Journal of Experimental Pharmacology最新文献

Background: Olinia rochetiana has been used traditionally to cure diarrheal disease. Therefore, this study aimed to investigate the acute toxicity and antidiarrheal effect of O. rochetiana leaf extracts.

Methods: Cold maceration was used to extract plant leaf powder with 80% methanol. The extract's antidiarrheal action was tested against a castor oil-induced diarrheal model, a charcoal meal test, and enteropooling tests at doses of 100, 200, and 400 mg/kg. Negative controls received the vehicle at 10 mL/kg, while positive controls received loperamide at 3 mg/kg.

Results: From the study, no apparent toxicity was observed when a single dose of 2000 mg/kg was administered. In the castor oil-induced model, the extract delayed the onset of diarrhea, reduced stool frequency, and decreased wet feces weight and number in a dose-dependent manner at 200 mg/kg (p < 0.05) and 400 mg/kg (p < 0.01). The percent reduction in moist feces at 100, 200, and 400 mg/kg was 54.2, 23.97, and 18.26%, respectively, indicating a significant dose-dependent decrease. In a charcoal meal test, the extracts at 200 and 400 mg/kg revealed a peristaltic index of 65 and 46%, respectively, with considerable inhibition of charcoal transport at 23 and 39%. The weight and volume of intestinal contents dropped significantly at a dose of 400 mg/kg (p < 0.01), which is 0.43 mg/kg, in the enteropooling test when compared with the tested dose. The computed in vivo antidiarrheal index revealed diarrheal inhibition values of 46.06 and 71.06% at 200 and 400 mg/kg, respectively.

Conclusion: In the current investigation, O. rochetiana showed significant antidiarrheal activity with no symptoms of toxicity in mice.

Purpose: This study evaluates the acute and sub-acute toxicity of 80% methanolic extracts of the leaves of Justicia schimperiana in Wistar albino rat models.

Methods: Dried powdered leaves of Justicia schimperiana were macerated in 80% methanol. The experiment was conducted in accordance with the Organization for Economic Co-operation and Development guideline 423 for acute and 407 for sub-acute toxicity testing. A single dose of 5000 mg/kg extract was orally administered to three female rats for the acute toxicity study. The plant extract was administered orally for 28 days in daily dosages of 250, 500, and 1000 mg/kg for the sub-acute study. Animals in a control group were given distilled water. A total of 40 rats (5 rats/group/sex) were used for the sub-acute toxicity testing. Daily food intake and weekly body weight measurements were done. The rats were sacrificed at the end of the 28-day treatment period for hematological, biochemical, and histopathological tests. One-way analysis of variance and Kruskal-Wallis tests were employed for the analysis.

Results: The single-dose oral administration of the plant resulted in no deaths or serious morbidity. The median lethal dose was >5000 mg/kg. The 28-day oral treatment of the plant extract had no significant effect on general behavior, food intake, organ weight, biochemical parameters, or the majority of the hematological markers, with the exception of the decrease in hemoglobin and hematocrit in the 1000 mg/kg extract-treated groups compared to the controls. Both sexes experienced significant weight increases at all dosage levels. With the exception of minor alterations in a few of the organs, no significant histological change was identified.

Conclusion: It is concluded that the single-dose and repeated-dose 28-day oral administration of the methanolic leaf extract of Justicia schimperiana is relatively safe.

Background: Because of the scarcity, high cost, and severe side effects of current medications, it is necessary to discover novel, safe, and affordable anti-diabetic drugs. The current study was conducted to evaluate the antidiabetic activities of Verbascum sinaiticum Benth leaves in mice.

Methods: Leaf coarse powder was extracted with 80% methanol and then fractionated with n-hexane, ethyl acetate, and distilled water. The glucose-lowering effects of V. sinaiticum at 100, 200, and 400mg/kg were then studied. Glibenclamide was used as a positive control at a dose of 5 mg/kg. For oral glucose tolerance tests and hypoglycemia tests, Tween 2% was used as a negative control, while citrate buffer was used as a negative control for antihyperglycemic investigations. The results from the study were evaluated using one-way ANOVA, and then Tukey's post hoc multiple comparison test was performed.

Results: Blood glucose levels were significantly reduced by the V. sinaiticum 80% methanol extract at 400 mg/kg (p<0.05). The blood glucose levels were significantly lowered by the aqueous residue at 400 mg/kg (p<0.05) and the ethyl acetate fractions at 200 mg/kg (p<0.01) and 400 mg/kg (p<0.001); however, none of the fraction extracts resulted in hypoglycemic shock in healthy mice. Higher glucose tolerance was seen in orally glucose-loaded mice after exposure to 80% methanol extracts at 200 and 400 mg/kg (p<0.05), the aqueous residual fraction at 200 mg/kg (p<0.01), and the ethyl acetate fraction at 200 and 400 mg/kg (p<0.05). The ethyl acetate fraction at 200 and 400 mg/kg (p<0.01), the 80% methanol extract at 400 mg/kg (p<0.05) and the aqueous residue at 400 mg/kg (p 0.01) significantly lowered blood glucose levels in streptozotocin-induced diabetic mice.

Conclusion: The results of this study revealed that the 80% methanol extract and solvent fractions of V. sinaiticum Benth leaves are endowed with antidiabetic activity.

Background: Azithromycin (AZM) is a macrolide antibiotic that exhibits anti-inflammatory and anti-viral infection properties by enhancing type-I interferon (IFN-I) responses. The stimulator of interferon genes (STING) can directly induce IFN-I production. However, elevated IFN-I induces auto-immune phenotypes such as systemic lupus erythematosus (SLE). The effects of AZM and STING on the production of IFN-I are unclear.

Objective: Therefore, this study aims to evaluate the role of AZM and STING on IFN-I responses in macrophages.

Methods: RAW 264.7 macrophages were treated with AZM with and without a STING-agonist (DMXAA), and the maturation of macrophages was determined using flow cytometry. Gene expression and pro-inflammatory cytokines were analyzed using qPCR and ELISA, respectively. Moreover, protein expression was investigated using Western blot assays and immunofluorescence.

Results: Our results show that AZM significantly induced M1 phenotypes, promoting surface molecule expansion of CD80 and MHC-II and production of IL-6 and TNF-α cytokines on DMXAA-stimulated macrophages. Furthermore, we found that AZM-increased mRNA levels of interferon-stimulated genes (ISGs) could be due to the high expression of STNG-TBK1 signaling in the presence of DMXAA.

Conclusion: Our data suggest that AZM enhancement of IFN-I responses was STING dependent in DMXAA-stimulated macrophages. These data underline a novel approach to AZM action-mediated STING-TBK1 signaling for regulating IFN-I responses and may further augment the scientific basis and potential use of AZM in clinical applications.

Background: Due to the limits of present antidiarrheal medications, it is critical to seek novel, safe, and inexpensive antidiarrheal agents. Thus, the goal of this study was to assess the antidiarrheal activity of 80% methanol crude extract and solvent fractions of Maesa lanceolata leaves in mice.

Methods: Leaf powder was extracted by 80% methanol and then fractionated with n-hexane, ethyl acetate, and distilled water. At 100, 200, and 400 mg/kg, the effects of the crude extract on castor oil-induced diarrhea, enteropooling, and gastrointestinal motility tests were investigated. Tween 2% and atropine used as negative and positive controls, respectively. A gastrointestinal motility test was used to explore the anti-motility effects. Data were analyzed with SPSS V. 26, and the significance was established with a one-way ANOVA followed by a post hoc Tukey's test.

Results: The crude extract delayed the onset of diarrhea and significantly reduced the number of fecal drops at 100 (p<0.05), 200 and 400 mg/kg (p<0.001). Similarly, the number and weight of wet feces, as well as total fresh feces, were reduced at 200 (p<0.05) and 400 mg/kg (p<0.001) compared to Tween 2%. The enteropooling test demonstrated that the extracts significantly reduced the volume and weight of intestine content at 200 (p<0.05) and 400 mg/kg (p<0.001). The anti-motility activity test revealed that the all extracts decreased gastrointestinal motility significantly (p<0.001). The ethyl acetate fraction significantly reduced gastrointestinal transit time at all doses (p<0.001). At 400 mg/kg, the activities of the n-hexane fraction were significant (p<0.01). The efficacy of the residual aqueous fraction on gastrointestinal motility was significant at 200 (p<0.05) and 400 mg/kg (p<0.001).

Conclusion: The 80% methanol extract of Maesa lanceolata Forssk leaf and solvent fractions were shown to exhibit potent antidiarrheal activity in the current study.

Background: Managing diabetes mellitus with currently available drugs is costly, and the chances of side effects are high, leading to further studies for new and better medications from plant sources with the affordable and lower side effects. This study aimed to evaluate the anti-diabetic effects of Datura stramonium Linn (Solanaceae) Leaves Extract in Streptozotocin- Induced Diabetic Mice.

Methods: Male Swiss albino mice were induced into diabetes using 150mg/kg of STZ. Mice were allocated randomly into six groups, five mice per group. Group I was a normal control, Group II was Diabetic negative control, group III was Diabetic positive control, Group IV-VI were Diabetic Mice that treated with extract (100, 200 and 400 mg/kg) for 14 days. The FBG measurements were done on 0, 7th, and 14th days of treatment. After 14th day of treatment the mice were anesthetized with diethyl ether. Then, blood was drawn by cardiac puncture to assess TC, TG, LDL-C, and HDL-C. The antioxidant activity of the extract was determined using a DPPH assay. The data were entered into Epi-Data version 4.6, exported to SPSS version 26.0, and analyzed using a one-way ANOVA followed by a Tukey post hoc test. P < 0.05 was considered statistically significant.

Results: The extract of D. stramonium reduced the FBG level by 19.71%, 30.27%, 40.95%, and 45.67%, respectively, for D. stramonium 100, 200, 400, and GLC 5 mg/kg on the 14th day of treatment. Diabetic mice treated with D. stramonium for 14 days   showed a significant decrease in serum TC, LDL, and serum TG and a significant increase in body weight, and HDL level as compared to diabetic negative control. Antioxidant activities of the leaves extract were comparable to ascorbic acid with an IC50 of 172.79 μg/mL.

Conclusion: These findings revealed that the D. stramonium leaves extract possesses significant Anti-diabetic activities.

Background: Interleukin 17 (IL-17) and interferon gamma (IFN-γ) play a role in the pathogenesis of psoriasis vulgaris (PV). Topical corticosteroids are still utilised as first-line therapy for mild to moderate PV. However, long-term use of corticosteroid is associated with various side effects. Physalis angulata Linn. (Ciplukan) possesses anti-inflammatory properties that could serve as a potential alternative topical therapy for PV.

Objective: To assess the efficacy of topical ciplukan as an anti-inflammatory agent targeting the expression of IL-17 and IFN-γ.

Methods: Psoriasis was induced using imiquimod cream, therefore divided into five groups. Group I, the psoriasis control group, received only imiquimod cream. Groups C1 and C2 received imiquimod cream followed by a mixture of Ciplukan and vaseline in a 1:2 and 1:4 ratio, respectively. Group M, the standard therapy group, received imiquimod cream, followed by mometasone furoate cream. Lastly, group V, the vehicle group, received imiquimod cream followed by vaseline album. Expression of IL-17 and IFN-γ in mice's skin tissue was analysed using reverse transcription polymerase chain reaction (RT-PCR) after seven days of treatment.

Results: The mean expression of IL-17 in Group C1 (22.60) was significantly lower (p = 0.012) than in the psoriasis control group (23.60), and there was no significant difference (p = 0.613) in Group M (22.41). The mean expression of IFN-γ in Group C1 (26.97) and Group C2 (27.03) was also significantly lower (p = 0.026 and p = 0.026, respectively) than Group I (28.80), and there was no significant difference (p = 0.180 and p = 0.093, respectively) than Group M (26.03).

Conclusion: Expression of IL-17 and IFN-γ in the ciplukan group is lower than in the psoriasis control group, and there is no significant difference compared to the standard therapy group.

Background: Vernonia auriculifera Hiern (Asteraceae) is among Ethiopian herbal medicines that are traditionally used to treat skin and gastrointestinal cancers. In this study, the chemopreventive potential of Vernonia auriculifera leaf extract in dimethylhydrazine (DMH)-induced colorectal carcinogenesis in rats was investigated.

Methods: Rats were assigned to nine groups (normal, positive, and negative control groups, and three pre- and three post-initiation groups). Except for the normal control group (administered with 1 mL/100 g distilled water), the remaining eight groups were given DMH (20 mg/kg) intraperitoneally (ip) for 15 consecutive weeks to induce colorectal tumours. The extract was given orally to the pre-initiation and post-initiation groups at doses of 100, 200, and 400 mg/kg before and after the induction of cancer, respectively. The positive control group was treated with aspirin (60 mg/kg/day) orally for the whole experimental period. Parameters including body weight, average tumour number, size, progression, incidence, total cholesterol, serum total protein, and triglyceride levels were determined. The cytotoxic activity of the extract in Caco-2 cells was evaluated using the MTT assay, and the antioxidant activity of the extract was also assessed using 2.2-diphenyl-1-picrylhydrazine (DPPH) and reducing power methods. Moreover, total phenol and flavonoid contents were determined using appropriate methods.

Results: Rats treated with the extract showed a lower incidence of up to 50% in the pre-initiation higher dose, average number (p<0.05),and size (p<0.05) of tumours compared to untreated rats. It also inhibited colorectal cancer-associated increases in serum total cholesterol and triglycerides. The extract's IC₅₀ value in the MTT assay was found to be higher than 200 µg/mL. The extract had an IC₅₀ of 74.88 ± 0.86 µg/mL and 84.69 ± 2.02 µg/mL in the reducing power and DPPH assays, respectively. Total flavonoid and phenol contents were 14.51 ± 0.41 mg quercetin acid equivalent/gm and 47.37 ± 0.72 mg gallic acid equivalent/gm of the crude extract, respectively.

Conclusion: The findings collectively indicated that the leaves of V. auriculifera possess chemopreventive activity, probably mediated through antioxidant mechanisms, which supports the traditional claim.