Repellent and larvicidal properties of selected indigenous plants in the control of Anopheles mosquitoes.

BACKGROUND OBJECTIVES: Widespread pyrethroid resistance and plastic-feeding behaviour of most malaria vectors across Africa threaten the efficacy of current insecticide-based vector control interventions like Insecticide-Treated Nets (ITNs) and Indoor Residual Spraying (IRS). This study examined the larvicidal activity ofMorinda citrifolia against Anopheles gambiae larvae and the repellent properties of Morinda citrifolia (Noni), Moringa oleifera (Moringa), and Ocimum basilicum (Basil) as complementary vector control tools against Anopheles gambiae sensu lato (s.l.). METHODS: Noni, Basil, and Moringa oil extracts were obtained with the extraction techniques; Soxhlet, steam distillation and maceration respectively, using hexane and ethanol. The effectiveness of the extracts was assessed using the WHO standard larval susceptibility bioassay and guidelines for repellent efficacy. Following bioassays, effective doses (ED) and lethal concentrations (LC) were determined. Gas Chromatography-Mass Spectroscopy analysis was performed to identify the bioactive chemical components of the extracts of Moringa oleifera and Ocimum basilicum. RESULTS: Emulsified Morinda citrifolia seed oil had LC50=68.3, LC90=130.9 and LC99.9=222.5, and ED99. 9=308.3%v/v, the ethanolic extract of Moringa oleifera leaves had ED99.9= 1.25g/ml, and essential oil of Ocimum basilicum leaves had ED99.9=0.28g/ml against Anopheles gambiae. INTERPRETATION CONCLUSION: The results obtained indicated that seed oil of Morinda citrifolia, essential oil of Ocimum basilicum, and crude extract of Moringa oleifera have repellent activity against An. gambiae s.l. The complete protection time (CPT) of Morinda citrifolia, Moringa oleifera, and Ocimum basilicum was 120 min, 72 min and 84 min at ED99.9 respectively. Morinda citrifolia oil exhibited larvicidal effects against the larvae of An. gambiae s.l. The results provide valuable information for the use of the plants as biocides.

Noni enhances the anticancer activity of cyclophosphamide and suppresses myelotoxicity and hepatotoxicity in tumor-bearing mice.

BACKGROUND AND AIM: Morinda citrifolia fruit juice (noni) is an herbal remedy documented to have antioxidant properties. It has been suggested that prevention of carcinogen-DNA adduct formation and the antioxidant activity of NJ may contribute to the cancer preventive effect. In the present study, the antitumor activity of noni was investigated in the presence of cyclophosphamide (CYL) in vitro and in vivo. METHODS: In vitro breast cancer cells (MDA-MB-468) were used to measure the percentage of inhibition and the IC50. The in vivo antitumor activity of noni was studied by monitoring the mean survival time (MST), percentage increase in life span (%ILS), viable and non-viable cell count, tumor volume, body weight, and hematological and serum biochemical parameters in mice. Treatment with noni and CYL exhibited dose- and time-dependent cytotoxicity toward breast cancer cells. RESULTS: Individual treatment of noni and CYL exhibited dose- and time-dependent cytotoxicity on breast cancer cell lines, while in combination therapy of noni and CYL, noni enhances cytotoxic effect of CYL at 48 h than that at 24 h. Similar result was found in in vivo studies, the results of which revealed that alone treatment of CYL and noni suppressed tumor growth. However, combination treatment with CYL and noni presented better tumor inhibition than that of alone treatment of CYL and noni. On the contrary, CYL alone drastically attenuated hematological parameters, i.e., RBC, WBC, and Hb compared to normal and control groups, and this change was reversed and normalized by noni when given as combination therapy with CYL. Moreover, the levels of serum biochemical markers, i.e., AST, ALP, and ALT, were significantly increased in the control and CYL-treated groups than those in the normal group. In the combination treatment of noni and CYL, the above biochemical marker levels significantly decreased compared to CYL alone-treated group. CONCLUSIONS: The present study suggested that CYL treatment can cause serious myelotoxicity and hepatic injury in cancer patients. In conclusion, the combined use of noni with CYL potentially enhances the antitumor activity of CYL and suppresses myelotoxicity and hepatotoxicity induced by CYL in tumor-bearing mice.

In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

A systematic review on polysaccharides from Morinda officinalis How: Advances in the preparation, structural characterization and pharmacological activities.

ETHNOPHARMACOLOGICAL RELEVANCE: Morinda officinalis How is called "Ba-Ji-Tian" in Traditional Chinese Medicine (TCM), which belongs to the genus Rubiaceae and is widely used for medicinal purposes in China and other eastern Asian countries. Morinda officinalis How polysaccharides (MOPs) are one of the key bioactive components, and have a variety of biological activities, such as antioxidation, antifatigue, enhanced immunity, antiosteoporosis, ect. AIM OF THE REVIEW: This review is aimed at providing comprehensive information of the latest preparation technologies, structural characterization, and pharmacological effects of MOPs. A more in-depth research on the structure and clinical pharmacology of the MOPs was explored. It could lay a foundation for further investigate the pharmacological activities and guide the safe clinical practice of MOPs. MATERIALS AND METHODS: The Web of Science, PubMed, Scifinder, Google Scholar, CNKI, Wanfang database, and other online database are used to search and collect the literature on extraction and separation methods, structural characterization, and pharmacological activities of MOPs publisher from 2004 to 2023. The key words are "Morinda officinalis polysaccharides", "extraction", "isolation", "purification" and "pharmacological effects". RESULTS: Morinda officinalis has been widely used in tonifying the kidney yang since ancient times, and is famous for one of the "Four Southern Medicines" in China for the treatment of depression, osteoporosis, rheumatoid arthritis, infertility, fatigue and Alzheimer's disease. The active ingredients of Morinda officinalis that have been researched on the treatment of depression and osteoporosis are mostly polysaccharides and oligosaccharides. The content of polysaccharides varies with different methods of extraction, separation and purification. MOPs have a wide range of pharmacological effects, including antioxidant, antifatigue, immunomodulatory, antiosteoporosis, and regulation of spermatogenesis activities. These pharmacological properties lay a foundation for the treatment of oxidative stress, osteoporosis, spermatogenic dysfunction, immunodeficiency, inflammation and other diseases with MOPs. CONCLUSIONS: At present, MOPs have been applied in the treatment of skeletal muscle atrophy, varicocele, osteoporosis, because of its effects of enhancing immunity, improving reproduction and antioxidant. However, the structure-activity relationship of these effects are still not clear. The more deeply study could be conducted on the MOPs in the future. The toxicology and clinical pharmacology, as well as mechanism of action of MOPs were also needed to deeply studied and clarified. This paper could lay the foundation for the application and safety of MOPs in multifunctional foods and drugs.

Ameliorative Effect of Morinda Officinalis Oligosaccharides on LPS-Induced Acute Lung Injury.

Acute lung injury (ALI) is a disease characterized by extensive lung damage and rampant inflammation, with a high mortality rate and no effective treatments available. Morinda officinalis oligosaccharides (MOOs), derived from the root of the traditional Chinese medicinal herb Morinda officinalis, known for its immune-boosting properties, presents a novel therapeutic possibility. To date, the impact of MOOs on ALI has not been explored. Our study aimed to investigate the potential protective effects of MOOs against ALI and to uncover the underlying mechanisms through an integrated approach of network pharmacology, molecular docking, and experimental validation. We discovered that MOOs significantly mitigated the pathological damage and decreased the expression of pro-inflammatory cytokines in LPS-induced ALI in mice. Complementary in vitro studies further demonstrated that MOOs effectively attenuated the M1 polarization induced by LPS. Network pharmacology analysis identified HSP90AA1, HSP90AB1, and NF-κB as key overlapping targets within a protein-protein interaction (PPI) network. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated the biological processes and signaling pathways implicated in MOOs' therapeutic action on ALI. Subsequently, molecular docking affirmed the binding of MOOs to the active sites of these identified targets. Corroborating these findings, our in vivo and in vitro experiments consistently demonstrated that MOOs significantly inhibited the LPS-induced upregulation of HSP90 and NF-κB. Collectively, these findings suggest that MOOs confer protection against ALI through a multi-target, multi-pathway mechanism, offering a promising new therapeutic strategy to mitigate this severe pulmonary condition.

[UPLC-Q-TOF-MS-based metabolomics reveals mechanism of Morinda officinalis iridoid glycosides in treating rheumatoid arthritis and bone loss].

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.

Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3.

Morinda officinalis polysaccharide (MOP) is the bioactive ingredient extracted from the root of Morinda officinalis, and Morinda officinalis is applied to treat osteoporosis (OP). The purpose of this study was to determine the role of MOP on human bone marrow mesenchymal stem cells (hBMSCs) and the underlying mechanism. HBMSCs were isolated from bone marrow samples of patients with OP and treated with MOP. Quantitative real-time polymerase chain reaction was adopted to quantify the expression of microRNA-210-3p (miR-210-3p) and scavenger receptor class A member 3 (SCARA3) mRNA. Cell Counting Kit-8 assay was employed to detect cell viability; Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling assay and flow cytometry were adopted to detect apoptosis; Alkaline Phosphatase (ALP) activity assay kit was applied to detect ALP activity; Western blot was executed to quantify the expression levels of SCARA3, osteogenic and adipogenic differentiation markers. Ovariectomized rats were treated with MOP. Bone mineral density (BMD), serum tartrate-resistant acid phosphatase 5b (TRACP 5b), and N-telopeptide of type I collagen (NTx) levels were assessed by BMD detector and Enzyme-linked immunosorbent assay kits. It was revealed that MOP could promote hBMSCs' viability and osteogenic differentiation and inhibit apoptosis and adipogenic differentiation. MOP could also upregulate SCARA3 expression through repressing miR-210-3p expression. Treatment with MOP increased the BMD and decreased the TRACP 5b and NTx levels in ovariectomized rats. MOP may boost the osteogenic differentiation and inhibit adipogenic differentiation of hBMSCs by miR-210-3p/SCARA3 axis.

Anthraquinones from the roots of Morinda scabrida Craib exhibit antiproliferative activity against A549 lung cancer cells and antitubulin polymerization.

Six anthraquinones were isolated from Morinda scabrida Craib, an unexplored species of Morinda found in the tropical forest of Thailand. All six anthraquinones showed cytotoxicity against A549 lung cancer cells, with the most active compound, nordamnacanthal (MS01), exhibiting the IC50 value of 16.3 ± 2.5 µM. The cytotoxic effect was dose-dependent and led to cell morphological changes characteristic of apoptosis. In addition, flow cytometric analysis showed dose-dependent apoptosis induction and the G2/M phase cell cycle arrest, which was in agreement with the tubulin polymerization inhibitory activity of MS01. Molecular docking analysis illustrated the binding between MS01 and the α/ß-tubulin heterodimer at the colchicine binding site, and UV-visible absorption spectroscopy revealed the DNA binding capacity of MS01.

Green synthesis, characterization, antibacterial, and antifungal activity of copper oxide nanoparticles derived from Morinda citrifolia leaf extract.

The green methodologies of nanoparticles with plant extracts have received an increase of interest. Copper oxide nanoparticles (CuO NPs) have been utilized in a many of applications in the last few decades. The current study presents the synthesis of CuO NPs with aqueous extract of Morinda citrifolia as a stabilizing agent. The leaf extract of Morinda citrifolia was mixed with a solution of copper sulphate (CuSO4·5H2O) and sodium hydroxide as a catalyst. UV-visible spectroscopy, FTIR, XRD, SEM, TEM, and EDAX analysis were performed to study the synthesized CuO NPs. Particle size distribution of the synthesized CuO NPs have been measured with dynamic light scattering. The CuO NPs synthesized were highly stable, sphere-like, and have size of particles from 20 to 50 nm. Furthermore, as-formed CuO NPs shown strong antibacterial activity against the Gram-positive bacteria (Bacillus subtilis, and Staphylococcus aureus), and Gram-negative bacteria (Escherichia coli). CuO NPs revealed a similar trend was analysed for antifungal activity. The zone of inhibition for the fungi evaluated for Aspergillus flavus (13.0 ± 1.1), Aspergillus niger (14.3 ± 0.7), and Penicillium frequentans (16.8 ± 1.4). According to the results of this investigation, green synthesized CuO NPs with Morinda citrifolia leaf extract may be used in biomedicine as a replacement agent for biological applications.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.

Phukettosides A-E, mono- and bis-iridoid glycosides, from the leaves of Morinda umbellata L.

Four undescribed bis-iridoid glycosides, named phukettosides A-D, and one iridoid glycoside, referred to as phukettoside E, were isolated and fully characterized from the leaves of Morinda umbellata L. Phytochemical analysis also revealed the presence of eight known compounds. The structures were determined through extensive analysis of 1D and 2D-NMR spectroscopic and HRMS spectral data, and the absolute configurations of the isolates were deduced through ECD calculations. Biogenetic pathways for the bis-iridoid glycosides, phukettosides A-C, through intermolecular Diels-Alder type reactions, were proposed. The isolated compounds, with the exception of phukettosides B and D, were evaluated against a panel of cancer cell lines (MOLT-3, HuCCA-1, A549, HeLa, HepG2, and MDA-MB-231) and a non-cancerous cell line (MRC-5) for their cytotoxicity. None of the isolates had significant cytotoxic effects on the tested cell lines.

A new iridoid glucoside from the roots of Morinda officinalis.

A new iridoid glucoside, moridoside (1), and nine known compounds, asperulosidic acid (2), 6-O-epi-acetylscandoside (3), geniposidic acid (4), 2-hydroxymethylanthraquinone (5), 2-hydroxymethyl-3-hydroxyanthraquinone (6), damnacanthol (7), lucidine-ω-methyl ether (8), 2-hydroxy-1-methoxyanthraquinone (9), and 3,8-dihydroxy-1,2-dimethoxyanthraquinone (10) were isolated from the methanol extract of Morinda officinalis How. roots. Their structural identification was carried out based on the spectroscopic evidence. All compounds were evaluated for their nitric oxide (NO) production inhibitory activities in LPS-stimulated RAW264.7 macrophages. Compounds 5-7 significantly inhibited the production of NO with IC50 values of 28.4, 33.6, and 30.5 µM, respectively.

Selenium Nanoparticles Based on Morinda officinalis Polysaccharides: Characterization, Anti-Cancer Activities, and Immune-Enhancing Activities Evaluation In Vitro.

Recently, selenium nanoparticles have been drawing attention worldwide, and it is crucial to increase the stability of nano-Se. Morinda officinalis polysaccharides (MOP) are the main active component in Morinda officinalis radix. However, their low activity has limited their application. A novel selenium nanoparticle (Se-MOP) was prepared to solve these problems using MOP as a dispersant. The zeta potential was measured to evaluate the stability, and UV and ATR-FTIR were used to investigate the binding type of selenium and MOP. The morphology was observed by the TEM method. Furthermore, the inhibitory effect on five selected cancer cells (HepG2, MCF-7, AGS, PC9, and HCT8) was evaluated, showing remarkable inhibition of all five cancer cells. The mechanism of inhibition was also investigated by cell circle assay, and it was found that Se-MOP could induce cell circle G0/G1 phase arrest. Immune-enhancing activities were evaluated by measuring the proliferation and cytokines of mouse spleen lymphocytes in vitro and quantitative RT-PCR. The results indicated that single stimulation of Se-MOP and synergistic stimulation with PHA or LPS increased immune capacity and improved immune by increasing the expression of cytokines.

Production of anthraquinones from cell and organ cultures of Morinda species.

Since ancient times, Morinda species, particularly Morinda citrifolia, have been used for their therapeutic benefits. Iridoids, anthraquinones, coumarins, flavonoids, lignans, phytosterols, and carotenoids are examples of natural substances with bioactivity. Anthraquinone derivatives are the most significant of these chemicals since they are utilized as natural coloring agents and have a wide range of medicinal functions. Utilizing cell and organ cultures of Morinda species, various biotechnological methods have been developed for the bioproduction of anthraquinone derivatives. The generation of anthraquinone derivatives in cell and organ cultures is summarized in this article. The methods used to produce these chemicals in bioreactor cultures have also been examined. KEY POINTS: • This review investigates the potential of cell and organ cultures for anthraquinone synthesis. • The overproduction of anthraquinones has been addressed using a variety of techniques. • The use of bioreactor technologies for anthraquinone manufacturing is highlighted.

[Chemical constituents from fruits of Morinda citrifolia and their inhibitory effects on proliferation of synoviocytes in vitro].

The chemical constituents from the fruits of Morinda citrifolia were systematically explored by chromatographic fractionation methods including silica gel, octadecylsilyl(ODS) gel, Sephadex LH-20 gel, and preparative high performance liquid chromatography(pre-HPLC). The chemical structures of all isolated compounds were identified on the basis of their physicochemical properties, spectroscopic analyses, as well as the comparisons of their physicochemical and spectroscopic data with the reported data in literature. As a result, 22 isolated compounds from the 90% ethanol extract of the fruits of M. citrifolia were identified, which were moricitritone(1), 2'-deoxythymidine(2), cyclo-(L-Pro-L-Tyr)(3), methyl-5-hydroxy-2-pyridinecarboxylate(4), methyl pyroglutamate(5), bisbenzopyran(6), epipinoresinol(7), 3, 3'-bisdemethyl pinoresinol(8), 3, 3'-bisdemethyltanegool(9), trimesic acid(10), crypticin B(11), kojic acid(12), vanillic acid(13), protocatechoic acid(14), 5-hydroxymethyl furfural(15), blumenol A(16), 1-O-(9Z, 12Z-octadecadienoyl) glycerol(17), mucic acid dimethylester(18), methyl 2-O-ß-D-glucopyranosylbenzoate(19), 2-phenylethyl-O-ß-D-glucoside(20), scopoletin(21), and quercetin(22). Among them, compound 1 was a new pyrone derivative, compounds 2, 4-7, 10-12, and 17 were isolated from the plants belonging to Morinda genus for the first time, and compound 18 was obtained from M. citrifolia for the first time. Moreover, on the basis of testing the activities of all isolated compounds on inhibiting the proliferation of synovial fibroblasts in vitro by MTS assay, the anti-rheumatoid arthritis activities of all isolated compounds were initially evaluated. The results showed that compounds 1-6, 9, 19, and 20 exhibited remarkable anti-rheumatoid arthritis activities, which displayed the inhibitory effects on the proliferation of MH7A synovial fibroblast cells with the IC_(50) values in the range of(3.69±0.08) to(168.96±0.98) µmol·L~(-1).

Computational assessment of chemicals from Morinda citrifolia as potential inhibitors of B-Raf kinase in hepatocellular carcinoma treatment.

Hepatocellular carcinoma (HCC) is a tumour pathology that lacks specific treatment and is predominantly resistant to chemotherapy. The inhibitory activity of Morinda citrifolia, an evergreen tree commonly called Noni, against various carcinomas especially HCC is widely acclaimed. This study was to assess the phytochemical constituents of the plant for inhibitory activity against B-Raf kinase (3C4C) in order to design drugs for HCC treatment. Molecular docking, pharmacophore modelling, induced-fit docking, molecular dynamics (MD) simulations and ADMET predictions were the computational techniques employed in this study to detect potential inhibitors of B-Raf kinase from 135 compounds of Morinda citrifolia. Soranjidiol, Thiamine, Lucidin, 2-Methyl-1,3,5-Trihydroxyanthraquinone and Rubiadin were the five top-scoring compounds ranging from -8.39 to -8.22 kcal/mol, however, the standard ligand, PLX4720, scored -11.26 kcal/mol. The five compounds, like PLX4720 demonstrated hydrogen bond interactions with active site amino acid residues such as GLN 530, CYS 532 and ASP 594. The main energy contributor to the interactions between the compounds and B-Raf kinase were pi-stacking, hydrogen bond, van der Waals and covalent energy. Better docking scores obtained in the induced-fit docking further validates the inhibitory potential of the Soranjidiol against the flexible protein. In MD simulations, Soranjidiol revealed good stability in the active site of the protein since significant conformational changes were not evident. These five compounds, unlike the standard compound, demonstrated adequate druglike properties and good safety profiles. Therefore, further studies should be undertaken so as to develop them into drugs against HCC.Communicated by Ramaswamy H. Sarma.

Methyl 2-naphthoates with anti-inflammatory activity from Morinda officinalis.

Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 µM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.

Effect of combined ultrasonic and enzymatic extraction technique on the quality of noni (Morinda citrifolia L.) juice.

In order to obtain noni juice with high yield and good quality, the effect of combined extraction technique of enzymatic treatment (EZ) and ultrasonication (US) on the overall quality of noni juice was investigated. Moreover, the extraction performance of the EZ-US combined extraction technique was compared with that of EZ-based extraction and the US-based extraction. Response surface methodology (RSM) was designed to optimize the parameters of ultrasonic treatment, by taking consideration of the extraction efficiency, quality parameters and bioactive ingredients of noni juice. The results indicated that combined ultrasonic and enzymatic treatment achieved a synergistic effect on promoting the quality of noni juice. The maximum juice yield of 67.95 % was obtained under ultrasonication for 10 min at 600 W after enzymatic treatment (EZU). In addition, EZU-treated juice exhibited the highest contents of total phenolic and flavonoid, which were 148.19 ± 2.53 mg gallic acid/100 mL and 47.19 ± 1.22 mg rutin/100 mL, respectively, thus contributing to better antioxidant activity. Moreover, the EZU treatment significantly reduced the particle size of noni juice, and improved its suspension stability and rheological properties. FTIR results indicated that the treatments did not bring major changes in the chemical structure and the functional groups of compounds in noni juice. Therefore, EZU treatment can be successfully applied to the extraction of noni juice with better nutritional properties and overall quality.

Bisabolane-type sesquiterpenoids with potential anti-inflammatory and anti-HIV activities from the stems and leaves of Morinda citrifolia.

The phytochemical study on the stems and leaves of Morinda citrifolia L. resulted in the isolation of a new naturally occurring bisabolane-type sesquiterpenoid, morincitrinoid A (1), together with five known analogues (2-6). The chemical structure of 1 was elucidated by comprehensive spectral analyses. The known compounds 2-6 were identified by comparing their spectral data with those reported in the literature, which were isolated from M. citrifolia for the first time. In addition, the anti-inflammatory and anti-HIV activities of compounds 1-6 were evaluated in vitro. Compounds 1-6 displayed significant inhibitory activities on NO (nitric oxide) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells with IC50 values ranging from 0.98 ± 0.07 to 6.32 ± 0.11 µM, which was comparable to hydrocortisone. Meanwhile, compounds 1-6 showed remarkable anti-HIV-1 reverse transcriptase (RT) effects with the EC50 values ranging from 0.16 to 6.29 µM.

Anthraquinones with potential antiproliferative activities from the fruits of Morinda citrifolia.

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.