We report a new approach that combines molecular dynamics trajectories with time-dependent linear response theory to compute the time evolution of residue fluctuation responses to force perturbations exerted at functional sites. Applying this new approach to TEM-1 beta-lactamase, we observe that the time-resolved response profiles of allosteric sites to perturbations of TEM-1 active sites are distinct from those of non-allosteric residues. Using Fourier transformations, we convert the time domain response profiles to the frequency domain and demonstrate that the frequency space representation of the perturbation response can capture the mutational behavior of each site when applied to deep sequencing mutational data. Furthermore, we show that classification models built on perturbation responses can accurately identify distal positions that regulate antibiotic resistance. These findings provide insights into the contributions of specific residues to resistance-encoded in time-resolved perturbation response behavior and highlight the importance of this new approach in identifying allosteric mutations, opening avenues for the potential characterization of additional allosteric positions without extensive computational simulations.

Introduction : Les atteintes hépatiques et rénales sont des altérations des fonctions du foie et des reins. 50 % de ces altérations seraient d’origine médicamenteuse. La prise en charge étant onéreuse, motive les personnes affectées à s’orienter vers la phytothérapie comme traitements alternatifs. Cette étude avait pour objectif l’évaluation des effets de l’extrait aqueux des feuilles de Solanum torvum sur quelques altérations des fonctions hépatique et rénale induite par la gentamicine. Matériel et Méthodes : Soixante rats ont été utilisés, divisés en trois lots, ils recevaient pendant 10 jours en dose quotidienne la gentamicine 100 mg/kg (i.p) pour les rats du lot 1 (n=45), le NaCl (0,9 %, i.p) pour le lot 2 (n=10) et l’extrait à la dose 530 mg/kg (p.o) pour le lot 3 (n=5). Au 11e jour, les rats du lot 1 ont été répartis en 05 groupes (n=9) et traités pendant 10 jours en dose quotidienne avec de l’ED (10 mL/kg, p.o) pour témoin négatif, la silymarine (150 mg/kg, p.o) pour le témoin positif et l’extrait aux doses 133, 265 et 530 mg/kg (p.o) pour les groupes tests ; le traitement du lot 2 (témoin normal) et 3 (témoin pharmacologique) était maintenus. Les analyses de quelques paramètres biochimiques sériques hépatiques (transaminases, PAL, γ-GT, albumine, protéines sériques et bilirubines), rénaux (créatinine sérique et Acide urique sérique) et tissulaires (statut oxydant et microarchitecture) ont été réalisés. Résultats et discussion : La gentamicine a provoqué au bout de 20 jours une baisse significative du poids corporel, une baisse de l’activité de la PAL, du taux d’albumine et une augmentation significative du poids des reins, de l’activité des transaminases et de la γ-GT. L’administration de l’extrait a significativement corrigé (p< 0,001) les troubles de la fonction hépatique en restaurant l’activité des transaminases, de la γ-GT et de la PAL, en améliorant les désordres du profil de bilirubine et de l’albumine. L’extrait a prévenu et corrigé l’augmentation du taux d’acide urique et de créatinine sérique. Il a été observé une amélioration du statut oxydant accompagné d’une restauration de la microarchitecture des tissus hépatique et rénale comparé au témoin normal. Conclusion : Les effets pharmacologiques de l’extrait prouvent qu’il posséderait des propriétés hépatoprotectrices et néphroprotectrices qui pourrait nous pousser à envisager la mise sur pied d’un médicament traditionnel amélioré.

This present work aimed to assess the subacute toxicity of the total aqueous extract of the dry bark of Albizia ferruginea in rats. Subacute toxicity was done in accordance with 2008 OECD Guideline 407, for oral toxicity at a daily dose for 28 days in rodents. The animals were divided into six groups of 10 rats each (5 males and 5 females). One control group received 10 mL/kg of distilled water, three groups received 200, 400 and 800 mg/kg of extract respectively, one satellite control group and one satellite treated group received 10 mL/kg of distilled water and 800 mg/kg extract respectively. After 28 days of treatment, the satellite groups were left under observation without treatment for an additional 14 days. Behavior, body weight and death rate were monitored during the experimental period. The relative weight of some organs, hematological and biochemical parameters and the histopathological study of the liver, kidneys and lungs were evaluated at the end of the experiment. There were no significant effects on body weight gain and the relative weight of organs investigated. At the 800 mg/kg dose, there was a significant increase in the level of monocytes by 26.53%; the mean corpuscular hemoglobin content (MCHT) of 18.18%; and in the corpuscular hemoglobin concentration (MCHC) of 20.70 %, only in male rats. ALT and ASAT activity were increased significantly in both male and female rats. These increases were not seen in satellite treated rats. The histology of the organs investigated showed no difference when comparing the treated rats to the control rats. The subacute toxicity study of total aqueous extract of the dry bark of Albizia ferruginea did not show any signs of significant toxicity for parameters studied in rats.

https://doi.org/10.30574/gscbps.2021.17.2.0327 Abstract Introduction: Kalanchoe pinnata extracts have been shown to possess beneficial cardiovascular effects, analgesic and myorelaxant activities. This study aimed at evaluating the haematological and anti-fatigue effects of its aqueous extract. Materials and methods : This was an in vivo pharmacological experiment, carried out in the Laboratory of Zoology, University of Buea, from January to May 2018. A total of 48 mice were subjected to a 90mins/day-free endurance swimming test for 14 days. Two groups of mice received distilled water and 12% NaCl solution, respectively. Five groups received the plant extract (25, 50, 100 and 200 mg/kg/day) and 200mg/kg/day+NaCl. One positive control group received 5% Vitamin C (1.97mg/kg/day). All administrations were by gavage. Maximum swimming time, glycaemia, lactatemia, uremia, triglyceridemia, haematological indices, tissue glutathion peroxidase, malondialdehyde, glucose and creatine kinase-MB in the heart or gastrocnemius muscle were measured. Results: K. pinnata (50 and 100mg/kg/day) induced a non-significant increase of the swimming duration, compared to neutral control. However, the 12%NaCl group recorded a significant (P<0.05) increase. In the blood, NaCl induced a decrease of platelets that was significantly reverted by the extract in the 200mg/kg+NaCl group. The extract prevented the increase of the level of CK-MB in NaCl group and decreased the serum triglycerides, glucose, urea nitrogen and Lactate levels. In the tissues, MDA and CK-MB levels significantly increased (P<0.001) in the negative control. These increases were significantly (P<0.001) prevented by K. pinnata (200mg/kg/day). Conclusions : Significant biochemical variations support the hypothesis that K. pinnata could be used to delay exercise induced

Aims: The present research was carried out to investigate the anti-inflammatory, analgesic and antipyretic potential of aqueous extract of Albizia ferruginea stem bark. Place and Duration of Study: Department of Animal Biology and Physiology (Animal Physiology Laboratory), Faculty of Sciences, University of Yaoundé I. between March 2012 and June 2016. Methods: Qualitative and quantitative phytochemical analyzes were done.The anti-inflammatory effect of the plant extract (100 and 200 mg/kg) was investigated on carrageenan, histamine, serotonin or dextran-induced paw oedema. The analgesic activity was evaluated on acetic acid-induced writhing, formalin-induced nociception, hot plate and tail immersion tests in Swiss albino mice. The antipyretic activity of A. ferruginea extract was assessed on brewer’s yeast induced pyrexia. Results: Qualitative phytochemical analysis of the AEAF revealed the presence of alkaloids, flavonoïds, phenols, saponins, tannins, glycosides, tannins and steroids. For quantitative phytochemical analysis, total flavonols represent 0.12±0.04 mg EQT/g dried extract and the total phenol content was 58.69±0.65 mg ECA/g dried extract. The total flavonoids content was 0.18±0.01mg EQT/g dried extract).The total alkaloids presented a grade of 27.45±0.14 mg EBER/g dried extract. Carrageenan, dextran, histamine and serotonin-induced inflammation were significantly inhibited by A. ferruginea’s extract (200 mg/kg), exhibiting 55.47%, 50.26%, 62.88% and 42.59% inhibition, respectively. Acetic acid-induced writhing was significantly reduced by the plant extract. The extract of Albizia ferruginea (200 mg/kg) significantly reduced the second phase of formalin test. The analgesic tests revealed that A. ferruginea had only peripheral analgesic effect. Additionally, the plant’s extract prevented brewer’s yeast-induced pyrexia in rats. Conclusion: Taken together, these results suggest that A. ferruginea’s aqueous extract has anti-inflammatory, anti-nociceptive and antipyretic properties and this strongly supports the ethnopharmacological uses.

Anxiety has become the most common mental health problem associated with immense health care costs and a high burden of disease. Current drugs used for the treatment of anxiety are associated with a wide variety of prominent side effects. Medicinal plant extracts have become popular due to their efficacy, fewer undesirable effects, and can serve as sources of new pharmaceutical drugs. The aim of this study was to assess the anxiolytic properties of the bark aqueous extract of Bridelia micrantha (Euphorbiaceae) and its possible mechanisms of action. Hyperthermia-induced stress (HIS), Open field (OF), elevated plus maze (EPM) and hole-board tests were used in this study. Groups mice were treated with distilled water, diazepam, phenobarbital or B. micrantha extract (30, 76, 152 and 305 mg/kg). Evaluations of behavioural profile were done 1 h post-treatment and the duration of observation was 5 minutes. The involvement of the GABA A receptor complex in the activity of B. micrantha extract was inferred from experiments with known GABA A -targeting agents. Extract administration caused significant dose-dependent decrease of HIS compared to negative control. Like diazepam, the extract significantly induced anxiolytic effects in mice in the open arms of the EPM, and during the open field and the hole-board tests. The plant extract significantly inhibited the anxiogenic activities of Bicuculline, Flumazenil and N-methyl-β-carboline-3-carboxamide. Thus, bark aqueous extract of B. micrantha possesses anxiolytic activity that might be due to interactions with the benzodiazepine-binding site of the GABA A receptor complex.

To evaluate the anti-inflammatory and protective effect of Cassia alata (Linn.) leaves is the objective of this study. The anti-inflammatory and protective effect of dichloromethan extract of Cassia alata (Linn.) leaves (CF-AECal) has been studied according to Freund's adjuvant-induced arthritic rat models. CF-AECal 50 mg/Kg, 100 mg/Kg and dexamethasone 1 mg/Kg were the doses of drugs receipt by rats. CF-AECal 100 mg/Kg showed a substantial anti-inflammatory and protective effect. CF-AECal 50 and 100 mg/Kg produced antioxidant effects in Freund's adjuvant-induced paw edema. Indeed, antioxidant enzymes are maintained more or less that their normal rate. These antioxidant effects protect the liver, the kidney and the spleen highly (p< 0.001). CF-AECal 50 and 100 mg/Kg lead to a significant decline in the rate of serum enzymes (AST, PAL and CREA) and a decrease of the serum concentration of total bilirubin and protein compared to animals of the control group ignited. At the doses of the extract used, the leukocyte infiltration is reduced in the cutaneous cloths of the paws of rats. In conclusionCassia alata leaves extractshows anti-inflammatory and protective effects

Background: In Burkina Faso, leaves of Cassia alata are used in the treatment of several diseases, including inflammation. This study evaluated the anti-inflammatory effects of the dichloromethane extract of Cassia alata leaves (CF-AECal) on different models of inflammation in wistar rats in order to enhance its use in traditional medicine. Materials and Methods: Acute inflammation was induced among rats with 0.1 ml of carrageenan, serotonin, histamine and dextrane 1%. The effects of the CF-AECal 50 mg/kg and 100 mg/kg were compared to the effects of diclofenal 5 mg/kg, prednisone 5 mg/kg, promethazine 1 mg/kg, cyproheptadin 2 mg/kg. Cotton pellet and air pouch - induced granuloma permitted to study CF-AECal effects on the subacute inflammation. The ways of administrations were intra peritoneal for the substances of inductions and oral for the molecules of references and CF-AECal. Result: Carrageenan-induced paw edema has been inhibited to 52.39% by CF-AECal 50 mg/kg and 50.17% by CF-AECal 100 mg/kg. Wet granulomas formation has been inhibited by CF-AECal 50 and 100 mg/kg to 20.94 and 57.82%. The dry granulomas were inhibited at 24.32 and 59.04% by CF-AECal 50 and 100 mg/kg. Air pouch fluid was significantly reduced by CF-AECal in comparison to the control group. There was a massive recruitment of leukocytes in the pocket granuloma of the control group. CF-AECal caused strong inhibition of this infiltration of leukocytes (p< 0.001). Conclusion: Dichloromethane extract of Cassia alata showed anti-inflammatory effects.

Several lines say that a number of natural products, mostly plant based, have been claimed to cure male sexual dysfunction. One of such botanicals is Carpolobia alba G. Don which is used in Cameroon to treat erectile dysfunction and related male sexual debilities. However, the traditional claim has not been scientifically tested. Thirty adult male rats (five groups of six animals) were orally treated daily with distilled water, sildenafil citrate (positive control), 75, 150, 300 mg/kg of C. alba G. Don roots aqueous extract. The erection and ejaculation properties were recorded on the first, seventh and fourteenth day of treatment by following copulation settings: number of erections (NE), mount frequency (MF), intromission frequency (IF), ejaculation frequency (EF), mount latency (ML), intromission latency (IL), ejaculation latency (EL), average interval of copulation (AIC) and post-ejaculatory interval (PEI). The extract resulted in an improvement of copulation parameters through significant reduction (p < .001) of PEI, ML and IL and significant increase (p < .001) in the NE, MF, IF, EF, EL and AIC. These results indicate a pro-erectile and pro-ejaculatory potential of aqueous root extract of this plant in male rats.

Background and Objective: The advocacy for the alternative use of some combined therapy in herbal medicine is currently gaining more grounds in Nigeria than before due to incessant drug resistance phenomenon. Thus, the study was focused on the evaluation of the antibacterial property of the combined extract from Kalanchoe pinnata and Citrus aurantifolia for the inhibition of the otitis-media isolates. Materials and Methods: The test organisms were isolated from otitis-media samples by standard bacteriological methods and identified by numerical taxonomic procedures using Jaccard Simple Matching Coefficient tool. The Kirby-Bauer disk diffusion susceptibility method was adopted for their sensitivity to varied concentrations of the combined extract. The obtained data were considered significant at p< 0.05 by using statistical package for social sciences (SPSS), version 15 for paired-t-test correlation analysis …

Aims: The stem bark of Eribroma oblongum (Malvaceae) is used in traditional Cameroonian medicine to treat various metabolic illnesses including the management of hypertension without scientific evidence to how relief is brought about. The present study was to evaluate the effect of the dried stem bark of hydroethanolic extract of E. oblongum on arterial blood pressure and heart rate in normotensive rat (NTR) and in atherogenic diet induced - hypertensive rats.Study Design: This was a prospective cross-sectional analytical study.Place and Duration of Study: Study was conducted in the Laboratories of Animal Physiology, Organic Chemistry and Natural Product of the Faculty of Sciences, and the Preclinical Animal Toxicology laboratory of the Faculty of Medicine and Biomedical Sciences of the University of Yaound 1-Cameroon, during the period August 2013 to April 2014. Fresh stem bark of Eribroma oblongum were collected at Eseka, Centre Region of Cameroon, in August 2013. The plant material was identified at the National Herbarium (HNC) of Yaounde-Cameroon where a voucher specimen No27489SRFCam has been deposited.Methodology: The effects of a hydroethanolic extract of Eribroma oblongum (HEEO; 10, 20, 30 mg/kg; i.v) was tested on systolic blood pressure (SBP) and heart rate (HR) of normotensive rat. The mechanism of HEEO (10 mg/kg) was studied in the presence of atropine, yohimbine, propranolol, L-NAME or reserpine. Preventive effects were studied after feeding atherogenic diet (AD) with oral administration of HEEO (100 mg/kg/day) in rats for 45 days. Body weight and food intake were measured every five days during the 45 days of study At the end of the experiment, SBP and HR were recorded. Aorta, heart, liver and kidneys were weighted, and biochemical assays of superoxide dismutase (SOD), catalase, reduced glutathione (GSH), malondialdehyde (MDA), nitrites (NO2-) and lipid profile, transaminases and creatinine were done.Results: HEEO (10-20 mg/kg) induced a significant hypotensive effect of SBP. The hypotensive effects of HEEO (10 mg/kg) were inhibited by pre-treatment of rats with atropine, reserpine, yohimbine and L-NAME. The AD significantly elevated SBP (P<0.01). Treatment with HEEO (100 mg/kg) reduced blood pressure and significantly decreased HR (P<0.01). HEEO significantly improved the plasma of triglycerides 35.08%, cholesterol total 33.71%, LDL-Cholesterol 73.73% with a significant low atherogenic index 1.73. HEEO significantly increased NO2- and SOD in aorta, CAT in heart P<0.01 and ASAT P<0.05.Conclusion: This study demonstrates the hypotensive and antihypertensive potential of the crude hydroethanolic extract of the stem bark of Eribroma oblongum. Our data validate the use of the extract traditional medicine against hypertension in Cameroon. The effect on blood pressure is, at least in part, due to a modulation of the orthosympathetic nervous system and to the improvement of the antioxidant status. Further studies are now needed to identify the bioactive compounds responsible for the cardiovascular effects of Eribroma oblongum.

The aim of the present study was to demonstrate vascular changes and the effect of Bidens pilosa extract in fructose induced hypertension. Interactive computerized microscopy was used to study the morphometric alterations in the mesenteric arterial bed of Wistar rats treated with fructose (10%) in drinking water during 3 weeks and for 3 subsequent weeks with fructose, fructose plus Bidens pilosa (75 mg/kg) or fructose plus nifedipine (10 mg/kg). Fructose feeding brought about structural changes in the blood vessels associated with a slight increase in the systolic pressure. The minimal and maximal diameters and lumen areas of the vessels were reduced. The total areas and lumen are as well as the number of nuclei in the media were reduced following 6 weeks of fructose feeding. The media/lumen ratios were reduced by 28%. The media area and the density of the nuclei in the media were significantly reduced after 6 weeks of fructose treatment compared with the 3 week fructose treatment. The morphometric study showed that the small arteries underwent structural alterations, which were reversed by Bidens pilosa treatment. Nifedipine, decreased like the plant extract the blood pressure but, fall to attenuated changes in morphological parameters in mesenteric arteries.

Mature male albino Wistar rats (180-210 g) were given aqueous extract of dry seeds of Aframomum melegueta K. Schum (Zingiberaceae) by gastric intubation during periods of 8 and 55 days. This was performed in two doses: 115 and 230 mg kg(-1) during 8 days and 115 mg kg(-1) during 55 days. Control rats received distilled water during the same periods. The animals were sacrificed and their blood, as well as testis, epididymis, seminal vesicle and prostate were collected and analysed. Results showed a significant increase in testosterone in serum and testis, cholesterol in testis, α-glucosidase in epididymis and fructose in seminal vesicle after 8 days of treatment of A. melegueta-treated rats (115 and 230 mg kg(-1) ). Results also showed that levels of cholesterol in testis, α-glucosidase in epididymis and fructose in seminal vesicle increased by 93.34%, 83.44% and 62.78%, respectively, after 55 days of A. melegueta treatment. From these findings, it was concluded that the aqueous extract of A. melegueta increased the secretions of epididymis and seminal vesicle, which are accessory sex organs.

Afrormosia laxiflora (A. laxiflora), Chenopodium ambrosioides (C. ambrosioides), Microglossa pyrifolia (M. pyrifolia) and Mimosa pudica (M. pudica) are plants used in traditional medicine in Cameroon to treat insomnia, epilepsy, anxiety, and agitation. They were evaluated for their anxiolytic like activity in mice. Animal models (elevated plus maze and stress-induced hyperthermia tests) were used. The four plants showed anxiolytic activity. In stress-induced hyperthermia test, A. laxiflora, C. ambrosioides, M. pyrifolia and M. pudica significantly antagonised the increase of temperature. ΔT° decreased from 0.75°C in the control group to 0.36°C at the dose of 110 mg/kg for A. laxiflora; from 1°C in the control group to -1.1°C at the dose of 120 mg/kg for C. ambrosioides; from 1.7°C in the control group to 0.2°C at the dose of 128 mg/kg for M. pyrifolia and from 1.3°C in the control group to 0.5°C at the dose of 180 mg/kg for M. pudica. In the elevated plus maze test, the four plants increased the number of entries into, percentage of entries into, and percentage of time in open arms. A. laxiflora, C. ambrosioides and M. pudica also reduced the percentage of entries and time in closed arms. In addition, C. ambrosioides, M. pyrifolia and M. pudica showed antipyretic activity by reducing the body temperature. The results suggested that C. ambrosioides, M. pyrifolia and M. pudica posses anxiolytic-like and antipyretic activities while A. laxiflora possesses only anxiolytic-like properties. These plants could be helpful in the treatment of anxiety and fever in traditional medicine in Cameroon.

The antidiabetic and antioxidant effect of ethyl acetate extract of Terminalia superba (combretaceae) was investigated in streptozotocin-nicotinamide induced type 2 diabetes. Diabetes was induced in adult male wistar rats by intraperitoneal injection of 110 mg/kg of nicotinamide, 15 min before an intravenous injection of 65 mg/kg of streptozotocin. The effects of the plant extract were evaluated on serum glucose, lipid profile, some parameters of oxidative stress, hepatic and renal function. The effects of plant extract on blood pressure were also monitored. Daily administration of the plant extract provoked a significant (P< 0.01) dose dependent reduction in serum glucose levels. At the end of treatment the percentages of reduction were 34.10% and 42.02% at the doses of 75 and 150 mg/kg respectively. Oral administration of the plant extract for 28 days showed a significant improvement in lipid profile and a significant reduction of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST). Treatment with the plant extract significantly provoked a reduction of aorta, liver and kidney malondialdehyde, and induced a significant improvement in reduced glutathione, superoxide dismutase activity when compared with diabetic control. Blood pressure measurement revealed that, at all doses (75 mg/kg and 150 mg/kg), the plant extract prevented (15.33% and 15.39% of reduction) the rise in mean blood pressure observed in diabetic control rats. These results suggest that ethyl acetate extract of T. superba lowers blood glucose and hyperlipidemia, prevents oxidative stress and reduces blood pressure in diabetic conditions, thus justify its traditional use for the management of diabetes and hypertension. Keywords: Antidiabetic, antioxidant, streptozotocin-nicotinamide induced diabetes , Terminalia superba