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The ethanol extract of Persea americana seeds was found to inhibit the development of estrogen-dependent conditions in female Wistar rats, suggesting the ability of its secondary metabolites to interact with estrogen receptors (ERs), either as partial agonists or as antagonists. To test this hypothesis, the abovementioned extract was assessed for its ability to mimic and/or antagonize estradiol effects. Two experiments were conducted in ovariectomized (OVX) rats: (1) animals were treated with estradiol valerate (E2V; 1 mg/kg) or P. americana at doses of 25 and 50 mg/kg; (2) animals were treated with E2V alone (0.75 mg/kg) or in combination with P. americana at the abovementioned doses. Treatments were given orally for 3 days and animals were sacrificed for biochemical and histological analyses of the uterus and vagina. When administered alone, P. americana did not change the histomorphology of both organs (uterus and vagina). In combination with E2V, P. americana decreased uterine weight [30 % decrease (p<0.001) at 25 mg/kg and 24 % (p<0.01) at 50 mg/kg] and epithelium height (37 % decrease). This was associated with decreased estradiol levels (at least 86 % decrease, p<0.001) in the uterus. Similarly, vagina epithelium height decreased by at least 34 % (p<0.05) when E2V was co-administered with P. americana. The seed extract of P. americana contains ER antagonist secondary metabolites accounting for its ability to inhibit the development of estrogen-dependent conditions in female rats. [ABSTRACT FROM AUTHOR]

In Nigeria, Annona muricata L. has been used to treat a variety of ailments. The mechanism of the antimalarial activity of ethanolic leaf extract of Annona muricata (EEAML) was investigated using both an in vivo and an in silico approach. The experimental mice were divided into five groups: A-F. The mice in groups B-F were inoculated with Plasmodium berghei NK-65 and treated accordingly. Groups A and B are the negative and positive controls (infected and untreated), respectively. Group C received 10 mg/kg chloroquine (standard drug), whereas groups D-F received 100, 200, and 300 mg/kg body weight of the extract orally respectively. The mice were euthanized eight days after infection, and their liver and blood were collected and used in biochemical tests. Molecular docking was performed using the extract's HPLC compounds and Plasmodium falciparum proteins. In the suppressive, prophylactic, and curative tests, there was a significant decrease (p < 0.05) in parasitemia levels in groups treated with the extract compared to the positive control and standard drug. When compared to the positive control, there was a significant (p < 0.05) reduction in liver MDA, total cholesterol, and total triglyceride levels. The binding energies of luteolin and apigenin-pfprotein complexes were significantly (p < 0.05) higher compared to their respective references. The anti-plasmodial activity of the extract may result from its hypolipidemic effect, which deprives the parasite of essential lipid molecules needed for parasite growth, as well as from the inhibitory effects of apigenin and luteolin on specific proteins required for the Plasmodium metabolic pathway. [ABSTRACT FROM AUTHOR]

A polyherbal formulation consisting of Mentha piperita L., Camellia sinensis L. Kuntze, and Elettaria cardamomum (L.) Maton with a ratio of 10 : 5 : 2, respectively, was recommended for curing nausea, vomiting, and diarrhea. Experimental validation is crucial to affirm its therapeutic property leads toward the development of modified antidiarrheal agents. This research aimed to investigate the in vivo antidiarrheal efficacy of traditionally used polyherbal recipe in a castor oil-induced animal model. Moreover, the study also presents the elemental screening and in vivo toxicity of tested polyherbal recipe. Individual plant parts of the polyherbal recipe were mixed according to the traditional prescription ratio, and hydromethanolic extract was prepared by the cold maceration process. The antidiarrheal activity was assessed by castor oil induction method, charcoal meal test, and enteropooling procedure in Sprague-Dawley rats. Elemental analysis and in vivo subacute toxicity were carried out, followed by biochemical, hematological, and histopathological analyses. Polyherbal extract significantly delayed the diarrhea onset in a dose-dependent manner and showed marked inhibition at 200 and 400 mg/kg. Fecal weight was reduced significantly (p < 0.05) at 200 mg/kg (0.26 ± 0.25) in comparison with the control (1.63 ± 0.15). The diarrhea score was zero at a concentration of 200 and 400 mg/kg. Antienteropooling effect of the extract was greater than that of loperamide. Following subacute toxicity, all the treated rats were normal, survived, and showed no changes in behavior. There were no significant differences between values of blood parameters in both the control and extract-treated groups except a significant decrease in monocytes (control 8.4; polyherbal 2.2). Elemental analysis showed a slight increase in the amount of manganese (Mn, 8.076 ppm) as compared to the WHO recommended level (2 ppm). Traditionally used polyherbal recipe is effective and safe for combating diarrheal diseases. In vivo evidence supported the use, safety, and efficacy of the polyherbal recipe that has been used as an alternative medicine for diarrhea in the study area. Inhibition of castor oil-induced diarrhea and antisecretory effect of the studied polyherbal recipe makes it a potent antidiarrheal drug without no or limited toxic effects at the tested dose after further analysis. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DCM) pathogenesis is multifarious, and there are insufficient therapeutic options to treat DCM. The present research explored the effects of Citrus grandis peel ethanolic extract (CGPE) in alloxan-induced DCM in rats. Diabetes was triggered by intraperitoneal (i.p.) injection of alloxan (150 mg/kg) in Wistar rats (200-250 g). CGPE (100, 200, and 400 mg/kg) or glibenclamide (Glib, 10 mg/kg) were administered orally for 2 weeks. After the treatment schedule, prooxidants (thiobarbituric acid reactive substances), antioxidants (glutathione, catalase, and superoxide dismutase), and inflammatory markers (tumor necrosis factor-α) were determined in cardiac tissues. Biomarkers of cell death, viz., lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) activity, glucose levels, total cholesterol (TC), and high-density lipoproteins (HDL), were assessed in the blood. Rats administered with alloxan showed a consistent increase in blood glucose level (days 7 and 14) that was lowered considerably (p < 0.001) by CGPE or Glib. Alloxan-induced increase in LDH, CK-MB, TC, and decline in HDL was attenuated (p < 0.001) in rats that were treated with CGPE or Glib. Alloxan significantly (p < 0.001) elevated oxidative stress, inflammation, and reduced antioxidants in the cardiac tissue of rats, and these pathogenic abnormalities were ameliorated (p < 0.001) by CGPE. Histopathological studies showed a decrease in morphological disruptions by alloxan in CGPE-treated rats. CGPE (400 mg/kg) significantly ameliorated biochemical parameters in comparison to the lower doses against alloxan cardiotoxicity. Citrus grandis peel extract can be an alternative in the management of DCM. [ABSTRACT FROM AUTHOR]

Humans have been using herbs to prevent and cure various ailments since antiquity, and Ipomoea wightii is a significant medicinal plant known for its wide ethnobotanical uses. Although the plant is known to treat ulcers, there is no significant scientific validation. The present study aimed to assess the acute toxicity, subacute toxicity, and antiulcer properties of the leaf methanol extract of I. wightii (IWL). In the subacute study, the extracts were given orally at 100, 200, and 400 mg/kg doses for 28 days, and we analyzed the biochemical and histological parameters to evaluate the toxicity of IWL. Two different models were assessed to explore antiulcer properties, such as indomethacin- and ethanol-induced ulcer model. Ulcer areas and ulceration percentage histopathology of the stomach were used to study the efficacy of extracts. The acute toxicity study showed that IWL was safe to the maximum dose of 2000 mg/kg body weight. In a subacute toxicity study, the oral administration of IWL did not produce any mortality in the tested animals. The analysis of haematological, liver biochemical, kidney profile, lipid profile, and in vivo antioxidant parameters depicted that all the values were within the control limits after the experimental period and were considered nontoxic to animals. Additionally, the antiulcer study demonstrated a positive response of IWL in a dose-related manner (indomethacin- and ethanol-induced models). Macroscopic analysis showed that pretreatment with I. wightii leaf methanol extract significantly reduced the gastric lesion and decreased the ulceration area (14.52 mm2), demonstrating superior results to the positive control group (27.71 mm2). The histopathological analysis revealed that pretreatment with a high dose of 400 mg/kg of I. wightii leaf methanol extract and positive control group (omeprazole) markedly protected pathological effects, and the gastric mucosa appeared normal. In conclusion, I. wightii has solid nontoxic potential as a promising native herb for an integral therapy for the treatment of ulcers. [ABSTRACT FROM AUTHOR]

Plukenetia volubilis Linneo (P. volubilis), or Sacha inca, is an oleaginous plant from the Euphorbiaceae family. The presence of terpenoids, saponins, tannins, glycosides, phytosterols, and phenolic compounds in the ethanol extracts of P. volubilis L leaves has been reported, showing a range of bioactivities including antimicrobial, anti-inflammatory, antioxidant, and analgesia. However, the safety of this plant has not yet been reported explicitly. This study thus is aimed at evaluating the toxicity of the ethanol extract of P. volubilis leaves (EtPV) by acute and subchronic toxicity tests in Swiss albino mice following standard procedures set by The Organization for Economic Cooperation and Development (OECD) with slight modifications. In the acute toxicity test, the treatment groups were administered orally with the EtPV at doses of 1000, 3000, 5000, and 7000 mg/kg body weight in small fractions during 16 hours, and the mice were then observed in 14 consecutive days. In the subchronic toxicity study, the EtPV was given at doses of 100, 300, 500, and 700 mg/kg body weight for 90 days. Changes in behavior, mortality rate, and body and the weights of vital organs, hematology, clinical biochemistry, urine analysis, and histologic morphology were evaluated. The acute toxicity study showed that the EtPV causes no sign of toxicity or mortality. The hematological, biochemical and urine analyses, changes in the weight of the body and vital organs (heart, liver and kidney), and histopathological analyses of organs indicated no evidence of toxicity at any doses. It was also revealed that oral administration of EtPV is safe at the oral doses set by acute and subchronic toxicity tests, and the oral lethal dose for the EtPV is higher than 7000 mg/kg. This study is the first to confirm the safety of P. volubilis leaf ethanol extract, and as a result, encouraging further investigation to examine EtPV potential for traditional medicine. [ABSTRACT FROM AUTHOR]