Cajanus cajan (L) Millsp. seed extract ameliorates scopolamine-induced amnesia through increase in antioxidant defense mechanisms and cholinergic neurotransmission.

Decline in cholinergic function and oxidative/nitrosative stress play a central role in Alzheimer's disease (AD). Previous quantitative HPLC profiling analysis has revealed the presence of Pinostrobin, formononetin, vitexin and other neuroprotective flavonoids in Cajanus cajan seed extract. This study was designed to investigate the protective action of Cajanus cajan ethanol seed extract (CC) on learning and memory functions using scopolamine mouse model of amnesia. Materials and methods: Adult mice were pretreated with CC (50, 100, or 200mg/kg, p.o) or vehicle (10ml/kg, p.o) for 16 days consecutively. Scopolamine, a competitive muscarinic cholinergic receptor antagonist (1mg/kg, i.p.) was given an hour after CC pretreatment from days 3 to 16.  The mice were subjected to behavioural tests from day 11 (open field test (OFT)/ Y-maze test (YMT) and Morris water maze task (MWM) from days 12-16. Animals were euthanized 1h after behavioral test on day 16 and discrete brain regions isolated for markers of oxidative stress and cholinergic signaling. Molecular docking analysis was undertaken to predict the possible mechanism(s) of CC-induced anti-amnesic action.  pre-administration of CC significantly reversed working memory and learning deficits caused by scopolamine in YMT and MWM tests, respectively. Moreover, CC prevented scopolamine-induced oxidative and nitrosative stress radicals in the hippocampus evidenced in significant increase in glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) activities with a marked decrease in malondialdehyde (MDA) production, as well as significant inhibition of hippocampal scopolamine-induced increase in acetylcholinesterase activity by CC. The molecular docking analysis showed that out of the 19 compounds, the following had the highest binding affinity; Pinostrobin (-8.7 Kcal/mol), friedeline (-7.5kCal/mol), and lupeol (-8.2 Kcal/mol), respectively, to neuronal muscarinic M1 acetylcholine receptor, α7 nicotinic acetylcholine receptor and amyloid beta peptide binding pockets, which further supports the ability of CC to enhance neuronal cholinergic signaling and possible inhibition of amyloid beta aggregation. This study showed that Cajanus cajan seeds extract improved working memory and learning through enhancement of cholinergic signaling, antioxidant capacity and reduction in amyloidogenesis.

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.

Antihyperglycemic profile of erinidine isolated from Hunteria umbellata seed.

Water decoction made from the seed of Hunteria umbellata is widely used in the traditional management of diabetes mellitus by Nigerian herbalists, particularly, in the southwest region of the country. Recently, a new bisindole alkaloid, erinidine, was isolated but its antihyperglycemic profile remains largely un-investigated scientifically. This forms the basis for the current study which is primarily designed at investigating the antihyperglycemic profile of erinidine and other fractions in both in vitro and in vivo models of diabetes mellitus. In the present study, erinidine was isolated and purified using the earlier described methods and its antihyperglycemic potentials tested in in vitro models such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity, aldose reductase assays and α-glucosidase inhibition assay testings. In addition, 50 mg/kg of erinidine and that of other fractions were evaluated in in vivo models of normal and chemically-induced hyperglycemic rats. Results showed that erinidine was a light yellow, amorphous solid with UV (CHCl3) λ max 256 nm, HRESIMS m/z 382.1881 [(M+H)(+)] (calculated for C22H26N4O2, 382.1876) and melting point of 230 °C. The in vitro study showed the antihyperglycemic action of erinidine to be weakly mediated via α-glucosidase inhibition mechanism as the results for other in vitro tests such as dipeptidylpeptidase (IV), glycogen phosphorylase, HIT-T15 cell insulin secretion, glucose uptake activity and aldose reductase assays were all negative. However, the in vivo results showed 50 mg/kg erinidine given per os to normal and alloxan-induced hyperglycemic rats to significantly (p<0.05, p<0.001) attenuate an increase in their post-absorptive blood glucose concentrations after 3 g/kg glucose loading in the rats, suggesting its antihyperglycemic mechanism to be via α-glucosidase inhibition. This result, although, further corroborated the in vitro findings but also suggests that erinidine needs to be biotransformed in vivo for its inhibitory activity on intestinal glucose absorption to become evident. Thus, the present study suggests erinidine to be the possible antihyperglycemic agent in Hunteria umbellata seed extract mediating its antihyperglycemic action via intestinal glucose uptake inhibition.

Combretum mucronatum and Capparis thonningii prevent scopolamine-induced memory deficit in mice.

CONTEXT: Roots of Combretum mucronatum Schumach. & Thonn. (Combretaceae) and Capparis thonningii Schum. (Capparaceae) are used in southwest Nigeria in the treatment of inflammatory disorders and mental illness. OBJECTIVE: This study evaluated the antidementic effect of the methanol root extracts of C. mucronatum and C. thonningii on scopolamine (3 mg/kg, i.p.) induced memory impairment in mice. MATERIALS AND METHODS: The effect of C. mucronatum and C. thonningii (50-200 mg/kg) administered orally for 3 days on memory impairments induced in mice by scopolamine was assessed in the passive avoidance and Morris water maze test and compared with that of tacrine (5 mg/kg, i.p.). The activities of acetylcholinesterase (AchE) and antioxidant enzymes were estimated in the brain after the completion of behavioral studies. RESULTS: C. mucronatum and C. thonningii root extracts (50-200 mg/kg) reversed scopolamine-induced memory deficit with significant (p < 0.05) increase in transfer latency in passive avoidance test. Similarly, the extracts (200 mg/kg) ameliorated memory deficit as a result of significant (p < 0.001) decrease in escape latency and path length in Morris water maze test. The increased AChE activity induced by scopolamine was significantly (p < 0.05) inhibited by C. mucronatum and C. thonningii (100 and 200 mg/kg) treatment which was similar to the effect of tacrine. Both extracts significantly (p < 0.05) attenuated scopolamine-induced increase in oxidative stress parameters as well as restoration of glutathione activity. DISCUSSION AND CONCLUSION: C. mucronatum and C. thonningii extracts possess significant anticholinesterase, antioxidant and antidementic properties, which may be useful in the management of Alzheimer's disease.

Analgesic activity of the aqueous seed extract of Hunteria umbellata (K. Schum.) Hallier f. in rodents.

The analgesic effect and possible mechanism(s) of action of 50-200 mg/kg of the aqueous seed extract of H. umbellata (HU) were investigated in different experimental models of analgesia using the tail flick, tail immersion, acetic acid-induced writhing tests and formalin-induced algesia. Oral pre-treatment with 50-200 mg/kg of HU caused significant and dose related analgesic effect in the treated rats in all the experimental models used. This analgesia was mediated via central and peripheral mechanisms. Overall, the results showed that HU possesses analgesic effect which lends support to its folkloric use in the local management of pain.

Anti-obesity and antihyperlipidaemic effect of Hunteria umbellata seed extract in experimental hyperlipidaemia.

AIM OF THE STUDY: In Nigerian folk medicine, water infusion of the dried seeds of Hunteria umbellata (K. Schum.) Hallier f. has a reputation for the local management of obesity and hyperlipidaemia. The present study is aimed at evaluating the anti-obesity and antihyperlipidaemic activities as well as the underlying mechanisms of action of the aqueous seed extract of Hunteria umbellata (HU) in normal, triton-induced, and olive oil-induced hyperlipidaemic rats. MATERIALS AND METHODS: Normal and olive oil-induced hyperlipidaemic, and triton-induced hyperlipidaemic rats were pre-treated with single, daily oral administration of 10 ml/kg of distilled water, 20 mg/kg of simvastatin, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in 10 ml/kg of distilled water for 28 days and 24 h. The effects of these drugs on % body weight change, feeding pattern, serum lipids, coronary artery risk index (CRI) and atherogenic index (AI) and Lee's index (LI) were investigated. RESULTS: Oral pre-treatment with simvastatin and graded oral doses of HU significantly (p<0.05) reduced the weight gain pattern and caused dose related (p<0.05, p<0.01 and p<0.001) reductions in the serum lipids, CRI, AI and LI. Also, HU pre-treatment significantly improved triton-induced hepatic histological lesions. CONCLUSIONS: Results of this study showed that HU has both anti-obesity and antihyperlipidaemic effects which may partly be mediated via inhibition of intestinal lipid absorption and de novo biosynthesis of cholesterol. Thus, the results justify the ethnopharmacological use of the extract in the management of obesity and hyperlipidaemia.

Further evaluation of antihyperglycaemic activity of Hunteria umbellata (K. Schum) Hallier f. seed extract in experimental diabetes.

ETHNOPHARMACOLOGICAL RELEVANCE: In African traditional medicine, water decoction made from the dry seeds of Hunteria umbellata (K. Schum) Hallier f. is highly valued in the management of diabetes mellitus. AIM: In the present study, the antihyperglycaemic activity of the seed aqueous extract of Hunteria umbellate (K. Schum) Hallier f. (HU) was investigated in alloxan-induced, high fructose- and dexamethasone-induced hyperglycaemic rats. MATERIALS AND METHODS: Alloxan-induced, dexamethasone-induced and high fructose-induced hyperglycaemic rats were treated with single, daily oral administration of 1 mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg and 200 mg/kg of HU in Groups III, IV, V and VI, for 14 days, 21 days and 8 weeks, respectively. The effects of these drugs on FBG, free plasma insulin levels, HbA(1c), serum TG and TC, and insulin resistance indices were investigated. RESULTS: Data generated in the current study showed that glibenclamide and graded oral doses of HU caused significant dose related (p < 0.05, < 0.01 and < 0.001) reductions in FBG when compared to the values obtained for the model control (Group II) rats. Similarly, daily oral administration of 66.7 g/kg fructose to rats for 8 weeks was associated with significant (p < 0.001) hyperglycaemia, elevations in plasma HbA(1c), free insulin, fasting insulin resistance indices, serum TG, and cholesterol. However, concomitant oral treatments with 1mg/kg of glibenclamide, 50 mg/kg, 100 mg/kg, and 200 mg/kg of HU extract significantly and dose dependently (p < 0.05, < 0.01 and < 0.001) attenuated development of hyperglycaemia, decreased levels of plasma HbA(1c), free insulin, and serum triglyceride and cholesterol, in the Groups III, IV, V and VI rats, respectively, when compared to fructose-induced hyperglycaemic (Group II) rats. Similar effect was also recorded in the dexamethasone-induced hyperglycaemic rats. CONCLUSION: Results of this study suggest that the hypoglycaemic and antihyperlipidaemic effects of HU are mediated via enhanced peripheral glucose uptake and improvements in hyperinsulinaemia.