Main Bioactive Metabolites Research Articles

Comprehensive utilization of in silico approach and in vitro experiment to unveil the molecular mechanisms of mono (2-ethylhexyl) phthalate-induced lung adenocarcinoma

Mono (2-ethylhexyl) phthalate (MEHP), the main bioactive metabolite of commonly used plasticizer Di (2-ethylhexyl) phthalate, has received increasing attention due to its carcinogenic toxicity. This study aims to systematically explore the molecular mechanisms underlying MEHP-induced lung adenocarcinoma (LUAD). Firstly, network toxicology was employed to construct the interaction network of MEHP-targeted LUAD-related proteins and identify core proteins. Subsequently, functional analyses were used to determine the key pathways of these proteins enriched. Next, expression and survival analyses of multiple public datasets were conducted to emphasize the importance of core genes, and an optimized prognostic model was constructed based on independent prognostic genes to explore the relationship of gene risk with immune infiltration and immunotherapy. Ultimately, molecular docking and dynamics simulation were used to predict the binding modes and affinities of MEHP with core proteins, and surface plasmon resonance experiments were utilized to further validate their direct interactions. The findings demonstrated that MEHP targets 167 LUAD-related proteins, including 28 core target proteins. These proteins form the critical networks that regulate cancer and immune-associated pathways to induce the occurrence and development of LUAD, and further coordinate patient prognosis and treatment by altering the immune microenvironment. Most importantly, their direct interactions (especially PTGS2) lay the structural foundation of MEHP regulating core proteins, greatly supporting its LUAD toxicity. In conclusion, this study introduces a novel approach for evaluating the safety of plasticizers and elucidates the molecular mechanisms behind MEHP-induced LUAD, thus offering new and effective targets and strategies for cancer prevention and treatment.

A comprehensive review of ethnomedicinal approaches, phytochemical analysis, and pharmacological potential of Vitex trifolia L.

Plants, renowned for their rich reservoir of metabolites, play a pivotal role in addressing health-related issues. The Verbenaceae family stands out, showcasing immense potential in preventing and treating chronic diseases. Vitex trifolia L. (V. trifolia), a shrub with a rich history in traditional medicine, particularly in Eastern Asia, has garnered attention for its diverse therapeutic applications. This comprehensive review aims to bridge traditional knowledge and contemporary insights by investigating ethnopharmacology, phytochemistry, and pharmacological effects of V. trifolia. The keyword "V. trifolia" and its synonyms were searched within the main scientific databases including PubMed, Web of Science, ScienceDirect, Google Scholar, and Baidu Scholar (from 1974 to 2022, last search: 21.10.2023). Phytochemical analyses reveal a spectrum of secondary metabolites in V. trifolia, including terpenoids, flavonoids, lignans, phytosterols, anthraquinones, and fatty acids. Notably, terpenoids and flavonoids emerge as the main bioactive metabolites. Pharmacological studies validate its therapeutic potential, demonstrating significant antioxidant, anti-inflammatory, hepatoprotective, anticancer, anti-amnesic, antimicrobial, antiviral, anti-malaria, antispasmodic activities, and reported insecticidal effects. Despite existing literature exploring pharmacological attributes and secondary metabolites of related species, a conspicuous gap exists, specifically focusing on the pharmacological activities and novel methods of purification of pure metabolites from V. trifolia. This review aimed to fill this gap by delving into traditional medicinal applications, exploring secondary metabolites comprehensively, and providing an in-depth analysis of pharmacological effects of pure metabolites. Combining traditional uses with contemporary pharmacological insights, this article sought to serve as a crucial reference for future research and practical application of V. trifolia. This approach contributes substantially to understanding the plant, fostering scientific inquiry, and facilitating its broader application in healthcare.

Evaluation of anti-cancer potential of saffron extracts against kidney and bladder cancer cells

Crocus Sativus L. (saffron) has been used for centuries as a medicinal plant in traditional medicine. Its main bioactive secondary metabolites, which include crocins, crocetin, picrocrocin and safranal, are known to possess significant antioxidant as well as anti-proliferative activities. With the aim to test the activity of saffron on kidney and bladder cancer cell lines, we tested the effect of extracts obtained from dried stigmas derived from different Italian regions (Lombardy and Tuscany) in two different years, on the cell viability. The treatment with saffron extracts showed a significant reduction of cell viability in most of our tumoral cellular systems, while the standards crocin and safranal alone at the same concentrations did not exerted any cytotoxicity. When the extracts and standards were mixed together, they exerted a milder inhibition of cell viability, indicating that the antitumor activity is likely a result of the synergy of the various compounds. In addition, in a circular economy vision, we recovered Crocus Sativus flowers and tested them on cancer cells, demonstrating a consistent reduction of cell viability, while kaempferol (main compound present in flower extracts) did not show compatible results. Our results extend the interests around saffron-derived bioactive molecules for their potential in therapeutics.

Metabolites from a Pleurotus tuber-regium collected in Madagascar

Pleurotus tuber-regium was isolated from a dead trunk of Raphia farinifera (Arecaceae) in a lowland moist forest in Antsohihy, Madagascar, and the species was confirmed by molecular analysis and morphological observations. The main bioactive metabolites of the mycelium extracts were identified by mass spectrometry techniques. Five structural diverse metabolites, tryptophol, pyroglutamic acid, prolyldiketopiperazine B, sporol and RKS-1778, were characterised by LC-MS qTOF analysis of the hydro-alcoholic extract. GC-MS analysis of both chloroform and ethyl acetate extracts revealed the presence of several saturated and ­unsaturated fatty acids and their esters derivatives.

A metabolic reprogramming in Bacopa monnieri plants induced by methyl-jasmonate and enhanced biosynthesis of triterpene saponins

The bacoside-A is the main bioactive metabolite present in Bacopa monnieri L. The yield of bacoside-A from plant sources is too less to meet industrial demand. This study investigated the effect of methyl jasmonate (MeJA) on metabolic profiles and bacoside-A biosynthesis in greenhouse-grown plants of B. monnieri. The greenhouse-grown plants were kept inside a closed plastic container and then elicited with MeJA vapour. It was found that MeJA treatment (200 µM for 2 h on day zero) followed by harvesting leaves on day three was the optimum treatment, resulting in an increase of 1.8-fold, 2.2-fold, 3.1-fold, and 2.5-fold in bacoside A3, bacopaside II, bacopaside X, and bacopasaponin C in comparison with control plants, respectively. The transcript levels of squalene synthase (SQS), a key gene involved in bacoside-A biosynthesis was transiently induced by MeJA and reached a peak of up to 3.7-fold at 24 h. The relationships between bacosides content and primary metabolites in plants treated with MeJA were analyzed by gas chromatography-mass spectrometry. MeJA enhances glycolysis and TCA cycles, generating acetyl-CoA, which acts as a precursor for bacosides synthesis, as revealed by untargeted metabolomics. Therefore, in planta application of MeJA appears to have a great impact on enhanced bacoside-A accumulation, in the greenhouse-grown plants of B. monnieri. In this study, farmers and the pharmaceutical industry will have access to a simple and time-saving elicitation strategy for improving bacosides production from greenhouse-grown plants without the need for expensive and time-consuming in vitro culture techniques.

Biological Activities of Lamiaceae Species: Bio-Guided Isolation of Active Metabolites from Salvia officinalis L.

Lamiaceae family includes various medicinal and aromatic plants used in cosmetics and pharmaceutical industries. The present study aimed to investigate in vitro the cytotoxic, photoprotective and antioxidant activities of ten Lamiaceae taxa; Melissa officinalis subsp. altissima (Sm.) Arcang., Rosmarinus officinalis L., Salvia officinalis L., Sideritis cypria Post, S. euboea Heldr., S. perfoliata L. subsp. perfoliata, S. scardica Griseb., S. sipylea Boiss., Stachys iva Griseb., and Thymus vulgaris L. The aqueous extract of Salvia officinalis was bio-guided fractionated to obtain the main bioactive metabolites, which were evaluated for the aforementioned effects and their wound-healing potential. In total, five compounds were isolated and identified through NMR spectra, namely salvianic acid A, rosmarinic acid, salvianolic acid K, luteolin-3′-O-β-D-glucuronide and hispidulin-7-O-β-D-glucuronide. All the compounds were photoprotective and non cytotoxic, while no statistically significant oxidative stress reduction was obtained. Regarding the wound-healing potential, salvianolic acid K was the most promising candidate. Overall, this study suggests photoprotective natural agents from various Lamiaceae species, widely found in Greece, and provides a better insight into Salvia officinalis and its bioactive constituents.

Isopropyl 3-(3, 4-dihydroxyphenyl)-2-hydroxypropanoate protects lipopolysaccharide-induced acute lung injury in mice by attenuating pyroptosis

Isopropyl 3-(3,4-dihydroxyphenyl)-2-hydroxypropanoate (IDHP) is one of the main bioactive metabolites of the Chinese medicinal herb Danshen, which can be absorbed into blood compounds by oral administration of Compound Danshen dripping pills (CDDPs). Previous study showed that IDHP exerted anti-inflammatory effects by abolishing the secretion of proinflammatory factors stimulated by lipopolysaccharide (LPS). However, the effects of IDHP on LPS-induced acute lung injury (ALI) are not fully understood. In the present study, we observed the effects of IDHP on mortality and lung injury in LPS-treated mice and on LPS-induced THP-1 macrophages. Pretreatment with high dose of IDHP was found to reduce the mortality of ALI mice, significantly improve LPS-induced pathological changes, and reduce protein leakage and inhibited myeloperoxidase (MPO) activity in lung tissue. IDHP also inhibited the release of inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissue. Meanwhile, IDHP treatment significantly reduced the expression of active-caspase1, Nlrp3, Asc speck formation, Gsdmd (part of the canonical pyroptosis pathway), caspase4 (part of the non-canonical pyroptosis pathway), therefore decreasing IL-1β, IL-18, and ROS secretion in LPS-stimulated THP-1 macrophages. Moreover, after co-culturing endothelial/epithelial cells with conditioned medium (CM) from LPS-stimulated THP-1 macrophages, we found that the protein levels of occludin and Zonula occludens-1 (Zo-1) were increased in IDHP CM-treated endothelial cells compared to those that were LPS CM-treated. Lactic dehydrogenase (LDH) assay shows that IDHP also alleviated LPS-induced endothelial/epithelial cell injury. These findings indicate that the protective effect of IDHP on LPS-induced lung injury may be partly due to the inhibition of pyroptosis pathways.

Effects of Sophora flavescens aiton and the absorbed bioactive metabolite matrine individually and in combination with 5-fluorouracil on proliferation and apoptosis of gastric cancer cells in nude mice.

Background: Sophora flavescens aiton (SFA) and its main bioactive metabolite matrine are widely used in traditional Chinese medicine (TCM) preparations and have achieved good curative effects for the treatment of various tumors. However, the mechanisms underlying SFA and matrine individually and in combination with chemotherapeutic drugs for treatment of gastric cancer (GC) remain unclear. Aim of the study: To elucidate the mechanisms underlying the ability of SFA and matrine individually and in combination with chemotherapeutic drugs to inhibit proliferation and promote apoptosis of human GCcells. Materials and methods: Forty-eight nude mice were randomly divided into six groups that were treated with normal saline (model group), 5-fluorouracil (5-FU), SFA decoction (SFAD), matrine, SFAD+5-FU, or matrine+5-FU. A subcutaneous heterotopic tumor model was established in nude mice by implantation of human GC BGC-823 cells. All mice were treated for 28days. Bioactive metabolites in SFA were determined by HPLC-MS/MS. The tumor volume, tumor weight, and tumor inhibition rate of mice were documented. Histopathology and ultramicroscopic pathology of tumor tissues were observed. The tumor cell cycle and apoptosis in vivo were detected. Serum levels of PCNA, BAX, Bcl-2, Caspase-9, Caspase-3 and cleaved Caspase-3 were measured. Protein levels of MS4A10, MS4A8, MS4A7, PCNA, BAX, Bcl-2, Caspase-3, and cleaved Caspase-3 were measured in tumor tissues. Results: Both SFAD and matrine inhibited the growth of transplanted GCcells, which was more effective when combined with 5-FU. The tumor inhibition rates of the 5-FU, SFAD, matrine, SFAD+5-FU, and matrine+5-FU groups were 53.85%, 33.96%, 30.44%, 59.74%, and 56.55%, respectively. The body weight of tumor-bearing nude mice was greater in the SFAD group than the normal saline and matrine groups. SFAD+5-FU and matrine+5-FU blocked BGC-823 cells in the G0-G1/S transition, promoted apoptosis, and significantly decreased the content of serum apoptosis-inhibitory proteins (PCNA and Bcl-2) as well as protein expression of MS4A8, MS4A10, Bcl-2, and PCNA in tumor tissues, while increasing serum levels of pro-apoptotic proteins (Caspase-9, Caspase-3 and cleaved-Caspase-3) and protein expression of BAX and cleaved-Caspase-3 in tumor tissues. Conclusion: SFAD and matrine both individually and in combination with 5-FU ameliorated malignancy of transplanted tumors by reducing proliferation and promoting apoptosis of BGC-823 cells. These findings confirm the anti-tumor synergistic effect of TCM and chemotherapeutic drugs.

Steviol, the aglycon of steviol glycosides, does not reduce hyperglycemia in mice with type 2 diabetes

BackgroundSteviol glycosides, constituents of Stevia rebaudiana Bertoni, are high-intensity sweeteners that enhance glucose-induced insulin secretion and decrease hyperglycemia in mice and rats. Given the extreme sweetness and bitter aftertaste of these compounds, the non-tasting aglycon steviol might be a promising alternative food additive that also harbors anti-hyperglycemic effects. Furthermore, it has been suggested that steviol glucuronide is the main bioactive metabolite of steviol and steviol glycosides that appears in blood. AimTo investigate whether steviol and/or steviol glucuronide reduce hyperglycemia in a high-fat diet (HFD)-induced diabetic mouse model. MethodsSteviol was administered acute per os (p.o.), chronic via drinking water and intravenous (i.v.) to HFD-induced diabetic mice. The effect on glucose homeostasis was assessed using glucose tolerance tests (GTTs). Following chronic and i.v. steviol administration, steviol and steviol glucuronide plasma levels were determined. Steviol glucuronide was administered i.v. and the effect on glycemia was assessed with GTTs. ResultsAcute and chronic oral steviol administration did not lower glycemia. This is due to the very limited and short-lived bioavailability of steviol in plasma. Only after high dosage i.v. steviol, glycemia was transiently reduced shortly after administration (Δ 15 min: 76.4 ± 30.9 mg dL−1, p = 0.035). In contrast, i.v. steviol glucuronide resulted in a 16.4 ± 5.9% lower AUCGlucose(0–120 min) compared to mice that received vehicle (p = 0.040). Moreover, steviol glucuronide enhanced the glucose-induced calcium oscillation frequency in insulin-secreting pancreatic islets. ConclusionOur findings demonstrate that steviol is not a useful derivative of steviol glycosides to improve hyperglycemia in type 2 diabetes. On the other hand, steviol glucuronide has significant anti-hyperglycemic effects in living mice with type 2 diabetes.

Description of Aliinostoc alkaliphilum sp. nov. (Nostocales, Cyanobacteria), a New Bioactive Metabolite-Producing Strain from Salina Verde (Pantanal, Brazil) and Taxonomic Distribution of Bioactive Metabolites in Nostoc and Nostoc-like Genera

Cyanobacteria are a group of oxygenic photosynthetic prokaryotes found in almost all habitats on earth including those characterized as extreme environments. It has been observed that the number of studies dealing with the biodiversity of extremophilic cyanobacteria is limited while studies exploring their bioactive potential are even scarcer. The taxonomy of three Nostoc-like cyanobacterial strains isolated from a shallow lake in Brazil was studied by applying a polyphasic approach. The bioactive potential of the strains was also evaluated using antimicrobial susceptibility testing. The metabolites present in the bioactive HPLC fractions were identified by UPLC/ESI/Q-TOF. Based on our phylogenetic inferences in combination with morphological and ecological information, we describe Aliinostoc alkaliphilum sp. nov., exhibiting antibacterial and antifungal activities. The main bioactive metabolite in all three strains was nocuolin A, which represents the first report of this metabolite in Aliinostoc. Our phylogenetic studies also revealed that many bioactive metabolite-producting strains that are currently assigned to Nostoc belong to other distinct evolutionary lineages. These findings highlight the importance of polyphasic approach studies in both cyanobacterial taxonomy and natural product discovery programs.

Kynurenic acid ameliorates lipopolysaccharide-induced endometritis by regulating the GRP35/NF-κB signaling pathway

Endometritis is a serious reproductive disease in mammals that commonly results in reproductive loss and even permanent infertility. Kynurenic acid (KYNA) is the main bioactive metabolite of tryptophan degradation and exhibits neuroprotective and anticonvulsant properties. However, little is known about the role of KYNA in achieving endometritis remission. This study investigated the protective effects and mechanisms of KYNA using a mouse model of against lipopolysaccharide (LPS)-induced endometritis. The endometritis model was induced by an intrauterine injection of LPS, and KYNA was intraperitoneally injected before and two hours after LPS treatment. Twenty-four hours after LPS administration, pathological changes in uterine tissues were observed by hematoxylin- and eosin (H&E) staining. The levels of the inflammatory factors, TNF-α and IL-1β, were measured by ELISA. The myeloperoxidase (MPO) activity in uterine tissues was detected using MPO kits and immunohistochemistry. Furthermore, the expression of signaling pathway proteins and tight junction proteins occludin and ZO-1 in uterine tissues was detected by western blot. KYNA prominently inhibited uterine pathological injury and neutrophil infiltration and restricted the secretion of TNF-α and IL-1β in the uteri of subjects with endometritis. Furthermore, KYNA upregulated the levels of the tight junction proteins (TJPs)occludin and ZO-1 in the uterus. In vitro, KYNA inhibited LPS-induced TNF-α and IL-1β production, and NF-κB activation in mouse endometrial epithelial cells (mEECs). In addition, KYNA increased the expression of G protein-coupled receptor 35 (GPR35) and inhibition of GPR35 reversed the anti-inflammatory effects of KYNA. In conclusion, KYNA protected against LPS-induced endometritis by maintaining epithelial barrier permeability and suppressing proinflammatory responses via the GRP35/NF-κB signaling pathway.

The traditional uses, phytochemistry, pharmacological, and botanical description of Quercus infectoria galls (Mazuphal): A review

Ethno-pharmacological relevance- In Unani system of medicine Quercus Infectoria galls (QIG) (known as Mazuphal), have a long history of use in the management of many human ailments like diarrhea, hemorrhage, skin diseases, and many other. The QIG is a protective product of small shrub Quercus Infectoria and its medicinal applications of have become increasingly popular in Greece, Syria, Iraq and Iran.
 Aim- The aim of the present paper is to provide a contemporary reviewed on the traditional uses and its toxinomy, phytochemical, analytical methods, pharmacological activities, toxicology, and drug interactions of QIG to assess the ethnopharmacological uses, explore its therapeutic potential, and identify future opportunities for research.
 Materials and methods- Information on studies of QIG was collected from the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Pubmed, Web of Science, CNKI, and EMBASE) and libraries. Additionally, information was also obtained from local books and PhD and MD’s dissertations.
 Results- QIG has played an important role in traditional Unani medicine. The main bioactive metabolites of QIG include tannins, phenolic acids, flavonoids, triterpenoids, steroids etc. Scientific studies on the QIG extract and its components have shown its extensive range of pharmacological activities, such as cholinesterase- and monoamine oxidase-inhibitory, antitumor, anti-hypertension, antidiabetic, antimicrobial, insecticidal, antiparasitic, antioxidant, and anti-inflammatory.
 Conclusions- In this review the traditional knowledge, ethnopharmacological, phytochemical, pharmacological, and analytical methods of QIG were highlighted, which gives the proper information for future studies and business exploration. QIG has a huge potential for pharmaceutical and nutraceuticals applications. Moreover the toxicity studies of QIG be reported for the enduring the safety. Additional investigations are recommended to transmute the ethnopharmacological claims of this plant in folklore medicines into scientific rationale-based information. Research on pharmacokinetics studies and potential drug interactions with standard-of-care medications is still limited, which calls for additional studies particularly on humans. Further assessments and clinical trials should be performed before it can be integrated into medicinal practices.
 Keywords: Quercus infectoria galls, Ethnopharmacology, Phytochemistry, Pharmacology

Anthocyanin-rich blueberry extracts and anthocyanin metabolite protocatechuic acid promote autophagy-lysosomal pathway and alleviate neurons damage in in vivo and in vitro models of Alzheimer's disease

ObjectivesAs the global aging phenomenon intensifies, the incidence of Alzheimer's disease (AD) is gradually increasing. Diet appears to be an effective way to prevent and delay the progression of AD. Previous studies have found that cognitive impairment and neuronal damage were effectively alleviated by blueberry extract (BBE) in AD mice, but its mechanism is still unclear. The aims of this study were to detect the main anthocyanins of BBE; then to verify the protective effects of anthocyanin-rich BBE on hippocampal neurons and the promotion of autophagy; and finally to investigate the main protective effects and mechanisms of protocatechuic acid (PCA), a major metabolite of BBE, for promoting autophagy and thus playing a neuroprotective role. MethodsAPP/PS1 mice were given 150 mg/kg BBE daily for 16 wk. Morphology of neurons was observed and autophagy-related proteins were detected. ResultsNeuron damage in morphology was reduced and the expression of autophagy-related proteins in APP/PS1 mice were promoted after BBE treatment. In vitro, Aβ25-35-induced cytotoxicity, including decreased neuron viability and increased levels of lactate dehydrogenase and reactive oxygen species, was effectively reversed by PCA. Furthermore, by adding autophagy inducers rapamycin and autophagy inhibitors Bafilomycin A1, it was verified that degradation of autophagosomes was upregulated and autophagy was promoted by PCA. ConclusionThis study elucidated the mechanism of BBE for reducing neuronal damage by promoting neuronal autophagy and proved PCA may be the main bioactive metabolite of BBE for neuroprotective effects, providing a basis for dietary intervention in AD.

Effect of Methyl Jasmonate, Salicylic Acid and Their Combination on Growth and Bioactive Constituents in Cichoriun intybus L. تأثير ميثايل حامض الجاسمونيک و حامض السالسيلک و مخلوطهما معآ على النمو و المحتوى من مرکبات التمثيل الثانوى ذات النشاط الحيوى فى نبات الشيکوريا Cichoriun intybus L.

The current study was conducted to evaluate the efficiency of seedling’s roots-feeding of the elicitor solution of methyl jasmonate (MeJ), salicylic acid (SA) and their combination as an elicitation approach for enhancing the biosynthesis of cichory’s main bioactive secondary metabolites. The long-lasting elicitation effect of both MeJ and SA was also evaluated through comparing the level of bioactive compounds in treated plants of the first harvest with those of the second one. Results indicated that MeJ, SA, and their combination decreased growth of cichory plants whereas increased their potential to biosynthesize their characteristic bioactive secondary metabolites. Shoots and roots of MeJ-, SA- and MeJ+SA-treated plants contained significantly higher contents from ascorbic acid as well as total antioxidants, total phenols as well as flavonoids and inulin compared with untreated plants of either the first or the second harvest. The effect of MeJ surpassed that of SA in inducing contents of the secondary metabolites. Control plants of the second harvest had, generally, higher contents from ascorbic acid, total antioxidants, total phenols total flavonoids and inulin compared with plants of the first harvest. It could be concluded that seedlings’ roots-feeding of the elicitor solution is feasible, easy and cost-effective approach for long-lasting elicitation effect, and that MeJ is superior to SA in eliciting cichory’s bioactive secondary metabolites.

Metabolomics as a Tool to Study Underused Soy Parts: In Search of Bioactive Compounds.

The valorization of agri-food by-products is essential from both economic and sustainability perspectives. The large quantity of such materials causes problems for the environment; however, they can also generate new valuable ingredients and products which promote beneficial effects on human health. It is estimated that soybean production, the major oilseed crop worldwide, will leave about 597 million metric tons of branches, leaves, pods, and roots on the ground post-harvesting in 2020/21. An alternative for the use of soy-related by-products arises from the several bioactive compounds found in this plant. Metabolomics studies have already identified isoflavonoids, saponins, and organic and fatty acids, among other metabolites, in all soy organs. The present review aims to show the application of metabolomics for identifying high-added-value compounds in underused parts of the soy plant, listing the main bioactive metabolites identified up to now, as well as the factors affecting their production.

MAJOR BIOACTIVE PROPERTIES OF GANODERMA POLYSACCHARIDES: A REVIEW

Ganoderma a white rot fungus has been used as a folk remedy for promoting health and longevity for centuries. The vast amount of study has been performed on the medicinal properties of Ganoderma in general and Ganoderma lucidum in particular. The bioactivities of the metabolites reported from G. lucidum are immense. The main bioactive metabolites of G. lucidum consist of mainly polysaccharides and triterpenoids. The major bioactive polysaccharides isolated from Ganoderma species are β (1→3), β (1→4), and β (1→6)-D glucans. With respect to the pure chemical and structural points of view, G. lucidum polysaccharides are mostly composed of β-glucans, heteropolysaccharides, and glycoptoteins. The major component of this sugar molecule is glucose together with xylose, mannose, galactose, and fructose in different conformations. Many of these bioactive polysaccharides have shown activities against the major diseases of our time and the list of effects shown is huge. Various important bioactivities, namely, antitumor, antioxidant, cytotoxic, immunomodulatory, antibacterial, anti-inflammation, neuroprotective, hepatoprotective, anti-HIV, and so on have been shown by these bioactive polysaccharides. The main purpose of this review is to report the most bioactive polysaccharides from G. lucidum and other species of Ganoderma and to report their potential health benefits.

Altitudinal impacts on chemical content and composition of Hypericum perforatum, a prominent medicinal herb

Altitudinal variations in the content of main bioactive secondary metabolites namely, hypericin, pseudohypericin, hyperforin, the chlorogenic, neochlorogenic, caffeic and 2,4-dihydroxybenzoic acids, isoquercitrin, quercitrin, avicularin, hyperoside, rutin, biapigenin, (+)-catechin, (-)-epicatechin and in the composition of essential oil (EO) among Hypericum perforatum populations from two growing sites of Northern Turkey were investigated in detail for the first time. Aerial parts of 30 individuals at full flowering were collected at five different altitudes (391, 631, 1318, 1586 and 1733 m) of “Anzer” upland and six different altitudes (1311, 1447, 1968, 2068, 20169 and 2210 m) of “Cimil” upland in territory of Rize province, Turkey. Air dried plant samples were assayed for polar ingredients by high-performance liquid chromatography (HPLC) and for EO components by solid-phase microextraction (SPME) supported gas chromatography-mass spectrometry (GC-MS) analyses. All the tested polar phytochemicals were detected at various levels depending on altitude in both uplands and the accumulation level of each compound showed a positive consistent and significant response to altitudinal gradient. A considerable diversity in quality and quantity of major EO components was also observed and 2,2,6-trimethyl-cyclohexanone, caryophyllene oxide, tricycloheptane, hexanoic acid, tetradecanol, 2-methyl-dodecane, tetradecane, α-amorphene, eicosene, β-cedrene, piperitone, spathulenol, β-caryophyllene, δ-cadinene and linalool were identified as major EO components depending on altitude. The present results suggest that altitude of plant habitat has an ultimate effect on secondary metabolism of Hypericum perforatum and indicate the investigated populations as new chemotypes in terms of their EO composition. Such kind of findings could be useful to characterize the unique strains with desired chemical composition and can provide new viewpoints for investigations on this valuable medicinal plant.

Antihypertensive and vasorelaxant mode of action of the ethanol-soluble extract from Tagetes lucida Cav. aerial parts and its main bioactive metabolites

Ethnopharmacological relevanceTagetes lucida Cav. commonly known as “yauhtli” or “pericón” is used in Mexican traditional medicine for the treatment of anxiety, depressant diseases, pain, hypertension, among others. AimTo evaluate the antihypertensive and vasorelaxant modes of action of a crude ethanolic extract from T. lucida aerial parts and to isolate the bioactive compounds. Materials and methodsEthanolic extract was tested in an in vivo assay in SHR rats by intragastric administration at 10 and 100 mg/kg dosages, to measure and to compare hemodynamic parameters like diastolic and systolic blood pressure and heart rate. Also, extract (3.03–1000 μg/ml), fractions (3.03–1000 μg/ml) and pure isolated compounds (1.75–550 μM) were evaluated on isolated aortic rings contracted with noradrenaline (0.1 μM) to determine their vasorelaxant effect and extract-mode of action. ResultsEthanolic extract of T. lucida lowered systolic and diastolic blood pressure on SHR rats without heart rate modification (P > 0.05). Moreover, the extract showed concentration-dependent relaxant effect in a partially endothelium-dependent manner (P < 0.05), through NO/cGMP system activation and calcium channel blockade. 6,7,8-trimethoxycoumarin (1), 6,7-dimethoxycoumarin (2), and 7-methoxycoumarin (3) from T. lucida are the main bioactive compounds of the extract and showed significant vasorelaxant activity. ConclusionsResults provide evidence and endorsed the antihypertensive properties attributed to T. lucida in traditional medicine, which is produced by vasorelaxant effect mainly through multitarget NO/cGMP system activation and calcium channel blockade. Coumarin derivatives 1, 2 and 3 are the responsible of the vasorelaxant activity.

Dietary protocatechuic acid ameliorates inflammation and up-regulates intestinal tight junction proteins by modulating gut microbiota in LPS-challenged piglets

BackgroundWeaning is one of the major factors that cause stress and intestinal disease in piglets. Protocatechuic acid (PCA) is an active plant phenolic acid which exists in Chinese herb, Duzhong (Eucommia ulmoides Oliver), and is also considered as the main bioactive metabolite of polyphenol against oxidative stress and inflammation. This study aimed to investigate the effect of PCA on growth performance, intestinal barrier function, and gut microbiota in a weaned piglet model challenged with lipopolysaccharide (LPS).MethodsThirty-six piglets (Pig Improvement Company line 337 × C48, 28 d of age, 8.87 kg ± 0.11 kg BW) were randomly allocated into 3 treatments and fed with a basal diet (CTL), a diet added 50 mg/kg of aureomycin (AUR), or a diet supplemented with 4000 mg/kg of PCA, respectively. The piglets were challenged with LPS (10 μg/kg BW) on d 14 and d 21 by intraperitoneal injection during the 21-d experiment. Animals (n = 6 from each group) were sacrificed after being anesthetized by sodium pentobarbital at 2 h after the last injection of LPS. The serum was collected for antioxidant indices and inflammatory cytokines analysis, the ileum was harvested for detecting mRNA and protein levels of tight junction proteins by PCR and immunohistochemical staining, and the cecum chyme was collected for intestinal flora analysis using 16S rRNA gene sequencing.ResultsDietary supplementation of PCA or AUR significantly increased the expression of tight junction proteins including ZO-1 and claudin-1 in intestinal mucosa, and decreased the serum levels of thiobarbituric acid reactive substances (TBARS) and IL-6, as compared with CTL group. In addition, PCA also decreased the serum levels of IL-2 and TNF-α (P < 0.05). Analysis of gut microbiota indicated that PCA increased the Firmicutes/Bacteroidetes ratio (P < 0.05). Spearman’s correlation analysis at the genus level revealed that PCA reduced the relative abundance of Prevotella 9, Prevotella 2, Holdemanella, and Ruminococcus torques group (P < 0.05), and increased the relative abundance of Roseburia and Desulfovibrio (P < 0.05), whereas AUR had no significant effect on these bacteria.ConclusionsThese results demonstrated that both PCA and AUR had protective effect on oxidative stress, inflammation and intestinal barrier function in piglets challenged with LPS, and PCA potentially exerted the protective function by modulating intestinal flora in a way different from AUR.Holdemanella

Phytochemical investigation of five herbal teas useful in mental disorders treatment

Mental disorders or illnesses are common and affect all countries. According to official estimates, in most countries at least one person in three is affected. Several researches have shown the benefits of plants in the management of these pathologies. This study focuses on five medicinal plants useful in the management of mental disorders, including Cymbopogon citratus, Lippia chevalieri, Combretum micratum, Chrysantellum americanum and Tetrapleura tetraptera. These plants are used in Burkina Faso in the form of herbal teas. The objective of this study is to enhance the value of these plants and improve their use by some physico-chemical analyses, a phytochemical study and the determination of antioxidant activity. Among the parameters that will be precisely investigated there are organoleptic analysis, moisture content, extraction yields, thin layer chromatographic fingerprinting, phytochemical screening and the determination of total phenol, total flavonoids. The DPPH method was used to evaluate the antioxidant power of the various aqueous extracts. The physico-chemical analysis gave satisfactory results on the main indices. The phytochemical study allowed to establish the chromatographic fingerprints of the aqueous extracts, to identify the main bioactive secondary metabolites and to determine the content of total phenols and total flavonoids in the extracts of the five plants. Interesting results are obtained, which confirms the use of these plants. Among the samples submitted to the different analyses, the extract of Combretum micratum presented high levels of total phenolics (395,38 ± 7,05 mg GAE/g extract) and total flavonoids (105,87 ± 0,05 mg Ru E/g extract). This extract also exhibited the highest antiradical activity.