Astragalus membranaceus ultrafine powder alleviates hyperuricemia by regulating the gut microbiome and reversing bile acid and adrenal hormone biosynthesis dysregulation

Ethnopharmacological relevanceMetabolic syndrome is closely related to the intestinal microbiota and disturbances in the host metabolome. Hyperuricemia (HUA), a manifestation of metabolic syndrome, can induce various cardiovascular diseases and gout, seriously affecting a patient’s quality of life. Astragalus membranaceus has a long history as a commonly used traditional Chinese medicine to treat kidney disease in China and East Asia.Materials and methodsWe compared the therapeutic effect of benzbromarone and two different doses Astragalus membranaceus ultrafine powder (AMUP) in rats with HUA. Ultra-performance liquid chromatography-mass spectrometer was used to analyze the AMUP metabolism in the plasma, urine, and feces. Further, 16S ribosome RNA sequencing and feces metabolomic were performed to capture the variation of the gut microbiota and metabolites changes before and after drug administration.ResultsAMUP had a notable impact on reducing blood uric acid levels while protecting the liver and kidney. Drug metabolism analysis demonstrated that effective constituent flavonoids are distributed in the blood, whereas saponins remain in the intestine. Gut microbiota analysis showed that low-dose AMUP ameliorated HUA-induced gut dysbiosis by reducing the abundance of harmful bacteria and increasing that of some beneficial bacteria with anti-inflammatory properties, such as Clostridia, Lachnospiraceae, and Muribaculaceae. In addition, HUA-induced changes in metabolite contents in bile acid and adrenal hormone biosynthesis pathways were restored after treatment with AMUP.ConclusionLow-dose AMUP exerts remarkable therapeutic effects on HUA by regulating the gut microbiome and mediating gut metabolism pathways associated with uric acid excretion.     

Antimycobacterial and anticancer activity of newly designed cinnamic acid hydrazides with favorable toxicity profile

A series of twelve novel hybrids of cinnamic acid and thiocarbohydrazones were designed, synthesized in high yield using a simple coupling strategy via acid chlorides, and evaluated for their impact against Mycobacterium tuberculosis (Mtb) and cancer cells survival. Among them, compound 3 demonstrated strong anti-Mtb activity by reducing bacilli survival for>90 % in all three treated Mtb isolates, whereas isoniazid and rifampicin did not. Moreover, compound 3 didn’t affect vitality of HepG-2 cells, implying on advantageous hepatotoxicity profile compared to current therapeutic options for tuberculosis. Compounds 2a and 3b displayed as strong inducers of apoptosis in A549 cells, both activating intrinsic caspase pathway and cell cycle arrest at the G0/G1 phase. Subsequent analyses disclosed differences in their activities, where 3b has ability to induce production of mitochondrial superoxide anions, while 2a significantly inhibited cellular mobility. More importantly, 3b considerably affected viability of HepG-2 and HaCaT cells, whereas 2a had moderate impact only on the later. Molecular modeling studies indicated high permeability and good absorption through the human intestine, and moderate aqueous solubility with poor blood–brain barrier permeability. In summary, our results reveal that novel compounds 3 and 2a represent promising agents for tuberculosis and cancer treatment, respectively, indicating that further investigation needs to be performed to clarify the mechanisms of their anti-Mtb and anticancer activity.     

Chemical profiling of Verbena officinalis and assessment of its anti-cryptosporidial activity in experimentally infected immunocompromised mice

Cryptosporidiosis is a global zoonotic infection that causes water-borne epidemics of diarrhea. Nevertheless, there are few available therapies for cryptosporidiosis. However, the gold standard drug nitazoxanide (NTZ) has limited efficacy in malnourished and immunocompromised patients. Furthermore, Verbena officinalisL. is a herbal plant widely used in traditional medicine to cure several health disorders and is recognized to possess numerous therapeutic applications. In the present study, the phytochemical composition of aerial part extract from Verbena officinalis was investigated via LC-ESI-MS/MS.Furthermore, the anti-cryptosporidial activity was also performed using an animal model. Fifty mice were divided into 5 groups; GI: non-infected (Negative control), GII: infected non treated (positive control), GIII: infected, treated with NTZ, GIV: infected, treated with V. officinalis n-butanol extract, GV: infected, treated with a combination of NTZ and V. officinalis. Parasitological examination revealed a highly significant difference (P-value < 0.001) between GIII, GIV, and GV compared to GII regarding the mean number of Cryptosporidium spp. oocyst in the stool. Moreover, GV showed the best efficacy with a percentage of 87%. Also, histopathological examination showed variable degrees of improvement in the villous broadening, and the inflammatory infiltrates in the small intestine with a reduction of hepatocyte degeneration and mononuclear infiltration in GIII, GIV, and GV compared to GII, with the best results seen in GV. Additionally, the chemical profiling of n-butanol extract identified 16 secondary metabolites comprising flavonoids, phenolic acids, phenylethanoids, and coumarins. In conclusion, V. officinalis is an intrinsic supplier of biologically active metabolites with outstanding anti-parasitic and possible anti-inflammatory effects.     

Biosynthesis of silver and gold nanoparticles using Sargassum horneri extract as catalyst for industrial dye degradation

This study focuses on the green synthesis of silver and gold nanoparticles using the marine algae extract, Sargassum horneri, as well as the degradation of organic dyes using biosynthesized nanoparticles as catalysts. The phytochemicals of the brown algae Sargassum horneri acted as reducing and capping agents for nanoparticle synthesis. Ultraviolet–visible absorption spectroscopy, dynamic light scattering, high-resolution transmission electron microscopy, selected area electron diffraction, energy dispersive X-ray spectroscopy, X-ray powder diffraction, and Fourier transform infrared spectroscopy were used to characterize the biosynthesized nanoparticles. The green-synthesized SH-AgNPs and SH-AuNPs exhibited high catalytic activity for degradation of organic dyes, such as methylene blue, rhodamine B, and methyl orange. The reduction reactions of dyes are based on pseudo-first-order kinetics.     

Integrating approach to discover novel bergenin derivatives and phenolics with antioxidant and anti-inflammatory activities from bio-active fraction of Syzygium brachythyrsum

Syzygium brachythyrsum is an important folk medicinal and edible plant in Yunnan ethnic minority community of China, however, little is known about the chemical and bio-active properties. The present study is aimed to identify the bioactive constituents with antioxidant and anti-inflammatory properties by an integrating approach. First, two new bergenin derivatives, brachythol A (1) and brachythol B (2), together with eleven known phenolic compounds (3–13) were isolated from bioactive fractions by phytochemical method. Among these isolated chemicals, five bergenin derivatives, along with 3 phenolics were found in Syzygium genus for the first time. Then, a further chemical investigation based on ultra-high-performance liquid chromatography-Q Exactive Orbitrap mass spectrometry resulted in a total of 107 compounds characterized in the bio-active fractions, including 50 bergenin derivatives, among which 14 bergenin derivatives and 14 phenolics were potential new natural chemicals. Most of the isolated compounds showed obvious antioxidant activities, while compounds 11, 12, and 13 had favorable performance. Eight compounds (2–5, 7, and 9–11) showed good inhibitory activity on nitric oxide (NO) production in macrophage RAW 264.7 cells. The structure–activity correlation analysis indicated that the antioxidation and anti-inflammatory activities enhanced when bergenin was esterified with gallic acid, caffeic acid or ferulic acid. This is the first report of bergenins in Syzygium genus and the richness in new bio-active bergenins and gallic acid derivatives indicated that Syzygium brachythyrsum is a promising functional and medicinal resource.     

Kinetic features of Gualou-Xiebai-Banxia decoction,a classical traditional Chinese medicine formula,in rat plasma and intestine content based on its metabolic profile

Gualou-Xiebai-Banxia decoction (GXB) is a famous classical traditional Chinese medicine (TCM) formula for the treatment of coronary heart disease (CHD, namely chest stuffiness and pain syndrome in Chinese medicine). Compared with Gualou-Xiebai-Baijiu decoction, which only consists of Trichosanthis Pericarpium (TP), Allii Macrostemonis Bulbus (AMB) and wine, GXB comprises one additional herbal medicine, Pinellinae Rhizoma Praeparatum (PRP). However, due to a lack of kinetic profile studies on GXB, its in vivo components with high exposure remain unknown, making it difficult to interpret bioactive components likely linked to its efficacy, but also fails to provide substance-related evidence for reflecting the compatibility in GXB. The goal of this study was to systematically characterize the kinetic features of GXB in rat plasma and intestine content for revealing its in vivo high-exposure components on the basis of their metabolic fates, and to compare the kinetic differences between GXB and GXB-dePRP (GXB deducted PRP) for describing the chemical contribution of PRP to the compatibility in GXB. Firstly, the metabolic profile of GXB was systematically investigated by UPLC-Q/TOF-MS. Subsequently, quantitative methods for representative xenobiotics in rat plasma and intestine content were respectively validated and developed by UPLC-TQ-MS. Then, the established approaches were successfully applied to characterize the kinetic features of GXB through estimating pharmacokinetic parameters. These results showed that only a few kinds of xenobiotics at low exposure levels were observed in plasma, while various xenobiotics possessed high exposure in intestine content. Among them, steroidal saponins and triterpenoid saponins displayed relatively high exposure in plasma and intestine content, which are likely associated with the therapeutic effects of GXB. Moreover, there were no significant differences between metabolic profiles of GXB and GXB-dePRP, whereas the pharmacokinetic parameters, including area under the concentration–time curve (AUC) and C_max (p < 0.05) for most xenobiotics in GXB were significantly larger than those in GXB-dePRP, implying that the introduction of PRP improved the bioavailability of constituents from TP and AMB. Altogether, this study laid a solid foundation and provided theoretical guidance for further clarification of bioactive components of GXB, as well as the synergistic effect of PRP to the compatibility in GXB.     

Pitanga (Eugenia uniflora L.) as a source of bioactive compounds for health benefits: A review

The pitangueira (Eugenia uniflora) is a tree native to Brazil but is cultivated in several subtropical countries. A great diversity of nutrients and bioactive compounds have been found in the leaves and fruits of E. uniflora, which supports its use in folk medicine to treat diseases such as stomach and intestinal disorders, fever and general inflammation. Antimicrobial, antiviral, antifungal and antioxidant effects on metabolism have been reported for this plant. This review discusses the phytochemical profile, toxicity and pharmacological action of E. uniflora leaves and fruits and points out that gaps in the literature that need to be investigated further. This review also discusses studies developed with E. uniflora demonstrating its promising therapeutic potential for several diseases with an apparent low toxicity in mammals. The compilation of the main pharmacological and toxicological results, as well as the phytochemical characterization of the varieties and constituents of E. uniflora are general aspects that this review attempts to demonstrate in order to contribute to the new approaches and developments to plant-derived natural product drug discovery. However, further studies are required to establish the nutraceutical effects and uses of E. uniflora as an important and safe supplement for human health.     

Derivatization of dihydrotetrabenazine for technetium-99m labelling towards a radiotracer targeting vesicular monoamine transporter 2

The development of technetium-99m-labelled dihydrotetrabenazine (DTBZ) derivative for vesicular monoamine transporter 2 (VMAT2) tracing could be a benefit for single photon emission computed tomography (SPECT) imaging due to easy labelling chemistry and great availability through nuclide generator system. Here, we successfully prepared a technetium-99m-labelled DTBZ derivative and subsequently evaluated its biological activity targeting VMAT2. A novel combination of the bisaminoethanethiol (BAT) chelator scaffold with the biologically active DTBZ vector was performed to synthesize the labelling precursor BAT-P-DTBZ, and it was accomplished in six steps. The technetium-99m labelling was carried out in the radiochemical study of BAT-P-DTBZ conjugate, and the radiolabelling conditions were investigated and optimized. Under the optimized labelling condition, ^99mTc-BAT-P-DTBZ was acquired with a good radiochemical purity of above 95 %. The quality control test showed that ^99mTc-BAT-P-DTBZ is stable over 6 h and it has a suitable lipophilicity, suggesting successful appositeness for the needs of routine biological evaluation experiments. The in vitro biological evaluation revealed that ^99mTc-BAT-P-DTBZ could bind to VMAT2 sites. The in vivo biodistribution study clearly indicated that the pancreas (VMAT2-enriched region) displays relatively high uptake of ^99mTc-BAT-P-DTBZ among all organs in mice. The specific VMAT2 binding signal of ^99mTc-BAT-P-DTBZ was separately detected in the in vitro and in vivo biological evaluation. Therefore, ^99mTc-BAT-P-DTBZ might be a potential imaging agent for monitoring VMAT2 binding sites in the pancreas.     

Synthesis,antifungal activity and in vitro mechanism of novel 1-substituted-5-trifluoromethyl-1H-pyrazole-4-carboxamide derivatives

Inspired by the wide application of amides in plant pathogens, a series of novel 1-substituted-5-trifluoromethyl?1H?pyrazole-4-carboxamide derivatives were designed and synthesized. Bioassay results indicated that some target compounds exhibited excellent and broad-spectrum in vitro and certain in vivo antifungal activities. Among them, the in vitro EC₅₀ values of Y₁₃ against G. zeae, B. dothidea, F. prolifeatum and F. oxysporum were 13.1, 14.4, 13.3 and 21.4 mg/L, respectively. The in vivo protective activity of Y₁₃ against G. zeae at 100 mg/L was 50.65%. SAR analysis revealed that the phenyl on the 1-position of the pyrazole ring was important for this activity. An antifungal mechanism study of Y₁₃ against G. zeae demonstrated that this compound may disrupt the cell membrane of mycelium, thus inhibiting the growth of fungi. These mechanistic study results were inconsistent with those for traditional amides and may provide a novel view for deep study of this series of pyrazole carboxamide derivatives.     

Fractionation and purification of antioxidant peptides from Chinese sturgeon (Acipenser sinensis) protein hydrolysates prepared using papain and alcalase 2.4L

Protein hydrolysates have the potential to be natural and safer sources of bioactive peptides. In this study, two proteases were used to hydrolyze Chinese sturgeon (Acipenser sinensis) protein, and the hydrolysates were then purified to yield antioxidant peptides. The degree of hydrolysis of 23.56 % and 18.14 % was obtained using papain and alcalase 2.4L, respectivly, and hydrolysates had 96.80 % and 87.24 % total amino acid content, respectivly. The papain hydrolysate (PH) and alcalase 2.4L hydrolysate (AH) showed good antioxidant activity against DPPH^? (IC₅₀ of 3.64 and 3.15 mg/mL) and ABTS^?+ (IC₅₀ of 1.92 and 1.58 mg/mL), respectively. The low-molecular-weight (<1000 Da) fraction of both hydrolysates demonstrated the highest antiradical activity (IC₅₀ of 2.59 and 2.31 mg/mL, DPPH) and (IC₅₀ of 1.54 and 1.36 mg/mL, ABTS), respectively. Nine peptides were separated from both hydrolysates using reverse phase high performance liquid chromatography (RP-HPLC). The IC₅₀ for ABTS^?+ scavenging activity of peptide P5 with valine, glycine and asparagine (MW of 282.13 Da) from PH, and peptide P3 with histidine, glycine and alanine (MW of 302.74 Da) from AH was 0.89 and 0.72 mg/mL, respectively. The fractions and purified peptides obtained from Chinese sturgeon hydrolysates could be utilized as natural antioxidant substitutes in pharmaceuticals and food products.     

The extraction,antioxidant and against β-amyloid induced toxicity of polyphenols from Alsophila spinulosa leaves

Alsophila spinulosa is a tree-like fern, and many evidences suggested that plant polyphenols had the potential therapeutic for Alzheimer s disease (AD). Herein, polyphenols (ASP) was isolated from A. spinulosa leaves and its major constituent were isoorientin and vitexin. ASP displayed excellent antioxidant activity and obvious anti-lipid peroxidation capacity in vitro. ASP improved the survival rate of C. elegans under high temperature by enhancing the antioxidant enzymes activities and decreasing the lipid peroxidation level. Moreover, ASP alleviated β-amyloid (Aβ) induced paralysis and reduced Aβ deposition, decreased reactive oxygen species (ROS) accumulation and improved the level of skn-1 mRNA. In addition, ASP decreased the levels of pdk-1 and akt-1 mRNA in P13K/AKT signaling pathway. In conclusion, ASP may be a potential ingredient for the alleviation of AD.     

Dynamic variations of bioactive compounds driven by enzymes in Psoralea corylifolia L. from growth to storage and processing

Fructus Psoraleae (FP), the dried ripe fruit of Psoralea corylifolia L., is a popular herbal medicine commonly applied for alleviating osteoporosis and vitiligo. But, until now, the dynamic variations of compounds in P. corylifolia have been less investigated during its growth, storage, and treatment by different temperatures, which is meaningful for guaranteeing the quality of FP. In this study, focused on these questions, with emphasis on the enzyme-driven dynamic transformation of coumarins, ultra-high performance liquid chromatography coupled with photodiode array detector (UHPLC-PDA) method was successfully established for the simultaneous determination of nine compounds. The distribution and accumulation of compounds were discussed and illuminated in different parts of P. corylifolia and samples harvested at different times. The characteristics of compounds' variation in flowers and fruits of P. corylifolia were identified. Through the market survey and quantitative study on FP, positive correlation was speculated between transformation from (iso)psoralenoside to (iso)psoralen via β-glucosidase and storage time, which was further confirmed by accelerated stability test. The effect of treated temperatures (40–210 °C) was unveiled on the enzyme activity and transformation from (iso)psoralenoside to (iso)psoralen in FP. And the focused compounds' transformation was mainly driven by β-glucosidase when the temperature was below 120 °C. Above 120 °C, β-glucosidase was completely inactivated, and the focused compounds' transformation was mediated by high-temperature, also the obvious degradation was found. Our results demonstrated that compounds' transformation characteristics arising from the growth, processing and storage of P. corylifolia are critical factors to ensure the quality of FP.     

Optimization of inoculum to substrate ratio for enhanced methane yield from leather fleshings in a batch study

One of the most significant issues of the last few decades has been tracing for renewable energy sources. Animal fleshing (ANFL) is the most common proteinaceous solid waste accured during the production of leather and it must be disposed of in an environmentally responsible manner. This paper is attempts to assess the biogas production from solid waste originating from the chrome based tannery. Anaerobic digestion of these wastes will be a viable option for waste stabilization and energy production in the form of biogas to be utilized in the industry. The bio-methane potential of the wastes were examined by mixing these wastes with various sources of inoculum and different inoculum to substrate (I/S) ratio considered. The batch experiments were carried out in 2.5 l glass reactors with a various source of inoculumviz., Cow Dung (CD), Elephant Dung (ED) and Bio-Digested Slurry (BDS) with varied inoculum to substrate (LFs) ratios for a retention time of 50 days with replications. The results obtained from the experiments showed that BDS:LF (25:75) had the highest gas production of 14505 ml (651.85 ml CH₄g^?1 VS) followed by CD:LF (50:50) produced 12072.5 ml (789.36 ml CH₄g^?1 VS) and ED:LF (75:25) produced 11252.5 ml (1492.08 ml CH₄g^?1 VS)with a methane content of 63.77, 61.92 and 62.72%, respectively.     

Pentacyclic Triterpenoids,Phytosteroids and Fatty Acid Isolated from the Stem-bark of Cola lateritia K. Schum. (Sterculiaceae) of Cameroon origin; Evaluation of Their Antibacterial Activity

The phytochemical investigation on the chemical constituents of dichloromethane-methanol (1:1) stem-bark extract of Cola lateritia K. Schum. (Sterculiaceae) led to the isolation and characterization of five pentacyclic triterpenoids, one fatty acid and two phytosteroids. The compounds were identified as heptadecanoic acid (1), maslinic acid (2), betulinic acid (3), lupenone (4), lupeol (5), friedelin (6), β-stigmasterol (7) and ß-sitosterol-3-O-ß-D-glucoside (8). Their structures were determined by NMR analysis (¹H, ¹³C, DEPT-135, COSY, HMBC and HSQC), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with published data in the literature. This work, to the best of our knowledge, is the first isolation and identification of these compounds in pure forms from Cola lateritia. Also, compounds 1–3 are reported for the first time from Cola genus. In vitro antibacterial activity of the isolated compounds (1–8) and the crude extract were evaluated against Bacillus subtilis, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium smegmatis, Staphylococcus aureus, Enterobacter cloacae, Klebsiella oxytoca, Proteus vulgaris, Klebsiella pneumonia, Escherichia coli, Proteus mirabilis and Klebsiella aerogenes with streptomycin, nalidixic acid and ampicillin as standard antibacterial drugs. Compound 2 was active against E. faecalis (MIC = 18.5 µg/mL), and it was 6.9 and 28 times lower and active than that of streptomycin (MIC 128 µg/mL) and nalidixic acid (MIC > 512 µg/mL) respectively. All the isolated compounds and crude extract showed significant activities against the tested bacterial strains.     

Camellia sinensis: Insights on its molecular mechanisms of action towards nutraceutical,anticancer potential and other therapeutic applications

The Camellia sinensis plant provides a wide diversity of black, green, oolong, yellow, brick dark, and white tea. Tea is one of the majorly used beverages across the globe, succeeds only in the water for fitness and pleasure. Generally, green tea has been preferred more as compared to other teas due to its main constituent e.g. polyphenols which contribute to various health benefits. The aim of this updated and comprehensive review is to bring together the latest data on the phytochemistry and pharmacological properties of Camellia sinensis and to highlight the therapeutic prospects of the bioactive compounds in this plant so that the full medicinal potential of Camellia sinensis can be realised. A review of published studies on this topic was performed by searching PubMed/MedLine, Scopus, Google scholar, and Web of Science databases from 1999 to 2022. The results of the analysed studies showed that the main polyphenols of tea are the four prime flavonoids catechins: epigallocatechin gallate (EGCG), epicatechin gallate (ECG), epigallocatechin (EGC), and epicatechin (EC) along with the beneficial biological properties of tea for a broad heterogeneity of disorders, including anticancer, neuroprotective, antibacterial, antiviral, antifungal, antiobesity, antidiabetes and antiglaucoma activities. Poor absorption and low bioavailability of bioactive compounds from Camellia sinensis are limiting aspects of their therapeutic use. More human clinical studies and approaching the latest nanoformulation techniques in nanoparticles to transport the target phytochemical compounds to increase therapeutic efficacy are needed in the future.     

Controlling the diffusion of micro-volume Pb solution on hydrophobic polyurethane membrane for quantitative analysis using laser-induced breakdown spectroscopy (LIBS)

This work reports a novel controlling mechanism of analyte diffusion in a micro volume solution (100 μL) into a hydrophobic membrane. This study was designed to facilitate the liquid–solid conversion using membrane for laser-induced breakdown spectroscopy (LIBS) in quantitatively analyzing aqueous lead (Pb) pollutant. Herein, we used the same analyte (Pb) solution applied on one side of the membrane (back side) to enhance the diffusion of the analyte administered from the other side (front side). The membrane was confirmed hydrophobic with contact angles ranged from 104.6°±1.3° to 106.28°±1.7°, where its morphology had smooth surface and randomly distributed small pores. We found the limit of detection (LOD) to reach 184.2 mg/L derived from a calibration curve with Pb I (405.7 nm) line intensity as the dependent variable, where the root-mean-square-errors (RMSE) and correlation (R²) were 1.08 M and 0.999, respectively. In comparison, the membrane back side with distilled water achieved LOD as low as 134.53 mg/L obtained from the similar calibration curve (RMSE = 5.8 M; R² = 0.986). Further analysis using the LIBS spectra confirmed the role of the analyte ion on the back side of the membrane in enhancing the analyte diffusion.     

An appraisal of Luffa aegyptiaca extract and its isolated triterpenoidal saponins in Trichinella spiralis murine models

Trichinella spiralis is an intestinal and tissue parasitic nematode, emerging and re-emerging causative agent of a serious foodborne parasitic infection. This study aimed to evaluate the effect of Luffa aegyptiaca leaf extract and its triterpene glycosides on the intestinal and muscle stages of T. spiralis infection in vitro and in vivo. Phytochemical investigations of the extract led to the isolation of five compounds, namely (1) 3-O-β-d-glucopyranosyl-16-O-β-hydroxyolea12-en 23, 28-β-d-diglucopyranoside ester, (2) 3β-hydroxylolea12-en-28-oic acid (Oleanoic acid), (3) oleanolic acid 3-O-α-l-rhamnopyranosyl-(1 → 4)-β-d-glucopyranoside, (4) 3-O-β-d-glucopyranosyl-28-β-d-glucopyranosyl oleanolate, and (5) stigmast-5, 22-dien-3-O-β-d-glucopyrano-side. Moreover, the in vitro study showed marked degeneration and destruction of adult worms and larval teguments with tested drugs. Also, in the in vivo study, mice were divided into six groups; group I: infected and untreated, group II: received leaf extract as prophylaxis, group III: infected and treated with leaf extract, group IV: treated with compound (4), group V: treated with compound (1), and group VI: treated with albendazole. Furthermore, the treatment efficacy was assessed by the adult and total larval counts, histopathological study of the small intestinal and muscle tissues, and immunohistochemical staining of CD34 in muscles. The results revealed a significant reduction of total adult and larval counts in prophylactic and treated groups compared to the positive control group, with a reduction of total adult count by 63.48% and 74.4% in compound (1) and compound (4) treated groups, respectively. Also, a reduction was detected in larval counts by 36.5%, and 93.6% in compound (1) and compound (4) treated groups during both the muscular and intestinal phases, respectively.Additionally, histopathological examination of the small intestine and muscles showed marked improvement with a reduction in the inflammatory infiltrates in treated groups. CD34 expressions were reduced in treated groups with more reduction in compound (4) treated group. In conclusion, this study implies that L. aegyptiaca leaf extract and its tested triterpene glycosides might be used for anti-trichinellosis treatments.     

Ethanol leaf extract of Ruspolia hypocrateriformis abrogated hepatic redox imbalance and oxidative damage induced by heavy metal toxicity in rats

Humans and animals are frequently exposed to heavy metals in the environment, which are highly toxic to the physiological milieu and organs of the body. We investigated the ameliorative potentials of ethanol leaf extract of Ruspolia hypocrateriformis against redox imbalance due to exposure of rats to heavy metals. The in vitro study explored the antioxidant potentials of the ethanol leaf extract using 1,1-diphenyl-2-picryl hydrazyl, nitric oxide and ferric reducing antioxidant potential assays respectively. HPLC was used to quantify the amount of flavonoids and phenolic acids in the extract. For in vivo study, 30 rats were randomly divided into 5 groups. Group A received normal saline. Group B received combined solution of Lead Nitrate and Mercury Chloride (11.25 mg/kg and 0.4 mg/kg) per Bwt/day. Group C, D and E were administered with the leaf extract at doses of 200, 400 and 600 mg/kg body weight respectively for 28 consecutive days. Biomarkers of hepatic dysfunctions and oxidative stress were investigated in the study rats. The HPLC study revealed high amount of gallic and ferulic acids (17.86 ± 2.68), which are the major phenolic compounds found in the extract. The extract further exhibited high antioxidant potentials in inhibiting the scavenging activity of free radicals produced in vitro. Interestingly, 600 mg/kg dosage of the leaf extract successfully ameliorated the distorted redox imbalance and oxidative damage in the liver of the rats caused by exposure to the heavy metals. Leaf extract of Ruspolia hypocrateriformis demonstrated strong antioxidant potentials, which could be exploited in pharmaceutical preparations.     

Multi-component pharmacokinetics assessment of Artemisia annua L. in rats based on LC-ESI-MS/MS quantification combined with molecular docking

Artemisia annua L. (A. annua) has been used as herbal medicine in China for thousands of years for clearing deficiency heat, treating malaria and removing jaundice. A rapid, sensitive and specific liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC–ESI–MS/MS) method was developed, validated, and successfully used for simultaneous quantification of the active components in rat plasma after oral administration of A. annua extract. Molecular docking of each component with drug metabolizing enzymes was carried out to explore the effect of each component on CYP-mediated drug metabolism. Two coumarins (scopolin (SPL) and scopoletin (SPLT)), three flavonoids (rutin (RUT), chrysosplenol D (CHD), casticin (CAS)) and three sesquiterpenes (arteannuin B (ARN), dihydroartemisinic acid (DARM) and artemisinic acid (ARM)) were detected in rat plasma after oral administration. CHD and CAS were rapidly absorbed into rat blood with the T_max values of 0.11 ± 0.04 h and 0.13 ± 0.05 h, respectively. Their half-lives (t_1/2 2.68 ± 3.62 h and 0.33 ± 0.07 h) were shorter. SPLT were also rapidly absorbed into the blood (T_max 0.15 ± 0.03 h), but exhibited a longer half-life (t_1/2 6.53 ± 1.84 h), indicating that it could be effective in vivo for a longer period of time. The peak time of SPL, RUT, DARM and ARM ranged from 1 ～ 4 h, demonstrating that they could maintain considerable concentrations for a longer time. ARN showed strong enterohepatic circulation in rats, leading to slower onset time and longer effect. A few components including SPLT, CHD, CAS and ARN could be metabolized into their corresponding II phase metabolites combining with glucuronic acid or sulfuric acid. RUT could decompose its glycosyl to generate genin. The molecular docking results indicated that those flavonoids and coumarins of A. annua interacting with CYPs mainly through hydrogen bonding and π-π stacking had better CYP450 enzyme binding ability than the sesquiterpenoids, which were easier to induce drug interactions. This study presented an integrated strategy for investigating the pharmacokinetic behaviors of eight components in A. annua and laid the foundation for revealing the mechanism of action of A. annua in the organism.     

Chemical composition,antioxidant, antimicrobial and antiproliferative activity of Laureliopsis philippiana essential oil of Chile,study in vitro and in silico

Chilean Laureliopsis philippiana has been used in traditional medicine by the Mapuche and their ancestors. To evaluate its pharmacological activity, Laureliopsis philippiana leaf essential oil extract (LP_EO) was chemically and biologically characterized in the present study. In vitro antioxidant potential was analyzed, and antitumor activity was evaluated in non-tumor and tumor cell culture lines. Caenorhabditis elegans was used as a model for evaluating toxicity, and the chemical composition of the essential oil was analyzed using gas chromatography–mass spectrometry. The oil contains six major monoterpenes: eucalyptol (27.7 %), linalool (27.6 %), isozaphrol (19.5 %), isohomogenol (12.6 %), α-terpineol (7.7 %), and eudesmol (4.8 %). Based on quantum mechanical calculations, isosafrole and isohomogenol conferred in vitro antioxidant and antimicrobial activity to LP_EO. In addition, LP_EO showed antimicrobial activity against clinical Helicobacter pylori isolates (MIC 64 and MBC > 128 μg·mL^?1), Staphylococcus aureus (MIC 32 and MBC > 64 μg·mL^?1), Escherichia coli (MIC 8 and MBC 16 μg·mL^?1) and Candida albicans (MIC 64 and > 128 μg·mL^?1). LP_EO could selectively inhibit the proliferation of epithelial tumor cell lines but showed low toxicity against Caenorhabditis elegans (0.39 to 1.56 μg·mL^?1). Therefore, LP_EO may be used as a source of bioactive compounds in novel pharmacological treatments for veterinary and human application, cosmetics, or sanitation.