Probiotic evaluation, adherence capability and safety assessment of Lactococcus lactis strain isolated from an important herb "Murraya koenigii".

Lactic acid bacteria (LAB) isolated from medicinal herb Murraya koenigii, commonly known as curry leaf, which promotes the growth and maintenance of gut microbiota, were studied for their probiotic potential. The key objective of this research was to isolate and evaluate probiotic characteristics, test adherence capabilities, and confirm their safety. Lactococcus lactis (MKL8), isolated from Murraya koenigii, was subjected to in vitro analysis to assess its resistance to the gastric environment, ability to adhere Caco-2 cells, anti-microbial activity, hydrophobicity, auto-aggregation, and safety profiling through MTT assay and hemolytic. MKL8 exhibited growth at 0.5% phenol concentrations (> 80%) and was able to survive in conditions with high bile concentrations (> 79%) and a relatively low pH (72%-91%). It shows high tolerance to high osmotic conditions (> 73%) and simulated gastric juice (> 72%). Additionally, MKL8 demonstrated strong hydrophobicity (85%), auto-aggregation (87.3%-91.7%), and adherence to Caco-2 cells. Moreover, it had an inhibitory effect against pathogens too. By performing the hemolytic and MTT assays, the non-toxicity of MKL8 isolate was examined, and it exhibited no harmful characteristics. Considering MKL8's resistance to gastrointestinal tract conditions, high surface hydrophobicity, non-toxicity, and ability to inhibit the tested pathogens, it can be concluded that MKL8 demonstrated promising probiotic properties and has potential for use in the food industry.

Green Synthesis of Silver Nanoparticles using Coriandrum sativum and Murraya koenigii Leaf Extract and its Thrombolytic Activity.

BACKGROUND: Plants have been used for ages in traditional medicine, and it is exciting to perceive how recent research has recognized the bioactive compounds liable for their beneficial effects. Green synthesis of metal nanoparticles is a hastily emergent research area in nanotechnology. This study describes the synthesis of silver nanoparticles (AgNPs) using Coriandrum sativum and Murraya koenigii leaf extract and its thrombolytic activity. OBJECTIVE: The aim of the study was to determine the clot lysis activity of Coriandrum sativum and Murraya koenigii synthesized silver nanoparticles. METHODS: Leaves of Coriandrum sativum and Murraya koenigii were collected. Methanolic extraction of the plant sample was done through a Soxhlet extractor. The methanolic extract obtained from both the leaves was subjected to GC-MS analysis. The synthesized NPs from leaf extracts were monitored for analysis, where the typical X-ray diffraction pattern and its diffraction peaks were identified. 3D image of the NPs was analysed by Atomic Force Microscopy. The surface charge of nanoparticles was identified by Zeta potential. The Clot lysis activity of Coriandrum sativum and Murraya koenigii synthesized silver nanoparticles were analysed by the modified Holmstorm method. RESULTS: The thrombolytic property of the methanolic extract of plants Coriandrum sativum showed clot lysis activity at 2.5 mg/mL with 45.99% activity, and Murraya koenigii extract with 66.56% activity. The nanoparticles (Nps) from Coriandrum sativum showed clot lysis activity at 2.5 mg/mL with 58.29% activity, and NPs from Murraya koenigii with 54.04% activity. Coriandrum sativum in GC-MS exhibited 3 peaks, whereas Murraya koenigii extract showed five peaks with notable bioactive compounds. CONCLUSION: These NPs were further used for biomedical applications after being fixed by an organic encapsulation agent. The present research reveals the usefulness of Coriandrum sativum and Murraya koenigii for the environmentally friendly manufacture of silver nanoparticles.

An alkaloid enriched fraction from Murraya koenigii (L.) Spreng. Leaves ameliorate HFD-induced obesity and metabolic complexities in C57BL/6J mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Murraya koenigii commonly known as curry leaf, is traditionally used in India to manage various ailments including diabetes mellitus. Curry leaves are well documented in Indian Ayurvedic system of medicine for beneficial effects in skin eruptions, dysentery, emesis, poisonous bites and bruises. The anti-hyperglycemic and anti-hyperlipidemic effects of curry leaf extracts have been demonstrated through several in vitro and in vivo experiments previously. AIM OF THE STUDY: To prepare an alkaloid enriched fraction (AEF) from M. koenigii and its evaluation on i) in vitro adipogenesis process and ii) in vivo high fat diet-induced obesity in C57BL/6J mice. MATERIALS AND METHODS: MKME and AEF were prepared from M. koenigii leaves. The four carbazole alkaloids (bioactive markers) isolated from AEF were quantitatively determined in the leaves by RP-HPLC method. MKME and AEF were studied for anti-obesogenic activity in adipocytes in vitro and in HFD-induced C57BL/6J obese mice in vivo. At the termination of the in vivo study, lipid profile, hepatic and renal injury and glucose levels were analyzed in the blood samples. Animal tissues were examined histopathologically to determine any signs of damage. Repeated dose oral toxicity study for 28 days on Sprague-Dawley rats was also performed to determine the safety profile of AEF. RESULTS: Both MKME and AEF displayed anti-obesogenic activity at 25 µg/ml concentration in vitro and showed 54.06 ± 3.86% and 37.46 ± 3.17% lipid accumulation, respectively compared to control. Further, supplementation of AEF and MKME in HFD-fed C57BL/6J mice helped in controlling weight gain, improved dyslipidemia and glucose intolerance significantly. AEF showed better anti-obesity activity than MKME both in vitro and in vivo study. Repeated administration of AEF up to 1 g/kg dose for 28 days showed no pathological tissue damage. Both MKME and AEF were standardized using a simple and validated RP-HPLC method. CONCLUSION: Present study was aimed at preparation of a novel alkaloid-enriched fraction from methanolic extract of M. koenigii leaf and its evaluation for anti-diabesity effect. Our results demonstrated AEF to be a promising plant-based therapy for ameliorating obesity and related metabolic complications in HFD-fed C57BL/6J mice.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Cytotoxicity of Mahanimbine from Curry Leaves in Human Breast Cancer Cells (MCF-7) via Mitochondrial Apoptosis and Anti-Angiogenesis.

Mahanimbine (MN) is a carbazole alkaloid present in the leaves of Murraya koenigii, which is an integral part of medicinal and culinary practices in Asia. In the present study, the anticancer, apoptotic and anti-invasive potential of MN has been delineated in vitro. Apoptosis cells determination was carried out utilizing the acridine orange/propidium iodide double fluorescence test. During treatment, caspase-3/7,-8, and-9 enzymes and mitochondrial membrane potentials (Δψm) were evaluated. Anti-invasive properties were tested utilizing a wound-healing scratch test. Protein and gene expression studies were used to measure Bax, Bcl2, MMP-2, and -9 levels. The results show that MN could induce apoptosis in MCF-7 cells at 14 µM concentration IC50. MN-induced mitochondria-mediated apoptosis, with loss in Δψm, regulation of Bcl2/Bax, and accumulation of ROS (p ≤ 0.05). Caspase-3/7 and -9 enzyme activity were detected in MCF-7 cells after 24 and 48 h of treatment with MN. The anti-invasive property of MN was shown by inhibition of wound healing at the dose-dependent level and significantly suppressed mRNA and protein expression on MMP-2 and -9 in MCF-7 cells treated with a sub-cytotoxic dose of MN. The overall results indicate MN is a potential therapeutic compound against breast cancer as an apoptosis inducer and anti-invasive agent.

Antihyperlipidemic property of Murraya koenigii ethanolic leaf extract on lipid profile of rats fed with cholesterol-enriched diets.

This study was designed to investigate the effect of orally administered ethanolic leaf extract of Murraya koenigii on lipid profile of rats fed with cholesterol-enriched diets for 14 days. The study was carried out on 20 male wistar rats divided into 4 groups (n=5). All animals were given ad libitum access to drinking water. Group A was the control group and received normal rat chow, group B received cholesterol-enriched diet (CED); while group C and D received cholesterol-enriched diet and were treated with 200mg and 400mg/kg body weight of ethanolic extract of Murraya koenigii leaf respectively. Blood samples were collected by cardiac puncture on the last day of the experiment for biochemical analysis. Lipid profile was determined by Colorimetric method. Data were expressed as mean ± SEM. Differences in means were compared using ANOVA and Students T-test, P-values ≤ 0.05 were taken as statistically significant. Results showed a significant increase (p ≤ 0.05) in Total cholesterol (TC) level (117.4 ± 4.6) and low density lipoprotein cholesterol (LDL-c) level (50.1 ± 4.7) of group B rats when compared to other groups. The MK (400 mg/kg) treated rats, showed a significant reduction in TC and LDL-c levels, and a significant increase in HDL-c level when compared to CED group. However, there were no significant changes in all the lipid parameters of the treated groups when compared to the control. This study shows that cholesterol-enriched diet causes dyslipidemia and Murraya koenigii exhibited significant hypolipidemic effect on serum TC and LDL-c and increases HDL-c. Hence, Murraya koenigii exhibit antihyperlipidemic properties. Keywords: Murraya Koenigii, hyperlipidemia, Lipid profile, Cholesterol-enriched diet.

Quantitative Analysis of Bioactive Carbazole Alkaloids in Murraya koenigii (L.) from Six Different Climatic Zones of India Using UPLC/MS/MS and Their Principal Component Analysis.

Murraya koenigii (L.) Spreng (Curry leaf) is a commercially important medicinal plant in South Asia, containing therapeutically valuable carbazole alkaloids (CAs). Thus, the quantitative evaluation of these compounds from different climatic zones of India are an important aspect for quality assessment and economic isolation of targeted compounds from the plant. In this study, quantitative estimation of CAs among 34 Indian natural populations of M. koenigii was assessed using UPLC/MS/MS. The collected populations represent the humid subtropical, tropical wet & dry, tropical wet, semi-arid, arid, and montane climatic zones of India. A total of 11 CAs viz. koenine-I, murrayamine A, koenigine, koenimbidine, koenimbine, O-methylmurrayamine A, girinimbine, mahanine, 8,8''-biskoenigine, isomahanimbine, and mahanimbine were quantified using multiple reaction monitoring (MRM) experiments within 5.0 min. The respective range for natural abundance of CAs were observed as 0.097-1.222, 0.092-5.014, 0.034-0.661, 0.010-1.673, 0.013-7.336, 0.010-0.310, 0.010-0.114, 0.049-5.288, 0.031-1.731, 0.491-3.791, and 0.492-5.399 mg/g in leaves of M. koenigii. The developed method shown linearity regression coefficient (r2 >0.9995), LOD (0.003-0.248 ng/mL), LOQ (0.009-0.754 ng/mL), and the recovery was between 88.803-103.729 %. The bulk of these CAs were recorded in their highest concentrations in the humid subtropical zone, followed by the tropical wet & dry zones of India. Further, principal component analysis (PCA) was performed which differentiated the climatic zones according to the dominant and significant CAs contents within the populations. The study concludes that the method established is simple, rapid, with high sample throughput, and can be used as a tool for commercial purposes and quality control of M. koenigii.

Trimeric and Dimeric Carbazole Alkaloids from Murraya microphylla.

Seventeen new carbazole alkaloid derivatives, including a trimeric carbazole racemate, (±)-microphyltrine A (1), 15 dimeric carbazole racemates, (±)-microphyldines A-O (2-16), and a C-6-C-3″-methyl-linked dimeric carbazole, microphyldine P (17), were isolated from the leaves and stems of Murraya microphylla (Merr. et Chun) Swingle. The structures of the new compounds were elucidated on the basis of HRESIMS and NMR data analysis. The optically pure isomers of these isolated carbazole alkaloids were obtained by chiral HPLC separation and their absolute configurations were determined by electronic circular dichroism (ECD) data analysis.

Comparison of the preventive effects of Murraya exotica and Murraya paniculata on alcohol-induced gastric lesions by pharmacodynamics and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Multi-source phenomenon is very common for traditional Chinese medicine (TCM). Both Murraya exotica L. (ME) and Murraya paniculata (L.) Jack (MP) are used as the source plants of Murrayae Folium et Cacumen (MFC), a traditional Chinese medicine recorded in Chinese Pharmacopoeia for promoting qi and relieving pain, mainly for the treatment of stomach pain, rheumatism and arthralgia. However, up to now, there has been no comparative study of these two plants on their efficacies and mechanisms, thus, further research is needed to evaluate their similarity and difference in order to judge the reasonability for their common usage. AIM OF THE STUDY: This study aims to compare the effects and potential mechanisms of ME and MP, the two source plants of MFC on gastric lesions in rats by pharmacodynamics and metabolomics. MATERIALS AND METHODS: A rat model of gastric lesions induced by 70% aqueous ethanol and 150 mmol/L HCl was established and adopted to evaluate the gastric protective effects of ME and MP by analysis of the lesion index, histopathological changes (observed by H&E staining and TUNEL staining) and cytokine levels (IL-1ß, IL-6, TNF-α, MTL, and GAS). The potential mechanisms were investigated by LC-MS metabolomic analysis of the rat plasma. RESULTS: ME and MP showed the similar effects on improving the lesions of rat stomachs and reducing the cytokine levels related to inflammation and digestion of rats. The metabolomics results showed that the metabolism of rats with gastric lesions was abnormal mainly in lipid metabolism, energy metabolism, and amino acid metabolism. ME and MP demonstrated a similar metabolic modulation for gastric lesions by acting on the similar pathways and metabolites. Also, PLA2 pathway was proved as an important pathway for ME and MP modulation of glycerophospholipid metabolism in gastric lesions. CONCLUSIONS: Our results proved that it is feasible and reasonable to use both of ME and MP as the source plants of MFC, at least for the treatment of gastric lesions, due to their similar pharmacodynamics and metabolic modulation ability. Moreover, the combination of pharmacodynamics and metabolomics is an efficient means for multi-source TCM study.