Acute and Chronic Toxicity Studies of Ethanol Leaf Extract of Merremia Tridentata (Linn) Hallier F.

The acute and chronic toxicity evaluation of Ethanol leaf extract of Merremia tridentata (Linn) Halier F. (MTELE) was carried out on albino wistar rats. Phytochemical screening and acute toxicity profile of the extract were determined using standard methods. The animals were assigned into groups and administered varying doses of MTELE (100, 200, 400 mg/kg body weight and 0.2 ml of distilled water) for a period of hundred days (fourteen weeks). The body weight, relative organ weight, haematology, serum biochemical indices and histopathological studies of the liver, kidney, spleen, heart, and lungs were appropriately carried out to determine propensity of possible toxicity. Phytochemical screening revealed the presence of alkaloids, tannins, cardiac glycosides, saponins, steroids, triterpenes, flavonoids while anthraquinone and cyanogenic glycosides were absent. The median lethal dose LD50 was estimated as 2200 mg/kg body weight. There was significant (p<0.05) reduction in the percentage change in body weight of rats administered 200 and 400 mg/kg/day dose of the extract for 100days when compared to the control group. Moreover, there was a significant (p<0.05) reduction in the relative weight of the spleen of rats and significant (p<0.05) increase in the relative weight of the liver, kidney, heart and lungs of rats administered 400 mg/kg/day dose. All serum biochemical parameters studied showed significant (p<0.05) increase in group administered 400 mg/kg body weight dose while alkaline phosphatase, aspartate amino transferase, creatine kinase, lactate dehydrogesase and potassium ion showed significant increase (p<0.05) in the group administered 200 mg/kg/day. There is no significant change in hematological parameters like RBC, hemoglobin, hematocrit, platelets, monocytes, basophils, MCV, MCH, MCHC, in the extract treated animals except the lymphocyte that showed a significant (p<0.05) reduction only in the group treated with 400 mg/kg body weight dose. Administration of MTELE at 200 mg/kg body weight did not occasioned any histo-architectural change in the liver and spleen but caused varying degree of remarkable histological derangement in the other tissues. Furthermore, there were remarkable pathologies in the liver, kidney, spleen, heart and lungs ranging from vascular congestion, haemorrhage, fibrosis, to renal and myocardial damage in the group treated with 400 mg/kg/day dose for hundred days. However, 100 mg/kg body weight dose showed no significant difference (p>0.05) in all the parameters evaluated indicating safety at this dosage. Ethanol leaf extract of Merremia tridentata (Linn) Halier F. (MTELE) may not be safe at chronic administration even at dosage as low as 200 mg/kg body weight. The plant should be cautiously employed to avoid unwarranted complication on long term administration.

Pharmacological Screening of Substituted Benzimidazole Derivatives

In the present study some substituted benzimidazole derivatives were screened for several biological activities. The synthesized compounds were subjected to evaluation of central analgesic, anti-inflammatory, cytotoxicity, antimicrobial and antioxidant activities by radiant heat induced tail flicking, carrageenan induced rat paw edema inhibition, brine shrimp lethality bioassay, disc diffusion and DPPH free radical scavenging methods, respectively. Compounds 2a, 2c and 2d elongated the tail flicking time by 58.07-, 51.59- and 76.65%, respectively (p < 0.001) at 50 mg/kg body weight dose compared to the standard morphine (87.17%). Compounds 2b, 2c and 2d showed prominent anti-inflammatory activity at 100 mg/kg body weight dose (% of paw edema inhibition 81.75%, 79.09% and 86.69%, respectively) compared to the standard aceclofenac (87.83%). Among the synthesized benzimidazole derivatives, compounds 1a, 1b, 1c, 2a and 2d exhibited potent cytotoxicity with the IC50 values of 5.47-, 11.92-, 4.55-, 7.63- and 7.94 μg/ml, respectively. In addition, compounds 1c and 2d displayed mild to moderate zone of inhibition (8-12 mm). On the other hand, 1a and 1b showed very mild antioxidant activity with IC50 values of 12.25 × 103 μg/ml and 87.33 ×103 μg/ml. Among all the derivatives, 2c, 2d and 1c can be potential candidates for designing new analgesic, anti-inflammatory and anti-cancer agents in future. Dhaka Univ. J. Pharm. Sci. 20(1): 95-102, 2021 (June)

In Vivo Anthelmintic Activity of Whole Plant Powder of Striga Hermonthica (Deli.) Benth

The fight against Gastro-Intestinal Nematodes is an urgent necessity for the sheep’s productivity improvement in Burkina Faso. The anthelmintic activity of S. hermonthica’s whole plant powder was evaluated on Mossi sheep artificially infested with H. contortus L3 larvae. The experiment lasted 21 days with 2 phases of 4 days of treatment separated by 6 days in station. Two (2) treated lots of 6 sheep each received respectively 17g/kg of body weight and 10g/kg of body weight while two (2) control lots of 6 sheep each, one negative without treatment and one positive treated with levamisole 1/2 bolus for 25 kg were constituted. The faecal egg count (FEC) reduction rate was high during treatment and reached 84.49% for the 17g/kg body weight dose and 83.69% for the 10g/kg body weight dose at D21. Statistical analysis shows no significant difference between the two doses tested and between the two doses and the positive control, whereas the difference is significant (P<0.05) with the negative control. The mean hematocrit level ranged from 24 at D0 to 30.5 at D21 for the 17g/kg body weight treatment and from 25.83 at D0 to 31 at D21 for the 10g/kg body weight dose. The average daily gain (ADG) of the treated lots was not significant compared to the negative control (P>0.05).

The Hypoglycemic Effects of Ethanol Leaves Extract of Cymbopogon citratus and Its Fractions in Alloxan-Induced Diabetic Mice

Varieties of plants including Cymbopogon citratus are traditionally used in controlling hyperglycemia by either stimulating insulin secretion, inhibition α- Glucosidase or α-amylase activity. Cymbopogon citratus leaves were shade dried, grinded into fine powder and then extracted by cold maceration using ethanol. Fractionation was done by VLC using dichloromethane, ethyl acetate and ethanol. OGTT was performed for both crude extract and fractions. Diabetes was induced in mice by intraperitoneal injection of freshly prepared alloxan monohydrate (170 mg/kilogram body weight). The mice were treated with ethyl acetate fraction once daily at 400 mg/kilogram body weight dose for the period of 20 days.FBG and weight were then recorded in days 1, 5, 10, 15 and 20 after six hours of fasting. Safety of crude water extract and ethyl acetate fractions were evaluated in mice by using Lorke’s method, followed by 5 days observation for their mortality and behavioral changes. Comparisons of results among groups were analyzed using One-way ANOVA. The difference between the means of the two population groups (each against negative control) was considered significant at p< 0.05. Results were expressed as mean ± SD. Both crude and ethyl acetate fractions from C. citratus showed significant hypoglycemic activity. Moreover, higher hypoglycemic activity was shown by ethyl acetate fraction (p = 0.004). No mortality was observed at 5000 mg/kilogram body weight dose but sleeping and tremor were observed at a 1000 -5000 mg/kilogram body weight dose. Good hypoglycemic and safety results from ethyl acetate fraction highly suggest that Cymbopogon citratus extracts are effective against insulin-dependent hyperglycemia, which may be contributed by the action of the present of alkaloids, saponins, antraquinone, phenol and tannins. Isolation and testing of the active ingredients from the C. citratus extract are thus warranted for use in developing pharmaceutical anti-hyperglycemic drugs from this herbal plant.

Semax for Epilepsy Treatment

Epilepsy is a disruption of brain function that is characterized by abnormal depolarization of neurons. One signs of epilepsy is seizures, it is caused by brain injury. Epilepsy can cause morbidity and mortality, so many drugs used to treat epilepsy. But these drugs have negative health effects. This research was using semax peptide as alternative therapy, because it is a neuropeptide that directly acts on the central nervous system and free from hormonal activity, so it were not cause negative health effects. Moreover semax peptide is an antioxidant and it can synthesize some proteins in brain. The potency of semax peptide therapy on epilepsy rats can be analyzed by MDA level and profil proteins in brain. The epilepsy rats were prepared by in vivo using LiCl and pilocarpine. Then rats treated with 50 æg/kg body weight dose semax peptide. Analysis of MDA level were measured using TBA test while protein profile were determined using SDS-PAGE method. The result showed that semax peptide were reduce MDA level up to 40.46% and synthesize 3 kinds of proteins were not synthesized on epilepsy rats. Those proteins have molecular weights of 93.54 kDa, 66.76 kDa, and 59.66 kDa. In Conclusion, 50 æg/kg body weight dose semax peptide can be used for the treatment of epilepsy.

Pharmacokinetics of Trastuzumab After Subcutaneous and Intravenous Administration in Obese Patients

Background: Subcutaneous trastuzumab (T-SC) administration does not allow the historical target concentration of 20 µg/mL for efficacy to be reached, from the start of treatment in patients with a body mass index (BMI) >30 kg/m2. Objectives: To analyze the influence of the strategy of dosification (fixed vs adjusted patient’s body weight dose) on the initial minimum plasma concentration ( Cmin) of trastuzumab in obese patients. Methods: This was an observational, prospective study, which included patients with HER2-positive nonmetastatic breast cancer treated with trastuzumab. The determination of the Cmin of trastuzumab was performed on day +21 of the first cycle using the ELISA technique. Patients were stratified according to the strategy of dosification and BMI. Results: A total of 50 patients were included; 16 patients received the drug intravenously and 34 in a fixed dosage subcutaneous (T-SC) regimen. The proportion of patients who achieved an adequate plasma concentration since the beginning of treatment was significantly higher when the drug was administered intravenously (93.8% vs 67.6%, P = 0.042). These differences are especially greater in T-SC patients with BMI >30 kg/m2, with only 20% of patients exceeding the pharmacokinetic target. Conclusion and Relevance: Our study suggests that trastuzumab SC fixed dose of 600 mg is not equivalent to IV administration, especially in obese patients. An adequate trastuzumab exposure in this population needs patient weight–adjusted IV dosage in the first administration. The clinical relevance of these findings remains to be elucidated, and further research, including larger controlled trials, is warranted.

Ethyl acetate Fraction of Garcinia Mangostana L Rind Study as Antimalaria and Antioxidant in Plasmodium berghei Inoculated Mice

BACKGROUND: Drug resistance to malaria is still a problem in various regions, and there have even been developments in resistance to the ACTs (artemisinin-based combination therapies) as standard antimalarial drugs included to artemisinin’s partner drugs. Ethyl acetate fraction of G. mangostana L rind, containing xanthones as an antioxidant, has antimalarial activity in vitro which has a synergistic effect with artemisinin. That’s why the activities of this fraction are needed to be studied in vivo. AIM: To explore the antimalarial and antioxidant activity of ethyl acetate fraction of Garcinia mangostana L rind in mice. METHODS: This was a complete randomised design true experimental study. Six groups of mice: a healthy mice group and 5 groups of Plasmodium berghei inoculated mice treated with various doses of the sample for 3 days compared to artemisinin. Parasitemia and total antioxidant status were examined and analysed using ANOVA, and probit analysis were done.RESULTS: The parasitemia level in all of the treatment groups were lower than the positive control group without treatment (p < 0.01) and the parasitemia level was the lowest in artemisinin group which was not significantly different from the 100 mg/kg body weight dose group (p > 0.05). The parasitemia level in 20 and 4 mg/kg body weight dose groups were higher than the artemisinin group (p < 0.01). Parasite growth inhibition rate from the highest to the lowest consecutively was: artemisinin, 100 mg/kg body weight, 20 mg/kg body weight, 4 mg/kg body weight, and positive control group (p < 0.05) and ED50 was 3.396 mg/kg body weight. Total antioxidant status was the highest in 20 mg/ kg body weight dose and higher than the negative control group (p < 0.05) while the lowest total antioxidant status was in the positive control group. CONCLUSION: Ethyl acetate fraction of G. mangostana L rind potentially showed antimalarial and antioxidant activity in vivo. Further study is needed to explore the detail of its mechanism of action and its quantitative phytochemical analysis to find the leading compound in it.

Comparative study of two different doses of nalbuphine attenuating hemodynamic response to laryngoscopy and intubation in patients undergoing general anesthesia

Background: Various anaesthetic agents have been tried to attenuate pressor response to laryngoscopy and intubation. Among the recommended groups intravenous nalbuphine satisfies without much undesired effects. The objective was to study efficacy of two different doses of nalbuphine to attenuate pressor response to laryngoscopy and intubation.Methods: This was hospital based comparative study was carried out at Karnataka institute of Medical Sciences Hospital, Hubli, India. Patients were divided into two groups of 50 each randomly. First group was named as N1 and the second group was named as N2. Patients in N1 were given 0.1mg/kg Nalbuphine in 10ml of normal saline and patients in N2 were given 0.2-0.1mg/kg Nalbuphine in 10ml of normal saline. Appropriated statistical tests were applied like t test, ANOVA. P value if found less than 0.05 was recorded as statistically significant.Results: There was marked increase in HR, SBP, DBP and MAP immediately following laryngoscopy and intubation in the both the groups. Intravenous Nalbuphine given 5 minutes before intubation in the dose of 0.2mgkg-1 body weight effectively attenuated the hemodynamic response after laryngoscopy and intubation. However, there was a rise in HR, SBP, DBP and MAP immediately following intubation in group N2 which was clinically not significant though statistically significant. Side effects like nausea, vomiting, respiratory depression and sedation was not observed in both study groups.Conclusions: Authors concluded that 0.2mg/kg body weight dose of Nalbuphine was found to be more effective than 0.1mg/kg body weight dose of nalbuphine in maintaining the haemodynamics of the patients.

In vitro anti-oxidant, hypotensive and diuretic activities of Origanum glandulosum in rat

The objective of this study was to evaluate the in vitro anti-oxidant, hypo-tensive and the diuretic activities of Origanum glandulosum leaves in rat. Chemical analysis revealed the isolation of katuranin and 5-isopropyl-3-methylphenol. Ethyl acetate extract possessed highest scavenging activity against DPPH and hydroxyl radicals. Intravenous administration of extracts (0.04 to 12 mg/kg body weight) dose-dependently decreased the blood pressure (systolic, diastolic and mean) of the anesthetized rat. Methanol extract showed dose-dependent diuretic activity by increasing the urine output (77%) and the urinary excretion of sodium and potassium. In conclusion, this study supports the use of O. glansulosum in traditional medicine as hypotensive and diuretic agents.

OR-054 A Comparative Study of Different Intervention Methods on Protein Expression of ERα in Uterus of Ovariectomized Osteoporosis Rats

Objective The aim of this study was to compare the effects of different intervention methods on the protein expression of estrogen receptor alpha (ERα) in the uterus of ovariectomized osteoporosis rats. Methods Eighty healthy female SD rats, aged 3 months, were randomly divided into the following two groups by body weight: sham-operation (Sham) and ovariectomized (OVX). After ten weeks, the OVX groups were randomly divided into the following six groups by body weight: OVX; 17β-estradiol (E2); Genisteine (G); treadmill exercise (TE); Lithium chloride (Licl); Whole-body vertical vibration (WBVV). Then the rats was began to be treated with different intervention methods. The WBVV group rats were vibrated on a vibration platform twice per day for 7 weeks according to the following schedule: 90 hertz a minute and 15 minutes a time. The TE group rats were running on 5-uphill treadmills 45 minutes per day, 4 times a week, at a speed of 18 meters per minute. The G group rats were lavaged by genistein once per day according to body weight (dose 1mg/kg).The E2 group rats were treated with neck subcutaneous injection with 17β-E2 three times a week according to their body weight (dose 25ug/kg). At the end of 8 weeks intervention, during 36-48 hours, took blood from the abdominal aorta, and extracted the protein. The proteinexpression of ERα in uterus was detected by western blot. Results After OVX, the uterus weight index and serum E2 was significantly decreased. Both the uterus weight index and the serum E2 level were significantly increased after treatment with E2. However, no significant differences were seen after treatment with the other four methods. As revealed by the western blot results, the protein expression of ERα in the OVX groups was significantly higher than that of in the Sham group. After treatment with E2, treadmill exercise, whole-body vertical vibration, and lithium chloride, the protein expression of ERα was significantly lower than that of in OVX group. However, the genistein treatment had no significant difference. Conclusions Apart from genistein treatment, the other four interventions had inhibitive effects on the protein expression of ERα in uterus of OVX osteoporosis rats.