Acute and subacute toxicological evaluation of the ethanol leaf extract of Morus mesozygia stapf. (Moraceae) in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the Morus mesozygia tree leaf has been used to manage maladies such as peptic ulcer, hyperglycemia, dermatitis, rheumatism, stomach-ache, arthritis, cough, malignancies, and malaria in parts of Africa. AIM OF THE STUDY: The study aimed to evaluate the potential of ethanol leaf extract of Morus mesozygia (EEMm) to induce toxicity by employing both acute and sub-acute oral toxicity experimental models. MATERIAL AND METHODS: The extract's cytotoxicity was studied using brine shrimps (Artemia salina) lethality assay (BSLA), while in the acute toxicity test, male and female mice were administered a single oral dose of EEMm (2000 mg/kg). Male and female Wistar rats received repeated doses of 100 or 500 mg/kg EEMm orally for 28 days in the sub-acute toxicity experiment. The phytochemical analysis of EEMm was done using the HPLC. RESULTS: The BSLA revealed a moderate cytotoxic potential of the extract, with an LC50 of 567.13 ± 0.27 µg/mL. All the animals survived the acute toxicity test, with no significant changes in the relative organ weights, suggesting that LD50 is greater than 2000 mg/kg. The animal weights did not vary significantly in the sub-acute toxicity test neither were the alterations in biochemical and hematological tests pronounced, although the histoarchitectures of the kidney, liver and spleen indicated slight anomalies in the evaluated animals. The HPLC analysis revealed the presence of quercetin, ferulic acid, rutin, caffeic acid, morin and gallic acid. CONCLUSIONS: Ethanol leaf extract of Morus mesozygia demonstrated a safe toxicity profile in rodents, supporting its broad folkloric use in African ethnomedicine.

Cardiac glycosides from Streblus asper with potential antiviral activity.

Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC50 values from 0.19 ± 0.08 to 1.03 ± 0.25 µM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75.

Protective Effects of Cudrania tricuspidata Against Helicobacter pylori-Induced Inflammation in C57BL/6 Mice.

Helicobacter pylori modulates the host inflammatory response, resulting in chronic gastritis, which contributes to gastric cancer pathogenesis. We verified the effect of Cudrania tricuspidata on H. pylori infection by inhibiting H. pylori-induced inflammatory activity. Five-week-old C57BL/6 mice (n = 8) were administered C. tricuspidata leaf extract (10 or 20 mg/kg per day) for 6 weeks. An invasive test (campylobacter-like organism [CLO]) and noninvasive tests (stool antigen test [SAT] and H. pylori antibody enzyme-linked immunosorbent assay) were performed to confirm the eradication of H. pylori. To evaluate the anti-inflammatory effect of C. tricuspidata, pro-inflammatory cytokines levels and inflammation scores were measured in mouse gastric tissue. C. tricuspidata significantly decreased the CLO score and H. pylori immunoglobulin G antibody optical density levels at both 10 and 20 mg/kg per day doses (P < .05). C. tricuspidata decreased the H. pylori antibody levels in a concentration-dependent manner, increased negative responses to SAT by up to 37.5%, and inhibited the pro-inflammatory cytokines interleukin (IL; IL-1ß, IL-6, 1L-8, and tumor necrosis factor alpha). C. tricuspidata also relieved gastric erosions and ulcers and significantly reduced the inflammation score (P < .05). We measured rutin in C. tricuspidata extract as a standard for high-performance liquid chromatography. C. tricuspidata leaf extract showed anti-H. pylori activity through the inhibition of inflammation. Our findings suggest that C. tricuspidata leaf extract is potentially an effective functional food material against H. pylori.

Milicia excelsa (Moraceae) reversed the effects of letrozole-induced aromatase inhibition in rats with polycystic ovary syndrome.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is an endocrinopathy affecting 5-20% of women of childbearing age. There is no single drug for the treatment of PCOS and current therapies have significant side effects. This study evaluated the ability of Milica excelsa to improve PCOS symptoms in rats. METHODS: Induction of PCOS was achieved using letrozole (a reversible aromatase inhibitor; 1 mg/kg; given orally for 21 days). From day 22, PCOS rats received the aqueous extract of M. excelsa roots (14 and 140 mg/kg). Clomiphene citrate (1 mg/kg) was administered to the positive control. The negative and the normal controls received the vehicle (5% DMSO). Treatments were given orally for 7 or 14 days. Vaginal smears were scrutinized daily during the experiment. Body weight was measured hebdomadal. Animals were sacrificed after the two treatment periods for biochemical and histological analyses. RESULTS: Aromatase inhibition caused hyperandrogenism (p<0.001), overweight (p<0.001) and fat accumulation (p<0.001). It also blocked the estrous cycle at the diestrus phase and altered ovarian dynamics as evidenced by the accumulation of cystic (p<0.001) and atretic (p<0.001) follicles. In contrast, M. excelsa induced weight loss (p<0.001), reduction in fat weight (p<0001), and lower serum androgen and LH levels (p<0.001). It also restored the estrous cycle and improved ovarian dynamics by increasing the amount of Graafian follicles (p<0.001) and corpora lutea (p<0.001), and decreasing that of cystic and atretic follicles (p<0.001). CONCLUSIONS: Milica excelsa corrected hyperandrogenism and overweight in PCOS animals, and reduced cyst formation and follicle atresia in their ovaries.

Cytotoxic and Pro-Apoptotic Effects of Leaves Extract of Antiaris africana Engler (Moraceae).

Antiaris africana Engler leaves have been used in Senegalese folk medicine to treat breast cancer. The present study aimed to investigate the anticancer potential of Antiaris africana Engler leaves using several human cancer cell lines. The leaves of Antiaris africana Engler were extracted in parallel with water or 70% ethanol and each extract divided into three parts by successive liquid-liquid extraction with ethyl acetate and butanol. The phytochemical components of the active extract were investigated using ultra-performance liquid chromatography-diode array detector-quadrupole time-of-flight tandem mass spectrometry (UPLC-DAD-QTOF-MS/MS). The cytotoxic and cytostatic effects of each extract, as well as their fractions, were evaluated in vitro via flow and image cytometry on different human cancer phenotypes, such as breast (MCF-7), pancreas (AsPC-1), colon (SW-620) and acute monocytic leukemia (THP-1). Both hydro-alcoholic and aqueous extracts induced strong apoptosis in MCF-7 cells. The water fraction of the hydro-alcoholic extract was found to be the most active, suppressing the cell growth of MCF-7 in a dose-dependent manner. The half maximum effective concentration (EC50) of this fraction was 64.6 ± 13.7 µg/mL for MCF-7, with equivalent values for all tested phenotypes. In parallel, the apoptotic induction by this fraction resulted in a EC50 of 63.5 ± 1.8 µg/mL for MCF-7, with again equivalent values for all other cellular tested phenotypes. Analysis of this fraction by UPLC-DAD-QTOF-MS/MS led to the identification of hydroxycinnamates as major components, one rutin isomer, and three cardiac glycosides previously isolated from seeds and bark of Antiaris africana Engler and described as cytotoxic in human cancer models. These results provide supportive data for the use of Antiaris africana Engler leaves in Senegal.

The Genus Broussonetia: An Updated Review of Phytochemistry, Pharmacology and Applications.

The Broussonetia genus (Moraceae), recognized for its value in many Chinese traditional herbs, mainly includes Broussonetia papyrifera (L.) L'Hér. ex Vent. (BP), Broussonetia kazinoki Siebold (BK), and Broussonetia luzonica (Blanco) Bureau (BL). Hitherto, researchers have found 338 compounds isolated from BP, BK, and BL, which included flavonoids, polyphenols, phenylpropanoids, alkaloids, terpenoids, steroids, and others. Moreover, its active compounds and extracts have exhibited a variety of pharmacological effects such as antitumor, antioxidant, anti-inflammatory, antidiabetic, anti-obesity, antibacterial, and antiviral properties, and its use against skin wrinkles. In this review, the phytochemistry and pharmacology of Broussonetia are updated systematically, after its applications are first summarized. In addition, this review also discusses the limitations of investigations and the potential direction of Broussonetia. This review can help to further understand the phytochemistry, pharmacology, and other applications of Broussonetia, which paves the way for future research.

Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

A Synbiotic Combination of Lactobacillus gasseri 505 and Cudrania tricuspidata Leaf Extract Prevents Stress-Induced Testicular Dysfunction in Mice.

This study investigated the effects of a synbiotic combination (Syn) of Lactobacillus gasseri 505 (505) and Cudrania tricuspidata leaf extract (CT) on the hypothalamic-pituitary-gonadal axis in mice under chronic stress. Unpredictable chronic mild stress (UCMS) significantly increased the serum levels of corticosterone, however, treatment with Syn suppressed UCMS-induced increases. Histopathological analysis of the testes showed that these organs experienced some damage during UCMS, but this was repaired following treatment with Syn. Similarly, the transcription levels of gonadotropin-releasing hormone (GnRH), GnRH receptor, and gonadotropins, moreover, testicular development (i.e., Adam5, Adam29, and Spam1) - and steroidogenesis (i.e., Lhr, Egfr, and StAR) -related genes were significantly downregulated by UCMS. These UCMS-induced changes were inhibited by the administration of Syn, which was confirmed by the results of in situ hybridization analysis. These results suggest that the administration of Syn could attenuate the testicular dysfunctions induced by UCMS.

Molecular networking-guided strategy for the pharmacokinetic study of herbal medicines: Cudrania tricuspidata leaf extracts.

In this study, the pharmacokinetic profiles of the bioactive components in the leaf extract of the medicinal herb, Cudrania tricuspidate, were investigated using an MS/MS-based molecular networking system. To identify the major active components of the C. tricuspidate leaf extract (CLE), HPLC-DAD analysis was conducted with a standard mixture of six flavonoids (rutin, isoquercitrin, nicotiflorin, kaempferol 3-O-glucoside, quercetin, and kaempferol). The unknown peaks were determined via molecular networking analysis using the mass dataset obtained by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). For the subsequent pharmacokinetic study, CLE (1 g/kg) was orally administered to rats, and plasma samples were collected. The product ion mass data of plasma samples using LC-QTOF/MS were obtained and subjected to molecular networking analysis. The resulting molecular networking map indicated that the glucuronide metabolites of quercetin and kaempferol were the major circulating species. Accordingly, quercetin and kaempferol were determined following ß-glucuronidase treatment, and their pharmacokinetic parameters were calculated. These findings indicate that the proposed molecular network-based approaches are potential and efficient methods for the pharmacokinetic study of herbal medicines.

Biological properties of aqueous extract and pyranocoumarins obtained from the bark of Brosimum alicastrum tree.

ETHNOPHARMACOLOGICAL RELEVANCE: Brosimum alicastrum is a tree used in Mexican traditional medicine for the treatment of several diseases, including uterine cancer. AIM OF THE STUDY: In this study, the cytotoxic activity of aqueous extract of B. alicastrum bark and isolated compounds xanthyletin (1), luvangetin (2), and 8-hydroxyxanthyletin (3) on three human cancer cell lines was determined. Moreover, the biological effects of 8-hydroxyxanthyletin (3) were investigated. MATERIALS AND METHODS: The aqueous extract was prepared according to the ethnomedical information reported from the bark. The compounds were purified using chromatographic methods and their structures were elucidated by spectroscopic techniques. The antiproliferative effect of aqueous extract and isolates was determined in three human tumor cell lines: HeLa, A2780, and MSTO-211H, and evaluated by trypan blue exclusion assay. The cell cycle and the mitochondrial transmembrane potential (ΔΨ) were measured by flow cytometry, while Reactive Oxygen Species (ROS) levels were determined using 2',7'-dichlorofluorescein diacetate (DCFH-DA) probe. The effect on the relaxation activity, mediated by topoisomerase I and II, was evaluated by electrophoresis, and docking studies were performed using Autodock 4.2 to analyze the interactions. RESULTS: Aqueous extract of B. alicastrum bark showed significant antiproliferative effect on the evaluated cancer cell lines (IC50 = 1.6, 8.5, and 21.4 µg/ml). Four coumarins were identified in the extract and three of them were also evaluated. A2780 cell line exhibited higher sensitivity against pyranocoumarins with IC50 values ranging from 32 to 47 µmol/l. 8-hydroxyxanthyletin (3) exerts an interesting effect on human topoisomerases I and II, by inhibiting the enzymes at concentrations comparable to those obtained in antiproliferative assay. Moreover, 8-hydroxyxanthyletin (3) arrests the cell cycle at G0/G1 phase and induces in A2780 cells a concentration-dependent increase in ROS levels. The results of molecular docking suggest the participation of the hydroxyl group in the interaction between 8-hydroxyxanthyletin (3) and topoisomerase I and II. CONCLUSION: This is the first report that demonstrates the cytotoxic activity of the aqueous extract of B. alicastrum bark, and determines the main metabolites.

Two new derivatives of 8-prenyl-5,7-dihydroxycoumarin from the stems of Streblus ilicifolius (S.Vidal) Corn.

From the EtOAc-soluble extract of the stems of Streblus ilicifolius (Moraceae), two new secondary metabolites named strebluses A (1) and B (2) were isolated. Their chemical structures have been concluded based on the chemical derivatisation and the spectroscopic interpretation. All compounds have been tested for their tyrosinase inhibitory activity. They showed weaker inhibitory activity than that of kojic acid (IC50, 44.6 µM).[Formula: see text].

Cudraxanthone D Ameliorates Psoriasis-like Skin Inflammation in an Imiquimod-Induced Mouse Model via Inhibiting the Inflammatory Signaling Pathways.

Psoriasis is a chronic inflammatory skin disease accompanied by excessive keratinocyte proliferation. Corticosteroids, vitamin D3 analogs, and calcineurin inhibitors, which are used to treat psoriasis, have diverse adverse effects, whereas natural products are popular due to their high efficiency and relatively low toxicity. The roots of the Cudrania tricuspidata (C. tricuspidata) are known to have diverse pharmacological effects, among which the anti-inflammatory effect is reported as a potential therapeutic agent in skin cells. Nevertheless, its effectiveness against skin diseases, especially psoriasis, is not fully elucidated. Here, we investigated the effect of cudraxanthone D (CD), extracted from the roots the C. tricuspidata Bureau, on psoriasis using an imiquimod (IMQ)-induced mouse model and the tumor necrosis factor (TNF)-α/interferon (IFN)-γ-activated keratinocytes. IMQ was topically applied to the back skin of C57BL/6 mice for seven consecutive days, and the mice were orally administered with CD. This resulted in reduced psoriatic characteristics, such as the skin thickness and Psoriasis Area Severity Index score, and the infiltration of neutrophils in IMQ-induced skin. CD inhibited the serum levels of TNF-α, immunoglobulin G2a, and myeloperoxidase, and the expression of Th1/Th17 cells in splenocytes. In TNF-α/IFN-γ-activated keratinocytes, CD reduced the expressions of CCL17, IL-1ß, IL-6, and IL-8 by inhibiting the phosphorylation of STAT1 and the nuclear translocation of NF-kB. Taken together, these results suggest that CD could be a potential drug candidate for the treatment of psoriasis.

Streblus asper attenuates alloxan-induced diabetes in rats and demonstrates antioxidant and cytotoxic effects.

CONTEXT: Streblus asper Lour. (Moraceae) is used for the treatment of different ailments, including diabetes, and requires scientific validation. OBJECTIVE: The study evaluates antidiabetic effects, antioxidant potential, and cytotoxicity of leaf and bark extracts of S. asper. MATERIALS AND METHODS: Antidiabetic effects were assessed by inducing diabetes in Wistar albino rats (n = 5, six groups included 30 rats) by injecting alloxan [0.25 mg/kg body weight (bw)] intraperitoneally, and efficacy of methanol extracts of leaf and bark, and aqueous extract of leaves were evaluated by oral administration of 300 mg/kg bw of extracts for 3 weeks. Glibenclamide (Dibenol™) was used as a control (10 mg/kg bw). Antioxidant properties were examined by DPPH free radical scavenging activity, and cytotoxicity was investigated using a brine shrimp lethality assay. RESULTS: Methanol extracts of leaves and bark, and the aqueous extract of leaves of S. asper, caused significant reductions in blood glucose levels in diabetic rats of 36.83, 70.33, and 52.71%, respectively, after 21 days of treatment. IC50 values in DPPH radical scavenging assessment for those extracts were 58.92, 88.54, and 111.36 µg/mL, respectively. LC50 values for brine shrimp lethality for the extracts were 173.80, 32.36, and 3235.9 µg/mL, respectively. DISCUSSION AND CONCLUSIONS: The methanol bark extract of S. asper showed significant antidiabetic activity. This study will significantly contribute to establishing the plant as an alternative medicinal resource for rural populations of Bangladesh and provides an opportunity for further research to identify the primary active compound(s) and establish new drug candidates.

Protective Effect of Polysaccharides Extracted from Cudrania tricuspidata Fruit against Cisplatin-Induced Cytotoxicity in Macrophages and a Mouse Model.

Although cisplatin is one of most effective chemotherapeutic drugs that is widely used to treat various types of cancer, it can cause undesirable damage in immune cells and normal tissue because of its strong cytotoxicity and non-selectivity. This study was conducted to investigate the cytoprotective effects of Cudrania tricuspidata fruit-derived polysaccharides (CTPS) against cisplatin-induced cytotoxicity in macrophages, lung cancer cell lines, and a mouse model, and to explore the possibility of application of CTPS as a supplement for anticancer therapy. Both cisplatin alone and cisplatin with CTPS induced a significant cytotoxicity in A549 and H460 lung cancer cells, whereas cytotoxicity was suppressed by CTPS in cisplatin-treated RAW264.7 cells. CTPS significantly attenuated the apoptotic and necrotic population, as well as cell penetration in cisplatin-treated RAW264.7 cells, which ultimately inhibited the upregulation of Bcl-2-associated X protein (Bax), cytosolic cytochrome c, poly (adenosine diphosphateribose) polymerase (PARP) cleavage, and caspases-3, -8, and -9, and the downregulation of B cell lymphoma-2 (Bcl-2). The CTPS-induced cytoprotective action was mediated with a reduction in reactive oxygen species production and mitochondrial transmembrane potential loss in cisplatin-treated RAW264.7 cells. In agreement with the results obtained above, CTPS induced the attenuation of cell damage in cisplatin-treated bone marrow-derived macrophages (primary cells). In in vivo studies, CTPS significantly inhibited metastatic colonies and bodyweight loss as well as immunotoxicity in splenic T cells compared to the cisplatin-treated group in lung metastasis-induced mice. Furthermore, CTPS decreased the level of CRE and BUN in serum. In summation, these results suggest that CTPS-induced cytoprotective action may play a role in alleviating the side effects induced by chemotherapeutic drugs.

Anti-Inflammatory Effects of Compounds from Cudrania tricuspidata in HaCaT Human Keratinocytes.

The root bark of Cudrania tricuspidata has been reported to have anti-sclerotic, anti-inflammatory, antioxidant, neuroprotective, hepatoprotective, and cytotoxic activities. In the present study, the effect of 16 compounds from C. tricuspidata on tumor necrosis factor-α+interferon-γ-treated HaCaT cells were investigated. Among these 16 compounds, 11 decreased IL-6 production and 15 decreased IL-8 production. The six most effective compounds, namely, steppogenin (2), cudraflavone C (6), macluraxanthone B (12), 1,6,7-trihydroxy-2-(1,1-dimethyl-2-propenyl)-3- methoxyxanthone (13), cudraflavanone B (4), and cudratricusxanthone L (14), were selected for further experiments. These six compounds decreased the expression levels of chemokines, such as regulated on activation, normal T cell expressed and secreted (RANTES) and thymus and activation-regulated chemokine (TARC), and downregulated the protein expression levels of intercellular adhesion molecule-1. Compounds 2, 6, 12, 4, and 14 inhibited nuclear factor-kappa B p65 translocation to the nucleus; however, compound 13 showed no significant effects. In addition, extracellular signal regulatory kinase-1/2 phosphorylation was only inhibited by compound 14, whereas p38 phosphorylation was inhibited by compounds 13 and 4. Taken together, the compounds from C. tricuspidata showed potential to be further developed as therapeutic agents to suppress inflammation in skin cells.

Cudraxanthone L inhibits gastric cancer by regulating the MAPK signalling and promoting FAS-mediated pathway.

Gastric cancer (GC) is one of the most common malignancies and has the second highest lethal rate in the world; thus, finding new medicines with high potency and low toxicity is urgent. Cudrania tricuspidata (Carr.) Bur. ex Lavallee (Moraceae) is a traditional medicinal herb that is considered to have antitumour efficacy. We extracted and isolated cudraxanthone L (CXL) from Cudrania tricuspidata and evaluated its anti-cancer efficacy. CXL treatment inhibited angiogenesis of chorioallantoic membrane (CAM) and repressed the cell viability of various human cancer cells, indicating it presented the antitumour potential. Among them, CXL presented the best inhibitory effects on MGC803 cells. In addition, the invasion, migration and clonogenicity were significantly repressed, S phase of the cell cycle was arrested, and apoptosis was induced when MGC803 cells were treated with CXL. The results of RNA sequencing, qRT-PCR and western blotting verified that CXL regulated the MAPK signalling pathway and induced apoptosis by FAS-mediated pathway. The in vivo data revealed that CXL arrested tumour growth without toxic effects and upregulated the protein levels in FAS-mediated pathway in MGC803 gastric cancer-bearing mice. In summary, we demonstrate CXL presents impactful anti-GC efficacy by regulating the MAPK signalling pathway and promoting the FAS-mediated pathway.

Seedling recruitment under isolated trees in a tea plantation provides a template for forest restoration in eastern Africa.

Natural regeneration is less expensive than tree planting, but determining what species will arrive and establish to serve as templates for tropical forest restoration remains poorly investigated in eastern Africa. This study summarises seedling recruitment under 29 isolated legacy trees (14 trees comprised of three exotic species and 15 trees comprised of seven native species) in tea plantations in the East Usambara Mountains, Tanzania. Among the findings were that pioneer recruits were very abundant whereas non-pioneers were disproportionately fewer. Importantly, 98% of all recruits were animal-dispersed. The size of legacy trees, driven mostly by the exotic Grevillea robusta, and to some extent, the native Milicia excelsa, explained abundance of recruits. The distribution of bird-dispersed recruits suggested that some bird species use all types of legacy trees equally in this fragmented landscape. In contrast, the distribution of bat-dispersed recruits provided strong evidence that seedling composition differed under native versus exotic legacy trees likely due to fruit bats showing more preference for native legacy trees. Native, as compared to exotic legacy trees, had almost two times more non-pioneer recruits, with Ficus and Milicia excelsa driving this trend. Implications of our findings regarding restoration in the tropics are numerous for the movement of native animal-dispersed tree species in fragmented and disturbed tropical forests surrounded by farmland. Isolated native trees that bear fleshy fruits can attract more frugivores, resulting not only in high recruitment under them, but depending on the dispersal mode of the legacy trees, also different suites of recruited species. When selecting tree species for plantings, to maximize visitation by different dispersal agents and to enhance seedling recruit diversity, bat-dispersed Milicia excelsa and Ficus species are recommended.

Chemical Characterization, Antioxidant and Cytotoxic Activities of the Edible Fruits of Brosimun gaudichaudii Trécul, a Native Plant of the Cerrado Biome.

In Brazil, there is a large diversity of species of small edible fruits that are considered sources of nutrients and functional properties. They present a high innovation domain for the pharmaceutical, cosmetic and food industries due to their health-promoting properties. Edible fruits from Brosimum gaudichaudii (Moraceae) are widely consumed and used in folk medicine and in feed by the population of the Brazilian Cerrado. Nevertheless, detailed information on the chemical fingerprint, antiradical activity and safety aspects of these fruits is still unknown. Thus, the aim of this work was to investigate the bioactive compounds of hydroethanolic extracts of fruits from Brosimum gaudichaudii using high-performance liquid chromatography combined with mass spectrometry using electrospray ionization (HPLC ESI-MS). Eighteen different compounds, including flavonoids, coumarins, arylbenzofurans, terpenoids, stilbenes, xanthones and esters, were detected. Moreover, the study indicated that the hydroethanolic extract of fruits from B. gaudichaudii presented low scavenging activity against 2,2-diphenyl-1-picrylhydrazyl radicals (IC50 >800 µg mL-1 ) and was cytotoxic (IC50 <30 µg mL-1 ) in Chinese hamster ovary cells (CHO-K1) by an in vitro assay. This is the first report of the chemical profile, antioxidant activity and cytotoxic properties of the hydroethanolic extract of fruits from B. gaudichaudii.

Cudrania tricuspidata Root Extract Prevents Methylglyoxal-Induced Inflammation and Oxidative Stress via Regulation of the PKC-NOX4 Pathway in Human Kidney Cells.

Diabetic nephropathy is a microvascular complication induced by diabetes, and methylglyoxal (MGO) is a reactive carbonyl species causing oxidative stress that contributes to the induction of inflammatory response in kidney cells. Cudrania tricuspidata (CT), cultivated in Northeast Asia, has been used as traditional medicine for treating various diseases, including neuritis, liver damage, and cancer. In this study, we determined whether a CT root extract (CTRE) can prevent MGO-induced reactive oxygen species (ROS) production and inflammation and assessed underlying mechanisms using a kidney epithelial cell line, HK-2. We observed that CTRE inhibited MGO-induced ROS production. Additionally, CTRE ameliorated the activation of MGO-induced inflammatory signaling pathways such as p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-JUN N-terminal kinase (JNK). Consistent with these results, expressions of p-nuclear factor-kappa B (NFκB) and inflammatory cytokines, tumor necrosis factor-α, interleukin- (IL-) 1ß, and IL-6, were decreased when compared with MGO-only exposed HK-2 cells. CTRE alleviated the MGO-induced decrease in nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and antioxidant enzyme mRNA expressions. MGO induced the expression of NADPH oxidase 4 (NOX4); CTRE pretreatment inhibited this induction. Further studies revealed that the NOX4 expression was inhibited owing to the suppression of MGO-induced protein kinase C (PKC) activation following CTRE treatment. Collectively, our data suggest that CTRE attenuates MGO-induced inflammation and oxidative stress via inhibition of PKC activation and NOX4 expression, as well as upregulating the Nrf2-antioxidant enzyme pathway in HK-2 cells.

A 75 kDa glycoprotein isolated from Cudrania tricuspidata Bureau induces colonic epithelial proliferation and ameliorates mouse colitis induced by dextran sulfate sodium.

Cudrania tricuspidata Bureau (CTB), a species of the Moraceae plant, has been used as a bruise recovery treatment. This study aimed to determine whether the 75 kDa phytoglycoprotein extracted from CTB has a regulatory effect on the proliferation of human colon epithelial cells and the pathological process of inflammatory bowel disease (IBD). We found that CTB glycoprotein significantly induces the proliferation of human colon epithelial HT-29 cells by activating protein kinase C. CTB glycoprotein stimulated the phosphorylation of c-Jun N-terminal kinase and transcription factor nuclear factor-κB, which are responsible for the expression of cell-cycle-related proteins (CDK2, CDK4, cyclin D1 and cyclin E) during its promotion of cell proliferation. Experimental colitis was induced in mice by adding dextran sulfate sodium to their drinking water at a concentration of 4% (W/V) for seven days. We found that CTB glycoprotein ameliorates the pathological process of IBD and lowers the disease activity index score, which was composed of body weight change, diarrhea, and hematochezia in ICR mice treated with dextran sulfate sodium. Hence, we suggest that CTB glycoprotein has the ability to prevent IBD by promoting cell proliferation signaling events via the activation of PKC, JNK and NF-κB in colon epithelial cells.