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Table of Contents
October-December 2016
Volume 8 | Issue 4
Page Nos. 219-315
Online since Tuesday, August 23, 2016
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ORIGINAL ARTICLES
In vivo
study on depressant effects and muscle coordination activity of
Galphimia glauca
stem methanol extract
p. 219
Baba Shankar Rao Garige, Srisailam Keshetti, Uma Maheshwara Rao Vattikuti
DOI
:10.4103/0974-8490.188878
PMID
:27695258
Background:
Galphimia glauca
is an evergreen shrub found across peninsular India, belonging to family
Malpighiaceae
.
Objective:
The objective of this study was to assess the
in vivo
depressant effects and muscle coordination activity of
G. glauca
stem methanol extract (GGSME).
Materials and Methods:
The stem methanol extract was administered in Swiss albino mice in 1 day to study the central nervous system (CNS) depressant and muscle coordination activity employing animal models such as sodium pentobarbital-induced sleep test, hole-board test, open field test, pentylenetetrazole (PTZ)-induced convulsions, picrotoxin-induced convulsions, grip strengthening test in mice, and Rota-rod test.
Results:
The LD
50
of GGSME was found to be >2000 mg/kg body weight (b.w.). Mice treated with stem methanol extract at 100, 200, and 400 mg/kg, b.w. doses extended the sleeping time induced by sodium pentobarbital (40 mg/kg. b.w., i.p.). The stem methanol extract at 400 mg/kg dose showed a significant (
P
≤ 0.001) dose-dependent decrease in the number of rears and head dipping number in the hole-board test. The extract exhibited a significant (
P
≤ 0.001) effect on the ambulatory behavior of mice in the open field test and also extended the onset of seizures induced by PTZ (90 mg/kg b.w., i.p.) and picrotoxin (10 mg/kg, b.w., i.p.). The extract also exhibited significant (
P
≤ 0.001) effects on muscle coordination in rota-rod and grip strengthening test in mice.
Conclusion:
The study results conclude that the GGSME has a potential CNS depressant and muscle relaxant effects compared to the standard drugs.
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Evaluation of antiulcer and antioxidant activity of
Barleria gibsoni Dalz
. leaves
p. 226
Firoj A Tamboli, Harinath N More
DOI
:10.4103/0974-8490.188879
PMID
:27695259
Background:
Peptic ulcer is a digestive disorder most commonly found in clinical practice. Given the many side effects of modern medicine, the initial acquisition of fewer side effects, and medication of indigenous drugs, it should be considered as a better alternative for the treatment of peptic ulcer.
Objective:
To assess antiulcer and antioxidant activity of ethanol extract of
Barleria gibsoni
(EBG) Dalz. leaves in ulcer-induced rats and
in vitro
antioxidants method, respectively.
Materials and Methods:
Ethanol EBG was screened for antiulcer activity in pylorus ligation-induced ulcer models in Wistar rats.
In vitro
antioxidant activity of the extracts was tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) radical scavenging activity. Total phenol and flavonoid content in the extracts were determined spectrophotometrically.
Results:
Oral administration of ethanol extract of leaves at doses of 250, 500 mg/kg p.o. reduced significant gastric lesions induced by pylorus ligation-induced ulcer as compared to standard omeprazole (20 mg/kg p.o.). The IC
50
values were found to be 150 μg/mL in leaves extract. The ethanol extracts showed good antioxidant capacity in DPPH radical scavenging assay and NO radical scavenging activity when compared to standard. The total phenolic content using Folin–Ciocalteu reagent estimated in 1 mg of leaves extracts was 368 μg and 481 μg with gallic acid equivalent and also the total flavonoid content found to be 240 and 410 μg, respectively, with quercetin equivalence.
Conclusion:
These findings suggest that the leaves of
B. gibsoni
possessed antiulcer potential and antioxidant compared to standard. This is the first ever report of antiulcer and antioxidant activities in
B. gibsoni
(
Acanthaceae
).
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Probing regenerative potential of
Moringa oleifera
aqueous extracts using
In vitro
cellular assays
p. 231
Evangeline E Fernandes, Anubha V Pulwale, Gauri A Patil, Alpana S Moghe
DOI
:10.4103/0974-8490.188877
PMID
:27695260
Background:
Molecules stimulating regeneration and proliferation of cells are of significance in combating ailments caused due to tissue injury, inflammation, and degenerative disorders.
Moringa oleifera
is one of the most valued food plants having the profile of important nutrients and impressive range of medicinal uses.
Objective:
To evaluate the potential of
M. oleifera
aqueous leaf and flower extracts to promote the proliferation of cells and explore their effect on cancer cell lines for assessment of safety.
Materials and Methods:
Aqueous leaf and flower extracts of
M. oleifera
were investigated for effect on rat-derived primary fibroblast, mesenchymal stem cells (MSCs), and cancer cell lines using cell proliferation assay. They were also tested and compared for wound healing, angiogenesis, and hepatoprotective effect using
in vitro
assays.
Results:
Statistically significant increase in the proliferation of primary rat fibroblast, MSCs, and angiogenesis was observed after treatment with aqueous flower extract. The aqueous leaf extract determined a comparatively moderate increment in the proliferation of MSCs and angiogenesis. It however showed prominent cytotoxicity to cancer cell lines and a significant hepatoprotective effect.
Conclusion:
A very clear difference in response of the two extracts to different types of cells was detected in this study. The aqueous flower extract exhibited a higher potential to stimulate cell proliferation while not exerting the same effect on cancer cell lines. The leaf extract on the other hand, had a prominent antitumor and hepatoptotective effects.
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High-performance thin-layer chromatography method development, validation, and simultaneous quantification of four compounds identified in standardized extracts of
Orthosiphon stamineus
p. 238
Suzana Hashim, Hooi Kheng Beh, Mohamad Shahrul Ridzuan Hamil, Zhari Ismail, Amin Malik Shah Abdul Majid
DOI
:10.4103/0974-8490.188872
PMID
:27695261
Context:
Orthosiphon stamineus
is a medicinal herb widely grown in Southeast Asia and tropical countries. It has been used traditionally as a diuretic, abdominal pain, kidney and bladder inflammation, gout, and hypertension.
Aims:
This study aims to develop and validate the high-performance thin layer chromatography (HPTLC) method for quantification of rosmarinic acid (RA), 3'-hydroxy-5,6,7,4'-tetramethoxyflavone (TMF), sinensitin (SIN) and eupatorin (EUP) found in ethanol, 50% ethanol and water extract of
O. stamineus
leaves.
Materials and Methods:
HPTLC method was conducted using an HPTLC system with a developed mobile phase system of toluene: ethyl acetate: formic acid (3:7:0.1) performed on precoated silica gel 60 F254 TLC plates. The method was validated based on linearity, accuracy, precision, limit of detection, limit of quantification (LOQ), and specificity, respectively. The detection of spots was observed at ultraviolet 254 nm and 366 nm.
Results:
The linearity of RA, TMF, SIN, and EUP were obtained between 10 and 100 ng/spot with high correlation coefficient value (
R
2
) of more than 0.986. The limit of detection was found to be 122.47 ± 3.95 (RA), 43.38 ± 0.79 (SIN), 17.26 ± 1.16 (TMF), and 46.80 ± 1.33 ng/spot (EUP), respectively. Whereas the LOQ was found to be 376.44 ± 6.70 (RA), 131.45 ± 2.39 (SIN), 52.30 ± 2.01 (TMF), and 141.82 ± 1.58 ng/spot (EUP), respectively.
Conclusion:
The proposed method showed good linearity, precision, accuracy, and high sensitivity. Hence, it may be applied in a routine quantification of RA, SIN, TMF, and EUP found in ethanol, 50% of ethanol and water extract of
O. stamineus
leaves.
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Kayeassamin a isolated from the flower of
Mammea siamensis
triggers apoptosis by activating caspase-3/-8 in hl-60 human leukemia cells
p. 244
Takuhiro Uto, Nguyen Huu Tung, Pinjutha Thongjankaew, Sorasak Lhieochaiphant, Yukihiro Shoyama
DOI
:10.4103/0974-8490.188884
PMID
:27695262
Background:
Mammea siamensis
(Miq.) T. Anders. is used as a medicinal plant in Thailand and has several traditional therapeutic properties. In a previous study, we isolated eight compounds from the flower of
M. siamensis
and demonstrated that kayeassamin A (KA) exhibited potent antiproliferative activity against human leukemia and stomach cancer cell lines.
Objective:
In this study, we investigated the effect of KA on cell viability and apoptotic mechanisms in HL-60 human leukemia cells.
Materials and Methods:
Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Nuclear morphology and DNA fragmentation were observed using Hoechst 33258 staining and agarose gel electrophoresis, respectively. The sub-G1 phase of cells was analyzed by flow cytometry after the cellular DNA had been stained with propidium iodide. The protein levels of poly (ADP-ribose) polymerase (PARP) and caspases were determined by Western blotting.
Results:
KA exhibited a significant cytotoxic effect in a dose- and time-dependent manner, and induced chromatin condensation, DNA fragmentation, and sub-G1 phase DNA content, known as molecular events associated with the induction of apoptosis. In addition, KA strongly induced the activation of PARP and caspase-3 and -8, with weak caspase-9 activation. Furthermore, KA-induced DNA fragmentation was abolished by pretreatment with z-VAD-FMK (a broad caspase inhibitor), z-DEVD-FMK (a caspase-3 inhibitor), and z-IETD-FMK (a caspase-8 inhibitor), but not by z-LEHD-FMK (a caspase-9 inhibitor) pretreatment.
Conclusion:
These results indicate that KA triggers apoptotic cell death by activation of caspase-3 and -8 in HL-60 cells.
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Effect of
Musa sapientum
stem extract on animal models of depression
p. 249
Aditya J Reddy, Shailendra S Handu, Ashok Kumar Dubey, Pramod Kumari Mediratta, Rimi Shukla, Qazi Mushtaq Ahmed
DOI
:10.4103/0974-8490.188876
PMID
:27695263
Background:
Musa sapientum
, the banana plant, has shown to possess antioxidant activity in previous studies. Oxidative stress has been linked to the pathogenesis of major depressive disorder (MDD) with evidence of increased serum levels of oxidative stress biomarkers in MDD patients.
Objective:
The present study aimed to evaluate the antidepressant activity of
M. sapientum
stem extract (MSSE) in experimental models in mice.
Materials and Methods:
Forced swim test (FST) and tail suspension test (TST) were carried out in five different groups (
n
= 6/group) of mice. The vehicle, standard drug, and the three test groups were orally administered distilled water (10 mL/kg), fluoxetine (25 mg/kg), and incremental doses of 25, 50, and 100 mg of MSSE, respectively, 45 min prior to the experiment.
Results:
On FST, the duration of immobility in control group, which was 161.5 ± 6.78 (in seconds, mean ± standard error of mean [SEM]), decreased to 149.33 ± 2.70 (25 mg/kg MSSE), 120.17 ± 8.35 (50 mg/kg MSSE), and 45.17 ± 4.11 (100 mg/kg MSSE) in the treated groups. On TST, the duration of immobility in control group, which was 173.83 ± 12.65 (mean ± SEM), decreased to 163.17 ± 6.91 (25 mg/kg MSSE), 139.0 ± 5.9 (50 mg/kg MSSE), and 124.0 ± 4.42 (100 mg/kg MSSE) in the treated groups. The difference in the duration of immobility was statistically significant at middle and higher doses, i.e. 50 and 100 mg/kg MSSE (
P
< 0.05) respectively, when compared with the control group in both the tests.
Conclusion:
A significant antidepressant-like activity was found in MSSE, which could be a potential natural compound for use in depression.
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Chemical characterization and cytoprotective effect of the hydroethanol extract from
Annona coriacea
Mart. (Araticum)
p. 253
Jose G.A.S Junior, Henrique D.M Coutinho, Ticiana C.C Boris, Janyketchuly S Cristo, Nara L.F Pereira, Fernando G Figueiredo, Francisco A.B Cunha, Pedro E.A Aquino, Polyana A.C Nascimento, Francisco J.C Mesquita, Paulo H.F Moreira, Saskia T.B Coutinho, Ivon T Souza, Gabriela C Teixeira, Najla M.N Ferreira, Eleonora O Farina, Cicero M.G Torres, Vanderlan N Holanda, Vandbergue S Pereira, Maria I.F Guedes
DOI
:10.4103/0974-8490.188882
PMID
:27695264
Introduction:
Annona coriacea
Mart. (araticum) is a widely distributed tree in the cerrado. Its value is attributed principally to the consumption of its fruit which possesses a large nutritive potential. The objective was to identify the chemical profile and evaluate the antimicrobial and cytoprotective activity of the hydroethanol extract of
A. coriacea
Mart. (HEAC) leaves against the toxicity of mercury chloride.
Materials and Methods:
The characterization of components was carried out using high-performance liquid chromatography (HPLC). The minimum inhibitory concentration (MIC) was determined by microdilution method in broth with strains of
Staphylococcus aureus
,
Escherichia coli
, and
Pseudomonas aeruginosa.
For evaluation of the modulatory and cytoprotective activity of aminoglycoside antibiotics (gentamicin and amikacin) and mercury chloride (HgCl
2
), the substances were associated with the HEAC at subinhibitory concentrations (MIC/8).
Results and Discussion:
The HPLC analysis revealed the presence of flavonoids such as Luteolin (1.84%) and Quercetin (1.19%) in elevated concentrations. The HEAC presented an MIC ≥512 μg/mL and significant antagonistic action in aminoglycosides modulation, and it also showed cytoprotective activity to
S. aureus
(significance
P
< 0.0001) and
E. coli
(significance
P
< 0.05) bacteria against the mercury chloride heavy metal with significance, this action being attributed to the chelating properties of the flavonoids found in the chemical identification.
Conclusions:
The results acquired in this study show that the HEAC presents cytoprotective activity over the tested strains
in vitro
and can also present antagonistic effect when associated with aminoglycosides, reinforcing the necessity of taking caution when combining natural and pharmaceutical products.
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In vitro
antioxidant activities and polyphenol contents of seven commercially available fruits
p. 258
Paramita Basu, Camelia Maier
DOI
:10.4103/0974-8490.188875
PMID
:27695265
Background:
Fruits are considered one of the richest sources of natural antioxidants. Their consumption has been linked to the prevention of oxidative stress-induced diseases.
Objective:
In this study,
in vitro
antioxidant activities of blueberry, jackfruit, blackberry, black raspberry, red raspberry, strawberry, and California table grape extracts were evaluated.
Materials and Methods:
Antioxidant activities were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), nitric oxide (NO), superoxide anion (O
2
−
) scavenging assays, and ferric reducing power.
Results:
Black raspberry extract had the highest phenolic (965.6 ± 2.9 mg gallic acid equivalents [GAE]/g), flavonoid (186.4 ± 1.7 mg quercetin equivalents/g), and proanthocyanidin (2677 ± 71.1 mg GAE/g) contents. All fruit extracts exhibited increasing radical scavenging activities with increased concentrations. At 100 μg/ml, red raspberry extract showed the highest ferric reducing power (A
700
=0.3 ± 0.0052) and FRAP activity (A
593
=11.43 mM Fe
2+
/g). Black raspberry extract (100 μg/ml) exhibited the highest DPPH activity (A
517
=89.03 ± 0.0471). Jackfruit extract (100 μg/ml) had the highest ABTS (A
734
=35.6 ± 0.613), NO (A
540
=81.7 ± 0.2), and O
2
−
radical scavenging (A
230
=55.5 ± 0.2) activities. Positive correlations were observed between IC
50
values for different radical scavenging activities and different polyphenolics. Red raspberry extract had the highest Pearson's coefficient values (0.952–1) between total phenolics, flavonoids, and proanthocyanidins and DPPH and superoxide radical scavenging activities.
Conclusions:
The antioxidant rich fruits in this study are good source of functional food and nutraceuticals that have the potential to improve human health.
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Evaluation of
In vitro
antiviral activity of
Datura metel
Linn. against rabies virus
p. 265
Soumen Roy, Sandeepan Mukherjee, Sandip Pawar, Abhay Chowdhary
DOI
:10.4103/0974-8490.188874
PMID
:27695266
Objective:
The soxhlet and cold extracts of
Datura metel
Linn. were evaluated for
in vitro
antirabies activity.
Materials and Methods:
Soxhlet and cold extraction method were used to extract
Datura
(fruit and seed) extracts.
In vitro
cytotoxicity assay was performed by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide assay. Based on the CC50 range, the
in vitro
antirabies activity of the extracts was screened by rapid fluorescent focus inhibition test and molecular method.
Results:
The
Datura
(fruit and seed) extracts were not cytotoxic below 5 mg/ml (CC50). Titer of 10
−4
rabies virus challenge virus standard (RV CVS) (1 50% tissue culture infective dose [1 TCID50]) was obtained by RFFT method and the challenge dose of 10 TCID50 was used for antirabies assay.
Datura
fruit and seed (soxhlet and cold) extracts showed 50% inhibition of RV CVS at 2.5 mg/ml and 1.25 mg/ml (inhibitory concentration 50% [IC50]), respectively. The tested extracts showed selectivity index (CC50/IC50) ranging from 2 to 4. The viral RNA was extracted and real-time reverse transcription-polymerase chain reaction was performed which also revealed a 2-fold reduction of viral load at 1.25 mg/ml of the
Datura
seed (soxhlet methanolic and cold aqueous) extracts.
Conclusion:
To the best of our knowledge, this is the first study of
in vitro
antiviral activity of
D. metel
Linn. against rabies virus.
Datura
seed extracts have a potential
in vitro
antirabies activity and, in future, can be further screened for
in vivo
activity against rabies virus in murine model.
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Influence of the extractive method on the recovery of phenolic compounds in different parts of
Hymenaea martiana
hayne
p. 270
Fernanda Granja da Silva Oliveira, Sarah Raquel Gomes de Lima-Saraiva, Ana Paula Oliveira, Suzana Vieira Rabelo, Larissa Araujo Rolim, Jackson Roberto Guedes da Silva Almeida
DOI
:10.4103/0974-8490.188885
PMID
:27695267
Background:
Popularly known as “jatobá,”
Hymenaea martiana
Hayne is a medicinal plant widely used in the Brazilian Northeast for the treatment of various diseases.
Objective:
The aim of this study was to evaluate the influence of different extractive methods in the production of phenolic compounds from different parts of
H. martiana
.
Materials and Methods:
The leaves, bark, fruits, and seeds were dried, pulverized, and submitted to maceration, ultrasound, and percolation extractive methods, which were evaluated for yield, visual aspects, qualitative phytochemical screening, phenolic compound content, and total flavonoids.
Results:
The highest results of yield were obtained from the maceration of the leaves, which may be related to the contact time between the plant drug and solvent. The visual aspects of the extracts presented some differences between the extractive methods. The phytochemical screening showed consistent data with other studies of the genus. Both the vegetal part as the different extractive methods influenced significantly the levels of phenolic compounds, and the highest content was found in the maceration of the barks, even more than the content found previously. No differences between the levels of total flavonoids were significant. The highest concentration of total flavonoids was found in the ultrasound of the barks, followed by maceration on this drug. According to the results, the barks of
H. martiana
presented the highest total flavonoid contents.
Conclusion:
The results demonstrate that both the vegetable and the different extractive methods influenced significantly various parameters obtained in the various extracts, demonstrating the importance of systematic comparative studies for the development of pharmaceuticals and cosmetics.
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Anti-Advanced glycation end-product and free radical scavenging activity of plants from the yucatecan flora
p. 276
Wendy del C Dzib-Guerra, Fabiola Escalante-Erosa, Karlina Garcia-Sosa, Severine Derbre, Patricia Blanchard, Pascal Richomme, Luis M Pena-Rodriguez
DOI
:10.4103/0974-8490.188883
PMID
:27695268
Background:
Formation and accumulation of advanced glycation end-products (AGE) is recognized as a major pathogenic process in diabetic complications, atherosclerosis and cardiovascular diseases. In addition, reactive oxygen species and free radicals have also been reported to participate in AGE formation and in cell damage. Natural products with antioxidant and antiAGE activity have great therapeutic potential in the treatment of diabetes, hypertension and related complications. Objective: to test ethanolic extracts and aqueous-traditional preparations of plants used to treat diabetes, hypertension and obesity in Yucatecan traditional medicine for their anti-AGE and free radical scavenging activities.
Materials and Methods:
ethanolic extracts of leaves, stems and roots of nine medicinal plants, together with their traditional preparations, were prepared and tested for their anti-AGE and antioxidant activities using the inhibition of advanced glycation end products and DPPH radical scavenging assays, respectively.
Results:
the root extract of C. fistula (IC
50
= 0.1 mg/mL) and the leaf extract of P. auritum (IC
50
= 0.35 mg/mL) presented significant activity against vesperlysine and pentosidine-like AGE. Although none of the aqueous traditional preparations showed significant activity in the anti-AGE assay, both the traditional preparations and the ethanolic extracts of E. tinifolia, M. zapota, O. campechianum and P. auritum showed significant activity in the DPPH reduction assay. <65
Conclusions:
the results suggest that the metabolites responsible for the detected radical-scavenging activity are different to those involved in inhibiting AGE formation; however, the extracts with antioxidant activity may contain other metabolites which are able to prevent AGE formation through a different mechanism.
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Elucidation of flavonoids from
Carissa congesta
,
Polyalthia longifolia
, and
Benincasa hispida
plant extracts by hyphenated technique of liquid chromatography-mass spectroscopy
p. 281
Gaurav M Doshi, Vivek V Nalawade, Aaditi S Mukadam, Pratip K Chaskar, Sandeep P Zine, Rakesh R Somani, Hemant D Une
DOI
:10.4103/0974-8490.186578
PMID
:27695269
Background:
Carissa congesta
(CC),
Polyalthia longifolia
(PL), and
Benincasa hispida
(BH) are economically important plants.
Objective:
Current research encompasses identification of quercetin and rutin and their analogues by liquid chromatography-mass spectroscopy (LC-MS) from the selected plant species.
Materials and Methods:
Fresh roots, leaves, and seeds of CC, PL, and BH plants respectively were shade-dried followed by extraction and elucidation of rutin and quercetin by LC-MS.
Results:
Structural elucidation of CC, PL, and BH extracts revealed the presence of flavonoids such as quercetin (m/z 301) and rutin (m/z 610) as the parent ions along with presence of close analogues such as quercetin-
O
-hexoside, Vicenin 2, quercetin-3-
O
-xyloside/arabinoside, and quercetin-3-
O
-glucoside were identified as fragments.
Conclusions:
Thus, CC, PL, and BH extracts revealed the presence of flavonoids belonging to the class of flavonols such as rutin and quercetin.
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Bioactivity of diterpens from the ethyl acetate extract of
Kingiodendron pinnatum
rox. hams
p. 287
Komal Kumar Javarappa, Attemode Girijanna Devi Prasad, AJ Mahadesh Prasad, Chetana Mane
DOI
:10.4103/0974-8490.188871
PMID
:27695270
Background:
Kingiodendron pinnatum
Rox. Hams. is an endangered medicinal plant used in gonorrhoe, catarrhal conditions of genito-urinary and respiratory tracts. The scientific and pharmacological formulation of
K. pinnatum
has not been established so far though it is being traditionally used by tribes of the region.
Objective:
P hytochemical screening and identification of the bioactive compounds from the ethyl acetate extract of
Kingiodendron pinnatum Rox. Hams.
Materials and Methods:
Chromatographic separation was carried out by thin layer chromatography and column chromatography. Bio-autography of the column fractioned extract and TLC chromatogram were evaluated
in vitro
for antibacterial activity. The PTLC, HP TLC were used for crude extract and HPLC, LCMS, FTIR,
1
HNMR and
13
CNMR were employed for the isolated compound in the ethyl acetate extract of
K. pinnatum.
Results:
Evaluation of solvent system for chromatographic separation revealed that ethyl acetate: petroleum ether in the ratio of 7:2.5 ml was the most appropriate one for the separation of diterpene compounds. The antibacterial bio-autography screening of TLC separated compound showed positive activity with
Staphylococcus aureus
and negative activity with
Escherichia coli
. Spectroscopic analysis of the isolated compound from the ethyl acetate extract of
K. pinnatum
revealed the presence of diterpene compound.
Conclusion:
It is evident from the present study that the ethyl acetate extract of
K. pinnatum
is rich in diterpene compounds and having potential antibacterial activity.
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Inhibition of human cytochrome p450 2c8-catalyzed amodiaquine n-desethylation: Effect of five traditionally and commonly used herbs
p. 292
Yasotha Devi Muthiah, Chin Eng Ong, Siti Amrah Sulaiman, Rusli Ismail
DOI
:10.4103/0974-8490.188886
PMID
:27695271
Background:
In Southeast Asia and many parts of the world, herbal products are increasingly used in parallel with modern medicine.
Objective:
This study aimed to investigate the effects of herbs commonly used in Southeast Asia on activity of cytochrome P450 2C8 (CYP2C8), an important human hepatic enzyme in drug metabolism.
Materials and Methods:
The selected herbs, such as
Eurycoma longifolia Jack
(ELJ),
Labisia pumila
(LP),
Echinacea purpurea
(EP),
Andrographis paniculata
(AP), and
Ginkgo biloba
(GB), were subjected to inhibition studies using an
in vitro
CYP2C8 activity marker, amodiaquine N-desethylase assay. Inhibition parameters, inhibitory concentration 50% (IC
50
), and K
i
values were determined to study the potency and mode of inhibition.
Results:
All herbs inhibited CYP2C8 with the following order of potency: LP > ELJ > GB > AP > EP. LP and ELJ inhibited potently at K
i
's of 2 and 4 times the K
i
of quercetin, the positive control. The inhibition by LP was uncompetitive in nature as compared to competitive or mixed type inhibition observed with other herbs. GB exhibited moderate inhibitory effect at a K
i
6 times larger than quercetin K
i
. AP and EP, on the other hand, showed only weak inhibition.
Conclusion:
The herbs we chose represented the more commonly used herbs in Southeast Asia where collision of tradition and modernization in healthcare, if not properly managed, may lead to therapeutic misadventures. We conclude that concurrent consumption of some herbs, in particular, LP and ELJ, may have relevance in drug-herb interactions via CYP2C8 inhibition
in vivo
.
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Wound healing activity of silibinin in mice
p. 298
Rojalini Samanta, Ashok K Pattnaik, Kishanta K Pradhan, Beena K Mehta, Shakti P Pattanayak, Sugato Banerjee
DOI
:10.4103/0974-8490.188880
PMID
:27695272
Background:
Silibinin is a semi-purified fraction of silymarin contained in milk thistle (
Silybum marianum Asteraceae
). Primarily known for its hepatoprotective actions, silymarin may also stimulate epithelialization and reduce inflammation in excision wound. Previous studies show antioxidant, anti-inflammatory, and antimicrobial actions of silibinin. However, wound healing property of silibinin is not well studied.
Objective:
This study investigates wound healing activity of silibinin topical formulation.
Materials and Methods:
Wound healing activity of 0.2% silibinin gel was assessed by incision and excision wound models in mice. Animals were divided into gel base, silibinin gel, and Mega Heal gel
®
treated groups with six animals in each group. Wound contraction, wound tissue tensile strength, and hydroxyproline content were measured, and histopathological evaluation of wound tissue of all the above treatment groups was carried out.
Results:
Application of 0.2% silibinin hydrogel for 8 days led to 56.3% wound contraction compared to 64.6% using standard Mega Heal gel with a subsequent increase in hydroxyproline content, which was significantly higher (
P
< 0.001) over control animals showing 33.2% contraction. After 14 days, percentage of contraction reached 96.1%, 97.6%, and 86.7%, respectively. Wound tissue tensile strength with silibinin (223.55 ± 3.82 g) and standard (241.38 ± 2.49 g) was significantly higher (
P
< 0.001) than control (174.06 ± 5.75 g). Histopathology of silibinin and standard gel treated wound tissue showed more fibroblasts, fewer macrophage infiltration, and well-formed collagen fibers.
Conclusion:
Here, we show potent wound healing activity of silibinin hydrogel formulation.
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Antihyperglycemic and insulin secretagogue activities of
Abrus precatorius
leaf extract
p. 303
Balekari Umamahesh, Ciddi Veeresham
DOI
:10.4103/0974-8490.188881
PMID
:27695273
Aim:
Abrus precatorius
leaves methanolic extract (APME) was evaluated for
in vivo
antihyperglycemic activity and
in vitro
insulinotropic effect.
Materials and Methods:
In vivo
antihyperglycemic and insulin secretagogue activities were assessed in streptozotocin-induced diabetic rats by oral administration of APME (200 mg/kg body weight [bw]) for 28 days.
In vitro
insulin secretion mechanisms were studied using mouse insulinoma beta cells (MIN6-β).
In vivo
body weight and blood glucose and
in vivo
and
in vitro
insulin levels were estimated.
Results:
In diabetic rats, APME treatment significantly restored body weight (26.39%), blood glucose (32.39%), and insulin levels (73.95%) in comparison to diabetic control rats. In MIN6-β cells, APME potentiated insulin secretion in a dependent manner of glucose (3–16.7 mM) and extract (5–500 μg/mL) concentration. Insulin secretagogue effect was demonstrated in the presence of 3-isobutyl-1-methyl xanthine, glibenclamide, elevated extracellular calcium, and K
+
depolarized media. Insulin release was reduced in the presence of nifedipine, ethylene glycol tetra acetic acid (calcium blocking agents), and diazoxide (potassium channel opener).
Conclusion:
The study suggests that APME antihyperglycemic activity might involve the insulin secretagogue effect by pancreatic beta cells physiological pathways via K
+
-ATP channel dependent and independently, along with an effect on Ca
2+
channels.
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Effects of
Curcuma xanthorrhiza
extracts and their constituents on phase ii drug-metabolizing enzymes activity
p. 309
Nurul Afifah Mohd Salleh, Sabariah Ismail, Mohd Rohaimi Ab Halim
DOI
:10.4103/0974-8490.188873
PMID
:27695274
Background:
Curcuma xanthorrhiza
is a native Indonesian plant and traditionally utilized for a range of illness including liver damage, hypertension, diabetes, and cancer.
Objective:
The study determined the effects of
C. xanthorrhiza
extracts (ethanol and aqueous) and their constituents (curcumene and xanthorrhizol) on UDP-glucuronosyltransferase (UGT) and glutathione transferase (GST) activities.
Materials and Methods:
The inhibition studies were evaluated both in rat liver microsomes and in human recombinant UGT1A1 and UGT2B7 enzymes.
p
-nitrophenol and beetle luciferin were used as the probe substrates for UGT assay while 1-chloro-2,4-dinitrobenzene as the probe for GST assay. The concentrations of extracts studied ranged from 0.1 to 1000 μg/mL while for constituents ranged from 0.01 to 500 μM.
Results:
In rat liver microsomes, UGT activity was inhibited by the ethanol extract (IC
50
=279.74 ± 16.33 μg/mL). Both UGT1A1 and UGT2B7 were inhibited by the ethanol and aqueous extracts with IC
50
values ranging between 9.59–22.76 μg/mL and 110.71–526.65 μg/Ml, respectively. Rat liver GST and human GST Pi-1 were inhibited by ethanol and aqueous extracts, respectively (IC
50
=255.00 ± 13.06 μg/mL and 580.80 ± 18.56 μg/mL). Xanthorrhizol was the better inhibitor of UGT1A1 (IC
50
11.30 ± 0.27 μM) as compared to UGT2B7 while curcumene did not show any inhibition. For GST, both constituents did not show any inhibition.
Conclusion:
These findings suggest that
C. xanthorrhiza
have the potential to cause herb-drug interaction with drugs that are primarily metabolized by UGT and GST enzymes.
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