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A new flavonoid and sulphur-containing amides from Glycosmis chlorosperma

Rahmani M, Leng KW, Ismail HB, Hin TY, Sukari MA, Ali AM, et al.

Nat Prod Res, 2004 Feb;18(1):85-8.
PMID: 14974620

A new flavonoid, dihydroglychalcone-A, was isolated from the leaves extract of Glycosmis chlorosperma in addition to two known sulphur-containing amides, dambullin and gerambullin. The structure of the new compound was assigned as 2'-hydroxy-4,6'-dimethoxy-3',4'-(2",2"-dimethylpyrano)dihydrochalcone. The extract of the leaves was also found to exhibit antimicrobial and cytotoxic activities.

Matched MeSH terms: Rutaceae/chemistry*
Constituents of the Edible Leaves of Melicope pteleifolia with Potential Analgesic Activity

Lee BW, Park JG, Ha TKQ, Pham HTT, An JP, Noh JR, et al.

J Nat Prod, 2019 08 23;82(8):2201-2210.
PMID: 31393125 DOI: 10.1021/acs.jnatprod.9b00224

Melicope pteleifolia has long been consumed as a popular vegetable and tea in Southeast Asian countries, including Malaysia and southern mainland China, and is effective in the treatment of colds and inflammation. In the search for active metabolites that can explain its traditional use as an antipyretic, six new phloroacetophenone derivatives (3-8) along with seven known compounds (1, 2, and 9-13) were isolated from the leaves of M. pteleifolia. Their chemical structures were confirmed by extensive spectroscopic analysis including NMR, IR, ECD, and HRMS. All compounds isolated from the leaves of M. pteleifolia (1-13) have a phloroacetophenone skeleton. Notably, the new compound 8 contains an additional cyclobutane moiety in its structure. The bioactivities of the isolated compounds were evaluated, and compounds 1, 6, and 7 inhibited tumor necrosis factor-α-induced prostaglandin E2. Moreover, the major constituent, 3,5-di-C-β-d-glucopyranosyl phloroacetophenone (1), was found to be responsible for the antipyretic activity of M. pteleifolia based on in vivo experiments.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines

Kabir MF, Mohd Ali J, Abolmaesoomi M, Hashim OH

BMC Complement Altern Med, 2017 May 05;17(1):252.
PMID: 28476158 DOI: 10.1186/s12906-017-1761-9

BACKGROUND: Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts.
METHOD: Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition.
RESULT: Overall, MP-HX extract exhibited the highest antioxidant potential, with IC50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC50 = 57.81 ± 3.49 μg/mL) and HCT116 (IC50 = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC50 = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines.
CONCLUSIONS: MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy.

Matched MeSH terms: Rutaceae/chemistry*
Isolation of antioxidative compounds from Micromelum minutum guided by preparative thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl (PTLC-DPPH) bioautography method

Kassim NK, Lim PC, Ismail A, Awang K

Food Chem, 2019 Jan 30;272:185-191.
PMID: 30309531 DOI: 10.1016/j.foodchem.2018.08.045

The application of preparative thin layer chromatography-2,2-diphenyl-1-picrylhydrazyl (PTLC-DPPH) bioautography technique successfully isolated a lignan sesamin (1), two prenylated coumarins (2 and 3) and a marmesin glycosides (4) from Micromelum minutum methanol bark extract. Compounds 2 and 3 were identified as new compounds whereas 1 and 4 were first isolated from Micromelum genus. Structural identification of all compounds were done by detailed spectroscopic analyses and comparison with literature data. Antioxidant capacities of extract, active fraction and compounds were measured based on DPPH free radical savenging activity, oxygen radical absorbance capacity (ORAC) and β-carotene bleaching. The DPPH activity of methanol extract and its fraction present the IC50 values of 54.3 and 168.9 µg/mL meanwhile the β-carotene bleaching results were 55.19% and 5.75% respectively. The ORAC measurements of M. minutum extract, compounds 2 and 4 showed potent antioxidant activity with the values of 5123, 5539 and 4031 µmol TE/g respectively.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Phytochemical Constituents and Biological Activities of Melicope lunu-ankenda

Eliaser EM, Ho JH, Hashim NM, Rukayadi Y, Ee GCL, Razis AFA

Molecules, 2018 Oct 20;23(10).
PMID: 30347850 DOI: 10.3390/molecules23102708

Natural products, either pure compounds or standardized plant extracts, have provided opportunities for the discovery of new drugs. Nowadays, most of the world's population still relies on traditional medicines for healthcare purposes. Plants, in particular, are always used as traditional medicine, as they contain a diverse number of phytochemicals that can be used for the treatment of diseases. The multicomponent feature in the plants is considered a positive phytotherapeutic hallmark. Hence, ethnopharmacognosy has been the focus for finding alternative treatments for diseases. Melicopelunu-ankenda, also known as Euodialunu-ankenda, is widely distributed in tropical regions of Asia. Different parts of M.lunu-ankenda have been used for treatment of hypertension, menstrual disorder, diabetes, and fever, and as an emmenagogue and tonic. It has also been consumed as salad and as a condiment for food flavorings. The justification of use of M.lunu-ankenda in folk medicines is supported by its reported biological activities, including its cytotoxic, antibacterial, antioxidant, analgesic, antidiabetic, and anti-inflammatory activities. This review summarizes the phytochemical compounds isolated from various parts of M.lunu-ankenda, such as root and leaves, and also its biological activities, which could make the species a new therapeutic agent for some diseases, including diabetes, in the future.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Neuroprotective Potential of Secondary Metabolites from Melicope lunu-ankenda (Rutaceae)

Abdulwanis Mohamed Z, Mohamed Eliaser E, Mazzon E, Rollin P, Cheng Lian Ee G, Abdull Razis AF

Molecules, 2019 Aug 27;24(17).
PMID: 31461914 DOI: 10.3390/molecules24173109

Plant natural compounds have great potential as alternative medicines for preventing and treating diseases. Melicope lunu-ankenda is one Melicope species (family Rutaceae), which is widely used in traditional medicine, consumed as a salad and a food seasoning. Consumption of different parts of this plant has been reported to exert different biological activities such as antioxidant and anti-inflammatory qualities, resulting in a protective effect against several health disorders including neurodegenerative diseases. Various secondary metabolites such as phenolic acid derivatives, flavonoids, coumarins and alkaloids, isolated from the M. lunu-ankenda plant, were demonstrated to have neuroprotective activities and also exert many other beneficial biological effects. A number of studies have revealed different neuroprotective mechanisms for these secondary metabolites. This review summarizes the most significant and recent studies for neuroprotective activity of M. lunu-ankenda major secondary metabolites in neurodegenerative diseases.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Neuroprotective Effects of 7-Geranyloxycinnamic Acid from Melicope lunu ankenda Leaves

Abdulwanis Mohamed Z, Mohamed Eliaser E, Jaafaru MS, Nordin N, Ioannides C, Abdull Razis AF

Molecules, 2020 Aug 15;25(16).
PMID: 32824120 DOI: 10.3390/molecules25163724

Neurodegenerative diseases (NDDs) are chronic conditions that have drawn robust interest from the scientific community. Phytotherapeutic agents are becoming an important source of chemicals for the treatment and management of NDDs. Various secondary metabolites have been isolated from Melicope lunu-ankenda plant leaves, including phenolic acid derivatives. However, their neuroprotective activity remains unclear. Thus, the aim of this study is to elucidate the in vitro neuroprotective activity of 7-geranyloxycinnamic acid isolated from Melicope lunu-ankenda leaves. The neuroprotective activity was evaluated in differentiated human neuroblastoma (SH-SY5Y) cells by monitoring cell viability using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the potential to impair apoptosis in differentiated cells was investigated employing the Annexin V-FITC assay, acridine orange and propidium iodide (AO/PI) staining, and fluorescence microscopy. Morphological assessment and ultrastructural analysis were performed using scanning and transmission electron microscopy to evaluate the effect of 7-geranyloxycinnamic acid on surface morphology and internal features of the differentiated cells. Pre-treatment of neuronal cells with 7-geranyloxycinnamic acid significantly protected the differentiated SH-SY5Y cells against H2O2-induced apoptosis. Cytoskeleton and cytoplasmic inclusion were similarly protected by the 7-geranyloxycinnamic acid treatment. The present findings demonstrate the neuroprotective potential of 7-geranyloxycinnamic acid against H2O2-induced neurotoxicity in neuronal cells, which is an established hallmark of neuronal disorders.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Antiarthritic activity of a polyherbal formulation against Freund's complete adjuvant induced arthritis in Female Wistar rats

Petchi RR, Parasuraman S, Vijaya C, Gopala Krishna SV, Kumar MK

J Basic Clin Pharm, 2015 Jun;6(3):77-83.
PMID: 26229343 DOI: 10.4103/0976-0105.160738

OBJECTIVES:
To formulate a polyherbal formulation and evaluate its antiarthritic activity against Freund's complete adjuvant induced arthritis in Female Wistar rats.

MATERIALS AND METHODS:
Glycosmis pentaphylla, Tridax procumbens, and Mangifera indica are well-known plants available throughout India and they are commonly used for the treatment of various diseases including arthritis. The polyherbal formulation was formulated using the ethanol extracts of the stem bark of G. pentaphylla , whole plant of T. procumbens, and leaves of M. indica. The polyherbal formulation contains the ethanol extracts of G. pentaphylla, T. procumbens, and M. indica in the ratio of 2:2:1. The quality of the finished product was evaluated as per the World Health Organization's guidelines for the quality control of herbal materials. Arthritis was induced in female Wistar rats using Freund's complete adjuvant (FCA), and the antiarthritic effect of polyherbal formulation was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, blood samples were collected for biochemical and hematological analysis. The radiological examination was carried out before terminating the study.

RESULTS:
Polyherbal formulation showed significant antiarthritic activity at 250 and 500 mg/kg, respectively, and this effect was comparable with that of indomethacin. The antiarthritic activity of polyherbal formulation is supported by biochemical and hematological analysis.

CONCLUSION:
The polyherbal formulation showed signinicant antiarthritic activity against FCA-induced arthritis in female Wistar rats.

KEYWORDS:
Arthritis; Fingerprint analysis; Glycosmis pentaphylla; Mangifera indica; Tridax procumbens

Matched MeSH terms: Rutaceae
Cytotoxic constituent of Melicope latifolia (DC.) T. G. Hartley

Lim PC, Ali Z, Khan IA, Khan SI, Kassim NK, Awang K, et al.

Nat Prod Res, 2021 Feb 12.
PMID: 33576269 DOI: 10.1080/14786419.2021.1885031

An undescribed conjugated sesquiterpene, amelicarin (1), together with nine known compounds (2-10) were isolated for the first time from Melicope latifolia. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric methods. The conjugated sesquiterpene possesses a unique 6/6/9/4-ring fused tetracyclic skeleton. The proposed biosynthesis pathway of 1 consist of three reactions steps: (1) polyketide formation, (2) cyclisation and (3) addition to form the conjugated sesquiterpenoid as final metabolite. Out of the ten isolated metabolites, amelicarin (1) showed activity against 4 cancerous cell lines namely SK-MEL skin cancer, KB oral cancer, BT-549 breast cancer, and SK-OV-3 ovarian cancer with IC50 values between 15 and 25 µg/mL.

Matched MeSH terms: Rutaceae
Fulltext Phytochemical screening and larvicidal activity of murraya koenigii leaves ethanolic extract against aedes aegypti

Norazsida Binti Ramli, Nur Elia Amira Mohd Roslin, Deny Susanti

International Journal of Allied Health Sciences, 2018;2(1):129-139.
MyJurnal

World Health Organization (WHO) estimated over 100 million dengue infections to happen annually worldwide involving more than 2.5 billion people. Temephos or abate is a larvicide that has been used in vector control to eradicate mosquito larvae. Though practically low risk, there had been resistance problem reported with continuous use. This study seeks to find an effective and safer alternative to abate by assessing the use of ethanolic extract of Murraya koenigii leaves as larvicidal agent against Aedes aegypti. M.koenigii leaves were macerated for 3 days with absolute ethanol and evaporated using rotary vapor to produce the crude extract. The crude extract was subjected to phytochemical screening using standard qualitative method. For bioassay, the crude
extract underwent a serial dilution to produce 3 concentrations of 100 ppm (C1), 50 ppm (C2) and 10 ppm (C3) with abate and absolute ethanol as negative and positive control respectively. Bioassay for larvicidal effect was conducted in accordance to WHO standard method. Phytochemical screening of ethanolic extract of M. koenigii leaves revealed the presence of alkaloid, steroid and saponin. The bioassay shows that after 24 hours, the mortality rate of C1, C2 and C3 larvae were 100%, 38% and 0% and when further extended to 48 hours, the rate increased to 100% and 46% for C2 and C3 respectively. The LC50 and LC99 post 24 hours were 54.489 ppm and 93.961 ppm respectively whilst at post 48 hours, the LC50 and LC99 were 10.263 ppm and 16.176 ppm respectively. The results show that up to 48 hours duration of exposure, the mortality
rate increase whilst the lethal concentration (LC50 and LC99) decreases. Upon examination on larvae deformities at post 24 and 48 hours, all test concentrations and negative control exhibit normal morphology. Positive control, however, exhibit deformities characterized by twisted and fragmented insides. When statistically analyzed, C1 larvicidal activity was proven comparable with abate at 24 hours while C2 needed 48 hours exposure to be on par. Based on the results, it could be argued that the ethanolic extract of M.koenigii leaves does hold promising value to be further developed as larvicidal.

Matched MeSH terms: Rutaceae
A new cytotoxic carbazole alkaloid from Clausena excavata

Taufiq-Yap YH, Peh TH, Ee GC, Rahmani M, Sukari MA, Ali AM, et al.

Nat Prod Res, 2007 Jul 20;21(9):810-3.
PMID: 17654285

A new carbazole alkaloid, 3-carbomethoxy-2-hydroxy-7-methoxycarbazole, Clausine-TY (1), together with two known carbazole alkaloid, Clausine-H (2) and Clausine-B (3), were isolated from the ethyl acetate extract of the stem bark of the Malaysian Clausena excavata. The structures of these compounds were elucidated by spectroscopic analyses. The new carbazole alkaloid shows significant cytotoxicity against CEM-SS cell line.

Matched MeSH terms: Rutaceae/chemistry*
Meliternatin: a feeding deterrent and larvicidal polyoxygenated flavone from Melicope subunifoliolata

Hung Ho S, Wang J, Sim KY, Ee GC, Imiyabir Z, Yap KF, et al.

Phytochemistry, 2003 Apr;62(7):1121-4.
PMID: 12591266

We screened more than 60 Malaysian plants against two species of insects and found that Melicope subunifoliolata (Stapf) T.G. Hartley (Rutaceae) showed strong feeding deterrent activity against Sitophilus zeamais Motsch. (Curculionidae) and very good larvicidal activity against Aedes aegypti L. (Diptera). One anti-insect compound, meliternatin (3,5-dimethoxy-3',4',6,7-bismethylendioxyflavone) (6) and six other minor polyoxygenated flavones were isolated from M. subunifoliolata.

Matched MeSH terms: Rutaceae/chemistry*
LAT is essential for the mast cell stabilising effect of tHGA in IgE-mediated mast cell activation

Tan JW, Israf DA, Md Hashim NF, Cheah YK, Harith HH, Shaari K, et al.

Biochem Pharmacol, 2017 Nov 15;144:132-148.
PMID: 28813645 DOI: 10.1016/j.bcp.2017.08.010

Mast cells play a central role in the pathogenesis of allergic reaction. Activation of mast cells by antigens is strictly dependent on the influx of extracellular calcium that involves a complex interaction between signalling molecules located within the cells. We have previously reported that tHGA, an active compound originally isolated from a local shrub known as Melicope ptelefolia, prevented IgE-mediated mast cell activation and passive systemic anaphylaxis by suppressing the release of interleukin-4 (IL-4) and tumour necrosis factor (TNF)-α from activated rat basophilic leukaemia (RBL)-2H3 cells. However, the mechanism of action (MOA) as well as the molecular target underlying the mast cell stabilising effect of tHGA has not been previously investigated. In this study, DNP-IgE-sensitised RBL-2H3 cells were pre-treated with tHGA before challenged with DNP-BSA. To dissect the MOA of tHGA in IgE-mediated mast cell activation, the effect of tHGA on the transcription of IL-4 and TNF-α mRNA was determined using Real Time-Polymerase Chain Reaction (qPCR) followed by Calcium Influx Assay to confirm the involvement of calcium in the activation of mast cells. The protein lysates were analysed by using Western Blot to determine the effect of tHGA on various important signalling molecules in the LAT-PLCγ-MAPK and PI3K-NFκB pathways. In order to identify the molecular target of tHGA in IgE-mediated mast cell activation, the LAT and LAT2 genes in RBL-2H3 cells were knocked-down by using RNA interference to establish a LAT/LAT2 competition model. The results showed that tHGA inhibited the transcription of IL-4 and TNF-α as a result of the suppression of calcium influx in activated RBL-2H3 cells. The results from Western Blot revealed that tHGA primarily inhibited the LAT-PLCγ-MAPK pathway with partial inhibition on the PI3K-p65 pathway without affecting Syk. The results from RNAi further demonstrated that tHGA failed to inhibit the release of mediators associated with mast cell degranulation under the LAT/LAT2 competition model in the absence of LAT. Collectively, this study concluded that the molecular target of tHGA could be LAT and may provide a basis for the development of a mast cell stabiliser which targets LAT.

Matched MeSH terms: Rutaceae*
Fulltext Antinociceptive activity of Melicope ptelefolia ethanolic extract in experimental animals

Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, et al.

J Biomed Biotechnol, 2010;2010:937642.
PMID: 21274262 DOI: 10.1155/2010/937642

Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.

Matched MeSH terms: Rutaceae/chemistry*
Potent Antidiabetic Activity and Metabolite Profiling of Melicope Lunu-ankenda Leaves

Al-Zuaidy MH, Hamid AA, Ismail A, Mohamed S, Abdul Razis AF, Mumtaz MW, et al.

J Food Sci, 2016 May;81(5):C1080-90.
PMID: 27074520 DOI: 10.1111/1750-3841.13293

Diabetes mellitus is normally characterized by chronic hyperglycemia associated with disturbances in the fat, carbohydrate, and protein metabolism. There is an increasing trend of using natural products instead of synthetic agents as alternative therapy for disorders due to their fewer side effects. In this study, antidiabetic and antioxidant activities of different Melicope lunu-ankenda (ML) ethanolic extracts were evaluated using inhibition of α-glucosidase and 2,2-diphenyl-l-picrylhydrazyl (DPPH) radicals scavenging activity, respectively; whereas, proton nuclear magnetic resonance ((1) H NMR) and ultra-high performance liquid chromatography-tandem mass spectrometric (UHPLC-MS/MS) techniques were used for metabolite profiling of ML leaf extracts at different concentrations of ethanol and water. Sixty percent of ethanolic ML extract showed highest inhibitory effect against α-glucosidase enzyme (IC50 of 37 μg/mL) and DPPH scavenging activity (IC50 of 48 μg/mL). Antidiabetic effect of ML extracts was also evaluated in vivo and it was found that the high doses (400 mg/Kg BW) of ML extract exhibited high suppression in fasting blood glucose level by 62.75%. The metabolites responsible for variation among ML samples with variable ethanolic levels have been evaluated successfully using (1) H-NMR-based metabolomics. The principal component analysis (PCA) and partial least squares(PLS) analysis scores depicted clear and distinct separations into 4 clusters representing the 4 ethanolic concentrations by PC1 and PC2, with an eigenvalue of 69.9%. Various (1) H-NMR chemical shifts related to the metabolites responsible for sample difference were also ascribed. The main bioactive compounds identified attributing toward the separation included: isorhamnetin, skimmianine, scopoletin, and melicarpinone. Hence, ML may be used as promising medicinal plant for the development of new functional foods, new generation antidiabetic drugs, as a single entity phytomedicine or in combinational therapy.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches

Quek A, Kassim NK, Lim PC, Tan DC, Mohammad Latif MA, Ismail A, et al.

Pharm Biol, 2021 Dec;59(1):964-973.
PMID: 34347568 DOI: 10.1080/13880209.2021.1948065

CONTEXT: Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones.
OBJECTIVE: This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents.
MATERIALS AND METHODS: Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays.
RESULTS: Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC50: 1464.32 μg/mL; DPP-4 IC50: 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (α-amylase IC50: 397.68 μg/mL; DPP-4 IC50: 37.16 μg/mL) and resulted in β-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC50: 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 μM).
DISCUSSION AND CONCLUSIONS: The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

Matched MeSH terms: Rutaceae/chemistry*
Fulltext Effects of Melicope Ptelifolia aqueous extract on sperm parameters and testosterone level in Sprague-Dawley rats

Nazizarini Binti Mohd Najib, Perimal, Enoch Kumar, Mohd. Roslan Bin Sulaiman, Ahmad Akira Omar Farouk, Tengku Azam Shah Bin Tengku Mohamad

Life Sciences, Medicine and Biomedicine, 2018;2(4):1-6.
MyJurnal

The increasing number of prevalence infertility cases is becoming a major public health problem in developing countries due to changes in diet and lifestyle. Melicope ptelefolia (M.ptelifolia) is known for its health benefit as a sex enhancing effect among the Malays folk however there is no clinical data to prove it until these days. The main aim of the present study is to identify the effects of Melicope ptelifolia Aqueous extract (MPAE) on Sperm Parameters and Testosterone Level . A total of 30 male Sprague Dawley rats were divided equally into five different groups. MPAE was given by orally gavage for 28 days at a dose of 100mg/kg, 200 mg/kg and 500 mg/kg body weight to the animals of group II (n=6), III (n=6) and IV (n=6), respectively. The animals of group I (control, n=6) had distilled water and group V had sildenafil citrate. Sperm Parameters were carried include sperm count, motility, mobility and morphology together with serum testosterone level for Testosterone level result. Results were analyzed using one way ANOVA test followed by Tukey test and the data were considered significant at p

Matched MeSH terms: Rutaceae
Fulltext Phenolics, flavonoids content and antioxidant activities of 4 Malaysian herbal plants

Azizah Othman, Nor Juwariah Mukhtar, Nurul Syakirin Ismail, Sui Kiat Chang

International Food Research Journal, 2014;21(2):759-766.
MyJurnal

Water and ethanolic extracts of four Malaysian local herbs, Tenggek burung (Melicope Iunu-ankenda), Kesum (Polygonum minus), Curry leave (Murraya Koenigii) and Salam (Eugenia polyantha) were investigated for their total phenolic content (TPC), total flavonoids content (TFC) and antioxidant activities (AA). Total phenolic content (TPC) of the herbs was determined using Folin-Ciocalteu reagent assay while the total flavonoid content (TFC) was determined based on aluminium chloride-flavonoid assay. The determination of AA was done using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activitiy and β-carotene bleaching assays (BCB). Different extraction solvents significantly affected the TPC, TFC and AA of all herbs studied (p < 0.05). Both Tenggek burung and Kesum showed highest TPC, TFC and AA regardless of extraction solvents compared to Curry leave and Salam. All herbs showed strong positive correlation between TPC and DPPH assay. However, negative and low correlation between TFC and AA were obtained for all herbs studied. This showed that phenolic compounds of certain structures were responsible for the AA of all the herbs in this study. In conclusion, all herbs in this study except curry leave could be inexpensive sources of good natural antioxidants with nutraceutical potential in food industry.

Matched MeSH terms: Rutaceae
Fulltext Microarray gene expression profiling in colorectal (HCT116) and hepatocellular (HepG2) carcinoma cell lines treated with Melicope ptelefolia leaf extract reveals transcriptome profiles exhibiting anticancer activity

Kabir MF, Mohd Ali J, Haji Hashim O

PeerJ, 2018;6:e5203.
PMID: 30042885 DOI: 10.7717/peerj.5203

Background: We have previously reported anticancer activities of Melicope ptelefolia (MP) leaf extracts on four different cancer cell lines. However, the underlying mechanisms of actions have yet to be deciphered. In the present study, the anticancer activity of MP hexane extract (MP-HX) on colorectal (HCT116) and hepatocellular carcinoma (HepG2) cell lines was characterized through microarray gene expression profiling.
Methods: HCT116 and HepG2 cells were treated with MP-HX for 24 hr. Total RNA was extracted from the cells and used for transcriptome profiling using Applied Biosystem GeneChip™ Human Gene 2.0 ST Array. Gene expression data was analysed using an Applied Biosystems Expression Console and Transcriptome Analysis Console software. Pathway enrichment analyses was performed using Ingenuity Pathway Analysis (IPA) software. The microarray data was validated by profiling the expression of 17 genes through quantitative reverse transcription PCR (RT-qPCR).
Results: MP-HX induced differential expression of 1,290 and 1,325 genes in HCT116 and HepG2 cells, respectively (microarray data fold change, MA_FC ≥ ±2.0). The direction of gene expression change for the 17 genes assayed through RT-qPCR agree with the microarray data. In both cell lines, MP-HX modulated the expression of many genes in directions that support antiproliferative activity. IPA software analyses revealed MP-HX modulated canonical pathways, networks and biological processes that are associated with cell cycle, DNA replication, cellular growth and cell proliferation. In both cell lines, upregulation of genes which promote apoptosis, cell cycle arrest and growth inhibition were observed, while genes that are typically overexpressed in diverse human cancers or those that promoted cell cycle progression, DNA replication and cellular proliferation were downregulated. Some of the genes upregulated by MP-HX include pro-apoptotic genes (DDIT3, BBC3, JUN), cell cycle arresting (CDKN1A, CDKN2B), growth arrest/repair (TP53, GADD45A) and metastasis suppression (NDRG1). MP-HX downregulated the expression of genes that could promote anti-apoptotic effect, cell cycle progression, tumor development and progression, which include BIRC5, CCNA2, CCNB1, CCNB2, CCNE2, CDK1/2/6, GINS2, HELLS, MCM2/10 PLK1, RRM2 and SKP2. It is interesting to note that all six top-ranked genes proposed to be cancer-associated (PLK1, MCM2, MCM3, MCM7, MCM10 and SKP2) were downregulated by MP-HX in both cell lines.
Discussion: The present study showed that the anticancer activities of MP-HX are exerted through its actions on genes regulating apoptosis, cell proliferation, DNA replication and cell cycle progression. These findings further project the potential use of MP as a nutraceutical agent for cancer therapeutics.

Matched MeSH terms: Rutaceae
Fulltext Satkara (Citrus macroptera) Fruit Protects against Acetaminophen-Induced Hepatorenal Toxicity in Rats

Paul S, Islam MA, Tanvir EM, Ahmed R, Das S, Rumpa NE, et al.

Evid Based Complement Alternat Med, 2016;2016:9470954.
PMID: 27034701 DOI: 10.1155/2016/9470954

Although Citrus macroptera (Rutaceae), an indigenous fruit in Bangladesh, has long been used in folk medicine, however, there is a lack of information concerning its protective effects against oxidative damage. The protective effects of an ethanol extract of Citrus macroptera (EECM) against acetaminophen-induced hepatotoxicity and nephrotoxicity were investigated in rats. Rats (treatment groups) were pretreated with EECM at doses of 250, 500, and 1000 mg/kg, respectively, orally for 30 days followed by acetaminophen administration. Silymarin (100 mg/kg) was administered as a standard drug over a similar treatment period. Our findings indicated that oral administration of acetaminophen induced severe hepatic and renal injuries associated with oxidative stress, as observed by 2-fold higher lipid peroxidation (TBARS) compared to control. Pretreatment with EECM prior to acetaminophen administration significantly improved all investigated biochemical parameters, that is, transaminase activities, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase activities and total bilirubin, total cholesterol, triglyceride and creatinine, urea, uric acid, sodium, potassium and chloride ions, and TBARS levels. These findings were confirmed by histopathological examinations. The improvement was prominent in the group that received 1000 mg/kg EECM. These findings suggested that C. macroptera fruit could protect against acetaminophen-induced hepatonephrotoxicity, which might be via the inhibition of lipid peroxidation.

Matched MeSH terms: Rutaceae

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