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Purpose: The COVID-19 pandemic led to major service disruptions in the healthcare sector, especially regarding sexual and reproductive health services. However, the impact of the pandemic on Canadian adolescents is relatively unknown. This study aimed to investigate the impacts of the COVID-19 pandemic and associated public health measures on the sexual and reproductive health (SRH) of adolescents in Alberta, Canada. Methods: A qualitative study using an interpretive description (ID) approach and community-based participatory research principles was conducted to capture the subjective experience and perceptions of adolescents and service providers. With the collaboration of the Adolescent Advisory Group and community partners, 18 adolescents and 15 service providers were recruited for the study through purposive sampling. Findings from the qualitative interviews were analyzed using thematic analysis. Results: Three major themes emerged from the analysis: (1) COVID-19 SRH experience, (2) barriers to SRH, and (3) adolescent SRH strategies. Our findings highlight numerous barriers and challenges that prevented adolescents from accessing SRH education, products, and services. Conclusion: The COVID-19 pandemic had a profound impact on the SRH and the well-being of adolescents. Our study reflects the need for diverse SRH strategies to maintain continued access to SRH resources during disruptive events, such as the pandemic. Plain language summary: Access to sexual and reproductive health (SRH) services is a basic human right. All individuals require access to appropriate SRH services to maintain their optimal sexual and reproductive health. Adolescents require special guidance, support, and youth-friendly services in matters of SRH as they enter puberty and explore their sexual identity. However, during the COVID-19 pandemic, many health and SRH services were suspended. Access to SRH products and services became difficult due to public health restrictions, which has possible negative consequences for adolescents' SRH. The experiences of adolescents during the COVID-19 pandemic regarding their SRH are not reported in Alberta, Canada. Therefore, we explored the impacts of these public health restrictions on adolescents' SRH. We performed qualitative interviews with adolescents and SRH service providers to know their perspectives on how the pandemic influenced the SRH of adolescents. This paper provides insights into the barriers faced by adolescents while accessing SRH services during the pandemic, as well as their perceptions of digital strategies, such as mobile applications, and other recommendations for supporting SRH education and services. Based on the study findings, an adolescent-friendly mobile application will be developed to provide a virtual platform connecting adolescents to SRH educational resources, services, and support. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic led to major service disruptions in the healthcare sector, especially regarding sexual and reproductive health services. However, the impact of the pandemic on Canadian adolescents is relatively unknown. This study aimed to investigate the impacts of the COVID-19 pandemic and associated public health measures on the sexual and reproductive health (SRH) of adolescents in Alberta, Canada. Methods: A qualitative study using an interpretive description (ID) approach and community-based participatory research principles was conducted to capture the subjective experience and perceptions of adolescents and service providers. With the collaboration of the Adolescent Advisory Group and community partners, 18 adolescents and 15 service providers were recruited for the study through purposive sampling. Findings from the qualitative interviews were analyzed using thematic analysis. Results: Three major themes emerged from the analysis: (1) COVID-19 SRH experience, (2) barriers to SRH, and (3) adolescent SRH strategies. Our findings highlight numerous barriers and challenges that prevented adolescents from accessing SRH education, products, and services. Conclusion: The COVID-19 pandemic had a profound impact on the SRH and the well-being of adolescents. Our study reflects the need for diverse SRH strategies to maintain continued access to SRH resources during disruptive events, such as the pandemic. Plain language summary: Access to sexual and reproductive health (SRH) services is a basic human right. All individuals require access to appropriate SRH services to maintain their optimal sexual and reproductive health. Adolescents require special guidance, support, and youth-friendly services in matters of SRH as they enter puberty and explore their sexual identity. However, during the COVID-19 pandemic, many health and SRH services were suspended. Access to SRH products and services became difficult due to public health restrictions, which has possible negative consequences for adolescents' SRH. The experiences of adolescents during the COVID-19 pandemic regarding their SRH are not reported in Alberta, Canada. Therefore, we explored the impacts of these public health restrictions on adolescents' SRH. We performed qualitative interviews with adolescents and SRH service providers to know their perspectives on how the pandemic influenced the SRH of adolescents. This paper provides insights into the barriers faced by adolescents while accessing SRH services during the pandemic, as well as their perceptions of digital strategies, such as mobile applications, and other recommendations for supporting SRH education and services. Based on the study findings, an adolescent-friendly mobile application will be developed to provide a virtual platform connecting adolescents to SRH educational resources, services, and support. [ABSTRACT FROM AUTHOR]

In the present study, a 50% ethanolic extract of Orthosiphon stamineus was tested for its α-glucosidase inhibitory activity. In vivo assays of the extract (containing 1.02%, 3.76%, and 3.03% of 3′hydroxy-5,6,7,4′-tetramethoxyflavone, sinensetin, and eupatorin, resp.) showed that it possessed an inhibitory activity against α-glucosidase in normal rats loaded with starch and sucrose. The results showed that 1000 mg/kg of the 50% ethanolic extract of O. stamineus significantly (P<0.05) decreased the plasma glucose levels of the experimental animals in a manner resembling the effect of acarbose. In streptozotocin-induced diabetic rats, only the group treated with 1000 mg/kg of the extract showed significantly (P<0.05) lower plasma glucose levels after starch loading. Hence, α-glucosidase inhibition might be one of the mechanisms by which O. stamineus extract exerts its antidiabetic effect. Furthermore, our findings indicated that the 50% ethanolic extract of O. stamineus can be considered as a potential agent for the management of diabetes mellitus. [ABSTRACT FROM AUTHOR]

The stepping forces of normal and Freund Complete Adjuvant (FCA)-induced arthritic rats were studied in vivo using a proposed novel analgesic meter. An infrared charge-coupled device (CCD) camera and a data acquisition system were incorporated intothe analgesic meter to determine and measure the weight of loads on the right hind paw before and after induction of arthritis by FCA injection into the paw cavity. FCA injection resulted in a significant reduction in the stepping force of the affected hind paw. The stepping force decreased to the minimum level on day 4 after the injection and then gradually increased up to day 25. Oral administration of prednisolone significantlyincreased the stepping forces of FCA-induced arthritic rats on days 14 and 21. These results suggest that the novel device is an effective tool for measuring the arthritic pain in in vivo studies even though walking is a dynamic condition. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000mg/kg/day for 28days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000mg/kg per day for 28days. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Coriolus versicolor, which is known as Yun Zhi, is one of the commonly used Chinese medicinal herbs. Recent studies have demonstrated its antitumor activities on cancer cells which led to its widespread use in cancer patient. However, little toxicological information is available regarding its safety. The present study evaluated the potential toxicity of Coriolus versicolor standardized water extract after acute and subchronic administration in rats. Materials and methods: In acute toxicity study, Coriolus versicolor water extract was administered by oral gavage to Sprague-Dawley (SD) rats (6 males, 6 females) at single doses of varying concentrations 1250, 2500 and 5000mg/kg. In subchronic toxicity study, the extract was administered orally at doses of 1250, 2500 and 5000mg/kg/day for 28 days to male and female SD rats respectively. General behavior, adverse effects and mortality were determined throughout the experimental period. Haematological and biochemical parameters, relative organ weights and histopathological were evaluated at the end of the experiment. Results: There were no mortality and signs of toxicity in acute and subchronic toxicity studies. In the single dose acute toxicity and repeated dose 28-day subchronic toxicity studies, there were no significant difference in body weight, relative organ weight, haematological parameters, clinical chemistry, gross pathology and histopathology between treatment and control groups. Conclusions: Coriolus versicolor water extract did not cause remarkable adverse effect in SD rats. The oral lethal dose of Coriolus versicolor water extract is more than 5000mg/kg and no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is 5000mg/kg per day for 28 days. [Copyright &y& Elsevier]

South Asians form Canada's largest visible minority but face notable health inequities. Specifically, South Asian immigrant youth (SAIY) confront challenges like racial discrimination, stigma, and acculturative stress due to their marginalised identities. Limited research exists on the barriers they face adjusting to Canadian life. We interviewed two groups: SAIY aged 15–24 (N = 23) and unrelated parents of SAIY (N = 13). Analysing both generations helped capture young SAIY's challenges and parental insights. Our findings underscore the varied experiences of SAIY in Edmonton, Alberta, highlighting the need for better accessibility to social and healthcare services. This study offers a foundation for future research on SAIY's needs. [ABSTRACT FROM AUTHOR]

Plant-parasitic nematodes constrain global food security. During parasitism, they secrete effectors into the host plant from two types of pharyngeal gland cells. These effectors elicit profound changes in host biology to suppress immunity and establish a unique feeding organ from which the nematode draws nutrition. Despite the importance of effectors in nematode parasitism, there has been no comprehensive identification and characterisation of the effector repertoire of any plant-parasitic nematode. To address this, we advance techniques for gland cell isolation and transcriptional analysis to define a stringent annotation of putative effectors for the cyst nematode Heterodera schachtii at three key life-stages. We define 717 effector gene loci: 269 "known" high-confidence homologs of plant-parasitic nematode effectors, and 448 "novel" effectors with high gland cell expression. In doing so we define the most comprehensive "effectorome" of a plant-parasitic nematode to date. Using this effector definition, we provide the first systems-level understanding of the origin, deployment and evolution of a plant-parasitic nematode effectorome. The robust identification of the effector repertoire of a plant-parasitic nematode will underpin our understanding of nematode pathology, and hence, inform strategies for crop protection. Author summary: Pathogenic organisms deliver so called "effectors", typically proteins, into their host to alter cell structure and function. Identifying and characterising the repertoire of effector-encoding genes is requisite to understanding infection. Here we advance methods and understanding, in combination with an extensive literature survey, to define a stringent annotation of putative effectors for the plant-parasitic cyst nematode, Heterodera schachtii. Using this effector definition, we provide the first systems-level understanding of the origin, deployment, and evolution of a plant-parasitic nematode effectorome. Given that plant-parasitic nematodes are major, and in some cases dominant, threats to global food security, it is widely cited that understanding how they infect their host (i.e. effectors) will deliver routes to alleviate their threat to agriculture. [ABSTRACT FROM AUTHOR]

Three series of ionic self-assembled materials based on anionic azo-dyes and cationic benzalkonium surfactants were synthesized and thin films were prepared by spin-casting. These thin films appear isotropic when investigated with polarized optical microscopy, although they are highly anisotropic. Here, three series of homologous materials were studied to rationalize this observation. Investigating thin films of ordered molecular materials relies to a large extent on advanced experimental methods and large research infrastructure. A statement that in particular is true for thin films with nanoscopic order, where X-ray reflectometry, X-ray and neutron scattering, electron microscopy and atom force microscopy (AFM) has to be used to elucidate film morphology and the underlying molecular structure. Here, the thin films were investigated using AFM, optical microscopy and polarized absorption spectroscopy. It was shown that by using numerical method for treating the polarized absorption spectroscopy data, the molecular structure can be elucidated. Further, it was shown that polarized optical spectroscopy is a general tool that allows determination of the molecular order in thin films. Finally, it was found that full control of thermal history and rigorous control of the ionic self-assembly conditions are required to reproducibly make these materials of high nanoscopic order. Similarly, the conditions for spin-casting are shown to be determining for the overall thin film morphology, while molecular order is maintained. [ABSTRACT FROM AUTHOR]

Orthosiphon stamineus Benth. (Lamiaceae) is an important plant in traditional folk medicine that is used to treat hypertension and kidney stones. In humans, this plant has been tested as an addition regiment for antihypertensive treatment. Among the treatments for hypertension, O. stamineus had been to have diuretic and vasorelaxant effects in animal models. There is still very little information regarding the vasorelaxant effect of O. stamineus. Therefore, the present study was designed to investigate the vasorelaxant activity and mechanism of action of the fractions of O. stamineus. The vasorelaxant activity and the underlying mechanisms of the chloroform fraction of the 50% methanolic extract of O. stamineus (CF) was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. CF caused relaxation of the aortic ring pre-contracted with phenylephrine in the presence and absence of endothelium, and pre-contracted with potassium chloride in endothelium-intact aortic ring. In the presence of endothelium, both indomethacin (a nonselective cyclooxygenase inhibitor) and -[1,2,4]Oxadiazolo[4,3-]quinoxalin-1-one (ODQ, selective soluble guanylate cyclase inhibitor) had a small effect on the vasorelaxation response. On the other hand, in the presence of Nω-nitro-L-arginine methyl ester (L-NAME, nitric oxide synthase inhibitor), methylene blue (cyclic guanosine monophosphate lowering agent), tetraethylammonium (, nonselective calcium activator channel blocker), 4-aminopyridine (4-AP, voltage-dependent channel blocker), barium chloride (, inwardly rectifying channel blocker), glibenclamide (nonspecific ATP-sensitive channel blocker), atropine (muscarinic receptor blocker) and propranolol (β-adrenergic receptor blocker), the vasorelaxant effect significantly reduced the relaxation stimulated by CF. CF was also found to be active in reducing release from the sarcoplasmic reticulum and blocking calcium channels. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that eupatorin content in Orthosiphon stamineus fractions correlated with their vasorelaxation activity. Even with previous studies, there is still very little information on the vasorelaxation effect of eupatorin, and not many scientific studies had been carried out. Therefore, the present study was designed to investigate the vasorelaxation activity and mechanism of action of eupatorin. The vasorelaxation activity and the underlying mechanisms of eupatorin was evaluated on thoracic aortic rings isolated from Sprague Dawley rats. Eupatorin caused the relaxation of aortic rings pre-contracted with phenylephrine with and without endothelium (pD2=6.66±0.13, E MAX =99.72±6.39%; pD2=6.10±0.22, E MAX =65.78±8.01%), and also the relaxation of endothelium-intact aortic rings pre-contracted with potassium chloride (pD2=6.20±0.30, E MAX =71.89±12.25%). In the presence of Nω-nitro-l-arginine methyl ester (pD2<4.60, E MAX =24.91±6.39%), methylene blue (pD2=6.05±0.38, E MAX =66.79±9.69%), ODQ (pD25.84±0.32, E MAX =60.47±9.6%), indomethacin (pD2=6.27±0.21, E MAX =76.03±9.45%), tetraethylammonium (pD2=6.09±0.35, E MAX =69.35±11.31%), 4-aminopyridine (pD2=6.34±0.12, E MAX =76±6.1%), barium chloride (pD2=6.47±0.14, E MAX =79.61±10.02%), atropine (pD2=6.36±0.29, E MAX =86.47±12.95%) and propranolol (pD2=6.49±0.26, E MAX= 83.2±12.01%), relaxation stimulated by eupatorin was significantly reduced. Eupatorin was also found to be active in reducing Ca 2+ release from sarcoplasmic reticulum and in blocking calcium channels. The present study demonstrates the vasorelaxation effect of eupatorin involving NO/sGC/cGMP and indomethacin pathways, calcium and potassium channels, and muscarinic and beta-adrenergic receptors. [ABSTRACT FROM AUTHOR]

(1) Background: An earlier study on the hypoglycemic activity of S. polyanthum (Wight.) leaf methanol extract identified squalene as the major chemical compound. The present study was conducted to assess the hypoglycemic effect of fractions and subfractions of the methanol extract of S. polyanthum compared to the squalene using a bioassay-guided in vivo study. (2) Methods: The methanol extract was fractionated using the liquid–liquid fractionation method. Streptozotocin-induced type 1 diabetic rat was used to study the hypoglycemic effect. (3) Results: The findings showed that chloroform fraction significantly (p < 0.05) lowered blood glucose levels of diabetic rats as compared to the control. Further fractionation of chloroform fraction yielded subfraction-1 and -2, whereby subfraction-1 exhibited a higher blood-glucose-lowering effect. The lipid profile test showed that the total cholesterol level of subfraction-1 and squalene-treated groups decreased significantly (p < 0.05). An immunohistochemistry study revealed that none of the treatments regenerated pancreatic β-cells. Gas chromatography–mass spectrophotometer analysis identified the presence of squalene in the active methanol extract, chloroform fraction, and subfraction-1. In silico analysis revealed a higher affinity of squalene against protein receptors that control lipid metabolism than metformin. (4) Conclusions: Data obtained from the present work suggested the crude methanol extract exerted the highest hypoglycemic effect compared to fraction, subfraction, and squalene, confirming synergistic effect may be responsible for the hypoglycemic activity of S. polyanthum. [ABSTRACT FROM AUTHOR]

Highlights: [•] The anti-diabetic property of V. amygdalina may not derive from antioxidant effect. [•] Fatty acids and phytols are involved in anti-diabetic mechanism of V. amygdalina. [•] Water is the best medium for antioxidant recipe of V. amygdalina leaves. [•] The functional role of V. amygdalina in nutrition and medicine has been substantiated. [•] The extraction solvent – biological activity specificity for vegetables was revealed. [Copyright &y& Elsevier]

Gynura procumbens (Lour.) Merr (family Compositae) is cultivated in Southeast Asia, especially Indonesia, Malaysia and Thailand, for medicinal purposes. This study evaluated the in vivo hypoglycemic properties of the water extract of G. procumbens following 14 days of treatment and in vitro in RIN-5F cells. Glucose absorption from the intestines and its glucose uptake in abdominal skeletal muscle were assessed. The antidiabetic effect of water extract of G. procumbens leaves was investigated in streptozotocin-induced diabetic rats. The intraperitoneal glucose tolerance test (IPGTT) was performed in diabetic rats treated with G. procumbens water extract for 14 days. In the IPGTT, blood was collected for insulin and blood glucose measurement. After the IPGTT, the pancreases were collected for immunohistochemical study of β-cells of the islets of Langerhans. The possible antidiabetic mechanisms of G. procumbens were assessed through in vitro RIN-5F cell study, intestinal glucose absorption and glucose uptake by muscle. The results showed that G. procumbens significantly decreased blood glucose levels after 14 days of treatment and improved outcome of the IPGTT. However, G. procumbens did not show a significant effect on insulin level either in the in vivo test or the in vitro RIN-5F cell culture study. G. procumbens also showed minimal effects on β-cells of the islets of Langerhans in the pancreas. However, G. procumbens only significantly increased glucose uptake by muscle tissues. From the findings we can conclude that G. procumbens water extract exerted its hypoglycemic effect by promoting glucose uptake by muscles. [ABSTRACT FROM AUTHOR]

Aim: The objective of the present study was to evaluate the in vitro effect of aqueous extract of Clinacanthus nutans leaves and the juice on the activity of UDP-glucuronosyltransferase (UGT), cytochrome P (CYP) 3A4, and CYP2E1 in human liver microsomes (HLMs). Materials and Methods: The herb-drug interactions of the leaf extracts and juice were determined by a specific enzyme activity of CYP isoforms with specific probe substrate using spectrophotometry. CYP3A4 activity was measured for aminopyrine-specific metabolite (formaldehyde) at 415 nm. CYP2E1 activity was determined using p-nitrophenol-specific metabolite (p-nitrocatechol) at 535 nm. UGT activity was quantified through the consumption of p-nitrophenol by UGT at 405 nm. Results: Results obtained showed that the juice and aqueous extract of C. nutans leaves exhibited significant inhibition (P < 0.05) in CYP3A4 and CYP2E1 activity in HLMs. The aqueous extract of C. nutans showed statistically significant (P < 0.05) activation on UGT activity at the concentration of 1000 ng/mL as compared to the negative control. Conclusion: There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4 and CYP2E1. The leaf preparation also activated UGT catalyzed metabolism which may result in a reduction of the potency of the drug metabolized by UGT pathway. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Citrus reticulatae Pericarpium (Chen pi) was widely used as an important ingredient in the prescription of TCM to treat phlegm fluid retention type hypertension. Since Chen pi is involved in treatment as antihypertensive TCM formula, we have reasonable expectation in believing that it might possess vasorelaxant activity. Aim of the study This study is designed to investigate the vasorelaxant effect of Chen pi and to study its pharmacology effects. Materials and methods The vasorelaxant effect of water extract of Chen pi (CRW) were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. The fingerprint of Chen pi and the extracts were developed with quantification of hesperidin content by HPTLC. Results CRW exhibited the strongest vasorelaxant activity. CRW caused the relaxation of the phenylephrine pre-contracted aortic rings in the presence and absence of endothelium as well as in potassium chloride pre-contracted endothelium-intact aortic ring. The incubation of propranolol (β-adrenergic receptor blocker), atropine (muscarinic receptor blocker), Nω-nitro- L -arginine methyl ester (NO synthase inhibitor), ODQ (sGC inhibitor), indomethacin (COX inhibitor), 4-aminopyridine (K V blocker), barium chloride (K ir blocker), and glibenclamide (K ATP blocker) significantly reduced the vasorelaxant effects of CRW. CRW was also found to be active in reducing Ca2+ releases from the sarcoplasmic reticulum and suppressing the voltage-operated calcium channels. Conclusion The vasorelaxant effect of CRW on rat aorta involves NO/sGC, calcium and potassium channels, muscarinic and β-adrenergic receptors. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

The seeds of Swietenia macrophylla King (SM) (Meliaceae) are used as a folk medicine for the treatment of hypertension in Malaysia. However, the antihypertensive and vasorelaxant effects of SM seeds are still not widely studied. Thus, this study was designed to investigate the in vivo antihypertensive effects and in vitro mechanism of vasorelaxation of a 50% ethanolic SM seed extract (SM50) and the fingerprint of SM50 was developed through tri-step Fourier transform infrared (FTIR) spectroscopy. The vasorelaxant activity and the underlying mechanisms of SM50 were evaluated on thoracic aortic rings isolated from Sprague-Dawley rats in the presence of antagonists. The pharmacological effect of SM50 was investigated by oral administration of spontaneously hypertensive rats (SHRs) with three different doses of SM50 (1000, 500, and 250 mg/kg/day) for 4 weeks and their systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were measured weekly using tail-cuff method. The tri-step FTIR macro-fingerprint of SM50 showed that SM50 contains stachyose, flavonoids, limonoids, and ester, which may contribute to its vasorelaxant effect. The results showed that the vasorelaxant activity of SM50 was mostly attributed to channel-linked receptors pathways through the blockage of voltage-operated calcium channels (VOCC). SM50 also acts as both potassium channels opener and inositol triphosphate receptor (IP3R) inhibitor, followed by β2-adrenergic pathway, and ultimately mediated through the nitric oxide/soluble guanylyl cyclase/cyclic 3′,5′-guanosine monophosphate (NO/sGC/cGMP) signaling pathways. The treatment of SM50 also significantly decreased the SBP and DBP in SHRs. In conclusion, the antihypertensive mechanism of SM50 was mediated by VOCC, K+ channels, IP3R, G-protein-coupled β2-adrenergic receptor, and followed by NO/sGC/cGMP signaling mechanism pathways in descending order. The data suggested that SM50 has the potential to be used as a herbal medicament to treat hypertension. [ABSTRACT FROM AUTHOR]

Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM. This study was designed to investigate the possible mechanism of actions involved in the vasodilatory activity of ABBT-50 by evaluating its vasodilative effect on isolated Sprague Dawley rats in the presence of absence of various antagonists. When pre-contracted with phenylephrine, relaxation was observed in endothelium intact (EC 50 = 0.027 ± 0.003 mg/ml, R max = 109.8 ± 2.12%) and denuded aortic rings (EC 50 = 0.409 ± 0.073 mg/ml, R max = 63.15 ± 1.78%), as well as in endothelium intact aortic rings pre-contracted with potassium chloride (EC 50 = 32.7 ± 12.16 mg/ml, R max = 34.02 ± 3.82%). Significant decrease in the vasodilative effect of ABBT-50 was observed in the presence of Nω-nitro- l -arginine methyl ester (EC 50 = 0.12 ± 0.021 mg/ml, R max = 75.33 ± 3.28%), 1 H -[1,2,4] Oxadiazolo[4,3- a ]quinoxalin-1-one (EC 50 = 0.463 ± 0.18 mg/ml, R max = 54.48 ± 2.02%), methylene blue (EC 50 = 0.19 ± 0.037 mg/ml, R max = 83.69 ± 3.19%), indomethacin (EC 50 = 0.313 ± 0.046 mg/ml, R max = 71.33 ± 4.12%), atropine (EC 50 = 0.146 ± 0.013 mg/ml, R max = 77.2 ± 3.41%), and 4-aminopyridine (EC 50 = 0.045 ± 0.008 mg/ml, R max = 95.55 ± 2.36%). ABBT-50 was also suppressing Ca 2+ release from sarcoplasmic reticulum and inhibiting calcium channels. Vasodilatory effects of ABBT-50 are mediated through NO/sGC/cGMP cascade and PGI 2 , followed by muscarinic pathways and calcium channels. [ABSTRACT FROM AUTHOR]

Hypertension, one of the famous 'silent killers' that can attack people at any age, is a current hot topic among scientists due to multiple syndromic behavior and concomitant diseases. The new scientific-based Traditional Chinese Medicine (TCM) formulation approach was used in a previous study by combining five TCM herbs, including Gastrodia elata Bl., Uncaria rhynchophylla (Miq.) Miq. ex Havil., Pueraria thomsonii Benth., Panax notoginseng (Burk.) F.H. Chen, and Alisma orientalis (Sam.) Juzep in optimized ratio (named BPAid). The objective of the present study was to evaluate the mechanism pathways employed by BPAid for vasodilatory effect with the use of an in vitro isolated aortic rings assay. Interestingly, all the mechanisms investigated were involved in the BPAid's vasodilation activity in which the majority contributed through the nitric oxide/soluble guanylyl cyclase/cyclic guanosine monophosphate (NO/sGC/cGMP) pathways, followed by prostacyclin (PGI2), β2-adrenergic, and M3-receptors pathways. Furthermore, the BPAid appeared to manage vascular tone by regulating action potential through potassium and both voltage-operated calcium channel and inositol triphosphate receptor (IP3R) pathways. The results obtained has confirmed the expected outcome that the benefits of TCM herbs in BPAid can meet the criteria of counteracting multiple signaling mechanism pathways involved in the etiology of hypertension. In addition to this study, the fingerprints and chemical properties of BPAid was identified by using tri-step Fourier transform infrared spectroscopy and compared with its derivatives. The results obtained suggested that the majority of the vasodilatory effects exerted by BPAid were attributed to the presence of saponins and aromatic ring-containing vasoactive compounds. [ABSTRACT FROM AUTHOR]

Context:Vernonia amygdalinaDel. (VA) (Asteraceae) is commonly used to treat hypertension in Malaysia. Objective:This study investigates the vasorelaxant mechanism of VA ethanol extract (VAE) and analyzes its tri-step FTIR spectroscopy fingerprint. Materials and methods:Dried VA leaves were extracted with ethanol through maceration and concentrated using rotary evaporator before freeze-dried. The vasorelaxant activity and the underlying mechanisms of VAE using the cumulative concentration (0.01–2.55 mg/mL at 20-min intervals) were evaluated on aortic rings isolated from Sprague Dawley rats in the presence of antagonists. Results:The tri-step FTIR spectroscopy showed that VAE contains alkaloids, flavonoids, and saponins. VAE caused the relaxation of pre-contracted aortic rings in the presence and absence of endothelium with EC50of 0.057 ± 0.006 and 0.430 ± 0.196 mg/mL, respectively. In the presence of Nω-nitro-l-arginine methyl ester (EC500.971 ± 0.459 mg/mL), methylene blue (EC501.203 ± 0.426 mg/mL), indomethacin (EC502.128 ± 1.218 mg/mL), atropine (EC500.470 ± 0.325 mg/mL), and propranolol (EC500.314 ± 0.032 mg/mL), relaxation stimulated by VAE was significantly reduced. VAE acted on potassium channels, with its vasorelaxation effects significantly reduced by tetraethylammonium, 4-aminopyridine, barium chloride, and glibenclamide (EC500.548 ± 0.184, 0.158 ± 0.012, 0.847 ± 0.342, and 0.304 ± 0.075 mg/mL, respectively). VAE was also found to be active in reducing Ca2+released from the sarcoplasmic reticulum and blocking calcium channels. Conclusions:The vasorelaxation effect of VAE involves upregulation of NO/cGMP and PGI2signalling pathways, and modulation of calcium/potassium channels, and muscarinic and β2-adrenergic receptor levels. [ABSTRACT FROM PUBLISHER]

Uncaria rhynchophylla is one of the major components included in Traditional Chinese Medicine prescriptions for hypertensive treatment. Previous studies have suggested that U. rhynchophylla might contain vasodilation-mediating active compounds, especially indole alkaloids. Hence, this study was carried out to determine the vasodilatory effects of U. rhynchophylla, which was extracted by different solvents. The most effective extract was then further studied for its signaling mechanism pathways. The authenticity of U. rhynchophylla was assured by using modernized tri-step Fourier transform infrared (FTIR), including conventional 1D FTIR, second derivative scanning combined with 2D-correlated IR spectroscopy. Results obtained proved that the fingerprint of U. rhynchophylla used was identical to the atlas. Isolated aortic rings from male Sprague-Dawley rats were preconstricted with phenylephrine (PE) followed by cumulative addition of U. rhynchophylla extracts. The signaling mechanism pathways were studied by incubation with different receptor antagonists before the PE precontraction. In conclusion, the 95% ethanolic U. rhynchophylla extract (GT100) was found to be most effective with an EC50 value of 0.028 ± 0.002 mg/mL and an Rmax value of 101.30% ± 2.82%. The signaling mechanism pathways employed for exerting its vasodilatory effects included nitric oxide/soluble guanylyl cylcase/cyclic guanosine monophosphate (NO/sGC/cGMP) and PGI2 (endothelium-derived relaxing factors), G protein-coupled M3- and β2 receptors, regulation of membrane potential through voltage-operated calcium channel, intracellular Ca2+ released from inositol triphosphate receptor (IP3R), and all potassium channels except the Kca channel. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Glycyrrhiza uralensis ( G. uralensis ) is one of the herbs used in traditional Chinese medicine (TCM) and serves as an envoy medicinal. Since G. uralensis plays a major role in the anti-hypertensive TCM formulae, we believe that G. uralensis might possess vasorelaxation activity. Aim of the study This study is designed to investigate the vasorelaxation effect of G. uralensis from various extracts and to study its pharmacology effect. Materials and methods The vasorelaxation effect of G. uralensis extracts were evaluated on thoracic aortic rings isolated from Sprague Dawley rats. Results Among these three extracts of G. uralensis, 50% ethanolic extract (EFG) showed the strongest vasorelaxation activity. EFG caused the relaxation of the aortic rings pre-contracted with phenylephrine either in the presence or absence of endothelium and pre-contracted with potassium chloride in endothelium-intact aortic ring. Nω-nitro- L -arginine methyl ester, methylene blue, or 1 H -[1,2,4]Oxadiazolo[4,3- a ]quinoxalin-1-one inhibit the vasorelaxation effect of EFG in the presence of endothelium. On the other hand, in the presence of the potassium channel blockers (tetraethylammonium and barium chloride), the vasorelaxation effect of EFG was not affected, but glibenclamide and 4-aminopyridine did inhibit the vasorelaxation effect of EFG. With indomethacin, atropine and propranolol, the vasorelaxation effect by EFG was significantly reduced. EFG was also found to be effective in reducing Ca 2+ release from sarcoplasmic reticulum and the blocking of calcium channels. Conclusions The results obtained suggest that EFG is involved in the NO/sGC/cGMP pathway. [ABSTRACT FROM AUTHOR]

Recently, a new syndromic disease combination theory of traditional Chinese medicine (TCM) for hypertensive treatment has been introduced. In the wake of this new concept, a new science-based TCM formula that counteracts various syndromes is needed. The objective of this study was to develop such a formula. Five of the most clinically prescribed TCM herbs that work on different syndromes, namely Gastrodia elata, Uncaria rhynchophylla, Pueraria thomsonii, Panax notoginseng, and Alisma orientale, were selected for this study. The fingerprints of these five herbs were analyzed by tri-step Fourier transform infrared spectroscopy. Three different solvents, 95% ethanol, 50% ethanol, and distilled water, were used for the maceration of the herbs and their vasodilatory effects were studied using in vitro precontracted aortic ring model. Among these, the 50% ethanolic extracts of G. elata (GE50) and A. orientale (AO50), and 95% ethanolic extracts of U. rhynchophylla (UR95), P. thomsonii (PT95), and P. notoginseng (PN95) were found to be the most effective for eliciting vasodilation. Thus, these five extracts were used for orthogonal stimulus-response compatibility group studies by using L25 (55) formula. The best combination ratio for GE50, UR95, PT95, PN95, and AO50, which was assigned as Formula 1 (F1), was found at EC0, EC25, EC20, EC20, and EC10, respectively. The vasodilatory effect of the extracts prepared from different extraction methods using F1 ratio was also studied. From the results, the EC50 and Rmax of total 50% ethanolic extract of five herbs using F1 ratio (F1-2) were 0.028 ± 0.005 mg/mL and 101.71% ± 3.64%, with better values than F1 (0.104 ± 0.014 mg/mL and 97.80% ± 3.12%, respectively). In conclusion, the optimum ratio and appropriate extraction method (F1-2) for the new TCM formula were revealed. [ABSTRACT FROM AUTHOR]

Endophthalmitis caused by Abiotrophia defectiva has never before been reported in a child. We report a case of a 12-year-old female with a history of penetrating keratoplasty, followed years later by open globe injury and repair, and subsequent anterior vitrectomy, which resulted in endophthalmitis caused by Abiotrophia defectiva. We review previous cases of endophthalmitis by this organism and argue that its detection will become more common with the use of 16S rDNA PCR and MALDI-TOF mass spectrometry. [ABSTRACT FROM AUTHOR]

This paper is a review on the types of antagonists and the signaling mechanism pathways that have been used to determine the mechanisms of action employed for vasodilation by test compounds. Thus, we exhaustively reviewed and analyzed reports related to this topic published in PubMed between the years of 2010 till 2015. The aim of this paperis to suggest the most appropriate type of antagonists that correspond to receptors that would be involved during the mechanistic studies, as well as the latest signaling pathways trends that are being studied in order to determine the route(s) that atest compound employs for inducing vasodilation. The methods to perform the mechanism studies were included. Fundamentally, the affinity, specificity and selectivity of the antagonists to their receptors or enzymes were clearly elaborated as well as the solubility and reversibility. All the signaling pathways on the mechanisms of action involved in the vascular tone regulation have been well described in previous review articles. However, the most appropriate antagonists that should be utilized have never been suggested and elaborated before, hence the reason for this review. [ABSTRACT FROM AUTHOR]

The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: A decoction from a combination of herbs is commonly used in Traditional African Medicine for the management of chronic ailments. In Nigeria, the leaves of Vernonia amygdalina Del. (VA) and Azadirachta indica A. Juss (AI) are used traditionally as a remedy against diabetes mellitus for which empirical evidence attests to its efficacy. Aim of the study: To evaluate the synergistic antidiabetic action of VA and AI, the biochemical effects and possible mechanism in streptozotocin-induced diabetic rat (SDR) models. Materials and methods: Ethanolic extracts of VA and AI were co-administered (200mg/kg, 50:50) to non-diabetic rats (NDRs) and SDRs for 28 days. Blood glucose and body weight were monitored during this period, and at end of treatment, serum glucose, insulin, triiodothyronine (T3), tetraiodothyronine (T4) and α-amylase activity were studied. Glucose and activities of antioxidant enzymes, e.g., catalase (CAT), glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in hepatocytes, along with the impact on the histology of the liver and pancreas. Medium acting insulin, HU (5IU/kg, s.c.) was used as a positive control. Results: The study reveals that compared with single extracts, the combined extract (VA/AI) promptly lowered blood glucose and maintained a relatively steady level over the study period, in tandem with HU. During this period, body weight gain successively increased. In SDRs, fasting blood glucose at days 0 and 28 was raised by 4.33 and 3.16 fold, respectively, and the serum glucose was raised by 7.70 fold vs. normal control (P <0.05). The discrepancies in the individual effects of VA and AI on hepatic glucose and α-amylase activity were also restored. In NDRs, VA/AI lowered blood and serum glucose (1.14 and 1.94 fold, respectively), although to a lesser extent when compared with HU. Furthermore, VA/AI was found to lower serum insulin, T3 and T4 by 1.66, 1.57 and 2.16 fold, respectively, in SDR (P <0.05). This was similar to HU, which demonstrated 1.79 and 1.68 fold reduction of insulin and T3, respectively (P <0.05), but had no effect on T4. Conversely, in NDRs, VA/AI caused 1.32, 4.93 and 1.04 fold increase in insulin, T3 and T4, respectively, reciprocal to its effect on blood and serum glucose. Oxidative stress in SDR, characterised by decreased GPx and CAT activities, was ameliorated, as the activities of the enzymes and SOD increased following a 28-day treatment with VA/AI (P <0.05). The features of diabetic pathology, indicated in the histology of the liver and pancreas, were reversed. However, the extent of recovery was partial with VA, better with AI, and distinct and total with VA/AI, compared with a null effect by HU. Conclusion: Taken together, our results contribute towards validation of enhanced antidiabetic efficacy of VA and AI when combined. This synergy may be exerted by oxidative stress attenuation, insulin mimetic action and β-cell regeneration. [Copyright &y& Elsevier]

An earlier anti-hyperglycemic study with serial crude extracts of Phaleria macrocarpa (PM) fruit indicated methanol extract (ME) as the most effective. In the present investigation, the methanol extract was further fractionated to obtain chloroform (CF), ethyl acetate (EAF), n-butanol (NBF) and aqueous (AF) fractions, which were tested for antidiabetic activity. The NBF reduced blood glucose (p < 0.05) 15 min after administration, in an intraperitoneal glucose tolerance test (IPGTT) similar to metformin. Moreover, it lowered blood glucose in diabetic rats by 66.67% (p < 0.05), similar to metformin (51.11%), glibenclamide (66.67%) and insulin (71.43%) after a 12-day treatment, hence considered to be the most active fraction. Further fractionation of NBF yielded sub-fractions I (SFI) and II (SFII), and only SFI lowered blood glucose (p < 0.05), in IPGTT similar to glibenclamide. The ME, NBF, and SFI correspondingly lowered plasma insulin (p < 0.05) and dose-dependently inhibited glucose transport across isolated rat jejunum implying an extra-pancreatic mechanism. Phytochemical screening showed the presence of flavonoids, terpenes and tannins, in ME, NBF and SFI, and LC-MS analyses revealed 9.52%, 33.30% and 22.50% mangiferin respectively. PM fruit possesses anti-hyperglycemic effect, exerted probably through extra-pancreatic action. Magniferin, contained therein may be responsible for this reported activity. [ABSTRACT FROM AUTHOR]

Behavioural assessment of experimental pain is an essential method for analysing and measuring pain levels. Rodent models, which are widely used in behavioural tests, are often subject to external forces and stressful manipulations that cause variability of the parameters measured during the experiment. Therefore, these parameters may be inappropriate as indicators of pain. In this article, a stepping-force analgesimeter was designed to investigate the variations in the stepping force of rats in response to pain induction. The proposed apparatus incorporates new features, namely an infrared charge-coupled device (CCD) camera and a data acquisition system. The camera was able to capture the locomotion of the rats and synchronise the stepping force concurrently so that each step could be identified. Inter-day and intra-day precision and accuracy of each channel (there were a total of eight channels in the analgesimeter and each channel was connected to one load cell and one amplifier) were studied using different standard load weights. The validation studies for each channel also showed convincing results whereby intra-day and inter-day precision were less than 1% and accuracy was 99.36-100.36%. Consequently, an in vivo test was carried out using 16 rats (eight females and eight males). The rats were allowed to randomly walk across the sensor tunnel (the area that contained eight channels) and the stepping force and locomotion were recorded. A non-expert, but from a related research domain, was asked to differentiate the peaks of the front and hind paw, respectively. The results showed that of the total movement generated by the rats, 50.27 ± 3.90% in the case of the male rats and 62.20 ± 6.12% in that of the female rats had more than two peaks, a finding which does not substantiate the assumptions made in previous studies. This study also showed that there was a need to use the video display frame to distinguish between the front and hind paws in the case of 48.80 ± 4.01% of the male rats and 66.76 ± 5.35% of the female rats. Evidently the assumption held by current researchers regarding stepping force measurement is not realistic in terms of application, and as this study has shown, the use of a video display frame is essential for the identification of the front and hind paws through the peak signals. [ABSTRACT FROM AUTHOR]

Abstract: Aims of the study: Gynura procumbens (Merr.), which is known as “Sambung nyawa”, is widely used in South East Asian countries in the traditional treatment of many ailments. However, there is little toxicological information available regarding safety following repeated exposure. The present investigation describes the toxicity of a methanol extract of Gynura procumbens leaves in rats. Materials and methods: For acute toxicity studies, a methanol extract of Gynura procumbens was orally administered to Sprague–Dawley rats (female and male) at a dose range of 1000–5000mg/kg. For sub-chronic toxicity studies, the rats were orally administered the methanol extract of Gynura procumbens at the doses of 125, 250, and 500mg/(kgday) for a period of 13 weeks. The animals were sacrificed, followed by examination of their organs and blood serum. Results and conclusions: Administration of the methanol extract from Gynura procumbens leaves at 1000–5000mg/kg did not produce mortality or significant changes in the general behaviour, body weight, or organ gross appearance of rats. There were no significant differences in the general condition, growth, organ weights, haematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. Therefore, the NOAEL for the Gynura procumbens methanol extract is 500mg/(kgday) administered orally for 13 weeks. [Copyright &y& Elsevier]

The current study evaluated the antioxidant and hepatoprotective activities of Elephantopus tomentosus L. (Asteraceae) ethanol extract (ET). In the experiment, total antioxidant capacity, reducing capacity, DPPH* and hydrogen peroxide scavenging, and Fe3 +-induced lipid peroxidation inhibiting activities of ET were determined. The results indicated that ET exhibited antioxidant (1 mg/mL ET was equal to 2.1 mM TEAC), lipid peroxidation inhibition, hydrogen peroxide, and free radical scavenging activities. The hepatoprotective activity of ET was studied using CCl4-induced liver toxicity in rats. Oral administration of ET (500 mg/kg) significantly reduced CCl4-induced hepatotoxicity in rats, as observed from the serum level of the liver enzyme aspartate aminotransferase (AST), alanine aminotransferase (ALT), and also from the histopathologic study. The total phenolic content in the lyophilized ethanol extract is approximately 10%. The results of the current study indicated that the hepatoprotective effect of E. tomentosus might be ascribable to its antioxidant and free radical scavenging properties. [ABSTRACT FROM AUTHOR]

The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day. [ABSTRACT FROM AUTHOR]