Anti-proliferative Effects of Pinocembrin Isolated From Anomianthus dulcis on Hepatocellular Carcinoma Cells.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer. Anomianthus dulcis (Dunal) J.Sinclair (syn. Uvaria dulcis) has been used in Thai traditional medicine in various therapeutic indications. Phytochemical constituents of A. dulcis have been isolated and identified. However, their effects on liver cancer and the associated mechanisms have not been elucidated. METHODS: Dry flowers of A. dulcis were extracted using organic solvents, and chromatographic methods were used to purify the secondary metabolites. The chemical structures of the pure compounds were elucidated by analysis of spectroscopic data. Cytotoxicity against HCC cells was examined using SRB assay, and the effects on cell proliferation were determined using flow cytometry. The mechanisms underlying HCC inhibition were examined by molecular docking and verified by Western blot analysis. RESULTS: Among 3 purified flavonoids, pinocembrin, pinostrobin, and chrysin, and 1 indole alkaloid (3-farnesylindole), only pinocembrin showed inhibitory effects on the proliferation of 2 HCC cell lines, HepG2 and Li-7, whereas chrysin showed specific toxicity to HepG2. Pinocembrin was then selected for further study. Flow cytometric analyses revealed that pinocembrin arrested the HCC cell cycle at the G1 phase with a minimal effect on cell death induction. Pinocembrin exerted the suppression of STAT3, as shown by the molecular docking on STAT3 with a better binding affinity than stattic, a known STAT3 inhibitor. Pinocembrin also suppressed STAT3 phosphorylation at both Tyr705 and Ser727. Cell cycle regulatory proteins under the modulation of STAT3, namely cyclin D1, cyclin E, CDK4, and CDK6, are substantially suppressed in their expression levels. CONCLUSION: Pinocembrin extracted from A. dulcis exerted a significant growth inhibition on HCC cells via suppressing STAT3 signaling pathways and its downstream-regulated genes.

Ethnomedicine, phytochemistry, and pharmacological activities of Uvaria chamae P. Beauv.: A comprehensive review.

The use of medicinal plants as food and medicine has been a common practice in the world, especially in tropical African countries. One such plant in West Africa is Uvaria chamae, also known as Bush banana, renowned for its diverse ethnomedicinal applications and, more recently, for its pharmacological activities attributed to a rich array of phytochemical constituents. Various parts of the plant have been traditionally employed for the treatment of diverse health issues such as digestive disorders, fever, dysmenorrhea, cancer, wound healing, and many more. To unravel the bioactive compounds responsible for these medicinal properties, a comprehensive phytochemical analysis has been undertaken. Notable isolates include chamanetin, dichamanetin, uvaretin, and uvarinol from different parts of the plant. The pharmacological evaluation of these compounds has revealed significant anticancer and antimicrobial properties. Therefore, this review provides a thorough examination of the phytochemicals derived from Uvaria chamae, detailing their associated pharmacological activities both in vitro and in vivo. The review emphasizes the potential of Uvaria chamae as a valuable source of lead compounds for cancer chemotherapy and antimicrobial drug discovery.

Antioxidant, Cytotoxic, Anti-Glycation, and Anti-Tyrosinase Compounds from the Leaves of Uvaria Siamensis.

A new oxidized heptene, 7-benzoyloxy-4-hydroxy-1-ethoxy-2E,4Z-heptadiene-1,6-dione, namely siamheptene A (1), together with eight known compounds (2-9), were isolated from the leaves of Uvaria siamensis. Their structures were elucidated by detailed analysis of spectroscopic (IR, 1D and 2D NMR) and mass spectrometric data. Compound 9 is reported for the first time from Uvaria genus. Siamheptene A was evaluated for cytotoxicity against HeLa (cervical cancer cells), A549 (lung cancer cells), and Vero cells using the MTT assay and screened for antibacterial activities. In addition, the isolated compounds (1-7, and 9) were investigated for their antioxidant (DPPH, FRAP and ABTS+ assays), anti-glycation, and anti-tyrosinase properties. Based on our results, compound 1 had mild cytotoxicity against Hela and A549 cancer cell lines, with IC50 ranging from 31.09 to 31.67 µg/mL. Compound 1 also showed antioxidant activities in all tasted assays. However, it showed no detectable activity (>128 µg/mL) against various bacterial strains, and it has no inhibitory effects on tyrosinase enzymes. Among of all tested compounds, chrysin (5), showcased highest anti-glycation and anti-tyrosinase activities. This comprehensive analysis provides highlighting the potential of 1 as a lead compound for further structural modification and development of cytotoxic or antioxidant agents.

Anti-inflammatory, Antinociceptive, and Toxicological Properties of Uvaria comperei Stem Crude Extract and Fractions.

The present study was carried out to investigate the anti-inflammatory activity of a methanolic extract and fractions of Uvaria comperei stems. The crude extract was obtained by maceration of the powder in methanol and fractions by vacuum chromatography from the methanolic extract. To study the anti-inflammatory activity in vitro, red blood cell lysis inhibition assay and albumin denaturation inhibition were performed, while in vivo measurements of carrageenan-induced paw oedema and formalin-induced pain in albino mice were performed. Acute toxicity and cytotoxicity studies of the fraction F2 were performed, as well as its HPLC, and some biochemical parameters were quantified. Uvaria comperei crude extract (UCCE) at 250 and 500 µg/mL completely inhibited albumin denaturation, while decreasing 75.5% of heat blood cell lysis at 500 µg/mL. The fractions 128-136 (F3), 10-11 (F1), and 56-62 (F2) at 500 µg/mL displayed a significant anti-inflammatory activity with percentages of inhibition of 60.5, 67.4, and 100%, respectively. Administration of fraction F2 (25, 50, and 100 mg/kg, p.o.) produced a dose-dependent inhibition of formalin-induced pain of 60.2% at 50 mg/kg in the neurogenic phase (p < 0.05) and 70.2% at 25 mg/kg in the inflammatory phase (p < 0.05). Similarly, the time-dependent increase in carrageenan-induced paw circumference induced by carrageenan was inhibited by pretreatment with F2: 50% of inhibition at 25 mg/kg after 30 min (p < 0.05) and 96.5% inhibition at 25 mg/kg after 6 h (p < 0.05). In this research, the fraction F2 presented its maximum analgesic property at 50 mg/kg, while it presented the highest anti-inflammatory property at 25 mg/kg. The oral lethal median dose (LD50) of F2 was determined to be greater than 2000 mg/kg; further low cytotoxicity in RAW cells was also observed. Overall, this work shows that the methanolic crude extract and fractions, mainly F2, of Uvaria comperei stem have interesting anti-inflammatory properties.

Anti-Streptococcus mutans, anti-adherence and anti-acidogenic activity of Uvaria chamae P. Beauv.

ETHNOPHARMACOLOGICAL RELEVANCE: Streptococcus mutans a key pathogen, produces biofilm, acids and extracellular polysaccharides in the oral cavity; which leads to the development of dental caries. Control of these pathogenic markers can prevent dental caries. Uvaria chamae P. Beauv. is a medicinal plant traditionally used for many ailments including oral infections. Root, leaves and bark extracts has proven antibacterial activity including activity against caries causing S. mutans. However, its effect on the virulence properties of S. mutans, responsible for the development of dental caries, has not been studied. AIM OF THE STUDY: This study investigated the phytochemical constituents, anti-S. mutans, anti-adherence and anti-acidogenic activity of U. chamae root extract. MATERIALS AND METHODS: Extracts were prepared and phytochemical analysis was performed. Minimum inhibitory concentrations (MIC) were determined, and MIC and sub-MIC concentrations of the best solvent were selected for their effect on the virulence factors of S. mutans. The results were analysed using one-way ANOVA and Wilcoxon Rank Sum Tests. RESULTS: The dichloromethane extract, with proanthocyanidin as a major chemical constituent, produced an MIC of 0.02 mg/ml. At 6 h, exposure to 0.005, 0.01, and 0.02 mg/ml extract significantly reduced S. mutans adherence by 39, 59, and 77% respectively (p < 0.05). Uvaria chamae also significantly inhibited acid production in S. mutans at 10, 12, 14 and 16 h (p < 0.05). At ½ MIC, the plant extract caused remarkable downregulation of the virulence genes responsible for the adherence, biofilm formation, extracellular polysaccharide synthesis and acid production. CONCLUSIONS: This suggests that U. chamae extract may potentially be used to inhibit the proliferation of S. mutans and silencing the expression of pathology-related genes, which will prevent the development of dental caries.

Anti-Inflammatory and Phytochemical Analysis of the Crude Leaves Extracts of Boscia Coriacea Graells and Uvaria Leptocladon Oliv.

Background: The objective of this study was to evaluate the anti-inflammatory activities and phytochemical composition of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv. Methods: The powdered leaves of Boscia coriacea Graells and Uvaria leptocladon Oliv were extracted by maceration and soxhlet extraction methods. Anti-inflammatory activity of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv were evaluated using carrageenan-induced paw edema model. Standard methods were used for analysis of phytochemical composition of the leaves extracts of Boscia coriacea Graells and Uvaria leptocladon Oliv. Data analysis was done using one way analysis of variance. Results: U. leptocladon Oliv (200 mg/kg) and B. coriacea Graells (200 mg/kg) showed percent inhibition on mice paw edema of 86% and 75% after six hours of carrageenan injection, respectively. The ethanol fraction (100 mg/kg) of U. leptocladon Oliv showed the highest anti-inflammatory effect after six hours of carrageenan injection. The phytochemical analysis of the leaves extracts of B. coriacea and U. leptocladon revealed the presence of tannins, alkaloids, cardiac glycoside, flavonoids, phenols, quinones, and saponins. Conclusion: The crude leaves extracts of B. coriacea Graells and U. leptocladon Oliv contain phytochemicals with anti-inflammatory activities.

Toxicity Study and Antibacterial Effects of the Leaves Extracts of Boscia coriacea and Uvaria leptocladon.

Background: The objective of this study was to evaluate the in vivo toxicity and antibacterial activity of the leaves extracts of Boscia coriacea and Uvaria leptocladon. Methods: Extraction was performed using 80% methanol by maceration and Soxhlet extraction method. Evaluation of the acute toxicity of the extracts was based on the Organization for Economic Cooperation and Development (OECD) guideline. Evaluation of antibacterial activity of the extracts was done by agar well diffusion assay. Determinations of minimum inhibitory concentrations (MIC) of the extracts were performed by broth macro-dilution method. The checkerboard method was used for the determination of combined effect of antibiotics and the extracts. Paired T-test and one way analysis of variance were used for statistical analysis. Results: B. coriacea and U. leptocladon have no toxic effect in Swiss albino mice up to dose of 5000 mg/kg. B. coriacea and U. leptocladon showed antibacterial activity at concentration of 500 mg/ml. The chloroform-methanol fraction of B. coriacea and U. leptocladon showed the highest antibacterial activity at concentration of 25 mg/ml. The MIC and minimum bactericidal concentration (MBC) of B. coriacea were 125 mg/ml and 250 mg/ml, respectively. The MIC of U. leptocladon ranged from 31.25 mg/ml to 62.5 mg/ml, while its MBC ranged from 62.5 to 125 mg/ml. The combination assay of B. coriacea and the antibiotics showed additive effect, while U. leptocladon and the antibiotics showed indifferent effect. Conclusion: The findings showed that U. leptocladon and B. coriacea leaves extracts have antibacterial activity and no toxicity in animal model.

Polyoxygenated cyclohexene derivatives and flavonoids from the leaves of Uvaria pandensis.

Three new oxygenated cyclohexene derivatives, pandensenol D - F (1-3), two new flavanoids, pandensone A and B (4-5), and seven known compounds (6-12) were isolated from the methanol extract of the leaves of Uvaria pandensis Verdc. (Annonaceae). The structures were characterized by NMR spectroscopic and mass spectrometric analyses. The isolated metabolites were evaluated for their antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis, the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum and Pseudomonas putida, and for cytotoxicity against the MCF-7 human breast cancer cell line. Out of the tested compounds, pandensenol D (1) and (6',7'-dihydro-8'α,9'ß-dihydroxy)-3-farnesylindole (12) showed weak activity, whereas (8'α,9'ß-dihydroxy)-3-farnesylindole (11) strong activity against B. subtilis. Four of the isolated compounds (1, 4, 11 and 12) showed moderate cytotoxicity against MCF-7 breast cancer cells (EC50 > 100 µM).

α-Glucosidase inhibitory and α-amylase inhibitory activities of compounds isolated from Uvaria rufa Blume.

A new C-benzylated flavone, uvariaruflavone (1), along with 13 known compounds (2-14) were isolated from the twig and leaf extracts of Uvaria rufa Blume. Their structures were established by extensive spectroscopic methods. Flavones (5-8) and cyclohexene (10) were isolated from U. rufa for the first time. Most of the isolated compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Of these, uvariaruflavone (1) showed the highest α-glucosidase inhibitory activity with an IC50 value of 44.3 µM, while ferrudiol (12) displayed the highest α-amylase inhibitory activity with an IC50 value of 73.5 µM.

Essential oils of Uvaria boniana - chemical composition, in vitro bioactivity, docking, and in silico ADMET profiling of selective major compounds.

Phytochemical investigation applying GC (gas chromatography)-MS (mass spectrometry)/GC-FID (flame ionization detection) on the hydro-distilled essential oils of the Vietnamese medicinal plant Uvaria boniana leaf and twig lead to the detection of 35 constituents (97.36%) in the leaf oil and 52 constituents (98.75%) in the twig oil. Monoterpenes, monoterpenoids, sesquiterpenes, and sesquiterpenoids were characteristic of U. boniana essential oils. The leaf oil was represented by major components (E)-caryophyllene (16.90%), bicyclogermacrene (15.95%), α-humulene (14.96%), and linalool (12.40%), whereas four compounds α-cadinol (16.16%), epi-α-muurolol (10.19%), α-pinene (11.01%), and ß-pinene (8.08%) were the main ones in the twig oil. As compared with the leaf oil, the twig oil was better in antimicrobial activity. With the same MIC value of 40 mg/mL, the twig oil successfully controlled the growth of Gram (+) bacterium Bacillus subtilis, Gram (-) bacterium Escherichia coli, fungus Aspergillus niger, and yeast Saccharomyces cerevisiae. In addition, both two oil samples have induced antiinflammatory activity with the IC50 values of 223.7-240.6 mg/mL in NO productive inhibition when BV2 cells had been stimulated by LPS. Docking simulations of four major compounds of U. boniana twig oil on eight relevant antibacterial targets revealed that epi-α-muurolol and α-cadinol are moderate inhibitors of E. coli DNA gyrase subunit B, penicillin binding protein 2X and penicillin binding protein 3 of Pseudomonas aeruginosa with similar free binding energies of -30.1, -29.3, and -29.3 kJ/mol, respectively. Furthermore, in silico ADMET studies indicated that all four docked compounds have acceptable oral absorption, low metabolism, and appropriated toxicological profile to be considered further as drug candidates.

Plant species of the genus Uvaria: ethnobotanical uses, biological activities and phytochemistry.

The genus Uvaria (Annonaceae) comprises of climbing or trailing shrubs and rarely trees. Its plant species are widely distributed across tropical Africa, Asia and Australia. The genus Uvaria is known for various ethnobotanical uses including the treatment of tumours and the control of fever. Some of plant species in this genus have been studied for their ethnobotanical uses, biological activities and phytochemistry. The aim of the present study is to give a comprehensive review of plant species from the genus Uvaria in terms of their ethnobotanical uses, biological activities and phytochemistry. This review is expected to lay a foundation for further studies of this genus in terms of ethnobotanical applicability, biological activities and phytochemistry. Since many compounds currently known from the genus Uvaria have not yet been investigated for their biological activities, this review will be useful for future studies in the phytochemical investigations of lead compounds from this genus.

Oxygenated Cyclohexene Derivatives from the Stem and Root Barks of Uvaria pandensis.

Five new cyclohexene derivatives, dipandensin A and B (1 and 2) and pandensenols A-C (3-5), and 16 known secondary metabolites (6-21) were isolated from the methanol-soluble extracts of the stem and root barks of Uvaria pandensis. The structures were characterized by NMR spectroscopic and mass spectrometric analyses, and that of 6-methoxyzeylenol (6) was further confirmed by single-crystal X-ray crystallography, which also established its absolute configuration. The isolated metabolites were evaluated for antibacterial activity against the Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis and the Gram-negative bacteria Enterococcus raffinosus, Escherichia coli, Paraburkholderia caledonica, Pectobacterium carotovorum, and Pseudomonas putida, as well as for cytotoxicity against the MCF-7 human breast cancer cell line. A mixture of uvaretin (20) and isouvaretin (21) exhibited significant antibacterial activity against B. subtilis (EC50 8.7 µM) and S. epidermidis (IC50 7.9 µM). (8'α,9'ß-Dihydroxy)-3-farnesylindole (12) showed strong inhibitory activity (EC50 9.8 µM) against B. subtilis, comparable to the clinical reference ampicillin (EC50 17.9 µM). None of the compounds showed relevant cytotoxicity against the MCF-7 human breast cancer cell line.

Potent Nrf2-inducing, antioxidant, and anti-inflammatory effects and identification of constituents validate the anti-cancer use of Uvaria chamae and Olax subscorpioidea.

BACKGROUND: Uvaria chamae (UC) and Olax subscorpioidea (OS) roots are included in traditional anti-cancer remedies and some studies have identified their chemopreventive/chemotherapeutic potential. This study aimed to identify some cellular/molecular mechanisms underlying such potential and the associated chemical constituents. METHODS: Effect on the viability of cancer cells was assessed using the Alamar Blue assay; ability to modulate oxidative stress was assessed using the 2',7'-dichlorofluorescein diacetate (DCFDA) assay; potential to modulate Nuclear factor erythroid 2-related factor like-2 (Nrf2) activity was assessed in the AREc32 luciferase reporter cell line; and anti-inflammatory effect was assessed using lipopolysaccharide-induced nitric oxide release model in the RAW264.7 cells (Griess Assay). Chemical constituents were identified through liquid chromatography-mass spectrometry (LC-MS). RESULTS: Extracts up to 100 µg/ml were non-toxic or mildly toxic to HeLa, AREc32, PC3 and A549 cells (IC50 > 200 µg/ml). Each extract reduced basal and peroxide-induced levels of reactive oxygen species (ROS) in HeLa cells. OS and UC activated Nrf2, with UC producing nearly four-fold induction. Both extracts demonstrated anti-inflammatory effects. Chamanetin, isochamanetin, isouvaretin, uvaricin I and other compounds were found in U. chamae root extract. CONCLUSION: As Nrf-2 induction, antioxidant and anti-inflammatory activities are closely linked with chemoprevention and chemotherapy of cancers, the roles of these plants in traditional anti-cancer remedies are further highlighted, as is their potential as sources of drug leads.

Anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae (P. Beauv) roots and associated biochemical changes in chlorpromazine-induced hyperprolactinemic female Wistar rats.

ETHNOPHARAMCOLOGICAL RELEVANCE: The age-long folkloric use of Uvaria chamae roots in the management of nipple discharge that is not related to pregnancy, childbirth or nursing but as a result of excessive production of prolactin (hyperprolactinemia) is yet to be substantiated with scientific data. AIM OF THE STUDY: This study investigated the anti-hyperprolactinemic activities of aqueous extract of Uvaria chamae roots (AEUCR) and associated biochemical changes in chlorpromazine (CPZ)-induced hyperprolactinemic female Wistar rats. MATERIALS AND METHODS: A total of sixty female rats (207.40 ± 2.69 g) were assigned into 6 groups: A-F. Animals in Group A received 0.5 ml of distilled water only whilst the 7 days CPZ-treated female rats (to induce hyperprolactinemia) in groups B, C, D, E, and F also received distilled water, 2.5 mg/kg body weight of bromocriptine (reference drug), 0.71, 1.41 2.83 mg/kg body weight of AEUCR for 28 days. RESULTS: AEUCR contained a total of 15 (75%) amino acids with seven (46.67%) being essential amino acids and eight (53.33%) as non-essential amino acids. Administration of CPZ increased (p < 0.05) the levels of prolactin and testosterone, and reduced (p < 0.05) the levels of estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), dopamine, triiodothyronine (T3) and tetraiodothyroxine (T4). Chlorpromazine also increased the levels of serum urea, creatinine, total protein, albumin, globulin, bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) of the animals. In contrast, AEUCR significantly (p < 0.05) reduced the CPZ-induced increases in the levels of prolactin and testosterone, and increased the levels of CPZ-induced reduction in the progesterone, estradiol, FSH, LH, dopamine, T3 and T4. The AEUCR also reversed (p < 0.05) the CPZ-induced related increases in the levels of urea, creatinine, total protein, albumin, globulin, bilirubin, ALT, AST and ALP similar to the trends in the distilled water- and bromocriptine-treated controls. The CPZ-induced remarkable increase in the size of lactating alveolus and lactiferous duct distribution in the mammary gland were restored to normal tubule-alveolar female pattern mammary glands, composed of branching ducts and small alveoli budding off the ducts. CONCLUSION: The study concluded that aqueous extract of Uvaria chamae root exhibited anti-hyperprolactinemic activity by restoring prolactin and dopamine levels and tubule-alveolar female pattern in female rats. It also ameliorated CPZ-induced changes in the liver and kidney function indices. This study justifies the folkloric use of Uvaria chamae root in the management of abnormal discharge by the nipples that is unrelated to pregnancy, childbirth and nursing.

(R)-3-(8'-Hydroxyfarnesyl)-indole and other chemical constituents from the flowers of Anomianthus dulcis and their antimalarial and cytotoxic activities.

A new farnesylindole, (R)-3-(8'-hydroxyfarnesyl)-indole (1), as a scalemic mixture (33% ee) along with nine known compounds (2-10), including one farnesylindole, three flavanones, three flavone derivatives and two chalcone derivatives were isolated from the methanolic crude extract of the flowers from Anomianthus dulcis. All compounds were purified by appropriate chromatographic techniques and their structures elucidated by spectroscopic methods. Compounds 1, 2 and 8 showed moderate antiplasmodial activities against TM4/8.Two and K1CB1 strains of which compound 2 displayed the best activity with IC50 values of 27.9 ± 2.57 and 21.4 ± 1.68 µM, respectively. In addition, compound 1 also presented modest cytotoxicity against a KB cell line with an IC50 value of 22.3 ± 0.39 µM. None of these compounds showed cytotoxicity against Vero cells.

Specialized metabolites contributing to colour and scent volatiles in Uvaria hamiltonii flowers.

The present study focuses on the emitted and endogenous scent profiles of Uvaria hamiltonii flowers. Among the 34 compounds identified, sesquiterpenoids were found to dominate the floral volatiles composition. Profiles from endogenous scent volatiles showed higher number of compounds than the emitted ones. The anthocyanin pigment responsible for the flower colour was also explored. It was found that a single anthocyanin compound, cyanidin-3-O-glucoside, was principally responsible for petal colour. Total phenolic content was evaluated and antioxidant capacities were studied with the help of DPPH, FRAP and ABTS assays. The total phenolic content and the antioxidant capacity were higher in methanolic extract as compared to aqueous, petroleum ether and ethyl acetate extracts of U. hamiltonii flowers.

Antifungal potential of extracts, fractions and compounds from Uvaria comperei (Annonaceae) and Oxyanthus unilocularis (Rubiaceae).

Phytochemical study of Uvaria comperei afforded an alkaloid, 8,9-dimethoxy-5H-phenanthridin-6-one (1), isolated and characterised (assignment of 1H and 13C NMR) for the first time from a natural source along with two flavonoids, (2S)-5-hydroxy-7,8-dimethoxyflavanone (2) and (2S)-7-hydroxy-5-methoxy-6,8-dimethylflavone (3). Clethric acid (4), oleanoic acid (5), ß-sitosterol 3-O-ß-D-glucopyranoside (9), ß-sitosterol palmitate (6) and a mixture of stigmasterol (7) and ß-sitosterol (8) were isolated from Oxyanthus unilocularis. The structures of these compounds were elucidated using modern spectroscopic techniques including1D and 2D Nuclear Magnetic Resonance (NMR) Spectroscopy (1H, 13C, 1H-1H COSY, HSQC, HMBC) and Mass Spectrometry. Some fractions and compounds from Uvaria comperei exhibited good antifungal activity against clinical isolates and standard strains of yeast species of Candida and Cryptococcus genera while extracts from Oxyanthus unilocularis displayed weak antifungal activity. The results obtained show that Uvaria comperei could be a potential source of antifungal drugs.

Uvarmicranones A and B, two new benzoquinones and cytotoxic constituents from the stems of Uvaria micrantha (A. DC.) Hook. f. & Thomson.

Two novel benzoquinones, uvarmicranones A (1) and B (2), along with 15 known compounds (3 - 17) were isolated from the stems of Uvaria micrantha (Annonaceae). Their structures were elucidated by analyses of NMR and high-resolution mass data. A plausible biosynthetic pathway of uvarmicranone A (1) via Diels-Alder cycloaddition reaction was also proposed. Some isolated compounds were evaluated for their cytotoxic activities. Compounds 1, 14, and 15 showed moderate cytotoxic effects against T-cell acute lymphoblastic cells (MOLT-3), with IC50 values of 7.83 ± 0.83, 6.53 ± 1.01, and 4.20 ± 0.29 µM, respectively. Additionally, compound 15 exhibited moderate cytotoxicity against cervical carcinoma cells (HeLa) with an IC50 value of 7.00 ± 3.15 µM.

In Vitro and In Vivo Neutralizing Activity of Uvaria chamae Leaves Fractions on the Venom of Naja nigricollis in Albino Rat and Bovine Blood.

BACKGROUND: Snakebite envenomation is a global priority ranked top among other neglected tropical diseases. There is a folkloric claim that Uvaria chamae is beneficial for the management of snakebite and wounds in African ethnobotanical surveys. Besides, there are many registered patents asserting the health benefits of U. chamae. OBJECTIVE: This study aimed to investigate U. chamae's potentials and identify candidates for the development of tools for the treatment and management of N. nigricollis envenomation. METHODS: Freshly collected U. chamae leaves were air-dried, powdered, and extracted in methanol. The median lethal dose of the extract was determined and further fractionated with n-hexane, n-butanol and ethyl acetate. Each fraction was tested for neutralizing effect against venom-induced haemolytic, fibrinolytic, hemorrhagic, and cytotoxic activities. RESULTS: U. chamae fractions significantly (p<0.05) neutralized the haemolytic activity of N. nigricollis venom in n-butanol; 31.40%, n-hexane; 33%, aqueous residue; 39.60% and ethyl acetate; 40.70% at the concentration of 100mg/ml of each fraction against 10mg/ml of the snake venom when compared to the positive control. The fibrinolytic activity of N. nigricollis venom was significantly (p<0.05) neutralized in n-hexane at 73.88%, n-butanol; 72.22% and aqueous residue; 72.22% by the fractions of U. chamae. In addition, haemorrhagic activity of N. nigricollis venom was significantly (p<0.05) neutralized by U. chamae fractions at the concentrations of 100mg/ml, 200mg/ml and 400mg/ml except for n-butanol and aqueous residues at 400 mg/ml. CONCLUSION: U. chamae leaves fractions possess a high level of protection against N. nigricollis venoms-induced lethality and thus validate the pharmacological rationale for its usage in the management of N. nigricollis envenomation.

Modulation of inflammatory pathways, medicinal uses and toxicities of Uvaria species: potential role in the prevention and treatment of inflammation.

The therapeutic efficacy of the contemporary anti-inflammatory drugs are well established; however, prolonged use of such can often lead to serious and life-threatening side effects. Natural product-based anti-inflammatory compounds with superior efficacy and minimum toxicity can serve as possible therapeutic alternatives in this scenario. Genus Uvaria is a part of Annonaceae family, while the majority of its species are widely distributed in tropical rain forest regions of South East Asia. Uvaria species have been used extensively used as traditional medicine for treating all sorts of inflammatory diseases including catarrhal inflammation, rheumatism, acute allergic reactions, hemorrhoids, inflammatory liver disease and inflamed joints. Phytochemical analysis of Uvaria species has revealed flavones, flavonoids, tannins, saponins, polyoxygenated cyclohexene and phenolic compounds as major phyto-constituents. This review is an attempt to highlight the anti-inflammatory activity of Uvaria species by conducting a critical appraisal of the published literature. The ethnopharmacological relevance of Uvaria species in the light of toxicological studies is also discussed herein. An extensive and relevant literature on anti-inflammatory activity of Uvaria species was collected from available books, journals and electronic databases including PubMed, ScienceDirect, Scopus, Proquest and Ovid. Extracts and isolates of Uvaria species exhibited significant anti-inflammatory activity through various mechanisms of action. 6,7-di-O-Methyl-baicalein, flexuvarol B, chrysin, (-)-zeylenol, 6-hydroxy-5,7-dimethoxy-flavone, and pinocembrin were the most potent anti-inflammatory compounds with comparable IC50 with positive controls. Therefore, it is suggested that further research should be carried out to determine the pharmacokinetics, pharmacodynamics and toxicity of these therapeutically significant compounds, to convert the pre-clinical results into clinical data for drug development and design.