Cytotoxic gelsedine-type indole alkaloids from Gelsemium elegans.

A chemical investigation on the 95% ethanol extract of the aerial part of Gelsemium elegans resulted in the isolation of three new gelsedine-type indole alkaloids, 14ß-hydroxygelselenidine (1), 11-methoxygelseziridine (2), and 14ß-hydroxygelsedethenine (3). Structural elucidation of all the compounds was accomplished by spectral methods such as 1 D and 2 D NMR, IR, UV, and HRESIMS. The isolated compounds were tested in vitro for cytotoxic activities against five human non-small-cell lung cancer cell lines. Consequently, alkaloid 3 exhibited cytotoxic activities for all tested tumor cell lines with IC50 values from 8.3 to 9.8 µM. [Formula: see text].

Cytotoxic gelsedine-type indole alkaloids from Gelsemium elegans.

The ethanol extract of the leaves and branches of Gelsemium elegans afforded three new gelsedine-type indole alkaloids, 11-methoxy-14,15-dihydroxyhumantenmine (1), 11-methoxy-14,15-dihydroxy-19-oxogelsenicine (2), and 11-methoxy-14-hydroxygelsedilam (3), along with one known alkaloid 11-methoxy-14-hydroxyhumantenmine (4). The structures of isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high-resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potential against four laryngeal tumor cell lines including Hep-2, LSC-1, TR-LCC-1, and FD-LSC-1. As a result, compounds 1 and 4 exhibited some cytotoxic activities against all tested tumor cell lines with IC50 values of 10.9-12.1 µM and 9.2-10.8 µM, respectively.

Geographic variation in resistance to nectar robbing and consequences for pollination.

PREMISE OF THE STUDY: Floral evolution is frequently ascribed to selection by pollinators, but may also be shaped by antagonists. However, remarkably few studies have examined geographic mosaics in resistance to floral antagonists or the consequences for other floral interactions. METHODS: Gelsemium sempervirens experiences frequent nectar robbing in northern Georgia, but rarely in southern Georgia. We conducted common-garden experiments in both locations using genotypes from each region and measured robbing, pollinator attraction, floral attractive and defensive traits, and plant reproduction. KEY RESULTS: Nectar robbing was more than four times higher in the north vs. south, and pollinator visits did not differ between gardens. Across both gardens, northern genotypes were half as likely to be nectar-robbed but received half as many pollinator visits as southern genotypes, suggesting evolution of resistance to robbing at a cost of reduced pollinator attraction. Plant-level traits, such as height and number of flowers, were more closely associated with resistance to robbing than floral size, shape, or chemistry. Northern genotypes had lower female and estimated male reproduction compared to southern genotypes at both locations, which could be due to costs of resistance to nectar robbing, or costs of adaptations to other biotic or abiotic differences between regions. CONCLUSIONS: Our study indicates that geographic variation can play a strong role structuring interactions with floral antagonists and mutualists and provides evidence consistent with the hypothesis that local resistance to nectar robbing imposes costs in terms of decreased pollinator attraction and reproduction.

Molecular systematics and biogeography of Logania R.Br. (Loganiaceae).

The angiosperm genus Logania R.Br. (Loganiaceae) is endemic to the mainland of Australia. A recent genetic study challenged the monophyly of Logania, suggesting that its two sections, Logania sect. Logania and Logania sect. Stomandra, do not group together. Additionally, the genus has a disjunct distribution, with a gap at the Nullarbor Plain in southern Australia. Therefore, Logania is a favourable candidate to gain insight into phylogenetic relationships and how these might intersect with Earth-history events. Our phylogenetic analyses of DNA sequences of two chloroplast markers (petD and rps16) showed that Logania sect. Logania and L. sect. Stomandra were each resolved as monophyletic, but the genus (as currently circumscribed) was not. Based on our Bayesian estimates of divergence times, the disjunct distributions within Logania sect. Stomandra could have been caused by flooding of the Eucla Basin. However, this biogeographical process cannot account for the distribution of Logania sect. Logania, with long-distance dispersal and establishment seeming more likely.

Gelselegine-gelsedine type bisindoles as well as the units from Gelsemium elegans with promoting proliferation of oral mucosa fibroblast cells.

Two undescribed bisindole alkaloids, gelseginedine A (1) and its rearranged gelseginedine B (2), and seven unreported gelselegine-type oxindole alkaloids (3-9) were isolated from the stems and leaves of Gelsemium elegans, together with five known alkaloids (10-14). Compounds 1 and 2 represented the first examples of gelselegine-gelsedine type alkaloids which bridged two units by a double bond. Their structures with absolute configurations were elucidated by means of HRESIMS, NMR and calculational chemistry. The performed bioassay revealed that 14 could promote the proliferation of human oral mucosa fibroblast cells.

Mitreolaquanruii (Loganiaceae), a new species from a karst region in Guangxi, China.

Mitreolaquanruii, a new species from Guangxi, China, is described and illustrated in this study. It is morphologically similar to M.liuyanii because of the terete stems, creeping and branched at the base, the leaves which are pilose on both surfaces and the bilobed capsules with two erect horns. The new species can be distinguished from M.liuyanii by its taller habit, up to 20-50 cm tall, its linear leaves, 4-18 × 0.3-1 cm with acuminate apex and 8-10 pairs of lateral veins, its narrowly triangular stipules, its linear bracts, ca. 1.0 cm long and glabrous and its glabrous calyx. Mitreolaquanruii is temporarily assessed as data deficient (DD) according to IUCN. The habitat of Mitreolaquanruii is extremely fragile. Therefore, this species deserves close attention and protection.

In vitro antimicrobial studies of some major bioactive compounds isolated from Strychnos innocua (Delile) root bark.

Plant based therapies are very essential in modern medicine, and have long been used to cure and prevent chronic diseases in many parts of the world. Medicinal herbs have been shown to have biological properties due to the presence of active compounds. Strychnos innocua, a medicinal plant from Loganiaceae, is commonly consumed for medicinal purposes in various African countries. The need to assess the usefulness of the plant's root bark in the treatment of disease spurred this study, which involved the isolation of six bioactive compounds and screening for antimicrobial properties against some pathogens using the agar well diffusion method. Chromatography separation led to first time isolation of Umbelliferone (1), Linalool (2), Nerolidol (3), Campesterol (4), ß-sitosterol (5), and 2,13-Octadecadien-1-ol (6). GC-MS and NMR spectra, as well as comparisons with published data, were used to determine their structures. The compounds exhibited strong antimicrobial activity comparable to ciprofloxacin and fluconazole against MRSA, B. subtilis, S. pyogenes, S. aureus, K. pneumoniae, E. coli, P. aeruginosa, S. typhii, A. fumigatus, C. albicans, C. krusei, and A. nigre. The MIC as well as the MBC/MFC were determined. In conclusion, the compounds (1 - 6) isolated from S. innocua root bark have remarkable antibacterial action against pathogenic microbes.

A molecular networking-based isolation of gardneria alkaloids from Gardneria distincta and their anti-inflammatory activity.

Gardneria distincta P. T. Li is traditionally applied as a herbal medicine for treatment various ailments, and is mainly distributed in Southwestern China. Under the guided separation of MS/MS-based molecular networking, eight undescribed oxindole alkaloids, gardistines A-H, as well as 17 known alkaloids were discovered from the whole parts of Gardneria distincta. Structural elucidation of these undescribed alkaloids was performed by various spectroscopic methods. Gardistine A is a rare oxindole gardneria alkaloid bearing an ester carbonyl group attached to C-18, which is the second reported alkaloid of oxindole gardneria-type. All of the identified monoterpene indole alkaloids were investigated for their anti-inflammatory activity in LPS-induced RAW 264.7 cells. Gardistines A-B and akuammidine demonstrated significant inhibitory effects on the expressions of nitric oxide, tumor necrosis factor alpha, and interleukin-6 at 20 µM.

Health benefits and biological activities of spiny monkey orange (Strychnos spinosa Lam.): An African indigenous fruit tree.

ETHNOPHARMACOLOGICAL RELEVANCE: Spiny monkey orange (Strychnos spinosa Lam.) is an African endemic fruit tree that is widely consumed by humans and animals for its nutritional value. In folk medicine, different parts of S. spinosa are widely used for the management of the health and well-being of humans and livestock. AIM: We provide a critical appraisal on the ethnobotanical uses, nutritional and pytochemical as well as the biological activities of S. spinosa. METHODS: Articles were mined from online databases such as Google Scholar, PubMed, Science Direct, SciELO and SpringerLink. We captured research outputs that aligned with the scope of the review. RESULTS: Strychnos spinosa remains a commonly consumed fruit due to its high nutritional (e.g. carbohydrates, crude protein and fats) content and energy. In folk medicine, different parts of S. spinosa are prescribed as remedy for diverse medical conditions especially for treating malaria, diabetes, snakebites, skin-related conditions and sexually transmitted infections in humans as well as sleeping sickness in livestock. Together with essential oils, more than 25 compounds have been profiled using Gas chromatography-mass spectrometry (GC-MS), and approximately 45 compounds have been isolated and structurally elucidated using diverse spectroscopic techniques such as UV-visible, Infrared (IR), Nuclear Magnetic Resonance (NMR) and mass spectroscopy (MS). Strychnos spinosa exerts varying degrees of biological activities against different microorganisms (bacteria and fungi) and parasites (plasmodia, trypanosomes and ticks) responsible for many diseases in humans and livestock. Furthermore, low to moderate enzyme-inhibitory effects of S. spinosa extracts suggest its ability to mitigate pains, inflammations and diabetics as well as snakebite venom. Increasing evidence from the in vivo studies support the use of the plant as a popular remedy for managing diabetics in folk medicine. The low cytotoxic effect of the plant extracts against different cell lines could be an indication of its relative safety. CONCLUSION: Strychnos spinosa exhibits various health-promoting benefits due to its diverse nutritional and phytochemical constituents. Given that the majority of the existing evidence on these aforementioned therapeutic properties and safety are in vitro-based, the clinical significance of these results remain limited.

Exploration by molecular networking of Strychnos alkaloids reveals the unexpected occurrence of strychnine in seven Strychnos species.

INTRODUCTION: Plants of the Strychnos genus, which include about 200 species, are used for multiple traditional purposes as hunting poison, for example, and have shown interesting pharmacological properties, especially curarizing and tetanizing, but also against malaria. Many monoterpene indole alkaloids have already been isolated and identified. Among them, there is strychnine, a famous alkaloid that can cause death by asphyxiation. OBJECTIVE: Investigate alkaloidic molecular diversity from Strychnos genus using molecular networking technique and study the Strychnos genus from a chemotaxonomic point of view. MATERIAL AND METHODS: Twenty-eight different species and different plant parts were ground into powder using a grinder. The methanolic extracts were carried out using a pressurized solvent extraction and the alkaloid extract was performed manually with a separating funnel. The extracts were analyzed by HPLC-ESI(+)-Q/TOF. The data were processed using MZmine 2 software and the molecular network was generated on the GNPS platform. The study of the generated molecular network allowed the detection of various alkaloids. Among these is the famous strychnine which has been detected in 7 new Strychnos species not yet described as strychnine producers. This identification was investigated using orthogonal approaches, namely TLC, NMR, HPLC-UV and UHPLC-ESI(+)-Q/TOF analyses. The LOD by HPLC-UV of strychnine was also determined. RESULTS: Further analyses allowed to confirm the presence of strychnine in S. densiflora trunk barks but also to show the presence of strychnine with high probability in the trunk barks of S. camptoneura, S. congolana, S. boonei, and S. tchibangensis, and in the leaves of S. usambarensis. About the trunk barks of S. tricalyisoides, the probability of a strychnine content remains low. CONCLUSION: This work exemplified the efficiency of molecular networking in identifying known metabolites (major and minor alkaloids) involved in the chemotaxonomic study of plants from Strychnos genus.

Anti-inflammatory and anti-arthritic effects of compounds from Buddleja coriacea.

Buddleja coriacea (B. coriacea) commonly known as 'Kiswara' is used as infusions for stomach and joint pain. This study aims to evaluate the in vitro and in vivo anti-inflammatory and anti-arthritic activity was evaluated by measuring inflammatory parameters (TNF-α, C-reactive protein and Fibrinogen) in murine models of the aqueous extract and isolated compounds of B. coriacea. A bio-guided phytochemical analysis based on NMR/MS was performed identifying three (1-3) compounds of the aqueous extract. All compounds inhibited the production of TNF-α in RAW 264.7 cell line, with IC50 of 13.44 (1), 1.13 (2) and 0.57 µM (3), respectively. In addition, compounds 2 and 3 decreased the levels of TNF-α, C-reactive protein and fibrinogen at a concentration of 5 mg/kg in murine models. Our research shows that the compounds isolated from B. coriacea have anti-inflammatory and anti-arthritic properties, providing scientific evidence for the traditional use of this plant species.

Glycosides from Buddleja officinalis with their protective effects on photoreceptor cells in light-damaged mouse retinas.

A new phenylethanoid, hebitol IV (1), along with fifteen known glycosides (2-16), were isolated from water extract of the flower buds of Buddleja officinalis. Their structures were elucidated on the basis of 1 D-NMR, 2 D-NMR and MS data. Molecular docking showed the potential activities of the natural products against VEGFR-2. Bioassay results revealed that the compounds 10 and 14 exhibited strong inhibitory activity against VEGFR-2 with IC50 values of 0.51 and 0.32 µM, respectively. Moreover, the potential retinal protective effects of 10 and 14 were then investigated in the mouse model featuring bright light-induced retinal degeneration. The results demonstrated remarkable photoreceptor protective activities of 10 and 14 in vivo.

Monoterpenoid indole alkaloids isolated from the stems and twigs of Strychnos cathayensis.

Seven undescribed monoterpenoid indole alkaloids, two N(4)-chloromethylation artifacts, and 10 known alkaloids were isolated from the stems and twigs of Strychnos cathayensis. The corresponding structures were elucidated via spectroscopic data interpretation and electronic circular dichroism. The absolute configuration of (17S)-12-hydroxy-11-methoxydiaboline, the major anomer of 12-hydroxy-11-methoxydiaboline, was characterized by X-ray diffraction analysis for the first time. At an intraperitoneal dose of 30 mg/kg, 12-hydroxy-11-methoxy-N(4)-chloromethyldiaboline and (-)-macusine A exhibited potential analgesic effects with prolongation rates of 99% and 47% for the latency time of hind-paw licking, respectively, compared to the blank control. 12-Hydroxy-11-methoxydiaboline, 12-hydroxy-11-methoxydiaboline N(4)-oxide, retuline N-oxide, and (-)-vincosamide exhibited antiviral activity against Coxsackie virus B3 (CVB3) with IC50 values of 33.33 µM.

Unveiling antiplasmodial alkaloids from a cumulative collection of Strychnos extracts by multi-informative molecular networks.

Malaria, a disease known for thousands of years and caused by parasites of the Plasmodium genus, continues to cause many deaths throughout the world today, particularly due to the emergence of parasite resistance to the current therapeutic arsenal. Plants of the Strychnos genus, remarkable due to their multiple traditional uses as well as their alkaloid content, are promising candidates to develop new antimalarial treatments. Indeed, previous research on this plant group has shown promising (≤ 5 µg/ml) or good (between 5 and 15 µg/ml) antiplasmodial activities. Using the chloroquine-sensitive strain of Plasmodium falciparum (3D7), and artemisinin as positive control, a screening of antiplasmodial activities from 43 crude methanolic extracts from 28 species of the Strychnos genus was carried out in three independent assays. A total of 12 extracts had good (6 extracts) or promising (6 extracts) antiplasmodial activities. These results allowed both to confirm known activities but also to detect new ones. These extracts were then analyzed by HPLC-ESI(+)-Q/TOF, and the processed MS/MS data allowed to generate a molecular network in which the antiplasmodial activities were implemented as metadata. The exploration of the molecular network revealed the presence of alkaloids still unknown, and potentially active against malaria, in particular alkaloids close to usambarensine and its derivatives. This study shows that the emergence of molecular networking offers new leads for identifications of alkaloids from the Strychnos genus. The presence of unknown alkaloids potentially active against malaria confirms all the interest to continue in studying the Strychnos genus. Bioassay- and mass-guided fractionations as well as various dereplication tools would allow to identify and characterize these interesting alkaloids further.

Undervalued Spiny Monkey Orange (Strychnos spinosa Lam.): An Indigenous Fruit for Sustainable Food-Nutrition and Economic Prosperity.

Strychnos spinosa Lam. is among the top nutrient-dense indigenous fruit species that are predominant in Southern Africa. It is a highly ranked indigenous fruit based on the nutrition and sensorial properties, which make it an important food source for the marginalized rural people. On the basis of the high vitamin C, iron, and zinc content, it has the capacity to improve the food- nutrition and the socioeconomic status of individuals, especially those in the rural areas of the developing nations. The nutritional composition of Strychnos spinosa compare favorably with many of the popular fruits, such as strawberries and orange. Additionally, Strychnos spinosa has antioxidant activity similar to well-known antioxidant fruits, which keeps it in the class of the popular fruits, giving it added nutrition-health-promoting benefits. In order to improve the availability of Strychnos spinosa, more research on the domestication, processing, preservation, value chain, and economic potential need to be further explored. Therefore, we recommend more concerted efforts from relevant stakeholders with interest in Strychnos spinosa fruit production as a possible sustainable solution to food shortage, food-nutrition insecurity, malnutrition, and austerity, mainly in the rural communities of the developing countries.

The complete chloroplast genome of Mitrasacme pygmaea (Loganiaceae).

The complete chloroplast genome of Mitrasacme pygmaea was sequenced and assembled for the first time. The chloroplast genome is 152,611 bp in length, containing a large single-copy (LSC) region of 83,881 bp and a small single-copy region (SSC) of 18,110 bp, separated by a pair of inverted repeats (IRs) of 25,310 bp. The genome contains 113 unique genes, including 79 protein-coding genes, 30 tRNA genes, and 4 rRNA genes. Among them, 15 genes have one intron each and 3 genes contain two introns. The overall GC content is 37.9%, while the corresponding values of LSC, SSC, and IR regions are 36.0%, 31.7%, and 43.4%, respectively. Phylogenetic analysis showed that M. pygmaea is sister to Gentiana tibetica and provided new insight into the evolution of Loganiaceae.

Acetylcholinesterase inhibitor from Anthocleista vogelii leaf extracts.

BACKGROUND: Anthocleista vogelii (Planch) is used in folk medicine in conditions related to inflammation and oxidative stress. This suggests that some of its constituents could possess ability to reduce oxidative damage to cells and ameliorate inflammatory conditions which are two prominent features in the brain of a person suffering from Alzheimer's disease. AIM OF STUDY: The leaf extracts were investigated for their bioactive constituents in our quest for novel compounds for the management of Alzheimer's disease. MATERIALS AND METHODS: Anthocleista vogelii crude leaf extract obtained from 80% methanol was successively partitioned with n-hexane, dichloromethane (DCM), ethyl acetate (EtOAc) and n-butanol. This gave four solvent fractions of the crude extract. These fractions and isolated compound were subjected to acetylcholinesterase (AChE) inhibitory activity test using the microplate assay method. The structure of the isolated compound was determined using spectroscopic methods (1D and 2D NMR, and MS). RESULTS: The results of the acetylcholinesterase inhibitory assay revealed that n-BuOH and ethyl acetate fractions had the best activity with IC50 of 564.58 and 727.63 µg/mL respectively. Activity directed fractionation of each of these fractions led to the isolation of the same compound identified as a C-glucosylflavone; isovitexin-7-O-methyl ether (swertisin). This rare C-glucosylflavone co-exist as two rotamers and exhibited duplication of NMR signals. It is reported from this plant for the first time. Swertisin displayed better acetylcholinesterase inhibitory activity with IC50 of 32.09 µg/mL than physostigmine (eserine) with IC50 of 56.09 µg/mL used as a standard. CONCLUSIONS: This study reports isolation and characterization of a rare C-glycosylflavone; isovitexin-7-O-methyl ether (swertisin). Isolated compound exhibited duplication of NMR signals and better acetylcholinesterase inhibitory activity than eserine used as a standard. The activity exhibited by this compound suggests that it could be useful in the management of Alzheimer's disease.

Gelsedine-type oxindole alkaloids from Gelsemium elegans and the evaluation of their cytotoxic activity.

Phytochemical investigation on the 70% EtOH extract of the leaves and branches of Gelsemium elegans resulted into the isolation of five new gelsedine-type oxindole alkaloids, gelseleganins A-E (1-5). The structures of the isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry. The isolated alkaloids were tested in vitro for cytotoxic potential against seven tumor cell lines. As a result, alkaloids 3 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC50 values <10µM.

A novel pyrrole alkaloid from the fruit peels of Strychnos nux-blanda.

A novel pyrrole alkaloid, strychnuxin (1), along with five known compounds (2-6) was isolated from the fruit peels of Strychnos nux-blanda. The structures of all the isolated compounds (1-6) were fully characterised using spectroscopic data, as well as comparison with the previous literature data. Moreover, all isolated compounds were assessed for their α-glucosidase and acetylcholinesterase inhibitory activities.

Effect of detoxification (tadbeer) in content of toxic metabolites of Strychnos nux-vomica: A Unani approach for its use in human.

BACKGROUND: Azaraqi (Strychnos nux-vomica, Loganiaceae) has been the important Unani medicine since long time as a stimulant, anti-inflammatory, and blood purifier. It has been used very frequently by the Unani practitioner. But the Unani system recommends application of azaraqi in medicine only after its detoxification (tadbeer) may be because of the presence of its deadly poisonous alkaloids (strychnine and brucine). In the present investigation, an attempt has been made to quantify the actual content of their toxic alkaloids before and after the tadbeer. MATERIALS AND METHODS: A sensitive high-performance thin layer chromatographic (HPTLC) method has been developed for estimation of strychnine and brucine in different samples of azaraqi before and after tadbeer. Precoated HPTLC silica gel plates were used as stationary phase and (toluene: Ethyl acetate: Dietylamine 7:2:1 v/v/v) was used as mobile phase. RESULT: The Rf value of strychnine and brucine was found as 0.53 and 0.41, respectively. Detection and quantification were performed by densitometry at 270 nm. The calibration plot was linear in the range of 50-1000 ng of strychnine and brucine, respectively, with the correlation coefficient (r (2)) 0.993 and 0.991 for strychnine and brucine, respectively, which confirms good linearity. The content of strychnine was 0.175, 0.07, 0.18, 0.051, and 0.075% w/w whereas brucine was 0.16, 0.117, 0.061, 0.045, and 0.057 in crude azaraqi, azaraqi without outer cover, azaraqi outer cover only, azaraqi mudabbar and azaraqi mudabbar by fried in ghee, respectively. CONCLUSION: The detoxification results in sharp decrease in content of toxic metabolites. The process by boiling in milk was found much effective but tedious as compare to frying method.