Antithrombotic, anticoagulant and antiplatelet activity of betulinic acid and 3β-acetoxybetulinic acid from Melaleuca bracteata ‘Revolution Gold’ (Myrtaceae) Muell leaf

Purpose: To investigate the antithrombotic, anticoagulant and antiplatelet activity of betulinic acid (BA) and 3β-acetoxybetulinic acid (BAA) from Melaleuca bracteata ‘Revolution Gold’.Methods: Betulinic acid was isolated from the ethyl acetate extract of M. bracteata leaves by column chromatography, from which BAA was subsequently synthesized by acetylation. Structural elucidation of the compounds was conducted using mass spectrometry (MS), infra-red (IR) spectroscopy and nuclear magnetic resonance (NMR). The antithrombotic potential of the compounds was assessed using chromogenic substrate. Anticoagulation studies were carried using bleeding tail time assay in a rat model. Plasma-rich platelets from rats were employed for platelet aggregation studies using light microscope.Results: The compounds significantly (p < 0.05) showed antithrombotic activities in a dose-dependent manner. BAA showed significantly (p < 0.05) higher half-maximal concentration (IC50) value of 1.10 ± 0.03 mg/mL than BA (2.36 ± 0.09 mg/mL) and aspirin (2.65 ± 0.01 mg/mL) which served as positive control. The compounds exhibited anticoagulation activity with poor bleeding time, compared to aspirin. Likewise, the compounds attenuated platelets aggregation induced by thrombin.Conclusion: BAA displays better antithrombotic, antiplatelet, and anticoagulant activities than BA. Therefore, it may be a promising remedy for the management of cardiovascular events.Keywords: Betulinic acid, Thrombin, Anticoagulation, Antiplatelet, Aspirin, Platelet

Phytodentistry in Africa: prospects for head and neck cancers

Background Orthodox dentistry has undergone significant changes in recent times with the introduction of various omics and molecular targeted therapies both at the experimental/trial and clinical implementation level. Although, significant milestones have been achieved in the molecular dentistry field in the past decade, there remains a dearth of application of phytopharmacological innovation in personalized and targeted therapies for dental diseases. Main body From time immemorial, plant products have long been an integral aspect of dental practice ranging from chewing sticks/herbal kinds of toothpaste to dental/impression materials. The current era of precision medicine seeks to apply a multipronged molecular and bio-computational approaches to solve fundamental medical problems that have hitherto remained difficult. Remarkable changes in the molecular/omics era, have transformed empirical therapies into personalized/individualized ones. Furthermore, the combinatorial application and the widespread introduction of high-throughput molecular tools such as pharmacogenomics, phytopharmacology, metabolomics, mathematical modelling, and genetic engineering inter alia, has tremendously improved the diagnostic and therapeutic landscape of medicine. Additionally, the variable molecular epidemiology of diseases among different population and emerging molecular evidence warrants the use of customized novel theranostic techniques. Unfortunately, the footprint of such emerging application is sparse in dental diseases such as maxillofacial cancers. Conclusion Hence, this review seeks to evaluate the potential application of phytopharmacological approaches to head and neck cancers in a resource-limited environment, such as Africa

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Methyl cellosolve-induced hepatic oxidative stress: The modulatory effect of syringic acid on Nrf2-Keap1-Hmox1-NQO1 signaling pathway in rats

Ethnopharmacological relevance: Syringic acid (SAC) is a phenolic compound and an antioxidant that has been identified in honey, grapes, red wine, marigold and sugar apple. Due to its potent antioxidant prowess, SAC possesses hepatoprotective, nephroprotective, neuroprotective, cardioprotective and anti-inflammatory activities. Aim of the study: Judging by these credentials, this study investigated the effect of 25, 50 and 75 mg/kg body weight of SAC on hepatotoxicity induced by 100 mg/kg body weight of methyl cellosolve (MECE) in male Wistar rats. Results: Compared with control, MECE decreased the liver relative weight, nitric oxide (NO) concentration, glutathione S-transferase (GST), glutathione peroxidase (GPx), catalase (CAT) and superoxide dismutase (SOD) activities, while liver malondialdehyde (MDA), nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like ECH associated protein 1 (Keap1), heme oxygenase 1 (Hmox1) and NAD(P)H quinone oxidoreductase 1 (NQO1) levels were significantly increased. Treatments with 25, 50 and 75 mg/kg of SAC significantly decreased the concentration of MDA, Nrf2, Keap1 (by 50 and 75 mg/kg only), mRNA expressions of Hmox1, NQO1 and increased the concentration of NO, activities of GPx, GST, SOD and CAT compared with MECE only administered rats. Conclusion: In conclusion, SAC demonstrated a strong hepatoprotective role against MECE-induced hepatic depletion of endogenous antioxidant enzymes and inhibition of MECE-induced cytosolic Nrf2 activation and antioxidant response element (ARE)-dependent genes in rats

Syringic acid demonstrates an anti-inflammatory effect via modulation of the NF-κB-iNOS-COX-2 and JAK-STAT signaling pathways in methyl cellosolve-induced hepato-testicular inflammation in rats

Syringic acid (SACI) is an emerging nutraceutical and antioxidant used in modern Chinese medicine. It has potential neuroprotective, anti-hyperglycemic, and anti-angiogenic properties. Methyl cellosolve (MCEL) has been reported to induce tissue inflammation in the testis, kidney, liver, and lung. This study aimed to investigate the effect and probable mechanism of action of SACI on MCEL-induced hepatic and testicular inflammation in male rats. Compared to the control group, administration of MCEL to rats significantly increased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB in the liver and testis. Additionally, the total mRNA expressions of JAK1 (in the liver only), STAT1, and SOCS1 were significantly increased in both the liver and testis, while testicular JAK1 total mRNA levels were significantly decreased.The expression of PIAS1 protein was significantly higher in the liver and testis. Treatments with SACI at 25 (except liver iNOS), 50, and 75 mg/kg significantly decreased the levels of IL-6, TNF-α, iNOS, COX-2, and NF-κB compared to the control group. Furthermore, the total mRNA expressions of JAK1 and SOCS1 in the liver were significantly reduced by all doses of SACI investigated, while the total mRNA levels of liver and testis STAT1 were significantly reduced by 25 and 50 mg/kg of SACI only. In the testis, the mRNA level of SOCS1 was significantly reduced by all doses of SACI compared to MCEL only. Additionally, SACI (at 75 mg/kg) significantly reduced PIAS1 protein expression in the liver, while in the testis, SACI at all investigated doses significantly reduced the expression of PIAS1. In conclusion, SACI demonstrated a hepatic and testicular anti-inflammatory effect by inhibiting the MCEL-induced activation of the NF-κB and JAK-STAT signaling pathways in rats

Antihyperglycaemia and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats

Context: Gongronema latifolium Benth (Asclepiadaceae) has been highly utilized in controlling diabetes mellitus traditionally in the eastern part of Nigeria. Objectives: Antihyperglycaemic and related gene expressions of aqueous extract of Gongronema latifolium leaf in alloxan-induced diabetic rats. Materials and methods: Forty-eight female Wistar rats were induced intraperitoneally using alloxan (150 mg/kg body weight). The rats were separated into six groups (n = 8) as follows: non-diabetic control, diabetic control, diabetic rats administered 5 mg/kg body weight of metformin, and diabetic rats administered 6.36, 12.72 and 25.44 mg/kg body weight (ethnobotanical doses) of G. latifolium orally daily. On the 14th day, the animals were sacrificed and different antihyperglycaemic parameters were evaluated as well as its related gene expressions. Results: Diabetic rats administered three doses of aqueous extract of G. latifolium significantly (p < 0.05) lowered the fasting blood glucose, glycated haemoglobin, serum lipid profiles, lipid peroxidation (5.62–1.2 μ/mg protein) levels, as well as gene expression of glucose-6-phosphatase in alloxan-induced diabetic rats. There was a significant (p < 0.05) increase in the liver glycogen content (16.23–112.5 mg glucose/2 g), antioxidant enzymes activities, glucose transporter (GLUT-2 and GLUT-4) levels and relative gene expression of hexokinase in diabetic rats administered different doses of aqueous extract of G. latifolium. Discussion and conclusions: It can be deduced that the aqueous extract of G. latifolium leaf at these doses may be useful in managing diabetes mellitus and its associated complications. Therefore, this extract may be a potent antidiabetic agent in clinical therapy in the future

Фітохімічний профіль та антидіабетичний потенціал in vitro фракціонованих екстрактів Entada Africana та Leptadenia Hastata

Aim: To confirm their use in the management of diabetes and to determine the numerous phytochemicals present that may be connected to the active performance of the plants, the fractionated extracts of Leptadenia hastata and Entada africana were subjected to an in vitro experiment. Material and methods: The plant leaves were dried, pulverized with a Sumeet CM/L 2128945 grinder, the particle size was 45.85 μm and extracted with methanol. The crude extracts were fractionated using a 30×8 cm diameter column and 60g of silica gel 60 F254 grade, using methanol as eluent and fractions were concentrated using a rotary evaporator, the fractionated extracts were run on thin layer Chromatographic plate (TLC) and their retardation factors (RF) were determined. Fractions of similar RF were pulled together and spotted again using TLC plate and the final (RF) were calculated. The crude extracts were quantified for the content of phytochemicals and the phytochemicals present in the fractionated extracts (LH1 and EA2) were identified using HPLC-UV detector. The extracts (LH1 and EA2) were tested for antidiabetic potentials using α -glucosidase and α-amylase enzymes in an in-vitro antidiabetic assay. Results: The yields of the fractionated extracts were 10.0 mg (Leptadenia hastata) and 11.5.0 mg (Entada Africana) and designated as LH1 and EA2, the RF for LH1 and EA2 were 0.75±0.01 and 0.77±0.03 respectively. The maximum amount of alkaloid was found in E. Africana (14.50±0.25 mg/g), while tannin was not found in L. Hastata. In the portion of L. Hastata (LH1), thirteen phytochemicals were discovered and out of these three were alkaloids. Thirteen phytochemicals were found in the E. Africana fraction (EA2), with eight of them being alkaloids and flavonoids. When compared to the usual acarbose, the plants' anti-diabetic properties were superior. EA2 had EC50 of 0.950.17 g/ml (α-amylase) and 0.970.41 g/ml (α-glucosidase), while LH1 had EC50 of 1.00±0.11 g/ml (α-amylase) and 0.90±0.35 g/ml (α-glucosidase). The presence of the detected phytochemicals may be linked to the active qualities of the plants' leaves. Conclusion: The phytochemical profile of fractionated extracts classified as flavonoids and alkaloids are stated to be antidiabetic agents, and this has proved that the researched plants have antidiabetic potentialМета дослідження: З метою підтвердження використання в лікуванні діабету та визначення наявності численних фітохімічних речовин, які можуть бути пов’язані з активною дією рослин, фракціоновані екстракти Leptadenia hastata та Entada africana було проаналізовано in vitro Матеріал і методи: листя рослин висушували, подрібнювали за допомогою подрібнювального апарату Sumeet CM/L 2128945, розмір частинок був 45,85 мкм і проводили екстрагування метанолом. Неочищені екстракти фракціонували за допомогою колонки діаметром 30×8 см і 60 г силікагелю марки 60 F254, використовуючи метанол як елюент, фракції концентрували за допомогою роторного випарника, фракціоновані екстракти пропускали на тонкошарову хроматографічну пластину (ТШХ) та визначено їх коефіцієнти затримки (КЗ). Фракції об’єднували за подібним КЗ і знову проявляли за допомогою ТШХ пластини, після чого розраховували кінцевий РФ. Неочищені екстракти кількісно визначали на вміст фітохімічних речовин, а фітохімічні речовини, присутні у фракціонованих екстрактах (LH1 і EA2), ідентифікували за допомогою ВЕРХ-УФ-детектора. Екстракти (LH1 і EA2) були протестовані на антидіабетичний потенціал за допомогою ферментів α-глюкозидази та α-амілази в антидіабетичному аналізі in vitro. Результати: Вихід фракціонованих екстрактів становив 10,0 мг (Leptadenia hastata) і 11,5,0 мг (Entada Africana) і позначений як LH1 і EA2, КЗ для LH1 і EA2 становив 0,75±0,01 і 0,77±0,03 відповідно. Найбільшу кількість алкалоїду виявлено в E. Africana (14,50±0,25 мг/г), тоді як у L. Hastata танін не виявлено. У складі L. Hastata (LH1) було виявлено тринадцять фітохімічних речовин, з яких три були алкалоїдами. Тринадцять фітохімічних речовин було виявлено у фракції E. Africana (EA2), вісім з них були алкалоїдами та флавоноїдами. У порівнянні зі звичайною акарбозою протидіабетичні властивості рослин були кращими. EA2 мав EC50 0,950,17 г/мл (α-амілаза) і 0,970,41 г/мл (α-глюкозидаза), тоді як LH1 мав EC50 1,00±0,11 г/мл (α-амілаза) і 0,90±0,35 г/мл. мл (α-глюкозидаза). Наявність виявлених фітохімічних речовин може бути пов’язана з активними властивостями листя рослин. Висновок: фітохімічний профіль фракціонованих екстрактів, класифікованих як флавоноїди та алкалоїди, є протидіабетичними засобами, і це довело, що досліджувані рослини мають антидіабетичний потенціа

Anti-platelet aggregation of mixtures of betulinic oleanolic and maslinic acids and derivatives from medicinal plants

Purpose: To evaluate the antiplatelet aggregation and cytotoxic potential of betulinic acid (BA), oleanolic acid (OA), maslinic acid (MA) and their derivatives (3-β-acetyloleanolic acid (OAA) and 3-β- acetylbeutulinic (BAA) from medicinal plants. Methods: The compounds were characterized by nuclear magnetic resonance (NMR, both carbon 13 and hydrogen 1) (NMR), infra-red (FTIR) and mass spectroscopy (MS). The platelet aggregation inhibitory activities of the compounds (1, 3, 5 and 10 mg/ml) were investigated separately on adenosine diphosphate (ADP) and thrombin-induced rat platelet aggregation. Cytotoxicity studies were carried out on human embryonic kidney (HEK293) and hepatocellular carcinoma (HEPG2) cell lines using 3, 4, 5- dimethylthiazol-2-yl)-2-5-diphenyltetrazoliumbromide assay. Results: The compounds significantly (p < 0.05) inhibited platelet aggregation in a dose-dependent manner on thrombin and ADP agonist. BAA/OAA showed the highest activity on both agonists with IC50 of 2.86 and 3.05 mg/mL respectively. BAA/OAA also showed better antiplatelet activity than aspirin (IC50 of 6.45 and 7.36 mg/mL, respectively). In addition the compound (BA/OA, BAA/OAA and MA/OA) exhibited low cytotoxic effect on both HEK293 cells (IC50: 724.43, 269.08 and 407.89 mg/mL respectively) and HEPG2 (IC50: 585.38, 499.78 and 499.78 mg/mL, respectively). Conclusion: BAA/OAA demonstrate the best antiplatelet potential and low cytotoxicity of in all the tests, and therefore can serve as safer antiplatelet agents.Univesity of Zululand Research committe

Phytochemicals Profile and In-vitro Antidiabetic Potentials of Fractionated Extracts of Entada Africana and Leptadenia Hastata

Aim: To confirm their use in the management of diabetes and to determine the numerous phytochemicals present that may be connected to the active performance of the plants, the fractionated extracts of Leptadenia hastata and Entada africana were subjected to an in vitro experiment. Material and methods: The plant leaves were dried, pulverized with a Sumeet CM/L 2128945 grinder, the particle size was 45.85 μm and extracted with methanol. The crude extracts were fractionated using a 30×8 cm diameter column and 60g of silica gel 60 F254 grade, using methanol as eluent and fractions were concentrated using a rotary evaporator, the fractionated extracts were run on thin layer Chromatographic plate (TLC) and their retardation factors (RF) were determined. Fractions of similar RF were pulled together and spotted again using TLC plate and the final (RF) were calculated. The crude extracts were quantified for the content of phytochemicals and the phytochemicals present in the fractionated extracts (LH1 and EA2) were identified using HPLC-UV detector. The extracts (LH1 and EA2) were tested for antidiabetic potentials using α -glucosidase and α-amylase enzymes in an in-vitro antidiabetic assay. Results: The yields of the fractionated extracts were 10.0 mg (Leptadenia hastata) and 11.5.0 mg (Entada Africana) and designated as LH1 and EA2, the RF for LH1 and EA2 were 0.75±0.01 and 0.77±0.03 respectively. The maximum amount of alkaloid was found in E. Africana (14.50±0.25 mg/g), while tannin was not found in L. Hastata. In the portion of L. Hastata (LH1), thirteen phytochemicals were discovered and out of these three were alkaloids. Thirteen phytochemicals were found in the E. Africana fraction (EA2), with eight of them being alkaloids and flavonoids. When compared to the usual acarbose, the plants' anti-diabetic properties were superior. EA2 had EC50 of 0.950.17 g/ml (α-amylase) and 0.970.41 g/ml (α-glucosidase), while LH1 had EC50 of 1.00±0.11 g/ml (α-amylase) and 0.90±0.35 g/ml (α-glucosidase). The presence of the detected phytochemicals may be linked to the active qualities of the plants' leaves. Conclusion: The phytochemical profile of fractionated extracts classified as flavonoids and alkaloids are stated to be antidiabetic agents, and this has proved that the researched plants have antidiabetic potentia