Human aldehyde dehydrogenases: potential pathological,pharmacological, and toxicological impact

Aldehyde dehydrogenases catalyze the pyridine nucleotide-dependent oxidation of aldehydes to acids. Seventeen enzymes are currently viewed as belonging to the human aldehyde dehydrogenase superfamily. Summarized herein, insofar as the information is available, are the structural composition, physical properties, tissue distribution, subcellular location, substrate specificity, and cofactor preference of each member of this superfamily. Also summarized are the chromosomal locations and organization of the genes that encode these enzymes and the biological consequences when enzyme activity is lost or substantially diminished. Broadly, aldehyde dehydrogenases can be categorized as critical for normal development and/or physiological homeostasis (1). even when the organism is in a friendly environment or (2). only when the organism finds itself in a hostile environment. The primary, if not sole, evolved raison d'être of first category aldehyde dehydrogenases appears to be to catalyze the biotransformation of a single endobiotic for which they are relatively specific and of which the resultant metabolite is essential to the organism. Most of the human aldehyde dehydrogenases for which the relevant information is available fall into this category. Second category aldehyde dehydrogenases are relatively substrate nonspecific and their evolved raison d'être seems to be to protect the organism from potentially harmful xenobiotics, specifically aldehydes or xenobiotics that give rise to aldehydes, by catalyzing their detoxification. Thus, the lack of a fully functional first category aldehyde dehydrogenase results in a gross pathological phenotype in the absence of any insult, whereas the lack of a functional second category aldehyde dehydrogenase is ordinarily of no consequence with respect to gross phenotype, but is of consequence in that regard when the organism is subjected to a relevant insult.     

Cotinus coggygria Scop.: An overview of its chemical constituents,pharmacological and toxicological potential

The Anacardiaceae Lindl. family comprises of many species which are used in nutrition and in traditional folk medicine for the treatment of several human diseases. Cotinus coggygria Scop. commonly known as “smoke tree”, is a commercial ornamental plant with high medicinal usages, belongs to the family Anacardiaceae. The present review provides a comprehensive report of empirical investigations on important pharmacological activities and phytochemical screening of essential oils and extracts. Relevant information was collected from scientific journals, books, and reports via library and electronic search using Medline, PubMed, Google Scholar, ScienceDirect, Web of Science, and Scopus. The plant has been extensively investigated in a broad range of studies to provide scientific evidence for folklore claims or to find new therapeutic uses. Numerous activities namely antioxidative, antibacterial, antifungal, antiviral, anticancer, antigenotoxic, hepatoprotective and anti-inflammatory have been demonstrated for all parts of these plants by in vivo and in vitro studies. Essential oils and extracts showed various pharmacological and biological properties which make them an effective remedy for various kinds of illnesses. Considering data from the literature, it could be demonstrated that C. coggygria possesses diverse bioactive properties and immense utilization in medicine, health care, cosmetics and as health supplements.     

Antiplatelet pyrazolopyridines derivatives: pharmacological,biochemical and toxicological characterization

Platelet aggregation is one of the main events involved in vascular thrombus formation. Recently, N′-substituted-phenylmethylene-3-methyl-1,6-diphenyl-1H-pyrazolo[3,4-b]pyridine-4-carbohydrazides were described as antiplatelet derivatives. In this work, we explore the properties of these antiplatelet agents through a series of pharmacological, biochemical and toxicological studies. The antiplatelet activity of each derivative was confirmed as 3a, 3b and 3?h significantly inhibited human platelet aggregation induced by arachidonic acid, with no detectable effect on clotting factors or healthy erythrocytes. Importantly, mice treated with derivative 3a showed a higher survival rate at an in vivo model of pulmonary thromboembolism with a lower bleeding risk in comparison to aspirin. The in silico studies pointed a series of structural parameters related to thromboxane synthase (TXS) inhibition by 3a, which was confirmed by tracking plasma levels of PGE₂ and TXB₂ through an in vitro enzyme immunoassay. Derivative 3a showed selective TXS inhibition allied with low bleeding risk and increased animal survival, revealing the derivative as a promising candidate for treatment of cardiovascular diseases.     

Micropropagation and encapsulation of medicinally important Chonemorpha grandiflora

Summary This study describes a protocol for in vitro propagation of Chonemorpha grandiflora (Roth) S.M. & M.R. Almeida (Apocynaceae) through axillary bud proliferation and rooting. For shoot induction, the combination of 13.3 μM N ⁶-benzyladenine (BA) and 2.46 μM indole-3-butyric acid (IBA) in Murashige and Skoog (MS) medium was better than other growth regulators. Liquid medium was superior over solid medium for root formation and growth. IBA was more effective than other auxins for root induction. Addition of silver nitrate in the presence of IBA significantly increased the number, length, and branching of roots. Shoot tips encapsulated in medium containing 0.49 μM IBA and 11.7 μM silver nitrate exhibited 95% conversion to plantlets. This protocol enables the production of 250 plantlets from a single nodal explant within 7 mo. Plantlets showed 90% survival after acclimatization in soil and were morphologically similar to the source plant under field conditions.     

Microbiological and toxicological quality of dried herbs

Aims: The microbiological and toxicological quality of 51 samples of dried herbs (Melissa officinalis, Salvia officinalis, Malva sylvestris, Matricaria chamomilla, Alchemilla vulgaris and Centaurea cyanus) cultivated in family‐managed farms in Molise Region (Italy) was evaluated. Methods and Results: All the samples were analysed by using conventional methods, and for samples preparation, an alternative Washing and Shaking (WaS) protocol was developed to reduce release of antimicrobial compounds. None of the samples were of unsatisfactory quality with respect to aflatoxin B1, and only three samples from Malva sylvestris exceeded the limit of total aflatoxins according to Recommendation 2004/24/EC. The International Commission on Microbiological Specifications for Foods limits for mesophilic bacteria and total coliforms were exceeded in the 29·4 and 3·9% of samples, respectively: 7·8% of samples also exceeded the limit for Escherichia coli established by European Spice Association. When the ‘WaS’ method was used, higher microbial counts were obtained, especially for A. vulgaris, S. officinalis and M. officinalis. Conclusions: Herbs cultivated in family‐managed small agricultural areas showed a good microbiological and toxicological quality, irrespectively of preliminary washing or selection procedures. Significance and Impact of the Study: Herb matrices may contain antimicrobial activity which should be considered when applying the conventional microbiological methods for sample preparation. Alternative preparation protocols may have advantages to reduce antimicrobial effects and should be further evaluated.     

Regulation of PUFA metabolism: pharmacological and toxicological aspects

Levels of the long-chain polyunsaturated fatty acids (LCP) of the n-6 and n-3 series in animal plasma and cells are directly or indirectly dependent upon the intakes of either their precursors, the short-chain polyunsaturated fatty acids (SCP), linoleic (LA, 18:2 n-6) and alpha linolenic acid (ALA, 18:3 n-3), respectively, and/or of the preformed products (arachidonic, 20:4 n-6) and eicosapentaenoic acid (EPA, 20:5 n-3) and docosahexaenoic acid (DHA, 22:6 n-3). We report here that pharmacological agents and cytotoxic compounds significantly affect the production of LCP from SCP in cultured cells. Using labelled substrates and radio HPLC separations, we observed that the potent hypocholesterolemic agent, simvastatin, activates the formation of AA from LA, mainly acting at the delta5 desaturation step, and increases also the mRNA levels, in cultured monocytic cells (THP-1). Elevation of AA occurs also in plasma lipids of hyperlipemic patients treated with statins (but not with fibrates). Conversely, oxysterols (mainly 7-beta-oxysterol), which are detected in circulating lipoproteins of rabbits on a hypercholesterolemic diet, potently inhibit the synthesis of AA from LA in hepatocytic cell lines (Hep-G2). At the same time plasma levels o AA are reduced vs controls, in spite of an identical intake of LA. Finally, on the basis of previous work showing reduced levels of LCP, mainly DHA, in the milk of cigarette-smoking mothers, we have observed that the incubation of human mammary gland cells with sera exposed to cigarette smoke results in marked inhibition of the production of DHA from ALA. The products in smoke responsible for this effect, are being identified through mass spectrometric techniques. In conclusion, pharmacological agents and toxic compounds, such as oxysterols and smoke products affect key steps in the synthesis of the LCP, major bioregulators in mammalian cells.     

An efficient micropropagation system for Tylophora indica: an endangered, medicinally important plant

An efficient protocol is described for the rapid in vitro multiplication of an endangered medicinal plant, Tylophora indica (Burm. f.) Merrill, via enhanced axillary bud proliferation from nodal explants collected from young shoots of a two-year-old plant. The physiological effects of growth regulators [6-benzyladenine (BA), kinetin (Kin) thidiazuron (TDZ), indole-3-acetic acid (IAA), indole-3-butyric acid (IBA) or α-naphthalene acetic acid (NAA)], ascorbic acid (AA), different strengths of Murashige and Skoog (MS) medium and various pH levels on in vitro morphogenesis were investigated. The highest number (8.6 ± 0.71) of shoots and the maximum average shoot length (5.2 ± 0.31 cm) were recorded on MS medium supplemented with 2.5 μM BA, 0.5 μM NAA and 100 mg/l AA at pH 5.8. Rooting was best achieved on half-strength MS medium augmented with 0.5 μM IBA. The plantlets regenerated in vitro with well-developed shoot and roots were successfully established in pots containing garden soil and grown in a greenhouse with a 90% survival rate. The regenerated plants did not show any immediate detectable phenotypic variation. The described method can be successfully employed for large-scale multiplication and long-term in vitro conservation of T. indica.     

Antimicrobial, antioxidant, and anti-inflammatory activities of essential oils from five selected herbs

Eucalyptus bridgesiana, Cymbopogon martinii, Thymus vulgaris, Lindernia anagallis, and Pelargonium fragrans are five species of herbs used in Asia. Their essential oils were analyzed by GC-MS, and a total of 36 components were detected. The results of our study indicated that, except for the essential oil of P. fragrans, all of the essential oils demonstrated obvious antimicrobial activity against a broad range of microorganisms. The C. martinii essential oil, which is rich in geraniol, was the most effective antimicrobial additive. All of the essential oils demonstrated antioxidant activities on 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay, β-carotene/linoleic acid assay, and nitric oxide radical scavenging assay. Furthermore, the T. vulgaris essential oil, which possesses plentiful thymol, exhibited the highest antioxidant activity. For P. acnes-induced secretion of pro-inflammatory cytokines, the essential oils of P. aeruginosa, C. martinii, and T. vulgaris reduced the TNF-α, IL-1β, and IL-8 secretion levels of THP-1 cells.     

An updated and comprehensive review on the ethnomedicinal uses,phytochemistry, pharmacological activity and toxicological profile of Tinospora crispa (L.) Hook. f. & Thomson

Phytochemistry Reviews - Tinospora crispa (L.) Hook. f. & Thomson (Menispermaceae) is a plant indigenous to Africa and South-East Asia. It is widely used in ethnomedicine to alleviate...     

In vitro study of some medicinally important Mannich bases derived from antitubercular agent

Biologically active Mannich bases with heteroaromatic ring system have been synthesised employing Mannich reaction of isonicotinyl hydrazide with various sulphonamides/secondary amines. They were analysed by elemental analysis and characterized by uv, ir, 1H nmr spectroscopic studies. The Mannich bases were screened for their antibacterial activity against various gram positive and gram negative bacteria and were analyzed statistically. The results have shown that the compounds are quiet active against pathogens under study and were nontoxic.     

Plant regeneration from alginate-encapsulated shoot tips of Phylianthus amarus schum and thonn, a medicinally important plant species

Summary A method was developed for plant regeneration from alginate-encapsulated shoot tips of Phyllanthus amarus. Shoot tips excised from in vitro proliferated shoots were encapsulated in calcium alginate beads. The best gel complexation was achieved using 3% sodium alginate and 75 mM CaCl₂·2H₂O. Maximum percentage response for conversion of encapsulated shoot tips into plantlets was 90% after 5 wk of culture on Murashige and Skoog (MS) medium without plant growth regulator. The regrowth ability of encapsulated shoot tips was affected by the concentration of sodium alginate, storage duration, and the presence or absence of MS nutrients in calcium alginate beads. Plantlets with well-developed shoot and roots were transferred to pots containing an autoclaved mixture of soilrite and peat moss (1∶1). The conversion of encapsulated shoot tips into plantlets also occurred when calcium alginate beads were directly sown in autoclaved soilrite moistened with 1/4-MS salts. Encapsulation of vegetative propagules in calcium alginate beads can be used as an alternative to synthetic seeds derived from somatic embryos.     

Development of polymorphic microsatellite loci in Nothapodytes nimmoniana, a medicinally important tree from the Western Ghats, India

Nothapodytes nimmoniana is a medicinally important tree species that occur in the Western Ghats, a megadiversity hotspot in southern India. Inner stem bark of the tree contains an important anti-cancer alkaloid, camptothecin for which the natural population of the tree is heavily harvested. In this paper, we report the isolation and characterization of eight polymorphic microsatellite loci using enrichment hybridization protocol. Analysis of 36 individuals representing two populations revealed three to 12 alleles per locus. Observed heterozygosity ranged from 0.21 to 0.94 for the two populations. None of the loci tested showed linkage disequilibrium. These markers are invaluable for evaluating the genetic structure and assessing the genetic impacts of harvesting of N. nimmoniana in the Western Ghats to formulate strategies for conservation of the species.     

Syringa microphylla Diels: A comprehensive review of its phytochemical,pharmacological, pharmacokinetic,and toxicological characteristics and an investigation into its potential health benefits

BackgroundSyringa microphylla Diels is a plant in the family Syringa Linn. For hundreds of years, its flowers and leaves have been used as a folk medicine for the treatment of cough, inflammation, colds, sore throat, acute hepatitis, chronic hepatitis, early liver cirrhosis, fatty liver, and oesophageal cancer.PurposeFor the first time, we have comprehensively reviewed information on Syringa microphylla Diels that is not included in the Pharmacopoeia, clarified the pharmacological mechanisms of Syringa microphylla Diels and its active ingredients from a molecular biology perspective, compiled in vivo and in vitro animal experimental data and clinical data, and summarized the toxicology and pharmacokinetics of Syringa microphylla Diels. The progress in toxicology research is expected to provide a theoretical basis for the development of new drugs from Syringa microphylla Diels, a natural source of compounds that are potentially beneficial to human health.MethodsThe PubMed, Google Scholar, China National Knowledge Infrastructure, Web of Science, SciFinder Scholar and Thomson Reuters databases were utilized to conduct a comprehensive search of published literature as of July 2021 to find original literature related to Syringa microphylla Diels and its active ingredients.ResultsTo date, 72 compounds have been isolated and identified from Syringa microphylla Diels, and oleuropein, verbascoside, isoacteoside, echinacoside, forsythoside B, and eleutheroside B are the main active components. These compounds have antioxidant, antibacterial, anti-inflammatory, and neuroprotective effects, and their safety and effectiveness have been demonstrated in long-term traditional applications. Molecular pharmacology experiments have indicated that the active ingredients of Syringa microphylla Diels exert their pharmacological effects in various ways, primarily by reducing oxidative stress damage via Nrf2/ARE pathway regulation, regulating inflammatory factors and inducing apoptosis through the MAPK and NF-κB pathways.ConclusionThis comprehensive review of Syringa microphylla Diels provides new insights into the correlations among molecular mechanisms, the importance of toxicology and pharmacokinetics, and potential ways to address the limitations of current research. As Syringa microphylla Diels is a natural low-toxicity botanical medicine, it is worthy of development and utilization and is an excellent choice for treating various diseases.     

Green chemistry appended synthesis,metabolic stability and pharmacokinetic assessment of medicinally important chromene dihydropyrimidinones

A green chemistry approach has been developed for the synthesis of chromene dihydropyrimidinone (CDHPM) using recyclable Fe/Al pillared clay catalyst. Pharmacokinetic parameters like aqueous solubility, lipophilicity, P-glycoprotein (P-gp) ATPase activity, permeability, plasma protein binding, red blood cell (RBC) partitioning, metabolic stability in liver microsomes and in silico computations have been studied for the most potent anticancer chromene dihydropyrimidinone hybrid 1. This compound exhibited low solubility, optimum lipophilicity, no P-gp inhibitory activity, intermediate permeability, high plasma protein binding, low RBC partitioning, acceptable metabolic stability in rat liver microsomes (RLM) as well as human liver microsomes (HLM) with transitional hepatic extraction ratio.     

Rapid in vitro multiplication of Drosera indica L.: a vulnerable, medicinally important insectivorous plant

An efficient protocol is described for rapid in vitro multiplication of the vulnerable medicinal herb Drosera indica L. by enhanced axillary bud proliferation from shoot tips as explants. In order to standardize in vitro multiplication of D. indica, the effects of different strengths of Murashige and Skoog (MS) medium (1/4, 1/3, 1/2 and full strength), different percentages of sucrose (1, 2 and 3%), various pH (3.7, 4.7, 5.7 and 6.7) and MS basal medium fortified with different concentrations of zeatin (Z), kinetin (KN) (0.1, 0.5, 1.0 and 2.0 mg/l) and 6-benzylaminopurine (BA) (0.01, 0.05 and 0.1 mg/l) were tried. Multiple shoot production was independent of different strengths of MS, various percentages of sucrose and also when pH was altered. Although the number of multiple shoots developed on MS medium supplemented with Z (0.1, 0.5, 1.0 and 2.0 mg/l), KN (0.5 and 1.0 mg/l) and BA (0.1 mg/l) separately was high, the maximum number was observed on MS fortified with Z (0.5 mg/l) and KN (0.5 mg/l), respectively, which clearly depicts that there is not much difference comparatively with a variation in hormone concentration in case of Z. High cytokinin concentrations resulted in retardation of shoot growth. Rooting was best achieved on MS basal medium. This protocol could be useful for production of large biomass within 6 weeks for plumbagin bioprospection and long term in vitro conservation.     

Vochysiaceae: secondary metabolites, ethnopharmacology and pharmacological potential

Many Vochysiaceae species, in special Qualea and Vochysia genera, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activity and the secondary metabolites reported so far for Vochysiaceae. The chemical constituents of this family include triterpenoids, steroids and polyphenols like flavonoids and ellagic acid derivatives.     

Chrysobalanaceae: secondary metabolites, ethnopharmacology and pharmacological potential

Many Chrysobalanaceae species, in special Licania and Parinari, are widely used in folk medicine to treat several diseases. This review describes some aspects of their ethnopharmacology potential, biological activities and the secondary metabolites reported so far for Chrysobalanaceae. The chemical constituents of this family include triterpenoids, diterpenoids, steroids and phenylpropanoids like flavonoids as well as chromones derivatives.     

Screening of selected ethnomedicinal plants from South Africa for larvicidal activity against the mosquito Anopheles arabiensis

ABSTRACT: BACKGROUND: This study was initiated to establish whether any South African ethnomedicinal plants (indigenous or exotic), that have been reported to be used traditionally to repel or kill mosquitoes, exhibit effective mosquito larvicidal properties. METHODS: Extracts of a selection of plant taxa sourced in South Africa were tested for larvicidal properties in an applicable assay. Thirty 3rd instar Anopheles arabiensis larvae were exposed to various extract types (dichloromethane, dichloromethane/methanol) (1:1), methanol and purified water) of each species investigated. Mortality was evaluated relative to the positive control Temephos (Mostop; Agrivo), an effective emulsifiable concentrate larvicide. RESULTS: Preliminary screening of crude extracts revealed substantial variation in toxicity with 24 of the 381 samples displaying 100% larval mortality within the seven day exposure period. Four of the high activity plants were selected and subjected to bioassay guided fractionation. The results of the testing of the fractions generated identified one fraction of the plant Toddalia asiatica as being very potent against the An. arabiensis larvae. CONCLUSION: The present study has successfully identified a plant with superior larvicidal activity at both the crude and semi pure fractions generated through bio-assay guided fractionation. These results have initiated further research into isolating the active compound and developing a malaria vector control tool.     

Regeneration of plants from alginate-encapsulated shoot tips of Withania somnifera (L.) Dunal, a medicinally important plant species

A protocol was developed for plant regeneration from encapsulated shoot tips collected from in vitro proliferated shoots of Withania somnifera. The best gel composition was achieved using 3% sodium alginate and 75 mM CaCl2.2H2O. The maximum percentage response (87%) for conversion of encapsulated shoot tips into plantlets was achieved on MS medium supplemented with 0.5 mg/l IBA after 5 weeks of culture. The conversion of encapsulated shoot tips into plantlets also occurred when calcium alginate beads having entrapped propagules were directly sown in autoclaved soilrite moistened with 14-MS salts.