stability except koenigicine. Therefore, mukonicine, o-methylmurrayamine A, koenine, and girinimbine may have the potential to restrict SARS-CoV-2 replication by inactivating the Mpro catalytic activity.

Diversity in Phytochemical Composition and Medicinal Value of Murraya paniculata.

Murraya paniculata is herbal medicinal plant which is traditionally being used for management of cardiovascular, intestinal and respiratory (air way) disorders. This evergreen plant of tropical regions is a member of Rutaceace family. The goal of this review is to analyze and report the biological activities and active phytochemicals reported from Murraya paniculata (M. paniculata) extracts and essential oil. The data was searched using different search engines and using specific key words including M. paniculata, herbal medicine, phytochemicals, extract, essential oil, pharmacological activities. M. paniculata has been found to have wide range of pharmacological activities, including antinociceptive, antianxiety, antioxidant, antidepressant, antibacterial, analgesic and anti-diabetic properties. A diverse range of phytochemicals, including phenols, coumarins, terpenoids, flavonoids, and alkaloids have been isolated from various portions of the plant and tested for a variety of biological activities. This review will provide more information and stimulate additional research to develop more effective and cost-efficient alternative medicine from this plant.

Antimicrobial activities and phytochemicals of Murraya paniculata L. flowers, leaves and bark crude extracts

Aims@#Murraya paniculata (L.) has been widely employed in medicine, has also been modified to serve as an ingredient in health foods and found application in cosmetics. This study was aimed to assess the biological activities of M. paniculata by analyzing the chemical compositions of its flowers, leaves and bark.@*Methodology and results@#Crude extracts drawn from the flowers, leaves and bark of M. paniculata underwent testing to determine the antibacterial properties in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC), as well as the overall chemical composition, total phenolic content, flavonoids and antioxidant activity. Crude extract of leaves exhibited the most potent antibacterial activity when tested against Staphylococcus aureus TISTR 1466, Bacillus subtilis ATCC 6633 and Pseudomonas aeruginosa ATCC 27853. The crude extract from bark delivered the most significant antibacterial activity when tested against Micrococcus luteus TISTR 9341, Escherichia coli ATCC 1261, Pseudomonas sp., Streptococcus sp. and Methicilin resistant S. aureus (MRSA). For all crude extracts, the MIC value against M. luteus TISTR 9341 was 12.5 mg/mL. Meanwhile, the MBC value for the crude extract of leaves against B. subtilis ATCC 6633 was 12.5 mg/mL, whereas, for flower and bark crude extracts, the MBC value against S. aureus TISTR 1466 was 25 mg/mL. Antioxidant activity was at its highest for the crude extract from bark (IC50 = 1.36 mg/mL). The highest phenolic content was recorded for the crude extract from bark, while the highest flavonoid content came from the crude extract of leaves (70.81 ± 0.31 mgGAE/g extract and 115.73 ± 1.18 mgQE/g extract, respectively).@*Conclusion, significance and impact of study@#The research findings suggest that the crude extracts of M. paniculata leaves and bark show greater significant levels of bioactivity than was the case for crude extracts from flowers. The research findings could help in exploring the possibilities of using M. paniculata for pharmaceutical purposes and in aquaculture.

In vivo antioxidants, chemical characterization and biochemical and medicinal potential of Murraya koenigii in cisplatin-induced nephrotoxicity.

Murraya koenigii (Mk) is an old plant with a significant therapeutic value throughout Africa, Asia, and Latin America. The excessive use of cisplatin (Cis> 50 mg/m2) is associated with nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. Remedial measures are needed for the protection of nephrotoxicity against cisplatin. Thus, we have investigated Mk leaf extract's nephroprotective effects to prevent cisplatin-induced nephrotoxicity in Wistar albino rats. The presence of polyphenols, phenolic compounds, tannins, and saponins was revealed during phytochemical investigation, and antioxidant activity was recorded. There were no toxicological symptoms in the treated rats, and no anatomical, physiological, or histological abnormalities were found compared to the control rats. The results of correcting cisplatin-induced nephrotoxicity revealed that the extract has a significant ability to treat kidney damage, with most parameters returning to normal after only three weeks of therapy. It was concluded that co-administered cisplatin with Mk leaves extract showed exceptional nephroprotective effects at a 400 mg/kg dose ratein Cis-induced nephrotoxicity.

Natural carbazole alkaloid murrayafoline A displays potent anti-neuroinflammatory effect by directly targeting transcription factor Sp1 in LPS-induced microglial cells.

Neuroinflammation is a leading cause for neurological disorders. Carbazole alkaloids, isolated from the medicinal plants of Murraya species (Rutaceae), have exhibited wide pharmacological activities particularly for neuroinflammation. However, its underlying cellular targets and molecular mechanisms still remain unclear. In current study, we found that murrayafoline A (MA), a carbazole alkaloid obtained from Murraya tetramera, potently inhibited the production of neuroinflammation mediators, such as nitric oxide (NO), TNF-α, IL-6 and IL-1ß in LPS-induced BV-2 microglial cells. Then, we performed thermal proteome profiling (TPP) strategy to identify Specificity protein 1 (Sp1) as a potential cellular target of MA. Moreover, we performed surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DRATS) assays to confirm the direct interaction between MA and Sp1. Furthermore, we downregulated Sp1 expression in BV2 cells using siRNA transfection, and observed that Sp1 knockdown significantly antagonized MA-mediated inhibition of neuroinflammation mediator production. Meanwhile, Sp1 knockdown also markedly reversed MA-mediated inactivation of IKKß/NF-κB and p38/JNK MAPKs pathways. Finally, in vivo studies revealed that MA significantly suppressed the expression of Iba-1, TNF-α, and IL-6, while increased the number of Nissl bodies in the brains of LPS-induced mice. Taken together, our study demonstrated that MA exerted obvious anti-neuroinflammation effect by directly targeting Sp1, thereby inhibiting NF-κB and MAPK signaling pathways. Our findings also provided a promising direction of pharmacological targeting Sp1 for anti-neuroinflammation therapeutics as well as novel agent development.

Mahanimbine isolated from Murraya koenigii inhibits P-glycoprotein involved in lung cancer chemoresistance.

P-glycoprotein (P-gp), a transmembrane glycoprotein, is mainly involved in lung cancer multidrug resistance. Several P-gp inhibitors have been developed to enhance the efficacy of chemotherapeutics and overcome drug resistance. However, most of them failed in the clinical stages due to undesirable side effects. Therefore, there is a requirement to develop P-gp inhibitors from natural sources. Dietary spice bioactives have been well-known for their anticancer activities. However, their role in modulating the P-gp activity has not been well investigated. Therefore, we have screened for the potential bioactives from various spice plants with P-gp modulatory activity using computational molecular docking analysis. The computational analysis revealed several key bioactives from curry leaves, specifically mahanimbine, exhibited a strong binding affinity with P-gp. Unfortunately, mahanimbine is available with few commercial sources at very high prices. Therefore, we prepared a curry leaves extract and isolated mahanimbine by a novel, yet simple, extraction method that requires less time and causes minimum environmental hazards. After purification, structure, and mass were confirmed for the isolated compound by IR spectrum and LC-MS/MS analysis, respectively. In the mechanistic study, hydrolysis of ATP and substrate efflux by P-gp are coupled. Hence, ATP binding at the ATPase-binding site is one of the fundamental steps for the P-gp efflux cycle. We found that mahanimbine demonstrated to stimulate P-gp ATPase activity. Concurrently, it enhanced the intracellular accumulation of P-gp substrates Rhodamine 123 and Hoechst stain, which indicates that mahanimbine modulates the function of P-gp. In addition, we have analyzed the complementary effect of mahanimbine with the chemotherapeutic drug gefitinib. We found that mahanimbine synergistically enhanced gefitinib efficiency by increasing its intracellular accumulation in lung cancer cells. Overall, mahanimbine has been shown to be a potent P-gp modulator. Therefore, mahanimbine can be further developed as a potential candidate to overcome chemoresistance in lung cancer.

Insecticidal activity, Chemical Constituents of Trachyspermum ammi, Withania coagulans and Murraya koenigii ethanloic extracts against Bemisia tabaci.

Whitefly is one of the most widespread agricultural pests in the world. Essential oils might be used to control this insect in an environmentally responsible way. The fumigant, repellent, and anti-oviposition activity of ethanol-extracted essential oils of Trachyspermum ammi, Withania coagulans, and Murraya koenigii against Bemisia tabaci was investigated in this study. In the experiment, three essential oil concentrations (2.5 mg/mL, 5 mg/mL, and 10 mg/mL) were used. Trachyspermum ammi had the highest percentage of whitefly death in laboratory experiments due to its fumigant toxicity; the same tendency was found in contact toxicity and repellent effect. Mortality percent rises as the concentration of essential oil increases with bioassay time. As the concentration of essential oil grows with bioassay time, so does the mortality rate. The most adult whiteflies escaped from the treated plants' greenhouse due to the highest essential oil concentration. The greatest repellency was found with Trachyspermum ammi essential oil at 10 mg/mL. The essential oil had the greatest anti-oviposition efficacy against whiteflies. Trachyspermum ammi possessed the most potent anti-oviposition deterrent, followed by Withania coagulans in second place. Murraya koenigii finished third with moderate anti-oviposition, which affects the number of eggs produced in comparison to the control. As a consequence, these three oils might be used as an effective and environmentally acceptable bio-insecticide to control B. tabaci.

5-Demethoxy-10'-ethoxyexotimarin F, a New Coumarin with MAO-B Inhibitory Potential from Murraya exotica L.

Rutaceae plants are known for being a rich source of coumarins. Preliminary molecular docking showed that there was no significant difference for coumarins in Clausena and Murraya, both of which had high scoring values and showed good potential inhibitory activity to the MAO-B enzyme. Overall, 32 coumarins were isolated from Murraya exotica L., including a new coumarin 5-demethoxy-10'-ethoxyexotimarin F (1). Their structures were elucidated on the basis of a comprehensive analysis of 1D and 2D NMR and HRMS spectroscopic data, and the absolute configurations were assigned via a comparison of the specific rotations and the ECD exciton coupling method. The potential of new coumarin (1) as a selective inhibitor of MAO-B was initially evaluated through molecular docking and pharmacophore studies. Compound (1) showed selectivity for the MAO-B isoenzyme and inhibitory activity in the sub-micromolar range with an IC50 value of 153.25 ± 1.58 nM (MAO-B selectivity index > 172).

Characterization of a coumarin C-/O-prenyltransferase and a quinolone C-prenyltransferase from Murraya exotica.

Prenyltransferases (PTs) play important roles in the biosynthesis and structural diversification of natural products. In the present study, two new PTs were characterized from a medicinal plant Murraya exotica. MePT1 unprecedentedly catalyses the formation of two C-geranylated products 8/6-C-geranylumbelliferone together with a trace product 7-O-geranylumbelliferone from umbelliferone. MePT2 regio-specifically catalyses the formation of C-3 dimethylallylated products from quinolone alkaloids. This is the first report that a plant PT catalyses the simultaneous formation of C- and O-prenylated products, and a plant PT specifically utilizes quinolone alkaloids as prenyl acceptors. The results not only provide important insight into the functional diversity of plant PTs and the biosynthesis of the prenylated coumarins, quinolone and carbazole alkaloids in Murraya plants, but also pave the way for the overproduction of the prenylated coumarins and alkaloids using metabolic engineering approaches.