A fruit extract of Styphnolobium japonicum (L.) counteracts oxidative stress and mediates neuroprotection in Caenorhabditis elegans.

BACKGROUND: Despite its widespread uses in Chinese and European medicine, Styphnolobium japonicum (Chinese scholar tree, formerly Sophora japonicum) has not been extensively investigated for its potential to protect against neurodegenerative processes and to promote resistance to oxidative stress. In this study, we evaluated the neuroprotective activities of a hydroalcoholic extract from Chinese scholar tree fruits that could be possibly linked to its antioxidant properties using Caenorhabditis elegans as a well-established in vivo model. METHODS: Survival rate in mutant daf-16 and skn-1 worms, stressed by the pro-oxidant juglone and treated with the extract, was tested. Localization of the transcription factors SKN-1 and DAF-16, and expression of gst-4 were measured. For evaluation of neuroprotective effects, formation of polyglutamine (polyQ40) clusters, α-synuclein aggregates, loss of amphid sensilla (ASH) neuronal function, and amyloid ß (Aß) accumulation (as markers for Huntington's, Parkinson's, and Alzheimer's) was examined. RESULTS: The extract, which contains substantial amounts of phenolic phytochemicals, showed an increase in the survival rate of worms challenged with juglone in daf-16 mutants but not in skn-1 mutants. The transcription factor SKN-1 was activated by the extract, while DAF-16 was not affected. Upon application of the extract, a significant decline in GST-4 levels, polyQ40 cluster formation, number of lost ASH sensory neurons, α-synuclein aggregation, and paralysis resulting from Aß accumulation was observed. CONCLUSIONS: Styphnolobium japonicum fruit extract activated the SKN-1/Nrf2 pathway, resulting in oxidative stress resistance. It revealed promising pharmacological activities towards treatment of Huntington's, Parkinson's, and Alzheimer's diseases. Polyphenolics from Styphnolobium japonicum may be a promising route towards treatment of CNS disorders, but need to be tested in other in vivo systems.

BAAE-AgNPs Improve Symptoms of Diabetes in STZ-induced Diabetic Rats.

OBJECTIVES: Nanoparticles can be employed to improve the therapeutic activity of natural products. Type 2 diabetes mellitus is a serious health condition that has spread like a "modern pandemic" worldwide. In the present study, we developed silver nanoparticles, Ag-NPs, with an aqueous extract from Balanites aegyptiaca to investigate their antioxidant and anti-inflammatory activity in STZ-induced diabetic rats. METHODS: Aqueous extracts of Balanites aegyptiaca seeds (BAAE) were used in the synthesis of BAAE-AgNPs, which were characterized using FTIR and TEM. Different doses of BAAE-AgNP (1/50 LD50; 29.4 mg/kg b.w. and 1/20 LD50: 73.5 mg/kg b.w.) were administered to STZ-induced diabetic rats to evaluate their potential antidiabetic activity. RESULTS: FTIR spectral data indicated the presence of flavonoids and polyphenols in BAAEAgNPs. The size of the BAAE-AgNPs, determined by TEM examination, was 49.33 ± 7.59 nm, with a zeta potential of +25.37. BAAE-AgNPs were characterized by an LD50 value of 1470 mg/kg b.w. In diabetic rats, the daily oral administration of both doses of BAAE-AgNPs (29.4 and 73.5 mg/kg b.w.) for 12 weeks resulted in a significant improvement in body weight, insulin homeostasis, HbA1c, HDL-C, MDA, and pancreatic SOD, CAT, and GSH. They reduced plasma glucose, cholesterol, and triglycerides. This treatment also resulted in a significant decrease in pancreatic IL-6, p53, and TNF-α in diabetic rats. Furthermore, BAAE-AgNPs down-regulated pancreatic TGF-ß1 and Akt gene expression in diabetic rats and resulted in a significant decrease in the regulation of hepatic GLUT-2, as well as an increase in the regulation of hepatic GK and pancreatic B-cl2 gene expression. The histopathological results obtained indicated that BAAEAgNPs improved pancreatic tissue metabolism by enhancing antioxidant enzymes, suppressing inflammatory cytokines, and scavenging free radicals. CONCLUSION: The findings implied that similar to the glibenclamide-treated groups, in the BAAEAgNPs treated group, the compromised antioxidant status normalized in STZ-induced diabetes. By scavenging free radicals, BAAE-Ag-NPs protected against lipid peroxidation while reducing the risk of complications from diabetes. Compared to the daily dose of 29.4 mg, the impact was more prominent at 73.5 mg.

Comparative metabolic profiling of olive leaf extracts from twelve different cultivars collected in both fruiting and flowering seasons.

Olea europaea is an economically significant crop native to Mediterranean countries. Its leaves exhibit several biological properties associated to their chemical composition. The aqueous ethanolic extracts of olive leaves from twelve different cultivars were analyzed by high performance liquid chromatography coupled to photodiode array and electrospray ionization mass spectrometry (HPLC/PDA/ESI-MS/MS). A total of 49 phytochemicals were identified in both positive and negative ionization modes. The identified compounds belonged to four classes of secondary metabolites including secoiridoids, flavonoids, pentacyclic triterpenoids and various phenolic compounds. Seasonal variation in chemical composition among the studied cultivars was apparent in autumn and spring. Secologanoside, oleuropein, hydroxy-oleuropein, demethyl oleuropein, gallocatechin, luteolin-O-hexoside, diosmetin, oleanolic acid and maslinic acid were detected in all cultivars in both seasons. Oleuropein-O-deoxyhexoside was tentatively identified for the first time in olive leaf extracts; detected only in the Spanish cultivar Picual (PIC) collected in spring. Also, dihydroxy-oxooleanenoic acid and hydroxy-oxooleanenoic acid, two bioactive pentacyclic triterpenes, were identified. Principle component analysis (PCA) showed good discrimination among the studied cultivars in terms of their botanical origin. This study is considered the first study for non-targeted metabolic profiling of different olive leaf cultivars cultivated in Egypt.

Salix subserrata Bark Extract-Loaded Chitosan Nanoparticles Attenuate Neurotoxicity Induced by Sodium Arsenate in Rats in Relation with HPLC-PDA-ESI-MS/MS Profile.

Pollution is a worldwide environmental risk. Arsenic (As) is an environmental pollutant with a major health concern due to its toxic effects on multiple body organs, including the brain. Humans are exposed to As through eating contaminated food and water or via skin contact. Salix species (willow) are plants with medicinal efficacy. Salix subserrata Willd bark extract-loaded chitosan nanoparticles (SBE.CNPs) was formulated, characterized, and evaluated against As-induced neurotoxicity. The stem bark was selected for nanoparticle formulation based on HPLC-PDA-ESI-MS/MS profiling and in vitro antioxidant assessment using free radical scavenging activity. SBE.CNPs demonstrated an average un-hydrated diameter of 193.4 ± 24.5 nm and zeta potential of + 39.6 ± 0.4 mV with an encapsulation efficiency of 83.7 ± 4.3%. Compared to As-intoxicated rats, SBE.CNP-treated rats exhibited anxiolytic activity and memory-boosting as evidenced in open field test, light-dark activity box, and Y-maze. Also, it increased the antioxidant biomarkers, including superoxide dismutase and glutathione peroxidase associated with reducing the malondialdehyde levels and apoptotic activity. Besides this, SBE.CNPs maintained the brain architecture and downregulated both nuclear factor-kappa B and heme oxygenase-1 expression. These results suggest that SBE.CNP administration showed promising potent neuroprotective and antioxidative efficiencies against arsenic-induced oxidative threats.

Euclea divinorum Hiern: Chemical Profiling of the Leaf Extract and Its Antioxidant Activity In Silico, In Vitro and in Caenorhabditis elegans Model.

Euclea divinorum Hiern is a medicinal plant widely distributed in the northeast parts of South Africa. This plant has been used to treat miscarriage and to alleviate gastrointestinal problems. It can also be used externally for the treatment of ulcers and gonorrhea. In this study, we investigated the phytochemical composition of E. divinorum leaf extract using LC-MS and explored its antioxidant properties in vitro and in vivo. The total polyphenolic content of the extract was determined by the Folin-Ciocalteu method. DPPH and FRAP assays were employed to confirm the plant's antioxidant potential in vitro. A survival assay in the Caenorhabditis elegans model was used to evaluate the extract's ability to counteract juglone-induced oxidative stress. Moreover, a docking study was performed for the extract's metabolites, in order to predict possible molecular targets that could explain the antioxidant effect of the plant on a molecular level. This in silico approach was accomplished on three different proteins; xanthine oxidase enzyme, heat shock protein 90 (Hsp90), and induced nitric oxide synthase (iNOS). Docking scores of the resulting poses and their interactions with binding sites' residues were explored for each protein and were compared to those of simultaneously docked respective co-crystallized and reference substrates. The extract furnished promising antioxidant activities in vitro and in vivo in the C. elegans model that might be attributed to the presence of 46 compounds, which showed several interactions and low binding scores with the tested enzymes. In conclusion, E. divinorum is a promising, safe, and effective antioxidant candidate that could be used to ameliorate oxidative stress-related disorders.

Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being.

Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review.

Oolonghomobisflavans exert neuroprotective activities in cultured neuronal cells and anti-aging effects in Caenorhabditis elegans.

Potential health benefits of tea has attracted significant scientific and public attention worldwide. Tea polyphenols are considered as natural promising complementary therapeutical agents for neurodegenerative diseases. However, the anti-neurodegeneration or anti-aging activities of oolong tea polyphenols have not been investigated. The current study aims to document beneficial effects of oolong tea polyphenols [dimers of epigallocatechin gallate (EGCG), oolonghomobisflavan A (OFA), and oolonghomobisflavan B (OFB)] with neuroprotective and neuritogenesis properties in cultured neuronal (Neuro-2a and HT22) cells and Caenorhabditis elegans models. In vitro, we found that the compounds (EGCG, OFA, and OFB) protect against glutamate-induced neurotoxicity via scavenging radical activity, suppression intracellular ROS and up-regulation of antioxidant enzymes. Moreover, the compounds induce neurite outgrowth via up-regulate Ten-4 gene expression. Interestingly, OFA and OFB exert stronger neuroprotective and neurite outgrowth properties than EGCG known as an excellent antioxidant agent in tea. In vivo, we found that the compounds protect against C. elegans Aß-induced paralysis, chemotaxis deficiency and α-synuclein aggregation. Moreover, the compounds are capable of extending the lifespan of C. elegans. OFA and OFB possess both anti-neurodegeneration and anti-aging activities, supporting its therapeutic potential for the treatment of age-related neurodegenerative diseases which need to be studied in more detail in intervention studies.

Curcuminoids for Metabolic Syndrome: Meta-Analysis Evidences Toward Personalized Prevention and Treatment Management.

The metabolic syndrome (MS) is a multifactorial syndrome associated with a significant economic burden and healthcare costs. MS management often requires multiple treatments (polydrug) to ameliorate conditions such as diabetes mellitus, insulin resistance, obesity, cardiovascular diseases, hypertension, and non-alcoholic fatty liver disease (NAFLD). However, various therapeutics and possible drug-drug interactions may also increase the risk of MS by altering lipid and glucose metabolism and promoting weight gain. In addition, the medications cause side effects such as nausea, flatulence, bloating, insomnia, restlessness, asthenia, palpitations, cardiac arrhythmias, dizziness, and blurred vision. Therefore, is important to identify and develop new safe and effective agents based on a multi-target approach to treat and manage MS. Natural products, such as curcumin, have multi-modalities to simultaneously target several factors involved in the development of MS. This review discusses the recent preclinical and clinical findings, and up-to-date meta-analysis from Randomized Controlled Trials regarding the effects of curcumin on MS, as well as the metabonomics and a pharma-metabolomics outlook considering curcumin metabolites, the gut microbiome, and environment for a complementary personalized prevention and treatment for MS management.

Phytochemical Profiling of the Leaf Extract of Ximenia americana var. caffra and Its Antioxidant, Antibacterial, and Antiaging Activities In Vitro and in Caenorhabditis elegans: A Cosmeceutical and Dermatological Approach.

We previously annotated the phytochemical constituents of a root extract from Ximenia americana var. caffra and highlighted its hepatoprotective and hypoglycemic properties. We here extended our study on the leaf extract and identified its phytoconstituents using HPLC-PDA-ESI-MS/MS. In addition, we explored its antioxidant, antibacterial, and antiaging activities in vitro and in an animal model, Caenorhabditis elegans. Results from HPLC-PDA-ESI-MS/MS confirmed that the leaves contain 23 secondary metabolites consisting of condensed tannins, flavonol glycosides, flavone glycosides, and flavonol diglycosides. The leaf extract demonstrated significant antioxidant activity in vitro with IC50 value of 5 µg/mL in the DPPH assay and 18.32 µg/mL in the FRAP assay. It also inhibited four enzymes (collagenase, elastase, hyaluronidase, and tyrosinase) crucially involved in skin remodeling and aging processes with comparable activities to reference drugs along with four pure secondary metabolites identified from the extract. In accordance with the in vitro result, in vivo tests using two transgenic strains of C. elegans demonstrated its ability to reverse oxidative stress. Evidence included an increased survival rate in nematodes treated with the prooxidant juglone to 68.9% compared to the 24.8% in untreated worms and a reduced accumulation of intracellular reactive oxygen species (ROS) in a dose-dependent manner to 77.8%. The leaf extract also reduced levels of the expression of HSP 16.2 in a dose-dependent manner to 86.4%. Nuclear localization of the transcription factor DAF-16 was up to 10 times higher in worms treated with the leaf extract than in the untreated worms. The extract also inhibited the biofilm formation of Pseudomonas aeruginosa (a pathogen in skin infections) and reduced the swimming and swarming mobilities in a dose-dependent fashion. In conclusion, leaves of X. americana are a promising candidate for preventing oxidative stress-induced conditions, including skin aging.

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.

Current Understanding of Modes of Action of Multicomponent Bioactive Phytochemicals: Potential for Nutraceuticals and Antimicrobials.

Plants produce a diversity of plant secondary metabolites (PSMs), which function as defense chemicals against herbivores and microorganisms but also as signal compounds. An individual plant produces and accumulates mixtures of PSMs with different structural features using different biosynthetic pathways. Almost all PSMs exert one or several biological activities that can be useful for nutrition and health. This review discusses the modes of action of PSMs alone and in combinations. In a mixture, most individual PSMs can modulate different molecular targets; they are thus multitarget drugs. In an extract with many multitarget chemicals, additive and synergistic effects occur. Experiments with the model system Caenorhabditis elegans show that polyphenols and carotenoids can function as powerful antioxidative and longevity-promoting PSMs. PSMs of food plants and spices often exhibit antioxidant, anti-inflammatory, and antimicrobial properties, which can be beneficial for health and the prevention of diseases. Some extracts from food plants and spices with bioactive PSMs have potential for nutraceuticals and antimicrobials.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential.

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

Function of selected natural antidiabetic compounds with potential against cancer via modulation of the PI3K/AKT/mTOR cascade.

Diabetes mellitus (DM) is a metabolic disorder with growing global incidence, as 387 million people were diagnosed in 2014 with an expected projection of 642 million in 2040. Several complications are associated with DM including heart attack, stroke, kidney failure, blindness, and cancer. The latter is the second leading cause of death worldwide accounting for one in every six deaths, with liver, pancreas, and endometrium cancers are the most abundant among patients with diabetes. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a vital role in developing a wide array of pathological disorders, among them diabetes and cancer. Natural secondary metabolites that counteract the deleterious effects of reactive oxygen species (ROS) and modulate PI3K/Akt/mTOR pathway could be a promising approach in cancer therapy. Here, 717 medicinal plants with antidiabetic activities were highlighted along with 357 bioactive compounds responsible for the antidiabetic activity. Also, 43 individual plant compounds with potential antidiabetic activities against cancer via the modulation of PI3K/Akt/mTOR cascade were identified. Taken together, the available data give an insight of the potential of repurposing medicinal plants and/or the individual secondary metabolites with antidiabetic activities for cancer therapy.

A Leaf Extract of Harrisonia abyssinica Ameliorates Neurobehavioral, Histological and Biochemical Changes in the Hippocampus of Rats with Aluminum Chloride-Induced Alzheimer's Disease.

Aluminum (Al) is an omnipresent mineral element in the environment. The brain is a central target of Al toxicity, being highly susceptible to oxidative damage. Therefore, recognition of drugs or natural products that guard against Al-mediated neuronal cell death is a powerful strategy for prevention and treatment of neurodegenerative disorders. This work aimed to explore the potential of a leaf extract from Harrisonia abyssinica to modulate the neurobehavioral, biochemical and histopathological activities induced experimentally by Al in vivo. Rats subjected to Al treatment displayed a reduction in learning and memory performance in a passive avoidance test accompanied by a decrease in the hippocampal monoamine and glutamate levels in addition to suppression of Bcl2 expression. Moreover, malondialdehyde (MDA), inflammatory markers (TNF-α, IL-1ß), apoptotic markers (caspase-3 and expression of Bax) and extracellular regulated kinase (ERK1/2) levels were elevated along with acetylcholinesterase (AChE) activity, histological changes and marked deposition of amyloid ß plaques in the hippocampus region of the brain tissues being observed in Al-treated animals. Concomitant administration of the high dose of H. abyssinica (200 mg/kg b.w.) restored nearly normal levels of all parameters measured, rather than the low dose (100 mg/kg b.w.), an effect that was comparable to the reference drug (rivastigmine). Molecular docking revealed the appropriate potential of the extract components to block the active site of AChE and ERK2. In conclusion, H. abyssinica leaf extract conferred neuroprotection against Al-induced neurotoxic effects, most likely due to its high phenolic and flavonoid content.

Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites.

Plant secondary metabolites (SMs) common natural occurrences and the significantly lower toxicities of many SM have led to the approaching development and use of these compounds as effective pharmaceutical agents; especially in cancer therapy. A combination of two or three of plant secondary metabolites together or of one SM with specific anticancer drugs, may synergistically decrease the doses needed, widen the chemotherapeutic window, mediate more effective cell growth inhibition, and avoid the side effects of high drug concentrations. In mixtures they can exert additive or even synergistic activities. Many SM can effectively increase the sensitivity of cancer cells to chemotherapy. In phytotherapy, secondary metabolites (SM) of medicinal plants can interact with single or multiple targets. The multi-molecular mechanisms of plant secondary metabolites to overcome multidrug resistance (MDR) are highlighted in this review. These mechanisms include interaction with membrane proteins such as P-glycoprotein (P-gp/MDR1); an ATP-binding cassette (ABC) transporter, nucleic acids (DNA, RNA), and induction of apoptosis. P-gp plays an important role in the development of MDR in cancer cells and is involved in potential chemotherapy failure. Therefore, the ingestion of dietary supplements, food or beverages containing secondary metabolites e.g., polyphenols or terpenoids may alter the bioavailability, therapeutic efficacy and safety of the drugs that are P-gp substrates.

Eugenia uniflora and Syzygium samarangense extracts exhibit anti-trypanosomal activity: Evidence from in-silico molecular modelling, in vitro, and in vivo studies.

The parasite Trypanosoma brucei is the main cause of the sleeping sickness threatening millions of populations in many African countries. The parasitic infection is currently managed by some synthetic medications, most of them suffer limited activity spectrum and/or serious adverse effects. Some studies have pointed out the promising therapeutic potential of the plant extracts rich in polyphenols to curb down parasitic infections caused by T. brucei and other trypanosomes. In this work, the main components dominating Eugenia uniflora and Syzygium samarangense plant extracts were virtually screened, through docking, as inhibitors of seven T. brucei enzymes validated as potential drug targets. The in vitro and in vivo anti-T. brucei activities of the extracts in two treatment doses were evaluated. Moreover, the extract effects on the packed cell volume level, liver, and kidney functions were assessed. Five compounds showed strong docking and minimal binding energy to five target enzymes simultaneously and three other compounds were able to bind strongly to at least four of the target enzymes. These compounds represent lead hits to develop novel trypanocidal agents of natural origin. Both extracts showed moderate in vitro anti-trypanosomal activity. Infected animal groups treated over 5 days with the studied extracts showed an appreciable in vivo anti-trypanosomal activity and ameliorated in a dose dependent manner the anaemia, liver, and kidney damages induced by the infection. In conclusion, Eugenia uniflora and Syzygium samarangense could serve as appealing sources to treat trypanosomes infections.

Phytochemistry, Pharmacology and Medicinal Uses of Plants of the Genus Salix: An Updated Review.

The Willows (genus Salix), with more than 330-500 species and 200 hybrids, are trees, shrubs or prostrate plants that are widely distributed in Africa, North America, Europe, and Asia. The genus is traditionally used in folk medicine and represents a valuable source of biologically active compounds among them salicin, a prodrug for salicylic acid. Altogether, 322 secondary metabolites were characterized in the genus including flavonoids 94) (flavonols, flavones, flavanones, isoflavones, flavan-3-ols (catechins and procyanidins), chalcones, dihydrochalcone, anthocyanins, dihydroflavonols), phenolic glycosides (76), organic acids (28), and non-phenolic glycosides (17), sterols and terpenes (17), simple phenolics 13) and lignans 7) in addition to volatiles and fatty acids (69). Furthermore, willows exert analgesic, anti-inflammatory, antioxidant, anticancer, cytotoxic, antidiabetic, antimicrobial, antiobesity, neuroprotective and hepatoprotective activities. The current review provides an updated summary of the importance of willows, their chemical composition and pharmacological activities.

The Genus Lagochilus (Lamiaceae): A Review of Its Diversity, Ethnobotany, Phytochemistry, and Pharmacology.

The genus Lagochilus (Lamiaceae) is native to Central, South-Central, and Eastern Asia. It comprises 44 species, which have been commonly used as herbal medicines for the treatments of various ailments for thousands of years, especially in Asian countries. This review aims to summarize the chemical constituents and pharmacological activities of species from the genus Lagochilus to unveil opportunities for future research. In addition, we provide some information about their traditional uses, botany, and diversity. More than 150 secondary metabolites have been reported from Lagochilus, including diterpenes, flavonoids, phenolic compounds, triterpenoids, iridoid glycosides, lignans, steroids, alkaloids, polysaccharides, volatile, non-volatile and aromatic compounds, lipids, carbohydrates, minerals, vitamins, and other secondary metabolites. In vitro and in vivo pharmacological studies on the crude extracts, fractions, and isolated compounds from Lagochilus species showed hemostatic, antibacterial, anti-inflammatory, anti-allergic, cytotoxic, enzyme inhibitory, antispasmodic, hypotensive, sedative, psychoactive, and other activities.

Neuroprotective Effects of Extracts from Tiger Milk Mushroom Lignosus rhinocerus Against Glutamate-Induced Toxicity in HT22 Hippocampal Neuronal Cells and Neurodegenerative Diseases in Caenorhabditis elegans.

Despite the Tiger Milk Mushroom Lignosus rhinocerus (LR) having been used as a traditional medicine, little is known about the neuroprotective effects of LR extracts. This study aims to investigate the neuroprotective effect of three extracts of LR against glutamate-induced oxidative stress in mouse hippocampal (HT22) cells as well as to determine their effect in Caenorhabditis elegans. In vitro, we assessed the toxicity of three LR extracts (ethanol extract (LRE), cold-water extract (LRC) and hot-water extract (LRH)) and their protective activity by MTT assay, Annexin V-FITC/propidium iodide staining, Mitochondrial Membrane Potential (MMP) and intracellular ROS accumulation. Furthermore, we determined the expression of antioxidant genes (catalase (CAT), superoxide dismutase (SOD1 and SOD2) and glutathione peroxidase (GPx)) by qRT-PCR. In vivo, we investigated the neuroprotective effect of LRE, not only against an Aß-induced deficit in chemotaxis behavior (Alzheimer model) but also against PolyQ40 formation (model for Morbus Huntington) in transgenic C. elegans. Only LRE significantly reduced both apoptosis and intracellular ROS levels and significantly increased the expression of antioxidant genes after glutamate-induced oxidative stress in HT22 cells. In addition, LRE significantly improved the Chemotaxis Index (CI) in C. elegans and significantly decreased PolyQ40 aggregation. Altogether, the LRE exhibited neuroprotective properties both in vitro and in vivo.

In vitro anti-proliferative activity of selected nutraceutical compounds in human cancer cell lines.

OBJECTIVE: We investigated the anti-proliferative or cytotoxic activities of five nutraceutical compounds: allyl isothiocyanate, ß-carotene, caffeine, capsaicin, and lupanine that we consume respectively, for example, from mustard seeds, carrot, coffee, pepper, and lupin seeds against cancer cell lines (human colon: HCT 116 p53 wild type, HCT 116 p53-/- and lymphoblastic: CEM/CCRF, CEM/ADR5000). RESULT: Out of the five compounds tested in vitro, capsaicin and ß-carotene were more cytotoxic than the other three compounds against the four cancer cell lines. The most potent nutraceutical compound was capsaicin and it exerted its highest cytotoxicity against HCT 116 p53-/- with IC50 value of 19.67 ± 0.06 µM. It is worth considering capsaicin for further development of anticancer drug against both colon and leukemia cancer types.