Morinda officinalis oligosaccharides modulate the default-mode network homogeneity in major depressive disorder at rest.

BACKGROUND: While prior studies have explored the efficacy of Morinda officinalis oligosaccharides (MOs) as a treatment for patients with major depressive disorder (MDD), the mechanistic basis for the effects of MOs on brain function or the default-mode network (DMN) has yet to be characterized. The objective of this was to examine the effects of MOs treatment on functional connectivity in different regions of the DMN. METHODS: In total, 27 MDD patients and 29 healthy control subjects (HCs) underwent resting-state functional magnetic resonance imaging. The patients were then treated with MOs for 8 weeks, and scanning was performed at baseline and the end of the 8-week treatment period. Changes in DMN homogeneity associated with MOs treatment were assessed using network homogeneity (NH) analyses of the imaging data, and pattern classification approaches were employed to determine whether abnormal baseline NH deficits could differentiate between MDD patients and controls. The ability of NH abnormalities to predict patient responses to MOs treatment was also evaluated. RESULTS: Relative to HCs, patients exhibited a baseline reduction in NH values in the right precuneus (PCu). At the end of the 8-week treatment period, the MDD patients showed reduced and increased NH values in the right PCu and left superior medial frontal gyrus (SMFG), respectively. Compared to these patients at baseline, the 8-week MOs treatment was associated with reduced NH values in the right angular gyrus and increased NH values in the left middle temporal gyrus and the right PCu. Support vector machine (SVM) analyses revealed that NH abnormalities in the right PCu and left SMFG were the most accurate (87.50%) for differentiating between MDD patients and HCs. CONCLUSION: These results indicated that MOs treatment could alter default-mode NH in patients with MDD. The results provide a foundation for elucidation of the effects of MOs on brain function and suggest that the distinctive NH patterns observed in this study may be useful as imaging biomarkers for distinguishing between patients with MDD and healthy subjects.

Morinda officinalis iridoid glycosides alleviate methotrexate-induced liver injury in CIA rats by increasing liver autophagy and improving lipid metabolism homeostasis.

ETHNOPHARMACOLOGICAL RELEVANCE: Morinda officinalis How. is a commonly used traditional Chinese herb with the pharmacological properties of tonifying liver and kidney, and enhancing bone and muscle. Iridoid glycosides are the predominant components of this plant, including monotropein, asperuloside, deacetylasperuloside and deacetylasperulosidic acid with their contents reaching more than 2%. Methotrexate (MTX) is the drug of choice for the treatment of rheumatoid arthritis (RA), but liver injury induced by MTX limits its wider use for RA. Morindaofficinalis iridoid glycoside (MOIG) is reported as having anti-RA and hepatoprotective effects, but the exact efficacy on MTX-induced liver injury and the underlying molecular mechanism remain unclear. AIM: To elucidate the mitigating effect of MOIG against liver injury in RA rats treated with MTX, and explore the possible mechanism. MATERIALS AND METHODS: The effect and mechanism of MOIG were investigated in Wistar rats with collagen-induced arthritis (CIA) which were then treated with MTX, and MTX-induced hepatocyte injury in vitro. Network pharmacological and transcriptomic analyses were conducted to predict the possible mechanisms of MOIG in mitigating MTX-induced liver injury, and lipidomic analysis was performed to further verify the regulatory effects of MOIG on lipid metabolism. BRL-3A hepatocytes were used to evaluate the regulatory effects of MOIG against MTX-associated liver injury. RESULTS: MOIG treatment enhanced the anti-RA effect of MTX, and mitigated oxidative damage, inflammation and apoptosis of liver tissues in CIA rats treated with MTX. Network pharmacological and transcriptomic analyses demonstrated that MOIG attenuated liver injury by regulating autophagy and lipid metabolism. The result of lipidomic analysis showed that MOIG reversed the disturbance of lipid metabolism of the liver tissue in CIA rats after MTX treatment. In addition, MOIG also inhibited the apoptosis, reduced the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (ALT) and alanine aminotransferase (AST), regulated oxidative stress, and increased the formation of autophagosome and translocation of LC3 in the nucleus and expression of autophagy regulatory genes Beclin-1, ATG5, LC3Ⅱ, ATG7 and ATG12 in hepatocytes subjected to MTX damage. CONCLUSION: Our findings demonstrated that MOIG could ameliorate MTX-induced liver injury in the treatment of RA through increasing hepatocyte autophagy and improving lipid metabolism homeostasis.

Effects and Mechanism of Morinda Officinalis How on Metabolism-Associated Fatty Liver Disease.

AIMS: This study aims to investigate the effects and mechanism of Morinda Officinalis How (MOH), a lianoid shrub with potential therapeutic properties, on Metabolism- Associated Fatty Liver Disease (MAFLD). bjective: The objective of this study was to construct a MOH-MAFLD network prediction model and explore the effect of MOH on MAFLD and its underlying mechanism in vivo. METHODS: Screening of MAFLD targets was performed using the DisGeNET database. Venny database was used to establish the MOH-MAFLD interaction network map, while the STRING database was applied to assess the Protein-Protein Interaction (PPI) network. The central target gene was screened using Gene Ontology (GO) function analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. RESULTS: GO function enrichment analysis revealed that MOH affected MAFLD through apoptosis and estrogen-related pathways. KEGG pathway enrichment and PPI network analysis indicated that MOH might mitigate MAFLD by reducing apoptosis and improving lipid metabolism. Additionally, 6 weeks of MOH treatment in rats decreased caspase-3 levels and increased Bcl-2, Estrogen receptor α(Esr1), and JUN proteins, thus ameliorating MAFLD progression. CONCLUSION: MOH could delay the progression of MAFLD by affecting estrogen-related pathways, reducing cell stress, and inhibiting apoptosis.

Morinda Officinalis-derived extracellular vesicle-like particles: Anti-osteoporosis effect by regulating MAPK signaling pathway.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is a systemic bone disease characterized by low bone mass and microstructural damage. Morinda Officinalis (MO) contains various components with anti-PMOP activities. Morinda Officinalis-derived extracellular vesicle-like particles (MOEVLPs) are new active components isolated from MO, and no relevant studies have investigated their anti-osteoporosis effect and mechanism. PURPOSE: To investigate the alleviating effect of MOEVLPs on PMOP and the underlying mechanism. METHODS: Differential centrifugation and ultracentrifugation were used to isolate MOEVLPs from MO. Transmission electron microscopy (TEM), flow nano analyzer, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), agarose gel electrophoresis, and thin-layer chromatography were employed to characterize MOEVLPs. PMOP mouse models were utilized to examine the anti-PMOP effect of MOEVLPs. H&E and immunohistochemical staining were used for drug safety and osteogenic effect assessment. Mouse embryo osteoblast precursor cells (MC3T3-E1) were used in vitro experiments. CCK-8 kit, alizarin red staining, proteomic, bioinformatic analyses, and western blot were used to explore the mechanism of MOEVLPs. RESULTS: In this study, MOEVLPs from MO were successfully isolated and characterized. Animal experiments demonstrated that MOEVLPs exhibited specific femur targeting, were non-toxic to the heart, liver, spleen, lung, kidney, and aorta, and possessed anti-PMOP properties. The ability of MOEVLPs to strengthen bone formation was better than that of alendronate. In vitro experiments, results revealed that MOEVLPs did not significantly enhance osteogenic differentiation in MC3T3-E1 cells. Instead, MOEVLPs promoted the proliferation of MC3T3-E1 cells. Proteomic and bioinformatic analyses suggested that the proliferative effect of MOEVLPs was closely associated with the mitogen-activated protein kinase (MAPK) signaling pathway, particularly the altered expression of cAMP response element-binding protein (CREB) and ribosomal S6 kinase 1 (RSK1). Western blot results further confirmed these findings. CONCLUSION: Our studies successfully isolated high-quality MOEVLPs and demonstrated that MOEVLPs can alleviate PMOP by promoting osteoblast proliferation through the MAPK pathway. MOEVLPs have the potential to become a novel and natural anti-PMOP drug.

Modulation of Gut Microbiota, and Morphometry, Blood Profiles and performance of Broiler Chickens Supplemented with Piper aduncum, Morinda citrifolia, and Artocarpus altilis leaves Ethanolic Extracts.

Bioactive plants such as P. aduncum, M. citrifolia, and A. altilis might improve intestinal health as an alternative to antibiotic growth promoters. The objective of this study was to determine the effect of the ethanolic extracts (EEs) of these plants on the intestinal health of broiler chickens. Cobb 500 chickens (n = 352) were distributed into eight treatments with four replicates and 11 chickens each. T1 received a base diet, and T2 received a base diet with 0.005% zinc bacitracin. T3, T5, and T7 were supplemented with 0.005% of P. aduncum, M. citrifolia, and A. altilis EE in the diet while T4, T6, and T8 with 0.01% of the extract. The EEs were supplemented with drinking water from 1 to 26 days of age. The following parameters were evaluated: hematological profiles at 28 days of age, blood metabolites profiles at 14, 21, and 28 days; Escherichia coli, Staphylococcus aureus, and Lactobacillus sp. abundance in the ileum mucosa and content at 21 and 28 days, and histomorphometry of the duodenum, jejunum, and ileum mucosa at 14, 21, and 28 d. Final weight (FW), weight gain (WG), feed intake (FI), and feed conversion rate (FCR) were evaluated at seven, 21, and 33 days of age. M. citrifolia and A. altilis EE at 0.01% increased blood glucose levels at 21 and 28 days of age, respectively, and P. aduncum and M. citrifolia EE at 0.01% increased triglycerides at 28 days of age; in addition, this EE did not have any effect on the AST and ALT profiles. The depths of the Lieberkühn crypts and the villi length to the crypt's depth ratio increased with age on supplementation with 0.01% M. citrifolia and A. altilis EE at 21 days of age (p < 0.05). In addition, the depth of the crypts increased at 28 days of age (p < 0.05) in chickens supplemented with 0.01% A. altilis EE. The 0.01% M. citrifolia EE in diet decreased in the Staphylococcus aureus population in the ileal microbiota (p < 0.05). The FW and WG during the fattening and in the three stages overall increased, and the FCR decreased; however, the FI and the carcass yield did not change in the broiler chickens supplemented with 0.01% M. citrifolia EE (p < 0.05). Conclusively, the M. citrifolia EE at 0.01% of the diet improved intestinal health and thus the performance indices of the broiler chickens and did not have a detrimental effect on any of the parameters evaluated, so it is postulated as a potential alternative to AGP in poultry.

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.

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.

Unraveling the potential of Morinda officinalis oligosaccharides as an adjuvant of escitalopram in depression treatment and exploring the underlying mechanisms.

ETHNOPHAMACOLOGICAL RELEVANCE: Morinda officinalis oligosaccharides (MOs) is a mixture of oligosaccharides extracted from the roots of Morinda officinalis (MO). It is approved by Chinese Food and Drug Administration (CFDA) for depression treatment. MOs could improve the antidepressant efficacy of escitalopram in clinic. AIM OF THE STUDY: We aim to explore the antidepressant activity and potential mechanism of the combination usage of MOs and escitalopram on animal model of depression. MATERIALS AND METHODS: Depressive animal model was induced by chronic mild stress (CMS). Behavioral tests were conducted to evaluate the antidepressant efficacy of MOs and escitalopram. Serum neurotransmitter levels were detected by High-performance liquid chromatography (HPLC). Quantitative real-time PCR and Western blotting were applied to assay the hippocampus neurotrophic factors' mRNA and protein levels. Peripheral cytokines levels were measured through Enzyme-Linked Immunosorbent Assay (ELISA). Micorglia polization phenotype was assayed by immunofluorescence and flow cytometry. RESULTS: MOs and escitalopram obviously attenuated depression-like behaviors of CMS mice. Importantly, MOs plus escitalopram exhibited better antidepressant activity on CMS mice than monotherapy. At the same time, MOs combined escitalopram treatment significantly increased hippocampus neurotransmitters and neurotrophic factor levels, stimulated hippocampus neurogenesis and relieved central nervous system (CNS) microglia over-activation of CMS mice. The combination therapy had greater effect on neuroprotection and inflammation attenuation of CMS mice than monotherapy. CONCLUSION: Our results indicates MOs combined escitalopram might produce antidepressant activity through protecting neuron activity, relieving inflammation and modulating microglia polarization process.

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.

Comparative evaluation of the effect of ultrasonic and rotary agitation of herbal irrigating solutions on smear layer: A SEM study.

Context: Instrumentation and irrigation balance helps in effective removal of endodontic microbes housing inside the smear layer. Aim: This study aimed to (1) evaluate whether activation of the irrigating solutions with two different systems during the final irrigation step can lead to smear layer formation in the middle and apical third of the root canal and (2) evaluate and compare the smear layer removal ability of the aqueous extracts of Emblica officinalis and Morinda citrifolia. Materials and Methods: A total of 72 single-rooted teeth were prepared up to F4 ProTaper. The specimens were assigned into eight groups of nine teeth each, according to the final irrigant and activation techniques. Further, the teeth were evaluated under SEM for endodontic smear layer at the middle and apical third. Statistical Analysis: Inferential statistics included Pearson's Chi-square. Level of significance was set at 0.05 at 95% confidence level. Results: Ultrasonic activation system showed significant (P = 0.000) amount of smear layer compared to XP-Endo Finisher file. A significant difference (P = 0.00) in the smear layer removal was observed when 6% M. citrifolia was activated with XP-Endo Finisher file both in the middle and apical third. Conclusion: Within the limitations of this in vitro study, it can be concluded that smear layer formation was noted with ultrasonic and XP-Endo Finisher file when saline was used as an irrigant. 6% M. citrifolia when activated with XP-Endo Finisher file showed best results among all other experimental groups.

Anti-inflammatory monoterpenes from morinda (Morinda officinalis How.).

Morinda (Morinda officinalis How.) is widely consumed as a functional food owing to its potential to promote health. This study investigated the anti-inflammatory phytochemicals of morinda and isolated 30 monoterpenes, including 6 undescribed iridoids (1, 6, 9-11 and 25), 2 undescribed acyclic monoterpenoids (28, 29), a known acyclic monoterpenoid and 21 known iridoids. Their chemical and stereo-structures were elucidated based on HR-ESI-MS, NMR, 13C-NMR calculations, ECD data and ECD calculations. Notably, compounds 11, 12 and 20 exerted pronounced inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 28.51 ± 1.70, 25.45 ± 4.17 and 29.17 ± 3.71 µM respectively (indomethacin, IC50 of 33.68 ± 2.19 µM). The same compounds exert anti-inflammatory effects by blocking nuclear translocation of nuclear factor κ-B, and down-regulating the expression of inflammatory cytokines such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-1ß and interleukin-6 at mRNA and protein levels in a dose-dependent manner. These results suggest that moderate consumption of morinda helps prevent and reduce the occurrence of inflammatory-related diseases.

Anticancer and chemopreventive potential of Morinda citrifolia L. bioactive compounds: A comprehensive update.

Morinda citrifolia L., commonly known as Noni, has a longstanding history in traditional medicine for treating various diseases. Recently, there has been an increased focus on exploring Noni extracts and phytoconstituents, particularly for their effectiveness against cancers such as lung, esophageal, liver, and breast cancer, and their potential in cancer chemoprevention. This study aims to provide a comprehensive review of in vitro and in vivo studies assessing Noni's impact on cancer, alongside an exploration of its bioactive compounds. A systematic review was conducted, encompassing a wide range of scientific databases to gather pertinent literature. This review focused on in vitro and in vivo studies, as well as clinical trials that explore the effects of Noni fruit and its phytoconstituents-including anthraquinones, flavonoids, sugar derivatives, and neolignans-on cancer. The search was meticulously structured around specific keywords and criteria to ensure a thorough analysis. The compiled studies highlight Noni's multifaceted role in cancer therapy, showcasing its various bioactive components and their modes of action. This includes mechanisms such as apoptosis induction, cell cycle arrest, antiangiogenesis, and immune system modulation, demonstrating significant anticancer and chemopreventive potential. The findings reinforce Noni's potential as a safe and effective option in cancer prevention and treatment. This review underscores the need for further research into Noni's anticancer properties, with the hope of stimulating additional studies and clinical trials to validate and expand upon these promising findings.

Morindone as a potential therapeutic compound targeting TP53 and KRAS mutations in colorectal cancer cells.

There is an increasing demand for anticancer agent in treating colorectal cancer (CRC) with frequently mutated TP53 and KRAS genes. Phytochemical compounds are suitable as chemoprevention for CRC since dietary factor is a major risk factor. Anthraquinones from Morinda citrifolia L. were previously reported with various pharmacological properties. Various in vitro experiments were conducted to investigate the effects of two anthraquinones: damnacanthal and morindone on the cell proliferation, cell cycle, apoptosis, gene expression and protein expression in two CRC cells: HCT116 and HT29. Real-time monitoring of CRC cells showed that both anthraquinones exerted significant anti-proliferative effects in a dose- and time-dependent manner. Next, cell cycle analysis revealed an increase in the percentage of CRC cells in the G1 phase under anthraquinones treatment. Fluorescence microscopy also showed an increment of apoptotic cells under anthraquinones' treatment. siRNA transfection was conducted to evaluate the mediating effect of gene knockdown on mutated TP53 and KRAS in CRC cells. Before transfection, qRT-PCR analysis showed that only morindone downregulated the gene expression of mutated TP53 and KRAS and then further downregulated them after transfection. Both damnacanthal and morindone treatments further downregulated the expression of these two genes but upregulated at the protein expression level. Furthermore, gene knockdown also sensitised CRC cells to both damnacanthal and morindone treatments, resulting in lowered IC50 values. The accumulation of cells at the G1 phase was reduced after gene knockdown but increased after damnacanthal and morindone treatments. In addition, gene knockdown has increased the number of apoptotic cells in both cell lines and further increment was observed after anthraquinone treatment. In conclusion, morindone could be a competitive therapeutic agent in CRC by exhibiting multiple mechanism of anti-cancer actions.

[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.

Biocontrol fungi induced stem-base rot disease resistance of Morinda officinalis How revealed by transcriptome analysis.

Introduction: Morinda officinalis How (MO) is a Rubiaceae plant, and its medicinal part is dried root, which is one of the "Four Southern Medicines" in China. At present, the plant MO breed seedlings mainly by cutting methods. Long-term asexual propagation makes pathogenic fungi accumulate in MO, leading to stem-base rot, which is caused by Fusarium oxysporum (Fon). Methods: In this study, we used Trichoderma harzianum and Pestalotiopsis sp. as biocontrol fungi to investigate their antagonistic ability to Fon through in vitro antagonism and pot experiments, and combined with transcriptome sequencing to explore the mechanism of biocontrol. Results: The results showed that both Trichoderma harzianum and Pestalotiopsis sp. could inhibit the growth of Fon. In addition, Trichoderma harzianum and Pestalotiopsis sp. could also enhance the basic immunity to Fon by increasing the activities of defensive enzymes such as POD and SOD, chlorophyll content, soluble sugar content, and oligosaccharide content of MO. The mechanism of biological control of stem-base rot of MO was discussed by transcriptome technology. MO was treated with two treatments, root irrigation with biocontrol fungi or inoculation with Fon after root irrigation with biocontrol fungi. Transcriptome sequencing revealed that nearly 11,188 differentially expressed genes (DEGs) were involved in the process of inducing MO systemic resistance to Fon by biocontrol fungi. Meanwhile, Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, as well as transcription factor (TFs) prediction showed that there were significant differences in the expression levels of MO roots under different treatments. Also, the genes of the "MAPK signaling pathway" and "plant hormone signaling pathway" were analyzed, in which the ERFs gene of the ethylene signal transduction pathway participated in the metabolism of glycosyl compounds. It is speculated that the ethylene signal may participate in the immune response of the sugar signal to the infection of Fon. After qRT-PCR verification of 10 DEGs related to the ethylene signal transduction pathway, the expression trend is consistent with the results of transcriptome sequencing, which proves the reliability of transcriptome sequencing. Discussion: In conclusion, this study preliminarily identified the molecular mechanism of the biological control of MO stem-base rot and provided a scientific basis for further research on the prevention and control mechanism of MO stem-base rot.

Isolation, phytochemistry, characterization, biological activity, and application of Morinda officinalis How oligosaccharide: a review.

Morinda officinalis How oligosaccharide (MOO) stands as one of the principal active constituents of M. officinalis How, widely employed in traditional Chinese medicine. The methods for MOO extraction predominantly encompass hot water extraction, ethanol extraction, ultrasonic-assisted extraction, and microwave-assisted extraction. Distinct extraction techniques yield varying MOO quantities. MOO encompasses a diversity of oligosaccharides, including bajijiasu, sucrose, 1-kestose, nystose, mannose, 1F-fructofuranosylnystose, 1,1,1,1-kestohexose, fructoheptasaccharide, inulin-type hexasaccharide, inulin-type heptasaccharide, inulotriose, inulotetraose, inulopentaose, and mannose. MOO exhibits a wide spectrum of biological activities, exerting specific effects on the nervous system, cardiovascular system, motor system, reproductive system, and immune system. It demonstrates antidepressant properties, offers potential in mitigating Alzheimer's disease, stimulates angiogenesis, and possesses anti-osteoporotic and other pharmacological effects. Clinically, when combined with various antidepressants, MOO exhibits specific therapeutic efficacy across multiple forms of depression. As a naturally occurring plant oligosaccharide, MOO holds diverse pharmaceutical applications. This article conducts a review of the latest extraction and purification methodologies, structural characterization analysis, biological activity assessment, and clinical applications of MOO. Such a comprehensive analysis yields innovative insights for advancing the research and application of MOO in the future.

Multi-analytical investigation of the physical, chemical, morphological, tensile, and structural properties of Indian mulberry (Morinda tinctoria) bark fibers.

In this study, micro-cellulosic fibers were isolated from the bark of Morinda tinctoria (MT) and characterized for the first time. The anatomical, physical, chemical, thermal, and mechanical properties of the M. tinctoria bark fiber (MTBF) were investigated. The mean diameter and density values were determined to be 32.013 ± 1.43 µm and 1.4875 g/cm³, respectively. Zeta potential analysis and particle size measurements provided the evidence of enhanced micro-particle behavior on the fiber's surface. Various structural characterizations confirmed the presence of polysaccharide structures, monosaccharide compositions, glycosidic residues (sugar linkages), and cohesive reactions of TMSA (Trimethylsilyl alditol) derivatives, indicating the fiber's potential for strong surface absorption properties. X-ray diffraction analysis revealed a crystallinity index of 51 % and a crystallite size of 3.086 nm for MTBF. Fourier transform infrared analysis indicated the presence of cellulose, hemicellulose, and lignin constituents, along with their corresponding functional groups. The calculated values of Young's modulus and tensile strength were determined to be 75.7 GPa and 746.77 MPa, respectively. Thermogravimetric analysis demonstrated the thermal stability of the extracted MTBF up to 240 °C. Based on these findings, the MT microfibrils derived from the bark can be considered as potential substitutes for existing synthetic composites, offering reinforcement for novel bio composites.

Physiological and transcriptomic analysis reveals the potential mechanism of Morinda officinalis How in response to freezing stress.

BACKGROUND: Morinda officinalis How (MO) is a vine shrub distributed in tropical and subtropical regions, known as one of the "Four Southern Herbal Medicines" in China. The unclear responsive mechanism by which MO adapt to freezing stress limits progress in molecular breeding for MO freezing tolerance. RESULTS: In this study, morphological, physiological and microstructure changes in MO exposed to -2℃ for 0 h, 3 h, 8 h and 24 h were comprehensively characterized. The results showed that freezing stress caused seedling dehydration, palisade cell and spongy mesophyll destruction. A significant increase in the content of proline, soluble protein and soluble sugars, as well as the activity of superoxide dismutase and peroxidase was observed. Subsequently, we analyzed the transcriptomic changes of MO leaves at different times under freezing treatment by RNA-seq. A total of 24,498 unigenes were annotated and 3252 unigenes were identified as differentially expressed genes (DEGs). Most of these DEGs were annotated in starch and sucrose metabolism, plant hormone signal transduction and MAPK signaling pathways. Family Enrichment analysis showed that the glucosyl/glucuronosyl transferases, oxidoreductase, chlorophyll a/b binding protein and calcium binding protein families were significantly enriched. We also characterized 7 types of transcription factors responding to freezing stress, among which the most abundant family was the MYBs, followed by the AP2/ERFs and NACs. Furthermore, 10 DEGs were selected for qRT-PCR analysis, which validated the reliability and accuracy of RNA-seq data. CONCLUSIONS: Our results provide an overall view of the dynamic changes in physiology and insight into the molecular regulation mechanisms of MO in response to freezing stress. This study will lay a foundation for freezing tolerance molecular breeding and improving the quality of MO.