ABSTRACT
Expression of concern for 'The anti-Alzheimer potential of Tamarindus indica: an in vivo investigation supported by in vitro and in silico approaches' by Abeer H. Elmaidomy et al., RSC Adv., 2022, 12, 11769-11785, https://doi.org/10.1039/D2RA01340A.
ABSTRACT
Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of Faucaria tuberculosa. Phytochemical investigation of F. tuberculosa extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2â1',4â2')-phloroglucinol (4). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2â1',4â2') phloroglucinol (4) and phloroglucinol (1) for their remarkable antioxidant activity, while isorhamnetin 3-O-rutinoside (3) and 3,5-dihydroxyphenyl ß-D-glucopyranoside (2) achieved the most potent inhibitory activity against tyrosinase (IC50 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC50 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC50 = 65.21 ± 0.47 µM) and luteolin, (IC50 = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds (3 and 2) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.
Subject(s)
Catechin , Plant Extracts , Plant Extracts/chemistry , Antioxidants/chemistry , Molecular Docking Simulation , Phytochemicals/pharmacology , PhloroglucinolABSTRACT
Livistona is a genus of family Arecaceae and widely grown in tropical areas. The phytochemical analysis of the leaves and fruits of two Livistona species, L. chinensis and L. australis were carried out using UPLC/MS and determination of the total phenolic and total flavonoid contents, in addition to the isolation and identification of five phenolic compounds and one fatty acid from L. australis fruits. The total phenolic compounds varied from 19.72 to 78.87 mg GAE g-1 dry plant, while the total flavonoid contents were in the range of 4.82-17.75 mg RE g-1 dry plant. The UPLC/MS analysis of the two species led to the characterization of forty-four metabolites belonging mainly to the different classes of flavonoids and phenolic acids, while the compounds isolated from L. australis fruits were identified as gallic acid, vanillic acid, protocatechuic acid, hyperoside, quercetin 3-O-α-d-arabinopyranoside and dodecanoic acid. The in vitro biological evaluation of L. australis leaves and fruits were estimated as anticholinesterase, telomerase reverse transcriptase (TERT) potentiation and anti-diabetic through measuring the capacity of the extracts to inhibit dipeptidyl peptidase (DPP-IV). The results revealed that the leaves showed remarkable anticholinesterase and antidiabetic activity compared to fruits with IC50 values of 65.55 ± 3.75 ng mL-1 and 90.8 ± 4.48 ng mL-1, respectively. In the TERT enzyme assay, the leaves extract triggered a 1.49-fold increase in telomerase activity. This work showed that the Livistona species are a good source for flavonoids and phenolics, which play an important role in anti-aging and the treatment of chronic diseases, such as diabetes and Alzheimer's.
ABSTRACT
Hepatocellular carcinoma (HCC) is one of the most fatal cancers around the world and remain asymptomatic in early stage. An alcoholic extract prepared from leaves of Tropaeolum majus L. (Tropaeolaceae) was assessed for its potential activity against diethylnitrosamine-induced liver carcinoma in vivo. Oral administration of the extract significantly decreased the inflammatory marker translation NF-kB and supressed HCC progression in combination with 0.5 Gy gamma radiation via EGF-HER-2 pathway. Histopathological and immunohistopathological features also showed the recovery of a hepatic architecture. Immunohistochemical study showed the T. majus and LDR enhancement effect on proapoptotic markers (caspase-3 and Bax) and inhibition of anti-apoptotic factor (BCl2). HPLC-DAD-MSn analysis of the extract revealed the annotation of twelve compounds. T. majus could mediate a defensive influence against diethylnitrosamine-induced hepatocarcinogenesis and serve as a respectable option in amelioration of the hepatocellular carcinoma development in combination with low dose of gamma radiation.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Tropaeolum , Tropaeolum/chemistry , Tropaeolum/metabolism , Carcinoma, Hepatocellular/chemically induced , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Plant Extracts/chemistry , Diethylnitrosamine/metabolism , Diethylnitrosamine/pharmacology , Gamma Rays , Liver Neoplasms/chemically induced , Liver Neoplasms/drug therapy , Signal Transduction , Liver , ErbB Receptors/metabolism , ApoptosisABSTRACT
BACKGROUND: Cryptosporidiosis is a crucial zoonotic global health concern which can be treated by alternative medicinal plants extracts. AIM OF THE STUDY: The study was carried out to assess the therapeutic efficacy of Citrus sinensis peel ethanolic extract on Cryptosporidium-infected mice. METHODS: Two doses of Citrus sinensis extract; high dose (30 mg/kg) and low dose (15 mg/kg) were investigated compared to the common commercial drug nitazoxanide (NTZ). Assessment of the extract was carried out by calculating oocysts count in fecal samples, in addition to histopathological and electron microscopic examination of intestinal mucosa.. RESULTS: There was a statistically significant reduction in the percentage of oocyst shedding more in high dose than low dose Citrus-treated mice group till negligible numbers of oocysts were found at day 22nd post infection. Histopathologically, the intestinal tissues from high dose Citrus-treated group showed improvement of the pathological changes, the villi retained their normal appearance with minimal inflammatory cells in comparison to infected control mice groups. Also, ultra-structurally, the high dose Citrus-treated mice showed few Cryptosporidium trophozoites, while moderate number of parasitic stages and mucous in the low dose Citrus-treated mice, and large numbers of parasitic stages with sever mucous in the control infected non-treated mice epithelium. CONCLUSION: Our study established for the first time that Citrus sinensis is a promising natural candidate that could be efficiently used for developing of new anti-cryptospordial drugs.
Subject(s)
Citrus sinensis , Cryptosporidiosis , Cryptosporidium , Mice , Animals , Cryptosporidiosis/parasitology , Oocysts , Feces/parasitologyABSTRACT
In late December 2019, a pandemic coronavirus disease 2019 (COVID-19) emerged in Wuhan, China and spread all over the globe. One of the promising therapeutic techniques of viral infection is to search for enzyme inhibitors among natural phytochemicals using molecular docking to obtain leads with the least side effects. The COVID-19 virus main protease (Mpro) is considered as an attractive target due to its pivotal role in controlling viral transcription and replication. Metabolic profiling of the crude extract of Livistona decipiens Becc. (Arecaceae) leaves and fruit dereplicated twelve metabolites using LC-HRESIMS. Molecular docking simulation and in silico ADME profiling of these annotated compounds proposed that tricin is a promising lead against COVID-19 virus Mpro. The alcoholic extract was shown to inhibit SARS-CoV-2 through in vitro culture and RT-PCR testing with EC50 = 0.122 and 1.53 µg mL-1 for leaves and fruit extracts, respectively, when compared with that of the FDA-approved anti-COVID-19 remdesivir (0.002 µg mL-1). Preliminary steps were also performed including the 3CL-protease inhibition assay and cytotoxicity study. It is worthwhile to find a cheap, safe, natural source for promising anti-SARS-CoV-2 agents that can be further tested in vivo against the COVID-19 virus Mpro. This study provides scientific basis for demonstrating beneficial effects of L. decipiens application on human health during the corona pandemic.
ABSTRACT
Tamarindus indica Linn. (Tamarind, F. Fabaceae) is one of the most widely consumed fruits in the world. A crude extract and different fractions of T. indica (using n-hexane, dichloromethane, ethyl acetate, and n-butanol) were evaluated in vitro with respect to their DPPH scavenging and AchE inhibition activities. The results showed that the dichloromethane and ethyl acetate fractions showed the highest antioxidant activities, with 84.78 and 86.96% DPPH scavenging at 0.10 µg mL-1. The n-hexane, dichloromethane, and ethyl acetate fractions inhibited AchE activity in a dose-dependent manner, and the n-hexane fraction showed the highest inhibition at 20 µg mL-1. The results were confirmed by using n-hexane, dichloromethane, and ethyl acetate fractions in vivo to regress the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. Phytochemical investigations of those three fractions afforded two new diphenyl ether derivative compounds 1-2, along with five known ones (3-7). The structures of the isolated compounds were confirmed via 1D and 2D NMR and HRESIMS analyses. The isolated compounds were subjected to extensive in silico-based investigations to putatively highlight the most probable compounds responsible for the anti-Alzheimer activity of T. indica. Inverse docking studies followed by molecular dynamics simulation (MDS) and binding free energy (ΔG) investigations suggested that both compounds 1 and 2 could be promising AchE inhibitors. The results presented in this study may provide potential dietary supplements for the management of Alzheimer's disease.
ABSTRACT
Fumaria parviflora Lam. is a rare herbaceous annual plant, with a well-known richness of isoquinoline alkaloids. It is threaten due to expansion on construction in the Mediterranean coastal region. We established callus culture protocol aiming at in vitro conservation of this plant. Murashige and Skoog medium fortified with a combination of 0.5 mg/l 1-naphthaleneacetic acid (NAA) and 1 mg/l 6-benzylaminopurine (BAP) showed optimal callus initiation. UPLC-MS/MS profiling revealed that calli induced on the tested media were able to produce isoquinoline alkaloids. Eight alkaloids were isolated from aerial parts of the cultivated plant and their cytotoxicity against Human skin fibroblast (HF) and wound healing activity using in vitro scratch assay were determined. Structural similarity between the isolated alkaloids enabled structure activity relationship (SAR) study. Sanguinarine displayed the potent activity compared to the other alkaloids. Iminium ion and methylenedioxy potentiated the activity.
Subject(s)
Alkaloids , Fumaria , Alkaloids/chemistry , Alkaloids/pharmacology , Chromatography, Liquid , Culture Media , Fumaria/chemistry , Humans , Isoquinolines/chemistry , Isoquinolines/pharmacology , Tandem Mass Spectrometry , Wound HealingABSTRACT
Legume sprouts are a fresh nutritive source of phytochemicals of increasing attention worldwide owing to their many health benefits. Nuclear magnetic resonance (NMR) was utilized for the metabolite fingerprinting of 4 major legume sprouts, belonging to family Fabaceae, to be exploited for quality control purposes. Thirty-two metabolites were identified belonging to different classes, i.e., fatty acids, sugars, amino acids, nucleobases, organic acids, sterols, alkaloids, and isoflavonoids. Quantitative NMR was employed for assessing the major identified metabolite levels and multivariate data analysis was utilized to assess metabolome heterogeneity among sprout samples. Isoflavones were detected exclusively in Cicer sprouts, whereas Trigonella was characterized by 4-hydroxyisoleucine. Vicia sprouts were distinguished from other legume sprouts by the presence of L-Dopa versus acetate abundance in Lens. A common alkaloid in all sprouts was trigonelline, detected at 8-25 µg/mg, suggesting its potential role in legume seeds' germination. Trigonelline was found at highest levels in Trigonella sprouts. The aromatic NMR region data (δ 11.0-5.0 ppm) provided a better classification power than the full range (δ 11.0-0.0 ppm) as sprout variations mostly originated from secondary metabolites, which can serve as chemotaxonomic markers.
Subject(s)
Cheminformatics , Fabaceae/chemistry , Fabaceae/metabolism , Magnetic Resonance Spectroscopy , MetabolomicsABSTRACT
Several studies are now underway as a worldwide response for the containment of the COVID-19 outbreak; unfortunately, none of them have resulted in an effective treatment. Salvadora persica L. (Salvadoraceae), commonly known as meswak, is one of the popular plants used by Muslims as an oral hygiene tool. It is documented that the meswak possesses antiviral activity, but no report discusses its use for coronavirus treatment. Herein, a mixture of 11 flavonoids prepared from the aqueous plant extract and its liposomal formulation were shown to inhibit SARS-CoV-2 in an in vitro A549 cell line culture and a RT-PCR test almost as well as the FDA-approved anti-COVID-19 agent, remdesivir. Encapsulation within liposomal formulation led to a highly significant increase in the percentage of inhibition of viral replication from 38.09 ± 0.83 to 85.56 ± 1.12% in a flavonoid mixture and its liposomal preparation, respectively, and this figure approached that obtained for remdesivir (91.20 ± 1.71%). Preliminary tests were also performed, including a total flavonoid assay, a molecular docking study, a 3CL-protease inhibition assay and a cytotoxicity study. It was worthy to find a cheap, readily available, safe natural source for promising anti-SARS-CoV-2 agents, that leak their phytochemicals into the aqueous saliva during regular use as a brushing agent.
ABSTRACT
[This corrects the article DOI: 10.1039/D0RA01697G.].
ABSTRACT
Silybum marianum (L.) Gaertn. (Asteraceae) was hydroponically cultured using a nutrient film technique system. Silibinin, isosilibinin and silychristin were detected in the fruits of the cultured plants. The effect of salicylic acid on the improvement of flavonolignans production by the fruits of the hydroponically cultured S. marianum was investigated. Salicylic acid was added to the nutrient solution at different concentrations (100, 200 and 400 µM) and the mature fruits of the plant were collected five days after elicitor addition. The fruits were then analyzed for their total flavonolignans contents and individual components using quantitative proton nuclear magnetic resonance spectroscopy (qHNMR) and high-performance liquid chromatography (HPLC). The results showed that elicitation with salicylic acid at 200 µM for five days increased production of total flavonolignans (1.7-fold by qHNMR and 1.6-fold by HPLC) higher than the control cultures and (1.4-fold by qHNMR and 1.1-fold by HPLC) higher than the cultivated plants. Silychristin was the major flavonolignan produced by the cultured plant. Elicitation by 200 µM salicylic acid increased silychristin production (1.6-fold by qHNMR and HPLC) higher than the control cultures and (1.3-fold by qHNMR and 1.0-fold by HPLC) higher than the cultivated plants. The present study provides a chance to improve secondary metabolite yield, serves as a useful tool for studying the biosynthesis of these medicinally valuable compounds and its regulation in plant and spots more light on hydroponic system as an important agricultural technique.
ABSTRACT
In December 2019, an outbreak of coronavirus disease 2019 (COVID-19) commenced in Wuhan, China and affected around 210 countries and territories in a matter of weeks. It has a phylogenetic similarity to SARS-CoV and it was named coronavirus 2 (SARS-CoV-2) and caused severe acute respiratory syndrome that could lead to death. One of the promising therapeutic strategies for virus infection is the search for enzyme inhibitors among natural compounds using molecular docking in order to obtain products with minimal side effects. COVID-19 virus main protease plays a vital role in mediating viral transcription and replication, introducing it as an attractive antiviral agent target. Metabolic profiling of the aqueous extract of Salvadora persica L. (Salvadoraceae) aerial parts dereplicated eleven known flavonol glycosides using LC-HRESIMS. All the annotated flavonoids exhibited significant binding stability at the N3 binding site to different degrees, except isorhamnetin-3-O-ß-d-glucopyranoside, when compared with the currently used COVID-19 main protease inhibitor, darunavir. Structural similarity between the identified flavonoids enabled the study of the relationship between their structure and interactions with the receptor in the N3 binding site of the COVID-19 main protease. The results indicate that the basic flavonol nucleus possesses activity itself. Moreover, the presence of a rutinose moiety at the 3 position of ring C and absence of an O-methyl group in ring B of the flavonol structure could increase the binding stability. This study provides a scientific basis for the health benefits of the regular use of S. persica as it leaches bioactive flavonoids in the aqueous saliva.
ABSTRACT
Quantitative correlations between the contents of the flavonolignans silychristin A and silybins A/B provide biosynthetic clues that support a pathway in which one mesomeric form of a taxifolin radical is undergoing an oxidative coupling with a coniferyl alcohol radical. The flavonolignan content and patterns reported in the literature for 53 samples, representing populations of the Silybum marianum plant growing in different parts of the world, were subject to a meta-analysis. Linear regression analyses were carried out on these data sets, and a mathematical model was derived that predicts the content of silychristin A relative to the metabolomic pattern of its congeners. The validity of the model was verified by applying it to test samples. This approach could potentially become a tool to enhance the understanding of both the relative composition of the silymarin complex and the biosynthetic pathways that underlie its formation.
Subject(s)
Biosynthetic Pathways , Regression Analysis , Silybin/analysis , Silybum marianum/chemistry , Silymarin/analysis , Antioxidants/metabolism , Biological Products , Flavonoids/metabolism , Models, Theoretical , Quercetin/analogs & derivatives , Quercetin/chemistryABSTRACT
Silymarin prepared from the fruits of Silybum marianum (L.) Gaertn. (Asteraceae) has long been used for the treatment of liver disorders. This study was carried out to evaluate the protective effect of the fruit extract of white-flowered S. marianum variety albiflorum Eig. (WSE) against paracetamol-induced liver toxicity in rats. Silyhermin, isosilandrins A/B were identified as the major flavonolignans in WSE. Cytotoxic activities of WSE and isolated flavonolignans compared to silymarin were carried out using sulforhodamine B assay. WSE, silyhermin and isosilandrins had no obvious harmful effect on normal human cell line compared to silymarin with IC50 values 78.95, 84.34, 72.14 and 16.83 µg/ml, respectively. The hepatoprotective activity of WSE at dose 50 mg/kg was comparable to silymarin (100 mg/kg). These data were supplemented with histopathological studies on liver sections. The hepatoprotective effects of WSE on oxidative stress induced by administration of paracetamol are probably associated with its antioxidant properties.
Subject(s)
Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Plant Extracts/pharmacology , Protective Agents/pharmacology , Silybum marianum/chemistry , Acetaminophen/toxicity , Animals , Cell Line , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/pathology , Egypt , Fruit/chemistry , Humans , Lignans/analysis , Lignans/chemistry , Lignans/pharmacology , Male , Oxidative Stress/drug effects , Plant Extracts/chemistry , Plants, Medicinal/chemistry , Protective Agents/chemistry , Rats, Wistar , Silymarin/toxicityABSTRACT
Bioassay-guided fractionation and chemical investigation of Colvillea racemosa stems led to identification of two new α, ß-dihydroxydihydrochalcones, colveol A (1) and colveol B (2) along with fifteen known compounds. The structures were elucidated via interpretation of spectroscopic data. The absolute configurations of the dihydrochalcones 1 and 2 were assigned by a combination of chemical modification and electronic circular dichroism data. The isolated compounds were evaluated for their inhibition activity toward recombinant human monoamine oxidases (rhMAO-A and -B). Compound 1 demonstrated preferential inhibition against hMAO-A isoenzyme (IC50 0.62µM, SIA/B 0.02) while S-naringenin (13) and isoliquiritigein (15) demonstrated preferential hMAO-B inhibition (IC50 0.27 and 0.51µM, SIA/B 31.77 and 44.69, respectively). Fisetin (11) showed inhibition against hMAO-A with IC50 value of 4.62µM and no inhibitory activity toward hMAO-B up to 100µM. Molecular docking studies for the most active compounds were conducted to demonstrate the putative binding modes. It suggested that 1 interacts with Gln215, Ala111, Phe352, and Phe208 amino acid residues which have a role in the orientation and stabilization of the inhibitor binding to hMAO-A, while S-naringenin (13) occupies both entrance and substrate cavities and interacts with Tyr326, a critical residue in inhibitor recognition in hMAO-B.
Subject(s)
Chalcones/isolation & purification , Fabaceae/chemistry , Monoamine Oxidase Inhibitors/isolation & purification , Humans , Isoenzymes/antagonists & inhibitors , Molecular Docking Simulation , Molecular Structure , Plant Stems/chemistryABSTRACT
Flavonolignans constitute an important class of plant secondary metabolites formed by oxidative coupling of one flavonoid and one phenylpropanoid moiety. The standardized flavonolignan-rich extract prepared from the fruits of Silybum marianum is known as silymarin and has long been used medicinally, prominently as an antihepatotoxic and as a chemopreventive agent. Principal component analysis of the variation in flavonolignan content in S. marianum samples collected from different locations in Egypt revealed biosynthetic relationships between the flavonolignans. Silybin A, silybin B, and silychristin are positively correlated as are silydianin, isosilychristin, and isosilybin B. The detection of silyamandin in the extracts of S. marianum correlates with isosilychristin and silydianin content. The positive correlation between silydianin, isosilychristin, and silyamandin was demonstrated using quantitative 1H nuclear magnetic resonance spectroscopy (qHNMR). These correlations can be interpreted as evidence for the involvement of a flavonoid radical in the biosynthesis of the flavonolignans in S. marianum. The predominance of silybins A & B over isosilybin A & B in the silybin-rich samples is discussed in light of the relative stabilities of their respective radical flavonoid biosynthetic intermediates.
Subject(s)
Flavonolignans/biosynthesis , Flavonolignans/chemistry , Silybum marianum/chemistry , Silymarin/chemistry , Egypt , Fruit/chemistry , Molecular Structure , Secondary Metabolism , Silybin , Silymarin/analogs & derivativesABSTRACT
CONTEXT: Eruca sativa Mill. (Brassicaceae), commonly known as rocket salad, is a popular leafy-green vegetable with many health benefits. OBJECTIVE: To evaluate the antidiabetic activities of this plant in major insulin-responsive tissues. MATERIALS AND METHODS: Five E. sativa leaf extracts of varying polarity were prepared (aqueous extract, 70% and 95% ethanol extracts, the n-hexane-soluble fraction of the 95% ethanol extract (ES3) and the defatted 95% ethanol extract). Eruca sativa extracts were investigated through a variety of cell-based in vitro bioassays for antidiabetic activities in C2C12 skeletal muscle cells, H4IIE hepatocytes and 3T3-L1 adipocytes. Guided by the results of these bioassays, ES3 was fractionated into the saponifiable (SM) and the unspaonifiable (USM) fractions. Glucose uptake was measured using [3H]-deoxy-glucose, while the effects on hepatic glucose-6-phosphatase (G6Pase) and adipogenesis were assessed using Wako AutoKit Glucose and AdipoRed assays, respectively. RESULTS: ES3 and its SM fraction significantly stimulated glucose uptake with EC50 values of 8.0 and 5.8 µg/mL, respectively. Both extracts significantly inhibited G6Pase activity (IC50 values of 4.8 and 9.3 µg/mL, respectively). Moreover, ES3 and SM showed significant adipogenic activities with EC50 of 4.3 and 6.1 µg/mL, respectively. Fatty acid content of SM was identified by GC-MS. trans-Vaccenic and palmitoleic acids were the major unsaturated fatty acids, while palmitic and azelaic acids were the main saturated fatty acids. DISCUSSION AND CONCLUSION: These findings indicate that ES3 and its fatty acid-rich fraction exhibit antidiabetic activities in insulin-responsive cell lines and may hence prove useful for the treatment of type 2 diabetes.
Subject(s)
Adipogenesis/drug effects , Fatty Acids/pharmacology , Hepatocytes/drug effects , Hypoglycemic Agents/pharmacology , Muscle, Skeletal/drug effects , Plant Extracts/pharmacology , 3T3-L1 Cells , Animals , Brassicaceae/chemistry , Cells, Cultured , Gas Chromatography-Mass Spectrometry , Glucose-6-Phosphatase/antagonists & inhibitors , Mice , Plant Leaves/chemistryABSTRACT
Cordia boissieri A. DC. (Boraginaceae) is traditionally used as an herbal remedy for diabetes by Hispanic women in Southwestern USA. A recent investigation showed the significant protective effect of ethyl acetate extract against metabolic syndrome (MS). However, the corresponding active principles responsible for this effect and relations between their structure and biological actions remain unclear. Thus, ethyl acetate extract was subjected to column chromatography, which yielded seven compounds identified on the basis of spectroscopic data as rutin, hesperidin, kaempferol-3-O-ß-d-glucopyranoside, rosmarinic acid, ß-sitosterol-3-O-ß-d-glucopyranoside, quercetin, and kaempferol. The isolated compounds (5 mg/kg/day) were tested in a fructose enriched-diet rat model using metformin as a standard drug. Blood samples were withdrawn for estimation of MS-associated biomarkers and liver samples were subjected to histopathological and immunohistochemical examination. The isolated compounds impaired most of the changes associated with MS as evidenced by improved insulin sensitivity, glucose tolerance, kidney function, lipid profiles and reduced oxidative stress and inflammation by different degrees. It is worth noting that quercetin and kaempferol showed the most potent effect. Structure-activity relationship study revealed that the presence of 2,3-double bond in ring C and ortho-hydroxylation in ring B increases the flavonoids activity while glycosylation or methylation decreased this activity.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Cordia/chemistry , Hypoglycemic Agents/pharmacology , Kaempferols/pharmacology , Metabolic Syndrome/drug therapy , Quercetin/pharmacology , Acetates/chemistry , Animals , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Flavonols/isolation & purification , Flavonols/pharmacology , Food, Formulated/adverse effects , Fructose/adverse effects , Hypoglycemic Agents/isolation & purification , Kaempferols/isolation & purification , Male , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , Metabolic Syndrome/pathology , Oxidative Stress/drug effects , Plant Extracts/chemistry , Plant Leaves/chemistry , Quercetin/isolation & purification , Rats , Rats, Wistar , Secondary Metabolism , Solvents/chemistry , Structure-Activity RelationshipABSTRACT
BACKGROUND: Calligonum polygonoides L. subsp. comosum (L'Hér.) Sosk. is a plant species belonging to family Polygonaceae. Susceptibility to threaten, presence of various chemical constituents, and many medicinal effects reported for this plant in addition to rareness of in vitro culture studies have fuelled the need for its micropropagation and phytochemical investigations of the produced cultures. OBJECTIVES: To employ in vitro culture technique for ex situ conservation of C. polygonoides, using the fruit as an explant; establish callus and cell suspension cultures from in vitro germinated plantlets; investigate the production of phenolics through callus, redifferentiated shoot, and cell suspension cultures; attempt to enhance cell capacity to accumulate phenolics using salicylic acid and yeast extract and provide a brief demonstration of biosynthetic pathway leading to phenolic production. MATERIALS AND METHODS: Modified Murashige and Skoog media supplemented with growth hormones such as kinetin, 1-naphthaleneacetic acid, 6-benzylaminopurine, and indole-3-acetic acid were used to establish callus, redifferentiated shoots, and cell suspension cultures. Elicitation of cell suspension culture was performed using salicylic acid and yeast extracts. A reversed phase-high performance liquid chromatography method for determination of phenolic content in the aforementioned cultures was developed. RESULTS: The unorganized callus and cell suspension cultures contained fewer amounts of phenolic compounds than redifferentiated shoots. Elicitation produced massive quantitative reprogramming of phenolic content. CONCLUSION: The present study offers an alternative and renewable source for this valuable natural plant, provide a chance to improve secondary metabolite yield and serve as a useful tool for studying the biosynthesis of these compounds and its regulation in plant cells. SUMMARY: In vitro culture techniques provided a strategy for ex situ conservation of the endangered C. polygonoides.Unorganized callus and cell suspension cultures accumulated less phenolic content than re-differentiated shoots.Elicitation produced massive quantitative reprogramming of phenolic content.Phenolic biosynthesis was discussed briefly. Abbreviation used: H2O2: Hydrogen peroxide, Kin: Kinetin, NAA: Naphthaleneacetic acid, BAP: 6-benzylaminopurine, IAA: Indole-3-acetic acid, HPLC: High-performance liquid chromatography.