In silico pharmacokinetic and therapeutic evaluation of Musa acuminata peels against aluminium chloride-induced hepatotoxicity in adult BALB/c mice.

East Africa (Musa spp.), notably Musa acuminata, "Matooke" a staple and economically important food in the region. Here, 12 selected M. acuminata peels extract (MAPE) bioactive compounds were studied for hepatoprotective potentials in aluminium chloride-induced hepatoxicity in adult BALB/c mice. GC-MS analysis was used to identify active components of MAPE. In silico estimation of the pharmacokinetic, the GCMS-identified compounds' toxicity profile and molecular docking were compared with the standard (Simvastatin) drug. Hepatotoxicity was induced using aluminium-chloride treated with MAPE, followed by biochemical and histopathological examination. Twelve bioactive compounds 2,2-Dichloroacetophenone (72870), Cyclooctasiloxane 18993663), 7-Hydroxy-6,9a-dimethyl-3-methylene-decahydro-azuleno[4,5-b]furan-2,9-dione (534579), all-trans-alpha-Carotene (4369188), Cyclononasiloxane (53438479), 3-Chloro-5-(4-methoxyphenyl)-6,7a-dimethyl-5,6,7,7a-tetrahydro-4H-furo[2,3-c]pyridin-2-one (536708), Pivalic acid (6417), 10,13-Octadecadienoic acid (54284936), Ethyl Linoleate (5282184), Oleic acid (5363269), Tirucallol (101257), Obtusifoliol (65252) were identified by GC-MS. Of these, seven were successfully docked with the target proteins. The compounds possess drug likeness potentials that do not inhibits CYP450 isoforms biotransformation. All the docked compounds were chemoprotective to AMES toxicity, hERGI, hERGII and hepatotoxicity. The animal model reveals MAPE protective effect on liver marker's function while the histological studies show regeneration of the disoriented layers of bile ducts and ameliorate the cellular/histoarchitecture of the hepatic cells induced by AlCl3. The findings indicate that MAPE improved liver functions and ameliorated the hepatic cells' cellular or histoarchitecture induced by AlCl3. Further studies are necessary to elucidate the mechanism action and toxicological evaluation of MAPE's chronic or intermittent use to ascertain its safety in whole organism systems.

Agaricus Subrufescens ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with Letrozole induced polycystic ovarian syndrome.

OBJECTIVE: The objective of this study is to investigate the effects of an ethanolic extract derived from Agaricus subrufescens on rat models exhibiting Polycystic Ovarian Syndrome (PCOS) induced by Letrozole. METHODS: A total of thirty female Wistar rats were divided into five groups, each consisting of six rats. The negative control group was administered a volume of 1 mL of a 0.5% solution of carboxy methylcellulose (CMC). Letrozole (1 mg/kg) was administered to additional groups for a duration of 21 days in order to induce polycystic ovary syndrome (PCOS). Animals designated as positive controls were euthanized on the 22nd day. Both the test group and the standard group were subjected to treatment from the 22nd day to the 36th day. The experimental group was administered ethanolic extract of Agaricus subrufescens at doses of 200 mg/kg and 400 mg/kg p.o, while the control group received clomiphene citrate at a dose of 1 mg/kg. The study observed various physiological markers in individuals with polycystic ovarian disease, including estimated blood glucose levels, total cholesterol levels, triglyceride levels, and hormonal fluctuations such as increased testosterone and estrogen levels, as well as decreased progesterone levels. The presence of menstrual irregularities was confirmed through the examination of vaginal smears and histopathological changes in the ovaries. RESULTS: The consumption of Agaricus subrufescens was found to have a significant impact on various physiological parameters, including blood glucose levels, testosterone levels, anovulation, and menstrual irregularity. All therapeutic interventions significantly normalized the levels of serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamic-pyruvic transaminase (SGPT). The rats with polycystic ovary syndrome (PCOS) that were induced by Letrozole exhibited increased levels of urea and creatinine. The findings of this study indicate that the administration of Agaricus subrufescens therapy has a protective effect on renal function, as evidenced by a reduction in serum levels of urea and creatinine. In rats with polycystic ovary syndrome (PCOS) induced by Letrozole, the inhibition of hepatic synthesis, promotion of ovarian follicle immaturity, and elevation of androgen secretions result in an increase in the weight of the liver and ovaries. The weight of endocrine organs exhibited a decrease across all treatment groups. The histopathological examination of PCOS specimens revealed an increased presence of cysts and theca lutein cells. The group of rats with polycystic ovary syndrome (PCOS) that did not receive treatment exhibited a higher number of cysts compared to the groups that received treatment. CONCLUSION: This study demonstrated that the administration of Letrozole orally resulted in the development of polycystic ovarian disease. The results indicated heightened levels of blood glucose, total cholesterol, and triglycerides, as well as alterations in hormone levels such as increased testosterone and estrogen, and decreased progesterone. These hormonal changes were accompanied by menstrual irregularities, which were confirmed through the examination of vaginal smears and histopathological analysis of the ovaries in the control group with polycystic ovarian disease. The treatment groups that received Agaricus subrufescens exhibited a decrease in blood glucose, total cholesterol, and testosterone levels.

Anxiety, Anger and Depression Amongst Low-Income Earners in Southwestern Uganda During the COVID-19 Total Lockdown.

Background: Low-income earners are particularly vulnerable to mental health, consequence of the coronavirus disease 2019 (COVID-19) lockdown restrictions, due to a temporary or permanent loss of income and livelihood, coupled with government-enforced measures of social distancing. This study evaluates the mental health status among low-income earners in southwestern Uganda during the first total COVID-19 lockdown in Uganda. Methods: A cross-sectional descriptive study was undertaken amongst earners whose income falls below the poverty threshold. Two hundred and fifty-three (n = 253) male and female low-income earners between the ages of 18 and 60 years of age were recruited to the study. Modified generalized anxiety disorder (GAD-7), Spielberger's State-Trait Anger Expression Inventory-2 (STAXI-2), and Beck Depression Inventory (BDI) tools as appropriate were used to assess anxiety, anger, and depression respectively among our respondents. Results: Severe anxiety (68.8%) followed by moderate depression (60.5%) and moderate anger (56.9%) were the most common mental health challenges experienced by low-income earners in Bushenyi district. Awareness of mental healthcare increased with the age of respondents in both males and females. A linear relationship was observed with age and depression (r = 0.154, P = 0.014) while positive correlations were observed between anxiety and anger (r = 0.254, P < 0.001); anxiety and depression (r = 0.153, P = 0.015) and anger and depression (r = 0.153, P = 0.015). Conclusion: The study shows the importance of mental health awareness in low resource settings during the current COVID-19 pandemic. Females were identified as persons at risk to mental depression, while anger was highest amongst young males.

Anti-nociceptive, anti-inflammatory and possible mechanism of anti-nociceptive action of methanol leaf extract of Nymphaea lotus Linn (Nymphaeceae).

The leaf of Nymphaea lotus has been used traditionally for the management of pain and inflammatory diseases. The methanol leaf extract of Nymphaea lotus (NLE) was evaluated for possible anti-nociceptive and anti-inflammatory activities in rats and mice (at the doses of 250, 500 and 1,000 mg/kg) to investigate the existence of scientific basis for the folkloric use of the plant. The standard drugs used were piroxicam (10 mg/kg) and morphine (10 mg/kg). The possible pharmacological mechanism involved in the anti-nociceptive activity was also investigated. The acute toxicity was determined in mice and rats using method of Lorke. The anti-nociceptive activity was evaluated using acetic acid-induced writhing and hot plate tests in mice, while the anti-inflammatory activity was evaluated using carrageenan-induced hind paw edema model in rats. The oral median lethal dose of NLE was found to be greater than 5,000 mg/kg in rats and mice. NLE demonstrated significant and dose-dependent protection against acetic acid induced writhes and increased the reaction time of mice in hot plate test. Pretreatment of the animals with naloxone (2 mg/kg) significantly (p < 0.05) attenuated the anti-nociception elicited by both NLE and morphine. NLE at the doses of 250 and 1,000 mg/kg significantly (p < 0.05) decreased rat paw edema at the 2nd hour in the carrageenan-induced paw edema test. The result of the study revealed that Nymphaea lotus possesses anti-nociceptive activities which may be mediated via the opioidergic system as well as mild anti-inflammatory activities thus providing scientific basis for the use of the plant in the management of pain and inflammatory diseases.

Antinociceptive activity of methanol extract of Chlorophytum alismifolium tubers in murine model of pain: Possible involvement of α2-adrenergic receptor and KATP channels.

The tubers of Chlorophytum alismifolium are used in Nigerian Herbal Medicine for the management of diabetes mellitus, painful and inflammatory conditions. The antinociceptive activity has been validated but the mechanism of this activity is yet to be explored. This study therefore, aimed to investigate the probable mechanism(s) of the antinociceptive activity of C. alismifolium tubers using experimental animal model of pain. HPLC and GC-MS analyses were carried out on the extract. Antinociceptive activity was investigated using acetic acid-induced writhing response test in mice. Three groups of mice were orally administered distilled water (10 ml/kg), C. alismifolium (400 mg/kg) and morphine (10 mg/kg) 60 min before administration of acetic acid and the resulting writhing were counted for 10 min. To establish the probable mechanism(s) of action of C. alismifolium, separate groups of animals were pretreated intraperitoneally with naloxone (2 mg/kg), prazosin (1 mg/kg), yohimbine (1 mg/kg), propranolol (20 mg/kg) and glibenclamide (5 mg/kg) 15 min before C. alismifolium administration. HPLC chromatogram of the extract revealed seventeen characteristic peaks with retention times ranging between 2.1 and 7.4 min. Administration of C. alismifolium significantly (p < 0.01) reduced the mean number of writhes compared to control group. Pretreatment with yohimbine and glibenclamide significantly (p < 0.05 and p < 0.01 respectively) reduced the antinociceptive activity of extract-alone treated group. However, pretreatment with prazosin, naloxone and propranolol showed no effect on its analgesic activity. The findings from this research revealed the possible involvement of α2-adrenergic receptor and KATP channels in the antinociceptive activity of Chlorophytum alismifolium tuber extract.

Elucidation of the possible mechanism of analgesic actions of butanol leaf fraction of Olax subscorpioidea Oliv.

ETHNOPHARMACOLOGICAL RELEVANCE: Preparations of Olax subscorpioidea have been used traditionally for the management of pains, inflammatory diseases, yellow fever, cancer and rheumatism. Previously, the analgesic activity of its leaf extract have been reported. Furthermore, an analgesic assay guided fractionation showed that the butanol soluble fraction is the most active. However, the mechanism of this activity remains to be elucidated. This present study investigated the possible pharmacological mechanisms involved in the analgesic activity of the butanol leaf fraction of Olax subscorpioidea (BFOS) using the acetic acid induced writhing test in mice. MATERIALS AND METHODS: Animals were orally administered distilled water (10ml/kg), BFOS (1,000mg/kg) and morphine (10mg/kg) 60minutes before i.p administration of acetic acid and the resulting writhing were counted for 10minutes. To establish the possible mechanism(s) of action of BFOS, separate group of animals were pretreated with naloxone (2mg/kg, i.p), prazosin (1mg/kg, i.p), yohimbine (1mg/kg, i.p), propranolol (20mg/kg, i.p), metergoline (2mg/kg, i.p), glibenclamide (5mg/kg, i.p) and l-arginine (50mg/kg, i.p) 15minutes before BFOS. RESULTS: BFOS and morphine showed marked analgesic activities (p<0.001); the pretreatment of animals with naloxone, metergoline and l-arginine significantly (p<0.05 and p<0.001) reduced the analgesic activity of BFOS; however, pretreatment with prazosin, yohimbine, propranolol and glinbenclamide showed no effect on its analgesic activity. CONCLUSION: Results obtained in this study suggest the involvement of opioidergic, serotonergic and nitric oxide-l-arginine pathways in the analgesic effect of butanol leaf fraction of Olax subscorpioidea.

Toxicological evaluation of the aqueous leaf extract of Moringa oleifera Lam. (Moringaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: The rapid increase in consumption of herbal remedies worldwide has been stimulated by several factors, including the notion that all herbal products are safe and effective. However, over the past decade, several news-catching episodes in developed communities indicated adverse effects, sometimes life-threatening, allegedly arising as a consequence to taking herbal products or traditional medicines from various ethnic groups. Despite the popular use of Moringa oleifera for treating various disorders, there is limited or no scientific data available regarding safety aspects of this remedy, nor are there any documented toxicological studies that can be used to ascertain the safety index of its herbal preparation. Therefore, this present study aimed to carry out extensive toxicological evaluation of the aqueous leaf extract of Moringa oleifera. MATERIALS AND METHODS: In an acute toxicity test, male Wistar albino mice were orally administered an aqueous extract up to 6400 mg/kg and intraperitoneally up to 2000 mg/kg. A sub-chronic toxicity test was performed by daily administration with the extract at 250, 500 and 1500 mg/kg orally for 60 days. Control rats received distilled water. Sperm quality was analyzed, haematological and biochemical (liver enzymes, urea and creatinine) parameters were determined and a histopathological examination was carried out. RESULTS: The LD(50) was estimated to be 1585 mg/kg. The extract did not elicit any significant difference (P≥0.05) in sperm quality, haematological and biochemical parameters in the treated rats compared to the control. Moreover, there was no significant difference in weight gain of the control and treated animals although there was a dose-dependent reduction in food consumption of the animals treated with 250 to 1500 mg/kg extract. CONCLUSIONS: Results obtained in this study suggest that the aqueous leaf extract of Moringa oleifera is relatively safe when administered orally.