GC-MS profiling and in vitro antioxidant, cytotoxic and antimicrobial activities of Trianthema triquetra Rottl. ex Willed.

Trianthema triquetra Rottl. ex Willed is being used as herbal remedy for chronic ulcer, wound healing, diabetes, skin and inflammatory diseases in India and Pakistan. Still, no scientific data is available about the therapeutic potential and phytochemistry of the plant. The aim of the current investigation is to perform GC-MS analysis, antioxidant (total phenolic and flavonoid content, DPPH assay), antimicrobial (disc diffusion assay) and cytotoxic (XTT and RBC's cellular membrane protection assay) studies. Whole plant material was dried and extracted with methanol to get crude methanolic extract and then it was fractionated with n-hexane, ethyl-acetate, chloroform, n-butanol and water. Results showed that n-butanol fraction exhibited a significant (p<0.05) antioxidant potential measured by DPPH assay (IC50=63.35±0.13µg/mL) and also possess highest phenolic content (177±4.36mg/g GAE). Whereas, n-hexane fraction showed highest flavonoid content (14.67±1.53mg/g QE). Two major components (2, 4-Ditert-butyl-6-nitrophenol (26.79%) and Squalene (25.64%) were detected in GC-MS analysis of chloroform fraction, eluted from column chromatography. Moreover, chloroform fraction also exhibited antibacterial activity towards all the tested strains of bacteria and fungi. Significant (p<0.05) dose dependent inhibition response on cell growth against CCRF-CEM cell lines was exhibited by methanolic extract. Furthermore, hemolytic potential of methanolic extract was found to be in safe range (2.23%-6.37%). So, it can be inferred that Trianthema triquetra can be exploited as an alternative remedy for cancer, oxidative stress related disorders and in various skin diseases.

Pharmacognostic screening, physico-chemical and cytotoxic potential of Sesuvium sesuvioides (Fenzyl) Verdc.

Sesuvium sesuvioides(Fenzl) Verdc. (Aizoaceae) is commonly known as BarriUlwaiti and used in folklore remedies; i.e. arthritis, gout, epistaxis, hemorrhage, smallpox, chickenpox, cold and flu by the local practitioners in the Cholistan desert. In the current study, fresh and dried plant material was examined macroscopically and microscopically. Transverse sections of plant parts such as leaf, stem, root and flower were also examined. Physico-chemical and fluorescence analysis according to WHO recommendations for standardization of plant material were performed. Phytochemical screening maybe helpful in determining the secondary metabolites responsible for their biological activities. Mineral analysis (Na+, K+, Li+, Ca2+, Mg2+, Cl-, Zn2+, Cu2+ and Fe2+), total fat and crude proteins were estimated to evaluate the nutritional value of the plant. In in-vitro cytotoxic activity, n-hexane fraction (50µg) showed significant results against Human T-lymphoblastic Leukemia CCRF-CEM cell lines followed by methanol and chloroform fractions. This study will be worthwhile for the correct identification and for observing any type of adulteration. This observation will be helpful for differentiating this species from closely related species of the same genus or family.

GC-MS profiling and in vitro antioxidant, cytotoxic and antimicrobial activities of Trianthema triquetra Rottl. ex Willed.

Trianthema triquetra Rottl. ex Willed is being used as a herbal remedy for various diseases in India and Pakistan. Still, no scientific data is available about therapeutic potential and phytochemistry of the plant. The aim of the current investigation is to perform GC-MS analysis, antioxidant (total phenolic and flavonoid content, DPPH assay), antimicrobial (disc diffusion assay) and cytotoxic (XTT and RBC's cellular membrane protection assay) studies. Methanolic extract and its fractions (n-hexane, ethyl-acetate, chloroform, n-butanol and water) were investigated for in vitro studies. Results showed that n-butanol fraction exhibited a significant (p<0.05) antioxidant potential (IC50=63.35±0.13 µg/mL) and also possess highest phenolic content (177±4.36 mg/g GAE). Whereas, n-hexane fraction showed highest flavonoid content (14.67±1.53 mg/g QE). 2, 4-Ditert-butyl-6-nitrophenol (26.79%) and Squalene (25.64%) were detected as major components through GC-MS analysis of chloroform fraction, eluted from column chromatography. Moreover, chloroform fraction also exhibited antimicrobial potential. Significant (p<0.05) dose dependent inhibition response on cell growth against CCRF-CEM cell lines was exhibited by methanolic extract. Furthermore, hemolytic potential of methanolic extract was found to be in safe range (2.23%-6.37%). So, it can be inferred that Trianthema triquetra can be exploited as an alternative remedy for cancer, oxidative stress related disorders and various skin diseases.

New Adenosine Derivatives from Aizoon canariense L.: In Vitro Anticholinesterase, Antimicrobial, and Cytotoxic Evaluation of Its Extracts.

Aizoaceae is a large succulent family characterized by many psychoactive species. Aizoon canariense L., a wild neglected plant traditionally used in gastrointestinal ailments, has been the subject of a limited number of phytochemical and biological studies. Therefore, herein, we investigated the in vitro cytotoxic, antimicrobial, and anticholinesteraseactivity of the aerial parts of A. canariense L. and analyzed the phytochemical compositions of the lipoidal and alkaloidal fractions. Petroleum ether extract showed the presence of behenic and tricosylic acid, while an in-depth investigation of the alkaloidal fraction revealed the identification of new adenine based alkaloids (1-5), which were isolated and identified for the first time from Aizoon canariense L. Their structures were elucidated based on extensive spectroscopic analyses. The alkaloidal extract showed a powerful cytotoxic effect (IC50 14-28 µg/mL), with the best effect against colon carcinoma, followed by liver and breast carcinomas. The alkaloidal extract also had a potent effect against Candida albicans and Escherichia coli, with minimum inhibitory concentrations (MIC) values of 312.5 and 625 µg/mL. The in vitro anticholinesterase activity was potent, with IC50 < 200 ng/mL for the tested extracts compared with 27.29 ± 0.49 ng/mL for tacrine.

Identification of Chemopreventive Components from Halophytes Belonging to Aizoaceae and Cactaceae Through LC/MS-Bioassay Guided Approach.

Six halophytes, namely, Aptenia cordifolia var. variegata, Glottiphyllum linguiforme, Carpobrotus edulis, Ferocactus glaucescens, F. pottsii and F. herrerae were investigated for chemopreventive effect. Prioritization of most promising plant for further investigation was carried out through an integrated liquid chromatography-high resolution electrospray ionization mass spectrometry profiling-bioassay guided approach. NAD(P)H: quinone oxidoreductase-1 (NQO-1) induction in cultured murine hepatoma cells (Hepa-1c1c7) and inhibition of nitric oxide (NO) production in lipopolysaccharide-activated macrophages (RAW 264.7) were carried out to investigate chemopreventive effect. Bioassay data revealed that F. herrerae, A. cordifolia, C. edulis and F. glaucescens were the most active with 2-, 1.7-, 1.6- and 1.5-folds induction of NQO-1 activity. Only F. glaucescens exhibited >50% inhibition of NO release. LCMS profiling of the F. glaucescens revealed its high content of flavonoids, a known micheal acceptor with possible NQO-1 induction, as proved by quantitative high-performance liquid chromatography analysis. Thus, the extract of F. glaucescens was subjected to chromatographic fractionation leading to the isolation of four compounds including (i) 2S-naringenin, (ii) trans-dihydrokaempferol (aromadendrin), (iii) 2S-naringenin-7-O-ß-d-glucopyranoside and (iv) kaempferol-7-O-ß-d-glucopyranoside (populnin). The current study through an LCMS dereplication along with bio guided approach reported the activity of populnin as NO inhibitor and NQO-1 inducer with promising chemopreventive potential.

Photodamage on Staphylococcus aureus by natural extract from Tetragonia tetragonoides (Pall.) Kuntze: Clean method of extraction, characterization and photophysical studies.

Photodynamic therapy (PDT) is a clinical modality that allows the destruction of tumor cells and microorganisms by reactive oxygen species, formed by the combination of photosensitizer (PS), molecular oxygen and adequate wavelength light. This research, through a clean methodology that involves pressurized liquids extraction (PLE), obtained a highly antimicrobial extract of Tetragonia tetragonoides, which rich in chlorophylls as photosensitizers. The Chlorophylls-based extract (Cbe-PLE) presented pharmacological safety, through the maintenance of cellular viability. In addition, Cbe-PLE showed great efficacy against Staphylococcus aureus, with severe dose-dependent damage to the cell wall of the pathogen. The obtained product has a high potential for the development of photostimulated phytotherapic formulations for clinical applications in localized infections, as a complementary therapeutic alternative to antibiotics.

Anti-Alzheimer potential, metabolomic profiling and molecular docking of green synthesized silver nanoparticles of Lampranthus coccineus and Malephora lutea aqueous extracts.

The green synthesis of silver nanoparticles (SNPs) using plant extracts is an eco-friendly method. It is a single step and offers several advantages such as time reducing, cost-effective and environmental non-toxic. Silver nanoparticles are a type of Noble metal nanoparticles and it has tremendous applications in the field of diagnostics, therapeutics, antimicrobial activity, anticancer and neurodegenerative diseases. In the present work, the aqueous extracts of aerial parts of Lampranthus coccineus and Malephora lutea F. Aizoaceae were successfully used for the synthesis of silver nanoparticles. The formation of silver nanoparticles was early detected by a color change from pale yellow to reddish-brown color and was further confirmed by transmission electron microscope (TEM), UV-visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), and energy-dispersive X-ray diffraction (EDX). The TEM analysis of showed spherical nanoparticles with a mean size between 12.86 nm and 28.19 nm and the UV- visible spectroscopy showed λmax of 417 nm, which confirms the presence of nanoparticles. The neuroprotective potential of SNPs was evaluated by assessing the antioxidant and cholinesterase inhibitory activity. Metabolomic profiling was performed on methanolic extracts of L. coccineus and M. lutea and resulted in the identification of 12 compounds, then docking was performed to investigate the possible interaction between the identified compounds and human acetylcholinesterase, butyrylcholinesterase, and glutathione transferase receptor, which are associated with the progress of Alzheimer's disease. Overall our SNPs highlighted its promising potential in terms of anticholinesterase and antioxidant activity as plant-based anti-Alzheimer drug and against oxidative stress.

Efficacy of Chrozophora plicata and Trianthema portuclacastrum weed plant extracts against Trogoderma granarium Everts under laboratory conditions.

The efficacy of Chrozophora plicata and Trianthema portuclacastrum extracts was investigated against Trogoderma granarium at 10%, 20% and 30% concentrations and 2, 4 and 6 days of exposure periods. It was found that T. portuclacastrum extract caused significantly higher larval mortality (37.47%) than C. plicata (27.03%). Maximum number of T. granarium larvae (91.11% and 82.22%) was repelled when exposed to 30% concentration. A significant reduction in percentage larval emergence was also found in F1 generation. A decrease in the activity of Acetylcholine Esterase (AChE), Acid Phosphatase (ACP), Alkaline Phosphatase (AKP), α-Carboxyl and ß-Carboxyl was also found. The FTIR analysis showed the presence of polyphenolic compounds in T. portuclacastrum extract. The overall results revealed that T. portuclacastrum extract was very effective against T. granarium than C. plicata.

Amaryllidaceae and Sceletium alkaloids.

Covering: July 2015 to June 2017. Previous review: Nat. Prod. Rep., 2016, 33, 1318-1343 Recent progress on the isolation, identification, biological activity and synthetic studies of the structurally diverse alkaloids from plants of family Amaryllidaceae has been summarized in this review. In addition, the structurally related alkaloids isolated from Sceletium species are discussed.

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

Tetragonia tetragonioides (Pall.) Kuntze protects estrogen-deficient rats against disturbances of energy and glucose metabolism and decreases proinflammatory cytokines.

Tetragonia tetragonioides (Pall.) Kuntze (TTK) and JakYakGamCho-Tang (JGT) have been used for improving women's health and treating inflammatory diseases. We determined that the long-term consumption of these herbal extracts alleviates the progression of postmenopausal symptoms in high-fat-diet fed ovariectomized (OVX) rats, and further explored the mechanisms involved. Five groups of OVX rats were fed high fat diets that were supplemented with either 2% dextrin (control), 2% TTK (70% ethanol extract), 2% JGT (water extract), 1% JGT + 1% TTK (JGTT), or 30 µg/kg body weight/day of 17ß-estradiol (positive control). After eight weeks of dietary intervention, the herbal treatments did not change the serum concentrations of 17ß-estradiol or uterine weight in control rats, but they were higher in the positive-control group. TTK rats exhibited higher daily energy expenditure, particularly fat oxidation, without modifying the energy intake than the controls. TTK lowered the fat mass but lean body mass of the abdomen and leg were increased. JGT decreased periuterine fat mass and lean body mass more than the control but the decrease was not as much as TTK. TTK resulted in substantially lower serum concentrations of the proinflammatory cytokines, tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1, than the control and JGT had lesser effect than TTK. Insulin resistance, determined by homeostasis model assessment estimate for assessing insulin resistance (HOMA-IR) and insulin tolerance test, was reduced in the decreasing order of control, JGT, JGTT, and TTK and the HOMA-IR of TTK was similar to the positive control. TTK, but not JGT, enhanced glucose tolerance compared with the control, although the serum insulin levels in TTK were lower compared to the control. Interestingly, the ß-cell masses were much greater in the TTK and JGTT groups than in the control, and they were comparable to the positive control. The increases in ß-cell masses in TTK and JGTT groups were associated with enhanced ß-cell proliferation and suppressed apoptosis, which was related to the decreased TNF-α and interleukin-1ß expressions. In conclusion, JGTT did not improve menopausal symptoms better than TTK itself. TTK itself prevented the OVX-induced impairments in energy, lipid, and glucose metabolism, similar to the positive control, without changing serum 17ß-estradiol levels and potentiating insulin signaling and decreasing proinflammatory cytokines. TTK may be a useful intervention to alleviate some menopausal symptoms similar to selective estrogen receptor modulators and should be investigated with further human study. Impact statement Menopause decreases the quality of life in middle-aged women and herbal remedies are sometimes used as alternatives for hormone replacement therapy, which may have detrimental side effects. Although several herbal extracts have been studied, no remedies improve all the menopausal symptoms. In this study, the 70% ethanol extract of Tetragonia tetragonioides (Pall.) Kuntze (TTK) reduced the symptoms of hot flushes and improved energy, glucose, and lipid metabolism in estrogen-deficient animals without increasing serum 17ß-estradiol levels. This extract acts like a selective estrogen receptor modulator and it may be a useful intervention for alleviating menopausal symptoms. This is the first study to show that the 70% ethanol extract of TTK has the potential to treat menopause-associated symptoms and metabolic disturbances. It may be a useful intervention for alleviating the symptoms of menopause in women if its efficacy can be confirmed in human studies.

Biochemical and Molecular Study of Carpobrotus edulis Bioactive Properties and Their Effects on Dugesia sicula (Turbellaria, Tricladida) Regeneration.

The traditional medicinal properties of Carpobrotus edulis are well recognized, particularly in Tunisia where it is used for wound healing. Thus, in this study, biochemical and molecular properties of its leaves' bioactive aqueous-acetone extract were investigated. The total phenolic content (TPC) of the extract was estimated to be 184 ± 5 mg/100 g of fresh matter (FM). The qualitative and quantitative polyphenolic profile was determined by ultra performance liquid chromatography with diode array detection (UPLC-DAD) and showed that chlorogenic acid was the major compound (43.7%). The extract exhibits potent antioxidant capacities with IC50 = 56.19 and 58.91 µg/ml, as accessed via the anionic DPPH and cationic ABTS radical scavenging assays, respectively. The extract has high antibacterial properties, especially against the Gram+ Staphylococcus aureus and Bacillus cereus strains. To investigate the extract effect on regeneration, the flatworm Dugesia sicula Lepori, 1948, was used as a model. The macroscopic analysis of planarian cultures in ordinary medium containing phenolic extract at non-toxic concentrations illustrated that the extract caused morphological changes. Additionally, the molecular study through the fluorescence-activated cell sorting (FACS) technique showed that C. edulis polyphenols can harm the stem cells' development. These results emphasize the ecotoxicological impact of phenolic rejections in the environment on flatworms' physiology.

Cadmium accumulation is enhanced by ammonium compared to nitrate in two hyperaccumulators, without affecting speciation.

Nitrogen fertilization could improve the efficiency of Cd phytoextraction in contaminated soil and thus shorten the remediation time. However, limited information is available on the effect of N form on Cd phytoextraction and associated mechanisms in plants. This study examined the effect of N form on Cd accumulation, translocation, and speciation in Carpobrotus rossii and Solanum nigrum Plants were grown in nutrient solution with 5-15 µM Cd in the presence of 1000 µM NH4 (+) or NO3 (-) Plant growth and Cd uptake were measured, and Cd speciation was analyzed using synchrotron-based X-ray absorption spectroscopy. Shoot Cd accumulation was 30% greater with NH4 (+) than NO3 (-) supply. Carpobrotus rossii accumulated three times more Cd than S. nigrum. However, Cd speciation in the plants was not influenced by N form, but it did vary with species and tissues. In C. rossii, up to 91% of Cd was bound to S-containing ligands in all tissues except the xylem sap where 87-95% were Cd-OH complexes. Furthermore, the proportion of Cd-S in shoots was substantially lower in S. nigrum (44-69%) than in C. rossii (60-91%). It is concluded that the application of NH4 (+) (instead of NO3 (-)) increased shoot Cd accumulation by increasing uptake and translocation, rather than changing Cd speciation, and is potentially an effective approach for increasing Cd phytoextraction.

Nitric Oxide and ERK mediates regulation of cellular processes by Ecdysterone.

The complex process of wound healing is a major problem associated with diabetes, venous or arterial disease, old age and infection. A wide range of pharmacological effects including anabolic, anti-diabetic and hepato-protective activities have been attributed to Ecdysterone. In earlier studies, Ecdysterone has been shown to modulate eNOS and iNOS expression in diabetic animals and activate osteogenic differentiation through the Extracellular-signal-Regulated Kinase (ERK) pathway in periodontal ligament stem cells. However, in the wound healing process, Ecdysterone has only been shown to enhance granulation tissue formation in rabbits. There have been no studies to date, which elucidate the molecular mechanism underlying the complex cellular process involved in wound healing. The present study, demonstrates a novel interaction between the phytosteroid Ecdysterone and Nitric Oxide Synthase (NOS), in an Epidermal Growth Factor Receptor (EGFR)-dependent manner, thereby promoting cell proliferation, cell spreading and cell migration. These observations were further supported by the 4-amino-5-methylamino- 2' ,7' -difluorofluorescein diacetate (DAF FM) fluorescence assay which indicated that Ecdysterone activates NOS resulting in increased Nitric Oxide (NO) production. Additionally, studies with inhibitors of both the EGFR and ERK, demonstrated that Ecdysterone activates NOS through modulation of EGFR and ERK. These results clearly demonstrate, for the first time, that Ecdysterone enhances Nitric Oxide production and modulates complex cellular processes by activating ERK1/2 through the EGF pathway.

Cadmium uptake by Carpobrotus rossii (Haw.) Schwantes under different saline conditions.

Plants used for phytoextraction of heavy metals from contaminated soils with high levels of salinity should be able to accumulate heavy metals and also be tolerant to salinity. Australian native halophyte species Carpobrotus rossii has recently been shown to tolerate and accumulate multiple heavy metals, especially cadmium (Cd). This study examined the effects of salt type and concentration on phytoextraction of Cd in C. rossii. Plants were grown in contaminated soil for 63 days. The addition of salts increased plant growth and enhanced the accumulation of Cd in shoots up to 162 mg kg(-1) which almost doubled the Cd concentration (87 mg kg(-1)) in plants without salt addition. The increased Cd accumulation was ascribed mainly to increased ionic strength in soils due to the addition of salts and resultantly increased the mobility of Cd. In comparison, the addition of Cl(-) resulted in 8-60 % increase in Cd accumulation in shoots than the addition of SO4 (2-) and NO3 (-). The findings suggest that C. rossii is a promising candidate in phytoextraction of Cd-polluted soils with high salinity levels.

Health-promoting and disease-preventive potential of Trianthema portulacastrum Linn. (Gadabani) -An Indian medicinal and dietary plant.

It is estimated that 80% of the world population depends on traditional medicine for primary healthcare need. Trianthema portulacastrum Linn. (family: Aizoaceae) is a small perennial weed found in the Americas, Africa, India, and other regions of the world. This plant is used extensively in Indian traditional medicines and is also consumed as a vegetable throughout Asia for its perceived health benefits. Phytochemical analysis of T. portulacastrum reveals the presence of alkaloids, flavonoids, terpenoids, saponins, and phenolic compounds. Emerging studies demonstrate that crude extracts as well as bioactive phytoconstituents of T. portulacastrum exhibit potent antioxidant, anti-infective, analgesic, and anti-inflammatory activities. A growing number of in vitro and in vivo studies demonstrate various biological and pharmacological activities, including prevention and amelioration of hepatotoxicity, nephrotoxicity, hyperglycemia, hyperlipidemia, infectious diseases and cancer. This review aims to present and analyze available literature to understand the full potential of T. portulacastrum in health promotion and disease prevention. Current limitations and future directions of research on this medicinal and dietary plant are also critically discussed.

Influence of nitrogen form on the phytoextraction of cadmium by a newly discovered hyperaccumulator Carpobrotus rossii.

Using hyperaccumulator plants is an important method to remove heavy metals from contaminated land. Carpobrotus rossii, a newly found Cd hyperaccumulator, has shown potential to remediate Cd-contaminated soils. This study examined the effect of nitrogen forms on Cd phytoextraction by C. rossii. The plants were grown for 78 days in an acid soil spiked with 20 mg Cd kg(-1) and supplied with (NH4)2SO4, Ca(NO3)2, urea, and chicken manure as nitrogen (N) fertilizers. Nitrification inhibitor dicyandiamide (DCD) was applied to maintain the ammonium (NH4(+)) form. Nitrogen fertilization increased shoot biomass but decreased root biomass with the highest shoot biomass occurring in the manure treatment. Compared to the no-N control, urea application did not affect shoot Cd concentration, but increased Cd content by 17% due to shoot biomass increase. Chicken manure significantly decreased CaCl2-extractable Cd in soil, and the Cd concentration and total Cd uptake in the plant. Rhizosphere pH was the highest in the manure treatment and the lowest in the NH4(+) treatments. The manure and nitrate (NO3(-)) treatments tended to have higher rhizosphere pH than their respective bulk soil pH, whereas the opposite was observed for urea and NH4(+) treatments. Furthermore, the concentrations of extractable Cd in soil and Cd in the plant correlated negatively with rhizosphere pH. The study concludes that urea significantly enhanced the Cd phytoaccumulation by C. rossii while chicken manure decreased Cd availability in soil and thus the phytoextraction efficiency.

HPLC-Based Activity Profiling for hERG Channel Inhibitors in the South African Medicinal Plant Galenia africana.

The human ether-a-go-go-related gene channel is a voltage-activated K(+) channel involved in cardiac action potential. Its inhibition can lead to QT prolongation, and eventually to potentially fatal arrhythmia. Therefore, it is considered a primary antitarget in safety pharmacology. To assess the risk of human ether-a-go-go-related gene channel inhibition by medicinal plants, 700 extracts from different parts of 142 medicinal plants collected in Southern Africa were screened on Xenopus laevis oocytes. A CH2Cl2 extract from the stems and leaves of Galenia africana (Aizoaceae) reduced the peak tail human ether-a-go-go-related gene current by 50.4 ± 5.5 % (n = 3) at a concentration of 100 µg/mL. By means of high-performance liquid chromatography-based activity profiling, nine flavonoids were identified in the active time windows. However, the human ether-a-go-go-related gene channel inhibition of isolated compounds was less pronounced than that of extract and active microfractions (human ether-a-go-go-related gene inhibition between 10.1 ± 5 and 14.1 ± 1.6 at 100 µM). The two major constituents, 7,8-methylenedioxyflavone (1) and 7,8-dimethoxyflavone (13), were quantified (4.3 % and 9.4 %, respectively, in the extract). Further human ether-a-go-go-related gene inhibition tests for compounds 1 and 13 at 300 µM showed a concentration-dependent inhibitory activity (33.2 ± 12.4 and 30.0 ± 7.4, respectively). In a detailed phytochemical profiling of the active extract, a total of 20 phenolic compounds, including six new natural products, were isolated and identified.

Trianthema portulacastrum Linn. displays anti-inflammatory responses during chemically induced rat mammary tumorigenesis through simultaneous and differential regulation of NF-κB and Nrf2 signaling pathways.

Trianthema portulacastrum, a medicinal and dietary plant, has gained substantial importance due to its various pharmacological properties, including anti-inflammatory and anticarcinogenic activities. We have recently reported that a characterized T. portulacastrum extract (TPE) affords a considerable chemoprevention of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis though the underlying mechanisms are not completely understood. The objective of this study was to investigate anti-inflammatory mechanisms of TPE during DMBA mammary carcinogenesis in rats by monitoring cyclooxygenase-2 (COX-2), heat shock protein 90 (HSP90), nuclear factor-kappaB (NF-κB) and nuclear factor erythroid 2-related factor 2 (Nrf2). Mammary tumors were harvested from our previous study in which TPE (50-200 mg/kg) was found to inhibit mammary tumorigenesis in a dose-response manner. The expressions of intratumor COX-2, HSP90, NF-κB, inhibitory kappaB-alpha (IκBα) and Nrf2 were determined by immunohistochemistry. TPE downregulated the expression of COX-2 and HSP90, blocked the degradation of IκBα, hampered the translocation of NF-κB from cytosol to nucleus and upregulated the expression and nuclear translocation of Nrf2 during DMBA mammary carcinogenesis. These results in conjunction with our previous findings suggest that TPE prevents DMBA-induced breast neoplasia by anti-inflammatory mechanisms mediated through simultaneous and differential modulation of two interconnected molecular circuits, namely NF-κB and Nrf2 signaling pathways.

GC-MS, LC-MS(n), LC-high resolution-MS(n), and NMR studies on the metabolism and toxicological detection of mesembrine and mesembrenone, the main alkaloids of the legal high "Kanna" isolated from Sceletium tortuosum.

Mesembrine and mesembrenone are the main alkaloids of Sceletium tortuosum, a plant species that was used for sedation and analgesia by the KhoiSan, previously known as Hottentots, a tribe in South Africa. After fermentation, the obtained preparation called "Kanna" or "Kougoed" was used by chewing, smoking, or sniffing. Today, Kanna gains popularity by drug users as legal high. For monitoring such consumption, metabolism studies are mandatory because the metabolites are mostly the analytical targets, especially in urine. Therefore, the metabolism of both alkaloids was investigated in rat urine and pooled human liver preparations after several sample work-up procedures. As both alkaloids were not commercially available, they were isolated from plant material by Soxhlet extraction, and their identity confirmed by NMR. The metabolites were identified using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography coupled to linear ion trap high resolution mass spectrometry (LC-HR-MS(n)). Both alkaloids were O- and N-demethylated, dihydrated, and/or hydroxylated at different positions. The phenolic metabolites were partly excreted as glucuronides and/or sulfates. Most of the phase I metabolites identified in rat urine could be detected also in the human liver preparations. After a common user's low dose application of mesembrine, mainly the O- and N demethyl-dihydro, hydroxy, and bis-demethyl-dihydro metabolites, and in case of mesembrenone only the N-demethyl and the N-demethyl-dihydro metabolite could be detected in rat urine using the authors' standard urine screening approaches (SUSA) by GC-MS or LC-MS(n). Thus, it should be possible to monitor a consumption of mesembrine and/or mesembrenone assuming similar pharmacokinetics in humans.