Antifungal, antiaflatoxigenic, and cytotoxic properties of bioactive secondary metabolites derived from Bacillus species.

Aflatoxins (AFs) are hazardous carcinogens and mutagens produced by some molds, particularly Aspergillus spp. Therefore, the purpose of this study was to isolate and identify endophytic bacteria, extract and characterize their bioactive metabolites, and evaluate their antifungal, antiaflatoxigenic, and cytotoxic efficacy against brine shrimp (Artemia salina) and hepatocellular carcinoma (HepG2). Among the 36 bacterial strains isolated, ten bacterial isolates showed high antifungal activity, and thus were identified using biochemical parameters and MALDI-TOF MS. Bioactive metabolites were extracted from two bacterial isolates, and studied for their antifungal activity. The bioactive metabolites (No. 4, and 5) extracted from Bacillus cereus DSM 31T DSM, exhibited strong antifungal capabilities, and generated volatile organic compounds (VOCs) and polyphenols. The major VOCs were butanoic acid, 2-methyl, and 9,12-Octadecadienoic acid (Z,Z) in extracts No. 4, and 5 respectively. Cinnamic acid and 3,4-dihydroxybenzoic acid were the most abundant phenolic acids in extracts No. 4, and 5 respectively. These bioactive metabolites had antifungal efficiency against A. flavus and caused morphological alterations in fungal conidiophores and conidiospores. Data also indicated that both extracts No. 4, and 5 reduced AFB1 production by 99.98%. On assessing the toxicity of bioactive metabolites on A. salina the IC50 recorded 275 and 300 µg/mL, for extracts No. 4, and 5 respectively. Meanwhile, the effect of these extracts on HepG2 revealed that the IC50 of extract No. 5 recorded 79.4 µg/mL, whereas No. 4 showed no cytotoxic activity. It could be concluded that bioactive metabolites derived from Bacillus species showed antifungal and anti-aflatoxigenic activities, indicating their potential use in food safety.

Bio-fabricated zinc oxide nanoparticles mediated by endophytic fungus Aspergillus sp. SA17 with antimicrobial and anticancer activities: in vitro supported by in silico studies.

Introduction: In recent years, the world's attention has been drawn to antimicrobial resistance (AMR) because to the frightening prospect of growing death rates. Nanomaterials are being investigated due to their potential in a wide range of technical and biological applications. Methods: The purpose of this study was to biosynthesis zinc oxide nanoparticles (ZnONPs) using Aspergillus sp. SA17 fungal extract, followed by characterization of the produced nanoparticles (NP) using electron microscopy (TEM and SEM), UV-analysis, X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FT-IR). Results and Discussion: The HR-TEM revealed spherical nanoparticles with an average size of 7.2 nm, and XRD validated the crystalline nature and crystal structure features of the generated ZnONPs, while the zeta potential was 18.16 mV, indicating that the particles' surfaces are positively charged. The FT-IR was also used to identify the biomolecules involved in the synthesis of ZnONPs. The antibacterial and anticancer properties of both the crude fungal extract and its nano-form against several microbial strains and cancer cell lines were also investigated. Inhibition zone diameters against pathogenic bacteria ranged from 3 to 13 mm, while IC50 values against cancer cell lines ranged from 17.65 to 84.55 M. Additionally, 33 compounds, including flavonoids, phenolic acids, coumarins, organic acids, anthraquinones, and lignans, were discovered through chemical profiling of the extract using UPLC-QTOF-MS/MS. Some molecules, such pomiferin and glabrol, may be useful for antibacterial purposes, according to in silico study, while daidzein 4'-sulfate showed promise as an anti-cancer metabolite.

Ipomoea carnea mitigates ethanol-induced ulcers in irradiated rats via Nrf2/HO-1 pathway: an in vivo and in silico study.

The aim of this study was to investigate the potential of Ipomoea carnea flower methanolic extract (ICME) as a natural gastroprotective therapy against ethanol-induced gastric ulcers, particularly in individuals exposed to ionizing radiation (IR). The study focused on the Nrf2/HO-1 signaling pathway, which plays a crucial role in protecting the gastrointestinal mucosa from oxidative stress and inflammation. Male Wistar rats were divided into nine groups, the control group received distilled water orally for one week, while other groups were treated with ethanol to induce stomach ulcers, IR exposure, omeprazole, and different doses of ICME in combination with ethanol and/or IR. The study conducted comprehensive analyses, including LC-HRESI-MS/MS, to characterize the phenolic contents of ICME. Additionally, the Nrf2/HO-1 pathway, oxidative stress parameters, gastric pH, and histopathological changes were examined. The results showed that rats treated with IR and/or ethanol exhibited histopathological alterations, increased lipid peroxidation, decreased antioxidant enzyme activity, and reduced expression levels of Nrf2 and HO-1. However, pretreatment with ICME significantly improved these parameters. Phytochemical analysis identified 39 compounds in ICME, with flavonoids, hydroxybenzoic acids, and fatty acids as the predominant compounds. Virtual screening and molecular dynamics simulations suggested that ICME may protect against gastric ulceration by inhibiting oxidative stress and inflammatory mediators. In conclusion, this study demonstrates the potential of ICME as a natural gastroprotective therapy for preventing gastric ulcers. These findings contribute to the development of novel interventions for gastrointestinal disorders using natural plant extracts particularly in individuals with a history of radiation exposure.

Comprehensive chemical profiling of Bassia indica Wight. aerial parts extract using UPLC-ESI-MS/MS, and its antiparasitic activity in Trichinella spiralis infected mice: in silico supported in vivo study.

BACKGROUND: Trichinellosis is a public health threat infected both animals and humans as a result of eating undercooked meat. It caused by Trichinella spiralis that has widespread drug resistance and even developed many sophisticated strategies for their survival, this increases the demand in searching for new anthelmintic drugs from natural source. METHODS: Our objectives were to test the in vitro and in vivo anthelmintic activity of Bassia indica BuOH frac., and to characterize its chemical composition using UPLC-ESI-MS/MS. Besides an in silico molecular docking study with the prediction of the PreADMET properties. RESULTS: In vitro investigation of B. indica BuOH frac., showed severe destruction of the adult worm and larvae, marked cuticle swelling, areas with vesicles, blebs and loss of annulations. This was assured via in vivo study, which revealed a significant reduction (P < 0.05) in the mean adult worm count with efficacy of 47.8% along with a significant decrease (P < 0.001) in the mean larval count per gram muscle with efficacy 80.7%. Histopathological examinations of the small intestine and muscular sections showed marked improvement. In addition, immunohistochemical findings demonstrated that B. indica BuOH frac. depressed the proinflammatory cytokines expressions of TNF-α, which was obviously upregulated by T. spiralis. Precise chemical investigation of the BuOH frac. using UPLC-ESI-MS/MS resulted in the identification of 13 oleanolic type triterpenoid saponins; oleanolic acid 3-O-6´-O-methyl-ß-D-glucurono-pyranoside (1), chikusetsusaponin-IVa (2) and its methyl ester (3), chikusetsusaponin IV (4) and its methyl ester (5), momordin-Ic (6) and its methyl ester (7), betavulgaroside-I (8), -II (9) -IV (10), -X (11), licorice-saponin-C2 (12) and -J2 (13). In addition, 6 more phenolics were identified as syringaresinol (14), 3,4-di-O-caffeoylquinic acid (15), 3-O-caffeoyl-4-O-dihydrocaffeoylquinic acid (16), 3,4-di-O-caffeoylquinic acid butyl ester (17), 3,5-di-O-galloyl-4-O-digalloylquinic acid (18) and quercetin 3-O-(6´´-feruloyl)-sophoroside (19). The auspicious anthelmintic activity was further ascertained using in silico molecular docking approach that targeted certain protein receptors (ß-tubulin monomer, tumor necrosis factor alpha (TNF-α), cysteine protease (Ts-CF1), calreticulin protein (Ts-CRT)), all the docked compounds (1-19) fit into the binding site of the active pocket with binding affinities noteworthy than albendazole. In addition, ADMET properties, drug score and drug likeness were predicted for all compounds.

Polyphenolic Profile of Herniaria hemistemon Aerial Parts Extract and Assessment of Its Anti-Cryptosporidiosis in a Murine Model: In Silico Supported In Vivo Study.

Herniaria hemistemon J.Gay is widely used in folk medicine to treat hernia. The present study aimed to annotate the phytoconstituents of H. hemistemon aerial-part extract and investigate its in vivo anticryptosporidial activity. The chemical characterization was achieved via the LC-ESI-MS/MS technique resulting in the annotation of 37 phytocompounds comprising flavonoids and phenolic acids. Regarding the anticryptosporidial activity, fifty dexamethasone-immunosuppressed mice were separated into five groups: GI, un-infected (normal control); GII, infected but not treated (model); GIII, infected and received NTZ, the reference drug; GIV, infected and received H. hemistemon extract (100 mg/kg); and GV, infected and received H. hemistemon extract (200 mg/kg). When GIII, GIV, and GV were compared to GII, parasitological analyses displayed highly significant differences in the mean numbers of Cryptosporidium parvum oocysts in the stool between the different groups. GV demonstrated the highest efficacy of 79%. Histopathological analyses displayed improvement in the small intestine and liver pathology in the treated groups (GIII, IV, and V) related to the model (GII), with GV showing the highest efficacy. Moreover, the docking-based study tentatively highlighted the potential of benzoic acid derivatives as lactate dehydrogenase inhibitors. The docked compounds showed the same binding interactions as oxamic acid, where they established H-bond interactions with ARG-109, ASN-140, ASP-168, ARG-171, and HIS-195. To sum up, H. hemistemon is a promising natural therapeutic agent for cryptosporidiosis.

Metabolite Profiling of Alocasia gigantea Leaf Extract and Its Potential Anticancer Effect through Autophagy in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a poor-prognosis type of cancer with high resistance to chemotherapy, making the search for safe drugs a mandatory issue. Plant-derived products have potential to reduce negative side effects of cancer treatments. In this work, ability of a defatted methanolic extract of Alocasia gigantea leaves to fight HCC was evaluated in an animal model. Overall, treatment of HCC-induced mice with the methanolic extract at 150 mg/kg body weight for four consecutive weeks caused induction of autophagy through silencing of the relative expression of autophagy suppressor (mTOR) and inducement of autophagy markers (AMPK, Beclin-1, and LC-3). Moreover, it improved preservation of the hepatic histological architecture of the animals, with minor hepatocytic changes but scattered foci of hepatocytic apoptosis. Chemical profiling of the methanolic extract via ultra-high-performance liquid chromatography coupled to a diode array detector and an electrospray mass spectrometer (UHPLC-DAD-ESI-MS/MS) allowed identification of di-C-glycosyl flavones, mostly represented by 6-C-hexosyl-8-C-pentosyl apigenin isomers, which may possibly be associated with inducement of the autophagy pathway in HCC. Overall, these outcomes gave an initial visualization of the operative effect of some compounds in A. gigantea leaves that are potential treatment for HCC.

Thais savignyi tissue extract: bioactivity, chemical composition, and molecular docking.

CONTEXT: Thais savignyi Deshayes (Muricidae) is widely distributed in the Red Sea. Its abundance and the history of Muricidae in traditional medicine make it a tempting target for investigation. OBJECTIVE: To investigate the chemical profile and biological activities of T. savignyi tissue extracts. MATERIALS AND METHODS: Methanol, ethanol, acetone, and ethyl acetate extracts from T. savignyi tissue were compared in their antioxidant by total antioxidant capacity, DPPH free radical scavenging, and total phenolic content. In addition, the antimicrobial, and antibiofilm properties (at 250 µg/mL) of the extracts were tested against Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris, Klebsiella pneumoniae, Staphylococcus aureus, and Candida albicans. The antioxidant extract with greatest activity was assessed for cytotoxicity (range 0.4-100 µg/mL) against 3 human cancer cell lines (UO-31, A549 and A431), and its chemical composition was investigated using GC-MS. Moreover, docking simulation was performed to predict its constituents' binding modes/scores to the active sites of thymidylate kinase. RESULTS: The ethyl acetate extract (Ts-EtOAc) showed the highest total antioxidant capacity (551.33 mg AAE/g dry weight), total phenolics (254.46 mg GAE/g dry weight), and DPPH scavenging (IC50= 24.0 µg/mL). Ts-EtOAc exhibited strong antibacterial (MIC: 3.9 µg/mL against K. pneumoniae), antibiofilm (MIC: 7.81 µg/mL against S. aureus), and antifungal (MIC: 3.9 µg/mL against C. albicans) activities and considerable cytotoxicity against cancer cells (UO-31: IC50= 19.96 ± 0.93, A549: IC50= 25.04 ± 1.15 µg/mL). GC-MS identified multiple bioactive metabolites in Ts-EtOAc extract belonging to miscellaneous chemical classes. Molecular docking studies revealed that the constituents of Ts-EtOAc have antibacterial potential. DISCUSSION AND CONCLUSIONS: T. savignyi extract has considerable antimicrobial and cytotoxic activities. Further studies are needed to isolate the active constituents of this snail for comprehensive drug discovery tests.

Antiproliferative potential of Physalis peruviana-derived magnolin against pancreatic cancer: a comprehensive in vitro and in silico study.

Physalis peruviana L. is a common edible fruit in Egypt and other regional countries. In the present study, we investigated its crude extract as a potential source of antiproliferative secondary metabolites. Upon bioactivity guided solvent fractionation, ethyl acetate extract showed preferential activity toward the human pancreatic cancer cell line PANC-1 with an IC50 value of 5.23 ± 0.2 µg mL-1. The subsequent HR-LCMS-guided and biological activity-guided isolation revealed magnolin as a potent preferential antiproliferative agent against PANC-1 with an IC50 of 0.51 ± 0.46 µM that was comparable to that of the positive control doxorubocin (IC50 of 0.17 ± 0.15 µM). Moreover, magnolin showed much less cytotoxicity in comparison with the positive control doxorubicin (6.96% and 30.48% growth inhibition, respectively, at 5 µg mL-1) towards normal human cells (i.e. dermal fibroblasts; HDFa). Furthermore, magnolin was able to induce a concentration-dependent suppression of the formation of PANC-1 colonies, where the treatment of the tumor cells with 25 nM, 50 nM, and 100 nM concentrations of the compound resulted in a 36%, 57, and 78% reduction, respectively, in the PANC-1 colony formation. Additionally, magnolin was observed to limit PANC-1 tumor cell migration in the tumor cell wound healing assay, indicating a substantial anti-migratory effect against the PANC-1 cell line. A subsequent in silico-based study of this compound structure putatively suggested matrix metalloproteinase-3 (MMP3) as the molecular target that mediates these observed effects on PANC-1 cells. Absolute binding free energy estimation (ΔGbinding) and 100 ns long molecular dynamics simulation (MDS) experiments indicated that the magnolin structure has good affinity towards the MMP3's active site and can achieve significantly stable binding inside it. Accordingly, upon experimental validation, magnolin was found to inhibit the catalytic activity of MMP3 in a dose-dependent manner with a nanomolar IC50 value of 185 nm ± 4.86 and a Ki of 112 nm ± 6.31. In conclusion, our results clearly revealed that magnolin derived from P. peruviana is an interesting antiproliferative and antimetastatic agent against PANC-1 cells with potent inhibitory activity against MMP3. Further in vivo evaluation will be of great interest in the future.

Co-treatment with Esculin and erythropoietin protects against renal ischemia-reperfusion injury via P2X7 receptor inhibition and PI3K/Akt activation.

Renal ischemia/reperfusion (RI/R) is a critical clinical outcome with slightly reported improvement in mortality and morbidity. Effective therapies are still crucially required. Accordingly, the therapeutic effects of esculin (ESC, LCESI-MS/MS-isolated compound from Vachellia farnesiana flowers extract, with reported P2X7 receptor inhibitor activity) alone and in combination with erythropoietin (EPO) were investigated against RI/R injury and the possible underlying mechanisms were delineated. ESC and EPO were administered for 7 days and 30 min prior to RI, respectively. Twenty-four hour following reperfusion, blood and kidney samples were collected. Results revealed that pretreatment with either ESC or EPO reduced serum nephrotoxicity indices, renal oxidative stress, inflammatory, and apoptosis markers. They also ameliorated the renal histopathological injury on both endothelial and tubular epithelial levels. Notably, ESC markedly inhibited P2X7 receptors and NLRP3 inflammasome signaling (downregulated NLRP3 and Caspase-1 gene expressions), whereas EPO significantly upregulated PI3K and Akt gene expressions, also p-PI3K and p-Akt levels in renal tissues. ESC, for the first time, demonstrated effective protection against RI/R-injury and its combination with EPO exerted maximal renoprotection when compared to each monotherapy, thereby representing an effective therapeutic approach via inhibiting oxidative stress, inflammation, renal tubular and endothelial injury, apoptosis, and P2X7 receptors expression, and activating PI3K/Akt pathway.

Antioxidant and anti-aging effects of Warburgia salutaris bark aqueous extract: Evidences from in silico, in vitro and in vivo studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Warburgia (family Canellaceae) is widely distributed over Afrotropical and Neotropical realms. Traditionally, W. salutaris (G. Bertol.) Chiov., and other Warburgia species are used as anti-inflammatory, antimalarial, antimicrobial, and for wound healing, and treating several skin complaints as well. Specifically, different extracts from W. salutaris were reported to possess diuretic, anti-inflammatory, and cytotoxic effects. AIM OF THE STUDY: This work aimed to investigate the phytochemical composition of an aqueous extract from W. salutaris bark, and evaluate its antioxidant and anti-aging activities in silico, in vitro, and in vivo. MATERIALS AND METHODS: HPLC-PDA-MS/MS was used to investigate the phytochemical components of the extract. The antioxidant potential of the extract was evaluated in vitro using DPPH and FRAP assays. The Caenorhabditis elegans nematodes model was adopted to investigate the antioxidant and the anti-aging effects in vivo by determining the worms' survival rate, level of ROS, HSP16 expression, and nuclear translocation of the transcription factor DAF16. Molecular operating environment (MOE) software was utilized for in silico molecular docking of the extract's components into different enzymes involved in the aging process. Anti-collagenase, anti-elastase, anti-tyrosinase, and anti-hyaluronidase assays were used to evaluate the anti-aging effects in vitro. RESULTS: HPLC-MS analysis furnished 30 compounds, among them catechin, 11α-hydroxy muzigadiolide, mukaadial, pereniporin B, and 11α-hydroxycinnamosmolide. The major components of the extract showed appropriate fitting in the binding site of the target enzymes adopted in the study with considerable minimum free binding energy relative to the standard inhibitors. The extract showed substantial in vitro antioxidant activity in DPPH and FRAP assays and in vitro anti-aging assays against collagenase, elastase, tyrosinase, and hyaluronidase with comparable IC50 values to the reference standards. Moreover, it attenuated oxidative stress in vivo as it significantly increased the survival rate of ROS stressed C. elegans worms, decreased intracellular ROS, decreased the juglone-induced HSP16 expression and enhanced the nuclear localization of DAF16 in a dose-dependent manner. CONCLUSION: Our results support the traditional use of W. salutaris to counteract inflammation and oxidative stress associated with several pathological conditions. In addition, W. salutaris bark extract can be considered as a substantial source for bioactive metabolites with strong potential as anti-aging and antioxidant agents.

Chemical Composition, Antioxidant, Anti-Tyrosinase, Anti-Cholinesterase and Cytotoxic Activities of Essential Oils of Six Algerian Plants.

In this study, the essential oils (EOs) of six Algerian plants (Artemisia campestris L., Artemisia herba-alba Asso, Juniperus phoenicea L., Juniperus oxycedrus L., Mentha pulegium L. and Lavandula officinalis Chaix) were obtained by hydrodistillation, and their compositions determined by GC-MS and GC-FID. The antioxidant activity of the EOS was evaluated via 2,2'-diphenyl-1-picrylhydrazyl (DPPH), ferric-reducing/antioxidant power (FRAP) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Moreover, their cytotoxic effect was evaluated-as well as their tyrosinase, acetyl- and butyryl-cholinesterase (AChE and BuChE) inhibitory activities. The chemical analyses detected 44, 45, 51, 53, 26 and 40 compounds in EOs of A. campestris, A. herba-alba, J. phoenicea, J. oxycedrus, M. pulegium and L. officinalis, respectively. A. campestris EO was mainly composed of ß-pinene (20.7%), while A. herba-alba EO contained davanone D (49.5%) as the main component. α-Pinene (41.8%) was detected as the major constituent in both J. phoenicea (41.8%) and J. oxycedrus (37.8%) EOs. M. pulegium EO was characterized by pulegone as the most abundant (76.9%) compound, while linalool (35.8%) was detected as a major constituent in L. officinalis EO. The antioxidant power evaluation revealed IC50 values ranging from 2.61 to 91.25 mg/mL for DPPH scavenging activity, while the FRAP values ranged from 0.97-8.17 µmol Trolox equivalents (TX)/g sample. In the ABTS assay, the values ranged from 7.01 to 2.40 µmol TX/g sample. In the presence of 1 mg/mL of the samples, tyrosinase inhibition rates ranged from 11.35% to 39.65%, AChE inhibition rates ranged from 40.57% to 73.60% and BuChE inhibition rates ranged from 6.47% to 72.03%. A significant cytotoxic effect was found for A. herba-alba EO. The obtained results support some of the traditional uses of these species in food preservation and for protection against several diseases.

Chemical Profiling of Polyphenolics in Eucalyptus globulus and Evaluation of Its Hepato-Renal Protective Potential Against Cyclophosphamide Induced Toxicity in Mice.

Cyclophosphamide (CP) is a potent anti-neoplastic and immunosuppressive agent; however, it causes multi-organ toxicity. We elucidated the protective activities of Eucalyptus globulus (EG) leaf extract against CP-induced hepato-renal toxicity. Mice were treated with EG for 15 days plus CP on day 12 and 13 of the experiment. Using HPLC-DAD-ESI-MS/MS, 26 secondary metabolites were identified in EG leaf extract. Out of them, 4 polyphenolic compounds were isolated: (1) 4-(O-ß-d-xylopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (2) 4-(O-α-l-rhamnopyranosyloxy)-3,5-di-hydroxy-benzoic acid, (3) gallic acid, and (4) methyl gallate. Effects of EG extract on biochemical parameters, gene expression, and immune-histopathological changes were assessed in comparison to mesna positive control. Results showed that EG improved CP-increased serum ALT, AST, creatinine, and blood urea nitrogen levels. The hepatic and renal tissue levels of MDA, nitric oxide, protein carbonyl, TNF-α, IL-6, and immunohistochemical expression of nuclear factor kappa-B (NF-kB) and caspase-3 were reduced. Also, hepatic and renal GSH contents, and nuclear factor E2-related factor 2 (NRf2)/ hemoxygenase-1 (HO-1) signaling levels were increased. Histopathological findings supported our findings where hepatic and renal architecture were almost restored. Results revealed the protective effects of EG against CP-induced hepato-renal toxicity. These effects may be related to EG antioxidant, anti-inflammatory, and anti-apoptotic properties coupled with activation of Nrf2/HO-1 signaling.

Identification, Quantification, and Antioxidant Activity of Hydroalcoholic Extract of Artemisia campestris from Algeria.

OBJECTIVES: Our study aimed to investigate the chemical profile of hydroalcoholic extract of Algerian Artemisia campestris and its antioxidant activity. MATERIALS AND METHODS: The hydroalcoholic extract of Algerian A. campestris was investigated for its phenolic constituents using high performance liquid chromatography (HPLC)-diode array detection (DAD)-electrospray ionization (ESI)-mass spectrometer (MS)/MS. The in vitro antioxidant activity and total phenolic content were also evaluated via oxygen radical absorbance capacity and Folin-Ciocalteu assays, respectively. RESULTS: HPLC-DAD-ESI-MS/MS analysis revealed that the main tentatively identified compounds were caffeoylquinic acid isomers, flavonoids, and benzoic acid derivatives. Additionally, the hydroalcoholic extract exhibited a promising antioxidant activity value of 120.5±10.4 µmol Trolox equivalent antioxidant capacity/g dry weight (DW), and a strong correlation exists between this activity and the total phenolic content value of 102.09±1.65 mg/g gallic acid equivalents DW. CONCLUSION: The hydroalcoholic extract of A. campestris is a promising candidate for the production of naturally occurring antioxidant agents.

HPLC-ESI-MS/MS Profiling of Polyphenolics of a Leaf Extract from Alpinia zerumbet (Zingiberaceae) and Its Anti-Inflammatory, Anti-Nociceptive, and Antipyretic Activities In Vivo.

Reactive oxygen species (ROS) have been linked to several health conditions, among them inflammation. Natural antioxidants may attenuate this damage. Our study aimed to investigate the chemical composition of a methanol leaf extract from Alpinia zerumbet and its possible antioxidant, anti-inflammatory, anti-nociceptive, and antipyretic effects. Altogether, 37 compounds, representing benzoic and cinnamic acid derivatives and flavonoids (aglycones and glycosides), were characterized. The extract showed substantial in vitro antioxidant effects, and inhibited both cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2) in vitro, with a higher selectivity towards COX-2. It also inhibited 5-lipoxygenase (LOX) activity in vitro with nearly double the potency of zileuton, a reference 5-lipoxygenase (LOX) inhibitor. The extract exhibited anti-inflammatory effects against carrageenan-induced rat hind paw edema, and suppressed leukocyte infiltration into the peritoneal cavity in carrageenan-treated mice. Furthermore, it possessed antipyretic effects against fever induced by subcutaneous injection of Brewer's yeast in mice. Additionally, the extract demonstrated both central and peripheral anti-nociceptive effects in mice, as manifested by a decrease in the count of writhing, induced with acetic acid and an increase in the latency time in the hot plate test. These findings suggest that the leaf extract from Alpinia zerumbet could be a candidate for the development of a drug to treat inflammation and ROS related disorders.

Tannin-rich extracts from Lannea stuhlmannii and Lannea humilis (Anacardiaceae) exhibit hepatoprotective activities in vivo via enhancement of the anti-apoptotic protein Bcl-2.

The potential hepatoprotective activities of two Lannea species were explored in vivo. Furthermore, the binding activities of their main polyphenols to the antiapoptotic protein Bcl-2 were investigated. Based on HPLC-MS/MS results, 22 secondary metabolites were characterized in L. stuhlmannii (mainly tannins), while 20 secondary metabolites (mainly sulphated tannins) were identified in L. humilis. Both extracts exhibited substantial antioxidant activities in vitro and counteracted D-galactosamine induced intoxication in rats in vivo and increased the total antioxidant capacity (TAC) of liver tissues. In addition to reducing the elevated levels of AST and total bilirubin, both extracts significantly attenuated the deleterious histopathologic changes in liver after D-galactosamine-intoxication. Also, both extracts protected hepatocytes from apoptotic cell death and increased the expression of the anti-apoptotic protein Bcl-2. The identified compounds from both extracts can bind to the Bcl-2: Bim (BH3) interface with an appreciable binding free energy. Hydrogen and ionic bonds and hydrophobic interactions with amino acid residues in the hydrophobic face of Bim (BH3) domain were discovered. To sum up, L. humilis and L. stuhlmanni exhibited promising hepatoprotective activities in vivo against D-GalN-induced liver injury and their hepatoprotection is due to the antioxidant and anti-apoptotic effects of tannins and proanthocyanidins.

Effect of Ficus sycomorus and Azadirachta indica extracts on liver state of mice infected with Schistosoma mansoni.

The potential role of hepatoprotective and antipathological effect of Ficus sycomorus and Azadirachta indica extracts was evaluated for scavenging the reactive oxygen species (ROS) and reduced the oxidative damage and pathological changes in the liver of S. mansoni infected mice. The levels of alanine aminotransferase (ALT), asparate aminotransferase (AST) and gamma glutamyl transferase (GGT) were evaluated in the infected mice and treated orally with each plant extract 12 weeks post infection (P.I.) in a dose of 500 mg/kg of each plant extract for five consecutive days and sacrificed two weeks P.I. The infection of mice showed an elevation of ALT, AST & GGT. Treatment of mice with 70% methanol extract of each plant extract reduced significantly ALT, AST & GGT elevation. The highest reduction was with the methanolic extract of F. sycomorus (42%, 35% &44% for ALT, AST & GGT respectively). Fractionation of the methanolic extract of each plant was carried out. The effect of ethyl acetate and butanolic fractions of each plant was also evaluated. The result showed that the two fractions lowered the levels of the tested enzymes and decreased the number and size of granuloma diameters with an increased in the percentage of degenerated ova.