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Fulltext Emerging pathways to neurodegeneration: Dissecting the critical molecular mechanisms in Alzheimer's disease, Parkinson's disease

Tan SH, Karri V, Tay NWR, Chang KH, Ah HY, Ng PQ, et al.

Biomed Pharmacother, 2019 Mar;111:765-777.
PMID: 30612001 DOI: 10.1016/j.biopha.2018.12.101

Neurodegenerative diseases are usually sporadic in nature and commonly influenced by a wide range of genetic, life style and environmental factors. A unifying feature of Alzheimer's disease (AD) and Parkinson's disease (PD) is the abnormal accumulation and processing of mutant or damaged intra and extracellular proteins; this leads to neuronal vulnerability and dysfunction in the brain. Through a detailed review of ubiquitin proteasome, mRNA splicing, mitochondrial dysfunction, and oxidative stress pathway interrelation on neurodegeneration can improve the understanding of the disease mechanism. The identified pathways common to AD and PD nominate promising new targets for further studies, and as well as biomarkers. These insights suggested would likely provide major stimuli for developing unified treatment approaches to combat neurodegeneration. More broadly, pathways can serve as vehicles for integrating findings from diverse studies of neurodegeneration. The evidence examined in this review provides a brief overview of the current literature on significant pathways in promoting in AD, PD. Additionally, these insights suggest that biomarkers and treatment strategies may require simultaneous targeting of multiple components.
Fulltext The roles of circular RNAs in human development and diseases

Lee ECS, Elhassan SAM, Lim GPL, Kok WH, Tan SW, Leong EN, et al.

Biomed Pharmacother, 2019 Mar;111:198-208.
PMID: 30583227 DOI: 10.1016/j.biopha.2018.12.052

For many years, circular ribonucleic acids (circRNAs) have been counted as aberrant splicing by-products. Advanced bioinformatics analysis and deep sequencing techniques have allowed researchers to discover more interesting facts about circRNAs. Intriguing evidence has shed light on the functions of circRNAs in many tissues. Furthermore, emerging reports showed that circRNAs are found abundantly in saliva and blood samples, suggesting that circRNAs are potential clinical biomarkers for human embryonic development, diseases progression and prognosis, in addition to its role in organogenesis and pathogenesis. The implementation of circRNAs in human developmental stages and diseases would be a tremendous discovery in the science and medical field. Therefore, circRNAs have been studied for its biological function as well as its implication in various human diseases. The aim of this review is to highlight the importance of circRNAs in cardiac, respiratory, nervous, endocrine and digestive systems. In addition, the role and impact of circRNAs in, cardiogenesis, neurogenesis and cancer have been discussed.
Fulltext Anticancer activity of grassy Hystrix brachyura bezoar and its mechanisms of action: An in vitro and in vivo based study

Khan AYF, Ahmed QU, Narayanamurthy V, Razali S, Asuhaimi FA, Saleh MSM, et al.

Biomed Pharmacother, 2019 Jun;114:108841.
PMID: 30981106 DOI: 10.1016/j.biopha.2019.108841

Porcupine bezoar (PB) is a calcified undigested material generally found in porcupine's (Hystrix brachyura) gastrointestinal tract. The bezoar is traditionally used in South East Asia and Europe for the treatment of cancer, poisoning, dengue, typhoid, etc. However, limited scientific studies have been performed to verify its anticancer potential to substantiate its traditional claims in the treatment of cancers. Hence, this study was aimed at investigating the in vitro and in vivo anticancer properties of two grassy PB aqueous extract (PB-A and PB-B) using A375 cancer cell line and zebrafish model, respectively. This paper presents the first report on in vitro A375 cell viability assay, apoptosis assay, cell cycle arrest assay, migration assay, invasion assay, qPCR experimental assay and in vivo anti-angiogenesis assay using the grassy PBs. Experimental findings revealed IC50 value are 26.59 ± 1.37 μg/mL and 30.12 ± 3.25 μg/mL for PB-A and PB-B respectively. PBs showed anti-proliferative activity with no significant cytotoxic effect on normal human dermal fibroblast (NHDF). PBs were also found to induce apoptosis via intrinsic pathway and arrest cell cycle at G2/M phase. Additionally, the findings indicated its ability to debilitate migration and invasion of A375 cells. Further evaluation using embryo zebrafish model revealed LC50 = 450.0 ± 2.50 μg/mL and 58.7 ± 5.0 μg/mL for PB-A and PB-B which also exerted anti-angiogenesis effect in zebrafish. Moreover, stearic acid, ursodeoxycholic acid and pregnenolone were identified as possible metabolites that might contribute to the anticancer effect of the both PBs. Overall, this study demonstrated that PB-A and PB-B possess potential in vitro and in vivo anticancer effects which are elicited through selective cytotoxic effect, induction of apoptosis, inhibition of migration and invasion and anti-angiogenesis. This study provides scientific evidence that the porcupine bezoar do possess anti-cancer efficacy and further justifies its traditional utility. However, more experiments with higher vertebrae models are still warranted to validate its traditional claims as an anticancer agent.
Fulltext Ardisia crispa root hexane fraction suppressed angiogenesis in human umbilical vein endothelial cells (HUVECs) and in vivo zebrafish embryo model

Wen Jun L, Pit Foong C, Abd Hamid R

Biomed Pharmacother, 2019 Oct;118:109221.
PMID: 31545225 DOI: 10.1016/j.biopha.2019.109221

Ardisia crispa Thunb. A. DC. (Primulaceae) has been used extensively as folk-lore medicine in South East Asia including China and Japan to treat various inflammatory related diseases. Ardisia crispa root hexane fraction (ACRH) has been thoroughly studied by our group and it has been shown to exhibit anti-inflammatory, anti-hyperalgesic, anti-arthritic, anti-ulcer, chemoprevention and suppression against inflammation-induced angiogenesis in various animal model. Nevertheless, its effect against human endothelial cells in vitro has not been reported yet. Hence, the aim of the study is to investigate the potential antiangiogenic property of ACRH in human umbilical vein endothelial cells (HUVECs) and zebrafish embryo model. ACRH was separated from the crude ethanolic extract of the plant's root in prior to experimental studies. MTT assay revealed that ACRH exerted a concentration-dependent antiproliferative effect on HUVEC with the IC50 of 2.49 ± 0.04 μg/mL. At higher concentration (10 μg/mL), apoptosis was induced without affecting the cell cycle distribution. Angiogenic properties including migration, invasion and differentiation of HUVECs, evaluated via wound healing, trans-well invasion and tube formation assay respectively, were significantly suppressed by ACRH in a concentration-dependent manner. Noteworthily, significant antiangiogenic effects were observed even at the lowest concentration used (0.1 μg/mL). Expression of proMMP-2, vascular endothelial growth factor (VEGF)-C, VEGF-D, Angiopoietin-2, fibroblast growth factor (FGF)-1, FGF-2, Follistatin, and hepatocyte growth factor (HGF) were significantly reduced in various degrees by ACRH. The ISV formation in zebrafish embryo was significantly suppressed by ACRH at the concentration of 5 μg/mL. These findings revealed the potential of ACRH as antiangiogenic agent by suppressing multiple proangiogenic proteins. Thus, it can be further verified via the transcription of these proteins from their respective DNA, in elucidating their exact pathways.
Fulltext Prospective role of mitochondrial apoptotic pathway in mediating GMG-ITC to reduce cytotoxicity in H2O2-induced oxidative stress in differentiated SH-SY5Y cells

Jaafaru MS, Nordin N, Rosli R, Shaari K, Bako HY, Noor NM, et al.

Biomed Pharmacother, 2019 Nov;119:109445.
PMID: 31541852 DOI: 10.1016/j.biopha.2019.109445

The antioxidant and neuroprotective activity of Glucomoringin isothiocyanate (GMG-ITC) have been reported in in vivo and in vitro models of neurodegenerative diseases. However, its neuroprotective role via mitochondrial-dependent pathway in a noxious environment remains unknown. The main objective of the present study was to unveil the mitochondrial apoptotic genes' profile and prospectively link with neuroprotective activity of GMG-ITC through its ROS scavenging. The results showed that pre-treatment of differentiated SH-SY5Y cells with 1.25 μg/mL purified isolated GMG-ITC, significantly reduced reactive oxygen species (ROS) production level, compared to H2O2 control group, as evidenced by flow cytometry-based evaluation of ROS generation. Presence of GMG-ITC prior to development of oxidative stress condition, downregulated the expression of cyt-c, p53, Apaf-1, Bax, CASP3, CASP8 and CASP9 genes with concurrent upregulation of Bcl-2 gene in mitochondrial apoptotic signalling pathway. Protein Multiplex revealed significant decreased in cyt-c, p53, Apaf-1, Bax, CASP8 and CASP9 due to GMG-ITC pre-treatment in oxidative stress condition. The present findings speculated that pre-treatment with GMG-ITC may alleviate oxidative stress condition in neuronal cells by reducing ROS production level and protect the cells against apoptosis via neurodegenerative disease potential pathways.
Fulltext Targets and mechanisms of sulforaphane derivatives obtained from cruciferous plants with special focus on breast cancer - contradictory effects and future perspectives

Jabbarzadeh Kaboli P, Afzalipour Khoshkbejari M, Mohammadi M, Abiri A, Mokhtarian R, Vazifemand R, et al.

Biomed Pharmacother, 2020 Jan;121:109635.
PMID: 31739165 DOI: 10.1016/j.biopha.2019.109635

Breast cancer is the most common type of cancer among women. Therefore, discovery of new and effective drugs with fewer side effects is necessary to treat it. Sulforaphane (SFN) is an organosulfur compound obtained from cruciferous plants, such as broccoli and mustard, and it has the potential to treat breast cancer. Hence, it is vital to find out how SFN targets certain genes and cellular pathways in treating breast cancer. In this review, molecular targets and cellular pathways of SFN are described. Studies have shown SFN inhibits cell proliferation, causes apoptosis, stops cell cycle and has anti-oxidant activities. Increasing reactive oxygen species (ROS) produces oxidative stress, activates inflammatory transcription factors, and these result in inflammation leading to cancer. Increasing anti-oxidant potential of cells and discovering new targets to reduce ROS creation reduces oxidative stress and it eventually reduces cancer risks. In short, SFN effectively affects histone deacetylases involved in chromatin remodeling, gene expression, and Nrf2 anti-oxidant signaling. This review points to the potential of SFN to treat breast cancer as well as the importance of other new cruciferous compounds, derived from and isolated from mustard, to target Keap1 and Akt, two key regulators of cellular homeostasis.
Fulltext African walnuts attenuate ectopic fat accumulation and associated peroxidation and oxidative stress in monosodium glutamate-obese Wistar rats

Uti DE, Atangwho IJ, Eyong EU, Umoru GU, Egbung GE, Nna VU, et al.

Biomed Pharmacother, 2020 Apr;124:109879.
PMID: 31991383 DOI: 10.1016/j.biopha.2020.109879

AIMS: African walnuts were previously shown to modulate hepatic lipid bio-accumulation in obesity. Herein, we investigated the impact of the nuts on fat accumulation in adipose and ectopic regions, and associated oxidatiive stress status in obese rats.
MATERIALS AND METHODS: Whole ethanol extract (WE) of the nuts, and its liquid-liquid fractions-ethyl acetate (ET) and residue (RES) were separately administered to obese rats for 6 weeks. The normal (NC) and obese (OC) controls received normal saline and the standard control (SC), orlistat (5.14 mg/kg b.w.), during the same period. Thereafter, the animals were euthanized and the adipose, brain, kidneys and heart tissues were studied.
RESULTS: The change in body weight to naso-anal length which increased by 63.52 % in OC compared to NC (p < 0.05), decreased by 57.88, 85.80 and 70.20 % in WE, ET and RES-treated groups, respectively, relative to the OC (p < 0.05). Also, adipose tissue weights were lowered upon treatment with the extracts and fractions versus OC (p < 0.05). Total lipids, phospholipids, triacylglycerol and cholesterol concentrations in the studied tissues which were higher in OC (p < 0.05) were lowered (p < 0.05) and compared favorably with SC. Further, malondialdehyde levels in the tissues were lowered upon treatment, compared to the OC (p < 0.05). Glutathione level and activities of glutathione peroxidase, superoxide dismutase and glutathione-S-transferase which were decreased (p < 0.05) in OC, were restored upon treatment with the extracts, relative to the obese control (p < 0.05).
SIGNIFICANCE: African walnuts assuaged lipogenesis, oxidative stress and peroxidation in extra-hepatic tissues of obese rats, hence, may attenuate ectopic fat accumulation and its associated pathogenesis.
Fulltext Irigenin treatment alleviates doxorubicin (DOX)-induced cardiotoxicity by suppressing apoptosis, inflammation and oxidative stress via the increase of miR-425

Guo L, Zheng X, Wang E, Jia X, Wang G, Wen J

Biomed Pharmacother, 2020 May;125:109784.
PMID: 32092815 DOI: 10.1016/j.biopha.2019.109784

Doxorubicin (DOX) is an eﬀ ;ective chemotherapeutic drug to suppress the progression of various types of tumors. However, its clinical application has been largely limited due to its potential cardiotoxicity. MicroRNAs (miRNAs) are emerged as critical regulators of cardiac injury. This study was aimed to explore the effects of irigenin (IR), as an isoflavonoid isolated from the rhizome of Belamcanda chinensis, on DOX-induced cardiotoxicity using the in vivo and in vitrostudies. The results indicated that DOX-induced fibrosis, cardiac dysfunction and injury were markedly attenuated by IR through reducing apoptosis, oxidative stress and inflammation in heart tissue samples. Importantly, DOX resulted in a remarkable decrease of miR-425 in heart tissues and cells, which was significantly rescued by IR. Receptor-interacting protein kinase 1 (RIPK1) was discovered to be a direct target of miR-425. DOX induced over-expression of RIPK1 both in vivo and in vitro, which were greatly decreased by IR. Transfection with miR-425 mimic could inhibit RIPK1 expression, whereas reducing miR-425 increased RIPK1 expression levels. In parallel to miR-425 over-expression, RIPK1 knockdown could attenuate apoptosis, reactive oxygen species (ROS) production and inflammation in HL-1 cells. However, over-expression of RIPK1 markedly abolished miR-425 mimic-induced apoptosis, ROS accumulation and inflammatory response in DOX-exposed cells. Herein, miR-425 could ameliorate cardiomyocyte injury through directly targeting RIPK1. Furthermore, activation of miR-425 by IR markedly improved DOX-induced cardiotoxicity, and therefore IR could be considered as a promising therapeutic agent for the treatment of cardiac injury.
Fulltext Pharmacokinetics and antiangiogenic studies of potassium koetjapate in rats

Jafari SF, Al-Suede FSR, Yehya AHS, Ahamed MBK, Shafaei A, Asif M, et al.

Biomed Pharmacother, 2020 Oct;130:110602.
PMID: 32771894 DOI: 10.1016/j.biopha.2020.110602

PURPOSE: Koetjapic acid is an active compound of a traditional medicinal plant, Sandoricum koetjape. Although koetjapic acid has a promising anticancer potential, yet it is highly insoluble in aqueous solutions. To increase aqueous solubility of koetjapic acid, we have previously reported a chemical modification of koetjapic acid to potassium koetjapate (KKA). However, pharmacokinetics of KKA has not been studied. In this study, pharmacokinetics and antiangiogenic efficacy of KKA are investigated.
METHODS: Pharmacokinetics of KKA was studied after intravenous and oral administration in SD rats using HPLC. Anti-angiogenic efficacy of KKA was investigated in rat aorta, human endothelial cells (EA.hy926) and nude mice implanted with matrigel.
RESULTS: Pharmacokinetic study revealed that KKA was readily absorbed into blood and stayed for a long time in the body with Tmax 2.89 ± 0.12 h, Cmax 7.24 ± 0.36 μg/mL and T1/2 1.46 ± 0.03 h. The pharmacological results showed that KKA significantly suppressed sprouting of microvessels in rat aorta with IC50 18.4 ± 4.2 μM and demonstrated remarkable inhibition of major endothelial functions such as migration, differentiation and VEGF expression in endothelial cells. Further, KKA significantly inhibited vascularization in matrigel plugs implanted in nude mice.
CONCLUSIONS: The results indicate that bioabsorption of KKA from oral route was considerably efficient with longer retention in body than compared to that of the intravenous route. Further, improved antiangiogenic activity of KKA was recorded which could probably be due to its increased solubility and bioavailability. The results revealed that KKA inhibits angiogenesis by suppressing endothelial functions and expression of VEGF.
Fulltext Visualising functional 5-HT3 receptors containing A and C subunits at or near the cell surface

Abad IPL, Fam RL, Nguyen DT, Nowell CJ, Trinh PNH, Manallack DT, et al.

Biomed Pharmacother, 2020 Dec;132:110860.
PMID: 33059258 DOI: 10.1016/j.biopha.2020.110860

Five different subunits of the human serotonin 3 (5-hydroxytrptamine 3; 5-HT3) receptor exist and these are present in both central and peripheral systems. Different subunits alter the efficacy of 5-HT3 receptor antagonists used to treat diarrhoea predominant-irritable bowel syndrome, chemotherapy induced nausea and vomiting and depression. Cell surface arrangement of 5-HT3 receptor complexes and the contribution of C, D and E subunits to receptor function is poorly understood. Here, we examine interactions of A and C subunits using 5-HT3 receptor subunits containing fluorescent protein inserts between the 3rd and 4th transmembrane spanning region. HEK293T cells that do not normally express 5-HT3 receptor subunits, were transiently transfected with A or C or both subunits. Patch clamp experiments show that cells transfected with either fluorescent protein tagged A or A and C subunits generate whole cell currents in response to 5-HT. These findings correlate with the apparent distribution of fluorescent protein tagged A and C subunits at or near cell surfaces detected using TIRF microscopy. In co-transfected cells, the A and C subunits are associated forming AC heteromer complexes at or near the cell surface and a proportion can also form A or C homomers. In conclusion, it is likely that both A homomers and AC heteromers contribute to whole cell currents in response to 5-HT with minimal contribution from C homomers.
Therapeutic promises of ginkgolide A: A literature-based review

Sarkar C, Quispe C, Jamaddar S, Hossain R, Ray P, Mondal M, et al.

Biomed Pharmacother, 2020 Dec;132:110908.
PMID: 33254431 DOI: 10.1016/j.biopha.2020.110908

Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent.
Fulltext Capilliposide B blocks VEGF-induced angiogenesis in vitro in primary human retinal microvascular endothelial cells

Han H, Yang Y, Wu Z, Liu B, Dong L, Deng H, et al.

Biomed Pharmacother, 2021 Jan;133:110999.
PMID: 33227710 DOI: 10.1016/j.biopha.2020.110999

Abnormal angiogenesis is associated with intraocular diseases such as proliferative diabetic retinopathy and neovascular age-related macular degeneration, and current therapies for these eye diseases are not satisfactory. The purpose of this study was to determine whether capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, can inhibit vascular endothelial growth factor (VEGF)-induced angiogenesis signaling events and cellular responses in primary human retinal microvascular endothelial cells (HRECs). Our study revealed that the capilliposide B IC50 for HRECs was 8.5 μM at 72 h and that 1 μM capilliposide B specifically inhibited VEGF-induced activation of VEGFR2 and its downstream signaling enzymes Akt and Erk. In addition, we discovered that this chemical effectively blocked VEGF-stimulated proliferation, migration and tube formation of the HRECs, suggesting that capilliposide B is a promising prophylactic for angiogenesis-associated diseases such as proliferative diabetic retinopathy.
Fulltext Pretreatment of Blumea lacera leaves ameliorate acute ulcer and oxidative stress in ethanol-induced Long-Evan rat: A combined experimental and chemico-biological interaction

Hossen MA, Reza ASMA, Ahmed AMA, Islam MK, Jahan I, Hossain R, et al.

Biomed Pharmacother, 2021 Mar;135:111211.
PMID: 33421733 DOI: 10.1016/j.biopha.2020.111211

Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5 mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500 mg/kg, p.o., b.w) and omeprazole (20 mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (p 
Fulltext Flavokawain C exhibits anti-tumor effects on in vivo HCT 116 xenograft and identification of its apoptosis-linked serum biomarkers via proteomic analysis

Phang CW, Abd Malek SN, Karsani SA

Biomed Pharmacother, 2021 May;137:110846.
PMID: 33761587 DOI: 10.1016/j.biopha.2020.110846

Chalcones and their derivatives belong to the flavonoid family. They have been extensively studied for their anticancer properties and some have been approved for clinical use. In this study, the in vivo anti-tumor activity of flavokawain C (FKC), a naturally occurring chalcone found in Kava (Piper methysticum Forst) was evaluated in HCT 116 cells (colon carcinoma). We also attempted to identify potential biomarkers and/or molecular targets in serum with applicability in predicting treatment outcome. The anti-tumor effects and toxicity of FKC were assessed using the xenograft nude mice model. Cisplatin was used as positive control. The anti-proliferative and apoptotic activities were then evaluated in tumor tissues treated with FKC. Furthermore, two-dimensional electrophoresis (2-DE) followed by protein identification using MALDI-TOF/TOF-MS/MS was performed to compare the serum proteome profiles between healthy nude mice and nude mice bearing HCT 116 tumor treated with vehicle solution and FKC, respectively. Our results showed that FKC treatment significantly inhibited HCT 116 tumor growth. In vivo toxicity studies showed that administration of FKC did not cause damage to major organs and had no significant effect on body weight. FKC was found to induce apoptosis in tumor, and this was associated with increased expression of cleaved caspase-3 and decreased expression of Ki67 in tumor tissues. Our proteomic analysis identified five proteins that changed in abundance - Ig mu chain C region (secreted form), GRP78, hemopexin, kininogen-1 and apolipoprotein E. Overall, our findings demonstrated the potential of FKC as an anti-cancer agent for the treatment of colon carcinoma.
Fulltext Therapeutic potential of annatto tocotrienol with self-emulsifying drug delivery system in a rat model of postmenopausal bone loss

Mohamad NV, Ima-Nirwana S, Chin KY

Biomed Pharmacother, 2021 May;137:111368.
PMID: 33582449 DOI: 10.1016/j.biopha.2021.111368

Tocotrienol has been shown to prevent bone loss in animal models of postmenopausal osteoporosis, but the low oral bioavailability might limit its use. A self-emulsifying drug delivery system (SEDDS) could increase the bioavailability of tocotrienol. However, evidence of this system in improving the skeletal effects of tocotrienol is scanty. This study aims to evaluate the therapeutic efficacy of annatto tocotrienol with SEDDS in a rat model of postmenopausal bone loss. Ten-month-old female Sprague Dawley rats were randomized into six groups. The baseline group was euthanatized at the onset of the study. Four other groups underwent ovariectomy to induce estrogen deficiency. The sham underwent similar surgery procedure, but their ovaries were retained. Eight weeks after surgery, the ovariectomized rats received one of the four different regimens orally daily: (a) SEDDS, (b) annatto tocotrienol [60 mg/kg body weight (b.w.)] without SEDDS, (c) annatto-tocotrienol (60 mg/kg b.w.) with SEDDS, (d) raloxifene (1 mg/kg b.w.). After eight weeks of treatment, blood was collected for the measurement of delta-tocotrienol level and oxidative stress markers. The rats were euthanized and their bones were harvested for the evaluation of the bone microstructure, calcium content and strength. Circulating delta-tocotrienol level was significantly higher in rats receiving annatto tocotrienol with SEDDS compared to the group receiving unformulated annatto-tocotrienol (p
Fulltext Oxidative stress cytotoxicity induced by platinum-doped magnesia nanoparticles in cancer cells

Al-Fahdawi MQ, Al-Doghachi FAJ, Abdullah QK, Hammad RT, Rasedee A, Ibrahim WN, et al.

Biomed Pharmacother, 2021 Jun;138:111483.
PMID: 33744756 DOI: 10.1016/j.biopha.2021.111483

The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.
Fulltext Swietenine potentiates the antihyperglycemic and antioxidant activity of Metformin in Streptozotocin induced diabetic rats

Shiming Z, Mak KK, Balijepalli MK, Chakravarthi S, Pichika MR

Biomed Pharmacother, 2021 Jul;139:111576.
PMID: 33862494 DOI: 10.1016/j.biopha.2021.111576

Diabetes mellitus or type-2 diabetes, commonly referred as diabetes, is a metabolic disorder that results in high blood sugar level. Despite the availability of several antidiabetic drugs in the market, they still do not adequately regulate blood sugar levels. Thus, in general people prefer to use herbal supplements/medicines along with antidiabetic drugs to control blood sugar levels. One of such herbal medicine is Swietenia macrophylla seeds. It is widely used in Asia for controlling blood sugar levels. One of the major bioactive compounds, Swietenine, is reported to be responsible for controlling blood glucose levels. However, there were no studies on its efficacy in controlling the blood glucose in diabetic rats. In this study, we evaluated the antihyperglycemic activity of Swietenine and its pharmacodynamic interaction with Metformin in Streptozotocin induced diabetes in rats. The activity of Swietenine was investigated at three different doses: 10, 20 and 40 mg/kg body weight (bw). Metformin (50 mg/kg bw) was used as a standard drug. Swietenine (20 and 40 mg/kg bw) and Metformin (50 mg/kg bw) showed significant effect in reducing the glucose, cholesterol, triglycerides, low-density lipoprotein, urea, creatinine, alanine transaminase, alkaline phosphatase, aspartate transaminase, alanine transaminase, and malondialdehyde level in serum while it had increased the high-density lipoprotein, glutathione, and total antioxidant capacity level. In addition, Swietenine (20 and 40 mg/kg) had shown significant synergistic effect with Metformin. Administration of Swietenine at 10 mg/kg bw neither showed activity nor influenced Metformin's activity. The results from this study confirmed the beneficial effects of Swietenine and its synergistic action with Metformin in controlling the dysregulated serum parameters in Streptozotocin induced diabetes in rats.
Fulltext The therapeutic potential of curcumin in alleviating N-diethylnitrosamine and iron nitrilotriacetate induced renal cell tumours in mice via inhibition of oxidative stress: Implications for cancer chemoprevention

Iqbal M, Shah MD, Vun-Sang S, Okazaki Y, Okada S

Biomed Pharmacother, 2021 Jul;139:111636.
PMID: 33957566 DOI: 10.1016/j.biopha.2021.111636

This study was designed to reveal the protective effects of dietary supplementation of curcumin against renal cell tumours and oxidative stress induced by renal carcinogen iron nitrilotriacetate (Fe-NTA) in ddY male mice. The results showed that mice treated with a renal carcinogen, Fe-NTA, a 35% renal cell tumour incidence was noticed, whereas renal cell tumour occurrence was elevated to 80% in Fe-NTA promoted and N-diethylnitrosamine (DEN)-initiated mice as compared with saline- treated mice. No incidence of tumours has been observed in DEN-initiated non-promoted mice. Diet complemented with 0.5% and 1.0% curcumin fed prior to, during and after treatment with Fe-NTA in DEN-initiated animals, tumour incidence was reduced dose-dependently to about 45% and 30% respectively. Immunohistochemical studies also revealed the increased formation of 4-hydroxy-2-nonenal (HNE)-modified protein adducts and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in kidney tissue of mice treated with an intraperitoneal injection of Fe-NTA (6.0 mg Fe/kg body weight.). Furthermore, Fe-NTA treatment of mice also resulted in significant elevation of malondialdehyde (MDA), serum urea, and creatinine and decreases renal glutathione. However, the changes in most of these parameters were attenuated dose-dependently by prophylactic treatment of animals with 0.5% and 1% curcumin diet, this may be due to its antioxidative impact of curcumin. These results suggest that intake of curcumin is beneficial for the prevention of renal cell tumours and oxidative stress damage mediated by renal carcinogen, Fe-NTA.
Fulltext The intraperitoneal ondansetron for postoperative pain management following laparoscopic cholecystectomy: A proof-of-concept, double-blind, placebo-controlled trial

Abdelaziz DH, Boraii S, Cheema E, Elnaem MH, Omar T, Abdelraouf A, et al.

Biomed Pharmacother, 2021 Aug;140:111725.
PMID: 34015580 DOI: 10.1016/j.biopha.2021.111725

BACKGROUND: Pain after laparoscopic cholecystectomy remains a major challenge. Ondansetron blocks sodium channels and may have local anesthetic properties.
AIMS: To investigate the effect of intraperitoneal administration of ondansetron for postoperative pain management as an adjuvant to intravenous acetaminophen in patients undergoing laparoscopic cholecystectomy.
METHODS: Patients scheduled for elective laparoscopic cholecystectomy were randomized into two groups (n = 25 each) to receive either intraperitoneal ondansetron or saline injected in the gall bladder bed at the end of the procedure. The primary outcome was the difference in pain from baseline to 24-h post-operative assessed by comparing the area under the curve of visual analog score between the two groups.
RESULTS: The derived area under response curve of visual analog scores in the ondansetron group (735.8 ± 418.3) was 33.97% lower than (p = 0.005) that calculated for the control group (1114.4 ± 423.9). The need for rescue analgesia was significantly lower in the ondansetron (16%) versus in the control group (54.17%) (p = 0.005), indicating better pain control. The correlation between the time for unassisted mobilization and the area under response curve of visual analog scores signified the positive analgesic influence of ondansetron (rs =0.315, p = 0.028). The frequency of nausea and vomiting was significantly lower in patients who received ondansetron than that reported in the control group (p = 0.023 (8 h), and 0.016 (24 h) respectively).
CONCLUSIONS: The added positive impact of ondansetron on postoperative pain control alongside its anti-emetic effect made it a unique novel option for patients undergoing laparoscopic cholecystectomy.
Fulltext Protective role of Mas Cotek (Ficus deltoidea) against the toxic effects of bisphenol A on morphology and sex steroid receptor expression in the rat uterus

Zaid SSM, Othman S, Kassim NM

Biomed Pharmacother, 2021 Aug;140:111757.
PMID: 34044283 DOI: 10.1016/j.biopha.2021.111757

BACKGROUND: Numerous scientific studies have found that young women are at a high risk of reproductive infertility due to their routine exposure to numerous bisphenol A (BPA) products. This risk is highly associated with the production of reactive oxygen species from BPA products. Ficus deltoidea, which has strong antioxidant properties, was selected as a potential protective agent to counter the detrimental effects of BPA in the rat uterus.
METHODS: Female Sprague-Dawley rats were allocated into four groups (n = 8) as follows: (i) the Normal Control group (NC), (ii) the BPA-exposed group (PC), (iii) the group concurrently treated with BPA and F. deltoidea (FC) and (iv) the group treated with F. deltoidea alone (F).
RESULTS: After 6 weeks of concurrent treatment with F. deltoidea, uterine abnormalities in the BPA-exposed rats showed a significant improvement. Specifically, the size of stromal cells increased; interstitial spaces between stromal cells expanded; the histology of the glandular epithelium and the myometrium appeared normal and mitotic figures were present. The suppressive effects of BPA on the expression levels of sex steroid receptors (ERα and ERβ) and the immunity gene C3 were significantly normalised by F. deltoidea treatment. The role of F. deltoidea as an antioxidant agent was proven by the significant reduction in malondialdehyde level in BPA-exposed rats. Moreover, in BPA-exposed rats, concurrent treatment with F. deltoidea could normalise the level of the gonadotropin hormone, which could be associated with an increase in the percentage of rats with a normal oestrous cycle.
CONCLUSION: F. deltoidea has the potential to counter the toxic effects of BPA on the female reproductive system. These protective effects might be due to the phytochemical properties of F. deltoidea. Therefore, future study is warranted to identify the bioactive components that contribute to the protective effects of F. deltoidea.

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