Antioxidant Activities and Chemical Constituents of Extracts from Cordyline fruticosa (L.) A. Chev. (Agavaceae) and Eriobotrya japonica (Thunb) Lindl, (Rosaceae)

Background and Objective: Cordyline fruticosa (Agavaceae) and Eriobotrya japonica (Rosaceae) are two medicinal plants used for the treatment of various diseases such as infections of mammary glands, sore throat and neck pain for the first plant, diabetes, cough, ulcers, protection against oxidative stress and cognitive deficits for the latter. The present study was designed to evaluate the antioxidant activity of the different extracts of these two plants as well as to isolate and identify their chemical constituents. Materials and Methods: The plant extract was prepared by maceration in methanol, compounds were isolated from EtOAc and n-BuOH extracts of the two plants using column chromatography and their structures were determined by means of NMR and MS analysis as well as in comparison with published data. Antioxidant tests (DPPH, ferric reduction antioxidant power and anti-hemolytic) were performed over the MeOH, EtOAc and n-BuOH extracts of the plants. Results: The antioxidant-guided phytochemical investigation of the MeOH extracts of the two plants led to the isolation of twelve compounds identified as: Farrerol 1, quercetin helichrysoside 2, apigenin 8-C-β-D-glucopyranoside 3, isoquercitrin 4 and rutin 5 from C. fruticosa, β-sitosterol 6, catechin 7, oleanolic acid 8, lyoniresinol 9, cinchonain IIb 10, lyoniresinol 2-a-O-β-D-xylopyranoside 11 and β-sitosterol-3-O-β-D-glucopyranoside 12 from E. japonica. Amongst the isolated compounds, the most important antioxidant ones were identified as helichrysoside and rutin from C. fruticosa, catechin, cinchonain IIb, lyoniresinol 2-a-O-β-D-xylopyranoside from E. japonica with EC50 of 8.73, 9.91, 4.11, 3.14 and 10.61 μg mL–1, respectively. Conclusion: Based on the obtained results, it can be concluded that the high ability to scavenge free radicals, reducing power of Fe3+ and hemolysis activity exerted by extracts of C. fruticosa and E. japonica were due to their high content of phenolic compounds, thus the structure-activity relationships of the isolated flavonoids were discussed. The results of this study suggest that the extracts from these two plants could serve as potential source of antioxidant compound

Antidiarrheal Activity of Aqueous Extract of the Stem Bark of Sapium Ellipticum (Euphorbiaceae)

Purpose: To investigate the antidiarrheal activity of the aqueous extract of the stem bark of S. ellipticum (Euphorbiaceae) (AESE).Methods: AESE was prepared by decoction of the powder from the dry stem bark of S. ellipticum. Its oral antidiarrheal effect was evaluated in vivo at the doses of 5.2, 10.4 and 20.8 mg/kg on castor oil induced diarrhea and on gastro-intestinal transit. AESE was also evaluated in vitro (0.125 – 4 mg/ml) on ileal smooth muscle motility. The acute oral toxicity of AESE (5, 10, 15, 20 and 25 mg/kg) was also assessed in mice.Results: AESE significantly and dose dependently delayed the time of appearance of the first stools, decreased the frequency of defecation and the intestinal transit with respective percentage of 319.14, 62.50 and 36.51 % at the dose of 20.8 mg/kg in comparison with negative control (distilled water). AESE, in a concentration-dependent manner, reduced the tone and amplitude of spontaneous contractions of the ileal smooth muscle with EC50 of 33.29 and 45.43 μg/ml, respectively. None of the doses used in acute toxicity test induced any significant behavioral changes or mortality.Conclusion: These results suggest that AESE possesses antidiarrheal properties mediated at least partially by the inhibition of intestinal motility and may be devoid of acute toxicity.Keywords: Sapium ellipticum, Antidiarrheal, Intestinal transit, Spasmolytic, Acute toxicity

Endothelium/Nitric Oxide Mediates the Vasorelaxant and Antihypertensive Effects of the Aqueous Extract from the Stem Bark of Mammea africana

This study evaluates the vasorelaxant and antihypertensive effects of the aqueous extract from the stem bark of M. africana (AEMA). AEMA was tested in vitro on intact or endothelium-denuded rats’ aorta rings precontracted with KCl or norepinephrine in absence or in presence of L-NAME or glibenclamide. The effect of a single concentration (300 μg/mL) of AEMA was also examined on the concentration-response curve of KCl. In vivo, the antihypertensive effects of AEMA (200 mg/kg/day) were evaluated in male Wistar rats treated with L-NAME (40 mg/kg/day) for 4 weeks. AEMA relaxed aorta rings precontracted with NE or KCl with respective EC50 values of 0.36 μg/mL and 197.60 μg/mL. The destruction of endothelium or pretreatment of aorta rings with L-NAME shifted the EC50 of AEMA from 0.36 μg/mL to 40.65 μg/mL and 20.20 μg/mL, respectively. The vasorelaxant activity of M. africana was significantly inhibited in presence of glibenclamide. AEMA also significantly inhibited the concentration-response curve of KCl. Administered orally, AEMA induced acute and chronic antihypertensive effects and normalized renal NO level. These results show that the vasorelaxant activity of AEMA might be mediated by the activation of the NO-cGMP-ATP-dependent potassium channels pathway and might predominantly account for its antihypertensive effect

Acute and sub-chronic oral toxicity assessment of the leaf aqueous extract of Kalanchoe crenata (Crassulaceae)

Previous studies demonstrated that the leaves of Kalanchoe crenata (Crassulaceae) possess analgesic, anti-inflammatory, anticonvulsant and cardiovascular activities but nothing is known about the toxicity of this plant material. The objective of the present study was to evaluate the acute and sub-chronic toxicities of the aqueous extract of the leaves of K. crenata (AEKC) prepared as a dry leaves decoction. Acute oral toxicity of the AEKC was evaluated in mice at doses 2, 4, 6, and 8 g/kg. Animals were observed for 3 hours post administration for signs and symptoms of intoxication. Survivors were followed up for 14 days after treatment. Wistar rats of both sexes were used for sub-chronic toxicity. They were orally treated with the AEKC at doses of 300, 600 and 1200 mg/kg/day for 4 consecutive weeks. They were further euthanized and blood was collected for biochemical and hematological analyses. A single acute administration of AEKC reduced the sensitivity to pain and the mobility of animals. These behavioral modifications disappeared 3 hours after administration. Only the dose of 8 g/kg caused the death of one female mouse out of 6, inferring a LD50 greater than 8 g/kg. The daily administration of AEKC did not induce mortality, behavioral modifications, significant variations of body weight, relative weights of the liver and kidney and plasma content of Alanine amino transferase (ALAT) and aspartate amino transferase (ASAT). Besides, no significant difference was observed on glomerular filtration rate and other parameters of renal excretion. Meanwhile, at the dose of 300 mg/kg/day, a significant increase in total bilirubin, free bilirubin and a significant decrease in conjugated bilirubin and plasma creatinine were registered. These results suggest that the aqueous extract of the leaves of K. crenata can be classified as a non-toxic substance. However, attention should be paid on the hepatic function.Keywords: Acute and sub-chronic toxicity, aqueous extract, Kalanchoe crenata, Crassulacea

Multimodal α-Glucosidase and α-Amylase Inhibition and Antioxidant Effect of the Aqueous and Methanol Extracts from the Trunk Bark of Ceiba pentandra

Postprandial hyperglycemia and oxidative stress are important factors that worsen the health condition of patients with type 2 diabetes. We recently showed that extracts from Ceiba pentandra mitigate hyperglycemia in dexamethasone- and high diet/streptozotocin-induced diabetes. Herein, we evaluated the postprandial regulatory properties and the antioxidant effects of the aqueous (AE) and methanol (ME) extracts from the stem bark of Ceiba pentandra. The phytochemical analysis of AE and ME was performed using the LC-MS technique and the total phenolic and flavonoid assays. Both extracts were tested for their ability to inhibit superoxide anion (O2•ـ), hydrogen peroxide (H2O2), protein oxidation, alpha-amylase, and alpha-glucosidase activities. The mode of enzyme inhibition was also determined in a kinetic study. AE and ME were both rich in phenolic and flavonoid compounds. ME was 2.13 and 1.91 times more concentrated than AE in phenolic and flavonoid compounds, respectively. LC-MS allowed the identification of 5 compounds in both extracts. ME and AE inhibited O2•ـ with IC50 of 51.81 and 34.26 μg/ml, respectively. On H2O2, they exhibited IC50 of 44.84 and 1.78 μg/ml, respectively. Finally, they exhibited IC50 of 120.60 and 140.40 μg/ml, respectively, in the inhibition of protein oxidation induced by H2O2, while showing IC50 of 39.26 and 97.95 μg/ml on the protein oxidation induced by AAPH. ME and AE inhibited alpha-amylase with IC50 of 6.15 and 54.52 μg/ml, respectively. These extracts also inhibited alpha-glucosidase, demonstrating IC50 of 76.61 and 86.49 μg/ml. AE exhibited a mixed noncompetitive inhibition on both enzymes, whereas ME exhibited a competitive inhibition on α-amylase and a pure noncompetitive inhibition on α-glucosidase. These results demonstrate that ME and AE scavenge reactive oxygen species and prevent their effects on biomolecules. Besides, ME and AE inhibit carbohydrate digestive enzymes. These properties may contribute to reduce postprandial hyperglycemia and regulate glycemia in diabetic patients

Assessment of the In Vitro Cytotoxicity Effects of the Leaf Methanol Extract of Crinum zeylanicum on Mouse Induced Pluripotent Stem Cells and Their Cardiomyocytes Derivatives

Crinum zeylanicum (C. zeylanicum) is commonly used in African folk medicine to treat cardiovascular ailments. In the present study, we investigated the cytotoxic effect of the leaf methanol extract of C. zeylanicum (CZE) using mouse pluripotent stem cells (mPSCs). mPSCs and their cardiomyocytes (CMs) derivatives were exposed to CZE at different concentrations. Cell proliferation, differentiation capacity, and beating activity were assessed using xCELLigence system and microscopy for embryoid body (EB) morphology. Expression of markers associated with major cardiac cell types was examined by immunofluorescence and quantitative RT-PCR. Intracellular reactive oxygen species (ROS) levels were assessed by dichlorodihydrofluorescein diacetate staining. The results showed that the plant extract significantly reduced cell proliferation and viability in a concentration- and time-dependent manner. This was accompanied by a decrease in EB size and an increase in intracellular ROS. High concentrations of CZE decreased the expression of some important cardiac biomarkers. In addition, CZE treatment was associated with poor sarcomere structural organization of CMs and significantly decreased the amplitude and beating rate of CMs, without affecting CMs viability. These results indicate that CZE might be toxic at high concentrations in the embryonic stages of stem cells and could modulate the contracting activity of CMs

Hypoglycemic Properties of the Aqueous Extract from the Stem Bark of Ceiba pentandra in Dexamethasone-Induced Insulin Resistant Rats

Parts of Ceiba pentandra are wildly used in Africa to treat diabetes and previous works have demonstrated their in vivo antidiabetic effects on type 1 diabetes models. In addition, it has been recently shown that the decoction and the methanol extract from the stem bark of C. pentandra potentiate in vitro, the peripheral glucose consumption by the liver and skeletal muscle slices. But nothing is known about its effect on type II diabetes, especially on insulin resistance condition. We investigated herein the antihyperglycemic, insulin-sensitizing potential, and cardioprotective effects of the dried decoction from the stem bark of Ceiba pentandra (DCP) in dexamethasone-induced insulin resistant rats. DCP phytochemical analysis using LC-MS showed the presence of many compounds, including 8-formyl-7-hydroxy-5-isopropyl-2-methoxy-3-methyl-1,4-naphthaquinone, 2,4,6-trimethoxyphenol, and vavain. Wistar rats were given intramuscularly (i.m.) dexamethasone (1 mg/kg/day) alone or concomitantly with oral doses of DCP (75 or 150 mg/kg/day) or metformin (40 mg/kg/day) for 9 days. Parameters such as body weight, glycemia, oral glucose tolerance, plasma triglycerides and cholesterol, blood pressure, and heart rate were evaluated. Moreover, cardiac, hepatic and aortic antioxidants (reduced glutathione, catalase, and superoxide dismutase), malondialdehyde level, and nitric oxide content were determined. DCP decreased glycemia by up to 34% and corrected the impairment of glucose tolerance induced by dexamethasone but has no significant effect on blood pressure and heart rate. DCP reduced the total plasma cholesterol and triglycerides as compared to animals treated only with dexamethasone. DCP also increased catalase, glutathione, and NO levels impaired by dexamethasone, without any effect on SOD and malondialdehyde. In conclusion, the decoction of the stem bark of Ceiba pentandra has insulin sensitive effects as demonstrated by the improvement of glucose tolerance, oxidative status, and plasma lipid profile. This extract may therefore be a good candidate for the treatment of type II diabetes

Endothelium/Nitric Oxide Mediates the Vasorelaxant and Antihypertensive Effects of the Aqueous Extract from the Stem Bark of Mammea africana Sabine (Guttiferae)

This study evaluates the vasorelaxant and antihypertensive effects of the aqueous extract from the stem bark of M. africana (AEMA). AEMA was tested in vitro on intact or endothelium-denuded rats' aorta rings precontracted with KCl or norepinephrine in absence or in presence of L-NAME or glibenclamide. The effect of a single concentration (300 μg/mL) of AEMA was also examined on the concentration-response curve of KCl. In vivo, the antihypertensive effects of AEMA (200 mg/kg/day) were evaluated in male Wistar rats treated with L-NAME (40 mg/kg/day) for 4 weeks. AEMA relaxed aorta rings precontracted with NE or KCl with respective EC50 values of 0.36 μg/mL and 197.60 μg/mL. The destruction of endothelium or pretreatment of aorta rings with L-NAME shifted the EC50 of AEMA from 0.36 μg/mL to 40.65 μg/mL and 20.20 μg/mL, respectively. The vasorelaxant activity of M. africana was significantly inhibited in presence of glibenclamide. AEMA also significantly inhibited the concentrationresponse curve of KCl. Administered orally, AEMA induced acute and chronic antihypertensive effects and normalized renal NO level. These results show that the vasorelaxant activity of AEMA might be mediated by the activation of the NO-cGMP-ATPdependent potassium channels pathway and might predominantly account for its antihypertensive effect

Acute and chronic antihypertensive effects of <it>Cinnamomum zeylanicum</it> stem bark methanol extract in L-NAME-induced hypertensive rats

Abstract Background Previous study showed that the aqueous extract of the stem bark of Cinnamomum zeylanicum possesses antihypertensive and vasodilatory properties. The present work investigates the acute and chronic antihypertensive effects of the methanol extract of Cinnamomum zeylanicum stem bark (MECZ) in L-NAME-induced hypertensive rats. Methods The acute antihypertensive effects of MECZ (5, 10 and 20 mg/kg) administered intravenously were evaluated in rats in which acute arterial hypertension has been induced by intravenous administration of L-NAME (20 mg/kg). For chronic antihypertensive effects, animals were treated with L-NAME (40 mg/kg/day) plus the vehicle or L-NAME (40 mg/kg/day) in combination with captopril (20 mg/kg/day) or MECZ (300 mg/kg/day) and compared with control group receiving only distilled water. All drugs were administered per os and at the end of the experiment that lasted for four consecutive weeks, blood pressure was measured by invasive method and blood samples were collected for the determination of the lipid profile. The heart and aorta were collected, weighed and used for both histological analysis and determination of NO tissue content. Results Acute intravenous administration of C. zeylanicum extract (5, 10 and 20 mg/kg) to L-NAME-induced hypertensive rats provoked a long-lasting decrease in blood pressure. Mean arterial blood pressure decreased by 12.5%, 26.6% and 30.6% at the doses of 5, 10 and 20 mg/kg, respectively. In chronic administration, MECZ and captopril significantly prevented the increase in blood pressure and organs’ weights, as well as tissue histological damages and were able to reverse the depletion in NO tissue’s concentration. The MECZ also significantly lower the plasma level of triglycerides (38.1%), total cholesterol (32.1%) and LDL-cholesterol (75.3%) while increasing that of HDL-cholesterol (58.4%) with a significant low atherogenic index (1.4 versus 5.3 for L-NAME group). Conclusion MECZ possesses antihypertensive and organ protective effects that may result from its ability to increase the production of the endogenous NO and/or to regulate dyslipidemia.</p