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   Table of Contents - Current issue
Coverpage
April 2020
Volume 16 | Issue 70
Suppl 2
Page Nos. 229-442

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ORIGINAL ARTICLES  

Naringenin sensitizes lung cancer NCI-H23 cells to radiation by downregulation of akt expression and metastasis while promoting apoptosis Highly accessed article p. 229
Taranga Jyoti Baruah, Kimrose Hauneihkim, Lakhon Kma
DOI:10.4103/pm.pm_535_19  
Background: Naringenin (NGN) is a flavonoid that has shown anticancer activities, but the ability of NGN to radiosensitize cells of the non-small cell variety of lung cancer has not been looked into yet. Objectives: The objective of the study was to check for the ability of NGN to promote radiosensitization of the lung cancer cell line – NCI-H23 (H23). Materials and Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, trypan blue exclusion assay, and colony-forming assay were performed to check the effect of NGN, with and without X-ray treatment, on the viability of cancer cells. Protein carbonylation, DNA fragmentation, and caspase-3 activity were determined. The levels of pAkt, Akt, matrix metalloproteinase-2 (MMP-2), RAD50, and p21 proteins were looked at by Western blotting. Messenger RNA (mRNA) levels of AKT1, CASPASE3, BAX, BCL2, and BCLXL were also checked. Results: When combined with radiation, NGN lowered the survivability of H23 cells. NGN showed a prooxidant effect while no DNA fragmentation was observed. mRNA levels of CASPASE3 and caspase-3 activity also showed an increase. pAkt, Akt, MMP-2, and p21 protein levels were lowered in the NGN-treated groups, while the RAD50 protein levels showed an increase. The mRNA levels of BCL2 and BCLXL were lowered, while BAX mRNA levels were elevated in response to NGN treatment. Conclusion: The results showed that NGN, used singularly or in combination with radiation, can lower the procancerous and prometastatic Akt, p21, and MMP-2 proteins while upregulating the apoptotic process.
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Polyphenol-enriched fraction and the compounds isolated from Garcinia indica fruits ameliorate obesity through suppression of digestive enzymes and oxidative stress Highly accessed article p. 236
Kavita Munjal, Sheeraz Ahmad, Apeksha Gupta, Abdul Haye, Saima Amin, Showkat R Mir
DOI:10.4103/pm.pm_587_19  
Background: The growing incidence of obesity has attracted the concern of researchers to look for effective interventions for its management. Garcinia indica is a widely known ethnomedicine used to treat gastritis, diabetes, and metabolic disorders. Recently, there has been a surge in the use of G. indica fruits in weight loss preparations. Objective: To explore the anti-obesity effect of polyphenol-enriched fraction and the compounds isolated from G. indica fruits through the inhibition of key metabolizing enzymes and oxidative stress. Materials and Methods: Fruits of G. indica were extracted with methanol that was subjected to liquid–liquid extraction to yield ethyl acetate fraction (FGIEF), chloroform, butanol, and aqueous fractions. The extract and the fractions were screened for the total polyphenols content (TPC), total flavonoids content (TFC), pancreatic lipase (PL) and α-amylase inhibition, and antioxidant activity. The effect of FGIEF on the viability of 3T3-L1 preadipocytes using 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide assay was assessed. FGIEF was subjected to normal-phase medium-pressure liquid chromatography (MPLC) to isolate compounds 1–3. Docking studies of representative polyphenols and the isolated compounds 1–3 with PL were undertaken to derive supporting evidence. Results: Among all the fractions, FGIEF was found to have the highest TPC (375.6 ± 4.5 gallic acid equivalent mg/g) and TFC (237.2 ± 6.2 quercetin equivalent mg/g). The extract and fractions showed concentration-dependent digestive enzyme inhibition and antioxidant effect. FGIEF inhibited PL and α-amylase (IC50values 257.3 ± 3.7 and 349.7 ± 5.8 μg/mL, respectively). FGIEF did not induce any cell death up to 800 μg/mL. MPLC of FGIEF led to the isolation of luteolin (1), napthyldioxolol (2), and oleantrienoic acid glucoside (3). Preferential inhibition by polyphenols compared to other compounds was notable in the docking studies. Conclusion: The study suggests that the fruits of G. indica exhibit anti-obesity effect through the inhibition of digestive enzymes that can be mainly attributed to the presence of polyphenols.
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New phytopharmaceutical formulations: Development and characterization of tablets containing the aerial part of the plant pulverized and the soft extract from Bidens pilosa standardized on rutin Highly accessed article p. 246
Aline Neves Pereira, Mariana Cristina de Morais, Nathália Olívia de Sousa Garcia, Nathalia Pedroso Barbosa, Maythsulene Inácio de Sousa Oliveira, Emannuel Ítalo Alves Campos, Edemilson Cardoso da Conceição
DOI:10.4103/pm.pm_374_19  
Background: Bidens pilosa, popularly known as black jack, has high interest as a medicinal plant. A large part of its biological activities are attributed to their constitution in predominance by secondary metabolites such as the flavonoids, like rutin. Objective: The aim of the present study was to obtain oral solid dosage forms (tablets) containing the aerial part of the plant pulverized and soft extract of B. pilosa standardized on rutin, as well as the validation of an analytical method for determination of the rutin content of the powder, soft extract and of the tablets. Materials and Methods: The liquid extract from B. pilosa was obtained by percolation and concentrated until it became a soft extract. An analytical method, by high-performance liquid chromatography, was validated for the quantification of rutin in the soft extract. Tablets containing the aerial part of the plant pulverized and the soft extract of B. pilosa quantified on rutin was obtained and characterized. After, the method for quantification of rutin on the tablets was covalidated. Results: The rutin content in the raw material was 0.71% (m/m), while in the soft extract was 7.29% (m/m). The dissolution efficiency of the tablets was significantly higher, for both formulations in the pH 6.8 medium compared to medium with pH 1.2. Pilot tablets PH and SE presented results above of that recommended after 120 days. Conclusion: Pilot tablets SE, with soft extract, presented higher content of rutin than pilot tablets PH, with powder of the aerial part from raw material. This new phytopharmaceuticals formulation proved to be promising to be a strategy to carry out the active principles of B. pilosa .
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Neurocognitive investigation of Morinda tinctoria against amyloid beta-induced oxidative insult and cognitive impairment in albino mice: A phytotherapeutic approach p. 255
D Sivaraman, M Arun, R Kannan, PS Pradeep, P Muralidharan
DOI:10.4103/pm.pm_284_19  
Background: Alzheimer's is a progressive neurodegenerative disorder characterized by cognitive declination associated with several clinicopathological changes. Due to consistent drawback in the conventional therapy, now the attentions toward herbal therapeutics have been increased in recent times. Morinda tinctoria Roxb (MT) is a novel medicinal herb reported with versatile therapeutic activity. Still now, there is no proper scientific data available to confirm its efficacy against neurodegeneration. Objectives: The objective of the present research is to investigate the neurocognitive enhancing potential of MT against amyloid beta (Aβ) (25–35)-induced memory dysfunction in mice. Materials and Methods: Animals were pretreated with ethanol extract of MT (EEMT) and standard donepezil followed by single intracerebro ventricular injection of Aβ25–35. Estimation of antioxidant enzymes, metabolic enzymes, and neurotransmitters was performed along with quantification of inflammatory cytokines using quantitative polymerase chain reaction method. Results: The outcome of the study clearly indicates that treatment with EEMT (200 and 400 mg/kg) and donepezil (5 mg/kg) had significantly ameliorated the cognitive stress induced by Aβ25–35, which was evident from the data obtained from memory and learning task. There was a sequential decrease in pro-inflammatory cytokines such as interleukin (IL)-6, tumor necrosis factor, IL-1, and nuclear factor-κ level in EEMT and donepezil treated groups. Histological finding of the samples belonging to EEMT and donepezil treated groups reveals the presence of dense network of pyramidal cell in CA layers with increased number of granular cells aligned on the dentate gyrus zone of the hippocampi. Conclusion: Neurotherapeutics from the herbal origin advocates the potential therapeutic efficacy against Alzheimer's and may become novel entity in the clinical management of neurodegenerative diseases.
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Turcuron: A standardized bisacurone-rich turmeric rhizome extract for the prevention and treatment of hangover and alcohol-induced liver injury in rats p. 263
HV Sudeep, K Venkatakrishna, K Sundeep, HS Vasavi, Amritha Raj, S Chandrappa, K Shyamprasad
DOI:10.4103/pm.pm_32_20  
Objectives: The present work investigated the hepatoprotective effects of Turcuron, a first-of-its-kind extract from Curcuma longa tubers containing 8% bisacurone, with respect to alcohol-induced liver injury in rats. We have further studied its efficacy in improving alcohol metabolism in rats. Materials and Methods: In vitro studies were performed using nitric oxide (NO) scavenging and xanthine dehydrogenase activity. Alcohol-induced liver injury was established in male Sprague Dawley rats by oral administration of 4 g/kg/day of 40% ethanol for 6 weeks. Turcuron (150 and 300 mg/kg) was administered to the rats after 3 weeks of alcohol treatment till the end of the study. In alcohol-induced hangover model, male Wistar rats were administered with single oral dose of 5 ml/kg b.w. of alcohol, 1 h after the treatment with Turcuron (200, 300, and 400 mg/kg). Results: In our preliminary study, Turcuron markedly inhibited the NO production and xanthine dehydrogenase activity in vitro . In the in vivo model rats, Turcuron restored the liver architecture and biochemical parameters and reduced the expression of inflammatory proteins in the liver. Furthermore, Turcuron reduced the blood alcohol and acetaldehyde levels in alcohol hangover model rats. It also increased the activity of Aldehyde dehydrogenase (ALDH) significantly in the liver. Conclusion: Here, we report for the first time, Turcuron-mediated liver protection attributing to the presence of high content of bisacurone in the turmeric extract. Collectively, our data provide valuable evidence for the application of bisacurone-rich turmeric extract as a functional food and/or medicine.
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Evaluation of antipropulsive activity of Decachaeta incompta (DC) king and robinson and its sesquiterpene lactones on induced hyperperistalsis in rats p. 272
Fernando Calzada, Miguel Valdés, Elizabeth Barbosa, Claudia Velázquez, Elihú Bautista
DOI:10.4103/pm.pm_540_19  
Background: Decachaeta incompta (DC) King and Robinson (Asteraceae ) is a plant used in Mexico especially in rural communities in the State of Oaxaca by traditional medicine practitioners to treat diarrhea. However, scientific evidence does not exist in any literature on antipropulsive activity of D. incompta and its sesquiterpene lactones that explain in part the traditional use of this plant. Objectives: The present study was undertaken to evaluate a possible antipropulsive activity of the dichloromethane crude extract and two sesquiterpene lactones from Decachaeta incompta. Materials and Methods: Charcoal-gum acacia, lactose and castor oil-induced hyperperistalsis assays were used to assess the antipropulsive activity of the crude extract from D. incompta and its sesquiterpene lactones, incomptines A and B. Results: The antipropulsive activity of D. incompta was investigated by studying the effect of the aerial parts dichloromethane extract and incomptines in three models of induced hyperperistalsis in rats. Dichloromethane extract showed significant inhibition of charcoal-gum acacia and castor oil-induced hyperperistalsis with values of ID5031.70 and 27.31 mg/kg, respectively. Incomptine A, showed significant inhibition of charcoal-gum acacia, lactose and castor oil induced hyperperistalsis with values of ID5021.10, 14.20 and 16.20 mmol/kg, respectively. In contrast, incomptine B showed inhibition of charcoal-gum acacia and lactose-induced hyperperistalsis with values of ID5011.90 and 9.60 mmol/kg, respectively. Conclusion: The results indicate that dichloromethane extract of D. incompta and its sesquiterpene lactones have antipropulsive activity. Furthermore, these results give additional support to the reports of the traditional use of D. incompta for the treatment of diarrhea.
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In vitro antiplasmodium and chloroquine resistance reversal effects of mangostin p. 276
Zaid Osamah Ibraheem, Roslaini Abdul Majid, Ashraf Alapid, Hasidah Mohammad Sedik, MN Sabariah, Mohammad Faruq, Voon Kin Chin, Rusliza Basir
DOI:10.4103/pm.pm_510_19  
Aim/Background: Chloroquine (CQ) resistance that appeared among different strains of Plasmodium falciparum is considered as the worst catastrophe in the realm of malaria chemotherapy. CQ is still the most favorable drug among other antimalarials especially in the poor endemic areas due to its high potency and cost-effectiveness. This urged the scientists to explore for other alternatives or sensitizers for CQ. Materials and Methods: In this experiment, the antiplasmodium and the CQ resistance reversing effects of mangostin were tested using the in vitro SYBRE green-1-based drug sensitivity assay and the isobologram technique, respectively. Furthermore, its safety level toward two types of mammalian cells, namely Vero cells and red blood cells (RBCs), was screened using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-based drug sensitivity and the RBCs hemolysis assays, respectively. On the other hand, its effect against hemozoin formation was screened using β-hematin formation. Meanwhile, its molecular characters were determined the in silico on-line free chemi-informatic Molinspiration software for the molecular characterization as well as the standard testes for the measurement of the antioxidant effect. Results: Mangostin was moderately effective and selective toward the plasmodium so it is unsuitable to be a substituent for CQ. But it improved the sensitivity of the parasite to CQ. The molecular elucidation suggests that its CQ resistance reversal effect can be ascribed to its ability to interfere with hemozoin formation or the intravacuolar accumulation of CQ. Conclusion: Overall, the study suggests mangostin as a possible pharmacophore to develop new CQ resistance reversing agents but further studies are recommended to confirm this notion.
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Amelioration of doxorubicin-induced cardiotoxicity by oral lyophilized Dunaliella salina supplement in a female wistar rat model with active estrous cycle and surgical menopause p. 284
Sankaranarayanan Gomathinayagam, Kodiveri Muthukaliannan Gothandam
DOI:10.4103/pm.pm_52_20  
Background: Whole-cell Dunaliella salina is effective in preventing doxorubicin (DOX)-induced cardiotoxicity in female Wistar rats with surgical menopause. Materials and Methods: In our experiment, we surgically induced menopause in a group of Wistar rats and given doses of DOX and/or D. salina lyophilized powder and compared its effects with the group of rats having a normal estrous cycle. A cumulative dose of 25 mg/kg BW of DOX was given to induce cardiotoxicity and was countered by 1000 mg/kg BW of D. salina oral supplement or 10 mg/kg BW of tamoxifen. Totally two groups of rats were supplemented with D. salina , in one of the groups it was given either a week before DOX initiation, and in the other group, it was given alongside DOX doses. Results: The concomitant D. salina supplement has been found to reduce the cardiac damage due to DOX better than the groups that received the supplement beforehand DOX initiation or tamoxifen. Besides, the supplement was also found to maintain nitroso-redox balance, thus preventing cardiomyocyte death as compared with the rats that received DOX alone. It was evident from the histopathological examination and serum levels of cardiac troponin-T. Conclusion: Thus, oral carotenoid supplementation can be a promising functional food over tamoxifen, which would help in recovering from menopause and prevent anthracycline cardiotoxicity.
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DNA barcoding of endemic and endangered orchids of India: A molecular method of species identification p. 290
Deepti Srivastava, K Manjunath
DOI:10.4103/pm.pm_574_19  
Background: Orchids are economically important, particularly in horticulture, floristry, pharmaceutical, and fragrance industries. India is a paradise for 1256 orchids, of which 31% (388 species) are endemic. Although Indian orchids are known in floristry, there is still a lot of room to use their bioactive compounds to promote their commercialization. Easy and accurate identification is first step towards conservation and commercial cultivation of endemic and endangered orchid species. This requirement can be accomplished using DNA barcoding technique. Materials and Methods: A total of 62 samples belonging to 35 species, 7 genera were collected for DNA barcoding studies. Evolutionary divergences and barcoding gap were calculated using MEGA-X software to screen the most suitable barcode region among the ITS, matK, rbcL , and trnH-psbA loci. BLAST analysis was used to identify barcoding locus presenting maximum species resolution. Phylogenetic analyses were performed to test harmony between barcoding and taxonomy. Results: We have generated 133 barcoding sequences, out of which, 46 sequences were found unique and new to GenBank database. Evolutionary divergence analysis showed the best result for ITS , where intra-specific and inter-specific divergence ranged between 0.0000–0.0300 and 0.0322–0.3765 correspondingly. It indicated clear barcoding gap, which was sufficient to robustly infer identities for taxa. BLAST-based evaluation concluded that largest number of barcode sequences (94.64%) could be identified using ITS locus followed by rbcL (78.69%) and matK (51.61%). In addition, the optimal phylogenetic tree was established using the ITS locus sequences, which complemented the orchid taxonomy. Conclusion: This study recommends ITS as best single locus barcoding region for identifying the orchids of India.
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Portulaca oleracea exposed to polycyclic aromatic hydrocarbon pollution: Mapping down nutraceutical and histochemical changes p. 300
Roshni Tandey, Kavi Bhushan Singh Chouhan, Vivekananda Mandal
DOI:10.4103/pm.pm_15_20  
Aim: Polycyclic aromatic hydrocarbons (PAHs) are extremely carcinogenic environmental pollutants which have now become a global environmental problem. Such pollutants can accumulate in soil and can adversely affect the growth and physiology of plants. The current study aims to investigate the effect of such pollutants on the plants secondary metabolism with special emphasis on the production of nutraceutical principles. Materials and Methods: A well-known dietary plant Portulaca oleracea was collected from agricultural land in close vicinity to thermal power units, and results were compared to a background sample. Pigment estimation, evaluation of total phenolics/flavonoids, and Non-enzymatic antioxidant principles, namely ascorbic acid and α-tocopherol were carried out. Primary metabolites, such as total proteins and carbohydrates, were also estimated. The identification of individual phenolic and flavonoid principles were also carried out. Results were supported with real-time histochemical evidence and scanning electron microscopy (SEM) studies. Results: Chlorophyll a showed a significant reduction of 40.85% when compared to control and so was the case with β-carotene, which recorded a decline of 33.5% when compared to control. Total phenolics and flavonoids, ascorbic acid, and α-toopherol showed a decline of 42.25%, 28.17%, 45.5%, and 81.9%, respectively, when compared to control. Gallic acid, p-coumaric acid, ferulic acid, naringenin, quercetin, ellagic acid, and rutin were found to be significantly lesser in pollution exposed plants. Significant cell death was evident from histochemical studies as well, along with blockage of stomata as reflected from SEM studies. Conclusion: P. oleracea exposed to PAH pollution showed a significant decline in the production of phytochemicals with special emphasis on nutraceutical contents.
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Neuroprotective effect of compounds isolated from Euonymus alatus on glutamate-induced oxidative stress in HT22 hippocampal cells p. 308
Youn Sik Jung, Hyeon Woo Lee, Choong Je Ma
DOI:10.4103/pm.pm_450_19  
Background: Euonymus alatus is used to treat diabetes in China. It is also known to have antioxidant and anti-inflammatory effects. Objectives: In this study, we isolated 10 compounds from E. alatus and confirmed that compounds whether protected neuroral cell (HT22) against glutamate induced toxicity. Materials and Methods: The n -hexane fraction of E. alatus was significantly protected HT22 cells injured by the excitotoxic amino acid, L-glutamate. We isolated ten compounds from n-hexane fraction of E. alatus , and they were identified as moretenone (1), moretenol (2), friedelanol (3), lupenone (4), β-sitosterol (5), betulin (6), undecanoic acid, 1,2-phenylene ester (7), glycerol 1-tetracosanoate (8), methyl hydrogen tetradecanedioate (9), and 10,13-nonadecadienoic acid, methyl ester (10) by spectroscopic data such as UV, IR, NMR, Mass spectroscopy. Results: Their neuroprotective activity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Betulin (6) and methyl hydrogen tetradecanedioate (9) had significant neuroprotective activity against glutamate-injured HT22 cells. Furthermore, reactive oxygen species level and intracellular Ca2+ was decresed by betulin (6) and methyl hydrogen tetradecanedioate (9) and these compounds increased mitochondrial membrane potential, total glutathione (GSH) level, GSH reductase activity and GSH peroxidase activity. Conclusion: Our results suggest that betulin (6) and methyl hydrogen tetradecanedioate (9) significantly protect HT22 cells against glutamate-induced oxidative stress, through anti-oxidative activities.
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Effect of poly herbal formulation “Karisalai chooranam ” against detrimental effects of psychological stress p. 315
S Mary Princess Sulekha, G Dayanand Reddy, A Muthuvel
DOI:10.4103/pm.pm_517_19  
Background: The association of psychiatric illness with altered cytokine profile and changes in neurobehavior are well known. “Karisalai chooranam” (KSC) is a polyherbal preparation, contains equal proportion of six ingredients namely Eclipta prostrata Linn., Acalypha indica Linn., Sphaeranthus indicus Linn., Indigofera tinctoria Linn., Centella asiatica Linn., and Wedelia chinensis. Restraint stress is reported to be a model for psychological stress. It was hypothesized that KSC might protect against restraint stress-induced detrimental effects. Objectives: The objective is to evaluate the efficacy of KSC against detrimental effects of psychological stress. Materials and Methods: Male Wistar albino rats were subjected to restraint stress (6 h/day, 21 days). At the end of stress, rats were subjected to elevated plus maze (EPM) and Moris Water Maze studies. Blood was collected and examined for interleukin-6 (IL-6), IL-10 by Enzyme-Linked Immuno Sorbent Assay. Results: Restraint stress produced raise in the plasma IL-6 and decrease in the IL-10 level. Abnormalities in memory and anxiety level were seen. The effects of KSC in preventing detrimental effects on spatial recognition skill and reference memory were observed in Morris water maze analysis. In EPM trail, the anxiety developed due to restraint stress was prevented by the KSC. Conclusion: KSC was found to have action against psychological stress-induced neurobehavioral changes and stress-induced alteration in cytokines which play important roles in the development of psychological stress.
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Ginkgo biloba ameliorates fluoride toxicity in rats by altering histopathology, serum enzymes of heme metabolism and oxidative stress without affecting brain mGluR5 gene p. 320
Sugavasi Raju, Senthilkumar Sivanesan, Kanchanalatha Gudemalla
DOI:10.4103/pm.pm_534_19  
Background: To evaluate the therapeutic potential of Ginkgo biloba extract (GBE) in experimental model of fluorosis. Objectives: To study the protective effect of GBE in fluoride toxicity by assessment of oxidative stress, serum biochemical parameters, acetylcholinesterase (AChE) activity, histopathology and brain mGluR5 gene expression. Materials and Methods: Fifteen adult male Wistar rats were randomly assigned to 5 groups (n = 3 rats in each group). Group 1 (control) received water, Groups 2–5 were treated with 100 ppm of sodium fluoride for 30 days, while the Groups 3, 4 and 5 were GBE treated with 50 mg/kg, 100 mg/kg and 200 mg/kg body weight for 15 days, after sodium fluoride treatment for 30 days. Results: Elevated serum delta aminolevulinic acid dehydratase and delta aminolevulinic acid synthatase levels in fluoride intoxicated rats were ameliorated by various doses of GBE treatment. Elevated serum glutathione and decreased oxidized gluatathione levels observed in fluoride intoxicated rats were also ameliorated by GBE treatment but effectively at 100 mg/kg dose. Reduced AChE activity of hippocampus in fluoride-induced toxicity was reverted by 50 mg/kg of GBE whereas other doses (100 and 200 mg/kg) caused significant inhibition of AChE activity in comparison with fluoride group. Fluoride group rats showed significant reduction of mGluR5 gene expression levels whereas in all GBE treatment groups those changes Were not significantly reverted. GBE treatment to fluoride intoxicated rats almost reverted the degenerative changes in liver and kidney caused by fluorosis. Conclusion: The present study concluded beneficial effects of GBE in experimental model of fluorosis.
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Chemical constituents of Litsea elliptica and their alpha-glucosidase inhibition with molecular docking p. 327
Sathianpong Phoopha, Chatchai Wattanapiromsakul, Thanet Pitakbut, Sukanya Dej-adisai
DOI:10.4103/pm.pm_18_20  
Background: Litsea elliptica (LE) is an edible plant in Thailand, which has been used as vegetables, flavoring materials, and traditional herbal medicine. Some species of Litsea have been reported on anti-diabetic activity. However, LE has not been reported of chemical constituents and their alpha-glucosidase activity. Objectives: The aim was to study on chemical constituents and anti-diabetic activity through in vitro models of LE. Materials and Methods: Chromatographic and colorimetric enzyme methods with computer molecular docking were used in this research. Results: Anew quercetin-diglycoside (1) and six compounds (2-7) were isolated from LE which were elucidated as quercetin-3-O -α-rhamnopyranoside-O -(1→2)-α-apiofuranoside (1), quercetin-3-O -α-rhamnopyranoside (2), quercetin-3-O -β-glucopyranoside (3), uridine (4), isoboldine (5), reticuline (6) and β-sitosterol-D-glucopyranoside (7). Four isolated compounds exhibited anti-alpha glucosidase activity by inhibition concentration at 50% (μg/mL) values as 5 (243.25) <3 (332.19) <1 (335.15) <2 (751.79), respectively. Furthermore, the molecular docking experiment was graphically computed for binding energy between effective compounds and the enzyme. The result suggested that the structure of compound 5 exhibited the lowest binding energy (−7.2 kcal/mol), which interacted at non-catalytic domain at the entrance of the active site. In addition, the mechanism of action of effective compounds could be predicted by the binding sites as non-competitive inhibitor (1 and 5) and competitive inhibitor (3). To sum up, the seven compounds which were isolated of LE are significantly reported for the first time in biological and phytochemical studies, and compound 1 is considerably interpreted as a new compound which presents anti-alpha glucosidase activity.
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Chrysin ameliorates ovalbumin-induced allergic response in allergic rhinitis: Potential role of GATA-3, T-box protein expressed in T cells, nuclear factor-kappa B, and nuclear factor erythroid 2-related factor 2 p. 335
Juan Wang, Amit Kandhare, Anwesha Mukherjee-Kandhare, Subhash L Bodhankar
DOI:10.4103/pm.pm_461_19  
Background: Rhinitis is an allergen-induced, immunoglobulin E (IgE)-mediated, chronic immune-inflammatory disease affecting individuals worldwide. Chrysin has been well documented for its anti-allergic potential. Aim: This study aimed to determine the efficacy and mechanism of action of chrysin against allergic rhinitis (AR) induced by ovalbumin (OVA) in experimental mice. Materials and Methods: Induction of AR was performed in BALB/c mice via intraperitoneal administration sensitization and intranasal challenge with of OVA. Chrysin was concomitantly administered in mice at doses of 10, 20, and 40 mg/kg, p.o. Results: OVA challenge caused statistically significant (P < 0.05) increase in nasal rubbing, sneezing, and discharge as well as elevated serum histamine, β-hexosaminidase, IgE (OVA-specific and total) levels, whereas chrysin treatment at a dose of 20 and 40 mg/kg significantly (P < 0.05) inhibited these biomarkers and thus reduced nasal symptoms. The elevated total and differential cell count, splenic oxido-nitrosative stress, and myeloperoxidase levels after OVA administration decreased statistically significantly (P < 0.05) by chrysin. There was a significant increase in the levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-4, IL-1β, IL-4/interferon-gamma, IL-6, and IL-13 in nasal lavage fluid after OVA challenge, which was inhibited statistically significantly (P < 0.05) by chrysin. It also statistically significantly (P < 0.05) downregulated spleen GATA-3 and nuclear factor-kappa B (NF-κB), whereas upregulated T-box protein expressed in T cells (T-bet) and nuclear factor erythroid 2-related factor 2 (Nrf2) mRNA expression in spleen. Histological alteration induced in nasal and spleen tissue after OVA challenge was statistically significantly (P < 0.05) ameliorated by chrysin treatment. Conclusion: Chrysin modulated GATA-3/T-bet pathways and inhibited NF-κB activation, thus attenuating the release of various inflammatory mediators (TNF-α, IL-1β, histamine, IgE, and β-hexosaminidase), Th2 cytokines (ILs), and oxido-nitrosative stress (Nrf2) to exert its anti-allergic potential in experimental AR.
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In vitro anti-inflammation, selective cytotoxicity, and inhibition of induced nitric oxide from lipopolysaccharide-stimulated raw 264.7 macrophages activities of flavonoids from Hermannia geniculata eckl and zeyh roots extract p. 345
Adeniran Lateef Ariyo, Ohanaka Judith Nkechinyere, Joy Lyndy McGaw, Anofi Omotayo Tom Ashafa
DOI:10.4103/pm.pm_447_19  
Aim: Evaluation of in vitro anti-inflammatory activities of flavonoids of Hermannia geniculata (FHG) roots extract, selective cytotoxicity of Vero and hepatocellular carcinoma (HepG2) cells, as well as its capabilities to inhibit the production of induced nitric oxide (iNO) in lipopolysaccharide (LPS)-activated RAW 264.7 macrophage was investigated. Materials and Methods: Soybean 5-lipoxygenase (5-LOX) Inhibition and the tetrazolium-based colorimetric (MTT) assay methods were used. Results: The extract exhibited 73% inhibition of 5-LOX enzyme better than indomethacin (standard) with their respective IC50(10.15 ± 0.02 and 12.03 ± 0.02). It was observed that 65% of the Vero cells were viable at the highest concentration of 1 mg/mL of FHG extract and the LC50value is 1 mg/mL. Furthermore, the LC50value of 0.02 mg/mL was recorded for HepG2 cells at the concentration of 0.75 mg/mL. Selectivity index (SI) for the FHG extract is 50 which is higher than the 31.2 SI value of the standard. Inhibition of iNO production was observed in LPS activated RAW 264.7 Macrophages with the highest concentration of 0.1 mg/mL decrease iNO production by 87%. Conclusion: This study indicated that FHG extract possesses anti-inflammatory and antiproliferation properties.
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Comparison of antioxidant levels and anti-inflammatory activities of kelulut honey harvested at different month of intervals and its chemical compositions p. 350
Muhammad Aiman Haiqal Ismail, Nurul Sharina Rasyidah Badrulhisham, Vuanghao Lim, Armania Nurdin, Hanis Hazeera Harith, Yoke Keong Yong
DOI:10.4103/pm.pm_451_19  
Background: Harvesting time might influence the biological activities of honey, which is crucial for honey quality. Objectives: This study aims to evaluate the optimum time for harvesting kelulut honey (KH) by determining its antioxidant and anti-inflammatory activities and chemical composition at different harvesting times. Materials and Methods: KH harvested at three different intervals (1, 2, and 3 months) was supplied by Rimbunan Hijau Bee Farm, located in Sarawak, Malaysia. The total phenolic content (TPC) and antioxidant level of KH were determined using Folin–Ciocalteu reagent and 2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), and ferric-reducing ability of plasma assays, respectively. The cytotoxicity and anti-inflammatory effects of KH were evaluated on murine macrophage cells (RAW 264.7) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lipopolysaccharide (LPS)-induced nitric oxide (NO) production. The chemical composition of KH was analyzed by gas chromatography-mass spectrometry (GC-MS). Results: TPC and antioxidant levels of KH collected at different intervals showed no statistically significant difference (P > 0.05). KH at 1% concentration showed no cytotoxic activity toward RAW 264.7 cells after 24 h incubation. However, 1% KH showed no inhibition on NO production in LPS-induced RAW cells compared to the control. GC-MS revealed that hydroxymethylfurfural was present with the highest concentration in all samples. Conclusion: This study suggests that harvesting time does not influence the biological activities of KH.
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Althea rosea seed extract ameliorates 1,2-dimethylhydrazine induced preneoplastic lesions in mouse model of colon cancer by modulating oxidative stress and inflammation p. 360
Arun Narota, Sandeep Kumar, Rhythmjot Kaur, Sachdeep Kaur, Ritu Aggarwal, Navneet Agnihotri
DOI:10.4103/pm.pm_559_19  
Background: Phytochemicals with strong antioxidant and anti-inflammatory properties are known to modulate the process of carcinogenesis. Althea rosea (AR) is an ornamental plant and is an integral part of traditional medicine for curing a wide range of inflammatory disorders such as asthma, inflammatory bowel diseases, and arthritis. Therefore, its potential as a chemopreventive agent in cancer needs to be evaluated using an appropriate animal model. Materials and Methods: In this study, different in vitro assays including total phenolic content, 1,1-diphenyl-2-picrylhydrazyl, 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate), and ferric reducing antioxidant power were used to evaluate the antioxidant capacity of AR seed extract. In addition, in vivo study at two different doses, i.e., 100 and 200 mg/kg body weight, was also conducted to analyze the chemopreventive potential of AR seed extract. The chemopreventive efficacy of AR seed extract was assessed by analysis of aberrant crypt foci (ACF), goblet cells/crypt, apoptotic index, and nuclear factor-kappa B (NF-κB) signaling pathway. Results: The results of in vitro assays suggested that AR seed extract exhibits a strong antioxidant potential. Administration of AR seed extract to 1,2-dimethylhydrazine group animals resulted in a marked reduction in ACF number, lymphocytic infiltration, and erosion of mucin layer from the intestinal epithelium. AR seed extract induced apoptosis in colonocytes as evident from the analysis of cleaved caspase-3, Bcl-2, and poly (ADP-ribose) polymerase 1/2 expression. Furthermore, treatment with AR seed extract inhibited the expression of NF-κB, a central mediator of chronic inflammation. The AR seed extract also ameliorated the damaging effects of oxidative stress by decreasing free radical generation and increasing the levels of enzymatic and non-enzymatic antioxidants. Conclusion: Taken together, these findings emphasized that AR seed extract could be considered as promising natural chemopreventive against colon carcinogenesis and should be further evaluated for the identification of active principle(s).
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Potential antileptospiral constituents from Phyllanthus amarus p. 371
S Chandan, S Umesha, K Shiva Prasad, V Balamurugan, S Chandrashekar, SR Santosh Kumar, Ramith Ramu, Prithvi S Shirahatti, Asad Syed, Abdallah M Elgorban
DOI:10.4103/pm.pm_10_20  
Background: Phyllanthus amarus (PA) is a well-known herb for its medicinal properties and widely used worldwide. PA has a significant role in Indian Ayurveda system of medicine for treating various ailments such as gonorrhea, menorrhagia, and other genital infections. Objectives: The aim of the study is to investigate antileptospiral activity and isolate the potential antileptospiral constituents of the methanol extract of PA (MPA). Materials and Methods: The primary pharmacological tests for leptospirosis were investigated by test tube dilution technique and microdilution technique. To examine the morphogenesis of experimental leptospirosis by morphologic and histological methods, albino mice were inoculated intraperitoneally with Leptospira interrogans sero group Icterohaemorrhagiae strains. Results: The activity-guided repeated fractionation for MPA through silica gel column chromatography yielded three compounds that exhibited antioxidant and in vitro, in vivo, and in silico antileptospiral activities. Based on diverse physicochemical and spectroscopic analyses (viz.,13C NMR,1H NMR, ultraviolet [UV], IR, and mass spectroscopy), the potential constituents were elucidated as 5-(3-(3,4-dimethoxybenzyl)-4-methoxy-2-(methoxymethyl)butyl)-4,7-dimethoxybenzo[d][1,3]dioxole(C1),1-(3-(3,4-dimethoxybenzyl)-4-methoxy-2-(methoxymethyl)butyl)-2,3,4,5tetramethoxybenzene(C2), and 4-(3-(3,4dimethoxybenzyl)-4-methoxy-2-(methoxymethyl)butyl)-3,6-dimethoxybenzene-1,2-diol (C3). The histopathological examinations of both kidney and liver showed promising activity with C3 at 75 and 100 μg/mL, respectively. Conclusion: The in vitro , in vivo, and in silico studies revealed that benzo methoxy class of compounds has great potential as antileptospiral agents.
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Protective effect of Carica papaya leaf extract against mercuric chloride-induced nephrotoxicity in wistar rats p. 379
Yuvaraj Maria Francis, J Vijayakumar, Gunapriya Raghunath, S Vijayalakshmi, Senthilkumar Sivanesan, R Vijayaraghavan, Ethirajan Sukumar
DOI:10.4103/pm.pm_11_20  
Introduction: Chronic kidney disease is the progressive loss of renal function, measured by creatinine, urea and proteinuria levels. Literatures show that renal damages can be ameliorated naturally by medicinal plants, one such plant is Carica papaya . Fresh leaves of C. papaya were collected, powdered, and extracted with ethanol to form ethanolic extract of C. papaya leaves (ECP). Aim and Objectives: The aim and objective of this study are to assess the remedial implications of ethanolic ECP leaves on mercuric chloride (HgCl2)-induced nephrotoxicity in female Wistar rats. The objectives of this study were to assess the effectiveness of two different oral doses of ECP using immunohistochemistry, histopathology, and serum biomarkers such as kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and semaphorin 3A. Materials and Methods: The rats were divided into five groups (n = 6): Control (Physiological saline, 2 ml/kg b. w), Negative control (HgCl2, 2.5 mg/kg b. w), Positive control (N-acetyl cysteine [NAC] 180 mg/kg b. w + HgCl2, 2.5 mg/kg b. w), Experimental group (C. papaya leaves, 300 and 600 mg/kg b. w + HgCl2, 2.5 mg/kg b. w) for 28 days orally through gavage. Collection of blood and renal tissue was done to determine the serum biomarkers, immunohistochemistry, and histopathology. Results: Pretreatment with 300 mg and 600 mg doses of ECP had protective effects slightly lower than NAC and equal to that of NAC on HgCl2-induced nephrotoxicity, respectively. Statistical analysis was performed using the one-way analysis of variance using SPSS version 17.0 with a statistical significance level of P < 0.001. Such pretreatment of C. papaya leaves, modified the following; (a) levels of serum marker enzymes (b) histopathological changes, and (c) immunohistochemistry expression caused by HgCl2. Conclusion: ECP plays a very significant role in the management of nephrotoxicity induced by HgCl2with equivalent to NAC.
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Anti-inflammatory activity of Zanthoxylum rhetsa bark fractions via suppression of nuclear factor-kappa B in lipopolysaccharide-stimulated macrophages p. 385
Ramesh Kumar Santhanam, Katyakyini Muniandy, Sivapragasam Gothai, Khozirah Shaari, Palani Kandasamy Senthilkumar, Palanivel Ganesan, Palanisamy Arulselvan
DOI:10.4103/pm.pm_486_19  
Background: Zanthoxylum rhetsa is a plant used in traditional medicine and is known to possess health benefits such as antibacterial, antidiabetic, and anti-diarrheal activities. Objectives: The objective of this study was to explore and demonstrate the anti-inflammatory activity of various solvent fractions of Z. rhetsa bark. Materials and Methods: The effect of crude methanolic extract and its fractions (hexane, chloroform, ethyl acetate, and butanol) on the levels of pro-inflammatory cytokines (interleukin-1β, tumor necrosis factor-alpha, and interleukin-6) and inflammatory factors was tested via targeting nuclear factor-kappa B (NF-κB) signaling pathways in lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. Results: Treatment with all the solvent fractions at various concentrations (50, 100, and 200 μg/ml) suppressed pro-inflammatory cytokine levels in a dose-dependent manner. Among the fractions, the chloroform fractions exhibited a significant inhibition of LPS-induced inflammation. Moreover, these fractions effectively suppressed the expression of various NF-κB signaling targets, including NF-κB, nitric oxide synthase, and cyclooxygenase-2 as well as inhibited the degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cell inhibitor, alpha (inhibitor of kappa B alpha [IκBα]). This anti-inflammatory effect was mediated by the prevention of IκBα degradation, as this protein prevents the translocation of NF-κB from the cytoplasm to the nucleus, initiating the transcription of pro-inflammatory genes. Conclusion: Thus, the Z. rhetsa chloroform fraction may be an effective natural anti-inflammatory agent against inflammation-associated diseases.
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Cytotoxic isoprenoids from Xanthium strumarium linn. p. 391
Hajer S Alorfi, Amani A Alshehry, Mohamed A Ghandourah, Nahed O Bawakid, Mahmoud A Elfaky, Aasim M Ali, Walied M Alarif
DOI:10.4103/pm.pm_585_19  
Background and Objective: Xanthium strumarium is a widespread medicinal plant species; particularly fruits and roots are known for improving memory, voice, and appetite as well as curing of poisonous bites of insects and epilepsy. Materials and Methods: The aerial parts of X. strumarium were extracted with a combination of organic solvents. The exhaustively dried organic extract was fractionated until obtaining pure individuals by employing the appropriate chromatographic techniques. The spectral information obtained from different nuclear magnetic resonance experiments, mass, infrared, and ultraviolet spectra were the keys to elucidate the chemical structures. Results: Nine compounds (1-9) were obtained: a germacrane sesquiterpene (1), five xanthatin-type sesquiterpenoids (5-9) with α-methylene-γ-lactone moiety, including the new one, methoxy xanthanol (9), a benzopyran derivative not previously found in nature 3,4-diepoxy-2,2-dimethyl-2H-1-benzopyran-6-carboxaldehyde (2), and coumarin (3), along with the C-28 steroid campesterol (4). Conclusion: Most of the compounds under the study showed an appreciated cytotoxic activity against HCT116 and HepG2 cancer cell lines.
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In vitro antitumor potential of methanol extract of Mimosa pudica in human breast cancer cell lines p. 396
Reni John, Bibu John Kariyil, PT A. Usha, S Surya, G Anu, Preethy John, S Sujith, Aziz Zarina
DOI:10.4103/pm.pm_527_19  
Background: Mimosa pudica belonging to the family Fabaceae , is a small sized shrub, used traditionally for its anti-spasmodic, analgesic, anti-spasmodic, antibacterial, and antitumor activities. Objectives: The present study was conducted to assess the anticancer activity of methanol extract of whole plant of M. pudica (MMP) in MCF-7 and MDA-MB-231 breast cancer cell lines. Materials and Methods: The antitumor activity of MMP was analyzed using 3-(4,5-dimethyl thazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay in MCF-7 and MDA-MB-231 cell lines. The cytological and metabolic alterations due to MMP were evaluated using acridine orange/ethidium bromide dual staining, hoechst 33258 and fluoroprobe, benzimidazol-carbocyanine iodide 5, 5', 6, 6'-tetrachloro-1, 1', 3,3'-tetra ethyl (JC-1) staining. Real-time polymerase chain reaction and Western blotting were carried out to assess Bcl-2, the antiapoptotic gene, and protein expression, respectively. Qualitative analysis and gas chromatography high-resolution mass spectrometry were performed for the presence of various phytochemicals. Results: The methanol extract exhibited a potent antitumor activity in both the cell lines in vitro . Conclusion: The plant extract was showing the mode of action through intrinsic pathway of apoptotic cell death and may be studied further to develop a potent drug against breast cancer.
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The potential aphrodisiac effect of Ferula drudeana korovin extracts and isolated sesquiterpene coumarins in male rats p. 404
Mohammed H Alqarni, Gamal A Soliman, Mohammad Ayman A. Salkini, Prawez Alam, Hasan S Yusufoglu, Sura Baykan, Bintug Oztürk, Maged S Abdel-Kader
DOI:10.4103/pm.pm_551_19  
Background: Many members of the genus Ferula are used in traditional medicine as aphrodisiac. Objectives: The aim of this study is to confirm the aphrodisiac potential of Ferula drudeana Korovin as listed in the Turkish traditional medicine and to isolate the active metabolites using male rats. Materials and Methods: The CHCl3soluble fraction showed promising activity. Chromatographic purification resulted in the isolation of three sesquiterpene coumarins. Isolated compounds structures were determined as feselol (1), samarcandin (2), and 3'-O-acetyl samarcandin (3) based on the physical and spectral characters. Single doses of F. drudeana CHCl3soluble fraction, aqueous fraction (200 mg/kg BW), 1 and 2 (10 mg/kg BW), and sildenafil citrate (10 mg/kg BW) were orally administered to male Wistar albino rats by gavages. Mount latency, mount frequency (MF), intromission latency, intromission frequency (IF), ejaculation latency, and postejaculatory interval (PEI) were studied. In addition, copulatory efficiency and intercopulatory efficiency were calculated. Results: Oral administration of F. drudeana roots extracts, 1 and 2 significantly increased MF and IF. The latencies of mount and intromission were reduced significantly and ELs were prolonged. Treatment with the extracts, 1 and 2 resulted in the reduction of the PEI. The highest aphrodisiac activity in male rats was exhibited by 2. Conclusion: The present findings provide experimental evidence that F. drudeana roots, 1 and 2 possess aphrodisiac activities by enhancing the sexual behavior of male rats. The obtained results supported the traditional claims about the use of Ferula species for male sexual dysfunction.
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Behavioral and physiological assessments to evaluate the effect of Acacia senegal and Acacia seyal in albino mice p. 410
Gadah Albasher, Nahed S Alharthi, Saad Alkahtani, Nada Aljarba, Nouf Al Sultan, Ahad A Alsaiari, Omaima Nasir, May Bin-Jumah, Wedad S Alqahtani
DOI:10.4103/pm.pm_20_20  
Background: Acacia senegal and Acacia seyal (family Leguminosae) are the sources of Gum Arabic that is widely used in food-processing and pharmaceutical industries. The neuropharmacological activities of A. senegal and A. seyal remain unexplored. Objective: The objective of the study was to investigate the neuropharmacological activities of A. senegal and A. seyal. Materials and Methods: Behavior, variations in selected blood parameters, acetylcholinesterase (AChE) activity, and lipid peroxidation level were studied in normal Albino mice that received A. senegal and A. seyal extracts. Results: The results revealed a significant decrease in the body weight of mice after the treatment with the extract of A. senegal and A. seyal compared to the control group. The locomotor activity in the treated mice decreased as well. In forced swimming test (FST), the treated mice showed a marked reduction in immobility respective to increase in the dose. The anxiety reflex test (FRT) revealed an increase in the percentage of time spent in the open arms of the maze. The treatment resulted in a notable decrease in motion balance and function. The active avoidance test revealed a dose-dependent reduction in avoidance. The study provided the evidence that A. senegal and A. seyal contributed to reduction in plasma cholesterol and glucose levels in treated mice, with no marked variations in hemoglobin level. Estimation of AChE resulted in minor decline in the activity in the treated group of mice. A. senegal was safer than A. seyal, but exerted toxicity at high dose. Conclusions: Low doses of A. senegal have the potential to be used for the development of the treatment for neurological disorders.
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Renoprotective effects of the hydroethanolic extract of Senecio serratuloides against Nw-nitro L-arginine methyl ester-induced oxidative stress in wistar rats p. 418
Charlotte Mungho Tata, Constance Rufaro Sewani-Rusike, Opeoluwa Oyehan Oyedeji, Ephraim Tobela Gwebu, Benedicta Ngwenchi Nkeh-Chungag
DOI:10.4103/pm.pm_375_19  
Background: Oxidative stress is implicated in the pathogenesis of many diseases. Proper management of oxidative stress requires antioxidants from external sources to supplement that of the body. Plants are considered as a major source of antioxidants because of their natural origin and therapeutic benefits. Objectives: This study was aimed at investigating the renoprotective and antioxidant capacity of hydroethanolic extract of Senecio serratuloides (HESS). Materials and Methods: In vitro and ex vivo antioxidant capacity of the extract was investigated. Female Wistar rats were treated with Nw-nitro L-arginine methyl ester (L-NAME) (40 mg/kg) for 4 weeks and then cotreating with L-NAME (20 mg/kg) and extract (HESS150 or HESS300 mg/kg) for 2 weeks and finally with plant extract or normal saline only for 2 weeks making a total of 8 weeks. Twenty-four-hour urine samples were collected during the study, and at the end of the study; blood and kidneys were harvested for biochemical and histological assays. Results: HESS exhibited high antiradical activity against 1,1-diphenyl-2-picrylhydrazyl and 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with IC50values of 0.1 and 0.4 mg/ml, respectively. HESS significantly (P < 0.01) augmented L-NAME-induced decrease in creatinine clearance, glomerular filtration rate, and serum calcium concentration. HESS significantly increased in vivo antioxidant capacity (P < 0.01), decreased malondialdehyde (P < 0.01), and Bax (P < 0.001) concentration. It showed renoprotection and significantly (P < 0.01) prevented collagen deposition in the kidneys. Conclusion: S. serratuloides has renoprotective and free radical-scavenging properties and therefore maybe important in combating oxidative stress-mediated diseases in the kidneys and other parts of the body.
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Protective mechanisms of piperine against renal ischemia–reperfusion injury in rats p. 425
Mohamed Aly Morsy, Mahmoud El-Daly, Anwaar S. M Abu Shnaf, Sherif W Mansour, Ahmed R N. Ibrahim
DOI:10.4103/pm.pm_586_19  
Background: Renal ischemia–reperfusion injury (IRI) is a major clinical problem associated with kidney transplantation, leading to high mortality and morbidity. IRI involves activation of oxidative stress and inflammatory pathways, eventually leading to cell death and organ failure. Piperine is a phenolic active ingredient of black pepper, which showed promising antioxidant and anti-inflammatory potential. Objectives: We hypothesized that piperine would protect against renal IRI in rats via inhibition of oxidative stress and inflammation. Materials and Methods: Male Sprague Dawley rats were subdivided into four groups; sham, IR, IR + piperine, and sham + piperine. All animals have been treated for 4 days with either vehicle or piperine (100 mg/kg/day). One hour after the last piperine or vehicle administration, animals were subjected to bilateral renal ischemia for 45 min by clamping both renal pedicles, followed by reperfusion for 24 h. At the end of the experiments, kidneys were harvested for the determination of lipid peroxidation (malondialdehyde [MDA]), reduced glutathione (GSH), inflammatory and apoptotic markers, and histopathology. Serum levels of creatinine and urea have been determined. Results: Induction of renal IR increased renal oxidative stress (increased MDA and decreased GSH) and the expression levels of inflammatory and proapoptotic genes (nuclear factor-kappa B, inducible nitric oxide synthase, cyclooxygenase-2, and caspase-3). Moreover, serum levels of creatinine and urea were significantly elevated. Alternatively, pretreatment of the animals with piperine resulted in normalization of these parameters. Conclusion: The results showed that piperine pretreatment protects against IRI in rat kidneys via mechanisms involving amelioration of oxidative stress along with inflammatory and apoptotic pathways.
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Protein expression patterns in hek-Blue™ - Cells treated with Clinacanthus nutans extracts p. 431
Shun-Kai Yang, Teik-Kee Leo, Chun-Wai Mai, Swee-Yee Chin, Dhilia Udie Lamasudin, Swee-Hua-Erin Lim, Ngai-Paing Tan, Kok-Song Lai
DOI:10.4103/pm.pm_281_19  
Background: Clinacanthus nutans (CN) is a small shrub native to tropical Asia known for their anti-oxidant, anti-inflammation, anti-cancer, and anti-viral activities. Objectives: This study aimed to investigate the effect of CN extract on human embryonic kidney cell line (HEK-Blue™-4) in a proteomic perspective. Materials and Methods: Comparative proteomic profiling through two-dimensional sodium dodecyl sulfate gel electrophoresis was performed on HEK-Blue™-4 treated with CN leaf polar extract. Results: We successfully identified seven upregulated proteins, of which five promoted the growth of the HEK-Blue™-4 cells. Interestingly, a potent antioxidant enzyme which neutralizes reactive oxygen or nitrogen species, peroxiredoxin-1 was also upregulated in HEK-Blue™-4 cell lines after treatment with CN leaf polar extract. Conclusion: CN leaf polar extract promotes the growth of HEK-Blue™-4 cells and induced the expression of peroxiredoxin-1, which protects the cells from reactive oxygen species during the inflammation process.
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Antitumoral effect of lawsonia inermis extract on melanoma tumor-bearing C57BL/6 mice p. 435
Wasim Raja, Sonam Pandey
DOI:10.4103/pm.pm_219_19  
Background: Medicinal plants occupy an important position for being the paramount sources of drug discovery against cancer. Medicinal plants have been used as cancer chemopreventive nutraceuticals, and functional food is promising. Thus, there is a need for exploring drugs/agents which act as best chemopreventive agents. Lawsonia inermis L. is a well-known medicinal plant which has been used in Ayurvedic medicine as hepatoprotective, antiviral, antibacterial, anti-inflammatory, antipyretic, and cytotoxic. Objectives: The main objective of the study is to investigate the in vivo antitumoral effect of L. inermis extract on melanoma tumor-bearing C57BL/6 mice. Materials and Methods: In in vivo experiments, about 5 × 105 B16F10 cells in 50 μL of phosphate-buffered saline were subcutaneously injected into C57BL/6 mice that had received plain drinking water for 40 days. Tumor volume was measured using digital calipers. The behavior of the antioxidant defenses (superoxide dismutase, catalase, and glutathione peroxidase) was evaluated after the termination of treatments. Results: Preventive oral administration of L. inermis leave extracts (500 and 1000 mg/kg body weight) significantly suppressed the growth of B16F10 tumors in mice on day 40th, with an increased tumor necrosis area, increased infiltration of mononuclear cells at the site of the tumor. L. inermis L. leaf extract dose dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Conclusion: Our study suggests that in vivo antitumoral effect of L. inermis extracts is directly linked with enhanced antioxidant activity and depicted a significant reduction in tumor size against melanoma tumor. Hence, further elucidation of active components of L. inermis extract could lead to the development of potent antitumor agent or complementary and alternative medicine for the treatment against skin melanoma tumors.
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