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.

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.

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.

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.

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.

Neuroprotective effects of Morinda officinalis How.: Anti-inflammatory and antioxidant roles in Alzheimer's disease.

Pharmacological studies have shown that some traditional Chinese medicines (TCMs) have applications in the treatment of Alzheimer's disease (AD). Morinda officinalis How. (MO) is a TCM with a long history and is widely used to tonify kidney Yang. In vitro and in vivo experiments have suggested that MO contains various effective pharmaceutical components and chemicals, including oligosaccharides, anthraquinones, iridoids, flavonoids, amino acids, and trace elements, conferring MO with anti-inflammatory and antioxidant properties. Neuroinflammation and oxidative stress are undoubtedly hallmarks of neurodegeneration, contributing to AD progression. In this mini-review, we summarize the molecular mechanisms, structure-activity relationships, and potential synergistic and antagonistic effects of active components in MO. This discussion highlights the roles of these active components, such as oligosaccharides, anthraquinones, and iridoid glycosides, in the treatment of AD via anti-inflammatory and antioxidant mechanisms, providing a scientific basis for further utilization of MO.

Quality markers for processed products of Morinda officinalis how based on the "oligosaccharides-spectrum-effect".

Morinda officinalis How (MO) possesses prominent tonifying kidney yang and strengthening bone and muscle effects in traditional Chinese medicine (TCM). Due to the complexity of MO components, the chemical mechanism leading to efficacy changes of MO caused by processing remain unclear. This study aimed to investigate and discover quality markers (Q-markers) related to the clinical efficacy of processed MO. The different processed products of MO have different clinical applications, although they originate from the same medicinal herb. The active chemical components from raw and processed MO that protect against reproductive oxidative stress damage were evaluated. The processed products of MO were prepared by different processing methods. The changes in oligosaccharides during processing were characterized by high-performance liquid chromatography with an evaporative light scattering detector (HPLC-ELSD), and the differential components in raw and processed MO were analyzed using SA, HCA, PCA, and OPLS-DA methods. The protective effects of raw and processed MO oligosaccharides (MOOs) against reproductive oxidative stress damage were evaluated based on the spermatic number, spermatic survival rate, abnormal sperm ratio and serum biochemical indicators in cyclophosphamide-induced (CTX-induced) male mice. The results revealed that processed MOOs had better pharmacological effects than raw MOOs. Therefore, gray correlation analysis (GRA) and the technique for order preference by similarity to ideal solution (TOPSIS) methods were used to investigate the spectrum-effect relationships of MOOs. Spectrum-effect relationship analysis revealed that all of the characteristic peaks contributed to the treatment of reproductive oxidative stress damage, and the relative correlation degrees were greater than 0.6. Among them, the peaks 1 F-fructofuranosylnystose, nystose, and 1-kestose and the peaks X2-X5, which were most closely correlated to the treatment of reproductive oxidative stress damage, were identified as inulin-oligosaccharides and inulo-oligosaccharides, respectively. It was proposed that these constituents could be considered Q-markers for processed products of MO. Thus, this study aimed to explore chemical markers that correlate with the clinical efficacy of processed MO.

[Morinda officinalis how extract up-regulates the expression of SPAG11T and inhibits that of miR-210 in the testis tissue of varicocele rats].

OBJECTIVE: To investigate the effects of morinda officinalis how (MOH) on SPAG11T and microRNA-210 (miR-210) in the testis tissue of SD rats with varicocele (VC). METHODS: Forty SD rats were randomly divided into four groups of an equal number: blank control, VC model control, low-dose MOH and high-dose MOH. The rats in the former two groups were treated intragastrically with normal saline and those in the latter two with MOH extract at 200 and 400 mg/kg/d, respectively, all for 30 days. Then, the testis tissues of the rats were harvested for measurement of the levels of SOD, MDA and AI and determination of the expressions of vimentin, sperm-associated antigen 11T (SPAG11T) protein and RNA, and miR-210. RESULTS: There were no statistically significant differences in the testicular and epididymal weights among the four groups of rats (P > 0.05). Compared with the rats in the VC model control group, those in the MOH groups showed a remarkably increased SOD content (P < 0.05) but a decreased MDA level and AI in the testis tissue (P < 0.05). The expression of vimentin mRNA in the testis tissue was significantly reduced in the VC model control in comparison with that in the blank control group (0.18 ± 0.03 vs 1.00 ± 0.02), but dramatically up-regulated after treated with low-dose MOH (0.68 ± 0.07) and high-dose MOH (0.92 ± 0.08) (F = 432.901, P< 0.01). The level of SPAG11T mRNA was also remarkably decreased in the VC model control group compared with the blank controls (0.32 ± 0.04 vs 1.00 ± 0.05), but markedly elevated after treated with low-dose MOH (0.61 ± 0.09) and high-dose MOH (0.82 ± 0.13) (F = 117.423, P< 0.01). The level of testicular miR-210, however, was significantly increased in the VC model controls compared with the blank controls (1.39 ± 0.12 vs 1.00 ± 0.06), but decreased in both the low-dose MOH (1.17 ± 0.08) and high-dose MOH groups (1.09 ± 0.08) (F = 36.136, P< 0.01). CONCLUSIONS: MOH extract can up-regulate the expressions of vimentin and SPAG11T and inhibit that of miR-210 in the testis tissue of varicocele rats.

Iridoids with anti-inflammatory effect from the aerial parts of Morinda officinalis How.

Morinda officinalis How was widely applied to alleviate symptom like impotence, menstrual disorders, osteoporosis, and rheumatoid arthritis. To expand resources usage, phytochemistry of the aerial parts was studied and the structures of compounds were elucidated based on NMR, HRESIMS, IR and UV. Moreover, the anti-inflammatory effect and possible mechanism were investigated by Griess kit, RT-qPCR, ELISA, western blot and molecular docking on LPS-induced inflammation in RAW 264.7 cells. Herein, we isolated and identified 16 iridoid derivatives, including seven new iridoids officinaloside A-G (1-7) and nine known iridoids. All the compounds were safe to RAW 264.7 cells. Luckily, compounds 5 and 6 showed inhibitory effect on production of NO, and decreased the expression of inflammatory cytokines at mRNA and protein levels in a dose-dependent way. The possible mechanism of their anti-inflammation may be the affinity interaction between 5 with COX-2 protein, and 6 with iNOS protein. Overall, compounds 5 and 6 exert promising effects in inhibiting inflammatory cytokines, indicating that they could be used as lead compounds for developing health products or clinical practice for inflammation, which provides a scientific basis for further sustainable development and usage of the aerial parts of Morinda officinalis How.

Anti-inflammatory naphthoates and anthraquinones from the roots of Morinda officinalis.

Morinda (Morinda officinalis) is widely consumed as a health-care herb in Asia and reported to possess various biological activities. In this study, anti-inflammatory phytochemicals were investigated and two pairs of new methyl-2-naphthoate enantiomers (1a/1b, 2a/2b), one new anthraquinone (3), three new natural unknown anthraquinones (5-6, 23), and eighteen known anthraquinones were isolated and elucidated from the roots of morinda. Anti-inflammatory activities of the isolated compounds were assessed in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compounds 2b and 19 significantly inhibited the production of NO with IC50 values of 34.32 ± 4.87 and 17.17 ± 4.13 µM (indomethacin, IC50 26.71 ± 6.32 µM), and they were further corroborated via immunoblotting, quantitative real-time PCR and immunofluorescence staining assays. They could dose-dependent suppress lipopolysaccharide-stimulated pro-inflammatory factors (COX-2 and iNOS) production and block nuclear translocation of NF-κB. The results implied that reasonable consumption of morinda may be beneficial for preventing and reducing the occurrence of inflammatory-associated diseases.

Network pharmacology-based investigation on the mechanisms of action of Morinda officinalis How. in the treatment of osteoporosis.

BACKGROUND: Osteoporosis is a systemic skeletal disease that leads to a high risk for bone fractures. Morinda officinalis How. has been used as osteoporosis treatment in China. However, its mechanism of action as an anti-osteoporotic herb remains unknown. METHODS: A network pharmacology approach was applied to explore the potential mechanisms of action of M. officinalis in osteoporosis treatment. The active compounds of M. officinalis and their potential osteoporosis-related targets were retrieved from TCMSP, TCMID, SwissTargetPrediction, DrugBank, DisGeNET, GeneCards, OMIM, and TTD databases. A protein-protein interaction network was built to analyze the target interactions. The Metascape database was used to carry out GO enrichment analysis and KEGG pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking. RESULTS: A total of 17 active compounds and 93 anti-osteoporosis targets of M. officinalis were selected for analysis. The GO enrichment analysis results indicated that the anti-osteoporosis targets of M. officinalis mainly play a role in the response to steroid hormone. The KEGG pathway enrichment analysis showed that M. officinalis prevents osteoporosis through the ovarian steroidogenesis signaling pathway. Moreover, the molecular docking results indicated that bioactive compounds (morindon, ohioensin A, and physcion) demonstrated a good binding ability with IGF1R, INSR, ESR1, and MMP9. CONCLUSION: M. officinalis contains potential anti-osteoporotic active compounds. These compounds function by regulating the proteins implicated in ovarian steroidogenesis-related pathways that are crucial in estrogen biosynthesis. Our study provides new insights into the development of a natural therapy for the prevention and treatment of osteoporosis.

Bioassay-guided isolation and evaluation of anti-osteoporotic polysaccharides from Morinda officinalis.

ETHNOPHARMACOLOGICAL RELEVANCE: Morinda officinalis is a well-known Chinese tonic herb that has shown clinical efficacy in the treatment of bone disease. However, its anti-osteoporotic potential and the M. officinalis polysaccharides (MOPs) responsible for activity require further investigation. AIM OF THE STUDY: This study aimed to investigate the anti-osteoporotic effects of different MOP fractions in ovariectomized (OVX) rats, and to identify the osteoprotective components by bioassay-guided isolation. MATERIALS AND METHODS: MOPs were prepared by hot water and alkali extraction, separated into three fractions (MO50, MO70, and MOB) and evaluated in the classic OVX rat model and in MC3T3-E1 cells for anti-osteoporotic activity. RESULTS: Administration of MOPs (400 mg/kg/day) provided significant protection against ovariectomy-induced bone loss and biomechanical dysfunction in rats. Treated animals exhibited reduced deterioration of trabecular microarchitecture and lower levels of bone turnover markers. Bioactivity-guided fractionation led to the isolation of two inulin-type fructans from MO50, MOW50-1 and MOP50-2, with potential anti-osteoporotic activities. These consisted of (2 → 1)-linked ß-D-fructosyl residues with degrees of polymerization (DP) of 7 and 13, respectively. Furthermore, MOW50-1 promoted osteogenic differentiation of MC3T3-E1 cells by increasing alkaline phosphatase activity. CONCLUSIONS: These data suggest very strongly that MOPs, especially MO50 and MOW50-1, may play important roles in the prevention and treatment of osteoporosis.

Iridoid glycosides from Morinda officinalis How. exert anti-inflammatory and anti-arthritic effects through inactivating MAPK and NF-κB signaling pathways.

BACKGROUND: The root of Morinda officinalis How. (MO, the family of Rubiaceae) has long been used to treat inflammatory diseases in China and other eastern Asian countries, and iridoid glycosides extracted from MO (MOIG) are believed to contribute to this anti-inflammatory effect. However, the mechanism underlying the anti-inflammatory and anti-arthritic activities of MOIG has not been elucidated. The aim of the present study was to determine how MOIG exerted anti-inflammatory and anti-arthritic effects in vivo and in RAW 264.7 macrophages. METHODS: MOIG were enriched by XDA-1 macroporous resin. The maximum feasible dose method was adopted to evaluate its acute toxicity. The analgesic effect of MOIG was evaluated by acetic acid writhing test and the anti-inflammatory effect was evaluated by cotton-pellet granuloma test in rats and air pouch granuloma test in mice. The anti-arthritic effect was evaluated by establishing an adjuvant arthritis model induced by Complete Freund's Adjuvant (CFA). The viability of the cultured RAW 264.7 macrophages was assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay. The anti-inflammatory activity was evaluated by measuring NO, IL-1ß, IL-6 and TNF-α levels in LPS-stimulated RAW 264.7 cells. The protein level of inflammatory responsive genes was evaluated by Western blot analysis. RESULTS: MOIG had no significant toxicity at maximum feasible dose of 22.5 g/kg. MO extracts and MOIG (50,100 and 200 mg/kg) all evoked a significantly inhibitory effects on the frequency of twisting induced by acetic acid in mice compared with the model control group. Administration of MO extracts and MOIG markedly decreased the dry and wet weight of cotton pellet granuloma in rats and air pouch granuloma in mice. MOIG significantly attenuated the paw swelling and decreased the arthritic score, weight loss, spleen index, and the serum level of inflammatory factors IL-1ß, IL-6 and IL-17a in CFA-induced arthritic rats. MOIG inhibited the production of inflammatory cytokines in LPS-stimulated RAW264.7 cells, and the expressions of iNOS, COX-2 and proteins related to MAPK and NF-κB signaling pathways in LPS-stimulated RAW 264.7 macrophages. CONCLUSION: MOIG exerted anti-inflammatory and anti-arthritic activities through inactivating MAPK and NF-κB signaling pathways, and this finding may provide a sound experimental basis for the clinical treatment of rheumatoid arthritis with MOIG.

Rubiadin-1-methyl ether from Morinda officinalis How. Inhibits osteoclastogenesis through blocking RANKL-induced NF-κB pathway.

Rubiadin-1-methyl ether (RBM) is a natural anthraquinone compound isolated from the root of Morinda officinalis How. In our previous study, RBM was found to have inhibitory effects on the TRAP activity of osteoclasts, which means that RBM may be a candidate for therapy of bone diseases characterized by enhanced bone resorption. However, the further effect of RBM on osteoclasts and the underlying mechanism remain unclear. In the present study, we investigated the effects of RBM isolated from Morinda officinalis How. on osteoclasts derived from bone marrow macrophages (BMMs) and the underlying mechanism in vitro. RBM at the dose that did not affect the viability of cells significantly inhibited RANKL-induced osteoclastogenesis and actin ring formation of osteoclast, while RBM performed a stronger effect at the early stage. In addition, RBM downregulated the expression of osteoclast-related proteins, including nuclear factor of activated T cells cytoplasmic 1 (NFATc1), cellular oncogene Fos (c-Fos), matrix metallopeptidase 9 (MMP-9) and cathepsin K (CtsK) as shown by Western blot. Furthermore, RBM inhibited the phosphorylation of NF-κB p65 and the degradation of IκBα as well as decreased the nuclear translocation of p65. Collectively, the results suggest that RBM inhibit osteoclastic bone resorption through blocking NF-κB pathway and may be a promising agent for the prevention and treatment of bone diseases characterized by excessive bone resorption.

Morinda officinalis How. - A comprehensive review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant Morinda officinalisHow. (MO) and its root have long been used in traditional medicines in China and northeast Asia as tonics for nourishing the kidney, strengthening the bone and enhancing immunofunction in the treatment of impotence, osteoporosis, depression and inflammatory diseases such as rheumatoid arthritis and dermatitis. AIM OF THE REVIEW: This review aims to sum up updated and comprehensive information about traditional usage, phytochemistry, pharmacology and toxicology of MO and provide insights into potential opportunities for future research and development of this plant. METHODS: A bibliographic investigation was performed by analyzing the information available on MO in the internationally accepted scientific databases including Pubmed, Scopus and Web of Science, SciFinder, Google Scholar, Yahoo, Ph.D. and M.Sc. dissertations in Chinese. Information was also obtained from some local and foreign books on ethnobotany and ethnomedicines. RESULTS: The literature supported the ethnomedicinal uses of MO as recorded in China for various purposes. The ethnomedical uses of MO have been recorded in many regions of China. More than 100 chemical compounds have been isolated from this plant, and the major constituents have been found to be polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides. Crude extracts and pure compounds of this plant are used as effective agents in the treatment of depression, osteoporosis, fatigue, rheumatoid arthritis, and infertility due to their anti-depressant, anti-osteoporosis, pro-fertility, anti-radiation, anti-Alzheimer disease, anti-rheumatoid, anti-fatigue, anti-aging, cardiovascularprotective, anti-oxidation, immune-regulatory, and anti-inflammatory activities. Pharmacokinetic studies have demonstrated that the main components of MO including monotropein and deacetyl asperulosidic acid are distributed in various organs and tissues. The investigation on acute toxicity and genotoxicity indicated that MO is nontoxic. There have no reports on significant adverse effect at a normal dose in clinical application, but MO at dose of more than 1000mg/kg may cause irritability, insomnia and unpleasant sensations in individual cases. CONCLUSION: MO has emerged as a good source of traditional medicines. Some uses of this plant in traditional medicines have been validated by pharmacological investigations. However, the molecular mechanism, structure-activity relationship, and potential synergistic and antagonistic effects of its multi-components such as polysaccharides, oligosaccharides, anthraquinones and iridoid glycosides need to be further elucidated, and the structural feature of polysaccharides also need to be further clarified. Sophisticated analytical technologies should be developed to comprehensively evaluate the quality of MO based on HPLC-fingerprint and content determination of the active constituents, knowing that these investigations will help further utilize this plant.