Exploring the Antioxidant Potential of Talisia esculenta Using In Vitro and In Vivo Approaches.

Medicinal plants, such as Talisia esculenta, are rich in antioxidant biomolecules, which are used in the treatment and prevention of many diseases. The antioxidant potential of T. esculenta extracts obtained from leaves and fruit peels was investigated using biochemical and 3T3 cell line assays as well as in vivo assays using an organism model Tenebrio molitor. Four extracts were tested: hydroethanolic extracts from leaves (HF) and from fruit peels (HC), and infusion extracts from leaves (IF) and from fruit peels (IC). The biochemical assays demonstrated an antioxidant capacity verified by TAC, reducing power, DPPH, and copper chelating assays. None of the extracts exhibited cytotoxicity against 3T3 cells, instead offering a protection against CuSO4-induced oxidative stress. The antioxidant activity observed in the extracts, including their role as free radical scavengers, copper chelators, and stress protectors, was further confirmed by T. molitor assays. The CLAE-DAD analysis detected phenolic compounds, including gallic acid, rutin, and quercitrin, as the main constituents of the samples. This study highlights that leaf and fruit peels extracts of T. esculenta could be effective protectors against ROS and copper-induced stress in cellular and invertebrate models, and they should be considered as coadjutants in the treatment and prevention of diseases related to oxidative stress and for the development of natural nutraceutical products.

Allophylus africanus Stem Bark Extract Modulates the Mitochondrial Apoptotic Pathway in Human Stomach Cancer Cells.

The present work aimed to detail the mechanisms elicited by Allophylus africanus P. Beauv. stem bark extract in human stomach cancer cells and to identify the bioactives underlying the cytotoxicity. MTT reduction and LDH leakage assays allowed characterizing the cytotoxic effects in AGS cells, which were further detailed by morphological analysis using phalloidin and Hoechst 33258. Proapoptotic mechanisms were elucidated through a mitochondrial membrane potential assay and by assessing the impact upon the activity of caspase-9 and -3. The extract displayed selective cytotoxicity against AGS cells. The absence of plasma membrane permeabilization, along with apoptotic body formation, suggested that pro-apoptotic effects triggered cell death. Intrinsic apoptosis pathway activation was verified, as mitochondrial membrane potential decrease and activation of caspase-9 and -3 were observed. HPLC-DAD profiling enabled the identification of two apigenin-di-C-glycosides, vicenin-2 (1) and apigenin-6-C-hexoside-8-C-pentoside (3), as well as three mono-C-glycosides-O-glycosylated derivatives, apigenin-7-O-hexoside-8-C-hexoside (2), apigenin-8-C-(2-rhamnosyl)hexoside (4) and apigenin-6-C-(2-rhamnosyl)hexoside (5). Isovitexin-2″-O-rhamnoside (5) is the main constituent, accounting for nearly 40% of the total quantifiable flavonoid content. Our results allowed us to establish the relationship between the presence of vicenin-2 and other apigenin derivatives with the contribution to the cytotoxic effects on the presented AGS cells. Our findings attest the anticancer potential of A. africanus stem bark against gastric adenocarcinoma, calling for studies to develop herbal-based products and/or the use of apigenin derivatives in chemotherapeutic drug development.

Potential anti-arthritic and analgesic properties of essential oil and viridiflorol obtained from Allophylus edulis leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Viridiflorol was identified and isolated from the essential oil of Allophylus edulis leaves (EOAE). A. edulis was used as "tereré", which is a drink made by the infusion of herbs in cold water, to treat pain (toothache and headache). All anti-nociceptive (analgesic) and anti-arthritic properties of EOAE and viridiflorol have not been completely scientifically clarified. AIM OF THE STUDY: The aim of the present study was to investigate the analgesic (anti-hyperalgesic and anti-nociceptive) and anti-arthritic properties of EOAE and viridiflorol using in vivo models. MATERIALS AND METHODS: The oral administration (p.o.) of EOAE (30, 100 and 300 mg/kg), viridiflorol (30, 100 and 200 mg/kg), morphine (1 mg/kg, subcutaneous route (s.c.)) and the intraplantar (local) administration (i.pl.) of viridiflorol (100 µg/paw) were tested using formalin model in Swiss mice. EOAE (100 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, s.c.) were tested by zymosan-articular inflammation and in open-field models. Viridiflorol (0.3, 20 and 200 µg/paw) was also tested in carrageenan model, and viridiflorol (200 µg/paw) was also tested in tumor necrosis factor-α (TNF-α), and dopamine (DOPA) models. RESULTS: The oral administration of EOAE (100 and 300 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), morphine (1 mg/kg, s.c.) (MOR) and local administration of viridiflorol (100 µg/paw) significantly inhibited edema and nociception in formalin model. Oral treatments with EOAE and viridiflorol (200 mg/kg) did not cause motor impairment in the open field test since they did not reduce locomotor activity. EOAE, viridiflorol and dexamethasone significantly reduced mechanical hyperalgesia, edema, total leukocytes, polymorphonuclear cells, nitric oxide and protein exudation in the zymosan-induced articular inflammation model. The local administration of viridiflorol (200 µg/paw, i.pl.) significantly inhibited mechanical hyperalgesia and edema induced by carrageenan, TNF-α and DOPA. CONCLUSIONS: This study confirms the potential anti-arthritic, anti-nocicepttive and anti-hyperalgesic properties of EOAE and viridiflorol. These properties could explain, at least in part, the folk use of A. edulis against including pain (toothache and headache). Viridiflorol could be partially responsible for the EOAE anti-hyperalgesic, anti-nociceptive and anti-arthritic properties and its mechanism of action could involve the inhibition of TNF-α and DOPA pathways.

Analgesic and anti-inflammatory potential of ethanolic extract from Serjania erecta leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: The infusion of Serjania erecta Radlk (Sapindaceae) (popular name "cipó-cinco-folhas") leaves is used in popular medicine to treat back pain. The anti-inflammatory, anti-hyperalgesic and anti-nociceptive properties of the ethanolic extract from S. erecta leaves (EESE) has not been yet completely clarified. AIM OF THE STUDY: The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice. MATERIAL AND METHODS: EESE was fractionated by chromatographic techniques and the compound was identified by nuclear magnetic resonance (NMR), infrared (IR) spectrum, ultraviolet (UV) methods. Mice received a single dose of EESE by oral route (30, 100, and 300 mg/kg, p.o.) and were submitted to nociception induced by formalin, pleurisy induced by carrageenan and peritonitis induced by zymosan models. Mice also received EESE (30 and 100 mg/kg, p.o.) for 22 days in Complete Freund Adjuvant (CFA) model and another group received EESE for 7 days (30 and 100 mg/kg, p.o.) in pleurisy induced by Bacillus Calmette-Guerin (BCG). The cytotoxicity (MTT), phagocytic and chemotactic inhibitory activities of EESE were performed in in vitro assays. RESULTS: The fractionation of EESE led to the identification of kaempferol-3-O-α-L-rhamnopyranoside. The oral administration of all doses of EESE decreased the nociceptive response induced by formalin. EESE significantly inhibited leukocyte migration in carrageenan-induced pleurisy and zymosan peritonitis models. The daily administration of EESE during for 7 days inhibited the leukocyte migration and the mycobacteria growth of pleural material obtained from animals which received BCG. EESE significantly reduced edema, cold allodynia and mechanical hyperalgesia responses induced by CFA. EESE did not induce cytotoxicity, and also decreased the leukocyte phagocytic activity, as well as, neutrophil chemotaxis. CONCLUSIONS: EESE showed analgesic and anti-inflammatory properties in acute and persistent experimental models in mice. EESE also reduced in vitro leukocyte chemotaxis and phagocytic activity without inducing cytotoxicity. The continuous oral treatment with EESE was effective against hyperalgesia and inflammation and these results could explain the popular use of S. erecta as an analgesic natural agent.

Genus Lepisanthes: Unravelling Its Botany, Traditional Uses, Phytochemistry, and Pharmacological Properties.

Extensive knowledge related to medicinal characteristics of plants by living in forest or semi-forest habitats and close observations of indigenous communities have led to the discoveries of the genus Lepisanthes and its traditional uses. The genus Lepisanthes is a member of the Sapindaceae family and is found in various regions of the world. Six species of Lepisanthes such as L. alata, L. amoena, L. fruticosa, L. senegalensis, L. rubiginosa, and L. tetraphylla are widely utilized in traditional and folk medicinal systems. They have been used for centuries for the treatment of ailments or symptoms such as pain, dizziness, high fever, frequent passing of watery stool (diarrhea), abscess, and healing of cuts and wounds. Various methodological approaches, mainly in vitro studies, have been employed to further explore the roles of the genus Lepisanthes. The studies identified that the genus Lepisanthes exerts beneficial effects such as antioxidant, antimicrobial, antihyperglycemic, antimalarial, analgesic, and antidiarrheal. However, the summary of the available literature remains inconclusive. This review aims to comprehensively address the botany, traditional uses, phytochemistry, methods, and pharmacological properties of the six commonly used Lepisanthes species. Hence, our review provides a scientific consensus that may be essential in translating the pharmacological properties of the genus Lepisanthes into future novel cost-effective medicines.

In vitro antiplasmodial activity and cytotoxicity of extracts and chromatographic fractions of twigs from Pappea capensis EckI & Zeyh. (Sapindaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The Vha-Venda people of South Africa use Pappea capensis EckI & Zeyh. (Sapindaceae) twigs to treat malaria and its related symptoms. AIM OF STUDY: The main aim of this study was to evaluate the antiplasmodial and cytotoxic activity of P. capensis extracts and chromatographic fractions. Spectroscopy analysis was conducted using 1H NMR and GC-MS to tentatively identify the major classes of compounds and phytoconstituents that can be attributed to the observed antiplasmodial bioactivity. MATERIALS AND METHODS: Pappea capensis twigs were dried and then ground to fine powder. A solvent mixture of dichloromethane: methanol: water (1:0.5:0.5, v/v) was used to extract. The polar extract was separated from the non-polar. The organic extract was dried to yield a DCM (I = 60 g) extract. The methanol in the aqueous extract was evaporated using a rotary vapour and the remaining water freeze dried to yield a water extract (II = 287 g). Extract I was further partitioned using a solvent mixture of DCM: MeOH (1:1, v/v), separated and concentrated under vacuum to yield dichloromethane (III = 40 g) and methanol (IV = 15 g) extracts. A water-based decoction (V = 10 g) was also prepared to establish the clinical relevance of the preparation administered by Vha-Venda people in South Africa. Extracts II, III and IV were further subjected to silica column chromatography, eluting with a series of different solvents with increasing polarity to yield a total of 25 fractions (A - Y). In vitro antiplasmodial tests on Plasmodium falciparum (NF54) and cytotoxicity screens on mammalian L-6 rat skeletal myoblast cells were performed on all extracts and fractions. Selectivity indices (SI) were also computed for all tested extracts and fractions which were further subjected to 1H NMR spectroscopy and GC-MS analysis for the identification of the major classes of compounds present in the extracts. RESULTS: From the assayed extracts, only extract I (IC50 = 2.93 µg/ml; SI = 14), III (IC50 = 2.59 µg/ml; SI = 21) and IV (IC50 = 3.56 µg/ml; SI = 13) demonstrated the best antiplasmodial activity and selectivity. Of all assayed fractions, only N (0.6 µg/ml; SI = 91), D (0.85 µg/ml; SI = 37) and E (0.91 µg/ml; SI = 30) depicted the best antiplasmodial activity and selectivity. The 1H NMR analysis of the extracts and fractions identified the prominent class of constituents to be aliphatic based which was tentatively identified as terpenoids. When further GC-MS analysis was conducted, the presence of lupin-3-one, lupeol acetate, α-amyrin, and ß-amyrin phytoconstituents were tentatively confirmed. These constituents are triterpenoids with established antiplasmodial activity which can be tentatively attributed to the bioactivity observed in P. capensis twigs. CONCLUSION: The study validates the ethnomedicinal use of P. capensis for malaria treatment. It demonstrated the potential of discovering novel antiplasmodial constituents that could serve as drug hits through dereplication approaches where known compounds with established antimalarial activity can be bypassed to focus on the unknown.

Antiplasmodial and Cytotoxic Flavonoids from Pappea capensis (Eckl. & Zeyh.) Leaves.

Ethnobotanical surveys indicate that the Masai and Kikuyu in Kenya, the Venda in South Africa, and the Gumuz people of Ethiopia use Pappea capensis for the treatment of malaria. The present study aimed to investigate the phytochemical and antiplasmodial properties of the plant leaves. The bioactive compounds were isolated using chromatographic techniques. The structures were established using NMR, HRMS, and UV spectroscopy. Antiplasmodial activity of P. capensis leaf extract and isolated compounds against chloroquine-sensitive 3D7 P. falciparum was evaluated using the parasite lactate dehydrogenase assay. Cytotoxicity against HeLa (human cervix adenocarcinoma) cells was determined using the resazurin assay. The extract inhibited the viability of Plasmodium falciparum by more than 80% at 50 µg/mL, but it was also cytotoxic against HeLa cells at the same concentration. Chromatographic purification of the extract led to the isolation of four flavonoid glycosides and epicatechin. The compounds displayed a similar activity pattern with the extract against P. falciparum and HeLa cells. The results from this study suggest that the widespread use of P. capensis in traditional medicine for the treatment of malaria might have some merits. However, more selectivity studies are needed to determine whether the leaf extract is cytotoxic against noncancerous cells.

Mineral Content, Antioxidant Activity and Essential Oil of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. Leaves: Plant from South American Biodiversity.

Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. (Sapindaceae) is an edible plant from the South American biodiversity that is a potential source of bioactive compounds. The mineral content and antioxidant activity of Allophylus edulis leaves were investigated, as well as the composition and the antioxidant activity of the essential oil. The mineral content was determined by ICP - OES and the antioxidant assays were assessed by ABTS, DPPH and FRAP. The essential oil was obtained by hydrodistillation and analyzed by GC/MS. Calcium, potassium, phosphorus, sulfur, and magnesium were the main minerals found in A. edulis leaves. Of the toxic metals that were present, a low level of aluminum was detected. The essential oil of A. edulis has (E)-nerolidol as major compound and both, the leaves, and the essential oil isolated from the leaves have antioxidant potential. These findings could provide a framework for developing new food and non-food products with A. edulis leaves.

Anti-phytopathogen terpenoid glycosides from the root bark of Chytranthus macrobotrys and Radlkofera calodendron.

Chytranthus macrobotrys and Radlkofera calodendron are two Sapindaceae characterized by a lack of phytochemical data. Both root barks from the two Sapindaceae species were processed by ethanol extraction followed by the isolation of their primary constituents by liquid chromatography. This process yielded four previously undescribed terpenoid glycosides together with eight known analogues. Extracts and isolated compounds from C. macrobotrys and R. calodendron were then screened for antimicrobial activity against fifteen phytopathogens. The biological screening also involved extracts and pure compounds from Blighia unijugata and Blighia welwitschii, two Sapindaceae previously studied by our group. Phytopathogens were chosen based on their economic impact on agriculture worldwide. The selection was composed primarily of fungal species including; Pyricularia oryzae, Gaeumannomyces graminis var. tritici, Zymoseptoria tritici, Fusarium oxysporum, Botrytis cinerea, Pythium spp., Trichoderma spp. and Rhizoctonia solani. Furthermore, pure terpenoid glycosides were tested for the first time against wood-inhabiting phytopathogens such as; Phaeomoniella chlamydospora, Phaeoacremonium minimum, Fomitiporia mediterranea, Eutype lata and Xylella fastidiosa. Raw extracts exhibited different levels of activity dependent on the organism. Some pure compounds, including 3-O-α-L-arabinopyranosyl-(1 â†’ 4)-ß-D-xylopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosylhederagenin, 3-O-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosylhederagenin (α-hederin), 3-O-ß-D-glucopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosylhederagenin (macranthoside A) and 3-O-α-L-arabinopyranosyl-(1 â†’ 3)-α-L-rhamnopyranosyl-(1 â†’ 2)-α-L-arabinopyranosylhederagenin (clemontanoside C), exhibited significant growth inhibitions on Pyricularia oryzae, Gaeumannomyces graminis var. tritici, Fomitiporia mediterranea and Zymoseptoria tritici. Monodesmoside triterpene saponins, in particular, exhibited MIC (IC100) values as low as 25 µg/ml and IC50 values as low as 10 µg/ml against these phytopathogens. Structure-activity relationships, as well as plant-microbe interactions, were discussed.

Chemical Composition of Magonia pubescens Essential Oils and Gamma-Radiation Effects on Its Constituents and Cytotoxic Activity in Leukemia and Breast Cancer Model.

Magonia pubescens A. St.-Hil. is a Brazilian species often used in ethnopharmacology for wound and pain healing and seborrhea treatment. For the first time, essential oils (EOs) obtained from M. pubescens inflorescences were studied. The plant materials (Montes Claros, Brazil, 2018) were submitted to different gamma-radiation doses and their chemical compositions were analyzed by GC/MS and GC-FID. The cytotoxic activity of the EOs was evaluated against K562 and MDA-MB-231 cancer cell lines. A total of 30 components were identified, being 24 compounds detected for the first time in M. pubescens. The main obtained components were hotrienol (35.9 %), cis-linalool oxide (17.0 %) and trans-linalool oxide (10.2 %). The chemical composition of the EO was slightly affected by the applied radiation doses. Irradiated and non-irradiated EOs showed cytotoxic activity against both cell lines and the non-irradiated EO sample was the most active against the K562 cell lines (IC50 =22.10±1.98).

Selective anticancer effects of Serjania marginata Casar. extract in gastric cells are mediated by antioxidant response.

Gastric cancer is the fifth most common malignancy worldwide. Serjania marginata Casar. (SM) displays anti-inflammatory properties and has been used to treat gastrointestinal disorders. In the current study, we examined whether the hydroethanolic extract of SM leaves exerted cytotoxic, mutagenic, and protective effects in non-tumor gastric epithelium cells (MNP01) and gastric adenocarcinoma cells (ACP02) in vitro and analyzed whether its action was selective. Initially, cell viability (MTT assay), cell cycle kinetics (flow cytometry), and cell proliferation (total protein content) were analyzed. In addition, genomic instability (cytokinesis-block micronucleus cytome assay), anti/pro-oxidant status (CM-H2 DCFDA probe), and transcriptional expression (RT-qPCR) of genes related to cell cycle, cell death, and antioxidant defense were also evaluated. The SM extract was cytotoxic toward MNP01 and ACP02 cells at concentrations greater than 300 and 100 µg·ml-1 , respectively, and decreased protein content only toward ACP02 cells at 200 µg ml-1 . In ACP02 cells, the SM extract at 100 µg·ml-1 associated with doxorubicin (DXR; 0.2 µg ml-1 ) clearly promoted cell cycle arrest at the G2/M phase. The extract alone was not mutagenic to either cell type and reversed DXR-induced DNA damage and H2 O2 -induced oxidative stress in MNP01 cells. The gene expression experiments showed that SM hydroethanolic extract exerts an antioxidant response via NFE2L2 activation in non-tumor gastric cells, and cell cycle arrest (G2/M) in ACP02 gastric cancer cells via the TP53 pathway. The selective action of SM indicates that it is a promising therapeutic agent to treat gastric diseases and merits further studies.

Isolation of Three New Diterpenes from Dodonaea viscosa.

An investigation into the methanol extracts obtained from the stems of Dodonaea viscosa led to the isolation of one nor-clerodane diterpene (1) and two labdane diterpenes (2, 3), as well as 17 known compounds (4-20). The structures of these compounds were elucidated based on chemical and spectral evidence. The stereochemical structure of the nor-clerodane diterpene was confirmed via its circular dichroism spectrum and calculated electronic circular dichroism spectrum. Isolated compounds were evaluated for their inhibitory effects on collagenase and tyrosinase. Since 5,7,4'-trihydroxy-3'-(4-hydroxy-3-methylbutyl)-5'-(3-methylbut-2-enyl)-3,6-dimethoxyflavone (9) showed collagenase inhibitory activity and scopoletin (12) had significant tyrosinase inhibitory activity, they were considered to be good candidates for cosmetic agents.

Variation in essential oil components and anti-inflammatory activity of Allophylus edulis leaves collected in central-western Brazil.

ETHNOPHARMACOLOGICAL RELEVANCE: An infusion obtained from the leaves of "chal-chal" (Allophylus edulis Radlk.) is used for popular treatment of intestinal disorders and as an anti-inflammatory throat treatment. Because of the anti-inflammatory medicinal folk use, a previous work reported scientific research confirming the anti-inflammatory activity of A. edulis essential oil collected in Dourados, MS, Brazil, in March 2015. AIM OF THE STUDY: The aim of this study was to evaluate the variation in the chemical profile of the essential oil of A. edulis plants collected in Dourados (EOAE-D) and Bonito (EOAE-B), two cities in Mato Grosso do Sul State, Brazil. Additionally, we evaluated the anti-inflammatory effects of the essential oil, as well as that of the major compounds (caryophyllene oxide and α-zingiberene), in experimental in vivo models of inflammation in mice. MATERIALS AND METHODS: Leaves were collected from plants at both sites in July 2018. The composition of the essential oil (EOAE-D and EOAE-B) was determined by GC/MS, and major compounds (caryophyllene oxide and α-zingiberene) were isolated and identified by chromatographic methods and NMR spectroscopy. Anti-inflammatory capacities were assessed using two classical models of inflammatory models, carrageenan- and CFA-induced paw inflammation (mechanical and thermal hyperalgesia). RESULTS: Both EOAE-D and EOAE-B showed sesquiterpenes as a major constituent, namely, caryophyllene oxide (29.5%) and α-zingiberene (45.0%), respectively. In tests, EOAE, caryophyllene oxide and α-zingiberene-induced antiedematogenic and antihyperalgesic effects were found in the different utilized models. CONCLUSIONS: The results indicate that samples from the two cities differed in chemical composition but not in their anti-inflammatory and antihyperalgesic effects. This finding corroborates the use of A. edulis as a medicinal plant and indicates its potential in the therapy of inflammatory conditions.

Farnesyl glycosides and one new triterpenoid saponin from the roots of Lecaniodiscus cupanioides Planch. ex Benth.

Chemical investigation of the methanol extract of the roots of Lecaniodiscus cupanioides led to the isolation and characterisation of three new sesquiterpene glycosides, named cupanioidesosides A (1), B (2) and C (3), together with one new triterpenoid saponin named lecanioside A (4), Their structures were established by extensive analysis of spectroscopic methods including 1D and 2D NMR techniques (COSY, NOESY, TOCSY, HSQC, and HMBC) and HRESIMS. The four new compounds were evaluated for their antiproliferative activity against the Caco-2 cell line (human epithelial cell line). None of the isolated compounds showed positive activity in our assay. Our findings represent a valuable contribution to the chemotaxonomy Lecaniodiscus genus of the subfamily of Sapindoideae of Sapindaceae family, known to be a rich source of farnesol glycosides.

Biological Characterization of an Edible Species from Brazilian Biodiversity: From Pharmacognostic Data to Ethnopharmacological Investigation.

Talisia esculenta (A. St.-Hil.) Radlk. is a large tree belonging to family Sapindaceae and popularly known as "pitombeira" or "pitomba." Although species have relevant economic and medicinal uses in Brazil, no study has investigated its effectiveness as a diuretic, hypotensive, and antihypertensive agent. The aim of this study was to present a detailed anatomical and histochemical study for T. esculenta and provide important safety and efficacy parameters. After morpho-anatomical and microchemical study, a purified aqueous extract (ethanol soluble fraction obtained from T. esculenta [ESTE]) was obtained, and detailed phytochemical investigation was performed. Subsequently, acute oral toxicity test was performed in male and female rats. Moreover, diuretic, hypotensive, and antihypertensive effects on normotensive and spontaneously hypertensive rats (SHR) were investigated. Finally, the effects of prolonged treatment with ESTE on serum levels of nitrite, thiobarbituric acid reactive species, and nitrotyrosine were also measured in SHR. Oral treatment with ESTE did not induce acute toxic effects and did not affect urine production, blood pressure, or heart rate of normotensive and SHR. Prolonged treatment with ESTE was able to increase serum nitrite levels and significantly reduce oxidative and nitrosative stress markers in SHR. Data obtained showed that ESTE has a significant antioxidant activity without showing any clinical signs of acute toxicity. The use of this species as a diuretic, hypotensive, or antihypertensive agent should be carried out with caution, since administration in rodents did not produce renal and/or hemodynamic responses that justify this indication.

Involvement of heme oxygenase-1 induction in anti-vascular inflammation effects of Xanthoceras sorbifolia in human umbilical vein endothelial cells.

OBJECTIVE: To define the effects of Xanthoceras sorbifolia (EXS) on vascular inflammation and the mechanisms in endothelial cells. METHODS: Vascular protective effects of an ethanol extract of seeds from EXS (1-50 µg/mL) against tumor necrosis factor-α (TNF-α)-induced vascular inflammation were examined in human umbilical vein endothelial cells (HUVECs). RESULTS: EXS significantly decreased TNF-α-induced expression of cell adhesion molecules, such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and endothelial cell selectin, in a dose-dependent manner. Pre-treatment with EXS significantly inhibited translocation and transcriptional activity of nuclear factor-κB (NF-κB) increased by TNF-α. EXS also significantly inhibited formation of intracellular reactive oxygen species (ROS). Moreover, the vascular protective effects of EXS were linked to up-regulation of heme oxygenase-1 (HO-1) and nuclear factor E2-related factor-2 (Nrf-2) expression. EXS-induced HO-1 expression was significantly decreased in SnPP (HO-1 inhibitor)- and HO-1 siRNA-treated cells, whereas an increase was found in cobalt protoporphyrin IX (CoPP) (HO-1 inducer)-treated cells. In addition, pretreatment with EXS increased HO-1 and Nrf-2 expression under TNF-α stimulation with or without N-acetyl-L-cysteine. Furthermore, the inhibitory effects of EXS on TNF-α-induced vascular inflammation were partially reversed in SnPP- and of HO-1 siRNA-treated cells but increased by CoPP. CONCLUSION: These results suggest that EXS may have important implications for prevention of vascular complications associated with vascular inflammation by inhibition of the NF-¦ÊB/ROS pathway and activation of the Nrf-2/HO-1 pathway.

Antiplasmodial Compounds from Leaves of Dodonaea angustifolia.

BACKGROUND: Dodonaea angustifolia is used in Ethiopian traditional medicine to treat malaria. The objective of this work was to conduct bioassay guided fractionation of the leaves of D. angustifolia using Plasmodium berghei infected mice. METHOD: The antiplasmodial activity of the extracts and pure compounds was evaluated using the standard Peter's four-day suppressive method. The structures of isolated compounds were elucidated using chemi-cal and spectroscopic methods. RESULTS: In this study, the ethyl acetate soluble portion of the 80% aqueous MeOH extract of the leaves significantly suppressed parasitaemia in Plasmodium berghei infected mice (80.28% at 150 mg/kg). Three active compounds which exhibited significant percent suppression of parasitaemia by 81% at 40 mg/kg, 80% at 50 mg/kg and 70% at 40 mg/kg, respectively were identified. These are the flavanone pinocembrin (1), the flavanol santin (2) and the clerodane diterpene 2-hydroxy-15,16-epoxyceloda-3,13(16),14-trien-18-oic acid (3). Under similar conditions, chloroquine suppressed parasitaemia by 100% at 25 mg/kg. Chemical study of the ethanol extract of the leaves yielded 5,7,4'-trihydroxy-3,6-dimethoxyflavone (4), ent-16-hydroxy-labdan-3α,8ß-dihydroxy,13(14)-en-15,16-olide (5) and 5,6,7-trihydroxy-3,4'-dimethoxyflavone (6). Compound 6 has not been reported before as a natural product. CONCLUSION: From the leaves of D. angustifolia, three compounds with significant antiplasmodial activi-ties were isolated and characterized, with pinocembrin as the most active compound.

Anti-inflammatory, antioxidant and anti-Mycobacterium tuberculosis activity of viridiflorol: The major constituent of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Allophylus edulis (A. St.-Hil., A. Juss. & Cambess.) Radlk. (Sapindaceae) are traditionally used as a natural anti-inflammatory agent; however, there are no scientific studies demonstrating its activity essential oil. The content of essential oil in A. edulis may be the chemical basis to explain its ethnobotanical uses, since infusions of this plant are used to treat inflammation in the traditional medicine in Brazil. AIM OF THE STUDY: This study evaluated the anti-inflammatory, antioxidant and anti-mycobacterial activities of the essential oil (EOAE) and viridiflorol, its main compound. MATERIAL AND METHODS: Essential oil from fresh leaves of A. edulis (EOAE) was obtained by hydrodistillation in a Clevenger-type apparatus. Forty-one compounds, accounting for 99.10% of the oil, were identified by gas chromatography-mass spectrometry (GC-MS). The major constituent of the oil was viridiflorol (30.88%). Additionally, the essential oil and viridiflorol were evaluated using an in vitro test against Mycobacterium tuberculosis and in 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assays. Both EOAE (30 and 100mg/kg) and viridiflorol (3 and 30mg/kg) by oral administration were assayed in carrageenan-induced mice paw oedema and pleurisy using subcutaneous injection of dexamethasone (0.5mg/kg) as the positive control. RESULTS: EOAE and viridiflorol displayed moderate in vitro activity in the M. tuberculosis assay. In all tests, EOAE and viridiflorol showed moderate antioxidant activity compared with reference standards. Both EOAE and viridiflorol showed significant inhibition in the carrageenan-induced mice paw oedema via oral administration of the oil (30 and 100mg/kg), compound (3 and 30mg/kg), and subcutaneous injection of dexamethasone (0.5mg/kg, reference drug). Also EOAE and viridiflorol significantly inhibited carrageenan (Cg) induced pleurisy, reducing the migration of total leucocytes in mice by 62±5% (30mg/kg of oil), 35±8% (100mg/kg of oil), 71±5% (3mg/kg of viridiflorol) and 57±3% (30mg/kg of viridiflorol). CONCLUSION: For the first time, the results from this work corroborate the literature, showing that A. edulis can be used as a natural anti-inflammatory agent. Moreover, both EOAE and viridiflorol exhibited biological activities, such as anti-mycobacterial, anti-inflammatory and antioxidant activity.

Aqueous root extract of Lecaniodiscus cupanioides restores nitric oxide/cyclic guanosine monophosphate pathway in sexually impaired male rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aqueous root extract of Lecaniodiscus cupanioides is widely used in the management of sexual dysfunction in Nigeria. The effect of aqueous root extract of L. cupanioides root on the concentrations of penile cyclic Guanosine Monophosphate (cGMP) and plasma nitric oxide in paroxetine-induced sexually impaired male rats was evaluated. METHODS: Thirty (30) albino rats were assigned into six groups (A, B, C, D, E and F) of five rats each such that animals in Group A (control) received distilled water while those in Groups B, C, D, E and F which were induced into sexual dysfunction (p.o 10mg/kg of paroxetine hydrochloride suspension in Tween-80) and in addition received distilled water, 7.14 mg/kg body weight of a reference herbal drug (PowmaxM), 25, 50 and 100mg/kg body weight of the extract respectively, orally, once daily for five days. RESULTS: Administration of paroxetine significantly reduced the levels of penile cyclic Guanosine Monophosphate (cGMP) and plasma nitric oxide. These decreases were dose dependently reversed by the aqueous extract of L. cupanioides root. The reversal by the 25 and 50mg/kg body weight of the extract compared favorably with the PowmaxM, whereas the 100mg/kg body weight of the extract compared favorably with the non-sexually impaired distilled water treated control animals. CONCLUSION: The results of this study show that aqueous extract of L. cupanioides root restored the levels of cGMP and nitric oxide in sexually impaired rats. This study further lends credence to the use of aqueous root extract of L. cupanioides in the management of sexual dysfunction in Nigeria.

Litchi chinensis: medicinal uses, phytochemistry, and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Litchi chinensis Sonn. (Sapindaceae) has been widely used in many cultures for the treatment of cough, flatulence, stomach ulcers, diabetes, obesity, testicular swelling, hernia-like conditions, and epigastric and neuralgic pains. The ethnopharmacologial history of L. chinensis indicated that it possesses hypoglycemic, anticancer, antibacterial, anti-hyperlipidemic, anti-platelet, anti-tussive, analgesic, antipyretic, hemostatic, diuretic, and antiviral activities. AIM OF THE REVIEW: The aim of this review is to provide up-to-date information on the botanical characterization, distribution, traditional uses, and chemical constituents, as well as the pharmacological activities and toxicity of L. chinensis. Moreover, the focus of this review is the possible exploitation of this plant to treat different diseases and to suggest future investigations. MATERIALS AND METHODS: To provide an overview of the ethnopharmacology, chemical constituents, and pharmacological activities of litchi, and to reveal their therapeutic potentials and being an evidence base for further research works, information on litchi was gathered from scientific journals, books, and worldwide accepted scientific databases via a library and electronic search (PubMed, Elsevier, Google Scholar, Springer, Scopus, Web of Science, Wiley online library, and pubs.acs.org/journal/jacsat). All abstracts and full-text articles were examined. The most relevant articles were selected for screening and inclusion in this review. RESULTS: A comprehensive analysis of the literature obtained through the above-mentioned sources confirmed that ethno-medical uses of L. chinensis have been recorded in China, India, Vietnam, Indonesia, and Philippines. Phytochemical investigation revealed that the major chemical constituents of litchi are flavonoids, sterols, triterpenens, phenolics, and other bioactive compounds. Crude extracts and pure compounds isolated from L. chinensis exhibited significant antioxidant, anti-cancer, anti-inflammatory, anti-microbial, anti-viral, anti-diabetic, anti-obesity, hepato-protective, and immunomodulatory activities. From the toxicological perspective, litchi fruit juice and extracts have been proven to be safe at a dose 1 g/kg. CONCLUSIONS: Phytochemical investigations indicated that phenolics were the major bioactive components of L. chinensis with potential pharmacological activities. The ethnopharmacological relevance of L. chinensis is fully justified by the most recent findings indicating it is a useful medicinal and nutritional agent for treating a wide range of human disorders and aliments. Further investigations are needed to fully understand the mode of action of the active constituents and to fully exploit its preventive and therapeutic potentials.