ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. is used in traditional Chinese medicine for the treatment of various diseases, including bacterial infections and inflammation. As a rich source of phenolic compounds, the plant is an object of many phytochemical and pharmacological studies. AIM OF THE STUDY: The aim of the study was to isolate and evaluate possible parallel antiviral, antibacterial, and anti-inflammatory activities of phenolic mulberry compounds. MATERIALS AND METHODS: Extensive chromatographic separation of mulberry root bark extract and in vitro biological screening of 26 constituents identified promising candidates for further pharmacological research. Selected compounds were screened for anti-infective and anti-inflammatory activities. Antiviral activity was determined by the plaque number reduction assay and by the titer reduction assay, antibacterial using broth microdilution method, and anti-inflammatory activity using COX Colorimetric inhibitor screening assay kit. One compound was evaluated in vivo in carrageenan-induced paw-edema in mice. RESULTS: Five prenylated compounds 1, 2, 8, 9, and 11, together with a simple phenolic ester 13, exhibited inhibitory activity against the replication of herpes simplex virus 1 (HSV-1) or herpes simplex virus 2 (HSV-2), with IC50 values ranging from 0.64 to 1.93 μg/mL, and EC50 values 0.93 and 1.61 μg/mL. Molecular docking studies demonstrated the effects of the active compounds by targeting HSV-1 DNA polymerase and HSV-2 protease. In antibacterial assay, compounds 1, 4, 11, and 17 diminished the growth of all of the Gram-positive strains tested, with MIC values of 1-16 μg/mL. The anti-inflammatory ability of several compounds to inhibit cyclooxygenase 2 (COX-2) was tested in vitro, and compound 16 displayed greater activity than the indomethacin, positive control. Mulberrofuran B (11) showed anti-inflammatory activity in vivo against carrageenan-induced paw-edema in mice. CONCLUSIONS: Experimental investigation showed promising antiviral, antibacterial, and/or anti-inflammatory activities of the phenolic mulberry constituents, often with multiple inhibitory effects that might be used as a potential source of new medicine.
- Klíčová slova
- Anti-inflammatory, Antibacterial, Antiviral, Docking, Mulberry, Phenolic,
- MeSH
- buněčné linie MeSH
- diabetes mellitus farmakoterapie metabolismus MeSH
- glukosa metabolismus MeSH
- glykogen metabolismus MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- inzulinová rezistence MeSH
- játra účinky léků metabolismus MeSH
- kosterní svaly účinky léků metabolismus MeSH
- krysa rodu Rattus MeSH
- listy rostlin MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- Morus * MeSH
- myši MeSH
- proteinkinasy aktivované AMP metabolismus MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rostlinné extrakty farmakologie terapeutické užití MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- glukosa MeSH
- glykogen MeSH
- hypoglykemika MeSH
- proteinkinasy aktivované AMP MeSH
- reaktivní formy kyslíku MeSH
- rostlinné extrakty MeSH
This review deals with cytotoxic and antiproliferative activity of fifty seven prenylated phenols isolated from Morus alba. Prenyl side chain, which can be variously modified, increases lipophilicity of the substances, thereby improving their penetration through biological membranes and thus results in an increased bioavailability. The objective was to describe the relationship between structure of the prenylated phenols and their cytotoxic effect and to clarify various mechanisms by which cytotoxic prenylated phenols induce apoptosis. The conclusions showed that the cytotoxicity of the substances increases with increasing number of the prenyl side chains and ketal groups. Conversely, modification of the prenyl side chain, such as hydroxylation, reduces cytotoxicity. The cytotoxic activity is also influenced by the presence of prenyl and hydroxyl groups at specific positions.
- Klíčová slova
- <i>Morus alba</i>, antiproliferative activity, cytotoxicity, prenylated phenols,
- MeSH
- cytotoxiny izolace a purifikace farmakologie MeSH
- fenoly izolace a purifikace farmakologie MeSH
- fytogenní protinádorové látky izolace a purifikace farmakologie MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- prenylace MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cytotoxiny MeSH
- fenoly MeSH
- fytogenní protinádorové látky MeSH
A water-soluble polysaccharide JS-MP-1 was isolated from Korean mulberry fruits Oddi (Morus alba L.). Sugar linkage analysis and NMR data confirmed that it is a rhamnogalacturonan type I (RG I) polymer carrying arabinan and arabinogalactan (AG II) side chains. JS-MP-1 reduced dose-dependently the viability of 3T3-L1 pre-adipocyte cells, significantly stimulated the cleavage of caspases 9 and 3 and poly (ADP-ribose) polymerase (PARP) and decreased the ratio of Bcl-2 to Bax expression level that led to mitochondrial dysfunction and apoptosis in pre-adipocyte cells. The apoptotic death was mediated by stimulation of MAPKs (ERK and p38) signalling pathway. These results suggest that JS-MP-1 is able to reduce the number of fat cells and the mass of adipose tissue via inhibition of pre-adipocyte proliferation and thus JS-MP-1 itself or a crude aqueous Oddi extract containing this polysaccharide can be used as functional ingredient of health-beneficial food supplements for the treatment or prevention of obesity disorders.
- Klíčová slova
- Apoptosis, Mulberry fruit, Pectic polysaccharide, Pre-adipocytes, Structure,
- MeSH
- aktivace enzymů účinky léků MeSH
- apoptóza účinky léků MeSH
- buňky 3T3-L1 MeSH
- buňky 3T3 MeSH
- látky proti obezitě chemie izolace a purifikace MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- Morus chemie MeSH
- myši MeSH
- obezita farmakoterapie MeSH
- ovoce chemie MeSH
- pektiny izolace a purifikace MeSH
- polysacharidy izolace a purifikace farmakologie MeSH
- proliferace buněk účinky léků MeSH
- regulace genové exprese enzymů účinky léků MeSH
- tukové buňky cytologie účinky léků MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- látky proti obezitě MeSH
- mitogenem aktivované proteinkinasy MeSH
- pektiny MeSH
- polysacharidy MeSH
Chromatographic separation of root extracts of Morus alba and M. nigra led to the identification of the 2-arylbenzofurans moracin C (1), mulberrofuran Y (2), and mulberrofuran H (3), and the prenylated flavonoids kuwanon E (4), kuwanon C (5), sanggenon H (6), cudraflavone B (7), and morusinol (8), and the Diels-Alder adducts soroceal (9), and sanggenon E (10). The cytotoxicity and their antiphlogistic activity, determined as the attenuation of the secretion of TNF-α and IL-1β and the inhibition of NF-κB nuclear translocation in LPS-stimulated macrophages, were evaluated for compounds 1-10.
- MeSH
- antiflogistika farmakologie MeSH
- benzofurany chemie izolace a purifikace farmakologie MeSH
- benzopyrany chemie izolace a purifikace farmakologie MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- kůra rostlin chemie MeSH
- lidé MeSH
- lipopolysacharidy farmakologie MeSH
- makrofágy účinky léků MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- myši MeSH
- NF-kappa B účinky léků MeSH
- prenylace MeSH
- TNF-alfa farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antiflogistika MeSH
- benzofurany MeSH
- benzopyrany MeSH
- cudraflavone B MeSH Prohlížeč
- flavonoidy MeSH
- lipopolysacharidy MeSH
- morusinol MeSH Prohlížeč
- NF-kappa B MeSH
- TNF-alfa MeSH
Dry matter, organic acids, ascorbic acid, minerals (nitrogen, phosphorus, potassium, calcium, magnesium, sodium) and polyphenolic profile of a number of non-traditional fruit species and their genotypes, namely blue honeysuckle (Lonicera spp.), Saskatoon berry (Amelanchier alnifolia), black mulberry (Morus nigra), Tomentosa cherry (Prunus tomentosa Thunb.) and jostaberry (Ribes nigrum x Grossularia uva-crispa) were investigated. The results showed that Lonicera genotypes displayed high levels of ascorbic acid and they were rich in minerals, with the cultivar ‘Amfora’ achieving the leading position in nitrogen, phosphorus and potassium content among all lesser known fruit species. Amelanchier cultivars represented a valuable source of ascorbic acid and calcium, ‘Tišňovský’ and ‘Smoky’ together with Morus nigra ‘Jugoslavska’ accumulated the highest level of examined polyphenolic compounds. Regular consumption of studied less common fruit species can bring health benefits so they can represent a high potential value for fruit growers and in addition they can be utilised as functional foods.
- MeSH
- genotyp MeSH
- kyseliny karboxylové analýza izolace a purifikace MeSH
- kyseliny nekarboxylové analýza izolace a purifikace MeSH
- Lonicera chemie MeSH
- minerály analýza izolace a purifikace MeSH
- Morus chemie MeSH
- nutriční hodnota * MeSH
- ovoce chemie MeSH
- polyfenoly analýza izolace a purifikace MeSH
- Ribes chemie MeSH
- Rosaceae chemie MeSH
- rostlinné extrakty analýza izolace a purifikace MeSH
- slivoň chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Geografické názvy
- Česká republika MeSH
- Názvy látek
- kyseliny karboxylové MeSH
- kyseliny nekarboxylové MeSH
- minerály MeSH
- polyfenoly MeSH
- rostlinné extrakty MeSH
Cudraflavone B (1) is a prenylated flavonoid found in large amounts in the roots of Morus alba, a plant used as a herbal remedy for its reputed anti-inflammatory properties. The present study shows that this compound causes a significant inhibition of inflammatory mediators in selected in vitro models. Thus, 1 was identified as a potent inhibitor of tumor necrosis factor α (TNFα) gene expression and secretion by blocking the translocation of nuclear factor κB (NF-κB) from the cytoplasm to the nucleus in macrophages derived from a THP-1 human monocyte cell line. The NF-κB activity reduction resulted in the inhibition of cyclooxygenase 2 (COX-2) gene expression. Compound 1 acts as a COX-2 and COX-1 inhibitor with higher selectivity toward COX-2 than indomethacin. Pretreatment of cells by 1 shifted the peak in an regulatory gene zinc-finger protein 36 (ZFP36) expression assay. This natural product has noticeable anti-inflammatory properties, suggesting that 1 potentially could be used for development as a nonsteroidal anti-inflammatory drug lead.
- MeSH
- aktiny účinky léků MeSH
- antiflogistika nesteroidní chemie izolace a purifikace farmakologie MeSH
- cyklooxygenasa 1 účinky léků MeSH
- flavonoidy chemie izolace a purifikace farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemie izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- lidé MeSH
- makrofágy účinky léků MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- NF-kappa B antagonisté a inhibitory MeSH
- TNF-alfa antagonisté a inhibitory genetika MeSH
- tristetraprolin účinky léků genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- aktiny MeSH
- antiflogistika nesteroidní MeSH
- cudraflavone B MeSH Prohlížeč
- cyklooxygenasa 1 MeSH
- flavonoidy MeSH
- inhibitory cyklooxygenasy 2 MeSH
- NF-kappa B MeSH
- PTGS1 protein, human MeSH Prohlížeč
- TNF-alfa MeSH
- tristetraprolin MeSH
- ZFP36 protein, human MeSH Prohlížeč
Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed.
- MeSH
- apoptóza účinky léků MeSH
- fibroblasty účinky léků MeSH
- flavanony chemie izolace a purifikace farmakologie MeSH
- fytogenní protinádorové látky chemie izolace a purifikace farmakologie MeSH
- kořeny rostlin chemie MeSH
- léčivé rostliny chemie MeSH
- lidé MeSH
- Magnoliopsida chemie MeSH
- molekulární struktura MeSH
- Morus chemie MeSH
- nukleární magnetická rezonance biomolekulární MeSH
- ovoce chemie MeSH
- screeningové testy protinádorových léčiv MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Turecko MeSH
- Názvy látek
- flavanony MeSH
- fytogenní protinádorové látky MeSH
- naringenin MeSH Prohlížeč
