Effect of P. corylifolia on the pharmacokinetic profile of tofacitinib and the underlying mechanism.

This work aimed to explore the mechanisms underlying the interaction of the active furanocoumarins in P. corylifolia on tofacitinib both in vivo and in vitro. The concentration of tofacitinib and its metabolite M8 was determined using UPLC-MS/MS. The peak area ratio of M8 to tofacitinib was calculated to compare the inhibitory ability of furanocoumarin contained in the traditional Chinese medicine P. corylifolia in rat liver microsomes (RLMs), human liver microsomes (HLMs) and recombinant human CYP3A4 (rCYP3A4). We found that bergapten and isopsoralen exhibited more significant inhibitory activity in RLMs than other furanocoumarins. Bergapten and isopsoralen were selected to investigate tofacitinib drug interactions in vitro and in vivo. Thirty rats were randomly allocated into 5 groups (n = 6): control (0.5% CMC-Na), low-dose bergapten (20 mg/kg), high-dose bergapten (50 mg/kg), low-dose isopsoralen (20 mg/kg) and ketoconazole. 10 mg/kg of tofacitinib was orally intervented to each rat and the concentration level of tofacitinib in the rats were determined by UPLC-MS/MS. More imporrantly, the results showed that bergapten and isopsoralen significantly inhibited the metabolism of tofacitinib metabolism. The AUC(0-t), AUC(0-∞), MRT(0-t), MRT(0-∞) and Cmax of tofacitinib increased in varying degrees compared with the control group (all p < 0.05), but CLz/F decreased in varying degrees (p < 0.05) in the different dose bergapten group and isopsoralen group. Bergapten, isopsoralen and tofacitinib exhibit similar binding capacities with CYP3A4 by AutoDock 4.2 software, confirming that they compete for tofacitinib metabolism. P. corylifolia may considerably impact the metabolism of tofacitinib, which can provide essential information for the accurate therapeutic application of tofacitinib.

Anthelmintic screening of Bangladeshi medicinal plants and related phytochemicals using in vitro and in silico methods: An ethnobotanical perspective.

ETHNOPHARMACOLOGICAL RELEVANCE: Infections caused by parasitic worms or helminth continue to pose a great burden on human and animal health, particularly in underdeveloped tropical and subtropical countries where they are endemic. Current anthelmintic drugs present serious limitations and the emergence of drug resistance has made it increasingly challenging to combat such infections (helminthiases). In Bangladesh, medicinal plants are often used by indigenous communities for the treatment of helminthiases. Knowledge on such plants along with screening for their anthelmintic activity has the potential to lead to the discovery of phytochemicals that could serve as novel molecular scaffolds for the development of new anthelminthic drugs. AIM OF THE STUDY: The purpose of this study was i) to conduct an ethnobotanical survey to gather data on Bangladeshi medicinal plants used in the treatment of helminthiases, ii) to test plants with the highest use values for their in vitro anthelmintic activity, and iii) to carry out in silico screening on phytochemicals present in the most active plant extract to investigate their ability to disrupt ß-tubulin function in helminths. METHODS: The ethnobotanical survey was conducted across three sub-districts of Bangladesh, namely Mathbaria, Phultala and Khan Jahan Ali. The in vitro screening for anthelmintic activity was performed in a motility test using adult Haemonchus contortus worms. Virtual screening using PyRx was performed on the phytochemicals reported from the most active plant, exploring their interactions with the colchicine binding site of the ß-tubulin protein target (PDB ID: 1SA0). RESULTS: The survey respondents reported a total of 32 plants for treating helminthiases. Based on their use values, the most popular choices were Ananas comosus (L.) Merr., Azadirachta indica A.Juss., Carica papaya L., Citrus maxima (Burm.) Merr., Curcuma longa L., Momordica charantia L., Nigella sativa L. and Syzygium cumini (L.) Skeels. In vitro anthelmintic testing revealed that A. indica leaves and bark had the highest activity with LC50 values of 16 mg/mL in both cases. Other plant extracts also exhibited good anthelmintic activity with LC50 values ranging from 16 to 52 mg/mL, while the value for albendazole (positive control) was 8.39 mg/mL. The limonoids nimbolide and 28-deoxonimbolide showed a binding affinity of -8.9 kcal/mol, and satisfied all drug-likeness parameters. The control ligand N-deacetyl-N-(2-mercaptoacetyl)colchicine had a binding affinity of -6.9 kcal/mol. CONCLUSION: Further in silico and in vitro studies are warranted on the identified limonoids to confirm the potential of these derivatives as novel drug templates for helminthiases. The current study supports the need for an ethnobotanical survey-based approach to discover novel drug templates for helminthiases.

Epidemiology of Caesarean section on maternal request in Australia: A population-based study.

OBJECTIVE: To explore the trends, determinants, and short-term maternal and neonatal health outcomes of Caesarean section on maternal request (CSMR). DESIGN: Population-based record linkage study. SETTING: Birth registry data for all births in Queensland, Australia, from 2008 to 2017. PARTICIPANTS: Pregnancies resulting in live or intrapartum stillbirth with >=20 gestational weeks and/or >=400 gm birth weight were the study population. The analytic sample was restricted to low-risk pregnancies by excluding preterm, non-cephalic pregnancies with medical risk factors. MEASUREMENTS: CSMR was defined as a first-time C-section in singleton, term pregnancies with an ICD-10-AM code of O-82/O-47. CSMR trend was reported in age-standardised rate using a join-point regression model. The determinants and perinatal outcomes of CSMR were tested against Spontaneous vaginal births (VBs) and planned VBs including assisted VBs and emergency C-sections in this group. The generalised estimating equation technique was used for regression analysis and reported in the odds ratio (OR) at a 95% Confidence Interval (CI). FINDINGS: Of total C-sections (n = 204,863), the average annual change in CSMR rate was 4.4% (95% CI: 2.1-6.7%, p<0.01) for the total pregnancies (N=613,375) Of the analytic sample (N=365568), nulliparous women with age ≥35 years (OR: 2.32,95% CI: 2.09-2.57), delivered at private hospitals (OR:4.90; 95% CI: 4.65-5.18); with mood disorders (OR: 2.15; 95% CI: 1.88-2.43) were positive and midwives birth attendant (OR 0.28; 95% CI: 0.26 to 0.30) was negative influencing factors for CSMR. In a propensity score matched sample; CSMR observed an increasedrisk of anaesthetic complications (OR: 8.00; 95% CI:1.95-32.82) and slightly reduced odds of birth asphyxia (OR:0.20;95%CI:0.06-0.60)against planned VBs while the overall incidence of birth-asphyxia was low (1.29%) However, neonatal morbidities (OR:1.61; 95% CI:1-2.59) and special care admission (OR:2.15; 95% CI:1.03-4.5) were higher after CSMR in comparison to SVBs CONCLUSION: Despite being linked with adverse perinatal health outcomes, the incidence of CSMR increased 1.75-fold during the past 10 years. Maternal educational interventions to provide adequate information, including the long-term risks and benefits of C-sections, can help reduce the growing rates of CSMR.

Antidiabetic Potential of Commonly Available Fruit Plants in Bangladesh: Updates on Prospective Phytochemicals and Their Reported MoAs.

Diabetes mellitus is a life-threatening disorder affecting people of all ages and adversely disrupts their daily functions. Despite the availability of numerous synthetic-antidiabetic medications and insulin, the demand for the development of novel antidiabetic medications is increasing due to the adverse effects and growth of resistance to commercial drugs in the long-term usage. Hence, antidiabetic phytochemicals isolated from fruit plants can be a very nifty option to develop life-saving novel antidiabetic therapeutics, employing several pathways and MoAs (mechanism of actions). This review focuses on the antidiabetic potential of commonly available Bangladeshi fruits and other plant parts, such as seeds, fruit peals, leaves, and roots, along with isolated phytochemicals from these phytosources based on lab findings and mechanism of actions. Several fruits, such as orange, lemon, amla, tamarind, and others, can produce remarkable antidiabetic actions and can be dietary alternatives to antidiabetic therapies. Besides, isolated phytochemicals from these plants, such as swertisin, quercetin, rutin, naringenin, and other prospective phytochemicals, also demonstrated their candidacy for further exploration to be established as antidiabetic leads. Thus, it can be considered that fruits are one of the most valuable gifts of plants packed with a wide spectrum of bioactive phytochemicals and are widely consumed as dietary items and medicinal therapies in different civilizations and cultures. This review will provide a better understanding of diabetes management by consuming fruits and other plant parts as well as deliver innovative hints for the researchers to develop novel drugs from these plant parts and/or their phytochemicals.

Biological Functions of Dillenia pentagyna Roxb. Against Pain, Inflammation, Fever, Diarrhea, and Thrombosis: Evidenced From in vitro, in vivo, and Molecular Docking Study.

Dillenia pentagyna Roxb. is traditionally used to treat cancer, wound healing, diabetes, and diarrhea in local tribes. This study was designed to evaluate the pharmacological potentiality of this plant. In vivo analgesic, anti-inflammatory, and antipyretic studies of the methanol extracts of D. pentagyna (MEDP) leaves were performed by using acetic acid-induced nociception, formalin-induced paw licking, and yeast-induced pyrexia assay methods, respectively. In vivo antidiarrheal activity was carried out in mice by following castor oil-induced diarrhea and gastrointestinal transit manner. In vitro thrombolytic experiment was performed employing the clot lysis activity. Besides, a molecular docking study was performed by executing the software (PyRx, Discovery Studio, and UCSF Chimera). In the acetic acid-induced writhing study, MEDP possesses significant writhing inhibition in a dose-dependent manner. It showed 50.86% of maximum inhibition of pain in the case of MEDP at a dose of 400 mg/kg body weight. In the anti-inflammatory study, maximum inhibition rate was observed at a value of 59.98 and 41.29% in early and late phases, respectively, at the dose of 400 mg/kg body weight. In the case of yeast-induced hyperpyrexia, MEDP reduced hyperpyrexia in a dose-dependent manner. In the antidiarrheal assay, MEDP moderately inhibited the occurrence of diarrhea in all the experiments. In the thrombolytic study, a moderate (17.76%) clot lysis potency has been yielded by MEDP. Again, the molecular docking simulation revealed strong binding affinities with almost all the targeted proteins. The present study suggests that the MEDP possesses remarkable pharmacological activity and this finding validated the ethnobotanical significance of D. pentagyna as the source of pain, fever, and diarrhea management agent.

Chemotherapeutic Activities of Dietary Phytoestrogens against Prostate Cancer: From Observational to Clinical Studies.

Prostate cancer remains one of the most frequent and deadliest malignancies in males, where the rate of disease progression is closely associated with the type of dietary intake, specifically a Western-style diet. Indeed intake of the Asian diet, which contains abundant phytoestrogens, is inversely correlated with a higher risk of prostate cancer, suggesting a chemoprotective effect of phytoestrogen against cancer progression. Although the role of phytoestrogens in cancer treatment has been well documented, their impact on prostate cancer is not well understood. Therefore, the present review discusses the possible chemopreventive effect of phytoestrogens, emphasizing their efficacy at the different stages of carcinogenesis. Furthermore, phytoestrogens provide a cytoprotective effect in conventional chemotherapy and enhance chemosensitivity to tumor cells, which have also been discussed. This compilation provides a solid basis for future research on phytoestrogens as a promising avenue for anticancer drug development and also recommends these beneficiary compounds in the daily diet to manage and prevent prostate cancer.

DL-3-n-butylphthalide ameliorates diabetes-associated cognitive decline by enhancing PI3K/Akt signaling and suppressing oxidative stress.

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

Assessment of food safety knowledge, attitudes and practices of fish farmers and restaurants food handlers in Bangladesh.

The study was conducted to assess the present status of knowledge, attitudes and practices (KAP) concerning the food safety and hygiene issues among fish farmers and food handlers in Noakhali, Bangladesh. Data were collected from 100 respondents (50 fish farmers and 50 food handlers) through face to face interviews. All the respondents agreed that training on hygiene practices was necessary and they were interested to attend training in their spare time. Food handlers (88%) agreed that raw foods must be kept separate from prepared foods and 68% of them believed that improper preservation of foods is harmful to health. About 52% of farmers used a face mask when spreading insecticides, fertilizers, and chemicals. Food handlers were wearing protective clothing (32%) and masks (12%) when touching and distributing unwrapped foods, however no handlers used a cap. A significant strong correlation coefficient (rs) was found between knowledge with attitudes, knowledge with practices and attitudes with practices of 0.73-0.99 among the three domains for fish farmers and food handlers. The correlation among the three levels was satisfactory, however, some food safety concepts and practices regarding hygiene were still insufficient. Therefore, an effective and appropriate training program on food safety and hygiene should be launched in a holistic approach for all fish farmers and food handlers to increase awareness and ensure safe food for consumers with a view to reducing the possibility of disease outbreak.

Proximate composition and fatty acid analysis of Lablab purpureus (L.) legume seed: implicates to both protein and essential fatty acid supplementation.

The high mortality rate in Bangladesh is related to poverty, which results in protein malnutrition, essential fatty acid deficiency and lacks in adequate vitamins, minerals and calorie. Exploring new food items with improved dietary nutrition factors may, therefore, help to decrease the mortality rate in the poor countries like Bangladesh. Accordingly, the present study was a proximate composition and fatty acid analysis of L. purpureus seed-a legume seed which is given no careful attention locally, though it might be a good source of valuable nutrition factors for both animals and humans. The purpose of the study was, therefore, to generate awareness that L. purpureus could also act as a good source of food components essential for good health. Proximate analysis revealed that the seed powder contained 8.47 ± 0.52% moisture; 3.50 ± 0.0.07% ash; 1.02 ± 0.06% total fat; 23.95 ± 0.15% total protein; 1.21 ± 0.16% total dietary fiber; 61.86 ± 0.70% total carbohydrate and 352.4 ± 2.66 kcal/100 g energy. Phytic acid content (%) was 1.014 ± 0.048. Major fatty acid composition (%): the essential fatty acid linoleic acid (C18:2, ω-6) was 9.50 ± 0.68, while the linolenic acid (C18:3, ω-3) was 1.95 ± 0.18. Palmitic acid (C16:0), stearic acid (C18:0) and oleic acid (C18:1) were, respectively, 2.96 ± 0.19, 0.77 ± 0.04 and 1.10 ± 0.06. Lignoceric acid (C24:0) was 0.11 ± 0.007%. Monounsaturated palmitoleic acid (0.006 ± 0.0), docosapentaenoic acid (DPA, C22:5, ω-3) and nervonic acid (0.002 ± 0.0) were present in trace amounts. Arachidonic acid (AA, C20:4, ω-6), eicosapentaenoic acid (C20:5, ω-3), and docosahexaenoic acid (C22:6, ω-3) were not detected. The fatty acid profile, thus, suggests that essential omega-6 fatty acid linoleic acid (C18:3, ω-6) and omega-3 linolenic acid (C18:3, ω-3) were the major polyunsaturated fatty acids (PUFA) present in L. purpureus seed. In addition, the seed contained high amount of proteins. Finally, these results suggest that L. purpureus seed could be used as a good source of quality food components, including protein and essential fatty acids.

Understanding the value of local ecological knowledge and practices for habitat restoration in human-altered floodplain systems: a case from Bangladesh.

Worldwide there is a declining trend in natural fish catch (FAO, The state of world fisheries and aquaculture. http://www.fao.org/documents/show_cdr.asp?url_file=/docrep/007/y5600e/y5600e00.htm , 2002) and Bangladesh is no exception. The vast inland fisheries of Bangladesh have been declining over the years, largely a result of human alteration of the aquatic habitats arising from human interventions in the floodplain systems such as the establishment of water control structures which favor agricultural production but reduce fish habitats. It can be assumed that conventional management measures are not adequate to conserve natural fisheries and exploring alternative knowledge systems to complement existing management is warranted. This paper focuses on local ecological knowledge and several other local practices held by fishers engaging directly with floodplain ecosystems. These knowledge systems and practices may be valuable tools for understanding ecosystems processes and related changes and developing local level responses to avert negative consequences of such changes. This may help in devising alternatives to ecosystem management and the conservation of floodplain fish habitats of Bangladesh and elsewhere in the world. This study was conducted in a natural depression (locally called beel) and its surrounding floodplain system located in north central Bangladesh which has become highly degraded. The results of the study indicate that the fishers and local users of the floodplain ecosystems are rich in local ecological knowledge concerning the hydrology of the floodplains and small lakes, the habitat preferences of fish, the role of agricultural crops on fish habitats, and the impact of habitat human interventions in aquatic ecosystems. Given the apparent inadequacy of the present management regime, this article argues for an inclusion of local knowledge and practices into habitat management as a more holistic approach to floodplain habitat restoration and conservation that encourages multi-level cooperation and which builds on diversified knowledge systems.

Clinical application of computer-aided diagnostic system for harmonious introduction of complementary dialysis therapy.

In chronic peritoneal dialysis (PD) therapy, peritoneal permeability is gradually enhanced over the duration of the therapeutic course, leading to a grave decline in the therapeutic efficiency. In recent years, a novel therapy (CD therapy), which integrates PD therapy with hemodialysis therapy, is being applied to end-stage PD patients to complement the decline of therapeutic efficiency caused by the grave degeneration of the peritoneal tissue. To realize a harmonious introduction of the CD therapy, this study developed a useful index (KAu/c), which evaluates both therapeutic efficiency and degeneration of peritoneal tissue. Using a mathematical model and KAu/c, we were able to validate the therapeutic efficiency in the PD patients, and, in one case, propose a better prescription for the patient by employing the CD therapy. The clinical implementation of this methodology is indispensable with regard to expanding the therapeutic monitoring system for renal replacement therapy.