New flavan trimer from Daemonorops draco as osteoclastogenesis inhibitor.

Dragon's blood is a red resin obtained from different plants and is considered highly efficacious and used in medicine owing its wound healing function. Two new compounds (7 and 8) were isolated from the dragon's blood of Daemonorops draco fruits, along with eight known compounds (1-6, 9, and 10). Their structures, including their absolute configurations, were elucidated by nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electronic circular dichroism (ECD) analysis. According to the spectroscopic data, 8 was determined to be a quinone methide derivative of flavan and 7 was deduced to be a flavan trimer. All compounds were evaluated for their anti-osteoclastogenesis activity, compound 1 and 7 exhibited anti-osteoclastogenesis activity with IC50 values of 31.3 and 36.8 µM, respectively.

Protein aggregation model to explain the bioactivity of condensed tannins.

Tannins are involved in the taste of foods and multi bioactivity of traditional herbal medicines. The characteristics of tannins are believed to derive from their connectivity with proteins. However, the mode of interaction between proteins and tannins is not yet understood because of the complexity of the tannin structure. Then this study aimed to elucidate the detail binding mode of tannin and protein by the 1H-15N HSQC NMR method using the 15N-labeled MMP-1that have not been used so far. The HSQC results suggested cross-link sites between MMP-1s, which cause protein aggregation and inhibit MMP-1 activity. This study presents the first 3D protein aggregation model of condensed tannins, which is important for understanding the bioactivity of polyphenols. Furthermore, it can broaden the understanding of the range of interactions between other proteins and polyphenols.

Arnica montana L. extract containing 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin accelerates growth and differentiation of human subcutaneous preadipocytes and leads volumizing of skin.

OBJECTIVE: An important factor in the aging of the face is a reduction in the volume of adipose tissue. This reduction in adipose tissue contributes to decreased skin elasticity, which is also part of the aging process. Overall, these lead to wrinkle formation. Fat injection is a common means of addressing this issue and is used to reduce the effects of aging on the face and to increase the fullness of the lips and breasts. However, fat injection is an invasive surgical procedure. This study aimed to discover novel cosmetic ingredients that increase the volume of subcutaneous (pre)adipocytes to create the appearance of more youthful skin. METHODS: We focused on the number of subcutaneous preadipocytes and the accumulation of lipid droplets. To discover natural ingredients that increase both of these, extracts of 380 natural products were prepared and screened for their effects on both growth and differentiation (i.e., lipid droplet accumulation) of human subcutaneous preadipocytes. One extract was found to have the desired effects, and this was further studied to determine the active compounds. We then evaluated its efficacy in a human clinical study. RESULTS: We found that Arnica montana L. flower extract (AFE) accelerates both the growth and the differentiation of human subcutaneous preadipocytes. AFE was found to significantly increase the volume of adipocyte spheroids. The active compounds 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin were found to be responsible for the effects of AFE on preadipocytes. In a human clinical study, gels containing 1% AFE successfully enhanced the volume of the lips and face with reduction of wrinkles with no adverse reactions. CONCLUSION: This is the first report to demonstrate that AFE and the included compounds, 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin, act on preadipocytes. AFE would be ideal for use in products that plump the face to reduce wrinkles and create a more youthful appearance.

OBJECTIF: Un facteur important du vieillissement du visage réside dans la réduction du volume du tissu adipeux. Cette réduction du tissu adipeux contribue à une diminution de l'élasticité de la peau qui fait également partie du processus de vieillissement. Globalement, ces facteurs induisent la formation des rides. L'injection de graisse est un moyen courant pour remédier à ce problème et sert à réduire les effets du vieillissement sur le visage et à augmenter la plénitude des lèvres et des seins. Cependant, l'injection de graisse est une intervention chirurgicale invasive. Cette étude visait à découvrir des ingrédients cosmétiques innovants qui augmentent le volume des (pré)adipocytes sous-cutanés pour créer l'apparence d'une peau plus jeune. MÉTHODES: Nous avons mis l'accent sur le nombre de préadipocytes sous-cutanés et sur l'accumulation de gouttelettes lipidiques. Pour découvrir des ingrédients naturels qui augmentent ces deux facteurs, des extraits de 380 produits naturels ont été préparés et analysés en vue de la détermination de leurs effets sur la croissance et la différenciation (c'est-à-dire l'accumulation de gouttelettes lipidiques) des préadipocytes humains sous-cutanés. Un extrait s'est avéré avoir les effets escomptés et il a fait l'objet d'études approfondies visant à déterminer les composés actifs. Nous avons ensuite évalué son efficacité dans une étude clinique chez l'homme. RÉSULTATS: Nous avons découvert que l'extrait de fleur de l'Arnica montana L. (AFE) accélère à la fois la croissance et la différenciation des préadipocytes humains sous-cutanés. L'AFE s'est avéré augmenter considérablement le volume des sphéroïdes des adipocytes. Les composés actifs 6-Ométhacryloyl-hélénaline et 6-O-isobutyryl-hélénaline se sont avérés responsables des effets de l'AFE sur les préadipocytes. Dans une étude clinique chez l'homme, des gels contenant 1 % d'AFE ont permis d'améliorer le volume des lèvres et du visage avec une réduction des rides sans effets indésirables. CONCLUSION: Il s'agit du premier rapport démontrant que l'AFE et les composés inclus, 6-O-méthacryloyl-hélénaline et 6-O-isobutyryl-hélénaline, agissent sur les préadipocytes. L'AFE serait idéal pour les produits qui repulpent le visage afin de réduire les rides et de donner un aspect rajeuni.

Ellagitannins from Rosa roxburghii suppress poly(I:C)-induced IL-8 production in human keratinocytes.

The anti-inflammatory effects of a 50% aqueous extract of Rosa roxburghii fruit (RRFE) and two ellagitannins (strictinin and casuarictin) isolated from the RRFE were evaluated in a cell model of skin inflammation induced by self-RNA released from epidermal cells damaged by UV ray (UVR) irradiation. The RRFE inhibited interleukin-8 (IL-8) mRNA expression in normal human epidermal keratinocytes (NHEKs) stimulated with polyinosinic:polycytidylic acid (poly(I:C)), a ligand of toll-like receptor-3 (TLR-3). The plant-derived anti-inflammatory agents, dipotassium glycyrrhizinate (GK2) and allantoin, had no influence on the IL-8 expression. The purified compounds, strictinin and casuarictin, inhibited the IL-8 mRNA expression and IL-8 release induced in NHEKs by poly(I:C). These ellagitannins were thus found to be responsible for the biological activity exhibited by the RRFE. This study demonstrates that RRFE and isolated RRFE compounds show promise as ingredients for products formulated to improve skin disorders induced by UVR irradiation.

6-Paradol and its glucoside improve memory disorder in mice.

In this study, the effects of 6-paradol (6P) and 6-paradol-ß-glucoside (6PG) on neuritogenesis were investigated using PC12 cells. Treatment with 200 µM 6P or 6PG and nerve growth factor (NGF) (5 ng mL-1) increased the number of elongated dendritic cells 8.7 and 5.4 times, respectively, compared to that with NGF (5 ng mL-1) treatment alone. 6P and 6PG did not stimulate the phosphorylation of extracellular regulated protein kinases (ERK)1/2 and cAMP response element-binding protein (CREB) in the tropomyosin receptor kinase A (TrkA) pathway as their activities were suppressed by the pathway inhibitor, k252a. 6P enhanced Ca2+ influx into the cells, whereas 6PG had no effect on Ca2+ influx, although it stimulated PC12 cell differentiation. High-performance liquid chromatography (HPLC) analysis of 6PG in PC12 culture medium suggested that 6PG was deglycosylated to generate 6P, which exhibited the effect. Furthermore, the bioactivities of 6P and 6PG were investigated in mice, and the results revealed that they ameliorated short-term memory loss in animals during behavioral testing.

Garcinoic Acids and a Benzophenone Derivative from the Seeds of Garcinia kola and Their Antibacterial Activities against Oral Bacterial Pathogenic Organisms.

In this study, three new garcinoic acid dimers, δ,δ-bigarcinoic acid (1), δ,δ-bi-O-garcinoic acid (2), and γ,δ-bi-O-garcinoic acid (3), and a new benzophenone derivative, (8E)-4-geranyl-3,5-dihydroxybenzophenone (4), as well as seven known compounds (5-11) were isolated from the seeds of Garcinia kola. The structures of the new compounds were elucidated using MALDI-TOF-MS and spectroscopic data, including 1D and 2D NMR and electronic circular dichroism spectra. All of the isolated compounds were evaluated for their antimicrobial activity against two oral pathogens, Porphyromonas gingivalis and Streptococcus sobrinus. Among them, 4 and δ-garcinoic acid (6) exhibited antimicrobial activity against both of these microorganisms (MICs of 31.3-62.5 µM for P. gingivalis and 15.6-31.3 µM for S. sobrinus). These results indicate that some chemical constituents in G. kola seeds have potential application in the prevention of oral diseases.

A review on osteoclast diseases and osteoclastogenesis inhibitors recently developed from natural resources.

Natural products have been investigated as potential candidates of novel therapeutics and play a crucial role in advanced medicinal drugs. Natural resources, including local medicinal plants (especially folk medicinal plants), animals, bacteria, and fungi have been used for more than a century, and are precious gifts from nature, providing potential medicines with high safety. Osteoclast-related diseases, such as osteoporosis, rheumatoid arthritis, Paget's disease, osteoclastoma, and periprosthetic osteolysis, are currently the most common reasons for bone inflammation, pain and fractures, resulting in low quality of life. However, the curative effects of current therapeutic drugs for these osteoclast-related diseases are limited, and long-term treatment is needed. Further, in severe cases, surgical treatments are necessary, which may cause unaffordable expenses and subsequent influences such as neuralgia, mental stress, and even development of cancer. Thus, safer inhibitors and potential drugs with enhanced curative effects and quick relief are needed to treat patients with osteoclast diseases. This review aims to introduce the main osteoclast-related diseases and some of the recently developed naturally sourced inhibitors against osteoclastogenesis, also it is desired to attract people's attention on using widely available natural resources for the evolution of new types of osteoclast inhibitors with minimal or no side-effects upon long-term treatments.

Identification and structure-activity relationship (SAR) of chemical constituents from Daemonorops draco (Willd.) Blume and selected commercial flavonoids on anti-osteoclastogenesis activity.

Osteoclastogenesis-related bone diseases including osteoporosis, rheumatoid arthritis, Paget's disease and periodontitis are worldwide occurred and cause severe health problems including bone fracture and bone cancer. However, A few studies have shown that Daemonorops draco (Willd.) Blume may decrease bone destruction and relieve bone cancer pain. In this research, we isolated and purified four known and two novel compounds from D. draco and investigated their anti-osteoclastogenesis activity using RAW264.7 cells. Among them, com.1 exhibited the most effective inhibitory activity on osteoclastogenesis with 78% inhibition at 10 µM and identified to be a novel natural flavan; and com.2 displayed a bit slighter inhibition (50% at 10 µM), indicating that the methylation of 7-hydroxyl group increased the anti-osteoclastogenesis activity. Moreover, nineteen commercial flavonoids were also performed in this study to investigate their inhibitory activity on osteoclastogenesis, and furtherly develop the SAR profile in flavonoid skeleton combined with the information of isolated compounds. Interestingly, the absence of substituents in B-ring and (3R)-hydroxyl group seems to play a crucial role in increasing anti-osteoclastogenesis activity.

Identification of vanilloid compounds in grains of paradise and their effects on sympathetic nerve activity.

BACKGROUND: Grains of paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. Anti-obesity effect of GP intake was demonstrated in a previous report. Aim of the present study was to isolate some compounds in GP and clarify the anti-obesity mechanism. RESULTS: Ten vanilloid compounds were isolated. Among them, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol and 6-shogaol were identified as the major constituents in GP extract. Moreover, the extract and 6-gingerol, which is one of the principal components of GP extract, were orally administered to rats to investigate the effect on sympathetic nerve activity (SNA) in brown adipose tissue (BAT). The injection of GP extract and 6-gingerol decreased BAT-SNA, whereas capsaicin, which is a major component of chili pepper, activates the sympathetic nervous system. CONCLUSION: This study suggested that GP extract and 6-gingerol were largely unrelated to the anti-obesity effect by the activation of interscapular BAT-SNA and had a different anti-obesity mechanism to capsaicin. © 2018 Society of Chemical Industry.

Methylquercetins stimulate melanin biosynthesis in a three-dimensional skin model.

In a previous study, we found that both synthetic 3-O-methylquercetin (3MQ) and 3,4',7-O-trimethylquercetin (34'7TMQ) increased extracellular melanin content. 34'7TMQ increased the activity of melanogenic enzymes by stimulating the p38 pathway and the expression of microphthalmia-associated transcription factor (MITF). In contrast, 3MQ increased the activity of melanogenic enzymes without the involvement of MITF, which suggests that 3MQ inhibits the degradation of melanogenic enzymes. In the present study, we investigated the effects of 3MQ and 34'7TMQ on melanogenesis in normal human melanocytes and using a commercial three-dimensional (3D) skin model system. Both 3MQ and 34'7TMQ elongated the dendrites of normal human melanocytes from a Caucasian donor, but did not stimulate melanogenesis in the melanocytes. In the 3D skin model, which included melanocytes from an Asian donor, 3MQ and 34'7TMQ increased and elongated the melanocytes and showed a tendency to stimulate melanogenesis. These results suggest that 3MQ and 34'7TMQ could be put to practical use in skin care products and agents aimed at preventing hair graying.

Melanogenesis inhibitory activity of components from Salam leaf (Syzygium polyanthum) extract.

In order to identify a novel whitening agent, the methanol extract of S. polyanthum leaf was focused on by the screening test using nine Indonesian medicinal plants for the inhibition of melanogenesis and tyrosinase activity in B16 melanoma cells. Three novel compounds [(1) 1-(2,3,5-trihydroxy-4-methylphenyl)hexane-1-one, (2) 1-(2,3,5-trihydroxy methylphenyl)octane-1-one, and (3) (4E)-1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one and one known compound [(4) 1-(2,3,5-trihydroxy-4-methylphenyl)decan-1-one were isolated from the methanol extract. Our study demonstrated that S. polyanthum leaf methanol extract at 25-200 µg/mL decreased extracellular melanin formation ca. 20-80%, with high cell viability. Compounds 1-4 were found to be active in melanogenesis and tyrosinase inhibition. Compound 3 was the most active against tyrosinase activity (83.98 µM), particularly when L-tyrosine was the substrate. Compounds 1-4 significantly diminished extracellular melanin formation in B16 melanoma cells (> 80%), with high cell viability. Thus, our study suggested that compounds 1-4 isolated from the methanol extract of S. polyanthum leaf play important roles in decreasing extracellular melanogenesis and inhibiting tyrosinase.

Anti-caries activity of selected Sudanese medicinal plants with emphasis on Terminalia laxiflora

Abstract In Sudan, some medicinal plants, such as Acacia seyal, Calotropis procera and Balanites aegyptiaca have been used to prevent or treat oral health problems. The stem and stem bark of Terminalia laxiflora Engl., Combretaceae, are used as antiseptics for mouthwash to prevent gingivitis and thrush in Africa. Methanol and 50% hydroethanolic extracts of 25 plants that are used in traditional Sudanese medicine for several diseases and cavity disorders were screened for anti-cavity activities. T. laxiflora methanolic wood extracts, which exhibited such activity, were investigated. The crude extracts were assayed for their antimicrobial activities against Streptococcus sobrinus in terms of minimum inhibitory concentration and glucosyltransferase inhibition. The active extract of T. laxiflora wood was subsequently fractionated by different chromatographic techniques. Isolated compounds were identified by spectroscopic methods and assessed for S. sobrinus and glucosyltransferase inhibitory effects. Methanolic extracts of Terminalia brownii (bark), T. laxiflora (wood), A. seyal (bark), Persicaria glabra (leaves) and Tamarix nilotica (stem) showed good activities against both S. sobrinus and glucosyltransferase (MIC ≤ 1 mg/ml, IC50 values <50 µg/ml). Over all plant extracts, T. laxiflora demonstrated the good combined activities (MIC 0.5 mg/ml, glucosyltransferase, IC50 10.3 µg/ml); therefore, its methanolic wood extracts were selected for further phytochemical studies. Four constituents were isolated by chromatographic techniques and identified by spectroscopic techniques. Pharmacological evaluation of the obtained compounds showed that flavogallonic acid dilactone had comparatively good antibacterial activity. In the glucosyltransferase inhibitory test, terchebulin displayed potent activity with an IC50 of 7.5 µM. The screening presented in this study showed that methanol extracts of T. laxiflora wood possessed promising anti-cavity effects.

Extracellular melanogenesis inhibitory activity and the structure-activity relationships of ugonins from Helminthostachys zeylanica roots.

Ugonin J, K, and L, which are luteolin derivatives, were isolated from Helminthostachys zeylanica roots by a series of chromatographic separations of a 50% ethanol/water extract. They were identified using nuclear magnetic resonance (NMR), ultraviolet (UV) spectra, and ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC-TOF-MS). In this study, the intra and extracellular melanogenic activity of the ugonins were determined using B16 melanoma cells. The results showed that ugonin J at 12.5, 25, and 50µM reduced extracellular melanin contents to 75, 16, and 14%, respectively, compared to the control. This indicates that ugonin J showed a stronger activity than arbutin, used as the positive control. Moreover, ugonin K showed a more potent inhibition with 19, 8, and 9% extracellular melanin reduction at the same concentrations, than that shown by ugonin J. In contrast, ugonin L did not inhibit intra- or extracellular melanogenic activity. Furthermore, in order to investigate the structure-activity relationships of the ugonins, the intra- and extracellular melanogenic activity of luteolin, methylluteolin, quercetin, eriodictyol, apigenin, and chrysin were determined. Consequently, it was suggested that the catechol and flavone skeleton of ugonin K is essential for the extracellular melanogenic inhibitory activity, and the low polarity substituent groups on the A ring of ugonin K may increase the activity.

Novel quercetin glucosides from Helminthostachys zeylanica root and acceleratory activity of melanin biosynthesis.

Two novel quercetin glucosides, namely 4'-O-ß-D-glucopyranosyl-quercetin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranoside (compound 1) and 4'-O-ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranosyl-quercetin-3-O-ß-D-glucopyranosyl-(1→4)-ß-D-glucopyranoside (compound 2), were isolated from Helminthostachys zeylanica root 50 % EtOH extract. Structural analysis of isolated compounds was achieved mainly by 600 MHz and 800 MHz NMR, UPLC-TOFMS and GC-MS. Of the two quercetin glucosides, compound 1 showed a high melanogenic acceleratory effect, 2.7 times higher than control, at 10 µM concentration in murine B16 melanoma cells, with no cytotoxic effect.