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... The literature survey assembled previously identified active compounds from P.emblica fruits (Liu et al., 2009;Yang and Liu, 2014;Yang et al., 2020). The collected compounds' information and drug resemblance properties were extracted and calculated using PubChem (http s://pubchem.ncbi.nlm.nih.gov/) and SWISSADME (http://www.swiss ...
Background
: Phyllanthus emblica L. fruits (PEf) are thought to be a good source of natural antidiabetic compounds. Nevertheless, the bioactive ingredients and molecular mechanisms of its type 2 diabetes mellitus (T2DM) properties have yet to be established. Here, we implemented a network pharmacology protocol to ascertain its essential compound and mechanisms of action over T2DM.
Methods
: PEf's bioactive ingredients were mined through a literature study and filtered by employing Lipinski's rule of five. Besides, genes associated with the screened compounds and T2DM were extracted from public databases. A Venn diagram was utilized for retrieving common genes. Cytoscape was used to plot and portray the interconnected network between compounds and intersecting genes. Finally, molecular docking simulations were performed between key compounds and targets.
Results
: The literature review yielded a total of 57 compounds in PEf, and 38 compounds were filtered based on Lipinski's rule for further investigations. A total of 244 compound-related and 4979 T2DM-targeted genes were extracted, and Venn pinpointed 183 commons among them. Gene set enrichment analysis manifested 15 signaling pathways which were strongly correlated with the mechanism of PEf against T2DM, with the pivotal mechanism being the diminution of oxidative stress, vascular calcification, and the augmentation of superoxide dismutase 1 expression via the inactivation of a number of co-regulated genes in the AGE-RAGE signaling pathway. In addition, the study of molecular docking affirms that Quercetin is the essential compound in T2DM therapy owing to its greater binding affinity among ten proteins connected with the AGE-RAGE signaling cascade.
Conclusion
: Our study illustrates the pharmacological proof that substantiates the PEf therapeutic effectiveness over T2DM and discovers largely potent PEf chemicals and mechanisms of action against T2DM. Overall, Quercetin might alleviate T2DM by inactivating the AGE-RAGE signaling pathway.
... The presence of various phytoconstituents such as chlorogenic acid (17.43 mg), gallic acid (37.95 mg), quercetin (2.01 mg), and ellagic acid (71.20 mg) was identified per 100 mL of E. officinalis fruit juice [76]. Ellagic acid, gallic acid, (3,6-di-O-galloyl-D-glucose), 1-Ogalloyl-beta-D-glucose, 3-Ethylgallic acid, quercetin, chebulagic acid, (1,6-di-O-galloyl beta D glucose), corilagin, chebulinic acid, and isostrictiniin are among the different compounds extracted and identified in amla [77]. Flavonoids contained in amla generally include kaempferol 3-O-a-L-(600-methyl)-rhamnopyranoside, quercetin, and kaempferol 3-O-a-L-(600-ethyl) rhamnopyranoside [78]. ...
The advancement within the food and nutrition sector has resulted in the development of a special category of food, particularly referred to as “superfoods”. Superfoods are special kind of foods capable of exhibiting different positive effects involving prevention of different ailments, pro- vide impetus to the immune system, and essential macro- and micro-nutrients in ample quantities. Nowadays, these are gaining considerable attention due to the increased health consciousness of consumers. In contrast to their exceptional health or even medicinal benefits, which are based on their long history of use, the concept of superfoods is still little understood. The category of super- foods mainly comprises different types of fruits, vegetables, grains, etc. This review sheds light on the nutritional composition as well as the possible intervention in the prevention of various chronic ailments of some significant superfoods. This manuscript could help consumers to use superfoods as part of their diet more often and very effectively.
The causal and functional connection between inflammation and cancer has become a subject of much research interest. Modulation of cell signaling pathways, such as those involving mitogen activated protein kinases (MAPKs), nuclear factor kappa β (NF-κB), phosphatidylinositol 3-kinase and protein kinase B (PI3K/Akt), and Wnt, and their outcomes play a fundamental role in inflammation and cancer. Activation of these cell signaling pathways can lead to various aspects of cancer-related inflammation. Hence, compounds able to modulate inflammation-related molecular targets are sought after in anticancer drug development programs. In recent years, plant extracts and their metabolites have been documented with potential in the prevention and treatment of cancer and inflammatory ailments. Plants possessing anticancer and anti-inflammatory properties due to their bioactive constituents have been reported to modulate the molecular and cellular pathways which are related to inflammation and cancer. In this review we focus on the flavonoids (astragalin, kaempferol, quercetin, rutin), lignans (phyllanthin, hypophyllanthin, and niranthin), tannins (corilagin, geraniin, ellagic acid, gallic acid), and triterpenes (lupeol, oleanolic acid, ursolic acid) of Phyllanthus amarus, which exert various anticancer and anti-inflammatory activities via perturbation of the NF-κB, MAPKs, PI3K/Akt, and Wnt signaling networks. Understanding the underlying mechanisms involved may help future research to develop drug candidates for prevention and new treatment for cancer and inflammatory diseases.
Medicinal plants have been documented over the years to play vital role in promoting human health. The study evaluated the anti-inflammatory and anti-oxidant activities of different fractions and isolated compound from Ricinodendron heudelotii leaves. The leaves of Ricinodendron heudelotii were extracted with ethanol and further partitioned sequentially using petroleum ether, ethylacetate and butanol. Bioassay–guided fractionation of the ethylacetate fraction was done using repeated column chromatographic technique while the structural elucidation of pure compound was carried out using mass spectra, 13C and 1H NMR analyses. Antioxidant potential of the fractions and isolated compound were evaluated with 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays and anti-inflammatory effect of fractions was measured by their inhibitory potency on nitric oxide (NO).Corilagin, an amorphous tannin was isolated and structurally elucidated. Corilagin showed scavenging effect against ABTS and DPPH radicals which vary in a dose dependent manner. It also showed an antioxidant potential with IC50 value of 0.003 mg/mL comparable to vitamin C 0.001 mg/mL) used as standard. The butanol and ethylacetate fractions exhibited significant (p < 0.05) NO inhibition of 60 and 69% respectively after treatment of RAW 264.7 macrophages with lipopolysaccharide. These results demonstrated the role of isolated corilagin as a promising potent antioxidant while the ethylacetate and butanol fractions suppressed the expression of an inflammation mediator by inhibiting nitric oxide. : Natural Product Chemistry, Antioxidant; anti-inflammatory; Ricinodendron heudelotii; tannins. Keywords: Natural product chemistry, Antioxidant, Anti-inflammatory, Ricinodendron heudelotii, Corilagin, Tannins
Phyllanthus species (family; Euphorbiaceae) have been intensively studied for their immunomodulating effects due to their wide-ranging uses to treat immune-related diseases in indigenous medicine, which are primarily lack of scientific basis. The focuses of this review are on the significance of Phyllanthus species and their bioactive metabolites particularly corilagin (1), geraniin (2), gallic acid (3), phyllanthin (4), hypophyllanthin (5), ellagic acid (6), phyltetralin (7), niranthin (8), catechin (9), quercetin (10), astragalin (11), and chebulagic acid (12) in the modulation of both innate and adaptive immune systems through various mechanisms and their possible therapeutic benefits for treatment of immune-related diseases. We have compiled all significant findings published in the literature, and the data were analyzed critically to provide perspectives and directions for future research for the plants as a prospective source of novel immunomodulating agents. Various Phyllanthus species particularly Phyllanthus amarus, Phyllanthus emblica, Phyllanthus niruri, and Phyllanthus urinaria have been documented to possess significant immunomodulatory effects. However, the possible challenges encountered by the application of extracts of various Phyllanthus species and their bioactive constituents as immunomodulators need to be addressed. Most reports on the biological and pharmacological studies of the plants were based on crude extracts. The extracts were not chemically characterized, and the contributions of their chemical constituents to the bioactivities were not identified. The underlying mechanisms involved in the immunomodulatory effects of the Phyllanthus species were not indepthly studied due to limitations in terms of design, conduct, and interpretation. Extensive experimental and preclinical studies on the immunomodulating potential of Phyllanthus species should be carried out to provide sufficient data to prove that their traditional uses are inherently effective and safe and will allow clinical trials to be pursued for their further development as therapeutic agents to treat immune-related disorders.
Phyllanthus phillyreifolius (Euphorbiaceae), poorly studied plant species, was fractionated using conventional and high pressure extraction techniques such as supercritical fluid and pressurized liquid extractions. Lipophilic substances were extracted with n-hexane and supercritical CO2 with or without co-solvent ethanol, meanwhile higher polarity fractions were recovered with acetone and 70% ethanol. Antioxidant potential was assessed by various chemical assays, which revealed that 70% ethanol was the most effective solvent for recovery of antioxidants. UPLC-MS phytochemical analysis of hydrophilic extracts confirmed geraniin as the main constituent of P. phillyreifolius. Other quantitatively important compounds were phyllanthusiin D and elaeocarpusin. Three isomers of tocopherol (α, β and γ) were quantified by HPLC in lipofhilic extracts. Generally, the results from this study revealed high antioxidant potential of P. phillyreifolius; consequently the plant may be considered as a promising source of antioxidants for functional foods, nutraceuticals and pharmaceutical formulations.
Phyllanthus muellerianus (Family Euphorbiaceae) is a shrub, which is widely distributed in West Africa and employed traditionally as a wound-healing agent especially in Ghana. The aim of the study was to determine the in vivo wound-healing activity of aqueous aerial part extract of P. muellerianus (PLE) and its major isolate, geraniin. Excision and incision wound models were used to determine the wound-healing activity. Wounds were treated with PLE (0.25, 0.5, and 1% w/w) and geraniin (0.1, 0.2, and 0.4% w/w) aqueous creams. PLE and geraniin significantly (p < 0.001) increased wound contraction rate and hydroxyproline production compared to untreated wounds. Histological studies of wound tissues showed high levels of fibroblasts and increased collagen content and cross-linking in PLE and geraniin-treated wound tissues. Immuno-histochemical investigations revealed high levels of TGF-β 1 in PLE and geraniin-treated wound tissues compared to the untreated wound tissues. Tensile strength of incised wounds was significantly (p < 0.05) high in PLE and geraniin-treated wounds. PLE (0.1-100 µg/mL) significantly (p < 0.001) reduce LDH release from HaCaT-keratinocytes compared to the untreated cells. PLE and geraniin possess wound healing and cytoprotective effect.
In the search for new antibacterial agents from natural sources, we revealed that a crude methanol extract of Sapium baccatum was highly active against Ralstonia solanacearum, a causal agent of a serious disease called bacterial wilt of tomato. The bioassay-guided fractionation of this extract resulted in the isolation of seven known active compounds, including gallic acid, methyl gallate, corilagin, tercatain, chebulagic acid, chebulinic acid, and quercetin 3-O-α-L-arabinopyranoside. Their chemical structures were determined by electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. An in vitro antibacterial bioassay using a broth microdilution method revealed that, except for quercetin 3-O-α-L-arabinopyranoside (MIC = 250 μg/mL), the isolated compounds exhibited strong antibacterial activity against R. solanacearum (MIC = 26–52 μg/mL). Among the seven compounds, methyl gallate exhibited the strongest broad-spectrum activity against most of the plant pathogenic bacteria tested (MIC = 26–250 μg/mL). In the in vivo experiments, the crude extract of S. baccatum at 2000 and 1000 μg/mL reduced the development of tomato bacterial wilt by 83 and 63%, respectively, under greenhouse conditions after 14 days of infection. The results suggested that the extracts of S. baccatum or isolated tannins could be used as natural bactericides for the control of bacterial wilt of tomato.
The discovery of the ellagitannin geraniin was made exactly 40 years ago. It is a secondary metabolite found in plants and is categorised as a hydrolysable tannin under the huge family of polyphenolic compounds. At present, the occurrence of geraniin has been verified in at least 71 plant species, many of which are used in traditional medicine. Hence, like other polyphenols, geraniin has also received widespread interest as a research focus to unearth its beneficial biological effects and therapeutic values apart from understanding its chemical properties, biosynthesis and interaction with the body system. Indeed, it has been demonstrated that geraniin possesses antioxidant, antimicrobial, anticancer, cytoprotective, immune-modulatory, analgesic properties besides exerting promising therapeutic effects on hypertension, cardiovascular disease and metabolic dysregulation. The objective of this review is to summarise the current knowledge about the basic chemistry, natural sources, isolation techniques, biosynthesis, pharmacokinetics and pharmacodynamics of geraniin. With reference to this information, the clinical significance, obstacles and future perspectives in geraniin research will also be scrutinised.
Recently, we have highlighted the immunomodulatory activity of the standardized extracts of Phyllanthus amarus and P. urinaria. The present study was carried out to correlate between the prevalent constituents of the herbs and their inhibitory effects on phagocytic activity of human neutrophils.
The compounds, gallic acid, ellagic acid, corilagin, geraniin, phyllanthin and hypophyllanthin were identified and quantitatively analyzed in the extracts of Phyllanthus amarus and P. urinaria obtained from Malaysia and Indonesia by using a validated reversed phase high performance liquid chromatography (RP-HPLC) method. The standardized extracts and the pure compounds were evaluated for their effects on chemotaxis, β2 integrin (CD18) expression, phagocytosis and chemiluminescence of human phagocytes. Chemotactic activity was assessed using the Boyden chamber technique, inhibition of CD18 expression and phagocytic ability were tested with the aid of flow cytometry, while effect on the respiratory burst was investigated using a luminol-based chemiluminescence assay.
All plant extracts strongly inhibited migration of the phagocytes with the Malaysian P. amarus depicting the highest inhibitory activity. Amongst the compounds tested, geraniin demonstrated the strongest inhibitory activity on chemotaxis of polymorphonuclear leukocytes (PMNs) and monocytes with IC50 values of 1.09 and 1.69 μM, respectively, which were lower than that of ibuprofen. All plant extracts and pure compounds exhibited high inhibitory activity on the oxidative burst of zymosan and PMA stimulated leukocytes. Geraniin and corilagin exhibited exceptionally strong inhibition on the reactive oxygen species (ROS) activity with IC50 values lower than aspirin. The plant extracts exhibited moderate inhibition of E. coli uptake by monocytes but weak effect on PMNs. Of all the compounds, phyllanthin at 50 μg/mL exhibited the highest engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for PMNs and monocytes, respectively. All plants and compounds tested possessed weak effect on CD18 expression on leukocytes except for hypophyllanthin and phyllanthin which exhibited significant inhibitory effect.
The strong inhibition of the extracts on the phagocytic activity of neutrophils was due to the presence of their major constituents especially geraniin, corilagin, phyllanthin and hypophllanthin which were able to modulate the innate response of phagocytes at different steps.
Chemical investigation of the whole plants of Phyllanthus cochinchinensis (Euphorbiaceae) led to the isolation of three new phenolic glycosides, phyllanthuosides A-C, together with 12 known compounds. Their structures were established on the basis of extensive spectroscopic analysis and chemical methods. Among them, phyllanthuosides A and B are two of the rare phenolic glycosides, featuring with a C6-C3-C6 skeleton. The absolute configurations of phyllanthuosides A and B were established by calculated electric circular dichroism (ECD) using time dependent density functional theory (TDDFT). The isolates were also tested for their cytotoxicity and antimicrobial activity.
Mallotus philippinensis
Muell. Arg (Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000 m and are reported to have wide range of pharmacological activities.
Mallotus philippinensis
species are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. The present review reveals that
Mallotus philippinensis
is a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited about
Mallotus philippinensis
and its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.
Vernicia montana Lour. (tung tree) is an oil-producing plant with multiple uses, especially with its great potential in biodiesel production, which was a small Asian tree of the spurge family (Euphorbiaceae) with big economic values. However, studies on small molecular compositions of V. montana are limited. As a result, seven new lignans and one new coumacrin, and 21 known lignans, were isolated from the testas of V. montana. These isolates were confirmed in the light of spectroscopic tools (containing 1D and 2D NMR), ECD spectra methods. These isolates and crude extracts were evaluated their inhibitory activities using LPS-induced BV2 cells by assessing the NO production. Among them, compounds 3, 5, 6, 22 displayed significant effects, IC50 values about 11.4-20.9 μM. Together, the results demonstrated that lignans might be potential neuroinflammatory inhibitors.
A phytochemical investigation of the aerial parts of Euphorbia formosana Hayata resulted in the isolation of 33 compounds, including various derivatives of ellagic acid and gallic acid. The chemical structures were elucidated by spectroscopic methods and comparison with relevant data from the literature. The chemotaxonomic significance and distribution of these derivatives of ellagic acid and gallic acid in the genus Euphorbia are discussed.
Seven new lignans, cleistonkinins A- E (1-5), cleistonkisides A and B (6-7) were isolated from the fruits of Cleistanthus tonkinensis (Euphorbiaceae), together with five known aryltetralin lignans, cleisindoside B (8), cleistantoxin (9), cleisindoside D (10), neocleistantoxin (11) and polygamain (12). Their structures were established from spectral analysis, including mass spectrometry and 2D-NMR. The absolute configurations of 4-7 were determined by analysis of their experimental CD spectra and comparison with calculated electronic circular dichroism (ECD) spectra. Compounds 2 and 6 had selective inhibition with moderate cytotoxicity against Pan C1 and A549 cell lines, respectively. Cleistantoxin (9) was significantly active against A549, HeLa, Hep3B, Pan C1 and MCF7 cell lines while it was less cytotoxic against HeLa cells. Neocleistantoxin (11) exhibited remarkable inhibition toward A549, HeLa, MCF7 and Pan C1. This is the first report for cytotoxicity of 9 and 11 against A549, Hep3B and Pan C1 cell lines.
Sapium baccatum has been traditionally used as therapeutic remedies. To support its medicinal benefits, our current phytochemical investigation attempted to further discover novel bioactive compounds from S. baccatum. Eight new phenolic compounds, namely, seven coumarins (1–7) and one monoterpene galloylglycoside (8), together with 23 (9–31) known compounds were isolated. Their structures were determined by extensive spectroscopic methods and comparison with literatures. The three pairs of enantiomers of 1, 2 and 7 were confirmed on the basis of HPLC chiral analysis, electronic circular dichroism data and optical rotations. Two coumarins (1–2) were proven to be artifacts through HPLC analysis. The inhibitory effects on TNF-α secretion were examined biologically in LPS-induced BV2 microglia cells and all of the tested compounds exhibited significant inhibitory activity, especially new compound 1 possessed stronger inhibitory effects compared to the positive control quercetin. In addition, compounds 14 and 15 showed weak antifungal activity against Candida albicans SC5314 with MIC values both at 64 μg/mL. The results laid a solid foundation for additional research on S.baccatum related to its anti-inflammatory and antifungal medicinal value.
Two new coumarinolignoids, sapiumins D (1) and E (2), a new lignanoid, lariciresinol 9′-benzoate (3), together with six known coumarinolignoids (4–9) and eight known lignanoids (10–17), were isolated from the stems and leaves of Sapium discolor. The structures of the isolated compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and single crystal X-ray diffraction experiments. Compounds 5, 10, 11, and 13 significantly inhibited nitric oxide production in lipopolysaccharide-induced BV-2 microglial cells, with IC50 values in the range of 2.13–11.37 μM.
Seventeen compounds, including three new pairs of coumarinolignoid enantiomers, (7' S,8' S)-sapiumins A-C (1a-3a) and (7' R,8' R)-sapiumins A-C (1b-3b), six new taraxerane triterpenoids, sapiumic acids A-F (4-9), and five known taraxerane triterpenoids (10-14), were isolated from an ethanol extract prepared from the stems and leaves of Sapium discolor. The structures of 1-9 and their relative configurations were determined by spectroscopic data analysis, and the absolute configurations of the coumarinolignoids 1a/1b-3a/3b and triterpenoids 6-9 were assigned using experimental and calculated ECD data. Compounds 1a/1b-3a/3b are the first coumarinolignoids to be reported from the genus Sapium. Among all the isolates, compounds 1b, 2a/2b, 3a/3b, and 6-9 inhibited nitric oxide production in lipopolysaccharide-stimulated BV-2 microglial cells, with IC50 values of 1.7-15.3 μM.
Three aryl-tetralin-type lignans, including 2 previously undescribed compounds, were isolated from the root of Sanguisorba officinalis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analyses and mass spectrometry. Experimental and calculated ECD were used to determine the absolute configurations. The isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-MB-231) and compound 1 exhibited moderate growth inhibition against MDA-MB-231 cell line with IC50 value of 15.76 μM.
To identify active compounds in the roots of Euphorbia pekinensis for treatment of diabetic complications, an active column fraction from a 70% EtOH extract of E. pekinensis root was purified by preparative reversed-phase high-performance liquid chromatography, leading to the isolation of a new ellagic acid derivative, 3,3′-di-O-methylellagic acid 4-O-(6ʺ-O-galloyl)-β-D-galactopyranoside (1), along with three known compounds, geraniin (2), 3,3′-di-O-methylellagic acid 4-O-β-D-xylopyranoside (3), and ellagic acid 3,3′-dimethyl ether (4). The structure of the new compound was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds 1–4 on advanced glycation end-products (AGEs) formation were examined. All compounds exhibited considerable inhibition of AGEs formation and IC50 values of 0.41 – 12.33 µM, compared with those of the positive controls aminoguanidine (IC50 = 1122.34 µM) and quercetin (IC50 = 27.80 µM). In addition, the effects of 2 and 4 on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were investigated; both compounds significantly reduced the HG-induced dilation of hyaloid-retinal vessels relative to the HG-treated control group.
There is no drug administration-approved therapy for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). In this study, eight compounds, gallic acid (1), methyl gallate (2), corilagin (3), 3,4,8,9,10-pentahydroxydibenzo[b,d]pyran-6-one (4), repandinin B (5), (Z)-3-hexenyl-β-D-glucopyranoside (6), (+)-lyoniresinol-3α-O-α-L-rhamnopyranoside (7) and mallophenol A (8) were isolated from the active fractions of Mallotus furetianus. Three compounds, (6, 7 and 8) revealed potent anti-steatosis activity in the oleic acid (OA)-induced steatosis cell model, with the minimum effective concentration of 0.05 (6), 0.0005 (7) and 0.0005 (8) μg/mL, which were much lower than the control compound, fibrate (72.4 μg/mL).
Nine hydrolyzable tannins, including three previously unknown and six artifacts, were isolated, together with thirty-nine known ones, from the fruits of Terminalia chebula Retz. (Combretaceae). They were identified as 1,2,3-tri-O-galloyl-6-O-cinnamoyl-β-d-glucose, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose, 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid, 1′-O-methyl neochebulanin, dimethyl neochebulinate, 6′-O-methyl neochebulagate, dimethyl neochebulagate, dimethyl 4′-epi-neochebulagate, and methyl chebulagate by the spectroscopic interpretation. After evaluation for α-glucosidase inhibition of all isolated compounds, 1,2,3,6-tetra-O-galloyl-4-O-cinnamoyl-β-d-glucose and 4-O-(2″,4″-di-O-galloyl-α-l-rhamnosyl)ellagic acid showed significant inhibitory activities with IC50 values of 2.9 and 6.4 μM, respectively. In addition, inhibition kinetic studies showed that both compounds have mixed-type inhibitory activities with the inhibition constants (Ki) of 1.9 and 4.0 μM, respectively.
Two new chalconoid analogues, emblirol A (1) and B (2), along with three known ones (3–5), were isolated from the root of the Phyllanthus emblica L. Their structures were elucidated on the basis of spectral data. Compound 1 and 2 showed moderate anti-TMV activity with inhibition rates 79.6 and 62.1% at a concentration of 1 mg/mL, respectively.
Ethnopharmacological relevance:
Fruits of Phyllanthus emblica Linn. or Emblica officinalis Gaertn. (Phyllanthaceae) are used in Ayurveda, Siddha, Unani, Arabic, Tibetan and various other folk medicinal systems to promote intelligence and memory. Recent study from our lab indicated the neuroprotective effect of tannoids principles of Emblica officinalis (EoT) against memory loss caused by aluminum chloride (AlCl3) intoxication through attenuating acetylcholine esterase activity and the expression of amyloid β protein biosynthesis related markers. However the molecular mechanism of EoT has not yet been fully elucidated.
Aim of the study:
The aim of the present study was to further investigate the neuroprotective mechanisms of EoT against AlCl3-induced cognitive deficits, tau hyperphosphorylation, oxidative stress and apoptosis.
Materials and methods:
Rats were treated with AlCl3 for 60 days to induce biochemical and physiological abnormalities similar to AD patients. AD rats were treated with EoT (100mg/kg., bw. oral) for 60 days. For the examination of neuroprotective effect of EoT, behavior analysis, biochemical estimations and western blot were performed in the hippocampus and cortex of control, EoT treated and untreated AD rats.
Results:
Intraperitoneal injections of AlCl3 (100mg/kg., b.w.) for 60 days enhanced the learning and memory deficits, levels of TBARS and diminished the levels of reduced glutathione and activities of enzymatic antioxidants as compared to control group. Moreover toxicity of AlCl3 is accompanied by the enhanced expressions of Bax, caspases-3,-9, cytosolic cytochrome c (cyto c), and pTau along with diminished expressions of Bcl-2, mitochondrial cyto c, pGSK-3β and pAkt. Coadministration of EoT nullified the cognitive deficits, biochemical abnormalities and apoptosis induced by AlCl3 treatment. Moreover EoT prevents tau hyperphosphorylation by targeting the GSK-3β/Akt signaling pathway.
Conclusions:
This study confirms that EoT would be used as a potential drug candidate for AD and other tau pathology-related neuronal degenerative diseases.
Fifty-eight phenolic compounds isolated from Phyllanthus emblica were screened and compared for their in vitro and in vivo antioxidant properties, as well as hyaluronidase (HAase) inhibitory activities. Among them, 20 compounds showed to be promising antioxidants due to the stronger scavenging activity in both DPPH radical and Danio rerio reactive oxygen species assays, while nine compounds were potential HAase inhibitors with 100-fold stronger activities than that of the positive control, DSCG. The structure activity relationship was discussed.
A chemical examination of the stems of Sapium japonicum PAX et H OFFM (Euphorbiaceae) has led to the isolation of seve n phenolic compounds. On the basis of UV, IR, MS, and NMR spectral data and the chemical reaction, the structures of these compounds were identified as gallic acid (1), ellagic acid (2), 3,3′-di-O-methylellagic acid (3), 4-O-(β-D- xylopyranosyl)-3,3′-di-O-methylellagic acid (4), 4-O-(a-D- arabinofuranosyl)-3,3′-di-O-methylellagic acid (5), isoquercitrin (6), and geraniin (7).
From the bark of Aegle marmelos Correa (Rutaceae), an Indonesian medicinal plant, two new lignan-glucosides, ( )-lyoniresinol 2α-O-β-D-glucopyranoside (3) and (-)-4-epi-lyoniresinol 3α-O-β-D-glucopyranoside (4), have been isolated together with two known lignan-glucosides, (+)-lyoniresinol 3α-O-β-D-glucopyranoside (1) and (-)lyoniresinol 3α-O-β-D-glucopyranoside (2).
In an effort to identify anti-viral and cytotoxic compounds from Phyllanthus spp., 14 highly oxygenated norbisabolane sesquiterpenoids, phyllaemblicins H1-H14, were isolated from the roots of Phyllanthus emblica Linn, along with phyllaemblicins B and C and glochicoccinoside D. Their structures were determined on the basis of detailed spectroscopic analysis and chemical methods. Determination of absolute configurations of these compounds was facilitated by theoretical calculations of electronic circular dichroism (ECD) spectra using time-dependent density functional theory (TDDFT) for the aglycone components, and pre-column derivative/chiral HPLC analysis for the monosaccharides. The known glochicoccinoside D displayed potent activity against influenza A virus strain H3N2 and hand, foot and mouth virus EV71, with IC50 values of 4.5±0.6 and 2.6±0.7μg/ml, respectively. Phyllaemblicin H1 showed moderate cytotoxicity against human cancer cell lines A-549 and SMMC-7721, with IC50 values of 4.7±0.7 and 9.9±1.3μM, respectively.
Copyright © 2015 Elsevier Ltd. All rights reserved.
The current study was aimed at evaluating the antihyperalgesic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich three standardized extracts of Phyllanthus amarus in a model of chronic musculoskeletal inflammatory pain. Three percent carrageenan injected in the gastrocnemius muscle produced hyperalgesia to mechanical and heat stimuli ipsilaterally, which spreads to the contralateral side within 7 to 9 days. To investigate the effects on chronic thermal and mechanical hypersensitivity, three extracts of P. amarus in three doses (100, 200, and 400 mg/kg) were administered to animals intraperitoneally from 14th day to 22nd day after intramuscular injection of carrageenan. It was observed that intraperitoneal administrations of Phyllanthus extracts showed antihyperalgesic activity, as they elevated thermal and mechanical threshold, which was supported by histopathological observations along with reduction in prostaglandin E2 (PGE2) concentration. In conclusion, we strongly suggest that the observed antihyperalgesic and antiinflammatory effects of P. amarus in current pain model are mediated via spinal or supraspinal neuronal mechanisms, mainly by inhibition of PGE2. Modulation of chronic muscular inflammation may be due to presence of phytoconstituents like phyllanthin, hypophyllanthin, and corilagin, which offers a promising means for treatment of chronic muscle pain. Copyright © 2015 John Wiley & Sons, Ltd.
Copyright © 2015 John Wiley & Sons, Ltd.
Two new ellagitannin dimers, euphorbins G (20) and H (21), together with 12 known polyphenols, were isolated from the leaves of Euphorbia prostrata (E. chamaesyce). Their structures, having 1C4 and 4C1 glucopyranose cores in each molecule, were established by spectroscopic and chemical methods. These new dimers, and 13 known hydrolyzable tannins, among which six are the same as those from E.prostrata, were also isolated from E.makinoi.
Together with ten hydolyzable tannins and related compounds (1-10), three novel dimeric ellagitannins, excoecarianin (11), and excoecarinins A (13) and B (16), possessing a dehydrohexahydroxydiphenoyl or an elaeocarpusinoyl group, have been isolated from the leaves of Excoecaria kawakamii HAYATA (Euphorbiaceae). The structures of these tannins were established on the basis of spectroscopic and chemical evidence.
Together with eleven known compounds (1-11), seven new tannins, 3-desgalloylterchebin (12), macaranins A, B and C, and macarinins A, B and C, have been isolated from the leaves of Macaranga sinensis (BAILL.) MUELL.-ARG. (Euphorbiaceae). Macaranins A (14), B (13) and C (17) have been determined on the basis of chemical and spectroscopic evidence to be hydrolyzable tannins possessing a novel acyl group (macaranoly group) at the 3, 6-positions of the 1C4 (or skew boat) β-D-glucopyranose ring, while macarinins A (18), B (15) and (16) were characterized as those having a tergalloyl group at the same positions.
Further chemical examination of the bark and the leaves of Mallotus japonicus (THUNB.) MUELLER-ARG. (Euphorbiaceae) has led to the isolation of two new tannins [named mallotannins A (16) and B (18)]. Based on chemical and spectroscopic evidence, the structures of 16 and 18 were established to be dimeric hydrolyzable tannins in which the free carboxylic acid in mallotinic acid is connected to the C-6 position of bergenin and D-glucose, respectively. On the other hand, fifteen known tannins and related compounds have been isolated from the leaves of M. philippinensis (LAM.) MUELLER-ARG. and identified by comparisons of their physical and spectral data with those of authentic samples. In addition, a survey of tannin patterns in Mallotus species is presented.
During the process of exploring bioactive lead compounds from Phyllanthus species, two new glycosides including an arylnaphthalene lignan, diphyllin 4-O-α-l-arabinopyranosyl-(1 → 3)-α-l-arabinopyranoside (1), and a phenolic compound, 3,4,5-trimethoxybenzyl alcohol 7-O-α-l-arabinofuranosyl-(1 → 6)-β-d-glucopyranoside (2), were isolated from the methanol extract of the whole plants of Phyllanthusglaucus Wall. ex Müll. Arg. In addition, 31 known compounds, including 19 lignan derivatives (3-21), four phenylpropanoids (22-25), seven simple phenolics (26-32) and one monoterpenoid (33) were obtained. Their structures were determined on the basis of the HR-ESI-MS, 1D and 2D NMR spectroscopic analysis, and pre-column derivative/chiral HPLC analysis in case of 1 for the absolute configurations. All these compounds were obtained from P. glaucus for the first time. Moreover, the known lignan glycoside, phyllanthusmin C (5) showed in vitro cytotoxicities against HL-60, MCF-7 and SW480 cells with IC50 values of 9.2 ± 0.2, 19.2 ± 1.7 and 20.5 ± 0.9, respectively.
Two new dimeric dehydroellagitannins, named euphorbin A (6) and euphorbin B (7), were isolated from the aerial parts of Euphorbia hirta, and their structures, containing 4C1 and 1C4 glucopyranose residues and a dehydrohexahydroxydiphenoyl group, were elucidated on the basis of chemical and spectral studies. Five monomeric hydrolyzable tannins, i.e., 2, 4, 6-tri-O-galloyl-D-glucose, 1, 3, 4, 6-tetra-O-galloyl-β-D-glucose, 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucose, geraniin and terchebin, as well as two quinic acid esters, i.e., 5-O-caffeoylquinic acid and 3, 4-di-O-galloylquinic acid, and three flavonol glycosides were also isolated.
A chemical examination of the leaves of Mallotus repandus (WILLD.) MUELLER-ARG. (Euphorbiaceae) has led to the isolation of four new hydrolyzable tannins, named repandusinin (10), repandusinic acids A (11a) and B (14a) (as monopotassium salts) and mallotinin (15), together with glucogallin (1), eugeniin (2), corilagin (3), punicafolin (4), geraniin (5), furosin (6), mallotinic acid (7), mallotusinic acid (8) and brevifolin carboxylic acid (9). Based on the chemical and spectroscopic evidence, repandusinin was assigned the structure (10) in which brevifolin carboxylic acid is attached to the C-4 position of the glucose moiety in mallotinic acid, while repandusinic acids A and B were characterized as 1-O-galloyl-3, 6-(R)-hexahydroxydiphenoyl-(11a) and 1-O-galloyl-3, 6-(R)-valoneayl-4-O-(4'-dehydrochebuloyl)-β-D-glucoses (14a), respectively. Similarly, mallotinin was found to have the structure (15) possessing a new acid, mallotic acid, linked to the C-2 position of the corilagin moiety.
A chemical examination of the tannins in the leaves of Macaranga tanarius (L.) MUELL. et ARG. (Euphorbiaceae) has led to the isolation of seven new hydrolyzable tannins (22-28), together with twenty-one known tannins (1-21). On the basis of chemical and spectroscopic evidence, the structures of compounds 22-28 were established as 1, 4-di-O- galloyl-α-D-glucopyranose (22), 3, 4-di-O-galloyl-D-glucopyranose (23), galloylpunicafolin (24), galloylgeraniin (25), 1-O- galloyl-3-O-brevifolincarboxyl-β-D-glucopyranose (26), 1, 2, 4-tri-O-galloyl-3, 6-(S)-hexahydroxydiphenoyl-β-D-glucopyranose (macaranganin) (27) and 1, 2, 4-tri-O-galloyl-3, 6-(R)-dehydrohexahydroxydiphenoyl-β-D-glucopyranose (tanarinin) (28).
Two new hydrolysable tannins, chebumeinin A (1) and chebumeinin B (2), together with eight known related compounds (3‒10), were isolated from the fruits of Terminalia chebula. The new compounds were structurally determined by analysis of their spectroscopic data and the known compounds characterized by comparing their spectroscopic data with literature values. All isolates were evaluated by an HCV protease inhibition assay, and some compounds were found to be potently active.
To investigate the chemical constituents of Euphorbia pekinensis roots. METHODS Column and liquid chromatography were used for the isolation of chemical constituents, and their chemical structures were determined using a spectroscopic method.
Four compounds were isolated and identified as ziyu glycoside I (1), 3β-α-L-arabinopyranosyloxyurs-12,19(29)-dien-28-oic acid 28-β-D-glucopyranosyl ester (2), lithospermic acid B (3), and senarguine B (4), which were obtained for the first time from the roots of Euphorbia pekinensis.
The air-dried fruit hull of Phyllanthus emblica L. was extracted with 95% ethanol, and then the extract was partitioned by diethyl ether and ethyl acetate (EA). The EA fraction was then subjected to separation and purification using silica gel and Sephadex LH-20 column chromatography repeatedly to obtain five hydrolysable tannins. They were identified as mucic acid 1,4-lactone 3-o-gallate (C1), isocorilagin (C2), chebulanin (C3), chebulagic acid (C4) and isomallotusinin (C5) using mass spectrometry and nuclear magnetic resonance (NMR) spectrometry. Isomallotusinin and chebulanin were identified from emblica dried fruit hull for the first time, and isomallotusinin was the first time identified from Phyllanthus. Furthermore, the antioxidant abilities of these hydrolysable tannins were investigated using DPPH and ABTS+ radical scavenging systems. All hydrolysable tannins showed strong DPPH and ABTS+ radical scavenging activities. Isomallotusinin and chebulagic acid exhibited the highest antioxidant activity compared to other purified compounds tested.
Phytochemical investigation of the leaves and stems of Glochidion wrightii Benth. led to the isolation of one new triterpenoid ester, 3β-tetradecanoyloxy-1β-hydroxylup-20(29)-ene (1), and twenty-nine known compounds (2–30), including (3β,16β)-lup-20(30)-ene-3,16,29-triol (8) reported as a natural product for the first time. Their structures were identified by spectroscopic analysis and by comparison of their spectral data with those reported in the literature. The chemotaxonomic analysis is concordant with the newest molecular phylogenetic and morphological classifications that the genus Glochidion is deeply embedded within the large Phyllanthus.
Three new bergenin derivatives were isolated from the bark of Mallotus japonicus and determined to be 11-O-galloylbergenin, 4-O-galloylbergenin and 11-O-galloyldemethylbergenin. The 13C resonances of bergenin were fully assigned.
The ichtyotoxic lignan justicidin B, ca 0.6% of the dry weight, and the lignan-glucoside phyllanthostatin A were isolated from the chloroform extract of Phyllanthus anisolobus. Two γ-lactones, menisdaurilide and aquilegiolide, were also isolated and their absolute stereostructures determined by the CD allylic benzoate method.
Two lignans, trivially named gaultherins A (1) and B (2), were isolated from the roots of Gaultheria yunnanensis (Ericaceae). Their structures were deduced as 5-methoxy-(+)-isolariciresinol-9,9′-diacetate (1) and (+)-lyoniresinol-9,9′-diacetate (2), based upon physicochemical properties, spectral analyses and chemical degradation.
A chemical investigation of the roots of Euphorbia fischeriana has led to the isolation of three novel gallotannins, 1,3,6-tri-O-, 1,2,6-tri-O- and 1,2,3,6-tetra-O-galloyl-β-d-allopyranoses, together with ellagitannins (corilagin, sanguiin H-5 and tercatain) and 3,4,6-tri-O-galloyl-d-glucose. The structures of these compounds were established from spectroscopic and chemical evidence.
Chemical investigation of Euphorbia thymifolia has led to the isolation and characterization of a new hydrolysable tannin named isomallotinic acid, in addition to 15 known tannins. The structure of isomallotinic acid was established on the basis of spectroscopic and chemical evidence.
Chemical study of Cunonia macrophylla, a New Caledonian Cunoniaceae, based on bioactive effects of a crude methanol extract of the leaves, detected bioactive tannins for the first time in this plant family. These ellagitannins have been identified as ellagic acid-4-O-beta-D-xylopyranoside (6), mallorepanin (3), mallotinic acid (1) along with corilagin (2), chebulagic acid (4), ellagic acid (5) and gallic acid (7) and have been shown to possess antimicrobial activity and to inhibit xanthine oxidase. Antimicrobial effects on bacterial human pathogens (Staphylococcus aureus, Corynebacterium accolans) and on a plant pathogen (Erwinia carotovora) as well as on a human pathogenic yeast (Candida albicans) were investigated. Activity is reported here for the first time for compounds 1, 3, 4 and 6. The inhibitory effects of all molecules against xanthine oxidase in relation to their structure was evaluated and compared. Compound 6 presented the best activity and seems to be of considerable interest for further studies.
Callus and cell suspension cultures of Sapium sebiferum were established and the production of Gallic acid, β-glucogallin, geraniin, furosin, tercatain, chebulagic acid, chlorogenic acid, 1,2,3,6-tetra-O- and 1,2,3,4,6-penta-O-galloyl-β-d-glucoses established. Both in the callus and cell suspension cultures, the main phenolic constituent was geraniin. 1. Ueki, S. Nonaka, G. Nishioka, 1. and Fujiwara, M. 1985 J. Med. Pharm. Soc. WakKAN-YAKU 2,502. 2. Nagasawa, T. Shibutani, S. and Oura, 1-1. 1978 Yakugaku Zasshi 98, 1642. 3. Nagasawa, T. Shibutani, S. and Oura, H. 1980 Yakugaku Zasshi 100, 434. 4. Nagasawa, T. Oura, H. Shoyama, Y. and Nishioka, 1. 1980 Chem. Pharm. Bull. 28,1736. 5. Shibutani, S. Nagasawa, T.' Oura, H. Nonaka, G. and Nishioka, 1. 1 983 Chem. Phllrm. Bull. 31, 2378. 6, Nishizawa, M. Yamagishi, T. Dutschman, G. E. Parker, W.B. Bodner, A.J. Kilkuskie, R. E. Cheng, Y.-C. and Lee, K.-H. 1989 J. Nat. Prod. 52,762. 7. Nonaka, G. Nishioka, I. Nishizawa, M. Yamagishi, T. Kashiwada, Y. Dutschman, G. E. Bodner, A. J. Kilkuskie, R. E. Cheng, Y.-C. and Lee, K.-H. 1990 J. Nat. Prod. 53, 587. 8. Mridula, M. K. Gupta, P. K. and Masearenhas, A. F. 1983 Plant Cell Tiss. Org. Cult. 2,133. 9. Murashige, T. and Skoog, F. 1962 Physiol. Plant. 15, 473. 10. Schmidt, 0. T. and Schmadel, H. 1961 Liebigs Ann. Chem. 649, 149. 11. Court, W. A. 1977 J. Chromatog. 130, 287. 12. Tanaka, T. Nonaka, G. and Nishioka, 1. 1986 Chem. Pharm. Bull. 34, 1039. 13. Haddock, E. A. Gupta, R. K. and Haslam, E. 1 982 J. Chem. Soc. Perkin Trans I 2535. 14. Okuda, T. Yoshida, T. and Hatano, T. 1982 J, Chem. Soc., Perkin Trans I 9. 15. Nishizawa, M. Yamagishi, T. Nonaka, G. and Nishioka, 1. 1982 J. Chem. Soc. Perkin Trans I 2963. 16. Saijo, R. Nonaka, G. and Nishioka, 1. 1989 Chem. Pharm. Bull. 37, 2063. 17. Nishizawa, M. Yamagishi, T. Nonaka, G. and Nishioka, 1. 1983 J. Chem. Soc. Perkin'Trans I 961.
The structure of a new acylated flavonol glycoside from the leaf extract of Euphorbiamaculata was characterized as quercetin 3-O-(2″,3″-di-O-galloyl)-β-D-glucopyranoside. Four new hydrolyzable tannins together with twelve known tannins were also isolated and their structures were established by spectral and chemical means as 1,2,6-tri-O-galloyl-α-D-glucose, 1-O-galloyl-2,4;3,6-di-O-chebuloyl-β-D-glucose (eumaculin E), and dimers (eumaculins B and D) having a tergalloyl and a macaranoyl group as the linking unit of monomers, respectively. Keywords: Euphorbiamaculata, Euphorbiaceae, tannin, eumaculin B, eumaculin E.