Toxicology of solvent extract and fractions of Alstonia boonei (DC.) Wild stem bark in Rats

Introduction: Toxic effects arising from the use of medicinal herbs have been frequently overshadowed by the therapeutic efficacy of phytomedicines. This study was carried out to assess the safety of extract and fractions of Alstonia boonei (de wild) stem bark, popularly used in the treatment of malaria especially in Africa. Methods: Rats were orally exposed to different doses (200 and 400 mg/kg body weight) of methanol extract (ME), n-hexane (HF), chloroform (CF), ethylacetate (EF) and aqueous fractions (AF) of A. boonei for 7 days. Furthermore, 10 mg/ kg body weight (bw) of chloroquine (CQN) was administered as standard drug for 7 days while, 5% tween 80 (TT) and distilled water (TW) were administered as control for 7 days. Group I (treatment group) was sacrificed after 7 days while group II (recovery group) was left for 21 days to recover and thereafter sacrificed. The effects of treatment and recovery were analyzed using serum biomarkers, hematological parameters and tissue histopathological evaluation. Results: There was reduction in hematological parameters after 7 days but recovered after 21 days. There was also increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), after 7 days. Compared to TW and TT treated groups, histopathological scores of liver and kidney were critical for all groups at 400 mg/kg bw after 21 days. Conclusion: The animals did not fully recover after 21 days, suggesting that 400 mg/kg bw of extract and fractions of A. boonei were both hepatotoxic and nephrotoxic. Hence this plant should be used with caution

Učinci nekih biljaka porodice mlječika na hematološke i biokemijske pokazatelje u štakora.

The effects of five suspected poisonous plants of the spurge family (Euphorbiaceae) i.e. Alchornea cordifolia Schum and Thorn, Cnidoscolus acontifolius Mill, Phyllanthus amarus Schum and Thorn, Phyllanthus muelleriarus Exell and Securinega virosa Baill, which are commonly found in Nigerian pasture were evaluated in albino rats using crude aqueous extracts for 14 days. All the extracts were administered orally. Changes in haematological and biochemical parameters were used as indices of toxicosis. The extracts of the plants caused a significant reduction (P<0.05) in the levels of PCV and haemoglobin concentration. All except C. acontifolius caused a significant reduction in RBC level. The extract of four plants (A. cordifolia, C. acontifolius, P. amarus and P. muellerianus) caused significant changes of the total white blood cells when compared to that of the control. The extracts also caused a significant increase in the levels of total protein, albumin and AST activity. The extracts of A. cordifolia, P. muellerianus and S. virosa caused a significant increase in the level of ALT. Only P. muellerianus and virosa produced significant changes in the globulin level.Učinci sirovih vodenih iscrpaka pripravljeni od pet vrsta biljaka porodice mlječika (Euphorbiaceae) sumnjivih da su otrovne: Alchornea cordifolia Schum i Torn, Cnidoscolus acontifolius Mill, Phyllanthus amarus Schum i Torn, Phyllanthus muellerianus Exell i Securinega virosa Baill, koje se često nalaze na nigerijskim pašnjacima, istraženi su na albino štakorima u tijeku 14 dana. Svi iscrpci davani su oralno. Promjene u hematološkim i biokemijskim pokazateljima uzete su kao znakovi otrovanja. Davanje iscrpaka prouzročilo je značajno smanjenje (P<0,05) vrijednosti hematokrita i koncentracije hemoglobina. Svi su, osim iscrpka Cnidoscolus acontifolius, uzrokovali značajno smanjenje broja crvenih krvnih stanica. Iscrpci biljaka Alchornea cordifolia, Cnidoscolus acontifolius, Phyllanthus amarus i Phyllanthus muellerinanus uzrokovali su značajne promjene ukupnog broja bijelih krvnih stanica u usporedbi s kontrolom. Iscrpci su također doveli do značajnog povećanja razina ukupnih bjelančevina, albumina i aktivnosti AST. Iscrpci Alchornea cordifolia, Phyllanthus muellerianus i Securinega virosa uzrokovali su značajno povećanje razine ALT. Samo Phyllanthus muellerianus i Securinega virosa uzrokovali su značajne promjene u razini globulina

In vitro induction of rat liver mitochondrial membrane permeability transition pore opening by solvent extracts of Momordica charantia leaves

Alteration of mitochondrial functions such as permeability transition (PT), a process associated with the uncoupling of oxidative phosphorylation, has been found to play a vital role in the apoptotic process induced by certain anti-cancer agents. When triggered, PT facilitates the release of mitochondrial apoptogenic proteins which in turn activate the caspase cascade of apoptosis. Thus, this study investigated the in vitro effects of varying concentrations (0.2, 0.4, 0.6, 0.8 and 1.0 mg/ml) of different leaf extracts [Crude Water-Soluble Extract (CWSE), Decoction (DE) and Methanol Extract (ME)] of Momordica charantia (M. charantia), a purported anti-cancer plant of the family Cucurbitaceae on normal rat liver mitochondria. Opening of mitochondrial membrane permeability transition pore (MMPTP) was spectrophotometrically assayed under succinate-energized condition. Results obtained showed concentration-dependent and significant (P&lt;0.05) increases in the extents to which MMPTP opening was induced by the three extract types when compared with the control group. Inductions caused by CWSE and DE increased with increasing concentrations while those caused by ME decreased with increasing concentrations, giving the maximum induction at 1.0 mg/ml (8.1-fold increase) of CWSE and the least induction at 1.0 mg/ml (4.3-fold increase) of ME, respectively. Spermine, a reference inhibitor of MMPTP opening, reversed all observed openings. These results indicate that the tested leaf extracts of M. charantia are potent (CWSE being the most potent) MMPTP opening inducers and the pathway by which M. charantia causes apoptosis in cancer cells is probably mitochondrial-mediated (intrinsic)

Toxicology of solvent extract and fractions of Alstonia boonei (DC.) Wild stem bark in Rats

Introduction: Toxic effects arising from the use of medicinal herbs have been frequently overshadowed by the therapeutic efficacy of phytomedicines. This study was carried out to assess the safety of extract and fractions of Alstonia boonei (de wild) stem bark, popularly used in the treatment of malaria especially in Africa. Methods: Rats were orally exposed to different doses (200 and 400 mg/kg body weight) of methanol extract (ME), n-hexane (HF), chloroform (CF), ethylacetate (EF) and aqueous fractions (AF) of A. boonei for 7 days. Furthermore, 10 mg/ kg body weight (bw) of chloroquine (CQN) was administered as standard drug for 7 days while, 5% tween 80 (TT) and distilled water (TW) were administered as control for 7 days. Group I (treatment group) was sacrificed after 7 days while group II (recovery group) was left for 21 days to recover and thereafter sacrificed. The effects of treatment and recovery were analyzed using serum biomarkers, hematological parameters and tissue histopathological evaluation. Results: There was reduction in hematological parameters after 7 days but recovered after 21 days. There was also increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP), after 7 days. Compared to TW and TT treated groups, histopathological scores of liver and kidney were critical for all groups at 400 mg/kg bw after 21 days. Conclusion: The animals did not fully recover after 21 days, suggesting that 400 mg/kg bw of extract and fractions of A. boonei were both hepatotoxic and nephrotoxic. Hence this plant should be used with cautious

Metformin induces apoptosis via uterus mitochondrial permeability transition pore opening and protects against estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female Wistar rats

Abstract Background Some antitumor or anticancer agents have been shown to execute cell death by induction of mitochondrial permeability transition (mPT) pore opening in order to elicit their chemotherapeutic effect. Therefore, this study investigated the effect of metformin on cell death via rat uterus mPT pore and estradiol benzoate-induced uterine defect and associated pathophysiological disorder in female rat. Mitochondria were isolated using differential centrifugation. The mPT pore opening, cytochrome c release and mitochondrial ATPase activity were determined spectrophotometrically. Caspases 9 and 3 activities, MDA and estradiol levels and SOD, GSH activities, were determined using ELISA technique. Histological and histochemical assessments of the uterine section were carried out using standard methods. Results Metformin at concentrations 10–90 μg/mL, showed no significant effect on mPT pore opening, mATPase activity and release of cytochrome c. However, oral administration of metformin caused mPT pore opening, enhancement of mATPase activity and activation of caspases 9 and 3 significantly at 300 and 400 mg/kg. Metformin protected against estradiol benzoate (EB)-induced uterine defect and other associated pathophysiological disorder. It also improved the antioxidant defense system. The histological evaluation revealed the protective effect of metformin on the cellular architecture of the uterus while the histochemical examination showed severe hyperplasia in the uterine section of EB-treated rats, remarkably reversed by metformin co-treatment. Conclusion This study suggests that metformin at high doses induces apoptosis via rat uterus mPT pore opening and protects against EB-induced uterine defect (hyperplasia) and associated pathophysiological disorder

Diverse mitochondrial effects, antiplasmodial and anti-inflammatory potentials of Costus afer (Ker Gawl), Nauclea latifolia (Sm) and Sphenocentrum jollyanum (Pierre) in mice infected with Plasmodium berghei

Objectives: This study reported the antiplasmodial, anti-inflammatory and mito-protrective effects of Costus afer (CA), Nauclea latifolia (NA) and Sphenocentrum jollyanum (SJ) methanol extracts in Plasmodium berghei-infected mice. Methods: Air-dried CA, NA and SJ were extracted with methanol. Antiplasmodial activity of these extracts were monitored using chloroquine-sensitive and resistant strains of Plasmodium berghei. Heme and hemozoin contents, interleukins and C-reactive protein as well as mitochondrial permeability transition (mPT) pore opening, lipid peroxidation (mLPO) and F0F1 ATPase activity were determined by spectrophotometry. Phytochemical constituents were determined using UPLC-QTOF-MS and NMR spectroscopy. Results and Conclusions: CA, NL and SJ decreased percentage parasitemia to 0.25 ± 0.07; 0.30 ± 0.14 and 0.25 ± 0.07% relative to control (8.60 ± 0.15%) in the chloroquine-sensitive model and to 0.40 ± 0.14; 0.30 ± 0.14 and 0.45 ± 0.07, respectively as against 10.88 ± 0.26% of the infected control in the chloroquine-resistant model. In chloroquine-resistant model, NL decreased mLPO (0.41 ± 0.04) F0F1 ATPase (0.15 ± 0.02 mmol pi/mg protein /min) while CA enhanced mPT pore opening at 100 mg/kg,and SJ (50 mg/kg) reversed parasite-induced mPT pore opening (1.66 vs 9.4 folds). The NL increased heme, decreased hemozoin, IL-6, CRP, TNF-α, while SJ dose-dependently increased IL-10. UPLC-QTOF-MS analysis showed that coumaric acid, divaricatinic acid, diocin and aferiosides A and C were present in CA, 3-caffeoylquinic acid, 18, 19-dihydroangustine, jatrorrhizine, 17-epinaucleidinal, strictosamide and quinovic acid 3-O-rhamnoside in NL and quinic acid, jatrorrhizine and mabioside B in SJ. While the three medicinal plants have varying antimalarial effects, their decoction will be better for a synergistic purpose

In vitro effects of 2-methyl-3-propylbutane-1,4-diol purified from Alstonia boonei on erythrocyte membrane stabilization and mitochondrial membrane permeabilization

A recent review on the ethnomedicinal, chemical, pharmacological, and toxicological properties of Alstonia boonei revealed the plant's potential in the treatment and management of a range of diseases. However, most of these pharmacological effects are only traceable to the crude form of the plant extract and not specific natural products. Phytochemical investigation of the methanol fraction of the methanol extract of the stem-bark of Alstonia boonei led to the isolation and identification of 2-methyl-3-propylbutane-1,4-diol. The structures were elucidated by the application of 1D-, and 2D-NMR spectroscopic analyses and by comparison with literature data. In this study, the membrane stabilizing activity, mitochondrial membrane permeability transition pore opening, cytochrome c release, mitochondrial ATPase activity, and prevention of mitochondrial lipid peroxidation activity of 2-methyl-3-propylbutane-1,4-diol (MPBD) isolated from A. boonei were determined. The results showed that MPBD significantly (p < .05) prevented peroxidation of mitochondrial membrane lipids and hemolysis using both the heat-induced and hypotonic solution-induced membrane stabilization assays. On the contrary, the compound caused large amplitude swelling of rat liver mitochondria in the absence of calcium, significant (p < .05) cytochrome c release and enhancement of mitochondrial ATPase activity in vitro. Our findings suggest that MPBD showed characteristic biological properties useful in modulating cell death.http://wileyonlinelibrary.com/journal/cbdd2023-11-02hj2023Chemistr

In vitro induction of rat liver mitochondrial membrane permeability transition pore opening by solvent extracts of Momordica charantia leaves

Alteration of mitochondrial functions such as permeability transition (PT), a process associated with the uncoupling of oxidative phosphorylation, has been found to play a vital role in the apoptotic process induced by certain anti-cancer agents. When triggered, PT facilitates the release of mitochondrial apoptogenic proteins which in turn activate the caspase cascade of apoptosis. Thus, this study investigated the in vitro effects of varying concentrations (0.2, 0.4, 0.6, 0.8 and 1.0 mg/ml) of different leaf extracts [Crude Water-Soluble Extract (CWSE), Decoction (DE) and Methanol Extract (ME)] of Momordica charantia (M. charantia), a purported anti-cancer plant of the family Cucurbitaceae on normal rat liver mitochondria. Opening of mitochondrial membrane permeability transition pore (MMPTP) was spectrophotometrically assayed under succinate-energized condition. Results obtained showed concentration-dependent and significant (P<0.05) increases in the extents to which MMPTP opening was induced by the three extract types when compared with the control group. Inductions caused by CWSE and DE increased with increasing concentrations while those caused by ME decreased with increasing concentrations, giving the maximum induction at 1.0 mg/ml (8.1-fold increase) of CWSE and the least induction at 1.0 mg/ml (4.3-fold increase) of ME, respectively. Spermine, a reference inhibitor of MMPTP opening, reversed all observed openings. These results indicate that the tested leaf extracts of M. charantia are potent (CWSE being the most potent) MMPTP opening inducers and the pathway by which M. charantia causes apoptosis in cancer cells is probably mitochondrial-mediated (intrinsic)

A novel compound purified from <i>Alstonia boonei</i> inhibits <i>Plasmodium falciparum</i> lactate dehydrogenase and plasmepsin II

A novel compound purified from <i>Alstonia boonei</i> inhibits <i>Plasmodium falciparum</i> lactate dehydrogenase and plasmepsin I