bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of medication storage and disposal questionnaire
Authors: Al-Qerem Walid , Hailat Mohammad Majed , Gassar Ezeddin Salem , Jarab Anan S
Published: January 2021

Objectives

Inappropriate medication storage and disposal is a global problem and has a negative impact on public health, economy and the environment. One of the main causes of this problem is the lack of knowledge among the population about medication storage and disposal. This study aimed to develop a tool to measure knowledge and practice about medication storage and disposal and measure it among the Jordanian population.

Methods

This web-based cross-sectional study developed a tool to evaluate medication storage and disposal knowledge attitude and practice. Exploratory factor analysis, analysis of variance and t-test were conducted to analyze the data.

Key findings

1132 responses were collected. The exploratory factor analysis suggested a three-factor model, the three models are knowledge-need, patient-related, and medication-related factors. Knowledge-need factor evaluates the participants’ perceptions of the need for awareness and regulations regarding medication storage and disposal. The patient-related factor evaluates medication discontinuation behaviours. Medication-related factor evaluates the handling of damaged or expired medication practices. The highest mean of all three factors was for the knowledge-need factor (mean = 4.13), while the lowest was for the patient-related factor (mean = 3.22). The education level was negatively associated with patient-related factor indicating good behaviours. The means of the three factors were significantly associated with the respondents reporting that they know the correct medication storage and disposal behaviours, and the respondents believing that there are consequences of keeping medication at home.

Conclusion

The questionnaire was a valid and reliable tool to assess the knowledge and practice of medication storage and disposal. This study’s findings suggest that the lack of knowledge is the main reason behind the inappropriate medication storage and disposal practice. There is a need for awareness-improvement, which should involve healthcare awareness campaigns and governmental regulations.
Impact of drug utilization management policy on prescription opioid use in Georgia Medicaid
Authors: Wang Yu , Perri Matthew , Young Henry , Abraham Amanda , Jayawardhana Jayani
Published: January 2021

Objective

To examine the effectiveness of changes in opioid prescription policies on opioid prescribing and health services utilization rates in Georgia Medicaid.

Methods

This study used data from the Georgia Medicaid patient enrollment, medical and pharmacy claims database from 2009 to 2014.We performed an interrupted time series analysis to examine the effect of the policy changes. Outcome measures assessed the trends in the indicators of potential inappropriate prescribing practices, including overlapping prescriptions of opioid + opioid, opioid + benzodiazepine and opioids + buprenorphine/naloxone, as well as health services utilization, including hospitalization, mean length of stay, outpatient office and emergency room visits.

Key findings

A total of 712 342 opioid users aged 18–64 were included in the study. The policies were associated with significant decreasing trend of opioid + opioid (−0.0011; 95% CI = −0.0020, −0.0002) and opioid + benzodiazepines (−0.001; 95% CI = −0.0022, −0.0006) overlapping while associated with a significant immediate decrease in and opioids + buprenorphine/naloxone after the implementations (−0.0014; 95% CI = −0.0025, −0.0003). Significant immediate decrease in level of office visits and ER visits were seen with the policy implementation (office visit: −0.2939; 95% CI = −0.5528, −0.0350, ER visit: −0.0740, 95% CI = −0.1294, −0.0185). The policies were not shown to be significantly associated with hospitalization and the mean length of inpatient stay.

Conclusions

Our analysis suggests that Georgia Medicaid opioid policies were useful to contain inappropriate opioid use.
Cost-benefit analysis of prevention of mother-to-child transmission of HIV services: a contingent valuation study of patients’ preferences from clinical pharmacists’ perspective
Authors: Isah Abdulmuminu , Adibe Maxwell Ogochukwu , Ukwe Chinwe Victoria , Okonta Mathew Jegbefume , Ubaka Chukwuemeka Michael , Aluh Deborah Oyine , Isah Abdulrouf , Ma’aji Hadiza Usman
Published: January 2021

Objectives

Cost-benefit analysis is the least reported economic analysis of prevention of mother-to-child transmission services. In cost-benefit analysis, consumers’ wellbeing is considered from their own perspective. This study determined the benefit-cost ratios of prevention of mother-to-child transmission services in two Nigerian tertiary hospitals.

Methods

This was a cross-sectional survey using willingness-to-pay. The study was conducted among patients at Ahmadu Bello University Teaching Hospital and the University of Nigeria Teaching Hospital. Potential benefit was measured as patients’ willingness-to-pay while cost was measured from pharmacists’ perspective. The benefit-cost ratio for each service was obtained as the average after 1000 iterations of Monte Carlo simulation in a probabilistic sensitivity analysis.

Key findings

A total of 219 patients responded to the questionnaires. Most of the patients were married, 149 (68.0%). Primary prevention of HIV had the highest ‘yes’ willingness-to-pay response of 152 (69.4%). It also had the highest mean willingness-to-pay amount of N7987.42 ± 4542.00, with willingness-to-pay minimum (maximum) amounts of N100 (N500 000). Primary prevention of HIV had the highest return-on-investment for 15 min of hospital pharmacists’ salary: benefit-cost ratio 19.286 ± 0.170 (95% CI: 18.954 – 19.618).

Conclusion

Primary Prevention of HIV had the highest benefit-cost ratio among the six prevention of mother-to-child transmission services. This suggests that healthcare systems will have the highest return-on-investment if they asked patients to pay for the service.
Applying medicines reconciliation indicators in two UK hospitals: a feasibility study
Authors: Aljamal Mohammed S , Abdel-Qader Derar H , Al Meslamani Ahmad Z
Published: January 2021

Objectives

The aim of this study was to apply the Medicines reconciliation (MR) indicators and to assess their feasibility for use with patients on admission.

Methods

This is a mixed-methods study conducted in two large teaching hospitals in the north-west of England. There were two phases: (1) a prospective direct non-participant observational study was conducted on a small sample of five pharmacists in each hospital, who were observed while they conducted the MR process without interference by the investigator and (2) pharmacy staff conducting MR were asked to complete the MR data collection form, comprising various clinical information during the working hours of a selected weekday for all MRs conducted for patients admitted to hospital during that day. SPSS V20 was used for data analysis.

Key findings

In the first phase, five MR indicators were found not to be feasible and three not adequately assessed, while 33 indicators were considered feasible to be used in a hospital setting. In the second phase, 33 indicators were considered feasible to assess MR on admission to the hospital, 14 indicators were found feasible to assess main aspects of the MR process, and 18 indicators were found feasible to assess detailed aspects of the MR process. The majority of admissions were unplanned. Roughly half 45.4% of the patients admitted to hospital A were reconciled, while in hospital B 52% were reconciled.

Conclusion

The use of different methods to collect data was effective in providing valuable information as well as overcoming the potential limitation of each method.
Pooled procurement program in the quality improvement of medicines of the National Catholic Health Service in Ghana: using the Donabedian model
Authors: Domfeh Kofi Ameyaw
Published: January 2021

Objectives

This study evaluates structures that determine the quality of medicines procured through the pooled procurement program (PPP) in the National Catholic Health Service (NCHS) using the Donabedian model. The challenges faced in the PPP are also revealed.

Method

A qualitative multiple case study was used to collect information from twenty top- and middle-level administrators in the NCHS through in-depth interviews. After the data transcription, it was then analysed using the thematic content analysis approach.

Key findings

The study found that the structures for quality of services in the health facilities are moderately satisfactory. The structures of the NCHS included experienced healthcare workers, adequate physical infrastructures, functional Drug and Therapeutic Committees (DTCs) and a rapid-testing laboratory facility to ensure that medicines procured were of high-quality. This paper established that suppliers of medicines to the health facilities in the NCHS had to register with the NCHS subject to annual renewal. Suppliers are also required to have the Pharmacy Council (PC) and the Food and Drug Authority (FDA), certification to supply medicines to health facilities. However, the predominant challenges that confronted the health facilities were delays in health insurance claims processing and payments, and lack of management commitment in implementing the PPP.

Conclusion

The study contributes to the pharmaceutical health services literature in the context of the pooled procurement approach in the sourcing of medical goods in the health sector. Significant implications for research and management are also presented.
Risk of fatal and nonfatal coronary heart disease and stroke events among adult patients with hypertension: basic Markov model inputs for evaluating cost-effectiveness of hypertension treatment: systematic review of cohort studies
Authors: Sorato Mende Mensa , Davari Majid , Kebriaeezadeh Abbas , Sarrafzadegan Nizal , Shibru Tamiru , Fatemi Behzad
Published: January 2021

Objectives

Hypertension is a risk factor for a number of vascular and cardiac complications. A Markov like simulation based on cardiovascular disease (CVD) policy model is being used for evaluating cost-effectiveness of hypertension treatment. Stroke, angina, myocardial infarction (MI), cardiac arrest and all-cause mortality were only included CVD outcome variables in the model. Therefore this systematic review was conducted to evaluate completeness of CVD policy model for evaluation of cost-effectiveness across different regions.

Key findings

Fourteen cohort studies involving a total of 1 674 773 hypertensive adult population and 499 226 adults with treatment resistant hypertension were included in this systematic review. Hypertension is clearly associated with coronary heart disease (CHD) and stroke mortality, unstable angina, stable angina, MI, heart failure (HF), sudden cardiac death, transient ischemic attack, ischemic stroke, sub-arachnoid hemorrhage, intracranial hemorrhage, peripheral arterial disease (PAD), and abdominal aortic aneurism (AAA). Lifetime risk of developing HF is higher among hypertensives across all ages, with slight variation among regions. Treatment resistant hypertension is associated with higher relative risk of developing major CVD events and mortality when compared with the non-resistant hypertension.

The CVD policy model can be used in most of the regions for evaluation of cost-effectiveness of hypertension treatment. However, hypertension is highly associated with HF in Latin America, Eastern Europe, and Sub-Saharan Africa. Therefore, it is important to consider HF in CVD policy model for evaluating cost-effectiveness of hypertension treatment in these regions. We do not suggest the inclusion of PAD and AAA in CVD policy model for evaluating cost-effectiveness of hypertension treatment due to lack of sufficient evidence. Researchers should consider the effect of treatment resistant hypertension either through including in the basic model or during setting the model assumptions.
Evaluation of the impact of anaemia on quality of life among breast cancer patients undergoing chemotherapy in Malaysia
Authors: Muthanna Fares Mohammed Saeed , Hassan Bassam Abdul Rasool , Karuppannan Mahmathi , Mohammed Ali Haider
Published: January 2021

Objectives

The purpose of this study was to evaluate the impact of anaemia on the quality of life (QOL) among breast cancer patients.

Methods

A total of 120 anaemic (haemoglobin < 12 g/dL) breast cancer patients were identified through chart review. Patients were followed-up for three cycles of chemotherapy filled in a QOL questionnaire Functional Assessment Chronic Therapy –Anaemia at each follow-up session. Data such as haemoglobin Hb levels and chemotherapy regimens were also recorded on each follow-up. Data were analysed using SPSS.

Key findings

The Hb level and QOL mean scores of all follow-ups were 10.34 ± 0.73 g/dL and 96.37 ± 16.15 g/dL, respectively. QOL was adversely affected by anaemia severity, and the curves declined significantly from the first follow-up to the third follow-up (P < 0.001).

Conclusion

It is crucial to consider developing a guideline for the treatment of anaemia, which is not available currently, and improve the QOL for the wellbeing of cancer patients.
Mitracarpus frigidus (Rubiaceae) inhibits inflammatory and oxidative stress mediators in Salmonella sp. mouse infection
Authors: Fabri Rodrigo Luiz , Campos Lara Melo , Florêncio Jônatas Rodrigues , Oliveira Luiz Gustavo , Aragão Danielle Maria de Oliveira , Ferreira Adriana Lúcia Pires , de Aguiar Jair Adriano Kopke , Apolônio Ana Carolina Morais , Alves Maria Silvana , Scio Elita
Published: January 2021

Objectives

Evaluation of the in-vivo anti-inflammatory activity of the methanolic extract obtained from the aerial parts of Mitracarpus frigidus (MFM) in the infection caused by two Salmonella strains and its chemical fingerprint by UFLC-quadrupole time of flight-MS.

Methods

The efficacy of MFM was investigated in a classical in-vivo Salmonella infection mouse model. A Salmonella reference strain (ATCC 13311) and a clinical isolate were used to infect mice and then MFM was orally administered during 14 days. At the end of the treatment with MFM, the infection and inflammatory levels were assayed.

Key findings

MFM treatment showed a significant reduction in mice mortality by Salmonella infection and, also, did not cause alterations in the liver function. Inhibitions of inflammatory and oxidative stress mediators [malondialdehyde (MDA), catalase, and metalloproteinase] were possibly involved in the observed effects. Chlorogenic acid, clarinoside, quercetin-pentosylhexoside, rutin, kaempferol-3O-rutinoside, kaempferol-rhamnosylhexoside and 2-azaanthraquinone were identified in MFM.

Conclusions

MFM was effective in some inflammatory parameters, in the experimental conditions that were used in the study. The results presented in this study and the previous in-vitro anti-Salmonella activity reported by our research group reinforce the importance of MFM studies to considerer it as an alternative treatment for salmonellosis.
Protective effects of duloxetine against chronic immobilisation stress-induced anxiety, depression, cognitive impairment and neurodegeneration in mice
Authors: Meejuru Glory Florence , Somavarapu Anushri , Danduga Ravi Chandra Sekhara Reddy , Nissankara Roa Lakshmi Sudeepthi , Kola Phani Kumar
Published: January 2021

Objectives

This study aimed to evaluate the effect of duloxetine (10 and 20 mg/kg) against chronic immobilisation stress (CIS)-induced anxiety, depression, cognitive impairment and neurodegeneration in mice.

Methods

CIS, 2 h/10 days (11:00 AM–1:00 PM) was applied after 30 min of pretreatment with saline, duloxetine 10 mg/kg and 20 mg/kg to the respective groups of animals, except the control group. Animals were examined for physiological (body weight, locomotion and grip strength), psychological (memory impairment, anxiety and depression), neurochemical (GABA and glutamate), biochemical (MDA, catalase, glutathione, superoxide dismutase) and histopathological changes.

Key findings

CIS exposure revealed anxiety-like behaviour, depression-like behaviour, motor in-coordination and learning and memory impairment in mice. Besides, CIS induction decreased the antioxidant enzymes (GSH, SOD and catalase), GABA and the viable neuronal cell count, whereas CIS exposure significantly elevated the MDA, AChE activity and glutamate content in the cortex and hippocampus. Pretreatment with duloxetine10 and 20 mg/kg showed dose-dependent ameliorated effect against the CIS-induced alterations in mice.

Conclusion

In conclusion, the results of this study demonstrated the protective effect of duloxetine against neuropsychiatric symptoms, memory impairment caused by CIS-induction through inhibition of oxidative stress, AChE activity and glutamate release.
Chronotoxicity of Semen Strychni is associated with circadian metabolism and transport in mice
Authors: Gao Lu , Lin Yanke , Wang Shuai , Lin Luomin , Lu Danyi , Zhao Yue , Xing Huijie , Wu Baojian
Published: January 2021

Objectives

We aimed to determine the circadian responses of mice to Semen Strychni and to investigate the role of pharmacokinetics in generating chronotoxicity.

Methods

Total extract of Semen Strychni was administered by oral gavage to wild-type (WT) and Bmal1−/− (a circadian clock-deficient model) mice at different circadian time points for toxicity (including survival) and pharmacokinetic characterization. Nephrotoxicity and neurotoxicity were evaluated by measuring plasma creatinine and creatine kinase BB (CK-BB), respectively. Drug metabolism and transport assays were performed using liver/intestine microsomes and everted gut sacs, respectively.

Key findings

Semen Strychni nephrotoxicity and neurotoxicity as well as animal survival displayed significant circadian rhythms (the highest level of toxicity was observed at ZT18 and the lowest level at ZT2 to ZT6). According to pharmacokinetic experiments, herb dosing at ZT18 generated higher plasma concentrations (and systemic exposure) of strychnine and brucine (two toxic constituents) compared with ZT6 dosing. This was accompanied by reduced formation of both dihydroxystrychnine and strychnine glucuronide (two strychnine metabolites) at ZT18. Bmal1 ablation sensitized mice to Semen Strychni-induced toxicity (with increased levels of plasma creatinine and CK-BB) and abolished the time dependency of toxicity. Metabolism of Semen Strychni (strychnine and brucine) in the liver and intestine microsomes of WT mice was more extensive at ZT6 than at ZT18. These time differences in hepatic and intestinal metabolism were lost in Bmal1−/− mice. Additionally, the intestinal efflux transport of Semen Strychni (strychnine and brucine) was more extensive at ZT6 than ZT18 in WT mice. However, the time-varying transport difference was abolished in Bmal1−/− mice.

Conclusions

Circadian responses of mice to Semen Strychni are associated with time-varying efflux transport and metabolism regulated by the circadian clock (Bmal1). Our findings may have implications for optimizing phytotherapy with Semen Strychni via timed delivery.
Possible roles of intestinal P-glycoprotein and cytochrome P450 3A on the limited oral absorption of irinotecan
Authors: Yamasaki Keishi , Hidaka Muneaki , Kawano Yohei , Furuya Yumiko , Ono Hiroshige , Arimori Kazuhiko
Published: January 2021

Objectives

Irinotecan is a widely intravenously used drug for the treatment of certain types of solid tumours. The oral administration of irinotecan has recently been recognized as being a more effective method for the treatment than intravenous administration. However, the limited oral bioavailability of irinotecan poses a problem for its oral delivery. In this study, we report on an investigation of the mechanism responsible for the limited oral absorption of irinotecan using rats as models.

Methods

The intestinal absorption of irinotecan in the absence and presence of several compounds was examined using intestinal loop method. The pharmacokinetics of irinotecan was investigated when verapamil, an inhibitor of the P-glycoprotein (P-gp) and cytochrome P450 3A (CYP3A) was pre-administered.

Key findings

The intestinal absorption of irinotecan was enhanced in the presence of verapamil, indicating that efflux by intestinal P-gp contributes to its limited oral absorption. Indeed, the oral bioavailability of irinotecan was increased when verapamil was orally pre-administered. This increased oral bioavailability was accompanied by a slight but significant decrease in the formation of a metabolite produced by the action of CYP3A.

Conclusion

The findings presented herein suggest that intestinal efflux by P-gp is mainly and intestinal metabolism by CYP3A is partially responsible for the limited oral absorption of irinotecan.
Combining 1H-NMR-based metabonomics and network pharmacology to dissect the mechanism of antidepression effect of Milletia speciosa Champ on mouse with chronic unpredictable mild stress-induced depression
Authors: Su Zhiheng , Ruan Junxiang , Liu Xi , Zheng Hua , Ruan Jingzhou , Lu Yuying , Cheng Bang , Wu Fang , Wu Jinxia , Liu Xuwen , Song Fangming , Chen Zhaoni , Song Hui , Liang Yonghong , Guo Hongwei
Published: January 2021

Objectives

Milletia speciosa Champ (MS), a traditional Chinese medicine, has the abilities of antistress, antifatigue, anti-oxidation and so on. In our previous study, MS was found to antidepression while the underlying mechanism of which needs further elucidation.

Methods

Here, a proton nuclear magnetic resonance (1H-NMR)-based metabonomics combined network pharmacology research approach was performed to investigate the antidepressive mechanism of MS act on mouse with chronic unpredictable mild stress-induced depression.

Key findings

Results showed that MS could alleviate the ethology of depression (including sucrose preference degree, crossing lattice numbers and stand-up times) and disordered biochemical parameters (5-hydroxytryptamine, norepinephrine and brain-derived neurotrophic factor). Metabonomics study and network pharmacology analysis showed that MS might improve depression through synergistically regulating five targets including Maoa, Maob, Ache, Ido1 and Comt, and three metabolic pathways such as tryptophan metabolism, synthesis of neurotransmitter and phospholipid metabolism.

Conclusions

This study for the first time preliminary clarified the potential antidepressive mechanism of MS and provided theoretical basis for developing MS into novel effective antidepressant.
Advantages of introducing an effective crystalline inhibitor in curcumin amorphous solid dispersions formulated by Eudragit E100
Authors: Fan Na , Li Jingyang , Li Jing
Published: January 2021

Objectives

This paper was to elucidate the advantages of using an effective crystalline inhibitor, which was hydroxypropyl methylcellulose E5 (HPMC), in inhibiting crystallisation for curcumin amorphous solid dispersion (Cur ASDs) formulated by Eudragit E100 (E100).

Methods

Physical characterisation such as differential scanning calorimetry and powder X-ray diffraction revealed the solid state during the formation of dispersion and clarified the compatibility between Cur and excipient.

Key findings

The liquidity of excipient and the change of Tg in Cur ASDs demonstrated that the addition of HPMC can reduce molecule motion of the whole system, improve Tg of Cur ASDs and inhibit crystallisation of Cur ASDs. The water uptake experiment and molecular dynamic modelling further confirmed the effective solution and matrix crystallisation inhibition role of HPMC.

Conclusions

The elucidation of HPMC as auxiliary excipient on inhibiting crystallisation for Cur ASDs will bring huge value in designing Cur ASDs in the future.
A simple and effective method for the preparation of high-purity shikimic acid from chromatography wash effluent of Ginkgo biloba leaf extract by macroporous resin considering the effect of varying feed solution compositions
Authors: Zhang Sijie , Gong Xingchu , Qu Haibin
Published: January 2021

Objectives

The present study investigated the feasibility of preparing high-purity shikimic acid (SA) from the chromatography wash effluent of Ginkgo biloba leaf extract by macroporous resin.

Methods

First, static/dynamic adsorption and desorption were conducted to screen out the optimal resin. Second, the key parameters of the chromatographic process were optimised with face-centred central composite design (CCD). Third, wash effluent indices were measured, different batches of wash effluent were used to prepare SA under the optimised parameters, and the effect of varying feed solution compositions on final products was investigated.

Key findings

It was found that the final purity and recovery rate of SA prepared with ADS-21 resin were not lower than 70 and 60%, respectively, when the purity of SA in the wash effluent was higher than 21.4%. The quality of the final product can be predicted based on the properties of wash effluent.

Conclusions

The proposed method could not only provide a simple, green and promising approach for the large-scale purification of SA from wash effluent but also be used to develop process intermediate quality standards for other natural products.
Pinus roxburghii alleviates bone porosity and loss in postmenopausal osteoporosis by regulating estrogen, calcium homeostasis and receptor activator of nuclear factor-κB, osteoprotegerin, cathepsin bone markers
Authors: Sharma Aditi , Sharma Lalit , Saini Reena V , Kumar Ashwani , Goyal Rohit
Published: January 2021

Objectives

The study was aimed to evaluate the potential of hydroalcoholic extract of Pinus roxburghii (PRE) stem bark in post-menopausal osteoporosis and its underlying mechanisms.

Methods

In silico docking of the markers was done using AutoDock version 4.2. for molecular targets: receptor activator of nuclear factor-κB (RANK), osteoprotegerin (OPG) and Cathepsin. Female Wistar rats of bodyweight 200–250 g were employed and surgical ovariectomy (OVX) was performed. PRE was administered at a dose of 100 and 200 mg/kg whereas standard drug, raloxifene given at 1 mg/kg orally for eight weeks.

Key findings

PRE (20 and 40 µg/mL) significantly increased the cellular proliferation in osteoblastic UMR cell lines 11.58 and 15.09% respectively. Eight weeks after surgical removal of ovaries, a significant bone porosity was confirmed by modulation in bone breaking strength of tibia, lumber, and femur; bone mineral density (BMD), calcium, phosphorus, hydroxyproline levels in OVX group. Treatment with PRE 100 and 200 mg/kg significantly restored the bone loss. Real-time polymerase chain reaction (RT-PCR) analysis of molecular markers RANK, OPG and cathepsin and histology also confirmed the attenuation of bone loss. The quantification of quercetin, gallic acid, caffeic acid, catechin, tannic acid and ascorbic acid was done by high-performance liquid chromatography (HPLC) and high performance thin layer chromatography.

Conclusions

P. roxburghii produced anti-osteoporotic effect possibly due to estrogenic modulation, and improved bone remodeling.
Rutin prevents inflammation induced by lipopolysaccharide in RAW 264.7 cells via conquering the TLR4-MyD88-TRAF6-NF-κB signalling pathway
Authors: Tian Chunlian , Liu Xin , Chang Yu , Wang Ruxia , Yang Mei , Liu Mingchun
Published: January 2021

Objectives

Inflammation widely exists in many diseases and poses a great threat to human and animal health. Rutin, quercetin-3-rhamnosyl glucoside, has a variety of pharmacological effects, including anti-oxidant, anti-inflammatory, antibacterial, anticancer and radioresistance effects. The current study focused on evaluation of its anti-inflammatory activity and described the mechanism of rutin in lipopolysaccharide-induced RAW 264.7 cells.

Methods

The related gene and protein expression levels were investigated by quantification real-time PCR and western blotting, respectively.

Key findings

This study revealed that rutin can decrease inducible nitric oxide synthase (iNOS) gene and protein expression levels, effectively increase IκB gene expression, reduce toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumour necrosis factor receptor-associated factor 6 (TRAF6) and p65 gene expression and inhibit the phosphorylation of IκB and p65 and the proteins expression of TLR4, MyD88 and TRAF6.

Conclusions

These results suggest that rutin might exert anti-inflammatory effect on LPS-stimulated RAW 264.7 cells and will be potentially useful as an adjuvant treatment for inflammatory diseases.
Hypericin-mediated photodynamic therapy for the treatment of cancer: a review
Authors: Dong Xiaoxv , Zeng Yawen , Zhang Zhiqin , Fu Jing , You Longtai , He Yuanyuan , Hao Yang , Gu Zili , Yu Zhenfeng , Qu Changhai , Yin Xingbin , Ni Jian , Cruz Luis J
Published: January 2021

Objectives

Hypericin is a polycyclic aromatic naphthodianthrone that occurs naturally. It is also an active ingredient in some species of the genus Hypericum. Emerging evidence suggests that hypericin has attracted great attention as a potential anticancer drug and exhibits remarkable antiproliferative effect upon irradiation on various tumour cells. This paper aims to summarise the anticancer effect and molecular mechanisms modulated by hypericin-medicated photodynamic therapy and its potential role in the cancer treatment.

Key findings

Hypericin-medicated photodynamic therapy could inhibit the proliferation of various tumour cells including bladder, colon, breast, cervical, glioma, leukaemia, hepatic, melanoma, lymphoma and lung cancers. The effect is primarily mediated by p38 mitogen-activated protein kinase (MAPK), JNK, PI3K, CCAAT-enhancer-binding protein homologous protein (CHOP)/TRIB3/Akt/mTOR, TRAIL/TRAIL-receptor, c-Met and Ephrin-Eph, the mitochondria and extrinsic signalling pathways. Furthermore, hypericin-medicated photodynamic therapy in conjunction with chemotherapeutic agents or targeted therapies is more effective in inhibiting the growth of tumour cells.

During the past few decades, the anticancer properties of photoactivated hypericin have been extensively investigated. Hypericin-medicated photodynamic therapy can modulate a variety of proteins and genes and exhibit a great potential to be used as a therapeutic agent for various types of cancer.
Zanthoxylum zanthoxyloides inhibits lipopolysaccharide- and synthetic hemozoin-induced neuroinflammation in BV-2 microglia: roles of NF-κB transcription factor and NLRP3 inflammasome activation
Authors: Ogunrinade Folashade A , Guetchueng Stephanie T , Katola Folashade O , Aderogba Mutalib A , Akande Idowu S , Sarker Satyajit D , Olajide Olumayokun A
Published: January 2021

Objectives

The effects of a root extract of Zanthoxylum zanthoxyloides on neuroinflammation in BV-2 microglia stimulated with LPS and hemozoin were investigated.

Methods

ELISA, enzyme immunoassay and Griess assay were used to evaluate levels of cytokines, PGE2 and NO in culture supernatants, respectively. Microglia-mediated neurotoxicity was evaluated using a BV-2 microglia-HT-22 neuron transwell co-culture.

Key findings

Treatment with Z. zanthoxyloides caused reduced elevated levels of TNFα, IL-6, IL-1β, NO and PGE2, while increasing the levels of IL-10. In addition, there were reduced levels of iNOS and COX-2 proteins. This was accompanied by a prevention of microglia-mediated damage to HT-22 mouse hippocampal neurons. Z. zanthoxyloides reduced elevated levels of phospho-IκB and phospho-p65, while preventing degradation of IκB protein and DNA binding of p65. Further mechanistic studies revealed that Z. zanthoxyloides reduced the levels of pro-IL-1β and IL-1β in hemozoin-activated BV-2 microglia. This was accompanied by a reduction in caspase-1 activity and NLRP3 protein expression. Bioassay-guided fractionation resulted in the isolation of skimmianine as an anti-inflammatory compound in Z. zanthoxyloides.

Conclusion

This is the first report showing the inhibition of neuroinflammation in LPS- and hemozoin-activated BV-2 microglia by the root extract of Z. zanthoxyloides by targeting the activation of both NF-κB and NLRP3 inflammasome.
Crude polysaccharide from the milky mushroom, Calocybe indica, modulates innate immunity of macrophage cells by triggering MyD88-dependent TLR4/NF-κB pathway
Authors: Ghosh Sandipta , Khatua Somanjana , Dasgupta Adhiraj , Acharya Krishnendu
Published: January 2021

Objectives

Calocybe indica is a famous nutritious food in Asian countries and one of the most widely cultivated mushrooms in the world. Here, we have isolated crude polysaccharides from this mushroom, characterized it and investigated its antioxidant and immunostimulatory potential.

Methods

The polysaccharide was chemically characterized by spectrophotometry, FTIR and high-performance thin layer chromatography and tested its antioxidant potential by in vitro assays. Immunomodulatory activity and its underlying signalling process were ascertained in RAW 264.7 cells.

Key findings

The polysaccharide consisted of D-glucose (β-linked sugars), D-mannose and D-galactose, where backbone was organized in random coil structure. Preliminary investigation of the bioactivity of the polysaccharide revealed its antioxidant potential. The polysaccharide could noticeably induce phagocytic activity and production of immune mediators in macrophage cells. The polysaccharide was found to enhance the expression of pro-inflammatory cytokines and activate NF-κB signalling pathway by overexpressing MyD88, Iκ-Bα and NF-κB. Further studies indicated the polysaccharide binds to the toll-like receptor 4 to manifest its immunostimulatory activity in macrophage cells.

Conclusions

Our findings indicate potential therapeutic properties of the crude polysaccharide of C. indica which might provide the means to treat various radical induced and immunodeficiency disorders in the days to come.
Combination of urine and faeces metabolomics to reveal the intervention mechanism of Polygala tenuifolia compatibility with Magnolia officinalis on gastrointestinal motility disorders
Authors: Ma Rong , Xie Qian , Wang Jian , Huang Lihua , Guo Xiaoqing , Fan Yamei
Published: January 2021

Objectives

To explore the intervention mechanism of combining Polygala tenuifolia (PT) with Magnolia officinalis (MO) on gastrointestinal motility disorders caused by PT.

Methods

Urine and faeces of rats were collected; the effects of PT and MO on the gastric emptying and small intestine advancing rates in mice were analysed via ultra-high performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–Q-TOF-MS) to determine the potential metabolites. Changes in the metabolic profiles of the urine and faeces were revealed by untargeted metabolomics, followed by multivariate statistical analysis. The integration of urine and faeces was applied to reveal the intervention mechanism of PT–MO on PT-induced disorders.

Key findings

PT + MO (1:2) improved the gastrointestinal function in mice suffering from PT-induced gastrointestinal motility disorder. Metabolomics indicated that the PT–MO mechanism was mainly associated with the regulations of 17 and 12 metabolites and 11 and 10 pathways in urine and faeces, respectively. The common metabolic pathways were those of tyrosine, purine, tricarboxylic acid cycle, pyruvate and gluconeogenesis, which were responsible for the PT–MO intervention mechanism.

Conclusions

The PT–MO (1:2) couple mechanism mitigated the PT-induced disorders, which were related to the energy, amino acid and fatty metabolisms.
Pharmacological characterisation of anticonvulsant effects elicited by erythrartine
Authors: dos Reis Suelen Lorenzato , Gelfuso Erica A , Fachin Ana Lúcia , Pereira Ana Maria Soares , Beleboni Renê O
Published: January 2021

Objectives

The erythrinan alkaloids erythravine and 11α-hydroxy-erythravine from Erythrina verna (Vell.) have been extensively investigated for their anxiolytic and anticonvulsant effects. Both are structurally similar to the erythrartine that also exhibit anxiolytic effects, but there is no report on its anticonvulsant potential. Since some anxiolytic drugs can be useful in the management of epileptic seizures, we investigated whether erythrartine could prevent seizures induced by different chemoconvulsants.

Methods

Experiments were performed using different concentrations of erythrartine injected via intracerebroventricular in rats submitted to pilocarpine, kainic acid, pentylenetetrazol or picrotoxin-induced seizures. Moreover, the rotarod test was performed to verify the effects of erythrartine on animal motor coordination.

Results

Our data showed for the first time that erythrartine prevented the occurrence of seizures induced by all of the chemoconvulsants tested and did not affect locomotor performance neither produced sedative effect on animals.

Conclusion

Obtained results validate the ethnopharmacological significance of E. verna and provide new information on erythrartine, another erythrinian alkaloid of biotechnological and medicinal interest.
Physcion-8-O-β-d-glucoside interferes with the nuclear factor-κB pathway and downregulates P-glycoprotein expression to reduce paclitaxel resistance in ovarian cancer cells
Authors: Li Xue , He Yuanqi , Wei Liqun , Zhang Jianzhong , Li Xiaoxiao , Cui Weiwei , Zhang Shihong
Published: January 2021

Objective

This study assessed whether physcion-8-O-beta-D-monoglucoside (PG) sensitises paclitaxel (PTX)-resistant ovarian cancer cells and explored the underlying mechanism.

Methods

Ovarian cancer SK-OV-3 cells were used to establish PTX-resistant SK-OV-3 (SK-OV-3/PTX) cells. The Cell Counting Kit-8 assay and crystal violet staining were used to determine cell viability. P-glycoprotein (P-gp) and nuclear factor (NF)-κB expression and cell distributions were detected using immunofluorescence. Cell apoptosis and protein expression changes were detected using flow cytometry and western blotting, respectively. Effect of PG in vivo was evaluated using a xenograft tumour model. P-gp expression in tumour tissues was detected using immunohistochemical staining.

Key findings

PG (1–10 μm) did not significantly affect SK-OV-3/PTX cell proliferation but significantly downregulated P-gp expression. PG pretreatment (1–10 μm) enhanced PTX cytotoxicity. PG treatment decreased the quantity of phosphorylated-NF-κB p65 in SK-OV-3/PTX cell total proteins and upregulated IKBα expression. Simultaneously, it decreased NF-κB p65 levels in nuclear proteins. PG (1–10 μm) inhibited NF-κB p65 entry into the nucleus. PTX plus PG significantly inhibited SK-OV-3/PTX xenograft tumour growth. PG (1–10 μm) reduced P-gp expression in transplanted tumour tissue.

Conclusions

PG can enhance the sensitivity of PTX-resistant ovarian cancer cells SK-OV-3/PTX to PTX, and this effect is related to inhibiting NF-κB from entering the nucleus and down-regulating the expression of P-gp protein.
Comparing the pharmacokinetics of 13α,21-dihydroeurycomanone and eurycomanone exclusively enriched in Eurycoma longifolia extracts and their spermatogenesis enhancement in andrographolide-induced oligospermia in rats
Authors: Chung Wan-Jie , Chan Kit-Lam , Lee Chong-Yew
Published: January 2021

Objectives

The quassinoids eurycomanone (EN) and 13α,21-dihydroeurycomanone (DHY) of Eurycoma longifolia Jack are reported to enhance spermatogenesis. This study aims to profile the pharmacokinetics of DHY, a minor and hitherto unstudied constituent, evaluate its spermatogenesis enhancement property and compare these attributes with that of the predominant EN.

Methods

Crude Eurycoma longifolia extract was chromatographed into a DHY-enriched extract (DHY-F) and an EN-enriched extract (EN-F). Male Sprague–Dawley rats were administered intravenously and orally with both extracts and their plasma levels of both quassinoids were determined. The extracts were then tested for their spermatogenesis augmentation ability in normal rats and an andrographolide-induced oligospermia model.

Key findings

Chromatographic enrichment resulted in a 28-fold increase of DHY in DHY-F and a 5-fold increase of EN in EN-F compared with non-chromatographed crude extracts. DHY showed better oral bioavailability (1.04 ± 0.58%) than EN (0.31 ± 0.19%). At 5 mg/kg, EN exhibited higher efficacy in spermatogenesis enhancement in normal rats and restoration of oligospermia to normal sperm profile versus DHY.

Conclusions

Despite the better pharmacokinetic profile of DHY, EN remains the main chemical contributor to plant bioactivity. DHY-F and EN-F represent improvements in developing Eurycoma longifolia as a potential phytomedicine for male infertility particularly oligospermia.
Cytotoxicity mechanisms of plumbagin in drug-resistant tongue squamous cell carcinoma
Authors: Xue Danfeng , Zhou Xiongming , Qiu Jiaxuan
Published: January 2021

Objectives

To evaluate the inhibitory effect and mechanism of plumbagin (PLB) against drug-resistant tongue squamous cell carcinoma (TSCC), and whether its antitumour effect is not affected by tumour drug resistance.

Methods

TSCC sensitive CAL27 cells and drug-resistant CAL27/RE cells were used to study the cytotoxicity and mechanism of PLB in vitro, including CCK-8 analysis, colony formation, DAPI staining, flow cytometry assay, transmission electron microscopy, western blotting assay, autophagy, apoptosis and ROS fluorescent probes. BALB/c nude mice xenograft models were used to study the growth inhibitory effect of PLB in vivo.

Key findings

The results showed that the cell viability and proliferation inhibition and apoptosis induction abilities of PLB on drug-resistant cells were more obvious than that on sensitive cells. And PLB induced protective autophagy in TSCC cells. Mechanistically, PLB induced apoptosis and autophagy by generating reactive oxygen species to mediate JNK and AKT/mTOR pathways. Finally, the growth inhibitory effect of PLB against drug-resistant TSCC was also confirmed in vivo.

Conclusions

PLB will be a promising anticancer agent to overcome drug-resistant TSCC without being affected by its drug resistance properties.
l-Borneol ameliorates cerebral ischaemia by downregulating the mitochondrial calcium uniporter-induced apoptosis cascade in pMCAO rats
Authors: Zhang Wenwen , Wen Jianxia , Jiang Yinxiao , Hu Qichao , Wang Jian , Wei Shizhang , Li Haotian , Ma Xiao
Published: January 2021

Objectives

Stroke is one of the leading causes of disability and death worldwide, and ischaemic stroke is the most common subtype. Moreover, we found that L-borneol has an obvious therapeutic effect on cerebral ischaemia. This study aimed to investigate the potential mechanism of L-borneol in permanent middle cerebral artery occlusion (pMCAO) rats via the mitochondrial calcium uniporter (MCU)-related apoptosis cascade.

Methods

A pMCAO model was used to simulate cerebral ischaemia, and neurological function was evaluated. Cerebral infarction was observed by TTC staining. HE staining was also used to reflect the pathophysiological changes in the rat hippocampus and cortex. Furthermore, MCU-related signals and apoptosis signalling pathways were detected at both the gene and protein levels.

Results

The neurological function scores of the high-dose L-borneol (H-B) group, medium-dose L-borneol (M-B) group and low-dose L-borneol (L-B) group were significantly lower than that of the model group at 24 h (P < 0.05, P < 0.01). High and medium doses of L-borneol could reverse the cerebral infarction area, similar to Nimotop. After HE staining, the cells in the H-B group and M-B group were neatly and densely arranged, with largely normal morphological structures. High-dose L-borneol could significantly reduce the gene and protein levels of Apaf-1, Bad and Caspase-3 and increase the expression of Bcl-2 (P < 0.05, P < 0.01). In addition, the MCU expression of the H-B group was significantly decreased compared with that of the model group at both the gene and protein levels (P < 0.05, P < 0.01). The expression of IDH2 was similar to that of MCU but not MEP (P < 0.05, P < 0.01).

Conclusion

L-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.
Transcriptomic and metabonomic profiling reveal the anti-obesity effects of Chikusetsusaponin V, a compound extracted from Panax japonicus
Authors: Qiu Yixing , Yu Huanghe , Hu Yi , Guo Shiyin , Lei Xinnuo , Qin Yan , Jian Yuqing , Li Bin , Liu Leping , Peng Caiyun , Wang Aibing , Wang Wei
Published: January 2021

Objectives

To explore the in vivo anti-obesity effect of chikusetsusaponin V and explore the underlying mechanism by transcriptomic and metabonomic methods.

Methods

The physiological parameters of high-fat-diet induced obese mice administered with or without 25 mg/kg and 100 mg/kg of chikusetsusaponin V by gavage for 16 weeks were recorded. In addition, the RNA-sequencing and UHPLC-Q-TOF techniques were applied to obtain the transcriptomic and metabolomic profiling, respectively.

Key findings

Chikusetsusaponin V could significantly alleviate the high-fat-diet induced increase in the weight of the whole body and obesity-related organs or tissues, and ameliorate the lipid content in the blood, the lipid accumulation in the livers, as well as the hypertrophy of the fat tissues. Importantly, transcriptomic results revealed that more than 30 genes involved in the pathway which closely associates with obesity, were significantly altered. Moreover, metabolomic data indicated the key differential metabolites enriched in the pathways such as the activated protein kinase signaling pathway which is a vital mediator of obesity and other processes.

Conclusions

The integrative analysis highlighted that chikusetsusaponin V significantly influenced the activated protein kinase signaling pathway at both transcriptomic and metabolomic levels, thereby exerting anti-obesity effects.
Antimicrobial and anthelmintic activities of the ethanolic extract, fractions and isolated compounds from Manilkara zapota L. P. Royen (Sapotaceae)
Authors: Mourão Mulvaney Layany Carolyny , Xavier-Júnior Francisco Humberto , Rodrigues Alice M S , Stien Didier , Allegretti Silmara Marques , Garcia Vera Lúcia
Published: January 2021

Objectives

To evaluate the antibacterial, antifungal and anthelmintic activities of the ethanolic extract (EEMz), fractions (LPFMz and HPFMz) and compounds isolated from the leaves of Manilkara zapota L. P. Royen.

Methods

Extract and fractions were produced by turbolization. LPFMz fraction was analysed by gas chromatography–mass spectrometry. The isolated compounds from HPFMz were purified by flash and preparative chromatographic methods, and chemically characterised by UPLC-ESITOFMS, optical rotation, and one- and two-dimensional 1H and 13C NMR techniques. Anthelmintic against Strongyloides venezuelensis and antimicrobial activities against Candida albicans, Trichophyton rubrum and Staphylococcus aureus were evaluated.

Key findings

EEMz showed mainly phenolic compounds and pentacyclic triterpenes from Δ12-oleane/Δ12-ursane series. Chlorogenic acid, myricetin-3-O-β-D-glucopyranoside, mearnsitrin, germanicol and germanicol acetate were reported to M. zapota leaves for the first time in this work. EEMz, HPFMz, LPFMz showed significative activity against C. albicans (16 µg/mL), while isolated flavonoids were active against S. aureus (<32 µg/mL). EEMz, phenolic-rich compounds (F2), and chlorogenic acid were potentially active against S. venezuelensis at 24 h.

Conclusions

M. zapota and its bioactive compound can be eligible such as a potential phytomedicine for the treatment of microbial and strongyloidiasis drug-resistant infections.