Antioxidant and antibacterial effects of a new macrocyclic bis(bibenzyl) ether from Combretum molle (Combretaceae).

A new compound, combrebisbibenzyl (1) as well as two sterols including stigmasterol (2) and 3-O-ß-D-glucopyranoside of ß-sitosterol (3) and seven triterpenoids namely mollic acid (4), oleanolic acid (5), ursolic acid (6), arjunglucoside I (7), arjungenin (8), bellericagenin B (9) and combregenin (10) were isolated from the root of Combretum molle. Compounds 1, 7 and 9, AcOEt and MeOH extracts exhibited moderate antioxidant activity with an IC50 value of 179.32, 185.21, 195.11 197.41 and 170.21 µg/mL, respectively, for reactive oxygen species inhibition and, inhibition percent value of 57.23, 64.52, 53.55, 67.42 and 65.04, respectively, for DPPH free-radical scavenging. The E. MeOH presented a moderate antibacterial activity against Staphylococcus aureus with DIZs value of 10.1 ± 0.2 from 800 µg/mL while the others tested strains were not sensitive. However, most of the tested bacteria, (S. aureus, Escherichia coli and Salmonella typhimurium) were moderately sensitive to E. AcOEt from 800 µg/mL with DIZs value of 8.2 ± 0.1. From the E. AcOEt, five of the isolated compounds were tested against four bacteria strains using the disc-dilusion method. The results showed that compound 1 and 2 exhibited very good antibacterial activity against all the tested bacteria at the concentration of 30 µg/mL with respective DIZ value of 22.2 and 25.4 for E. coli, 20.2 and 30.2 for S. typhimurium, 22.3 and 23.1 for S. aureus and, 22.1 and 24.1 for Streptococcus faecalis. This antibacterial activity significantly depends on the concentration.

Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae): A review of the traditional uses, phytochemistry and pharmacology of African birch.

Anogeissus leiocarpus (DC.) Guill. & Perr. belongs to the family Combretaceae and is used both by African traditional medical practitioners and livestock rearers to treat diseases such as African trypanosomiasis, animal diarrhoea, asthma, cancer, cough, diabetes, dysentery, erectile dysfunction, fever, giardiasis, helminthiases, meningitis, menstrual disorders, monkeypox, oral infections, poliomyelitis, sickle cell anaemia, snake bites, toothache, urinary schistosomiasis, and yellow fever. Some of these activities have been associated with the presence of polyphenols in the plant which include ellagic acid derivatives, flavonoids, stilbenes, tannins, and triterpenes. Several bioactive molecules have been identified from A. leiocarpus. These include the main active constituents, ellagitannins, ellagic acid derivates, flavonoids and triterpenes. Pharmacological studies have confirmed its antibacterial, antifungal, antihyperglycemic, antihypertensive, antimalarial, antioxidative, antiparasitic, antitumour and anti-ulcer effects. The stem bark has been investigated mainly for biological activities and phytochemistry, and it is the most mentioned plant part highlighted by the traditional users in ethnomedicinal surveys. In vitro and in vivo models, which revealed a wide range of pharmacological actions against parasites causing helminthiasis, leishmaniasis, malaria and trypanosomiasis, have been used to study compounds from A. leiocarpus. Because of its uses in African traditional medicine and veterinary practices, A. leiocarpus has received considerable attention from researchers. The current review provides a comprehensive overview and critical appraisal of scientific reports on A. leiocarpus, covering its traditional uses, pharmacological activities and phytochemistry.

Terminalia ferdinandiana Exell. extracts reduce pro-inflammatory cytokine and PGE2 secretion, decrease COX-2 expression and down-regulate cytosolic NF-κB levels.

Based on their high antioxidant capacity and noteworthy phytochemistry, Terminalia ferdinandiana fruit and leaves have attracted considerable recent interest for their therapeutic potential. Whilst those studies have reported a variety of therapeutic properties for the fruit, the anti-inflammatory potential of T. ferdinandiana has been largely neglected and the leaves have been almost completely ignored. This study investigated the immune-modulatory and anti-inflammatory properties of T. ferdinandiana fruit and leaf extracts by evaluating their inhibition of multiple pro- and anti-inflammatory cytokines and chemokines secretion in lipopolysaccharide (LPS)-stimulated and unstimulated RAW 264.7 macrophages using multiplex bead immunoassays and ELISA assays. The methanolic extracts were particularly good immune-modulators, significantly inhibiting the secretion of all the cytokines and chemokines tested. Indeed, the methanolic extracts completely inhibited IL-10, IFN-γ, IL-1ß, IL-6, MCP-1, and MIP-2a secretion, and almost completely inhibited the secretion of TNF-α. In addition, the methanolic T. ferdinandiana extracts also significantly inhibited cytosolic COX-2 levels (by 87-95%) and the synthesis of the PGE2 (by ~ 98%). In contrast, the methanolic extracts stimulated LTB4 secretion by ~ 60-90%, whilst the aqueous extracts significantly inhibited LTB4 secretion (by ~ 27% each). Exposure of RAW 264.7 cells to the methanolic T. ferdinandiana extracts also significantly down-regulated the cytosolic levels of NF-κB by 33-44%, indicating that the immune-modulatory and anti-inflammatory properties of the extracts may be regulated via a decrease in NF-κB transcription pathways. Taken together, these results demonstrate potent anti-inflammatory properties for the extracts and provide insights into their anti-inflammatory mechanisms.

Comtrifosides A and B, two new triterpenoid saponins from the leaves of Combretum trifoliatum.

The phytochemical composition of the Combretum trifoliatum leaves was studied for the first time. Two new triterpenoid saponins, named comtrifoside A (1) and comtrifoside B (2), together with two other saponins (3-4) were purified by variously chromatographic techniques. For the first time, compound 3 was informed from the Combretum genus, as well as all of the isolated compounds (1-4) were reported from C. trifoliatum. The chemical structures of them were clearly characterised using extensive UV-VIS, IR, HRMS-ESI, and NMR experimental data. The in vitro anti-inflammatory activities of 1 & 2 were examined against NO overproduction in LPS activation of RAW264.7.

In Vitro Antioxidant and Antitrypanosomal Activities of Extract and Fractions of Terminalia catappa.

Chagas disease is a severe infectious and parasitic disease caused by the protozoan Trypanosoma cruzi and considered a public health problem. Chemotherapeutics are still the main means of control and treatment of the disease, however with some limitations. As an alternative treatment, plants have been pointed out due to their proven pharmacological properties. Many studies carried out with Terminalia catappa have shown several biological activities, but its effect against T. cruzi is still unknown. The objective of this work is to evaluate the therapeutic potential of extracts and fractions obtained from T. catappa on the parasite T. cruzi, in addition to analyzing its antioxidant activity. T. catappa ethyl acetate fraction were produced and submitted the chemical characterization by Liquid Chromatography Coupled to Mass Spectrometry (LC-MS). From all T. catappa extracts and fractions evaluated, the ethyl acetate and the aqueous fraction displayed the best antioxidant activity by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical scavenging method (IC50 of 7.77 ± 1.61 and 5.26 ± 1.26 µg/mL respectively), and by ferric ion reducing (FRAP) method (687.61 ± 0.26 and 1009.32 ± 0.13 µM of Trolox equivalent/mg extract, respectively). The ethyl acetate fraction showed remarkable T. cruzi inhibitory activity with IC50 of 8.86 ± 1.13, 24.91 ± 1.15 and 85.01 ± 1.21 µg/mL against epimastigotes, trypomastigotes and intracellular amastigotes, respectively, and showed no cytotoxicity for Vero cells (CC50 > 1000 µg/mL). The treatment of epimastigotes with the ethyl acetate fraction led to drastic ultrastructural changes such as the loss of cytoplasm organelles, cell disorganization, nucleus damage and the loss of integrity of the parasite. This effect could be due to secondary compounds present in this extract, such as luteolin, kaempferol, quercetin, ellagic acid and derivatives. The ethyl acetate fraction obtained from T. catappa leaves can be an effective alternative in the treatment and control of Chagas disease, and material for further investigations.

Untargeted GC-MS metabolomics to identify and classify bioactive compounds in Combretum platypetalum subsp. oatesii (Rolfe) Exell (Combretaceae).

INTRODUCTION: Combretum platypetalum is used in traditional African healing practices against different infections. Unfortunately, no scientific knowledge of its phytochemical composition exists, except for the isolation of two compounds from the leaves. Scientific study has been limited to the leaves only, despite the applications of stems and roots in traditional medicine practice and natural product drug discovery programs. OBJECTIVE: Omics was applied to identify and classify different volatile and semivolatile bioactive compounds in the leaf, stem, and root parts of C. platypetalum. The thermal stability of the plant constituents at 60-65°C extraction temperature by Soxhlet and maceration at room temperature on the type, class, and concentration of compounds in the leaf was further investigated. METHOD: A GC-MS untargeted metabolomics approach, automated deconvolution by the Automated Mass Spectral Deconvolution and Identification System (AMDIS) for GC-MS data, preprocessing by Metab R, and multivariate statistical data analysis were employed in this study. RESULTS: A total of 97 phytoconstituents, including 17 bioactive compounds belonging to the terpenoids, flavonoids, long-chain fatty acids, and other unclassified structural arrangements distributed across C. platypetalum, were identified for the first time. A correlation (r = 0.782; P = 0.000) between Soxhlet and maceration extraction methods relative to resolved chromatographic peak areas of metabolites was established. CONCLUSION: Findings corroborate the reported bio-investigation of its leaf extracts, its traditional uses, and previous findings from the Combretum genus. The results substantiate the possible applications of C. platypetalum in natural product drug discovery and provide a guide for future investigations.

Isolation of two new triterpene glycoside from the fruits of Terminalia arjuna and their in vitro and in silico studies.

Two new triterpene glycoside, Arjunoglycoside VI (1) and Arjunursglycoside I (2) alone with five previously known analogues (3-7) were isolated from methanolic extract of the fruits of Terminalia arjuna. The structures were elucidated by extensive spectroscopic studies (1 D and 2 D NMR and mass). Compound 1 and 2 showed moderate activity on α-chymotrypsin enzyme inhibition with IC50 values 53.8 ± 1.39 and 64.27 ± 1.27 µg/mL respectively. Molecular docking was performed for compound 1 and 2 with the 1CGI co crystals of α-chymotrypsin enzyme protein of Bovine from protein data bank showed -7.7 and -7.6 kcal/mol binding energy, respectively.

A novel pentacyclic triterpene acid from the stem barks of Combretum fragrans F. Hoffm (Combretaceae).

A phytochemical study was carried out on stem bark of Combretum fragrans F. Hoffm., a medicinal plant belonging to the Combretaceae family and used traditionally in the treatment of various ailments. Column chromatography separation on silica gel of the crude methanol extract from stem barks of C. fragrans led to the isolation of a new pentacyclic triterpene acid, with a 3,6-epoxide bridge and trivially named as fragransinic acid (1), along with four known compounds: betulin (2), betulinic acid (3), bellericagenin B (4) and a mixture of ß-sitosterol (5) and stigmasterol (6). Structures were elucidated by extensive spectroscopic analyses including 1D and 2D NMR, mass spectrometry as well as by comparison with literature data. The above compounds were isolated for the first time from C. adenogonium. Implications for chemosystematics and traditional medicine were briefly discussed.

Molecular Modeling Study of Novel Lancifolamide Bioactive Molecule as an Inhibitor of Acetylcholinesterase (AChE), Herpes Simplex Virus (HSV-1), and Anti-proliferative Proteins.

Combretaceae, an immense family involving species (500) or genera (20), originates in tropical and subtropical regions. This family has evinced medicinal values such as anti-leishmanial, cytotoxic, antibacterial, antidiabetic, antiprotozoal, and antifungal properties. Conocarpus lancifolius (C. lancifolius) methanol extract (CLM) was prepared, then compound isolation performed by open column chromatography, and compound structure was determined by spectroscopic techniques (13C NMR, IR spectroscopy, 1H-NMR, mass spectrometry UV-visible, and 2D correlation techniques). Molecular docking studies of ligand were performed on transcriptional regulators 4EY7 and 2GV9 to observe possible interactions. Phytochemical screening revealed the presence of secondary metabolites including steroids, cardiac glycosides, saponins, anthraquinones, and flavonoids. The isolated compound was distinguished as lancifolamide (LFD). It showed cytotoxic activity against human breast cancer, murine lymphocytic leukemia, and normal cells, human embryonic kidney cells, and rat glioma cells with IC50 values of 0.72 µg/mL, 2.01 µg/mL, 1.55 µg/mL, and 2.40 µg/mL, respectively. Although no cytotoxic activity was noticed against human colon cancer and human lung cancer, LFD showed 24.04% inhibition against BChE and 60.30% inhibition against AChE and is therefore beneficial for Alzheimer's disease (AD). AChE and LFD interact mechanistically in a way that is optimum for neurodegenerative disorders, according to molecular docking studies. Methanol and dichloromethane extract of C. lancifolius and LFD shows antibacterial and antifungal activity against antibiotic resistance Bacillus subtilis, Streptococcus mutans, Brevibacillus laterosporus, Salmonella Typhi, Candida albicans, and Cryptococcus neoformans, respectively. LFD shows antiviral activity against HSV-1 with 26% inhibition IP. The outcomes of this study support the use of LFD for cognitive disorders and highlight its underlying mechanism, targeting AChE, DNA-POL, NF-KB, and TNF-α, etc., for the first time.

Bioautography-guided HPTLC-MS as a rapid hyphenated technique for the identification of antimicrobial compounds from selected South African Combretaceae species.

INTRODUCTION: Many species within Combretaceae are traditionally used for the treatment of bacterial infections. The similarity in chemistry and antimicrobial activities within the family pose a challenge in selecting suitable species for herbal drug development. OBJECTIVE: This study aimed at rapidly identifying antimicrobial compounds using bioautography-guided high-performance thin-layer chromatography coupled with mass spectrometry (HPTLC-MS). METHODS: Hierarchical cluster analysis of ultra-performance liquid chromatography-mass spectrometry data from the methanol extracts of 77 samples, representing four genera within Combretaceae, was carried out. Based on groupings on the dendrogram, 15 samples were selected for bioautography analysis against four pathogens (Staphylococcus aureus, Bacillus cereus, Escherichia coli and Salmonella typhimurium). Active compounds were identified using HPTLC-MS analysis of bands corresponding to the inhibition zones. RESULTS: Bioautography revealed 15 inhibition zones against the four pathogens, with the most prominent present for Combretum imberbe. Analysis of the active bands, using HPTLC-MS indicated that flavonoids, triterpenoids and combretastatin B5 contributed to the antibacterial activity. The compounds corresponding to molecular ions m/z 471 (Combretum imberbe) and 499 (Combretum elaeagnoides) inhibited all four pathogens, and were identified as imberbic acid and jessic acid, respectively. Chemotaxonomic analysis indicated that arjunic acid, ursolic acid and an unidentified triterpenoid (m/z 471) were ubiquitous in the Combretaceae species and could be responsible for their antibacterial activities. CONCLUSION: Application of HPTLC-MS enabled the rapid screening of extracts to identify active compounds within taxonomically related species. This approach allows for greater efficiency in the natural product research workflow to identify bioactive compounds in crude extracts.

Comparison of the antibacterial activity of Australian Terminalia spp. extracts against Klebsiella pneumoniae: a potential treatment for ankylosing spondylitis.

Traditional medicines prepared using Terminalia species have been used globally to treat inflammation and pathogenic infections. Recent studies have demonstrated that multiple Asian and African Terminalia spp. inhibit bacterial triggers of some autoimmune inflammatory diseases, including ankylosing spondylitis. Despite this, the effects of Australian Terminalia spp. on a bacterial trigger of ankylosing spondylitis (K. pneumoniae) remain unexplored. Fifty-five extracts from five Australian Terminalia spp. were investigated for K. pneumoniae growth inhibitory activity. Methanolic, aqueous and ethyl acetate extracts of most species and plant parts inhibited K. pneumoniae growth, with varying potencies. Methanolic leaf extracts were generally the most potent bacterial growth inhibitors, with minimum inhibitory concentration (MIC) values of 66 µg/mL (T. ferdinandiana), 128 µg/mL (T. carpenteriae) and 83 µg/mL (T. petiolares). However, the aqueous leaf extract was the most potent T. grandiflora extract (MIC = 87 µg/mL). All T. catappa extracts displayed low growth inhibitory activity. The Terminalia spp. methanolic leaf extracts were examined by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). All contained a relative abundance of simple gallotannins (particularly gallic and chebulic acids), the flavonoid luteolin, as well as the monoterpenoids cineole and terpineol. Notably, all Terminalia spp. were non-toxic or of low toxicity in ALA and HDF toxicity assays, highlighting their potential for preventing the onset of ankylosing spondylitis and treating its symptoms once the disease is established, although this needs to be verified in in vivo systems.

Selective tumor cell growth inhibition by lignans and a seco-triterpenoid from Combretum mellifluum.

Two new tetrahydrofuran lignans 1-2, along with 2,3-seco-lup-20(29)-en-2,3-dioic acid (3), (-)-larreatricin (4), and 15 additional compounds were isolated from Combretum mellifluum (Combretaceae). Their structures were determined by 1D- and 2D- NMR spectroscopic data and HRESIMS. Another 15 compounds were identified after HPLC-DAD-MS/MS analysis. Tested against HT-29 (colon) neoplastic cells, lignan 1 showed marked cytotoxicity (GI50 = 3.9 µM) and high selectivity (SI > 227), compared with non-neoplastic NIH/3T3 cells, while 2 proved less cytotoxic, despite exhibiting SI > 75. Seco-triterpene 3 was strongly cytotoxic to 786-0 (kidney) and HT-29 cells (GI50 = 0.5 and 2.9 µM, respectively), proving roughly 107 and 18 times more selective for these cell lines, respectively, than for NIH/3T3 cells. After 48 h of incubation, 1-3 exhibited potent cytostatic activity against HT-29 cells at all concentrations tested, while 3 had a cytocidal effect on 786-0 cells at 25 µg.mL-1.

Four new cycloartane-type triterpenoids from the leaves of Combretum mellifluum Eichler: assessment of their antioxidant and antileishmanial activities.

The beneficial pharmacological actions including antioxidant effects as an antileishmanial, antibacterial, antifungal, antidiabetic, anti-inflammatory, antitumor, antiviral, and analgesic of compounds isolated from Combretum mellifluum Eichler (Combretaceae) are well established. The aim of the present study was to determine the phytochemistry as well as assess the antioxidant and antileishmanial activities of the leaves from Combretum mellifluum Eichler (Combretaceae). Analysis of ethanolic extract resulted in isolation and identification of two epimeric mixtures of four previously unknown cycloartane-type triterpenoids, methyl quadrangularate M and methyl 24-epiquadrangularate M, and 2α,3ß,24ß-trihydroxy-cycloart-25-ene and 2α, 3ß, 24α-trihydroxy-cycloart-25-ene, and eight known compounds. Their structures were using one-dimensional nuclear magnetic resonance (1D NMR), 2D NMR and high-resolution electrospray ionization mass spectroscopy (HRESIMS) analysis. Further, the extract and fractions were tested for antioxidant potential. The ethyl acetate and aqueous fractions demonstrated the highest antioxidant activity against 2,2-dipheny-1-picrylhydrazl (DPPH) free radicals, which correlated directly with total flavonoid content. All extracts and fractions from C. mellifluum Eichler were assessed for antileishmanial activity. The supernatant fraction exhibited highest potential, inhibiting the growth of Leishmania amazonensis with IC50 value 31.29 µg/ml. Our findings provide information on the chemical composition of C. mellifluum and the potential beneficial therapeutic usefulness as an antioxidant agent in various diseases.

Norquandrangularic acid D, a new trinorcycloartane isolated from the leaves of Combretum quadrangulare.

Phytochemical investigation on the leaves of Combretum quadrangulare growing in Vietnam afforded a new trinorcycloartane triterpenoid, norquandrangularic acid D (1), along with three known compounds, betulinic acid (2), luteolin (3), and apigenin (4). Their structures were elucidated using spectroscopic methods and comparison was made with reports in the literature. Compounds 1 and 3 were evaluated for α-glucosidase inhibition. Compound 3 showed significant activity, with an IC50 value of 11.39 µM, (acarbose, used as a positive control, had an IC50 of 367 µM).

A nuclear phylogenomic study of the angiosperm order Myrtales, exploring the potential and limitations of the universal Angiosperms353 probe set.

PREMISE: To further advance the understanding of the species-rich, economically and ecologically important angiosperm order Myrtales in the rosid clade, comprising nine families, approximately 400 genera and almost 14,000 species occurring on all continents (except Antarctica), we tested the Angiosperms353 probe kit. METHODS: We combined high-throughput sequencing and target enrichment with the Angiosperms353 probe kit to evaluate a sample of 485 species across 305 genera (76% of all genera in the order). RESULTS: Results provide the most comprehensive phylogenetic hypothesis for the order to date. Relationships at all ranks, such as the relationship of the early-diverging families, often reflect previous studies, but gene conflict is evident, and relationships previously found to be uncertain often remain so. Technical considerations for processing HTS data are also discussed. CONCLUSIONS: High-throughput sequencing and the Angiosperms353 probe kit are powerful tools for phylogenomic analysis, but better understanding of the genetic data available is required to identify genes and gene trees that account for likely incomplete lineage sorting and/or hybridization events.

Multiple in vitro biological effects of phenolic compounds from Terminalia chebula var. tomentella.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia chebula (TC), a well-known Indian Ayurvedic medicine introduced into China in the Sui and Tang Dynasties, has been recorded and used medicinally as Fructus Chebulae, together with its variety tomentella (TCT) in the Chinese Pharmacopoeia. They have been also used commonly for the treatment of diabetes mellitus by Tibetan medicine. AIM OF THE STUDY: To investigate the main bioactive and therapeutic principles in the fruits of TCT, based on the extensive evaluation of their anti-inflammatory and hypoglycemic activities. MATERIALS AND METHODS: The TCT fresh fruits were analyzed by HPLC and separated further by column chromatography and preparative HPLC. The isolated compounds were identified by extensive spectroscopic analyses, including 1D/2D NMR, MS, UV, IR and ECD. Anti-inflammatory activity was evaluated by inhibition of NO production in RAW264.7 cells. The specific iNOS (PDB ID: 3E7G) structure was prepared by Discovery Studio 4.0, and the molecular docking simulation was performed on GOLD (version 5.2.2). Hypoglycemic activity was measured using the substrate solution of 4-nitrophenyl-α-d-glucopyranoside enzyme and buffer solution. RESULTS: The HPLC analysis method of polyphenols in the fruits of TCT was established, and 13 main chromatographic peaks were identified, including six hydrolyzable tannins (2, 4-7, 10-11), three simple phenols (12-14), and one oleanane pentacyclic triterpene, arjungenin. Extensive chromatographic separation of TCT fresh fruits yielded 14 compounds, including one new natural hydrolyzable tannin, 2,3-(S)-HHDP-6-O-galloyl-d-glucose (1). The known compounds were identified as 10 hydrolyzable tannins (2-11) and three simple phenols (12-14). Compounds 10 (IC50 = 36.43 ± 0.21 µM), 11 (IC50 = 42.28 ± 0.09 µM) displayed stronger NO inhibitory activity than the positive control L-NMMA (IC50 = 42.34 ± 0.66 µM), while 2, 4, and 9 showed moderate inhibitory activity against NO production. Further molecular docking simulation of specific iNOS on 10 and 11, as well as five previously isolated lignans 15-19 showed that there were no obvious rules between docking results and the in vitro NO inhibitory activity for hydrolyzable tannins (10 and 11), while the mechanism of anti-inflammatory activity for lignans was related to the substitution of conjugated aldehyde groups. Moreover, most of the hydrolyzable tannins (1-2, 4-5, 9-11) and simple phenol (12) displayed stronger inhibitory effects on α-glucosidase than the positive control, quercetin (IC50 = 6.118 ± 0.071 µM), with IC50 values ranging from 0.079 to 16.494 µM. Among these bioactive isolates, the hydrolyzable tannins 2, 4-5, and 9-11, and simple phenol 12 are major chemical components in TCT fruit. CONCLUSIONS: The results showed that lignans and hydrolyzed tannins are the main active ingredients of TCT fruits, responsible for the traditional treatment of sore throat and cough. Moreover, hydrolyzed tannins and simple phenolic compounds with potential hypoglycemic activity are closely related to the ethno-pharmacological uses of TCT fruits on diabetes in Tibetan medicine.

Bioactive tetrahydrofuran lignans from roots, stems, leaves and twigs of Anogeissus rivularis.

Four previously undescribed tetrahydrofuran lignans, named anorisols A-D (1-4) and fourteen known compounds (5-18) were isolated from the roots, stems, leaves and twigs of Anogeissus rivularis. The chemical structures were elucidated on the basis of their spectroscopic data and by comparison with the literature data. The absolute configurations of 1-4 were established by comparison of the experimental ECD spectra with the calculated ECD spectra. Some isolated compounds were evaluated for their cytotoxic activity as well as anti-HIV-1 activity employing reverse transcriptase (RT) and syncytium reduction assays using the ΔTat/RevMC99 virus in 1A2 cell line systems. Compound 6 displayed the most potent activity in syncytium inhibition assay with effective concentration at 50% (EC50) value of 13.3 µM (SI >3.0). In the reverse transcriptase assay, compound 1 exhibited moderate activity with IC50 value of 213.9 µM.

Nephroprotective potential of Anogeissus latifolia Roxb. (Dhava) against gentamicin-induced nephrotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark of Anogeissus latifolia Roxb. (Family: Combretaceae) is used traditionally and ethnomedicinally for correction of kidney disorders. AIM OF THE STUDY: The present study demonstrates the nephroprotective potential of stem bark of A. latifolia Roxb. MATERIALS AND METHODS: The HPTLC fingerprint and HPLC analysis were carried out to standardize the ethanolic extract of stem bark of A. latifolia (ALEE) using ellagic acid as a marker. Nephrotoxicity was induced in adult Wistar albino rats by gentamicin (100 mg/kg, intraperitoneally for 8 days) and they were treated with ALEE (100, 200 and 400 mg/kg, orally for 8 days), ellagic acid (10 mg/kg, orally for 8 days) and cystone syrup (5 ml/kg, orally), a standard reference a polyherbal formulation. Urine volume, serum and urine levels of creatinine, urea and uric acid, oxidative stress parameters (lipid peroxidation, catalase, superoxide dismutase and reduced glutathione), inflammatory markers (TNF-α and IL-6) and kidney weight along with its histological changes were studied in experimental animals. RESULTS: HPTLC, HPLC and LC-MS analysis of ALEE revealed the presence of ellagic acid and other various phytoconstituents. Administration of gentamicin caused significant increase in urine output and kidney weight, elevated biochemical, inflammatory and oxidative stress parameters as well as caused histological damage in the kidney tissue. These parameters were attenuated by the concurrent treatment with ALEE and ellagic acid. The effects were comparable to cystone. CONCLUSION: Present investigations concluded that ALEE exhibited nephroprotective potential and validated the traditional use of stem bark of A. latifolia in kidney disorders. The nephroprotective effect may be attributed to the antioxidant and anti-inflammatory phytoconstituents in ALEE.

Investigating antimicrobial compounds in South African Combretaceae species using a biochemometric approach.

ETHNOPHARMACOLOGICAL RELEVANCE: Many species within the family Combretaceae are popular medicinal plants that are used traditionally to treat various conditions, of which many are related to bacterial infections. Global concerns regarding the increasing resistance of pathogens towards currently available antibiotics have encouraged researchers to find new drugs with antibacterial activity, particularly from plant sources. AIM OF THE STUDY: This study was aimed at exploring the broad-spectrum antibacterial potential of methanol extracts of species representing four genera of Combretaceae (Combretum, Pteleopsis, Quisqualis, Terminalia), indigenous to South Africa, using a biochemometric approach. MATERIALS AND METHODS: The microdilution assay was used to determine the antibacterial activities, measured as minimum inhibitory concentrations (MICs), of the 51 methanol extracts representing 35 Combretaceae species, against nine species of pathogenic bacteria. Integrative biochemometric analysis was performed, thereby correlating the MIC values with the metabolomic data obtained from ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA) models were constructed for six pathogens displaying variation in their susceptibility towards the extracts. RESULTS: Evaluation of the overall MIC values obtained indicated that extracts of species from the four genera displayed the highest activity towards Bacillus cereus ATCC 11778 (average MIC 0.52 mg/mL) and Salmonella typhimurium ATCC 14028 (average MIC 0.63 mg/mL). These bacteria were the most sensitive Gram-positive and Gram-negative bacteria, respectively. Extracts from Combretum acutifolium, Combretum imberbe and Combretum elaeagnoides were the most active, with average MIC values of 0.70 mg/mL, 0.52 mg/mL and 0.45 mg/mL, respectively. Five triterpenoid compounds were tentatively identified as biomarkers from the biochemometric analysis. CONCLUSION: Correlation of the phytochemistry of species from four genera in the Combretaceae family with antibacterial activity revealed that triterpenoids are responsible for the broad-spectrum antibacterial activity observed.

Bioassay-guided isolation of antiplasmodial and antimicrobial constituents from the roots of Terminalia albida.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia albida (Combretaceae), widely used in Guinean traditional medicine, showed promising activity against Plasmodium falciparum and Candida albicans in previous studies. Bioassay-guided fractionation was carried out in order to isolate the compounds responsible for these activities. MATERIALS AND METHODS: Fractionation and isolation were performed by flash chromatography, followed by semi-preparative HPLC-DAD-MS. The structural elucidation of the isolated compounds was carried out by 1D and 2D NMR as well as HR-ESI-MS. Isolated compounds were evaluated against Plasmodium falciparum, Candida albicans, Staphylococcus aureus and Escherichia coli, and their cytotoxicity against MRC-5 cells was determined. RESULTS: Bioassay-guided fractionation of Terminalia albida root resulted in the isolation of 14 compounds (1-14), and their antimicrobial properties were evaluated. Pantolactone (1) (IC50 0.60 ± 0.03 µM) demonstrated significant activity against P. falciparum. Other compounds, including 3,4,3'-tri-O-methyl-ellagic acid (3), the triterpenes arjunolic acid (5), arjungenin (6), arjunic acid (7) and arjunglucoside II (10), and the phenol glycoside calophymembranside-B (14), were less active and showed IC50 values in the range 5-15 µM. None of the tested compound showed antibacterial or antifungal activity. CONCLUSION: These results may explain at least in part the activity of the root extract of T. albida against P. falciparum.