Evaluating the hepatoprotective, ameliorative and antioxidant potentials of the crude aqueous leafy extracts of Mangifera indica plant against acute paracetamol-induced hepatotoxicity in a mouse model.

Background: Drug-induced hepatotoxicity is a major public health issue of concern. It significantly affects the development of new pharmaceutical drugs and has led to the withdrawal of many promising pharmaceutical drugs from the pharmaceutical market. Aim: The aim of this study was to evaluate the hepatoprotective, ameliorative and antioxidant effects of the crude aqueous leafy extract of Mangifera indica plant and its different separating medium fractions against acute acetaminophen (paracetamol)-induced hepatotoxicity in a mouse model. Methods & materials: Twelve different groups of six mice (three males and three females) were used for this study. Acetaminophen at a single lethal hepatotoxic dose of 3 g/kg was orally administered on the seventh day to the mice in groups 2 to 12 after their 6-day pretreatment duration for the induction of hepatotoxicity; and were then left for 24 hours before the collection of specimen samples were completed, while group 1 served as control. Results: The crude aqueous leafy extract of M. indica (125-250 mg/kg) produced a dose-dependent reversal of the lethal hepatotoxic effect of oral 3 g/kg dose of paracetamol. At the dose of 250 mg/kg, it significantly (p < 0.0001) reduced the levels of hepatic enzymes markers (alanine transaminase [ALT], aspartate transaminase [AST] and alkaline phosphatase [ALP]) in the serum of treated animals. Also, the effects of the crude aqueous leafy extract were found to be statistically significant (p < 0.0001) more than that of its different separating medium fractional components. Conclusion: The findings from this study demonstrated that the crude aqueous leafy extract of M. indica possesses hepatoprotective effect, possibly mediated through the induction of antioxidant enzymes to prevent the occurrence of oxidative stress damage or most likely through the inhibition of pro-inflammatory mediators which are being induced by the lethal hepatotoxic dose of paracetamol.

Alterations of haemodynamic parameters in spontaneously hypertensive rats by Aristolochia ringens Vahl. (Aristolochiaceae).

Aristolochia ringens Vahl. (Aristolochiaceae (AR); mǎ dou líng) is used traditionally in Nigeria for the management of various disorders including oedema. Preliminary investigation revealed its modulatory effect on the cardiovascular system. This study was aimed at investigating the effect of the aqueous root extract of A. ringens (AR) on haemodynamic parameters of spontaneously hypertensive rats (SHRs). The effect of oral subacute (21 days) and intravenous acute exposure of SHRs to the extract were assessed using tail cuff and carotid artery canulation methods respectively. In the latter, the effect of chloroform, butanol and aqueous fractions of AR were also evaluated. The extract significantly reduced systolic and diastolic blood pressures in SHRs, with peak reductions of 20.3% and 26.7% respectively at 50 mg/kg by the 21st day of oral subacute exposure. Upon intravenous exposure, AR (50 mg/kg) reduced systolic and diastolic blood pressure by as much as 53.4 ± 2.2 and 49.2 ± 2.8 mmHg respectively. A dose-dependent reduction in heart rate, significant at 25 and 50 mg/kg was also observed. Hexamethonium (20 mg/kg) and atropine (1 mg/kg) inhibited the extract's reduction of systolic blood pressure, diastolic blood pressure and heart rate significantly. The extract's butanol fraction produced the greatest systolic and diastolic blood pressures reduction of 67.0 ± 3.8 and 68.4 mmHg respectively at 25 mg/kg and heart rate reduction of 40 ± 7 beats per minute at 50 mg/kg. HPLC analysis revealed the presence of 4-hydroxybenzoic acid and quercetin in AR. The extract's alterations of haemodynamic parameters in this study show that it has hypotensive effect on spontaneously hypertensive rats.

Anticancer activity of Aristolochia ringens Vahl. (Aristolochiaceae).

Cancer is a leading cause of death worldwide and sustained focus is on the discovery and development of newer and better tolerated anticancer drugs especially from plants. The sulforhodamine B (SRB) in vitro cytotoxicity assay, sarcoma-180 (S-180) ascites and solid tumor, and L1210 lymphoid leukemia in vivo models were used to investigate the anticancer activity of root extracts of Aristolochia ringens Vahl. (Aristolochiaceae; mǎ dou líng). AR-A001 (IC50 values of 20 µg/mL, 22 µg/mL, 3 µg/mL, and 24 µg/mL for A549, HCT-116, PC3, and THP-1 cell lines, respectively), and AR-A004 (IC50 values of 26 µg/mL, 19.5 µg/mL, 12 µg/mL, 28 µg/mL, 30 µg/mL, and 22 µg/mL for A549, HCT-116, PC3, A431, HeLa, and THP-1, respectively), were observed to be significantly active in vitro. Potency was highest with AR-A001 and AR-A004 for PC3 with IC50 values of 3 µg/mL and 12 µg/mL, respectively. AR-A001 and AR-A004 produced significant (p < 0.05-0.001) dose-dependent inhibition of tumor growth in the S-180 ascites model with peak effects produced at the highest dose of 120 mg/kg. Inhibition values were 79.51% and 89.98% for AR-A001 and AR-A004, respectively. In the S-180 solid tumor model, the inhibition of tumor growth was 29.45% and 50.50% for AR-A001 (120 mg/kg) and AR-A004 (110 mg/kg), respectively, compared to 50.18% for 5-fluorouracil (5-FU; 20 mg/kg). AR-A001 and AR-A004 were also significantly active in the leukemia model with 211.11% and 155.56% increase in mean survival time (MST) compared to a value of 211.11% for 5-FU. In conclusion, the ethanolic (AR-A001) and dichloromethane:methanol (AR-A004) root extracts of AR possess significant anticancer activities in vitro and in vivo.