Two new triterpenoid fatty acid esters from Schefflera barteri Harms (Araliaceae)§.

Two new fatty acid esters of triterpenoids (1-2) together with eleven known compounds (3-13) were obtained after investigation of the CH2Cl2-MeOH (1:1) crude extract from the leaves of Schefflera barteri Harms. All these compounds (1-13) were isolated for the first time from this plant among which compounds 3, 4, 6 and 9-13 were also isolated from the genus Schefflera for the first time. The structures of the isolated compounds were elucidated by analyses of their spectroscopic data (1D and 2D NMR, and MS). The antibacterial and cytotoxic activities of crude extracts, fractions and compounds (1, 2, 5, 6, 8 and 9) were investigated against both Gram-negative and Gram-positive bacteria strains as well as on human cervix carcinoma and colon adenocarcinoma cancer cell lines, respectively. They showed weak to significant activity towards the strains and malignant cells used.

Kinetic Study on Chlorophyll and Antioxidant Activity from Polyscias fruticosa (L.) Harms Leaves via Microwave-Assisted Extraction.

Polyscias fruticosa (L.) leaves contain significant bioactive compounds with high antioxidant activity such as chlorophylls, total polyphenols, etc. but these have still been underutilized. In this study, the kinetics of chlorophyll and antioxidant activity extraction from P. fruticosa leaves by microwave-assisted extraction (MAE) were investigated. Microwave power was 300, 450, or 600 (W); the ratio of material/solvent varied from 1:40 to 1:80 (g/mL). In this study, the second-order kinetic model successfully predicted the change of chlorophyll and antioxidant activity during MAE. The increase of microwave power or/and the solvent amount increased saturated extraction efficiency and the extraction rate constant. However, the saturated concentration of chlorophyll and antioxidant activity increased with the increment of microwave power and the decrease in solvent amount.

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice.

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg-1∙d-1 had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg-1∙d-1. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.

Polyscias filicifolia (Araliaceae) Hairy Roots with Antigenotoxic and Anti-Photogenotoxic Activity.

Hairy root cultures are considered as a valuable source of bioactive phytoconstituents with expanding applicability for their production. In the present study, hairy root cultures of Polyscias filicifolia (Araliaceae), a traditional Southeast Asian medicinal plant, were established. The transformation with Agrobacterium rhizogenes ATCC 15834 allowed to obtain 15 root lines. The K-1 line, demonstrating the highest growth capabilities, was subjected to further investigations. To enhance the biosynthetic potential of hairy roots, methyl jasmonate elicitation approach was applied (MeJA; at different doses and exposure time), with subsequent transfer of elicited roots to control medium. This strategy resulted in chlorogenic acid production up to 1.59 mg/g dry weight. HPLC-PDA-ESI-MS analysis demonstrated variation in extracts composition and allowed to identify different caffeic and ferulic acid derivatives. Next, cytotoxic, antigenotoxic, and anti-photogenotoxic properties of hairy roots extracts were determined. None of the tested extracts were cytotoxic. In addition, they demonstrated significant antigenotoxic activity with the highest protective potential; up to 52% and 49% of inhibition of induction ratio (IR) induced by the 2-aminoanthracene was revealed for extracts derived from hairy roots elicited for 3 days with 50 µM MeJA and roots elicited for 7 days with 100 µM MeJA and then transferred for 30 days to control medium, respectively. These same extracts exhibited the highest anti-photogenotoxic potential, up to 36% of inhibition of chloropromazine-induced genotoxicity.

The genus Schefflera: A review of traditional uses, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Schefflera is the largest genus in the family Araliaceae, which contains 602 known species indigenous to Asia, Africa, and the southwest Pacific region, several of which are used in traditional medicine. AIM OF THE REVIEW: The review discusses current knowledge of the traditional uses, phytochemistry, and biological activities of Schefflera species, to assess the medicinal potential of this genus. MATERIALS AND METHODS: The literature were explored using the keyword "Schefflera" in SciFinder®, Google Scholar®, and PubMed® databases. The taxonomy of all reported plants was authenticated using "The Plant List". Additional data on traditional uses was obtained from secondary references including books and online resources. RESULTS: Fourteen species were documented as traditional medicines in China, India, Vietnam, Thailand, and Indonesia, specifically to manage rheumatism, pain, and trauma. Other species are used in the treatment of liver disorders, skin conditions, respiratory infections, cancer, diarrhea, malaria, paralysis, and many other conditions. The main phytochemical constituents identified were triterpenoids and saponins, with sesquiterpenes, phenylpropanoids, and lignans. Pharmacological properties of extracts and pure isolated compounds included analgesic, anti-inflammatory, anticancer, hypoglycemic, antimicrobial, hepatoprotective, neuroprotective, antimalarial, and antiallergic effects. CONCLUSION: The reported biological activities of Schefflera species support their traditional uses, although the available data, even for medicinal species, was limited. Reports of chemical constituents or biological activities could be found for only about 20 species, but suggest that further investigation of efficacy and safety of the largely unexplored genus Schefflera is necessary.

Dendropanax dentiger (Harms) Merr. root and its major constituents exert therapeutic effect on adjuvant-induced arthritis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The root of Dendropanax dentiger (Harms) Merr. is a pivotal folk Chinese medicine against rheumatoid arthritis (RA) with no scientific validation. AIM OF THE STUDY: This study was conducted to explore the anti-RA effect of the D. dentiger extract on complete Freund's adjuvant-induced arthritis (AIA) in rats and identified its major bio-constituents. MATERIALS AND METHODS: Dendropanax dentiger roots extracts (127.5, 255.0 and 510.0 mg/kg, once daily) were orally at day 7 post-administration adjuvant and lasting for 22 days. The therapeutic effects of D. dentiger roots extract on AIA rats were investigated by body weight growth, arthritis score, thymus and spleen indices, and histopathological analysis. Moreover, the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-4, IL-6, IL-10, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2) were also evaluated. Finally, the major constituents were isolated and identified from D. dentiger roots extract with COX-2 inhibitory and antioxidant activities. RESULTS: Dendropanax dentiger roots extract remarkably alleviated the histological lesions of knee joint, increased body weight growth, decreased arthritis score, and reduced thymus and spleen indices in model rats. In parallel, the levels of RF, CRP, TNF-α, IL-1ß, IL-6, IL-17, COX-2, 5-LOX and MMP-2 were observably downregulated, while the levels of IL-4 and IL-10 were prominently upregulated in D. dentiger roots extract-treated rats. Meanwhile, 14 compounds were isolated and identified from D. dentiger roots extract, and four phenol derivatives (1, 4, 6 and 7) exhibited remarkable COX-2 inhibitory and antioxidant activities. CONCLUSIONS: Dendropanax dentiger roots extract possessed persuasive anti-RA effect may be partly responsible for phenol derivatives via modulation of inflammatory biomarkers, and supports the traditional folk use of D. dentiger in China.

Phytochemical Analysis, Anti-inflammatory, and Antioxidant Activities of Dendropanax dentiger Roots.

Dendropanax dentiger root is a traditional medicinal plant in China and used to treat inflammatory diseases for centuries, but its phytochemical profiling and biological functions are still unknown. Thus, a rapid, efficient, and precise method based on ultra high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) was applied to rapidly analyse the phytochemical profiling of D. dentiger with anti-inflammatory and antioxidant activities in vitro. As a result, a total of 78 chemical compositions, including 15 phenylpropanoids, 15 alkaloids, 14 flavonoids, 14 fatty acids, 7 phenols, 4 steroids, 4 cyclic peptides, 3 terpenoids, and 2 others, were identified or tentatively characterized in the roots of D. dentiger. Moreover, alkaloid and cyclic peptide were reported from D. dentiger for the first time. In addition, the ethanol crude extract of D. dentiger roots exhibited remarkable anti-inflammatory activity against cyclooxygenase- (COX-) 2 inhibitory and antioxidant activities in vitro. This study is the first to explore the phytochemical analysis and COX-2 inhibitory activity of D. dentiger. This study can provide important phytochemical profiles and biological functions for the application of D. dentiger roots as a new source of natural COX-2 inhibitors and antioxidants in pharmaceutical industry.

Melissopalynology and antioxidant properties used to differentiate Schefflera abyssinica and polyfloral honey.

Honey can be categorized as monofloral and polyfloral honey. There is a strong interest in science and commerce, to further differentiate honey. In the present study, Schefflera abyssinica and polyfloral honey from Sheka Forest, Ethiopia was investigated. Botanical origin was determined based on Melissopalynology. Refractive index, moisture, sugars, ash, pH, free acidity, hydroxymethylfurfural, optical density, diastase activity, protein, and color were determined based on the standard method of the international honey commission (IHC) and AOAC. Antioxidant activity and Antioxidant content were determined using UV- visible spectroscopy. The level of pollen dominancy for monofloral honey (Schefflera abyssinica) ranged from 76.2 to 85.8%. The polyfloral honey stuffed with a variety of pollen grain ranged from 2.2% (Coffea arabica) to 23.2% (Schefflera abyssinica). Schefflera abyssinica honey contained more total phenolic compounds (75.08 ± 2.40 mg GAE/100g), and total flavonoids (42.03 ± 1.49 mg QE/100 g), as well as had stronger DPPH (44.43 ± 0.97%) and hydrogen peroxide (78.00 ± 4.82%) scavenging activity. The principal component analysis revealed that Schefflera abyssinica honey associated with the antioxidant properties of total phenolic, total flavonoids, DPPH, and H2O2., which revealed that floral honey sources can essentially differentiated by antioxidant patterns. The higher electrical conductivity (0.42 ± 0.02 mS/cm), ash (0.41 ± 0.05 g/100g), pH (4.01 ± 0.08), optical density (0.26 ± 0.03) and diastase activity (5.21 ± 0.17 Schade units) were recorded in polyfloral honey. Schefflera abyssinica and polyfloral honey satisfy the requirement of national and international standards. The pollen analysis in combination with antioxidant properties distinguishes Schefflera abyssinica from polyfloral honeys.

Bioassay-guided isolation of cyclooxygenase-2 inhibitory and antioxidant phenylpropanoid derivatives from the roots of Dendropanax dentiger.

The root of Dendropanax dentiger (Harms) Merr. is a traditional Chinese medicine that has been used to treat inflammation-related diseases with little scientific validation. In this study, a bioassay-guided phytochemical investigation of D. dentiger led to the isolation of 19 phenylpropanoid derivatives including one new compound (1) and 18 known ones (2-19). Their structures were elucidated by NMR and HRMS as well as comparison with literature data. The ability of cyclooxygenase-2 (COX-2) inhibition and antioxidant of all isolated compounds were measured in vitro. Chlorogenic acid derivatives (14-19) exhibited outstanding COX-2 inhibitory (IC50 = 5.1-93.4 µM) and antioxidant (IC50 = 13.2-31.9 µM) activities. Moreover, the tight structure-activities relationships were proposed. This is the first report on the COX-2 inhibitory activity of phenylpropanoids and D. dentiger.

Antigenotoxic, Anti-photogenotoxic, and Antioxidant Properties of Polyscias filicifolia Shoots Cultivated In Vitro.

Traditional medicinal plants are an important source of active compounds with potential antimutagenic activity. Polyscias filicifolia Bailey (Araliaceae) is a South Asian traditional herb used as an adaptogenic and cardiac drug. Extracts of P. filicifolia contain a wide range of biologically active compounds like phenolic acids and triterpenoid saponins. In the present study. antigenotoxic potential of three naturally occurring phenolic acids and extracts of P. filicifolia growing in vitro with the addition of elicitors was evaluated against direct (4-nitroquinoline-N-oxide (4NQO) and mitomycin C (MMC)) and indirect mutagens (2-aminoanthracene (2AA)). The evaluation was made using a bacterial umu-test. Moreover, the ability to prevent photogenotoxicity induced by chlorpromazine (CPZ) under UVA irradiation was measured. The phytochemical profiling of examined extracts revealed the presence of numerous compounds with the prevelance of chlorogenic, caffeic, and ferulic acid derivatives; however, saponin fractions were also determined. The antioxidant potential of extracts strictly correlated with their composition. The tested extracts exhibited high antigenotoxic activity if the assay was performed with 2AA and metabolic activation. Moreover, the extracts slightly decreased the MMC-induced genotoxicity. However, an increase of the genotoxic effect was observed in the assay performed with 4NQO. In addition, photo-antigenotoxic activity was observed. In our study, phenolic acids exhibited lower activity than the extracts.

Polysciosides J and K, two new oleanane-type triterpenoid saponins from the leaves of Polyscias fruticosa (L.) harms. cultivating in An Giang Province, Viet Nam.

For the first time, the phytochemical constituents of the leaves of Polyscias fruticosa (L.) Harms. cultivating in An Giang Province, Viet Nam were investigated and led to purify two new oleanane-type triterpenoid saponins, named polyscioside J (1) and polyscioside K (2) together with two known saponins, ladyginoside A (3) and chikusetsusaponin IVa (4) using variously chromatographic methods. Saponin (4) was reported for the first time from this species. Their structures were verified by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments and compared with previous literatures.

Triterpenoid saponins with hepatoprotective effects from the fresh leaves of Metapanax delavayi.

The fresh leaves of Metapanax delavayi (Araliaceae) have been used as a common wild vegetable for salad and soup, and also herbal tea by the local people living in its growing areas of Yunnan province, China. Detailed chemical investigation led to the identification of a new triterpenoid saponin, 3-O-α-L-arabinopyranosyl-28-O-ß-D-glucopyranosyl-(1→6)-O-ß-D-glucopyranosyl-3ß-hydroxyolean-12-ene-28,29-dioic acid (1) from the fresh leaves, together with 11 known compounds, including six triterpenoid saponins (2-7), two caffeoylquinic acid derivatives (8-9), and three flavonoid glycosides (10-12). Their structures were determined on the basis of spectroscopic analysis and acidic hydrolysis. Compounds 3-5 and 8-12 were isolated from M. delavayi for the first time. Moreover, the known saponins 3-O-ß-D-xylopyranosyl-3ß-hydroxyolean-12-ene-28,29-dioic acid (3) and yiyeliangwanoside IV (5) exhibited protective effects on HepG2 cells damaged by the alcohol intakes, at a concentration of 1.0 µg/mL. The results indicated M. delavayi is an ideal dietary vegetable and herbal tea with potential hepatoprotective activity.[Formula: see text].

Inhibition of IL-6 expression by lignans and other constituents isolated from Schefflera rubriflora C. J. Tseng & G. Hoo.

Schefflera rubriflora, a plant native to Yunnan Province in China, is often used to treat ailments such as neuropathic pain, tracheitis, and cough. However, the active components imparting these pharmacological effects are largely unexplored. In this study, five novel lignans and three new derivatives of benzoid or pyran were isolated from the leaves and twigs of S. rubriflora. The structures of these compounds were determined by the comprehensive analyses of the 1D and 2D NMR spectra and ESI mass spectra and a comparison of the obtained data with those of the literature data. All the compounds were tested for the inhibition of IL-6 expression. Three of the isolated compounds could inhibit the expression by 52% to 72%.

New Chemical Constituents from the Bark of Dendropanax morbifera Leveille and their Evaluation of Antioxidant Activities.

Four new constituents, as cis-6-oxogeran-4-enyl-10-oxy-O-ß-arabinopyranosyl-4'-O-ß-arabinopyranosyl-2''-octadec-9''',12''',15'''-trienoate (1), geran-3(10)-enyl-1-oxy-O-ß-arabinopyranosyl-4'-O-ß-arabinopyranosyl-2''-octadec-9''',12''',15'''-trienoate (2), geranilan-8-oxy-O-α-d-xylopyranosyl-2'-n-octadec-9'',12'',15''-trienoate (3), 1-cyclohex-2', 5'-dienyl 1-cyclohexylethanol-O-ß-d-xylopyranoside (4), along with six known constituents, guaiacol-O-ß-d-arabinopyaranoside (5), n-tetradecanyl oleate (6), oleyl-O-ß-d-xyloside (7), n-octadec-9,12-dienoyl-O-ß-d-arabinopyranoside (8), linolenyl-O-ß-d-arabinofuranoside (9) andglyceryl-1,3-dipalmito-2-olein (10), were isolated and identified from the Dendropanax morbifera bark. The new structures were established by one-and two-dimensional NMR (and in combination with IR, FAB-MSand HR-ESI-FTMS. The comparative evaluation of antioxidant potential by phosphomolybdenum, DPPH, FRAP and the NO assay of four different compounds (1-4), we have found that the compounds 1 and 2 have power as a natural antioxidant, whereas the compound 3 and 4 exhibited mild activity in comparison to compounds 1 and 2.

Dendropanax morbifera Branch Water Extract Increases the Immunostimulatory Activity of RAW264.7 Macrophages and Primary Mouse Splenocytes.

Polyacetylenes in the bark of Dendropanax morbifera trees have been reported to promote immune cell proliferation and to strengthen the innate immune system. The immunomodulatory potential of D. morbifera branch water extract (DBW) was evaluated by determining its effect on cell viability and the expression of cytokines and immune effector molecules in mouse RAW264.7 macrophages and splenocytes. Production of nitric oxide (NO), inducible nitric oxide synthase (iNOS), and cytokines (interleukin [IL]-1ß, IL-2, and IFN-γ) in RAW264.7 macrophages increased after treatment with DBW. The activation of components of the NF-κB signaling pathway, including the phospho-IκBα and the expression and translocation of p65, a subunit of NF-κB, were also increased in RAW264.7 mouse macrophage cells after treatment with DBW. In addition, when mice were orally administered DBW, splenocyte cytokines and NO production were increased in a dose-dependent manner relative to control-treated mice. Furthermore, natural killer cell activity in DBW-treated mice was determined by lactate dehydrogenase (LDH) release assay. LDH release also increased in response to DBW treatment. Taken together, these results indicate that D. morbifera extract enhances innate immunity by promoting NF-κB signaling, leading to increased expression of proinflammatory cytokines and effector molecules. DBW therefore has potential therapeutic use in the context of immune stimulation.

Study of anti-inflammatory activity of Fatsiphloginum™ (Fatsia japonica) and a new purified triterpene-rich extract of saponins (PS-551) in experimental model of arthritis.

In this study, two extracts from Fatsia japonica-Fatsiphloginum™ (extract of triterpene glycosides containing 45-50 % of fatsiosides (FS)) and purified triterpene-rich extract of saponins with code name PS-551 (PS) were administered in combination with methotrexate (MTX) and in monotherapy to rats suffering adjuvant arthritis (AA). The anti-inflammatory activities of extracts were evaluated as monotherapies in comparison with untreated AA. PS administered in higher dose showed on day 28 effective decrease of hind paw volume (HPV), decreased activity of gamma-glutamyl transferase (GGT) in joints, and also interleukin-17A was decreased significantly on day 14. The higher dose of PS was more effective than both doses of FS. Further, we evaluated the higher doses of PS and FS in combination with MTX. PS improved the effect of MTX in combination more effective than FS (HPV, body weight and activity of GGT in joint). However, FS was more effective in reducing the level of IL-17A on day 14 and activity of GGT in spleen than PS. In conclusion, our study showed that generally FS has higher anti-arthritic activity comparing to PS. Thus, the novel combination of Fatsiphloginum™ and methotrexate could be interesting for future clinical studies in patients suffering auto-immune diseases.

Efficient Extraction of Anti-Inflammatory Active Ingredients from Schefflera octophylla Leaves Using Ionic Liquid-Based Ultrasonic-Assisted Extraction Coupled with HPLC.

Schefflera octophylla (Lour.) Harms, a kind of traditional Chinese medicine (TCM), is commonly used for anti-inflammatory, analgesic, rheumatism, fever, and hemostasis therapy. In our previous studies, two major triterpenoids were isolated and identified from leaves of S. octophylla, and evaluated for their inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide production in RAW264.7 cells; both of them displayed significant anti-inflammatory activities at their noncytotoxic concentrations. Therefore, it is very useful to establish an efficient and green extraction method to isolated the two major triterpenoids from leaves of S. octophylla. In this paper, ionic liquid based ultrasonic-assisted extraction (ILUAE) was successfully applied to extract the two major triterpenoids from leaves of S. octophylla. Four single factors (ionic liquids (ILs) concentration, solid-liquid ratio, centrifugal speed, mesh number), with a greater impact on extraction rate, were selected from a variety of influencing factors, and the optimal conditions were obtained by Box-Behnken response surface methodology (RSM). Under optimal conditions, the total extraction yield and extraction rate of two triterpenoids were 288.03 mg/g and 28.80%, respectively, which was 6.80% higher than that of 70% Ethanol (220 mg/g and 22%, respectively).

Leaf extracts from Dendropanax morbifera Léveille mitigate mercury-induced reduction of spatial memory, as well as cell proliferation, and neuroblast differentiation in rat dentate gyrus.

BACKGROUND: The brain is susceptible to methylmercury toxicity, which causes irreversible damage to neurons and glia and the leaf extract Dendropanax morbifera Léveille (DML) has various biological functions in the nervous system. In this study, we examined the effects of DML on mercury-induced proliferating cells and differentiated neuroblasts. METHODS: Dimethylmercury (5 µg/kg) and galantamine (5 mg/kg) was administered intraperitoneally and/or DML (100 mg/kg) was orally to 7-week-old rats every day for 36 days. One hour after the treatment, novel object recognition test was examined. In addition, spatial probe tests were conducted on the 6th day after 5 days of continuous training in the Morris swim maze. Thereafter, the rats were euthanized for immunohistochemical staining analysis with Ki67 and doublecortin and measurement for acetylcholinesterase (AChE) activity. RESULTS: Dimethylmercury-treated rats showed reduced discrimination index in novel object recognition test and took longer to find the platform than did control group. Compared with dimethylmercury treatment alone, supplementation with DML or galatamine significantly ameliorated the reduction of discrimination index and reduced the time spent to find the platform. In addition, the number of platform crossings was lower in the dimethylmercury-treated group than in controls, while the administration of DML or galantamine significantly increased the number of crossings than did dimethylmercury treatment alone. Proliferating cells and differentiated neuroblasts, assessed by Ki67 and doublecortin immunohistochemical staining was significantly decreased in the dimethylmercury treated group versus controls. Supplementation with DML or galantamine significantly increased the number of proliferating cells and differentiated neuroblasts in the dentate gyrus. In addition, treatment with dimethylmercury significantly increased AChE activity in hippocampal homogenates, while treatment with dimethylmercury+DML or dimethylmercury+galantamine significantly ameliorated this increase. CONCLUSIONS: These results suggest that DML may be a functional food that improves dimethylmercury-induced memory impairment and ameliorates dimethylmercury-induced reduction in proliferating cells and differentiated neuroblasts, and demonstrates corresponding activation of AChE activity in the dentate gyrus.

Schekwanglupaside C, a new lupane saponin from Schefflera kwangsiensis, is a potent activator of sarcoplasmic reticulum Ca2+-ATPase.

Schefflera kwangsiensis Merr. ex H.L. Li (Araliaceae) is a widely used traditional Chinese medicine for pain management in the clinic. In the present study, we isolated a previously undescribed lupane saponin, designated as schekwanglupaside C (Sch C) from the ethanolic extract of S. kwangsiensis. The structure of Sch C was determined by comprehensive spectroscopic and spectrometric analyses and chemical degradation. In primary cultured cortical neurons, Sch C altered the pattern of spontaneous Ca2+ oscillation (SCO) with a slight increase in the frequency of SCO right after addition and a gradual decrease in the frequency and amplitude of SCO, that dynamic change mimicked by an activator of sarcoplasmic reticulum Ca2+-ATPase (SERCA). The IC50 values for Sch C suppression of the frequency and amplitude of SCO were 1.75 and 2.51 µM, respectively. Furthermore, we demonstrated that Sch C is a potent SERCA activator (EC50 = 1.20 µM). Given the pivotal role of SERCA in the progression of neuropathic pain and neurodegenerative diseases, Sch C represents a new drug lead compound to develop the treatment of neuropathic pain and Alzheimer's disease.

Ethanol extract of Polyscias fruticosa leaves suppresses RANKL-mediated osteoclastogenesis in vitro and LPS-induced bone loss in vivo.

BACKGROUND: Many bone-related diseases such as osteoporosis and rheumatoid arthritis are commonly associated with the excessive activity of osteoclasts. Polyscias fruticosa has been used as traditional medicine for the treatment of ischemia and inflammation and also eaten as a salad. However, its effect on the bone related diseases has not been investigated yet. PURPOSE: This study aimed to investigate the effect of ethanol extract of P. fruticosa on RANKL-induced osteoclastogenesis in vitro and LPS-induced bone loss in mouse, and evaluate anti-osteoclastogenic activities of its major constituents. METHODS: BMMs or RAW264.7 cells were treated with ethanol extract from P. fruticose leaves (EEPL), followed by an evaluation of cell viability, RANKL-induced osteoclast differentiation, actin-ring formation, and resorption pits activity. Effects of EEPL on RANKL-induced phosphorylation of MAPKs were evaluated by Western blotting. The expression levels of NFATc1 and c-Fos were evaluated by Western blotting or immunofluorescence assay. The expression levels of osteoclast-specific marker genes were evaluated by Western blotting and reverse transcription-qPCR analysis. A LPS-induced murine bone loss model was used to evaluate the protective effect of EEPL on inflammation-induced bone loss. HPLC analysis was performed to identify the major constituents of EEPL. RESULTS: EEPL significantly inhibited RANKL-induced osteoclast differentiation by decreasing the number of osteoclasts, osteoclast actin-ring formation, and bone resorption. EEPL suppressed RANKL-induced phosphorylation of p38 and JNK MAPKs, as well as the expression of c-Fos and NFATc1. EEPL decreased the expression levels of osteoclast marker genes, including MMP-9, TRAP and CtsK. Mice treated with EEPL significantly protected the mice from LPS-induced osteoclast formation and bone destruction as indicated by micro-CT and histological analysis of femurs. We also identified 3-O-[ß-d-glucopyranosyl-(1→4)-ß-d-glucuronopyranosyl] oleanolic acid 28-O-ß-d-glucopyranosyl ester (1) and quercitrin (3) as the active constituents in EEPL for inhibiting RANKL-induced osteoclast differentiation. CONCLUSION: The results showed that EEPL exerted anti-osteoclastogenic activity in vitro and in vivo by inhibiting RANKL-induced osteoclast differentiation and function, and suggested that EEPL could have beneficial applications for preventing or inhibiting osteoclast-mediated bone diseases.