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Jul-Sep 2021
Volume 17 | Issue 75
Page Nos. 399-656

Online since Thursday, November 11, 2021

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ORIGINAL ARTICLES  

Scientometric analysis of pharmacognosy magazine: A decade of quality publishing Highly accessed article p. 399
M Chaman Sab, Mallikarjun Kappi, KK Mueen Ahmed
DOI:10.4103/pm.pm_221_21  
Objective: This study attempt to quantitative assessment of journal productivity by the number of articles published in Pharmacognosy Magazine publications between 2011 and 2020. The present study provides a detailed scientometric analysis of publications by year-wise and citation count, document type, highly productive institutions, highly productive authors, most cited papers, country collaborations, and most used keywords of the journal. Methodology: The publication data on Pharmacognosy Magazine publications have been retrieved by using Web of Science database and the journal web page. The collected data were tabulated using MS Excel, later, we used the VOSviewer and biblioshiny for network graphs. Results: Results found that the 1494 publications and average citations per author 5.807. Average publication per year is 4.51, average citations per documents is 5.807, and majority of publications are published as articles, i.e. 1477, total 1574 institutes contributed 1494 papers, 29 (1.941%) papers published by single author, and the rest 1465 papers were published in collaborations. Conclusion: These results indicate that Pharmacogn Mag is one of the leading journals in where the journal is indexed, with publications from a wide range of authors, institutions, and countries around the world. The study summarizes using various scientometric techniques and analyzing the journal impact, prominent topics, most prolific authors and their affiliations, collaborative countries output, and most used keywords.
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In vitro genotoxicity and in vivo single-dose oral toxicity of polysaccharide fraction from the leaves of Diospyros kaki thunb p. 406
Chang-Won Cho, Young-Ran Song, Youn-Hwan Hwang, Young Kyoung Rhee, Won-Chul Lim, Jae Woong Choi, Kyung-Tae Lee, Hee-Do Hong
DOI:10.4103/pm.pm_94_20  
Background: Polysaccharides isolated from medicinal herbs are regarded as important bioactive materials due to their various physiological activities. In our previous study, the polysaccharide fraction (PLE0) was separated from pectinase-digested persimmon (Diospyros kaki Thunb.) leaves and showed immunostimulatory and anti-osteoporotic effects. However, there is currently no information regarding the toxicity of PLE0. Materials and Methods: As a toxicological evaluation, acute oral toxicity and in vitro genotoxicity assays (chromosomal aberration and bacterial reverse mutation tests) were performed. Results: In the single-dose acute oral toxicity test in female and male Sprague-Dawley (SD) rats, the median lethal dose of PLE0 was higher than 5000 mg/kg and adverse effects were not observed in terms of mortality and abnormal changes in clinical signs. Furthermore, chromosomal abnormality and bacterial reverse mutation tests showed that PLE0 displays no mutagenicity or clastogenicity. Conclusion: Based on these results, PLE0 was not mutagenic and did not induce chromosomal aberration in vitro under our experimental conditions and exhibited no acute oral toxicity at up to 5000 mg/kg in SD rats.
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Onjisaponin B attenuates glutamate release via inhibition of calmodulin-dependent protein kinase II and connexin 43 pathways in rat astrocytes subjected to oxygen and glucose deprivation p. 413
Yingqi Mao, Yuyang Chen, Xiaoyun Pan, Lingfeng Gao, Lidan Wang, Da Li, Tao Qiu
DOI:10.4103/pm.pm_497_20  
Background: Post-stroke depression (PSD) is one of the most common complications of stroke. Many studies have confirmed that PSD is associated with the abnormal release of glutamic acid (Glu) via the Ca2+/calmodulin (CaM)/CaM-dependent protein kinase II (CaMKII) and connexin 43 (Cx43) hemichannel pathways. Onjisaponin B, a traditional Chinese medicine, has been discovered to have neuroprotective effects. Objectives: In this study, we aimed to investigate the effects and underlying mechanisms of onjisaponin B on the release of glutamate in rat astrocytes subjected to oxygen and glucose deprivation (OGD). Materials and Methods: The ischemic and anoxic cell model was established in rat astrocytes through OGD injury. Rat astrocytes were randomly divided into control, model, 10 μM onjisaponin B, and 20 μM onjisaponin B groups. Cell viability was assessed by acridine orange/ethidium bromide bilabel assay. The intracellular Ca2+ level was measured with Fluo-3-AM as the fluorescence indicator. Western blot analysis and quantitative polymerase chain reaction were used to detect the expressions of Cx43 and CaMKII in the samples. The glutamate level of the extracellular fluid was determined using high-performance liquid chromatography-mass spectrometry. Results: The intracellular Ca2+ levels and the mRNA and protein expression of CaMKII and Cx43 in the onjisaponin B group were significantly lower than that of the model group. The glutamate level in the extracellular fluid was significantly reduced by onjisaponin B in comparison to that in the model group. Moreover, onjisaponin B attenuated the inhibitory effect of OGD on the cell viability of astrocytes. Conclusion: The results of this study suggest that onjisaponin B reduced the release of glutamate via inhibition of the Ca2+/CaMKII and Cx43 pathways in the rat astrocytes, thus inhibiting the downstream glutamic pathway and reinforcing the cell viability of astrocyte.
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Zerumbone ameliorates the induced atherosclerosis-initiated inflammatory conditions through suppression of proinflammatory mediators and inflammatory cytokines p. 419
Hemn Hassan Othman, Heshu Sulaiman Rahman, Sherwan Hamasalih Omer, Syam Mohan, Mohammed Abdulabbas Hasan, Kawa Amin, Nagi A AL.Haj, Hareth Yahya Ahmed, Noordin Mohamed Mustapha
DOI:10.4103/pm.pm_549_20  
Background: Zerumbone (ZER) is a naturally occurring monosesquiterpine and dietary compound from Zingiber zerumbet Smith, an edible ginger. It has been shown to possess anti-inflammatory activities. Inflammation plays an important role in all stages of atherosclerosis. However, little is known about ZER's anti-inflammatory role in atherosclerosis. Objectives: This study investigated the anti-inflammatory effect of ZER in mitigating the formation and development of early atherosclerotic lesions in rabbits fed with high-cholesterol diet. Materials and Methods: A total of 72 New Zealand White rabbits were used in two experimental studies carried out at different times. The first experiment was carried out to investigate the prophylactic effects of ZER in preventing premature atheromas plaque formation. In contrast, the second experiment was carried out to assess the therapeutic efficacy of ZER in reducing atheromas lesion progression and dissemination. Results: ZER significantly (P < 0.05) reduced the inflammatory response through suppression of proinflammatory mediators (nuclear factor kappa-light-chain-enhancer of activated B-cells, inducible nitric oxide synthase, and cyclooxygenase-2), which leads to decrease in the secretion of inflammatory cytokines (tumor necrosis factor alpha, interleukin [IL]-6, IL-1, and IFN-γ) evaluated by western blotting and enzyme immunoassay techniques, respectively. Conversely, suppression and reduction of inflammatory mediators then contribute to minimizing macrophages recruitment, which is evident by immunohistochemistry and immunofluorescent assays of regulation of ACE2 and morphogenesis 11 (RAM-11). In addition, ZER significantly (P < 0.05) reduces the expression of RAM-11 in the intimal plaque in all supplemented and treated groups in a dose-dependent manner, which is much profound in the prophylactic trial. Conclusion: The results of the study clearly concluded that ZER is an anti-inflammatory agent alone as a prophylactic measure or in combination with simvastatin as a remedy. In effect, dietary consumption of ZER can be viewed as beneficial in preventing and attenuating early atherosclerosis.
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Systematic analysis of bioactive components of Distinct medicinal organs of mulberry by high-performance liquid chromatography with electrospray ionization mass spectrometry and molecular docking p. 428
Jingqiong Wan, Shengrong Cheng, Yuting Wang, Chongwei Wen, Yuan Wei, Dujun Wang, Zhen Ouyang
DOI:10.4103/pm.pm_533_20  
Background: Mori Folium, Mori Ramulus, Mori Fructus, and Mori Cortex are traditional Chinese medicines derived from distinct organs of mulberry (Morus alba L.). Intriguingly, their efficacies are different. Objectives: In this study, we aimed to systematically analyze the similarities and differences in the chemical composition of the aforementioned four medicines and to explore their bioactive components of anti-inflammatory and antitussive activity. Materials and Methods: High-performance liquid chromatography with electrospray ionization mass spectrometry (HPLC-ESI-MSn) was used to identify the various compounds present in each of the four medicines from the methanolic extracts and different polar fractions of aqueous extracts. Moreover, the identified compounds were docked against anti-inflammatory or antitussive targets by means of the molecular docking tool, molecular operating environment 2018. Results: A total of 77 compounds were identified from the four study materials, of which 30 were identified in Mori Folium, 27 compounds in Mori Ramulus, 23 compounds in Mori Fructus, and 46 compounds in Mori Cortex, and they had 14, 4, 3, and 26 compounds that were specific to them, respectively. The results of molecular docking indicated that quercetin, chlorogenic acid, and isoquercitrin, the shared compounds of the four medicines showed strong anti-inflammatory activity. Of note, the top 10% of compounds with better anti-inflammatory activity were mostly identified in Mori Cortex, whereas the least in Mori Fructus. Moreover, out of the top 10% of compounds with better antitussive activity, 11 compounds were identified in Mori Cortex, and only 2 or 3 compounds were identified in the other three medicines. Conclusion: The results of this study are consistent with the clinical application of the four study medicines derived from mulberry, which further supports the fact that their efficacy is dependent on their chemical composition.
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Anti-inflammatory of Alhagi sparsifolia Shap. extract: Network pharmacology analysis and experimental verification p. 438
Chunliu Wang, Qiqi Liu, Zhibiao Di, Hong Zhang, Ye Li, Jun Mu
DOI:10.4103/pm.pm_502_20  
Background: Alhagi sparsifolia Shap. (ASS) is a treasured medicinal plant and has long been employed for treating human diseases including physiological process of pain and inflammation in China. However, very tiny information has been stated about active ingredients and action mechanisms of ASS. Objective: The main determination of this article is to examine analgesic and anti-inflammatory properties of chloroform fraction of Alhagi sparsifolia Shap. (CASS), wishing to deliver some basic data for further growth of new drugs for the treatment of inflammation and pain. Materials and Methods: The acute toxicity of CASS was assessed. Essential compositions of CASS were entreated by ultra-performance liquid chromatography/tandem mass spectrometry. Network pharmacology analysis comprising Herb-Chemical component-Targets-Pathway (H-C-T-P) network conducting and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. The anti-inflammatory property of CASS and regulation of two core targets prophesied by network pharmacology were confirmed by a carrageenan-induced paw edema model. Results: CASS was safe even at the maximum oral administration dose of 20 g/kg. Twelve active ingredients were preliminary recognized by ultra-performance liquid chromatography/tandem mass spectrometry. Tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were found to be the core targets projected by H-C-T-P network. By oral administration, CASS could suggestively relieve carrageenan-induced edema and downregulate TNF-α and IL-1 β concentration in rats' swelling paw since dose of 250 mg/kg. Conclusion: CASS has anti-inflammatory effect through complex mechanisms which encompass downregulating the activation of IL-1 β and TNF-α.
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Comparative assessment of α-amylase and α-glucosidase inhibition and in vitro antioxidant capacity of Garcinia schomburgkiana bark, fruit, and leaf extracts p. 445
Sunan Jaisamut, Boonyadist Vongsak
DOI:10.4103/pm.pm_455_20  
Background: Garcinia schomburgkiana is a conventionally used as an herb for the treatment of diabetes, coughs, and menstrual disturbances. Objectives: The study was to examine in vitro antioxidant potentials and inhibitory effect against α-amylase and α-glucosidase of the bark, fruit, and leaf extracts of G. schomburgkiana using different traditional extraction methods and investigate the bioactive compound using spectroscopic and chromatographic techniques. Materials and Methods: The extracts were prepared by maceration with 80% ethanol and decoction with distilled water. The anti-free radical activities of the extracts were tested through decolorization of 2,2-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and lipid peroxidation assays. The active compound was elucidated and quantified. Results: The ethanolic bark extract displayed the highest activities of DPPH, ABTS, lipid peroxidation, α-glucosidase, and α-amylase inhibition assays with EC50 values of 28.96 ± 1.62, 9.79 ± 0.14, 574.89 ± 14.68, 20.40 ± 1.33 and 2.81 ± 0.43 μg/mL, respectively. Thus, the ethanolic bark extract was selected to assess the bioactive compound by bioactivity-guided isolation. The active biflavonoid, named morelloflavone, was isolated and elucidated. Morelloflavone exhibited high activities comparable with positive controls (ascorbic acid and acarbose). Moreover, the content of morelloflavone from different extracts was analyzed by high-performance liquid chromatography. The bark maceration with ethanol yielded the highest contents of morelloflavone. Conclusion: The bark ethanolic extract of G. schomburgkiana has more potentials than other extracts. The isolated compound demonstrated the strong activities and could be the alternative source of natural antioxidants and α-amylase and α-glucosidase inhibitor.
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Deguelin treatment attenuated the lipopolysaccharides-provoked inflammation in murine macrophage and dextran sulfate sodium-inflamed acute colitis in mice through suppression of inflammatory markers p. 451
Furong Wei, Xirong Lu, Xiaomin Guo, Penglin Liu, Aiting Di, Arunachalam Chinnathambi, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Lize Zhang
DOI:10.4103/pm.pm_570_19  
Background: Inflammatory bowel disease was a chronic inflammatory disease associated with the gastrointestinal region along with its two main types, i.e., ulcerative colitis and Crohn's disease. The occurrences of colitis were quickly expanding in recent decades worldwide. Objectives: In this investigation, we anticipated to examine the curative usefulness of deguelin, a natural herbal rotenoid against the lipopolysaccharide (LPS)-provoked inflammatory responses in murine macrophages and dextran sulfate sodium (DSS)-inflamed acute colitis in replica of mice. Materials and Methods: The inflammation response in RAW-264.7 cells was triggered with the LPS administration. The acute colitis was stimulated in BALB/c mice through administering the DSS. The colon length and disease activity index score was evaluated. The statuses of inflammatory arbitrators such as interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and nitric oxide (NO) and enzymatic function of myeloperoxidase were inspected via commercial kits. The matrix metalloproteinase-2 expression in the colon tissues and colon histological examination were done to assess the deleterious effects of DSS in mice. Results: The deguelin treatment markedly alleviated the proinflammatory markers augmentation such as IL-6, TNF-α, and NO in the murine macrophages, as well as in DSS-provoked colitic mice. Deguelin markedly reversed the colon shortening and also improved the colon weight. The histopathological investigation of colon tissues exposed the protective effect of deguelin. A marked alleviation in DSS-incited colon inflammation was noted in the deguelin-supplemented mice. Conclusion: The findings of this research were established the remedial values of deguelin against the DSS-inflamed colitis in mice. It was clinched that the deguelin can be a promising therapeutic agent to treat the colitis.
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Effects of grape seed proanthocyanidin extract on cisplatin-Induced renal oxidative damage and apoptosis in rats p. 460
Yuemei Du, Yunfan Liu, Zhang Hailian, Zhao Yanmeng, Liping Gao
DOI:10.4103/pm.pm_257_20  
Background: Grape seed proanthocyanidin extract (GSPE) shows a protective effect against cisplatin (cis-dichlorodiammine-platinum (II) [CDDP])-induced nephrotoxicity, but the protection mechanism is still not clear. Objectives: Herein, protective effects of GSPE on cisplatin (CDDP) relevant to oxidative Damage and apoptosis were investigated in rats. Materials and Methods: Randomly divide the experimental animals into five groups: Respectively are normal control group, CDDP model group, GSPE (400 mg/kg) group, CDDP + GSPE (200 mg/kg) group, and CDDP + GSPE (400 mg/kg) group. Each group was administered with distilled water or the corresponding doses of GSPE via gavage for 15 consecutive days. Subsequently, a single intraperitoneal injection of CDDP (8 mg/kg) was administered to the CDDP and CDDP + GSPE groups, and the remaining groups were administered with normal saline via intraperitoneal injection. Results: Based on the histopathological analysis, cisplatin caused structural and functional renal impairment and elevated the levels of serum creatinine and blood urea nitrogen, respectively. Renal injury was caused due to increased lipid peroxidation (LPO)/oxidative stress as evidenced by the increased levels of malondialdehyde and decreased levels of antioxidants including reduced superoxide dismutase, glutathione peroxidase and glutathione. Cisplatin administration also observably increased the rate of apoptosis of renal cortical cells, decreased the expression of Bcl-2, and increased the expression of Bax and caspase-3. The pretreatment of GSPE significantly improved renal function and attenuated the cisplatin-induced LPO/oxidative stress and apoptosis. Conclusion: Our results suggest that that GSPE had a good protective effect against CDDP-induced renal oxidative stress and apoptosis in rats. In addition, the co-administration of GSPE might prove to be a novel and promising preventive strategy against cisplatin-induced nephrotoxicity.
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Comparison of seven chemical components in Callicarpa nudiflora from different regions by liquid chromatography quadrupole time of flight mass spectrometry and its analgesic effect p. 468
Yunlu Peng, Yuanyan Hu, Lin Sheng, Jianping Tian, Jianlei Zhang
DOI:10.4103/pm.pm_365_20  
Background: Callicarpa nudiflora has been usually employed as a traditional Chinese medicine for acesodyne, dispersing edema, and hemostasis; however, its analgesic effects have been poorly considered. Objectives: This article focused on the differences in the contents of seven active chemical constituents in C. nudiflora grown in different regions. Moreover, we examined the analgesic effect of C. nudiflora from five arbitrarily designated regions and studied the relationship between the compound contents and analgesic effect. Materials and Methods: A simple and delicate qualitative tandem liquid chromatography quadrupole time of flight mass spectrometry method was first established for the immediate determination of seven active components (luteolin, apigenin, quercetin, oleanolic acid, ursolic acid, protocatechuic acid, and caffeic acid) in C. nudiflora. Ethanol extracts were prepared from the mature leaves of C. nudiflora from five regions and the writhing test was performed by intragastric administration in mice. SPSS 13.0 and Graph Pad Prism 8.01 software were used to analyze the correlation of all data. Results: Calibration curves presented satisfactory linearity, with correlation coefficients >0.99 for all compounds within the concentration range. The compound contents were uppermost in plants from Hainan Province. The contents of the seven active chemical components inclined in the order of caffeic acid > luteolin > apigenin > oleanolic acid > ursolic acid > protocatechuic acid > quercetin. Pharmacological studies showed that C. nudiflora from all five regions had obvious analgesic effects. Conclusion: These results might be helpful for the screening and cultivation of C. nudiflora and its realistic clinical application.
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Quercetin and flavonoids from Cuscuta chinensis lam. inhibit tripterygium glycoside-induced premature ovarian failure progression via PI3K-AKT signaling pathway p. 475
Changsheng Huang, Yan Ning, Yancheng Guan, Mingli Luo, Ning Tan, Shicun Luo, Shoudi He, Deyu Li
DOI:10.4103/pm.pm_25_20  
Objective: In this study, we aimed to explore the effects of quercetin and flavonoids extracted from Cuscuta chinensis Lam. on tripterygium glycoside (TG)-induced premature ovarian failure (POF). Materials and Methods: Rats in the POF model were administered with 17β-estradiol (E2), quercetin, or flavonoids that were extracted from C. chinensis. Serum levels of anti-Müllerian hormone (AMH), luteinizing hormone (LH), follicular-stimulating hormone (FSH), and E2 were determined via enzyme-linked immunosorbent assay. The mRNA and protein expressions of PI3K-AKT signaling pathway- and apoptosis-related genes in the ovarian tissues were determined by immunohistochemistry, real-time polymerase chain reaction and western blot analysis. Results: After the administration of E2, quercetin, and flavonoids, there was a decrease in the estrus cycle, which was accompanied by an increase in weight and ovarian indices. TG reduced the thickness of the layer of granulosa cells in the antral follicles, the ratio of primitive follicles, secondary follicles, and sinusoidal follicles, and the number of cells in the corpus luteum and increased the ratio of atresia follicles; however, E2, quercetin, and flavonoids reversed these effects. In the POF group, serum levels of E2 and AMH were decreased, whereas FSH and FSH/LH levels were increased. TG downregulated the expression of PI3K, p-AKT, Atg5, and cyclin D2 and upregulated the expression of caspase-3. However, the changes in the levels of hormones and proteins were reversed after the administration of E2, quercetin, and flavonoids. Conclusion: Quercetin and flavonoids extracted from C. chinensis Lam. inhibited TG-induced POF by modulating the PI3K/AKT signaling pathway.
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Sclerocarya birrea fruit peel ameliorates diet-induced obesity and selected parameters of metabolic syndrome in female wistar rats p. 482
Constance R Sewani-Rusike, Othembela Ntongazana, Godwill Azeh Engwa, Hannibal T Musarurwa, Benedicta N Nkeh-Chungag
DOI:10.4103/pm.pm_546_20  
Background: We have shown Sclerocarya birrea fruit peels to possess in vitro antioxidant activity but yet to demonstrate its medicinal potential in vivo. Objectives: To investigate the effect of S. birrea fruit peel on diet-induced obesity and metabolic syndrome (MetS) in female Wistar rats. Materials and Methods: S. birrea fruit peels extract was profiled for phytochemicals by liquid chromatography-mass spectrometer. Total polyphenols, flavonoid, and total antioxidant capacity was determined by the colorimetric methods. Four groups of female rats (n = 6/group) were administered high energy diet (HED) formulation for 15 weeks then treated daily for 4 weeks as follows: normal diet and HED control groups received distilled water; HED treated with S. birrea hydroethanolic (70% ethanol) extract at 100 mg/kg BW (HED 100) and 200 mg/kg BW (HED200). Fasting glucose and body weights were monitored weekly. Oral glucose tolerance test and blood pressure (BP) were measured before and after treatment. After termination, visceral fat, total liver fat, lipid profiles, adiponectin, leptin, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) were determined. Results: S. birrea fruit peel was rich in polyphenols and had higher antioxidants activity than the fruit pulp. Untreated HED-fed rats showed increased body weight gain, visceral fat deposition, increased total cholesterol, glucose tolerance, serum insulin and HOMA-IR, increased BP and inflammation (increased serum leptin, leptin: adiponectin ratio and reduced adiponectin) as compared to normal control. Treatment with S. birrea extract at both doses fully or partially stabilized all these parameters except BP, triglycerides and low-density lipoprotein cholesterol which remained elevated after the 4-week treatment period. Histological examination showed reduced hepatic steatosis, thereby reducing non-alcoholic fatty liver disease. Conclusion: S. birrea fruit peel extract ameliorated obesity and MetS by reversing diet-induced visceral fat accumulation, hepatosteatosis, hypercholesterolemia, improving insulin resistance and inflammation and stabilizing leptin: adiponectin balance.
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Geographical origin discrimination of Amomi fructus using an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics approach combined with antioxidant activity analysis p. 492
Cai-lin Tang, De-Po Yang, Jia-li Chen, Li-Xia Zhang, Ping Ding, Xin-Jun Xu, Wen-Jian Lan, Jian-Chun Xian, Zhi-Min Zhao
DOI:10.4103/pm.pm_59_20  
Background: Amomi fructus as edible and medicinal food can be used as a flavoring in the daily cooking and herbal tea, the consumption of A. fructus is gradually aggregate in recent years. The quality of A. fructus from Yangchun city of Guangdong province in China is familiar as the best and the value is higher than other areas, the flavor and pharmacological activities is mostly affected by its quality. However, geographical origin confusion often occurs in the market, so it is obligatory to develop technology to differentiate the geographical origin of A. fructus. Objectives: The objective of this study is to assess the antioxidant activity of A. fructus and discriminate the geographical origin of A. fructus using nontarget metabolomics technology. Materials and Methods: Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used for acquired data in positive ionization modes, principal component analysis, and orthogonal partial least-squares discrimination analysis. The online analysis website Metabo Analyst 4.0 (https://www.metaboanalyst.ca/) was used for the ensuing analysis. A reducing power test, chelating power of ferrous ions test, 1,1-diphenyl-2-picryl-hydrazyl-hydrate assay, and hydroxyl radicals scavenging ability assays were used to assess the differences in antioxidant activity between the samples from the two geographical locations. Results: Eleven differential metabolites were attained, among which eight were established as marker compounds with the greatest contribution to the discernment between the two production areas. The antioxidant activity happens obvious differences due to dissimilar geographical origin. Conclusion: Untargeted metabolomics combined with multivariate statistical analysis is a commanding strategy to extricate the samples from the same species and to comprehend the quality differences from the viewpoint of overall metabolic profile.
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Effect of 1,8-Dihydroxyanthraquinone on the imbalance of lipid metabolism via regulation of expression of CYP7A1 and 3-hydroxy-3-methylglutaryl coenzyme a reductase mRNA in hyperlipidemic mice p. 499
Jiao Ma, Xu Liu, Jiahui Yu, Jinghui Sun
DOI:10.4103/pm.pm_419_20  
Background: Cassia obtusifolia is a traditional Chinese medicine used in lowering blood lipids, but the specific compounds and mechanisms responsible for this action are still unknown. Anthraquinones are the primary active components of C. obtusifolia, among which 1,8-dihydroxyanthraquinone (DHAQ) exhibits strong biological activities. Aim: The effects of DHAQ on blood lipids and the underlying mechanisms were investigated in this study to provide a reliable experimental basis for the development and application of C. obtusifolia. Materials and Methods: Mice were fed with a high-fat diet for the establishment of a hyperlipidemia mouse model. After the establishment of the model, the mice were intragastrically administered with 5 mg/kg DHAQ once daily, continuously for 6 weeks. Then, the mice were weighed; their lipid/body ratios were calculated; their serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were measured. TG and TC contents in the liver tissue samples were measured by the enzyme-linked immunosorbent assay. Reverse transcription–polymerase chain reaction was performed to detect the levels of 7α-hydroxylase (CYP7A1) and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) mRNA, and Western blot analysis was performed to detect the expression levels of HMGCR and CYP7A1 proteins in the liver tissue of mice. Results: Body weights and lipid/body ratios of the hyperlipidemic mice were significantly reduced, and the levels of TG, TC, and LDL-C were significantly reduced in the serum samples. However, the HDL-C content in the serum was significantly increased, and TG and TC contents in the liver tissue were significantly reduced in the DHAQ-treated hyperlipidemic mice. In addition, the expression of CYP7A1 and HMGCR proteins was respectively increased and decreased significantly in the liver tissue of the hyperlipidemic mice. Conclusion: DHAQ revealed a hypolipidemic effect in hyperlipidemia mice fed on a high-fat diet, which may be related to the regulation of cholesterol metabolism in the liver.
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Plant extract-derived betulinic acid chalcone inhibits the development of type 2 diabetes mellitus via targeting peroxisome proliferator-activated receptor-γ-Regulated gene expression p. 505
Juehui Ren, Ying Wan, Yi Zhao, Min Yang
DOI:10.4103/pm.pm_321_20  
Aim: Diabetes mellitus is a syndrome related to metabolism having complicated pathogenesis and its morbidity rate is quickly increasing every year. In the present study, the antagonistic effect of betulinic acid chalcone for peroxisome proliferator-activated receptor-γ (PPARγ) was explored with possible implications in diabetic treatment. Materials and Methods: The adipocyte differentiation following betulinic acid chalcone treatment was evaluated using Oil Red O staining. Reverse transcription–polymerase chain reaction was employed for gene expression and Western blot for analysis of differentiation linked protein expression. Results: Betulinic acid chalcone repressed PPARγ-ligand-binding domain level and transcriptional property of retinoid X receptor α-PPARγ in 293T cells. The rosiglitazone suggestively (P < 0.01) augmented grease droplet accumulation in adipocytes in comparison to control adipocytes. The improved grease droplet accumulation by rosiglitazone in adipocytes was suppressed on treatment with betulinic acid chalcone. The surge in grease droplet accumulation by rosiglitazone was lessened completely on treatment with 16-μM betulinic acid chalcone. Treatment of adipocytes with betulinic acid chalcone suppressed rosiglitazone-induced expression of fatty acid synthase (FAS), CCAAT/enhancer-binding protein-α (C/EBPα), adipocyte fatty acid-binding protein 2 (aP2), and HMG-CoA genes pointedly. Treatment of adipocytes with betulinic acid chalcone instigated a marked decrease in rosiglitazone-induced expression of aP2, carboxyl terminus of the Hsc70-interacting protein (CHIP), and C/EBPα. The suppressive effect of rosiglitazone on expression of p-Akt/t-Akt, PPARa, p-FoxO1/t-FoxO1, and p-AMP protein kinase (AMPK)/t-AMPK was expressively (P < 0.01) assuaged in the adipocytes by betulinic acid chalcone. Conclusion: The present study established that betulinic acid chalcone suppressed PPARγ activity and adipocyte differentiation. Moreover, the activation of FoxO1/Akt/AMPK was upregulated and FAS/EBPα/aP2/HMG-CoA expression was subdued by betulinic acid chalcone in the adipocytes. Therefore, betulinic acid chalcone may be appraised further for a possible role in the treatment of diabetes.
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Neuroprotective effect of Cucurbita pepo in lipopolysaccharide-induced toxicity in C57BL/6 mice p. 511
Chao Zhang, Liang Chen, Xiaoling Wang, Pingkang Pan, Yong Tang, Pengli Hui
DOI:10.4103/pm.pm_170_20  
Background: Although the powerful scientific studies discover Cucurbita pepo probable in the treatment of various ailments, Cucurbita pepo being employed as food material in various part of the world, there is indeterminate in the neuroprotective potential of Cucurbita pepo in LPS induced neuroinflammation experimental model. Aim and Objectives: This study is intended to examine the protective effect of Cucurbita pepo against LPS induced neuro-inflammation in C57BL/6 mice. Materials and Methods: A single dose intraperitoneal (i.p) injection of lipopolysaccharide liquefied in saline was given to C57BL/6 mice. (n=10 per group). Aqueous extract of Cucurbita pepo (AECP) at a concentration of (100 mg/kg b.w.) was administered orally to C57BL/6 mice 1 hour before LPS induction (7 days) and continuous till 30 days (n=10 per group). Results: Levels of enzymatic antioxidants such as catalase (43.26±4.61 %) and superoxide dismutase (43.16±3.82%) restored decidedly and non-enzymatic antioxidants GPx and GSH restored up to 20.81±4.22 and 58.28±2.44 percentage respectively upon AECP treatment. Oxidative stress markers NO and LPO abridged to 57.64±3.17 and 53.25±2.53 percentage compared to LPS induction group. AECP treatment lessened the protein expression level of proinflammatory cytokines Tumor Necrosis Factor-α (TNF-α), Interleukin 1 beta (IL1-β) and Interleukin 6 (IL-6) significantly (P < 0.05) detected by ELISA. Signs of prolong inflammation caused higher expression of isoforms of nitric oxide synthases genes (eNOS, nNOS and iNOS) signifies NO productivity. In the cortex of LPS challenged mice, AECP significantly (P <0.05) condensed the LPS persuaded expressions of eNOS (1.98±0.41 fold), nNOS (1.74±0.26 fold) and iNOS (1.81±0.52 fold) genes. Also, oral administration of AECP significantly (P < 0.05) reduced the expression of ionized calcium binding adaptor molecule (Iba-1) in LPS induced mice brain cortex (30.37%), were additional supports the anti-inflammatory potential of AECP. Conclusion: In summary AECP displays antioxidant and anti-inflammatory potential against LPS induced neuroinflammation. However, the mechanistic insights of Cucurbita pepo in neuroprotection potential have explained in detail.
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Anti-inflammatory effects of Malus toringoides extract in lipopolysaccharide-induced human umbilical vein endothelial cells p. 518
Chengde Fan, Zhuoma Dongzhi, Linsha Dong, Ruiying Yuan, Jule Wang, Bin Li, Shan Huang
DOI:10.4103/pm.pm_357_20  
Background: Malus toringoides (Rehd.) Hughes is a traditional Tibetan medicine. It demonstrates significant hypoglycemic and hypolipidemic potential. However, the protective effects of M. toringoides extracts on endothelial cells and the mechanisms that underlie their activity have not yet been reported. Objectives: The aim of the study was to explore the anti-inflammatory effects and cellular mechanisms of extracts of M. toringoides (CBTM-E375) in lipopolysaccharide (LPS)-induced human umbilical vein endothelial cells (HUVECs). Materials and Methods: HUVECs were exposed to LPS, and the level of proinflammatory mediators was measured by enzyme-linked immunosorbent assay. Furthermore, the activation of heme oxygenase-1 (HO-1), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitogen-activated protein kinase (MAPK) was examined by Western blot and immunofluorescence analysis. Results: CBTM-E375 significantly downregulated the levels of inflammatory mediators and upregulated the expression of HO-1 by modulating Nrf2 translocation in HUVECs. The transfection of HO-1 small interfering RNA into HUVECs actively reversed the effects of CBTM-E375 in suppressing the expression of proinflammatory cytokines. Furthermore, MAPK activation in response to LPS was also blocked by CBTM-E375. Conclusion: CBTM-E375 exerts anti-inflammatory effects, possibly by modulating the translocation of Nrf2 and expression of HO-1, and inhibiting the phosphorylation of MAPK signaling pathway.
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Anti-osteoclastogenesis potential agents from plants naturalized in Vietnam p. 525
Thanh Huong Le, Thu Trang Duong, Phuong Thao Tran, Van Cuong Pham, Hai Dang Nguyen, Jeong-Hyung Lee
DOI:10.4103/pm.pm_562_20  
Background: The balance between bone formation and bone resorption which is attributed to osteoblast and osteoclast is required to maintain skeleton homeostasis. Osteoclast differentiation is regulated by a tumor necrosis factor–receptor activator of nuclear factor NF-kB ligand (RANKL). The dysregulation of bone-resorbing osteoclast differentiation can lead to osteoporosis. The adverse effects of the long-term use of bone resorption inhibitors are of concern and so the development of new osteoporosis therapy treatment is desirable. Objective: In this study, 67 plants (70 samples) were screened for osteoclastogenesis inhibitory activities on RAW264.7 mouse macrophages and bone marrow-derived macrophages (BMMs). Materials and Methods: The RAW264.7 cells and the BMMs isolated from male ICR mice were treated with various doses of plant extracts and TRAP histochemical staining of the cells was performed. TRAP-positive multinucleated cells were photographed under microscopy to observe the effects of the extracts on osteoclast differentiation. Results: Among 70 methanol extracts, we found that nine samples exhibited significant inhibitory effects in RANKL-induced osteoclast differentiation. They included Aleurites moluccana (S16 and S17), Aporosa dioca (S19), Antidesma bunius (S21), Cinnamomum balansae (S32), Macrosolen cochinchinensis (S41), Pinus kesiya (S52), Photinia benthamiana (S54), and Mischocarpus pentapetalus (S59). Conclusion: In the present study, 70 plant extracts were screened for the osteoclastogenesis inhibitory effects in RAW264.7 murine macrophages and BMMs. Nine extracts have the potential as effective agents against osteoclastogenesis. This is the first report on the anti-osteoclastogenetic activity of these plants.
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Antiresproative potency of D-carvone on ovariectomy-induced osteoporosis in rats p. 529
Xiliang Dong, Tahani Awad Alahmadi, Sulaiman Ali Alharbi, Yanqiong Yang
DOI:10.4103/pm.pm_449_20  
Background: Osteoporosis is a quiet disease with a pathological condition of reduced bone mineral density (BMD) leading to weakened bone. In this study, we evaluated the bone formation potency of D-carvone, an unsaturated monoterpenoid ketone phytochemical present in essential oil of aromatic plants with pharmacological prominence against the ovariectomy-induced rats. Materials and Methods: Ovariectomy was achieved in Sprague–Dawley rats and was employed for the present study. The rats were clustered into four sham-operated control, ovariectomized, ovariectomized treated with 5 mg/kg b. wt and 10 mg/kg b. wt, respectively. Body weight of rats was observed once a week and after the completion of treatment the rats were euthanized to isolate uterus, vagina, and femur. Results: The weight of the uterus, vagina, and femur were restrained to perceive the impact of D-carvone on reproductive organ and bone. The effect of D-carvone treatment in maintaining the BMD was evaluated with dual-energy X-ray absorptiometry scan and the biomechanical properties were measured with three-point bending test. Microcomputed tomography analysis was performed to scrutinize the D-carvone potency in trabecula of ovariectomized rats. Further to confirm D-carvone osteoblastic potency the bone turnover markers levels were enumerated. The bone healing effect of D-carvone in ovariectomized rats was considered with histological examination of femoral metaphysis. The impact of D-carvone on suppressing inflammation in ovariectomized rats was judged by estimating the levels of lipid profile and inflammatory cytokines. The osteoblastic potency of D-carvone was established by quantifying the gene expression osteblastic protein using quantitative polymerase chain reaction analysis. Conclusion: In conclusion, our results evidenced that the D-carvone effectively inhibited the osteclastic activity in ovariectomized rats and augmented the expression of osteblastic proteins via suppressing the inflammatory markers. However, the additional experiments in future could endorse the D-carvone as a potential anti-osteoporotic drug.
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Curcumin Mediates the Proliferation and Apoptosis of Colorectal Cancer Cells by Downregulating the Expression of Interleukin-1β through the Nuclear Factor-κB Signaling Pathway p. 539
Xiaowu Qian, Chun Jiang, Zhengtai Zhu, Gaohua Han, Ruixing Wang, Changhe Zhang
DOI:10.4103/pm.pm_388_19  
Background: Colorectal cancer (CRC) is a frequently occurring malignant tumor, which is mainly observed in elderly men with no significant symptoms at the early stage. Among the malignant tumors of the digestive system, the incidence and mortality of CRC rank second only to hepatic and gastric cancer. Curcumin is an antioxidant and anti-inflammatory compound extracted from the roots of Curcuma longa plant. The antitumor effects of curcumin have been widely reported for various types of cancers, including CRC. Objective: In this study, we aimed to elucidate the protective effects and mechanism of interleukin (IL)-1 β on curcumin-induced apoptosis in SW480 cells. Materials and Methods: Expression levels of IL-1 β in CRC tissues and cells were detected by the quantitative reverse transcription polymerase chain reaction and Western blot assays. Followed by the incubation of cells with curcumin, the effect on IL-1 β was measured. Moreover, after transfection, the effects of IL-1 β on curcumin-induced SW480 cellular processes were analyzed by cell counting kit-8 and flow cytometric analysis. Results: According to the results of this study, IL-1 β was significantly increased in CRC tissues and cells. However, after incubation of the cells with curcumin, IL-1 β was downregulated and overexpression of IL-1 β counteracted the antitumor functions of curcumin in SW480 cells. Further studies have shown that curcumin could promote apoptosis of SW480 cells by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Conclusion: Our study validated that curcumin inhibits SW480 cell proliferation but promotes apoptosis by downregulating the expression of IL-1 β probably through NF-κB signaling pathway. IL-1 β may an important target for the treatment of CRC.
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Acute Toxicity of Oroxylum indicum Fruit Extracts in Rats p. 545
Ampa Konsue, Teeraporn Katisart
DOI:10.4103/pm.pm_92_21  
Background: The fruit parts of Oroxylum indicum have been used as local vegetables and folklore medicine among Southeast Asian people including Thailand. There is no report on their safety evaluation. Objectives: The present study was aimed to evaluate the acute toxicity of O. indicum fruit extracts in male and female rats. Materials and Methods: The acute toxicity study was performed according to OECD guideline. The male and female Wistar rats were once and orally administered with the extracts at doses of 5, 50, 300, and 2000 mg/kg. The acute toxicity symptoms and mortality rates were observed within 24 h after administrations and until 14 days of the experiments. Body weight was measured in weeks 0, 1, and 2. At the end of the experiment, internal organ weights were measured. Hematological values, blood biochemistry values, and histology of liver and kidney were also examined. Results: All doses of the extracts did not affect body weight and relative organ weight. The rats from all treatments tend to gain weight. Hematological values are not affected by oral administrations of the extracts to the rats. Lipid profiles in rats from all experimental groups were similar, except triglyceride which is increased (P < 0.05) in male rats while cholesterol and high-density lipoprotein were not changed. Blood biochemical values in rats from all experimental groups were similar, but alkaline phosphatase in male rats statistically increased (P < 0.05). In addition, the inflammation was not found in liver tissue. While the histology study found that there was fatty liver incidence in the male rats treated with 2000 mg/kg fruit extracts. No change in histopathology of kidney in rats treated with the extracts was found. Conclusion: These findings indicate that O. indicum fruit extracts caused hepatotoxicity in rats. Therefore, the dose less than 2000 mg/kg was recommended for consumption.
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Tanshinone IIA alleviates amyloid β-Induced neurotoxicity of SH-SY5Y cells through GSK-3β pathway p. 552
Rongrong Huang, Songxia Lu
DOI:10.4103/pm.pm_249_20  
Background: The deposition of amyloid β (Aβ) proteins and hyperphosphorylation of tau proteins are the two notable features of Alzheimer's disease. During the past decades, novel drug candidates have been found from natural herbs and its derived compounds due to their broad spectra of therapeutic effects with low toxicity. Among the different compounds studied, tanshinone IIA, which is derived from Salvia miltiorrhiza, has been reported to attenuate Aβ-induced neurotoxicity. Materials and Methods: In this study, we studied the effects of tanshinone IIA on the neurotoxicity, proliferation, and apoptosis of Aβ25–35-induced SH-SY5Y cells. We applied various methods such as Western blot, fluorescence staining, and flow cytometry. We analyzed the tau phosphorylation and inflammatory response of SH-SY5Y cells, and we further discuss the relationship between phosphorylated tau and GSK-3β pathway. Results: Tanshinone IIA promoted proliferation and inhibited neurotoxicity of Aβ25–35-induced SH-SY5Y cells. In addition, it downregulated the level of phosphorylation of tau protein, leading to the inhibition of inflammatory response. The Y216 phosphorylation level of GSK-3β was downregulated by tanshinone IIA, whereas the S9 phosphorylation level was upregulated. Conclusion: The results of this study provide evidence that tanshinone IIA exerts its beneficial effects by attenuating the neurotoxicity induced by Aβ25–35 through the GSK-3β pathway.
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Trichomes of Coleus forskohlii: Morphology and Volatile Compounds p. 558
Xiao Huang, Pengtao You, Yulin Chen, Tian Zhang, Ling Gong, Pencheng Zou, Weisong Li, Lei Wang, Yanwen Liu, Kun Yu, Bisheng Huang
DOI:10.4103/pm.pm_427_20  
Background: Coleus forskohlii (Lamiaceae) cultivates imperishably over the tropical and subtropical regions of Asia; extracts from the roots and aerial parts of C. forskohlii are widely employed for the therapy of respiratory disorders, gastro-intestinal disturbance, heart diseases, and central nervous system disorders. The morphologies and structures of trichomes from C. forskohlii, as well as phytochemicals they secrete in China-origin plants are poorly unstated. Objectives: This study was intended to characterize the morphology and structure of trichomes and the profile of their secretory materials. Materials and Methods: To characterize the morphology and structure of trichomes, which happen on the vegetative and reproductive organs of C. forskohlii, it was employed light microscopy and scanning electron microscopy. The chemical qualities of volatile compounds from Glandular trichomes (GTs) of C. forskohlii were also studied using gas chromatography mass spectrometry (GC-MS) and histochemical reactions. Results: Four morphologically distinct trichomes, i.e., non GTs, peltate GTs, Type 1 and 2 capitate GTs, were categorized. Histochemical study naked the presence of polyphenols, flavonoids, lipids, and terpenes in the GTs. Essential oils, isolated from mature leaves by hydro-distillation, were investigated by GC-MS and 41 compounds were acknowledged with oxygen-containing sesquiterpenes and monoterpenes as the major compounds. Conclusion: Secretory materials of GTs attained by surface extraction also indicated the precise features in the China-origin samples.
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Atractylodis macrocephalae rhizoma decoction and its chemically profiled subfractions alleviate the side effects of rhubarb in TCM pair medicine p. 565
Pei-Yuan Dou, Lian-Lian Zhu, Bin Li, Xia Liu, Makhotso Rose Lekhooa, De-Qiang Dou, Muhammad Riaz
DOI:10.4103/pm.pm_97_21  
Background: Pair medicine is a unique feature of Chinese medicine. It refers to a specific composition of the two drugs usually used in the formulation of composite medicine, which could increase synergistically or decrease the side effects of one medication. Atractylodis macrocephalae Rhizoma (AMR), a generally used drug, possessed the spleen-tonifying action always used with Rhubarb as a pair medicine to decrease the side effect of Rhubarb. Aim: To investigate the effect of Atractylodis macrocephalae Rhizoma (AMR) and its effective constituents to alleviate the Rhubarb's side effect in their pair medicine. Materials and Methods: The mice were administered Rhubarb until the induction of diarrhea followed by gastrointestinal injury. The gastrointestinal injured mice were treated with AMR's water decoction and its subfractions for 5 consecutive days. The decoction and subfraction were chemically characterized using the High-performance liquid chromatography (HPLC) with a diode-array detector (DAD) analysis. Results: The results showed that AMR's water decoction (6 g/kg) was discovered to be the most effective dose to treat gastrointestinal injury induced by Rhubarb. Body weight, thymus and spleen indexes, the intestinal propulsion rate, and D-xylose absorption in mice with diarrhea and intestinal injury were analyzed to reveal the significant difference between the tested and control groups (P < 0.01). The Water Eluated Fraction (WEF), Petroleum Ether Fraction (PEF), and Crude Polysaccharide Fraction (CPF) could not only increase the levels of amylase, gastrin, and vasoactive intestinal peptide significantly but also ease diarrhea and intestinal injury situation compared with the control group (P < 0.01). Conclusion: AMR and its subfractions effectively ameliorate gastrointestinal side effects of Rhubarb and its components. WEF mainly contained 5-hydroxymethyl furfural and small molecular sugar. PEF mainly composed of sesquiterpene lactone-atractylenolides, while CPF mainly composed of inulin-type oligosaccharides elucidated by HPLC analysis, was the most effective subfraction to alleviate diarrhoea and gastrointestinal injury induced by Rhubarb.
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Antioral cancer effect of fucoxanthin on 7,12-dimethylbenz[a] anthracene-induced experimental cancer model hamster through changes of apoptosis and cell proliferation p. 578
Zhizheng Zhuang, Jingxuan Wang, Yingshun Yang, Yujiao Hou, Song Li, Yifan Wang, Yan Hu, Fan Wu
DOI:10.4103/pm.pm_482_19  
Background: In this study, we investigated the chemopreventive efficacy of fucoxanthin (Fx) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced oral cancer in hamsters. Materials and Methods: Twenty-four male Syrian golden hamsters were randomly allotted to four groups with six hamsters each. Squamous cell carcinogenesis was initiated by administering 0.5% DMBA in the left oral mucosa of hamsters for 10 weeks. The complete formation of oral tumor (OT) was confirmed via hematoxylin and eosin staining and biochemical analysis, as well as via molecular markers using plasma samples and in buccal and liver tissue samples. Results: Significant increase in the level of antioxidant, lipid peroxides (LPOs), and liver marker enzymes was observed in control animals. Increased rate of cell proliferation and decreased expression of apoptotic proteins were observed in buccal tumor in control animals. Treatment of DMBA-induced animals with Fx (50 mg/kg body weight) resulted in mild-to-moderate premalignant lesions, such as hyperplasia and dysplasia, but control animals showed the development of OT. Furthermore, the levels of LPO, antioxidants, and xenobiotic agents were altered due to Fx-administered DMBA-induced hamster showed reduced expression pattern of proliferating cell nuclear antigen and moderate expression pattern of caspases-9 and 3 and p53 were observations. Conclusion: In this study, the chemoprotective potential of Fx was due to the antiproliferative, antiapoptotic, and antioxidant effects of Fx, as well as due to anti-LPO effects in the DMBA-induced hamster cheek pouch carcinogenesis.
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Aloperine improves renal fibrosis via regulation of toll-like receptor 4/myeloid differentiation factor 88 signaling pathway p. 587
Zhen-Tian Cheng, Xiang-Ping Yuan
DOI:10.4103/pm.pm_137_20  
Objectives: The primary goal of this study was to elucidate the effects and mechanisms of aloperine (Alo) in the renal fibrosis mice with unilateral ureteral obstruction (UUO). Materials and Methods: C57BL/6 mice were randomly separated into five groups: sham, model, Alo-L, Alo-M, and Alo-H. Serum creatinine and blood urea nitrogen were measured by chemical methods. The histopathological changes and collagen deposition in the affected kidney were evaluated under optical microscope by performing hematoxylin and eosin and Masson staining. The expression of alpha smooth muscle actin, fibronectin, Toll-like receptor (TLR)-4, and myeloid differentiation factor 88 (MyD88) proteins was evaluated by immunohistochemistry, and the protein expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-α was evaluated via Western blot analysis. Results: The degree of fibrosis and histopathological damage was most clear in the kidney tissues obtained from model group. Furthermore, the expression of TLR4 and MyD88 was the maximum in the model group. However, Alo decreased the injury to the kidney, thereby improving their condition. It also decreased the levels of terminal inflammatory cytokines (i.e., TNF-α and IL-6). Conclusion: Alo may progress renal fibrosis by inhibiting TLR4/MyD88 pathway.
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Antimicrobial activity, bioactive constituents, and functional groups in aqueous methanol extract of Polyalthia longifolia (Sonn.) thwaites leaves p. 594
Feyisara Banji Adaramola, Roger Murugas Cooposamy, Olufunmiso Olusola Olajuyigbe
DOI:10.4103/pm.pm_66_20  
Background: Polyalthia longifolia is an ornamental plant with various applications in traditional medicine. There is a need to identify its bioactive compounds to justify its medicinal use. Objectives: In this study, the functional groups and bioactive compounds in aqueous methanol extract of P. longifolia leaves and its antimicrobial potential were investigated. Materials and Methods: Bioactive constituents of the extract were assayed with gas chromatography-mass spectrometry (GC-MS) and functional groups by Fourier transform infra-red (FT-IR), while its phytochemical screening and antimicrobial activity were investigated in vitro using standard protocols. Results: Qualitative phytochemical screening showed the presence of therapeutically important phytochemicals, namely, alkaloids, steroidal and cardiac glycosides, saponins, triterpenes, steroids, phytosterols, resins, phenols, flavonoids, tannins, and diterpenes. The extract showed promising bactericidal and fungicidal properties against the test organisms. Staphylococcus aureus was the most resistant of all the test organisms, while other test organisms were significantly inhibited by the extract in a concentration-dependent fashion. FT-IR analysis showed different characteristic peak values confirming the presence of important functional groups, namely, alcohol, alkane, ester, alkene, nitro compounds, amine, carboxylic acid, aromatics, and alkyl halide in the extract. GC-MS analysis identified 25 bioactive compounds in the leave extract. Some of these compounds include 2-methoxy-4-vinylphenol, copaene, aromadendrene, alpha-curcumene, caryophyllene oxide, palmitic acid methyl ester, cis-Z-alpha-Bisabolene epoxide, phytol, alpha-Santoline alcohol, and linolenic acid ethyl ester reportedly possessing antimicrobial, antioxidant, antigenotoxic, antiproliferative, anti-inflammatory, anticarcinogenic, cardio-protective, insecticidal, pesticidal, nematicidal, antiandrogenic, antiviral, and analgesic activities. Conclusion: This study underscores the vast therapeutic importance of P. longifolia leaves as an important source of potentially useful bioactive principles.
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Modulator effect of mangiferin on biochemical characterization in 7,12-dimethylbenz[a]anthracene-induced oral cancer in experimental hamsters p. 605
Min Liu, Chengquan Wen, Shengqi Pan
DOI:10.4103/pm.pm_313_19  
Background: Newly, chemopreventive technique might be a hopeful advancement in developing countries for treating cancers with the aid of toxic less natural-based constituents. Malignancy urges to augment effectual chemopreventive agents that are looking forward to suppressing the tumors which may be stimulated by chewing and smoking of tobacco and over alcohol consumption related to the high prevalence of human oral cancer (OC) patients. Materials and Methods: In the present research, we examined to assess antioxidants, lipid peroxidation (LPO), and detoxification enzymes levels of anticancer activity of mangiferin on 0.5% 7,12-dimethylbenz[a]anthracene (DMBA) provoked hamster cheek pouch carcinoma. OC on hamster buccal pouch (HBP) was incited by DMBA treatment for thrice per week for over 14 weeks. Results: About 100% well-defined OC establishment with body weight (b.wt), tumor burden, antioxidant, LPO and liver marker enzymes, and also histological changes were observed on DMBA-challenged buccal pouch carcinoma (BPC) in hamsters. Orally treated mangiferin at an effective dosage of 50 mg/kg b.wt, to DMBA painted hamsters were significantly averted the b.wt, succession of tumor, the biochemical as well as histopathological changes. Conclusion: The findings of this work clearly suggest that the anti-carcinoma effect of mangiferin possess the modulatory effects on potent antioxidant, anti-LPO, and detoxification agents to expel the metabolites of malignant cells, on DMBA-provoked BPC in hamsters.
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Liquiritin enhancing intestinal absorption of paeoniflorin in in situ single-pass intestinal perfusion and in vitro Caco-2 cell monolayer absorption models p. 615
Rui He, Sihui Wang, Qing Liu, Kaili Xie, Yongsong Xu, Jinli Shi, Zhimin Wang, Muxin Gong
DOI:10.4103/pm.pm_47_21  
Background: Paeoniflorin and liquiritin are the primary active components of Shaoyao-Gancao-tang (SGT), a classical prescription for reducing pains. However, the interaction of paeoniflorin and liquiritin during intestinal absorption needs to be further studied. Objectives: In this study, we aimed to determine the interaction of paeoniflorin and liquiritin during intestinal absorption. Materials and Methods: The interaction between paeoniflorin and liquiritin (100 μM) was studied using in situ single-pass intestinal perfusion (SPIP) model use the whole small intestine and in vitro Caco-2 cell monolayer bidirectional transport model. Results: In situ SPIP research demonstrated that liquiritin significantly increased the Ka, Papp, absorption rate, and cumulative amount of paeoniflorin up to 7.97, 8.98, 7.07, and 10.71 folds, respectively, even higher than that of verapamil, a specific P-gp inhibitor, and control. Furthermore, 18 β-glycyrrhetinic acid (18 β-GA) markedly increased the Ka, Papp, absorption rate, and cumulative amount of paeoniflorin up to 3.30, 3.27, 3.42, and 4.04 folds, respectively. Bidirectional transport studies indicated that liquiritin and paeoniflorin could prompt the absorption of each other by increasing the Papp (AP-BL) of paeoniflorin and liquiritin from (3.83 ± 0.51) ×10−7 to (5.60 ± 0.51) ×10−7 cm/s and (3.86 ± 0.34) ×10−7 to (8.26 ± 0.51) ×10−7 cm/s, respectively. The 18 β-GA significantly prompted the Papp (AP-BL) of paeoniflorin to (5.54 ± 0.92) ×10−7 cm/s. Conclusion: Liquiritin and paeoniflorin increased the absorption of each other. This could provide essential reference to predict the oral bioavailability, the pharmacokinetics, and the clinical application of coadministration of liquiritin-and paeoniflorin-containing SGT and other herbal formulas.
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Antiosteoporotic effect of fisetin in an estrogen deficient model of osteoporosis p. 623
Cong Xu, Fei Liu, Yu Yang, Feng Yuan, Bo Zhou, Yadong Liu
DOI:10.4103/pm.pm_339_20  
Background: Osteoporosis is a serious health problem, especially in the geriatric populations. World widely, it exaggerated the 8.9 million people every year roughly. In the current analysis, we assessed the antiosteoporotic effect of fisetin on the osteoporosis model ovariectomized (OVX) rat. Materials and Methods: Fisetin was orally administrated at dose of 5, 10, and 20 mg/kg to OVX rats for 16 weeks. Different biochemical parameters such as alkaline phosphatase (ALP), osteocalcin, phosphorus, calcium, and urinary deoxypyridinoline were also projected. 3-point bending test, bone mineral density (BMD), and histomorphometric feature of the femoral bone were also examined. Results: Fisetin significantly decreased the body weight and increased the uterine weight. A significant decrease detected in the level of ALP, serum calcium, while the level of the serum phosphorus, OC augmented after fisetin administration. Fisetin significantly (P < 0.001) reduced the homocysteine, C-terminal crosslinked telopeptides of collagen type I, interferon gamma, and increased the level of OC. Fisetin also augmented the level of BMD. Fisetin considerably increased the energy, maximum load, maximum stress, young modulus, and stiffness. The level of cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-1 β also diminished pointedly after fisetin treatment. Fisetin significantly boosted the estrogen (E2) level and reduced the level of follicle-stimulating hormone and luteinizing hormone. Conclusion: Communally, we can accomplish that fisetin exhibited the better protection against osteoporosis through augmenting the bone density and bone mineral content in addition to biomechanical parameters.
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Evaluation of in vitro Cytochrome P450 inhibition and hepatotoxicity potential of a herbal formula (Xiang Bei Yang Rong Tang) for treatment of cancer-related fatigue p. 630
Ning Yi Yap, Sheela Packiaraj David, Huang Fang Zheng, Quan Ming Tan, Leona Yan Peng Quek, Tze Kiat Tan, Han Kiat Ho, Alexandre Chan
DOI:10.4103/pm.pm_522_20  
Background: The modified Xiang Bei Yang Rong Tang (XBYRT) is a Chinese herbal medicine formulated to mitigate symptoms of cancer-related fatigue. XBYRT comprises of 15 herbal components which are commonly used in traditional Chinese medicine. Objectives: In this study, the in vitro inhibition of cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) activities, along with the in vitro liver cell toxicity were evaluated for XBYRT and the individual herbal components. Materials and Methods: CYP3A4 and CYP2D6 inhibitions were assayed using the Vivid® CYP450 screening kits and liver cell toxicity in L-02 cells was analyzed using the 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium cell viability kit. The half maximal inhibitory concentrations (IC50) for CYP450 inhibition and cell viability were determined using the non-linear regression from GraphPad Prism. Results: The IC50 for CYP3A4 and CYP2D6 activities were 980 (942–1019) μg/ml and 1159 (1066–1261) μg/ml, respectively, for the XBYRT. The herbal components with the lowest IC50 values for CYP3A4 activity were Radix Paeoniae Alba (144 μg/ml) and Rhizoma Cyperi (278 μg/ml), while herbal components with the lowest IC50 values for CYP2D6 activity were Radix Codonopsis pilosulae (437 μg/ml) and Fructus Ligustri Lucidi (447 μg/ml). At the concentration of 256 μg/ml, XBYRT did not exhibit liver cell toxicity, with a 100% cell viability. Conclusion: The herbal components assessed did not demonstrate potent inhibitions of CYP3A4 and CYP2D6; however, precaution is recommended for breast cancer patients taking tamoxifen as the long-term impact of the herb-drug interaction is unclear. Further, in vivo and pharmacokinetic studies are required to ascertain the actual clinical significance of potential herb–drug interactions.
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Metabolite profiling and in vitro evaluation of Lepisanthes fruticosa fruit pulp extract as inhibitor against dengue and West Nile virus NS2B-NS3 proteases p. 636
Suhaina Supian, Machap Chandradevan, Muhamad Aizuddin Ahmad, Lina Rozano, Mohd Shukri Mat Ali, Sanimah Simoh
DOI:10.4103/pm.pm_113_21  
Background: Dengue virus serotype 2 (DENV2) and West Nile virus (WNV) fevers are mosquito-borne diseases with no effective treatment at present. In recent years, the development of plant-based antivirals targeting the viral NS2B-NS3 serine proteases has been the main focus as the synthetic antivirals available are not specific and less safe. Objectives: To evaluate the inhibitory activity of Lepisanthes fruticosa pulp extract against NS2B-NS3 proteases from DENV2 and WNV and identify the metabolites from this fruit extract. Materials and Methods: In vitro DENV2 and WNV NS2B-NS3 proteases assays were carried out using the methanolic extract of L. fruticosa pulp. Liquid chromatography-electron spray ionization-mass spectrometry/mass spectrometry (LC-ESI-MS/MS) and gas chromatography-mass spectrometry/mass spectrometry (GC-MS/MS) were performed to determine the metabolites present in this fruit species extract. Results: L. fruticosa extract exhibited inhibitory activity toward DENV2 and WNV NS2B-NS3 proteases with 50% inhibitory concentration value of 1.733 ± 0.195 and 9.245 ± 0.938 mg/mL, respectively. LC-ESI-MS/MS of L. fruticosa extract identified epigallocatechin-catechin, epigallocatechin, epicatechin, catechin, cyanidin rutinoside, procyanidin trimer, rutin, myricetin rhamnohexoside, luteolin glucoside and its derivative which were from the flavonoid group. In addition, GC-MS/MS identified fatty acids and sterols. Conclusion: The inhibitory activity of L. fruticosa pulp extract toward NS2B-NS3 proteases from DENV2 and WNV suggests this fruit species as a potential source for the development of antiviral. Metabolites from the groups of flavonols, flavones, and sterols identified in L. fruticosa pulp may contribute to the inhibitory properties of L. fruticosa.
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Cardioprotective effect of plumbagin and amelioration of pro-inflammatory cytokines through suppression of Na+/K+-ATPase on myocardial ischemia p. 643
Guorong Zhang, Xinghua Ni, Yizhong Zhou
DOI:10.4103/pm.pm_565_20  
Background: Ischemia heart disease in acute phase has formed Myocardial Infarction (MI) due to imbalance between the vascular supply of oxygen and nutrients and myocardial remands leads necrosis. Objective: Herein, we investigated the cardioprotective effect of plumbagin in isoprenaline hydrochloride (ISO)-induced inflammatory response and increase in antioxidant enzymes and Na+/K+-ATPase activity in MI rats. Materials and Methods: The animals were divided into four groups: Vehicle control group (0.1%), plumbagin group (25 mg/kg/b.w.), ISO group (85 mg/kg/b.w.) injected subcutaneously for 2 days at 24 h interval after a week to induce MI, and plumbagin (25 mg/kg/b.w.) by oral administration for 1 month. The inflammatory and cardiac markers were examined using ELISA kits. The oxidative markers, antioxidant markers, and Na+/K+-ATPase activity was detected using standard methods. Results: According to our results, plumbagin significantly increased the activities of creatine kinase and cardiac troponin T (cTnT). It significantly restored the levels of lipid peroxidation markers (thiobarbituric acid reactive substances [TBARS] and lipid hydroperoxide), increased the antioxidative enzymes (superoxide dismutase, catalase, glutathione [GSH] peroxidase, and the content of GSH), and decreased the levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and nuclear factor kappa B). Histological studies also reveal the decreased inflammatory signs and tissue damages. Conclusion: Our results indicate that plumbagin increased antioxidant enzymes, reduced inflammatory response, and reduced Na+/K+-ATPase activity in rats with MI. Hence, we recommended that plumbagin confers effective cardioprotective activity against ISO-induced MI heart injury.
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Pachymic acid alleviates TNBS-induced intestine mucosal injury in mice p. 649
Jianying Zhou, Guoping Jiang, Qin Zhu, Xiaoyan Zhang, Shan Xu, Weiguang Wang, Lun Zhang, Caijuan Si
DOI:10.4103/pm.pm_475_20  
Objective: Pachyman might reduce the intestinal dysfunction and inflammation. Therefore, in this study, we aimed to explore the effect of pachymic acid on repairing the intestine mucosal injury in mice. Materials and Methods: Male BALB/c mice were randomly divided into six groups: control group, trinitrobenzenesulfonic acid (TNBS)-induced group, pachymic acid (50, 100, and 200 mg/kg) groups, and mesalazine group. In addition to the mice in the control group, all mice in other groups were induced by TNBS, an inducer of colitis, to establish the intestine mucosal injury model. To study the effect of pachymic acid on the intestine mucosal injury in mice, we assessed the disease activity index (DAI) and the morphology colon specimen in mice. Histopathological examination was also used to access the effects of different concentrations of pachymic acid on the intestinal mucosal injury in mice. Enzyme-linked immunosorbent assay (ELISA) tests were performed to detect the level of glutathione (GSH), myeloperoxidase (MPO), (MDA), and pro-inflammatory factors (tumor necrosis factor-α [TNF-α], interleukin (IL)-1 β, and IL-8) to evaluate the effect of pachymic acid on the biomarkers of oxidative stress and pro-inflammatory factors. At the in vitro level, the human colon carcinoma cells (Caco-2) were induced by TNBS to establish the in vitro intestinal mucosal injury model. After treatment with the pachymic acid, the cell viability was examined by methyl thiazolyl tetrazolium assay, and the cell apoptosis was detected by flow cytometric analysis. The expression levels of apoptosis-related proteins were analyzed by Western blot analysis. Meanwhile, the secretion level of TNF-α, IL-1 β, and IL-8 in the supernatant of Caco-2 cells was detected by ELISA kits. Results: Pachymic acid was found to reduce the DAI of intestine mucosal injury in treated mice and improved the hyperemia, edema, and necrosis in intestinal mucosal tissue. Pachymic acid decreased the secretion levels of pro-inflammatory factors TNF-α, IL-1 β, and IL-8, as well as the oxidative stress markers, MPO and MDA. In contrast, the serum levels of GSH were found to be increased. After being challenged by TNBS, the cell viability of Caco-2 cells was inhibited, while after treated with pachymic acid, inhibitory effect was partially blocked. Similarly, the TNBS-induced Caco-2 cells' apoptosis was abolished by pachymic acid. Conclusion: Pachymic acid repaired the intestine mucosal injury and attenuated inflammatory response in experimental mice. It provides an alternative therapeutic strategy for intestine mucosal injury and highlights the protective effects of traditional Chinese medicine in these diseases.
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RETRACTION Top

Retraction: In vitro antioxidant potentials of Cyperus Rotundus L. rhizome extracts and their phytochemical analysis p. 656

DOI:10.4103/0973-1296.330202  
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