Inhibition of neuroinflammation in BV2 microglia by the biflavonoid kolaviron is dependent on the Nrf2/ARE antioxidant protective mechanism

Kolaviron is a mixture of bioflavonoids found in the nut of the West African edible seed Garcinia kola, and it has been reported to exhibit a wide range of pharmacological activities. In this study, we investigated the effects of kolaviron in neuroinflammation. The effects of kolaviron on the expression of nitric oxide/inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2)/cyclooxygenase-2, cellular reactive oxygen species (ROS) and the pro-inflammatory cytokines were examined in lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Molecular mechanisms of the effects of kolaviron on NF-B and Nrf2/ARE signalling pathways were analysed by immunoblotting, binding assay, and reporter assay. RNA interference was used to investigate the role of Nrf2 in the anti-inflammatory effect of kolaviron. Neuroprotective effect of kolaviron was assessed in a BV2 microglia/HT22 hippocampal neuron co-culture. Kolaviron inhibited the protein levels of NO/iNOS, PGE2/COX-2, cellular ROS and the proinflammatory cytokines (TNFα and IL-6) in LPS-stimulated microglia. Further mechanistic studies showed that kolaviron inhibited neuroinflammation by inhibiting IB/NF-B signalling pathway in LPS-activated BV2 microglia. Kolaviron produced antioxidant effect in BV2 microglia by increasing HO-1 via the Nrf2/ antioxidant response element (ARE) pathway. RNAi experiments revealed that Nrf2 is need for the anti-inflammatory effect of kolaviron. Kolaviron protected HT22 neurons from neuroinflammation-induced toxicity. Kolaviron inhibits neuroinflammation through Nrf2-dependent mechanisms. This compound may therefore be beneficial in neuroinflammation-related neurodegenerative disorders

Antibacterial, Anti-HIV-1 Protease and Cytotoxic Activities of Aqueous Ethanolic Extracts from Combretum Adenogonium Steud. Ex A. Rich (Combretaceae).

\ud \ud Records have shown that Combretum adenogonium Steud. Ex A. Rich (Combretaceae) is used in traditional medicine systems of several tribes in Tanzania. This study focused on the investigation of antibacterial activity, anti-HIV-1 protease activity, toxicity properties and classes of phytochemicals in extracts from C. adenogonium Steud. Ex A. Rich (Combretaceae) to evaluate potential of these extracts for development as herbal remedies. Dried plant material were ground to fine powder and extracted using 80% aqueous ethanol to afford root, leaf and stem bark extracts. The extracts were assayed for anti-HIV-1 protease activities, antibacterial activities using microdilution methods and cytotoxicity using brine shrimps lethality assay. Screening for major phytochemical classes was carried out using standard chemical tests. All extracts exhibited antibacterial activity to at least one of the test bacteria with MIC-values ranging from 0.31-5.0 mg/ml. Two extracts, namely, root and stem bark exhibited anti-HIV-1 PR activity with IC50 values of 24.7 and 26.5 μg/ml, respectively. Stem bark and leaf extracts showed mild toxicity with LC50 values of 65.768 μg/ml and 76.965 μg/ml, respectively, whereas roots were relatively non-toxic (LC50 = 110.042 μg/ml). Phytochemical screening of the extracts indicated presence of flavonoids, terpenoids, alkaloids, tannins, glycosides and saponins. These results provide promising baseline information for the potential development of C. adenogonium extracts in treatment of bacterial and HIV/AIDS-related opportunistic infections

Clinical effects of Garcinia kola in knee osteoarthritis

<p>Abstract</p> <p>Objectives</p> <p>Over the past years, there has been a growing number of knee osteoarthritis (KOA) patients who are not willing to comply with long-term non-steroidal anti-inflammatory drugs (NSAID) treatment and wish to use herbal anti- rheumatic medicine. This study assessed the clinical effects of <it>Garcinia kola </it>(GK) in KOA patients.</p> <p>Patients and methods</p> <p>Prospective randomized, placebo controlled, double blind, clinical trial approved by the institutional medical ethics review board and written informed consent obtained from each patient. All KOA patients presenting at the Obafemi Awolowo University Teaching Hospital complex were recruited into the study. The patients were grouped into four (A = Placebo, B = Naproxen, C = <it>Garcinia kola</it>, D = Celebrex). The drugs and placebo were given twice a day per oral route. Each dose consisted of 200 mg of <it>G. kola</it>, Naproxen (500 mg), Celebrex (200 mg) and Ascorbic acid (100 mg). The primary outcome measure over six weeks study period was the change in mean WOMAC pain visual analogue scales (VAS). Secondary outcome measures included the mean change in joint stiffness and physical function (mobility/walking).</p> <p>Results</p> <p>143 patients were recruited, 84 (58.7%, males – 24, females – 60) satisfied the selection criteria and completed the study. The effect of knee osteoarthritis bilateralism among the subjects was not significant on their outcome (p > 0.05). The change in the mean WOMAC pain VAS after six weeks of <it>G. kola </it>was significantly reduced compared to the placebo (p < 0.001). Multiple comparisons of the mean VAS pain change of <it>G. kola </it>group was not lowered significantly against the naproxen and celebrex groups (p > 0.05). The onset of <it>G. kola </it>symptomatic pain relief was faster than the placebo (p < 0.001). However, it was slower than the active comparators (p > 0.05). The duration of therapeutic effect of <it>Garcinia kola </it>was longer than the placebo (p > 0.001). <it>G. kola </it>period of effect was less than naproxen and celebrex (p < 0.001). <it>G. kola </it>subjects had improved mean change mobility/walking after six weeks better than the control group(p < 0.001). The mean change in mobility of the <it>G. kola </it>group when compared to the active comparators was not significantly better (p < 0.05). The mean change of knee joint stiffness (p < 0.001) and the change of mean WOMAC score (p < 0.001) were improved on <it>Garcinia kola </it>as compared to the placebo. The mid term outcome of eleven <it>Garcinia kola </it>subjects after cessation of use had a mean pain relief period of 17.27 +/- 5.15 days (range: 9–26 days). There was no significant cardiovascular, renal or drug induced adverse reaction to <it>Garcinia kola</it>.</p> <p>Conclusion</p> <p><it>Garcinia kola </it>appeared to have clinically significant analgesic/anti-inflammatory effects in knee osteoarthritis patients. <it>Garcinia kola </it>is a potential osteoarthritis disease activity modifier with good mid term outcome. Further studies are required for standardization of dosages and to determine long-term effects.</p

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact

Justification for the use of Ocimum gratissimum L in herbal medicine and its interaction with disc antibiotics

<p>Abstract</p> <p>Background</p> <p>The ethanolic extract of the leaves of <it>Ocimium gratisimum </it>L. (Lamiaceae), used in traditional medicine for the treatment of several ailments such as urinary tract, wound, skin and gastrointestinal infections, was evaluated for its antibacterial properties against four clinical bacteria isolates namely: <it>Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Pseudomonas aeruginosa </it>and the antifungal properties using a clinical isolate of <it>Candida albicans</it>. A typed bacterium of <it>Escherichia coli </it>ATCC 11775 and another typed fungal strain of <it>Candida albicans </it>(ATCC 90028) were also included. The study also intended to verify if the concomitant administration of conventional antibiotics with <it>Ocimium gratisimum </it>which is normally taken as food (spice) will negatively affect its activity.</p> <p>Methods</p> <p>The agar diffusion method was used to test the in vitro activity of the plant extract. The interaction of the plant extract with some disc antibiotics namely: ciprofloxacin, septrin, streptomycin, ampicillin, nystatin and ketoconazole was tested using the agar overlay inoculum susceptibility disc method. Phytochemical analysis of the extract was performed following established methods.</p> <p>Results</p> <p>The extract showed good but varying <it>in vitro </it>activities against all the isolates tested. While ampicillin showed synergistic interaction with the plant extract against clinical isolates of <it>E. coli </it>and <it>P. mirabilis</it>, septrin was synergistic against the clinical isolate of <it>E. coli </it>only. Similarly, the activity of the extract against <it>C. albicans </it>isolate was synergistic with ketoconazole and nystatin.</p> <p>Conclusion</p> <p>The study has validated the folkloric use of <it>O. gratissimum </it>in traditional medicinal practice and goes further to show that the use of this plant material as food spice may not really threaten the efficacy of some conventional antibiotics that may have been taken concomitantly with it as is the popular belief in the practice of herbal medicine in local/rural communities of many countries in the world.</p

Potentials of leaves of Aspilia africana (Compositae) in wound care: an experimental evaluation

<p>Abstract</p> <p>Background</p> <p>The potentials of the leaves of the haemorrhage plant, <it>Aspilia africana </it>C. D Adams (Compositae) in wound care was evaluated using experimental models. <it>A. africana</it>, which is widespread in Africa, is used in traditional medicine to stop bleeding from wounds, clean the surfaces of sores, in the treatment of rheumatic pains, bee and scorpion stings and for removal of opacities and foreign bodies from the eyes. The present study was undertaken to evaluate the potentials for use of leaves of this plant in wound care.</p> <p>Methods</p> <p>The effect of the methanol extract (ME) and the hexane (HF) and methanol (MF) fractions (obtained by cold maceration and graded solvent extraction respectively) on bleeding/clotting time of fresh experimentally-induced wounds in rats, coagulation time of whole rat blood, growth of microbial wound contaminants and rate of healing of experimentally-induced wounds in rats were studied as well as the acute toxicity and lethality (LD₅₀) of the methanol extract and phytochemical analysis of the extract and fractions.</p> <p>Results</p> <p>The extract and fractions significantly (<it>P </it>< 0.05) reduced bleeding/clotting time in rats and decreased coagulation time of whole rat blood in order of magnitude of effect: MF>ME>HF. Also, the extract and fractions caused varying degrees of inhibition of the growth of clinical isolates of <it>Pseudomonas fluorescens </it>and <it>Staphylococcus aureus</it>, as well as typed strains of <it>Ps. aeruginosa </it>(ATCC 10145) and <it>Staph. aureus </it>(ATCC 12600), and reduced epithelialisation period of wounds experimentally-induced in rats. Acute toxicity and lethality (LD₅₀) test in mice established an i.p LD₅₀of 894 mg/kg for the methanol extract (ME). Phytochemical analysis revealed the presence of alkaloids, saponins, tannins, flavonoids, resins, sterols, terpenoids and carbohydrates.</p> <p>Conclusion</p> <p>The leaves of <it>A. africana </it>possess constituents capable of arresting wound bleeding, inhibiting the growth of microbial wound contaminants and accelerating wound healing which suggest good potentials for use in wound care.</p

Ethnobotanical study of medicinal plants used by people in Zegie Peninsula, Northwestern Ethiopia

An ethnobotanical study was conducted from October 2005 to June 2006 to investigate the uses of medicinal plants by people in Zegie Peninsula, northwestern Ethiopia. Information was gathered from 200 people: 70 female and 130 males, using semistructured questionnaire. Of which, six were male local healers. The informants, except the healers, were selected randomly and no appointment was made prior to the visits. Informant consensus factor (ICF) for category of aliments and the fidelity level (FL) of the medicinal plants were determined. Sixty-seven medicinal plants used as a cure for 52 aliments were documented. They are distributed across 42 families and 64 genera. The most frequently utilized plant part was the underground part (root/rhizome/bulb) (42%). The largest number of remedies was used to treat gastrointestinal disorder and parasites infections (22.8%) followed by external injuries and parasites infections (22.1%). The administration routes are oral (51.4%), external (38.6%), nasal (7.9%), and ear (2.1%). The medicinal plants that were presumed to be effective in treating a certain category of disease, such as 'mich' and febrile diseases (0.80) had higher ICF values. This probably indicates a high incidence of these types of diseases in the region, possibly due to the poor socio-economic and sanitary conditions of this people. The medicinal plants that are widely used by the local people or used as a remedy for a specific aliment have higher FL values (Carissa spinarum, Clausena anisata, Acokanthera schimperi, Calpurnia aurea, Ficus thonningii, and Cyphostemma junceum) than those that are less popular or used to treat more than one type of aliments (Plumbago zeylanicum, Dorstenia barnimiana)

Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders

BACKGROUND: Carbon tetrachloride (CCl(4)) is a well-known hepatotoxin and exposure to this chemical is known to induce oxidative stress and causes liver injury by the formation of free radicals. Acute and chronic renal damage are also very common pathophysiologic disturbances caused by CCl(4). The present study has been conducted to evaluate the protective role of the aqueous extract of the bark of Termnalia arjuna (TA), an important Indian medicinal plant widely used in the preparation of ayurvedic formulations, on CCl(4 )induced oxidative stress and resultant dysfunction in the livers and kidneys of mice. METHODS: Animals were pretreated with the aqueous extract of TA (50 mg/kg body weight) for one week and then challenged with CCl(4 )(1 ml/kg body weight) in liquid paraffin (1:1, v/v) for 2 days. Serum marker enzymes, namely, glutamate pyruvate transaminase (GPT) and alkaline phosphatase (ALP) were estimated in the sera of all study groups. Antioxidant status in both the liver and kidney tissues were estimated by determining the activities of the antioxidative enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST); as well as by determining the levels of thiobarbutaric acid reactive substances (TBARS) and reduced glutathione (GSH). In addition, free radical scavenging activity of the extract was determined from its DPPH radical quenching ability. RESULTS: Results showed that CCl(4 )caused a marked rise in serum levels of GPT and ALP. TBARS level was also increased significantly whereas GSH, SOD, CAT and GST levels were decreased in the liver and kidney tissue homogenates of CCl(4 )treated mice. Aqueous extract of TA successfully prevented the alterations of these effects in the experimental animals. Data also showed that the extract possessed strong free radical scavenging activity comparable to that of vitamin C. CONCLUSION: Our study demonstrated that the aqueous extract of the bark of TA could protect the liver and kidney tissues against CCl(4)-induced oxidative stress probably by increasing antioxidative defense activities

Psychoimmunological effects of dioscorea in ovariectomized rats: role of anxiety level

<p>Abstract</p> <p>Background</p> <p>Anxiety levels in rats are correlated with interleukin-2 (IL-2) levels in the brain. The aim of the present study was to investigate the effects of dioscorea (wild yam), a Chinese medicine, on emotional behavior and IL-2 levels in the brain of ovariectomized (OVX) rats.</p> <p>Methods</p> <p>One month after ovariectomy, female Wistar rats were screened in the elevated plus-maze (EPM) test to measure anxiety levels and divided into low anxiety (LA) and high anxiety (HA) groups, which were then given dioscorea (250, 750, or 1500 mg/kg/day) by oral gavage for 27 days and were tested in the EPM on day 23 of administration and in the forced swim test (FST) on days 24 and 25, then 3 days later, the brain was removed and IL-2 levels measured.</p> <p>Results</p> <p>Compared to sham-operated rats, anxiety behavior in the EPM was increased in half of the OVX rats. After chronic dioscorea treatment, a decrease in anxiety and IL-2 levels was observed in the HA OVX rats. Despair behavior in the FST was inhibited by the highest dosage of dioscorea.</p> <p>Conclusion</p> <p>These results show that OVX-induced anxiety and changes in neuroimmunological function in the cortex are reversed by dioscorea treatment. Furthermore, individual differences need to be taken into account when psychoneuroimmunological issues are measured and the EPM is a useful tool for determining anxiety levels when examining anxiety-related issues.</p